[Opioid-sparing effect of ketamine during tonsillectomy in children].
In the adult population, Ketamine is currently used as an antihyperalgesic and opioid-sparing agent during the perioperative period. However, for doses of ketamine up to 0.5mg/kg, these effects have not been found in pediatric population. The aim of the present study was to evaluate the efficacy of a preoperative bolus of 1mg/kg of ketamine on postoperative pain intensity and morphine consumption in children undergoing tonsillectomy. We have undertaken a retrospective comparison of 60 consecutive children operated for tonsillectomy in our institution before (first 30 patients) and after (last 30 patients) the introduction of a preoperative bolus of 1mg/kg of ketamine. Data collected were: age, ASA score, dose of intraoperative sufentanil, OPS score during PACU stay and the first postoperative day, morphine consumption during PACU stay and the first postoperative day, psychodysleptic manifestations, pain at first solid oral intake and postoperative respiratory complications or haemorrhage. No difference was found between the two groups in terms of demographic characteristics. Perioperative doses of sufentanil, postoperative opioid consumption or pain score in PACU or during 24hours were similar between the two groups. The two groups did not differ in terms of pain at first oral intake, or other adverse effects. These results suggest that 1mg/kg of ketamine administered right after anaesthesia induction in children undergoing tonsillectomy did not result in an opioid sparing effect.


An intramolecular disulphide bond reduces the efficacy of a lipoprotein plasma membrane sorting signal.
To study lipoprotein sorting in Escherichia coli, we devised a novel screen in which sensitivity or resistance to bacteriophage T5 and colicin M reflects the membrane localization of the bacteriophage T5-encoded lipoprotein Llp, which inactivates the outer membrane (OM) T5 receptor (FhuA). When processed by lipoprotein signal peptidase, Llp has a serine at position +2, immediately after the fatty acylated N-terminal cysteine. As predicted by the '+2 lipoprotein sorting rule' that determines the localization of lipoproteins in the cell envelope, Llp is located in the OM. However, contrary to expectations, when serine +2 was replaced by aspartate, the canonical plasma membrane lipoprotein retention signal, Llp was still > or =40% targeted to the OM and protected cells against colicin M and phage T5. OM association of this Llp derivative was abolished when a peptide spacer was inserted between the aspartate and the rest of Llp or when the formation of an intramolecular disulphide bond in Llp was prevented by substituting one or other of the cysteines involved. Furthermore, analysis of a MalE-Llp hybrid protein with or without a lipid moiety demonstrated that fatty acylation of Llp is essential for its OM association and for protection against colicin M and bacteriophage T5. These data suggest (i) that phage-encoded Llp uses the endogenous E. coli Lol pathway for lipoprotein sorting to the OM and (ii) that the conformation of a lipoprotein can affect its sorting within the cell envelope.


When noisy neighbors are a blessing: analysis of gene expression noise identifies coregulated genes.
In this issue of Molecular Cell, Stewart-Ornstein et al. (2012) use systematic pair-wise correlation analysis of expression noise in a large number of yeast genes to identify clusters of functionally related genes and signaling pathways responsible for elevated noise.


Equity-relevant sociodemographic variable collection in emergency medicine: A systematic review, qualitative evidence synthesis, and recommendations for practice.
The objective was to conduct a systematic review and qualitative evidence synthesis (QES) to identify best practices, benefits, harms, facilitators, and barriers to the routine collection of sociodemographic variables in emergency departments (EDs). This work is a systematic review and QES. We conducted a comprehensive search of Medline (Ovid), CINAHL (Ebsco), Cochrane Central (OVID), EMBASE (Ovid), and the multidisciplinary Web of Science Core database using peer-reviewed search strategies, complemented by a gray literature search. We included citations containing perspectives on routine sociodemographic variable collection in EDs and recommendations on definitions or processes of collection or benefits, harms, facilitators, or barriers related to the routine collection of sociodemographic variables in EDs. We conducted this systematic review and QES adhering to the Joanna Briggs Institute guidelines. Two reviewers independently selected included studies and extracted data. We conducted a best-fit framework synthesis and paired inductive thematic analysis of the included studies. We generated recommendations based on the QES. We included 21 unique reports that enrolled 10,454 patients or respondents in our systematic review and QES. Publication dates of included studies ranged from 2011 to 2021. Included citations were published in Australia, Canada, and the United States. We synthesized 11 benefits, 14 potential harms, 15 barriers, and 19 facilitators and identified 14 best practice recommendations from included citations. Health systems should routinely collect sociodemographic variables in EDs guided by recommendations that minimize harms and maximize benefits and consider relevant barriers and facilitators. Our recommendations can serve as a guide for the equity-focused reformation of emergency medicine health information systems.


Platinum resistance after neoadjuvant chemotherapy compared to primary surgery in patients with advanced epithelial ovarian carcinoma.
Primary debulking surgery (PDS) has historically been the standard treatment for advanced ovarian cancer. Recent data appear to support a paradigm shift toward neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) for a subset of women with advanced ovarian cancer. It remains unresolved whether NACT-IDS increases the risk of platinum resistance. We compared response to chemotherapy in patients that received NACT-IDS vs. PDS. From our Cancer Registry database we identified patients with stages IIIC and IV epithelial ovarian cancer who underwent treatment from January, 2005 to December, 2010. Standard univariate analyses were performed, as were multivariable analysis with logistic regression. The Kaplan-Meier method was used to generate survival data. The study population consisted of 425 patients, 95 (22.3%) underwent NACT-IDS and 330 (77.6%) PDS. After the initial platinum-based chemotherapy, 42 (44.2%) women in the NACT-IDS group were considered to have platinum resistant disease, compared to 103 (31.2%) in the PDS group (P=0.01). When multivariate logistic regression was used to control for factors independently associated with platinum resistance, NACT-IDS was no longer associated with an initial increased risk. However, in women that had a recurrence and were retreated with platinum-based chemotherapy, 32 (88.8%) in the NACT-IDS group had developed a recurrence within six months and were considered platinum resistant, compared to 62 (55.3%) in the PDS (P<0.001). In women with EOC that have a recurrence and are treated again with platinum-based chemotherapy, NACT-IDS appears to increase the risk of platinum resistance.


Regulation of circuit organization and function through inhibitory synaptic plasticity.
Diverse inhibitory neurons in the mammalian brain shape circuit connectivity and dynamics through mechanisms of synaptic plasticity. Inhibitory plasticity can establish excitation/inhibition (E/I) balance, control neuronal firing, and affect local calcium concentration, hence regulating neuronal activity at the network, single neuron, and dendritic level. Computational models can synthesize multiple experimental results and provide insight into how inhibitory plasticity controls circuit dynamics and sculpts connectivity by identifying phenomenological learning rules amenable to mathematical analysis. We highlight recent studies on the role of inhibitory plasticity in modulating excitatory plasticity, forming structured networks underlying memory formation and recall, and implementing adaptive phenomena and novelty detection. We conclude with experimental and modeling progress on the role of interneuron-specific plasticity in circuit computation and context-dependent learning.


Landscape epidemiology in urban environments: The example of rodent-borne Trypanosoma in Niamey, Niger.
Trypanosomes are protozoan parasites found worldwide, infecting humans and animals. In the past decade, the number of reports on atypical human cases due to Trypanosoma lewisi or T. lewisi-like has increased urging to investigate the multiple factors driving the disease dynamics, particularly in cities where rodents and humans co-exist at high densities. In the present survey, we used a species distribution model, Maxent, to assess the spatial pattern of Trypanosoma-positive rodents in the city of Niamey. The explanatory variables were landscape metrics describing urban landscape composition and physiognomy computed from 8 land-cover classes. We computed the metrics around each data location using a set of circular buffers of increasing radii (20m, 40m, 60m, 80m and 100m). For each spatial resolution, we determined the optimal combination of feature class and regularization multipliers by fitting Maxent with the full dataset. Since our dataset was small (114 occurrences) we expected an important uncertainty associated to data partitioning into calibration and evaluation datasets. We thus performed 350 independent model runs with a training dataset representing a random subset of 80% of the occurrences and the optimal Maxent parameters. Each model yielded a map of habitat suitability over Niamey, which was transformed into a binary map implementing a threshold maximizing the sensitivity and the specificity. The resulting binary maps were combined to display the proportion of models that indicated a good environmental suitability for Trypanosoma-positive rodents. Maxent performed better with landscape metrics derived from buffers of 80m. Habitat suitability for Trypanosoma-positive rodents exhibited large patches linked to urban features such as patch richness and the proportion of landscape covered by concrete or tarred areas. Such inferences could be helpful in assessing areas at risk, setting of monitoring programs, public and medical staff awareness or even vaccination campaigns.


A comparison of three assays used for the in vitro chemosensitivity testing of human tumours.
In this study cell lines have been used to determine the level of correlation between three assays which are in use for in vitro prediction of human tumour chemosensitivity. The methods which were compared included a clonogenic assay, a monolayer assay and a short-term biochemical assay. The results indicated that the monolayer and clonogenic assays were either directly comparable or could be made comparable by reducing the drug exposure time in the monolayer assay. The biochemical assay also gave comparable results for 3 of the 5 drugs tested. It was concluded that although the 3 assays did not produce identical dose-response curves, the assays were equally valid when used for predictive testing because selection of cut-off points which were based on retrospective correlations between in vitro sensitivity data and response data, as established by other authors, compensated for differences in sensitivity between the assays.


A Mouse Model of Hypospadias Induced by Estradiol Benzoate.
We wished to establish a mouse model of hypospadias using injections of estradiol benzoate for investigating the molecular mechanisms of hypospadias. Fifty timed pregnant mice were randomly divided into five study groups: A, B, C, D, and E. These groups were injected subcutaneously with estradiol benzoate mixed with sesame oil at, respectively, the doses of 0, 0.1, 0.5, 2.5, or 12.5 mg kg(-1) days(-1) from gestation day (GD) 12 to GD 16. The pups' mortality was recorded on the day of delivery. Urethras and positions of testes were examined on postnatal day 28. The numbers of live pups were significantly lower in the study groups D and E compared to study group A (p < 0.01). Hypospadias was seen in groups C (3.3 %; 1/30), D (18.2 %; 4/22), and E (21.4 %; 3/14), while cryptorchidism was observed in groups C (10 %; 3/30), D (31.8 %; 7/22), and E (57.1 %; 8/14) on postnatal day 28. The experimental model of hypospadias induced by estradiol benzoate in the group D (2.5 mg kg(-1) days(-1)) was more reliable considering high mortality of the study group E. The dose of estradiol benzoate used in the group D is suitable for establishing mouse model of hypospadias.


