Protein release in a Saccharomyces cerevisiae mutant does not depend on mitochondrial genome integrity and function.
A mutant allele the of Saccharomyces cerevisiae NUD1 gene causes a thermosensitive phenotype of the yeast cells and increases release of proteins into the culture medium at the restrictive temperature (37 degrees C). The release of proteins does not depend on the process of oxidative phosphorylation, because protein release is not stopped in the presence of inhibitors of oxidative phosphorylation. NUD1 transcription is not under retrograde regulation. This type of transcriptional regulation depends on the nuclear Rtg transcription factors and on the integrity of the mitochondrial genome.


Current Concepts of Periapical Surgery: 2020 Update.
Although conventional endodontic procedures are very successful, failure of the initial treatment can occur. Consideration for surgical treatment versus endodontic retreatment needs to be part of the decision along with thoughts of extraction with implant replacement. Apical surgery can preserve many teeth that remain symptomatic after conventional endodontic treatment especially because endodontic failure can occur after 1 year, usually after a definitive restoration is placed. This article reviews current indications for periapical surgery and discusses factors that can predict successful outcomes.


Understanding Potentially Preventable Mortality Following Oesophago-Gastric Cancer Surgery: Analysis of a National Audit of Surgical Mortality.
At a national level, understanding preventable mortality after oesophago-gastric cancer surgery can direct quality-improvement efforts. Accordingly, utilizing the Australian and New Zealand Audit of Surgical Mortality (ANZASM), we aimed to: (1) determine the causes of death following oesophago-gastric cancer resections in Australia, (2) quantify the proportion of potentially preventable deaths, and (3) identify clinical management issues contributing to preventable mortality. All in-hospital mortalities following oesophago-gastric cancer surgery from 1 January 2010 to 31 December 2020 were analysed using ANZASM data. Potentially preventable and non-preventable cases were compared. Thematic analysis with a data-driven approach was used to classify clinical management issues. Overall, 636 complications and 123 clinical management issues were identified in 105 mortalities. The most common causes of death were cardio-respiratory in aetiology. Forty-nine (46.7%) deaths were potentially preventable. These cases were characterized by higher rates of sepsis (59.2% vs 33.9%, p = 0.011), multiorgan dysfunction syndrome (40.8% vs 25.0%, p = 0.042), re-operation (63.3% vs 41.1%, p = 0.031) and other complications compared with non-preventable mortality. Potentially preventable mortalities also had more clinical management issues per patient [median (IQR): 2 (1-3) vs 0 (0-1), p < 0.001), which adversely impacted preoperative (30.6% vs 7.1%, p = 0.002), intraoperative (18.4% vs 5.4%, p = 0.037) and postoperative (51.0% vs 17.9%, p < 0.001) care. Thematic analysis highlighted recurrent areas of deficiency with preoperative, intraoperative and postoperative patient management. Almost 50% of deaths following oesophago-gastric cancer resections were potentially preventable. These were characterized by higher complication rates and clinical management issues. We highlight recurrent themes in patient management to improve future quality of care.


Stimulation of D-aspartate efflux by mercuric chloride from rat primary astrocyte cultures.
Mercuric chloride (HgCl2; MC) was shown to increase D-aspartate release from preloaded astrocytes in a dose-dependent fashion. Two sulfhydryl (-SH) protecting agents, a cell membrane non-penetrating compound, reduced glutathione (GSH), and the membrane-permeable dithiothreitol (DTT), were found to inhibit the stimulatory action of MC on the efflux of radiolabeled D-aspartate. MC-induced D-aspartate release was completely inhibited by the addition of 1 mM DTT or GSH during the actual 5 min perfusion period with MC (5 microM). However, when added after MC treatment, this inhibition could not be sustained by GSH, while DTT fully inhibited the MC-induced release of D-aspartate. Neither DTT nor GSH alone had any effect on the rate of astrocytic D-aspartate release. Accordingly, it is postulated that the stimulatory effect exerted by MC on astrocytic D-aspartate release is associated with vulnerable -SH groups located within, but not on the surface of the cell membrane. Omission of Na+ from the perfusion solution did not accelerate MC-induced D-aspartate release, suggesting that reversal of the D-aspartate carrier can not be invoked to explain MC-induced D-aspartate release. Furthermore, MC did not appear to be associated with astrocytic swelling.


Brain regional pharmacology of GABA(A) receptors in alcohol-preferring AA and alcohol-avoiding ANA rats.
Compounds interacting with the GABA(A) receptor system modulate voluntary alcohol consumption in alcohol-preferring AA (Alko, Alcohol) rats. Therefore, we compared the central GABA(A) receptor pharmacology of the AA rats to that of their counterpart, alcohol-avoiding ANA (Alko, Non-Alcohol) rats with receptor autoradiography. Total flumazenil-sensitive [(3)H]Ro 15-4513 binding to the benzodiazepine site of GABA(A) receptor was slightly lower in the hippocampus, striate cortex and lateral hypothalamus of the AA than ANA rats. The proportions of zolpidem- and diazepam-sensitive components were similar in both rat lines. Basal picrotoxin-sensitive [(35)S]TBPS binding to the convulsant site of GABA(A) receptor was similar in most regions between the rat lines, but the up-modulation of the binding by 10 microM diazepam in the hippocampal, amygdaloid and entorhinal cortical areas was greater in the AA than ANA rats. These results do not reveal any general genetic defect in the GABA(A) receptors of AA or ANA rats, but the regional profile of the ligand binding differences between the lines, especially in the coupling of the benzodiazepine and chloride channel sites, suggests receptor subtype-specific changes in brain regions implicated in behavioural reward and anxiolysis.


Bowel complications after radiotherapy for carcinoma of the prostate: the volume effect.
Late radiation-induced bowel complications were studied in 218 patients treated for localized carcinoma of the prostate by radical radiotherapy at the Prince of Wales Hospital between 1980 and 1986. Mild to moderate toxicity was seen in 38 cases, and severe toxicity requiring surgery occurred in 3 patients. The total actuarial complication rate (by 5 years) for all grades was 24% and for severe complications was 1.8%. Significant patient-related risk factors were older age at the time of radiotherapy (p = 0.035) and a previous history of abdominal operations (p = 0.028). Among treatment-related risk factors only inclusion of the whole pelvis in the irradiated volume had a significant association with this complication (p = 0.015). The risk of bowel complications was not related to the total radiation dose or to the use of interstitial implants as employed in this series.


5-Phenyl-3-(2-phosphono-eth-yl)-1,2,3-triazol-1-ium chloride.
The new triazole-functionalized phospho-nic acid 5-phenyl-3-(2-phosphono-eth-yl)-1,2,3-triazol-1-ium chloride, C10H13N3O3P+·Cl- (PTEPHCl), was synthesized by the 'click' reaction of the alkyl azide diethyl-(2-azido-eth-yl)phospho-nate with phenyl-acetyl-ene to give the dieth-yl[2-(4-phenyl-1H-1,2,3-triazol-1-yl)eth-yl]phospho-nate ester, which was then hydrolyzed under acidic conditions (HCl) to give the 'free' phospho-nic acid. The use of HCl for the hydrolysis caused protonation of the triazole ring, rendering the compound cationic, charged-balanced by a Cl- anion. There are extensive hydrogen-bonding inter-actions in the structure of PTEPHCl, involving the phospho-nic acid (-PO3H2) group, the triazolium ring and the Cl- anion.


Myocardial perfusion imaging for detection of silent myocardial ischemia.
Despite the widespread use of the exercise stress test in diagnosing asymptomatic myocardial ischemia, exercise radionuclide imaging remains useful for detecting silent ischemia in numerous patient populations, including those who are totally asymptomatic, those who have chronic stable angina, those who have recovered from an episode of unstable angina or an uncomplicated myocardial infarction, and those who have undergone angioplasty or received thrombolytic therapy. Studies show that thallium scintigraphy is more sensitive than exercise electrocardiography in detecting ischemia, i.e., in part, because perfusion defects occur more frequently than ST depression and before angina in the ischemic cascade. Thallium-201 scintigraphy can be performed to differentiate a true- from a false-positive exercise electrocardiographic test in patients with exercise-induced ST depression and no angina. The development of technetium-labeled isonitriles may improve the accuracy of myocardial perfusion imaging.


Eldecalcitol induces apoptosis and autophagy in human osteosarcoma MG-63 cells by accumulating ROS to suppress the PI3K/Akt/mTOR signaling pathway.
Eldecalcitol (ED-71) is a new type of vitamin D analog, and vitamin D has been reported to have therapeutic effects in infectious disease, autoimmune disease, and cancer. However, the anti-cancer effect of ED-71 remains unclear. The objective of this study was to explore the anti-cancer effect of ED-71 in human osteosarcoma cells and to identify the related mechanism. The CCK8 assay results showed that ED-71 inhibited MG-63 cell viability in dose and time dependent manners. Cloning and Transwell invasion assays showed that ED-71 inhibited clonal and invasion ability of MG-63 cells. Flow cytometry results showed ED-71 the G2/M cycle arrest rate, apoptosis, and intracellular ROS. Western blot was used to detect cleaved-caspase-3, Bax, Bcl-2, LC3-II/LC3-I, and P62 levels and the mTOR pathway. The increase of LC3-II and P62 indicated that ED-71 induced the formation of autophagosomes and inhibited autophagy flux. Furthermore, ED-71-induced apoptosis was weakened after adding 3-methyladenine and ED-71-induced early autophagy was weakened by caspase-3 inhibitor (Z-VAD-FMK), which indicated the two processes active each other in the presence of ED-71. Furthermore, N-acetylcysteine (NAC) pretreatment reversed the ED-71-treatment outcomes, including increased apoptosis and autophagy and inhibition of the PI3K/Akt/mTOR pathway. In conclusion, our results reveal that ED-71 induced G2/M arrest, apoptosis and autophagy in MG-63 cells by accumulating ROS to suppress the PI3K/Akt/mTOR signaling pathway.


Precise Functionalization of a Multiple-Resonance Framework: Constructing Narrowband Organic Electroluminescent Materials with External Quantum Efficiency over 40.
It is of important strategic significance to develop high-efficiency narrowband organic electroluminescent materials that can be employed to fabricate ultrahigh-definition displays with wide color gamut. This topic implies a great challenge to molecular design and synthesis, especially for the development of universality, diversity, scalability, and robustness of molecular architectonics. In this work, a synthetic methodology is demonstrated for functionalizing brominated BN-containing multiple-resonance (MR) frameworks with multifarious functional groups, such as donors, acceptors, and moieties without obvious push-pull electron properties. The m-DPAcP-BNCz-based organic light-emitting diode (OLED) exhibits green emission with a full-width at half-maximum (FWHM) of 28 nm and a maximum external quantum efficiency (EQE) of 40.6%. The outstanding performance of m-DPAcP-BNCz is attributed to the perfect integration of the inherent advantages of the MR framework and the donor-acceptor configuration, which can not only achieve bathochromic shift and narrowband emission, but also obtain high photoluminescence (PL) quantum yield (ΦPL ) and horizontal emitting dipole orientation ratio (Θ// ). This straightforward and efficient approach provides insightful guidance for the construction and enrichment of more high-efficiency narrowband emitters.


