Estimates of excess mortality for the five Nordic countries during the COVID-19 pandemic 2020-2021.
Excess mortality during the COVID-19 pandemic is of major scientific and political interest. We critically reviewed different estimates of all-cause excess mortality for the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), which have been much studied during the COVID-19 pandemic, using the latest register data to discuss uncertainties and implications. We show using back-calculation of expected deaths from Nordic all-cause deaths that the Institute for Health Metrics and Evaluation model is a clear outlier in the compared estimates and likely substantially overestimates excess mortality of Finland and Denmark, and probably Sweden. Our review suggests a range of total Nordic excess deaths of perhaps 15 000-20 000, but results are sensitive to assumptions in the models as shown. We document substantial heterogeneity and uncertainty in estimates of excess mortality. All estimates should be taken with caution in their interpretation as they miss detailed account of demographics, such as changes in the age group populations over the study period.


Quantification of copepod gut content by differential length amplification quantitative PCR (dla-qPCR).
Quantification of feeding rates and selectivity of zooplankton is vital for understanding the mechanisms structuring marine ecosystems. However, methodological limitations have made many of these studies difficult. Recently, molecular based methods have demonstrated that DNA from prey species can be used to identify zooplankton gut contents, and further, quantitative gut content estimates by quantitative PCR (qPCR) assays targeted to the 18S rRNA gene have been used to estimate feeding rates in appendicularians and copepods. However, while standard single primer based qPCR assays were quantitative for the filter feeding appendicularian Oikopleura dioica, feeding rates were consistently underestimated in the copepod Calanus finmarchicus. In this study, we test the hypothesis that prey DNA is rapidly digested after ingestion by copepods and describe a qPCR-based assay, differential length amplification qPCR (dla-qPCR), to account for DNA digestion. The assay utilizes multiple primer sets that amplify different sized fragments of the prey 18S rRNA gene and, based on the differential amplification of these fragments, the degree of digestion is estimated and corrected for. Application of this approach to C. finmarchicus fed Rhodomonas marina significantly improved quantitative feeding estimates compared to standard qPCR. The development of dla-qPCR represents a significant advancement towards a quantitative method for assessing in situ copepod feeding rates without involving cultivation-based manipulation.


Synergistic effect of atorvastatin and Cyanidin-3-glucoside on angiotensin II-induced inflammation in vascular smooth muscle cells.
Statins have often been used in atherosclerosis treatment because of its pleiotropic effects on inflammation. However, some adverse effects of high doses of statin show reverse effects after withdrawal. Cyanidin-3-glucoside (C3G) is a powerful anti-inflammation and antioxidant that has been of interest for use in combination with low doses of statin, which may be alternative treatment for atherosclerosis. The objective is to investigate the synergistic effect of atorvastatin and C3G in angiotensin II (Ang II)-induced inflammation in vascular smooth muscle cells. Human aortic smooth muscle cells (HASMCs) were exposed to Ang II with or without atorvastatin and C3G alone, or in combination. The results revealed that the combination of atorvastatin and C3G produces synergism against inflammation and oxidative stress. The mechanism of the combination of atorvastatin and C3G suppressed the translocation of the p65 subunit of NF-κB from cytosol to nucleus, and attenuated the expression of proteins including inducible nitric oxide synthase, intracellular adhesion molecule 1(ICAM-1), and vascular cell adhesion molecule 1(VCAM-1), in addition to nitric oxide (NO) production. Moreover, C3G exerts the antioxidative properties of atorvastatin through down-regulating NOX1 and promoting the activity of the Nrf2(-)ARE signaling pathway and downstream proteins including heme oxygenase (HO-1), NAD(P)H:quinoneoxidoreductase 1 (NQO-1), and glutamate-cysteine ligase catalytic subunit (γ-GCLC), besides increasing the activity of superoxide dismutase (SOD) enzymes. Taken together, these results suggest that a combination of low dose statins and C3G might serve as a potential regulator of the atherosclerosis process which is mediated by attenuating oxidative stress, thereby inhibiting NF-κB and activating Nrf2 signaling pathways induced by Ang II.


New potent 5-substituted benzofuroxans as inhibitors of Trypanosoma cruzi growth: quantitative structure-activity relationship studies.
Benzofuroxan derivatives have been shown to inhibit the growth of Trypanosoma cruzi, the etiological agent of Chagas' disease. Therefore, 2D- and 3D-QSAR models of their in vitro antichagasic activity were developed. Six new derivatives were synthesized to complete a final set of 26 structurally diverse benzofuroxans. The 2D-QSAR model (r = 0.939, r(adj)(2) = 0.849) was generated using multiple regression analysis of tabulated substituents' physicochemical properties and indicator variables. In addition, a 3D-QSAR model (r(2) = 0.997, q(2) = 0.802) was obtained using a comparative molecular field analysis (CoMFA). Due to the well-known benzofuroxan tautomerism, in both approaches (2D- and 3D-QSAR) it was necessary to include an indicator variable to consider the N-oxide position (I(6)). This parameter was established using low-temperature NMR experiments. Both QSAR models identified the electrophilic character of the substituent alpha-atom as a requirement for activity. Further support was found using a density functional theory (DFT) approach.


Proliferative glomerulonephritis with monoclonal immunoglobulin deposits and atypical pathological findings treated with corticosteroid and rituximab.
A 16-year-old girl with fever that appeared after taking the second COVID-19 vaccine presented to the clinic with a serum creatinine of 0.89 mg/dL and C-reactive protein of 6.9 mg/dL. She had proteinuria and microscopic hematuria, with slowly worsening kidney function. Her kidney biopsy showed fibrocellular crescents in seven of nine glomeruli that were observed under light microscopy. Another glomerulus showed endocapillary hypercellularity and mesangial cell proliferation. Electron-dense deposits were significant in the mesangial area, with monoclonal IgG1-κ and C3 deposition by immunofluorescence. The patient was diagnosed with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) and atypical pathological finding of diffuse crescent formation. The treatment regimen for PGNMID has not yet been established, and the appropriate duration of treatment is unknown. In our case, considering that rituximab acts by binding to CD20 on the surface of B cells through its crystallizable fragment, it was administered in addition to prednisolone, which successfully decreased the proteinuria over time.


Bacillus megaterium-induced biocorrosion on mild steel and the effect of Artemisia pallens methanolic extract as a natural corrosion inhibitor.
Methanolic extract of Artemisia pallens (MEAP) (Asteraceae) was explored as greenbiocorrosion inhibitor for mild steel 1010 in 1.5% sodium chloride environment. Bacillus megaterium SKR7 induces the development of biofilm on the metal surface and forms the pitting corrosion. MEAP was showed (25 ppm) optimum inhibition effect of biocorrosion and further corrosion rate was highly reduced (0.3335 mm/year) than the control system (0.009 mm/year). The electrochemical study has supported the results with a higher value of total resistance (34 Ω cm2) when compared to control systems. It reveals the formation of a protective layer on the metal surface and reduces the adsorption of biofilm. This was due to the antimicrobial effect of MEAP. Overall, the results recognized that MEAP used as a green corrosion inhibitor for MS 1010 with 83% inhibition efficiency.


How much of my true self can i show? social adaptation in autistic women: a qualitative study.
Social adaptation is often aimed at supporting autistic people, yet its specific goals may not include their actual perspectives. That is, the state of adaptation is judged based on the standards and values of non-autistic people. This qualitative study focused on autistic women's perceptions of social adaptation and examined their lived experiences in daily life, as adaptive behaviors have often been reported as a "female autism phenotype." Semi-structured interviews were conducted face-to-face with ten autistic women aged 28-50 years (M = 36.7; standard SD = 7.66). The analysis was conducted based on the grounded theory approach. Two core perceptions were identified: maintaining stable relationships and fulfilling social roles based on past experiences of "maladaptation." The participants sought adaptations within a reasonable range and adjusted their balance with society to maintain stability in their daily lives. The findings indicated that autistic women's perceptions of adaptation were based on the accumulation of past negative experiences. Further harmful efforts should be prevented. Support for autistic people to make their own choices in life is also important. Moreover, autistic women need a place where they can be themselves and be accepted as they are. This study showed the importance of changing the environment rather than modifying autistic people to adapt to a society.


Ablative Limbic System Surgery: Review and Future Directions.
The limbic system is a network of interconnected brain regions regulating emotion, memory, and behavior. Pathology of the limbic system can manifest as psychiatric disease, including obsessive-compulsive disorder and major depressive disorder. For patients with these disorders who have not responded to standard pharmacological and cognitive behavioral therapy, ablative surgery is a neurosurgical treatment option. The major ablative limbic system procedures currently used are anterior capsulotomy, dorsal anterior cingulotomy, subcaudate tractotomy, and limbic leucotomy. In this review, we include a brief history of ablative limbic system surgery leading up to its current form. Mechanistic justification for these procedures is considered in a discussion of the pathophysiology of psychiatric disease. We then discuss therapeutic efficacy as demonstrated by recent trials. Finally, we consider future directions, including the search for predictors of treatment response, the development of more precise targeting methods, and the use of advances in neuroimaging to track treatment response.


Studies to evaluate the effectiveness of sex pheromone-impregnated formulations for control of populations of the American dog tick, Dermacentor variabilis (Say) (Acari: Ixodidae).
The sex pheromone, 2,6-dichlorophenol, was combined with a pesticide to control populations of the American dog tick, Dermacentor variabilis (Say). This pheromone persisted in the fur of treated dogs for at least 18 days. The mixture of pheromone and pesticide was much more effective in reducing mating among the surviving ticks than the treatments without pheromone. The pheromone-pesticide mixture also killed significantly more ticks than the treatment without pheromone. This increased effectiveness was due almost entirely to the significantly greater kill of male ticks. Combining the sex pheromone with pesticide treatments offers a means of suppressing tick populations by curtailing their mating and subsequent reproductive success. The potential applications of this technique and the benefits to be expected are discussed.


