Discovery of a Potent and Orally Bioavailable Hypoxia-Inducible Factor 2α (HIF-2α) Agonist and Its Synergistic Therapy with Prolyl Hydroxylase Inhibitors for the Treatment of Renal Anemia.
Activation of hypoxia-inducible factor 2 (HIF-2) has emerged as a potent renal anemia treatment strategy. Here, the benzisothiazole derivative 26 was discovered as a novel HIF-2α agonist, which first demonstrated nanomolar activity (EC50 = 490 nM, Emax = 349.2%) in the luciferase reporter gene assay. Molecular dynamics simulations indicated that 26 could allosterically enhance HIF-2 dimerization. Furthermore, compound 26 had a good pharmacokinetic profile (the oral bioavailability in rats was 41.38%) and an in vivo safety profile (the LD50 in mice was greater than 708 mg·kg-1). In the in vivo efficacy assays, the combination of 26 and the prolyl hydroxylase inhibitor, AKB-6548, was confirmed for the first time to synergistically increase the plasma erythropoietin level in mice (from 260 to 2296 pg·mL-1) and alleviate zebrafish anemia induced by doxorubicin. These results provide new insights for HIF-2α agonists and the treatment of renal anemia.


High-efficient and sustainable biodegradation of microcystin-LR using Sphingopyxis sp. YF1 immobilized Fe3O4@chitosan.
The microcystin-LR (MC-LR) produced due to harmful cyanobacterial blooms have brought great harm to human and aquatic organisms, attracting a wide public health attention. To deal with MC-LR contamination, we synthesized a novel bio-functionalized composite for the high-efficient and sustainable biodegradation of microcystin-LR by covalent immobilizing Sphingopyxis sp. YF1 onto chitosan-grafted Fe3O4 magnetic particles (Fe3O4@CTS). The Fourier transform infrared spectroscopy (FTIR), Field emission scanning electron microscopy (SEM) and vibrating sample magnetometry (VSM) were utilized to characterize the structural properties of Fe3O4@CTS/Sphingopyxis sp. YF1. The immobilization conditions were optimized. And the MC-LR-degrading capabilities of Fe3O4@CTS/Sphingopyxis sp. YF1 were assessed under various conditions. The results showed that the optimal immobilization conditions containing 1.0 % (v/v) glutaraldehyde, immobilization for 4 h at 30 ℃. The Fe3O4@CTS/Sphingopyxis sp. YF1 showed an attractive degradation performance which possesed a wide torlerance to pH (6.0-9.0) and temperature (25-35 ℃). More interesting is that the Fe3O4@CTS/Sphingopyxis sp. YF1 exhibited significantly increased MC-LR-degrading capabilities after recycling and reusing which degradation rate reached 1.50 μg/mL/h in the sixth cycle, and it was easily recycled by using a magnet (Ms 21.5 emug-1). Two intermediates (tetrapeptide and Adda) and three degradation related genes (mlrA, mlrB and mlrC) were obtained in this study and the pathway for the degradation was proposed. These results revealed that Fe3O4@CTS/Sphingopyxis sp. YF1 can be potentially used for treatment of MC-LR contaminated environment.


Improving motion robustness of 3D MR fingerprinting with a fat navigator.
To develop a 3D MR fingerprinting (MRF) method in combination with fat navigators to improve its motion robustness for neuroimaging. A rapid fat navigator was developed using the stack-of-spirals acquisition and non-Cartesian spiral GRAPPA. The fat navigator module was implemented in the 3D MRF sequence with high scan efficiency. The developed method was first validated in phantoms and five healthy subjects with intentional head motion. The method was further applied to infants with neonatal opioid withdrawal symptoms. The 3D MRF scans with fat navigators acquired with and without acceleration along the partition-encoding direction were both examined in the study. Both phantom and in vivo results demonstrated that the added fat navigator modules did not influence the quantification accuracy in MRF. In combination with non-Cartesian spiral GRAPPA, a rapid fat navigator sampling with whole-brain coverage was achieved in ˜0.5 s at 3T, reducing its sensitivity to potential motion. Based on the motion waveforms extracted from fat navigators, the motion robustness of the 3D MRF was largely improved. With the proposed method, the motion-corrupted MRF datasets yielded T1 and T2 maps with significantly reduced artifacts and high correlations with measurements from the reference motion-free MRF scans. We developed a 3D MRF method coupled with rapid fat navigators to improve its motion robustness for quantitative neuroimaging. Our results demonstrate that (1) accurate tissue quantification was preserved with the fat navigator modules and (2) the motion robustness for quantitative tissue mapping was largely improved with the developed method.