Venovenostomy for outflow venous obstruction in patients with upper extremity autogenous hemodialysis arteriovenous access.
Outflow venous obstruction is a common problem in patients with autogenous upper extremity hemodialysis access. Surgical revision to divert blood flow into the patent vein is sometimes possible to restore unobstructed flow. The result of this type of procedure is not yet well known. The purpose of this report is to describe our experience with outflow venovenostomy (VV) to salvage dysfunctional autogenous upper extremity arterial venous access (AVF) threatened by venous outflow obstruction in hemodialysis-dependent patients. All patients who underwent VV procedures between September 1999 and October 2004 were reviewed. Data regarding patient demographics, comorbidities, procedure indications, perioperative complications, as well as postoperative AVF function and patency were gathered from patient charts and dialysis records. A total of 11 patients underwent VV in the study period. The median age of the AVF prior to VV was 14 months, with a range of 4-45 months. Two patients had radial cephalic AVF, and they had VV done in the antecubital fossa. Nine patients had brachial cephalic AVF. Seven of them underwent cephalic vein transposition VV, while two patients had basilic vein transposition. Functional AVF was achieved after 1 month in 10 out of 11 patients. Five patients had no further access interventions, four patients required angioplasty at the VV site to maintain access function, and one patient had access infection requiring surgical revision during follow-up. One patient never achieved access function. Postintervention assisted functional patency was 90% +/- 9.5% at 39 months. Median follow-up after VV was 16 months. Outflow VV is a viable surgical option for selected patients with failing AVF due to venous outflow obstruction.


Echocardiographic diagnosis of interrupted aortic arch with an aortopulmonary communication.
The association of interrupted aortic arch and an aortopulmonary communication is extremely rare and represents a diagnostic challenge. We report the case of a 15-hour-old infant presenting with these malformations with emphasis on the echocardiographic diagnosis. We conclude that cardiac catheterisation is not mandatory and indeed, is best avoided.


'I don't think there are great sex differences there': Processes of discursive bridging and othering in a discussion of gendered norms related to alcohol, sexual behaviour, and aggression.
Existing research indicates that sexual behaviour and aggression are particularly important to the reproduction of gendered drinking norms, both in the media and in face-to-face interaction. However, research has yet to understand in more detail the discursive processes whereby actors negotiate gendered norms related to alcohol, sexual behaviour, and aggression. This article examines how actors make symbolic distinctions between themselves and others in discussing alcohol, aggression, and sexual desire, and analyses the similarities and differences within and across gender that they identify in this process. The study relies on individual qualitative interviews with 25 Swedish women and men. To elicit participants' normative positions, we used a newspaper article as a probe during the interviews. Findings show that participants highlight similarities between women and men, and variation and individual differences among men and among women in discussing alcohol's effects on sexual desire and 'sexually active behaviour'. Differences, by contrast, are most salient when they discuss alcohol and aggression and seek to distance themselves from 'shabby bar men', rural men, and male football hooligans who drink and fight, outgroups that are marked as working-class in the participants' narratives. Two general discursive patterns were identified: discursive bridging across gender and discursive othering across class. For the participants, drinking norms are not as much about general gender differences as they are about the 'dysfunctional' drinking of certain groups of working-class men. These findings contribute to a more specific understanding of the reconstitution of gender boundaries in relation to drinking norms.


The use of autologous pericardium for ventricular aneurysm closure.
Closure of the ventriculotomy following ventricular aneurysm resection usually requires buttressing material to provide strength and hemostasis. Although Teflon felt has usually been used, this material is bulky, noncompliant, and prone to infection. Autologous pericardium appears to offer an ideal substitute without the disadvantages of artificial material. A simple technique is described to apply pericardial tissue as a natural buttressing agent for ventriculotomy closure.


Predictors of urinary tract infection after lower gastrointestinal surgery.
Urinary tract infections (UTIs) cause postoperative morbidity in patients undergoing lower gastrointestinal (GI) surgery that can prolong postoperative hospital stays. In patients with a fever of unknown origin (FUO), clinicians ignore what to do while waiting for the results of the urine culture test. This study aimed to develop a nomogram predicting UTI in the case of postoperative FUO. This observational, retrospective study included all consecutive patients from 1 November 2020 to 1 November 2021 undergoing lower-GI surgery at the Chirurgia Generale 3, University Hospital of Padua, Italy. A nomogram was created and externally validated in 90 consecutive patients undergoing urine culture tests for FUO at the Chirurgia Oncologica Unit, Veneto Institute of Oncology. In the development cohort, 109 (N = 109) patients performed a urine culture test for FUO, and 39 were diagnosed with UTI. In a multivariate analysis of patients who underwent urine culture tests for FUO, UTI was associated with female sex, older age, and duration of catheterization at the date of the urine culture test. We developed a nomogram to predict UTI in surgical patients with a C-index of 0.76. In the validation cohort, 90 consecutive patients, who had lower-GI surgery, underwent a urine culture test for FUO and were tested with this nomogram. In the validation cohort, the C-index of the nomogram for predicting a positive urine culture test was 0.71. UTIs are a common problem in patients undergoing lower-GI surgery. A nomogram including the major risk factors may help to reduce the inappropriate use of antibiotics during the period awaiting the result of the urine culture test.


Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53-MDM2 interaction. Part 2.
Five series of novel 3,4,5-trisubstituted aminothiophene derivatives and analogs were designed and synthesized based on our previous studies. All target compounds were evaluated for their p53-MDM2 binding inhibitory activities and anti-proliferation activities against A549 and PC3 tumor cell lines. Twelve compounds displayed comparable p53-MDM2 binding inhibitory activities to that of Nutlin-3. Among them, compound 7a exhibited marked binding affinity (IC50=0.086 μM). In addition, most target compounds showed potent anti-proliferation activities with IC50 values at low micromolar level. A good selective profile for wild-type p53 expression cell line was also observed. Molecular docking analysis was performed as well to predict possible binding modes of target compounds with MDM2.


Chemical derivatization as a novel strategy for selective and sensitive determination of intracellular di-and triphosphate anabolites in peripheral blood mononuclear cells.
Quantitation of intracellular tri-phosphate anabolite, GSK1-TP, was required to understand drug efficacy of a proprietary molecule, GSK1; while quantitation of the di-phosphate, GSK1-DP, provided an indicator of potential GSK1-TP instability during sample processing and storage. A novel derivatization approach with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and hexylamine was developed to mitigate the challenges associated with the analysis of GSK1-DP and GSK1-TP, rendering them more amendable to reversed-phase LC-MS/MS detection. Extensive effort was spent to minimize the analyte loss and cell counts variability during peripheral blood mononuclear cells (PBMC) collection and best practices were thoroughly discussed. A solution of 30/70/2 (v/v/v) RPMI-1640/methanol/trichloroacetic acid proved to be an effective method of analyte stabilization and recovery. Methods were developed for simultaneous analysis of GSK1-DP and GSK1-TP with a limit of quantitation of 2.0 ng/mL in dog and rat PBMC lysate, with a subsequent improvement to 0.1 ng/mL for the analysis of GSK1-TP in human PBMC lysate. All three assays were found to be robust over the PBMC concentration range of 1-25 × 106 lysed cells/mL. This novel methodology could alleviate some challenges associated with the bioanalysis of intracellular phosphorylated anabolites such as PBMC collection variability, analyte instability, poor chromatographic retention, high carryover, matrix effect and insufficient assay sensitivity.


Backstroke organization in physical education students as a function of skill and sex.
This study assessed how stroking in backstroke varies with performance status and sex. A total of 36 subjects were separated into two groups of 18 by sex and further divided into two subgroups of nine, faster and slower, based on velocity in the 100-m event. Stroking parameters and coordination indexes were measured at this 100-m pace. Index 1 characterizes the continuity between propulsive phases of each arm and Index 2, the simultaneity between the beginning of the pull of one arm and of the recovery of the other arm. It is shown that the entry-catch and clearing vary (p<.05) between men (4.5%+/-3.7 and 27.1%+/-9.0) and women (8.3%+/-8.5 and 20.0%+/-4.6). Index 1 indicates that women have a better continuity than men (7.4%+/-6.3 vs -10.7%+/-3.6; p<.05). Performance is mainly explained (p<.05) by the increase in the entry and catch (r=.58 for men and .75 for women) at the expense of clearing (respectively, r=-.70 and -.53, p<.05). For men, Index 2 indicates that the simultaneity is higher in faster than in slower swimmers (10.6+/-7.0% vs 15.5+/-7.4%; p<.05) and is correlated with performance (r=-.47, p<.05). Index 2 is related to the clearing (r=.71), the number of kicks per cycle (K x C(-1), r=-.61), and the pull (r=.60). For women, the performance is explained by Index 1 (r=.48, p<.05). Index 1 is related (p<.05) to stroke rate (r=.84), the clearing (r=-.70), and K x C(-1) (r=-.61). K x C(-1) increases from 6.4+/-.70 for the faster to 7.8+/-2.0 for the slower group (p<.05).


Nineteen cases of persistent pruritic nodules and contact allergy to aluminium after injection of commonly used aluminium-adsorbed vaccines.
Rare cases of persistent pruritic nodules, sometimes associated with aluminium (Al) allergy, have been reported after the use of several Al adsorbed vaccines. During vaccine trials in the 1990s a high incidence of pruritic nodules (645 cases/76,000 recipients), in 77% associated with Al allergy, was observed after the administration of diphtheria-tetanus / acellular pertussis (DT/aP) vaccines from a single producer. In the present report 19 children with pruritic nodules after vaccination with Al hydroxide-adsorbed DTaP/polio+Hib (Infanrix, Pentavac) are described. The children had intensely itching nodules at the injection site, often aggravated during upper respiratory tract infections, and local skin alterations. So far, the symptoms have persisted for up to 7 years. The median time between vaccination and onset of symptoms was 1 month. 16 children were epicutaneously tested for Al, all with positive reactions indicating delayed hypersensitivity to Al. The condition is not commonly known but is important to recognise, as the child and the family may suffer considerably. Future vaccinations with Al-adsorbed vaccines may cause aggravation of the symptoms and the Al allergy. Al-containing skin products, such as antiperspirants, may cause contact dermatitis. Nodules may be mistaken for tumours. Even though the incidence of itching nodules and Al allergy after administration of Infanrix, Pentavac and other Al-adsorbed vaccines is probably low, research to replace Al adjuvants seems appropriate. We conclude that intensely itching subcutaneous nodules, lasting for many years, and hypersensitivity to aluminium may occur after DTaP/polio+Hib vaccination of infants.