Psychiatric and non-psychiatric drugs causing false-positive amphetamines urine test in psychiatric patients: a pharmacovigilance analysis using FAERS.
Immunoassay urine drug screen (UDS) is frequently used in clinical practice for initial screening process, being generally available, fast, and inexpensive. Exposure to widely prescribed drugs might determine false-positive UDS amphetamines, leading to diagnostic issues, wrong therapeutic choices, impairment of physician-patient relationship, and legal implications. To summarize and comment on a comprehensive list of compounds responsible for UDS false positives for amphetamines, we conducted a literature review on PubMed along with a comparison with Real-World Data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database analysis between 2010 and 2022. Forty-four articles and 125 Individual Case Safety Reports (ICSR) involving false-positive amphetamine UDS in psychiatric patients were retrieved from FAERS. False-positive results were described in literature for antidepressants, atomoxetine, methylphenidate, and antipsychotics, but also for non-psychiatric drugs of common use, such as labetalol, fenofibrate, and metformin. Immunoassay method is usually responsible for false-positive results, and in most cases, mass spectrometry (MS) does not eventually confirm the UDS positivity. Physicians should be aware of immunoassays' limitations and when turning to a confirmatory test. Any new cross-reaction should be reported to pharmacovigilance activities.


Critical values of hematocrit and mixed venous oxygen saturation as parameters for a safe cardiopulmonary bypass.
Mixed venous oxygen saturation (SvO2) is high despite a low hematocrit implies that the relationship between oxygen demand and supply is in a safe state. This study was sought to determine the critical values for hematocrit and SvO2 for safe cardiopulmonary bypass. Study 1: To evaluate the limit of hemodilution without cardiopulmonary bypass, normovolemic hemodilution with Dextran 40 (10%) was performed in 14 rabbits. SvO2 was monitored from the right atrium, and the hemodynamic parameters were recorded continuously. Study 2: To determine the critical values for hematocrit and SvO2 during cardiopulmonary bypass, normothermic and hypothermic cardiopulmonary bypass were performed in 13 rabbits and hemodynamic parameters were corrected. Study 1: The heart rate decreased to unsafe levels abruptly, when the SvO2 was < or = 43% or the hematocrit was < or = 10%. The lactate concentration increased when the SvO2 was < or = 46% or the hematocrit was < or = 12%. Study 2: When the hematocrit was < or = 12%, the SvO2 decreased gradually. Even when weaning was possible, the animals with a hematocrit < or = 12% collapsed hemodynamically within 40 minutes after cardiopulmonary bypass. Most of the animals could not be weaned from cardiopulmonary bypass during either normothermic or hypothermic cardiopulmonary bypass when the SvO2 was < or = 46%. Continuous monitoring of hematocrit and SvO2 provides evidence-based guidelines for safe cardiopulmonary bypass. The lower limits of critical range for a safer cardiopulmonary bypass are hematocrit of 12% and SvO2 of 46%.


Pellino 3 promotes the colitis-associated colorectal cancer through suppression of IRF4-mediated negative regulation of TLR4 signalling.
The incidence of colitis-associated colorectal cancer (CAC) has increased due to a high-nutrient diet, increased environmental stimuli and inherited gene mutations. To adequately treat CAC, drugs should be developed by identifying novel therapeutic targets. E3 ubiquitin-protein ligase pellino homolog 3 (pellino 3; Peli3) is a RING-type E3 ubiquitin ligase involved in inflammatory signalling; however, its role in the development and progression of CAC has not been elucidated. In this study, we studied Peli3-deficient mice in an azoxymethane/dextran sulphate sodium-induced CAC model. We observed that Peli3 promotes colorectal carcinogenesis with increased tumour burden and oncogenic signalling pathways. Ablation of Peli3 reduced inflammatory signalling activation at the early stage of carcinogenesis. Mechanistic studies indicate that Peli3 enhances toll-like receptor 4 (TLR4)-mediated inflammation through ubiquitination-dependent degradation of interferon regulatory factor 4, a negative regulator of TLR4 in macrophages. Our study suggests an important molecular link between Peli3 and colonic inflammation-mediated carcinogenesis. Furthermore, Peli3 can be a therapeutic target in the prevention and treatment of CAC.


[Impact of the new screening criteria on the gestational diabetes prevalence].
To evaluate the impact of the new IADPSG thresholds on gestational diabetes mellitus (GDM) prevalence. Universal screening for GDM was performed in 200 consecutive patients at 24 to 28 weeks with 75 g oral glucose tolerance test. The prevalence of GDM was 14.0%. We observed that among the 28 patients with GDM, 16 (57.1%) had only one abnormal value, 10 (35.7%) two abnormal values and only two (7.2%) had three abnormal values. For the 16 patients with one abnormal value, 13 of them (81.2%) have an abnormal fasting plasma glucose (FPG). Patients with GDM had an increased body mass index (29.6 kg/m(2) vs 25.1 kg/m(2), P<0.001) and more important rates of familial history of type II diabetes (46.4% vs 21.5%, P<0.005) and history of GDM in a previous pregnancy (21.4% vs 2.9%, P<0.002) compared to non-GDM patients. Birth weight was increased in offspring of mothers with GDM (3451.3g vs 3387.4 g, P<0.05). Our study found an increased rate of GDM with the new IADPSG criteria compared to previous published data. Higher rates of GDM represent a challenge for the organization of perinatal teams involved in GDM care.


The overlap technique versus end-to-end approximation technique for primary repair of obstetric anal sphincter rupture: a randomized controlled study.
To compare the outcome of end-to-end approximation versus the overlap technique for primary repair of obstetric anal sphincter rupture (OASR) at 12 month follow-up. Prospective, randomized controlled study. University hospital. Sample. One hundred and twenty-eight patients with grade 3b, 3c or 4 OASR were randomized; 119 (end-to-end 60, overlap 59) received the allocated treatment. We obtained information concerning fecal incontinence from 101 (85%) patients. The obstetric team on call performed the repairs. Wexner score, endoanal ultrasound (EAUS), and manometry were used to evaluate anal sphincter function at 12 months post-surgery. Primary outcome was incidence of solid stool leakage at least once a week. Secondary outcomes were flatus incontinence, Wexner score, external anal muscle defect examined by EAUS, and anal manometry results. One patient in the end-to-end group and none in the overlap group reported leakage of solid stool once a week or more. Fourteen patients in the end-to-end group and 10 in the overlap group reported flatus incontinence (p = 0.48). Mean Wexner score was similar in both groups, 2.4 versus 2.2. One patient in the end-to-end group and none in the overlap group had a Wexner score >10 (severe anal incontinence) (NS). External sphincter defect was found in 2/46 in the end-to-end group compared to 0/41 in the overlap group (NS). Anal manometry findings were similar in both groups. The overlap repair was not superior to the approximation technique with regard to fecal incontinence at 12 months.


Publisher Correction: Long noncoding RNAs in the model species Brachypodium distachyon.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Epidemiology of suicide after natural disasters: a review on the literature and a methodological framework for future studies.
On one hand, there is an association between exposure to natural disasters and becoming mentally distressed, and on the other hand, there is also a relation between being mentally distressed and committing suicide; therefore, it is possible that one finds a relation between exposure to natural disasters and committing suicide. This review, therefore, will not only seek such relations in the literature but also try to highlight the most important methodological issues of finding such connection.


Recent advances in methanogenesis through direct interspecies electron transfer via conductive materials: A molecular microbiological perspective.
Conductive materials can serve as biocatalysts during direct interspecies electron transfer for methanogenesis in anaerobic reactors. However, the mechanism promoting direct interspecies electron transfer in anaerobic reactors, particularly under environments in which diverse substrates and microorganisms coexist, remains to be elucidated from a scientific or an engineering point of view. Currently, many molecular microbiological approaches are employed to understand the fundamentals of this phenomenon. Here, the direct interspecies electron transfer mechanisms and relevant microorganisms identified to date using molecular microbiological methods were critically reviewed. Moreover, molecular microbiological methods for direct interspecies electron transfer used in previous studies and important findings thus revealed were analyzed. This review will help us better understand the phenomena of direct interspecies electron transfer using conductive materials and offer a framework for future molecular microbiological studies.


Microwave assisted synthesis of pyrido[2,3-a]carbazoles; investigation of in vitro DNA binding/cleavage, antioxidant and cytotoxicity studies.
We have developed an effective microwave assisted p-TsOH catalyzed synthesis of pyrido[2,3-a]carbazoles via a one pot reaction of ethanolamine and 1-chloro-2-formyl carbazoles. The structure has been characterized by spectroscopic methods. The electronic spectroscopic experimental evidence strongly showed that the compounds could interact with calf thymus DNA (CT-DNA) through intercalation with a binding constant value of 1.2-3.0×10(4)M(-)(1). All the compounds showed weak to moderate capacity of scavenging with DPPH. The cytotoxicity has been evaluated by MTT assay against MCF-7 cell line and compared with standard drug cisplatin.


Frequency Dependence of Coercive Fields of [001]- and [011]-Poled Rhombohedral Pb(In1/2Nb1/2)O₃-Pb(Mg1/3Nb2/3)O₃-PbTiO₃ Single Crystals.
Relaxor-PbTiO3 (PT-based) ferroelectric single crystals are important for many piezoelectric applications because of their outstanding performances. In order to expand their usage and avoid the failure during application, frequency dependence of coercive fields EC for [001]- and [011]-poled rhombohedral Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 (PIN-PMN-PT) single crystals was investigated from the frequency of 1 Hz to 300 kHz by using hysteresis loop measurement (frequency: from 1 Hz to 2 kHz) and a critical value method (frequency: from 5 to 300 kHz). The results showed that the coercive field EC , remnant polarization Pr , and saturation polarization Ps strongly depended on the crystal orientation and frequency. Compared with the [001]-poled crystals, the [011]-poled PIN-PMN-PT single crystals possessed higher EC , Pr , and Ps at the same testing frequencies. With increasing frequency from 1 Hz to 300 kHz, the coercive fields EC of the [001]- and [011]-poled PIN-PMN-PT single crystals increased from 4.0 and 4.8 kV/cm to 11.5 and 14.9 kV/cm, respectively. Moreover, the frequency dependence of the coercive fields was found to be consistent with the growth kinetics model, where the coercive fields EC were proportional to fβ . This work benefits to the design of piezoelectric devices based on PIN-PMN-PT single crystals operated at high frequencies and high driving fields.


Rubella outbreak on Tokunoshima Island in 2004: a population-based study of pregnant women.
The purpose of this study was to clarify the risk of rubella infection for pregnant women in the outbreak area. We performed a retrospective, population-based study on all 232 pregnant women during the rubella outbreak period in Tokunoshima Island. All women had a rubella hemagglutination inhibition (HI) titer drawn during their current pregnancy. In 61 women, HI titers were compared between the current and past pregnancies. Rubella IgG antibody titers were measured and IgG avidity index (AI) was calculated for 92 non-infected pregnant women. Of the 232 candidates, 22 pregnant women contracted rubella infection (congenitally infected infants: 2). Seventeen of 61 pregnant women showed a four-fold or greater elevation in HI titer when compared with previous titers. Their previous HI titers were all ≤64. Low IgG AIs (<30%) were only observed in women with a HI titer of ≤64 (92 non-infected women). The risk of maternal rubella infection in the outbreak was as follows: non-immunized pregnant woman and pregnant woman with a rubella HI antibody titer ≤64 and low IgG AI.


