Acetaminophen inhibits prostanoid synthesis by scavenging the PGHS-activator peroxynitrite.
The primary pharmacological target of acetaminophen is prostaglandin endoperoxide H2 synthase (PGHS). The enzymatic catalytic mechanism is radical-based, initiated, and maintained by the persistent presence of peroxides, particularly peroxynitrite, which is termed "peroxide tone". Whereas the prevailing concept assumes a direct reduction of the active, oxidized enzyme by acetaminophen, here we show that acetaminophen is a potent scavenger of peroxynitrite (peroxynitrite-mediated phenol nitration, IC50 approximately 72 microM; Sin-1-mediated DHR123 oxidation, IC50 approximately 11 microM) and thus inhibits PGHS by eliminating the peroxide tone. Nanomolar concentrations of peroxynitrite increased the activity of isolated PGHS and prostacyclin formation by aortic endothelial cells. This elevated activity was efficiently inhibited by pharmacologically relevant concentrations of acetaminophen (IC50 approximately 10 microM for 6-keto-PGF1alpha) and other free radical scavengers. However, when the peroxide tone was provided by H2O2 or tert-butyl-OOH, acetaminophen had only negligible inhibitory effects. Our concept could help to explain the efficacy of acetaminophen to inhibit PGHS in cell types with moderate oxidant formation. However, high levels of peroxynitrite or other peroxides such as lipid peroxides formed at inflammatory sites might overwhelm the ability of acetaminophen to decrease PGHS activation. The concept presented herein provides a molecular basis to explain the excellent analgesic and antipyretic properties of acetaminophen together with its minimal anti-inflammatory effects.


Organocatalytic asymmetric 1,4-addition of aldehydes to acridiniums catalyzed by a diarylprolinol silyl ether.
The organocatalytic enantioselective 1,4-addition of aldehydes to acridiniums catalyzed by diarylprolinol silyl ether was achieved to furnish chiral acridanes in both high yields (82-96%) and excellent enantioselectivities (up to 99% ee), which also provides the highly enantioselective intermolecular α-alkylation of aldehydes with acridiniums salt.


[Sequelae of tick-born encephalitis in cases treated in the infection observatory ward of Regional Hospital in Gizycko].
The paper reveals the description of the sequels of tick-born encephalitis among patients treated in Infectious Observatory Ward of Country Hospital in Gizycko during 2000-2002.


Yarn-ball-shaped CNF/MWCNT microspheres intercalating Ti3C2Tx MXene for electromagnetic interference shielding films.
Ti3C2Tx MXenes with excellent metallic conductivity have proved promising in its application of electromagnetic interference (EMI) shielding. A hierarchical hybrid film with ultrathin thickness composed of Ti3C2Tx MXene layers embedded with yarn-ball-shaped microspheres of cellulose nanofibrils (CNF) and multiwalled carbon nanotube (MWCNT) was designed to improve the absorption of electromagnetic waves (EMWs). The addition of yarn-ball-shaped microspheres is to shield more EMWs via multiple reflections in the inner space and reduce the undesirable emissions into the air. After thermal annealing treatment, the ultrathin film with intercalation of the carbonized yarn-ball-shaped CNF/MWCNT microspheres exhibited enhanced EMWs absorption as an important part of shielding effectiveness (45.1±0.9 dB) as well as excellent mechanical stability (≈0.9 million bending times). Thus, the well-designed structure of multilayered hybrid films with intercalated conductive microspheres can be a good candidate for higher absorption in EMI shielding effectiveness and outstanding mechanical properties.


Esc peptides as novel potentiators of defective cystic fibrosis transmembrane conductance regulator: an unprecedented property of antimicrobial peptides.
Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein lead to persistent lung bacterial infections, mainly due to Pseudomonas aeruginosa, causing loss of respiratory function and finally death of people affected by CF. Unfortunately, even in the era of CFTR modulation therapies, management of pulmonary infections in CF remains highly challenging especially for patients with advanced stages of lung disease. Recently, we identified antimicrobial peptides (AMPs), namely Esc peptides, with potent antipseudomonal activity. In this study, by means of electrophysiological techniques and computational studies we discovered their ability to increase the CFTR-controlled ion currents, by direct interaction with the F508del-CFTR mutant. Remarkably, this property was not explored previously with any AMPs or peptides in general. More interestingly, in contrast with clinically used CFTR modulators, Esc peptides would give particular benefit to CF patients by combining their capability to eradicate lung infections and to act as promoters of airway wound repair with their ability to ameliorate the activity of the channel with conductance defects. Overall, our findings not only highlighted Esc peptides as the first characterized AMPs with a novel property, that is the potentiator activity of CFTR, but also paved the avenue to investigate the functions of AMPs and/or other peptide molecules, for a new up-and-coming pharmacological approach to address CF lung disease.


Transcription patterns of human papillomavirus type 16 in genital intraepithelial neoplasia: evidence for promoter usage within the E7 open reading frame during epithelial differentiation.
Human papillomavirus (HPV) type 16 transcription was analysed by in situ hybridization using 125I-labelled subgenomic riboprobes, from 26 genital intraepithelial neoplastic (IN) lesions, in formalin-fixed biopsies from 18 different cases. Distinct transcription patterns separable by the presence or absence of late gene transcription were detected. In 12 lesions, late gene expression was absent; HPV transcripts corresponding to the E6 and E7 open reading frame (ORF) were detectable in all basal cells and were usually evenly distributed through all layers of the epithelium. Transcripts corresponding to the E1, E2 and E2/E4 ORFs were present in nine of 12 lesions and displayed a similar distribution. In 14 lesions late gene transcripts were present. E6 and E7 transcripts were detectable basally in all but one lesion. The levels of E7 but not E6 transcripts were markedly increased in the superficial cells of differentiating epithelia, with an identical distribution and at similar levels to those of the E2/E4 transcript. We propose that the most abundant transcript in genital IN lesions containing late gene expression is an E7/E1 [symbol: see text] E2/E4 transcript corresponding to that reported in HPV-6/11 condylomata and which is derived from a similar promoter within the E7 ORF.


Stimulant and atypical antipsychotic medications for children placed in foster homes.
The purpose of this study is to examine the use of prescribed psychoactive medications in a prospective cohort of children shortly after they entered foster homes; and to identify demographics, maltreatment history, psychiatric diagnoses including ADHD comorbidity, and level of aggression that contribute to prescribed use of stimulant and atypical antipsychotic medication over time. The sample included N = 252 children (nested in 95 sibling groups) followed for three years up to 4 yearly waves. Nearly all (89%) met criteria for at least one of eight psychiatric diagnoses and 31% (75/252) used one or more prescribed psychoactive medications. Over half (55%) were diagnosed with Attention Deficit Hyperactivity Disorder (ADHD); of these 38% used stimulants and 36% used atypical antipsychotics. Of the 75 medicated children, 19% received ≥3 different classes of drugs over the course of the study. Stimulants (69%) and atypical antipsychotics (65%) were the most frequently used drugs among medicated children. Adjusted odds ratios (AOR) showed that male gender (AOR = 3.2; 95% CI = 1.5-9.3), African American vs Latino ethnicity (AOR = 5.4; 95% CI = 2.1-14.2), ADHD regardless of Oppositional Defiant (ODD) or Conduct (CD) comorbidity (AOR = 6.0, 95% CI = 1.3-27.5), ODD or CD (AOR = 11.1, 95% CI = 2.1-58.6), and Separation Anxiety (AOR = 2.0, 95% CI = 1.0-4.0) psychiatric disorders were associated with the use of prescribed stimulants; while male gender (AOR = 3.8, 95% CI = 1.5-9.3), African American vs Latino (AOR = 5.1, 95% CI = 1.2-9.2) or Mixed/Other ethnicity (AOR = 3.3, 95% CI = 1.9-13.7), ADHD regardless of ODD or CD comorbidity (AOR = 5.8, 95% CI = 1.2-28.7), ODD or CD (AOR = 13.9, 95% CI = 3.3-58.5), Major Depression/Dysthymia (AOR = 2.8, 95% CI = 1.1-6.7) psychiatric disorders, and history of sexual abuse (AOR = 4.6, 95% CI = 1.3-18.4) were associated with the use of prescribed atypical antipsychotics. The aggressive use of atypical antipsychotics, which has unknown metabolic risks, suggests that the efficacy and safety of such treatment strategies for psychiatrically ill children in foster care should be monitored.


Translation of a patient-surgeon relationship assessment instrument (Q-PASREL) into six languages.
The Questionnaire for Patient-Surgeon Relationship (Q-PASREL) is a French "Patient-Reported Experience Measure" for hand surgery patients. It is the only one which considers the impact of the patient-surgeon relationship on time to return to work and cooperation by the surgeon for administrative issues. It has been shown that a good Q-PASREL score is associated with shorter sick leave and faster return to work. To make this instrument available to more countries, we translated the Q-PASREL into six languages (English, Spanish, German, Italian, Arabic and Persian), following a validated "translation and cultural adaptation" process guideline. This process includes multiple forward and backward translations, discussions and reconciliations with final harmonization and cognitive debriefing. For each language, a team was set up, comprising a key in-country hand surgery consultant, native target-language speaker and fluent in French, and several forward and back translators. The final translated versions were reviewed and approved by the project manager. The six versions of Q-PASREL are now available in the appendices of this publication.


Hepatitis C in chronic liver disease: an epidemiological study based on 566 consecutive patients undergoing liver biopsy during a 10-year period.
We analysed the presence of hepatitis C virus (HCV) antibodies in 566 patients undergoing liver biopsy. While over 20% of the patients were anti-HCV positive according to ELISA, only 13.8% had HCV antibodies when tested with a four-antigen recombinant immunoblot assay (RIBA 2). At the time of inclusion in the study, most patients were asymptomatic, irrespective of whether they were HCV-positive. Histological findings in anti-HCV-positive patients were chronic persistent hepatitis, chronic active hepatitis or cirrhosis in greater than 75% of cases. Only four of the patients who were anti-HCV-positive according to the RIBA 2 had autoimmune chronic active hepatitis. Risk behaviour could be identified in the majority of cases. Community-acquired sporadic cases were rare (12%). Of the 153 patients who died during follow-up, 23 subjects were anti-HCV positive. Although age- and sex-adjusted survival was not shorter in anti-HCV-positive patients than in anti-HCV-negatives, the risk of hepatocellular cancer was higher (P = 0.01). We conclude that HCV infection is associated with chronic liver disease, even when critical evidence of viral aetiology is slight. Truly sporadic cases are rare. Patients infected with HCV are at increased risk of developing hepatocellular cancer.


