Single-atom Pt-anchored Zn0.5Cd0.5S boosted photoelectrochemical immunoassay of prostate-specific antigen.
Photoelectrochemical immunoassays/immunosensors have been employed for biomarker detection, but most are lack of high-efficiency photo-electron transfer nanomaterials for widespread utilization. Herein we synthesized single-atom platinum-anchored Zn0.5Cd0.5S nanostructures to construct an innovative photoelectrochemical (PEC) immunosensor for photocurrent determination of prostate-specific antigen (PSA). Improvement of the photocurrent on the sensing interface derived from the ion-exchange reaction between cupric oxide nanoparticle (CuO NP)-labeled secondary antibody and single-atom platinum-anchored Zn0.5Cd0.5S. The experimental results showed that the doping of zinc ions and atomically dispersed platinum into CdS could significantly enhance the photocurrent, which further improved the sensitivity of immunoassay. Specifically, upon sensing the target PSA, a CuO-labeled detection antibody was introduced by sandwich immunoreaction and numerous copper ions (Cu2+) were released from CuO by acid to participate in the ion-exchange reaction. Thereafter, the ion-exchange reaction between Cu2+ ions and single-atom platinum-anchored Zn0.5Cd0.5S resulted in the quenching of the photocurrent from single-atom platinum-anchored Zn0.5Cd0.5S owing to weak photoactive material CuxS formation. Under optimized conditions, single-atom platinum-anchored Zn0.5Cd0.5S-based photoelectrochemical immunoassay gave good PEC signals toward PSA from 1.0 to 10000 pg/mL with a limit of detection of 0.22 pg/mL. Additionally, good repeatability, intermediate precision, strong anti-interference and high accuracy (relative to commercialized ELISA kit) for the measurement of human serum specimens were acquired. Importantly, use of single-atom platinum-anchored Zn0.5Cd0.5S can provide an important idea for early tumor screening and diagnosis.


Malignant duodenocolic fistula: a case report.
A 65 year-old female presented with diarrhea, body weight loss, malnutrition, elevated serum carcinoembryonic antigen (CEA) and electrolyte disturbances. A series of examinations showed colon cancer with a malignant duodenocolic fistula. Patient received extended right hemicolectomy with wide local excision of the duodenum (en bloc resection of the tumor). Recovery was smooth without local recurrence or metastasis after a six-month follow-up. Wide en bloc resection provides the only hope of cure in such cases. Treatment with extended right hemicolectomy with Whipple's procedure, or extended right hemicolectomy with extended local wide excision of duodenum, should be chosen, depending upon the extent of tumor invasion.


Influence of surfactant on CO2 adsorption of amine-functionalized MCM-41.
Concerning the increasing greenhouse effect, the development of efficient CO2 adsorbents is very important. In this study, the influence of surfactant on the adsorption performance of amine-functionalized MCM-41 was analysed. The results showed that the residual amount of surfactant in MCM-41 was gradually decreased with the increase of calcination temperature which improved the pore structure. The maximum adsorption capacity (5.495 mmol/g) appeared at PEI-MCM-41-100°C indicated that the adsorption capacity could be improved under the function of surfactant. By calculating the diffusion coefficient of CO2 adsorption process in PEI-MCM-41-100/200/300/400/550°C, the diffusion resistance of CO2 was the lowest in PEI-MCM-41-100°C, which directly proved that the synergism of surfactant and organic amine could reduce the diffusion resistance of CO2 in the pore.


Function of Rhizodermal Transfer Cells in the Fe Stress Response Mechanism of Capsicum annuum L.
A variety of red pepper (Capsicum annuum L., cv Yaglik) responds to Fe deficiency stress with simultaneously enhanced H(+) extrusion, reduction of ferric ions and synthesis of malic and citric acid in a swollen subapical root zone densely covered with root hairs. It is demonstrated that these stress responses temporally coincide with the development of rhizodermal and hypodermal transfer cells in this root zone. During stress response the transfer cells show a marked autofluorescence which could arise from endogenous iron chelators of the phenolic acid type. The presence of organelle-rich cytoplasm which often exhibits rotational cytoplasmic streaming points to high physiological activity and makes these cells, with their increased plasmalemma surface, particularly well suited for the entire stress response mechanism. Since Fe stress-induced acidification is diminished by vanadate and erythrosin B, both specific inhibitors of plasmalemma ATPases, it seems reasonable to suppose that H(+) pumping from transfer cells is activated by an ATPase located in their plasmamembrane. H(+) extrusion is also shown to be inhibited by abscisic acid. Raised phosphoenolpyruvate carboxylase activity and simultaneous accumulation of malate in the swollen root zone point to the action of a pH stat preventing a detrimental rise in cytoplasmic pH of transfer cells during enhanced H(+) extrusion. The simultaneous increase in citric acid concentration favors chelation of iron at the site of its uptake and thus ensures long distance transport to the areas of metabolic demand. A direct link between citrate accumulation and ferric ion reduction as proposed in recent literature further supports the crucial role of transfer cells in the response to Fe deficiency stress.


Histochemical study of mucopolysaccharides in epidermal mucous cells and subjacent granular cells of Glossoscolex uruguayensis L. (Righi, 1978).
Histochemical study of mucopolysaccharides of both mucous secreting and subjacent granular cells of the epidermis of Glossoscolex uruguayensis L (Righi, 1978), has been done. Histochemical tests revealed two major types of mucous cells: large ortochromatic mucous cells and metachromatic mucous cells. The first ones possess alpha-amylase resistant, PAS-positive material, together with little mucic acid, and the latter present a very low rate of neutral mucopolysaccharides and to a variable degree, both carboxylate and sulphate mucopolysaccharides. A third cell type was also detected, presenting a frothy acid like material. Subjacent epidermal granular cells display alpha-amylase resistant, PAS-positive granules, with no acid mucus.


Should we care: a qualitative exploration of the factors that influence the decision of early marriage among young men in urban slums of Bangladesh.
To explore how adolescent and young men negotiate the complex realities of lives to explain their pathways into and reasons for early marriage in urban slums of Bangladesh. The qualitative data used here came from a larger 3-year study that used both quantitative and qualitative research methods. Interviews were conducted in two of the largest slums in Dhaka and Chittagong city of Bangladesh between December 2015 and March 2018. This paper uses qualitative data from 22 in-depth interviews (IDIs) and three focus group discussions (FGDs) with adolescent and young men aged 15-24 years; 13 IDIs and 4 FGDs with parents and 11 key-informant interviews with community leaders. The purposively selected respondents were interviewed in their respective settings. In the context of urban slums, this study revealed multiple factors influence early marriage decision-making processes among young men. These factors include socially perceived phenomenon of adulthood and readiness of marriage, poverty leading to drop out from schools and early initiation to earning livelihood, manifestations of increasing individual aspiration and agency, fulfilment of romance and erotic desires and dreams of forming one's own family. In addition, parental and immediate societal interference to preserve norms around gender and society can act as catalysts for this decision. Study findings imply that complex structural factors, social and gender norms that are contributing to the early marriage for both adolescent boys and young men in Bangladesh's urban slums. These are locations where conservatism, poverty and urbanisation intersect resulting in early and often unprepared entry to adulthood for young men impacting on their development and well-being. It is, therefore, critical that young men should be included in the national and global conversations around child marriage and child marriage prevention programme.


An international study to develop the EAR-Q patient-reported outcome measure for children and young adults with ear conditions.
There is currently a lack of patient-reported outcome measures for ear reconstruction. We developed the EAR-Q to measure ear appearance and post-operative adverse effects from the patient perspective. Field-test data were collected from children and young adults in eight countries between 13 May 2016 and 12 December 2019. Rasch measurement theory (RMT) analysis was used to refine the scales and to examine their psychometric properties. Participants had microtia (n = 607), prominent ears (n = 145) or another ear condition (n = 111), and provided 960 assessments for the Appearance scale (e.g., size, shape, photos), and 137 assessments for the Adverse Effects scale (e.g., itchy, painful, numb). RMT analysis led to the reduction of each scale to 10-items. Data fit the Rasch model for the Appearance (X2(80) = 90.9, p = 0.19) and Adverse Effects (X2(20) = 24.5, p = 0.22) scales. All items in each scale had ordered thresholds and good item fit. There was no evidence of differential item function for the Appearance scale by age, gender, language, or type of ear condition. Reliability was high for the Appearance scale, with person separation index (PSI) and Cronbach alpha values with and without extremes ≥0.92. Reliability for the Adverse Effects scale was adequate (i.e., PSI and Cronbach alpha values ≥0.71). Higher scores (liked appearance more) correlated with higher scores (better) on Psychological, Social and School scales. The EAR-Q can be used in those 8-29 years of age to understand the patient perspective in clinical practice and research, and in addition, can be used to benchmark outcomes for ear reconstruction internationally.


Distribution of materno-fetus materno-suckling transfer of tritium after single injection of tritiated water in mice.
The metabolism and transfer of tritium from pregnant mice to fetus after injection of tritiated water intraperitoneally was investigated in this paper. The study was composed of three experiments. 1. Pregnant mice were injected with tritium water on the first day of pregnancy, in order to obtain a transfer coefficient of tritium from pregnant mice to fetus through placenta. 2. Pregnant mice were injected with tritiated water on the first day of parturition to study the transfer of tritium via mother milk from nursing mice to the baby-animals. 3. Pregnant mice were injected with tritiated water in different periods of gestation. The results showed that tritiated water was uniformly distributed in all of the tissues measured, including placenta, fetal membrane and amniotic fluid in experiment 1. No effect of placentas on tritium transfer from pregnant mice to fetus was found. Concentration of tritium in the baby's tissues was evidently higher than that in the pregnant mice in experiments 2 and 3, and the transfer coefficient in experiments 2 and 3 was generally higher than that in experiment 1.


Esters of 3-pyridylacetic acid that combine potent inhibition of 17 alpha-hydroxylase/C17,20-lyase (cytochrome P45017 alpha) with resistance to esterase hydrolysis.
Esters of 3- and 4-pyridylacetic acid have been prepared and tested for inhibitory activity toward the human testicular 17 alpha-hydroxylase/C17,20-lyase and human placental aromatase enzymes. The structural features required for optimal inhibition of the hydroxylase/lyase enzyme were a 3-pyridine ring, methyl substitution alpha to the carbonyl group, and a bulky alkoxycarbonyl substituent. The compounds with the greatest selectivity were isopinocampheyl 2-methyl-2-(3-pyridyl)propanoate, 9, 1-adamantyl 2-methyl-2-(3-pyridyl)propanoate, 12, and 2-methyl-2-adamantyl 2-methyl-2-(3-pyridyl)propanoate, 14, which, while inhibiting the aromatase activity with IC50 values of 30, 35, and 40 microM, respectively, exhibited IC50 values toward hydroxylase/lyase of between 13 and 90 nM. For comparison, ketoconazole gave an IC50 value of 15 microM against aromatase and values of 65 and 26 nM for inhibition of the hydroxylase and lyase activities, respectively. Some of the structural features required for enzyme inhibition also conferred resistance to esterase hydrolysis, in vitro using rat liver microsomes as a source of the esterase activity. Therefore these esters are lead compounds in the development of inhibitors of androgen biosynthesis for the treatment of hormone-dependent prostatic cancer.