Comparative study of label and label-free techniques using shotgun proteomics for relative protein quantification.
The analytical performance of three different strategies, iTRAQ (isobaric tag for relative and absolute quantification), dimethyl labeling (DML) and label free (LF) for relative protein quantification using shotgun proteomics have been evaluated. The methods have been explored using samples containing (i) Bovine proteins in known ratios and (ii) Bovine proteins in known ratios spiked into Escherichia coli. The latter case mimics the actual conditions in a typical biological sample with a few differentially expressed proteins and a bulk of proteins with unchanged ratios. Additionally, the evaluation was performed on both QStar and LTQ-FTICR mass spectrometers. LF LTQ-FTICR was found to have the highest proteome coverage while the highest accuracy based on the artificially regulated proteins was found for DML LTQ-FTICR (54%). A varying linearity (k: 0.55-1.16, r(2): 0.61-0.96) was shown for all methods within selected dynamic ranges. All methods were found to consistently underestimate Bovine protein ratios when matrix proteins were added. However, LF LTQ-FTICR was more tolerant toward a compression effect. A single peptide was demonstrated to be sufficient for a reliable quantification using iTRAQ. A ranking system utilizing several parameters important for quantitative proteomics demonstrated that the overall performance of the five different methods was; DML LTQ-FTICR>iTRAQ QStar>LF LTQ-FTICR>DML QStar>LF QStar.


Prescribing indicators for UK general practice: Delphi consultation study.
To identify prescribing indicators based on prescribing analysis and cost (PACT) data that have face validity for measuring quality or cost minimisation. Modified two round Delphi questionnaire requiring quantitative and qualitative answers. Health authorities in England. All health authority medical and pharmaceutical advisers in the first round and lead prescribing advisers for each health authority in the second round. Face validity (median rating of 7-9 on a nine point scale without disagreement) and reliability (rating 8 or 9) of indicators for assessing quality and cost minimisation. Completed second round questionnaires were received from 79 respondents out of 99. The median rating was 7 for cost minimisation and 6 for quality, and in all except four cases individual respondents rated indicators significantly higher for cost than for quality. Of the 41 indicators tested, only seven were rated valid and reliable for cost minimisation and five for quality. The 12 indicators rated as valid by leading prescribing advisers had a narrow focus and would allow only a limited examination of prescribing at a general practice, primary care group, or health authority level.


Effects of Mands on Instructional Control: A Laboratory Simulation.
The effects of two types of mands on participants' adherence to instructions were examined across two groups using procedures based on Hackenberg and Joker (Journal of the Experimental Analysis of Behavior 62:367-383, 1994). Participants were presented with instructions describing a pattern of responding for producing points later exchanged for money and were exposed to choice trials in which a progressive-time (PT) and a fixed-time (FT) schedule were concurrently available. The instructions initially described how to optimize point production; however, the PT schedule was manipulated over the course of the experiment such that response patterns maximizing point production differed across conditions. All participants experienced the same experimental arrangement, and the two groups differed only in the form of the mand contained in the instructions presented to them. The instructions for the directive group contained the mand "you must…" (i.e., command) preceding the instructed response pattern, whereas the non-directive group instructions contained the mand "you might consider…" (i.e., suggestion) preceding the instructed response pattern. Results indicated that instruction type influenced response patterns across changing contingencies. The directive group exhibited greater adherence to the instruction than the non-directive group when instruction following was less profitable. Results are interpreted in terms of Skinner's analysis of verbal behavior, and implications for practical application are discussed.


Facial nerve monitoring during acoustic neuroma removal.
As the surgeon's ability to perform total acoustic tumor removal without major neurologic deficit has reached a pinnacle, preservation of facial nerve function has assumed a higher priority. Satisfactory postoperative facial function depends upon an anatomically and physiologically intact facial nerve. Precise localization of the facial nerve is the first step toward preservation of function. Intraoperative facial nerve (FN) stimulation allows the surgeon to safely locate the facial nerve. Monitoring evoked electromyographic activity with an audio speaker provides direct, ongoing information regarding trauma to the nerve during dissection. Intraoperative FN monitoring was used in 18 consecutive translabyrinthine acoustic tumor removals. Seventeen patients had an excellent facial nerve result (Grade I or II using the House 6-point scale). The authors conclude that intraoperative FN stimulation and monitoring during acoustic tumor removal is a safe and reliable method of locating and protecting the facial nerve during cerebellopontine angle surgery.


Development of analytical method of melamine in placenta from pregnant women by isotope-dilution liquid chromatography/tandem mass spectrometry.
Melamine is ubiquitously present in our daily life. It has a known effect on the kidneys, but it may also adversely affect the reproduction system. We have developed an analytical method for measuring melamine levels in maternal placenta and correlated these levels with melamine concentrations in urine, a necessary step in finding out if melamine might cross the placenta and enter the circulation of the fetus. We used liquid-liquid extraction, clean up by solid-phase extraction (SPE), and isotope-dilution liquid chromatography/tandem mass spectrometry (LC/MS/MS) to measure melamine in placenta specimens. The results of this method were assessed for linearity, limits of quantitation (LOQs), and intra- and inter-assay precision as well as accuracy, matrix effect, and recovery rate. Calibration curves indicated good linearity (r >0.995) over concentrations ranging from 5 to 500 ng/mL in placenta specimens, intra- and inter-assay precision from 0.89% to 27.07%, and accuracy from 92.4% to123.5%. Recovery ranged from 63.9 to 83.9%, and the LOQ was 5 ng/mL in placenta (0.2 g). Placental melamine levels ranged from 7.87 to19.64 ng/mL, all detectable (n = 8). Pregnant women with higher levels of urinary melamine had higher placenta melamine levels than those with non-detectable urinary melamine, though the results were not significantly different (p = 0.149, n = 4 in each group). The results of this study suggest that pregnant women were exposed to low doses of melamine in their daily lives as measured in urine samples and placenta specimens. It is unclear whether placenta melamine concentrations can better represent long-term exposure than urine or whether melamine in the uterus can enter the fetus via this route.