Prevalence of internalisation-associated gene, prtF1, among persisting group-A streptococcus strains isolated from asymptomatic carriers.
The failure of antibiotic treatment to eradicate group-A streptococci in up to 30% of patients with pharyngotonsillitis is unexplained. Some strains of group-A streptococci can enter respiratory epithelial cells, where they would be inaccessible to antibiotics unable to penetrate the cell membrane, such as penicillins. The fibronectin-binding proteins, F1 and SfbI, are needed for this process. We hypothesised, therefore, that an intracellular reservoir of group-A streptococci could account, at least partly, for failure to eradicate throat carriage, and that the presence of the gene for fibronectin-binding protein (F1) might be linked to the ability of a strain to persist in the throat after therapy. We investigated the frequency of prtF1-containing strains among 67 patients with pharyngotonsillitis. All patients were clinically cured, although 13 of them continued to carry group-A streptococci in the throat during or after therapy. To distinguish between persisting and recolonising strains, isolates from the 13 patients were serologically tested and compared by polymorphic DNA-amplification technique. 12 (92%) of the 13 patients with symptomless carriage had prtF1-containing strains in the throat, compared with 16 (30%) of the 54 patients with successful eradication (p=0.0001). Three of the 13 eradication-failure patients were recolonised with strains that differed from the pretreatment strains. Nine of the ten (90%) persisting strains carried prtF1 (p=0.0009). Our findings suggest that protein-F1-mediated entry to cells is involved in the causative process of the carriage state.


Detailed heart rate variability analysis in athletes.
Heart rate variability (HRV) analysis has been used to evaluate patients with various cardiovascular diseases. While the vast majority of HRV studies have focused on pathological states, our study focuses on the less explored area of HRV analysis across different training intensity and sports. We aimed to measure HRV in healthy elite and masters athletes and compare to healthy, but non-athletic controls. Time-domain HRV analysis was applied in 138 athletes (male 110, age 28.4 ± 8.3) and 100 controls (male 56, age 28.3 ± 6.9) during Holter monitoring (21.3 ± 3.0 h). All studied parameters were higher in elite athletes compared to controls [SDNN (CI) 225.3 (216.2-234.5) vs 158.6 (150.2-167.1) ms; SDNN Index (CI) 99.6 (95.6-103.7) vs 72.4 (68.7-76.2) ms; pNN50 (CI) 24.2 (22.2-26.3) vs 14.4 (12.7-16.3) %; RMSSD (CI) 71.8 (67.6-76.2) vs 50.8 (46.9-54.8) ms; p < 0.001]. Masters had higher HRV values than controls, but no significant differences were found between elite athletes and masters athletes. Some parameters were higher in canoeists-kayakers and bicyclists than runners. Lower cut-off values in elite athletes were SDNN: 147.4 ms, SDNN Index: 66.6 ms, pNN50: 9.7 %, RMSSD: 37.9 ms. Autonomic regulation in elite athletes described with HRV is significantly different than in healthy controls. Sports modality and level of performance, but not age- or sex-influenced HRV. Our study provides athletic normal HRV values. Further investigations are needed to determine its role in risk stratification, optimization of training, or identifying overtraining.


Increased FGF23 serum level is associated with unstable carotid plaque in type 2 diabetic subjects with internal carotid stenosis.
The object of this study was to investigate the potential role of FGF23 on plaque stability in type 2 diabetic patients with internal carotid artery stenosis. In this retrospective observational study, we analyzed FGF23 serum level in 361 type 2 diabetic patients with internal carotid artery stenosis undergoing carotid endarterectomy and in 598 diabetic controls without carotid atherosclerosis. We found that FGF23 median serum levels was significantly higher in patients than in diabetic controls [67.7 (59.5-77.8) pg/mL and 43.89 (37.5-50.4), P < 0.001] and was significantly and independently associated with unstable plaque in patients with internal carotid artery stenosis [OR, 5,71 (95% CI, 2.09-15.29]. We have found, for the first time, that FGF23 could be associated with unstable plaque in type 2 diabetic patients with internal carotid artery stenosis.


RNA-responsive elements for eukaryotic translational control.
The ability to control translation of endogenous or exogenous RNAs in eukaryotic cells would facilitate a variety of biotechnological applications. Current strategies are limited by low fold changes in transgene output and the size of trigger RNAs (trRNAs). Here we introduce eukaryotic toehold switches (eToeholds) as modular riboregulators. eToeholds contain internal ribosome entry site sequences and form inhibitory loops in the absence of a specific trRNA. When the trRNA is present, eToeholds anneal to it, disrupting the inhibitory loops and allowing translation. Through optimization of RNA annealing, we achieved up to 16-fold induction of transgene expression in mammalian cells. We demonstrate that eToeholds can discriminate among viral infection status, presence or absence of gene expression and cell types based on the presence of exogenous or endogenous RNA transcripts.


The future of susceptibility contrast for assessment of anatomy and function.
The magnetic properties of tissues affect MR images and differences in magnetic susceptibility can be utilized to provide impressive image contrast. Specifically, phase images acquired with gradient echo MRI provide unique and superb contrast which reflects variations in the underlying tissue composition. There is great interest in extracting tissue susceptibility from image data since magnetic susceptibility is an intrinsic tissue property that reflects tissue composition much more closely than MRI phase. Still, this major tissue contrast mechanism is largely unexplored in magnetic resonance imaging because non-conventional reconstruction and dipole deconvolution are required to quantitatively map tissue susceptibility properly. This short review summarizes the current state of susceptibility contrast and susceptibility mapping and aims to identify future directions.


Post-proline cleaving enzyme. Synthesis of a new fluorogenic substrate and distribution of the endopeptidase in rat tissues and body fluids of man.
Synthesis and application of the first fluorogenic substrate, N-carbobenzoxyglycylprolyl-4-methylcoumarinyl amide (Z-Gly-Pro-MeCouNH) for the determination of the post-proline cleaving enzyme (EC 3.4.21.-) were reported. Maximal activity of the enzyme purified from lamb kidney for the new substrate was observed at pH 7.0. This substrate showed a higher affinity (Km = 0.02 mM) for the enzyme than the proline containing substrates studied previously and allowed the detection of 10-50 ng post-proline cleaving enzyme activity per ml sample after a 1 min incubation period. Distribution of post-proline cleaving enzyme and other proline specific peptidases in rat tissues was studied using Z-Gly-Pro-MeCouNH and other proline-containing substrates. High post-proline cleaving enzyme activity was observed in testis, liver and skeletal muscle. Inhibition experiments indicated that post-proline cleaving enzyme activity was completely inactivated by 0.1 mM diisopropylphosphofluoridate and Z-Gly-Pro-chloromethylketone, as had been found in the case of the enzyme isolated from lamb kidney. Activity in human body fluids was also tested for levels of post-proline cleaving enzyme activity using Z-Gly-Pro-MeCouNH and semen was found to show the highest cleaving activity.


Organization of projections from the superior colliculus to the thalamic lateral posterior nucleus in the rat.
Injections of horseradish peroxidase into the lateral posterior nucleus (LP) of the rat thalamus resulted in retrograde labeling of neurons in the superior colliculus (SC). Approximately 80% of the labeled cells occurred in the stratum opticum and 20% in the stratum griseum superficiale. The system of projections is organized such that medial parts of SC project to dorsal LP and lateral parts of SC project to ventral LP.


Age, race, comorbidity, and insurance payer type are associated with outcomes after total ankle arthroplasty.
To assess whether age, race/ethnicity, comorbidity, and insurance payer status are associated with outcomes after total ankle arthroplasty (TAA). Using the US National Inpatient Sample (NIS) data and multivariable-adjusted logistic regression, we assessed the association of age, race/ethnicity, comorbidity ,and insurance payer status, with healthcare utilization and in-hospital complications (infection, transfusion, and revision surgery) after TAA. We calculated odds ratio (OR) and 95% confidence intervals (CI). The cohort consisted of 6280 TAAs with a mean age of 62 years; 52% were female, 70% White, and 62% had osteoarthritis as the underlying diagnosis. Compared to age < 50 years, older age categories had higher ORs of total hospital charges above the median, length of hospital stay above the median (>2 days) and discharge to a rehabilitation facility, 1.26-19.41, and a lower OR of in-hospital infection, 0.07-0.09. Compared to Whites, Blacks had higher OR (95% CI) of: discharge to a rehabilitation facility, 1.45 (1.06, 1.98); length of hospital stay >2 days, 2.21 (1.37, 3.57); in-hospital transfusion, 4.39 (1.87, 10.30); and in-hospital revision, 8.25 (1.06, 64.21); and Hispanics were more likely to have total hospital charges above the median, OR 1.49 (1.10, 2.02), and infection, 9.30 (1.27, 68.05). Higher comorbidity and Medicare payer status were each associated with higher ORs of healthcare utilization, ORs ranging 1.20-2.57 and 1.74-2.19, respectively. Age, race/ethnicity, comorbidity, and insurance payer status were independently associated with post-TAA outcomes. Further insight into modifiable mediators of these associations can pave the way for improving these outcomes in the future.Key Points• Older age was associated with higher healthcare utilization post-ankle arthroplasty.• Compared to Whites, Blacks or Hispanics had higher healthcare utilization and in-hospital complications post-ankle arthroplasty.• Higher comorbidity and Medicare payer status were each associated with higher healthcare utilization post-ankle arthroplasty.


A comparison of radiotherapy and surgery as primary treatment in the management of T3 N0 M0 glottic tumours.
Seventy-four patients with Stage T3 N0 M0 squamous carcinoma of the glottis were treated initially by either surgery or radiotherapy between 1980 and 1985. The treatment adopted was determined by consultant preference. The long-term survival in both groups was approximately the same. Of 38 patients treated initially by radiotherapy, 25 had local recurrence. Fifteen of these underwent salvage surgery and 10 died of disease. Thirteen patients (33 per cent) retained their larynx. One of the major advantages of treating patients with stage T3 N0 M0 carcinoma of larynx by radiotherapy initially is that approximately one-third will retain their larynx. Local recurrences can usually be treated readily by salvage surgery.