Giant Renner-Teller vibronic coupling in the BF2 radical: an ab initio study of the X (2)A1 and A (2)Pi electronic states.
The potential energy surfaces (PESs) of the ground X (2)A(1) and the first excited A (2)Pi (1 (2)B(1), 2 (2)A(1)) electronic states of the BF(2) radical have been studied ab initio, using a large basis set and CCSD(T) and EOM-CCSD techniques. The calculated PESs were used to variationally calculate the energy levels up to approximately 36,000 cm(-1) above the ground state. The Renner-Teller splitting parameter (epsilon=0.928) found for the A (2)Pi state of this radical is very large which results in an unusual excited state energy level structure.


Effect of Field of View on Detection of Condyle Bone Defects Using Cone Beam Computed Tomography.
In maxillofacial imaging, cone beam computed tomography (CBCT) is currently the modality of choice for assessment of bony structures of the temporomandibular joint (TMJ). Factors affecting the quality of CBCT images can change its diagnostic accuracy. This study aimed to assess the effect of field of view (FOV) and defect size on the accuracy of CBCT scans for detection of bone defects of the TMJs. This study was conducted on 12 sound TMJs of 6 human dry skulls. Erosions and osteophytes were artificially induced in 0.5, 1, and 1.5-mm sizes on the anterior-superior part of the condyle; CBCT scans were obtained with 6, 9, and 12-inch FOVs by NewTom 3G CBCT system. Two maxillofacial radiologists evaluated the presence/absence and type of defects on CBCT scans. The Cohen kappa was calculated to assess intra- and interobserver reliability. The Mann-Whitney U test was applied to compare the diagnostic accuracy of different FOVs.In comparison of 6- and 12-inch, 9- and 12-inch FOVs in detection of different sizes of erosive lesions, difference was significant (P <0.05), whereas difference between 6- and 9 inch just in 0.5-mm erosive lesion was significant (P = 0.04). In comparison of 6- and 12-inch FOVs in detection of different sizes of osteophyte lesion, difference was significant (P < 0.05), whereas between 6- and 9-inch FOVs statistically significant difference was not observed (P > 0.05). The highest and the lowest diagnostic accuracy of CBCT scans for condyle defects were obtained with 6-inch and 12-inch FOVs, respectively. Diagnostic accuracy of CBCT scans increased with an increase in size of bone defects.


Management of second-trimester missed abortion with intramuscular 15-methyl-prostaglandin F2 alpha.
Midtrimester missed abortion was successfully managed by serial intramuscular injections of 15(S)-15-methyl-prostaglandin F2alpha (PGF2alpha) in 255 patients, the cumulative abortion rates after 24 and 36 hours being 97.6 and 99.6%, respectively. The mean 1st-dose-to-expulsion interval was significantly shorter in the paras, but the period after fetal death was not significant in this respect. In 60% of the cases, abortion was complete. No serious complications occurred. 2/3 of the patients developed gastrointestinal side effects. These side effects were not improved by standardized antiemetic and antidiarrheal treatment, but they were strongly reduced by priming the cervix with extraamniotic PGE2 gel before the PGF2alpha analog was administered.


Malignant paroxysmal positional vertigo.
An insidious percentage of paroxysmal positional vertigo appears to be intractable with canalith repositioning maneuver and also is not self-limiting. This type of positional vertigo is sustained by the action of intracranial tumors that mimics the clinical aspects of benign paroxysmal positional vertigo.Aim of this study is to clarify the features of these forms of positional vertigo, which we indicate as malignant paroxysmal positional vertigo. We retrospectively reviewed the clinical records of all the patients who presented with vertigo spells and were managed at our tertiary care referral centre over a three years period. Two hundred and eleven patients with diagnosis of positional paroxysmal vertigo were included in the final study. Seven patients were affected by intracranial tumors causing a positional vertigo and were classified as malignant paroxysmal positional vertigo patients after radiological and histological diagnosis. These patients were affected by an internal auditory canal mass alone or with extension in the cerebello pontine angle that mimicked a benign positional vertigo. We can conclude that the clinician should keep in mind the differentiation between benign positional vertigo and malignant positional vertigo. When the patients with positional vertigo presents a strange behaviour of symptoms, nystagmus or response to the canalith repositioning maneuver a radiological investigation must be undertaken in every doubtful case.


Sox9-regulated miRNA-574-3p inhibits chondrogenic differentiation of mesenchymal stem cells.
The aim of this study was to identify new microRNAs (miRNAs) that are modulated during the differentiation of mesenchymal stem cells (MSCs) toward chondrocytes. Using large scale miRNA arrays, we compared the expression of miRNAs in MSCs (day 0) and at early time points (day 0.5 and 3) after chondrogenesis induction. Transfection of premiRNA or antagomiRNA was performed on MSCs before chondrogenesis induction and expression of miRNAs and chondrocyte markers was evaluated at different time points during differentiation by RT-qPCR. Among miRNAs that were modulated during chondrogenesis, we identified miR-574-3p as an early up-regulated miRNA. We found that miR-574-3p up-regulation is mediated via direct binding of Sox9 to its promoter region and demonstrated by reporter assay that retinoid X receptor (RXR)α is one gene specifically targeted by the miRNA. In vitro transfection of MSCs with premiR-574-3p resulted in the inhibition of chondrogenesis demonstrating its role during the commitment of MSCs towards chondrocytes. In vivo, however, both up- and down-regulation of miR-574-3p expression inhibited differentiation toward cartilage and bone in a model of heterotopic ossification. In conclusion, we demonstrated that Sox9-dependent up-regulation of miR-574-3p results in RXRα down-regulation. Manipulating miR-574-3p levels both in vitro and in vivo inhibited chondrogenesis suggesting that miR-574-3p might be required for chondrocyte lineage maintenance but also that of MSC multipotency.


The guanine nucleotide exchange factor trio activates the phagocyte NADPH oxidase in the absence of GDP to GTP exchange on Rac. "The emperor's nw clothes".
The superoxide-generating NADPH oxidase complex of phagocytes consists of a membrane-associated flavocytochrome b(559) and four cytosolic components as follows: p47(phox), p67(phox), p40(phox), and the small GTPase Rac (1 or 2). Activation of the oxidase is the result of assembly of the cytosolic components with cytochrome b(559) and can be mimicked in vitro by mixtures of membrane and cytosolic components exposed to an anionic amphiphile, serving as activator. We reported that prenylation of Rac1 endows it with the ability to support oxidase activation in conjunction with p67(phox) but in the absence of amphiphile and p47(phox). We now show the following 6 points. 1) The Rac guanine nucleotide exchange factor Trio markedly potentiates oxidase activation by prenylated Rac1-GDP. 2) This occurs in the absence of exogenous GTP or any other source of GTP generation, demonstrating that the effect of Trio does not involve GDP to GTP exchange on Rac1. 3) Trio does not potentiate oxidase activation by prenylated Rac1-GTP, by nonprenylated Rac1-GDP in the presence or absence of amphiphile, and by a prenylated [p67(phox)-Rac1] chimera in GDP-bound form. 4) Rac1 mutants defective in the ability to bind Trio or to respond to Trio by nucleotide exchange fail to respond to Trio by enhanced oxidase activation. 5) A Trio mutant with conserved Rac1-binding ability but lacking nucleotide exchange activity fails to enhance oxidase activation. 6) The effect of Trio is mimicked by displacement of Mg(2+) from Rac1-GDP. These results reveal the existence of a novel mechanism of Rac activation by a guanine nucleotide exchange factor and suggest that the induction by Trio of a conformational change in Rac1, in the absence of nucleotide exchange, is sufficient for enhancing its effector function.


Renal tolerance of ofloxacin, a new gyrase inhibitor.
An open study was carried out in 12 male, healthy volunteers to investigate the renal tolerance of ofloxacin, a new, broad-spectrum oral antibacterial agent. Subjects received single doses of 300 mg and then repeated doses of 300 mg ofloxacin twice daily for 7 days. Urine was collected in several fractions during the study and the excretion of creatinine, alanine-aminopeptidase (AAP), gamma-glutamyl transferase (GGT) and n-acetyl-beta-glucose aminidase (NAG) was calculated in 12-hour fractions. Serum creatinine, beta 2-microglobulin concentrations and creatinine clearance were also determined. Based on the findings for the kidney enzymes AAP, GGT and NAG, renal tolerance was good. This was confirmed by creatinine clearance and serum beta 2-microglobulin values. Ofloxacin showed no nephrotoxic potential in this study.


Degenerate sequence-based CRISPR diagnostic for Crimean-Congo hemorrhagic fever virus.
CRISPR (clustered regularly interspaced short palindromic repeats), an ancient defense mechanism used by prokaryotes to cleave nucleic acids from invading viruses and plasmids, is currently being harnessed by researchers worldwide to develop new point-of-need diagnostics. In CRISPR diagnostics, a CRISPR RNA (crRNA) containing a "spacer" sequence that specifically complements with the target nucleic acid sequence guides the activation of a CRISPR effector protein (Cas13a, Cas12a or Cas12b), leading to collateral cleavage of RNA or DNA reporters and enormous signal amplification. CRISPR function can be disrupted by some types of sequence mismatches between the spacer and target, according to previous studies. This poses a potential challenge in the detection of variable targets such as RNA viruses with a high degree of sequence diversity, since mismatches can result from target variations. To cover viral diversity, we propose in this study that during crRNA synthesis mixed nucleotide types (degenerate sequences) can be introduced into the spacer sequence positions corresponding to viral sequence variations. We test this crRNA design strategy in the context of the Cas13a-based SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) technology for detection of Crimean-Congo hemorrhagic fever virus (CCHFV), a biosafety level 4 pathogen with wide geographic distribution and broad sequence variability. The degenerate-sequence CRISPR diagnostic proves functional, sensitive, specific and rapid. It detects within 30-40 minutes 1 copy/μl of viral RNA from CCHFV strains representing all clades, and from more recently identified strains with new mutations in the CRISPR target region. Also importantly, it shows no cross-reactivity with a variety of CCHFV-related viruses. This proof-of-concept study demonstrates that the degenerate sequence-based CRISPR diagnostic is a promising tool of choice for effective detection of highly variable viral pathogens.