Growth of self-perceived clinical competence in postgraduate training for general practice and its relation to potentially influencing factors.
To examine the increase in self-perceived clinical competence during a three-year postgraduate training in general practice and to explore the relation between the growth of self-perceived competence and several background variables. Cohort, 1995-1998. Three-year Postgraduate Training for General practice in the Netherlands All Dutch trainees who followed postgraduate training from September 1995 to September 1998 (N=191). We asked the trainees at the start and at the end of their postgraduate training to complete a questionnaire, which assessed their self-perceived knowledge, clinical skills and consultations skills. We collected information about potentially influencing background variables. Amongst these were variables such as: age, gender, prior medical experience, the effort someone has spent upon her/his education, insight in weak and strong areas of clinical competence and knowledge and skills levels. Self-perceived competence. A total of 127 trainees completed both questionnaires (190 at the first administration and 128 at the second one). We found statistically significant growth of self-perceived clinical competence. Self-perceived consultation skills increased more than self-perceived knowledge and clinical skills. The afore mentioned background variables did not relate in any way with the growth of self-perceived clinical competence. This study shows that a 3-year postgraduate training in general practice enhances self-perceived clinical competence. However, we still do not know how to explain this improvement. Further study into the theoretical concept of self-assessment in medical education and into the factors contributing to the feeling of being competent, is required.


Complete chloroplast genome data for Cryptocoryne elliptica (Araceae) from Peninsular Malaysia.
The aquatic plant genus Cryptocoryne, a popular plant genus in the aquarium industry, is made up of more than 50 described species and some 15 naturally occurring named and unnamed interspecific hybrids. Cryptocoryne elliptica has a restricted distribution in the north part of Peninsular Malaysia. Destruction of its natural habitats for various human activities has led to a decline in numbers. Here, we report the complete chloroplast genome of C. elliptica and establish a molecular dataset for a maternally inherited genome. Here, we utilized an Illumina NovaSeq 6000 protocol to sequence the partial genome of C. elliptica and used bioinformatic tools to reconstruct the chloroplast genome in de novo mode. The assembled chloroplast genome is a circular DNA molecule 159,968 bp in length. The chloroplast genome has a quadripartite structure composed of a large single-copy region of 96,273 bp and a small single-copy (SSC) region of 15,205 bp, separated by a pair of inverted repeats (IRa and IRb), each of which is 24,245 bp. The chloroplast genome of C. elliptica encodes a total of 108 genes, comprising 74 protein-coding genes, 30 tRNA genes and 4 rRNA genes. In total, 204 SSR loci were identified, most of which were located within intergenic regions.


Phosphorus recovery from sewage sludge ash (SSA): An integrated technical, environmental and economic assessment of wet-chemical and thermochemical methods.
Incineration is a promising disposal method for sewage sludge (SS), enriching more than 90% of phosphorus (P) in the influent into the powdered product, sewage sludge ash (SSA), which is convenient for further P recovery. Due to insufficient bioavailable P and enriched heavy metals (HMs) in SSA, it is limited to be used directly as fertilizer. Hence, this paper provides an overview of P transformation in SS incineration, characterization of SSA components, and wet-chemical and thermochemical processes for P recovery with a comprehensive technical, economic, and environmental assessment. P extraction and purification is an important technical step to achieve P recovery from SSA, where the key to all technologies is how to achieve efficient separation of P and HMs at a low economic and environmental cost. It can be clear seen from the review that the economics of P recovery from SSA are often weak due to many factors. For example, the cost of wet-chemical methods is approximately 5∼6 €/kg P, while the cost of recovering P by thermochemical methods is about 2∼3 €/kg P, which is slightly higher than the current P fertilizer (1 €/kg P). So, for now, legislation is significant for promoting P recovery from SSA. In this regard, the relevant experience in Europe is worth learning from countries that have not yet carried out P recovery from SSA, and to develop appropriate policies and legislation according to their own national conditions.


Time-resolved x-ray diffraction studies on the intensity changes of the 5.9 and 5.1 nm actin layer lines from frog skeletal muscle during an isometric tetanus using synchrotron radiation.
Time-resolved x-ray diffraction studies have been made on the 5.9- and 5.1-nm actin layer lines from frog skeletal muscles during an isometric tetanus at 6 degrees C, using synchrotron radiation. The integrated intensities of these actin layer lines were found to increase during a tetanus by 30-50% for the 5.9-nm reflection and approximately 70% for the 5.1-nm reflection of the resting values. The intensity increase of both reflections was greater than that taking place in the transition from rest to rigor state. The intensity change of the 5.9-nm reflection preceded those of the myosin 42.9-nm off-meridional reflection and of the equatorial reflections, as well as the isometric tension development. The intensity profile of the 5.9-nm layer line during contraction was found to be different from that observed in the rigor state.


Characterization of quinoa (Chenopodium quinoa) fermented by Rhizopus oligosporus and its bioactive properties.
Quinoa is a pseudocereal that contains high quality protein, minerals, vitamins, polyphenols, and phytosterols. In this study, quinoa was fermented by Rhizopus oligosporus (R. oligosporus) up to 5 days and the functional compounds (L-carnitine, GABA, vanillic acid and gallic acid) were analyzed by LC/MS. The amounts of L-carnitine and GABA were 0.13 mg/kg and 540 mg/kg for nonfermented quinoa (NF), 3.15 mg/kg and 1040 mg/kg for fermented quinoa at 3 days (3F), and 1.54 mg/kg and 810 mg/kg for fermented quinoa at 5 days (5F). The vanillic acid and gallic acid were 1.3 and 0.1 mg/kg for NF, 1.55 and 2.37 mg/kg for 3F, and 1.83 and 0.84 mg/kg for 5F, respectively. Total phenolic contents and total flavonoids contents were 41 mg gallic acid (GAE)/kg and 13 mg quercetin equivalent (QE)/kg for NF, 74 mg GAE/kg and 16 mg QE/kg for 3F, and 80 mg GAE/kg and 19 mg QE/kg for 5F, respectively. Antioxidant activity (SC50) was 3.6 mg/mL for NF, 3.4 mg/mL for 3F, and 2.3 mg/mL for 5F. Nitric oxide production on RAW264.7 macrophages of fermented quinoa revealed 29% and 56% inhibition of nitric oxide production for NF and 5F, respectively. Therefore, fermented quinoa can be used as a healthy and valuable food product.


Cost-Effectiveness of Therapeutic Use of Safety-Engineered Syringes in Healthcare Facilities in India.
Globally, 16 billion injections are administered each year of which 95% are for curative care. India contributes 25-30% of the global injection load. Over 63% of these injections are reportedly unsafe or deemed unnecessary. To assess the incremental cost per quality-adjusted life-year (QALY) gained with the introduction of safety-engineered syringes (SES) as compared to disposable syringes for therapeutic care in India. A decision tree was used to compute the volume of needle-stick injuries (NSIs) and reuse episodes among healthcare professionals and the patient population. Subsequently, three separate Markov models were used to compute lifetime costs and QALYs for individuals infected with hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Three SES were evaluated-reuse prevention syringe (RUP), sharp injury prevention (SIP) syringe, and syringes with features of both RUP and SIP. A lifetime study horizon starting from a base year of 2017 was considered appropriate to cover all costs and consequences comprehensively. A systematic review was undertaken to assess the SES effects in terms of reduction in NSIs and reuse episodes. These were then modelled in terms of reduction in transmission of blood-borne infections, life-years and QALYs gained. Future costs and consequences were discounted at the rate of 3%. Incremental cost per QALY gained was computed to assess the cost-effectiveness. A probabilistic sensitivity analysis was undertaken to account for parameter uncertainties. The introduction of RUP, SIP and RUP + SIP syringes in India is estimated to incur an incremental cost of Indian National Rupee (INR) 61,028 (US$939), INR 7,768,215 (US$119,511) and INR 196,135 (US$3017) per QALY gained, respectively. A total of 96,296 HBV, 44,082 HCV and 5632 HIV deaths are estimated to be averted due to RUP in 20 years. RUP has an 84% probability to be cost-effective at a threshold of per capita gross domestic product (GDP). The RUP syringe can become cost saving at a unit price of INR 1.9. Similarly, SIP and RUP + SIP syringes can be cost-effective at a unit price of less than INR 1.2 and INR 5.9, respectively. RUP syringes are estimated to be cost-effective in the Indian context. SIP and RUP + SIP syringes are not cost-effective at the current unit prices. Efforts should be made to bring down the price of SES to improve its cost-effectiveness.


Risks of developing psychiatric disorders in pediatric patients with psoriasis.
Symptoms of psoriasis can be embarrassing and distressing, and may increase risk of developing psychiatric disorders in young people. We sought to compare incidences of psychiatric disorders between pediatric patients with psoriasis and psoriasis-free control subjects. Patients (<18 years) with continuous health plan enrollment 6 months before and after first psoriasis diagnosis (index date) were selected (Thomson Reuters MarketScan database, 2000-2006 [Thomson Reuters, New York, NY]). Patients with psoriasis (N = 7404) were matched 1:5 on age and sex to psoriasis-free control subjects (N = 37,020). Patients were followed from index date to first diagnosis of a psychiatric disorder (ie, alcohol/drug abuse, depression, anxiety disorder, bipolar disorder, suicidal ideation, eating disorder), end of data availability, or disenrollment. Patients with psychiatric diagnoses or psychotropic medication use before the index date were excluded. Cox proportional hazard models controlling for age, sex, and comorbidities were used to estimate the effect of psoriasis on risks of developing psychiatric disorders. Patients with psoriasis were significantly more at risk of developing psychiatric disorders versus control subjects (5.13% vs 4.07%; P = .0001; hazard ratio = 1.25; P = .0001), especially depression (3.01% vs 2.42%; P = .0036; hazard ratio = 1.25; P = .0053) and anxiety (1.81% vs 1.35%; P = .0048; hazard ratio = 1.32; P = .0045). Retrospective, observational studies of medical claims data are typically limited by overall quality and completeness of data and accuracy of coding for diagnoses and procedures. Pediatric patients with psoriasis had an increased risk of developing psychiatric disorders, including depression and anxiety, compared with psoriasis-free control subjects.