Temporal continuity of self: Long autocorrelation windows mediate self-specificity.
The self is characterized by an intrinsic temporal component consisting in continuity across time. On the neural level, this temporal continuity manifests in the brain's intrinsic neural timescales (INT) that can be measured by the autocorrelation window (ACW). Recent EEG studies reveal a relationship between resting state ACW and self-consciousness. However, it remains unclear whether ACW exhibits different degrees of task-related changes during self-specific compared to non-self-specific activities. To this end, participants in our study initially recorded an eight-minute autobiographical narrative. Following a resting-state session, participants were presented with their own narrative and the narrative of a stranger while undergoing concurrent EEG recording. Behaviorally, subjects evaluated both of the narratives and indicated their perceptions of positivity or negativity on a moment-to-moment basis by positioning a cursor relative to the center of the computer screen. Our results indicate: (a) greater spatial extension and velocity in the behavioral cursor movement during the self narrative assessment compared to the non-self narrative assessment; and (b) longer neural ACWs in response to the self- compared to the non-self narrative and rest. These findings demonstrate the importance of longer temporal windows in neural activity measured by ACW for self-specificity. More broadly, the results highlight the relevance of temporal continuity for the self on the neural level. Such temporal continuity may, correspondingly, also manifest on the psychological level as a "common currency" between brain and self.


AGE-TXNIP axis drives inflammation in Alzheimer's by targeting Aβ to mitochondria in microglia.
Alzheimer's disease (AD) is the most common form of dementia characterized by progressive memory loss and cognitive decline. Although neuroinflammation and oxidative stress are well-recognized features of AD, their correlations with the early molecular events characterizing the pathology are not yet well clarified. Here, we characterize the role of RAGE-TXNIP axis in neuroinflammation in relation to amyloid-beta (Aβ) burden in both in vivo and in vitro models. In the hippocampus of 5xFAD mice microglial activation, cytokine secretion, and glial fibrillary acidic protein-enhanced expression are paralleled with increased TXNIP expression. TXNIP silencing or its pharmacological inhibition prevents neuroinflammation in those mice. TXNIP is also associated with RAGE and Aβ. In particular, RAGE-TXNIP axis is required for targeting Aβ in mitochondria, leading to mitochondrial dysfunction and oxidative stress. Silencing of TXNIP or inhibition of RAGE activation reduces Aβ transport from the cellular surface to mitochondria, restores mitochondrial functionality, and mitigates Aβ toxicity. Furthermore, Aβ shuttling into mitochondria promotes Drp1 activation and exacerbates mitochondrial dysfunction, which induces NLRP3 inflammasome activation, leading to secretion of IL-1β and activation of the pyroptosis-associated protein Gasdermin D (GSDMD). Downregulation of RAGE-TXNIP axis inhibits Aβ-induced mitochondria dysfunction, inflammation, and induction of GSDMD. Herein we unveil a new pathway driven by TXNIP that links the mitochondrial transport of Aβ to the activation of Drp1 and the NLRP3 inflammasome, promoting the secretion of IL-1β and the pyroptosis pathway associated with GSDMD cleavage. Altogether these data shed new light on a novel mechanism of action of RAGE-TXNIP axis in microglia, which is intertwined with Aβ and ultimately causes mitochondria dysfunction and NLRP3 inflammasome cascade activation, suggesting TXNIP as a druggable target to be better deepened for AD.


Introduction to the pathways involved in the activation and regulation of sperm motility: A review of the relevance of ion channels.
To participate in sperm-oocyte fusion, spermatozoa need to be motile. In the testes, spermatozoa are immotile, although these gametes acquire the capacity for motility during the transit through the epididymis. During the period of epididymal transport from the male genital tract to the female genital tract, spermatozoa exhibit various types of motility that are regulated by complex signalling and communication mechanisms. Because motility is very dynamic, it can be affected by small changes in the external or internal environment of spermatozoa within a very short time. This indicates that regulatory membrane proteins, known as sperm ion channels, are involved in the regulation of sperm motility. Research results from studies, where there was use of electrophysiological, pharmacological, molecular and knock-out approaches, indicate ion channels are possibly involved in the regulation of sperm membrane polarisation, intracellular pH, motility, energy homeostasis, membrane integrity, capacitation, hyperactivity, acrosome reaction and fertilisation processes. In this review, there is summarisation of the key functions that ion channels have in the regulation, initiation, maintenance, and modulation of sperm motility. In addition, in this review there is highlighting of novel insights about the pathways of ion channels that are activated in spermatozoa while these gametes are located in the oviduct leading to the fertilisation capacity of these cells.


Influence of the implant scan body bevel location, implant angulation and position on intraoral scanning accuracy: An in vitro study.
To assess the influence of the scan body geometry bevel location and implant angulation and position of complete-arch implant digital scans. Two definitive casts with 4 implant analogs placed parallel (P group) or angulated up to 30° (NP group) were fabricated. Five subgroups were created based on the scan body geometry bevel position: facial, mesial, distal, lingual, or random (F, M, D, L, and R subgroup). Casts were digitized using a laboratory scanner (reference) (7Series Desktop Scanner) and an intraoral scanner (TRIOS 3). The implant position discrepancies between the reference and experimental scans were calculated. Data was analyzed using 3-way ANOVA and Tukey tests (α = .05). The scan body geometry bevel position (P < .001) and the inter-implant distance (P < .001) were shown as significant predictors of the linear discrepancies obtained. The L subgroup had a significantly lower discrepancy compared with the other subgroups. Implant angulation (P < .001), the scan body geometry bevel position (P < .001), and the inter-implant distance (P < .001) were all significant predictors on the angular discrepancies obtained. The scan body geometry bevel location and implant angulation and position influenced the accuracy of the IOS tested. The lingual orientation obtained significantly better accuracy values compared with the other positions. The parallel implant analog position obtained better accuracy than the angulated positions. Lastly, the implant positioned in the dental arch where the intraoral digital scan was finished obtained significantly higher distortion than the contralateral implant.


Reducing post-caesarean surgical wound infection rate: an improvement project in a Norwegian maternity clinic.
During 2006 and 2007 the rate of caesarean section surgical wound infection was 17,4 % in Baerum Hospital. The objective was to reduce the incidence to below the Norwegian national level of 8 %. The intervention (a quality improvement project) was implemented in September 2008. A bundle of measures were introduced. Staff from all aspects of patient flow was recruited. Cochrane literature was used as gold standard. Data registration was based upon CDC criteria. were based on data collected through the Norwegian national surveillance system for infections in health care, NOIS. Study setting This Maternity clinic has about 2500 births annually and a caesarean section rate pushing 15 %. The study was conducted on caesarean section patients registered in NOIS (2008-2010). From September 2009 data were harvested continuously. Data were monitored as cumulative incidence rate and by statistical process control as g chart (number of surgeries between infections including a delayed moving average). Infection control staff reported results to Head of Maternity Clinic monthly. The overall rate of caesarean section surgical wound infections was significantly reduced to 3,1 % (2008-2010 about 1 % in 2010). This result was demonstrated elegantly as a marked shift in process in g-chart. We found the g-chart was efficient, sensitive and simple to handle.


Development and validation of the Spirituality Instrument-27© (SpI-27©) in individuals with chronic illness.
To develop and validate the Spirituality Instrument 27 (SpI-27©) in individuals with chronic illness (n = 249). A need for a rigorously developed spirituality instrument that can be used with people who are religious and non-religious was identified. The initial 46-item instrument was developed from a concept analysis, a review of theoretical and empirical literature, and an appraisal of instruments measuring spirituality. Content validity was established with user focus groups and an expert panel review. A pilot study evaluated the online mode of administration and a descriptive correlational design assessed the reliability and validity of the instrument. Results of exploratory factor analysis concluded a five-factor solution with 27 items: Connectedness with Others, Self-Transcendence, Self-Cognisance, Conservationism, and Connectedness with a Higher Power. Cronbach's alpha coefficients ranged from 0.823 to 0.911 for the five factors, and 0.904 for the overall scale. Paired t-tests, intra-class correlations, and weighted kappa values supported the temporal stability of the instrument. A significant and positive correlation was found between the SpI-27© and the Spirituality Index of Well-Being (p < 0.01), supporting convergent validity. Findings support the validity and reliability of the SpI-27©, which was developed with patient input and is underpinned by theoretical and empirical literature. The SpI-27© should be validated for use with other samples. The conceptual framework that guided the study can be used to enhance healthcare professionals' understanding of spirituality and its core dimensions.


Susceptibility of human ocular melanoma cells to spontaneous and interferon-augmented natural cytotoxicity.
Due to the current interest in natural killer (NK) cells as a host defence mechanism against neoplasia, we have investigated the susceptibility of short-term cultures of human ocular melanoma cells to spontaneous and interferon (IFN)-augmented natural cytotoxicity. Cultures of ocular melanoma cells were readily established and identified as bipolar and multipolar pigmented melanoma cells. In short-term cytotoxicity assays these cell lines demonstrated a weak susceptibility to spontaneous human PBL natural cytotoxicity, and increased killing was observed using IFN-augmented cytotoxic effector cells. These findings may be pertinent in relation to the role of NK cells in vivo.


Acceptability and Feasibility of Peer Specialist-Delivered Virtual Reality Job Interview Training for Individuals with Serious Mental Illness: A Qualitative Study.
This study explored peer specialists' perspectives on delivering vocational interventions, especially Virtual Reality Job Interview Training (VR-JIT). Five focus groups of peer specialists (N = 34) explored their beliefs about vocational services, including VR-JIT. We trained eight peer specialists to be VR-JIT "instructors" and interviewed them about using VR-JIT in their mental health practice. Generally, participants discussed tailoring their vocational services to include sharing their story of recovery. Specifically, participants perceived VR-JIT as acceptable and feasibly implemented within their practice. Overall, participants viewed VR-JIT as a higher level of service and they would be uniquely qualified to support consumers using the tool.


Take a Number? Surgical Waiting Times for Transurethral Bladder and Prostate Surgery in Albany, New York.
Surgical waiting times are considered an important measure of quality of health care delivery. We determined the surgical waiting times for transurethral bladder tumor resection and transurethral prostate resection at our institution, and examined the factors that affected these waiting times. We performed a retrospective chart review of 272 consecutive patients who underwent transurethral bladder tumor resection and 113 consecutive patients who underwent transurethral prostate resection. We determined dates of referral, initial evaluation, decision for surgery and date of surgery. We also examined patient factors such as age, gender, indication for surgery, specific surgeon, type of insurance, new vs established patient, ASA® score and final tissue pathology. Median time from the decision for surgery to the date of surgery was 22 days for patients undergoing transurethral bladder tumor resection. Factors associated with a shorter waiting time were year of surgery and specific surgeon. Median waiting time for patients undergoing transurethral prostate resection from decision for surgery to date of surgery was 27 days. Factors associated with a shorter waiting time included age, Medicare insurance coverage, ASA score greater than 2 and indication for surgery. These are the first data to our knowledge from the U.S. health care system in examining wait times for transurethral bladder cancer surgery and transurethral prostate surgery. With the increasing focus on improving quality of care, surgical waiting times may be used in the U.S. as a quantifiable measure of quality in health care systems. The factors associated with longer waiting times in this study may allow health care systems to target areas for improvement.