Low zinc levels may contribute to gynecomastia in puberty.
This study aimed to determine whether there were any differences in trace element levels between adolescent boys with gynecomastia and control boys and to determine the correlations between the levels of trace elements and body mass index (BMI) and sex hormones. The pubertal gynecomastia group comprised of 41 patients (mean age=13.2 ±0.9 years), who were admitted to Hacettepe University İhsan Doğramacı Children's Hospital in Ankara. Control group comprised of 21 healthy male children. Analyses of trace element levels were performed atomic absorption spectrometry. The mean zinc level of control group was 101.33±16.87μg/dL and the mean zinc level of gynecomastia group was 81.36±17,43μg/dL (20% lower in gynecomastia patients, p=0.0001). However, the mean copper and manganese levels of gynecomastia patients were not statistically different than the control group. There were significant positive correlations between plasma zinc and total testosterone levels in gynecomastia group (r=0.592; p<0.05). There was a significant negative correlation between plasma zinc levels and BMI (r=-0.311; p<0.05). These results indicate that zinc deficiency might be one of the underlying factors of gynecomastia, the importance of which needs to be further elucidated.


A Multisite Study of Interprofessional Teamwork and Collaboration on General Medical Services.
Teamwork and collaboration are essential to providing high-quality care. Prior research has found discrepancies between nurses' and physicians' perceptions in operating rooms, ICUs, and labor and delivery units. Less is known about health care professionals' perceptions of teamwork and collaboration on general medical services. This cross-sectional study included nurses, nurse assistants, and physicians working on general medical services in four mid-sized hospitals. Researchers assessed teamwork climate using the Safety Attitudes Questionnaire and asked respondents to rate the quality of collaboration experienced with their own and other professional categories. Data for 380 participants (80 hospitalists, 13 resident physicians, 193 nurses, and 94 nurse assistants) were analyzed. Hospitalists had the highest median teamwork climate score (83.3, interquartile range [IQR] = 72.3-91.1), and nurses had the lowest (78.6, IQR = 69.6-87.5), but the difference was not statistically significant (p = 0.42). Median teamwork climate scores were significantly different across the four sites (highest = 83.3, IQR = 75.0-91.1; lowest = 76.8, IQR = 66.7-88.4; p = 0.003). Ratings of the quality of collaboration differed significantly based on professional category. Specifically, 63.3% (50/79) of hospitalists rated the quality of collaboration with nurses as high or very high, while 48.7% (94/193) of nurses rated the quality of collaboration with hospitalists as high or very high. This study found significant differences in perceptions of teamwork climate across sites and in collaboration across professional categories on general medical services. Given the importance in providing high-quality care, leaders should consider conducting similar assessments to characterize teamwork and collaboration on general medical services within their own hospitals.


The antimicrobial peptide chensinin-1b alleviates the inflammatory response by targeting the TLR4/NF-κB signaling pathway and inhibits Pseudomonas aeruginosa infection and LPS-mediated sepsis.
Excessive inflammatory responses are a major contributor to the high mortality associated with sepsis, a prevalent global complication. Therefore, the potential therapeutic strategy for sepsis involves targeting macrophages and reducing proinflammatory cytokine release. Chensinin-1b, an analog of the natural antimicrobial peptide derived from Rana chensinensis skin secretion, exhibits broad-spectrum antibacterial activity and adopts a random coil conformation in both PBS and membrane solution. By efficiently neutralizing LPS, chensinin-1b holds promise in alleviating LPS-induced inflammatory responses. In this study, we established a mouse septic shock model by exposing mice to multiple-drug-resistant Pseudomonas aeruginosa, as well as an endotoxin-mediated sepsis model induced by LPS. Administering chensinin-1b significantly prolonged the survival of the experimental mice, concurrently mitigating inflammatory responses and reducing organ damage. Additionally, we investigated the anti-inflammatory mechanism of chensinin-1b using a constructed LPS-induced mouse macrophage RAW264.7 inflammatory model. Our findings demonstrated that chensinin-1b effectively mitigated the excessive activation of the TLR4/NF-κB signaling pathway by directly neutralizing extracellular LPS, thus ameliorating the inflammatory response. Moreover, upon blocking the TLR4 signaling pathway, chensinin-1b further reduced the release of proinflammatory cytokines induced by LPS, indicating alternative modes of regulation. Notably, chensinin-1b rapidly entered RAW264.7 cells within 30 min via endocytosis, diffusing into the cytoplasm while retaining its anti-inflammatory properties intracellularly. Although further investigations are warranted to comprehensively elucidate the intracellular anti-inflammatory mechanism of chensinin-1b, our findings substantiate its possession of anti-inflammatory properties both intracellularly and extracellularly. Thus, chensinin-1b emerges as a promising candidate for mitigating excessive inflammatory responses associated with sepsis.