The relationship of α-hydroxybutyrate dehydrogenase with 1-year outcomes in patients with intracerebral hemorrhage: A retrospective study.
Cardiac enzymes are recognized as a valuable tool for predicting the prognosis of various cardiovascular diseases. The prognostic value of alpha-hydroxybutyrate dehydrogenase (α-HBDH) in patients with intracerebral hemorrhage (ICH) was ambiguous and not evaluated. Two hundred and thirteen Chinese patients with ICH participated in the study from December 2018 to December 2019. Laboratory routine tests and cardiac enzymes, including α-HBDH level, were examined and analyzed. All the patients were classified into two groups by the median value of α-HBDH: B1 <175.90 and B2 ≥175.90 U/L. The clinical outcomes included functional outcome (according to modified Rankin Scale (mRS) score ≥3), all-cause death, and recurrent cerebro-cardiovascular events 1 year after discharge. Associations between the α-HBDH and the outcomes were evaluated using logistic regression analysis. Univariate survival analysis was performed by the Kaplan-Meier method and log-rank test. Of the 213 patients, 117 had α-HBDH ≥175.90 U/L. Eighty-two patients had poor functional outcomes (mRS≥3). During the 1-year follow-up, a total of 20 patients died, and 15 of them had α-HBDH ≥175.90 U/L during the follow-up time. Moreover, 24 recurrent events were recorded. After adjusting confounding factors, α-HBDH (≥175.90) remained an indicator of poor outcome (mRS 3-6), all-cause death, and recurrent cerebro-cardiovascular events. The ORs for B2 vs. B1 were 4.78 (95% CI: 2.60 to 8.78, P = 0.001), 2.63 (95% CI: 0.80 to 8.59, P = 0.11), and 2.40 (95% CI: 0.82 to 7.02, P = 0.11) for poor functional outcomes with mRS ≥ 3, all-cause death, and recurrent cerebro-cardiovascular events, respectively. Increased α-HBDH at admission was independently related to poor functional outcome and all-cause mortality in patients with ICH at 1-year follow-up.


Infrared autofluorescence, short-wave autofluorescence and spectral-domain optical coherence tomography of optic disk melanocytomas.
To investigate the findings of infrared fundus autofluorescence (IR-AF) and spectral-domain optical coherence tomography (SD-OCT) in eyes with optic disc melanocytoma (ODM). IR-AF findings and those of other ophthalmologic imaging examinations, including short-wave autofluorescence (SW-AF), fluorescein angiography (FA), fundus color photography, and SD-OCT of 8 eyes of 8 consecutive cases with ODM were assessed. The ODMs in all cases (100%) presented similar IR-AF, SW-AF, and FA findings. On IR-AF images, ODMs showed outstanding hyper-AF with well-defined outline. On SW-AF images, the area of ODMs presented as hypo-AF. FA images revealed the leaking retinal telangiectasia on the surface of the ODMs. On SD-OCT images in 8 cases (100%), the ODMs were sloped with highly reflective surface, which were disorganized retina and optic nerve layers. In 7 cases (87.5%), peripapillary choroids were involved. The melanocytomas of 8 cases (100%) presented as optically empty spaces. Vitreous seeds were found in one case (12.5%). IR-AF imaging may provide a new modality to evaluate the pathologic features of ODMs, and together with SW-AF imaging, offers a new tool to study biological characteristics associated with ODMs. SD-OCT is a valuable tool in delimitating the tumor extension and providing morphological information about the adjacent retinal tissue.


[Characteristics of thrombus formation in arterioles and venules].
The model of laser-induced thrombosis revealed a greater thromboresistance in arterioles rather than in venules of the rat small intestine mesentery, which accounts for a less frequent thrombosis and a lesser size of thrombus along the blood flow direction, whereas their greater thrombogenic potential accounts for a faster growth of thrombus and a shorter time of the primary hemostasis.


LncRNA-AK137033 inhibits the osteogenic potential of adipose-derived stem cells in diabetic osteoporosis by regulating Wnt signaling pathway via DNA methylation.
Bone tissue engineering based on adipose-derived stem cells (ASCs) is expected to become a new treatment for diabetic osteoporosis (DOP) patients with bone defects. However, compared with control ASCs (CON-ASCs), osteogenic potential of DOP-ASCs is decreased, which increased the difficulty of bone reconstruction in DOP patients. Moreover, the cause of the poor osteogenesis of ASCs in a hyperglycemic microenvironment has not been elucidated. Therefore, this study explored the molecular mechanism of the decline in the osteogenic potential of DOP-ASCs from the perspective of epigenetics to provide a possible therapeutic target for bone repair in DOP patients with bone defects. An animal model of DOP was established in mice. CON-ASCs and DOP-ASCs were isolated from CON and DOP mice, respectively. AK137033 small interfering RNA (SiRNA) and an AK137033 overexpression plasmid were used to regulate the expression of AK137033 in CON-ASCs and DOP-ASCs in vitro. Lentiviruses that carried shRNA-AK137033 or AK137033 cDNA were used to knockdown or overexpress AK137033, respectively, in CON-ASCs and DOP-ASCs in vivo. Hematoxylin and eosin (H&E), Masson's, alizarin red, and alkaline phosphatase (ALP) staining, micro-computed tomography (Micro-CT), flow cytometry, qPCR, western blotting, immunofluorescence, and bisulfite-specific PCR (BSP) were used to analyze the functional changes of ASCs. The DOP mouse model was established successfully. Compared with CON-ASCs, AK137033 expression, the DNA methylation level of the sFrp2 promoter region, Wnt signaling pathway markers, and the osteogenic differentiation potential were decreased in DOP-ASCs. In vitro experiments showed that AK137033 silencing inhibited the Wnt signaling pathway and osteogenic ability of CON-ASCs by reducing the DNA methylation level in the sFrp2 promoter region. Additionally, overexpression of AK137033 in DOP-ASCs rescued these changes caused by DOP. Moreover, the same results were obtained in vivo. LncRNA-AK137033 inhibits the osteogenic potential of DOP-ASCs by regulating the Wnt signaling pathway via modulating the DNA methylation level in the sFrp2 promoter region. This study provides an important reference to find new targets for the treatment of bone defects in DOP patients.


Obesity and recurrent vascular risk after a recent ischemic stroke.
Although obesity is an established risk factor for the occurrence of a primary stroke, little is known about the impact of baseline obesity on recurrent vascular risk among patients with recently symptomatic cerebrovascular disease. We evaluated the association of obesity with future vascular risk in patients with a recent history of stroke. We analyzed the database of a multicenter trial involving 20 332 patients with recent ischemic stroke followed for 2.5 years. Subjects were divided into 3 groups according to recognized body mass index categories representing lean, overweight, and obese. Primary outcome was time to first recurrent stroke and secondary outcome time to stroke, myocardial infarction, or vascular death. The independent association of obesity with outcome was assessed by controlling for other known risk factors. Of 20 246 eligible subjects, 4805 (24%) were obese. After adjusting for confounders, compared with the lean group, being overweight (hazard ratio, 0.95; 95% CI, 0.85-1.06) or obese (hazard ratio, 0.95; 95% CI, 0.83-1.08) was not associated with increased recurrent stroke risk, but being overweight (hazard ratio, 0.84; 95% CI, 0.77-0.92) or obese (hazard ratio, 0.86; 95% CI, 0.77-0.96) was associated with lower risk of a major vascular event. Obesity is not related to recurrent stroke risk, but obese patients with stroke are at lower overall vascular risk than their leaner counterparts, supporting the widely held notion of the existence of a cardiovascular "obesity paradox."


Establishment and molecular mechanisms of HIV-1 latency in T cells.
Treatment of an HIV infected individual with antiretroviral drugs is a successful way to suppress the plasma viral RNA load below the limit of detection (50 copies HIV RNA/ml plasma). This can provide lifelong protection against virus-induced pathogenesis in drug-adherent patients. Unfortunately, even after many years of continuous treatment, the virus persists and the plasma viral load will rebound rapidly when therapy is interrupted. The reason for this rapid rebound is the presence of a long-lived reservoir of latent HIV-1 proviruses that can be reactivated in resting memory T cells. Attempts to eliminate these proviruses have thus far not been successful and this long-lived latent reservoir is therefore considered a major obstacle toward a cure for HIV-1. A detailed understanding of the molecular mechanisms causing HIV latency and knowledge on the establishment of this reservoir may give us clues for future strategies aiming at the eradication of this reservoir.


Ancestry markers from the human chromosome 6: Alu repeats from the MHC in autochthonous Basques.
Polymorphic Alu insertions from the MHC class I region were analyzed in 215 autochthonous Basques from Guipuzcoa and Navarre provinces, with the aim of contributing new MHC Alu data in European ancestry populations. We also seek to assess both the genetic position of native Basques among worldwide samples and the efficiency of the MHC Alu elements as ancestry informative markers (AIMs). According to the MDS and AMOVA results, worldwide populations included in the comparative analyses were grouped in three major clusters defined by genetic ancestry (Africans, Asians and Europeans). The δ values (differences in weighted allele frequencies) among ancestry groups indicated that Alu elements within the alpha-block (AluHF, AluHJ and AluHG) showed an adequate resolving power to discriminate appropriately between some of the major ancestry groups. Alpha block Alu were also revealing of the exceptionality of Basques, as they allowed for the detection of genetic heterogeneity even between Basques and the other Iberian collection considered in the analysis (Valencia). Thus, analysis of the Alu loci within the alpha-block may represent a reliable, informative and cost-effective method to explore the ancestry, geographic origins and demographic history of human populations, which can be very helpful for studies into epidemiological, forensic or evolutionary perspectives.


Assessing new strategies for TB diagnosis in low- and middle-income countries.
In this manuscript, we report the current situation of tuberculosis globally and in Brazil, the need for new strategies toward tuberculosis control, focusing on new diagnostic technologies. Critical comments are given on the state of the art regarding the evaluation of new health technologies, degree of scientific evidence needed, evaluation of clinical impact, cost-effectiveness of incorporation into the health system and the social impact.


[Comparative study of relative biovailability of several spironolactone formulations in a steady-state test (author's transl)].
By the US Food and Drug Administration spironolactone is regarded as a drug with problems related to bioavailability. A steady-state study was performed comparing the 50- and 100-mg formulations of two manufacturers with each other. Applying a fluorimetric method to both canrenone and canrenoate--the major biologically active metabolites of spironolactone--the two brands were compared in 11 volunteers for the 50 mg, and in 10 volunteers for the 100 mg dosage form.


Transsacral removal of rectal leiomyomas from the same patient on two occasions: report of a case.
An unusually large rectal leiomyoma was excised by the transsacral approach. It recurred six years later and was removed once again in similar fashion. Reoperation was found to be not difficult, though added care is necessary to identify the sphincters, which have a paler appearance. Nerve damage can be kept to a minimum if the same incision is employed. Despite the palliative nature of the operation, the patient was spared total rectal excision and colostomy.