Brain regions associated with the expression and contextual regulation of anxiety in primates.
A key to successful adaptation is the ability to regulate emotional responses in relation to changing environmental demands or contexts. High-resolution PET 18fluoro-deoxyglucose (FDG) scanning in rhesus monkeys was performed during two contexts (alone, and human intruder with no eye contact) during which the duration of anxiety related freezing behavior was assessed. Correlations between individual differences in freezing duration and brain activity were performed for each of the two conditions, as well as for the contextual regulation between the two conditions. In both conditions, activity in the basal forebrain, including the bed nucleus of the stria terminalis and the nucleus accumbens were correlated with individual differences in freezing duration. In contrast, individual differences in the ability to regulate freezing behavior between contexts were correlated with activity in the dorsal anterior cingulate cortex, the thalamus and the dorsal raphe nucleus. These findings demonstrate differences in the neural circuitry mediating the expression compared to the contextual regulation of freezing behavior. These findings are relevant since altered regulatory processes may underlie anxiety disorders.


Obstructive sleep apnea and ambulatory blood pressure abnormalities in children with chronic kidney disease.
Obstructive sleep apnea (OSA) and hypertension are common complications in children with chronic kidney disease (CKD). Progression of CKD can aggravate OSA and hypertension whereas worsening sleep apnea can make hypertension difficult to treat in CKD patients. We, therefore, conducted a prospective study to evaluate the association between OSA and hypertension in pediatric patients with CKD. In this prospective observational study consecutive children with CKD stage 3-5 (nondialysis dependent) underwent overnight polysomnography and 24-h ambulatory blood pressure monitoring (ABPM). The detailed clinical features and investigations were recorded in a prestructured performa. Twenty-two children completed overnight polysomnography and 24-h ABPM was performed within 48 h of performing polysomnography. The median (IQR) age of the study population was 11 (8.5-15.5) years, with an age range of 5-18 years. Moderate-severe OSA defined as apnea-hypopnea index (AHI ≥5) was seen in 14 (63.6%) children, periodic limb movement syndrome in 20 (91%) and poor sleep efficacy in 9 (40.9%) children. Ambulatory blood pressure was abnormal in 15 (68.2%) children with CKD. Of them, 4 (18.2%) had ambulatory hypertension, 9 (40.9%) had severe ambulatory hypertension and 2 (9.1%) had masked hypertension. A statistically significant correlation of sleep efficiency with nighttime DBP SD score/Z score (SDS/Z) (r = -0.47; P = 0.02); estimated glomerular filtration rate with SBP loads (r = -0.61; P < 0.012); DBP loads (r = -0.63; P < ) and BMI with SBP load (r = 0.46; P = 0.012) was found. Our preliminary findings suggest that ambulatory blood pressure abnormalities, OSA, periodic limb movement syndrome and poor sleep efficiency are highly prevalent in children with CKD stages 3-5.


Epidural bupivacaine and morphine plus systemic indomethacin eliminates pain but not systemic response and convalescence after cholecystectomy.
We studied 24 patients undergoing elective cholecystectomy and randomized to either conventional postoperative pain treatment, with intermittent nicomorphine (10 to 15 mg) and acetaminophen (1 gm) on request, or thoracic epidural analgesia with plain bupivacaine for 48 hours and epidural morphine 4 mg every 8 hours for 96 hours plus systemic indomethacin 100 mg every 8 hours for 96 hours. Epidural analgesia for pin prick extended from the fourth thoracic to the first lumbar nerve for 48 hours. Assessments of pain, various injury response parameters, peak flow, and subjective feeling of fatigue were performed preoperatively, 3 and 6 hours after skin incision, and 1, 2, 4, and 8 days postoperatively. The epidural analgesia-systemic indomethacin treatment eliminated postoperative pain during rest and coughing. In contrast, only a minor and clinically unimportant modulation of the conventional perioperative and postoperative changes in plasma cortisol, glucose, transferrin, orosomucoid, leukocyte and differential counts, rectal temperature, peak flow, and fatigue was observed. Our results suggest that factors other than pain per se must be controlled in order to reduce postoperative morbidity.


Local Ancestry-Informed Candidate Pathway Analysis of Warfarin Stable Dose in Latino Populations.
Accuracy of warfarin dose prediction algorithms may be improved by including data from diverse populations in genetic studies of dose variability. Here, we surveyed single nucleotide polymorphisms in vitamin K-related genetic pathways for association with warfarin dose requirements in two admixed Latino populations in standard-principal component adjusted and contemporary-local ancestry adjusted regression models. A total of five variants from vitamin K-related genes/pathways were associated with warfarin dose in both cohorts (P < 0.0125) in standard models. Local ancestry-adjusted analysis unveiled 35 associated variants with absolute effects ranging from β = 9.04 ( ±2.23) to 39.18 ( ±10.89) per ancestral allele in the discovery cohort and β = 6.47 (± 2.02) to 17.82 (± 6.83) in the replication cohort. Importantly, we demonstrate the technical validity of the Tractor model in cohorts with admixed ancestry from three founder populations and bring attention to the technical hurdles obstructing the inclusion of diverse, especially admixed, populations in pharmacogenomic research.


A domain-specific marker for the hepatocyte plasma membrane. II. Ultrastructural localization of leucine aminopeptidase to the bile canalicular domain of isolated rat liver plasma membranes.
Leucine aminopeptidase (LAP) is an integral membrane glycoprotein localized to the apical membrane domain of intestinal and kidney epithelial cells. By indirect immunofluorescence, we have shown that antibodies raised against rat intestinal LAP recognized a similar protein concentrated in the bile canalicular (BC) domain of the hepatocyte in situ (Roman, L.M., and A.L. Hubbard, 1983, J. Cell Biol., 96:1548-1558). We have extended this localization to the ultrastructural level. When a saponin-permeabilized, agarose-embedded plasma membrane (PM) fraction was incubated with affinity-purified anti-LAP, 85% of the protein A-gold particles associated with the three recognizable PM domains were present in the BC. The levels of labeling on the other two domains (sinusoidal and lateral) did not exceed that observed with nonimmune controls. The concentration of LAP in the BC domain in isolated PM sheets prompted us to use this antigen for the affinity isolation of BC membrane (Roman, L.M., and A.L. Hubbard, 1984, J. Cell Biol., 98:1497-1504, companion paper).


Endoplasmic reticulum stress targeted therapy for breast cancer.
Recurrence, metastasis, and drug resistance are still big challenges in breast cancer therapy. Internal and external stresses have been proven to substantially facilitate breast cancer progression through molecular and systemic mechanisms. For example, endoplasmic reticulum stress (ERS) results in activation of the unfolded protein response (UPR), which are considered an important cellular stress response. More and more reports indicate its key role in protein homeostasis and other diverse functions involved in the process of breast cancer progression. Therefore, therapies targeting the activation of ERS and its downstream signaling pathways are potentially helpful and novel tools to counteract and fight breast cancer. However, recent advances in our understanding of ERS are focused on characterizing and modulating ERS between healthy and disease states, and so little attention has been paid to studying the role and clinical application of targeting ERS in a certain cancer. In this review, we summarize the function and main mechanisms of ERS in different molecular types of breast cancer, and focus on the development of agents targeting ERS to provide new treatment strategies for breast cancer. Video Abstract.


Role of exosomes in transferring chemoresistance through modulation of cancer glycolytic cell metabolism.
Chemoresistance constitute a major obstacle in cancer treatment, leading to limited options and decreased patient survival. Recent studies have revealed a novel mechanism of chemoresistance acquisition: the transfer of information via exosomes, small vesicles secreted by various cells. Exosomes play a crucial role in intercellular communication by carrying proteins, nucleic acids, and metabolites, influencing cancer cell behavior and response to treatment. One crucial mechanism of resistance is cancer metabolic reprogramming, which involves alterations in the cellular metabolic pathways to support the survival and proliferation of drug-resistant cancer cells. This metabolic reprogramming often includes increased glycolysis, providing cancer cells with the necessary energy and building blocks to evade the effects of chemotherapy. Notably, exosomes have been found to transport glycolytic enzymes, as identified in proteomic profiling, leading to the reprogramming of metabolic pathways, facilitating altered glucose metabolism and increased lactate production. As a result, they profoundly impact the tumor microenvironment, promoting tumor progression, survival, immune evasion, and drug resistance.Understanding the complexities of such exosome-mediated cell-to-cell communication might open new therapeutic avenues and facilitate biomarker development in managing cancers characterized by aggressive glycolytic features. Moreover, given the intricate nature of metabolic abnormalities combining future exosome-based-targeted therapies with existing treatments like chemotherapy, immunotherapy, and targeted therapies holds promise for achieving synergistic effects to overcome resistance and improve cancer treatment outcomes.


Effects of nutrients on gastrointestinal motility and gastric emptying after distal gastrectomy with Roux-Y gastrojejunostomy in dogs.
The aim of the study was to clarify whether nutrients are still capable of slowing gastric emptying following Roux-Y gastrectomy, as in normal dogs. Gastrointestinal motility and gastric emptying of acaloric and nutritive meals with different viscosities were measured in normal dogs and after a two-thirds Roux-Y gastrectomy. In gastrectomized dogs low-viscosity nutritive meals emptied unduly rapidly in an initial phase, although the frequency and spread of contractions, ie, the propulsive activity of the jejunal Roux limb were diminished. A slow emptying rate during the following period was due to a long-lasting inhibition of gastric and jejunal motility. Medium-viscosity nutritive meals emptied in gastrectomized dogs as slowly as in normal animals, but this effect was primarily caused by the meal viscosity and only secondarily by the nutrients. It is concluded that following Roux-Y gastrectomy a regulation of gastric emptying is preserved; however, the onset of an effective control is delayed, resulting in a rapid initial emptying of low-viscosity meals.


