Prevalence and characteristics of restless legs syndrome in patients with pulmonary hypertension.
Patients with pulmonary hypertension (PH) have an increased prevalence of risk factors for restless legs syndrome (RLS). We performed a cross-sectional study to determine the prevalence and characteristics of RLS in this population. Patients filled out two questionnaires during a visit: (1) a diagnostic tool for RLS, based on the core clinical features; and (2) a 10-question rating scale used to assess severity. Data were obtained by medical record review with regard to demographics, characteristics of PH and known RLS risk factors. Restless legs syndrome was found in 43.6% (24 of 55) (mean age +/- SD: 49 +/- 14 years; 41 women, 14 men) of patients and 54% of these had moderate or severe RLS. Patients with RLS were younger but gender differences were not appreciated. Presence of RLS did not correlate with measures of PH severity; however, patients with RLS were more likely to have a better 6-minute walk distance (p = 0.015) and lower BNP level (p = 0.07) and less likely to be WHO Class IV or require oxygen during the 6-minute walk test. Patients with a history of hypothyroidism (67%; p = 0.04) and those on opioids for relief of leg pain (69%) were more likely to have RLS. Patients with PH had a very high prevalence of RLS and most had moderate or severe symptoms. RLS was more common in more active patients and those who were hypothyroid or on opioids for relief of leg pain. Patients with PH should be screened for RLS because good treatment options are available.


CeBRC-2 stimulates D-loop formation by RAD-51 and promotes DNA single-strand annealing.
The BRCA2 tumour suppressor regulates the RAD-51 recombinase during double-strand break (DSB) repair by homologous recombination (HR) but how BRCA2 executes its functions is not well understood. We previously described a functional homologue of BRCA2 in Caenorhabditis elegans (CeBRC-2) that binds preferentially to single-stranded DNA via an OB-fold domain and associates directly with RAD-51 via a single BRC domain. Consistent with a direct role in HR, Cebrc-2 mutants are defective for repair of meiotic and radiation-induced DSBs due to an inability to regulate RAD-51. Here, we explore the function of CeBRC-2 in HR processes using purified proteins. We show that CeBRC-2 stimulates RAD-51-mediated D-loop formation and reduces the rate of ATP hydrolysis catalysed by RAD-51. These functions of CeBRC-2 are dependent upon direct association with RAD-51 via its BRC motif and on its DNA-binding activity, as point mutations in the BRC domain that abolish RAD-51 binding or the BRC domain of CeBRC-2 alone, lacking the DNA-binding domain, fail to stimulate RAD-51-mediated D-loop formation and do not reduce the rate of ATP hydrolysis by RAD-51. Phenotypic comparison of Cebrc-2 and rad-51 mutants also revealed a role for CeBRC-2 in an error-prone DSB repair pathway independent of rad-51 and non-homologous end joining, raising the possibility that CeBRC-2 may have replaced the role of vertebrate Rad52 in DNA single-strand annealing (SSA), which is missing from C. elegans. Indeed, we show here that CeBRC-2 mediates SSA of RPA-oligonucleotide complexes similar to Rad52. These results reveal RAD-51-dependent and -independent functions of CeBRC-2 that provide an explanation for the difference in DNA repair defects observed in Cebrc-2 and rad-51 mutants, and define mechanistic roles for CeBRC-2 in HR and in the SSA pathway for DSB repair.


Immunohistochemistry as a screening tool for NTRK gene fusions: results of a first Belgian ring trial.
A Belgian ring trial for pan-TRK immunohistochemistry (IHC) staining was organised to harmonise pan-TRK IHC staining protocols and interpretation. As a reference method, the VENTANA pan-TRK Assay (clone EPR17341) on the Benchmark Ultra platform was selected. Six samples were selected: 2 negative, 2 fusion positive and 2 samples with wild-type endogenous TRK expression. Each participating laboratory stained the slides using their routine pan-TRK IHC and reported their results. In addition, they were asked to return one TRK-stained slide from each case. The coordinating lab evaluated these slides, compared them with the reference method and scored them. Two clones were used during the ring trial: A7H6R (Cell Signaling) and EPR17341 (Abcam/Ventana). Seven protocols achieved a sufficient performance mark, and three labs were advised to further optimise the protocol. Interpretation of pan-TRK IHC proved to be challenging in cases with physiological TRK expression. In addition, depending on the NTRK fusion partner, the staining can vary strongly in both intensity and staining pattern. Labs using the Ventana ready-to-use system based on the EPR17341 clone and using the recommended protocol settings scored best. However, given some small optimisation, all labs scored well on the technical staining and the succeeding evaluation.


Delayed administration of parecoxib, a specific COX-2 inhibitor, attenuated postischemic neuronal apoptosis by phosphorylation Akt and GSK-3β.
Parecoxib is a recently described novel COX-2 inhibitor whose functional significance and neuroprotective mechanisms remain elusive. Therefore, in this study, we aimed to investigate whether delayed administration of parecoxib inhibited mitochondria-mediated neuronal apoptosis induced by ischemic reperfusion injury via phosphorylating Akt and its downstream target protein, glycogen synthase kinase 3β (GSK-3β). Adult male Sprague-Dawley rats were administered parecoxib (10 or 30 mg kg(-1), IP) or isotonic saline twice a day starting 24 h after middle cerebral artery occlusion (MCAO) for three consecutive days. Cerebral infarct volume, apoptotic neuron, caspase-3 immunoreactivity and the protein expression of p-Akt, p-GSK-3β and Cytochrome C in cerebral ischemic cortex were evaluated at 96 h after reperfusion. Parecoxib significantly diminished infarct volume and attenuated neuron apoptosis in a dose-independent manner, compared with MCAO group alone. Increased p-Akt and p-GSK-3β was observed in the ischemic penumbra of parecoxib group after stroke. Moreover, parecoxib also reduced the release of Cytochrome C from mitochondrial into cytosol and attenuated the caspase-3 immunoreactivity in the penumbra. Taken together, these results suggested that parecoxib ameliorated postischemic mitochondria-mediated neuronal apoptosis induced by focal cerebral ischemia in rats and this neuroprotective potential is involved in phosphorylation of Akt and GSK-3β.


Hierarchically porous organic polymers: highly enhanced gas uptake and transport through templated synthesis.
Porous organic polymers (POPs) possessing meso- and micropores can be obtained by carrying out the polymerization inside a mesoporous silica aerogel template and then removing the template after polymerization. The total pore volume (tpv) and specific surface area (ssa) can be greatly enhanced by modifying the template (up to 210% increase for tpv and 73% for ssa) as well as by supercritical processing of the POPs (up to an additional 142% increase for tpv and an additional 32% for ssa) to include larger mesopores. The broad range of pores allows for faster transport of molecules through the hierarchically porous POPs, resulting in increased diffusion rates and faster gas uptake compared to POPs with only micropores.


A survey on usage of personal care products especially cosmetics among university students in Saudi Arabia.
The harmful health effects of personal care products especially cosmetics have engulfed many societies of the world especially the female section without an alarm. To estimate the prevalence of cosmetic usage and to assess the experiences of Saudi female undergraduate students in Wadi Al Dawasir province in an attempt to arouse general awareness among Saudi students about the harmful effects of the chemicals present therein. It is a cross-sectional study carried out with a total of randomly selected 106 college students (female) at undergraduate level. Two colleges for girls of Prince Sattam Bin Abdul Aziz University at Wadi Al Dawasir region were included. Standard questionnaire was set in Arabic and English both. T test and data was analyzed using SPSS version 20. Chi-square/Fisher's exact tests and a P value of <0.05 were considered statistically significant. The overall prevalence of using cosmetics (makeup) and average age of first use of the cosmetics was found to be quite high. Statistical analysis shows that 69.8% students applied daily and 23.6% students applied twice to thrice daily. Consequently, this makes a gross percentage of 93.4% among college going Saudi students who applied makeup on daily basis. The findings have shown that 93.2% female and married medical students use cosmetics twice/thrice daily. Similarly, 6.8% female and married medical students use cosmetics once daily. The findings have shown that 82.9% female and unmarried medical students possess knowledge about cosmetics. Similarly, 17.1% female and married medical students possess knowledge about cosmetics. The usage of cosmetics was found to be extremely high among the college going Saudi students in Wadi Al Dawasir Region, Kingdom of Saudi Arabia. Un-awareness regarding the harmful effects of cosmetics was found to be high among these students.


Tissue expression of human epididymal secretory protein 4 may be useful in the differential diagnosis of uterine cervical tumors.
Human Epididymal Secretory Protein 4 was firstly described as an epididymis-specific protein but more recently it has been demonstrated to be a putative serum tumor marker for different malignancies, especially ovarian epithelial cancers. The aim of this study is to investigate the association between tissue Human Epididymal Secretory Protein 4 expression and the clinicopathological features of uterine cervical tumors. This retrospective study was designed to evaluate the differences of tissue expressions of Human Epididymal Secretory Protein 4 protein in a spectrum of cervical neoplasms. One hundred and seven patients recently diagnosed as having cervical intraepithelial neoplasm or invasive squamous cell carcinoma, adenosquamous carcinoma and adenocarcinoma based on pathology databases. Decreased or negative Human Epididymal Secretory Protein 4 expressions were determined in both normal cervical epithelia and in intraepithelial carcinomas, while increased HE4 expression was observed in invasive tumors. This study demonstrated that altered expression of Human Epididymal Secretory Protein 4 may involve in tumorigenesis in the uterine cervix. Our findings also suggested the presence of a correlation between Human Epididymal Secretory Protein 4 expression and the invasive potential of uterine tumors. Therefore it may be thought that the tissue expression of HE4 can be used to differentiate high grade intraepithelial tumors from carcinomas.


Light protection of parenteral nutrition, cholestasis, and other prematurity-related morbidities in premature infants.
Parenteral Nutrition (PN) can lead to intestinal failure associated liver disease (IFALD). There are no human studies to date studying specifically the benefits of light-protection on neonatal IFALD. Recently, the European Medicines Agency and the American Society for Parenteral and Enteral Nutrition (ASPEN) both recommended full light protection of PN to reduce the risk of adverse clinical outcomes. The primary objective of this study was to evaluate the impact of light-protecting PN on the incidence of cholestasis and peak direct bilirubin levels in premature infants. Retrospective chart review of preterm infants requiring PN for a minimum of 2 weeks with or without light-protection. After light protection of the PN solution, primary outcomes (including cholestasis and direct bilirubin levels) of both groups were compared. Secondary outcomes include evaluation of bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), sepsis and mortality. A total of 50 preterm infants <37 weeks gestation were included, 25 infants in each group. There was a statistically significant decrease in the rate of cholestasis (12 vs. 3, p = 0.005), median peak direct bilirubin levels (1.7 vs. 0.9 mg/dL, p = 0.02) and total bilirubin levels (4.1 vs. 3.4, p = 0.05) in the light-protection group compared to no light-protection group. There was a decrease in the incidence of severe BPD (with an increase of mild BPD, resulting in the same overall BPD rate) in the light-protection compared to no light-protection group (7 vs. 15, p = 0.0223). There was no difference in NEC, ROP, sepsis or mortality. Our study supports that the practice of light-protecting PN may reduce the incidence of IFALD in premature infants. Moreover, there was a trend toward decreased incidence of severe BPD in the light-protection group. Further light protection studies are needed to confirm these findings.