Arthroscopic Evaluation of the Long Head of the Biceps Tendon: Traditional Versus Allis Clamp Techniques.
Using a probe to retract the long head of the biceps tendon (LHBT) into the joint is common practice for visualizing the extra-articular portions during arthroscopy. However, extra-articular lesions may be missed in up to half of cases. Greater excursion of the LHBT may be achieved with an Allis clamp grasper. Our goal was to quantify portions of the extra-articular LHBT that could be visualized during shoulder arthroscopy with the Allis clamp and probe techniques. Shoulder arthroscopy was performed on 8 forequarter cadaveric specimens in the simulated beach chair position, and the most distal extent of the intra-articular LHBT was marked. The tendon was pulled into the joint with both techniques, and the additional exposed tendon portion was marked. An open approach was performed, and the locations of the 3 marks were assessed relative to total tendon length. Mean LHBT total length was 96.25 mm. Diagnostic arthroscopy allowed visualization of a mean of 21.75 mm of the intra-articular tendon (22.6% of the total length). The traditional probe technique provided visualization of 31.13 mm (32.8%). The Allis clamp technique provided visualization of 49.38 mm (52%) and increased visualization of the LHBT by 58.6% (P<.0001). A mean of 46.87 mm (48%) of the LHBT remained unvisualized. The Allis clamp technique maximizes arthroscopic visualization of extra-articular LHBT. The distal 48% eludes evaluation, but can be visualized when combined with an open technique without the need to divide the transverse humeral ligament. The Allis clamp technique facilitates additional identification of LHBT pathology that could otherwise remain hidden during shoulder arthroscopy. Because the LHBT is a major source of pain in the shoulder, this technique may improve outcomes of shoulder arthroscopy and reduce the need for revision because of remnant anterior shoulder pain. [Orthopedics. 2022;45(1):38-42.].


Preparation of Practical High-Performance Electrodes for Acidic and Alkaline Media Water Electrolysis.
The synthesis of electrocatalyst and the electrode preparation were merged into a one-step process and proved to be a versatile method to synthesize metal oxide electrocatalysts on the conductive carbon paper (CP). Very simply, the metal precursor deposited on the CP was thermally treated by a torch-gun for just 6 s, resulting in the formation of RuO2 , Co3 O4 , and mixed oxide nanoparticles. The material could be directly used as working electrode for oxygen evolution reaction (OER). Compared with commercial and other state-of-the-art electrocatalysts, the fabricated electrode showed a superior electrocatalytic activity for OER in 1 m HClO4 and 1 m KOH in terms of not only a low overpotential to reach 10 mA cm-2 but also a high current density at 1.6 VRHE with satisfying a long-term stability. The novel strategy without requiring time-consuming and uneconomical steps could be expanded to the preparation of various metal oxides on conductive substrates towards diverse electrocatalytic applications.


Nitrotyrasacutuminine from Menispermum dauricum.
Nitrotyrasacutuminine, an unusual nitrated morphine-type alkaloid was isolated from the roots of Menispermum dauricum. Its structure was determined by various 2D spectra and chemical methods.


Adrenal masses: differentiation with chemical shift, fast low-angle shot MR imaging.
The purpose of this study was to investigate the efficacy of chemical shift, fast low-angle shot (FLASH) imaging at 1.5 T to differentiate adrenal masses. The materials included patients with adrenocortical adenomas (n = 32), metastatic tumors (n = 17), and pheochromocytomas (n = 4). FLASH images were obtained with breath holding at 100/11 (repetition time msec/echo time msec) (out-of-phase images) and 100/13 (in-phase images) and a flip angle of 20 degrees to differentiate the lipid contents in the adrenal tumors. The signal-intensity (SI) indexes of adrenal masses ([SI on IP - SI on OP]/[SI on IP x 100]), where IP = in-phase image and OP = out-of-phase image, were calculated. All adenomas had SI indexes of more than 5%, while SI indexes of metastatic tumors and pheochromocytomas were less than 5%, with accuracy of 100% in the differentiation between adenoma and nonadenoma. Hyperfunctioning adenoma, however, could not be differentiated from nonhyperfunctioning adenoma. Chemical shift FLASH imaging was superior to the calculated T2 in the characterization of adrenal masses.


Approach to the adolescent requesting contraception.
It is essential to develop contraceptive counseling skills given the potential complications associated with an unplanned pregnancy, especially for adolescents. Multiple factors must be considered when reviewing contraceptive options with an adolescent: maturity, finances, access to care and prescriptions, confidentiality, medical risks and benefits, and contraindications to use of certain hormonal agents. Many adolescents will be concerned about the possibility of weight gain or the development of acne associated with the use of certain contraceptive agents. They are usually unaware of the risks of thrombosis, stroke, or adverse bone health effects. Providers must be able to speak to these issues using an evidence-based approach.


[Soil dust as a factor which changes the histochemical picture of the rat lung].
White Wistar female rats only once were administered intratracheally a suspension of the soil dust in the physiologic saline. The respirable fraction of the soil dust was used for preparing the suspension of the latter. The experiment was carried out in 2 groups of rats. The animals of the 1st group received the soil dust suspension which was the mixture of the soil samples from 3 different places in Poland, the animals of the 2nd group from 3 other places in Poland. The control animals were once administered the physiologic saline. 9 months after the application of dust, the specimen of the left lung were taken for histochemical examinations. The reactions to the activity of succinic and lactate dehydrogenase, of tetrazole reductase NADP, and of acid phosphatase and ATP-ase were performed. The changes in the activity of the studied respiratory enzymes and the increase of the reaction to the acid phosphatase were observed. The results reveal the disorders of the oxidation-reduction processes and the intensification of the lytic processes in the pulmonary parenchyma of the animals exposed to the action of the soil dust.


Nitrogen metabolism of lactating ewes fed rumen-protected methionine and lysine.
Twenty multiparous, crossbred, black-faced ewes and their newborn twin lambs were assigned to one of four dietary treatments in a 2 x 2 factorial experiment to examine the effects of increased supply of CP or a mixture of encapsulated methionine and lysine or both on the performance of ewes and their nursing twin lambs. Ewes were fed ad libitum amounts of either a 10.2% low CP diet or a 16.2% moderate CP diet with or without additional encapsulated amino acids. Nitrogen metabolism trials were conducted simultaneously on both ewes and lambs at wk 2, 4, and 8 of lactation. Analyses were conducted for blood urea N, plasma 3-hydroxybutyrate, lactate, NEFA, insulin, and amino acids (plasma, feed, and milk). Ewe DMI, BW, BW gain, and milk yield were not changed by dietary treatments. Balance of N and N digested were increased by moderate CP treatment. The portion of retained N used for milk synthesis was increased by low CP treatment. Methionine and total branched-chain amino acids were increased by encapsulated amino acids and by protein treatment. Gains in BW and N balance were increased in lambs nursing ewes fed protected amino acids. Increased growth of nursing lambs would be an important beneficial effect of supplementing diets of ewes with encapsulated methionine and lysine.


Iron deficiency generates secondary thrombocytosis and platelet activation in IBD: the randomized, controlled thromboVIT trial.
Secondary thrombocytosis is a common clinical feature. In patients with cancer, it is a risk factor for venous thromboembolic events. In inflammatory bowel disease (IBD), thrombocytosis is so far considered a marker of active disease and may contribute to the increased thromboembolic risk in this population. Observed effects of iron therapy on normalization of platelet counts led us to hypothesize that iron itself may regulate megakaryopoiesis. Here, we want to test the effect of iron replacement on platelet count and activity in IBD-associated thrombocytosis. We performed a randomized, single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose (FCM) in patients with IBD with secondary thrombocytosis (platelets > 450 G/L). Changes in platelet counts, hemoglobin, iron parameters, disease activity, megakaryopoietic growth factors, erythropoietin, and platelet activity were assessed. Patients received placebo or up to 1500 mg iron as FCM. Endpoints were evaluated at week 6. A total of 26 patients were included in the study, 15 patients were available for the per protocol analysis. A drop in platelets >25% (primary endpoint) was observed in 4 of 8 (50%, iron group) and 1 of 7 patients (14%, placebo group, P = 0.143). Mean platelet counts dropped on FCM but not on placebo (536 G/L to 411 G/L versus 580 G/L to 559 G/L; P = 0.002). Disease activity and megakaryopoietic growth factors remained unchanged and hemoglobin and iron parameters increased on FCM. The normalization of platelet counts was associated with a decrease in platelet aggregation and P-selectin expression. FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis.


Lipoprotein-associated phospholipase A2 as a predictive biomarker of sub-clinical inflammation in cardiovascular diseases.
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a predictor biomarker for incident atherosclerotic disease. Lp-PLA2 has been identified in atherosclerotic plaques, however, its role in atherosclerosis is still under investigation. Lp-PLA2 belongs to the superfamily of phospholipase A2 enzymes. It is produced by macrophages that appears to play a role in the atherosclerotic vessel wall. Emerging data seem to suggest that Lp-PLA2 may be proatherogenic, which is an effect thought to be mediated by lypophosphatidylcholine and oxidized nonesterified fatty acids, two mediators generated by Lp-PLA2. Phospholipase A2 plays an essential role in metabolism of membrane phospholipids, it is related to inflammatory reactions, secretion of amyloid precursor protein. Several studies have documented the strong association of Lp-PLA2 with coronary heart disease and stroke in the general population. Lp-PLA2 may be a stronger predictor of recurrent stroke risk. Inflammatory markers have been associated with ischemic stroke risk. Their relationship to prognosis after stroke is unsettled. The present review article focuses particularly on the characteristics of the Lp(a)-associated Lp-PLA2 and discusses the possible role of this enzyme in view of the new data.


Agnathia-otocephaly complex: report of three cases with involvement of two different Carnegie stages.
Three fetuses with agnathia-otocephaly complex representing different degrees of embryonic maldevelopment are reported. The study of the three cases and of the anterior embryonic disc supports the concept that an altered embryologic development might have taken place at Carnegie stages 10 (embryonic days 22 or 23) and 11 (embryonic days 23-26). Karyotypic abnormalities and aberrant gene expression of sonic hedgehog and paired-related homeobox genes are discussed as the cytogenetic and molecular basis of agnathia-otocephaly complex.


