Facilitation by a Spiny Shrub on a Rhizomatous Clonal Herbaceous in Thicketization-Grassland in Northern China: Increased Soil Resources or Shelter from Herbivores.
The formation of fertility islands by shrubs increases soil resources heterogeneity in thicketization-grasslands. Clonal plants, especially rhizomatous or stoloniferous clonal plants, can form large clonal networks and use heterogeneously distributed resources effectively. In addition, shrubs, especially spiny shrubs, may also provide herbaceous plants with protection from herbivores, acting as 'shelters'. The interaction between pre-dominated clonal herbaceous plants and encroaching shrubs remains unclear in thicketization-grassland under grazing pressure. We hypothesized that clonal herbaceous plants can be facilitated by encroached shrubs as a 'shelter from herbivores' and/or as an 'increased soil resources' under grazing pressure. To test this hypothesis, a total of 60 quadrats were chosen in a thicket-grassland in northern China that was previously dominated by Leymus chinensis and was encroached upon by the spiny leguminous plant Caragana intermedia. The soil and plant traits beneath and outside the shrub canopies were sampled, investigated and contrasted with an enclosure. The soil organic matter, soil total nitrogen and soil water content were significantly higher in the soil beneath the shrub canopies than in the soil outside the canopies. L. chinensis beneath the shrub canopies had significantly higher plant height, single shoot biomass, leaf length and width than outside the shrub canopies. There were no significantly differences between plant growth in enclosure and outside the shrub canopies. These results suggested that under grazing pressure in a grassland undergoing thicketization, the growth of the rhizomatous clonal herbaceous plant L. chinensis was facilitated by the spiny shrub C. intermedia as a 'shelter from herbivores' more than through 'increased soil resources'. We propose that future studies should focus on the community- and ecosystem-level impacts of plant clonality.


6-[F-18]fluoro-L-DOPA positron emission tomography in the imaging of Merkel cell carcinoma: preliminary report of three cases with 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography or pentetreotide-(111In) SPECT data.
Merkel cell carcinoma (MCC) is an uncommon and aggressive cutaneous neoplasm of neuroendocrine origin. Somatostatin receptor scintigraphy (SRS) and positron emission tomography (PET) using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) have been proposed to stage MCC and to detect early recurrences. As 6-[F-18]fluoro-L-DOPA (FDOPA) is taken up by other neuroendocrine tumors, we speculated that FDOPA-PET could image MCC. FDOPA-PET was performed together with FDG-PET (three patients) and SRS (two patients) in different clinical settings: localization of the primary tumor, staging, and suspicion of recurrence. Uptake of FDOPA-(18F) by MCC was observed in the two true-positive cases, with an agreement between the results of FDOPA-PET, FDG-PET, and SRS; however, the contrast was lower on FDOPA-PET than on FDG-PET images. In the last patient suspected of recurrence repeatedly on SRS and with inconclusive FDG-PET, FDOPA-PET was negative, and a 12-month follow-up demonstrated a true-negative result. MCC takes up FDOPA-(18F). The potential role of FDOPA-PET in its management warrants clarification.


Overcoming gaps: regional collaborative to optimize capacity management and predict length of stay of patients admitted with COVID-19.
Ensuring an efficient response to COVID-19 requires a degree of inter-system coordination and capacity management coupled with an accurate assessment of hospital utilization including length of stay (LOS). We aimed to establish optimal practices in inter-system data sharing and LOS modeling to support patient care and regional hospital operations. We completed a retrospective observational study of patients admitted with COVID-19 followed by 12-week prospective validation, involving 36 hospitals covering the upper Midwest. We developed a method for sharing de-identified patient data across systems for analysis. From this, we compared 3 approaches, generalized linear model (GLM) and random forest (RF), and aggregated system level averages to identify features associated with LOS. We compared model performance by area under the ROC curve (AUROC). A total of 2068 patients were included and used for model derivation and 597 patients for validation. LOS overall had a median of 5.0 days and mean of 8.2 days. Consistent predictors of LOS included age, critical illness, oxygen requirement, weight loss, and nursing home admission. In the validation cohort, the RF model (AUROC 0.890) and GLM model (AUROC 0.864) achieved good to excellent prediction of LOS, but only marginally better than system averages in practice. Regional sharing of patient data allowed for effective prediction of LOS across systems; however, this only provided marginal improvement over hospital averages at the aggregate level. A federated approach of sharing aggregated system capacity and average LOS will likely allow for effective capacity management at the regional level.


Vibrational spectroscopy investigation using ab initio and density functional theory on p-anisaldehyde.
The FTIR and FT Raman spectra of p-anisaldehyde has been recorded in the regions 4,000-400 and 3,500-100 cm(-1), respectively. The optimized geometry, frequency and intensity of the vibrational bands of p-anisaldehyde were obtained by ab initio and DFT levels of theory with complete relaxation in the potential energy surface using 6-31G(d,p) basis set. A complete vibrational assignment aided by the theoretical harmonic frequency analysis has been proposed. The harmonic vibrational frequencies calculated have been compared with experimental FTIR and FT Raman spectra. The observed and the calculated frequencies are found to be in good agreement. The experimental spectra also coincide satisfactorily with those of theoretically constructed bar type spectrograms.


The constitutive activation of Egr-1/C/EBPa mediates the development of type 2 diabetes mellitus by enhancing hepatic gluconeogenesis.
The sequential secretion of insulin and glucagon delicately maintains glucose homeostasis by inhibiting or enhancing hepatic gluconeogenesis during postprandial or fasting states, respectively. Increased glucagon/insulin ratio is believed to be a major cause of the hyperglycemia seen in type 2 diabetes. Herein, we reveal that the early growth response gene-1 (Egr-1) can be transiently activated by glucagon in hepatocytes, which mediates glucagon-regulated gluconeogenesis by increasing the expression of gluconeogenesis genes. Blockage of Egr-1 function in the liver of mice led to lower fasting blood glucose, better pyruvate tolerance, and higher hepatic glycogen content. The mechanism analysis demonstrated that Egr-1 can directly bind to the promoter of C/EBPa and regulate the expression of gluconeogenesis genes in the later phase of glucagon stimulation. The transient increase of Egr-1 by glucagon kept the glucose homeostasis after fasting for longer periods of time, whereas constitutive Egr-1 elevation found in the liver of db/db mice and high serum glucagon level overactivated the C/EBPa/gluconeogenesis pathway and resulted in hyperglycemia. Blockage of Egr-1 activation in prediabetic db/db mice was able to delay the progression of diabetes. Our results suggest that dysregulation of Egr-1/C/EBPa on glucagon stimulation may provide an alternative mechanistic explanation for type 2 diabetes.


Good healing potential of patellar chondral defects after all-arthroscopic autologous chondrocyte implantation with spheroids: a second-look arthroscopic assessment.
To report second-look arthroscopic assessment after all-arthroscopic autologous chondrocyte implantation (ACI) for articular cartilage defects at the patella. A second-look arthroscopy after all-arthroscopic ACI using chondrospheres® (ACT3D) was performed in 30 patients with 30 full-thickness retropatellar cartilage defects. The mean time from ACI to second-look arthroscopy was 14.9 ± 16.3 (6-71) months. The quality of cartilage regeneration was evaluated by the International Cartilage-Repair Score (ICRS)-Cartilage Repair Assessment (CRA). Eleven lesions (36.7%) were classified as CRA grade I (normal) and 19 lesions (63.3%) as grade II (nearly normal). Concerning the degree of defect repair, 25 lesions (83.3%) were repaired up to the height of the surrounding articular retropatellar cartilage. Five lesions (16.7%) showed 75% repair of defect depth. The border zone was completely integrated into the surrounding articular cartilage shoulder in 28 lesions (93.3%) and demarcated within 1 mm in 2 lesions (6.7%). Macroscopically and by probing, 12 lesions (40%) had intact smooth surface, 17 lesions (56.7%) had fibrillated surface and 1 lesion (3.3%) had small, scattered fissures. A negative correlation was found between the overall repair assessment score and the defect size (r2 = - 0.430, p = 0.046) and between integration into border zone and defect size (r2 = - 0.340, p = 0.045). A positive correlation was found between macroscopic appearance and age (r2 = + 0.384, p = 0.036). All-arthroscopic ACI using chondrospheres® (ACT3D) for full-thickness retropatellar articular cartilage defects proved to be reproducible and reliable. The advantage of the procedure is that it is minimal invasive. Arthroscopic second-look demonstrated a high grade of normal or nearly normal cartilage regeneration. Although statistically significant differences were not observed, larger defect size and younger age may compromise the result of overall repair. III.


[Peer visits to community-based general practitioners and pediatricians as part of the "Antibiotics only when necessary" campaign in the Alpes-Maritimes district. Methodology, feasibility, and interest].
As part of a public health campaign promoting prudent antibiotic use to combat bacterial resistance in southeastern France, a multidisciplinary group organized peer-conducted educational outreach (academic detailing) visits to all the community-based general practitioners and pediatricians in the district. The visits, which took place in 2000 and were repeated in 2003, were intended to provide epidemiological data and professional guidelines to these doctors. A group of local experts created special academic detailing sheets based on French and international recommendations. Peers with similar experience received special training in the relevant scientific material and in communications skills and then visited the local physicians and discussed the detailing sheets. The project contacted 95% of the target doctors (1079/1174 in 2000 and 1119/1135 in 2003), 94% (1024/1079 and 1042/1119, respectively) of whom agreed to be visited. The visitors reported positive feedback in over 80% of cases. Many of the visited doctors showed keen interest that led to ongoing dialogue, including participation in a regional influenza surveillance program. A sample of the visited doctors received a questionnaire to evaluate the method in 2001: 93% of the responders endorsed the method and 92% requested for more recommendations and guidelines. Carefully prepared individual academic detailing visits conducted by peers succeeded in visiting nearly all the physicians in the district twice, two years apart, and provided them with useful support for implementing important guidelines in everyday practice. This method can be used to improve cooperation between healthcare providers and improve the quality of health care in France.