Principles of Insect Path Integration.
Continuously monitoring its position in space relative to a goal is one of the most essential tasks for an animal that moves through its environment. Species as diverse as rats, bees, and crabs achieve this by integrating all changes of direction with the distance covered during their foraging trips, a process called path integration. They generate an estimate of their current position relative to a starting point, enabling a straight-line return, following what is known as a home vector. While in theory path integration always leads the animal precisely back home, in the real world noise limits the usefulness of this strategy when operating in isolation. Noise results from stochastic processes in the nervous system and from unreliable sensory information, particularly when obtaining heading estimates. Path integration, during which angular self-motion provides the sole input for encoding heading (idiothetic path integration), results in accumulating errors that render this strategy useless over long distances. In contrast, when using an external compass this limitation is avoided (allothetic path integration). Many navigating insects indeed rely on external compass cues for estimating body orientation, whereas they obtain distance information by integration of steps or optic-flow-based speed signals. In the insect brain, a region called the central complex plays a key role for path integration. Not only does the central complex house a ring-attractor network that encodes head directions, neurons responding to optic flow also converge with this circuit. A neural substrate for integrating direction and distance into a memorized home vector has therefore been proposed in the central complex. We discuss how behavioral data and the theoretical framework of path integration can be aligned with these neural data.


Metal distribution in soils of an in-service urban parking lot.
Increasing traffic is becoming one of the main sources of metal pollution in urban areas. To investigate the possible impacts of traffic-related activities on metal distribution in soils, a total of 370 soil samples were collected in a ground parking space in service for about 20 years in Chengdu, China. The concentrations of Cu, Fe, Mn, Pb, Rb, Sr, Ti, and Zn in soils were measured using portable energy-dispersive X-ray fluorescence. Soil samples exhibited various levels of metal pollution ranging from no pollution to borderline moderate pollution for Zn and Pb, with median enrichment factors following the order of Zn (2.7), Pb (2.2), Sr (1.9), Cu (1.8), Fe (1.3), Rb (1.1), and Mn (0.5). Both cluster analysis and spatial distribution mapping demonstrated that Pb, Zn, Cu, Mn, Sr, and Fe concentrations in the parking space were influenced by traffic, with strong spatial variation in different areas of the parking space. These metals shared similar spatial distribution patterns with relatively elevated concentrations in the four corners, left and right sides and entrance and rear areas, compared with the metal concentrations in the central area. Such spatial patterns revealed the influences of yellow road paint, wear and tear of vehicular parts including brakes and tires, as well as tailpipe emissions. The pollution sources in the parking space were identified as yellow road paint and vehicular emissions. This study highlights that metal pollution in the parking areas should be given more attention.


Psychological models of mental disorder, human rights, and compulsory mental health care in the community.
Recent amendments to the 1983 Mental Health Act in the UK (Mental Health Act 2007) include the controversial provision for: "supervised treatment in the community for suitable patients following an initial period of detention and treatment in hospital". This provision is widespread, and more formal, in other English-speaking jurisdictions. Reviews of the international literature, human rights considerations and the perspective of psychological approaches to mental health care suggest that proposed 'supervised community treatment orders' are valuable, lawful, and compatible with the European Convention on Human Rights if certain specific conditions are met. Provisions for 'supervised community treatment orders' in the UK should be supported, but with the provisos that: the powers of the Mental Health Act are limited as in Scotland, to persons whose "ability to make decisions about the provision of [care] is significantly impaired", that each order is time-limited and subject to review by a properly constituted Tribunal, and that the use of such orders should represent a benefit to people in terms of more appropriate treatment, or be a least restrictive alternative, or better preserve the person's private and family life.


Longitudinal genetic analysis of EEG coherence in young twins.
During middle childhood, continuous changes occur in electroencephalogram (EEG) coherence, an index of cortico-cortical connectivity of the brain. In the gradual development of EEG coher ence, occasional "growth spurts" are observed which coincide with periods of discontinuous development in cognition. Discontinuous development may reflect changes in the genetic architecture of a trait over time, for instance, by the emergence of new genetic factors. To examine stability and change in genetic and environmental influences on EEG coherence from ages 5 to 7 years, intrahemispheric EEG coherences from 14 connections were collected twice in 209 twin pairs. Overall, heritabilities (h2) were moderate to high for all EEG coherences at both ages (average: 58%). For occipito-cortical connections in the right hemisphere, h2 increased with age due to a decrease in environmental variance. For prefronto-cortical connections in the left hemisphere, h2 decreased with age due to a decrease in genetic variance. New genetic factors at age 7 were found for prefronto-parietal coherence, and centro-occipital and parieto-occipital EEG coherences in both hemispheres and, in the left hemisphere, for prefronto-frontal EEG coherences. Mean genetic correlation for these cortico-cortical connections over time was 0.72, indicating that at least part of the genetic influences is age-specific. We argue that this is convincing evidence for the existence of stage-wise brain maturation from years 5 to 7, and that growth spurts in EEG coherence may be part of the biological basis for discontinuous cognitive development at that age range.


A practical method for predicting and analyzing the consequences of ammonium nitrate explosion accidents adjacent to densely populated areas.
Several catastrophic ammonium nitrate (AN) explosion accidents have been reported during the last decades. Previous studies have been mainly focused on investigating adverse effects caused by the AN explosion, while only a few systematically analyzed the consequences and impacts of AN explosions. This study collects data from three typical AN explosions (accidental explosion of the US fertilizer plant in 2013; an accidental explosion of China's Tianjin port in 2015, and a recent explosion (2020) of the Beirut port in Lebanon). The consequences of accidental explosions were analyzed by mathematical equations that further provide scientific explanations for AN explosions. Based on the explosives' properties on-site, these accidental explosions were caused by condensed phase explosives. Comparison with the conditions at the explosion site indicated that blast overpressure was the primary factor in the loss of life and damage to the building, while ground shock was a secondary factor. The severity of loss of life and building damage from explosions decreased with increasing distance. These distances could be calculated by the scaling law, which was replaced by the equivalent TNT mass of the explosive and the damage scale's overpressure boundary value. In addition, mapping the damaged area on a map helped in the visual presentation of the consequence assessment. The long-term environmental and ecological impact due to the explosions was also an important issue that could not be ignored. Overall, this study establishes a simple and easy-to-use method to rapidly predict and assess the consequences of an explosion, and provides technical guidance for future emergency response to similar large-scale accidents.


Sweat testing for cystic fibrosis: characteristics of a combination chloride ion-selective electrode.
Filling solution leakage, reproducibility, stability, interferences and temperature effects have been studied in relation to the use of the Orion 96-17-01 combination chloride ion-selective electrode in sweat testing for cystic fibrosis. While stability and reproducibility is good, certain antiseptic systems and especially Hibitaine (chlorhexidine gluconate) interfere with the electrode and therefore need to be absent during sweat testing. Temperature conditions during calibration and sweat testing need to be controlled in view of the extent of response variations for even modest temperature differences between sensor-skin interface and electrode stem.


Partial elimination of Epstein-Barr virus plasmids from Burkitt's lymphoma cells by transfecting the BZLF1 gene.
Epstein-Barr virus (EBV) nonproducer Raji cells stably maintain approximately 45 copies of the EBV genome per cell, depending on the presence of the EBV-determined nuclear antigen 1 (EBNA-1) protein. We found that transfection of the EBV BZLF1 gene causes the disappearance of EBNA proteins on Western blots (immunoblots). On the basis of these results, we attempted to eliminate EBV plasmids in Raji cells by transfecting a BZLF1 plasmid. Among 33 clones that were cotransfected with a BZLF1 plasmid and a hygromycin B resistance plasmid and selected resistant for hygromycin B, 24 clones had decreased numbers of EBV plasmids, as revealed by the decrease in the intensity of the EBV band on Southern blots compared with that of nontransfected Raji cells.


Once in a blue moon: Primaquine-induced methemoglobinemia - A case report.
Methemoglobinemia is a rare blood disorder that should be suspected in patients with cyanosis and low oxygen saturation of around 85%, especially when both do not improve despite supplemental oxygen. We describe the case of a 67-year-old lung transplant patient who was treated with primaquine and clindamycin because of a positive Pneumocystis jirovecii polymerase chain reaction on bronchoalveolar lavage fluid. Soon thereafter the patient developed increasing shortness of breath, central cyanosis and hypoxia, with an oxygen saturation of 86% on pulse oximetry despite supplemental oxygen. Arterial blood gas analysis showed a peculiar dark brown color and a significantly increased methemoglobin percentage. A diagnosis of methemoglobinemia due to primaquine was made. As treatment option, we preferred ascorbic acid over methylene blue because of concerns of possibly eliciting a serotonin syndrome. Our patient recovered rapidly after initiation of appropriate treatment. A high index of suspicion is crucial since this condition is potentially fatal.


The need to reduce cold ischemia time in kidney transplantation.
Hypothermic preservation is a prerequisite for kidney exchange in transplantation. The severity of tissue damage caused by hypothermic preservation influences the level of ischemia/reperfusion injury and subsequent graft function. With the purpose of reviewing the implications of prolonged cold ischemia time (CIT) in kidney transplantation, its pathophysiology, effects on early and late outcome of transplantation for different types of deceased organ donors, and preservation methods are discussed based on recent literature. The main findings are that the consequences of a prolonged CIT are mainly identifiable in the early posttransplant period as delayed graft function, especially in expanded criteria donors, and possibly in an increased acute rejection rate. The preferred method of hypothermic preservation in expanded criteria donors and donors after cardiac death appears to be machine preservation. The effects of CIT on the long-term outcome of renal transplantation in the form of impaired graft function and graft survival are less evident.


Resource partitioning and competition for shells between intertidal hermit crabs on the outer coast of Washington.
Resource partitioning was quantified for 6 species of intertidal hermit crabs in the genus Pagurus, that occur on the outer coast of Washington. This, together with field evidence of shell shortage and with laboratory experiments to quantify the mechanism of interactions for shells, allowed estimation of the relative intensities of inter-and intraspecific competition between these species. The findings were that: (1) the magnitude of intraspecific competition was greater than any single interspecific competitive effect for all of the species; and (2) the relative proportion of intraspecific competition was greater for the middle and upper intertidal species than for the lower intertidal species. Studies at several outer coast sites supported these generalizations. Both of these findings are consistent with the hypothesis that competitive divergence has occurred in the past. The structure of the outer coast hermit crab assemblage is compared with that of the San Juan Archipelago hermit crab assemblage. Differences between the two do not seem to be the result of adaptive responses to the presence of more competing species in the former group.