Cadmium exposure and risk of lung cancer: a meta-analysis of cohort and case-control studies among general and occupational populations.
The association between cadmium exposure and risk of lung cancer is still unclear. We quantitatively reviewed the observational studies that investigated the association between cadmium exposure and lung cancer risk in both general and occupational populations published through April 2015. The final data set is comprised of three cohort studies in the general population totaling 22,551 participants (354 events) with a mean follow-up of 15 years, five occupational cohort studies including 4205 individuals (180 events) with an average follow-up of 31 years, and three occupational case-control studies including 4740 cases and 6268 controls. Comparing the highest to the lowest category of cadmium exposure, the weighted relative risk and 95% confidence interval of lung cancer in the general population was 1.42 (95% CI (0.91, 2.23)); the weighted risk estimates (95% CIs) of lung cancer in three occupational cohort studies and three case-control studies were 0.68 (95% CI (0.33, 1.41)) and 1.61 (95% CI (0.94, 2.75)), respectively. No linear association was found. When comparing participants exposed to cadmium with non-exposed based on available data, the association became statistically significant. According to findings from this meta-analysis, the possibility that cadmium exposure may increase risk of lung cancer cannot be completely ruled out in either general or occupational population.


Plasma and urinary digoxin in thyroid dysfunction.
The response to a single oral dose of 0.5 mg digoxin has been studied in eight patients, of whom four were hyperthyroid and four were hypothyroid, both before and after treatment for their thyroid dysfunction. The post-dose plasma digoxin levels were significantly lower in the hyperthyroid patients when they were thyrotoxic than when they became euthyroid. In only one hypothyroid patient was the post-dose plasma digoxin level significantly higher before treatment than it was after and in the others the digoxin values reached were either the same as, or lower than, before treatment. There was a significant correlation between the creatinine clearance and the urinary concentrations of digoxin and these both altered with change in thyroid status. Total urinary digoxin excretion did not change. Pharmacokinetic analysis suggested that digoxin was distributed in a way compatible with a two-compartment model and that the volume of the central compartment was high in thyrotoxic patients and low in hypothyroid patients. In both cases it reverted to a median value after treatment. It is recommended that plasma digoxin levels should be monitored in all patients with thyroid dysfunction who require therapeutic digoxin.


Evaluation of diplopia as a vital and remarkable ocular finding among cancer patients.
Diplopia is an important and debilitating symptom of malignancies due to different pathogenetic mechanisms. Data is lacking in the literature because of the rarity of the diplopia in patients with cancer. We aimed to evaluate the etiological and clinical factors of diplopia in patients with different types of cancer. We retrospectively investigated 22 cancer patients with diplopia who were admitted between 2018 and 2021. The diagnosis of primary cancer, the underlying factors causing diplopia, and the life expectancy after diplopia were evaluated. Among available data of 620 cancer patients applied to our ophthalmology department, 22 (3.55%) had diplopia. Paralytic strabismus was found in 19 patients and restrictive strabismus was found in 3 patients. Among the paralytic cases, 6th nerve palsy was found to be the most common with a rate of 68%. In 18 of 22 (82%) patients, the cause of diplopia was due to orbital or brain metastasis or local invasion. Two patients had diplopia secondary to radiotherapy and 2 had diplopia due to chemotherapy. Metastasis is the most common cause of diplopia in patients with cancer and screening for metastasis is crucial as soon as diplopia begins for a better life expectancy.


Actions of vanadate on vascular tension and sodium pump activity in cat isolated cerebral and femoral arteries.
1. The mechanisms involved in the responses induced by sodium vanadate (Va3 VO4) on cat cerebral and femoral arteries were studied. The possibility that these responses were due to Na+, K+-ATPase inhibition was investigated by measuring the effect of vanadate on [3H]-ouabain binding to arterial membrane fractions, K+-induced vasodilatation and ouabain-sensitive 86Rb+ uptake. 2. The vanadium compounds (Na3VO4, VOSO4, VCl3 and O5V3) induced similar, concentration-dependent contractions in each kind of artery, the cerebral vessels being the most sensitive to these compounds. 3. Exposure of the arteries to a low-Na+ (25 mM) solution suppressed the contraction caused by vanadate in femoral but not in cerebral arteries. 4. Vanadate-induced contractions were reduced in Ca2+-free medium but remained unaffected by 3 x 10(-6) M phentolamine, reserpine pretreatment or 3 x 10(-6) M verapamil in both kinds of artery. 5. The addition of 7.5 mM K+ to the arteries immersed in a K+-free solution induced vasodilatation, which was not modified by 10(-3) M vanadate. 6. The consecutive administration of ouabain (10(-4) M) and vanadate (10(-3) M) (or vice versa), or the simultaneous administration of both agents (10(-8) to 10(-3) M) appeared to produce an additive contraction in both types of artery. 7. Vanadate (10(-7) to 10(-3) M) did not displace the [3H]-ouabain binding to arterial membrane fractions of these arteries, whereas 10(-4) M ouabain did. 8. In both kinds of artery, total 86Rb+ uptake was reduced by ouabain (10(-8) to 10(-3) M), in a concentration-dependent manner, whereas it was not modified by vanadate (10(-8)-10(-3) M). 9. These results suggest that vanadate induces contraction in both types of artery by a mechanism unrelated to Na+, K+-ATPase inhibition. Such a mechanism is likely to be related to inhibition of the Ca2-ATPase of the cell membrane and/or the sarcoplasmic reticulum.


Attenuation of Th1 effector cell responses and susceptibility to experimental allergic encephalomyelitis in histamine H2 receptor knockout mice is due to dysregulation of cytokine production by antigen-presenting cells.
Histamine, a biogenic amine with both neurotransmitter and vasoactive properties, is well recognized as an immunomodulatory agent in allergic and inflammatory reactions. It also plays a regulatory role in the development of antigen-specific immune responses. CD4+ T-cells from histamine H1 receptor (H1R)-deficient (H1RKO) mice produce significantly less interferon-gamma and more interleukin (IL)-4 in in vitro recall assays compared to wild-type controls. H1RKO mice are also less susceptible to acute early-phase experimental allergic encephalomyelitis indicating that H1R signaling in CD4+ T cells plays a central role in regulating pathogenic T-cell responses. In this study, we show that mice lacking histamine H2 receptor (H2RKO) are similar to H1RKO mice in that they develop encephalitogen-specific T-cell responses as assessed by proliferation and IL-2 production and present with less severe acute early-phase experimental allergic encephalomyelitis. However, unlike T cells from H1RKO mice, which exhibit a strong Th2 bias, T cells from H2RKO mice do not. Rather, they are uniquely characterized by a significant inhibition of Th1 effector cell responses. Given that both histamine and adjuvants such as pertussis toxin modulate antigen-presenting cell (APC) maturation and function, including T-cell-polarizing activity, we analyzed the cytokines/chemokines secreted by APCs from wild-type, H1RKO, and H2RKO mice. Significant differences in cytokine/chemokine production by APCs from unimmunized and immunized mice were delineated. APCs from H2RKO mice produce significantly less IL-12 and IL-6 and markedly greater amounts of MCP-1 compared to wild-type and H1RKO mice. Because MCP-1 is known to inhibit IL-12 production, the failure of H2RKO mice to generate encephalitogenic Th1 effector cell responses is consistent with inhibition of negative regulation of MCP-1 secretion by H2R signaling in APCs.


Colonoscopy in the elderly. Low risk, high yield.
An evaluation of the utility, morbidity, and patient tolerance of colonoscopy in elderly (> or = 70 years) patients was undertaken and compared to data for a similar group of younger patients (50-70 years) who underwent colonoscopy during the same 48 months. Data reviewed for both groups included demographics, indications for colonoscopy, effectiveness of bowel preparation, colonoscopy completion, endoscopic findings, and complications. The mean age of the entire 656-patient population was 69 +/- 10 years; 87 (25%) of the 354 elderly patients were greater than 80 years of age and the average age of the 302-member control group was 59.8 +/- 5.8 years. Indications for colonoscopy were the same in both groups and included rectal bleeding, 134 (20%); prior colorectal operation, 115 (18%); a history of adenomatous polyps, 82 (12%); guaiac-positive stools, 49 (8%); abnormal finding on barium enema, 19 (3%); and miscellaneous other gastrointestinal symptoms, 151 (23%). Screening colonoscopy was performed in 106 (16%). Colonoscopy was successfully completed to the cecum or the ileocolic anastomosis in 85% (555/656) of the entire population. Only 78% (275/354) of elderly patients had colonoscopy successfully completed compared to 93% (281/302) of their younger counterparts (P = 0.001). Elderly patients were significantly more likely to have an abnormality than younger patients (74% vs 60%, P < 0.05). Malignant colorectal neoplasia was more common in the elderly (6% vs 2%, P = 0.03); however, benign neoplasia was equally present in both age groups (30% vs 27%, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)


[Traumatic tricuspid valve insufficiency with right-to-left shunt: bridging using extracorporeal venovenous membrane oxygenation].
The case of a young male motor vehicle driver is reported who suffered multiple trauma in a car accident with pulmonary and cardiac contusions. In the course of severe pneumonia and traumatic tricuspid valve insufficiency a right-to-left shunt with refractory hypoxemia developed across a pre-existing atrial septal defect (ASD). The patient could be successfully treated by the combination of extracorporeal membrane oxygenation for bridging, interventional ASD occlusion and in the long-term by operative reconstruction of the tricuspid valve.


Qualitative changes in the proteome of extracellular vesicles accompanying cancer cell transition to mesenchymal state.
Transitions of the cancer cell phenotype between epithelial and mesenchymal states (EMT) are likely to alter the patterns of intercellular communication. In this regard we have previously documented that EMT-like changes trigger quantitative rearrangements in exosomal vesicle emission in A431 cancer cells driven by oncogenic epidermal growth factor receptor (EGFR). Here we report that extracellular vesicles (EVs) produced by these cancer cells in their epithelial and mesenchymal states exhibit profound qualitative differences in their proteome. Thus, induction of the EMT-like state through blockade of E-cadherin and EGFR stimulation provoked a mesenchymal shift in cellular morphology and enrichment in the CD44-high/CD24-low immunophenotype, often linked to cellular stemness. This change also resulted in reprogramming of the EV-related proteome (distinct from that of corresponding cells), which contained 30 unique protein signals, and revealed enrichment in pathways related to cellular growth, cell-to-cell signaling, and cell movement. Some of the most prominent EV-related proteins were validated, including integrin α2 and tetraspanin CD9. We propose that changes in cellular differentiation status translate into unique qualitative rearrangements in the cargo of EVs, a process that may have implications for intercellular communication and could serve as source of new biomarkers to detect EMT-like processes in cancer.