Manipulating tablets and capsules given to hospitalised children in Norway is common practice.
This study provided an overview of manipulating oral medicines given to hospitalised children and evaluated this practice in two hospitals. It focused on the type of manipulation and the dosage forms that were manipulated. This was a cross-sectional, prospective study, carried out on the paediatric wards at two Norwegian hospitals for four weeks in 2013. A medicine was said to have been manipulated if it was not administered as described in the Norwegian summary of product characteristics. This study showed that 17% of the 3070 administrations of oral medicines to the hospitalised children involved manipulation. Tablets, including modified release preparations, were the most frequently manipulated medicines. In approximately half of these cases, only a segment of the unit dose was administered. No manipulation of oral liquids was seen. The bioavailability of as much as 44% of the most frequent given substances may be sensitive to such manipulations due to limited aqueous solubility. Various routines for splitting and handling the unit doses were observed. Manipulation of oral medication was regularly performed on paediatric wards. There is an urgent need for age-appropriate medicines, documented and standardised processes for manipulating medicines and staff training on the consequences of manipulation.


Prolonged esophageal acid exposures induce synaptic downscaling of cortical membrane AMPA receptor subunits in rats.
We recently reported the involvement of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor subunit upregulation and phosphorylation in the rostral cingulate cortex (rCC) as the underlying mechanism of acute esophageal acid-induced cortical sensitization. Based on these findings, we proposed to investigate whether prolonged esophageal acid exposures in rats exhibit homeostatic synaptic scaling through downregulation of AMPA receptor expression in rCC neurons. We intended to study further whether this compensatory mechanism is impaired when rats are pre-exposed to repeated esophageal acid exposures neonatally during neuronal development. Two different esophageal acid exposure protocols in rats were used. Since AMPA receptor trafficking and channel conductance depend on CaMKIIα-mediated phosphorylation of AMPA receptor subunits, we examined the effect of esophageal acid on CaMKIIα activation and AMPA receptor expression in synaptoneurosomes and membrane preparations from rCCs. In cortical membrane preparations, GluA1 and pGluA1Ser(831) expression were significantly downregulated following prolonged acid exposures in adult rats; this was accompanied by the significant downregulation of cortical membrane pCaMKIIα expression. No change in GluA1 and pGluA1Ser(831) expression was observed in rCC membrane preparations in rats pre-exposed to acid neonatally followed by adult rechallenge. This study along with our previous findings suggests that synaptic AMPA receptor subunits expression and phosphorylation may be involved bidirectionally in both esophageal acid-induced neuronal sensitization and acid-dependent homeostatic plasticity in cortical neurons. The impairment of homeostatic compensatory mechanism as observed following early-in-life acid exposure could be the underlying mechanism of heightening cortical sensitization and esophageal hypersensitivity in patients with gastroesophageal reflux disease.


Molecular Phylogeography Analysis Reveals Population Dynamics and Genetic Divergence of a Widespread Tree Pterocarya stenoptera in China.
The geological events, past climatic fluctuations, and river systems played key roles in the spatial distribution, population dynamics, and genetic differentiation of species. In this work, we selected Pterocarya stenoptera, a widespread tree species in China, to test the roles of these factors. Four noncoding spacers, eight microsatellite (simple sequence repeat) markers, and species distribution modeling were used to examine the phylogeographical pattern of P. stenoptera. Based on chloroplast DNA data, populations of P. stenoptera were clearly clustered into three groups. The divergence time of these groups fell into the stage of the Qinghai-Tibet Movement, 1.7-2.6 Ma. For simple sequence repeat data, only one western marginal population YNYB could be separated from other populations, whereas other populations were mixed together. Our results indicated that the environmental heterogeneity resulting from the Qinghai-Tibet movement might be response for this genetic divergence. The climatic fluctuations in the Pleistocene did not cause the substantial range shift of P. stenoptera, while the fluctuations affected its population size. Moreover, we also confirmed the river systems did not act as channels or barrier of dispersal for P. stenoptera.


Control of disease activity and tumor size after introduction of pegvisomant in a lanreotide-resistant acromegalic patient.
We report on a 30-year-old female acromegalic patient treated with the growth hormone (GH) receptor antagonist pegvisomant at a low dose after the failure of long-acting lanreotide, neurosurgery and radiotherapy treatment to restore IGF-1 levels. The combination treatment was well tolerated and produced a dramatic improvement in the patient's condition (reduction in visual field defects, relief of headache and excessive perspiration), normalization of IGF-I levels and a considerable decrease in tumor size, enabling a dramatic decrease in lanreotide dosage and, ultimately, its withdrawal.


ZmRFP1, the putative ortholog of SDIR1, encodes a RING-H2 E3 ubiquitin ligase and responds to drought stress in an ABA-dependent manner in maize.
Drought is one of the most important limiting factors in crop production. To identify genes required for the drought stress response in the cereal crop maize, a gene coding for RING-finger protein (ZmRFP1), which is highly responsive to PEG-induced drought stress, was isolated by mRNA differential display and rapid amplification of cDNA ends. The ZmRFP1 encodes a protein of 280 amino acids and contains a single C(3)H(2)C(3)-type RING motif in its C-terminal region. ZmRFP1 is an ortholog of Arabidopsis SDIR1 (salt- and drought-induced RING finger 1) (66% identity to AtSDIR1).The recombinant ZmRFP1 protein purified from Escherichia coli exhibited an in vitro E3 ubiquitin ligase activity. Real-time PCR analysis indicates that the transcript levels of ZmRFP1 were higher in aerial tissues including stems, leaves, tassels and immature ears, and were markedly up-regulated by drought stress, and exogenous ABA, but not by salt, heat and cold stresses. Transient expression of the green fluorescent protein (GFP)-ZmRFP1 fusion protein in onion cells revealed a plasma membrane localization of the protein. Further analysis of ZmRFP1 transcripts between an ABA-deficient transposon mutant viviparous14 (vp14) and its isogenic wild-type line W22 showed that ZmRFP1 transcript levels were induced significantly in the wild-type line under drought stress, but not in the mutant line VP14. These results indicate that ZmRFP1 responds to drought stress in an ABA-dependent way and is likely to function in the ubiquitin conjunction pathway. The ZmRFP1 might serve as a candidate gene in genetic improvement for drought tolerance engineering in cereal crop plants.


Mechanism of action of DRB. III. Effect on specific in vitro initiation of transcription.
5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole, an adenosine analogue, has been used previously as an inhibitor of heterogeneous nuclear and messenger RNA synthesis. In an in vitro transcriptional system, we have detected inhibition of synthesis of full-length runoff RNAs at concentrations at which in vivo mRNA synthesis is inhibited. By hybridization of RNA synthesized in vitro to single-stranded DNA and gel analysis, we were able to reduce the background of the transcription reaction, detect DRB-induced inhibition of full-length runoff RNAs and DRB-insensitive transcription of short RNAs. To establish further the effect of DRB on initiation of transcription, preincubation experiments with template, whole cell extract and two initial nucleotides of the transcript were performed. Elongation was then measured as discrete-sized RNAs transcribed from the truncated template after addition of the other triphosphates (one of them labeled), in the presence or absence of DRB. An effect on initiation but not on elongation or termination was detected. Fingerprint analysis of these runoff RNAs indicates that the labeling of U in the presence of DRB is uniform throughout the molecule. A model to explain a novel interpretation of the action of DRB is presented.


Dataset on the diversity of helminth parasites of freshwater fish in the headwaters of the Coatzacoalcos river, in Oaxaca, Mexico.
The data presented in this article are related to the research article entitled " Diversity of helminth parasites of freshwater fish in the headwaters of the Coatzacoalcos river, in Oaxaca, Mexico " published in International Journal for Parasitolology: Parasites and Wildlife. This dataset document the diversity of helminth parasites found in 25 fish species from 8 families from rivers in the headwaters of the Coatzacoalcos river basin at the border between Oaxaca and Veracruz states, Isthmus of Tehuantepec zone, southeastern Mexico, in the northernmost end of Central America. We record here 48 species, 44 genera and 29 helminth families. Most of the helminth species recorded in this area has also been collected from Central American bodies of freshwater south of Mexico. The material in this Data in Brief paper comprised the raw data on the abundance distribution of each helminth taxa recorded in each of the host and location; i. e. the number of helminth individuals of each helminth taxa found in each one individual fish from each species from each of the localities sampled. The data set is contained in one text-table matrix per fish-host, date of collection and locality of helminth taxa (lines) per fish host species (columns).


Unified Focal loss: Generalising Dice and cross entropy-based losses to handle class imbalanced medical image segmentation.
Automatic segmentation methods are an important advancement in medical image analysis. Machine learning techniques, and deep neural networks in particular, are the state-of-the-art for most medical image segmentation tasks. Issues with class imbalance pose a significant challenge in medical datasets, with lesions often occupying a considerably smaller volume relative to the background. Loss functions used in the training of deep learning algorithms differ in their robustness to class imbalance, with direct consequences for model convergence. The most commonly used loss functions for segmentation are based on either the cross entropy loss, Dice loss or a combination of the two. We propose the Unified Focal loss, a new hierarchical framework that generalises Dice and cross entropy-based losses for handling class imbalance. We evaluate our proposed loss function on five publicly available, class imbalanced medical imaging datasets: CVC-ClinicDB, Digital Retinal Images for Vessel Extraction (DRIVE), Breast Ultrasound 2017 (BUS2017), Brain Tumour Segmentation 2020 (BraTS20) and Kidney Tumour Segmentation 2019 (KiTS19). We compare our loss function performance against six Dice or cross entropy-based loss functions, across 2D binary, 3D binary and 3D multiclass segmentation tasks, demonstrating that our proposed loss function is robust to class imbalance and consistently outperforms the other loss functions. Source code is available at: https://github.com/mlyg/unified-focal-loss.


Contribution of the factors to EuroQol 5 Dimensions in rheumatoid arthritis patients achieving low disease activity/remission with abatacept treatment: post-hoc subgroup analyses of the Japanese real-world observational "ORIGAMI" study.
To address improvements in quality of life (QOL), we analysed the relative contributions of factors to EuroQol 5 Dimensions (EQ-5D) in abatacept-treated rheumatoid arthritis (RA) patients in the ORIGAMI study. Patients who were evaluable for disease activity through to Week 52 in the ORIGAMI study were divided into those achieving Simplified Disease Activity Index-remission/low disease activity (remission/LDA; n=178) and patients with moderate/high disease activity (MDA/HDA; n=99). We compared the changes in EQ-5D and other outcomes through to Week 52. Focusing on the remission/LDA group, the contribution of each factor to the variance of EQ-5D at baseline and Week 52 was examined using analysis of variance. The remission/LDA group showed greater improvements than the MDA/HDA group in EQ-5D, Japanese Health Assessment Questionnaire, visual analogue scale for pain (Pain VAS), and patient global assessment (PtGA). In the remission/LDA group, factors significantly contributing to EQ-5D were sex, C-reactive protein, and Pain VAS at baseline, and PtGA and age at Week 52. In RA patients who achieved remission/LDA during abatacept treatment, PtGA and age at Week 52 contribute to the variance of EQ-5D, suggesting that identification of factors associated with PtGA may be important to address improvements of QOL.