Retracted: Analysis of Legal Attributes and Rights Attributes of Personal Information from the Perspective of Big Data.
[This retracts the article DOI: 10.1155/2022/9731414.].


Impact of BMI on patient outcome in acute myeloid leukaemia patients receiving intensive induction therapy: a real-world registry experience.
Acute myeloid leukaemia (AML) is treated with intensive induction chemotherapy (IT) in medically fit patients. In general, obesity was identified as a risk factor for all-cause mortality, and there is an ongoing debate on its impact on outcome and optimal dosing strategy in obese AML patients. We conducted a registry study screening 7632 patients and assessed the impact of obesity in 1677 equally IT treated, newly diagnosed AML patients on the outcome (OS, EFS, CR1), comorbidities, toxicities and used dosing strategies. Obese patients (BMI ≥ 30) displayed a significant inferior median OS (29.44 vs. 47.94 months, P = 0.015) and CR1 rate (78.7% vs. 84.3%, P = 0.015) without differences in median EFS (7.8 vs. 9.89 months, P = 0.3) compared to non-obese patients (BMI < 30). The effect was predominantly observed in older (≥60 years) patients. Obesity was identified as an independent risk factor for death, and obese patients demonstrated higher rates of cardiovascular or metabolic comorbidities. No differences for OS, EFS, CR1 or treatment-related toxicities were observed by stratification according to used dosing strategy or dose reduction. In conclusion, this study identifies obesity as an independent risk factor for worse OS in older AML patients undergoing curative IT most likely due to obesity-related comorbidities and not to dosing strategy.


Chemically induced senescence in human stem cell-derived neurons promotes phenotypic presentation of neurodegeneration.
Modeling age-related neurodegenerative disorders with human stem cells are difficult due to the embryonic nature of stem cell-derived neurons. We developed a chemical cocktail to induce senescence of iPSC-derived neurons to address this challenge. We first screened small molecules that induce embryonic fibroblasts to exhibit features characteristic of aged fibroblasts. We then optimized a cocktail of small molecules that induced senescence in fibroblasts and cortical neurons without causing DNA damage. The utility of the "senescence cocktail" was validated in motor neurons derived from ALS patient iPSCs which exhibited protein aggregation and axonal degeneration substantially earlier than those without cocktail treatment. Our "senescence cocktail" will likely enhance the manifestation of disease-related phenotypes in neurons derived from iPSCs, enabling the generation of reliable drug discovery platforms.


Sporadic Burkitt lymphoma of the jaw: case report and review of the literature.
Sporadic Burkitt lymphoma of the jaw is a rare neoplasm with an exceedingly fast doubling rate. This article presents a case of sporadic Burkitt lymphoma initially managed as an odontogenic infection. The early radiographic features and histologic criteria are discussed. Burkitt lymphoma should be considered in the differential diagnosis of any rapidly expanding or swelling jaw masses in young patients.


Identifying unmet information needs of advanced cancer patients in Iran: An in-depth qualitative study.
One of the main vital needs for self-care in patients with advanced cancer is information need. Meeting this need has significant positive effects on improving their treatment and care. This study was conducted to identify the unmet information needs of patients with advanced cancer in Iran. This exploratory study was performed from July to February 2021 in the Kerman University of Medical Sciences cancer treatment centers. Oncologists selected eligible patients by purposeful sampling method. Semistructured and in-depth interviews were conducted with selected patients to collect data. Interviews continued until data saturation. Each interview was audio-recorded and transcribed verbatim. In the interviews, 15 patients with advanced cancer ranging in age from 43 to 65 years participated. The most common type of cancer in women was breast (71.4%) and prostate (50%) in men. The two main categories of "types of unmet information needs" and "reasons for not meeting information needs" were extracted from the analysis of patient interviews, with six and four subcategories, respectively. Cancer patients had a large number of unmet information needs. At the time of identifying the unmet information needs of cancer patients, the basic reasons for not meeting these needs should also be considered because cultural differences and social gaps in societies are inevitable.


The association between ethylene oxide exposure and asthma risk: a population-based study.
Ethylene oxide (EO) is a reactive epoxide. However, the association between EO exposure and the risk of developing asthma in humans is unknown. The aim of this study was to investigate the relationship between EO exposure and the risk of developing asthma in the general US population. In this cross-sectional study, data of 2542 patients from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2016 were obtained and analyzed. Hemoglobin adducts of EO (HbEO) level be used as the main factor for predicting EO exposure. The association between the level of EO exposure and the risk of developing asthma was evaluated with logistic regression models and dose-response analysis curves of restricted cubic spline function. Mediation analysis and linear regression analysis were utilized to evaluate the association between EO exposure and inflammation indicators. According to the quartiles of HbEO level, the patients were divided into four groups. The results indicated that an increased HbEO level was associated with a higher risk of asthma onset. Compared with the lowest quartile, the odds ratio (OR) with the 95% confidence interval (CI) for the highest quartile was 1.960 (95% CI: 1.348-2.849, P = 0.003). After being adjusted for numerous potential confounders, the OR of quartile 4 relative to quartile 1 was 1.991 (95% CI: 1.359-2.916, P = 0.001). Consistent results were also obtained in most subgroup analyses and dose-response analysis curves. In addition, EO levels were positively correlated with the inflammatory indicators (P = 0.006 for WBC, P = 0.015 for lymphocyte, and P = 0.015 for neutrophil). This study revealed a positive correlation between the level of EO exposure and the risk of asthma in a representative US population. In addition, inflammatory response may prove to be a potential biological mechanism underlying EO-induced asthma.


The role of stress-reactivity, stress-recovery and risky decision-making in psychosocial stress-induced alcohol consumption in social drinkers.
Chronic alcohol misuse can escalate into alcohol use disorder (AUD). The causal mechanisms through which recreational social drinking develops into compulsive uncontrolled alcohol misuse are multifaceted. For example, stress is an important risk factor that influences alcohol craving in both healthy and addicted individuals. In addition, those that are high in impulsivity/risk taking drink more and are at greater risk of developing addiction. At present, however, it is not possible accurately to predict those at risk of escalation in alcohol use, or of developing AUD. The aim of this study was to investigate how underlying physiological and personality traits affect stress-induced craving for, and consumption of, alcohol, in a sample of social drinkers. The primary hypothesis was that impulsivity/risk-taking would modulate stress-induced alcohol craving and consumption. Thirty-nine participants (22 male and 17 female; mean age = 23.92 years [SD = 4.90]) were randomly allocated to 'stress' and 'no-stress' groups; in the stress group, participants took part in the Trier Social Stress Test (TSST). Participants completed several questionnaires and computer tasks in order to assess prior alcohol use, impulsivity/risk-taking, stress-reactivity, craving and physiological biomarkers of stress. Finally, participants completed a voluntary drinking task, in which increasing numbers of presses on a computer keyboard were reinforced with 5-ml shots of 37% ABV vodka (plus mixer). Participants exposed to the TSST showed an increase in craving following the stressor. Several factors predicted voluntary drinking, including risky decision making, slow HR recovery from stress, poor vagal tone during recovery from stress and greater stress reactivity. Surprisingly, we found no correlation between craving and consumption. Our data suggest that variation in physiological stress parameters and poor decision-making abilities increase risk of stress-induced alcohol consumption. This may provide a useful translational framework through which we can further study early predictive markers for the shift between controlled recreational drinking to uncontrolled alcohol misuse, including AUD.


Evaluation of potential Stat3-regulated genes in human breast cancer.
The constitutive activation of signal transducer and activator of transcription 3 (Stat3) is frequently detected in breast cancer tissues and cell lines. Stat3 has been classified as a proto-oncogene, because an activated form of Stat3 can mediate oncogenic transformation in cultured cells and tumor formation in nude mice. Since Stat3 may play an important role in breast cancer, it is of interest to investigate the expression of phosphorylated Stat3, an activated form of Stat3, and its downstream mediators specifically in breast cancer, and to explore the possible mechanisms of Stat3 signaling pathway in oncogenesis of breast cancer. We analyzed Stat3 phosphorylation and expression of Stat3-regulated genes in breast cancer cell lines as well as invasive breast cancer tissues using tissue microarray slides. Our results showed that elevated levels of phosphorylation of Stat3 protein (Tyr705) were detected in 48 out of total 136 invasive breast tumors (35%) whereas normal breast tissues express much lower levels of Stat3 phosphorylation. The increased levels of Stat3 phosphorylation were associated with the metastasis in regional lymph nodes (P=0.042) and the expression of progesterone receptor (P=0.028) but not with distant metastasis, nor the expression of estrogen receptor. Our results also indicate that elevated levels of Stat3 phosphorylation were significantly associated with increased expression of potential downstream targets of Stat3 which include apoptosis inhibitors (Survivin, Mcl-1, HSP27, Adrenomedullin, and Bcl-xL), cell-cycle regulators (c-Fos, MEK5, and c-Myc), and inducer of tumor angiogenesis (VEGF, COX-2, MMP-2, MMP-10, and MMP-1) in invasive breast cancer tissues. Therefore, our findings suggest that constitutive Stat3 signaling may be one of the key upstream regulators to induce these downstream proteins, which may play important roles in Stat3-mediated oncogenesis in breast cancer.


The antifungal activity of fatty acids of all stages of Sarcophaga carnaria L. (Diptera: Sarcophagidae).
Fatty acids as components of cuticular lipids of insects play a significant role in antifungal in protection against fungal infection. The chemical composition of cuticular and internal extracts obtained from all developmental stages of flesh flies Sarcophaga carnaria was identified. The fatty acids were detected using gas chromatography coupled with mass spectrometry and the most abundant for all examined stages were: 18:1 > 16:0 > 16:1 > 18:0 > 18:2. Polyunsaturated fatty acids (PUFA) C20 were found in both, cuticular and internal extracts. GC-MS analysis showed higher relative content of PUFA in adults than in preimaginal stages. Fatty acids alone as well as their cuticular and internal extracts obtained from larvae, pupae male and female of S. carnaria were tested according to their potential antimicrobial activity against entomopathogenic fungi: Paecilomyces lilacinus, Paecilomyces fumosoroseus, Lecanicillium lecanii, Metarhizium anisopliae, Beauveria bassiana (Tve-N39) and B. bassiana (Dv-1/07). FA presented diverse antimicrobial activity depending on the length of the chain and the presence of unsaturated bonds. Short chain and unsaturated FA (6:0, 11:0, 13:0) have shown significantly stronger activity against fungi but they were detected in lower concentrations. PUFA inhibit fungal growth more effectively than unsaturated long chain fatty acids. Cuticular and internal extracts of all living forms of S. carnaria exhibited approximately equal activity against tested entomopathogenic fungi. We presumed that the most abundant saturated long chain FA and additionally PUFA founded in our analysis are involved in protecting the flies against fungal infection.