Interaction of visceral and somatic afferent systems in the cerebral cortex.
Using the method of evoked potentials on chloralose-anesthetized and suxamethonium-immobilized cats, a comparative study was made of the effects of interaction of somatic and visceral afferent systems in the second somatosensory area and in the parietal cortex of the brain. It was found that a common property of the interaction of the two afferent systems is an inhibition of the second response irrespective of which of the systems is activated first. Fairly prolonged inhibition was noted in the association region of the parietal cortex. Preliminary stimulation of visceral nerves caused less prolonged depression on subsequent stimulation of somatic nerves both in the second somatosensory and in the association regions of the cortex. It was demonstrated that the anatomic coincidence of visceral and somatic afferent projections both in the second somatosensory and in the parietal regions of the cortex is evidently responsible for the interaction of these afferent systems.


Silk-derived nitrogen-doped porous carbon electrodes with enhanced ionic conductivity for high-performance supercapacitors.
Supercapacitors are attracting extensive attention in energy storage fields thanks to their high safety, cost-effectiveness, and environmental friendliness. The carbon materials, especially for the porous carbon materials derived from renewable biomass materials, are important electrode materials with cost-effective feature for supercapacitors. However, the inferior ionic conductivity of biomass materials inhibits their electrochemical performance in energy storage devices. Herein, an immiscible liquid-mediated method is provided to improve the ionic conductivity of silk-derived nitrogen-doped porous carbon (NPC) electrodes. Natural Bombyx mori (silkworm) silk is used as a carbon source for the preparation of electrode of supercapacitor. Further introducing immiscible organic liquid into the NPCs promotes the ion transport in the inner pores of the electrodes. With the assistance of organic liquid, the supercapacitor presents a specific capacitance of 565.3 F g-1 at a current density of 1 A g-1. The supercapacitor shows the maximum specific energy and power density of 26.2 Wh kg-1 and 263.9 W kg-1, and holds a capacitance retention of approximately 93.3% after 10 000 cycles. This work provides a facile method for the rational design of carbon material derived from biomass material to fabricate electrode with high ionic conductivity, and the strategy will be extendable to other biomass materials for a wide range of applications.


Dual-Energy Computed Tomography for Fat Quantification in the Liver and Bone Marrow: A Literature Review.
With dual-energy computed tomography (DECT) it is possible to quantify certain elements and tissues by their specific attenuation, which is dependent on the X-ray spectrum. This systematic review provides an overview of the suitability of DECT for fat quantification in clinical diagnostics compared to established methods, such as histology, magnetic resonance imaging (MRI) and single-energy computed tomography (SECT). Following a systematic literature search, studies which validated DECT fat quantification by other modalities were included. The methodological heterogeneity of all included studies was processed. The study results are presented and discussed according to the target organ and specifically for each modality of comparison. Heterogeneity of the study methodology was high. The DECT data was generated by sequential CT scans, fast-kVp-switching DECT, or dual-source DECT. All included studies focused on the suitability of DECT for the diagnosis of hepatic steatosis and for the determination of the bone marrow fat percentage and the influence of bone marrow fat on the measurement of bone mineral density. Fat quantification in the liver and bone marrow by DECT showed valid results compared to histology, MRI chemical shift relaxometry, magnetic resonance spectroscopy, and SECT. For determination of hepatic steatosis in contrast-enhanced CT images, DECT was clearly superior to SECT. The measurement of bone marrow fat percentage via DECT enabled the bone mineral density quantification more reliably. DECT is an overall valid method for fat quantification in the liver and bone marrow. In contrast to SECT, it is especially advantageous to diagnose hepatic steatosis in contrast-enhanced CT examinations. In the bone marrow DECT fat quantification allows more valid quantification of bone mineral density than conventional methods. Complementary studies concerning DECT fat quantification by split-filter DECT or dual-layer spectral CT and further studies on other organ systems should be conducted. · DECT fat quantification in the liver and bone marrow is reliable.. · DECT is clearly superior to SECT in contrast-enhanced CT images.. · DECT bone marrow fat quantification enables better bone mineral density determination.. · Complementary studies with split-filter DECT or dual-layer spectral CT as well as studies in other organ systems are recommended.. · Molwitz I, Leiderer M, Özden C et al. Dual-Energy Computed Tomography for Fat Quantification in the Liver and Bone Marrow: A Literature Review. Fortschr Röntgenstr 2020; 192: 1137 - 1152.


Crystal structure of 1-methylimidazole 3-oxide monohydrate.
1-Methylimidazole 3-N-oxide (NMI-O) crystallizes as a monohydrate, C4H6N2O·H2O, in the monoclinic space group P21 with Z' = 2 (mol-ecules A and B). The imidazole rings display a planar geometry (r.m.s. deviations = 0.0008 and 0.0002 Å) and are linked in the crystal structure into infinite zigzag strands of ⋯NMI-O(A)⋯OH2⋯NMI-O(B)⋯OH2⋯ units by O-H⋯O hydrogen bonds. These chains propagate along the b-axis direction of the unit cell.


Modified RECIST to assess tumor response after transarterial chemoembolization of hepatocellular carcinoma: CT-pathologic correlation in 178 liver explants.
To retrospectively evaluate agreement between modified RECIST (mRECIST) assessed at Computed Tomography (CT) and pathology in a large series of patients with hepatocellular carcinoma (HCC) who were transplanted after transarterial chemoembolization (TACE). IRB approval was obtained. The study included 178 patients (M/F=155/23; mean age 55.8 ± 6.3 years) with HCC who were transplanted after TACE from January 1996 to December 2010 and with at least one CT examination before liver transplantation (LT). Two blinded independent readers retrospectively reviewed CT examinations, to assess tumor response to TACE according to mRECIST. Patients were classified in responders (complete and partial response) and non-responders (stable and progressive disease). On the explanted livers, percentage of tumor necrosis was classified as 100, >50 and <50%. The mean interval between latest CT and LT was 57.4 ± 39.8 days. At latest CT examination, the objective response rate was 78.1% (139/178), with 86 cases (48.3%) of complete response (CR). A good intra- (k=0.75 and 0.86) and inter-observer (k=0.81) agreement was obtained. On a per-patient basis, agreement between mRECIST and pathology was obtained in 120 patients (67.4%), with 19 cases (10.7%) of underestimation and 39 cases (21.9%) of overestimation of tumor response at CT. CT sensitivity and specificity in differentiating between responders and non-responders were 93 and 82.9%, respectively. Out of 302 nodules, sensitivity and specificity of CT in detecting complete necrosis were 87.5 and 68.9%, respectively. CT can overestimate tumor response after TACE. Nonetheless, mRECIST assessed at CT after TACE are reproducible and reliable in differentiating responders and non-responders.


Regulation and action of interferon-stimulated gene 15 in breast cancer cells.
Interferon-stimulated gene 15 (ISG15) is a critical ubiquitin-like protein that can be conjugated to proteins via the ISGylation system to modify them posttranslationally. Furthermore, ISG15 can be detected as non-conjugated or free, intracellularly and/or extracellularly. Both conjugated and free ISG15 participate in different cancer types, including breast cancer. Here, we highlighted the findings on ISG15 and protein ISGylation, and their implications in the field of breast cancer research. ISG15 emerges as a central element in mammary tumors and may become a crucial protein in the strategies for detection, prognosis, and therapy of breast cancer.


Farnesoid X receptor antagonizes Wnt/β-catenin signaling in colorectal tumorigenesis.
Farnesoid X receptor (FXR, encoded by NR1H4), a critical regulator of bile acid homeostasis, is widely implicated in human tumorigenesis. However, the functional role of FXR in colorectal cancer (CRC) and the precise molecular mechanism remain unclear. In this study, we demonstrated that FXR expression was downregulated in colon cancer tissues and decreased expression of FXR predicted a poor prognosis. Knockdown of FXR promoted colon cancer cell growth and invasion in vitro, and facilitated xenograft tumor formation and distant metastasis in vivo, whereas ectopic expression of FXR had the reserved change. Mechanistic studies indicated that FXR exerted its tumor suppressor functions by antagonizing Wnt/β-catenin signaling. Furthermore, we identified an FXR/β-catenin interaction in colon cancer cells. The FXR/β-catenin interaction impaired β-catenin/TCF4 complex formation. In addition, our study suggested a reciprocal relationship between FXR and β-catenin, since loss of β-catenin increased the transcriptional activation of SHP by FXR. Altogether, these data indicated that FXR functions a tumor-suppressor role in CRC by antagonizing Wnt/β-catenin signaling.


A four-step approach improves long-term functional outcomes in patients suffering from chronic ankle instability: a retrospective study with a follow-up of 7-16 years.
The aim of the present study was to assess the long-term outcomes of the treatment of chronic ankle instability (CAI) with a four-step protocol. Fifty-four patients with isolated anterior talo-fibular ligament (ATFL) lesion suffering from CAI who underwent surgical treatment between 2000 and 2009 were assessed. All the patients underwent a four-step protocol including synovectomy, debridement of ATFL lesion borders, capsular shrinkage, and 21-day immobilization and nonweightbearing. Median age at surgery was 31.6 years (18-48). Patients were examined preoperatively and at follow-up. Clinical assessment included the American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot scoring system, Karlsson-Peterson score, Tegner activity level, and objective examination comprehending range of motion (ROM) and manual laxity tests. AOFAS (preoperative, 64.8; postoperative, 92.4; p < 0.001) and Karlsson-Peterson score (preoperative, 62.5; postoperative, 88.8; p < 0.001) significantly improved after a median 11 years follow-up (7-16 years). Similarly median Tegner activity level significantly increased at follow-up compared to pre-operatory status (6.0 and 4.0 respectively, p < 0.001). Objective examination documented a statistically significant improvement in terms of ankle stability compared to pre-operative manual laxity tests, with negative anterior drawer test observed in 48 (88.9%) patients (p < 0.001). Sagittal ROM was full in 50 patients (92%). Nine patients had subsequent ankle sprains (15.6%), two patients required further surgery, while seven were treated conservatively. No major complications were reported. Satisfying subjective and objective clinical outcomes in selected patients with isolated ATFL lesion suffering from CAI were reported with a treatment protocol including arthroscopic synovectomy, debridement of ATFL remnants, capsular shrinkage, and immobilization. These findings are of clinical relevance because they provide a suitable minimally invasive method for the treatment of mild to moderate ankle instability. Level IV.