Tiamulin activity against fastidious and nonfastidious veterinary and human bacterial isolates: initial development of in vitro susceptibility test methods.
Tiamulin is a pleuromutilin derivative used in veterinary practice for the control and specific therapy of infections in swine. This report summarizes studies to establish standardized susceptibility testing methods, interpretive criteria, and reagent details for use in veterinary methods recently developed by the National Committee for Clinical Laboratory Standards (NCCLS) (standards M31-A and M37-A, NCCLS, Wayne, Pa., 1999). A total of 636 fastidious and nonfastidious animal and human pathogens were processed by using media and procedures described by the NCCLS. Tiamulin disk diffusion tests used a 30-microg disk concentration, and the proposed MIC breakpoints corresponding to levels achievable in animal target tissues (lung) were < or =4 microg/ml for susceptibility and > or =32 microg/ml for resistance. Correlate zone diameters for specific nonfastidious species were as follows: for Pasteurella multocida and staphylococci tested on Mueller-Hinton agar, susceptibility at > or =19 mm and resistance at < or =11 mm, and for Actinobacillus suis, Erysipelothrix rhusiopathiae, and Streptococcus suis tested on enriched chocolate Mueller-Hinton agar, susceptibility at > or =16 mm and resistance at < or =8 mm. When Actinobacillus pleuropneumoniae was tested, a susceptibility breakpoint of < or =16 microg/ml (> or =9 mm) was suggested for veterinary fastidious medium broth and enriched chocolate Mueller-Hinton agar. Absolute categorical agreement between NCCLS dilution and disk diffusion test results with these criteria ranged from 90.5 to 96.2%. Tiamulin susceptibility testing methods appear to be accurate in their categorical classification for indicated species, and their availability will allow immediate testing of animal isolates to guide therapy via appropriate levels of dosing and to monitor the development of resistance for agents in this unique class.


Effectors of Escherichia coli aspartate transcarbamoylase differentially perturb aspartate binding rather than the T-R transition.
New systematic methods developed for equilibrium isotope exchange kinetics have been used to analyze the effects of activator ATP and inhibitor CTP with Escherichia coli aspartate transcarbamoylase. This indepth approach requires (a) variation of [modifier] with fixed subsaturating levels of substrates, and (b) variation of at least three combinations of reactant-product pairs in constant ratio at equilibrium: [A,B,P,Q], [A,P], and [B,Q] with the co-substrates held constant, in the presence and absence of added modifier. Both ATP and CTP had much stronger effects on the [14C]Asp in equilibrium C-Asp exchange rate than on [32P]C-P in equilibrium Pi. The bisubstrate analog N-phosphonacetyl-L-aspartate activated, then inhibited, Asp in equilibrium C-Asp more strongly than C-P in equilibrium Pi. N-Phosphonacetyl-L-aspartate gave complete (100%) inhibition, whereas CTP inhibition of either exchange was only partial. Substrate saturation curves in the presence and absence of effectors indicate that ATP and CTP perturb the observed values of Rmax and S0.5 in different fashions without appreciably changing the observed Hill number. Computer simulations indicate that the primary site of ATP and CTP action is the association rate for Asp, not the allosteric T-R transition. This finding is substantiated by previous studies in which modified aspartate transcarbamoylase had lost cooperative Asp binding without loss of sensitivity to effectors, or in which sensitivity to one effector could be deleted selectively. The present results, with newly devised computer simulation and analysis methods, illustrate the usefulness of equilibrium isotope exchange kinetic probes for providing unique insights to enzyme regulatory mechanisms, to define exactly which steps are altered in a given kinetic mechanism.


Naloxone requires circulating catecholamines to attenuate the cardiovascular suppression of endotoxic shock.
The opiate antagonist naloxone (NAL) improves cardiovascular performance in canine hemorrhagic and endotoxic shock. If the release of neural and adrenal catecholamines is attenuated, NAL does not produce the expected improvement in cardiovascular function in canine hemorrhagic shock. This study tests the hypothesis that an endorphin-catecholamine interaction at the heart is responsible for a part of the cardiovascular depression of endotoxic shock. Two groups of five dogs were instrumented to measure mean arterial pressure (MAP), the first derivative of left ventricular pressure over time (LV dP/dt max), cardiac output, and heart rate (HR); they were then subjected to bilateral adrenalectomy and given chlorisondamine to produce ganglionic blockade. At t = 0 min the dogs were given Escherichia coli endotoxin at 1 mg/kg (LD80). Group I animals received NAL at 2 mg/kg + 2 mg/kg.hr iv from t = 30 to t = 60. At t = 45 these animals were treated with epinephrine (EPI) at 20 micrograms/kg.hr iv until t = 60. Group II animals got EPI from t = 30 to t = 60 and NAL from t = 45 to t = 60 at the same doses as Group I. In Group I, NAL alone had no effect on MAP, LV dP/dt max, or HR. EPI significantly increased (P less than 0.002) cardiovascular parameters with MAP increasing from 52 +/- 7 to 159 +/- 14 mm Hg. In Group II, EPI produced a significant increase in all parameters, and the addition of NAL produced a further significant increase; MAP increased from 37 +/- 3 to 126 +/- 16 mm Hg with EPI and then to 175 +/- 11 mm Hg with NAL. These data support the above hypothesis and indicate that circulating catecholamines need to be present to allow naloxone to reverse the cardiovascular depression in endotoxic shock.


Stress-reducing effects of indoor plants in the built healthcare environment: the mediating role of perceived attractiveness.
Natural elements in the built healthcare environment have shown to hold potential stress-reducing properties. In order to shed light on the underlying mechanism of stress-reducing effects of nature, the present study investigates whether the stress-reducing effects of indoor plants occur because such an environment is perceived as being more attractive. A single-factor between-subjects experimental design (nature: indoor plants vs. no plants) was used in which participants (n=77) were presented with a scenario describing hospitalization with a possible legionella diagnosis. The study was conducted from March to May 2007 in the Netherlands. Subsequently, they were exposed to a photo of a hospital room. In this room were either indoor plants, or there was a painting of an urban environment on the wall. Afterwards, perceived stress and the perceived attractiveness of the hospital room were measured. Participants exposed to the hospital room with indoor plants reported less stress than those in the control condition. Mediation analysis confirmed that indoor plants in a hospital room reduce feelings of stress through the perceived attractiveness of the room. This study confirms the stress-reducing properties of natural elements in the built healthcare environment. It also sheds light on the underlying mechanism causing this stress-reduction.


Changes in knowledge of cervical cancer prevention and human papillomavirus among women with human immunodeficiency virus.
To estimate changes in high-risk women's knowledge of cervical cancer prevention, human papillomavirus (HPV), and HPV vaccination since introduction and marketing of HPV vaccines. At study visits in 2007 and 2008-2009, women with the human immunodeficiency virus (HIV) and at-risk comparison women in a multicenter U.S. cohort study completed 44-item self-report questionnaires exploring their knowledge of cervical cancer prevention, HPV, and HPV vaccination. Results from 2007 were compared with those obtained in 2008-2009. Knowledge scores were correlated with demographic variables, measures of education and attention, and medical factors. Significant associations were assessed in multivariable models. HIV-seropositive women had higher knowledge scores than seronegative women at baseline (13.2 ± 5.7 compared with 11.8 ± 6.0, P < .001) and follow-up (14.1 ± 5.3 compared with 13.2 ± 5.5, P = .01), but the change in scores was similar (0.9 ± 5.3 compared with 1.5 ± 5.5, P = .13). Knowledge that cervical cancer is caused by a virus rose significantly (P = .005), but only to 24%. Belief that cervical cancer is preventable only rose from 52% to 55% (P = .04), but more than 90% of women in both periods believed regular Pap testing was important. In analysis of covariance models, higher baseline score, younger age, higher education level, higher income, and former- as opposed to never-drug users, but not HIV status, were associated with improved knowledge. High-risk women's understanding of cervical cancer and HPV has improved, but gaps remain. Improvement has been weakest for less educated and lower-income women. II.


Chromosomal location of a race-specific resistance gene to Mycosphaerella graminicola in the spring wheat ST6.
Septoria tritici blotch, caused by Mycosphaerella graminicola, is a serious foliar disease of wheat worldwide. Qualitative, race-specific resistance sources have been identified and utilized for resistant cultivar development. However, septoria tritici blotch resistant varieties have succumbed to changes in virulence of M. graminicola on at least three continents. The use of resistance gene pyramids may slow or prevent the breakdown of resistance. A clear understanding of the genetics of resistance and the identification of linked PCR-based markers will facilitate the recovery of wheat lines carrying multiple septoria tritici blotch resistance genes. The resistance gene in ST6 to isolate MG2 of M. graminicola was mapped with microsatellite markers in two populations, ST6/Erik and ST6/Katepwa. Bulk segregant analysis identified a marker on chromosome 4AL putatively linked to the resistance gene. A large linkage group was identified in each population using additional microsatellite markers mapping to chromosome 4AL. The resistance gene in ST6 mapped to the distal end of chromosome 4AL in each mapping population and was designated Stb7. Three of the microsatellite loci, Xwmc313, Xwmc219 and Xgwm160, mapped within 3.5 cM of Stb7; however, none flanked Stb7. Xwmc313 was the closest and mapped 0.3 and 0.5 cM from Stb7 in the crosses ST6/Katepwa and ST6/Erik, respectively. WMC313 will be very useful for marker-assisted selection of Stb7 in Canadian breeding programs because the ST6 allele of Xwmc313 was not identified in any of the Canadian common wheat cultivars tested.


Surgical treatment of Kommerell's diverticulum and other saccular arch aneurysms.
Saccular aneurysms of the aortic arch are rare, and their surgical repair is challenging with potentially significant morbidity and mortality. We examined our experience over a 3-year period with nine consecutive patients that include nine hybrid repairs with initial extra-anatomic carotid and/or subclavian bypass and subsequent endovascular exclusion of the saccular arch aneurysm. Three patients presented with dysphagia from aberrant right subclavian arteries with aneurysm at the origin of the artery, two had asymptomatic aneurysms at the origin of the left subclavian, and four patients had isolated saccular aneurysms of the arch, three of whom presented with thoracic pain. A total of 16 extra-anatomic bypasses were done in the nine patients. Ten endografts and one nitinol plug were used for exclusion in the nine hybrid cases. There were no perioperative deaths, no strokes, or myocardial infarction events. During follow-up, two patients (22%) were found to have type II endoleaks, but no reinterventions were required. Symptoms resolved in six patients, whereas persistent dysphagia and pain occurred in one. Repair of saccular aneurysms of the aortic arch by hybrid approach can be done with minimal morbidity and mortality and a reasonable rate of symptom resolution.