Seasonal variations and other changes in the geographical distributions of different cytospecies of the Simulium damnosum complex (Diptera: Simuliidae) in Togo and Benin.
Simulium damnosum s.l., the most important vector of onchocerciasis in Africa, is a complex of sibling species described on the basis of differences in their larval polytene chromosomes. These (cyto) species differ in their geographical distributions, ecologies and epidemiological roles. In Togo and Benin, distributional changes have been recorded as a consequence of vector control and environmental changes (e.g. creation of dams, deforestation), with potential epidemiological consequences. We review the distribution of cytospecies in Togo and Benin and report changes observed from 1975 to 2018. The elimination of the Djodji form of S. sanctipauli in south-western Togo in 1988 seems to have had no long-term effects on the distribution of the other cytospecies, despite an initial surge by S. yahense. Although we report a general tendency for long-term stability in most cytospecies' distributions, we also assess how the cytospecies' geographical distributions have fluctuated and how they vary with the seasons. In addition to seasonal expansions of geographical ranges by all species except S. yahense, there are seasonal variations in the relative abundances of cytospecies within a year. In the lower Mono river, the Beffa form of S. soubrense predominates in the dry season but is replaced as the dominant taxon in the rainy season by S. damnosum s.str. Deforestation was previously implicated in an increase of savanna cytospecies in southern Togo (1975-1997), but our data had little power to support (or refute) suggestions of a continuing increase, partly because of a lack of recent sampling. In contrast, the construction of dams and other environmental changes including climate change seem to be leading to decreases in the populations of S. damnosum s.l. in Togo and Benin. If so, combined with the disappearance of the Djodji form of S. sanctipauli, a potent vector, plus historic vector control actions and community directed treatments with ivermectin, onchocerciasis transmission in Togo and Benin is much reduced compared with the situation in 1975.


Impact of GTF2H1 and RAD54L2 polymorphisms on the risk of lung cancer in the Chinese Han population.
Repair pathway genes play an important role in the development of lung cancer. The study aimed to assess the correlation between single nucleotide polymorphisms (SNPs) in DNA repair gene (GTF2H1 and RAD54L2) and the risk of lung cancer. Five SNPs in GTF2H1 and four SNPs in RAD54L2 in 506 patients with lung cancer and 510 age-and gender-matched healthy controls were genotyped via the Agena MassARRAY platform. The influence of GTF2H1 and RAD54L2 polymorphisms on lung cancer susceptibility was assessed using logistic regression analysis by calculating odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). RAD54L2 rs9864693 GC genotype increased the risk of lung cancer (OR = 1.33, 95%CI: 1.01-1.77, p = 0.045). Stratified analysis found that associations of RAD54L2 rs11720298, RAD54L2 rs4687592, RAD54L2 rs9864693 and GTF2H1 rs4150667 with lung cancer risk were found in subjects aged ≤ 59 years. Precisely, a protective effect of RAD54L2 rs11720298 on the occurrence of lung cancer was observed in non-smokers and drinkers. GTF2H1 rs4150667 was associated with a decreased risk of lung cancer in subjects with BMI ≤ 24 kg/m2. RAD54L2 rs4687592 was associated with an increased risk of lung cancer in drinkers. In addition, GTF2H1 rs3802967 was associated with a reduced risk of lung squamous cell carcinoma. Our study first revealed that RAD54L2 rs9864693 was associated with an increased risk of lung cancer in the Chinese Han population. This study may increase the understanding of the effect of RAD54L2 and GTF2H1 polymorphisms on lung cancer occurrence.


Myocardial strain changes in Duchenne muscular dystrophy without overt cardiomyopathy.
Patients with Duchenne muscular dystrophy (DMD) are at risk of the development of dilated cardiomyopathy and heart failure, thus making early identification of high-risk patients necessary. Myocardial strain imaging (MSI) can be used for quantitative analysis of wall motion of the left ventricle (LV). The aim of this study was to determine whether MSI could detect early changes in myocardial properties in presymptomatic DMD patients with normal LV function. Two-dimensional echocardiographic and tissue Doppler examinations were performed in 13 DMD patients (age range, 11 to 20 years) with normal LV function and in 10 healthy controls. MSI was obtained from tissue Doppler information. In control subjects, strain values in both inner and outer layers of the myocardium were positive at the short-axis image showing the radial systolic thickening. In 10 of the 13 DMD patients, however, myocardial strain showed a negative strain value in systole in the outer layer of the posterolateral wall at the parasternal short-axis image for each cardiac cycle. In 5 of these 10 patients, the timing of the peak systolic velocity at the inferoposterior wall was delayed more than 60 ms than that at the posterolateral wall (mean 80.0+/-17.5 ms). In some DMD patients with normal LV function, myocardial strain profiles at the posterolateral wall of the LV were different from those in healthy controls, suggesting abnormal myocardial contraction. MSI appears to detect early changes in myocardial features in DMD patients before the onset of overt cardiomyopathy.


Neurocognitive dimensions of lexical complexity in Polish.
Neuroimaging studies of English suggest that speech comprehension engages two interdependent systems: a bilateral fronto-temporal network responsible for general perceptual and cognitive processing, and a specialised left-lateralised network supporting specifically linguistic processing. Using fMRI we test this hypothesis in Polish, a Slavic language with rich and diverse morphology. We manipulated general perceptual complexity (presence or absence of an onset-embedded stem, e.g. kotlet 'cutlet' vs. kot 'cat') and specifically linguistic complexity (presence of an inflectional affix, e.g. dom 'house, Nom' vs. dom-u 'house, Gen'). Non-linguistic complexity activated a bilateral network, as in English, but we found no differences between inflected and uninflected nouns. Instead, all types of words activated left inferior frontal areas, suggesting that all Polish words can be considered linguistically 'complex' in processing terms. The results support a dual network hypothesis, but highlight differences between languages like English and Polish, and underline the importance of cross-linguistic comparisons.


PTBP1 knockdown overcomes the resistance to vincristine and oxaliplatin in drug-resistant colon cancer cells through regulation of glycolysis.
Drug-resistant cancer cells exhibit increased glycolysis, and targeting glycolysis is considered as a novel strategy to overcome drug resistance. Polypyrimidine tract-binding protein (PTBP1) has been found to be a regulator of glycolysis, however, the role of PTBP1 in drug resistance remains to be elucidated. Herein, we found that PTBP1 was highly expressed in two drug-resistant colon cancer cell lines, vincristine-resistant HCT-8 cell line (HCT-8/V) and oxaliplatin-resistant HCT116 cell line (HCT116/L-OHP). The levels of glucose consumption and lactate production as well as expression of pyruvate kinase M2 isoform (PKM2) and hexokinase II (HK2) were elevated, while PKM1 level was reduced in HCT-8/V and HCT116/L-OHP cells when compared with the HCT-8 and HCT116 cells. PTBP1 knockdown enhanced the sensitivity of HCT-8/V and HCT116/L-OHP cells to vincristine and oxaliplatin, and caused reduction in glucose consumption and lactate production. PKM2 expression, but not HK2, was decreased and PKM1 expression level was increased in cells transfected with si-PTBP1. In addition, PTBP1 overexpression significantly induced glycolysis and reduced drug sensitivity, whereas the effects were attenuated by si-PKM2. Treatment with 2-deoxyglucose (2-DG) also attenuated the effect of PTBP1 overexpression on drug sensitivity. In conclusion, PTBP1 knockdown enhanced the sensitivity of drug-resistant colon cancer cells to vincristine and oxaliplatin through repression of glycolysis. Our study provided a promising therapeutic strategy to overcome drug resistance in colon cancer cells.


Determination of the expression of three fimbrial subunit proteins in cultured Trueperella pyogenes.
Trueperella pyogenes is a commensal and a significant opportunistic pathogen in animals. A variety of identified or putative virulence factors are considered to significantly contribute to the occurrence of T. pyogenes infection in different species. However, these virulence factors are not fully understood. In the current study, the genes encoding putative fimbrial proteins, i.e. Fim A, Fim C, and Fim E, were cloned. Recombinant Fim A (rFim A), Fim C (rFim C), and Fim E (rFim E) were prepared and used to generate rabbit anti-rFim A, anti-rFim C, and anti-rFim E serum, respectively. Using these sera, we found that only Fim E was constitutively expressed in T. pyogenes. The expression level of Fim E in T. pyogenes peaked within 6-10 h of culture period in pH 7.5. Fim E protein expression was unaffected by anaerobic condition, but was inhibited by the microaerophilic condition. Tube agglutination tests indicated that Fim E was exhibited on the surface of T. pyogenes cells because anti-rFim E serum caused strong agglutination. Additionally, the blots for Fim A detection showed nonspecific reactions. Furthermore, the tube agglutination tests showed that anti-Fim A serum failed to cause agglutination of T. pyogenes cells, which indicated that Fim A was not, or poorly, expressed in cultured T. pyogenes. Anti-rFim C serum caused strong agglutination. However, the blots for Fim C detection showed a strong nonspecific reaction. Thus, the expression of Fim C was difficult to be determined using the current method. Fim E was expressed in cultured T. pyogenes. However, Fim A was either not or poorly expressed in cultured T. pyogenes. Moreover, Fim C expression was not determined using the current strategy.


Weight loss and hypernatremia in breast-fed babies: frequency in neonates with non-hemolytic jaundice.
The aim of this study was to determine what proportion of newborns admitted with idiopathic non-hemolytic hyperbilirubinemia exhibit severe weight loss and hypernatremia. The prospective study involved 115 infants >48 h old who were admitted with jaundice between July 2002 and July 2003, and had unconjugated bilirubin levels >12 mg/dL. Premature babies (gestational age <37 weeks) and those with hemolytic jaundice and other pathologic causes of non-hemolytic jaundice were excluded. Postnatal age (days) at admission, bodyweight at admission, weight change since birth (percentage weight loss calculated at admission) and mode of feeding (breast-feeding, formula feeding, mixed feeding) were recorded. Severe weight loss was defined in babies who showed >10% weight loss or had not regained enough to reach birthweight by postnatal day 10. Serum Na levels and breast-milk Na levels were also measured. Twenty-eight (33%) of the 86 newborns with idiopathic hyperbilirubinemia in the study exhibited severe weight loss. Almost all the 86 babies were exclusively breast-fed, and 10 babies (12%) had severe weight loss combined with hypernatremia. The group with severe weight loss and hypernatremia had higher breast-milk Na levels than the other infants. The results indicate that a large proportion of babies with non-hemolytic jaundice have severe weight loss, and that breast-fed newborns with the combination of weight loss and hypernatremia may present with non-hemolytic jaundice.