Novel oral absorption system containing polyamines and bile salts enhances drug transport via both transcellular and paracellular pathways across Caco-2 cell monolayers.
The combinatorial use of spermine (SPM), a typical polyamine, and sodium taurocholate (STC), a typical bile salt, was found to be a promising safe preparation for improving the oral absorption of poorly water-soluble and/or poorly absorbable drug in our previous studies utilizing rats and dogs. To clarify the mechanisms behind the synergistic enhancement effect of the polyamine and bile salt, the transport of rebamipide, which is classified into Biopharmaceutics Classification System Class IV, was investigated in Caco-2 cell monolayers. The synergistic enhancement of rebamipide transport by SPM and STC was certainly observed in Caco-2 cells as well, while the separate use of either SPM or STC did not significantly improve the transport of rebamipide. The combinatorial use of SPM and STC significantly decreased the transepithelial electrical resistance (TEER) in Caco-2 cell monolayers, suggesting that the opening of paracellular pathway. On the other hand, it was also confirmed that the decrease in TEER was transient and reversible after removal of SPM and STC and that cell viability was maintained. Voltage-clamp study clearly showed that their combinatorial use improved rebamipide transport via both paracellular and transcellular pathways, and that the contribution of transcellular route could be larger than paracellular route.


Wnt-cadherin connections in normal and neoplastic mammary epithelium.
Since the early recognition that the murine Wnt locus is frequently activated by insertion of the mouse mammary tumour virus, the Wnt pathway has become increasingly associated with both normal and abnormal mammary gland development. This link is further underlined by an emerging role for Wnt deregulation in human mammary neoplasia. The control of transcription through the Wnt signaling pathway is clearly a prime element of this role; however, components of the Wnt pathway possess many functions in addition to their signaling activity, interacting with multiple factors implicated in cellular control processes. Prominent amongst these are the cadherins, which have characterized roles in mediating cell-cell adhesion, and which have been independently implicated in mammary neoplasia. The close interplay between these 2 systems will be discussed in this review with reference both to the normal development of the mammary gland and to the onset of neoplasia in this tissue.


Imaging of gastrointestinal absorption and biodistribution of an orally administered probe using positron emission tomography in humans.
The purpose of this study was to establish a method for imaging the process of gastrointestinal (GI) absorption and subsequent biodistribution in the human body after oral drug administration, using positron emission tomography (PET) with 2-[(18)F]fluoro-2-deoxy-D-glucose ([(18)F]FDG). First, we developed a method to deliver the radiotracer safely into the stomach using soft gelatin capsules to avoid any significant exposure to the pharyngoesophageal region. Second, we performed pharmacokinetic (PK) analyses on time-radioactivity profiles in GI tissues and blood to calculate the gastric emptying and intestinal elimination rate constants and to estimate the fluid volume in the lumen of the small intestine from PET image analysis. This is the first study involving oral administration of a PET probe in humans, and the results demonstrate the high potential of PET technology to investigate the GI absorption and PK profiles of drugs in humans.


Critical organ dosimetry in permanent seed prostate brachytherapy: defining the organs at risk.
Although permanent seed prostate brachytherapy is associated with a low risk of serious morbidity, proctitis and prolonged irritative and obstructive urinary symptoms may occur. Data are accumulating to help establish thresholds or guidelines for minimizing toxicity, however, no uniform method of defining and calculating the dose to critical organs currently exists. We set out to examine the existing data and propose a uniform method of reporting such that results from different centers can more easily be compared. In preparation for a panel discussion at the American Brachytherapy Society 2004 Annual Meeting, four members with expertise in prostate dosimetry and critical organ assessment performed a literature search and, supplemented with their clinical experience, formulated a proposal for defining and reporting dose in a standardized fashion to the critical organs for permanent seed prostate brachytherapy. As previously recommended by the American Brachytherapy Society, postimplant dosimetry should be performed on all patients undergoing permanent prostate brachytherapy. The standard imaging for postplan assessment is the CT scan. The interval between seed implantation and postplan assessment should be reported. For rectal and urinary morbidities, the critical organs are considered to be the anterior rectum and the prostatic urethra, respectively. For erectile dysfunction, both the neurovascular bundle and penile bulb have been implicated. The rectum should be contoured on all CT scan slices where radioactive seeds are visible. Both the inner and outer walls should be contoured. The dose should be reported as RV100 and RV150, the volumes in cubic centimeters of the rectal wall receiving 100% and 150% of the prescribed dose, respectively. The urethra should be contoured as a structure on each slice where seeds can be seen. The urethra should be identified by either catheterization or fusion with transrectal ultrasound. The dose should be reported as UrD5 and UrD30, which are, respectively, the dose to 5% and 30% of the urethra in Gray. As well, a UrV150 should be reported, which is the volume in cubic centimeters of the urethra receiving 150% of the prescribed dose. No recommendations can be made at this time for reporting neurovascular bundle or penile bulb doses. It is essential that toxicity data be collected and reported in a uniform fashion. Thus, the critical organs for toxicity must be defined and the corresponding dosimetry reported in a standard fashion such that guidelines can be established in the future based on data from a cross-section of centers.


Hemorrhage induced by intrauterine devices: control by local proteinase inhibition.
The intrauterine application of proteinase inhibitors, tranexaminc acid and the pancreatic trypsin inhibitor (Trasylol), reduces or eliminates menorrhagia and intermenstrual bleeding (spotting) produced by an intrauterine device (IUD). A decrease in pain and vaginal (cervical) discharge is also frequently observed. A single application is usually sufficient, more than three never being required. The effect lasts for an average of three cycles. In addition to the clinical use of these agents for the treatment of uterine hemorrhage, the slow release of proteinase inhibitors from an IUD may well be useful in minimizing its side effects without interfering with its contraceptive activity.


Circadian rhythm and sudden death in heart failure: results from Prospective Randomized Amlodipine Survival Trial.
The purpose of this study was to address the timing of sudden death in advanced heart failure patients. Sudden death is a catastrophic event in cardiovascular disease. It has a circadian pattern prominent in the early AM, which has been thought to be due to a surge of sympathetic stimulation. We postulated that the distribution of events in advanced heart failure, with chronic sympathetic activation, would be more uniform implicating other potential mechanisms. We analyzed data from Prospective Randomized Amlodipine Survival Trial (PRAISE). Sudden deaths were analyzed by time of death in 4-h and 1-h blocks for uniformity of distribution in the entire cohort, and in the prespecified ischemic and nonischemic stratum. Further analyses were undertaken in the treatment groups of amlodipine and placebo, and among those receiving background therapy of aspirin and warfarin. Sudden deaths in the overall cohort showed a nonuniform distribution with a PM peak but not an AM peak. The ischemic stratum also showed a PM peak, but sudden deaths within the nonischemic stratum were uniformly distributed. Neither amlodipine treatment nor aspirin or warfarin use altered the distribution. Sudden death in advanced heart failure did not show an AM peak, suggesting that circadian sympathetic activation did not strongly influence these events. The PM peak noted is likely complex in origin and was not affected by antiischemic or antithrombotic medications.


Cultivating the uncultivated: a community genomics perspective.
Current isolation methods access only a small subset of the total microbial diversity. Although an isolate traditionally has been required for genomic characterization, the advent of sequencing of entire natural microbial communities enables culture-independent genomic analysis. Information about the genetic potential of uncultivated organisms can be used to predict the form of metabolic interdependencies and nutritional requirements. We believe that this could provide the information necessary to bypass bottlenecks that have inhibited cultivation of many microorganisms. However, it might not be practical or possible to isolate all of the vast number of microbial species and strains for laboratory-based characterization. Ultimately, cultivation-independent genomic and genomically enabled approaches could provide a way to directly analyze microbial activity in its geochemical and ecological context.


Radiographic determination of lordosis and kyphosis in normal and scoliotic children.
We conducted a radiographic retrospective study in children to determine spinal lordosis and kyphosis. A total of 218 lateral standing full-length radiographs were studied: 104 normal and 114 scoliotic patients. Normal X-ray films were defined as those obtained for suspected disorder (e.g., scoliosis) with no abnormalities detected by the radiologist or orthopedist. Thoracic kyphosis is defined as the angle between perpendiculars drawn from the inferior endplate of T5 and the superior endplate of T12. Lordosis is the angle between perpendiculars from the inferior endplate of L1 and the superior endplate of L5. The angle between the inferior endplate of L5 and the top of the sacrum is the L5-S1 angle. Statistical analysis was undertaken to compare lordosis and kyphosis radiographic measurements with age, sex, height, and weight employing the SAS package program. No significant relationships were noted between degree of scoliosis, age, sex, height or weight, and kyphosis, lordosis, or L5-S1 angle. Neither could correlations among the three radiographic measurements be made. Lordosis measured 40 degrees (range 31-49.5 degrees) in normal and 48.5 degrees (range 40-55 degrees) in scoliotic patients. Kyphosis measured 27 degrees (range 21-33 degrees) in normal and 28 degrees (range 16.5-36 degrees) in scoliotic patients.


Evaluation of a strict protocol approach in managing women with severe disease due to hypertension in pregnancy: a before and after study.
To evaluate whether the introduction of a strict protocol based on the systemic evaluation of critically ill pregnant women with complications of hypertension affected the outcome of those women. Indigent South African women managed in the tertiary hospitals of the Pretoria Academic Complex. Since 1997 a standard definition of women with severe acute maternal morbidity (SAMM), also referred to as a Nearmiss, has been used in the Pretoria Academic Complex. All cases of SAMM and maternal deaths (MD) were entered on the Maternal Morbidity and Mortality Audit System programme (MaMMAS). A comparison of outcome of severely ill women who had complications of hypertension in pregnancy was performed between 1997-1998 (original protocol) and 2002-2003 (strict protocol). Data include women referred from outside the Pretoria Academic Complex area to the tertiary hospitals. Between 1997-1998 there were 79 women with SAMM and 18 maternal deaths due to complications of hypertension, compared with 91 women with SAMM and 13 maternal deaths in 2002-2003. The mortality index (MI) declined from 18.6% to 12.5% (OR 0.62, 95% CI 0.27-1.45). Statistically significant fewer women had renal failure (RR 0.37, 95% CI 0.21-0.66) and cerebral complications (RR 0.52, 95% CI 0.34-0.81) during the second period, and liver dysfunction (RR 0.27 95% CI 0.06-1.25) tended to be lower. However, there tended to be an increase in the number of women, who had immune system failure (RR 4.2 95% CI 0.93-18.94) and respiratory failure (RR 1.42 95% CI 0.88-2.29) although it did not reach significance. Cardiac failure remained constant (RR 0.84 95% CI 0.54-1.30). The strict protocol approach based on the systemic evaluation of severely ill pregnant women with complications of hypertension and an intensive, regular feedback mechanism has been associated with a reduction in the number of patients with renal failure and cerebral compromise.