Adaptation of nitrifying microbial biomass to nickel in batch incubations.
Nitrification-microbial oxidation of ammonia to nitrate-is sensitive to an array of inhibitors. Currently, little is known regarding the ecological processes that enable adaptation to inhibitors and recovery of nitrification. This study evaluated inhibition and recovery of nitrification in batch cultures of activated sludge incubated with different levels of nickel (Ni), a model inhibitor. Incubation with 1 mg/L of added Ni did not adversely affect nitrification, and little inhibition occurred at 5 and 10 mg/L Ni. Incubation with 50 mg/L Ni resulted in significant inhibition, decreased amoA transcript abundance, and delayed recovery of nitrification until amoA transcript abundance rebounded after 24 h. For this dosage, recovery of nitrification occurred without a significant change in ammonia-oxidizing bacteria (AOB) community structure. By contrast, incubation with 150 mg/L of added Ni strongly inhibited nitrification and delayed recovery until a shift in AOB community structure occurred after ∼6 weeks of incubation. The results indicate that inhibitor-resistant nitrifying cultures can be obtained from long-term batch incubations of decaying activated sludge incubated with high levels of added inhibitor.


Postoperative digestive function after radical versus conservative surgical philosophy for deep endometriosis infiltrating the rectum.
To compare delayed digestive outcomes in women managed by two different surgical philosophies: a radical approach mainly related to colorectal resection, and a conservative approach involving rectal shaving and rectal nodule excision. "Before and after" comparative retrospective study. University tertiary referral center. Seventy-five patients managed by surgery for deep endometriosis infiltrating the rectum. Twenty-four women were managed during a period when surgeons pursued a radical philosophy toward treatment, and 51 women were managed during a period when a conservative philosophy was adopted. Standardized gastrointestinal questionnaires: the Gastrointestinal Quality of Life Index, the Knowles-Eccersley-Scott Symptom Questionnaire, the Bristol Stool Score, and the Fecal Incontinence Quality of Life Score. Preoperative patient characteristics, rectal nodule features, and associated localizations of the disease were comparable between the two groups. During the radical period, colorectal resection was carried out in 67% of patients, whereas during the second period only 20% of women underwent colorectal resection. Women managed according to the conservative philosophy had significantly improved results on the Knowles-Eccersley-Scott Symptom Questionnaire, Gastrointestinal Quality of Life Index, and depression/self-perception Fecal Incontinence Quality of Life Score, and significantly improved values for various items related to postoperative constipation: unsuccessful evacuatory attempts, feeling incomplete evacuation, abdominal pain, time taken to evacuate, difficulty evacuating causing a painful effort, and stool consistency. It seems that reducing the rate of colorectal resection leads to better functional outcomes in women presenting with rectal endometriosis, lending support to the conservative surgical philosophy over mandatory colorectal resection.


Heavy metals in the spinal cord of normal rats and of animals treated with chelating agents: a quantitative (zinc, copper, and lead) and histochemical study.
The amounts of zinc, copper, and lead in the rat spinal cord were determined by means of flameless atomic absorption spectrophotometry. Zinc was present in a concentration about 100 p.p.m. (dry weight), copper in a concentration about 5 p.p.m., and lead in slightly more than 1 p.p.m. Analysis of various levels along the cranio-caudal axis of the rat spinal cord revealed differences in the heavy metal content. The Timm sulfide silver staining method has demonstrated that metals in the spinal cord have a distinct regional distribution. To obtain a differentiation between the stainable metals, the effects of six chelating agents (DEDTC, dithizone, oxine, EDTA, dipyridyl, and phenantroline) on the Timm pattern were tested. EDTA left the pattern unchanged, while the other compounds showed individual differences in their influence on the Timm pattern, suggesting that the heavy metal pattern of the spinal cord consists of multiple compartments. The effect of intravital multiple low dose treatment with three of the chelating agents on the histochemical pattern and the metal content of the spinal cord was also investigated. It was found that a decrease in the metal content was not followed by reduction of stainability and vice versa.


Detecting the content of the bright blue pigment in cream based on deep learning and near-infrared spectroscopy.
The excessive content of additives in food is a radical problem that affects human health. However, traditional chemical methods are limited by a long cycle, low accuracy, and strong destructiveness, so a fast and accurate alternative is urgently needed. This paper proposes a prediction model introducing near-infrared spectroscopy and deep learning to perform fast and accurate non-destructive detection of artificial bright blue pigment in cream. The model results show that R2 is 0.9638, RMSEP is 0.0157, and RPD is 4.4022. In the preprocessing part, this paper compares the traditional preprocessing methods (SNV, MSC, SG) horizontally and innovatively proposes the use of autoencoders to mitigate the dimensionality of data, which has immensely improved the follow-up prediction effect. In addition, it tries to perform regression prediction on spectral data and establish a fully connected convolutional neural network model through deep learning, whose result indicators prove better than those of traditional methods such as PLSR and MLR. When constructing the deep learning model, this paper applies knowledge evolution to compress the model to achieve a lower calculation cost and higher accuracy. Compared with the traditional methods, the model proposed in this paper has greater accuracy and higher speed with samples undamaged, which is worth popularizing.


Guanidylated hollow fiber membranes based on brominated poly (2,6-dimethyl-1,4-phenylene oxide) (BPPO) for gold sorption from acid solutions.
Novel guanidylated hollow fiber membranes are prepared based on brominated poly (2,6-dimethyl-1,4-phenylene oxide) (BPPO) under mild reaction conditions. 1H-pyrazole-1-carboxamidine hydrochloride (HPCA) is employed for the guanidylation in aqueous solution at room temperature. The obtained guanidylated PPO hollow fiber membranes (GPPO HFMs) contain 0.31-0.95 mmol/g guanidyl groups and show high affinity to tetrachloroauric anions (AuCl(4)(-)) in acid solutions. For 0.1M HCl solution containing 57.8 mg gold/L, the sorption amount can get as high as 130 mg/g. Besides, the GPPO HFMs show preferable selectivity toward gold in multicomponent solution containing Mg(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Pb(II). A system of comparison experiments involving the sorption behavior of GPPO HFMs and quaternary aminated HFMs are also performed. The results reveal that driving forces for the high adsorption of gold mainly involve complexation mechanism. Overall, the obtained GPPO HFM is a promising chelating material for the recovery of gold.


The adjustment mechanism of the spike and wave discharges in thalamic neurons: a simulation analysis.
Different from many previous theoretical studies, this paper explores the regulatory mechanism of the spike and wave discharges (SWDs) in the reticular thalamic nucleus (TRN) by a dynamic computational model. We observe that the SWDs appears in the TRN by changing the coupling weights and delays in the thalamocortical circuit. The abundant poly-spikes wave discharges is also induced when the delay increases to large enough. These discharges can be inhibited by tuning the inhibitory output from the basal ganglia to the thalamus. The mechanisms of these waves can be explained in this model together with simulation results, which are different from the mechanisms in the cortex. The TRN is an important target in treating epilepsy, and the results may be a theoretical evidence for experimental study in the future.


Metabolite involvement in the behavioral effects of bromocriptine in cats.
There is a lag phase of 30-60 min before the onset of bromocriptine (BC) action. This delay may be necessary for the formation of active metabolites. The objective was to determine whether the abnormal behavioral effects induced by BC involve active hepatic metabolites. Thus, we studied the effect of an inhibitor of hepatic hydroxylation metabolism (SKF 525A) on the behavior of BC-treated cats. Experiments began after six weeks of habituation and involved i.p. injections of: (1) propylene glycol (drug vehicle); (2) SKF 525A (70 mg/kg); (3) BC (10 mg/kg); and (4) SKF 525A followed 30 min later by BC. Each cat received the four treatments with two weeks elapsing between consecutive experiments. The frequency of 12 behaviors was scored for 60 min after 1 h posttreatment. BC alone induced emergent behavioral changes (hallucinatory-like, limb flicks, abortive grooms) that were not observed following control injections (vehicle and SKF 525A). There was a complete elimination of BC-induced hallucinatory-like behavior/escape by SKF 525A pretreatment. Other emergent behaviors were similarly reduced but persisted in all cats. The large frequency of grooming induced by BC was significantly reduced. SKF 525A pretreatment was correlated with a significant increase in staring and quiet sitting and a failure of BC to increase activities such as rubbing, treading and kneading. But many other BC-induced behaviors showed no changes. The data demonstrated that particular BC-induced changes in cats are antagonized by SKF 525A. The behavioral suppression caused by SKF 525A is compatible with the involvement of active hepatic metabolites from BC.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluation method for the cytotoxicity of cigarette smoke by in vitro whole smoke exposure.
An in vitro whole smoke (WS) exposure method was established to evaluate the toxicological effects of fresh cigarette smoke using the VITROCELL(®) system associated with the neutral red uptake (NRU) cytotoxicity assay. The VITROCELL(®) system is a newly representative culture and exposure system for in vitro studies of gases or complex mixtures. The impacts of two factors on cytotoxicity measurements of cigarette smoke were investigated using this WS exposure system. The factors include synthetic air exposure and optimal time to perform the NRU assay after smoke exposure. Results showed that synthetic air exposure used in the system did not significantly alter cell survival; 24h after smoke exposure appeared to be an optimal time-point to assess the cytotoxicity of cigarette smoke. A clear dose-response relationship between smoke exposure and cell viability was demonstrated using this system, and the evaluation method was sensitive to distinguish the differences in smoke-induced cytotoxic effects from different cigarettes. In addition, we tried converting the values of EC50 from WS exposure testing into the values in unit used in total particulate matter (TPM) testing for a purpose of comparison, and the data indicate that the cytotoxicity of smoke measured by WS exposure is greater than that measured by TPM exposure.