The G894T polymorphism on endothelial nitric oxide synthase gene is associated with premature coronary artery disease in a Turkish population.
The aim of the present study was to investigate the association between premature coronary artery disease and Glu298Asp polymorphism of the endothelial nitric oxide synthase gene. The eNOS gene polymorphism was analysed in 115 (mean age, 48.1+/-7.9 years) Turkish patients with a diagnosis of premature coronary artery disease and 83 (mean age, 44.6+/-1.4 years) control subjects. The Glu298Asp polymorphism of the endothelial nitric oxide synthase gene was determined by polymerase chain reaction and restriction fragment length polymorphism. The patients group showed an increase in the frequency of the T allele compared to controls (0.456 versus 0.169, p=0.0001). There was a significant association between the TT genotype and premature coronary artery disease [eNOS TT vs. TG and GG; OR=17.000 (CI 95% 3.952-73.125, p=0.0001)]. The eNOS T/G genotypes were not associated with the number of affected vessels (p>0.05). In addition, the family history of premature coronary artery disease, smoking, diabetes, obesity, dyslipidemia and eNOS TT genotype were independent risk factors of coronary artery disease. The patients with eNOS TT genotype had 15 fold risk of coronary artery disease compared with the control group [OR=15.356(CI 95% 3.262-77.289, p=0.001)]. These results suggest that premature coronary artery disease is associated with the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene in our population.


Intra-atrial pressure increases rate and organization of waves emanating from the superior pulmonary veins during atrial fibrillation.
Atrial fibrillation (AF) commonly associates with atrial dilatation by poorly understood mechanisms. We hypothesized that elevation of intra-atrial pressure elicits high-frequency and spatio-temporally organized left atrial (LA) sources emanating from the superior pulmonary veins. We used a stretch-related AF model in the sheep heart to induce stable episodes of AF (>40 minutes) in 9 animals. Video movies of the LA free wall (LAFW) and LA superior pulmonary vein junction (JPV) were obtained by using di-4-ANEPPS. Electrograms from the right atrium were recorded. At intra-atrial pressures >10 cm H2O, the maximum dominant frequency (DFMax) was significantly higher in the JPV than in the LAFW (12.0+/-0.2 and 10.5+/-0.2 Hz, respectively [mean+/-SEM]; P<0.001). Below 10 cm H2O, DFMax was similar in the JPV and LAFW (10.8+/-0.3 versus 10.2+/-0.3 Hz; P=0.6); DFMax in both JPV and LAFW was significantly higher than in the right atrium (7.8+/-0.3 Hz; P<0.001). Analysis of excitation direction in JPV showed positive correlation between intra-atrial pressure and the number of waves emanating from the left superior pulmonary vein (r=0.79, P=0.02) but not from the LAFW (r=0.54, P=0.09). The number of spatio-temporally periodic waves in the JPV correlated with pressure (r=0.92, P=0.002). In 3 cases, JPV rotors were identified with a cycle length equal to 1/DFMax. We demonstrate for the first time that an increase in intra-atrial pressure increases the rate and organization of waves emanating from the superior pulmonary veins underlying stretch-related AF.


Mild asthma: Lessons learned and remaining questions.
Patients living with mild disease represent the largest proportion of asthma patients. There are significant challenges in proposing a definition that would best describe these patients, while also accurately identifying at-risk individuals. Current literature suggests considerable inflammatory and clinical heterogeneity within this group. Research has shown that these patients are at risk of poor control, exacerbations, lung function decline, and death. Despite conflicting data on its prevalence, eosinophilic inflammation appears to be a predictor of poorer outcomes in mild asthma. There is an immediate need to better understand phenotypic clusters in mild asthma. It is also important to understand factors that influence disease progression and remission, as it is evident that both vary in mild asthma. Guided by robust literature that supports inhaled corticosteroid-based strategies over short-acting beta-agonist (SABA) reliant regimens, the management of these patients has evolved considerably. Unfortunately, SABA use remains high in clinical practice despite strong advocacy from the Global Initiative for Asthma. Future mild asthma research should explore the role of biomarkers, develop prediction tools based on composite risk scores, and explore targeted therapies at least for at-risk individuals.


Dressed Gain from the Parametrically Amplified Four-Wave Mixing Process in an Atomic Vapor.
With a forward cone emitting from the strong pump laser in a thermal rubidium atomic vapor, we investigate the non-degenerate parametrically amplified four-wave mixing (PA-FWM) process with dressing effects in a three-level "double-Λ" configuration both theoretically and experimentally. By seeding a weak probe field into the Stokes or anti-Stokes channel of the FWM, the gain processes are generated in the bright twin beams which are called conjugate and probe beams, respectively. However, the strong dressing effect of the pump beam will dramatically affect the gain factors both in the probe and conjugate channels, and can inevitably impose an influence on the quantum effects such as entangled degree and the quantum noise reduction between the two channels. We systematically investigate the intensity evolution of the dressed gain processes by manipulating the atomic density, the Rabi frequency and the frequency detuning. Such dressing effects are also visually evidenced by the observation of Autler-Townes splitting of the gain peaks. The investigation can contribute to the development of quantum information processing and quantum communications.


Overnight observation in former premature infants undergoing inguinal hernia repair.
Overnight observation for apneic events is standard practice in former preterm infants. However, the literature supporting current protocols is dated. Therefore, we retrospectively evaluated the post-anesthetic risks in these patients. A retrospective review was conducted on former preterm infants admitted after an inguinal herniorrhaphy between 1/00 and 10/09. The protocol for overnight admission was for patients born before 37 weeks gestation who are less than 60 weeks post-conceptional age (PCA). There were 363 patients, of which 23 were <40 weeks PCA (group 1), 244 were 40 to 49.9 weeks PCA (group 2), and 96 were 50 to 60 weeks PCA (group 3). Events registered by alarms occurred in 4 patients (1.1%), 2 from group 1 and 2 from group 2. In Group 1, one occurred during nasogastric tube placement and resolved spontaneously. In group 2, one was apnea-induced bradycardia that resolved spontaneously, and one was in a patient on home monitors with an event similar to home reports. There were no events in group 3. Conservative guidelines for overnight observation after inguinal hernia repair could be set for patients born before 37 weeks gestation who are under 50 weeks PCA.


Markers of proliferative activity are predictors of patient outcome for low-grade endometrioid adenocarcinoma but not papillary serous carcinoma of endometrium.
On the basis of pathogenesis, two types of endometrial cancer can be recognized. Type 1 endometrial carcinomas are relatively indolent tumors that develop after prolonged estrogen stimulation, on a background of endometrial hyperplasia. Type 2 endometrial carcinomas are aggressive tumors that are not associated with hyperplasia or estrogen excess. The aim of this study is to evaluate the prognostic significance of tumor proliferative activity in early-stage endometrial cancer by using mitotic index and immunostaining, comparing Type 1 (endometrioid) and Type 2 (papillary serous carcinoma) tumors. The mitotic index, MIB-1, and p53 immunostaining in 39 tumors from patients with low-grade Stage Ia or Ib endometrioid adenocarcinoma; as well as 23 tumors from patients with Stage I papillary serous carcinoma. In low-grade endometrioid adenocarcinoma, mitotic and MIB-1 indices were statistically significant independent prognostic indicators (P =.004 and P =.018, respectively), and both were strongly correlated with p53 expression (P =.01 and P =.006, respectively). The mean mitotic index was 5 mitoses/10 high-power fields, and mean MIB-1 index was 27.5%. There was no significant correlation between mitotic or MIB-1 indices and patient outcome or p53 expression in papillary serous carcinoma. The mean mitotic index was 31 mitoses/10 high-power fields, and mean MIB-1 index was 30.5% in these tumors. p53 expression and proliferative indices are strongly correlated in low-grade endometrioid adenocarcinoma. MIB-1 and mitotic indices are independent prognostic indicators in these tumors. Papillary serous carcinoma of endometrium is rapidly proliferative in tumors even at an early stage, and quantification of proliferative activity in these tumors does not allow prediction of patient outcome.


Lead distribution in the nervous system of 8-month-old rats intoxicated since birth by lead.
Lead levels in the nervous system of rats intoxicated for 8 months by lead acetate (0.2% in drinking water) varied according to the region: the lowest levels were observed in sciatic nerve and the highest in hippocampus and cerebral neocortex, while intermediate levels were observed in pons medulla, cerebellum, midbrain, hypothalamus and striatum.


Density dependence in rangeland grasshoppers (Orthoptera: Acrididae).
We tested for the existence of density dependence in annual adult rangeland grasshopper (Orthoptera: Acrididae) data from Montana, USA (1951-1991). Statistical density dependence was, in the sense of a stochastic equilibrium or return tendency, detected in all of the grasshopper mean density time-series from the three major physiographic regions of the state, Northern Glaciated Plains, Southern Unglaciated Plains, and Western Mountains. Parameters were estimated for a model that described the stochastic equilibrium characteristics of regional mean densities. The analyses showed that rangeland grasshopper regional densities fluctuate according to gamma distribution with a mean of 6.1-6.3 grasshoppers per m2. Further, when regions exhibit outbreaks, the resulting infestation period (duration of outbreak) is short, spanning only a few generations.


Neonatal Gastric Necrosis and Perforation Treated by Subtotal Gastrectomy and Esogastric Anastomosis: A Case Report.
BACKGROUND Gastric necrosis and perforation are rare life-threatening conditions in preterm neonates, which require urgent diagnosis and surgical intervention. CASE REPORT We report a case of a 4-day-old patient with neonatal gastric necrosis. The patient presented with sudden acute abdominal distension, respiratory distress, and metabolic acidosis. The abdomen was markedly distended, tender, and tympanic with collateral circulation. An X-ray of the abdomen showed a huge pneumoperitoneum. An urgent exploratory laparotomy revealed 2 wide horizontal perforations and necrosis of the fundus and gastric body. Subtotal gastrectomy with esogastric anastomosis was done. Postoperatively, the patient was administered total parenteral nutrition and triple antibiotics and improved gradually. He passed stool and the abdomen was soft, lax, and non-distended and the wound healed. An upper gastrointestinal tract (UGIT) contrast study 1 week after the operation showed no leakage or stricture. The patient was discharged 2 months postoperatively with a bodyweight of 2 kg and was followed in the Outpatient Department (OPD). The patient survived after 80% gastric resection for necrosis of the stomach, which was a unique outcome for this major surgery. CONCLUSIONS Gastric perforation is a rare life-threatening condition in preterm neonates, usually managed by direct closure in layers. Exceptionally, partial gastrectomy is needed, which is a major operation, with a high mortality rate and poor outcome. We present a case of a preterm neonate who survived after 80% gastric resection for stomach necrosis.