Seasonal Variation in Stable Isotope Ratios of Cow Milk in Vilnius Region, Lithuania.
Various studies have shown that stable isotope analysis has the potential to verify the geographic origin of foods and drinks. However, stable isotope composition is not always constant in the environment and can even change in the same area. Dairy products are of particular interest as a group of foods that play an important role in feeding the population. The composition of milk is fundamentally dependent on the feeding of the cows, and thereby on a particular environment. To better understand the amount of variation in δ18O, δ13C, and δ15N values in the milk from the same area, we measured stable isotope ratios in cow milk water, artesian water, and precipitation (δ18O) as well as in bulk milk samples (δ13C and δ15N) collected in 2014⁻2016. Different water and food sources were available during the winter (artesian water only and dry grass) and summer (artesian water and fresh grass), and spring and autumn seasons reflected transitional periods. Oxygen stable isotope ratios in milk water were relatively lower in winter and transitional seasons and higher in summer, showing the dependence on the main water source. δ13C values reflected particular food sources. This study shows the applicability of the stable isotope ratio method in linking cow milk to specific environments and reveals the amount of variation in stable isotope ratios in the same area. These results could be valuable for other studies on geographical origin determination of dairy products.


Pachyonychia congenita with laryngeal involvement.
Pachyonychia congenita (Jadassohn-Lewandowsky Syndrome) is a rare autosomal dominant disorder characterized by nail dystrophy, hyperkeratosis of the palms and soles, leukoplakia of the mucosa of the upper respiratory tract and anus, follicular keratoses especially about the knees and elbows, and palmar and plantar hyperhidrosis. We present a patient with pachyonychia congenita and an exophytic lesion in the larynx at the posterior commissure. He is the youngest of 4 family members with this disorder covering 3 generations. Each of the 4 patients also exhibited both oral leukoplakia compatible with the Jadassohn-Lewandowsky syndrome (Ikonograph Dermatol. Lab., 1 (1906) p. 29), and subcutaneous cysts of the face and scalp as described by Jackson and Lawler (Ann. Eugenics (1951) 142.


Development of an integral assessment approach of health status in patients with obstructive airway diseases: the CORONA study.
Traditional assessment of patients with obstructive lung diseases (asthma and chronic obstructive pulmonary disease; COPD) relies on physiological tests. The COPD and Asthma Rotterdam Integrated Care Approach (CORONA) study aims to develop a diagnostic pathway with a more comprehensive approach to the assessment of patients with asthma and COPD in secondary care. An eight-step method was used to develop and implement the pathway for patients with asthma or COPD referred to an outpatient hospital setting. The diagnostic pathway consists of an evidence-based set of measurements prioritized by a Delphi procedure. The pathway incorporates three innovative diagnostics: the metronome-paced hyperventilation test to measure dynamic hyperinflation, an activity monitor to objectively evaluate physical activity in daily life, and the Nijmegen Clinical Screening Instrument as a comprehensive assessment tool to acquire detailed insight into symptoms, functional limitations, and quality of life. An innovative diagnostic pathway was developed and implemented for patients with obstructive lung diseases referred to secondary care. As this pathway aims to provide a comprehensive analysis of health status, it focuses on biomedical aspects and also reviews behavioral aspects that further elucidate the patient's health status. The added value of the diagnostic pathway needs to be determined from both an organizational perspective and from the individual patient's viewpoint.


The kidney anion exchanger 1 affects tight junction properties via claudin-4.
In the renal collecting duct, intercalated cells regulate acid-base balance by effluxing protons through the v-H+-ATPase, and bicarbonate via apical pendrin or the basolateral kidney anion exchanger 1 (kAE1). Additionally, collecting duct cells play an essential role in transepithelial absorption of sodium and chloride. Expression of kAE1 in polarized MDCK I cells was previously shown to decrease trans-epithelial electrical resistance (TEER), suggesting a novel role for kAE1 in paracellular permeability. In our study, we not only confirmed that inducible expression of kAE1 in mIMCD3 cells decreased TEER but we also observed (i) increased epithelial absolute permeability to both sodium and chloride, and (ii) that this effect was dependent on kAE1 activity. Further, kAE1 regulated tight junction properties through the tight junction protein claudin-4, a protein with which it physically interacts and colocalizes. These findings unveil a novel interaction between the junctional protein claudin-4 and the kidney anion exchanger, which may be relevant to ion and/or pH homeostasis.