Solitary plasmacytoma of thoracic vertebra in a woman with Lynch syndrome: A case report.
One of the major disabling health conditions among elderly is back pain due to degenerative diseases. Less than 1% of spine disorders are caused by malignancies. Among the rare primary vertebral neoplasms the multiple myeloma and the plasmacytoma account for 26% of these cases. We are reporting a case of 64 year-old woman, who suffered from progressive upper back pain and intermittent neurological symptoms including lower limb weakness and voiding disorder under axial loading. Her medical history includes a Lynch syndrome (LS). Computed tomography (CT) and magnetic resonance imaging (MRI) detected a single malignant osteolytic process of the spine involving T5. Urgent surgery with laminectomy intralesional tumor removal and posterior stabilization (Th4-Th6) due to unstable pathologic fracture with spinal cord compression was conducted after interdisciplinary decision. Histopathological examination of the tumor revealed a solitary plasmacytoma. To our knowledge this is the first case report of a solitary plasmacytoma of the bone (SPB) that arise in a patient who suffers from LS. Similar DNA mismatch repair malfunction is existent in LS and SPB. Hence, a hereditary correlation might be imaginable. When detecting a lytic spinal tumor in a patient who suffers from LS a SPB should be taken under consideration.


Application of non-contact scanning to forensic podiatry: A feasibility study.
Foot impression evidence recovered from crime scenes can be available in the form of barefoot prints, sock-clad footprints, or as impressions within footwear. In some cases, suspects leave their footwear at the scene of the crime, and the insoles from the footwear can be important in linking a person to the footwear. The application of 3D data-collecting technology is becoming more and more popular within forensic science and has been used to recover footwear impression evidence. The present study is a feasibility study to discover if 3D data capturing devices can be applied to insoles; to capture the footprint impression for measurement using the Gunn method (a method used in forensic podiatry casework). Three different methods of data capture were conducted; Adobe Photoshop, MeshLab, and calipers used directly on the insole. Paired t-tests and Intraclass Correlation Coefficient (ICC) were conducted for all three data capture methods. Seven measurements used in this study were significantly different across all three methods. ICC scores were moderate to excellent for the Photoshop method, poor to good for the 3D method, and moderate to excellent for the Direct method.


Photobleaching-induced changes in the optical and photochemical properties of algal organic matter.
Algal organic matter (AOM), a significant source of endogenous dissolved organic matter (DOM) is released in high concentrations during cyanobacterial blooms, along with cyanotoxins. Subsequent photobleaching of AOM is an important phenomenon to investigate. In this study, intracellular organic matter (IOM) and extracellular organic matter (EOM) were extracted from cultured cyanobacteria taken from Taihu Lake in China. The formation of photochemically produced reactive intermediates in different stages of IOM and EOM photobleaching was compared to Suwannee River DOM (SRDOM, reference standard DOM). Results revealed notable differences influenced by the pigment component among IOM, EOM, and SRDOM. The pigment in IOM contributed to a triplet state pool with strong energy-transfer but limited electron-transfer capabilities. Notably, IOM exhibited the highest triplets state quantum yield value in the visible region, suggesting its potential significance in pollutant degradation in deeper water layers. For EOM, one of the pools exhibits photolability and remarkable electron-transfer capability, indicating it as a high-energy triplet state component. Moreover, three cyanotoxins (MC-LR, ACA, and ATX-a) were detected in the extracted AOM, and their photodegradation was monitored during the AOM photobleaching process. This highlights the potential role of AOM as a photosensitizer in the natural self-cleaning mechanisms of water bodies, facilitating the degradation of organic pollutants through photochemical reactions. The findings of this study contribute to understanding the dynamic nature of AOM and its implications in environmental processes.


Invasive potential of superficial bladder cancer. A study of the relative merits of predictive parameters.
The indirect immunoperoxidase test to detect urothelial cell surface blood group antigens was performed in an attempt to assess the loss of these antigens as a prognostic predictor. In our technique A, B and O(H) blood group specific monoclonal antibodies were used. It was possible to perform the test satisfactorily on histological material from 55 cases which were superficial on presentation; 15 subsequently became invasive. The loss of surface antigens correlated well with histological grade--44.4% of G1, 87.2% of G2 and 94.1% of G3 tumours were antigen-negative. The blood group phenotype of 114 patients was studied. In the group that subsequently became invasive, 14 of 26 (54%) were of blood group A phenotype compared with 37 of 88 (42%) in the non-invasive category. Acetylation studies were performed on 47 cases. In the group that subsequently became invasive, 5 of 10 (50%) had the slow phenotype of the enzyme N-acetyltransferase compared with 13 of 37 (35%) in the group that remained superficial.


Evaluation of CYP3A4 inhibition and hepatotoxicity using DMSO-treated human hepatoma HuH-7 cells.
A human hepatoma cell line (HuH-7) was evaluated as a metabolically competent cell model to investigate cytochrome P450 3A4 (CYP3A4) inhibition, induction, and hepatotoxicity. First, CYP3A4 gene expression and activity were determined in HuH-7 cells under three culture conditions: 1-week culture, 3-week culture, or 1 % dimethyl sulfoxide (DMSO) treatment. HuH-7 cells treated with DMSO for 2 weeks after confluence expressed the highest CYP3A4 gene expression and activity compared to the other two culture conditions. Furthermore, CYP3A4 activity in DMSO-treated HuH-7 cells was compared to that in a human hepatoma cell line (HepG2/C3A) and human bipotent progenitor cell line (HepaRG), which yielded the following ranking: HepaRG > DMSO-treated HuH-7 >> HepG2/C3A cells. The effects of three known CYP3A4 inhibitors were evaluated using DMSO-treated HuH-7 cells. CYP3A4 enzyme inhibition in HuH-7 cells was further compared to human recombinant CYP3A4, indicating similar potency for reversible inhibitors (IC 50 within 2.5-fold), but different potency for the irreversible inhibitor. Next, induction of CYP3A4 activity was compared between DMSO-treated HuH-7 and HepaRG cells using two known inducers. DMSO-treated HuH-7 cells yielded minimal CYP3A4 induction compared to that in the HepaRG cells after 48-h treatments. Finally, the cytotoxicity of five known hepatotoxicants was evaluated in DMSO-treated HuH-7, HepG2/C3A, and HepaRG cells, and significant differences in cytotoxic sensitivity were observed. Overall, DMSO-treated HuH-7 cells are a valuable model for medium- or high-throughput screening of chemicals for CYP3A4 inhibition and hepatotoxicity.


A retrospective analysis of perioperative complications associated with retropubic tension-free vaginal tape in 960 women.
The purpose is to analyse perioperative complications associated with the retropubic tension-free vaginal tape (TVT) procedure and their management. This retrospective, monocentric cohort study included 960 women after retropubic TVT procedure performed by one surgeon from 2011 to 2016. Complications were identified up to 6 weeks after the procedure, divided into specific and general complications and classified based on the Clavien-Dindo (CD) Classification. A visit 6 weeks after the surgical procedure was attended by all patients. 77 complications, of which 74 occurred postoperatively and 3 intraoperatively, affecting 72 (7.5%) out of 960 women. Urinary retention and voiding problems were the most common complication. The mean age of women suffering complications was 3.4 years higher in comparison to the mean age of women without complications (p = 0.036). The Body Mass Index (BMI) of the group of women with perioperative complications had an average BMI which was 0.5 kg/m2 lower than the average BMI of the women without complications. 22 (12.8%) out of 172 women with recurrent stress incontinence had postoperative complications, of which 21 were related to the TVT. The retropubic TVT is a surgical procedure associated with a low number of perioperative complications, even in the group of elderly and overweight women, as well as in cases of recurrent stress incontinence.


[An initial assessment of therapeutic value of strontium 85 isotope in treatment of chronic osteomyelitis in adults].
An initial assessment of treatment of chronic osteomyelitis in 16 adults with Strontium 85 is presented. A dose 3.5-5 times greater than standard scintigraphic one was administered. In 3 cases the dose has been repeated because of the persistence of infection. The radionuclide was well tolerated. In 14 cases ceasing of osteomyelitis have been achieved. Laboratory tests showed no abnormalities.


Differential requirement for RhoH in development of TCRαβ CD8αα IELs and other types of T cells.
RhoH is a new member of the atypical G proteins exclusively expressed in hematopoietic lineage cells. It has been shown to act as an adaptor for ZAP70, Syk, Lck and Csk kinases in signal transduction, and is required for positive selection of thymocytes as well as activation of peripheral T cells and mast cells. In the present study, we showed that RhoH is required not only for positive selection but also for negative selection of thymocytes. Regarding development of unconventional T cell subsets, development of NKT and regulatory T cells was also inhibited, whereas development of TCRαβ CD8αα intestinal intraepithelial lymphocytes (IEL) was not affected by the absence of RhoH. TCR-dependent in vitro activation of TCRαβ CD8αα IEL required RhoH, suggesting that overall development of IEL does not critically depend on TCR signaling but more on cytokine-dependent expansion and survival in the periphery. Our current results indicate differential requirements for RhoH in the development of TCRαβ CD8αα IELs compared to other subsets of T cells including agonist selected T cells.


Oral microbiota in Swiss adolescents.
The purpose of the study was to determine the prevalence of different oral microbes in gingival plaque samples and in samples from the dorsum of the tongue in a Swiss adolescent population. Ninety-nine adolescents between 15 and 18 years were enrolled. Plaque index, bleeding on probing (BOP), the periodontal screening index, and decayed missed filled tooth (DMFT) index were recorded. Samples from subgingival plaque and swabs from the tongue were analyzed by the Checkerboard DNA-DNA hybridization method. Additionally, counts of Streptococus mutans and Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola were determined by real-time PCR. Periodontitis was not diagnosed in any of the subjects but all of them presented signs of gingival inflammation displaying a mean BOP of 28%. Ten (10.1%) subjects were tested positive for P. gingivalis, each 22 (22.2%) for A. actinomycetemcomitans and T. forsythia, (47.5%) for T. denticola. T. denticola and S. mutans showed a high affinity to the gingival plaque, whereas T. forsythia was often detected from the dorsum of the tongue. DMFT was associated with S. mutans counts, and BOP correlated with counts of P. gingivalis and T. denticola. The present data indicate that: (a) gingivitis but not periodontitis is a common finding among Swiss adolescents, and (b) bacteria associated with periodontitis were frequently detected in the subgingival dental plaque and on the dorsum of the tongue in Swiss adolescents with gingivitis. Although gingivitis was a frequent finding in Swiss adolescents, periodontitis was not detected in this population. The dorsum of the tongue appears to represent an important reservoir for periodontopathic bacteria.