The therapeutic potential of the cerebellum in schizophrenia.
The cognitive role of the cerebellum is critically tied to its distributed connections throughout the brain. Accumulating evidence from anatomical, structural and functional imaging, and lesion studies advocate a cognitive network involving indirect connections between the cerebellum and non-motor areas in the prefrontal cortex. Cerebellar stimulation dynamically influences activity in several regions of the frontal cortex and effectively improves cognition in schizophrenia. In this manuscript, we summarize current literature on the cingulocerebellar circuit and we introduce a method to interrogate this circuit combining opotogenetics, neuropharmacology, and electrophysiology in awake-behaving animals while minimizing incidental stimulation of neighboring cerebellar nuclei. We propose the novel hypothesis that optogenetic cerebellar stimulation can restore aberrant frontal activity and rescue impaired cognition in schizophrenia. We focus on how a known cognitive region in the frontal cortex, the anterior cingulate, is influenced by the cerebellum. This circuit is of particular interest because it has been confirmed using tracing studies, neuroimaging reveals its role in cognitive tasks, it is conserved from rodents to humans, and diseases such as schizophrenia and autism appear in its aberrancy. Novel tract tracing results presented here provide support for how these two areas communicate. The primary pathway involves a disynaptic connection between the cerebellar dentate nuclei (DN) and the anterior cingulate cortex. Secondarily, the pathway from cerebellar fastigial nuclei (FN) to the ventral tegmental area, which supplies dopamine to the prefrontal cortex, may play a role as schizophrenia characteristically involves dopamine deficiencies. We hope that the hypothesis described here will inspire new therapeutic strategies targeting currently untreatable cognitive impairments in schizophrenia.


Sarcopenia for outcomes in patients undergoing spinal surgery: A protocol for a systematic review and pooled analysis of observational studies.
Sarcopenia is a progressive age-related skeletal muscle disorder characterized by decreased muscle mass and loss of muscle function. Recent studies have shown that sarcopenia is able to predict a variety of clinical outcomes after spinal surgery. Controversy still exists among previous reports in terms of the definition and measurement of sarcopenia, these findings are heterogeneous so far. Therefore, the aim of the current study is to assess the up-to-date evidence of sarcopenia for postoperative outcomes among people undergoing spinal surgery. This protocol was carried out based on the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) statement. It has been pre-registered in PROSPERO with the registration number of CRD42021260459. Three databases (including Pubmed, EMBASE, and Cochrane Library) will be searched from inception through May 10, 2021 to determine related cohort studies examining sarcopenia on multidimensional outcomes in patients undergoing spinal surgery. Major outcomes will be involved including mortality, morbidity, length of stay, postoperative complications or adverse events. DerSimonian & Laird random-effects meta-analysis will be used to calculate pooled odds ratio (OR) for binary data and pooled weighted mean differences (WMDs) or standardized mean differences (SMDs) for continuous data. The Newcastle-Ottawa Scale (NOS) will be used to assess the risk of bias of included studies. Narrative synthesis will be carried out if a pooled analysis is not possible. Ethical approval is not required for this study as the data involved are from the published literatures. We intend to disseminate or share the results of the study in a peer-reviewed journal or at relevant conferences. CRD42021260459.


Energy Cost of Running in Well-Trained Athletes: Toward Slope-Dependent Factors.
This study aimed to determine the contribution of metabolic, cardiopulmonary, neuromuscular, and biomechanical factors to the energy cost (ECR) of graded running in well-trained runners. Eight men who were well-trained trail runners (age: 29 [10] y, mean [SD]; maximum oxygen consumption: 68.0 [6.4] mL·min-1·kg-1) completed maximal isometric evaluations of lower limb extensor muscles and 3 randomized trials on a treadmill to determine their metabolic and cardiovascular responses and running gait kinematics during downhill (DR: -15% slope), level (0%), and uphill running (UR: 15%) performed at similar O2 uptake (approximately 60% maximum oxygen consumption). Despite similar O2 demand, ECR was lower in DR versus level running versus UR (2.5 [0.2] vs 3.6 [0.2] vs 7.9 [0.5] J·kg-1·m-1, respectively; all P < .001). Energy cost of running was correlated between DR and level running conditions only (r2 = .63; P = .018). Importantly, while ECR was correlated with heart rate, cardiac output, and arteriovenous O2 difference in UR (all r2 > .50; P < .05), ECR was correlated with lower limb vertical stiffness, ground contact time, stride length, and step frequency in DR (all r2 > .58; P < .05). Lower limb isometric extension torques were not related to ECR whatever the slope. The determining physiological factors of ECR might be slope specific, mainly metabolic and cardiovascular in UR versus mainly neuromuscular and mechanical in DR. This possible slope specificity of ECR during incline running opens the way for the implementation of differentiated physiological evaluations and training strategies to optimize performance in well-trained trail runners.


A novel model of dermatomyositis induced by membrane antigen and calciphylaxis in rats.
Dermatomyositis (DM) is a severe autoimmune disease of the connective tissue characterized by inflammatory and degenerative changes in the skin and muscle. However, the lack of experimental models of DM represents a challenge for the development of effective drugs. The aim of the present study was to establish a pharmacodynamic rat model of DM that would recapitulate the clinical manifestation seen in patients. The DM model was established using membrane antigen-induced autoimmune injury, followed by toxin-induced subcutaneous calciphylaxis. The rats were divided into five groups and were subcutaneously injected with membrane antigen. Of these, four antigen-immunized groups then received dihydrotestosterone (DHT), iron-dextrin (Fe-Dex), polymyxin (PMX) either individually or in combination to induce cutaneous calciphylaxis. The clinical manifestation score, ratio of infiltrated lymphocytes, ratio of arteriole calcified nodules in skeletal muscles, serum antibody levels [anti-histidyl tRNA synthetase (Jo-1) and anti-melanoma differentiation-associated protein 5 (MDA5)] and serum cytokine levels [tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)] were then detected. The results demonstrated that all five autoimmune groups displayed local cutaneous swelling and weakness, increased serum antibody and cytokine levels, and T lymphocyte infiltration in perimysial and perivascular sites. Moreover, pathological changes indicative of calciphylaxis were observed in the PMX and DHT + Fe-Dex + PMX. Among all groups, the rats in the PMX and DHT + Fe-Dex + PMX displayed characteristics most closely resembling those of DM pathogenesis in patients. In conclusion, membrane antigen immunization combined with toxin-induced calciphylaxis can be used as a DM model in rats. This model may be used for the development of effective drugs for DM treatment.


Rapid identification of novel genes expressed in a circadian manner in rat suprachiasmatic nuclei.
The circadian clock in mammals is located in the suprachiasmatic nuclei (SCN). There is evidence that changes in gene expression are central to its mechanism. We are engaged in identifying the genes involved. The small size of the SCN, the large number of mammalian genes and the need to identify those differentially expressed over 24 h have required novel experimental procedures. mRNA differential display and an improved tissue micropunching method have been used to examine temporal changes in gene expression in the SCN of rats maintained in constant darkness. Several of the displayed cDNA species were found to be differentially expressed; they show no homology with published sequences. Riboprobes of these cDNA species were used for in situ hybridization. Emulsion-dipped sections confirmed that at least two of these differentially displayed mRNAs are expressed in a circadian manner.


Impact of water-deficit stress on tritrophic interactions in a wheat-aphid-parasitoid system.
Increasing temperature and CO2 concentrations can alter tritrophic interactions in ecosystems, but the impact of increasingly severe drought on such interactions is not well understood. We examined the response of a wheat-aphid-parasitoid system to variation in water-deficit stress levels. Our results showed that arid area clones of the aphid, Sitobion avenae (Fabricius), tended to have longer developmental times compared to semiarid and moist area clones, and the development of S. avenae clones tended to be slower with increasing levels of water-deficit. Body sizes of S. avenae clones from all areas decreased with increasing water-deficit levels, indicating their declining adaptation potential under drought. Compared to arid area clones, moist area clones of S. avenae had a higher frequency of backing under severe water stress only, but a higher frequency of kicking under well-watered conditions only, suggesting a water-deficit level dependent pattern of resistance against the parasitoid, Aphidius gifuensis (Ashmead). The number of S. avenae individuals attacked by the parasitoid in 10 min showed a tendency to decrease with increasing water-deficit levels. Clones of S. avenae tended to have lower parasitism rates under treatments with higher water-deficit levels. The development of the parasitoid tended to be slower under higher levels of water-deficit stress. Thus, the bottom-up effects of water-deficit stressed plants were negative on S. avenae. However, the top-down effects via parasitoids were compromised by water-deficit, which could favor the growth of aphid populations. Overall, the first trophic level under water-deficit stress was shown to have an indirect and negative impact on the third trophic level parasitoid, suggesting that parasitoids could be increasingly vulnerable in future warming scenarios.


MMPI-2 profiles of worker's compensation claimants who present with complaints of harassment.
This study intended to differentiate among worker's compensation claimants with psychological problems who presented with work-related harassment and non-harassment complaints on the basis of their MMPI-2 profiles. Analysis of MMPI-2 mean scores revealed that the Harassment group scored significantly higher than the Non-harassment group on scale 6 of the MMPI-2. This was interpreted to mean that the Harassment group was more oversensitive, suspicious, and angry than the other group. There was no evidence that the Harassment group was more likely to exaggerate or malinger than the Non-harassment group. The profile pattern for both groups was otherwise very similar to those found in previous studies that have used MMPI worker's compensation claimants who present with psychological problems.


Effect of cortisol on C-type natriuretic peptide in ovine pregnancy: differential responses in fetal and placental tissues.
We have used aminoterminal pro C-type natriuretic peptide (NTproCNP)--a stable marker of CNP secretion--to study the effect of cortisol on CNP secretion and fetal growth. In ovine pregnancy, maternal plasma NTproCNP (largely sourced from the placenta) increases at the end of the first trimester and then decreases abruptly preterm during the phase of fetal surge in cortisol secretion. Postulating that increases in cortisol, as occurs in the fetal or maternal circulation in late pregnancy, will reduce CNP secretion, we studied the fetal and maternal responses in NTproCNP to sustained low-dose infusions of cortisol (1.2 mg/d/kg for 11 d) delivered to the fetus from d 117 gestation. Fetal plasma NTproCNP was progressively reduced during fetal cortisol infusions, whereas fetal girth growth was unchanged. In contrast, maternal NTproCNP was unaffected by cortisol. We conclude that fetal but not placental tissue production of CNP is reduced by small increments in fetal cortisol. Failure to reduce maternal NTproCNP may relate to the continuing presence of the placental barrier to cortisol at this stage of pregnancy.