Impact of sulphate-reducing bacteria on the performance of engineering materials.
Microbiologically Influenced Corrosion (MIC) is an electrochemical corrosion influenced by the presence/action of biological agents such as, but not limited to, bacteria. One of the key elements of MIC is sulphate-reducing bacteria (SRB). There are still many misunderstandings about these bacteria, their role in the deterioration of engineering materials and their importance over other types of corrosion-related micro-/macro-organisms. SRB do not require oxygen, yet they can be found in oxygenated environments; they are capable of tolerating a relative wide range of temperature, pH, chloride concentration and pressure values. Not only can SRB have deteriorating impact on engineering materials, they are also capable of inducing harm to health and agriculture. In this paper, after reviewing facts and figures regarding ecological and economical impacts of corrosion in general and MIC, in particular, the central concept of MIC, that is, biofilm formation and its deterioration mechanisms and the role of SRB in such mechanisms are described. Also, the possible enhancing role of SRB on stress corrosion cracking of steels and the controversial concept of no relationship between the number of SRB and corrosion rate are addressed and reviewed.


Identification of residual metabolic-active areas within NSCLC tumours using a pre-radiotherapy FDG-PET-CT scan: a prospective validation.
It was recently described that high FDG-uptake areas pre-radiotherapy largely correspond with residual metabolic-active areas post-radiotherapy. Here, an independent prospective validation of these results was performed using an overlap-fraction (OF) calculation of various FDG-uptake based thresholds. Data from twelve patients treated at Radboud University Nijmegen Medical Center with lung cancer were analyzed. All patients underwent two FDG-PET-CT scans, one pre-radiotherapy (pre-RT) and one approximately three months after treatment (post-RT). Of the twelve analyzed patients, eight patients showed residual FDG uptake on the post-RT scan and were included for analysis. One of these patients had a residue that was not clearly distinguishable from the surrounding tissue due to FDG avid inflammation. Therefore, seven patients remained for further analysis. The mean volume of the residual metabolic-active areas post-RT was 14.6±10.0% (mean±SD) of the mean volume of the gross tumour volume (GTV) pre-RT. The residual metabolic-active areas largely corresponded with the pre-RT GTV (OF=93.7±7.2%). The pre-RT-scan threshold delineations of 34%, 40% and 50% of the SUV(max) had a large OF with the residual region, 86.9±8.3%, 77.4±8.1% and 67.9±6.8%, respectively. In this independent dataset, we confirmed that the location of residual FDG-uptake areas after radiotherapy corresponds with the high FDG-uptake areas pre-radiotherapy. Therefore, a pre-radiotherapy FDG-PET-CT scan can potentially be used for radiotherapy dose redistribution.


Management of inflammatory root resorption using MTA obturation - a four year follow up.
A case report of severe external inflammatory root resorption is presented. The patient reported with a complaint of increased tooth mobility after avulsion and replantation. The case was treated with full root canal obturation with mineral trioxide aggregate. A 48 month follow up review showed arrest of root resorption with satisfactory clinical results. This article discusses the aetiology of inflammatory root resorption and the use of the latest root canal obturation materials in improving healing outcomes.


Late coil displacement after interventional closure of a perimembranous ventricular septal defect: a case report.
Muscular and perimembranous ventricular septal defects can be closed with nitinol plugs or spiral coils. Displacement and embolization of the device are well known complications that usually occur during or early after the procedure. We present the case of a 12-year-old boy with asymptomatic coil displacement detected at a routine examination 5 months after closure of a perimembranous ventricular septal defect.


Collaborative virtual screening to elaborate an imidazo[1,2-a]pyridine hit series for visceral leishmaniasis.
An innovative pre-competitive virtual screening collaboration was engaged to validate and subsequently explore an imidazo[1,2-a]pyridine screening hit for visceral leishmaniasis. In silico probing of five proprietary pharmaceutical company libraries enabled rapid expansion of the hit chemotype, alleviating initial concerns about the core chemical structure while simultaneously improving antiparasitic activity and selectivity index relative to the background cell line. Subsequent hit optimization informed by the structure-activity relationship enabled by this virtual screening allowed thorough investigation of the pharmacophore, opening avenues for further improvement and optimization of the chemical series.


Top 10 principles for designing healthy coastal ecosystems like the Salish Sea.
Like other coastal zones around the world, the inland sea ecosystem of Washington (USA) and British Columbia (Canada), an area known as the Salish Sea, is changing under pressure from a growing human population, conversion of native forest and shoreline habitat to urban development, toxic contamination of sediments and species, and overharvest of resources. While billions of dollars have been spent trying to restore other coastal ecosystems around the world, there still is no successful model for restoring estuarine or marine ecosystems like the Salish Sea. Despite the lack of a guiding model, major ecological principles do exist that should be applied as people work to design the Salish Sea and other large marine ecosystems for the future. We suggest that the following 10 ecological principles serve as a foundation for educating the public and for designing a healthy Salish Sea and other coastal ecosystems for future generations: (1) Think ecosystem: political boundaries are arbitrary; (2) Account for ecosystem connectivity; (3) Understand the food web; (4) Avoid fragmentation; (5) Respect ecosystem integrity; (6) Support nature's resilience; (7) Value nature: it's money in your pocket; (8) Watch wildlife health; (9) Plan for extremes; and (10) Share the knowledge.


Inversion of selectivity in anion recognition with conformationally blocked calix[4]pyrroles.
Two calixpyrrole derivatives were synthesised. A p-dimethylaminobenzoyl group was electronically attached to a pyrrole ring, establishing an intramolecular hydrogen bond in a 1,3-alternate conformation. The formation of the H-bond was corroborated by IR, NMR, and X-ray measurements. NMR titration studies reveal that the H-bond is strong enough to block the conversion to a cone conformation, allowing them to only acquire a partial cone conformation. Affinity constants for several anions were calculated, and a noticeable increase was observed for tridentate tetrahedral anions, while the K(a) of spheric or bidentate anions decreased. In the presence of several acids, the synthesised compounds can act as chemosensors by a double process: protonation of the amino group and coordination of the generated anion. In addition, a displacement approach gives rise to a proof of concept for sulphonate recognition.


Surgical risk of vessel injury: an unusual anatomical variant of the right medial basal segmental pulmonary artery.
Video-assisted right basal segmentectomy was successfully performed on a 72-year-old man with an anomalous pulmonary artery. Multidetector row angiography showed the A7 branch arising from the right main pulmonary artery proximal to the branches of the superior trunks, lying under the middle bronchus, and reaching segment S7. Metastatic tumor (diameter 7 mm) was identified in the periphery of this vessel. This anomaly appears to be rare but seems also to be easily overlooked and could cause serious vessel injury even for video-assisted thoracoscopic right lower lobectomy.


Inhibition of trypsins and chymotrypsins from different animal species: a comparative study.
The effect of 3 purified trypsin inhibitors and 4 legume seed extracts on teh trypsins and chymotrypsins of the activated pancreata of 11 animal species, including man, was measured. The activation was performed by either homologous enterokinase or by bovine trypsin. Several trypsinogens were not activated by the latter. Rabbit trypsin was the most sensitive to all inhibitor preparations, while the human trypsin was the most resistant, except to the black bean extract. The response of the chymotrypsins was more variable and those of capybara and rabbit showed extreme sensitivity. Considerable differences between the extracts of black and white garden beans, both Phaseolus vulgaris, with respect to their reactivity toward different animal enzymes were detected. No relation between relative pancreas weight and susceptibility toward soybean trypsin inhibitor could be observed.


Facial skin temperature and overall thermal sensation of sub-tropically acclimated Chinese subjects in summer.
This study explored the facial skin temperature and thermal sensation of sub-tropically acclimated subjects in summer. We conducted a summer experiment that simulated the common indoor temperatures in Changsha, China. Twenty healthy subjects experienced five exposure conditions: 24, 26, 28, 30 and 32 °C with a relative humidity of 60%. During exposure (140min), the sitting participants documented their thermal sensation, comfort and acceptability of the environment. Their facial skin temperatures were continuously and automatically recorded by using iButtons. These facial parts include the forehead, nose, left and right ears, left and right cheeks and chin. The results found that the maximum facial skin temperature difference increased with air temperature reduction. The forehead skin temperature was the highest. Nose skin temperature is lowest when air temperature is not higher than 26 °C during summer. Correlation analysis confirmed that the nose is the potential facial part that is most suitable to evaluate thermal sensation. Based on the published winter experiment, we further explored their seasonal effects. The seasonal analysis showed that, compared with winter, thermal sensation is more sensitive to indoor temperature changes and facial skin temperatures were less susceptible to thermal sensation changes in summer. Facial skin temperatures were higher in summer under the same thermal conditions. It suggests that seasonal effects should be considered when facial skin temperature can be used as an important parameter for indoor environment control in the future through monitoring thermal sensation.


[Postoperative dissection of the vertebral artery in two steps].
The diagnosis of perioperative vertebral artery dissection can be difficult because of non-specific clinical signs. We report a case revealed by a tegmento-thalamic stroke after an abdominal second surgical look. The interest of this observation is related to a particular evolution in two steps separated by a 2-month-interval and an intercurrent cervical manipulation. After the second anesthesia, neck pain associated with a third cranial nerve palsy and a supranuclear ophtalmoplegia revealed a tegmento-thalamic ischemic stroke due to vertebral artery dissection. We discuss here the different factors possibly involved in the pathophysiology of postoperative vertebral artery dissection: positioning, cervical manipulation, subclavian central venous access and cisplatin toxicity. Vertebral artery dissection should be discussed in case of postoperative neck pain, especially with non-typical symptomatology.


Nursing student attitudes toward dying patient care: A European multicenter cross-sectional study.
Background and aim of the work Nursing education plays a key role in preparing future nurses to deal with dying patients, which represents one of the most emotionally involving aspect of nursing. The aims of the study were to explore nursing students' attitudes towards care of dying patients in three different European contexts and to analyze the variables that can influence them. Methods We conducted an international multicenter cross-sectional study. We administered the Frommelt Attitude Toward Care of the Dying Scale form B (FATCOD-B) and a demographic form to 569 students, enrolled in the Nursing Programmes in three different countries (Italy, Spain and the United Kingdom), who accepted to participate in the study. The data were analyzed using SPSS software version 26.0. Results Median total FATCOD-B scores indicated intermediate levels of students' attitudes towards care for dying patients, with a statistically significant difference among the three student groups. The median total FATCOD-B scores did not statistically significantly change in students with different age, gender, year of study, religious believes, nursing education on palliative care, previous experiences of dying patient care and personal grieving. Conclusions In our study, nursing students feel partially prepared in caring for dying patients and their attitudes do not change as the course of study progresses. No selected variables had an impact on students' attitudes towards palliative care. Since nurses play a vital role in ensuring the quality of care, education on end-of-life care should be offered as a core part of undergraduate nursing programs.


