Three-dimensional assessment of the sella turcica: comparison between cleft lip and palate patients and skeletal malocclusion classes.
The main aim of the present study was to investigate the dimensions and morphological appearance of the sella turcica in cleft lip and palate patients using cone-beam computed tomography (CBCT) images, compared to non-cleft individuals. CBCT images of 40 (20 females and 20 males) cleft lip and palate patients and 60 (27 males and 33 females) non-cleft individuals were assessed, retrospectively. The linear dimensions (depth, diameter and length) of the sella turcica and inter-clinoid distance were measured. Sella turcica shapes were examined in the cleft lip and palate patients and non-cleft individuals. Non-cleft individuals were divided into skeletal malocclusion classes. All variables were analyzed using the Kruskal-Wallis test, Mann-Whitney U tests and Chi-square test. No significant difference was observed between individuals with and without cleft in the linear dimensions (depth, diameter and length) of the sella turcica (p > 0.05). However, a significant difference was found in the inter-clinoid distance between patients with cleft and non-cleft individuals (p < 0.05). Comparison of the sella turcica shape between skeletal malocclusion classes and patients with cleft showed significant differences (p < 0.05). No significant difference was determined in the depth, diameter, or length of the sella turcica in cleft patients when compared with non-cleft individuals. The inter-clinoid distance was lower in cleft patients than in non-cleft individuals, and this difference was statistically significant.


The proteolytic activity of the HtrA (DegP) protein from Escherichia coli at low temperatures.
The HtrA (DegP) protein from Escherichia coli is a periplasmic protease whose function is to protect cells from the deleterious effects of various stress conditions. At temperatures below 28 degrees C the proteolytic activity of HtrA was regarded as negligible and it was believed that the protein mainly plays the role of a chaperone. In the present work we provide evidence that HtrA can in fact act as a protease at low temperatures. Under folding stress, caused by disturbances in the disulfide bond formation, the lack of proteolytic activity of HtrA lowered the survival rates of mutant strains deprived of a functional DsbA/DsbB oxidoreductase system. HtrA degraded efficiently the unfolded, reduced alkaline phosphatase at 20 degrees C, both in vivo and in vitro. The cleavage was most efficient in the case of HtrA deprived of its internal S-S bond; therefore we expect that the reduction of HtrA may play a regulatory role in proteolysis.


Measles virus mutants possessing the fusion protein with enhanced fusion activity spread effectively in neuronal cells, but not in other cells, without causing strong cytopathology.
Subacute sclerosing panencephalitis (SSPE) is caused by persistent measles virus (MV) infection in the central nervous system (CNS). Since human neurons, its main target cells, do not express known MV receptors (signaling lymphocyte activation molecule [SLAM] and nectin 4), it remains to be understood how MV infects and spreads in them. We have recently reported that fusion-enhancing substitutions in the extracellular domain of the MV fusion (F) protein (T461I and S103I/N462S/N465S), which are found in multiple SSPE virus isolates, promote MV spread in human neuroblastoma cell lines and brains of suckling hamsters. In this study, we show that hyperfusogenic viruses with these substitutions also spread efficiently in human primary neuron cultures without inducing syncytia. These substitutions were found to destabilize the prefusion conformation of the F protein trimer, thereby enhancing fusion activity. However, these hyperfusogenic viruses exhibited stronger cytopathology and produced lower titers at later time points in SLAM- or nectin 4-expressing cells compared to the wild-type MV. Although these viruses spread efficiently in the brains of SLAM knock-in mice, they did not in the spleens. Taken together, the results suggest that enhanced fusion activity is beneficial for MV to spread in neuronal cells where no cytopathology occurs, but detrimental to other types of cells due to strong cytopathology. Acquisition of enhanced fusion activity through substitutions in the extracellular domain of the F protein may be crucial for MV's extensive spread in the CNS and development of SSPE. Subacute sclerosing panencephalitis (SSPE) is a fatal disease caused by persistent measles virus (MV) infection in the central nervous system (CNS). Its cause is not well understood, and no effective therapy is currently available. Recently, we have reported that enhanced fusion activity of MV through the mutations in its fusion protein is a major determinant of efficient virus spread in human neuronal cells and brains of suckling hamsters. In this study, we show that those mutations render the conformation of the fusion protein less stable, thereby making it hyperfusogenic. Our results also show that enhanced fusion activity is beneficial for MV to spread in the CNS but detrimental to other types of cells in peripheral tissues, which are strongly damaged by the virus. Our findings provide important insight into the mechanism for the development of SSPE after MV infection.


A SEROLOGIC SURVEY OF PATHOGENS IN WILD BOAR ( SUS SCROFA) IN SWEDEN.
The wild boar ( Sus scrofa) population has increased markedly during the last three decades in Sweden and in other parts of Europe. This population growth may lead to increased contact between the wild boar and the domestic pig ( Sus scrofa scrofa), increasing the risk of transmission of pathogens. The objective of our study was to estimate the seroprevalence of selective pathogens, known to be shared between wild boars and domestic pigs in Europe, in three wild boar populations in Sweden. In total, 286 hunter-harvested female wild boars were included in this study. The sera were analyzed for antibodies against nine pathogens using different commercial or in-house enzyme-linked immunosorbent assays. Antibodies were detected against porcine parvovirus (78.0%), porcine circovirus type 2 (99.0%), swine influenza virus (3.8%), Erysipelothrix rhusiopathiae (17.5%), Mycoplasma hyopneumoniae (24.8%), and Toxoplasma gondii (28.6%). No antibodies were detected against porcine respiratory and reproductive syndrome virus, Brucella suis, or Mycobacterium bovis. Our results highlight the potential importance of the wild boar as a reservoir for pathogens potentially transmissible to domestic pigs and which also may affect human health.


Insights from engraftable immunodeficient mouse models of hyperinsulinaemia.
Hyperinsulinaemia, obesity and dyslipidaemia are independent and collective risk factors for many cancers. Here, the long-term effects of a 23% Western high-fat diet (HFD) in two immunodeficient mouse strains (NOD/SCID and Rag1 -/-) suitable for engraftment with human-derived tissue xenografts, and the effect of diet-induced hyperinsulinaemia on human prostate cancer cell line xenograft growth, were investigated. Rag1 -/-and NOD/SCID HFD-fed mice demonstrated diet-induced impairments in glucose tolerance at 16 and 23 weeks post weaning. Rag1 -/- mice developed significantly higher fasting insulin levels (2.16 ± 1.01 ng/ml, P = 0.01) and increased insulin resistance (6.70 ± 1.68 HOMA-IR, P = 0.01) compared to low-fat chow-fed mice (0.71 ± 0.12 ng/ml and 2.91 ± 0.42 HOMA-IR). This was not observed in the NOD/SCID strain. Hepatic steatosis was more extensive in Rag1 -/- HFD-fed mice compared to NOD/SCID mice. Intramyocellular lipid storage was increased in Rag1 -/- HFD-fed mice, but not in NOD/SCID mice. In Rag1 -/- HFD-fed mice, LNCaP xenograft tumours grew more rapidly compared to low-fat chow-fed mice. This is the first characterisation of the metabolic effects of long-term Western HFD in two mouse strains suitable for xenograft studies. We conclude that Rag1 -/- mice are an appropriate and novel xenograft model for studying the relationship between cancer and hyperinsulinaemia.


Computational modeling of blood clot lysis considering the effect of vessel wall and pulsatile blood flow.
Stroke is one of the major causes of global death, which can occur due to blockage in a blood vessel by a clot. The immediate dissolving of the clot is essential to restore the blood flow and prevent tissue necrosis. Clot dissolution can be achieved via thrombolytic therapy using plasminogen activators. In this study, a clot dissolution model is developed for a three-dimensional patient-specific carotid artery that investigates the effect of different vessel wall models on clot dissolution. The lysis pattern of the clot and hemodynamics of blood flow are evaluated using three different models of the vessel wall, namely, rigid, linear elastic, and Mooney-Rivlin hyperelastic. The effect of flow condition is considered by solving the Navier-Stokes equations for the free flow domain and the Brinkman equation for the clot domain with the same pressure and velocity fields. This will result in continuous pressure and velocity over the interfaces of the free flow and clot domains. The blood inflow is assumed to be pulsatile. In addition, the species transport driven by diffusion and convection is considered to be different in the porous medium and plasma. The obtained results show that in all models, the starting time of clot volume decrease is almost the same and the clot starts dissolving from the inner curvature of the artery. However, in the hyperelastic model, dissolving the clot takes longer compared to the other two models. By monitoring the vessel wall deformation, the exact time of vessel recanalization is determined.


[Increase of IgE in asthmatic children: correlation with eosinophilia, skin tests and the value of the other gamma-globulins].
After considering IgE behaviour in various forms of atopic diseases the authors examine the importance of serum IgE levels in bronchial asthma diagnosis. They herein underline the correlation between IgE and positive skin test, its relationship with other immunoglobulines and its proportional increase to the age of the patient and the eosinophilia. As far as this study is concerned, 91% of asthmatic children register an IgE increase, against 9% only, this being the case of children under three years of age; 91% skin tests are positive and 41% register an increase of IgA, while the eosinophilia is unsignificant. The anamnestic data of atopic dermatitis and asthmatic bronchitis affecting 15 among our patients are found to be of great importance.


Fluorous microgel star polymers: selective recognition and separation of polyfluorinated surfactants and compounds in water.
Immiscible with either hydrophobic or hydrophilic solvents, polyfluorinated compounds (PFCs) are generally "fluorous", some of which have widely been employed as surfactants and water/oil repellents. Given the prevailing concern about the environmental pollution and the biocontamination by PFCs, their efficient removal and recycle from industrial wastewater and products are critically required. This paper demonstrates that fluorous-core star polymers consisting of a polyfluorinated microgel core and hydrophilic PEG-functionalized arms efficiently and selectively capture PFCs in water into the cores by fluorous interaction. For example, with over 10 000 fluorine atoms in the core and approximately 100 hydrophilic arms, the fluorous stars remove perfluorooctanoic acid (PFOA) and related PFCs in water from 10 ppm to as low as a parts per billion (ppb) level, or an over 98% removal. Dually functionalized microgel-core star polymers with perfluorinated alkanes and additional amino (or ammonium) groups cooperatively recognize PFOA or its ammonium salt and, in addition, release the guests upon external stimuli. The "smart" performance shows that the fluorous-core star polymers are promising PFC separation, recovery, and recycle materials for water purification toward sustainable society.