Design of reflective phase compensator filters for telecommunications.
Reflective phase compensator (RPC) filters provide a solution to the phase-dispersion problem of narrow bandpass (NBP) filters when the data rate is 40 Gbits/s or greater. By use of an RPC filter to compensate for the excessive group-delay (GD) ripple of an NBP filter, the GD ripple of the combined NBP+RPC filter is well under the required 2.5 ps.


Senior High School Students' Knowledge and Attitudes Toward Information on Their Health in the Kumasi Metropolis.
The study examines senior high school students' understanding and attitudes toward information on their health in the Kumasi Metropolis. Multiple sampling techniques (convenient and simple random sampling techniques) were used in the study. A questionnaire was used to collect data from 391 respondents for the study. Frequencies and percentages were used to analyze the sociodemographic data. Again, the study used Pearson's correlation coefficient to show the degree of relationship between the level of knowledge of health information and attitudes toward seeking and sharing health information. The study found students' knowledge of the causes and symptoms of malaria, cholera, and Sexually Transmitted Infections (STIs) to be appreciably high as a result of readings from textbooks and health professionals. Again, the study found that the students preferred sharing their health information with friends than their parents and schools' authorities. The study further found that the major sources of students' health information included health professionals and textbooks. Lastly, even though some of the students claimed internet sources to their health information, it was not a major source to the student body at large. The study recommends strong health systems on the campuses of senior high schools as they have become communities on their own as a result of the emergence of the free senior high school program. The monitored positive peer-counseling group should also be encouraged by the schools' management and by extension the counseling units for the students to share views on themselves, particularly on health issues where they deem fit.


National Rules for Drug-Drug Interactions: Are They Appropriate for Tertiary Hospitals?
The application of appropriate rules for drug-drug interactions (DDIs) could substantially reduce the number of adverse drug events. However, current implementations of such rules in tertiary hospitals are problematic as physicians are receiving too many alerts, causing high override rates and alert fatigue. We investigated the potential impact of Korean national DDI rules in a drug utilization review program in terms of their severity coverage and the clinical efficiency of how physicians respond to them. Using lists of high-priority DDIs developed with the support of the U.S. government, we evaluated 706 contraindicated DDI pairs released in May 2015. We evaluated clinical log data from one tertiary hospital and prescription data from two other tertiary hospitals. The measured parameters were national DDI rule coverage for high-priority DDIs, alert override rate, and number of prescription pairs. The coverage rates of national DDI rules were 80% and 3.0% at the class and drug levels, respectively. The analysis of the system log data showed an overall override rate of 79.6%. Only 0.3% of all of the alerts (n = 66) were high-priority DDI rules. These showed a lower override rate of 51.5%, which was much lower than for the overall DDI rules. We also found 342 and 80 unmatched high-priority DDI pairs which were absent in national rules in inpatient orders from the other two hospitals. The national DDI rules are not complete in terms of their coverage of severe DDIs. They also lack clinical efficiency in tertiary settings, suggesting improved systematic approaches are needed.


The importance of the ene reaction for the C(2)-C(6) cyclization of enyne-allenes.
The present study establishes the ene reaction as a competing reaction mechanism to the diradical mechanism for the thermal C(2)-C(6) cyclization of enyne-allenes which possess bulky substituents at the alkyne terminus. Both reaction routes are found to possess nearly equal free energies of activation. As shown by our computations, primary H/D isotope effects could be used for a definite decision about the mechanism. Concerning the regioselectivity of the cyclization reactions of enyne-allenes our study resolves a long-standing deviation between theoretical results and experimental findings.


Analysis of miRNAs Involved in Mouse Heart Injury Upon Coxsackievirus A2 Infection.
Coxsackievirus A2 (CVA2) has recently been constantly detected, and is associated with viral myocarditis in children. Our previous study demonstrated that CVA2 led to heart damage in a neonatal murine model. However, the molecular mechanism of heart injury caused by CVA2 remains largely unknown. Emerging evidence suggests the significant functions of miRNAs in Coxsackievirus infection. To investigate potential miRNAs involved in heart injury caused by CVA2, our study, for the first time, conducted a RNA-seq in vivo employing infected mice hearts. In total, 87, 101 and 76 differentially expressed miRNAs were identified at 3 days post infection (dpi), 7 dpi and 7 dpi vs 3 dpi. Importantly, above 3 comparison strategies shared 34 differentially expressed miRNAs. These results were confirmed by quantitative PCR (qPCR). Next, we did GO, KEGG, and miRNA-mRNA integrated analysis of differential miRNAs. The dual-luciferase reporter assay confirmed the miRNA-mRNA pairs. To further confirm the above enriched pathways and processes, we did Western blotting and immunofluorescence staining. Our results suggest that inflammatory responses, T cell activation, apoptosis, autophagy, antiviral immunity, NK cell infiltration, and the disruption of tight junctions are involved in the pathogenesis of heart injury caused by CVA2. The dysregulated miRNAs and pathways recognized in the current study can improve the understanding of the intricate interactions between CVA2 and the heart injury, opening a novel avenue for the future study of CVA2 pathogenesis.


Antiviral strategies: the present and beyond.
Historically, vaccine strategies have proven to be most effective at eradicating the targeted virus infections. With the advent of new or re-emerging altered viruses, some of which jump species to infect humans, the threat of viral pandemics exists. The protracted time to develop a vaccine during a pandemic necessitates using antiviral drugs in the intervening months prior to vaccine availability. Antiviral drugs that are pathogen specific, for example Amantidine, Tamiflu and Relenza, targeted against influenza viruses, are associated with the emergence of virus strains that are drug resistant. The use of ribavirin, a more broad spectrum antiviral, in combination therapies directed against influenza and hepatitis C virus, has proven effective, albeit to a modest extent. Attention is focused on the potential use of interferons (IFN)-alpha/beta as broad spectrum antivirals in acute infections, to invoke both direct antiviral effects against viruses and activation of specific immune effector cells.


Metal Ion Activation of Clostridium sordellii Lethal Toxin and Clostridium difficile Toxin B.
Lethal Toxin from Clostridium sordellii (TcsL) and Toxin B from Clostridium difficile (TcdB) belong to the family of the "Large clostridial glycosylating toxins." These toxins mono-O-glucosylate low molecular weight GTPases of the Rho and Ras families by exploiting UDP-glucose as a hexose donor. TcsL is casually involved in the toxic shock syndrome and the gas gangrene. TcdB-together with Toxin A (TcdA)-is causative for the pseudomembranous colitis (PMC). Here, we present evidence for the in vitro metal ion activation of the glucosyltransferase and the UDP-glucose hydrolysis activity of TcsL and TcdB. The following rating is found for activation by divalent metal ions: Mn(2+) > Co(2+) > Mg(2+) >> Ca(2+), Cu(2+), Zn(2+). TcsL and TcdB thus require divalent metal ions providing an octahedral coordination sphere. The EC50 values for TcsL were estimated at about 28 µM for Mn(2+) and 180 µM for Mg(2+). TcsL and TcdB further require co-stimulation by monovalent K⁺ (not by Na⁺). Finally, prebound divalent metal ions were dispensible for the cytopathic effects of TcsL and TcdB, leading to the conclusion that TcsL and TcdB recruit intracellular metal ions for activation of the glucosyltransferase activity. With regard to the intracellular metal ion concentrations, TcsL and TcdB are most likely activated by K⁺ and Mg(2+) (rather than Mn(2+)) in mammalian target cells.


Aging, Immunity, and COVID-19: How Age Influences the Host Immune Response to Coronavirus Infections?
The novel coronavirus severe acute respiratory syndrome coronavirus 2 causing the Coronavirus disease (COVID-19) pandemic has ravaged the world with over 72 million total cases and over 1.6 million deaths worldwide as of early December 2020. An overwhelming preponderance of cases and deaths is observed within the elderly population, and especially in those with pre-existing conditions and comorbidities. Aging causes numerous biological changes in the immune system, which are linked to age-related illnesses and susceptibility to infectious diseases. Age-related changes influence the host immune response and therefore not only weaken the ability to fight respiratory infections but also to mount effective responses to vaccines. Immunosenescence and inflamm-aging are considered key features of the aging immune system wherein accumulation of senescent immune cells contribute to its decline and simultaneously increased inflammatory phenotypes cause immune dysfunction. Age-related quantitative and qualitative changes in the immune system affect cells and soluble mediators of both the innate and adaptive immune responses within lymphoid and non-lymphoid peripheral tissues. These changes determine not only the susceptibility to infections, but also disease progression and clinical outcomes thereafter. Furthermore, the response to therapeutics and the immune response to vaccines are influenced by age-related changes within the immune system. Therefore, better understanding of the pathophysiology of aging and the immune response will not only help understand age-related diseases but also guide targeted management strategies for deadly infectious diseases like COVID-19.


The cost of implantable defibrillators: perceptions and reality.
Recent guidelines have recommended more wide-ranging indications for the use of implantable cardioverter defibrillator (ICD) therapy, yet even more restrained previous guidelines have not been implemented for a variety of reasons. This brief review critically examines the reasons most frequently put forward to explain this failure. Contrary to the frequently repeated speculation that the risk stratification for sudden death and hence prophylactic placement of ICDs is reasonably accurate, there is little cost difference between pharmacotherapy and ICD treatment over the long term. ICD therapy does not utilize an undue proportion of the healthcare budget, and the healthcare systems in Europe can afford this therapy. Financial reasons are neither accurate nor adequate explanations for the failure of the European medical community to implement European guidelines for the implantation of ICDs for primary and secondary prevention of sudden cardiac death.


Elemental composition of nanoparticles with the nano aerosol mass spectrometer.
The nano aerosol mass spectrometer (NAMS) irradiates individual, size selected nanoparticles with a high energy laser pulse to generate a mass spectrum consisting of multiply charged atomic ions. The elemental composition of the particle is determined from the ion signal intensities of each element, which requires deconvoluting isobaric ion signals at 4 m/z (O(4+) and C(3+)) and at 8 m/z (O(2+) and S(4+)). A method to deconvolute these ion signals using sucrose and ammonium sulfate as calibrants is presented. The approach is based on the assumption that the charge state distribution of a given element is independent of the chemical form of that element in the particle. Relative to previously reported methodology, the new approach permits accurate and precise determination of sulfur, which is crucial for interpretation of ambient nanoparticle data sets. With this approach, the differences between expected and measured elemental ratios of C, O, N, and S for a variety of test particles were generally much less than 10%, although a difference as high as 16% was observed.