Lack of effect of conduction direction on action potential durations in anisotropic ventricular strips of pig heart.
The influence of activation sequence on the rate of rise of the depolarization phase of action potentials in atrial or ventricular muscles has been well established. However, whether myocardial fiber orientation is important in modulating the repolarization process is unclear. We examined the influence of activation sequence on the repolarization phase of action potentials in epicardial tissues from the right and left ventricles of domestic pigs. Whereas cells from the right ventricle exhibited direction-dependent differences in action potential duration at 30%, 50%, and 90% of full repolarization (190.6 +/- 31.1 msec vs 181.8 +/- 32.8 msec, 240.3 +/- 23.5 msec vs 236.7 +/- 25.4 msec, and 291.3 +/- 23.7 msec vs 287.4 +/- 25.1 msec for longitudinal and transverse propagation, respectively; P < 0.001), a similar duration of repolarization during both directions of propagation was observed in cells from the left ventricle at 50% and 90% of full repolarization (241.4 +/- 39.4 msec and 285.5 +/- 39.5 msec vs 240.4 +/- 38.9 msec and 284.9 +/- 39.6 msec for longitudinal and transverse propagation respectively; P = NS). A slight but significant difference was found at 30% of full repolarization in cells from the left ventricle (190.4 +/- 39.0 msec vs 187.0 +/- 38.0 msec for longitudinal and transverse propagation, respectively; P < 0.05). In the left ventricle, the duration of repolarization did not change as the distance between the recording site and stimulation site increased. The direction of wavefront propagation with respect to fiber orientation may not play an important role in modulating the duration of repolarization in epicardial cells from the left ventricle.


Tannic acid-assisted in-situ interfacial formation of Prussian blue-assembled adsorptive membranes for radioactive cesium removal.
There is a growing interest in advanced materials that can effectively treat wastewater contaminated with radioactive cesium (137Cs), which is an extremely hazardous material. Here, we report a new class of Cs-adsorptive membranes compactly assembled with Cs-adsorptive Prussian blue (PB) particles. The PB particle assembly was formed via an in-situ interfacial reaction between two PB precursors in the presence of tannic acid (TA) as a binder on a porous support. While the interfacial reaction enabled the formation of a defect-less PB network, TA enhanced the PB-PB and PB-support compatibilities, consequently producing a uniform, densely packed PB assembly near the support surface. The fabricated TA-assisted PB membrane (PB/TA-M) synergistically rejected Cs via a combination of adsorption and membrane filtration, although adsorption predominantly determined Cs rejection initially. Hence, the PB/TA-M membrane showed considerably higher Cs removal performance than commercial nanofiltration (NF) and reverse osmosis (RO) polyamide (PA) membranes for a sufficiently long operation time. Furthermore, the PB/TA-M membrane displayed excellent radioactive 137Cs removal performance, significantly exceeding those of commercial NF and RO PA membranes due to its higher radiation stability, indicating its viability for application in treating actual radioactive wastewater.


LncRNA GATA6-AS inhibits cancer cell migration and invasion in gallbladder cancer by downregulating miR-421.
Long non-coding RNS (lncRNA) GATA6-AS regulates endothelial cell growth, which is involved in many types of human diseases. Our study was carried out to investigate the involvement of GATA6-AS in gallbladder cancer (GBC). Sixty-two patients with GBC were recruited in this study. PCR analysis was performed to determine the expression of GATA6-AS, miR-421 and TIMP-2 in tissues or cell lines. Transwell migration and invasion assay was applied. We found that GATA6-AS was downregulated in tumor tissues than in adjacent healthy tissues of GBC patients, and GATA6-AS expression levels in tumor tissues decreased with the increase of clinical stages. MiR-421 was upregulated in tumor tissues than in adjacent healthy tissues of GBC patients and was inversely correlated with the expression levels of GATA6-AS. MiR-421 overexpression failed to significantly affect GATA6-AS in GBC cells, while GATA6-AS overexpression resulted in inhibited miR-421 expression. GATA6-AS overexpression led to decreased migration and invasion rates of GBC cells. MiR-421 overexpression led to increased migration and invasion rates of GBC. Rescue experiments (co-transfection) showed that miR-421 overexpression led to attenuated effects of GATA6-AS overexpression. GATA6-AS may inhibit cancer cell migration and invasion in GBC by downregulating miR-421.


Protein binding displacement interactions and their clinical importance.
The binding of drugs to proteins is an important pharmacokinetic parameter. Many methods are available for the study of drug protein binding phenomena and there are also many ways to interpret the binding data. Although much emphasis has been placed on the binding of drugs in the plasma, binding also takes place in the tissues. Displacement interactions involving plasma or tissue binding sites have been implicated as the causative mechanisms in many drug interactions. However, the importance of plasma binding displacement as a mechanism of drug interactions. However, the importance of plasma binding displacement as a mechanism of drug interaction has been overestimated and overstated, being based largely on in vitro data. Because displaced drug can normally distribute out of the plasma compartment, increases of free drug concentrations are usually transient and therefore will not give rise to changed pharmacological effects in the patient. Those clinically important drug interactions formerly considered to be caused via displacement from plasma binding sites usually have another interaction mechanism involved; commonly decreased metabolism or renal elimination also takes place. Plasma binding displacement interactions, however, do become important clinically in certain specific situations, namely, when the displacing drug is administered quickly to the patient by the intravenous route, during therapeutic drug monitoring, and in certain drug disposition studies which involve the use of a heparin lock for blood sampling. Tissue binding displacement interactions have a greater potential to cause adverse effects in the patient as in this case drug will be forced from extravascular sites back into the plasma. The resulting increased drug plasma levels will lead to enhanced pharmacological effects and, possibly, frank toxicity. Displacement of drugs from binding sites simultaneously in both the plasma and in the tissues will combine the effects seen after displacement from the separate areas. Due to decreased binding in both areas, the free drug concentration in the plasma will increase leading to overactivity of the displaced drug.


A tension between surrendering and being involved: An interview study on person-centeredness in clinical reasoning in the acute stroke setting.
To explore how stroke survivors experience and prefer to participate in clinical reasoning processes in the acute phase of stroke care. An explorative qualitative design was used. Individual interviews were conducted with 11 stroke survivors in the acute phase of care and analyzed using reflexive thematic analysis. The analysis identified five themes: What's going on with me?; Being a recipient of care and treatment; The need to be supported to participate; To be seen and strengthened; and Collaboration and joint understanding. Stroke survivors experience many attributes of person-centeredness in the acute phase of care but, according to their stories, their participation in clinical reasoning can be further supported. The tension between surrendering and the desire to be more actively involved in the care needs to be considered to facilitate participation in clinical reasoning. Stroke survivors' participation in clinical reasoning in the acute phase can be facilitated by health professionals noticing signs prompting a shift towards increased willingness to participate. Furthermore, health professionals need to take an active role, sharing their expertise and inviting the stroke survivors to share their perspective. The findings can contribute to further develop person-centered care in acute settings.


Migration from new-accession countries and duration expectancy in the EU-15: 2002-2008.
European Union (EU) enlargements in 2004 and 2007 were accompanied by increased migration from new-accession to established-member (EU-15) countries. The impacts of these flows depend, in part, on the amount of time that persons from the former countries live in the latter over the life course. In this paper, we develop period estimates of duration expectancy in EU-15 countries among persons from new-accession countries. Using a newly developed set of harmonised Bayesian estimates of migration flows each year from 2002 to 2008 from the Integrated Modelling of European Migration (IMEM) Project, we exploit period age patterns of country-to-country migration and mortality to summarize the average number of years that persons from new-accession countries could be expected to live in EU-15 countries over the life course. In general, the results show that the amount of time that persons from new-accession countries could be expected to live in the EU-15 nearly doubled after 2004.


Clinical and microbiological profiles in post-chemotherapy neutropenic fever in hematological malignancy: exploration of clinical phenotype patterns by two-step cluster analysis.
Epidemiology of infectious diseases causing febrile illness varies geographically with human attributes. Periodic institutional surveillance of clinical and microbiological profiles in adding data to updating trends, modulating pharmatherapeutics, signifying possible excessive treatments and risk of drug resistance in post-chemotherapy neutropenic fever (NF) in hematological malignancy (HM) is limited. We aimed to review institutional clinical and microbiological data and explore clinical phenotype pattern groups among data. Available data from 372 NF episodes were included. Demographics, types of malignancies, laboratory data, antimicrobial treatments and febrile-related outcome data such as predominant pathogens and microbiological diagnosed infections (MDIs) were collected. Descriptive statistics, two-step cluster analysis and non-parametric tests were employed. The occurrences of microbiological diagnosed bacterial infections (MDBIs; 20.2%) and microbiological diagnosed fungal infections (MDFIs; 19.9%) were almost equal. Gram-negative pathogens (11.8%) were comparable with gram-positive pathogens (9.9%), with gram-negative being slightly predominant. Death rate was 7.5%. Two-step cluster analysis yielded four distinct clinical phenotype pattern (cluster) groups: cluster 1 'lymphomas without MDIs', cluster 2 'acute leukemias MDBIs', cluster 3 'acute leukemias MDFIs' and cluster 4 'acute leukemias without MDIs'. Considerable NF events with antibiotic prophylaxis being not identified as MDI might have cases in low-risk with non-infectious reasons causing febrile reactions that might possibly not require prophylaxis. Regular institutional surveillance with active parameter assessments to signify risk levels in the post-chemotherapy stage, even prior to the onset of fever, might be an evidence-based strategy in the management of NF in HM.