Autofluorescence endoscopy with "real-time" digital image processing in differential diagnostics of selected benign and malignant lesions in the oesophagus.
Oesophageal papilloma and Barrett's oesophagus are benign lesions known as risk factors of carcinoma in the oesophagus. Therefore, it is important to diagnose these early changes before neoplastic transformation. Autofluorescence endoscopy is a fast and non-invasive method of imaging of tissues based on the natural fluorescence of endogenous fluorophores. The aim of this study was to prove the diagnostic utility of autofluorescence endoscopy with digital image processing in histological diagnosis of endoscopic findings in the upper digestive tract, primarily in the imaging of oesophageal papilloma. During the retrospective analysis of about 200 endoscopic procedures in the upper digestive tract, 67 cases of benign, precancerous or cancerous changes were found. White light endoscopy (WLE) image, single-channel (red or green) autofluorescence images, as well as green and red fluorescence intensities in two modal fluorescence image and red-to-green (R/G) ratio (Numerical Colour Value, NCV) were correlated with histopathologic results. The NCV analysis in autofluorescence imaging (AFI) showed increased R/G ratio in cancerous changes in 96% vs. 85% in WLE. Simultaneous analysis with digital image processing allowed us to diagnose suspicious tissue as cancerous in all of cases. Barrett's metaplasia was confirmed in 90% vs. 79% (AFI vs. WLE), and 98% in imaging with digital image processing. In benign lesions, WLE allowed us to exclude tissue as malignant in 85%. Using autofluorescence endoscopy R/G ratio was increased in only 10% of benign changes causing the picture to be interpreted as suspicious, but when both methods were used together, 97.5% were cases excluded as malignancies. Mean R/G ratios were estimated to be 2.5 in cancers, 1.25 in Barrett's metaplasia and 0.75 in benign changes and were statistically significant (p=0.04). Autofluorescence imaging is a sensitive method to diagnose precancerous and cancerous early stages of the diseases located in oesophagus. Especially in two-modal imaging including white light endoscopy, autofluorescence imaging with digital image processing seems to be a useful modality of early diagnostics. Also in observation of papilloma changes, it facilitates differentiation between neoplastic and benign lesions and more accurate estimation of the risk of potential malignancy.


Impact of COVID-19 pandemic on plastic surgery training in Europe.
The COVID-19 pandemic has disrupted the functioning of global society and healthcare systems, including surgical departments. We aimed to assess alterations in plastic surgery training in Europe during the COVID-19 pandemic. A 34-question survey was emailed in January and February 2021 to 54 National Associations of Plastic, Reconstructive, and Aesthetic Surgeons throughout European countries. The questions concerned the general profile of plastic surgery trainees, plastic surgery department, and training organization during the COVID-19 pandemic and its influence on respondents' health. The acquisition of responses was finalized at the end of February 2021. All 71 of the respondents reported alterations in planned courses, workshops, and conferences. Organizational changes included team rotation 62%, followed by redeployment to another department 45.1%. Reduction in admissions to the plastic surgery departments was more significant during the 1stt wave than the 2nd wave of COVID-19 pandemics. During the interim period, admission restrictions were proportional to the infection number. The most frequently reported surgical procedures performed were skin cancer surgeries, trauma, and burns (79%, 77%, and 77%). The majority, 62% of the respondents, noticed the negative impact of pandemics on training; 53.5% think their manual skills and clinical knowledge may deteriorate because of the pandemic. Respondents noticed that their mental (50.7%) and physical (32%) health worsened, along with feeling more stressed in general (57%). The COVID-19 pandemic limited plastic surgery departments' activities and implementation of the plastic surgery training program in all European countries involved in our study.


Oil fly ash as a promise larvicide against the Aedes aegypti mosquitoes.
Two environmental problems exist in some tropical and subtropical areas: the Aedes aegypti (L.) (Ae. aegypti) mosquito and thousands of tons of heavy oil fly ash (HOFA) from power plants. Herein, micro/nanoparticles of HOFA have been utilized as a larvicide against Ae. aegypti without any chemical or biological additive materials. We estimated the accumulative mortalities in the third instar after 24/48 h (h). We found that after 24 h of exposing the larvae to the HOFA microsized, the LC50 and LC90 were 0.55 and 4.87 mg/ml, respectively, while they were 0.10 and 0.36 mg/ml after 48 h. At the same time, the LC50 and LC90 were respectively 0.12 and 0.60 mg/ml after 24 h exposing the larvae to the HOFA nanosized, and they were 0.06 and 0.23 mg/ml after 48 h. These results showed that the HOFA nanoparticles as larvicides were more effective than HOFA microparticles. The microscopy images also revealed deformations such as pigmentations, segment shrinkage, larva swelling, segment body contraction, siphon swelling, intermediate stage, head deformations, and thorax swelling in the larvae exposed to the HOFA. These deformations could indicate alterations in the hormones that control the biochemistry of the larvae body. The findings of this study could suggest the possibility of using HOFA, particularly in nanosized, as a promising larvicide against the Ae. aegypti mosquito.