Workplace levels of psychosocial factors as prospective predictors of registered sickness absence.
We sought to investigate whether workplace levels of psychosocial work environment factors predict individual sickness absence. Data were collected in a prospective study in 52 Danish workplaces in three organizations: municipal care, technical services, and a pharmaceutical company. Psychosocial factors were aggregated as workplace means. We used multilevel Poisson regression models with psychosocial factors as predictors and individual level sickness absence from absence registries as outcome. High workplace levels of decision authority predicted low sickness absence in the technical services (rate ratio = 0.66, 95% confidence interval = 0.51-0.86) and high workplace levels of skill discretion predicted low sickness absence in the pharmaceutical company (rate ratio = 0.74, 95% confidence interval = 0.62-0.88) after control for relevant confounders. Workplaces in municipal care did not differ with respect to the psychosocial factors. Psychosocial factors at the workplace level may be important predictors of sickness absence.


Thymic carcinoma - an unusual cause for unilateral breast oedema.
An 83-year-old lady presented with oedema of the right breast with no focal masses and was found to have a tumour of thymic origin in the anterior mediastinum. We describe this interesting case along with a review of the causes of unilateral breast oedema.


Psychological risk factors for increased post-operative length of hospital stay following coronary artery bypass graft surgery.
To date, researchers have examined the role of psychological factors in longer-term adaptation to coronary artery bypass graft surgery (CABG), but few have investigated the role of such factors in the immediate post-operative period. Thus, the current study examined psychological risk factors for increased post-operative length of hospital stay in 119 consecutive elective CABG patients (100 men and 19 women). When controlling for operative/post-operative factors, medical factors accounted for 24.5% of the variance. However, pre-operative psychological factors accounted for a further 4.4% of the variance, with increased depression and lower PTSD symptomatology identified as significant independent risk factors for longer post-operative length of hospital stay. Hence, while post-operative length of hospital stay is largely determined by medical factors, psychological factors also influence this outcome. Further research is required to replicate the current findings and to determine the mechanisms through which these variables may act.


[Practical risk analysis].
Risk analysis is typically considered from two complementary points of view: predictive analysis performed prior, and retrospective analysis, which follows the internal reporting of adverse situations or malfunctions, both on the organizational and material or human aspects. The purpose of these additional analyzes is to ensure that planned or implemented measures allow to keep risks to a level deemed tolerable or acceptable at a given time and in a given situation. Where a risk is deemed unacceptable, risk reduction measures should be considered (prevention, limiting the consequences and protection).


Vitamin D receptor expression and neoadjuvant therapy in esophageal adenocarcinoma.
Esophageal adenocarcinoma carries a poor prognosis. Tumor response to neoadjuvant therapy is a key prognostic factor in patients with adenocarcinoma of the esophagus, but is inconsistent. Identifying tumor characteristics that portend a favorable response to neoadjuvant therapy would be a valuable clinical tool. The anticancer actions of vitamin D and its receptor may have implications. In this study, 15 biopsy specimens were procured retrospectively from patients being treated for adenocarcinoma of the esophagus. The tissue was immunostained for the vitamin D receptor and compared on the basis of response to neoadjuvant therapy. Tumors that did not respond to neoadjuvant therapy had greater expression of VDR than tumors that responded completely. Expression of VDR declined with tumor de-differentiation. The data suggest that a relationship between vitamin D receptor expression and response to neoadjuvant therapy is plausible.


Temporal patterns in bacterial communities in three temperate lakes of different trophic status.
Despite considerable attention in recent years, the composition and dynamics of lake bacterial communities over annual time scales are poorly understood. This study used automated ribosomal intergenic spacer analysis (ARISA) to explore the patterns of change in lake bacterial communities in three temperate lakes over 2 consecutive years. The study lakes included a humic lake, an oligotrophic lake, and a eutrophic lake, and the epilimnetic bacterial communities were sampled every 2 weeks. The patterns of change in bacterial communities indicated that seasonal forces were important in structuring the behavior of the bacterial communities in each lake. All three lakes had relatively stable community composition in spring and fall, but summer changes were dramatic. Summertime variability was often characterized by recurrent drops in bacterial diversity. Specific ARISA fragments derived from these lakes were not constant among lakes or from year to year, and those fragments that did recur in lakes in different years did not exhibit the same seasonal pattern of recurrence. Nonetheless, seasonal patterns observed in 2000 were fairly successful predictors of the rate of change in bacterial communities and in the degree of autocorrelation of bacterial communities in 2001. Thus, seasonal forces may be important structuring elements of these systems as a whole even if they are uncoupled from the dynamics of the individual system components.


Avoiding Spurious Low Platelet Counts by Redrawing Specimens with First Time Low Platelet Counts.
We reviewed our policy of redrawing our pediatric patients with first time platelet counts <100 K/ml to assess the frequency of correction. In a Children's Hospital 25-month review of patients that underwent automatic redraws due to low first time platelet counts, we determined the frequency of corrected counts and the sites where these original low platelet counts originated. Only the repeat draw results were reported. Of 99 children with redrawn specimens, 62% of platelet counts corrected. The most frequent corrections occurred in specimens from the emergency department (74%), pediatric intensive care (71%), and operating room (67%), the fewest from the cardiac intensive care (38%) and general hospital floors (44%). The policy of redrawing patients with first time platelet counts <100 K resulted in correction in 62%, and avoided delays and additional charges for repeat testing ordered by the provider.


A longitudinal study of the association between dietary factors, serum lipids, and bone marrow lesions of the knee.
Bone marrow lesions (BMLs) play an important role in knee osteoarthritis, but their etiology is not well understood. The aim of this longitudinal study was to describe the association between dietary factors, serum lipids, and BMLs. In total, 394 older men and women (mean age, 63 years; range, 52 to 79) were measured at baseline and approximately 2.7 years later. BMLs were determined by using T2-weighted fat-saturation magnetic resonance imaging (MRI) by measuring the maximal area of the lesion. Nutrient intake (total energy, fat, carbohydrate, protein, and sugar) and serum lipids were assessed at baseline. Cross-sectionally, dietary factors and lipids were not significantly associated with BMLs. Energy, carbohydrate, and sugar intake (but not fat) were positively associated with a change in BML size (β = 15.44 to 19.27 mm2 per 1 SD increase; all P < 0.05). High-density lipoprotein (HDL) cholesterol tended to be negatively associated with BML change (β = -11.66 mm2 per 1 SD increase; P = 0.088). Energy, carbohydrate, and sugar intake may be risk factors for BML development and progression. HDL cholesterol seems protective against BMLs. These results suggest that macronutrients and lipids may be important in BML etiology and that dietary modification may alter BML natural history.


An unusual pulmonary perforation case after chest tube placement.
Pulmonary laceration is an uncommon complication of tube thoracostomy technique that is expected vigorous clinically and may be fatal. In this study, we report a case of pulmonary laceration owing to a tube thoracostomy, with no clinical signs, and detected incidentally on thorax computed tomography.


Bayesian analysis of dynamic phosphoproteomic data identifies protein kinases mediating GPCR responses.
A major goal in the discovery of cellular signaling networks is to identify regulated phosphorylation sites ("phosphosites") and map them to the responsible protein kinases. The V2 vasopressin receptor is a G-protein coupled receptor (GPCR) that is responsible for regulation of renal water excretion through control of aquaporin-2-mediated osmotic water transport in kidney collecting duct cells. Genome editing experiments have demonstrated that virtually all vasopressin-triggered phosphorylation changes are dependent on protein kinase A (PKA), but events downstream from PKA are still obscure. Here, we used: 1) Tandem mass tag-based quantitative phosphoproteomics to experimentally track phosphorylation changes over time in native collecting ducts isolated from rat kidneys; 2) a clustering algorithm to classify time course data based on abundance changes and the amino acid sequences surrounding the phosphosites; and 3) Bayes' Theorem to integrate the dynamic phosphorylation data with multiple prior "omic" data sets covering expression, subcellular location, known kinase activity, and characteristic surrounding sequences to identify a set of protein kinases that are regulated secondary to PKA activation. Phosphoproteomic studies revealed 185 phosphosites regulated by vasopressin over 15 min. The resulting groups from the cluster algorithm were integrated with Bayes' Theorem to produce corresponding ranked lists of kinases likely responsible for each group. The top kinases establish three PKA-dependent protein kinase modules whose regulation mediate the physiological effects of vasopressin at a cellular level. The three modules are 1) a pathway involving several Rho/Rac/Cdc42-dependent protein kinases that control actin cytoskeleton dynamics; 2) mitogen-activated protein kinase and cyclin-dependent kinase pathways that control cell proliferation; and 3) calcium/calmodulin-dependent signaling. Our findings identify a novel set of downstream small GTPase effectors and calcium/calmodulin-dependent kinases with potential roles in the regulation of water permeability through actin cytoskeleton rearrangement and aquaporin-2 trafficking. The proposed signaling network provides a stronger hypothesis for the kinases mediating V2 vasopressin receptor responses, encouraging future targeted examination via reductionist approaches. Furthermore, the Bayesian analysis described here provides a template for investigating signaling via other biological systems and GPCRs. Video abstract.


Cerebellopontine angle tumors causing hemifacial spasm: types, incidence, and mechanism in nine reported cases and literature review.
Although hemifacial spasm is usually caused by vascular compression around the root exit zone of the facial nerve, it is sometimes brought on by a cerebellopontine angle tumor. We reviewed and analyzed data from past experience with hemifacial spasm induced by cerebellopontine angle tumors. Nine patients of a total 2,050, who had presented with hemifacial spasms associated with cerebellopontine angle tumors between 1986 and 2009, were reviewed. Two vestibular schwannomas, five meningiomas, and two epidermoid tumors were included in this study. Hemifacial spasm occurred on the same side of the lesion in eight patients whereas it occurred on the opposite side of the lesion in one patient. With respect to the pathogenesis of hemifacial spasms, offending vessels were found in six patients, tumor encasement of the facial nerve in one patient, hypervascular tumor compression of the facial nerve without offending vessels in one patient, and a huge tumor compressing the brain stem and, thus, contralateral facial nerve compression in one patient. Hemifacial spasm was resolved in seven patients, whereas in two patients with a vestibular schwannoma and an epidermoid tumor, it improved transiently and then recurred in a month. Each type of tumor had different characteristics with respect to the induction of hemifacial spasm; therefore, it is suggested that neurosurgeons, who are planning surgeries both for the purposes of relieving hemifacial spasm and removal of cerebellopontine angle tumor, should thoroughly prepare appropriate approaches and specific dissecting strategies according to each causative lesion.