The use of oral contraceptive is inversely associated with the risk of type 2 diabetes mellitus among middle-aged women.
To assess the cross-sectional association between oral contraceptive (OC) use and type 2 diabetes mellitus (T2DM) risk among US women. The data was obtained from the National Health and Nutrition Examination Survey (NHANES 2007-2018). OC use was assessed by questionnaires and the diagnosis of T2DM was confirmed by the glycosylated hemoglobin, fasting blood glucose, and self-report. Binary logistic regression models and the restricted cubic spline model were adopted to evaluate whether OC use was associated with T2DM. Compared with non-users, the odds ratio (OR) with 95% confidence interval (CI) of T2DM risk for the OC users was 0.71 (0.57-0.89) in unadjusted Model. The association remained significant in fully adjusted models, and the OR with 95%CI was 0.78 (0.62-0.99). In the stratified analyses, there was an inverse association of OC use with T2DM risk when women were overweight. Dose-response analysis also revealed an inversely nonlinear relationship between the duration of OC use and T2DM (p-value for linearity = .589). Our findings suggested that OC use may be inversely associated with T2DM risk.


Identification Of Mutation Sites In Hepatitis C Virus Genotype 3a In Non-Responders To Combination Therapy With Interferon- Αlfa And Ribavirin In Residents Of Khyber Pakhtunkhwa Province Pakistan.
This study was carried out to search for mutations in the gene encoding for Non- Structural Protein 5A, specifically in the interferon sensitivity determining region of hepatitis C virus (HCV) genotype 3a, isolated from serum samples of patients not responding to treatment with oral Ribavirin and Interferon alpha injections. This descriptive case series was conducted on HCV patients reporting in the attached teaching hospitals of Peshawar Medical College selected by consecutive sampling technique from 1st July to 31st December 2012. Amino acid sequencing was performed at the Centre of Applied Molecular Biology Lahore. Patients showing no clinical response after 6 months of combination therapy with Injection Interferon alpha + Ribavirin and still having positive polymerase chain reaction (Declared Non-Responders) were included in this study. Amino acid sequencing was performed on HCV isolates from twenty non-responder and five responder patients. All these sequences were compared with Newzealand1 (NZL1) sequence from the gene bank for mutations; 0-7 mutations were observed in responders as compared to 10-27 mutations in non-responder patients (p value <0.005). We were able to determine that there is a positive correlation between the number of mutations in NS5A ISDR and non-response to combination therapy. Synonymous mutations >10 and non-synonymous mutations >7 in this region suggest poor response to treatment.


Bimodal antibacterial system based on quaternary ammonium silane-coupled core-shell hollow mesoporous silica.
Hollow mesoporous silica (HMS) have been extensively investigated as a biomaterial for drug delivery. The present study developed quaternary ammonium silane-grafted hollow mesoporous silica (QHMS) to create a metronidazole (MDZ) sustained delivery system, MDZ@QHMS, with bimodal, contact-kill and release-kill capability. The QHMS was assembled through a self-templating method. Metronidazole was incorporated within the QHMS core using solvent evaporation. Antibacterial activities of the MDZ@QHMS were investigated using single-species biofilms of Staphylococcus aureus (ATCC25923), Escherichia coli (ATCC25922) and Porphyromonas gingivalis (ATCC33277). The MDZ@QHMS maintained a hollow mesoporous structure and demonstrated sustained drug release and bacteridal actvity against the three bacterial strains at a concentration of 100 μg/mL or above. These nanoparticles were not relatively cytotoxic to human gingival fibroblasts when employed below 100 µg/mL. Compared with HMS, the MDZ@QHMS system at the same concentration demonstrated antibiotic-elution and contact-killing bimodal antibacterial activities. The synthesized drug carrier with sustained, bimodal antibacterial function and minimal cytotoxicity possesses potential for localized antibiotic applications. STATEMENT OF SIGNIFICANCE: The present study develops quaternary ammonium silane-grafted hollow mesoporous silica (QHMS) to create a metronidazole (MDZ) sustained delivery system, MDZ@QHMS, with bimodal, contact-kill and release-kill capability. This system demonstrates sustained drug release and maintained a hollow mesoporous structure. The synthesized drug carrier with sustained, bimodal antibacterial function and excellent biocompatibility possesses potential for localized antibiotic applications.


Impact of the COVID-19 Pandemic on Funerals: Experiences of Participants in the 2020 Dying2Learn Massive Open Online Course.
A Massive-Open-Online-Course (MOOC) on death and dying (Dying2Learn) was offered in 2020, designed to build conversations about death as a natural part of life. In week 1, the content focused on how today's society engages with death through the language we use, humour, public mourning and funerals. This study investigated 2020 MOOC participants' responses to an online activity reflecting on funerals and memorials during the time of COVID-19. From this activity, n = 204 responses were analysed qualitatively. Themes included the positives and negatives of virtual funeral attendance (e.g. opportunity to have a way to participate when travel barriers existed, versus a sense of impersonal voyeurism); and the challenges related to the inability to physically comfort the bereaved due to physical distancing requirements. Comments made as part of this MOOC activity provide a unique insight into the community's experience of funeral changes necessitated by COVID-19, with important implications for the grieving process.


Oxidation of X-ray compound ditrizoic acid by ferrate(VI).
Iodinated X-ray contrast media (ICM) such as diatrizoic acid (DTZA) is used in large amounts in hospitals to enhance imaging of organs and blood vessels during radiography. Due to its persistence and non-biodegradability, it is found in treated water, sewage effluent, surface waters, and aquatic environments. This paper presents the kinetics of the oxidation of DTZA by ferrate(VI) (Fe(VI)O4(2-), Fe(VI)) as a function of pH (7.1-9.6) at 25 degrees C in order to determine the effectiveness of Fe(VI) to remove DTZA from water. The reaction was determined to be first-order with respect to concentrations of Fe(VI) and DTZA. The rate of the reaction was found to be pH dependent and the rate decreased nonlinearly as the pH increase from 7.1 to 9.6. The speciation of Fe(VI) (HFeO4(-) and FeO4(2-)) was used to explain the rate dependence on pH. The calculated rate constant of Fe(VI) with DTZA at pH 7.0 was compared with nitrogen-containing pollutants and is briefly discussed.


Fluoroquinolone antibiotics in infants and children.
The use of fluoroquinolones in children is limited because of the potential of these agents to induce arthropathy in juvenile animals and to potentiate development of bacterial resistance. No quinolone-induced cartilage toxicity as described in animal experiments has been documented unequivocally in patients, but the risk fro rapid emergence of bacterial resistance associated with widespread, uncontrolled fluoroquinolones use in children is a realistic threat. Overall, the fluoroquinolones have been safe and effective in the treatment of selected bacterial infections in pediatric patients. There are clearly defined indications for these compounds in children who are ill.


The effects of acoustic trauma that can cause tinnitus on spatial performance in rats.
Previous studies have shown that acoustic trauma can disrupt the firing of place cells in the hippocampus and also inhibit hippocampal neurogenesis, suggesting that such trauma might impair spatial memory. In this study, we investigated performance in the alternating T maze and Morris water maze of rats exposed to acoustic trauma (16 kHz, 110 dB SPL pure tone for 1 h), who had elevated auditory brainstem response thresholds and the psychophysical attributes of tinnitus (using a conditioned lick suppression task). To our surprise, we found that rats with tinnitus did not perform significantly differently from sham control animals in either the alternating T maze task or any aspect of the reference or working memory versions of the Morris water maze task except for a faster acquisition in T maze alternation. These results suggest that acoustic trauma and tinnitus may not impair spatial memory in rats.


Prevalence of delirium in intensive care patients and association with sedoanalgesia, severity and mortality.
To establish the prevalence of delirium and its subsyndrome in intensive care and to associate it with the use of sedative and analgesia, severity and mortality. Carried out in two intensive care units of adult patients, this is a quantitative and transversal study, with 157 patients, using the Richmond Agitation-Sedation Scale to assess the level of sedation and the Intensive Care Delirium Screening Checklist for delirium. The T test and Chi-square test were applied for statistical analysis. The prevalence of delirium was 22.3%, and 49.7% of the subsyndrome. Associations of the use of midazolam with the presence of delirium (p=0.05) and subsyndromal delirium (p<0.01), use of clonidine with the appearance of delirium (p<0.01) and of fentanyl with subsyndromal delirium (p=0.09). There were no significant differences between the mortality of patients with delirium (p=0.40) and subsyndromal delirium (p=0.86), as well as association with the mortality score. The use of sedoanalgesia is associated with the presence of delirium and subsyndromal delirium. No significant statistical associations were found between the severity and mortality scores.


Mortality and causes of death in patients with end-stage renal failure.
Using data from the Michigan Kidney Registry, the survival of patients with end-stage renal disease (ESRD) was evaluated by multivariate analysis. Black patients had a significantly better outcome overall. A significantly worse outcome was found for older patients and diabetics, among both races and for black females. Causes of death were analyzed for dialysis patients and specific comments address discontinuation of dialysis leading to death.


Nutrient recovery from domestic wastewater using a UASB-duckweed ponds system.
The pilot-scale wastewater treatment system used in this study comprised a 40-l UASB reactor (6-h HRT) followed by three duckweed ponds in series (total HRT 15 days). During the warm season, the treatment system achieved removal values of 93%, 96% and 91% for COD, BOD and TSS, respectively. Residual values of ammonia, TKN and total phosphorus were 0.41 mg N/l, 4.4 mg N/l and 1.11 mg P/l, with removal efficiencies of 98%, 85% and 78%, respectively. The system achieved 99.998% faecal coliform removal during the warm season with final effluent containing 4 x 10(3) cfu/100 ml. During the winter, the system was efficient in removing COD, BOD and TSS but not nutrients. The system was deficient in the removal of faecal coliforms during the winter, producing effluent with 4.7 x 10(5) cfu/100 ml. During the warm season, the N removal consisted of 80% by plant uptake, 5% by sedimentation and 15% unaccounted for. A duckweed production rate of 33 t dry matter per hectare per 8 months was achieved.


Selective Catalytic Frustrated Lewis Pair Hydrogenation of CO2 in the Presence of Silylhalides.
The frustrated Lewis pair (FLP) derived from 2,6-lutidine and B(C6 F5 )3 is shown to mediate the catalytic hydrogenation of CO2 using H2 as the reductant and a silylhalide as an oxophile. The nature of the products can be controlled with the judicious selection of the silylhalide and the solvent. In this fashion, this metal-free catalysis affords avenues to the selective formation of the disilylacetal (R3 SiOCH2 OSiR3 ), methoxysilane (R3 SiOCH3 ), methyliodide (CH3 I) and methane (CH4 ) under mild conditions. DFT studies illuminate the complexities of the mechanism and account for the observed selectivity.