The enrichment of a ruminal bacterium (Megasphaera elsdenii YJ-4) that produces the trans-10, cis-12 isomer of conjugated linoleic acid.
To isolate predominant ruminal bacteria that produce trans-10, cis-12 conjugated linoleic acid (CLA) from linoleic acid (LA). Mixed bacteria from ruminal contents of a cow fed grain were enriched with DL-lactate and trypticase. They produced more trans-10, cis-12 CLA than those that were not enriched (7 vs 2 microg mg protein(-1), P < 0.05). Enrichments had an abundance of large cocci that produced trans-10, cis-12 CLA from LA. Strain YJ-4 produced the most trans-10, cis-12 CLA (approx. 7 microg mg protein(-1)) and 16S rDNA sequencing indicated that YJ-4 was a strain of Megasphaera elsdenii. Megasphaera elsdenii T81 produced approx. 4 microg trans-10, cis-12 CLA mg protein(-1) while strains B159, AW106 and JL1 produced < 0.5 microg mg protein(-1). The trans-10, cis-12 CLA production of YJ-4 was first order with respect to cell concentration (0-800 microg protein ml(-1)), but kinetics were not first order with respect to substrate concentration. Some M. elsdenii strains produce significant amounts of trans-10, cis-12 CLA. Trans-10, cis-12 CLA appears to cause milk fat depression in cattle fed diets supplemented with grain and polyunsaturated fatty acids, but predominant ruminal bacteria that produced trans-10, cis-12 CLA from LA had not previously been isolated.


A study on the engraftment and trafficking of bovine peripheral blood leukocytes in severe combined immunodeficient mice.
Bovine lymphoid cells were engrafted into untreated and into sublethally irradiated scid/scid mice, following intraperitoneal (i.p.) injection of bovine peripheral blood leukocytes (PBL). To distinguish bovine from murine cells, bovine PBL were stained prior to i.p. injection with a fluorescent cell linker compound, PKH26-GL and, after cell recovery, labelled with a monoclonal antibody (mAb) reactive with the bovine pan leukocyte cell surface marker, CD45, and analyzed by flow cytometry. This dual labelling system was used to monitor tissue localization and migration of bovine cells within PBL-SCID-bo from 30 min to 64 days after bovine PBL injection. Inoculated bovine PBL were rapidly cleared from the peritoneal cavity of PBL-SCID-bo over the first 24 h after injection, then bovine cell numbers within the peritoneal cavity increased gradually over the next 35 days. No bovine cells were observed in the peritoneal wash from either non-irradiated or irradiated mice after Day 56. Bovine cells were detected in the spleens of both non-irradiated and irradiated mice 12-14 days after inoculation, but were undetectable in non-irradiated and irradiated mice after Day 56, and in irradiated mice after Day 35. This decrease coincided with a significant reduction in both the numbers of bovine cells in the peritoneal cavity, and in the levels of bovine Ig detected in the sera. Bovine IgG and bovine IgM were detected in both normal and irradiated PBL-SCID-bo by 4 days after PBL injection, and remained detectable to 8 weeks after inoculation. T-cells appeared to be the predominant bovine cell population in the spleens. In a small proportion of both normal and irradiated PBL-SCID-bo, spleens three to 20 times the size of a normal SCID mouse spleen were observed. Relatively high levels of bovine cells were detected in the thymuses of some irradiated PBL-SCID-bo. Sporadic, low levels of bovine cells were observed in the mesenteric lymph nodes, peripheral blood, and kidneys of normal and irradiated mice, and in the lungs and livers of non-irradiated but not irradiated PBL-SCID-bo. Sublethal gamma irradiation of SCID recipients appeared to enhance engraftment of bovine cells into the murine spleen and thymus.


Releasing the Brakes on Cancer Immunotherapy.
This year's Lasker∼DeBakey Clinical Research Award goes to James Allison for discovering that antibody blockade of the T cell molecule CTLA-4 unleashes the body's immune response against malignant tumors. This has led to development of multiple "immune checkpoint therapies" that are prolonging and saving the lives of thousands of cancer patients.


Complications of compressive neuropathy: prevention and management strategies.
Compressive neuropathies of the upper extremity are common and can result in profound disability if left untreated. Nerve releases are frequently performed, but can be complicated by both iatrogenic events and progression of neuropathy. In this review, we examine the management of postoperative complications after 2 common nerve compression release procedures: carpal tunnel release and cubital tunnel release.


[Ability of Heidelberg Retina Tomograph III to predict progression in patients with early glaucoma or suspected primary open-angle glaucoma].
To study the ability of Heidelberg Retina Tomography III (HRT 3) measurements to predict perimetry changes in patients with early glaucoma or suspected primary open-angle glaucoma. One hundred and thirty two eyes with early glaucoma or suspected glaucoma with no changes in basal perimetry were prospectively selected and periodically evaluated over five years. The eyes were divided in two groups depending on the presence or absence of progression (changes in glaucoma perimetry). The association between morphometric parameters and baseline HRT 3 indices, glaucoma probability score (GPS) and Moorefield's Regression Analysis (MRA), and perimetry progression were studied using Cox multivariate regression analyses. Kaplan-Meier curves were used to illustrate the results. Forty-eight eyes (36.36%) showed perimetry progression. Perimetry progression showed higher correlations with the disc area (p = 0.001), the cup area (p = 0.002) and the vertical cup disc area (p = 0.001). Multivariate regression analyses showed that eyes with baseline MRA or baseline GPA changes were at a higher risk of having perimetry abnormalities and a faster progression. MRA and GPA indices are useful to predict perimetry progression in patients with early primary open-angle glaucoma or suspected glaucoma. These indices can be used as risk markers of functional progression in glaucoma.


An Examination of the Nature of Erotic Talk.
Using a mixed-methods study, we provided the first systematic documentation and exploration of erotic talk. In Study 1 (N = 95), participants provided 569 erotic talk statements in an anonymous online survey, which we classified, using a modified thematic analysis, as being representative of eight themes. In Study 2 (N = 238), we quantified individual differences in these themes, subjected them to factor analysis, and examined the nomological network surrounding them with measures of relationship and sexual satisfaction, sociosexuality, and personality. The eight initial categories represented two higher order factors, which we call individualist talk and mutualistic talk. These factors were orthogonal in factor analysis and distinct in their nomological network. While the majority of people reported using erotic talk, we found few sex differences in its use.


Antibody response to human papillomavirus (HPV) type 11 in children with juvenile-onset recurrent respiratory papillomatosis (RRP).
We previously established, using an ELISA, the presence of specific antibodies directed at human papillomavirus (HPV) type 11 virions in the sera of patients with condylomata acuminata, mostly a disease of young adults that, like recurrent respiratory papillomatosis (RRP), is caused by two closely related HPVs, types 6 and 11. The present study was done to investigate if children with RRP can make viral-specific antibodies to an infection that is acquired at birth. Using the same ELISA, we studied the sera of 32 children with biopsy-documented juvenile-onset RRP and compared them to the sera of 31 control children. The median (and interquartile range) of the OD values in the controls and the cases was 0.078 (0.003, 0.101) and 0.230 (0.063, 0.725), respectively, a statistically significant difference (P = 0.001). Among the cases, there was no difference in seroreactivity between children with HPV-11-induced RRP and those with HPV-6-induced RRP (P = 0.31). Since HPV-11 viral particles do bind to the ELISA plate and remain intact and accessible to antibodies, we conclude that children with RRP, like adults with condylomata acuminata, develop antibodies directed at HPV-11 virions.


Testicular mixed germ cell tumor in a transgender woman.
Transgender women who have not undergone orchiectomy remain at risk for the development of testicular cancer. Unfortunately, many physicians self-report a weak fund of knowledge around transgender health issues and some are uncomfortable performing proper exams or advising patients on self-exams. Here we report the first case of a testicular mixed germ cell tumor that developed in a transgender woman and discuss the salient points of caring for transgender patients.


Genetics and biology of coloration in reptiles: the curious case of the Lemon Frost geckos.
Although there are more than 10,000 reptile species, and reptiles have historically contributed to our understanding of biology, genetics research into class Reptilia has lagged compared with other animals. Here, we summarize recent progress in genetics of coloration in reptiles, with a focus on the leopard gecko, Eublepharis macularius. We highlight genetic approaches that have been used to examine variation in color and pattern formation in this species as well as to provide insights into mechanisms underlying skin cancer. We propose that their long breeding history in captivity makes leopard geckos one of the most promising emerging reptilian models for genetic studies. More broadly, technological advances in genetics, genomics, and gene editing may herald a golden era for studies of reptile biology.


Author Correction: First crystal structure of an endo-levanase - the BT1760 from a human gut commensal Bacteroides thetaiotaomicron.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Activation of K+ channels in renal medullary vesicles by cAMP-dependent protein kinase.
ADH, acting through cAMP, increases the potassium conductance of apical membranes of mouse medullary thick ascending limbs of Henle. The present studies tested whether exposure of renal medullary apical membranes in vitro to the catalytic subunit of cAMP-dependent protein kinase resulted in an increase in potassium conductance. Apical membrane vesicles prepared from rabbit outer renal medulla demonstrated bumetanide- and chloride-sensitive 22Na+ uptake and barium-sensitive, voltage-dependent 86Rb+ influx. When vesicles were loaded with purified catalytic subunit of cAMP-dependent protein kinase (150 mU/ml), 1 mM ATP, and 50 mM KCl, the barium-sensitive 86Rb+ influx increased from 361 +/- 138 to 528 +/- 120 pM/mg prot.30 sec (P less than 0.01). This increase was inhibited completely when heat-stable protein kinase inhibitor (1 microgram/ml) was also present in the vesicle solutions. The stimulation of 86Rb+ uptake by protein kinase required ATP rather than ADP. It also required opening of the vesicles by hypotonic shock, presumably to allow the kinase free access to the cytoplasmic face of the membranes. We conclude that cAMP-dependent protein kinase-mediated phosphorylation of apical membranes from the renal medulla increases the potassium conductance of these membranes. This mechanism may account for the ADH-mediated increase in potassium conductance in the mouse mTALH.


[Lower limb paresis after total hip arthroplasty. A rare differential diagnosis].
We report on a case of complex nerve damage during total hip arthroplasty. The most severe clinical symptom was proximal leg paresis with diffuse sensory loss. There was an extensive causal Iliopsoas hematoma which developed during the postoperative rehabilitation under therapeutic anticoagulation for atrial fibrillation. An iliopsoas hematoma with subsequent neurological deficits are rare events in the field of hip arthroplasty and a literature review is provided. The treatment of retroperitoneal hemorrhage is controversial but in most instances a conservative approach is favored. The prognosis of neurological damage is sobering as only 20 % of victims are expected to achieve complete restitution.