[Epileptic encephalopathies of onset in neonates and infants].
The International League Against Epilepsy (ILAE) recently socialized the proposed classification for epileptic syndromes of neonatal onset and up to the first 2 years of age, dividing them into self-limited epileptic syndromes and epileptic and developmental encephalopathies (DEEs). In this review we will focus on DEEs, defined as disorders in which there is developmental impairment related to both the underlying aetiology independent of epileptiform activity and epileptic encephalopathy. These include early infantile epileptic encephalopathy or Ohtahara syndrome and early myoclonic encephalopathy in the neonatal period, now grouped under the name of epileptic and early childhood developmental encephalopathies (EIDEE). Infantile epileptic spasms syndrome, childhood epilepsy with migratory crises and Dravet syndrome are part of the infant-onset encephalopathies. The importance of early recognition of epileptic encephalopathies lies not only in the control of epileptic seizures, but also in stopping deterioration by trying to change the course of the disease. It is essential to know the etiology, avoiding medications that can exacerbate seizures and worsen the course, applying precision m edicine as well as identifying candidate patients for early epilepsy surgery.


The Structure and Species Co-Occurrence Networks of Soil Denitrifying Bacterial Communities Differ Between A Coniferous and A Broadleaved Forests.
Acacia mangium (AM) and Pinus massoniana (PM) are widely planted in tropical regions, whereas their effects on soil microbial communities remain unclear. We did a comprehensive investigation of soil denitrifying bacterial communities in AM and PM monoculture plantations in Southern China based on the high throughput sequencing data of their functional genes: nirK, nirS, and nosZ. The average abundance of nosZ (1.3 × 107) was significantly higher than nirS (5.6 × 106) and nirK (4.9 × 105). Shannon estimator revealed a markedly higher α-diversity of nirS and nosZ communities in PM than in AM plantations. The AM and PM plantations were dominated by different nirS and nosZ taxa belonging to proteobacteria, actinobacteria, thermoleophilia, chloroflexia, and acidobacteria, while the dominant nirK taxa were mainly categorized into proteobacteria in both types of plantations. The structure of nirS and nosZ communities shifted substantially from AM to PM plantations with changes in soil moisture, NH4+, and microbial biomass nitrogen content. The species co-occurrence network of nirK community was better organized in a more modular manner compared to nirS and nosZ communities, and the network keystone species mostly occurred in PM plantations. These results indicated a highly species corporation of nirK community in response to environmental changes, especially in PM plantations. AM and PM plantations can form different soil denitrifying microbial communities via altering soil physicochemical properties, which may further affect soil N transformations.


Quantification of carious pathogens in the interdental microbiota of young caries-free adults.
The majority of caries lesions in adults occur on the proximal tooth surfaces of the posterior teeth. A comprehensive study of the composition of the oral microbiota is fundamental for a better understanding of the etiology of interdental caries. Twenty-five caries-free subjects (20-35 years old) were enrolled in the study. The interdental biofilm of four interdental sites were collected. The real-time polymerase chain reaction (PCR) methodology were used to quantify (i) the following bacteria: Streptococcus spp., Streptococcus mutans, Lactobacillus spp., Enterococcus spp., and Enterococcus faecalis; (ii) the fungus Candida albicans; and (iii) total bacteria. Streptococcus spp. was the most abundant species, followed by Lactobacillus spp. and Enterococcus spp. Streptococcus spp. and Lactobacillus spp. were detected at all tested sites and Enterococcus spp. at 99% of sites. S. mutans was detected at only 28% of the tested sites and C. albicans was detected at 11% of sites. E. faecalis was never detected. In 54.5% of the biofilm inhabited by C. albicans, S. mutans was present. Moreover, 28% of the ID sites co-expressed S. mutans and Lactobacillus spp. The studied pathogens were organized into two correlated groups of species. Strikingly, the fungus C. albicans and the bacteria Enterococcus spp. cluster together, whereas Streptococcus spp., S. mutans and Lactobacillus spp. form one distinct cluster. The interdental biofilm of young caries-free adults is comprised of pathogens that are able to induce interproximal caries. That several of these pathogens are implicated in heart disease or other systemic diseases is an argument for the disruption of interdental biofilms using daily oral hygiene.


Sinusitis of odontogenic origin: pathophysiological implications of early treatment.
Although sinusitis is a common condition its pathogenesis is not clearly understood and there is lack of consensus concerning its treatment and prevention. Sinusitis is regarded as being primarily rhinogenous in origin, and oral/dental infections are considered to be predisposing factors. A review of the literature suggests that many cases of recurrent acute sinusitis are due to secondary rhinogenous bacterial colonization of antral mucosa that have been weakened and degenerated by chronic dental infection/inflammation. Unless the underlying dental condition, which may be asymptomatic or mildly symptomatic, is diagnosed and treated, the value of antibiotic treatment in such cases is questionable. In order to halt disease progression and avoid excessive antibiotic treatment, early intervention (both preventive and therapeutic) is necessary. Further research is required to establish the sequence of events by which infection of odontogenic origin initiates degenerative changes in the antral mucosa, culminating eventually in sinusitis.


Possible substantive improvements in the structure of the Quality of Life in Adult Cancer Survivors (QLACS) scale? A study based on its Spanish version.
Quality of Life in Adult Cancer Survivors (QLACS) scale is one of the most commonly used and validated measures to assess the Health-Related Quality of Life (HRQoL) in this population. However, there are some aspects related to its structure that still deserve consideration. The aim of this study was to test the substantive improvement over the original QLACS structure resulting from several proposals reflected in the literature. Using a cross-sectional design and Confirmatory Factorial Analysis, we explored those proposals. Reliability, convergent validity, and factor invariance across three cancer survivorships phases (re-entry, early, and long term) were also analyzed. 1.862 post-treatment survivors of diverse cancer types completed the Spanish versions of QLACS, Brief Symptom Inventory-18 (BSI-18), and Subjective Happiness Scale (SHS). The original model with twelve domains, grouped (with the exception of benefits) into a single total score, versus two subtotal (Generic and Cancer-specific) obtained a good fit. The values of Cronbach's alpha, Composite reliability, Average Variance Extracted indexes, and Pearson correlations supported the internal consistency and temporal stability (interval of 2-3 weeks) of the QLACS. Results also showed its adequate convergent validity and an invariant factor structure across survival periods (re-entry survivorship, early survivorship, long-term survivorship). In its original structure, albeit the replacement of the scores on the two subscales by a total score, our results support QLACS as a valid and useful tool for the assessment of HRQoL in post-treatment cancer survivors throughout the different survival phases.


Stage-stratified analysis of prognostic significance of Bax-interacting factor-1 expression in resected colorectal cancer.
Bax-interacting factor-1 (Bif-1) plays a crucial role in apoptosis and autophagy. The aim of this study was to evaluate Bif-1 protein expression and its prognostic significance in colorectal cancer (CRC). We analyzed Bif-1 protein expression in 251 resected specimens from patients with CRC by immunohistochemistry using tissue microarray. Low Bif-1 expression was observed in 131 patients (52.2%) and high Bif-1 expression in 120 patients (47.8%). No significant differences were observed in clinicopathological parameters between patients with high and low Bif-1 expression. Kaplan-Meier survival analysis showed no difference in survival between patients with high and low Bif-1 expression. Stratified analysis of Bif-1 according to TNM stage demonstrated that low Bif-1 expression was significantly associated with a poor outcome in patients with stages I and II (P = 0.034). Stratified multivariate analysis demonstrated that low Bif-1 expression was an independent indicator of poor prognosis (hazard ratio, 0.459; 95% confidence interval, 0.285-0.739; P = 0.001). Patients with low levels of Bif-1 expression have shortened survival rates in CRC of stages I and II. This suggests that Bif-1 protein expression may be a useful prognostic marker in early-stage CRC.


Three distinct auditory areas of cortex (AI, AII, and AAF) defined by optical imaging of intrinsic signals.
Using pure-tone sound stimulation, three separate auditory areas are revealed by optical imaging of intrinsic signals in the temporal cortex of the chinchilla (Chinchilla laniger). These areas correlate with primary auditory cortex (AI) and two secondary areas, AII and the anterior auditory field (AAF). We have distinguished AI on the basis of concurrent single-unit electrophysiological recording; neurons within the AI intrinsic signal region have short (<15 ms) onset-response latencies compared with neurons recorded in AII and the AAF. Within AI, AII, and AAF we have been able to define cochleotopic or tonotopic organization from the differences in intrinsic signal areas evoked by pure tones at octave-spaced frequencies from 500 Hz to 16 kHz. The maps in AI and AII are arranged orthogonal to each other.


Increased risk of cognitive impairment in patients with components of metabolic syndrome.
The number of old adults with cognitive impairment or dementia is anticipated to increase rapidly due to the aging population, especially the number of patients with multiple chronic conditions or metabolic perturbation. Metabolic syndrome (Mets) is among the most hazardous risk factors for cardiovascular disease and is linked to a chronic inflammatory disease. We investigated the National Health and Nutrition Examination Survey (NHANES) database for the years 1999 to 2002 to explore the connection between Mets and cognitive decline.A total of 2252 NHANES (1999-2002)-registered individuals who were stroke-free and aged ≧60 years were enrolled in this study. This study surveyed the effects of the existence of diverse characteristics of Mets on the individuals' cognitive performances as measured with the digit symbol substitution test (DSST).The individuals with more features of Mets achieved lower DSST scores than those with fewer constituents of Mets (P < 0.001 for the trend) after adjustments for covariates. The β coefficients for the DSST scores of the participants with 1, 2, 3, and ≥4 features of Mets were -1.545, -3.866, -4.763, and -5.263, respectively. Cognitive decline was correlated with each of the constituents of Mets, which included high plasma glucose, elevated blood pressure, abdominal obesity, and decreased high-density lipoprotein cholesterol (P < 0.05 for the above factors), with the exception of high triglyceride levels (P > 0.05).Mets was positively associated with cognitive decline in individuals aged ≧60 years. The characteristics of Mets that were most strongly associated with cognitive decline were high plasma glucose and elevated blood pressure.