Contrast-enhanced modified 3D T1-weighted TSE black-blood imaging can improve detection of infectious and neoplastic meningitis.
To evaluate the diagnostic value of a contrast-enhanced 3D T1-weighted-modified volumetric isotropic turbo spin-echo acquisition sequence (T1-mVISTA) in comparison with a conventional 3D T1-weighted magnetization-prepared rapid gradient-echo (T1-MP-RAGE) sequence for the detection of meningeal enhancement in patients with meningitis. Thirty patients (infectious meningitis, n = 12; neoplastic meningitis, n = 18) and 45 matched controls were enrolled in this retrospective case-control study. Sets of randomly selected T1-mVISTA and T1-MP-RAGE images (both with 0.8-mm isotropic resolution) were read separately 4 weeks apart. Image quality, leptomeningeal and dural enhancement, grading of visual contrast enhancement, and diagnostic confidence were compared using the Kruskal-Wallis rank sum test. Image quality was rated to be good to excellent in 75 out of 75 cases (100%) for T1-mVISTA and 74 out of 75 cases (98.7%) for T1-MP-RAGE. T1-mVISTA detected significantly more patients with leptomeningeal enhancement (p = 0.006) compared with T1-MP-RAGE (86.7 vs. 50.0%, p < 0.001), each with specificity of 100%. Similarly, sensitivity of T1-mVISTA for the detection of dural and/or leptomeningeal enhancement was also significantly higher compared with that of T1-MP-RAGE (96.7 vs. 80.0%, p = 0.025) without significant differences regarding specificity (97.8 vs. 95.6%, p = 0.317). No significant differences were found for dural enhancement alone. Diagnostic confidence in T1-mVISTA was significantly higher (p = 0.01). Visual contrast enhancement was tendentially higher in T1-mVISTA. T1-mVISTA may be an adequate and probably better alternative to T1-MP-RAGE for detection of leptomeningeal diseases. • Black-blood T1-mVISTA showed a significant higher sensitivity for the detection of leptomeningeal enhancement compared with MP-RAGE without losses regarding specificity. • Diagnostic confidence was assessed significantly higher in T1-mVISTA. • T1-mVISTA should be considered a supplement or an alternative to T1-MP-RAGE in patients with suspected leptomeningeal diseases.


[Medication-induced impairment of renal function: what is important?].
Non-steroidal antiphlogistics and COX-2 inhibitors routinely cause sodium retention and a blood pressure increase by about 5 mmHg, a decrease in renal function (by about 10 ml/min) and in 1-2% an acute renal failure. Prevention is possible by short-term, low-dose application, avoidance of dehydration, controlling serum creatinine levels 1 week after start of treatment in high-risk groups. Aminoglycosides cause acute renal failure in 10-20% which can be prevented by once daily dosing, meticulous drug monitoring. Radio contrast media cause, mostly dependent on baseline renal function, in 0-50% a radiocontrast-induced nephropathy. This can be prohibited with hydration, low volume of contrast medium, and low- (or iso)osmolar contrast medium. New preparations of vancomycin go along with a greatly reduced rate of nephrotoxicity. Drug monitoring and avoidance of a combination therapy with aminoglycosides will help to reduce toxicity. Medication-induced acute interstitial nephritis is a relevant differential diagnosis in acute renal failure: stop implicated medication, consider steroid application!


Dissecting the History of Anatomy in the Third Reich -: 1989-2010: A Personal Account.
(Reprinted with permission from Annals of Anatomy Vol. 194, No. 3, 2012).


Ultradian rhythms in cognitive performance: no evidence for a 1.5-h rhythm.
In the past, Kleitman's notion of a basic rest-activity cycle (BRAC), which states an approximate 1.5-h rhythm of arousal, has received some empirical support in studies investigating physiological or psychological parameters. Our study investigated this ultradian rhythm in human cognitive performance. Sixty subjects were tested every 10 min for 9 h with an elementary cognitive task, the sentence-verification test (SVT), and provided ratings of alertness and mood. Heart period was always measured during performance of the SVT. Using rather conservative statistical methods, spectral analyses of time series revealed no significant 90-min periodicity for any of the variables. Instead, longer periodicities were the major sources of variance. Reanalyses using detrended and/or smoothed time series suggest that emergence of the BRAC might depend also on statistical methods. In conformity with recent studies it was concluded that several positive reports for the BRAC might be due to lack of conservatism in statistical methods.