Diagnostic needle muscle biopsy. A practical and reliable alternative to open biopsy.
The technique of needle muscle biopsy using the Bergstr öm needle has been in routine use in our muscle clinic since 1978. In an initial feasibility study 24 children had a needle and an open biopsy performed simultaneously through extension of the same incision and 22 had identical interpretation of the needle and open biopsies. Needle biopsies have subsequently been performed in 674 children and have been satisfactory for diagnostic assessment in 656. The samples have been of adequate size and comparable in quality to our previous open biopsies, with good preservation and orientation. Needle muscle biopsy under local anaesthetic is quicker and less traumatic than open biopsy and leaves only a very small scar. Sufficient muscle can be obtained for routine histological, histochemical, and electronmicroscopic diagnosis, as well as for specialised biochemical and research purposes. There seems little justification for the continued use of open biopsy for routine investigation of neuromuscular disease.


[Aspergillosis following liver transplantation as a hospital infection].
In the first four weeks after a liver transplantation, there was an invasive aspergillosis with a lethal course in three out of five patients who were treated postoperatively in the same room. The clinical symptoms were very different. One patient was asymptomatic, and the diagnosis could only be made by autopsy. In another patient, pulmonary symptoms, and in the third patient, cerebral symptoms were the most prominent. In the two latter patients, the infection was demonstrated in the sputum and by bronchoalveolar lavage. The disease course was fulminant in all patients, and therapy was without success. Owing to this high incidence, mycological investigations were carried out on the ward. A flower bench in the hall beside the ward was probably the main focus of distribution. To avoid such nosocomial infections, foci of aspergillus distribution should if possible be removed from the surroundings of patients with weakened immune resistance.


[Purification and characterization of L-amino acid oxidase from Agkistrodon halys pallas venom].
L-amino acid oxidase (LAO, EC 22.214.171.124) is widely found in snake venoms and is thought to contribute to the toxicity in envenoming. By using of Sephadex G-150, DEAE-Sepharose CL-6B and FPLC Superose 12 chromatography, a protein with L-amino acid oxidase activity was purified and characterized from Agkistrodon haly Pallas venom. Its molecular mass was 57 kD as determined by SDS-PAGE analysis under both reducing and non-reducing conditions, and its pI was about 4.9. The protein catalysed the stereospecific oxidative deamination of L-amino acid substrate. It inhibited the platelet aggregation induced by ADP and collagen dose-dependently, even at low concentrations of 0.2 micromol/L and 0.08 micromol/L, respectively. The LAO had antibacterial effect to E.coli K12D31, and the effective concentration was as low as 0.03 g/L. Furthermore, the LAO showed cytotoxicity in crystal violet assay and apoptosis-inducing activity in the A549 cells. After 24h treatment with 5 mg/L LAO, the typical DNA fragmentation pattern of apoptotic cells was observed by using of agrose gel electrophoresis.


ADHD: a critical update for educational professionals.
A medical approach towards behavioural problems could make professionals without a medical background, like teachers and other educational professionals feel inapt. In this article, we raise six scientifically grounded considerations regarding ADHD, currently the most prevalent childhood psychiatric diagnosis. These "need to knows" show just how misguided and potentially stigmatizing current conceptualizations of unruly behaviour have become. Some examples are given of how teachers are misinformed, and alternative ways of reporting about neuropsychological research are suggested. A reinvigorated conceptual understanding of ADHD could help educational institutions to avoid the expensive outsourcing of behavioural problems that could also-and justifiably better-be framed as part of education's primary mission of professionalized socialization.


Draft Genome Sequence of Streptomyces sp. M1013, a Close Relative of Streptomyces ambofaciens and Streptomyces coelicolor.
We report the draft genome sequence of Streptomyces sp. M1013, a strain isolated from the Medicago arborea rhizosphere in Izmir, Turkey. An average nucleotide identity (ANI) analysis reveals that this strain belongs to the same species as Streptomyces canus ATCC12647 and is closely related to Streptomyces ambofaciens and Streptomyces coelicolor.


Closed suction wound drainage and lower-segment caesarean section.
In a randomized controlled study of wound suction drainage after transverse suprapubic incision for lower-segment caesarean section no significant advantages could be demonstrated for routine drainage in terms of wound infection, haematoma formation, duration of hospital stay or analgesic requirements.


Regulation of Small Mitochondrial DNA Replicative Advantage by Ribonucleotide Reductase in Saccharomyces cerevisiae.
Small mitochondrial genomes can behave as selfish elements by displacing wild-type genomes regardless of their detriment to the host organism. In the budding yeast Saccharomyces cerevisiae, small hypersuppressive mtDNA transiently coexist with wild-type in a state of heteroplasmy, wherein the replicative advantage of the small mtDNA outcompetes wild-type and produces offspring without respiratory capacity in >95% of colonies. The cytosolic enzyme ribonucleotide reductase (RNR) catalyzes the rate-limiting step in dNTP synthesis and its inhibition has been correlated with increased petite colony formation, reflecting loss of respiratory function. Here, we used heteroplasmic diploids containing wild-type (rho+) and suppressive (rho-) or hypersuppressive (HS rho-) mitochondrial genomes to explore the effects of RNR activity on mtDNA heteroplasmy in offspring. We found that the proportion of rho+ offspring was significantly increased by RNR overexpression or deletion of its inhibitor, SML1, while reducing RNR activity via SML1 overexpression produced the opposite effects. In addition, using Ex Taq and KOD Dash polymerases, we observed a replicative advantage for small over large template DNA in vitro, but only at low dNTP concentrations. These results suggest that dNTP insufficiency contributes to the replicative advantage of small mtDNA over wild-type and cytosolic dNTP synthesis by RNR is an important regulator of heteroplasmy involving small mtDNA molecules in yeast.


Testing the feasibility and acceptability of an online 'Fatigue and Activity Management Education for Work (FAME-W) programme' for individuals with inflammatory arthritis.
Fatigue and Activity Management Education for Work (FAME-W) is a four-week, occupational therapy led programme focussing on fatigue management strategies. FAME-W was designed to be delivered in person; however, due to COVID-19 pandemic it was modified to be an online group-based self-management intervention. The purpose of this study was to test the feasibility and acceptability of the online delivery format of FAME-W. This was a mixed methods study. Participants were randomly allocated to intervention or control group. Participants in the intervention group received a four-week online FAME-W. The control group participants received a FAME-W handbook. Participants were required to complete questionnaires on work presenteeism, fatigue, mood, Health Related Quality of Life and pain at baseline, and 3 months post-intervention. Participants in the intervention group attended a focus group immediately following the completion of the programme and the control group participated in individual interviews. Seven of ten individuals recruited participated in the study. Majority of participants had Rheumatoid Arthritis and were working full-time. The mean age of intervention participants was 53 ± 10.4 and 56.5 ± 3.7 for the controls. All participants in the intervention group had 100% attendance, completed all study measures and activities. Participants had positive comments about the programme format, content, and delivery. Improvements were observed in most measures at follow up. Results suggest that an online programme to improve work ability was feasible and acceptable to individuals with inflammatory arthritis. The online delivery format was favoured over attending a centre-based programme. The findings support a definitive intervention trial of online FAME-W.


A pattern confirmed and refined--synaptic, nonsynaptic and parasynaptic exocytosis.
Neurons are now known to produce a variety of types of chemical transmitters. Classical transmitters are stored within synaptic vesicles which undergo synaptic exocytosis in association with presynaptic thickenings. The larger, dense-cored secretory granules present in most neurons contain neuropeptides and mainly discharge their contents at morphologically undifferentiated (i.e. nonsynaptic) sites. The synaptic character of vesicle discharge enables transmitters to exercise a highly focal action, whereas nonsynaptic release probably relates to the slow rate of degradation of many neuropeptides and their consequent widespread diffusion and sphere of action. However, one variant of the basic pattern, involving the restriction of granule discharge to areas of the terminal plasmalemma situated adjacent to the postsynaptic cells (i.e. a parasynaptic configuration), enables a degree of targeted peptide discharge to be achieved. The diversity of patterns of neural exocytosis adds a further dimension to the complexity of nervous function.


Rapid and sensitive LC-MS approach to quantify non-radioactive transition metal impurities in metal radionuclides.
A rapid and sensitive LC-MS approach for the quantification of non-radioactive metal contaminants present in metal radionuclide formulations was developed. Traditional (12)C/(1)H and heavy stable isotope (13)C/(2)H-labeled chelator-amino acid conjugates are used as chelating agents to quantify contaminating transition metals, allowing for determination of effective specific activity of radio-metals.


Adverse outcomes of Chinese medicines used for threatened miscarriage: a systematic review and meta-analysis.
Threatened miscarriage is very common in early pregnancy. Chinese medicines have been widely used to prevent spontaneous pregnancy loss. However, the safety of Chinese medicines is still unknown. A systematic review was performed to identify and describe adverse events of Chinese medicines used for threatened miscarriage. Clinical studies of Chinese medicines for threatened miscarriage were selected. Primary outcomes were occurrence of adverse effects or toxicity of Chinese medicines. Secondary outcomes were failure of treatment and adverse pregnancy and perinatal outcomes. Thirty-two relevant articles included 9 randomized controlled trials, 1 quasi-randomized controlled trial and 2 controlled trials comparing Chinese medicines alone or combined medicines with pharmaceuticals and 20 case series with no controls. Sample sizes of each study were generally small. There was variation in Chinese medicine formulation, dosage and duration of treatment. In the pooled randomized controlled trials, dry mouth, constipation and insomnia (2-10%) and intervention failure (3.1-22.3%), diabetic complications (3%), preterm delivery (5%) and neurodevelopmental morbidity (1.8%) were recorded. Meta-analysis demonstrated that intervention failure was significantly lower in the combined Chinese medicines groups than in the Western medicines controls (relative risk = 0.46; 95% confidence interval: 0.30-0.70, I(2)= 0%). No significant differences were found between these groups for adverse effects and toxicity or for adverse pregnancy and perinatal outcomes. Studies varied considerably in design, interventions and outcome measures, therefore conclusive results remain elusive. In the absence of placebo-controlled trials, the safety of Chinese medicines for the treatment of threatened miscarriage is unknown. Rigorous scientific and clinical studies to assess the possible risks of Chinese medicines are needed.