Exchange rate stability in the emerging economies: does renewable energy play a role-a panel data analysis.
Due to the high and rising rates of carbon emissions, the use of renewable energy sources has been encouraged to help achieve carbon neutrality goal. However, renewable energy sources are said to be expensive than fossil fuels. Major studies have been undertaken to ascertain the association between renewable energy and many economic indicators, such as gross domestic product, employment rate, and inflation rate. The current study is aimed at investigating whether renewable energy use helps stabilize the foreign exchange rate of emerging economies, which has not been widely examined in the past, hence the study originality. Stability in the foreign exchange rate of a nation is very crucial as this helps to stabilize the inflation rate. This study employs the fully modified ordinary least and dynamic ordinary least square methods to analyze panel data of emerging economies. The findings indicate that high real interest rate and gross domestic product causes appreciation in the currency exchange of a country, while high balance of payment, inflation rate and renewable energy consumption are found to cause currency depreciation. The Pedroni and Kao cointegration tests are employed and the results show that a long-run relationship exists among the variables examined. This research recommends balance of payments and inflation rate to be minimized if exchange rate stability is to be achieved, while gross domestic product and real interest rate should be increased.


A new approach of presenting reversible logic gate in nanoscale.
Conventional lithography-based VLSI design technology deployed to optimize low-powered-computing and higher scale integration of semiconductor components. However, this downscaling trend confronts serious challenges of tunneling and leakage current increment to the Complementary Metal-Oxide-Semiconductor (CMOS) technology on nanoscale regimes. To resolve the physical restriction of the CMOS, Quantum-dot Cellular Automata (QCA) technology dedicates for the nanoscale technology that embrace a new information transformation technique. However, QCA is limited to the design of the sequential and combinational circuits only. This paper presents some highly scalable features reversible logic gate for the QCA technology. In addition, proposed layout compared with CMOS technology, offer a better reduction in size up to 233 times.


Purification and initial characterization of a novel Porphyromonas gingivalis HmuY protein expressed in Escherichia coli and insect cells.
Porphyromonas gingivalis acquires iron and heme from the host environment using gingipains, lipoproteins, and outer-membrane receptors. Recently, we identified and characterized a heme receptor HmuR. The hmuR gene is localized in an operon together with a hmuY gene encoding a putative heme-binding protein. The aim of this study was to overexpress and perform a preliminary analysis of the recombinant HmuY protein. We constructed and examined several recombinant HmuY variants which were overexpressed and purified from Escherichia coli and insect cells. Recombinant HmuY protein was expressed in insect cells at levels similar to those in E. coli cells. This protein is predominantly present in a monomeric form but also dimerizes and several other oligomerization forms were found. Hemin and ATP binding to the purified HmuY showed that this protein may play a regulatory function in hemin utilization in P. gingivalis.


Efferents from the supracommissural ventral telencephalon in the hime salmon (landlocked red salmon, Oncorhynchus nerka): an anterograde degeneration study.
Efferents from the area ventralis telencephali pars supracommissuralis (Vs) of hime salmon (landlocked red salmon, Oncorhynchus nerka) were studied using anterograde degeneration methods. It was found that Vs sends intratelencephalic fibers bilaterally to the internal cell layer of the olfactory bulb and wide areas of telencephalon, while it sends extratelencephalic fibers bilaterally to habenulae, inferior lobes and midbrain tegmenti through medial and lateral forebrain bundles and lateral preoptic area. A possibility was pointed out that some of these extratelencephalic projections are involved in the pathway controlling the sexual behavior which are suggested from behavioral experiments.


Influence of chronic alcohol consumption on hepatic heme and porphyrin metabolism.
To study the effect of prolonged alcohol consumption on hepatic heme and porphyrin metabolism, female Wistar rats were fed for 60 days a nutritionally adequate liquid diet containing 36% of total calories as ethanol, whereas the control diet was isocaloric and contained no alcohol. Compared to pair-fed controls, the administration of the alcohol diet resulted in an increased hepatic activity of delta-aminolevulinic acid synthase by 223% (112.3 +/- 19.6 nmoles/hr/100 g b.wt. vs. 362.8 +/- 42.5; P less than 0.01), an enhanced urinary excretion of delta-aminolevulinic acid by 101% (64.8 +/- 11.8 nmoles/day vs. 130.8 +/- 22.4; P less than 0.05), and an augmented urinary output of total porphyrins by 142% (1.2 +/- 0.2 nmoles/day vs. 2.9 +/- 0.5; P less than 0.05). Concomitantly, the hepatic content of cytochrome P-450 was significantly enhanced and that of hepatic catalase activity marginally increased, whereas the hepatic iron content remained unaltered. In summary, the feeding of rats with a liquid alcohol diet for 60 days results in changes of hepatic heme and porphyrin metabolism which are associated and may be causally related with an induction of hepatic hemoproteins and subsequent derepression of hepatic delta-aminolevulinic acid synthase, whereas hepatic iron appears to play no pathogenic role.


Paroxysmal non-kinesigenic dyskinesia due to a PNKD recurrent mutation: report of two Southern European families.
Paroxysmal non-kinesigenic dyskinesia (PNKD) is an autosomal dominant disorder characterized by attacks of dystonic or choreathetotic movements precipitated by stress, fatigue, coffee, alcohol or menstruation. In this report we present two families with PNKD of Southern European origin carrying a PNKD recurrent mutation. Incomplete penetrance and intrafamilial variability was detected in both families. Treatment with valproic acid and levetiracetam provided favorable response.


Incidence of Bartholin duct cysts and abscesses in the Republic of Korea.
To estimate the incidence of Bartholin duct cysts and abscesses in the Republic of Korea during 2009. A national patient sample (n=599 186) was obtained from Korean Health Insurance Review and Assessment Service data and analyzed to estimate the incidence of Bartholin duct cysts and abscesses among Korean women in 2009. There were 587 Bartholin duct cysts and 757 Bartholin duct abscesses during 2009. The total incidence of Bartholin duct cysts and abscesses was 0.55 per 1000 person-years and 0.95 per 1000 person-years, respectively. In women aged 35-50 years, the incidence was 1.21 per 1000 person-years and 1.87 per 1000 person-years, respectively. In multivariate logistic regression analysis, the incidence of Bartholin duct cysts and abscesses was associated with age (P<0.01), but not with season or socioeconomic status, among women aged 15-50 years. The main operation performed was marsupialization (45.2%) for Bartholin duct cysts and incision (71.5%) for Bartholin duct abscesses. The incidence of Bartholin duct cysts and abscesses increased with age until menopause, decreasing thereafter.


Effectiveness of care models for chronic disease management: A scoping review of systematic reviews.
To conduct a scoping review of models of care for chronic disease management to identify potentially effective components for management of chronic traumatic brain injury (TBI). Information sources: Systematic searches of three databases (Ovid MEDLINE, Embase, and Cochrane Database of Systematic Reviews) from January 2010 to May 2021. Systematic reviews and meta-analyses reporting on the effectiveness of the Chronic Care Model (CCM), collaborative/integrated care, and other chronic disease management models. Target diseases, model components used (n = 11), and six outcomes (disease-specific, generic health-related quality of life and functioning, adherence, health knowledge, patient satisfaction, and cost/health care use). Narrative synthesis, including proportion of reviews documenting outcome benefits. More than half (55%) of the 186 eligible reviews focused on collaborative/integrated care models, with 25% focusing on CCM and 20% focusing on other chronic disease management models. The most common health conditions were diabetes (n = 22), depression (n = 16), heart disease (n = 12), aging (n = 11), and kidney disease (n = 8). Other single medical conditions were the focus of 22 reviews, multiple medical conditions of 59 reviews, and other or mixed mental health/behavioral conditions of 20 reviews. Some type of quality rating for individual studies was conducted in 126 (68%) of the reviews. Of reviews that assessed particular outcomes, 80% reported disease-specific benefits, and 57% to 72% reported benefits for the other five types of outcomes. Outcomes did not differ by the model category, number or type of components, or target disease. Although there is a paucity of evidence for TBI per se, care model components proven effective for other chronic diseases may be adaptable for chronic TBI care.


Nonhongiella spirulinensis gen. nov., sp. nov., a bacterium isolated from a cultivation pond of Spirulina platensis in Sanya, China.
A Gram-negative, aerobic, motile rod strain, designated Ma-20(T), was isolated from a pool of marine Spirulina platensis cultivation, Sanya, China, and was subjected to a polyphasic taxonomy study. Strain Ma-20(T) can grow in the presence of 0.5-11 % (w/v) NaCl, 10-43 °C and pH 6-10, and grew optimally at 30 °C, pH 7.5-9.0 in natural seawater medium. The polar lipids were composed of phosphatidylethanolamine, three unidentified phospholipids and three unidentified polar lipids. The respiratory quinone was ubiquinone 8 (Q-8) and the major fatty acids were C18:1ω6c/C18:1ω7c (summed feature 8, 32.84 %), C16:1ω6c/C16:1ω7c (summed feature 3, 30.76 %), C16:0 (13.54 %), C12:03-OH (4.63 %), and C12:0 (4.09 %). The DNA G+C content of strain Ma-20(T) was 58 mol %. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain Ma-20(T) belonging to Gammaproteobacteria, it shared 88.46-91.55 and 89.21-91.26 % 16S rRNA gene sequence similarity to the type strains in genus Hahella and Marinobacter, respectively. In addition to the large 16S rRNA gene sequence difference, Ma-20(T) can also be distinguished from the reference type strains Hahella ganghwensis FR1050(T) and Marinobacter hydrocarbonoclasticus sp. 17(T) by several phenotypic characteristics and chemotaxonomic properties. On the basis of phenotypic, chemotaxonomic and phylogenetic properties, strain Ma-20(T) is suggested to represent a novel species of a new genus in Gammaproteobacteria, for which the name Nonhongiella spirulinensis gen. nov., sp. nov. is proposed. The type strain is Ma-20(T) (=KCTC 32221(T)=LMG 27470(T)).