Landscape ecological security response to land use change in the tidal flat reclamation zone, China.
As coastal development becomes a national strategy in Eastern China, land use and landscape patterns have been affected by reclamation projects. In this study, taking Rudong County, China as a typical area, we analyzed land use change and its landscape ecological security responses in the tidal flat reclamation zone. The results show that land use change in the tidal flat reclamation zone is characterized by the replacement of natural tidal flat with agricultural and construction land, which has also led to a big change in landscape patterns. We built a landscape ecological security evaluation system, which consists of landscape interference degree and landscape fragile degree, and then calculated the landscape ecological security change in the tidal flat reclamation zone from 1990 to 2008 to depict the life cycle in tidal flat reclamation. Landscape ecological security exhibited a W-shaped periodicity, including the juvenile stage, growth stage, and maturation stage. Life-cycle analysis demonstrates that 37 years is required for the land use system to transform from a natural ecosystem to an artificial ecosystem in the tidal flat reclamation zone.


Phase II trial of methotrexate-FAM (m-FAM) in adenocarcinoma of unknown primary.
Nineteen patients with adenocarcinoma of unknown primary were treated with the m-FAM regimen, consisting of methotrexate 50 mg/m2 days 0, 28; 5-fluorouracil 600 mg/m2 days 1, 8, 29, 36; Adriamycin 30 mg/m2 days 1, 29; and mitomycin-C 10 mg/m2 day 1. All drugs were recycled every 56 days. No complete responses were seen. Seven patients (37%) achieved partial remission for a median duration of 11 months. An additional nine patients (47%) had stable disease for a median duration of 6 months. Median survival for responders was 16 months and was 10 months for those with stable disease. Toxicity was acceptable. This Phase II study attempted to evaluate the clinical impact of the pharmacological modulation of 5-fluorouracil with methotrexate, the goal being improvement of the results of FAM alone in adenocarcinoma of unknown primary. However, the addition of methotrexate, at least in the schedule employed in this study, did not appear superior to FAM.


Sustainable changes in beauty market trends focused on the perspective of safety in the post-coronavirus disease-19 period.
In February 2020, WHO announced the outbreak of coronavirus disease-19 (COVID-19) in a global epidemic, and the COVID-19 vaccine has recently been developed and approved in many countries to release disease radio waves. Immediately distributed and used to control and control infections. During the COVID-19 pandemic, the world closed extensively in beauty and beauty services to control the spread of the virus. Therefore, this study for the first time that the perspective of safety in sustainable may be applied to the entire alteration of beauty industry market in the post-COVID-19 pandemic for literature review. A Narrative Review is proposed as a new report and commentary on the sustainable change of beauty market trends centered on safety due to the COVID-19 pandemic in December 2020. It was written with reference to keywords such as "Covid Beauty Market," "Covid Sustainable," "Covid clean beauty," and "Safety beauty." This study was performed by searching on PubMed, Google Scholar, Scopus, and ResearchGate. A total of 383 papers were retrieved, of which 36 were successfully included in this study. Analysis of customers and markets in the beauty industry since COVID-19 was absolutely required at this time. Harmful and safe edible ingredients of clean beauty perspective should be compared and analyzed. In addition, importance of sustainability value from a clean beauty perspective should be considered. There is an era in which the perspective of safety in sustainable may be applied to the entire beauty industry today. In addition, depending on the customer's perception change, beyond the ingredients, raw material procurement of products, manufacturing process, product experiments, etc. are part of clean beauty to minimize carbon emissions, water use, recycle product containers, and reduce waste.


Regiospecific Benzoylation of Electron-Deficient N-Heterocycles with Methylbenzenes via a Minisci-Type Reaction.
A regioselective cross-dehydrogenative coupling between electron-deficient N-heterocycles (isoquinoline, quinolines, and quinoxalines) and methylbenzenes leading to regiospecific C-aroylation has been accomplished using AlCl3 as the catalyst in the presence of oxidant TBHP. This protocol is a practical alternative to the classical Minisci reaction.


Characterization of basolateral K+ channels underlying anion secretion in the human airway cell line Calu-3.
Transepithelial anion secretion in many tissues depends upon the activity of basolateral channels. Using monolayers of the Calu-3 cell line, a human submucosal serous cell model mounted in an Ussing chamber apparatus, we investigated the nature of the K+ channels involved in basal, cAMP- and Ca2+-stimulated anion secretion, as reflected by the transepithelial short circuit current (I(sc)). The non-specific K+ channel inhibitor Ba2+ inhibited the basal I(sc) by either 77 or 16 % when applied directly to the basolateral or apical membranes, respectively, indicating that a basolateral K+ conductance is required for maintenance of basal anion secretion. Using the K+ channel blockers clofilium and clotrimazole, we found basal I(sc) to be sensitive to clofilium, with a small clotrimazole-sensitive component. By stimulating the cAMP and Ca2+ pathways, we determined that cAMP-stimulated anion secretion was almost entirely abolished by clofilium, but insensitive to clotrimazole. In contrast, the Ca2+-stimulated response was sensitive to both clofilium and clotrimazole. Thus, pharmacologically distinct basolateral K+ channels are differentially involved in the control of anion secretion under different conditions. Isolation of the basolateral K+ conductance in permeabilized monolayers revealed a small basal and forskolin-stimulated I(sc). Finally, using the reverse transcriptase-polymerase chain reaction, we found that Calu-3 cells express the K+ channel genes KCNN4 and KCNQ1 and the subunits KCNE2 and KCNE3. We conclude that while KCNN4 contributes to Ca2+-activated anion secretion by Calu-3 cells, basal and cAMP-activated secretion are more critically dependent on other K+ channel types, possibly involving one or more class of KCNQ1-containing channel complexes.


An investigation of a spread energy method for medical ultrasound systems. Part two: proposed system and possible problems.
A medical ultrasound device using a Golay code is proposed and investigated theoretically. The code enables the spread energy method to be used to help overcome the restraints of the parameters of resolution, peak power and penetration.


The association of problematic usage of the internet with burnout, depression, insomnia, and quality of life among Hungarian high school students.
The extensive availability of the internet has led to the recognition of problematic usage of the internet (PUI) or so called internet addiction (IA), probably mostly involving adolescents. Here we present a study focusing on the incidence and consequences (including burnout, which is relatively rarely studied) of internet addiction among high school students using a questionnaire-based non-random sampling cross-sectional survey. Included questionnaires were the Problematic Internet Use Questionnaire, the Maslach Burnout Inventory General Survey for Students MBI-GS (S), the 9-item short version of Beck Depression Inventory (BDI-SF), the Athens Insomnia Questionnaire and the EQ-5D (quality of life) questionnaire. Data were evaluated the exertion of Student's t-test, chi square test and Pearson's rank-order correlation. Logistic regression analysis was used to determine the significance of the different parameters as independently associated with PUI. Overall 3,000 paper-based questionnaires were successfully delivered and 2,540 responses received (response rate of 84.6%). 1,309 males (mean age 17.6 ± 1.43 years) (51.5%) and 1,231 females (mean age 17.5 ± 1.4 years) (48.5%) took part in our study. Problematic usage of the internet was detected in 486 (19.1%) students (232 males, mean age 17.6 ± 1.35 years and 254 females, mean age 17.34 ± 1.37 years). In a logistic regression analysis sleep disturbance (OR: 1.84, 95% CI: 1.83-2.03), depression (OR: 1.97, 95% CI: 1.77-2.02) and burnout (OR: 1.8, 95% CI: 1.16-1.94) were significantly associated with PUI. Nearly one fifth of our study population suffered from PUI, which was strongly associated with school burnout, insomnia and depression, which underlines the importance of this phenomenon.


Malignancy risk models for oral lesions.
The aim of this work was to assess risk habits, clinical and cellular phenotypes and TP53 DNA changes in oral mucosa samples from patients with Oral Potentially Malignant Disorders (OPMD), in order to create models that enable genotypic and phenotypic patterns to be obtained that determine the risk of lesions becoming malignant. Clinical phenotypes, family history of cancer and risk habits were collected in clinical histories. TP53 gene mutation and morphometric-morphological features were studied, and multivariate models were applied. Three groups were estabished: a) oral cancer (OC) group (n=10), b) oral potentially malignant disorders group (n=10), and c) control group (n=8). An average of 50% of patients with malignancy were found to have smoking and drinking habits. A high percentage of TP53 mutations were observed in OC (30%) and OPMD (average 20%) lesions (p=0.000). The majority of these mutations were GC TA transversion mutations (60%). However, patients with OC presented mutations in all the exons and introns studied. Highest diagnostic accuracy (p=0.0001) was observed when incorporating alcohol and tobacco habits variables with TP3 mutations. Our results prove to be statistically reliable, with parameter estimates that are nearly unbiased even for small sample sizes. Models 2 and 3 were the most accurate for assessing the risk of an OPMD becoming cancerous. However, in a public health context, model 3 is the most recommended because the characteristics considered are easier and less costly to evaluate.


[Ultrastructural changes in the cells of bone marrow capillaries in chronic lead exposure].
Prolonged influence of lead on the laboratory white rats was studied. The interchange of the "light" and "dark" endothelial cells in the bone marrow capillaries, pseudomyelination of mitochondria, periendothelial space extension, more dense or loose basement layer and clasmatosis in the adventitial cells of sinusoids were observed. These alterations were observed in both adult and newborn rats whose parents were influenced by lead before the coupling.


Endogenous peptides work at multiple sites in the nervous system in the control of gill behaviors in Aplysia.
The suprafusion of two endogenous neuropeptides, arginine vasotocin (AVT) and small cardioactive peptide B (SCPB), over the abdominal ganglion of Aplysia californica significantly affects the ability of a central gill motor neuron to elicit a gill withdrawal response. Gill motor neurons L7 or LDG1 were depolarized to produce the same number of action potentials (APs) on each trial. When AVT (10(-6)M) was suprafused, the motor neurons' ability to elicit a gill movement was suppressed; while SCPB (10(-6)M) superfusion facilitated the response. Neither peptide altered the passive membrane properties of the motor neurons nor did they affect the duration of their APs. These results are consistent with the hypothesis that the peptides act via central control neurons which exert both suppressive and facilitatory control over gill reflex behaviors and associated neural activity.