Hazard estimation for the chosen work stands in metallurgical industry.
The research has been carried out on the chosen work stands of various strenuousness level in metallurgical industry. Microclimate conditions were estimated, together with noise exposure, dust density and the exposure to the chosen chemical agents, among others carbon monoxide, nitric oxides, manganese and iron. The analysis of the resulting figures showed exceeding of the binding quotas of Wet Bulb Globe Temperature (WBGT) indicator for some stands, leading sometimes to thermal discomfort. The exposure to noise exceeded NDN coefficient for equal sound levels. Dust density on the stands did not exceed binding quotas. The concentration of chemical agents did not exceed the norms, except for single exceeding of manganese, and does not constitute toxicity hazard.


Endocrine status versus chronologic age as predictors of altered luteinizing hormone secretion in the "aging" rat.
LH release in response to GnRH injected at 1400 h was measured in young (3-4 months), middle-aged (10-11 months), and old (19-20 months) female rats. Data were compared when animals were grouped by chronological age or according to their vaginal smear pattern 3-4 weeks before treatment, i.e. regular 4-day cycles, constant vaginal cornification (CVC), or persistently leukocytic smears (PL). Compared to young, regularly cycling females (injected on vaginal estrus or diestrus II), the amount of LH released by all age groups with CVC or PL smears was significantly diminished. However, regardless of age, the amount of LH released by CVC females was similar for each dose of GnRH. Similarly, there was no difference in the amount of LH released by the young, middle-aged, and old PL females at each dose of GnRH. Finally, the amount of LH released by the CVC females was uniformly higher than the amount of LH released by age-matched PL females. In contrast, comparison of LH release after GnRH injection in young and middle-aged rats with regular 4-day vaginal cycles showed that the middle-aged rats released significantly less LH on proestrus. These data suggest that changes in the ability of the pituitary to release LH in the older noncycling female rat occurs as a consequence of the altered endocrine status in the animal and not as a result of the chronological age per se. Changes in the ability of the pituitary of the middle-aged, regularly cycling female rat to release LH in response to GnRH may contribute to the age-related disruption of regular ovarian cycling.


Effect of 6F urethral catheterization on urinary flow rates during repeated pressure-flow studies in healthy female volunteers.
To prospectively examine the effect of a 6F urethral catheter on the urinary flow rate in healthy women without lower urinary tract symptoms undergoing pressure-flow studies. Women between the ages of 30 and 70 years, without lower urinary tract complaints and without a history of surgery for incontinence, were recruited. All women completed the Urogenital Distress Inventory-6 questionnaire, and only women with mild or no symptoms were enrolled. After a free flow rate was determined, cystometry and pressure-flow studies were performed once and then repeated using a 6F urethral catheter. The peak flow rates during the first and second studies were compared with one another and with the nonintubated values. Of the 59 women that applied, 20 volunteers (mean age 41.7 years) met the entry criteria and were evaluated. The mean nonintubated flow rate was 22.65 mL/s. With a 6F urethral catheter in place, our cohort had a mean peak flow rate of 16.25 mL/s on the first study and 15.25 mL/s on the second. A significant difference was demonstrated between the free and intubated peak flow rates for both the first (P = 0.0006) and the second (P = 0.0001) study. No significant difference was detected between the two intubated peak flow rates (P = 0.262). Our data suggest that the presence of a 6F urethral catheter significantly reduces the maximal flow rate compared with free flow studies. Whether these findings represent a truly obstructive effect of the catheter, detrusor fatigue, or other possible effect of the catheter remains to be elucidated.


A catalogue of the type and figured fossil decapod crustaceans in the collections of the Geological Survey of Austria in Vienna.
The present catalogue lists and figures the type and figured material of fossil decapod crustaceans housed in the collections of the Geological Survey of Austria in Vienna. Specimens previously believed to be lost were relocated. Lectotypes and paralectotypes are chosen herein for 11 species. Taxonomic affinity of taxa originally described in open nomenclature is discussed.


The Benefits and Harms of Cleansing for Acute Traumatic Wounds: A Narrative Review.
Acute traumatic wound cleansing is currently a controversial issue demonstrated by the variability in solutions and techniques used to clean wounds in clinical practice. Although there is evidence of improved infection outcomes in wounds cleansed with antiseptics, these observations are often undermined by concurrent use of antibiotics in addition to poor study design. Cleansing techniques including pressurized irrigation have also been investigated indicating potential harms such as edema and inconsistencies in irrigation pressures. The purpose of this article is to provide a narrative review on the contemporary evidence indicating the potential harms and benefits of wound cleansing in the context of acute traumatic wounds.This literature review reveals that acute wound cleansing in clinical practice remains heavily dependent on tradition rather than robust clinical evidence. The evidence base remains limited because of methodological and pragmatic issues in obtaining definitive data on the efficacy of specific agents and techniques. Future studies should focus on establishing the relative benefits of different cleansing solutions and techniques. Establishing the most effective use of antiseptic cleansing solutions may also help reduce further antimicrobial resistance as observed in recent studies. Clinicians responsible for cleansing wounds must consider patient preference when deciding which solution and techniques are used. In addition, a risk assessment considering the potential harms and benefits of different solutions and techniques must be performed.


Factors influencing the reading of small irregular opacities in a radiological survey of asbestos miners in South Africa.
A cross-sectional radiological survey of 2,245 men who were employed in South African asbestos mines was conducted in 1976. Since 1976, the lungs of 172 of these men who died have been examined to establish the presence of asbestosis or other pneumoconiosis. The x-ray readings (ILO/UC 1971) were compared with the pathological findings. A high prevalence of false positive readings, particularly for two of the three readers, was found. False negative readings were also very prevalent. Detailed information about asbestos and other mining exposure, smoking habit, age, height, and weight were examined to determine what influence they may have had in inducing false positive findings. Other dust exposure and smoking appeared to be possible factors, whereas age and obesity were probably not. It is suggested that the term "small irregular opacities" requires more precise definition.


Use of benzodiazepines in obsessive-compulsive disorder.
This study aimed to determine the frequency of benzodiazepine (BDZ) use in a large sample of patients with obsessive-compulsive disorder (OCD) and ascertain the type of BDZ used and the correlates and predictors of BDZ use in OCD. The sample consisted of 955 patients with OCD from a comprehensive, cross-sectional, multicentre study conducted by the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders between 2003 and 2009. The rate of BDZ use over time in this OCD sample was 38.4%. Of individuals taking BDZs, 96.7% used them in combination with other medications, usually serotonin reuptake inhibitors. The most commonly used BDZ was clonazepam. Current age, current level of anxiety and number of additional medications for OCD taken over time significantly predicted BDZ use. This is the first study to comprehensively examine BDZ use in OCD patients, demonstrating that it is relatively common, despite recommendations from treatment guidelines. Use of BDZs in combination with several other medications over time and in patients with marked anxiety suggests that OCD patients taking BDZs may be more complex and more difficult to manage. This calls for further research and clarification of the role of BDZs in the treatment of OCD.


Calcium-Sensitive Receptors Alters Intestinal Microbiota Metabolites Especially SCFAs and Ameliorates Intestinal Barrier Damage in Neonatal Rat Endotoxemia.
The calcium-sensing receptor (CaSR) acts as a major modulator of tissue responses related to calcium homeostasis and expresses highly in the mammalian intestine. Endotoxemia tends to impair intestinal barrier function and poses significant obstacles in clinical treatment. This work is designed to decipher whether CaSR can protect lipopolysaccharide (LPS)-induced intestinal barrier dysfunction in neonatal rats by targeting intestinal metabolites. In this study, we utilized gas chromatography (GC) combined with liquid chromatography-mass spectrometry (LC-MS) to quantitatively analyze SCFAs and metabolites in fecal samples of 24 neonatal rats with LPS induced endotoxemia. Our results showed that CaSR alleviated endotoxin damage to the intestinal tight junction structure and upregulated the levels of butyric acid, propionic acid, valeric acid, and isovaleric acid in short-chain fatty acids (SCFAs). Non-targeted metabolomics analysis indicated that CaSR improved intestinal metabolic disorders by regulating glycerophospholipid metabolism, α-linolenic acid metabolism, as well as sphingolipids metabolism. CaSR can alter intestinal microbiota metabolites, especially SCFAs, and improve intestinal barrier damage in neonatal rat endotoxemia.


Substrate analogs as mechanistic probes for the bifunctional chorismate synthase from Neurospora crassa.
Analogs of EPSP (4-8) have been prepared, and their activity as substrates for the chorismate synthase from Neurospora crassa has been characterized kinetically. The enzyme appears to show strict discrimination against substitution at the Z-position of the enol ether side chain as well as against substitution at the S-position of the reduced analogs. Both the glycolyl and (R)-lactyl analogs 4 and (R)-5 are good substrates, with (R)-5 having a higher V value than the natural substrate. Three substrates, including EPSP, have been found to show significant substrate inhibition with this enzyme, which at present can be explained by a noncompetitive model involving formation of a catalytically incompetent, ternary ES2 complex. A significant secondary kinetic isotope effect on V of 1.10 +/- 0.02 has been observed at C-3 with EPSP, indicating that C-O bond cleavage is kinetically significant at saturating substrate concentration; this effect is severely depressed at limiting substrate, with D(V/K) = 0.97 +/- 0.02. A similar effect is found for the primary deuterium isotope effect at C-6R, as observed previously [Balasubramanian, S., Davies, G. M., Coggins, J. R., & Abell, C. (1991) J. Am. Chem. Soc. 113, 8945-8946]. The primary isotope effects at C-6R with reduced analogs (R)-5 and (S)-6 are significantly larger than those with EPSP. The larger values of V and DV for (R)-5, when compared to EPSP, are evidence that release of chorismate is partially rate-limiting under saturating conditions. Incubation of the enzyme with reduced 5-deazaFMN does not result in any observable formation of chorismate, consistent with previous results indicating that reduced flavin is chemically involved in the synthesis of chorismate from EPSP [Ramjee, M. N., Balasubramanian, S., Abell, C., Coggins, J. R., Davies, G. M., Hawkes, T. R., Lowe, D. J., & Thorneley, R. N. F. (1992) J. Am. Chem. Soc. 114, 3151-3153].


Uveal melanoma in congenital ocular melanocytosis mimicking malignant transformation of the optic disc melanocytoma (a controlled case).
A case of a 57-year old woman with uveal melanoma of the posterior pole arising in the congenital ocular melanocytosis mimicking clinically malignant transformation of the optic disc melanocytoma is presented.