Perilunate injuries.
Perilunate dislocations and fracture dislocations are most often a result of high-energy trauma, exerting an axial load with hyperextension and ulnar deviation of the wrist, along with intercarpal supination. Early treatment of perilunate injuries is necessary to optimize the clinical outcome. Although closed management has been the more commonly reported treatment for perilunate injuries, the current consensus is that anatomic restoration of carpal alignment has better results. The combined dorsal-volar approach offers the advantages of both approaches and is the preferred choice for the authors since it allows assessment of all the injured structures. The surgical techniques to restore carpal alignment and repair the scapholunate interosseous ligament are discussed. Current literature regarding treatment and prognosis is also included.


Independent director compensation and stock price collapse: Inhibition or promotion-based on a financial background perspective.
This paper takes the financial independent directors' compensation of listed companies from 2014 to 2020 as the research object and uses empirical analysis to study whether the compensation of financial independent directors promotes or inhibits stock price collapse. The research results show that there is a significant positive correlation between the compensation of financial independent directors of listed companies and stock price collapse. In state-owned enterprises, the compensation of financial independent directors has an inhibitory effect on stock price collapse, but it is not significant. In non-state-owned enterprises, the compensation of financial independent directors has a significant promoting effect on stock price collapse. Further research finds that the improvement of internal control quality can weaken the promoting effect of financial independent directors' compensation on stock price collapse to a certain extent, and the weakening effect is particularly evident in non-state-owned enterprises. The attendance frequency of financial independent directors cannot effectively suppress stock price collapse, but instead has a promoting effect.


The effect of pharmacist-initiated perioperative multidisciplinary pharmaceutical care model and clinical pathway on pain management in patients undergoing orthopedic surgery: a before-after study.
Poor pain control is common in perioperative orthopedic surgeries. However, there is a lack of exploration of the clinical pharmacy practice model for this population. To construct a perioperative pharmaceutical care model and clinical pathway for patients undergoing orthopedic surgeries and assess their impact on pain management. This historical before-and-after study was conducted in the Department of Orthopedics of a tertiary hospital in Guangdong Province, China. The control group was surgical patients who received routine diagnosis and treatment. The intervention group received pain management from a multidisciplinary team based on a pharmacist-initiated pharmaceutical care practice model and clinical pathways for medication management. The primary outcome measures were postoperative pain at rest (PAR) and movement-evoked pain (MEP) scores, number of breakthrough pains, and length of hospital stay. A total of 320 orthopedic surgery patients were included. Among patients with expected moderate or severe postoperative pain (82.5%), significantly lower PAR and MEP scores were observed in the intervention group 24 h after surgeries compared to the control group (p < 0.05). Compared to the control group, hospital stay in the intervention group was shortened by 2.3 days (p < 0.001). However, there were no significant differences in the control of breakthrough pain and the incidence of adverse drug reactions (p > 0.05). Multidisciplinary perioperative pain management practice models and clinical pathways initiated by pharmacists could improve outcome indicators related to pain management and support the role and value of pharmacists.


Substitution of a conserved alanine in the domain IIIS4-S5 linker of the cardiac sodium channel causes long QT syndrome.
Congenital long QT syndrome type 3 (LQT3) is an inherited cardiac arrhythmia disorder due to mutations in the cardiac sodium channel gene, SCN5A. Although most LQT3 mutations cause a persistent sodium current, increasing diversity in the disease mechanism is shown. Here we present the electrophysiological properties of the A1330T sodium channel mutation (DIIIS4-S5 linker). Like the A1330P, LQT3 mutation, A1330T, causes LQT3 in the absence of a persistent current. A1330T, A1330P and wild-type sodium channels were expressed in HEK-293 cells and characterized using the whole-cell configuration of the patch-clamp technique. The A1330T mutation shifts positively the voltage-dependence of inactivation and speeds recovery from inactivation. Measurements of sodium window (I(Na, window)) currents revealed a positive shift of the I(Na, window) voltage range for both 1330 mutants, with in addition an increase in I(Na, window) magnitude for the A1330P mutant. Action potential (AP) clamp experiments revealed that these changes in I(Na, window) properties cause an increased inward current during the initial part of phase 4 repolarization of the AP. Our findings indicate that the alanine at position 1330 in the DIIIS4-S5 linker of the cardiac sodium channel has a role in channel fast inactivation. Substitution by a threonine shifts the voltage range of I(Na, window) activity to more positive potentials. Here the counter-acting effect of outward K+ current is reduced and may delay AP repolarization, explaining the LQT3 phenotype.


ICU research: the impact of invasiveness on informed consent.
Studies into the preferences of patients and relatives regarding informed consent for intensive care unit (ICU) research are ongoing. We investigated the impact of a study's invasiveness on the choice of who should give consent and on the modalities of informed consent. At ICU discharge, randomized pairs of patients and relatives were asked to answer a questionnaire about informed consent for research. One group received a vignette of a noninvasive study; the other, of an invasive study. Each study comprised two scenarios, featuring either a conscious or unconscious patient. Multivariate models assessed independent factors related to their preferences. A total of 185 patients (40 %) and 125 relatives (68 %) responded. The invasiveness of a study had no impact on which people were chosen to give consent. This increased the desire to get more than one person to give consent and decreased the acceptance of deferred or two-step consent. Up to 31 % of both patients and relatives chose people other than the patient himself to give consent, even when the patient was conscious. A range of 3 to 17 % of the respondents reported that they would accept a waiving of consent. Younger respondents and individuals feeling coerced into study participation wanted to be the decision makers. Study invasiveness had no impact on patients' and relatives' preferences about who should give consent. Many patients and relatives were reluctant to give consent alone. Deferred and two-step consent were less acceptable for the invasive study. Further work should investigate whether sharing the burden of informed consent with a second person facilitates participation in ICU research.


Expression of Aspergillus fumigatus virulence-related genes detected in vitro and in vivo with competitive RT-PCR.
We have measured the transcription of several genes that have been implicated as virulence factors in Aspergillus fumigatus, including fos-1, a histidine kinase, two-component signal protein, rhbA, a ras-related protein required for signaling, pksP, a polyketide synthase involved in biosynthesis of melanin, pabA synthetase, an enzyme catalyzing a late step in the biosynthesis of folate, lysF, a homoconitase related to lysine biosynthesis, and cpcA, the transcriptional activator of the cross-pathway control system of amino acid biosynthesis. Transcription levels were determined from in vitro grown organism as well as from lung tissue from mice infected with A. fumigatus. Our data indicate that fos-1 and rhbA transcription increased significantly during the infection in mice, compared to the other genes whose transcription remained the same (pksP, cpcA, pabA) or decreased slightly (lysF). In vitro measurements of transcription compared to transcription in infected lung tissue demonstrated low levels of fos-1 and rhbA, 20-40-fold increases (cpcA, lysF, pabA), while pksP was not detected from cultures. Our data demonstrate that transcription of these genes differs in vitro versus during disease.


2,5-Hexanedione modifies skeletal proteins of the red blood cells and increases the binding of hemoglobin to the membrane.
The effects of 2,5-hexanedione (2,5 HD) on skeletal proteins of red blood cells (RBCs) were investigated both in vitro (human RBCs) and in vivo in male Sprague-Dawley rats which had been treated with the drug for several days. We found that 2,5 HD induced the following major changes in the electrophoretic pattern of the skeletal proteins: (i) the appearance of high-molecular weight bands, (ii) a dose-dependent decrease in spectrin Bands 1 and 2, and (iii) a dose-dependent increase in the amount of hemoglobin (Hb) associated with the membrane. Membranoskeletons, prepared from resealed ghosts which had been previously treated with 2,5 HD, were able to bind an increased amount of Hb from untreated RBCs, thus suggesting a drug-induced modification of the membrane. Extraction of spectrin and actin from ghosts did not remove the membrane-bound Hb and, furthermore, Hb bound to 2,5 HD-treated membranes mainly bearing Band 3 and free of peripheral proteins. These data suggested a 2,5 HD-induced modification of an intrinsic membrane protein, probably Band 3. This hypothesis was consistent with the observation that 2,5 HD also induced a modification of Band 3 aminogroups, as evidenced by a dose-dependent decrease in the binding of eosin probes. Furthermore, RBCs treated in vitro with 2,5 HD bound an increased amount of autologous immunoglobulins (IgG). As reported by Kay and Low et al. the binding of autologous IgG is a phenomenon associated with the aging process of RBCs and may involve a modification of Band 3. Our data show that RBCs treated with 2,5 HD acquired various characteristics of senescent cells such as spectrin cross-linking, Hb-membrane binding and increased IgG binding, and suggest that 2,5 HD treatment might affect RBC survival.


Antibody-induced changes on rabbit sperm surface inhibit gamete interaction.
Interaction of specific ligands with cell surface molecules may induce reorganization of surface components. A monoclonal antibody (B-12) against sperm surface antigens of 40kDa size induced molecules on the plasma membrane overlying the acrosome of rabbit sperm to cluster in small aggregates at 0 degree C (patching). At an elevated temperature of 37 degrees C these clusters of antigen antibody complexes collected into a large aggregate on one pole of the cell forming a cap (capping). This cap-like structure showed a reduction in size over a period of time and eventually disappeared from the sperm surface. Inhibition of capping by sodium azide indicated that it is an energy-dependent process. Patching of antigens did not require energy. Involvement of sperm head cytoskeleton in the process of capping was evident from potentiation of cap formation by cytoskeleton disrupting agents like cytochalasin B and D. Patching of antigen antibody complexes was not affected by either of the agents. The loss of antigen antibody complexes from sperm surface was mainly due to shedding of the complexes in the surrounding media. Sperm with patches of antigen antibody complexes did not adhere to oocytes. Sperm from the group where a majority of the sperm were denuded of the antigen antibody complexes also did not bind to oocytes.