Changes in the circadian rhythmicity of hydroxyindole-O-methyl transferase (HIOMT) activity in the synthesis of 5-methoxyindoles in the pineal gland of 28 day old male Wistar rats exposed to white, red and green light.
Hydroxyindole-O-methyl transferase activity for the synthesis of 5-methoxyindoles was investigated in the pineal gland of 28 day old male Wistar rats after exposure to white, red and green light for 12 hours daily. It could be demonstrated that, in comparison to white light, red light causes a shift of HIOMT activity for the synthesis of melatonin/5-methoxytryptophol towards an earlier period being highest between 12 and 16 hours. The synthesis of 5-methoxytryptamine and of 5-methoxytryptophan is shifted to 16 hours, while the synthesis of 5-methoxyindole-3-acetic acid, which normally peaks at 16 hours, is increased at this same hour. Green light shifts HIOMT activity for the synthesis of melatonin/5-method being highest between 12 and 16 hours. The synthesis of 5-methoxytryptamine and of 5-methoxytryptophan is shifted to 16 hours, while the synthesis of 5-methoxyindole-3-acetic acid, which normally peaks at 16 hours, is increased at this same hour. Green light shifts HIOMT activity for the synthesis of melatonin/5-method being highest between 12 and 16 hours. The synthesis of 5-methoxytryptamine and of 5-methoxytryptophan is shifted to 16 hours, while the synthesis of 5-methoxyindole-3-acetic acid, which normally peaks at 16 hours, is increased at this same hour. Green light shifts HIOMT activity for the synthesis of melatonin/5-methoxytryptophol to a later period, showing a peak at 24 hours. The synthesis of 5-methoxytryptamine is significantly increased at 24 hours. An increase is also observed in the synthesis of 5-methoxyindole-3-acetic acid at 12 and at 4 hours, times at which this synthesis is also maximal using white light, whereas the synthesis of 5-methoxytryptophan is generally decreased. A possible relationship between the present results and those obtained after exposure to different wavelengths of light on N-acetyltransferase activity, the effect of pterins on HIOMT activity and the effect of different wavelengths on gonadal growth are discussed.


The emerging role of bacterial regulatory RNAs in disease.
Pathogenic bacteria have evolved to sense their surrounding environments and regulate their gene expression to evade host immune defences and cause disease. RNA-mediated gene expression offers a fast and energy efficient alternative to conventional transcription factors. A myriad of regulatory RNAs have been identified, especially in pathogenic bacteria. However, whether these RNAs partake in disease remains largely unexplored. Here, we review current knowledge of regulatory RNAs in human-adapted upper respiratory tract pathogens. We propose that bacterial regulatory RNAs could play important roles in disease. Elucidating the function of regulatory RNAs and identifying polymorphisms among disease isolates would provide valuable insight into their pathogeneses. Finally, we discuss the outstanding issues of regulatory RNAs in research and their applications as drug targets, therapeutics, and in providing diagnostic information predictive of disease prognosis.


Childhood cancer research in Oxford I: the Oxford Survey of Childhood Cancers.
Significant research on the epidemiology and natural history of childhood cancer took place in the Universities of Oxford and Birmingham over sixty years. This is the first of three papers recording this work and describes the Oxford Survey of Childhood Cancers (OSCC), the largest case-control survey of childhood cancer ever undertaken. The OSCC studied deaths in Britain from 1953 to 1981. Parents were interviewed and medical records from ante-natal clinics and treatment centres were followed up and abstracted. The survey left Oxford in 1975 and was run subsequently from Birmingham. The data are now being documented and archived to make them available for future study. Many papers have resulted from this survey, most notably those relating to the association first reported therein between childhood cancer and ante-natal X-raying. This paper is a historical review of the OSCC. In spite of many analyses of the study, this historic data set has continuing value because of the large number of examples of some very rare tumours and the detailed clinical and family history data that are available; and also because of the possibility of carrying out new analyses to investigate emerging research issues.


Chain length-dependent cooperativity in fatty acid binding and oxidation by cytochrome P450BM3 (CYP102A1).
Fatty acid binding and oxidation kinetics for wild type P450(BM3) (CYP102A1) from Bacillus megaterium have been found to display chain length-dependent homotropic behavior. Laurate and 13-methyl-myristate display Michaelis-Menten behavior while there are slight deviations with myristate at low ionic strengths. Palmitate shows Michaelis-Menten kinetics and hyperbolic binding behavior in 100 mmol/L phosphate, pH 7.4, but sigmoidal kinetics (with an apparent intercept) in low ionic strength buffers and at physiological phosphate concentrations. In low ionic strength buffers both the heme domain and the full-length enzyme show complex palmitate binding behavior that indicates a minimum of four fatty acid binding sites, with high cooperativity for the binding of the fourth palmitate molecule, and the full-length enzyme showing tighter palmitate binding than the heme domain. The first flavin-to-heme electron transfer is faster for laurate, myristate and palmitate in 100 mmol/L phosphate than in 50 mmol/L Tris (pH 7.4), yet each substrate induces similar high-spin heme content. For palmitate in low phosphate buffer concentrations, the rate constant of the first electron transfer is much larger than k (cat). The results suggest that phosphate has a specific effect in promoting the first electron transfer step, and that P450(BM3) could modulate Bacillus membrane morphology and fluidity via palmitate oxidation in response to the external phosphate concentration.


Overview of in situ and ex situ remediation technologies for PCB-contaminated soils and sediments and obstacles for full-scale application.
Polychlorinated biphenyls (PCB) are persistent organic pollutants used worldwide between the 1930s and 1980s. Although their use has been heavily restricted, PCB can be found in contaminated soils and sediments. The most frequent remediation solutions adopted are "dig and dump" and "dig and incinerate", but there are currently new methods that could be more sustainable alternatives. This paper takes a look into the remediation options available for PCB-contaminated soils and sediments, differentiating between biological, chemical, physical and thermal methods. The use of combined technologies was also reviewed. Most of them are still in an initial development stage and further research in different implementation issues is needed. There is no single technology that is the solution for PCB contamination problem. The successful remediation of a site will depend on proper selection, design and adjustment of the technology or combined technologies to the site characteristics.


Sex differences in adrenocortical structure and function. XII. Stereologic studies of rat adrenal cortex in the course of maturation.
This paper reports a stereological study of the cellular aspects of development of the adrenal cortex of male and female rats in the course of maturation. Rats of the Wistar strain were studied at weekly intervals from day 21 to day 77 of postnatal life. From day 42 homogenates of adrenals from female rats produced more corticosterone than homogenates from males of corresponding age. In the strain of rats studied sex differences in adrenal weight appeared at about day 49. From this day onward relative, and subsequently absolute adrenal weights were higher in females than in males. In the course of maturation the total volume of all adrenocortical zones gradually increased. From day 70 the zona glomerulosa and from day 49 the zona fasciculata were larger in female than in male rats, while no distinct sex difference was observed in the volume of the zona reticularis. The appearance of sex-related differences in the adrenal cortex depends mainly on changes in the zona fasciculata, the cells of which markedly increased in volume in female rats by comparison with males. The total number of all adrenocortical cells increased from ca 13 million on day 21 to ca 25 million on day 77 and at all intervals studied adrenal glands of male and female rats contained a similar number of parenchymal cells.


Students' views of enquiry-based learning in a continuing professional development module.
The purpose of this study was to explore whether qualified nurses who had undertaken a continuing professional development module at a UK university, which utilised enquiry-based learning (EBL) as the educational strategy, believed that their nursing practice had been influenced by this educational approach. This study was underpinned by the assumptions of Gadamerian hermeneutic phenomenology; semi-structured interviews were conducted with eight nurses who had undertaken a continuing education module utilising an EBL approach. The responses in this study indicate that participants believed that their practice of nursing had been positively influenced by engaging in EBL. They felt that by becoming self-directed, critical, reflective practitioners, they were better able to deliver evidence-based practice/care. Self reports of practice change attributed to engaging in EBL were provided, with the patient identified as the principal beneficiary, echoing the espoused aims of continuing professional development. EBL was credited with being a motivating, energizing and enjoyable way of learning but participants were critical of the lack of preparedness of both the students and facilitators. Consideration needs to given as to whether EBL is viewed as a philosophy of learning or as a facilitative strategy used alongside other educational methods.


Infiltration of peritumoural but tumour-free parenchyma with IgG4-positive plasma cells in hilar cholangiocarcinoma and pancreatic adenocarcinoma.
Recently, new guidelines for diagnosing IgG4-associated cholangitis have been published devaluing the diagnostic significance of IgG4-positive plasma cells and steroid trials. We sought to evaluate the utility of IgG4-positive plasma cells in discriminating IgG4-associated cholangitis from hilar cholangiocarcinoma and autoimmune pancreatitis from pancreatic adenocarcinoma under conditions when malignancy is likely to be missed. Resection specimens obtained from patients with hilar cholangiocarcinoma, pancreatic adenocarcinoma or hepatocellular carcinoma were re-evaluated for IgG4-positivity. Histological analysis focussed on peritumoural but tumour-free sections. Perioperative biochemical and clinical data were reviewed. Nineteen patients with hilar cholangiocarcinoma and 29 patients with pancreatic adenocarcinoma were eligible for histological re-evaluation. Six of 19 (32%) patients with hilar cholangiocarcinoma and 5 of 29 (17%) patients with pancreatic adenocarcinoma were IgG4-positive (≥20 IgG4-positive plasma cells per high power field). Patients with IgG4-positive hilar cholangiocarcinoma showed significantly higher levels of serum total bilirubin (3.6mg/dl vs. 1.8mg/dl; P<0.05) and serum alanine-aminotransferase (median 343U/l vs. 63U/l, P<0.05) compared to IgG4-negative patients with hilar cholangiocarcinoma. IgG4-positive plasma cells are of limited utility especially in distinguishing hilar cholangiocarcinoma from IgG4-associated cholangitis even when combined with clinical parameters and may be misleading under conditions when malignancy is missed.


Associations of sire estimated breeding values and objective meat quality measurements with sensory scores in Australian lamb.
The impact of selecting for lean meat yield using breeding values for increased eye muscle depth (PEMD) and decreased fat depth (PFAT) on the consumer acceptance of lamb meat was evaluated. Consumer sensory scores (tenderness, juiciness, flavour, odour, overall liking) were obtained for the longissimus lumborum (loin) and semimembranosus (topside) muscles of 1471 lambs. On average loin samples were more acceptable for consumers. Sensory scores increased with higher IMF levels, with lower shear force levels, and when animals were younger and less muscular. Increasing PEMD decreased tenderness, overall liking and flavour scores in both muscles, and decreasing PFAT reduced tenderness within the loin samples only. This negative impact of PEMD and PFAT is not solely driven through the phenotypic impact of IMF and shear force on sensory scores. Our results confirm the growing concerns that selecting for lean meat yield would reduce consumer eating quality, and highlight that careful monitoring of selection programmes is needed to maintain lamb eating quality.