Treatment of intrahepatic congenital portosystemic shunts in dogs: a systematic review.
The aim of this study was to establish the evidence base for the treatment of intrahepatic congenital portosystemic shunts in dogs through a systematic review of the pertinent literature. Studies were filtered for evidence to answer the question "Which of the treatment options for intrahepatic CPSS in dogs offers the best short- and long-term outcome?" Studies were assigned a level of evidence based on a system published by the Oxford Centre for Evidence-Based Medicine. Thirty-two studies were included in the review. Twenty-six provided level 4 evidence and six provided level 5 evidence. There were no level 1, 2 or 3 studies. One study compared surgical treatment with medical management and one study compared suture ligation with ameroid constrictor placement. The remaining studies were case series describing the outcome for one treatment method alone. Methods and timings of assessments of short- and long-term outcomes were highly varied, making direct comparisons challenging. The evidence regarding the treatment of intrahepatic congenital portosystemic shunts in dogs is weak, with only two studies directly comparing treatments. There is a lack of evidence regarding short- and long-term outcomes on which to base clinical decisions.


Non-genetic heterogeneity, criticality and cell differentiation.
The different cell types in a living organism acquire their identity through the process of cell differentiation in which multipotent progenitor cells differentiate into distinct cell types. Experimental evidence and analysis of large-scale microarray data establish the key role played by a two-gene motif in cell differentiation in a number of cell systems. The two genes express transcription factors which repress each other's expression and autoactivate their own production. A number of theoretical models have recently been proposed based on the two-gene motif to provide a physical understanding of how cell differentiation occurs. In this paper, we study a simple model of cell differentiation which assumes no cooperativity in the regulation of gene expression by the transcription factors. The latter repress each other's activity directly through DNA binding and indirectly through the formation of heterodimers. We specifically investigate how deterministic processes combined with stochasticity contribute in bringing about cell differentiation. The deterministic dynamics of our model give rise to a supercritical pitchfork bifurcation from an undifferentiated stable steady state to two differentiated stable steady states. The stochastic dynamics of our model are studied using the approaches based on the Langevin equations and the linear noise approximation. The simulation results provide a new physical understanding of recent experimental observations. We further propose experimental measurements of quantities like the variance and the lag-1 autocorrelation function in protein fluctuations as the early signatures of an approaching bifurcation point in the cell differentiation process.


Activity and density of the Na+/H+ antiporter in normal and transformed human lymphocytes and fibroblasts.
The turnover number for the sodium-hydrogen exchanger isoform 1 (NHE-1) has been determined in human lymphocytes and MRC5 fibroblasts and in their virally transformed counterparts. Using fluorometric methods, we have determined the intracellular pH and Na+/H+ antiport activity of these cells. Intracellular pH was elevated in both lines of transformed cells. In contrast, Na+/H+ antiport activity was apparently unchanged in simian virus 40-transformed MRC5 fibroblasts (MRC5 SV1 TV1 28.9 +/- 5.2 mM/min compared with MRC5 fibroblasts 26.5 +/- 5.3 mM/min) but slightly increased in Epstein-Barr virus-transformed lymphoblasts (16.7 +/- 1.0 mM/min compared with lymphocytes 13.5 +/- 2.3 mM/min, P < 0.05). With the use of specific antisera to NHE-1, viral transformation was associated with a decreased number of NHE-1 molecules per cell in fibroblasts (from 441,504 +/- 53,428 to 64,745 +/- 7,151 sites/cell, P < 0.001) but an increased number in lymphocytes (from 14,066 +/- 3,100 to 22,474 +/- 4,050 sites/cell, P < 0.01). The NHE-1 density per cell yielded very similar turnover numbers for NHE-1 in the untransformed cells (lymphocytes, 3,161 +/- 833 cycles/s; MRC5 fibroblasts, 3,026 +/- 441 cycles/s), which were significantly elevated in the transformed cells (lymphoblasts, 8,471 +/- 1,177 cycles/s; MRC5 SV1 TV1, 10,521 +/- 2,299 cycles/s, P < 0.001 compared with untransformed cells). We conclude that viral transformation has different effects on Na+/H+ antiport activity and NHE-1 density per cell in different cell types, but the turnover number of NHE-1 is significantly increased after viral transformation, which correlates with the increased proliferation rate of these transformed cells.


Safe Transitions and Congregate Living in the Age of COVID-19: A Retrospective Cohort Study.
COVID-19 represents a grave risk to residents in skilled nursing facilities (SNFs). To determine whether establishment of an appropriate-use committee was associated with a reduction in SNF utilization. Retrospective cohort study at NorthShore University HealthSystem, a multihospital integrated health system in northern Illinois. Participants were patients hospitalized from March 19, 2019, to July 16, 2020. Creation of a multidisciplinary committee to assess appropriateness of discharge to SNF following hospitalization. Primary outcome was total discharges to SNFs. Secondary outcomes were new discharges to SNFs, readmissions, length of stay (LOS), and COVID-19 incidence following discharge. Matched populations pre and post intervention were each 4424 patients. Post intervention, there was a relative reduction in total SNF discharges of 49.7% (odds ratio [OR], 0.42; 95% CI, 0.38-0.47) and in new SNF discharges of 66.9% (OR, 0.29; 95% CI, 0.25-0.34). Differences in readmissions and LOS were not statistically significant. For patients discharged to a SNF, 2.99% (95% CI, 1.59%-4.39%) developed COVID-19 within 30 days, compared with 0.26% (95% CI, 0.29%-0.93%) of patients discharged to other settings (P < .001). Implementing a review committee to assess for appropriateness of SNF use after a hospitalization during the COVID-19 pandemic is highly effective. There was no negative impact on safety or efficiency of hospital care, and reduced SNF use likely prevented several cases of COVID-19. This model could serve as a template for other hospitals to reduce the risks of COVID-19 in SNFs and as part of a value-based care strategy.


A phase II study of modified deGramont 5-fluorouracil, leucovorin, and oxaliplatin in previously treated patients with metastatic colorectal cancer.
To evaluate the toxicity and efficacy of a modified deGramont regimen of 5-fluorouracil (5-FU), leucovorin, and oxaliplatin in patients with advanced colorectal cancer who have progressed on at least one but not more than two prior chemotherapy regimens. Patients with stage 4 colorectal cancer were treated with oxaliplatin 85 mg/m2 by a 2-hour intravenous infusion, followed by leucovorin 500 mg/m2 by a 2-hour intravenous infusion, followed by 5-FU 400 mg/m2 by bolus injection, followed by 5-FU 2.4 g/m2 administered by a 46-hour continuous infusion. Cycles were administered every 2 weeks. Seventy patients were treated and 68 patients had previously received irinotecan. Eleven percent of patients had a partial response, 33% of CEA-evaluable patients had a > or = 50% drop in their CEA level. The median time to progression was 6.2 months, and the median overall survival was 8.7 months. Toxicity was mild to moderate, as 14% of patients experienced grade 3 or 4 neutropenia and 3% of patients experienced grade 3 neuropathy. The modified deGramont regimen of 5-FU, leucovorin, and oxaliplatin is tolerable and is associated with a modest degree of antitumor activity in patients who have progressed on both 5-FU and irinotecan.


Magnetofection based on superparamagnetic iron oxide nanoparticle-mediated low lncRNA HOTAIR expression decreases the proliferation and invasion of glioma stem cells.
Glioma stem cells (GSCs) are a special subpopulation of glioma cells that are key to the sensitivity of tumors to treatments and to the possibility of tumor recurrence. Identifying new strategies that inhibit the growth of GSCs are therefore important for developing novel therapies for glioblastoma multiforme (GBM). In this study, CD133+ human glioma stem cells were isolated and cultured. Magnetic nanoparticles were used to mediate the expression of siRNAs targeting the HOTAIR (si-HOTAIR) sequence in human gliomas. Effect of downregulation of HOTAIR expression on proliferation, invasion and in vivo tumorigenicity of human GSCs and underlying molecular mechanisms were further evaluated. The results of the MTT assay and flow cytometric analysis showed that downregulation of HOTAIR expression inhibited cell proliferation and induced cell cycle arrest. Transwell assays demonstrated that downregulation of HOTAIR expression resulted in a decrease in the invasive capability of GSCs. Moreover, magnetic nanoparticle-mediated low expression of HOTAIR effectively reduced the tumorigenic capacity of glioma stem cells in vivo. In addition, the results of qRT-PCR and western blot analysis demonstrated that downregulation of HOTAIR expression significantly increased the expression of PDCD4 in GSCs, in addition to reducing the expression of CCND1 and CDK4. An in-depth mechanistic analysis showed that downregulation of HOTAIR expression reduced the recruitment of downstream molecules, EZH2 and LSD1, thereby activating the expression of PDCD4 at the transcriptional level. In conclusion, downregulation of HOTAIR expression effectively promoted the expression of PDCD4, thereby inhibiting the proliferation, invasion and in vivo tumorigenicity of human GSCs.


Non-destructive enhancement of latent fingerprints on stainless steel surfaces by electrochemiluminescence.
Visualization and detection of latent fingerprints (LFPs) on metal surfaces are of highly practical importance, e.g., in identifying gun cartridges. We report herein the visualization of LFPs on stainless steel surfaces by electrochemiluminescence (ECL). Since organic residues, such as fatty acids, in the fingerprint deposit make the underlying surface electrochemically inert or less active, an ECL reaction occurs only on the metal portions untouched by the fingertip, hence generating a negative image of the fingerprint. The popular ECL reaction solution, consisting of ruthenium(ii) tris(2,2'-bipyridyl) and tri-n-propylamine, was used for this imaging purpose. Factors, including the applied potential and the concentration of ECL luminophore, as well as the stability of ECL negative images, were investigated to achieve a satisfactory visualization enhancement. This imaging approach is simple, rapid, non-invasive, and no pre-treatment either on the background or on the fingerprint itself is needed. It constitutes a powerful tool for visualizing LFPs on metal surfaces. This method was also demonstrated to be suitable for enhancing LFPs collected from various surfaces.


Eczema and ceramides: an update.
Although normal epidermal barrier function depends on numerous factors, including corneocytes, lipids, enzymes, pH, and calcium gradient, the key players are lipids and proteins in the stratum corneum. Atopic dermatitis is characterized by barrier abnormalities, such as the presence of filaggrin mutations in almost 50% of patients with moderate/severe atopic dermatitis, and lipid disturbances, mainly expressed as insufficient ceramides. In this review, with an emphasis on human studies, we consider the latest research on ceramides, on ceramides in different types of eczema and following various types of treatment. We also consider the genetic influence on stratum corneum lipids. The review is an update on research indexed in PubMed following the discovery of the filaggrin mutations in atopic dermatitis in 2006, but when newer publications cannot stand alone, we include publications from before 2006.