Cloning of the netropsin resistance genes from Streptomyces flavopersicus NRRL 2820.
Streptomyces flavopersicus NRRL 2820 (synonym: Streptomyces netropsis DSM40093) is resistant to the N-methylpyrrole-containing oligopeptide antibiotic netropsin. A 9.38 kb DNA-fragment was isolated from a genomic library of Streptomyces flavopersicus using an Escherichia coli-Streptomyces lividans shuttle vector which enables S. lividans to grow on netropsin-containing agar plates. By subcloning, the resistance was conferred to a 5.9 kb Eco RV fragment. DNA sequence analysis of this Eco RV fragment revealed two open reading frames (netP1 , 1556 bp and netP2 , 1773 bp). The deduced proteins share significant similarity to each other (27% identity) and to the large family to ABC-type multidrug resistance proteins. In each protein a conserved transmembrane and ATP binding domain was identified. Deletion analysis showed that both proteins are necessary for netropsin resistance indicating that the proteins form a heterodimeric ABC-transporter exporting netropsin.


The impact of New Zealand's 2008 prohibition of piperazine-based party pills on young people's substance use: results of a longitudinal, web-based study.
The last decade has seen the emergence of a new phenomenon in recreational substance use with the availability of herbal and synthetic, unregulated, psychoactive drugs in the market place; alongside this, international concern has developed in relation to their use and associated harms. New Zealand (NZ) was one of the first countries to experience this new phenomenon, with products containing chemicals of the piperazine group - mainly benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP). In 2008, the NZ Government prohibited these substances, but allowed a 6-month amnesty period for possession. Our study aimed to obtain a measure of change in BZP use over time. This study used a longitudinal, web-based survey, with data collected at two time points from the same participants. The first survey was carried out 3 months after BZP prohibition, and included retrospective questions for the 6 months preceding the survey. The second survey was conducted 9 months after prohibition and also included retrospective questions for the 6 months preceding the survey. 273 sets of paired data were identified. The use of BZP party pills (p<0.0001) and legally available smokeable products (p=0.002) reduced over time. A majority of users of party pills obtained them from friends or from their own stockpiled supplies. The misuse of prescription drugs (p=0.02) increased over time, whereas statistically significant increases in stimulant or alcohol use were not noted. Following prohibition of piperazine-based party pills, we noted a significant reduction in the proportions of participants using them. The observed increase in the misuse of prescription medicines may relate to their perceived 'quality', or as being less 'illegal' than illicit drugs.


Sex and the media: three decades of best-selling books and major motion pictures.
The expression of sexuality in best-selling novels and major motion pictures was examined. There are two reasons that such stimuli merit systematic analysis. First and foremost is the finding that best-selling novels and major motion pictures exist as a primary source of sexual information. Of equal importance, however, is the need to examine such stimuli for myths and fallacies. The novels and films analyzed in the present study were selected from the last years of three consecutive decades: 1959, 1969, and 1979. Inclusion in this study was based on ranking in either a best-seller list (i.e., books) or a rental-receipts list (i.e., movies). The use of such criteria serves the dual purpose of allowing for the examination of stimuli that are accessible to large masses of people and at the same time allowing for the examination of sexually relevant stimuli. The results are discussed in terms of historical changes (over the three decades) and manifest themes (i.e., general characteristics or consistent themes). An additional section was included to address the broader implications of the present findings and to suggest alternatives.


Spatiotemporal assessment of the environmental quality of bottom waters through the study of benthic foraminifera in a semi-enclosed gulf.
The evolution of the bottom water in Amvrakikos Gulf in Ionian Sea at western Greece for a 50-year timespan was assessed by benthic foraminifera assemblages. The degradation of the bottom water of Amvrakikos has been a catalyst for the surface water degradation. The east basin has shown permanent low environmental quality in bottom waters since 1980, while the west basin has been under seasonal hypoxic regime since 2000. The most adverse environmental conditions occurred in 1990-2000 and 2005-2010 coinciding with the recorded fish mortality events. The major cause of the environmental quality improvement of the bottom water is the intrusion of seawater. In western areas of the gulf, where the influence of the seawater is high, the decreased temperature improves the environmental conditions, while in the areas influenced by river discharges (east and northern), the environmental conditions are depended on multiple causes like organic matter input and surface salinity.


Drug-induced alterations in the efflux of 5-hydroxytryptamine and of 5-hydroxyindoleacetic acid into superfusates of the rat spinal cord.
The effect of dl-p-chloroamphetamine, fluoxetine and probenecid on the efflux of endogenous 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid (5HIAA) into superfusates of the spinal cord of anesthetized rats was examined. Mean basal efflux of 5HT and 5HIAA was 0.27 and 15.56 ng/ml superfusate, respectively. The addition of dl-p-chloroamphetamine to the superfusate produced a dose-dependent increase in the efflux of 5HT into the superfusate, but did not increase the efflux of 5HIAA. Probenecid (200 mg/kg i.p.) increased the basal efflux of both 5HT and 5HIAA as compared to control values. When administered systemically, fluoxetine (10 mg/kg i.p. or s.c.) decreased the basal efflux of 5HIAA, but did not alter the basal efflux of 5HT as compared to control values. In contrast, when administered in the superfusate, fluoxetine produced a dose-dependent increase in the basal efflux of 5HT, but did not alter the basal efflux of 5HIAA. The release of 5HT produced by the addition of 2.5 X 10(-4) M dl-p-chloroamphetamine to the superfusate was not prevented in rats pretreated systemically with fluoxetine, although when administered in the superfusate fluoxetine inhibited the dl-p-chloroamphetamine-induced release of 5HT.


Accuracy of whole-body PET and PET-CT in initial M staging of head and neck cancer: a meta-analysis.
A meta-analysis was conducted to evaluate the accuracy of whole-body positron emission tomography (PET) and PET-CT in initial M staging of head and neck cancer. After a systematic review of English language studies, sensitivity, specificity, and other measures of whole-body PET and PET-CT were pooled. Summary receiver operating characteristic (SROC) curves were also used to summarize overall test performance. Eight PET and 7 PET-CT studies were identified. The pooled sensitivity estimates for PET and PET-CT were 0.848 (95% confidence interval [CI], 0.776-0.905) and 0.875 (95% CI, 0.787-0.936). The pooled specificity estimates were 0.952 (95% CI, 0.933-0.967) and 0.950 (95% CI, 0.931-0.964). The Q* index estimates for PET-CT (0.9409) were not significantly higher than for PET (0.9154; p > .05). Whole-body PET and PET-CT have good diagnostic performance in initial M staging of head and neck cancer; although PET-CT tends to have higher accuracy than PET.


Difference equation model of ventricular parasystole as an interaction between cardiac pacemakers based on the phase response curve.
A model of extended ventricular parasystole proposed by Moe et al. (1977) was formulated as a system of nonlinear difference equations by using the phase response curve of myocardial pacemakers. A number of ECG patterns of ventricular arrhythmia such as bigeminy, trigeminy etc. were explained from the property of periodic solutions of the equation. Characteristic properties of special kinds of arrhythmia called "concealed bigeminy" and "concealed trigeminy" were derived mathematically by assuming the model, in relation to the equation of the analog neuron model. The present study was considered to be of clinical significance as a theoretical foundation for the study of genesis of cardiac arrhythmias.


Optimization of Iodinated Contrast Media Inventory Management: Effect of Inventory Diversification on Waste Reduction.
Iodinated contrast medium (ICM) is available in single- and multi-use vials of varying sizes, but CT departments often preferentially stock only a single or a limited number of vial sizes. The aims of this study were to assess actual ICM waste at a large safety-net hospital and to compare with estimated waste if single-use vials in a variety of vial sizes or multiuse vials were used. ICM administrations were retrospectively reviewed for all CT examinations performed in 2021 in a department that stocked only 100-mL ICM vials. Administered ICM dose, opened ICM volume and number of vials, and wasted ICM were compared with hypothetical models using optimally sized single-use vials and multiuse vials. Contrast use was also compared by patient class. In total, 40,393 ICM administrations over 49,670 CT examinations among 26,028 patients were reviewed, totaling 4,168,335 mL of contrast media. The mean dose was 103 mL, with mode of 100 mL. Exclusive use of 100-mL vials resulted in 1,006,165 mL waste (mean waste, 26 mL/administration). Optimally sized single-use vials resulted in 436,515 mL waste (mean waste, 11 mL/administration). Multiuse vials resulted in 537,074 mL waste (mean waste, 13 mL/administration). The distribution of optimal single-use vial size differed significantly by patient class (P < .001), with inpatient examinations more amenable to the use of smaller single-use vials. Optimizing ICM inventory can reduce contrast waste by 50% to 59%. Regular monitoring of contrast use may help optimize inventory selection across care settings. This retrospective review supports scrutiny of ICM inventory management to reduce waste, save costs, and mitigate the impacts of supply-chain disruptions.


Simultaneous determination of "earthy-musty" odorous haloanisoles and their corresponding halophenols in water samples using solid-phase microextraction coupled to gas chromatography with electron-capture detection.
Certain haloanisoles present at trace levels cause a large part of earthy-musty off-flavor problems in drinking water. These potent odorous chemicals come mainly through biomethylation of their corresponding halopenols. To enable the investigation of both families of compounds, a method involving solid-phase microextraction (SPME) was developed and the main parameters governing SPME were optimized. This method allows the simultaneous quantification of haloanisoles and halophenols at levels ranging from 1 to 100 or 250 ng/l, with detection limits of about 0.5 ng/l and could be applied to potable as well as raw surface waters.


Prevalence and severity of external auditory exostoses in breath-hold divers.
To explore the prevalence and severity of external auditory exostoses in a population of experienced breath-hold divers, and to compare these to the same parameters within surfing and self-contained underwater breathing apparatus diving populations. A stepwise, multiple regression analysis of cross-sectional data examining the relative contributions of sea surface temperature, latitude of exposure and years of exposure to the prevalence and severity of stenosis due to external auditory exostoses. A chi-square analysis of the prevalence and severity of external auditory exostosis stenosis in the breath-hold divers was compared with previously published data for surfers and self-contained underwater breathing apparatus divers. Seventy-six male and thirty-five female breath-hold divers attending an international 'freedive' competition completed a questionnaire describing aquatic sports habits, geography of participation and symptomatology. Those completing the questionnaire (111/154 attendees) were examined otoscopically for evidence of external auditory exostoses. Images were digitally recorded, scored and graded. Exostoses were evident in 87.7 per cent of the 204 ears scored and graded for severity of stenosis due to external auditory exostoses. The prevalence of exostoses was no different from that found in previous studies of surfers and self-contained underwater breathing apparatus divers (p = 0.101). However, the pattern of affliction was more similar to that found in surfers. The severity of exostoses was significantly less than that found in surfing populations (p < or = 0.001 to 0.007), but greater than that found in self-contained underwater breathing apparatus diving populations (p < or = 0.001). Sea surface temperature at the location of open-water exposure was the most significant predictor of the prevalence and severity of external auditory exostoses in breath-hold divers (p = 0.019). The prevalence and severity patterns of stenosis due to external auditory exostoses in breath-hold divers are more similar to previously published results for surfing populations than to previously published results for self-contained underwater breathing apparatus diving populations. In breath-hold divers, sea surface temperature is the strongest predictor of severity of stenosis due to external auditory exostoses.