Securing genetic integrity in freshwater pearl mussel propagation and captive breeding.
Securing genetic integrity is of key importance in conservation-oriented captive breeding programs releasing juveniles into the wild. This is particularly true for species such as the endangered freshwater pearl mussel (Margaritifera margaritifera) for which a number of captive breeding facilities has been established in Europe. The core objective of this study was to compare the genetic constitution of 29 cohorts of captive-bred freshwater pearl mussels from five different breeding facilities in Austria, France, Luxembourg and Germany, with their original 14 source populations from nine major European drainages, based on microsatellite markers. Captive-bred mussels represented 11 different genetic clusters, suggesting an important contribution of the breeding stations to securing the genetic diversity of the species. In almost all cases, the cultured offspring closely resembled the genetic constitution of the source mussels as revealed from the STRUCTURE analysis and the generally high assignment of offspring to the original source populations. The majority of captive-bred cohorts had an increased inbreeding coefficient and decreased genetic variability compared to their source populations as measured by AR and HO. Highest numbers of deformed juveniles coincided with very low levels of HO < 0.05. Since erosion of genetic diversity in captive breeding was mostly evident in individual year-cohorts, long-term breeding over multiple years can minimize such effects. The systematic selection of priority populations for conservation, effective breeding strategies avoiding effects of in- and outbreeding by genetically informed selection of parent individuals, and a network of collaboration among the different breeding facilities would be very useful to increase resilience and effectiveness.


Lipidomics study of the therapeutic mechanism of Plantaginis Semen in potassium oxonate-induced hyperuricemia rat.
Plantaginis Semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but its pharmacological mechanism remains unclear. This study investigated the therapeutic mechanism of Plantaginis Semen extract on potassium oxonate -induced HUA rats based on a lipidomics approach. A model of HUA was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis Semen groups (n = 7). The Plantaginis Semen groups were treated orally with Plantaginis Semen, 0.9375, 1.875 or 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used for the serum lipidomics analysis, multivariate statistical analysis and independent samples t-test were carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors were determined by quantitative real-time polymerase chain reaction (RT-qPCR). Compared with the model group, the levels of serum UA, Cr, TG and TNF-α were significantly (p < 0.05) decreased in benzbromarone and three Plantaginis Semen groups. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was most affected. These perturbations were partially restored via treatment of benzbromarone and Plantaginis Semen. Additionally, the mRNA expression levels of urate anion transporter 1 (URAT1) and phosphatidylinositol 3-kinase/protein kinases B (PI3K/Akt) were significantly decreased (p < 0.01) after treatment with benzbromarone and high dose of Plantaginis Semen. Plantaginis Semen had significant effects on anti-HUA, anti-inflammatory and renal protection. It attenuated potassium oxonate-induced HUA through regulation of lipid metabolism disorder.


Postoperative futile care: stopping the train when the family says "keep going".
All surgeons must take risks when providing medical care. No guarantees of protection from a lawsuit exist in any guise. Concerning postoperative futile care, the stakes are high when withdrawal of support seems to be indicated but the surrogate believes in sanctity-of-life and demands continued aggressive care. Open-ended questions posed to the family may initiate a dialog that help the surgeon understand their values and negotiate a resolution. Other preventive measures can also reduce the chance of conflict and potential liability. "Do what's right" is a proverbial motto in surgical training and clinical practice. To some surgeons, it may be to honor the wishes of the family surrogate. To others, the right thing may be to withdraw care in the best interest of the patient. If so, "do what's right" is not just to "stop the train." It also consists of a range of clinical activities, including effective communication, emotional care, and pursuing a fair and open negotiation process established by the institution. Properly conducted, "stopping the train" should incur no greater risk for professional liability than any other challenging procedure that surgeons perform. Withdrawal of futile care should be considered as a procedure, and as such, the skills to deliver it should be mastered like any other.


Neural-inducing activity of newly mesodermalized ectoderm.
The neural-inducing activity of artificially mesodermalized ectoderm was examined. The competent ectoderm of earlyCynops gastrula was mesodermalized by being placed in contact withCarassius swimbladder. The mesodermalized ectoderm was combined with ectoderm isolated from various developmental stages of a gastrula. Neural differentiation were observed in half the combinants, even in 18 h ectoderm, which is considered to have lost its neural competence within 6 h. This indicates that mesodermalized ectoderm is capable of inducing neural tissues at the very time it comes into contact with 18 h ectoderm. From the present study, the neural-inducing activity of mesodermalized cells may possibly be closely connected to the early process of their mesodermalization.


Lower myocardial infarction and all-cause mortality with laparoscopic cholecystectomy compared with open cholecystectomy.
Aim: We compared inpatient outcome data of open (OC) versus laparoscopic cholecystectomy (LC). Patients & methods: We used the National Inpatient Samples database from 2010-2014. Results: LC was done in 340,999 and OC in 68,529 OC patients. In 2010, ST-elevation myocardial infarction (STEMI) prevalence was 0.2 versus 0% (OR: 3.1, CI: 1.7-5.5; p < 0.001), non-STEMI 1 versus 0.4% (OR: 2.5 CI: 2.0-3.0; p < 0001), mortality 3.4 versus 0.4% (OR: 9.2, CI: 7.9-10.6; p < 0001). After multivariate adjustment, OC remained independently associated with STEMI, non-STEMI and all-cause inpatient mortality (mortality multivariate OR: 6.4, CI: 5.5-7.4; p < 0001, STEMI OR: 2.2. CI: 1.2-3.9; p = 0.007, non-STEMI OR: 1.5, CI: 1.3-1.9; p < 0001). Conclusion: OC is independently associated with STEMI, non-STEMI and all-cause inpatient mortality compared with LC.


Variation of Aujeszky's disease viruses in wild swine in USA.
In the United States of America, Aujeszky's disease (pseudorabies) has been eradicated from all domestic swine. Some re-emergence of infection occurred as vaccine use diminished. Sporadic outbreaks have also occurred because of the reservoir of infection in feral swine that have spread across the southern two-thirds of the country and Hawaii. In order to be able to understand the origins of re-emerging virus, sequence analysis of variable genes in pseudorabies virus (PRV) has been used to differentiate strains. Most PRV from feral swine can be distinguished from virus circulating in domestic pigs during the national epizootic. However, several feral swine isolates of PRV from south central states are closely related or identical in sequence to strains from domestic pigs. Extensive study by PCR for the presence of virus in the oral cavity of feral pigs disclosed that the viral DNA is distributed widely in tonsils salivary glands, taste buds and even mucosa in the vicinity of tusks. Clearly the virus in feral swine has multiple mechanisms of transmission to insure persistent infection and the threat of re-emergence in domestic swine continues.


The presence of congenital hypertrophy of the retinal pigment epithelium in a subgroup of patients with adenomatous polyposis coli mutations.
Patients expressing congenital hypertrophy of the retinal pigment epithelium (CHRPE) are clustered within specific families with familial adenomatous polyposis (FAP). CHRPE has been found to be dependent on the position of the mutation in the adenomatous polyposis coli (APC) gene. The significance of the CHRPE finding in view of this new evidence is discussed.


Immunohistochemical localization of protein kinase C (PKC) beta I in the pig retina during postnatal development.
In order to investigate the expression of protein kinase C (PKC) beta I in the retinas of pigs during postnatal development, we analyzed retinas sampled from 3-day-old and 6-month-old pigs by Western blotting and immunohistochemistry. Western blot analysis detected the expression of PKC beta I in the retinas of 3-day-old piglets and it was increased significantly in the retinas of 6-month-old adult pigs. Immunohistochemical staining showed PKC beta I in the retinas of both groups. Immunohistochemistry of 3-day-old retinas revealed weak PKC beta I reactivity in the ganglion cell layer, inner plexiform layer, inner nuclear cell layer, outer plexiform layer and rod and cone cell layer. In the 6-month-old pig retina, the cellular localization of PKC beta I immunostaining was similar to that of the 3-day-old retina, where PKC beta I was localized in some glial fibrillary acidic protein-positive cells, glutamine synthetase-positive cells, parvalbumin-positive cells, and PKC alpha-positive cells in the retina. This is the first study to show the expression and cellular localization of PKC beta I in the retina of pigs with development, and these results suggest that PKC beta I, in accordance with PKC alpha, plays important roles in signal transduction pathways in the pig retina with development.


Modulation of Hb-O2 affinity to improve hypoxemia in COVID-19 patients.
This opinion paper aims at discussing the potential impact of modulating the Hb-O2 affinity by the nutritional supplement 5-HMF on patients affected by COVID-19. The paper describes the critical role of the oxygen affinity in hypoxemic COVID-19 patients and the potential positive effect of 5-HMF, a compound shown to increase the Hb-O2 affinity.


Vitamin C-treated murine bone marrow-derived dendritic cells preferentially drive naïve T cells into Th1 cells by increased IL-12 secretions.
Vitamin C has been reported to shift immune responses toward Th1. In this study, we evaluated whether this effect was by way of dendritic cells. Murine dendritic cells (DCs) were prepared from bone marrow precursors. DCs treated with vitamin C secreted an increased amount of IL-12p70 after activation with LPS. These cells rendered naïve T cells to secrete more Th1 cytokine, IFN-γ, and less Th2-cytokine, IL-5 in the culture supernatants. Vitamin C-treatment also increased phosphorylation of p38 and ERK1/2 in DCs. p38 inhibitor in culture media suppressed the effect of vitamin C to elevate IL-12p70 secretion. In contrast, ERK inhibitor elevated IL-12p70 secretion. In summary, vitamin C taken up into DCs increased IL-12p70 secretion of these cells by modulating the activation of signal molecules, and thus shifted immune responses toward Th1. These data provide us a new insight on the role of vitamin C in modulating immune responses.


Adolescents and media violence: six crucial issues for practitioners.
The mass media are rife with violent images and messages and youth spend a great deal of time with media. A rich tradition of research shows that exposure to media violence leads to aggressive thoughts, emotions, and behavior, and also to fear and desensitization. Certain youth are more vulnerable to violent media messages and images; the impact of media violence is modified by its nature and context. Parents, teachers, and the media industry should work toward mitigating the effects of media violence on youth; pediatricians and other health care providers play a key role in fostering healthy family media habits.