Senile Cardiac Calcification Syndrome: A Rare Case of Extensive Calcification of Left Ventricular Papillary Muscle.
Extensive papillary muscle calcification is uncommon and only scarce literature about causes and the clinical significance is available, whereas small calcific deposits are common findings in elderly people and are located most commonly at the apex. Papillary muscle calcification has been associated with coronary artery disease, dilated cardiomyopathy, mitral valve disease, hypercalcemia, and increased calcium phosphate product in end stage renal disease. We reported a rare case of extensive calcification of anterolateral papillary muscle diagnosed by echocardiography and multidetector computed tomography.


Takotsubo Cardiomyopathy in a Post-COVID Case.
Takotsubo cardiomyopathy (TTC) is a unique heart disease that mimics the clinical presentation of acute coronary syndrome and is seen more commonly in post-menopausal females. Here, we report a case that presents an ideal documentation of TTC depicting its characteristic clinical features and possible outcomes. TTC usually culminates in a complete reversal of both systolic and diastolic dysfunctions, however in our case of a post-COVID scenario, the persisting, rather worsening diastolic dysfunction might be a residual manifestation of COVID-19 myocarditis. Recent reports have found an increasing prevalence of TTC amidst the COVID-19 pandemic possibly as a result of the emotional and physical stress, and subsequent catecholamine surge caused by the virus in such patients. There might exist an independent association between TTC and the COVID-19 virus. Increased clinical evidence is required to establish the strength of this relationship, if any.


IL-2 and IL-15 receptor alpha-subunits are coexpressed in a supramolecular receptor cluster in lipid rafts of T cells.
The private alpha-chains of IL-2 and IL-15 receptors (IL-2R and IL-15R) share the signaling beta- and gamma(c)-subunits, resulting in both common and contrasting roles of IL-2 and IL-15 in T cell function. Knowledge of the cytokine-dependent subunit assembly is indispensable for understanding the paradox of distinct signaling capacities. By using fluorescence resonance energy transfer and confocal microscopy, we have shown that IL-2R alpha, IL-15R alpha, IL-2/15R beta and gamma(c)-subunits, as well as MHC class I and II glycoproteins formed supramolecular receptor clusters in lipid rafts of the T lymphoma line Kit 225 FT7.10. Fluorescence crosscorrelation microscopy demonstrated the comobility of IL-15R alpha with IL-2R alpha and MHC class I. A model was generated for subunit switching between IL-2R alpha and IL-15R alpha upon the binding of the appropriate cytokine resulting in the formation of high-affinity heterotrimeric receptors. This model suggests a direct role for the alpha-subunits, to which no definite function has been assigned so far, in tuning cellular responses to IL-2 or IL-15. In addition, both alpha-chains were at least partially homodimerized/oligomerized, which could be the basis of distinct signaling pathways by the two cytokines.


Race and Sex Disparities in Outcomes of Dialysis Access Maintenance Interventions.
To determine whether utilization and outcomes of dialysis access maintenance interventions vary by patient race or sex. Data for this retrospective cohort study of first-time arteriovenous (AV) access recipients were drawn from a 5% sample of Medicare beneficiaries, containing claims from all clinical settings (2009-2014) in 2,693 patients who received their first AV fistula/graft in 2009. Maintenance interventions-angiography, angioplasty, thrombolysis, stent placement, and venous embolization-were identified by corresponding Current Procedural Terminology codes. Outcomes of primary patency (PP), postinterventional primary patency (PIPP), and postinterventional secondary patency (PISP) were calculated with utilization records. Associations between demographic data and patency times were evaluated by a multivariate survival approach, controlling for baseline differences in patient age, comorbid disease, type of dialysis access, and interventionist specialty. AV grafts (AVGs) were created with greater frequency in women (32% vs 23% in men; P < .001) and minority patients (39% in black, 32% in Hispanic, and 29% in Asian patients vs 21% in white patients; P < .001). Women were at greater hazards for loss of PP (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.09-2.14) and PIPP (HR, 1.42; 95% CI, 1.01-2.00). Black patients were at greater hazards for loss of PP (HR, 1.37; 95% CI, 1.23-1.54) and PISP (HR, 1.29; 95% CI, 1.01-1.65). AVG creation predisposed patients to patency loss in all models (P < .001). Dialysis access patency rates are lower for women and black patients. More frequent primary AVG creation in women and minority patients additionally predisposes these patients to patency loss.


Reflections on learning and teaching medical ethics in UK medical schools.
The development of learning, teaching and assessment of medical ethics and law over the last 40 years is reflected upon with particular reference to the roles of the London Medical Group, the Society for the Study of Medical Ethics, its successor Institute of Medical Ethics; the Journal of Medical Ethics and the General Medical Council. Several current issues are addressed. Although the situation seems incomparably better than it was 40 years ago, the relatively recent events in Mid Staffordshire National Health Service (NHS) Foundation Trust show we cannot be complacent. Whatever role we have in the NHS or medical education, we must all strive to make sure it never happens again.


Alterations in the myocardial beta-adrenoceptor system of streptozotocin-diabetic rats.
Previous investigations in our laboratory revealed subsensitivity of right ventricular tissue, isolated from one month STZ-diabetic rats, to the inotropic effects of isoproterenol. The present study was concerned with the characterization of this subsensitivity phenomenon. Observations of supersensitivity to methoxamine accompanied by decreased responsiveness to glucagon without a change in responsiveness to forskolin suggested a specific effect of diabetes on pathways involving receptor-mediated activation of adenylate cyclase. Radioligand binding analysis further revealed a specific decrease in the population of the high affinity state of the beta-adrenoceptor. Since the high affinity receptor state is a necessary intermediate for adenylate cyclase activation and enhanced myocardial contractility, it is proposed that the specific decrease in the high affinity population of the beta-adrenoceptor contributes to myocardial subsensitivity to isoproterenol observed in the diabetic animals. It is further proposed that the decrease in receptor population is related to increases in circulating epinephrine levels which were evident in the diabetic animals.


A quantitative description in three dimensions of oxygen uptake by human red blood cells.
Oxygen uptake by human erythrocytes has been examined both experimentally and theoretically in terms of the influence of unstirred solvent layers that are adjacent to the cell surface. A one-dimensional plane sheet model has been compared with more complex spherical and cylindrical coordinate schemes. Although simpler and faster, the plane sheet algorithm is an inadequate representation when unstirred solvent layers are considered. The cylindrical disk model most closely represents the physical geometry of human red cells and is required for a quantitative analysis. In our stopped-flow rapid mixing experiments, the thickness of the unstirred solvent layer expands with time as the residual turbulence decays. This phenomenon has been quantified using a formulation based on previously developed hydrodynamic theories. An initial 10(-4) cm unstirred layer is postulated to occur during mixing and expand rapidly with time by a (t)0.5 function when flow stops. This formula, in combination with the three-dimensional cylinder scheme, has been used to describe quantitatively uptake time courses at various oxygen concentrations, two different external solvent viscosities, and two different internal heme concentrations.


Perioperative management and outcomes of aortic surgery during pregnancy.
Pathology of the aortic valve and ascending thoracic aorta is an uncommon but life-threatening complication of pregnancy. Cardiac surgery during pregnancy is known to carry a high risk of mortality to both the mother and fetus. We present our experience of performing aortic surgery during the patients' pregnancy. All patients undergoing aortic surgery during pregnancy at St George's Hospital, from January 2004 until October 2013, were identified. Surgery was performed using cardiopulmonary bypass at 36°C, with pulsatile perfusion at 70 mm Hg. Fetal blood flow parameters were serially monitored during surgery, via transabdominal and/or transvaginal Doppler ultrasonography. Surgery was performed in the second trimester when possible to allow completion of organogenesis and minimize hemodynamic compromise. Eleven patients underwent aortic surgery. The median age was 28 years (range, 26-31 years), with gestational age 19 weeks (range, 16-21 weeks). Six patients had aortic root dilatation with aortic regurgitation, and 5 had aortic stenosis, one of whom presented with acute type A dissection. Four patients had Marfan syndrome, and 2 had undergone previous cardiac surgery. The operative procedures were aortic root replacement (tissue valve, n = 5; homograft, n = 1), aortic valve replacement (n = 3), valve-sparing root replacement (n = 1), and aortic and mitral valve replacements (n = 1). Mean cardiopulmonary bypass and cross-clamp times were 105 and 89 minutes, respectively. There were no maternal deaths; 8 healthy babies were born at term, and 3 pregnancies resulted in intrauterine demise within 1 week of surgery. Major aortic surgery during pregnancy carries a high risk to both mother and baby. With appropriate maternal and fetal monitoring, attention to cardiopulmonary bypass, pulsatile perfusion, near-normothermia, and avoidance of vasoconstrictors, these risks may be minimized.


Intraepithelial and invasive squamous cell carcinoma of the conjunctiva: analysis of 60 cases.
To evaluate the clinical features, treatment results, and recurrence rates in patients with either intraepithelial or invasive squamous cell carcinoma of the conjunctiva. Retrospective analysis of 60 cases (22 conjunctival intraepithelial and 38 invasive squamous cell carcinomas) to determine patterns of clinical presentation, aetiological factors, and treatment results. The mean patient age was 64 years old. 70% of the patients were male. Patients were treated with a variety of therapies, depending on the degree of tumour involvement; most cases were treated with frozen section controlled excision and adjunctive cryotherapy. Modified eye wall resection or enucleation was done for intraocular invasion and exenteration was done for orbital involvement. Red eye (68%) and ocular irritation (57%) were the most common presenting symptoms. 44% of the patients had other eye findings consistent with extensive solar exposure. 20% of the patients had a history of malignant skin tumours. Visceral malignancies developed in 8%. Scleral involvement was present in 14 (37%), intraocular involvement in five (13%), and orbital invasion in four (11%) cases with invasive squamous cell carcinoma. After a mean follow up of 56 months (18-226 months) the rate of new or recurrent tumours was 4.5% for intraepithelial squamous carcinoma and 5.3% for invasive squamous cell carcinoma. No patient developed metastases or tumour related deaths. Excision with intraoperative control of the surgical margins and adjunctive cryotherapy results in good tumour control rates.