Extensive nodal involvement increases the positivity of blue nodes in the axillary reverse mapping procedure in patients with breast cancer.
The axillary reverse mapping (ARM) technique has been proposed to prevent arm lymphedema. We conducted this study to assess the feasibility of the technique and the outcomes of patients with neoadjuvant chemotherapy (NAC). From July 2009 to May 2010, a prospective study was performed in 36 patients with breast cancer undergoing an ALND. The ARM technique was performed injecting 3 cm(3) of Patent Blue in the ipsilateral arm. Of the 36 patients, 29 patients received NAC previously to the ARM and 7 patients had an ALND and ARM performed as first treatment for positive axillary nodes. The identification rate of blue nodes was 83.3% (30 patients). Sentinel lymph node (SLN) was performed in 15 of 29 (42%) patients in the NAC group. Of these 15, two patients (13%) had a concordance between the blue and the hot node. Blue nodes were positive in 4 (13%) of the 30 patients. The ARM technique is feasible in patients undergoing NAC. Patients with extensive nodal involvement have increased risk of having positive blue nodes. More studies are needed to assess the subgroup of patients with positive axilla that may have the blue node spared without compromising the oncological treatment.


Closed reduction and minimally invasive surgical treatment of type IIIa fragility fractures of the pelvis associated with ipsilateral periprosthetic femur fracture: A case report.
Patients with fragility fractures of the pelvic ring (FFP) are elderly and, from the perspective of surgical invasion, percutaneous and stable fixation may be a superior surgical method than open reduction and internal fixation (ORIF). While in the case of FFP type IIIa, ORIF, as a rule, typically requires open reduction of the displaced ilium via an anterior intrapelvic approach and/or lateral window of the ilioinguinal approach. We have reported here the case of an 89-year-old woman who suffered from FFP type IIIa with ipsilateral periprosthetic femur fracture that was surgically treated. The iliac fracture was approached in a minimally invasive manner using the traction operation while preparing for femoral shaft fracture surgery, which did not require open reduction, and showed favorable outcomes.


Leflunomide in dermatology.
Leflunomide is an oral disease-modifying antirheumatic drug administered to patients with rheumatoid and psoriatic arthritis. This drug inhibits dihydroorotate dehydrogenase, an enzyme critical in the production of intracellular pyrimidines, and down-regulates tumor necrosis factor-alfa activity. Leflunomide has demonstrated usefulness in treating cutaneous psoriasis along with other dermatologic and rheumatologic conditions.


Knockdown of astrocyte elevated gene-1 inhibited cell growth and induced apoptosis and suppressed invasion in ovarian cancer cells.
Emerging evidence has demonstrated that AEG-1 (astrocyte elevated gene-1) plays a pivotal oncogenic role in tumorigenesis. However, the molecular mechanism by which AEG-1 exerts its oncogenic function is elusive in ovarian cancer. To explore the role and molecular insight on AEG-1-mediated tumorigenesis in ovarian cancer, multiple approaches are performed including MTT assay, flow cytometry for apoptosis and cell cycle assay, gene transfection, real-time RT-PCR, Western blotting, and Transwell assay. Our MTT assay showed that knockdown of AEG-1 by its siRNA significantly inhibited cell growth in ovarian cancer cells. Moreover, AEG-1 siRNA treatment induced G0/G1 cell cycle arrest and triggered cell apoptosis in ovarian cancer cells. Notably, inhibition of AEG-1 suppressed cell migration and invasion in ovarian cancer cells. Intriguingly, we identified that knockdown of AEG-1 remarkably inhibited the activation of Akt pathway. Our results also validated that knockdown of AEG-1 inhibited the expression of MMP-2 and VEGF, which could lead to inhibition of cell migration and invasion. These data suggest that AEG-1 could be a potential therapeutic target for the treatment of ovarian cancer.


Protective up-regulation of CK2 by mutant huntingtin in cells co-expressing NMDA receptors.
Huntington's disease is caused by a polyglutamine expansion in the huntingtin (htt) protein, and previous data indicate that over-activation of NMDA receptors (NMDARs) may be involved in the selective degeneration of cells expressing NR1/NR2B NMDARs. We used Kinetworkstrade mark multi-immunoblotting screens to examine expression of 76 protein kinases, 18 protein phosphatases, 25 heat shock/stress proteins, and 27 apoptosis proteins in human embryonic kidney 293 cells transfected with NR1/NR2B and htt containing 15 (htt-15Q; wild-type) or 138 (htt-138Q; mutant) glutamine repeats. Follow-up experiments revealed several proteins involved in the heat-shock response pathway to be up-regulated in the soluble fraction from cells expressing htt-138Q, including protein phosphatase 5 and cyclin-dependent kinase 5. Increased expression in the soluble fraction of htt-138Q-expressing cells was also noted for the stress- and calcium-activated protein-serine/threonine kinase casein kinase 2, a change which was confirmed in striatal tissue of yeast artificial chromosome transgenic mice expressing full-length mutant htt. Inhibition of casein kinase 2 activity in cultured striatal neurons from these mice significantly exacerbated NMDAR-mediated toxicity, as assessed by labeling of apoptotic nuclei. Our findings are consistent with up-regulation of components of the stress response pathway in the presence of polyglutamine-expanded htt and NR1/NR2B which may reflect an attempt at the cellular level to ameliorate the detrimental effects of mutant htt expression.


The relevance of malaria pathophysiology to strategies of clinical management.
Malaria claims 1-2 million lives a year, mostly children in sub-Saharan Africa. The majority of hospital deaths occur within 24 h of admission despite adequate treatment with antimalarial chemotherapy. Understanding the pathophysiological disturbances of malaria should allow the development of supportive therapy to "buy time" for antimalarial chemotherapy to clear the infection. It is sobering, however, that despite many trials over the last quarter of a century all large trials of adjunctive therapy so far have resulted in either increased morbidity or mortality, or both. Severe malaria may be divided broadly into neurological and metabolic complications. We review recent findings about the pathophysiology of these complications and the implications for future adjunctive therapy of malaria, including the proposed importance of fluid volume depletion and sequestration of parasitized red cells in severe malaria. We also consider other anaemia, hyperparasitaemia and renal failure, which also require urgent treatment in severe malaria. We review the important pathophysiological features of severe malaria and promising adjunctive therapies such as dichloroacetate that warrant further larger trials to determine whether they improve the so-far intractable death rate of severe malaria.


Does atlantoaxial dislocation influence the subaxial cervical spine?
Previous studies have reported that the alignments of the occipital-cervical and subaxial spine were closely interrelated in asymptomatic individuals; however, none have focused on a population with atlantoaxial dislocation. From 2007 to 2011, 298 patients with atlantoaxial dislocation and atlas occipitalization were studied. Angles formed between Occiput-C2 and C2-C7 were measured. The relationship between the alignment of the occipital-cervical junction and the subaxial cervical spine was evaluated. The range of values for the angles measured was as followed: the Occiput-C2 angles were -35.2° to 44.8°, and the C2-C7 angles were -17.4° to 77.8°. Statistically significant negative correlations were observed between the Occiput-C2 and C2-C7 angles. Anterior dislocations of the atlas are associated with diminished lordosis or even kyphosis of the occipital-cervical junction, and result in compensatory hyperlordosis of the subaxial cervical spine, collectively presenting as a "swan neck" deformity. Atlantoaxial dislocation may influence the global cervical alignment.


A novel 17 apoptosis-related genes signature could predict overall survival for bladder cancer and its associations with immune infiltration.
Apoptosis-related genes (ARGs) were used to develop a novel signature for forecasting overall survival (OS) and examining their relationships with immune infiltrates in bladder cancer (BC). Gene expression matrices as well as related clinical data were acquired for BC samples from online datasets. According to differentially expressed ARGs acquired from normal bladder tissues and cancer samples, functional enrichment analyses were conducted. With the assistance of LASSO and Cox regression analysis, a novel model was successfully established and evaluated by external and internal validations. Eventually, 17 ARGs (SLC5A6, GULP1, TAP1, MMP9, P4HB, FOXL2, CIDEC, EN2, NES, EPHA7, SUSD2, TMPRSS3, HOXB7, SATB1, MEST, PCDHGC3, ASPM) were utilized to construct the signature. Our constructed signature significantly distinguished high-risk from low-risk BC patients of OS by internal and external validations and was also proven to be able to serve as an independent prognostic biomarker (all P < 0.05). Furthermore, a prognostic nomogram was also constructed based on TCGA dataset to predict OS prognosis in BC suffers. Besides, this ARG based model was markedly associated with clinical characteristics like tumor stage (P = 3.98e-06), race (P = 8.255e-06), N stage (P = 0.002), T stage (P = 3.679e-05) and M stage (P = 0.002). As for immune infiltration, our established model was significantly associated with seven tumor-infiltrating immune cells. A prognostic signature was successfully developed by us according to 17 ARGs in BC using external and internal verifications, enabling clinicians to predict BC suffers' OS and promote specific individualization of patient care.


Histopathological and CT features of pulmonary sclerosing haemangiomas.
To demonstrate the computed tomography (CT) features of pulmonary sclerosing haemangiomas. Six pathologically proven sclerosing haemangiomas were included in this retrospective review. Patients consisted of five women and one man aged 20-54 years (mean, 34.5 years). Their CT features were recorded according to enhancement patterns and the presence of a tail sign, prominent pulmonary artery sign, air-trapping sign, presence of calcification or cystic spaces, consolidation, and interstitial infiltration. The predominant composition of an individual sclerosing haemangioma was documented by means of microscopy. Inhomogeneous enhancement was frequently present and depended on the various compositions of the tumours, especially those in sclerotic and predominantly papillary predominant types. The presence of a tail sign, intra-tumoural cystic areas, and a prominent artery sign were the frequent features in our cases. Sclerosing haemangioma should be considered in young or middle-aged female patients whose CT images show them having an inhomogeneous enhancing soft tissue mass with a smooth outline and with above the aforementioned features.