Assessment of groundwater pollution near Aba-Eku municipal solid waste dumpsite.
Municipal solid waste (MSW) dumpsite constitutes a major anthropogenic point source of leachate contamination to the ambient groundwater and poses a significant threat to the geo-ecosystem. This study investigated the pollution of groundwater by leachate emanating from Aba-Eku MSW dumpsite in Ibadan, Nigeria, using bacteriological, hydrochemical, and geophysical techniques. There is a diversity of bacteria in the leachate and the dominant phyla being proteobacteria (83%) and firmicutes (17%). The mean concentrations (mg/L) of Mn, Fe, Al, Cu, Mo, and Cr in the leachate samples were above the World Health Organization wastewater discharge limits. The hydrochemical parameters of the groundwater samples around the dumpsite were generally within the permissible limits, except for K and Cl-; which invariably indicate major inputs from water-rock interaction and minor contributions from the dumpsite. Three geoelectrical layers were indicated from the vertical electrical sounding data, which are the topsoil, the lateritic clay layer, and the weathered basement. Low resistivity values of 5-33 Ωm and 3-24 Ωm were obtained within 2 m and 5.5 m depths for the topsoil and the lateritic layer, respectively; while the 2-D subsurface model reveals leachate plume beyond 5 m. Although the MSW leachate is heterogeneous, the hydrochemical data show that the aquifer around the dumpsite has not been seriously polluted with the leachate, but there is a continuous percolation of leachate into the soil subsurface, based on the geophysical findings. Discontinuing waste dumping and groundwater extraction, which would over time reduce the leachate plume, are measures to enhance the groundwater quality in the area.


[Clinical predictors of chronic chagasic myocarditis progression].
Previous prognostic studies of Chagas' disease have focused on mortality associated with end-stage cardiopathy (i.e., heart failure). Our aim was to identify indicators of progression in early-stage Chagas' heart disease. The study included 856 patients with 3 positive anti-Trypanosoma cruzi test results. Those with heart failure were excluded. Patients were divided into 3 clinical groups: those without heart disease (Group I); those with heart disease but without left ventricular enlargement (Group II); and those with left ventricular enlargement but without heart failure (Group III). The endpoint was progression to a more severe clinical stage or death due to cardiovascular disease. A Cox regression model was used to derive a clinical risk score from clinical, electrocardiographic and echocardiographic variables. At study entry, the patients' mean age was 43.7 years. They were followed up for a mean of 8 years. The following were predictors of heart disease progression: age at entry (HR=1.05; 95% CI, 1.02-1.07; P<.001), left ventricular systolic diameter (HR=1.06; 95% CI, 1.04-1.09; P<.001), intraventricular conduction abnormalities (HR=1.85; 95% CI, 1.02-3.36; P=.04), and sustained ventricular tachycardia (HR=3.97; 95% CI, 1.65-9.58; P=.002). Treatment with benznidazole reduced the risk of progression (HR=0.40; 95% CI, 0.23-0.72; P=.002). The devised clinical risk score was effective in stratifying the likelihood of cardiopathy progression. Specific clinical indicators and a derived clinical risk score can be used to predict the progression of chronic chagasic myocarditis in patients without heart failure.


Transfusion of murine red blood cells expressing the human KEL glycoprotein induces clinically significant alloantibodies.
Red blood cell (RBC) alloantibodies to nonself antigens may develop after transfusion or pregnancy, leading to morbidity and mortality in the form of hemolytic transfusion reactions or hemolytic disease of the newborn. A better understanding of the mechanisms of RBC alloantibody induction, or strategies to mitigate the consequences of such antibodies, may ultimately improve transfusion safety. However, such studies are inherently difficult in humans. We recently generated transgenic mice with RBC-specific expression of the human KEL glycoprotein, specifically the KEL2 or KEL1 antigens. Herein, we investigate recipient alloimmune responses to transfused RBCs in this system. Transfusion of RBCs from KEL2 donors into wild-type recipients (lacking the human KEL protein but expressing the murine KEL ortholog) resulted in dose-dependent anti-KEL glycoprotein immunoglobulin (Ig)M and IgG antibody responses, enhanced by recipient inflammation with poly(I:C). Boostable responses were evident upon repeat transfusion, with morbid-appearing alloimmunized recipients experiencing rapid clearance of transfused KEL2 but not control RBCs. Although KEL1 RBCs were also immunogenic after transfusion into wild-type recipients, transfusion of KEL1 RBCs into KEL2 recipients or vice versa failed to lead to detectable anti-KEL1 or anti-KEL2 responses. This murine model, with reproducible and clinically significant KEL glycoprotein alloantibody responses, provides a platform for future mechanistic studies of RBC alloantibody induction and consequences. Long-term translational goals of these studies include improving transfusion safety for at-risk patients.