Comparison of prognostic nomograms based on different nodal staging systems in patients with resected gastric cancer.
Purpose: Previous studies addressing the optimal nodal staging system in patients with resected gastric cancer have shown inconsistent results, and the optimal system for development of prognostic nomograms remains unclear. In this study, we compared prognostic nomograms based on the metastatic lymph node (MLN) count, lymph node ratio (LNR), and log odds of metastatic lymph nodes (LODDS) to predict the 5-year overall survival in patients with resected gastric cancer. Methods: We analysed 15,320 patients with resected gastric cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 1988 and 2010. Missing data were handled using multiple imputation. When assessed as a continuous covariate with restricted cubic splines, each MLN, LNR, and LODDS variable was incorporated into a nomogram with other significant prognosticators to predict the 5-year overall survival. A two-centre Chinese dataset (1,595 cases) was used as external validation data. Results: The discriminatory abilities of the MLN-, LNR-, and LODDS-based nomograms were comparable (concordance indices: 0.744, 0.741, and 0.744, respectively, in the SEER set, P > 0.152 for all pairwise comparisons; 0.715, 0.712, and 0.713, respectively, in the Chinese set, P > 0.445 for all pairwise comparisons). The discriminatory abilities of the three nomograms were all superior to the American Joint Committee on Cancer (AJCC) TNM classification (concordance indices: 0.713, P < 0.001 for all in the SEER set; and 0.693, P < 0.001 for all in the Chinese set). The discriminatory abilities of the nomograms were comparable regardless of the number of nodes examined. Moreover, decision curve analyses indicated similar net benefits of using the nomograms. Conclusion: MLN-, LNR-, and LODDS should be considered equally in the development of multivariate prognostic models and nomograms to refine the prediction of survival among patients with resected gastric cancer.


Arabidopsis-expressing lysine-null SUMO1 reveals a non-essential role for secondary SUMO modifications in plants.
The reversible conjugation of small ubiquitin-like modifier (SUMO) to other proteins has pervasive roles in various aspects of plant development and stress defense through its selective attachment to numerous intracellular substrates. An intriguing aspect of SUMO is that it can be further modified by SUMOylation and ubiquitylation, which isopeptide-link either or both polypeptides to internal lysines within previously bound SUMOs. Although detectable by mass spectrometry, the functions of these secondary modifications remain obscure. Here, we generated transgenic Arabidopsis that replaced the two related and essential SUMO isoforms (SUMO1 and SUMO2) with a lysine-null SUMO1 variant (K0) immune to further SUMOylation/ubiquitylation at these residues. Remarkably, homozygous SUMO1(K0) sumo1 sumo2 plants developed normally, were not hypersensitive to heat stress, and have nearly unaltered SUMOylation profiles during heat shock. However, subtle changes in tolerance to salt, paraquat, and the DNA-damaging agents bleomycin and methane methylsulfonate were evident, as were increased sensitivities to ABA and the gibberellic acid biosynthesis inhibitor paclobutrazol, suggesting roles for these secondary modifications in stress defense, DNA repair, and hormone signaling. We also generated viable sumo1 sumo2 lines expressing a SUMO1(K0) variant specifically designed to help isolate SUMO conjugates and map SUMOylation sites, thus offering a new tool for investigating SUMO in planta.


Azurin Regulates P21 and Enhances the Sensitivity of Osteosarcoma Cells to Cisplatin.
Osteosarcoma (OS) is the most common bone malignancy, with a high mortality rate in adolescents. Despite advancements in therapeutic interventions, OS prognosis remains poor due to drug resistance. P21, a cyclin-dependent kinase inhibitor, plays a critical role in cell cycle regulation and has been implicated in OS pathogenesis. Cisplatin (DDP) is a conventional chemotherapeutic agent for OS, but its efficacy is often limited due to drug resistance. Azurin, a bacterial redox protein, has been reported to exhibit antitumor activity. However, its interaction with P21 in OS remains unexplored. In this study, we sought to investigate the impact of azurin on the cytotoxic effect of DDP against OS cells in relation to P21 expression. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to determine the level of p21 and apoptosis-related factors in U2OS cells. A Cell Counting Kit-8 (CCK-8) was used to examine the effects of azurin-p21 on the U2OS cell proliferation rate. Flow cytometry (FCM)was used to analyze the impact of azurin-P21 on the apoptosis/cell cycle. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the effects of azurin-P21 on the secretion of oxygen free radicals, glutathione and glutathione peroxidase. Azurin exhibited significant cytotoxic activity against U2OS cells expressing wild-type (WT) P21, with minimal impact on SAOS-2 and MG63 cells lacking endogenous P21. Azurin treatment resulted in increased expression of procaspase-3 and Bax, decreased expression of B-cell lymphoma-2 (Bcl-2) and a consequential increase in apoptosis. The depletion of P21 attenuated these effects, suggesting the crucial role of P21 in azurin-mediated cytotoxicity. Furthermore, azurin synergistically enhanced the cytotoxic effect of DDP against U2OS cells, which was mitigated by P21 depletion. Our findings demonstrated that azurin selectively induces apoptosis and cell cycle arrest in U2OS cells, which is mediated via P21. This study highlights the potential of azurin as a sensitizer for DDP in the treatment of OS. Future studies on DDP-resistant OS cells may further elucidate the clinical relevance of our findings.


Collagen-induced arthritis.
The mouse model collagen-induced arthritis (CIA) is a widely studied autoimmune model of rheumatoid arthritis. In this model, autoimmune arthritis is induced by immunization with type II collagen (CII) emulsified in complete Freund's adjuvant. This unit describes the steps necessary for the acquisition, handling, and preparation of CII, in addition to the selection of mouse strains, proper immunization technique, and methods for evaluation of the incidence and severity of arthritis. In this model, the first signs of arthritis appear approximately 21 to 28 days after immunization. The protocols in this unit should provide the investigator with all the necessary information required to reproducibly induce a high incidence of CIA in genetically susceptible strains of mice, and to critically evaluate the pathology of the disease.


[Results of a randomized polychemotherapy study in malignant melanoma].
A polychemotherapy (DTIC, vincristine, ftorafur, hydroxycarbamide) devised with reference to the results of short-term sensitivity tests in cell culture is compared with single-agent chemotherapy with DTIC in malignant melanoma. Effectiveness was investigated in a randomized prospective study in cases of high-risk melanoma in clinical stage I, in clinical stage II after lymphadenectomy and in clinical stage III after tumour debulking. The results recorded allow no positive effects of either form of chemotherapy in stage I disease compared with surgical treatment only in a control group. In contrast, a statistically significant advantage of the polychemotherapy was noted in stage II compared with a control group. There was no significant difference in the results of treatment between the two forms of chemotherapy in stage III. No complete remissions of long duration have been achieved.


Autophagy controls resource allocation and protein storage accumulation in Arabidopsis seeds.
Autophagy is essential for nutrient recycling and plays a fundamental role in seed production and grain filling in plants. Autophagy participates in nitrogen remobilization at the whole-plant level, and the seeds of autophagy mutants present abnormal C and N contents relative to wild-type (WT) plants. It is well known that autophagy (ATG) genes are induced in leaves during senescence; however, expression of such genes in seeds has not yet been reported. In this study we show that most of the ATG genes are induced during seed maturation in Arabidopsis siliques. Promoter-ATG8f::UIDA and promoter-ATG8f::GFP fusions showed the strong expression of ATG8f in the phloem companion cells of pericarps and the funiculus, and in the embryo. Expression was especially strong at the late stages of development. The presence of many GFP-ATG8 pre-autophagosomal structures and autophagosomes confirmed the presence of autophagic activity in WT seed embryos. Seeds of atg5 and WT plants grown under low- or high-nitrate conditions were analysed. Nitrate-independent phenotypes were found with higher seed abortion in atg5 and early browing, higher total protein concentrations in the viable seeds of this mutant as compared to the WT. The higher total protein accumulation in atg5 viable seeds was significant from early developmental stages onwards. In addition, relatively low and early accumulation of 12S globulins were found in atg5 seeds. These features led us to the conclusion that atg5 seed development is accelerated and that the protein storage deposition pathway is somehow abnormal or incomplete.


Absolute ethanol intake predicts ethanol preference in Drosophilamelanogaster.
Factors that mediate ethanol preference in Drosophila melanogaster are not well understood. A major confound has been the use of diverse methods to estimate ethanol consumption. We measured fly consumptive ethanol preference on base diets varying in nutrients, taste and ethanol concentration. Both sexes showed an ethanol preference that was abolished on high nutrient concentration diets. Additionally, manipulating total food intake without altering the nutritive value of the base diet or the ethanol concentration was sufficient to evoke or eliminate ethanol preference. Absolute ethanol intake and food volume consumed were stronger predictors of ethanol preference than caloric intake or the dietary caloric content. Our findings suggest that the effect of the base diet on ethanol preference is largely mediated by total consumption associated with the delivery medium, which ultimately determines the level of ethanol intake. We speculate that a physiologically relevant threshold for ethanol intake is essential for preferential ethanol consumption.


Long Noncoding RNA LINC00909 Induces Epithelial-Mesenchymal Transition and Contributes to Osteosarcoma Tumorigenesis and Metastasis.
Osteosarcoma (OS) is a malignant tumor that is highly metastatic with a high mortality rate. Although mounting evidence suggests that LINC00909 is strongly associated with the malignant progression of various tumors, the exact role of LINC00909 in OS remains unknown. Therefore, the current study was designed to investigate the relationship between LINC00909 and the malignant progression of OS. LINC00909 expression was measured in OS cell lines and clinical specimens using RT-qPCR assays. The effects of LINC00909 on OS proliferation, invasion, and migration were calculated both in vitro and in vivo. Apart from that, bioinformatics analyses, FISH, RIP, and luciferase reporter assays were carried out to investigate the downstream target of LINC00909. Rescue experiments were also conducted to investigate the potential mechanisms of action of competitive endogenous RNAs (ceRNAs). In this study, we found that LINC00909 was highly expressed in OS cell lines and clinical specimens. In vivo and in vitro experiments demonstrated that LINC00909 induces epithelial-to-mesenchymal transition (EMT) and contributes to OS tumorigenesis and metastasis. FISH, RIP, and luciferase assays indicated that miR-875-5p is a direct target of LINC00909. Moreover, HOXD9 was validated as the downstream target of miR-875-5p in a luciferase reporter assay and western blotting experiments. Rescue experiments revealed that HOXD9 reversed the effect of LV-sh-LINC00909 on OS cells by positively regulating the PI3K/AKT/mTOR signaling pathway. Collectively, LINC00909 induces EMT and contributes to OS tumorigenesis and metastasis through the PI3K/AKT/mTOR pathway by binding to miR-875-5p to upregulate HOXD9 expression. Targeting the LINC00909/miR-875-5p/HOXD9 axis may have potential in treating OS.