Utility of biomarkers and temporal artery biopsy length for investigating giant cell arteritis in Western Australia.
To explore demographic characteristics, biopsy length, and blood biomarker performance in an Australian cohort of patients who have undergone temporal artery biopsy (TAB) for giant cell arteritis (GCA). We extracted data on biopsies performed for GCA between January 2016 and December 2020 at public hospitals in Perth. Sensitivity, specificity, and area under the curve (AUC) were calculated for blood results. We evaluated the proportion of biopsies with post-fixation length less than 15 mm and explored several length associations. We retrospectively reviewed biopsies of 360 patients (65.8% female, mean age 72.1 years). Biopsy-positive patients were older (6.0 years, P < 0.01), and had higher C-reactive protein (CRP) (44.5 mg/L, P < 0.01), erythrocyte sedimentation rate (ESR) (18.9 mm/h, P < 0.01), and platelets (86.8 × 103 /μL, P < 0.01) compared with biopsy-negative patients. CRP and platelets had the highest AUCs at 0.76 and 0.71, respectively. Sensitivities for CRP and ESR were 96.2% and 91.5%, respectively. Specificities were comparatively low at 41.3% for CRP and 37.4% for ESR. The proportion of biopsies with sub-optimal length was 55.9% and this varied significantly by site (P < 0.01). Smaller sites performed worse, with a sub-optimal biopsy rate of 87% amongst the three smallest sites. ESR and CRP are helpful preliminary investigations, especially in identifying low-risk patients, but their specificity is limited. Smaller centers had a higher proportion of biopsies with sub-optimal length. Considering the importance of biopsy length for TAB diagnostic value, reviewing biopsy data may assist services in developing improvement strategies.


Flux-weighted average cross sections of medical isotopes in the 127I(γ,xn) reactions with the bremsstrahlung end-point energies of 50 and 70MeV.
The flux-weighted average cross sections of 127I(γ,xn)126,124,123I reactions were experimentally determined with the bremsstrahlung end-point energies of 50 and 70 MeV by activation and off-line γ-ray spectrometric technique, using the 100 MeV electron linac at the Pohang Accelerator Laboratory, Korea. The 127I(γ,xn)126-121I reaction cross sections as a function of photon energy were theoretically calculated using the TALYS 1.8 code. The flux-weighted average cross sections of 127I(γ, xn)126,124,123I reactions as a function of bremsstrahlung end-point energies were also obtained from the literature and TALYS data based on mono-energetic photons and are found to be in close agreement with the present data. The experimental and theoretical 127I(γ, xn)126-121I reaction cross-sections increase with bremsstrahlung energy, which indicates the role of excitation energy. After a certain energy, the individual 127I(γ, xn)126-121I reaction cross sections decrease with increase of bremsstrahlung energy due to opening of other reactions, which indicates sharing of energy in different reaction channels. The radioactive iodine isotopes production cross-sections are important for the useful medical purpose.


Mutagenicity and cytotoxicity of N-methyl-2-pyrrolidinone and 4-(methylamino)butanoic acid in the Salmonella/microsome assay.
The industrial solvent N-methyl-2-pyrrolidinone (NMP) and its hydrolysis product, 4-(methylamino)butanoic acid (N-MeGABA), were examined for mutagenicity and cytotoxicity in the Ames Salmonella/microsome assay. In order to detect a broad range of possible mutagenic endpoints, the following strains were used in the assay: base-pair substitution strains TA100, TA102 and TA104; frameshift strains TA97 and TA98; and repair proficient strains TA2638, UTH8413 and UTH8414. In the standard plate incorporation assay, six log-linear doses of each compound were tested; doses ranged from 0.01 to 1000 mumol/plate for NMP, and 0.01 to 316 mumol/plate for N-MeGABA. Neither compound was detectably mutagenic when tested in the presence and absence of metabolic activation by Aroclor-induced rat liver S9. NMP did show significant responses with strains TA102 and TA104 that were less than two-fold over background, but no clear dose-response relationships were evident. A preincubation modification of the assay was also performed, using strains TA98 and TA104. Mutagenic activity was not observed for NMP, while N-MeGABA showed significant responses with TA104 but dose-related mutagenicity was not established. Preincubation testing revealed both NMP and N-MeGABA to be cytotoxic to the test population of Salmonella at the highest treatment doses.


Molecular biology of transitional cell carcinoma.
Transitional cell carcinoma (TCC) is the fifth most common solid malignancy in the USA. Radical cystectomy will cure a substantial fraction of patients with minimally invasive TCC, but approximately 50% of patients with muscle-invasive or extravesical disease treated by radical cystectomy alone die of metastatic TCC. Transitional cell carcinoma have a diverse collection of biologic and functional characteristics. This is reflected in a differing clinical course. The limited value of established prognosticators, make the analysis of new molecular parameters of interest in predicting the prognosis of bladder cancer patients; in particular, high-risk patient groups that are at risk of progression and recurrence. Over the past decade, there had been major progress in the elucidation of the molecular genetic changes leading to the development of TCC. This review will highlight these important advances and emphasize the ways in which molecular biology is likely to affect the development of future therapies.


Mechanism of mRNA-STAR domain interaction: Molecular dynamics simulations of Mammalian Quaking STAR protein.
STAR proteins are evolutionary conserved mRNA-binding proteins that post-transcriptionally regulate gene expression at all stages of RNA metabolism. These proteins possess conserved STAR domain that recognizes identical RNA regulatory elements as YUAAY. Recently reported crystal structures show that STAR domain is composed of N-terminal QUA1, K-homology domain (KH) and C-terminal QUA2, and mRNA binding is mediated by KH-QUA2 domain. Here, we present simulation studies done to investigate binding of mRNA to STAR protein, mammalian Quaking protein (QKI). We carried out conventional MD simulations of STAR domain in presence and absence of mRNA, and studied the impact of mRNA on the stability, dynamics and underlying allosteric mechanism of STAR domain. Our unbiased simulations results show that presence of mRNA stabilizes the overall STAR domain by reducing the structural deviations, correlating the 'within-domain' motions, and maintaining the native contacts information. Absence of mRNA not only influenced the essential modes of motion of STAR domain, but also affected the connectivity of networks within STAR domain. We further explored the dissociation of mRNA from STAR domain using umbrella sampling simulations, and the results suggest that mRNA binding to STAR domain occurs in multi-step: first conformational selection of mRNA backbone conformations, followed by induced fit mechanism as nucleobases interact with STAR domain.


Physical fitness and frailty status of frail older adults in long-term care facilities after acupunch exercises: A cluster-randomized controlled trial.
Frailty is a complex geriatric syndrome and serves as an indicator for functional degradation in older adults. Regular exercise intervention could reduce the level of frailty and improve general physical fitness. The aim of this study was to test the effects of the Vitality Acupunch (VA) exercise on the promotion of physical fitness and the improvement of frailty status among frail older adults in long-term care facilities. This study was a cluster-randomized controlled trial adopted a pretest-posttest design. Using convenience sampling, 81 frail adults older than 65 years of age from 10 long-term care facilities participated in this study. The older adults were cluster-randomized by facility into an intervention group (5 long-term care facilities, n = 40) and a control group (5 long-term care facilities, n = 41). The intervention group engaged in the VA exercise 3 times a week, each lasting 40 min, for 24 weeks. The control group maintained regular activities of daily living. The outcome measures for physical fitness were assessed before study began (pretest), at the 12th week (posttest 1), and at the 24th week (posttest 2) in the study. After a 24-week intervention, the frail older adults who engaged in the VA exercise program showed significant improvements in handgrip strength, upper-limb muscle endurance, lung function, shoulder flexibility, forward flexion, shoulder joint flexion, and shoulder joint abduction (all p < 0.05) but not in lower-limb muscle endurance (p = 0.502) compared against their pretest data. The intervention group had significantly better physical fitness and positive changes in frailty status than the control group (all p < 0.001), except for the lower-limb muscle endurance (p = 0.557). Regular engagement in the VA exercise program for 24 weeks significantly improved the physical fitness and frailty status of frail older adults in long-term care facilities.


Polypurine (A)-rich sequences promote cross-kingdom conservation of internal ribosome entry.
The internal ribosome entry sites (IRES), IRES(CP,148)(CR) and IRES(MP,75)(CR), precede the coat protein (CP) and movement protein (MP) genes of crucifer-infecting tobamovirus (crTMV), respectively. In the present work, we analyzed the activity of these elements in transgenic plants and other organisms. Comparison of the relative activities of the crTMV IRES elements and the IRES from an animal virus--encephalomyocarditis virus--in plant, yeast, and HeLa cells identified the 148-nt IRES(CP,148)(CR) as the strongest element that also displayed IRES activity across all kingdoms. Deletion analysis suggested that the polypurine (A)-rich sequences (PARSs) contained in IRES(CP,148)(CR) are responsible for these features. On the basis of those findings, we designed artificial PARS-containing elements and showed that they, too, promote internal translation from dicistronic transcripts in vitro, in tobacco protoplasts and in HeLa cells. The maximum IRES activity was obtained from multiple copies of either (A)(4)G(A)(2)(G)(2) or G(A)(2-5) as contained in IRES(CP,148)(CR). Remarkably, even homopolymeric poly(A) was moderately active, whereas a poly(G) homopolymer was not active. Furthermore, a database search for existing PARS sequences in 5'-untranslated regions (5'UTR) of genes in tobacco genome allowed the easy identification of a number of IRES candidates, in particular in the 5'UTR of the gene encoding Nicotiana tabacum heat-shock factor 1 (NtHSF1). Consistent with our prediction, the 5'UTR of NtHSF1 turned out to be an IRES element active in vitro, in plant protoplasts and HeLa cells. We predict that PARS elements, when found in other mRNAs, will show a similar activity.


Cumulative Febrile, Respiratory, and Gastrointestinal Illness Among Infants in Rural Guatemala and Association With Neurodevelopmental and Growth Outcomes.
Infectious disease exposures in early life are increasingly recognized as a risk factor for poor subsequent growth and neurodevelopment. We aimed to evaluate the association between cumulative illness with neurodevelopment and growth outcomes in a birth cohort of Guatemalan infants. From June 2017 to July 2018, infants 0-3 months of age living in a resource-limited region of rural southwest Guatemala were enrolled and underwent weekly at-home surveillance for caregiver-reported cough, fever, and vomiting/diarrhea. They also underwent anthropometric assessments and neurodevelopmental testing with the Mullen Scales of Early Learning (MSEL) at enrollment, 6 months, and 1 year. Of 499 enrolled infants, 430 (86.2%) completed all study procedures and were included in the analysis. At 12-15 months of age, 140 (32.6%) infants had stunting (length-for-age Z [LAZ] score < -2 SD) and 72 (16.7%) had microcephaly (occipital-frontal circumference [OFC] < -2 SD). In multivariable analysis, greater cumulative instances of reported cough illness (beta = -0.08/illness-week, P = 0.06) and febrile illness (beta = -0.36/illness-week, P < 0.001) were marginally or significantly associated with lower MSEL Early Learning Composite (ELC) Score at 12-15 months, respectively; there was no association with any illness (cough, fever, and/or vomiting/diarrhea; P = 0.27) or with cumulative instances of diarrheal/vomiting illness alone ( P = 0.66). No association was shown between cumulative instances of illness and stunting or microcephaly at 12-15 months. These findings highlight the negative cumulative consequences of frequent febrile and respiratory illness on neurodevelopment during infancy. Future studies should explore pathogen-specific illnesses, host response associated with these syndromic illnesses, and their association with neurodevelopment.