[The relationship between polymorphism of angiotensin converting enzyme gene and cough caused by angiotensin converting enzyme inhibitors].
To investigate the relationship between the polymorphism of angiotensin converting enzyme (ACE) gene and ACE inhibitor (ACEI)-induced cough in Chinese elderly with essential hypertension. ACE I/D polymorphism was performed on DNA samples from patients using the polymerase chain reaction (PCR) followed by agarose gel electrophoresis. Serum ACE levels were measured using a colorimetric assay. The frequencies of ACE II genotype were 40% in patients with cough and 20% in those without cough, respectively (P < 0.05). The frequencies of I allele were 60% in patients with cough and 41% in those without cough (P < 0.01); The serum ACE level was highest in the DD genotype, followed by the ID genotype and the II genotype. The ACE level in patients with cough was significantly lower than that in patients without cough (P < 0.001). The sensitivity and specificity were 81% and 78% respectively when the serum ACE levels were used to predict ACEI-induced cough. ACEI-induced cough was related to the serum ACE level and ACE gene polymorphism in Chinese elderly with essential hypertension.


Catalytides derived from the Box A region in the ANA/BTG3 protein cleave amyloid-β fragment peptide.
We have recently reported about shorter proteolytic peptides termed Catalytide as general name. JAL-TA9 (YKGSGFRMI), a fragment peptide derived from Box A region of Tob1 protein, is the first Catalytide and cleaves Aβ42 and its fragment peptides. Herein, we demonstrate the enzymatic properties of ANA-TA9 corresponding region to JAL-TA9 in ANA/BTG3 protein. ANA-TA9 showed the auto-proteolytic activity and cleaved 3 kinds of synthetic fragment peptides derived from Aβ42, especially on the central region of Aβ42 with a serine protease like activity. Interestingly, 2 kinds of components, ANA-SA5 (SKGQA) and ANA-YA4 (YRMI), also showed similar proteolytic activity. These results indicate that ANA-TA9 is composed of two different Catalytides.


The satisfaction regarding handovers between ambulance and emergency department nurses: an observational study.
A thorough handover in the emergency department (ED) is of great importance for improving the quality and safety in the chain of care. The satisfaction of handover may reflect the quality of handover. Research to discover the variables influencing the satisfaction of handovers is scarce. The goal of this study was to determine the factors influencing the satisfaction regarding handovers from ambulance and ED nurses. We performed a prospective observational study in the University Medical Center of Groningen. Data regarding prehospital-hospital handovers has been collected by observing handovers and assessing patient chart information. Data regarding the satisfaction has been collected with a questionnaire including a 5-point scale for the level of satisfaction. In total, 97 handovers were observed and 97 ambulance nurses and 89 ED nurses completed the questionnaire. The satisfaction of ambulance nurses showed a negative correlation with the waiting time prior to handover (r = -.287, p = .004) and a positive correlation with the presence of a physician in the receiving team (r = .224, p = .028). The satisfaction of ED nurses showed a positive correlation with the use of the ABCDE (r = .288, p = .006) and AMPLE instrument (r = .208, p = .050). The satisfaction of ambulance and ED nurses as sender or receiver of the handover is determined by different factors. The satisfaction of ambulance nurses is mainly affected by the waiting time and presence of a physician, while the satisfaction of ED nurses is affected by the use of handover instruments and the completeness of medical information.


Hypermethylation of the thrombospondin-1 gene is associated with poor prognosis in penile squamous cell carcinoma.
To evaluate the presence of human papillomavirus (HPV) infection, the methylation status in the promoter region of thrombospondin-1 (TSP-1), RAS association domain family 1A (RASSF1-A) and p16 genes, and the expression of TSP-1, CD31, p16 and p53 proteins in patients diagnosed with penile cancer, and the possible associations between these variables and clinical and pathological features. HPV types, gene promoter hypermethylation and protein expression were analysed by reverse line blot, methylation-specific polymerase chain reaction, and immunohistochemistry, respectively, in 24 penile squamous cell carcinomas. HPV infection was detected in 11 of 24 cases (46%), and TSP-1, RASSF1-A and p16 genes were hypermethylated in 46%, 42% and 38% of the tumours, respectively. TSP-1 hypermethylation was associated with unfavourable histological grade (grade 3; P = 0.033), vascular invasion (P = 0.023), weak expression of TSP-1 protein (P = 0.041), and shorter overall survival (P = 0.04). TSP-1 expression was not associated with microvessel density. However, RASSF1-A hypermethylation was more frequent in T1 tumours (P = 0.01), and p16 hypermethylation was not associated with any of the tested variables except for absence of p16 expression (P = 0.022). In summary, the epigenetic inactivation of TSP-1 and RASSF1-A genes is associated with pathological variables and seems to be of prognostic significance in penile cancer.


Investigations of the anal sphincter before and after restorative proctocolectomy.
Twenty-eight patients who underwent sphincter-saving proctocolectomy and formation of an ileoanal reservoir had clinical evaluation of resting and maximal anal sphincter pressures and perfused catheter manometry. The clinical estimate of resting tone, heretofore believe to be a good predictive parameter of postoperative function, was inaccurate. This suggests the advisability of manometric evaluation. There were significant changes in sphincter pressures postoperatively. Operation did not effect the preoperative electromyographic findings of the puborectalis muscle and external sphincter in our small postoperative population. The mechanism by which operation might influence these parameters has been discussed. Factors such as parity and the descending perineum syndrome may effect continence. Due to the length of time the sphincter is required to function in these patients and the multiplicity of factors involved, we believe that long-term studies are needed.


Bio-based active food packaging materials: Sustainable alternative to conventional petrochemical-based packaging materials.
In food industry, a growing concern is the use of suitable packaging material (i.e., biodegradable coatings and films) with enhanced thermal, mechanical and barrier characteristics to prevent from contamination and loss of foodstuff. Biobased polymer resources can be used for the development of biodegradable bioplastics. To achieve this goal, biopolymers should be economic, renewable and abundantly available. Bioplastic packaging materials based on renewable biomass could be used as sustainable alternative to petrochemically-originated plastic materials. This review summarizes the recent advancements in biopolymer-based coatings and films for active food packaging applications. Microbial polymers (PHA and PLA), wood-based polymers (cellulose, hemicellulose, starch & lignin), and protein-based polymers (gelatin, keratin, wheat gluten, soy protein and whey protein isolates) were among the materials most widely exploited for the development of smart packaging films. These biopolymers are able to synthesize coatings and films with good barrier properties against food borne pathogens and the transport of gases. Biobased reinforcements e.g., plant essential oils and natural additives to bioplastic films improve oxygen barrier, antibacterial and antifungal properties. To induce the desired functionality the simultaneous utilization of different synthetic and biobased polymers in the form of composites/blends is also an emerging area of research. Nanoscale reinforcements into bioplastic packaging have also been reported to improve packaging characteristics ultimately increasing food shelf life. The development of bioplastic/biocomposite and nanobiocomposites exhibits high potential to replace nonbiodegradable materials with characteristics comparable to fossil-based plastics, additionally, giving biodegradable and compostable characteristics. The idea of utilization of renewable biomass and the implications of biotechnology can firstly reduce the burden from fossil-resources, while secondly promoting biobased economy.


Changes in granulocytic hemopoietic stem and their mechanisms during hypoxia of different genesis.
We studied reactions of the granulocytic hemopoietic stem during hypoxia of different genesis and severity. Stimulation of granulocytopoiesis was determined by an increase in functional activity of granulomonocytic precursors due to changes in feeder capacity of cells in the hemopoiesis-inducing microenvironment and colony-stimulating activity of the plasma. The development of encephalopathy caused by oxygen deficiency was accompanied by a decrease in the number of bone marrow granulomonocytic precursors due to reduction of proliferative activity (despite the increase in secretory activity of microenvironmental cells and increase in plasma colony-stimulating activity). Severe hypoxia accelerated maturation of hemopoietic cells and produced neutrophilic leukocytosis.


A comparison of the facilitatory actions of 4-aminopyridine methiodide and 4-aminopyridine on neuromuscular transmission.
1 4-Aminopyridine methiodide (4-APMI), a quaternary analogue of aminopyridine (4-AP), was tested for neuromuscular facilitatory actions on the chick biventer cervicis and frog sartorius nerve-muscle preparations. 2 In the chick, 4-APMI (10(-4) to 10(-2) M) augmented indirectly elicited twitches and reversed tubocurarine-induced neuromuscular block. Reversal of tubocurarine block was observed after treatment of the muscle with an anticholinesterase. 4-APMI did not itself produce contracture but augmented responses to added acetylcholine. 3 4-APMI (10(-4) M) prolonged the time courses of endplate potentials (e.p.ps) and miniature endplate potentials (m.e.p.ps) in the frog. 4 4-APMI (10(-4) M) increased e.p.p. quantal content. 4-AP was about 100 times more active than 4-APMI in increasing quantal content. Both compounds prolonged muscle action potentials at similar concentrations. 5 4-APMI (10(-3) to 3 X 10(-3) M) possessed anticholinesterase activity in homogenates of chick biventer cervicis muscle. 6 It is concluded that 4-APMI increases evoked acetylcholine release and also possesses a weak anticholinesterase action. The greater action of 4-AP on quantal content is probably due to an intracellular action, possibly involving the release of calcium ions.


The Risk of Glioblastoma with TNF Inhibitors.
To quantify the risk of glioblastoma (GBM) and its most aggressive form, glioblastoma multiforme (GBM-M), in patients treated with tumor necrosis factor (TNF) inhibitors. Data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and the World Health Organization (WHO) Collaborating Centre for International Drug Monitoring were used to perform a disproportionality analysis. We computed reporting odds ratios (RORs) and corresponding 95% confidence intervals for the association between use of TNF inhibitors (infliximab, adalimumab, etanercept, certolizumab, and golimumab) and GBM or GBM-M compared to all other drugs with adverse events reported in the databases. A harmful signal was deemed for a lower limit of the 95% confidence interval above 1. We identified 81 cases of GBM or GBM-M with adalimumab in the U.S. FDA FAERS and 49 cases in the WHO drug monitoring database. For infliximab, 40 and 32 cases were identified in the FAERS and WHO databases, respectfully. Infliximab had the highest association with GBM (WHO: ROR = 7.41 (5.19-10.57), FAERS: ROR = 2.80 [1.89-4.15]). Adalimumab was also highly associated with GBM (WHO: ROR = 3.54 [2.58-4.89], FAERS: ROR = 1.99 [1.41-2.80]). Several TNF inhibitors appear to be more strongly associated with GBM compared to other drugs in both the FAERS and WHO databases. Large epidemiologic studies are needed to confirm these findings. Although these results do not demonstrate a cause-and-effect relationship, they warrant further investigation by well-designed epidemiologic studies.