Chiral boron enolate aldol additions to chiral aldehydes.
We have examined the double-diastereodifferentiating aldol addition reactions of chiral enolborinate 1a with chiral aldehydes leading to the corresponding aldol adducts with excellent levels of 1,5-anti diastereoselection.


Thiol redox switches regulate the oligomeric state of cyanobacterial Rre1, RpaA and RpaB response regulators.
Cyanobacteria employ two-component sensor-response regulator systems to monitor and respond to environmental challenges. The response regulators RpaA, RpaB, Rre1 and RppA are integral to circadian clock function and abiotic stress acclimation in cyanobacteria. RpaA, RpaB and Rre1 are known to interact with ferredoxin or thioredoxin, raising the possibility of their thiol regulation. Here, we report that Synechocystis sp. PCC 6803 Rre1, RpaA and RpaB exist as higher-order oligomers under oxidising conditions and that reduced thioredoxin A converts them to monomers. We further show that these response regulators contain redox-responsive cysteine residues with an Em7 around -300 mV. These findings suggest a direct thiol modulation of the activity of these response regulators, independent of their cognate sensor kinases.


Oncology social workers' perceptions of barriers to discussing fertility preservation with cancer patients.
Infertility is a common result of cancer treatment; however, opportunities exist that allow patients to preserve their fertility prior to treatment. Evidence suggests health care providers, including social workers, do not consistently discuss this topic with patients. This study used a qualitative, cross-sectional design using a focus group and in-depth interviews to explore knowledge, attitudes, barriers, and behaviors related to social workers' discussion of fertility preservation with cancer patients. Factors that influence the discussion of fertility preservation among social workers include: (1) Knowledge (e.g., Fertility Preservation Resources); (2) Attitudes (e.g., Cost, Perceived Role, Comfort Level, Fertility Preservation Discussion Difficulty/Priority); (3) Barriers (e.g., Cost, Urgency to start Treatment/Time, Patient Factors, Physician Attitudes/Beliefs); (4) Behaviors; and (5) Suggestions. Results show social workers are not typically discussing fertility preservation methods with patients; however, they may be in an ideal position to facilitate the conversation between the physician and the patient. There is a strong need to develop educational interventions aimed at oncology social workers, to help facilitate discussions with patients.


Risk factors affecting third molar autotransplantation in males: a retrospective survey in dental clinics.
The aim of this study was to investigate the risk factors affecting long-term prognosis of autotransplantation of third molars with complete root formation in males at dental clinics. Participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. After data screening and elimination, participants of this study consisted of 183 teeth of 171 males ranging from 20 to 72 years of age (mean age, 44·8 years). The cumulative survival rate was 86·0% at the 5-year mark, 59·1% at 10 years and 28·0% at 15 years. The mean survival time was 134·5 months, as calculated by the Kaplan-Meier method. Single factor analysis using the log-rank test showed that the following factors had significant influence (P < 0·05) on survival of transplanted teeth: periodontal disease as the reason for recipient site tooth extraction, fewer than 25 present teeth and Eichner index Groups B1 to C. Cox regression analysis examined five factors: age, smoking habit, recipient site extraction caused by periodontal disease, fewer than 25 present teeth and Eichner index. This analysis showed that two of these factors were significant: fewer than 25 present teeth was 2·63 (95% CI, 1·03-6·69) and recipient site extraction caused by periodontal disease was 3·80 (95% CI, 1·61-9·01). The results of this study suggest that long-term survival of transplanted teeth in males is influenced not only by oral bacterium but also by occlusal status.


Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial.
A 12-week, double-blind, parallel, multi-center randomized controlled trial in 316 adult patients with major depressive disorder (MDD) was conducted to evaluate the effectiveness of pharmacogenetic (PGx) testing for drug therapy guidance. Patients with a CGI-S ≥ 4 and requiring antidepressant medication de novo or changes in their medication regime were recruited at 18 Spanish public hospitals, genotyped with a commercial PGx panel (Neuropharmagen®), and randomized to PGx-guided treatment (n = 155) or treatment as usual (TAU, control group, n = 161), using a computer-generated random list that locked or unlocked psychiatrist access to the results of the PGx panel depending on group allocation. The primary endpoint was the proportion of patients achieving a sustained response (Patient Global Impression of Improvement, PGI-I ≤ 2) within the 12-week follow-up. Patients and interviewers collecting the PGI-I ratings were blinded to group allocation. Between-group differences were evaluated using χ2-test or t-test, as per data type. Two hundred eighty patients were available for analysis at the end of the 12-week follow-up (PGx n = 136, TAU n = 144). A difference in sustained response within the study period (primary outcome) was not observed (38.5% vs 34.4%, p = 0.4735; OR = 1.19 [95%CI 0.74-1.92]), but the PGx-guided treatment group had a higher responder rate compared to TAU at 12 weeks (47.8% vs 36.1%, p = 0.0476; OR = 1.62 [95%CI 1.00-2.61]), and this difference increased after removing subjects in the PGx-guided group when clinicians explicitly reported not to follow the test recommendations (51.3% vs 36.1%, p = 0.0135; OR = 1.86 [95%CI 1.13-3.05]). Effects were more consistent in patients with 1-3 failed drug trials. In subjects reporting side effects burden at baseline, odds of achieving a better tolerability (Frequency, Intensity and Burden of Side Effects Rating Burden subscore ≤2) were higher in the PGx-guided group than in controls at 6 weeks and maintained at 12 weeks (68.5% vs 51.4%, p = 0.0260; OR = 2.06 [95%CI 1.09-3.89]). PGx-guided treatment resulted in significant improvement of MDD patient's response at 12 weeks, dependent on the number of previously failed medication trials, but not on sustained response during the study period. Burden of side effects was also significantly reduced. European Clinical Trials Database 2013-002228-18 , registration date September 16, 2013; ClinicalTrials.gov NCT02529462 , retrospectively registered: August 19, 2015.


The Relationship of the Facial Nerve to the Condylar Process: A Cadaveric Study with Implications for Open Reduction Internal Fixation.
Introduction. The mandibular condyle is the most common site of mandibular fracture. Surgical treatment of condylar fractures by open reduction and internal fixation (ORIF) demands direct visualization of the fracture. This project aimed to investigate the anatomic relationship of the tragus to the facial nerve and condylar process. Materials and Methods. Twelve fresh hemicadavers heads were used. An extended retromandibular/preauricular approach was utilized, with the incision being based parallel to the posterior edge of the ramus. Measurements were obtained from the tragus to the facial nerve and condylar process. Results. The temporozygomatic division of the facial nerve was encountered during each approach, crossing the mandible at the condylar neck. The mean tissue depth separating the facial nerve from the condylar neck was 5.5 mm (range: 3.5 mm-7 mm, SD 1.2 mm). The upper division of the facial nerve crossed the posterior border of the condylar process on average 2.31 cm (SD 0.10 cm) anterior to the tragus. Conclusions. This study suggests that the temporozygomatic division of the facial nerve will be encountered in most approaches to the condylar process. As visualization of the relationship of the facial nerve to condyle is often limited, recognition that, on average, 5.5 mm of tissue separates condylar process from nerve should help reduce the incidence of facial nerve injury during this procedure.


Psychophysiological Effects of Downregulating Negative Emotions: Insights From a Meta-Analysis of Healthy Adults.
Assessing psychophysiological responses of emotion regulation is a cost-efficient way to quantify emotion regulation and to complement subjective report that may be biased. Previous studies have revealed inconsistent results complicating a sound interpretation of these findings. In the present study, we summarized the existing literature through a systematic search of articles. Meta-analyses were used to evaluate effect sizes of instructed downregulation strategies on common autonomic (electrodermal, respiratory, cardiovascular, and pupillometric) and electromyographic (corrugator activity, emotion-modulated startle) measures. Moderator analyses were conducted, with moderators including study design, emotion induction, control instruction and trial duration. We identified k = 78 studies each contributing multiple sub-samples and performed 23 meta-analyses for combinations of emotion regulation strategy and psychophysiological measure. Overall, results showed that effects of reappraisal and suppression on autonomic measures were highly inconsistent across studies with rather small mean effect sizes. Electromyography (startle and corrugator activity) showed medium effect sizes that were consistent across studies. Our findings highlight the diversity as well as the low level of standardization and comparability of research in this area. Significant moderation of effects by study design, trial duration, and control condition emphasizes the need for better standardization of methods. In addition, the small mean effect sizes resulting from our analyses on autonomic measures should be interpreted with caution. Findings corroborate the importance of multi-channel approaches.


Comparison of cellular and protein changes in bronchial lavage fluid of symptomatic and asymptomatic patients with red cedar asthma on follow-up examination.
Seventeen patients with occupational asthma due to western red cedar had bronchial lavage during follow-up examination after removal from exposure for at least 1 year. Seven patients were asymptomatic while ten continued to have symptoms of asthma requiring treatment. Symptomatic patients had evidence of airway inflammation, as reflected by a significantly higher total cell count, neutrophils and eosinophils, as well as an increase in protein and albumin in their bronchial lavage fluid compared to those without symptoms. Asymptomatic patients had no evidence of airway inflammation in the lavage fluid. There was no correlation between the degree of non-specific bronchial hyperresponsiveness and the number or percentage of inflammatory cells to suggest that cellular infiltration is the sole cause of persistent bronchial hyperresponsiveness.