Two stress sensor proteins for the expression of sigmaE regulon: DegS and RseB.
In E. coli, sigmaE-dependent transcription is controlled by regulated-proteolysis of RseA. RseA, which holds sigmaE as an anti-sigma factor, is sequentially digested by DegS, RseP and cytoplasmic proteases to liberate sigmaE in response to dysfunction in outer-membrane biogenesis. Additionally, the sequential proteolysis is regulated by RseB binding to RseA (Fig. 1A). Direct interaction between RseA and RseB inhibits RseA-cleavage by DegS. Both proteolytic activation of DegS and binding disruption of RseB are thus required to initiate sigmaE-stress response. For the induction of sigmaEstress response, DegS and RseB recognize the states of OMP and LPS for outer-membrane biogenesis. DegS is activated by binding of unfolded OMPs and RseB binding to RseA is antagonized by LPS accumulated in periplasm. In this regard, DegS and RseB are proposed to be stress sensor proteins for sigmaE signal transduction. Interestingly, biogenesis of OMP and LPS appears to cross-talk with each other, indicating that dysfunction of either OMP or LPS can initiate RseA proteolysis. This review aims to briefly introduce two stress sensor proteins, DegS and RseB, which regulate sigmaEdependent transcription.


Temporomandibular joint arthroscopy in advanced stages of internal derangement: a retrospective cohort study on the influence of age.
The aim of this investigation was to evaluate the outcomes of patients with advanced internal derangement of the temporomandibular joint who underwent operative arthroscopy, according to age stratified into two groups: <45 years and ≥45 years. The study included a series of 194 patients. Outcome variables were pain intensity and mandibular mobility. Additionally, the difference in arthroscopic findings in these age groups was studied. The data analysis included the paired t-test, χ2 test, and two-way analysis of variance, with a P-value <0.05 indicating statistical significance. A significant reduction in pain and an improvement in maximum inter-incisal opening (MIO) was observed in both groups starting at 1 month of follow-up (P < 0.01). However, the results for MIO were worse in the ≥45 years group (P=0.036) at 12- and 18-months follow-up. Regarding arthroscopic findings, the study showed a higher prevalence of severe chondromalacia in the ≥45 years group (P = 0.031) and disc displacement without reduction in the <45 years group (P = 0.020). Analysis of variance showed a greater pain reduction if no obliteration of the articular space was observed (P = 0.039). In young and older patients, operative arthroscopy can be useful for short-term treatment in advanced stages of internal derangement of the temporomandibular joint.


Synthesis, binding and intracellular retention of methotrexate polyglutamates by cultured human breast cancer cells.
Synthesis, binding, and intracellular retention of methotrexate polyglutamates by cultured human breast cancer cells were investigated by gel filtration and high-pressure liquid chromatography to separate methotrexate from its metabolites. MCF-7, ZR-75-1, and MDA-231 human breast cancer cells were found to readily convert methotrexate to higher polyglutamates during a 24-hr incubation period, although at differing rates. Examination of that portion of intracellular methotrexate specifically bound to dihydrofolate reductase revealed that, with prolonged incubation, methotrexate polyglutamates become the predominant drug form bound to the enzyme. Similarly, methotrexate polyglutamates accumulated free in the cytosol and when cells were suspended in drug-free medium, were retained intracellularly both bound to dihydrofolate reductase and in the unbound fraction, indicating their slow passage through the cell membrane. Studies of methotrexate polyglutamate binding to purified bacterial dihydrofolate reductase revealed high affinity binding for compounds with up to 6 additional glutamyl residues. These studies demonstrate that methotrexate polyglutamates are readily formed in human breast cancer cells, bind intracellularly to dihydrofolate reductase, and are selectively retained both bound to the enzyme and free in the cell cytosol.


Results from the european survey on preoperative management and optimization protocols for PeriHilar cholangiocarcinoma.
Major surgery, along with preoperative cholestasis-related complications, are responsible for the increased risk of morbidity and mortality in perihilar cholangiocarcinoma (pCCA). The aim of the present survey is to provide a snapshot of current preoperative management and optimization strategies in Europe. 61 European centers, experienced in hepato-biliary surgery completed a 59-questions survey regarding pCCA preoperative management. Centers were stratified according to surgical caseload (<5 and ≥ 5 cases/year) and preoperative management protocols' application. The overall case volume consisted of 6333 patients. Multidisciplinary discussion was routinely performed in 91.8% of centers. Most respondents (96.7%) recognized the importance of a well-structured preoperative protocol. The preferred method for biliary drainage was percutaneous transhepatic biliary drainage (60.7%) while portal vein embolization was the preferred technique for liver hypertrophy (90.2%). Differences in preoperative pathologic confirmation of malignancy (35.8% vs 28.7%; p < 0.001), number of mismanaged referred patients (88.2% vs 50.8%; p < 0.001), biliary drainage (65.1% vs 55.6%; p = 0.015) and liver function evaluation (37.2% vs 5.6%; p = 0.001) were found between centers according to groups' stratification. The importance of a correct preoperative management is recognized. Nevertheless, the current lack of guidelines leads to wide heterogeneity of behaviors among centers. This survey can provide recommendations to improve pCCA perioperative outcomes.


Does load influence shoulder muscle recruitment patterns during scapular plane abduction?
Load is used to increasingly challenge muscle function and has been shown to increase muscle activity levels with no change in activation patterns during shoulder flexion, extension, adduction and rotation. However, the effect of load during shoulder abduction, a movement commonly used in assessment of shoulder dysfunction and to improve shoulder function, has not been comprehensively examined. Therefore, the purpose of this study was to determine if load influences shoulder muscle activation patterns and levels during scapular plane abduction in normal subjects. Experimental study. Fourteen volunteers performed shoulder abduction in the scapular plane at 25%, 50% and 75% of maximum load. Eight shoulder muscles were investigated using a combination of indwelling and surface electromyographic recordings: middle deltoid, infraspinatus, subscapularis, supraspinatus, serratus anterior, upper and lower trapezius and rhomboid major. All muscles tested showed increasing average muscle activation levels with increasing load and strong correlations in the activation patterns between loads. Increasing shoulder abduction load not only increases activity in middle deltoid but also in the rotator cuff (infraspinatus, subscapularis, supraspinatus) and axioscapular (serratus anterior, upper and lower trapezius, rhomboid major) muscles. The functional stabilising role of both the rotator cuff and axioscapular muscles is considered an important contribution to the increased activation levels in these muscle groups as they function to counterbalance potential translation forces produced by other muscles during shoulder abduction. The activation patterns of all shoulder muscle groups during abduction can be trained at low load and progressively challenged with increasing load.


Mathematical modeling analysis of hepatic uric acid disposition using human sandwich-cultured hepatocytes.
Uric acid is biosynthesized from purine by xanthine oxidase (XO) mainly in the liver and is excreted into urine and feces. Although several transporters responsible for renal and intestinal handling of uric acid have been reported, information on hepatic transporters is limited. In the present study, we studied quantitative contribution of transporters for hepatic handling of uric acid by mathematical modeling analysis in human sandwich-cultured hepatocytes (hSCH). Stable isotope-labeled hypoxanthine, hypoxanthine-13C2,15N (HX), was incubated with hSCH and formed 13C2,15N-labeled xanthine (XA) and uric acid (UA) were measured by LC-MS/MS time dependently. Rate constants for metabolism and efflux and uptake transport across sinusoidal and bile canalicular membranes of HX, XA and UA were estimated in the presence of inhibitors of XO and uric acid transporters. An XO inhibitor allopurinol significantly decreased metabolisms of HX and XA. Efflux into bile canalicular lumen was negligible and sinusoidal efflux was considered main efflux pathway of formed UA. Transporter inhibition study highlighted that GLUT9 strongly and MRP4 intermediately contribute to the sinusoidal efflux of UA with minor contribution of NPT1/4. Modeling analysis developed in the present study should be useful for quantitative prediction of uric acid disposition in liver.


Dual effect of bombesin and gastrin releasing peptide on gastric emptying in conscious cats.
The effect of bombesin (BBS) and gastrin releasing peptide (GRP) on gastric emptying was studied in conscious cats. This effect was measured simultaneously with antral motility. Acid and pepsin secretions as well as blood hormonal peptide release were additionally measured. A dual effect was observed. First, BBS and GRP slowed gastric emptying of liquids, while antral motility was decreased, then after 60 minutes of continuous intravenous infusion, antral motility returned to basal values and gastric emptying effect reversed. The mechanism of this peculiar action is independent of gastrin, pancreatic polypeptide, somatostatin and motilin release and most probably connected with a cholinergic stimulation induced by the peptides, the late predominance of which counterbalances the inhibitory effect of bombesin-like peptides on antral motility.


[New methods of radiologic diagnosis: ultrasonography and tomoradiometry (computer assisted tomography)].
The evolution of new and more accurate methods of examination is a welcome complement to current diagnostic resources. However, it is essential to use them intelligently to avoid a further undesirable rise in the cost of health. Now more than ever, the programme of radiologic examinations should be established by common consent between the practising physician and the consultant radiologist.


Deoxyribonucleic acid base composition and taxonomy in the genus Geotrichum Link.
The molar percentage of guanine + cytosine (% GC) in the DNA from 25 yeast-like fungi related to the genus Geotrichum has been measured. This criterion together with the biochemical characteristics allow the division of the species into 3 groups: one group resembling G. candidum (% GC: 31.5--42) and containing 8 imperfect and 6 perfect forms. In this group only G. capitatum has a lower % GC (31.5). A second group of 6 species resembling the genus Trichosporon (57--60%) and a third intermediate category of 4 species (42--53.5%) were observed. The GC-values correlate well with biochemical characters, e.g. the presence of urease, the number of organic substrates assimilated, and also with the presence of characters typical of the Ascomycetes or the Basidiomycetes.


Quantitative MRI in leukodystrophies.
Leukodystrophies constitute a large and heterogeneous group of genetic diseases primarily affecting the white matter of the central nervous system. Different disorders target different white matter structural components. Leukodystrophies are most often progressive and fatal. In recent years, novel therapies are emerging and for an increasing number of leukodystrophies trials are being developed. Objective and quantitative metrics are needed to serve as outcome measures in trials. Quantitative MRI yields information on microstructural properties, such as myelin or axonal content and condition, and on the chemical composition of white matter, in a noninvasive fashion. By providing information on white matter microstructural involvement, quantitative MRI may contribute to the evaluation and monitoring of leukodystrophies. Many distinct MR techniques are available at different stages of development. While some are already clinically applicable, others are less far developed and have only or mainly been applied in healthy subjects. In this review, we explore the background, current status, potential and challenges of available quantitative MR techniques in the context of leukodystrophies.