Stem cells: balancing resistance and sensitivity to DNA damage.
Embryonic stem cells (ESCs) are known to be very sensitive to DNA damage and undergo rapid apoptosis even after low-damage doses. By contrast, adult stem cells show variable sensitivity to damage. Here we describe the multiple pathways that have been proposed to affect the sensitivity of stem cells to damage, including proximity to the apoptotic threshold (mitochondrial priming) and the p53 signaling pathway, through activation of transcription or direct interaction with proapoptotic proteins in the cytoplasm. We also discuss which cellular factors might connect mitochondrial priming with pluripotency and the potential therapeutic advances that can be achieved by better understanding of the molecular mechanisms leading to sensitivity or resistance of embryonic or adult stem cells from different tissues.


Central retinal artery occlusion as a first sign of atrial fibrillation: A 3-year retrospective single-center analysis.
Central retinal artery occlusion ((C)RAO) is known to be associated with stroke and/or atrial fibrillation (AF). Nevertheless, patients often present at the ophthalmologist initially and it is unknown how many of these receive an adequate cardiological/neurological work-up (CWU/NWU), including a 24 h-Holter-ECG. Hypothesis of this study was that patients with (C)RAO do not undergo CWU on regular basis and that new-onset AF is more often detected in patients with CWU. We performed a retrospective analysis of n = 292 consecutive patients who presented at an ophthalmology department with the diagnosis of (C)RAO during a 3-year period. After excluding patients with known AF, meeting exclusion criteria, inability to comply with the protocol, missed land phoneline, or death during follow-up a total of 174 patients were enrolled; mean follow-up was 20 ± 12 months. The CHA2 DS2 -VASc score of the cohort was 5.3 ± 1.4. Our analysis revealed that only 50.6% of patients received a CWU including a single Holter-ECG after the index-event. In 12.6% cases new-onset AF was diagnosed, while the rate was higher in patients with CWU compared to patients without CWU (18.2 vs. 7.0%; p = 0.26). Evaluation of oral anticoagulation (OAC) therapy showed that only 66% of patients with AF were treated according to guidelines. Only half of patients with (C)RAO underwent CWU. Despite minimal monitoring, rate of new diagnosed AF was high. Our results confirm that (C)RAO identifies a high-risk population for AF. These results illustrate the importance to implement standardized CWU in (C)RAO patients presenting at the ophthalmologist.


Steroid receptor expression in the developing copulatory system of the green anole lizard (Anolis carolinensis).
In adulthood, the copulatory system in male green anole lizards is characterized by the presence of two hemipenes, each controlled by ipsilateral muscles. These structures are present in both sexes early in development, but prior to hatching regress completely in females. Embryonic treatment with steroid hormones alters the morphology of the copulatory system, suggesting active roles for both androgens and estrogens in sexual differentiation. To elucidate the timing and sites of steroid hormone action in the embryonic copulatory system, the distributions of androgen receptor (AR) and estrogen receptor-alpha (ER alpha) mRNA expression were examined. In situ hybridization was conducted on the rostral tail of anoles at three stages spanning differentiation of the copulatory structures: embryonic days (E) 13, 18, and 24 (hatching occurs at approximately E34). At E13, males expressed significantly higher levels of AR mRNA in both hemipenes and muscles than did females, while females at the same age tended to express higher levels of ER alpha mRNA in these structures. By E18, hemipenes and copulatory muscles were regressed in most females, and were not present in any females at E24. In males, no effect of age was detected on the expression of either AR or ER alpha. These data suggest that peripheral copulatory structures in the embryonic anole are direct targets for the actions of both androgens and estrogens in sexual differentiation, consistent with the idea that estradiol facilitates regression in females and androgen promotes survival in males. However, the issue of whether or not a critical period exists remains open.


Measles outbreak amidst COVID-19 pandemic in Africa: grappling with looming crises.
Coronavirus disease 2019 (COVID-19) and measles are major threats to the health and wellbeing of Africans. Measles is an endemic disease in Africa with a high mortality rate especially in children despite available vaccines. This letter aims to discuss the impact of the COVID-19 pandemic on prevention and management of measles in Africa. The emergence of COVID-19 has exacerbated the morbidities of measles due to multi-factors like the disruption of mass measles routine vaccination, a monopolistic focus on COVID-19 eradication, malnutrition, and poor surveillance. Currently, the COVID-19 pandemic and looming measles epidemic pose a double burden on the African health sector. We recommend urgent interventions from government and other stakeholders including community leaders to strengthen measles research and vaccination programs in Africa amidst the pandemic.


A real-time PCR-based amelogenin Y allele dropout assessment model in gender typing of degraded DNA samples.
Allelic dropout due to stochastic variation in degraded small quantity DNA appears to be one of the most serious genotyping errors. Most methods require PCR replication to address this problem. The small amounts of valuable samples are often a limitation for such replications. We report a real-time PCR-based amelogonin Y (AMELY) allele dropout estimation model in an AMEL-based gender typing. We examined 915 replicates of AMELY-positive modern male DNA with varying amounts of DNA and humic acid. A male-specific AMEL fragment (AMELy) dropped out in 143 genuine male replicates, leading to gender typing errors. By graphing a scatter plot of the crossing point versus the end cycle fluorescence of the male replicates, a standard graph model for the estimation of the AMELy allele dropout was constructed with the dropout-prone and dropout-free zones. This model was then applied to ancient DNA (aDNA) samples. Nine samples identified as female were found in the dropout-prone zone; with higher DNA concentrations, six were shifted to the dropout-free zone. Among them, two female identifications were converted to male. All the aDNA gender was confirmed by sex-determination region Y marker amplification. Our data suggest that this model could be a basic approach for securing AMELy allele dropout-safe data from the stochastic variation of degraded inhibitory DNA samples.


Applications of magnetic resonance in model systems: tumor biology and physiology.
A solid tumor presents a unique challenge as a system in which the dynamics of the relationship between vascularization, the physiological environment and metabolism are continually changing with growth and following treatment. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) studies have demonstrated quantifiable linkages between the physiological environment, angiogenesis, vascularization and metabolism of tumors. The dynamics between these parameters continually change with tumor aggressiveness, tumor growth and during therapy and each of these can be monitored longitudinally, quantitatively and non-invasively with MRI and MRS. An important aspect of MRI and MRS studies is that techniques and findings are easily translated between systems. Hence, pre-clinical studies using cultured cells or experimental animals have a high connectivity to potential clinical utility. In the following review, leaders in the field of MR studies of basic tumor physiology using pre-clinical models have contributed individual sections according to their expertise and outlook. The following review is a cogent and timely overview of the current capabilities and state-of-the-art of MRI and MRS as applied to experimental cancers. A companion review deals with the application of MR methods to anticancer therapy.


Fibrinogen, Neutrophil-to-Lymphocyte Rate and Platelet-to-Neutrophil Rate as Novel Acute Phase Indicators in Patients with Thromboangiitis Obliterans.
The acute exacerbations and progressive deterioration seen in thromboangiitis obliterans (TAO) have been related to poor clinical outcomes. Here, we have studied the association of laboratory biomarkers with the acute phase of TAO (AP-TAO). We conducted a retrospective case-control study on 112 patients with TAO and 98 healthy controls; comparing the neutrophil-to-lymphocyte rate (NLR), lymphocyte-to-monocyte rate (LMR), platelet-to-neutrophil rate (PNR), fibrinogen (FIB), and apolipoprotein A-I (ApoA-I). Significantly higher NLR level, as well as lower LMR, PNR, and ApoA-I levels were observed in patients with TAO, particularly the acute phase. Significantly increased FIB was only observed in AP-TAO. A positive correlation was found between NLR and with C-reactive protein (CRP) in the acute phase (r = 0.817, P < 0.001). Moreover, NLR, PNR, and FIB levels of 3.38, 45.12, and 3.69 were shown to be the predictive cut-off values for the AP-TAO (sensitivity 72.5, 82,4, and 66,7%, specificity 92.2, 78.4, and 96.1%; area under the curve [AUC] 0.875, 0.855, and 0.872), respectively. The FIB level was independently associated with the AP-TAO (OR = 11.420, P = 0.007). NLR, PNR, and FIB may be useful markers for the identification of inflammation and the AP-TAO. FIB may be an independent risk factor for the acute phase.


Alteration of oral bacteriome of smokeless tobacco users and their association with oral cancer.
Smokeless tobacco (SLT) is certainly one of the major risk factors associated with oral cancer. Disruption of oral microbiota-host homeostasis contributes to the progression of oral cancer. Here, we profiled SLT users' oral bacterial composition and inferred their functions by sequencing 16S rDNA V3-V4 region and PICRUSt2, respectively. Oral bacteriome of SLT users (with or without oral premalignant lesions), SLT with alcohol co-users, and non-SLT consumers were compared. Oral bacteriome is shaped primarily by SLT use and the incidence of oral premalignant lesions (OPL). A significantly increased bacterial α-diversity was monitored in SLT users with OPL compared to in SLT users without OPL and non-users, whereas β-diversity was significantly explained by OPL status. Overrepresented genera were Prevotella, Fusobacterium, Veillonella, Haemophilus, Capnocytophaga, and Leptotrichia in SLT users having OPL. LEfSe analysis identified 16 genera as a biomarker that were differentially abundant in SLT users having OPL. The functional prediction of genes significantly increased for several metabolic pathways, more importantly, were nitrogen metabolism, nucleotide metabolism, energy metabolism, and biosynthesis/biodegradation of secondary metabolites in SLT users having OPL. Furthermore, HPV-16 and EBV, but not HPV-18, were considerably connected with the SLT users having OPL. Overall, this study provides evidence that SLT utilization and OPL development are associated with oral bacteriome dysbiosis indicating the enrichment of bacterial species known for their contribution to oral carcinogenesis. Therefore, delineating the cancer-inducing bacterial population in SLT users will facilitate the future development of microbiome-targeted therapies. KEY POINTS: • SLT consumption significantly elevates oral bacterial diversity. • Prevalent significant genera are Prevotella, Veillonella, and Haemophilus in SLT users with OPL. • SLT promotes the occurrence of the cancer-inducing bacterial population.