Inverse association between changes in energetic cost of walking and vertical accelerations in non-metastatic breast cancer survivors.
With accelerometry, the utility to detect changes in physical activity are predicated on the assumption that walking energetics and gait mechanics do not change. The present work examined associations between changes (∆) in walking energetics, exercise self-efficacy, and several accelerometer-derived metrics. Secondary analyses were performed among a sub-sample (n = 29) of breast cancer survivors participating in a larger randomized trial. During 4 min of treadmill walking (0.89 m s-1, 0% grade), indirect calorimetry quantified steady-state energy expenditure (EE), wherein, participants were fitted with a heart rate monitor and hip-worn triaxial accelerometer. Exercise self-efficacy was measured using a 9-item questionnaire, while vector magnitude (VM) and individual planes (e.g., mediolateral, vertical, and anteroposterior) of the movement were extracted for data analyses. Evaluations were made at baseline and after 3 months. From baseline to 3 months, the energetic cost of walking (kcals min-1) significantly decreased by an average of - 5.1% (p = 0.001; d = 0.46). Conversely, VM significantly increased (p = 0.007; d = 0.53), exclusively due to greater vertical accelerations (acc) (+ 5.7 ± 7.8 acc; p = 0.001; d = 0.69). Changes in vertical accelerations were inversely and positively associated with ∆walking EE (r = - 0.37; p = 0.047) and ∆exercise self-efficacy (r = 0.39; p = 0.034), respectively. Hip-worn accelerometers do not appear well-suited to correctly detect changes in ease of walking as evidenced by reduced energetic cost. Further research should determine if a divergence between measured EE and vertical accelerations could contribute to erroneous inferences in free-living physical activity.


Mapping Genetic Interactions in Human Cancer Cells Using a One-Step tRNA-CRISPR System.
While well studied in yeast, mapping genetic interactions in mammalian cells has been limited due to many technical obstacles. We have recently developed a new one-step tRNA-CRISPR method called TCGI (tRNA-CRISPR for genetic interactions) which generates high-efficiency, barcode-free, and scalable pairwise CRISPR libraries to identify genetic interactions in mammalian cells. Here we describe this method in detail regarding the construction of the pairwise CRISPR libraries and performing high throughput genetic interacting screening and data analysis. This novel TCGI dramatically improves upon the current methods for mapping genetic interactions and screening drug targets for combinational therapies.


Systemic hemodynamic changes raising brain temperature in REM sleep.
The present research studied the mechanisms underlying the increase in brain temperature during REM sleep in the unrestrained rabbit carrying chronically implanted electrodes, thermistors and common carotid artery occluders. During the ultradian wake-sleep cycle at constant ambient temperature (25+/-2 degrees C), we recorded: (i) the ear pinna temperature as an indirect indicator of blood flow affecting heat loss from the systemic heat exchangers of the head, (ii) the temperature of the pons and hypothalamus as indirect indicators of the temperature of vertebral artery blood (systemic cooling only) and carotid artery blood (both systemic and selective cooling), respectively, and (iii) the changes induced in these temperatures by short-lasting bilateral common carotid artery occlusion. The results show that during REM sleep both systemic and selective brain cooling are depressed by a spontaneous decrease in the common carotid artery blood flow and the associated autoregulatory increase in the vertebral artery share of the cerebral blood supply.


Influence of Crescentia cujete and Launaea taraxacifolia leaves on growth, immune indices, gut microbiota, blood chemistry, carcass, and meat quality in broiler chickens.
The rising concerns pertaining to the safety of synthetic supplements in livestock production have encouraged the exploration of potential alternatives. This study investigated the growth, gut microbiota, blood chemistry, immune indices, meat quality, and antioxidant status in broiler chickens supplemented with Crescentia cujete leaf (CCL), Launaea taraxacifolia leaf (LTL), and a combination of antibiotic (70% oxytetracycline + 30% neomycin) and tert-Butylhydroxyanisole. One-day-old Ross 308 chicks (n = 420) were randomly assigned to either T-1, basal diet (BD) only; T-2, BD + 0.4 g/kg antibiotic + 0.13 g/kg tert-butylhydroxyanisole; T-3, BD + 2.5 g/kg LTL; T-4, BD + 5 g/kg LTL; T-5, BD + 2.5 g/kg CCL; or T-6, BD + 5 g/kg CCL for 42 days. Each dietary group had seven replicates with ten chicks per replicate. Body weight gain and carcass weight were higher (P < 0.05) in the T-2, T-4, T-5, and T-6 birds compared with those of other birds. At 1-21 days, the T-2 and T-4 birds consumed more feed than the T-1 and T-3 birds. At 22-42 days, the T-4 birds consumed more (P < 0.05) feed than the T-1 and T-3 birds. During 1-42 days, the T-1 and T-3 birds consumed less (P < 0.05) feed than other birds. At 22-42 days and 1-42 days, the T-1 had lower feed efficiency (P < 0.05) than other birds except for the T-3 birds. The CCL and LTL birds had lower (P < 0.05) serum LDL cholesterol and higher HDL cholesterol compared with other birds. Hematology, splenic interleukin-1β, immunoglobulin M, ileal and caecal total aerobic bacteria counts, caecal Lactobacillus spp., and meat physicochemical properties were unaffected by diets. The T-1 birds had higher (P < 0.05) ileal and caecal Clostridium spp., E. coli, and Salmonella spp. compared with birds fed other diets. The CCL and LTL birds had higher ileal Lactobacillus counts. Splenic IL-10 was higher (P < 0.05) in the T-2, T-4, and T-6 birds compared with that in other birds. Dietary supplementation with CCL, LTL, and a combination of antibiotic and tert-butylhydroxyanisole repressed (P < 0.05) splenic tumor necrosis-α and immunoglobulin G. The T-1 breast meat had lower glutathione peroxidase and catalase. The T-4 meat had higher (P < 0.05) superoxide dismutase, glutathione peroxidase, catalase, and total antioxidant capacity compared with other meats. On day 3 postmortem, meats obtained from birds supplemented with CCL, LTL, and a combination of antibiotic and tert-butylhydroxyanisole had lower (P < 0.05) carbonyl and malondialdehyde contents than the meat from the non-supplemented birds. The 5 g/kg CCL and 5 g/kg LTL could be used as antimicrobial and antioxidant in broiler diets.


A phase II study of ifosfamide in children with recurrent solid tumours.
Twenty children with recurrent or unresponsive tumours (10 Wilms', 3 rhabdomyosarcoma, 4 Ewings's, 1 osteosarcoma, 1 hepatoblastoma, 1 hepatoma) and one untreated patient with renal carcinoma were given ifosfamide as a 24-h infusion (5 mg/m2), with mesna as uroprotective. The number of courses ranged from 1 to 13 (median 3), and the interval between them was 2-3 weeks. Sixteen of these patients had previously received cyclophosphamide. Complete clinical responses were seen in 3 cases (2 Wilms' and 1 Ewing's) and lasted 5, 7, and 9 months. Partial responses were seen in 3 instances, mixed response or stable disease in 4, and progressive disease in 11. Treatment was well tolerated in most patients, with no cystitis or severe myelosuppression, but 2 children developed transient neurological symptoms and 1 became hypertensive. Nausea and vomiting were controlled by high-dose dexamethasone in most children. Plasma ifosfamide levels were estimated by means of gas-liquid chromatography in 10 patients. Peak concentrations ranged from 38 to 125 micrograms/ml (median 80). The elimination half-life, at 2.5-5.2 h (median 3.2) was shorter than previously reported in adults. Future studies should test the possibility that ifosfamide-containing combination chemotherapy may be more effective than the regimens, usually including cyclophosphamide, that are currently used as front-line treatment of embryonal and Ewing's sarcoma.


Assembly and characterization of lipid-lipid binding protein particles.
Lipid-protein complexes, lipoplexes, are currently of great interest because of their immunogenic, gene free, and low cost properties. For their applications as potential vaccines, it is critical to display a target protein on the surface of lipoplex particles to allow external interactions to take place. However, how to effectively assemble lipoplexes with target proteins externally accessible is a constant challenge. In this study, human liver fatty acid binding protein 1 (hl-FABP1) was used as a model protein in lipoplex assembly with a non-lipid binding protein, bovine serum albumin (BSA), serving as a comparison. The protein-lipid particles were assembled by four different processes and characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), flow cytometry (FCM), and a modified ELISA. Results indicate that by incubating the target protein with pre-formed liposomes at a temperature higher than all transition temperatures (T(m)) of the lipids used through an extended period of time, 1.48×10(-6)nmol per lipoplex of incorporated proteins can be detected by ELISA and are externally accessible. Additional experiments showed that most of those externally accessible proteins are likely embedded in the lipid bilayer structure and are not subject to dissociation from the lipoplex particles at elevated salt concentrations.


The use of mRNA translation in vitro and in ovo followed by crossed immunoelectrophoretic autoradiography to study the biosynthesis of human cholinesterases.
The synthesis of various cholinesterases in different fetal human tissues was studied using in vitro and in ovo translation of poly(A)+ RNA, followed by crossed immunoelectrophoretic autoradiography. When unfractionated poly(A)+ mRNA from fetal brain, muscle, or liver was translated in vitro, in the reticulocyte lysate cell-free system, polypeptides were synthesized which reacted with antibodies against either "true" acetylcholinesterase (acetylcholine hydrolase; EC 126.96.36.199) or "pseudo", butyrylcholinesterase (acylcholine acylhydrolase; EC 220.127.116.11). The two nascent cholinesterases could be separated by crossed immunoelectrophoresis followed by autoradiography, suggesting that acetylcholinesterase and butyrylcholinesterase are produced in all three tissues from nascent polypeptides containing different immunological domains. To examine whether the biosynthesis of cholinesterases includes posttranslational processing events, Xenopus oocytes were microinjected with mRNA from these tissues. Immunoelectrophoretic analysis of oocyte intracellular homogenates and incubation medium revealed various precipitation arcs, reflecting the synthesis and posttranslational processing of multiple forms of tissue-specific exported and intracellular acetylcholinesterase and butyrylcholinesterase. These findings demonstrate that polymorphic cholinesterases are produced from nascent polypeptide products which undergo further posttranslational processing events in a tissue-specific manner before they become mature compartmentalized cholinesterases.