Idiopathic neonatal giant cell hepatitis presenting with acute hepatic failure on postnatal day one.
We report a term male infant presenting on postnatal day 1 with fulminant hepatic failure. Described congenital infection, metabolic disorders, and cardiovascular etiologies of acute neonatal liver failure were assessed and eliminated. A liver biopsy on postnatal day 10 showed neonatal giant cell hepatitis (NGCH) with an unusual degree of fibrosis for this early postnatal age. NGCH is a clinical diagnosis of cholestatic disorders of unknown etiology in the newborn, and, to our knowledge, has not been previously associated with immediate neonatal hepatic failure. The giant cell transformation is a common response to a variety of insults and only rarely occurs beyond the neonatal period. Most cases present with cholestatic jaundice and varying degrees of coagulopathy, and, many, as in this case, show progressive resolution.


MEKK2 kinase association with 14-3-3 protein regulates activation of c-Jun N-terminal kinase.
MEKK2 (MAP/ERK kinase kinase-2) is a serine/threonine kinase that belongs to the MEKK/STE11 family of MAP kinase kinase kinases (MAP(3)Ks). MEKK2 integrates stress and mitogenic signals to the activation of NF-κB, JNK1/2, p38, and ERK5 pathways. We have found that MEKK2 is regulated through a phosphorylation-dependent association with 14-3-3, a group of adapters that modulate dimerization and association between proteins. We found that MEKK2 was phosphorylated at Thr-283, which resulted in decreased activation loop phosphorylation at Ser-519 and consequently reduced activity. Mechanistically, we found that MEKK2 associated with inactive MEKK2 in the absence of 14-3-3 binding, which led to trans-autophosphorylation of Ser-519. Enforced binding with 14-3-3 reduced Ser-519 trans-autophosphorylation. Expression of T283A MEKK2 within a MEKK2(-/-) background enhanced stress-activated c-Jun N-terminal kinase activity while elevating IL-6 expression, but also reduced ERK activation with a corresponding reduced proliferation rate. These results indicate that Thr-283 phosphorylation is an important regulatory mechanism for MEKK2 activation.


Two Tightly Linked Genes at the hsa1 Locus Cause Both F1 and F2 Hybrid Sterility in Rice.
Molecular mechanisms of hybrid breakdown associated with sterility (F2 sterility) are poorly understood as compared with those of F1 hybrid sterility. Previously, we characterized three unlinked epistatic loci, hybrid sterility-a1 (hsa1), hsa2, and hsa3, responsible for the F2 sterility in a cross between Oryza sativa ssp. indica and japonica. In this study, we identified that the hsa1 locus contains two interacting genes, HSA1a and HSA1b, within a 30-kb region. HSA1a-j (japonica allele) encodes a highly conserved plant-specific domain of unknown function protein (DUF1618), whereas the indica allele (HSA1a-i(s)) has two deletion mutations that cause disruption of domain structure. The second gene, HSA1b-i(s), encodes an uncharacterized protein with some similarity to a nucleotide-binding protein. Homozygous introgression of indica HSA1a-i(s)-HSA1b-i(s) alleles into japonica showed female gamete abortion at an early mitotic stage. The fact that the recombinant haplotype HSA1a-j-HSA1b-i(s) caused semi-sterility in the heterozygous state with the HSA1a-i(s)-HSA1b-i(s) haplotype suggests that variation in the hsa1 locus is a possible cause of the wide-spectrum sterility barriers seen in F1 hybrids and successive generations in rice. We propose a simple genetic model to explain how a single causal mechanism can drive both F1 and F2 hybrid sterility.


Pharmacotoxic myocardial disease: an endomyocardial study.
Drug-induced toxic changes in the myocardium have become an increasing problem. The effect of drugs on heart morphology may be acute or cumulative. In general, adverse drug reactions manifest themselves as myocarditis (toxic or hypersensitivity), cardiomyopathy with chamber dilatation, or restrictive disease. Drugs affecting embryologic development of the heart will not be discussed. Drugs causing myocarditis can be divided into: toxic myocarditis, e.g., cyclophosphamide. The morphologic changes are dose-related and have lesions of different ages, which include myocyte necrosis with hemorrhage and vasculitis. Fibrous endocarditis, e.g., methysergide. These reactions include thickening of the endocardium and sometimes the cardiac valves with fibrosis. Drugs causing hypersensitivity myocarditis, e.g., thiazide diuretics. In this case, the lesions are not dose-related, are the same age, and there is an eosinophilic infiltrate. Drugs causing cardiomyopathic-like changes of ventricular dilatation and failure, e.g., anthracyclines, particularly adriamycin. This group of drugs cause a gradual myofibrillar loss within cardiac myocytes and a sarcotubular dilatation which is characteristic. The damaged cells are replaced by fibrosis and ventricular failure ensues. With the rapid synthesis of new drugs, the problem of drug cardiotoxicity may be an ever-increasing problem. With the more widespread use of the endomyocardial biopsy, drug-induced heart disease can be documented and the effects of different methods of drug delivery and pharmacologic antagonists studied.


Evaluation of uranium removal by Hydrilla verticillata (L.f.) Royle from low level nuclear waste under laboratory conditions.
The present study evaluated uranium (U) removal ability and tolerance to low level nuclear waste (LLNW) of an aquatic weed Hydrilla verticillata. Plants were screened for growth in 10%-50% waste treatments up to 3 d. Treatments of 20% and 50% waste imposed increasing toxicity with duration assessed in terms of change in fresh weight and in the levels of photosynthetic pigments and thiobarbituric acid-reactive substances. U concentration, however, did not show a progressive increase and was about 42 μg g(-1) dw from 20% to 50% waste at 3 d. This suggested that a saturation stage was reached with respect to U removal due to increasing toxicity. However, in another experiment with 10% waste and 10% waste+10 ppm U treatments, plants showed an increase in U concentration with the maximum level approaching 426 μg g(-1) dw at 3 d without showing any toxicity as compared to that at 20% and 50% waste treatments. Hence, plants possessed significant potential to take up U and toxicity of LLNW limited their U removal ability. This implies that the use of Hydrilla plants for U removal from LLNW is feasible at low concentrations and would require repeated harvesting at short intervals.


Effect of placental transfusion on the blood volume and clinical outcome of infants born by cesarean section.
Delay in cord clamping up to 30 to 40 seconds is feasible and should be practiced in preterm and term infants born by cesarean section. In term infants, this maneuver may decrease iron deficiency anemia at 6 months of age. Premature infants may have a higher blood volume and hematocrit initially requiring fewer transfusions. They also have a decreased incidence of intraventricular hemorrhage. The effect of compounding factors, such as maternal blood pressure, uterine contraction, medications, bleeding, and their effects on the infant's immediate and long-term outcome are unclear.


Architectural organization in E. coli nucleoid.
In contrast to organized hierarchical structure of eukaryotic chromosome, bacterial chromosomes are believed not to have such structures. The genomes of bacteria are condensed into a compact structure called the nucleoid. Among many architectural, histone-like proteins which associate with the chromosomal DNA is HU which is implicated in folding DNA into a compact structure by bending and wrapping DNA. Unlike the majority of other histone-like proteins, HU is highly conserved in eubacteria and unique in its ability to bind RNA. Furthermore, an HU mutation profoundly alters the cellular transcription profile and consequently has global effects on physiology and the lifestyle of E. coli. Here we provide a short overview of the mechanisms by which the nucleoid is organized into different topological domains. We propose that HU is a major player in creating domain-specific superhelicities and thus influences the transcription profile from the constituent promoters. This article is part of a Special Issue entitled: Chromatin in time and space.


High human cytomegalovirus loads and diverse linked variable genotypes in both HIV-1 infected and exposed, but uninfected, children in Africa.
Human cytomegalovirus, HCMV, was analysed using real-time quantitative PCR in symptomatic or asymptomatic pediatric cohorts from HIV-1 infected, exposed (HIV-1+ mothers), or uninfected groups in Zambia, an HIV-1/AIDS endemic region of Africa. HCMV infections were identified in 94% samples from HIV-1+ respiratory pediatric mortalities, 50% with high DNA loads of 10(3)-10(8) copies/10(6) cells. In comparison, HCMV viremia with high DNA loads, indicative of acute infections, were in 10% hospitalised febrile infants, with 50% HIV-1+. Whereas high sera loads were in 1% of asymptomatic infants, with 2% HIV-1+, and higher levels in both HIV-1 infected or exposed, but negative infants. All 8 linked-hypervariable glycoprotein gN-gO genotypes were shown, including identification of a new gN4d group with gO5 linkage (previously only Merlin reference strain), and samples with multiple infections. Overall, this shows global genotypes in Africa (unlike some herpesviruses) and acute pediatric HCMV infections in both HIV-1+ plus exposed, but uninfected infants, an emerging group.


Outcome at age 7 of epilepsy presenting in the first 2 years of life. A population-based study.
Existing data suggest that epilepsy presenting in the first few years of life carries a worse prognosis than later onset. However, studies are few and methods differ, making interpretations of data uncertain. This study analyzes outcome at age 7 and potential prognostic factors in a well-characterized population-based cohort with epilepsy onset during the first 2 years of life. An incidence cohort of 116 prospectively identified cases of epilepsy with seizure onset before age 2 years was described in Stödberg et al. (2020). Cases were originally retrieved from the Stockholm Incidence Registry of Epilepsy (SIRE), which registered all cases with a first unprovoked epileptic seizure from September 1, 2001, in Northern Stockholm. Data on treatment and outcome at age 7 years were collected from electronic medical records and through interviews with parents. Outcome and potential prognostic factors were analyzed with descriptive statistics and multivariable log binomial regression analysis. Eleven children (9.5%) died before age 7. Polytherapy was common. Epilepsy surgery was performed in two children. At age 7 years, 61 of 116 children (53%) had been seizure-free for the last 2 years or longer. Intellectual disability was diagnosed in 57 of 116 children (49%), autism spectrum disorder in 13 (11%), and cerebral palsy in 28 (24%). West syndrome had a similar seizure remission rate but a worse cognitive outcome. There was no difference in outcome between first and second year onset. Six predictors, including etiology, remained associated with two or more outcome variables after regression analysis. About half of children with infantile-onset epilepsy will become seizure-free and half of them will have intellectual disability. Etiology was confirmed as a major independent predictor of outcome. Our study contributes to a more firm knowledge base when counseling parents of infants diagnosed with epilepsy.