Endovascular treatment of cerebral vasospasm following aneurysmal subarachnoid hemorrhage.
Endovascular treatment by balloon angioplasty or intra-arterial papaverine infusion has been established as a valuable treatment option in patients with cerebral vasospasm refractory to maximal medical therapy. A summary of the indications, applications and limitations is provided for microcatheter guided selective papaverine infusion and transluminal balloon angioplasty in patients who sustain cerebral vasospasm following subarachnoid haemorrhage. Structured neuro-intensive and endovascular treatment of imminent vasospasm integrate papaverine administration and balloon angioplasty as complimentary rather than alternative techniques.


Positional uncertainty in peripheral and amblyopic vision.
Three experiments were performed to examine positional acuity and the role of spatial sampling in central, peripheral and amblyopic vision. In the first experiment, 3-line bisection acuity was compared to grating acuity. In normal foveal vision bisection acuity represents a hyperacuity. In anisometropic amblyopes, bisection acuity is reduced in rough proportion to their grating acuity. In strabismic amblyopes, and in the normal periphery, bisection acuity is reduced to a greater extent than grating acuity. This result implies that reduced contrast sensitivity of the spatial filters is not sufficient to account for the increased positional uncertainty found in peripheral vision and in strabismic amblyopia. In order to test the hypothesis that the high degree of positional uncertainty evident in these visual systems is a consequence of sparse spatial sampling, bisection thresholds and width discrimination thresholds were measured with stimuli comprised of discrete samples. The results showed that normal foveal vision and the vision of anisometropic amblyopes show little benefit from adding discrete samples to the stimulus. In contrast, the normal periphery, and the central field of strabismic amblyopes demonstrate marked positional uncertainty which can be efficiently reduced in proportion to the square root of the number of samples (up to about 10) comprising the stimulus in the direction orthogonal to the discrimination cue. In aggregate the results suggest that anisometropic and strabismic amblyopia are fundamentally different. The positional uncertainty in anisometropic amblyopia is consistent with the reduced sensitivity of the spatial filters. The data of the normal periphery and of the central field of strabismic amblyopes suggest that the cortical sampling grain imposes a fundamental limit upon their positional acuity.


Transfer learning for predicting human skin sensitizers.
Computational prioritization of chemicals for potential skin sensitization risks plays essential roles in the risk assessment of environmental chemicals and drug development. Given the huge number of chemicals for testing, computational methods enable the fast identification of high-risk chemicals for experimental validation and design of safer alternatives. However, the development of robust prediction model requires a large dataset of tested chemicals that is usually not available for most toxicological endpoints, especially for human data. A small training dataset makes the development of effective models difficult with insufficient coverage and accuracy. In this study, an ensemble tree-based multitask learning method was developed incorporating three relevant tasks in the well-defined adverse outcome pathway (AOP) of skin sensitization to transfer shared knowledge to the major task of human sensitizers. The results show both largely improved coverage and accuracy compared with three state-of-the-art methods. A user-friendly prediction server was available at https://cwtung.kmu.edu.tw/skinsensdb/predict . As AOPs for various toxicity endpoints are being actively developed, the proposed method can be applied to develop prediction models for other endpoints.


Are spinal precautions necessary in all seizure patients?
The purpose of this retrospective chart review study was to evaluate the necessity of spinal precautions in uncomplicated seizure patients. The population was all patients from the Emergency Department with a primary diagnosis of seizure over a 10.5-year period. The setting was a university-affiliated county teaching hospital with an annual patient volume of over 58,000. The key outcome measure was an association of spinal injuries to uncomplicated seizures. A total of 1,656 cases were reviewed. No spinal injuries were found. Three nonspinal fractures were associated with seizure activity. Transportation costs increased approximately 113% and nursing costs increased approximately 57% for patients with seizure placed in spinal precautions. Quality Assurance and Risk Management files showed no complaints or litigation secondary to missed spinal injuries. This retrospective chart review study seriously questions routine use of spinal precautions in uncomplicated seizure cases. If spinal precautions were not used in this group, there would be a significant potential cost savings without increased morbidity. A prospective study is needed to confirm these findings.


The Clinical Study of Bladder Flap Ureteroplasty (Psoas Hitch) in the Treatment of Lower Ureteral Injuries and Strictures (19 Cases).
The aim of this study was to investigate the efficacy and safety of bladder flap ureteroplasty (psoas hitch) in the treatment of lower ureteral injuries and strictures. 19 patients with lower ureteral injuries and strictures scheduled for a bladder flap ureteroplasty (psoas hitch) in our hospital from January 2020 to January 2021 were recruited. The outcome measures included treatment efficacy and safety. The operative time, intraoperative bleeding, catheter extubation time, hospital stay, extubation time of ureteral stent, and follow-up time were (125.36 ± 15.38) min, (75.37 ± 11.09) ml, (7.25 ± 1.04) d, (8.76 ± 1.11) d, (46.34 ± 7.66) d, and(19.27 ± 1.27) months, respectively. No serious perioperative adverse reactions were observed, and all the symptoms of patients were relieved. Bladder flap ureteroplasty (psoas hitch) is safe and effective for the treatment of lower ureteral injuries, with advantages such as less intraoperative bleeding and trauma and rapid recovery, so it is worthy of promotion. This was a retrospective study supervised by the Ethics Committee of Hebei Yanda Hospital.This trial is registered with no. hebYD076.


Ethanolamine metabolism in cultured bovine aortic endothelial cells.
The role of extracellular ethanolamine in phospholipid synthesis was examined in cultured bovine aortic endothelial cells. Serine and ethanolamine were both readily accumulated by these cells and incorporated into phospholipid. Exposing cells to extracellular ethanolamine for 4-6 weeks had no effect on cell growth, yet increased the phosphatidylethanolamine content of these cells by 31% as compared to control cells. The intracellular content of ethanolamine was measured by high performance liquid chromatography, and results showed that the ethanolamine-treated cells contained a significantly greater amount of free ethanolamine compared to control cells (0.62 +/- 0.07 nmol/mg of protein versus 0.27 +/- 0.05 nmol/mg of protein, respectively). Ethanolamine-treated cells also had decreased accumulation and incorporation into lipid of [3H]ethanolamine throughout a 48-h incubation and increased K'm and V'max parameters of ethanolamine transport as compared to control cells. Studies were also done to examine the effect of ethanolamine on the generation of free ethanolamine from phosphatidylserine. In pulse-chase experiments with [3H]serine, a physiological concentration of ethanolamine (25 microM) decreased the amount of 3H-labeled phosphatidylethanolamine produced from 3H-labeled phosphatidylserine by 12 h as compared to the amount of 3H-labeled phosphatidyl-ethanolamine produced in the absence of ethanolamine in the chase incubation. Furthermore, ethanolamine-treated cells accumulated 20% less labeled ethanolamine in the aqueous pool from [3H]serine after 24 h of incubation than did control cells. These results can be explained by isotope dilution with the ethanolamine pool that accumulates in these cells with time when exposed to media supplemented with a physiological concentration of ethanolamine and by an effect of ethanolamine on ethanolamine generation from phosphatidylserine. The results show that an extracellular source of ethanolamine significantly influences the phospholipid metabolism of cultured bovine aortic endothelial cells.


High-speed integrated optical logic based on the protein bacteriorhodopsin.
The principle of all-optical logical operations utilizing the unique nonlinear optical properties of a protein was demonstrated by a logic gate constructed from an integrated optical Mach-Zehnder interferometer as a passive structure, covered by a bacteriorhodopsin (bR) adlayer as the active element. Logical operations were based on a reversible change of the refractive index of the bR adlayer over one or both arms of the interferometer. Depending on the operating point of the interferometer, we demonstrated binary and ternary logical modes of operation. Using an ultrafast transition of the bR photocycle (BR-K), we achieved high-speed (nanosecond) logical switching. This is the fastest operation of a protein-based integrated optical logic gate that has been demonstrated so far. The results are expected to have important implications for finding novel, alternative solutions in all-optical data processing research.


Etiological diagnosis in sinusitis: ultrasonography as clinical complement.
Accumulation of purulent sinus secretion reflects an inflammation caused by pyogenic bacteria, whereas the accumulation of nonpurulent effusion may have origins other than a bacterial infection. Ultrasonography differentiates the disordered sinus from the healthy one, but not purulent from nonpurulent secretion. In 90 patients, supposed to suffer from sinusitis, a correct diagnosis, sinus empyema vs. not sinus empyema, was established in a majority of cases by means of clinical evaluation alone. By introducing ultrasonography as a complement to the clinical evaluation, the diagnostic reliability became lower. It is concluded that ultrasonography seems to have little or no implication in the therapeutic decision unless diagnostic puncture is also performed.


Transcatheter Closure of Atrial and Ventricular Septal Defects: JACC Focus Seminar.
The field of congenital interventional cardiology has experienced tremendous growth in recent years. Beginning with the development of early devices for transcatheter closure of septal defects in the 1970s and 1980s, such technologies have evolved to become a mainstay of treatment for many atrial septal defects (ASDs) and ventricular septal defects (VSDs). Percutaneous device closure is now the preferred approach for the majority of secundum ASDs. It is also a viable treatment option for selected VSDs, though limitations still exist. In this review, the authors describe the current state of transcatheter closure of ASDs and VSDs in children and adults, including patient selection, procedural approach, and outcomes. Potential areas for future evolution and innovation are also discussed.


Pediatric anesthesia and postoperative analgesia.
Children are not "small adults," particularly when it comes to anesthesia and pain management. The psychological and physiologic uniqueness of children must not be forgotten. Cooperation and communication between the anesthesiologist, surgeon, and pediatrician are essential for successful anesthesia and pain management. Pediatric anesthesiologists involved in the perioperative management of infants and children are very much a part of the "continuity of care" concept.


A note on simultaneous and interleaved masking.
Speech and noise were switched periodically from ear to ear at a rate high enough to create a binaurally fused image. Two masking conditions were investigated. In one the speech and noise were switched in unison from ear to ear such that both speech and noise were presented simultaneoully to the same ear. In the other case, the speech and noise were interleaved such that there was no simultaneous overlap of the speech and noise at any one ear. The difference in masking levels between these two conditions was found to be on the order of 20 dB. The technique offers some interesting possibilities for investigating the relative effects of central and peripheral masking in both normal and hearing-impaired listeners.


From CuFeS2 to Ba6Cu2FeGe4S16: rational band gap engineering achieves large second-harmonic-generation together with high laser damage threshold.
A new germanium-based sulfide, Ba6Cu2FeGe4S16, achieves a band-gap broadening of more than 1 eV relative to CuFeS2. Remarkably, Ba6Cu2FeGe4S16 exhibits excellent comprehensive NLO performance (SHG, 1.5 × AgGaSe2; LDT, 2 × AgGaSe2), satisfying the essential requirements of mid-IR NLO candidates.