Deficits in Seizure Threshold and Other Behaviors in Adult Mice without Gross Neuroanatomic Injury after Late Gestation Transient Prenatal Hypoxia.
Intrauterine hypoxia is a common cause of brain injury in children resulting in a broad spectrum of long-term neurodevelopmental sequela, including life-long disabilities that can occur even in the absence of severe neuroanatomic damage. Postnatal hypoxia-ischemia rodent models are commonly used to understand the effects of ischemia and transient hypoxia on the developing brain. Postnatal models, however, have some limitations. First, they do not test the impact of placental pathologies on outcomes from hypoxia. Second, they primarily recapitulate severe injury because they provoke substantial cell death, which is not seen in children with mild hypoxic injury. Lastly, they do not model preterm hypoxic injury. Prenatal models of hypoxia in mice may allow us to address some of these limitations to expand our understanding of developmental brain injury. The published rodent models of prenatal hypoxia employ multiple days of hypoxic exposure or complicated surgical procedures, making these models challenging to perform consistently in mice. Furthermore, large animal models suggest that transient prenatal hypoxia without ischemia is sufficient to lead to significant functional impairment to the developing brain. However, these large animal studies are resource-intensive and not readily amenable to mechanistic molecular studies. Therefore, here we characterized the effect of late gestation (embryonic day 17.5) transient prenatal hypoxia (5% inspired oxygen) on long-term anatomical and neurodevelopmental outcomes in mice. Late gestation transient prenatal hypoxia increased hypoxia-inducible factor 1 alpha protein levels (a marker of hypoxic exposure) in the fetal brain. Hypoxia exposure predisposed animals to decreased weight at postnatal day 2, which normalized by day 8. However, hypoxia did not affect gestational age at birth, litter size at birth, or pup survival. No differences in fetal brain cell death or long-term gray or white matter changes resulted from hypoxia. Animals exposed to prenatal hypoxia did have several long-term functional consequences, including sex-dichotomous changes. Hypoxia exposure was associated with a decreased seizure threshold and abnormalities in hindlimb strength and repetitive behaviors in males and females. Males exposed to hypoxia had increased anxiety-related deficits, whereas females had deficits in social interaction. Neither sex developed any motor or visual learning deficits. This study demonstrates that late gestation transient prenatal hypoxia in mice is a simple, clinically relevant paradigm for studying putative environmental and genetic modulators of the long-term effects of hypoxia on the developing brain.


Comparative digestibility of energy and nutrients and fermentability of dietary fiber in eight cereal grains fed to pigs.
Cereal grains provide a large portion of caloric intake in diets for humans, but not all cereal grains provide the same amount of energy. Therefore, an experiment was conducted to determine and compare the metabolizable energy (ME), the apparent ileal digestibility (AID), and the apparent total tract digestibility (ATTD) of gross energy (GE) and nutrients in eight cereal grains when fed to pigs. Rice had greater (P < 0.05) AID of GE than other cereal grains, greater (P < 0.05) AID of starch than yellow dent corn, dehulled barley, rye, and wheat, and greater (P < 0.05) ATTD of GE than yellow dent corn, rye, sorghum, and wheat. Dehulled barley, rye, and sorghum had less (P < 0.05) AID of starch than other cereal grains. Dehulled barley had greater (P < 0.05) ATTD of GE than rye. Dehulled oats had the greatest (P < 0.05) ME compared with other cereal grains, whereas rye had the least (P < 0.05) ME. Dehulled oats provide more energy to diets and should be used if the goal is to increase caloric intake. In contrast, sorghum and rye may be more suitable to control diabetes and manage body weight of humans.


PEGylated Graphene Quantum Dot Improved Cardiac Function in Rats with Myocardial Infarction: Morphological, Oxidative Stress, and Toxicological Evidences.
The biocompatibility and potential application of graphene-based nanomaterials in biomedicine have been documented. The effects of polyethylene glycol-graphene quantum dots (GQDs-PEG) on cardiac function in rats with myocardial infarction (MI) were examined. Wistar rats were randomly assigned to two main groups, each consisting of sham-Veh., MI-Veh., and MI+GQDs-PEG at doses of 5, 10, and 20 mg/kg. MI was induced by the closure of the left anterior descending (LAD) coronary artery. After MI, GQDs-PEG were injected at different doses IP every other day for two weeks. In the end, hemodynamic and heart contractility indices were assessed. The levels of myocardial MDA (malondialdehyde), SOD (superoxide dismutase), GPX (glutathione peroxidase), and TAC (total antioxidant capacity) were measured by the ELISA method. The serum ALP, ALT, AST, creatinine, and urea levels were measured using the photometric method. The infarct size was assessed by TTC staining. GQDs-PEG decreased the infarct size at doses of 10 and 20 mg/kg and recovered the MI-induced reductions of +dp/dt max and -dp/dt max in the study groups. GQDs-PEG normalized systolic blood pressure and left ventricular systolic pressure reduction at the dose of 20 mg/kg in the MI group. Heart SOD, GPX, and TAC increased in the GQDs-PEG 10 and 20 groups. Almost no signs of toxic effects due to GQDs-PEG administration were observed on the liver and kidneys. The results provided clear evidence that GQDs-PEG improve cardiac performance and hemodynamic parameters in rats with MI by reducing oxidative stress. GQDs-PEG is proposed as a therapeutic target for the treatment of MI.


Occupational lung disease and the role of peptide growth factors.
Occupational lung disease can take many forms, including obstructive airway disease, asthma, and restrictive parenchymal fibrosis. It would not be useful to attempt an all-encompassing review of such a broad topic, even if one were restricted to the most recent literature. Thus, I have chosen a small corner of one disease process that relates to work ongoing in my laboratory, ie, the potential role of growth factors in the pathogenesis of fibroproliferative lung disease. This process is the cornerstone of interstitial pulmonary fibrosis, which is caused by inhaling such commonly used materials as asbestos and silica. Diffuse interstitial pulmonary fibrosis results from chronic exposures in the workplace, and the initial lesions of the fibroproliferative process that culminate in interstitial pulmonary fibrosis are readily produced in the laboratory by exposing rats and mice. The disease could be mediated by a combination of peptide growth factors and cytokines that are expressed at sites of lung injury.


Contribution of street food on dietary acrylamide exposure by youth aged nineteen to thirty in Perugia, Italy.
Acrylamide dietary intakes from selected street foods in youth population are estimated. The intake evaluation was carried out by combining levels of acrylamide in food, analytically determined by high performance liquid chromatography, with individual consumption data recorded using a questionnaire applied to a group of 200 students aged 19 to 30. The mean value of acrylamide exposure was recorded to be 0.452 µg/kg bw/day, while the average intakes at 50th and 95th percentile were 0.350 µg/kg bw/day and 1.539 µg/kg bw/day, respectively. The street food categories that contributed the most to acrylamide intake are pizza and French fries. The margins of exposure, based on benchmark dose limits defined for neoplastic effects and peripheral neuropathy, are within the range of values that indicate a concern for public health as defined by European Authority for Food Safety (EFSA), confirming the needed effort to reduce acrylamide dietary exposure.


Uptake of mercury vapor by wheat: an assimilation model.
Using a whole-plant chamber and (203)Hg-labeled mercury, a quantitative study was made of the effect of environmental parameters on the uptake, by wheat (Triticum aestivum), of metallic mercury vapor, an atmospheric pollutant. Factors were examined in relation to their influence on components of the gas-assimilation model, [Formula: see text]where U(Hg) is the rate of mercury uptake per unit leaf surface, C(a)' is the ambient mercury vapor concentration, C(l)' is the mercury concentration at immobilization sites within the plant (assumed to be zero), r(l.Hg) is the total leaf resistance to mercury vapor exchange, and r(m.hg) is a residual term to account for unexplained physical and biochemical resistances to mercury vapor uptake.Essentially all mercury vapor uptake was confined to the leaves. r(l.hg) was particularly influenced by illumination (0 to 12.8 klux), but unaffected by ambient temperature (17 to 33 C) and mercury vapor concentration (0 to 40 mug m(-3)). The principal limitation to mercury vapor uptake was r(m.hg), which was linearly related to leaf temperature, but unaffected by mercury vapor concentration and illumination, except for apparent high values in darkness.Knowing C(a)' and estimating r(l.hg) and r(m.hg) from experimental data, mercury vapor uptake by wheat in light was accurately predicted for several durations of exposure using the above model.


Increased Risk of Cancer in Men With Peyronie's Disease: A Cohort Study Using a Large United States Insurance Claims Database.
Men with Peyronie's disease (PD) may have an increased prevalence of certain comorbidities, including malignancy. We sought to examine the clinical relationship between PD and subsequent diagnosis of malignancy. Using data from the IBM Health MarketScan claims database from 2007 to 2013, we compared men with PD to a control group of men without PD or erectile dysfunction matched for age and duration of follow-up. We compared incidence of 18 categories of malignancy between both groups using a Cox regression model. In total, 48,423 men with PD and 484,230 controls were identified. The mean age within both cohorts was 50 ± 9.4 years old, and mean follow-up time was approximately 4.4 ± 2.1 years. After being controlled for age, year of evaluation, obesity, smoking, number of outpatient visits, number of urologist visits, and duration of follow-up, men with PD had an increased risk of all cancers (hazard ratio = 1.10, 95% CI = 1.06-1.14), stomach cancer (1.43, 1.06-1.14), testis cancer (1.39, 1.05-1.84), and melanoma (1.19, 1.02-1.38) when compared with controls. The strengths in using the MarketScan database are the anonymous nature of the data, accessibility, and the power provided by the large number of patient visits recorded. Limitations include a lack of detail in certain facets of patient clinical data, and the lack of long-term follow-up to assess the impact of time on other potentially associated conditions. This manuscript is the first to our knowledge to describe a relationship between PD and cancer. Men with PD may be at increased risk for certain malignancies compared with age-matched controls. Further investigation is needed to explore the clinical implications of these findings. Pastuszak AW, Thirumavalavan N, Kohn TP, et al. Increased Cancer Risk in Men With Peyronie's Disease: A Cohort Study Using a Large US Insurance Claims Database. Sex Med 2019;7:403-408.


α1D-Adrenoceptor blockade increases voiding efficiency by improving external urethral sphincter activity in rats with spinal cord injury.
Ideal therapy for lower urinary tract dysfunction in patients with spinal cord injury (SCI) should decrease detrusor overactivity, thereby promoting urine storage at low intravesical pressure and promoting efficient voiding at low pressure by decreasing detrusor-sphincter dyssynergia. Here we investigated blockade of various α-adrenoceptors to determine the subtype that was principally responsible for improving the voiding dysfunction. The effects of the intravenous α-blocker naftopidil, the α-blocker BMY 7378, and the α-blocker silodosin were evaluated using cystometrography and external urethral sphincter-electromyography (EMG) in decerebrated, unanesthetized female Sprague-Dawley rats with chronic SCI following transection at Th8. Parameters measured included the voided volume, residual volume, voiding efficiency, and burst and silent periods on EMG. Compared with values in decerebrated non-SCI rats, EMG of decerebrated SCI rats revealed more prominent tonic activity, significantly shorter periods of bursting activity, and a reduced ratio of the silent to active period during bursting. Compared with the value before drug administration (control), the voiding efficiency was significantly increased by naftopidil (1 and 3 mg/kg) (<0.05 each), and the burst (<0.01 and <0.05, respectively) and silent periods (<0.01 each) on EMG were significantly lengthened. BMY 7378 (1 mg/kg) significantly increased voiding efficiency and lengthened the burst periods (<0.05 each). Silodosin did not affect any parameters. These results suggest that α-blockade reduces the urethral resistance associated with detrusor-sphincter dyssynergia, thus improving voiding efficiency in SCI rats.