Widespread production of nonmicrobial greenhouse gases in soils.
Carbon dioxide (CO2 ), methane (CH4 ), and nitrous oxide (N2 O) are the three most important greenhouse gases (GHGs), and all show large uncertainties in their atmospheric budgets. Soils of natural and managed ecosystems play an extremely important role in modulating their atmospheric abundance. Mechanisms underlying the exchange of these GHGs at the soil-atmosphere interface are often assumed to be exclusively microbe-mediated (M-GHGs). We argue that it is a widespread phenomenon for soil systems to produce GHGs through nonmicrobial pathways (NM-GHGs) based on a review of the available evidence accumulated over the past half century. We find that five categories of mechanistic process, including photodegradation, thermal degradation, reactive oxidative species (ROS) oxidation, extracellular oxidative metabolism (EXOMET), and inorganic chemical reactions, can be identified as accounting for their production. These pathways are intricately coupled among themselves and with M-GHGs production and are subject to strong influences from regional and global change agents including, among others, climate warming, solar radiation, and alterations of atmospheric components. Preliminary estimates have suggested that NM-GHGs could play key roles in contributing to budgets of GHGs in the arid regions, whereas their global importance would be enhanced with accelerated global environmental changes. Therefore, more research should be undertaken, with a differentiation between NM-GHGs and M-GHGs, to further elucidate the underlying mechanisms, to investigate the impacts of various global change agents, and to quantify their contributions to regional and global GHGs budgets. These efforts will contribute to a more complete understanding of global carbon and nitrogen cycling and a reduction in the uncertainty of carbon-climate feedbacks in the Earth system.


Reevaluation of bilateral same-day surgery for bilateral perforated chronic otitis media.
To evaluate the results of bilateral same-day surgery for bilateral perforated chronic otitis media in comparison with our previous report. Prospective study. Seventeen patients ranging in age from 5 to 70 years (mean, 52.5 yr), with bilateral perforated chronic otitis media. Two hundred cases of chronic otitis media were operated on at the Department of Otolaryngology, Hyogo College of Medicine from December 1998 to November 2002. Fifty-nine patients (29.5%) had bilateral disease and 17 patients (8.5%) underwent bilateral same-day surgery. The postoperative air-bone gap was less than 10 dB on both sides in 5 of 17 (29%) and less than 20 dB in 15 of 17 (88%). The postoperative hearing level was less than 20 dB in both ears in 4 of 17 (24%), less than 30 dB in 7 of 17 (41%), and less than 40 dB in 10 of 17 (59%). The rate of closure of the ear drum was 20 of 22 (91%) in the simple underlay myringoplasty series and 9 of 12 (75%) in the conventional myringoplasty/tympanoplasty series. The rate of closure of the ear drum on both sides was successful in 4 of 5 (80%) that underwent simple underlay myringoplasty/simple underlay myringoplasty and 8 of 12 (67%) that underwent simple underlay myringoplasty/conventional myringoplasty/tympanoplasty, whereas that on at least one side was successful in 100%. Bilateral same-day surgery for bilateral perforated chronic otitis media is possible if operative indications are considered. Furthermore, it will help patients save time and money.


Long-term effects of military service on mental health among veterans of the Vietnam War era.
Comparing outcomes of veterans who served in Vietnam and those who served elsewhere, we examined treatment of post-traumatic stress disorder, treatment of other mental health conditions, psychiatric treatment location, and six mental health well-being measures. The analytic sample consisted of nationally representative data from the 2001 National Survey of Veterans. Analyses included multivariate logistic regression that controlled for sociodemographic characteristics. Of Vietnam War-era veterans in the National Survey of Veterans (N = 7,914), 3,937 served in Vietnam and 3,977 served elsewhere. These veterans were stratified into < 60 years of age (N = 6,141) and > or = 60 years of age (N = 1,766). Veterans who served in Vietnam had notably poorer mental health than did those who served elsewhere. There were striking mental health differences between younger and older veterans; younger veterans had substantially worse measures of mental health. These results suggest greater resource needs among younger Vietnam War veterans. Clinicians and the Department of Veterans Affairs should focus on mental health services for younger veterans.


Experimental study of vibrational behavior of laminated annular disks.
The purpose of this paper is to present an experimental study of the vibrational behavior of laminated annular disks, and effects of laminations on the vibrations of the disks. The vibrations of a series of solid annular disks were calculated using the finite-element method in order to provide a basis for comparison with experimental data. An extensive range of experiments was performed on both a series of solid disks and a series of laminated disks under a range of normal clamping pressures. Based on the calculated and experimental results, it was found that the vibrational behavior of the laminated disks was dominated by that of the individual disk, of which the laminated disks were composed. Laminations had great effects on the vibrational behavior of the laminated disks and the effects depended upon the mode type, the clamping pressure, and the number of disk assembly. Laminations increased damping and reduced the amplitude of frequency response function for both the transverse modes and in-plane modes of disks. The resonant frequency of transverse modes shifted higher because of the effects of laminations. For the in-plane vibrational modes, the effects on the resonant frequency could be neglected and the resonant frequency could be considered to be a constant.


Early Oseltamivir After Hospital Admission Is Associated With Shortened Hospitalization: A 5-Year Analysis of Oseltamivir Timing and Clinical Outcomes.
Neuraminidase inhibitors (NAIs) are the only effective therapy for influenza, but few studies have assessed the impact of early NAI therapy on clinical outcomes or the patient-level factors that determine early NAI delivery in hospitalized patients. We conducted a retrospective cohort study of all adults hospitalized in a metropolitan tertiary care hospital with confirmed influenza from April 2009 to March 2014. We performed logistic regression to determine patient-level factors that were associated with early NAI therapy. We analyzed the association of early NAI therapy with hospital lengths of stay (LOS) and in-hospital mortality rates using linear and logistic regression, respectively. In total, 699 patients were admitted with influenza during the 5 influenza seasons. Of those, 582 (83.4%) received NAI therapy; however, only 26.0% received the first dose within 6 hours of hospitalization (early NAI). Patients with diabetes mellitus or pregnancy were more likely to receive early NAI (P = .01, vs. P < .001 in those without these conditions), as were those reporting fever or myalgias at presentation (P = .002, vs. P = .005 without). Immunosuppressed patients were less likely to receive early NAI (P = .04). Early NAI was associated with shorter hospital LOS (P < .001). No patients died in the early NAI group, compared to 18 deaths in the 399 patients receiving NAI after 6 hours (4.5%) and 4 deaths in the 116 patients not receiving NAI (3.4%). Over multiple influenza seasons, early NAI therapy was associated with shorter LOS in patients admitted with influenza. This suggests that efforts should focus on facilitating earlier therapy in patients with suspected influenza.


Post-surgical neuropathic pain.
Surgeons and anaesthetists are involved in Pain Medicine, as they have a responsibility to contribute to postoperative pain management and are often consulted about longer-term pain problems as well. A large component of persistent pain after surgery can be defined as neuropathic pain (NP). Nerves are injured during surgery and pain can persist after the surgical wound has healed. NP is because of a primary lesion or dysfunction of the peripheral or central nervous system. Prevalence estimates indicate that 2-3% of the population in the developed world experience NP. Persistent post-surgical NP is a mostly unrecognized clinical problem. The chronicity and persistence of post-surgical NP is often severely debilitating and impinges on the psychosocial, physical, economic and emotional well-being of patients. Options for treatment of any neuropathic factors are based on understanding the pain mechanisms involved. The current understandings of the mechanisms involved are presented. There is reasonable evidence for the efficacy of pharmacological management for NP. The aim of this article was to appraise the prevention, diagnostic work-up, the physical and particularly the pharmacological management of post-surgical NP and to provide a glimpse of advances in the field. It is a practical approach to post-surgical NP for all surgeons and anaesthetists. The take-home message is that prevention is better than waiting for post-surgical NP to become persistent.


Search for 5'-leader regulatory RNA structures based on gene annotation aided by the RiboGap database.
The discovery of noncoding RNAs (ncRNAs) and their importance for gene regulation led us to develop bioinformatics tools to pursue the discovery of novel ncRNAs. Finding ncRNAs de novo is challenging, first due to the difficulty of retrieving large numbers of sequences for given gene activities, and second due to exponential demands on calculation needed for comparative genomics on a large scale. Recently, several tools for the prediction of conserved RNA secondary structure were developed, but many of them are not designed to uncover new ncRNAs, or are too slow for conducting analyses on a large scale. Here we present various approaches using the database RiboGap as a primary tool for finding known ncRNAs and for uncovering simple sequence motifs with regulatory roles. This database also can be used to easily extract intergenic sequences of eubacteria and archaea to find conserved RNA structures upstream of given genes. We also show how to extend analysis further to choose the best candidate ncRNAs for experimental validation.


Compliance in a randomized clinical trial of dietary fat reduction in patients with breast dysplasia.
Dietary compliance was studied in 57 women participating for 1 y in a randomized clinical trial of dietary fat reduction. Nutrient analysis of food records, collected at 0, 6, and 12 mo, was compared with changes observed in lipid profiles and with chemical analysis of duplicate diets. Both food records and duplicate meals showed a significant decrease in fat intake (from 36 to 23% of total calories, p less than 0.0001) and a significant increase in carbohydrate (from 43 to 56% of total calories, p less than 0.0001) in the intervention group. The calculated nutrient intake from food records tended to overestimate the intake of protein, fat, and carbohydrate compared with the chemically analyzed method. The mean level of plasma cholesterol in the intervention group was significantly reduced (7.3%, p less than 0.01) in the first 6 mo after a reduction in dietary fat but the levels observed did not differ significantly between the groups at any time.


Human adipose tissue-derived mesenchymal stem cells in rheumatoid arthritis: Regulatory effects on peripheral blood mononuclear cells activation.
Mesenchymal stem cells (MSCs) are multipotent adult stem cells with immunomodulatory properties. The mechanisms by which MSCs inhibit the proliferation of pro-inflammatory T cells have not been fully elucidated yet. It is assumed that pro-inflammatory T-cells play an important role in the development of autoimmune diseases. We investigated the potential therapeutic effects of human adipose tissue derived (Ad)-MSCs on the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and healthy individuals, with a particular focus on Th17-associated cytokines. PBMCs from RA patients and healthy donors were co-cultured with Ad-MSCs and HeLa with or without Phytohemagglutinin (PHA). Finally, IL-6, IL-17, IL-21, IL-23 and TGF-β levels were determined by ELISA and quantitative real-time RT-PCR on co-culture supernatants and PBMCs, respectively. In co-culture interaction, Ad-MSCs inhibited IL-17 secretion by PBMCs compared to unstimulated PBMCs cultured alone. In addition, IL-21 expressions in PBMCs of the patient group, and IL-17 and IL-21 in healthy group were inhibited by Ad-MSCs compared to PBMCs cultured alone. TGF-β expression in healthy individuals remarkably increased in both MSC-treated groups with and without PHA in comparison to PHA-stimulated and -unstimulated PBMCs. This study demonstrates that human Ad-MSCs act as key regulators of immune tolerance by inhibiting the inflammation. Therefore, they can be attractive candidates for immunomodulatory cell-based therapy in RA.