Gln40 deamidation blocks structural reconfiguration and activation of SCF ubiquitin ligase complex by Nedd8.
The full enzymatic activity of the cullin-RING ubiquitin ligases (CRLs) requires a ubiquitin-like protein (that is, Nedd8) modification. By deamidating Gln40 of Nedd8 to glutamate (Q40E), the bacterial cycle-inhibiting factor (Cif) family is able to inhibit CRL E3 activities, thereby interfering with cellular functions. Despite extensive structural studies on CRLs, the molecular mechanism by which Nedd8 Gln40 deamidation affects CRL functions remains unclear. We apply a new quantitative cross-linking mass spectrometry approach to characterize three different types of full-length human Cul1-Rbx1 complexes and uncover major Nedd8-induced structural rearrangements of the CRL1 catalytic core. More importantly, we find that those changes are not induced by Nedd8(Q40E) conjugation, indicating that the subtle change of a single Nedd8 amino acid is sufficient to revert the structure of the CRL catalytic core back to its unmodified form. Our results provide new insights into how neddylation regulates the conformation and activity of CRLs.


Sorption of selenium anionic species on apatites and iron oxides from aqueous solutions.
The sorption of selenite and selenate ions from aqueous solutions was investigated on hydroxyapatite, fluorapatite, goethite and hematite, in order to simulate the behavior of radioactive selenium in natural or artificial sorbing media. Correlation studies with acido-basic properties and solubility of the solids were also performed. The sorption is pH dependant, but these solids are very efficient for retaining selenite at pH values generally encountered in natural waters, with however higher K(d) values for oxides than apatites. Selenate ions are much less sorbed than selenite. Several methods such as electron microscopy and spectroscopic techniques were used to identify the sorption mechanisms. In the case of hydroxyapatite, sorption proceeds by substitution of phosphate groups in the lattice of the apatite crystal in the superficial layers of the solid. In the case of goethite and hematite, sorption can be interpreted and modeled by a surface complexation process, but there is a discrepancy between sorption site densities for selenite and for protons.


Gender differences in binge-eating: a population-based twin study.
To assess whether genetic and environmental effects on liability to binge-eating (BE) are of equal importance for males and females and whether the same genetic risk factors predispose to BE in the two sexes. Questionnaire data on 8045 same sex and opposite sex twins, aged 19-31 years, from a population-based Norwegian registry, was used to estimate the relative contribution of genetic and environmental factors to liability for BE utilizing structural equation modeling. In the best-fitting model, the magnitude of genetic and environmental effects on BE was the same for males and females. Heritability was 51%. The correlation between genetic risk factors in men and women was estimated to be +0.57. Binge-eating appears to be equally heritable in males and females. Although the majority of the genetic risk factors are shared between the sexes, there may exist gender-specific genetic effects on liability.


Comparative Analysis of Human Mesenchymal Stem Cells Derived From Bone Marrow, Placenta, and Adipose Tissue as Sources of Cell Therapy.
Various source-derived mesenchymal stem cells (MSCs) with multipotent capabilities were considered for cell therapeutics of incurable diseases. The applicability of MSCs depends on the cellular source and on their different in vivo functions, despite having similar phenotypic and cytological characteristics. We characterized MSCs from different sources, including human bone marrow (BM), placenta (PL), and adipose tissue (AT), in terms of the phenotype, surface antigen expression, differentiation ability, proteome reference map, and blood flow recovery in a hindlimb ischemic disease model. The MSCs exhibit different differentiation potentials depending on the cellular source despite having similar phenotypic and surface antigen expression. We identified approximately 90 differentially regulated proteins. Most up- or down-regulated proteins show cytoskeletal or oxidative stress, peroxiredoxin, and apoptosis roles according to their functional involvement. In addition, the PL-MSCs retained a higher therapeutic efficacy than the BM- and AT-MSCs in the hindlimb ischemic disease model. In summary, we examined differentially expressed key regulatory factors for MSCs that were obtained from several cellular sources and demonstrated their differentially expressed proteome profiles. Our results indicate that primitive PL-MSCs have biological advantages relative to those from other sources, making PL-MSCs a useful model for clinical applications of cell therapy.


A comparison of serial halving and the rule of nines as a pre-hospital assessment tool in burns.
Following endorsement of serial halving by the Faculty of Pre-Hospital Care of the Royal College of Surgeons of Edinburgh this study aimed to determine whether the technique was comparable to the rule of nines in making initial assessments of body surface area burned. Ten 'casualties' were made up to represent burn victims (range 6-61%). An external panel of six consultants and one specialist registrar in plastic surgery were invited to assess the simulated casualties. They gave individual and a consensus estimate of the burned areas. One hundred and twenty-five members of local emergency services and military paramedical staff were given a brief video and slide presentation describing either the rule of nines or serial halving method of burn area assessment. These techniques were then used to assess the 10 simulated casualties, giving 1250 estimates of burn surface area. The understanding of both techniques appeared adequate in both test groups. Estimates from serial halving and rule of nines groups differed from the assessments of the external panel. No statistical difference was demonstrated between serial halving and the rule of nines as an initial assessment tool when determining disposal. Serial halving has an inherent weakness when assessing certain sizes of burn. The rule of nines requires that the assessor knows and understands the proportionate areas of the body. The mathematics of percentages and fractions appeared to confuse some assessors.


Immune-directed gene therapeutic development for Alzheimer's, prion, and Parkinson's diseases.
The development of novel immune-based therapeutics for neurodegenerative diseases is an area of intense focus. Neurodegenerative diseases represent a particular challenge since in many cases the onset of symptoms occurs after considerable degeneration has ensued. Based on human genetic and histopathological evidence from patients with neurodegenerative diseases, animal models that recapitulate specific pathologic features have been developed. Utilizing these animal models in combination with viral vector-based gene therapeutics, specific epochs of disease can be targeted. One common feature of several neurodegenerative diseases is misfolded proteins. The mechanism by which these altered protein conformers lead to neurodegeneration is not completely understood but much effort has been put forward to either degrade aberrant protein or prevent the formation of misfolded conformers. In this review, we will summarize work that employs viral vector gene therapeutics to modulate the brain's response to misfolded proteins with a specific focus on neurodegeneration.


Morphologic features of the root canal system of the maxillary fourth premolar and the mandibular first molar in dogs.
Root canal morphology was evaluated in 72 maxillary fourth premolar and 59 mandibular first molar teeth. An apical delta was present in all roots (n = 334). The apical delta represented approximately 12-18% of the total root length for all roots. Non-apical ramifications from the main canal were observed in 25.1% of roots. Secondary canal(s) were present in 20.6% of roots, while lateral canal(s) were present in 6.9% of roots. The distal root of the maxillary fourth premolar had the highest incidence (47.2%) of non-apical ramifications. Overall, 68.0 and 20.4% of maxillary fourth premolar and mandibular first molar teeth had non-apical ramifications, respectively. The prevalence and location of non-apical ramifications may influence clinical decision making when performing endodontic therapy.


Diazepam treatment blocks the elevation of hippocampal activity and the accelerated proliferation of hippocampal neural stem cells after focal cerebral ischemia in mice.
Hippocampal neurogenesis is accelerated during the elevation of hippocampal neural activities under both physiological and pathophysiological conditions. One of these conditions, middle cerebral artery occlusion (MCAO), induces both the hyperactivities of hippocampal network and the elevation of neural stem cell (NSC) proliferation. However, the causal relationship between the elevated activity and the elevation of NSC proliferation is still unclear. In this study, to block the elevation of hippocampal activity after MCAO in mice, we utilized a typical γ-aminobutyric acid type A (GABAA ) receptor active modulator, diazepam. With MCAO mice treated with diazepam, we observed complete disappearance of the elevation of hippocampal activity. Additionally, the diazepam treatment blocked the elevation of NSC proliferation after MCAO. From this result, it is speculated that the increased NSC proliferation is blocked by the suppression of elevated neural activity. However, diazepam might have effects other than the suppression of hippocampal activity, so we performed additional experiment and found that diazepam did not affect the number of bromodeoxyuridine-positive cells under the normal condition, whereas the GABA agonist pentobarbital stimulated NSC/neural progenitor cell proliferation and differentiation. Next, we evaluated the expression of the diazepam-binding inhibitor (DBI) protein and found that the cells expressed DBI in soma and on the surface of cell membrane. From these observations, we can propose that diazepam blocks the elevation of hippocampal activity and also NSC proliferation after MCAO.


Association between dental agenesis and delay in dental development: a preliminary study in a Spanish paediatric population in relation with Dental Anomaly Pattern (DAP).
The association between dental anomalies has been studied, giving rise to the concept of Dental Anomaly Pattern (DAP). Tooth agenesis has been associated with alterations such as molar infracclusion, taurodontism and delayed dental development. The aim of this study was to evaluate the dental development pattern in patients with non-syndromic dental agenesis, in comparison with a control group. Dental and chronological age was analysed in a sample size of 204 orthopantomographs divided into a study group (n = 104) and a control group (n = 100) with the Demirjian Method. Intra and intergroup differences in chronological and dental age, and the correlation between them were calculated by statistical analysis with a 95% confidence level (p < 0.05). Dental age exceeded chronological age both in the control group and in the study group. Statistically significant differences (p = 0.004) were found when comparing the difference between chronological and dental age in the study (-0.16 ± 1.12) and control group (-0.58 ± 0.90). Regarding sex and age intergroup differences, the results were only statistically significant in the girls' group (p = 0.017), and the age over 8 years old (p < 0.05). There were no significant differences in tooth development depending on the number of missing teeth or the affected tooth group, but there was a delay in the development of the homologous tooth contralateral to the absent one in 14.9% of patients. The difference between chronological and dental age in permanent dentition is significantly lower in Spanish children with non-syndromic agenesis compared to a control group, presenting a lower dental age than chronological age than children without non-syndromic agenesis.