A phase II evaluation of elesclomol sodium and weekly paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer: An NRG oncology/gynecologic oncology group study.
Preclinical data suggest elesclomol increases oxidative stress and enhances sensitivity to cytotoxic agents. The objective of this prospective multicenter phase 2 trial was to estimate the activity of IV elesclomol plus weekly paclitaxel in patients with platinum-resistant recurrent ovarian, tubal or peritoneal cancer through the frequency of objective tumor responses (ORR). Patients with measurable disease, acceptable organ function, performance status ≤ 2, and one prior platinum containing regimen were eligible. A two-stage design was utilized with a target sample size of 22 and 30 subjects, respectively. Prior Gynecologic Oncology Group studies within the same population involving single agent taxanes showed an ORR of approximately (20%) and served as a historical control for direct comparison. The present study was designed to determine if the regimen had an ORR of ≥40% with 90% power. Fifty-eight patients were enrolled, of whom 2 received no study treatment and were inevaluable. The median number of cycles was 3 (268 total cycles, range 1-18). The number of patients responding was 11 (19.6%; 90% CI 11.4% to 30.4%) with one complete response. The median progression-free survival and overall survival was 3.6 months and 13.3 months, respectively. The median ORR duration was 9.2 months. Percentages of subjects with grade 3 toxicity included: Neutropenia 9%; anemia 5%; metabolic 5%; nausea 4%; infection 4%; neurologic (mostly neuropathy) 4%; and vascular (mostly thromboembolism) 4%. There were no grade 4 toxicities reported. This combination was well tolerated but is unworthy of further investigation based on the proportion responding [ClinicalTrials.gov Identifier: NCT00888615].


Implementation of a computer-guided consultation in the assessment of suspected obstructive sleep apnoea syndrome.
We describe implementation of a clinical decision support system, a computer-guided consultation (CGC), in the assessment of subjects referred with suspected obstructive sleep apnoea syndrome (OSAS). Two cohorts of patients were assessed. The first 100 cases had data collected with the CGC by a specialist sleep physician (stage1). A further 100 cases were assessed by a nonspecialist using the CGC (stage 2). For each case, the diagnosis suggested by the CGC was compared with the final diagnosis made by a second specialist sleep physician blinded to the CGC diagnosis. Stage 1: of 100 people evaluated, a final diagnosis of OSAS was made by both the sleep specialist and CGC in 88% of cases. In 7 of the remaining 12 cases, both agreed there was "No evidence of OSAS"; in 5 cases the CGC did not reach a final diagnosis instead prompting specialist referral. Stage 2: 100 people were evaluated; 95% were evaluable. Both CGC and the sleep specialist made a diagnosis of OSAS in 83 cases (87%), in 5 cases both agreed there was no OSAS, whereas in 7 cases the CGC prompted a specialist review due to unexplained symptoms. The CGC was concordant with the final diagnosis in 95% and 93% of cases in the two cohorts, respectively and where there was doubt, prompted for clinical review. No OSAS cases were overlooked by the CGC. An intelligent CGC program creates opportunities in sleep medicine management pathways to safely yet effectively utilise nonspecialists working under specialist supervision.


Effects of a nanocomposite containing Orbignya speciosa lipophilic extract on Benign Prostatic Hyperplasia.
Lower urinary tract symptoms (LUTS) are a common complaint among aging men and are usually caused by Benign Prostatic Hyperplasia (BPH). A number of medical treatments for LUTS/BPH exist, such as α-blockers, 5α-reductase inhibitors, phytotherapeutical drugs and combination therapies. Babassu is the common name of a Brazilian native palm tree called Orbignya speciosa, whose kernels are commonly used (eaten entirely or as a grounded powder), in parts of Brazil for the treatment of urinary disorders. This study investigates the effects of Orbignya speciosa nanoparticle extract, a newly developed phytotherapic formulation derived from the kernels of babassu, in the treatment of BPH. Orbignya speciosa extract was obtained from the kernels, a nanoparticulate system was developed and acute toxicity test was performed. BPH primary stromal cell and tissue cultures were established and treated with 300μg/mL Orbignya speciosa nanoparticle (NanoOse) extract in order to evaluate its effects on apoptosis induction, cytotoxicity, cell morphology and proliferation. Our results indicated that NanoOSE shows no toxicity in animals and acts incisively by promoting morphological cell changes, reducing cell proliferation as well as inducing necrosis/apoptosis on BPH cells and tissues. This study provided the first report of the successful use of NanoOSE on BPH treatment which corroborates with the popular use of the kernels of this plant. The results also suggest the potential of NanoOSE as a candidate new phytotherapeutic agent on the management of BPH.


Factors Influencing Physical Medicine & Rehabilitation Trainee Research Engagement.
Research engagement during Physical Medicine and Rehabilitation (PM&R) residency and fellowship training is essential for advancing evidence-based medicine and fostering the development of clinician-scientists. Current Accreditation Council for Graduate Medical Education (ACGME) guidelines regarding research requirements during PM&R training are ambiguous, and it is unknown whether PM&R trainees receive adequate support to pursue research at the level they desire. This anonymous survey study aimed to identify perceived barriers and facilitators to research engagement among United States PM&R residents and fellows. Our findings suggest that PM&R trainees value research engagement. However, research productivity during PM&R residency is limited, with many trainees reporting inadequate support and time to participate in research in a meaningful way. Additional support from residency and fellowship programs, including protected time for research, as well as research-specific education and mentorship should be considered to enhance PM&R trainee research engagement.


Coordinate-based meta-analysis of experimentally induced and chronic persistent neuropathic pain.
Differences in brain activation in experimentally induced and chronic neuropathic pain conditions are useful for understanding central mechanisms leading to chronic neuropathic pain. Many mapping studies investigating both pain conditions are now available, and the latest tools for coordinate-based meta-analysis offer the possibility of random effects statistics. We performed a meta-analysis based on a literature search of published functional magnetic resonance imaging group studies to compare patterns of activity during experimentally induced and chronic neuropathic pain, for the later including four fibromyalgia studies. Stimulus-dependent activation in experimental pain was further divided into "thermal" and "non thermal" stimuli. A conjunction of experimentally induced and chronic neuropathic pain revealed activation of the bilateral secondary somatosensory cortex, right middle cingulate cortex, right inferior parietal lobe, supplementary motor area, right caudal anterior insula, and bilateral thalamus. Primary somatosensory activation was only observed during experimental non-thermal stimulation. Chronic neuropathic pain studies showed increased activation in the left secondary somatosensory cortex, anterior cingulate cortex, and right caudal anterior insula when compared to experimentally induced pain. Activation clusters in the anterior cingulate cortex and caudal anterior insula suggest a strong emotional contribution to the processing of chronic neuropathic pain.


Emerging insights into inflammatory bowel disease from the intestinal microbiota perspective: a bibliometric analysis.
Inflammatory bowel disease (IBD) has caused severe health concerns worldwide. Studies on gut microbiota have provided new targets for preventing and treating IBD. Therefore, it is essential to have a comprehensive understanding of the current status and evolution of gut microbiota and IBD studies. A bibliometric analysis was performed on documents during 2003-2022 retrieved from the Scopus database, including bibliographical profiles, citation patterns, and collaboration details. Software programs of VOSviewer, CiteSpace, and the Bibliometrix R package visually displayed the mass data presented in the scientific landscapes and networks. 10479 publications were retrieved, showing a steadily growing tendency in interest. Xavier Ramnik J. group led the total number of publications (73 papers) and 19787 citations, whose productive work aroused widespread concern. Among the 1977 academic journals, the most prolific ones were Inflammatory Bowel Diseases, Frontiers in Immunology, and Nutrients. Research outputs from the United States (US, 9196 publications), China (5587), and Italy (2305) were highly ranked. Our bibliometric study revealed that the role of gut microbiota has become a hot topic of IBD research worldwide. These findings are expected to improve understanding of research characteristics and to guide future directions in this field.


[Observational study of links of interest disclosure at the Congress of General Medicine France and links of interest of French physicians attending].
Medical opinion leaders represent a marketing tool whose effectiveness is well documented in France and worldwide. They are less distrusted than pharmaceutical representatives, but this trust declines when they declare their ties. In France, the public database "Transparence-Santé" presents the financial ties of each professional with the health industries since 2012. These ties must be declared at the beginning of any public intervention since 2002 to improve the transparency of healthcare stakeholders. This study assessed the compliance with the obligation to disclose conflicts of interests at the Congress of General Medicine France 2020. Its secondary objective was to assess the financial ties of French physicians attending the congress using the data listed in "Transparence-Santé" through the Eurosfordocs project. Prospective cross-sectional observational study of all the interventions available on the congress' internet platform. All speakers, making either an oral or a written and commented presentation, who must declare their conflicts of interest, were included. A descriptive analysis of "Transparence-Santé" data was carried out for the doctors attending the congress. Among 253 interventions, 34% complied with the disclosure requirement. The doctors participating in symposiums links of interests represented 92% of the global amount of congress' links of interests, with an average of 11,2k€/year, significantly higher than the 126€/year of other physicians. The legal obligation to declare one's conflict of interest at congresses is little respected in France. Involvement of the organizers and using pre-established disclosure formats would improve transparency. It is necessary to develop the independence of speakers to improve research and medical expertise.


[Light- and electron-microscopic examinations of deep keratomycosis (aspergillosis) (author's transl)].
Light-microscopic and ultrastructural examinations of a corneal button with deep keratomycosis revealed that keratocytes are partly injured and partly of normal structure. In the cellular reaction, macrophages especially, are found that encircle hyphae with pseudopodia or cover the apical end of the fungi. In many sections, the fungal walls are very resistant to phygocytosis, but, on the contrary, the cytoplasm is damaged earlier and more severely. The cellular reaction in the anterior chamber is massive and intensive with predominance of macrophages.