Shear-Wave Elastography-Guided Core Needle Biopsy for the Determination of Breast Cancer Molecular Subtype.
To investigate whether shear-wave elastography (SWE) guidance during core-needle biopsy can improve diagnostic accuracy and accurate determination of the molecular subtypes of breast cancer. This controlled, randomized prospective cohort study included 58 patients (mean age: 56.9 ± 16.2) who were referred for image-guided core-needle biopsy between May 2018 and April 2019 for lesions larger than 1 cm. In Group 1, 30 lesions were biopsied without SWE guidance and recorded as Biopsy A. In Group 2, 30 lesions were examined with SWE before biopsy, and then two different parts of the lesions were biopsied; biopsies from the relatively rigid areas of the lesions were recorded as Biopsy B, and biopsies from the less rigid areas of the lesions were recorded as Biopsy C. The histopathological and immunohistochemical results of biopsies were compared with the surgical results. The sensitivity of Biopsy A, B and C were 96.7%, 100% and 100%, respectively. The benign-malignant concordance rates were 94.7%, 100%, and 90% and the diagnostic concordance rates were 89.5%, 100%, and 90% in Biopsies A, B, and C, respectively. When the 10% differences in the estrogen receptor (ER), progesterone receptor (PR), and Ki67 rates were considered significant, the concordance rate of ER was highest in Biopsy B (77.8%; p = 0.040). The concordance rate of immunohistochemical subtyping was 100% in Biopsy B and 71.4% in Biopsies A and C (p = 0.086). SWE-guided core-needle biopsy of breast lesions increased the sensitivity, diagnostic accuracy, and accuracy of immunohistochemical subtyping to 100%.


Evaluation of the pharmacological benefit and determination of the influencing factors of intraarterial cis-diamminedichloroplatinum administration in patients with uterine cervical cancer.
cis-Diamminedichloroplatinum (100 mg/m2) was administered to the same patients (n = 9) with advanced uterine cervical tumors, via i.v. and intraarterial (i.a.) (bilateral hypogastric arteries) routes. Measurement of plasma pharmacokinetic parameters enabled us to show up areas under the curve (AUC) of free cis-diamminedichloroplatinum versus time significantly (P less than 0.01) lower after i.a. injection (mean value, 3.9 mg.h/liter) than after i.v. injection (mean value, 5 mg.h/liter). However, the increase in intratumoral concentrations after i.a. administration was only at the limit of statistical significance (P = 0.05). Consequently, the benefit of local i.a. administration, evaluated according to the method of Collins, was small (1.2-2.3). An explanation of the phenomena observed can be given using the generalized compartmental model of Collins. We have demonstrated that the parameters of this model can be entirely calculated by taking into account both the i.v. and i.a. pharmacokinetic measurements. Calculations from experimental data of the model parameters, clearances of the body (ClB), and exchange rate between the site of administration and the rest of the body (Q) were in accordance with the physiological values. On the basis of the parameter values, it was confirmed that the low benefit of i.a. administration was due to the fast blood exchange between the injection site and the rest of the body and the probable cis-diamminedichloroplatinum binding on healthy tissues irrigated by the hypogastric artery.


Prevalence and Diversity of Staphylococcus aureus and Staphylococcal Enterotoxins in Raw Milk From Northern Portugal.
Staphylococcus aureus and staphylococcal enterotoxins are a serious public health concern associated with hospital and community-acquired illnesses. Dairy animals frequently shed S. aureus into the milk supply which can lead to food poisoning in humans. This study aims to investigate the prevalence and genetic diversity of S. aureus and staphylococcal enterotoxins in raw milk from the main dairy region of mainland Portugal. S. aureus was found in 53.0% (95% CI: 40.6-65.4%) of 100 raw cow's milk samples collected from bulk cooling tanks. The highest contamination level was 3.4 log10 CFU.mL-1, and in some samples more than one S. aureus strain was identified. Staphylococcal enterotoxins (SEA-SEE) were detected in one sample. Spa typing revealed 62 distinct S. aureus isolates, being t529 (17.7%, 95% CI: 8.2-27.3%) and t1403 (16.1%, 95% CI: 7.0-25.3%) the predominant types, commonly associated with livestock infection or carriage. The antimicrobial susceptibility test showed that 35.5% of the S. aureus isolates were resistant to at least one antimicrobial agent, with resistance to penicillin being the highest (32.3%, 95% CI: 20.6-43.9%) followed by tetracycline (24.2%, 95% CI: 13.5-34.9%), ciprofloxacin (16.1%, 95% CI: 7.0-25.3%) and chloramphenicol (16.1%, 95% CI: 7.0-25.3%). Moreover, five isolates (8.1%, 95% CI: 1.3-14.8%) were identified as methicillin-resistant S. aureus (MRSA, cefoxitin resistant). Regarding virulence/resistance genes, 46,8% (95% CI: 34.4-59.2%) isolates harbored at least one enterotoxin-encoding gene, and the seg gene was the most frequently detected (41.9%, 95% CI: 29.7-54.2%) followed by the sei (40.3%, 95% CI: 28.1-52.5%), sec (6.5%, 95% CI: 0.3-12.6%), seh (4.8%, 95% CI: 0.0-10.2%), and sea (1.6%, 95% CI: 0.0-4.7%) genes. Five (8.1%, 95% CI: 1.3-14.8%) non-enterotoxigenic isolates carried the mecA gene (corresponding to isolates phenotypically classified as MRSA), and 4.8% (95% CI: 0.0-10.2%) enterotoxigenic strains also had the tsst-1 gene. Our study confirm that raw milk can be a zoonotic source of S. aureus, including enterotoxigenic and MRSA strains. Furthermore, the majority of enterotoxigenic isolates were found to contain genes encoding SEs (SEG, SEH and SEI) not routinely screened. This shows the need for a broader SE screening in food safety control, as well as the relevance of risk mitigation measures to control S. aureus transmission along the food chain in Portugal.


Conventional Radiology in Spondyloarthritis.
Spondyloarthritides are of a group of inflammatory rheumatic diseases, with negative rheumatoid factor, associated with the HLA-B27 gene. They comprise ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic-related spondylitis. The presence of sacroiliitis represents the most characteristic feature of these disorders and is an important criterion in diagnosis. Nonradiographic axial spondyloarthritis is a new classification concept. Conventional radiography is recommended as the first imaging method to diagnose sacroiliitis and different entities and to monitor established structural changes.


Detection of spontaneous CD4+ T-cell responses in melanoma patients against a tyrosinase-related protein-2-derived epitope identified in HLA-DRB1*0301 transgenic mice.
The frequently expressed differentiation antigen tyrosinase-related protein-2 (TRP-2) has repeatedly been described as a target of spontaneous cytotoxic T-cell responses in melanoma patients, suggesting that it might be an ideal candidate antigen for T cell-based immunotherapy. As a prerequisite for immunization, T-cell epitopes have to be identified. Whereas a number of HLA class I-presented TRP-2-derived epitopes are known, information about HLA class II-presented antigenic ligands recognized by CD4+ T helper (Th) cells is limited. The search for TRP-2-derived Th epitopes was carried out by competitive in vitro peptide binding studies with predicted HLA-DRB1*0301 ligands in combination with peptide and protein immunizations of HLA-DRB1*0301 transgenic mice. In vivo selected candidate epitopes were subsequently verified for their immunogenicity in human T-cell cultures. This strategy led to the characterization of TRP-2(60-74) as an HLA-DRB1*0301-restricted Th epitope. Importantly, TRP-2(60-74)-reactive human CD4+ Th cell lines, specifically recognizing target cells loaded with recombinant TRP-2 protein, could be established by repeated peptide stimulation of peripheral blood lymphocytes from several HLA-DRB1*03+ melanoma patients. Even short-term peptide stimulation of patients' peripheral blood lymphocytes showed the presence of TRP-2(60-74)-reactive T cells, suggesting that these T cells were already activated in vivo. Peptide TRP-2(60-74) might be a useful tool for the improvement of immunotherapy and immune monitoring of melanoma patients.


Nek8 couples renal ciliopathies to DNA damage and checkpoint control.
In this issue, Choi et al. (2013) discover a molecular link between the Nek8 kinase, mutated in the renal ciliopathy nephronophthisis, and DNA damage control by cyclin A/Cdk2 and ATR-Chk1, providing new ideas for targeted therapies limiting tissue degeneration.


Human monoclonal antibody fragment specific for glycoprotein G in herpes simplex virus type 2 with applications for serotype-specific diagnosis.
A combinatorial library was used to select a human monoclonal antibody fragment (Fab) with high affinity for G glycoprotein in herpes simplex virus type 2 (HSV-2). Tests with 112 clinical specimens demonstrated successful discrimination between HSV-2 and HSV-1, showing the potential of Fab as a low-cost tool for HSV subtyping in clinical diagnosis.


Mechanism of progression of diabetic kidney disease mediated by podocyte mitochondrial injury.
Diabetic kidney disease (DKD) is an important diabetic microvascular complication, which has become the main cause of end-stage renal disease (ESRD) all over the world. It is of great significance to find effective therapeutic targets and improve the prognosis of the disease. Traditionally, it is believed that the activation of the renin-angiotensin-aldosterone system (RAAS) is the main reason for the progression of DKD, but with the progress of research, it is known that the production of proteinuria in patients with DKD is also related to podocyte injury and loss. Many studies have shown that mitochondrial dysfunction in podocytes plays an important role in the occurrence and development of DKD, and oxidative stress is also the main pathway and common hub of diabetes to the occurrence and development of microvascular and macrovascular complications. Thus, the occurrence and progression of DKD is correlated with not only the activation of the RAAS, but also the damage of mitochondria, oxidative stress, and inflammatory mediators. Besides, diabetes-related metabolic disorders can also cause abnormalities in mitochondrial dynamics, autophagy and cellular signal transduction, which are intertwined in a complex way. Therefore, in this review, we mainly explore the mechanism and the latest research progress of podocyte mitochondria in DKD and summarize the main signal pathways involved in them. Thus, it provides feasible clinical application and future research suggestions for the prevention and treatment of DKD, which has important practical significance for the later treatment of patients with DKD.


Regulation of intestinal apolipoprotein A-IV synthesis.
Apolipoprotein (apo) A-IV is a protein synthesized, in humans, only by the small intestine. It has a molecular weight of 46 000 Da. This paper summarizes the evidence supporting its role as a satiety factor following the ingestion of fat. This function of apo A-IV is unique and not shared by other apolipoproteins, including apo A-I. The satiety effect of apo A-IV is centrally mediated. The mechanism of how apo A-IV inhibits food intake is not clear but it probably acts by inhibiting both gastric acid secretion as well as gastric motility. Lipid absorption stimulates apo A-IV synthesis and secretion by the jejunum. In addition to lipid feeding, there is evidence that a factor which is released as a result of lipid absorption in the distal small intestine also stimulates the synthesis and release of apo A-IV by the jejunum. This factor is probably PYY.