Hypoxic tolerance induction in rat brain slices following 3-nitropropionic acid pretreatment as revealed by dynamic changes in glucose metabolism.
Pretreatment with 3-nitropropionic acid (3-NPA) has been shown to induce tolerance to ischemic/hypoxic brain damage. However, regional differences in tolerance induction by 3-NPA and the degree to which impaired glucose metabolism due to 3-NPA pretreatment itself is directly involved remain unknown. To evaluate these issues using dynamic positron autoradiography with [(18)F]2-fluoro-2-deoxy-D-glucose, the cerebral glucose metabolic rate (CMRglc) was serially measured before and after hypoxia-loading in rat brain slices pretreated with 3-NPA. CMRglc before hypoxia did not significantly differ between the 3-NPA pretreatment group and control group. The 3-NPA-associated recovery of CMRglc after reoxygenation was observed in the frontal cortex, hippocampus, and cerebellum, but not in the striatum and thalamus. Thus, we demonstrated the induction of region-specific hypoxic tolerance after 3-NPA pretreatment using CMRglc maintenance as an index of neuronal viability, and it is unlikely that this induction is associated with the persistence of impaired glucose metabolism due to 3-NPA pretreatment.


Complex molecular mechanism of ammonia-induced apoptosis in chicken peripheral blood lymphocytes: miR-27b-3p, heat shock proteins, immunosuppression, death receptor pathway, and mitochondrial pathway.
Ammonia gas, a toxic environmental pollutant, is a vital component of PM2.5 aerosols, and can decrease human and animal immunity. Peripheral blood lymphocytes (PBLs) are main immune cells. Nevertheless, poisoning mechanism of PBLs under ammonia exposure remains unclear. Here, we established an ammonia poisoning model of chicken PBLs to explore poisoning mechanism of ammonia-caused apoptosis in chicken PBLs. Cell viability and apoptosis rate were detected using CCK8 assay and flow cytometry, respectively. Mitochondrial membrane potential (MMP) was observed using fluorescent staining. In addition, qRT-PCR was performed to measure mRNA levels of apoptosis-related genes (tumor necrosis factor-α (TNF-α), tumor necrosis factor receptor 1 (TNFR1), TNF receptor-associated death domain (TRADD), Fas-associated death domain (FADD), Caspase-8, BH3-interacting domain death agonist (Bid), Bcl-2-associated X protein (Bax), Bcl-2 homologous antagonist/killer (Bak), B-cell lymphoma-2 (Bcl-2), Cytochrome-c (Cytc), apoptotic protease activating factor-1 (APAF1), Caspase-9, and Caspase-3), immune-related genes (interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, IL-6, IL-1β, IL-10, transforming growth factor-β1 (TGF-β1), IL-17, IL-21, and IL-22), heat shock protein (HSP) genes (HSP25, HSP40, HSP60, HSP70, HSP90, and HSP110), as well as miR-27b-3p. Western blot was used to determine protein levels of apoptosis-related factors (TNF-α, Caspase-8, Bcl-2, Caspase-9, and Caspase-3), as well as HSPs (HSP40, HSP60, HSP70, and HSP90). The results indicated that TRADD, FADD, and APAF1 were target genes of miR-27b-3p, as well as miR-27b-3p participated in molecular mechanism of apoptosis through targeting TNF-α/TNFR1/Caspase-8 death receptor pathway-triggered Bid/Cytc/Caspase-9 mitochondrial pathway in ammonia-treated chicken PBLs. In addition, our findings demonstrated that excess ammonia led to immunosuppression via Th1/Th2 imbalance and Treg/Th17 imbalance. Simultaneously, ammonia stress activated HSPs. In summary, for the first time, our data demonstrated that HSPs-triggered immunosuppression led to apoptosis under ammonia exposure. Our findings provided a new insight into molecular mechanism of ammonia poisoning and an important reference for environmental risk assessment related to ammonia.


The effects of ionic conditions, temperature, and chemical modification on the fluorescence of myosin during the steady state of ATP hydrolysis. A comparison of the fluorescnece and electron spin resonance spectra of the spin-labeled enzyme.
The ATP-induced enhancement of the intrinsic fluorescence of myosin and heavy meromyosin (HMM) that persists during the steady state of hydrolysis has been investigated. To compare the substrate-induced changes in fluorescence with those in the electron spin resonance spectrum of the spin-labeled enzyme, we studied the influence of temperature, pH, and ionic strength, as well as the effect of chemical modification (spin labeling) of the SH-1 sulfhydryl groups. Changing the pH between 6 and 9 does not affect the enhancement of fluorescence of myosin or HMM; changing the ionic strength, which could be studied only with HMM, also has no effect; and decreasing the temperature from 20 to 5 degrees slightly diminishes the enhancement with both myosin and HMM. Chemical modification with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl) iodoacetamide, which blocks the SH-1 thiol groups, reduces the enhancement of fluorescence, induces a strong dependence on ionic strength and pH, and substantially increases the dependence on temperature. The enhancement with labeled myosin or labeled HMM increases with increasing pH, ionic strength, and temperature, closely paralleling the effects of these parameters on the electron spin resonance spectrum of spin-labeled myosin (SEIDEL, J.C. and GERGELY, J. (1973) Arch. Biochem. Biophys. 158, 853), suggesting that the same molecular change, induced by ATP and associated with formation of the MADP-P1 complex, underlies both the change in fluorescence and the change in ESR spectrum. Those analogues of ATP that produce the maximal enhancement of fluorescence (WERBER, M., SZENT-GYORGYL, A.G., and FASMAN, G. (1972) Biochemistry 11, 2872) also produce the maximal change in the ESR spectra. Both an amino group at position 6 of the substrate and an unmodified triphosphate chain are required for maximal change in either fluorescence or ESR spectra. The smaller enhancement of fluorescence produced by spin labeling the SH-1 groups persists after the nitroxide has been chemically changed to a diamagnetic species. Thus the small enhancement cannot be attributed to paramagnetic quenching of tryptophan fluorescence by the spin label. An initial burst of phosphate liberation accompanies the hydrolysis of ATP, cytidine 5'-triphosphate, uridine 5'-triphosphate, guanosine 5'-tryphosphate, iosine 5'-triphosphate, 2'-deoxyadenosine 5'-tryphosphate, adenosine 5'-tetraphosphate, and tripolyphosphate. The presence or absence of the burst does not correlate with the extent of the spectral change.


[Importance of the quality of the discharge report in the management of a surgical clinical unit].
The discharge report is a basic document at the end of a care process, and is a key element in the coding process, since its correct wording, reliability and completeness are factors used to determine the hospital production. From a hypothesis based on the analysis of the consistency between the discharge report and data collected from the routine clinical notes during admission, we should be able to re-code all those mis-coded, thus placing them in a more appropriate diagnosis-related group (DRG). A total of 24 patient outliers were analysed for the correct filling in of the type and reason for admission, personal history, medication, anamnesis, primary and secondary diagnosis, sugical procedure, outcome, number of diagnostic and procedures cited, concordance between discharge report and history and recoding of the DRG. From a total of 24 episodes, 6 had precise and valid reports, 4 were valid but not precise enough, 9 were insufficient, and 5 were clearly invalid. The recoded DRG after the documentation review was not significantly different, according to the Wilcoxon test, being changed in only 5 cases (P = .680). Quality in discharge reports depends on an adequate minimum data set (MDS) in concordance with the source documentation during admission. Discordance can change the DRG, despite it not being significantly different in our series. Self-audit of discharge reports allows quality improvements to be developed along with a reduction in information mistakes.


A clinical and bacteriological evaluation of a re-use system for disposable haemodialysers.
Re-use of disposable haemodialysers, cleaned and disinfected with sodium hypochlorite and benzoic acid, was evaluated bacteriologically and clinically during the course of 514 dialysis treatments, performed with 206 RP6 dialysers used up to three times. Microbial contamination of the dialysers, which may be ascribed to the re-use system, was not observed. At the start of the dialyses, contamination of the dialysate compartment was lower in re-used dialysers, but during the dialyses it increased more rapidly than in dialysers used for the first time. Contamination of the blood compartment was the same with new and re-used dialysers. Clinical side effects, which may be ascribed to the re-use of dialysers, were not observed. The tested re-use system is hygienically acceptable and can be recommended for routine use, provided that the contamination of the dialysate is kept at a level below 10(4) cfu/ml and restricted to micro-organisms of low pathogenicity. A continuing bacteriological test sampling system is advisable.


Dephosphorylation of histone H1 after mengovirus infection of Ehrlich ascites tumor cells.
The effect of mengovirus infection on the extent of phosphorylation of histone H1 was studied in Ehrlich ascites tumor cells. After prelabeling of the nuclear protein with [32P] orthophosphate, the excorporation of radioactivity was followed as a function of time postinfection. Employing high-resolution polyacrylamide gradient slab gel electrophoresis and autoradiography, it was found that, compared to a relatively slow turnover of phosphate groups in histone H1 in mock-infected cells, in mengovirus-infected cells the excorporation of radiolabel from histone H1 was significantly enhanced. In the latter case, the decrease of histone-bound radioactivity was paralleled by a reduction of the band multiplicity in the histone H1 region of the electrophoresis profile. It was also shown that the microheterogeneity in the histone H1 complements isolated at various times postinfection was reduced to the same basal 3-band level by incubation of the nuclear protein fractions in the presence of alkaline phosphatase. After this treatment, the band multiplicity equaled that found in histone H1 from stationary cells.


Playing High School Football Is Not Associated With an Increased Risk for Suicidality in Early Adulthood.
To determine if playing high school football is associated with suicide ideation between the ages of 24 and 32 years. Data were analyzed from the National Longitudinal Study of Adolescent to Adult Health. This prospective cohort study sampled nationally representative US participants at 4 time points from 1994 to 2008. In-home assessment. There were 3147 boys (age: median = 14.9, SD = 1.8) who participated during adolescence in 1994 to 1995 (wave I), of whom 2353 were reinterviewed in 2008 (wave IV, age: median = 29.1, SD = 1.8). Football participation, history of psychological counseling, suicide ideation, and a suicide attempt in the past year during high school. Lifetime history of depression, suicide ideation within the past year, and feeling depressed in the past 7 days at wave IV. Men who played high school football, compared with those who did not, reported similar rates of lifetime diagnosis of depression, suicide ideation in the past year, and feeling depressed in the past 7 days. Those who played football reported similar rates of suicide ideation in the past year when they were in their early 20s. Individuals who underwent psychological counseling during adolescence were more likely to report a lifetime history of depression and suicide ideation in the past year. Young men who played high school football are not at an increased risk for suicide ideation during both their early 20s and late 20s. By contrast, those who experienced mental health problems in high school were much more likely to experience suicide ideation during their 20s.