[What are the real indications for hepatectomies in metastases of colorectal origin?].
To ascertain the real impact of classical contraindications (relative or absolute according to various authors) represented by: a high number of liver metastases (LM), the presence of associated extra-hepatic localizations (EHL), and a surgical margin less than 10 mm. A prospective study was conducted in 269 consecutive hepatectomized patients. Inclusion criteria were only the resection of all tumoral tissue, and lack of major operative risk. Fifty-nine patients had at least 4 LM, 62 had an associated EHL, and 187 had a surgical margin < 10 mm. Altogether, 83% of the patients did not match the classical selection criteria. Sixty-two parameters were registered. A uni- and multivariate study of prognostic factors was performed. Although 18% of the resections were palliative (R1 or R2 according to the UICC classification), and the hospital mortality was 3.3% (2.2% during the first postoperative month), global and disease-free 5-year survival rates were 34.4% and 23.3%, respectively. The number of LM had no prognostic implication. A surgical margin > 9 mm improved significantly the prognosis. Between 0 and 9 mm, it had no important prognostic impact if the cut surface was histologically disease-free. A margin < 10 mm was greatly associated with a high number of LM, a bilateral localization of LM, and extended hepatectomy. Among the EHL, only those discovered during laparotomy had a significant adverse impact on prognosis. Fundamental principles of the indications of hepatectomy for colorectal LM are to resect all the lesions and to avoid major operative risk. In complex cases, the most frequent, these principles can only be completely followed in a specialized center.


Inhibitation of cellular toxicity of gold nanoparticles by surface encapsulation of silica shell for hepatocarcinoma cell application.
Nanotechnology, as a double-edged sword, endows gold nanoparticles (GNPs) more "power" in bioimaging and theragnostics, whereas an outstanding issue associated with the biocompatibility of GNPs should also be addressed. Especially for the silica-coated gold nanospheres (GNSs) and gold nanorods (GNRs), there is increasing attention to explore the application, because the surface silica encapsulation has been proved to be an alternative strategy for other organic surface coatings. However, among those reports there are very limited publications to focus on the toxicity of silica-coated GNSs and GNRs. Besides, the existing detoxification methods via surface chemistry on GNPs greatly improve the biocompatibility but still undergo challenges for high dose (>100 pM) demand and long-term stability. Here, we demonstrated a straightforward, low-cost, universal strategy for the surface chemistry on GNPs via silica encapsulating. Different size, shape, dose, and surface capping of GNPs for the nanotoxicity test have been carefully discussed. After silica encapsulating, the detoxification for all GNPs presents significantly from HepG2 cell proliferation results, especially for the GNRs. This new straightforward strategy will definitely rationalize the biocompatibility issue of GNPs and also provide potential for other surface chemistry methodology in biomedical fields.


Dauricine inhibits viability and induces cell cycle arrest and apoptosis via inhibiting the PI3K/Akt signaling pathway in renal cell carcinoma cells.
Renal cell carcinoma (RCC), which is derived from the proximal tubules of nephrons, is one of the most common solid cancers. Due to its inherent insensitivity to radiotherapy and chemotherapy, surgery remains the only curative strategy for RCC. Therefore, a novel strategy for treating RCC is urgently needed. This study aims to investigate the effects of dauricine, a bisbenzylisoquinoline alkaloid, in RCC cells and the underlying mechanisms of its action. The effects of dauricine on viability, cell cycle distribution and apoptosis in RCC cells were determined in vitro by MTT assay, flow cytometry and nucleosome ELISA assay, respectively. Mechanism studies were performed by analyzing related proteins using western blotting assays. We show that dauricine effectively inhibits the viability of four RCC cell lines (786‑O, Caki‑1, A‑498 and ACHN). In addition, dauricine induces cell cycle arrest at the G0/G1 phase in RCC cells. Dauricine also induces apoptosis via the intrinsic pathway, since caspase‑9 and caspase‑3 but not caspase‑8 activation was detected after the treatment. Moreover, dauricine was able to inhibit the PI3K/Akt signaling pathway. Our findings suggest inhibitory effects of dauricine in renal cancer cells and provide a better understanding of its underlying mechanism. Our findings suggest that dauricine could be a potential therapeutic agent for treating RCC.


Reference genes for the normalization of gene expression in eucalyptus species.
Gene expression analysis is increasingly important in biological research, with reverse transcription-quantitative PCR (RT-qPCR) becoming the method of choice for high-throughput and accurate expression profiling of selected genes. Considering the increased sensitivity, reproducibility and large dynamic range of this method, the requirements for proper internal reference gene(s) for relative expression normalization have become much more stringent. Given the increasing interest in the functional genomics of Eucalyptus, we sought to identify and experimentally verify suitable reference genes for the normalization of gene expression associated with the flower, leaf and xylem of six species of the genus. We selected 50 genes that exhibited the least variation in microarrays of E. grandis leaves and xylem, and E. globulus xylem. We further performed the experimental analysis using RT-qPCR for six Eucalyptus species and three different organs/tissues. Employing algorithms geNorm and NormFinder, we assessed the gene expression stability of eight candidate new reference genes. Classic housekeeping genes were also included in the analysis. The stability profiles of candidate genes were in very good agreement. PCR results proved that the expression of novel Eucons04, Eucons08 and Eucons21 genes was the most stable in all Eucalyptus organs/tissues and species studied. We showed that the combination of these genes as references when measuring the expression of a test gene results in more reliable patterns of expression than traditional housekeeping genes. Hence, novel Eucons04, Eucons08 and Eucons21 genes are the best suitable references for the normalization of expression studies in the Eucalyptus genus.


Expression profiling of baculovirus genes in permissive and nonpermissive cell lines.
The baculoviruses Bombyx mori nucleopolyhedrovirus (BmNPV) and Autographa californica multicapsid NPV (AcMNPV) are highly homologous at the genomic level, but they have essentially nonoverlapping host ranges. In order to characterize baculovirus replication in permissive and nonpermissive cell lines, the expression profiles of baculovirus-specific genes (at 2, 6, 12, 24, 36, 48 or 72 h post-infection) were examined in BmN (BmNPV-permissive) or Sf-9 (AcMNPV-permissive) cells that were inoculated with BmNPV or AcMNPV. Surprisingly, nearly all of the 154 genes of AcMNPV appeared to be expressed in both Sf-9 and BmN cells although the peak expression levels of these genes were delayed by roughly 12 h in the nonpermissive BmN cells. In addition, the expression levels of the very late AcMNPV polyhedrin and p10 genes were dramatically reduced in BmN cells, which presumably led to the inability of AcMNPV to form polyhedral inclusion bodies in BmN cells. Nearly all of the 136 genes of BmNPV appeared to be expressed in BmN cells, however, BmNPV gene expression was dramatically reduced in Sf-9 cells inoculated with BmNPV. Experiments in which BmNPV DNAs were transfected to Sf-9 cells suggested that this dramatic reduction in gene expression was not the result of poor attachment, penetration or uncoating of the BmNPV virion into Sf-9 cells. In conclusion, we established a system to monitor global gene expression patterns during baculovirus infection in permissive and nonpermissive cell lines. This system was used to identify global trends in the transcription of baculovirus genes during productive and nonproductive infection.


Outcomes of transplants from patients with small renal tumours, live unrelated donors and dialysis wait-listed patients.
We report the outcomes of renal transplant patients (n = 43) who received grafts from donors (n = 41) with small (<3 cm) renal tumours removed before transplantation covering the period from May 1996 to September 2007. Patient and graft survival were compared with the outcomes of conventional live unrelated transplants (LURTs) (n = 120) and to patient survival on the transplant waiting list for those who did not receive a kidney during this period (n = 153). Patient survival at 1, 3 and 5 years were 92%, 88% and 88% for recipients of tumourectomized kidneys (TKs), 99%, 97% and 97% for LURTs, and 98%, 92% and 74% for dialysis patients waiting for a deceased donor kidney (log rank score 10.4, P = 0.005). One patient experienced a local tumour recurrence at 9 years following transplantation. This patient declined intervention and is currently under active surveillance. Transplantation of tumourectomized kidneys from patients with small, localized, incidentally detected renal tumours results in similar outcomes to conventional LURTs and confers a significant survival advantage for patients who would otherwise be unable to receive a transplant.


Primary isolated skull base eosinophilic granuloma confined to the anterior clinoid process: illustrative case.
Solitary eosinophilic granuloma (EG) occurs anecdotally in the skull base region, and it has been described in only three previous publications. The authors report the first case of EG of the anterior clinoid process (ACP), which was confined to the ACP and presented with decreased vision. A 38-year-old woman presented with decreased vision of the left eye of 5 months' duration. Her visual acuity was 3/10, other neurological examinations were intact, and there were no other osseous or soft tissue lesions. The lesion was excised using a left-sided craniotomy and transdural clinoidectomy, decompressing the optic nerve both intra- and extradurally. The lesion was characteristic for EG, and no recurrence was detected after 2 years. EG can be confined to the ACP and impair vision. Imaging studies are sensitive but not specific, and surgical decompression is both diagnostic and treatment oriented. Close observation and even adjuvant therapy may be indicated in similar cases.


Bilingualism and executive attention: Evidence from studies of proactive and reactive control.
According to some accounts, the bilingual advantage is most pronounced in the domain of executive attention rather than inhibition and should therefore be more easily detected in conflict adaptation paradigms than in simple interference paradigms. We tested this idea using two conflict adaptation paradigms, one that elicits a list-wide proportion-congruent effect and one that elicits an item-specific proportion-congruent effect. In both cases, the relevant finding is that congruency effects are reduced when the proportion of congruent to incongruent items is smaller. These effects are validated measures of proactive and reactive control, respectively, and are aspects of executive attention known to be associated with individual differences in working memory capacity. We reasoned that if bilingualism affects executive attention in a similar way as does working memory capacity, indices of proactive and reactive control should be comparably associated with continuous variation in language status and working memory capacity. In two experiments, we replicated previous findings that working memory capacity is associated with variation in congruency effects (suggesting greater reliance on proactive control). In contrast, language status had no consistent association with performance, save for a hint that bilingualism may be associated with greater reliance on reactive control. Thus, the bilingual advantage may exist, but not in proactive control or any other aspects of executive attention that have been proposed thus far. (PsycInfo Database Record (c) 2022 APA, all rights reserved).