Characterizing polycyclic aromatic hydrocarbons on road dusts in Shenzhen, China: implications for road stormwater reuse safety.
Urban road stormwater reuse is one of the most effective ways to mitigate water resource shortage. However, due to a diversity of human activities such as traffic, various toxic pollutants can be deposited on road surfaces during dry periods and washed off during wet periods, threatening stormwater reuse safety. Among these pollutants, polycyclic aromatic hydrocarbons (PAHs) have been widely found in road stormwater. This study selected twelve road sites in Shenzhen, China, and investigated PAHs deposited on urban roads and their influential factors (traffic characteristics, land use and road surface condition). The research outcomes showed that high-molecular-weight PAH species (5-6 benzene rings) had higher concentrations and variability on spatial distributions than light-molecular-weight ones (2-4 benzene rings). Additionally, more PAHs were attached to dusts with small particle sizes (< 150 µm), and among influential factors, commercial land use showed a stronger correlation with PAHs distributions, regardless of particle sizes. Furthermore, it is noteworthy that traffic volume did not have an important influence on PAH generations on roads, while the source tracking results did indicate that traffic activities were the main contributor of PAHs. This implies that other traffic characteristics such as frequent go-and-stop activities might also contribute PAHs on roads. This means that areas with frequent traffic congestions could be the "hot spot" areas of PAHs, although the traffic volume might be not high. These research outcomes can provide useful insight into effective stormwater management and ensuring their reuse safety.


Vitamin D-binding protein in the perinatal period.
The molecular polymorphism and quantitative levels of serum vitamin D-binding protein (DBP) were ascertained in a group of preterm, full-term and hypocalcaemic full-term newborn infants. The serum concentration of DBP is not influenced by phenotype and increases with fetal age from the 32nd-33rd week of gestation until the 35th week of gestation. Neither different DBP allele distribution nor abnormal quantitative levels found among 29 hypocalcaemic full-term newborn infants.


NH2-CuO-MCM-41 covalently cross-linked multipurpose membrane for applications in water treatment: Removal of hazardous pollutants from water, water desalination and anti-biofouling performance.
The current study was planned to fabricate a new set of membranes to target multiple application areas such as desalting, removal of micropollutants and antibiofouling performance. In-situ incorporated copper oxide to MCM-41 (CuO-MCM-41) was synthesized and amine (-NH2) functionalized by reacting with N1-(3-trimethoxy silylpropyl) diethylenetriamine (NTSDETA) yielding NH2-CuO-MCM-41. Different concentrations of NH2-CuO-MCM-41 were covalently cross-linked in polyamide active layer during interfacial polymerization (IP) between N, N'-bis(3-aminopropyl)ethylenediamine and terephthaloyl chloride (TPC) on polysulfone/poly ester terephthalate (PS/PET) support. The membranes were extensively characterized by Water Contact Angle (WCA), Scanning Electron Microscopy (SEM), Fourier Transform Infra-red (FTIR) spectroscopy, Energy Dispersive X-ray (EDX) analysis, Elemental mapping and Powder X-ray Diffraction (PXRD). From among the different versions of X-CuO-MCM-41/PA@PS/PET membranes, the 0.05%-CuO-MCM-41/PA@PS/PET membrane showed best performance in terms of rejecting a variety of salts, micropollutants and antibiofouling. The 0.05%-CuO-MCM-41/PA@PS/PET showed >98% rejection of MgCl2 and 78% rejection of caffeine with a permeate flux of 16 LMH at 25 bar. The 0.1-NH2-CuO-MCM-41inhibited S. aureus growth by 51.7%. Hence, the current strategy of membrane fabrication proved to be highly efficient for multipurpose applications in water treatment.


Total knee arthroplasty using modified measured resection: a five-year retrospective review of midterm outcomes.
Deforming arthrosis, or osteoarthritis, is the most common rheumatic disease that involves the musculoskeletal system. The purpose of this research is to perform a retrospective review of the quality of life of patients with knee arthrosis, who underwent total knee arthroplasty (TKA) no less than 5 years ago, to evaluate, based on the Knee Society Scoring System, the efficacy of a modified measured resection technique, and to investigate factors that affect the outcomes. The research sample consisted of 44 patients who had severe osteoarthrosis, Kellgren-Lawrence grade III and grade IV. The post-operative complications occurred in seven knee joints. Among them there were 2 cases of infection, 2 cases of periprosthesis fracture, and 2 cases of aseptic instability, each pair accounting for 4.3%, and 1 case of femoropatellar pain (2.3%). The remaining 38 knee joints (84.8%) were free of complications. Knee arthrosis is a serious health problem, given the significant rate of disability among patients and the significant reduction in the quality of life. Patients often seek medical help at the later stages of the disease, when pain is strong and knee function is significantly reduced. The approach to rehabilitation procedures and, in some cases, to lifestyle improvement should be more responsible.


Phylogenetic analysis of the gag region encoding the matrix protein of small ruminant lentiviruses: comparative analysis and molecular epidemiological applications.
Little sequence information exists on the matrix-protein (MA) encoding region of small ruminant lentiviruses (SRLV). Fifty-two novel sequences were established and permitted a first phylogenetic analysis of this region of the SRLV genome. The variability of the MA encoding region is higher compared to the gag region encoding the capsid protein and surprisingly close to that reported for the env gene. In contrast to primate lentiviruses, the deduced amino acid sequences of the N- and C-terminal domains of MA are variable. This permitted to pinpoint a basic domain in the N-terminal domain that is conserved in all lentiviruses and likely to play an important functional role. Additionally, a seven amino acid insertion was detected in all MVV strains, which may be used to differentiate CAEV and MVV isolates. A molecular epidemiology analysis based on these sequences indicates that the Italian lentivirus strains are closely related to each other and to the CAEV-CO strain, a prototypic strain isolated three decades ago in the US. This suggests a common origin of the SRLV circulating in the monitored flocks, possibly related to the introduction of infected goats in a negative population. Finally, this study shows that the MA region is suitable for phylogenetic studies and may be applied to monitor SRLV eradication programs.


Levels and distribution of polychlorinated biphenyls in two edible fish species from Izmir Bay (eastern Aegean): a health risk assessment.
The concentrations of polychlorinated biphenyl (PCB) congeners were examined in two fish species from the Izmir Bay. A total of 624 individuals of different fish samples were sampled by trawling from three regions in Izmir Bay between 2010 and 2013. The total levels of indicator PCBs in all samples varied LOD (limit of detection) to 34.3 ng g-1 (dry weight) in the study area. The highest concentrations of PCBs were found in Gulbahce for Mullus barbatus and Diplodus annularis in 2011 and 2010, respectively. PCB153 was the major contributed congener in both fish species during sampling periods. Principal component analysis (PCA) was performed to evaluate the correlation of the determined variables in fish species. According to PCA, the PCBs are not related with fish length. One-way ANOVA test indicated that significant temporal variations were generally detected for PCBs, while non-significant spatial variations were examined between sampling sites. Six PCB congeners were found as 0.59-6.64 ng g-1 (wet weight, wwt) and compared with iPCB6 limits of 75 ng g-1 (wwt) revealed by the Environmental Food Safety Authority. Accordingly, all fish species analyzed did not surpass the safe limits of iPCB6 suggested by EU. The estimated daily intake of 6 PCB congeners by the people were less than the tolerable daily intake (TDI, 10-ng kg-1 body weight day-1) recommended by WHO (2003), suggesting that this intake would not cause adverse effects to residents of Izmir.


Calorimetric and spectroscopic investigations of the thermal denaturation of wild type nitrite reductase.
Nitrite reductase (NiR) is a multicopper protein, with a trimeric structure containing two types of copper site: type 1 is present in each subunit whereas type 2 is localized at the subunits interface. The paper reports on the thermal behaviour of wild type NiR from Alcaligenes faecalis S-6. The temperature-induced changes of the copper centres are characterized by optical spectroscopy and electron paramagnetic resonance spectroscopy, and by establishing the thermal stability by differential scanning calorimetry. The calorimetric profile of the enzyme shows a single endothermic peak with maximum heat absorption at T(m) approximately 100 degrees C, revealing an exceptional thermal stability. The thermal transition is irreversible and the scan rate dependence of the calorimetric trace indicates that the denaturation of NiR is kinetically controlled. The divergence of the activation energy values determined by different methods is used as a criterion for the inapplicability of the one-step irreversible model. The best fit of the DSC profiles is obtained when the classical Lumry-Eyring model, N<-->U-->F, is considered. The simulation results indicate that the irreversible step prevails on the reversible one. Moreover, it is found that the conformational changes within the type-1 copper environments precede the denaturation of the whole protein. No evidence of protein dissociation within the temperature range investigated was observed.


Genetic testing in hereditary melanoma.
Advances in our understanding of molecular genetics bring about unique challenges in our ability to practice molecular medicine. With the availability of commercial testing for various genetic cancer syndromes, including hereditary melanoma, specific issues regarding its use and limitations require attention before full translation of this tool into the clinical setting.


Occupational Exposures and Smoking in Eosinophilic Granulomatosis With Polyangiitis: A Case-Control Study.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Environmental agents and occupational exposures may confer susceptibility to EGPA, but data are scarce. This study was undertaken to investigate the association between occupational exposures (e.g., silica, farming, asbestos, and organic solvents) and other environmental agents (e.g., smoking) and the risk of EGPA. Patients with newly diagnosed EGPA (n = 111) and general population controls (n = 333) who were matched for age, sex, and geographic area of origin were recruited at a national referral center for EGPA. Exposures were assessed using a dedicated questionnaire administered by a specialist in occupational medicine, under blinded conditions. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Exposures to silica (OR 2.79 [95% CI 1.55-5.01], P = 0.001), organic solvents (OR 3.19 [95% CI 1.91-5.34], P < 0.001), and farming (OR 2.71 [95% CI 1.71-4.29], P < 0.001) were associated with an increased risk of EGPA. Co-exposure to silica and farming yielded an OR of 9.12 (95% CI 3.06-27.19, P < 0.001), suggesting a multiplicative effect between these 2 exposures. Smoking (current and former smokers combined) was significantly less frequent among patients with EGPA compared to controls (OR 0.49 [95% CI 0.29-0.70], P < 0.001). The pack-year index was also lower among patients with EGPA (OR 0.96 [95% CI 0.94-0.98], P < 0.001). The association of silica and farming was primarily aligned with ANCA-positive EGPA, while the association of smoking status and organic solvents was primarily aligned with ANCA-negative EGPA. The environment can influence susceptibility to EGPA. Exposure to silica, farming, or organic solvents is associated with an increased risk of EGPA, while smoking is associated with a lower risk. These exposures seem to have distinct effects on different EGPA subsets.