A foundational theoreticalAl12E12(E = N, P) adsorption and quinolone docking study: cage-quinolone pairs, optics and possible therapeutic and diagnostic applications.
This combined Al12E12 (E = N, P) surface adsorption and docking study describes the new possibility of prospective potential probing(photophysical/optical) and therapy(medicinal/biochemical) with these adsorbent conjugates. DFT investigations were undertaken herein to help generate geometrical models and better understand the possible favorable adsorption energetics. We attempt to explain their adsorption behaviors and docking involving SARS-CoV-2 viruses (PDB)to assess their possible pharmaceutical potential against the pandemic virus (COVID-19). The adsorption behavior of 8-hydroxy-2-methylquinoline (MQ) and its halogenated derivatives, 5,7-diiodo-8-hydroxy-2-methylquinoline (MQI), 5,7-dichloro-8-hydroxy-2-methylquinoline (MQCl), and 5,7-dibromo-8-hydroxy-2-methylquinoline (MQBr), with aluminum-nitrogen (AlN), and aluminum-phosphorous (AlP) fullerene-like nanocages is reported. A decrease in the hardness of the nanoclusters when adsorbed with drug molecules resulted in an incrementally improved chemical softness (see e.g., Hard-Soft Acid Base theory) indicating that reactivity of the drug molecule in the resulting complex increases upon cluster chemical adsorption. The energy gap is found to be maximized for AlN-MQ and minimized for AlP-MQI; the reduced density gradient (RDG) iso-surfaces and AIM studies also corroborated this. Therefore, these two were found, respectively, to be the least and most electrically conductive of the species under study. We selected a simple medicinal building block (chelator)in addition to selecting the cluster based on previous literature reports. Important parameters such as gap energies and global indices were determined. We assessed NLO properties. The SARS-CoV-2 virus PDB docking data for 6VW1, 6VYO, 6WKQ, 7AD1, 7AOL, 7B3C, were enlisted as ligand targets for studies of docking (PatchDock Server) using the requisite PDB geometries (For the structure of 6VW1, kindly see reference, 2020; For the structure of 6VYO kindly see reference, 2020; For the structure of 6WKQ kindly see reference, 2020; For the structure of 7AD1 kindly see reference, 2021; For the structure of 7AOL kindly see reference, 2021; For the structure of 7B3C kindly see reference, 2021). Such findings indicate that the AlN-drug conjugation have inhibitory effect against these selected receptors.Communicated by Ramaswamy H. Sarma.


Artificial gravity with ergometric exercise preserves the cardiac, but not cerebrovascular, functions during 4 days of head-down bed rest.
Cardiovascular and musculoskeletal deconditioning occurring in long-term spaceflight requires new strategies to counteract these adverse effects. We previously reported that a short-arm centrifuge produced artificial gravity (AG), together with ergometer, has an approving effect on promoting cardiovascular function. The current study sought to investigate whether the cardiac and cerebrovascular functions were maintained and improved using a strategy of AG combined with exercise training on cardiovascular function during 4-day head-down bed rest (HDBR). Twelve healthy male subjects were assigned to a control group (CONT, n=6) and an AG combined with ergometric exercise training group (CM, n=6). Simultaneously, cardiac pumping and systolic functions, cerebral blood flow were measured before, during, and after HDBR. The results showed that AG combined with ergometric exercise caused an increase trend of number of tolerance, however, there was no significant difference between the two groups. After 4-day HDBR in the CONT group, heart rate increased significantly (59±6 vs 66±7 beats/min), while stroke volume (98±12 vs 68±13 mL) and cardiac output (6±1 vs 4±1 L/min) decreased significantly (p<0.05). All subjects had similar drops on cerebral vascular function. Volume regulating hormone aldosterone increased in both groups (by 119.9% in CONT group and 112.8% in the CM group), but only in the CONT group there were a significant changes (p<0.05). Angiotensin II was significantly increased by 140.5% after 4-day HDBR in the CONT group (p<0.05), while no significant changes were observed in the CM group. These results indicated that artificial gravity with ergometric exercise successfully eliminated changes induced by simulated weightlessness in heart rate, volume regulating hormones, and cardiac pumping function and partially maintained cardiac systolic function. Hence, a daily 1h alternating +1.0 and +2.0 Gz with 40 W exercise training appear to be an effective countermeasure against cardiac deconditioning.


Graft-recipient-weight ratio and lowered immunosuppression is important for the success of adult liver retransplantation.
This study analyzed the risk of liver retransplantation and factors related to better outcome. Adult liver transplantations performed during 1996-2021 were included. Comparison between first transplantation and retransplantation were performed. Among retransplantation cases, comparison between whole liver and partial liver graft was performed. Multivariable Cox analyses for analyzing risk factors for primary graft and overall patient survival were performed for the entire cohort as well as the subgroup of patients with retransplantation. A total 2237 transplantations from 2135 adults were included and 103 cases were retransplantation. A total of 44 cases (42.7%) were related to acute graft dysfunction while 59 cases (57.3%) were related to subacute or chronic graft dysfunction. Retransplantation was related poor primary graft (HR 3.439, CI 2.230-5.304, P < 0.001) and overall patient survival. (HR 2.905, CI 2.089-4.040, P < 0.001) Among retransplantations, mean serum FK506 trough level ≥ 9 ng/mL was related to poor primary graft (HR 3.692, CI 1.288-10.587, P = 0.015) and overall patient survival. (HR 2.935, CI 1.195-7.211, P = 0.019) Graft-recipient-weight ratio under 1.0% was related to poor overall patient survival in retransplantations. (HR 3.668, CI 1.150-11.698, P = 0.028). Retransplantation can be complicated with poor graft and patient survival compared to first transplantation, especially when the graft size is relatively small. Lowering the FK506 trough level during the first month can be beneficial for outcome.


Prognostic value of histologic factors in adult cerebral astrocytoma.
Surgical specimens from 165 adults with cerebral astrocytoma were reviewed to establish the prognostic value of histologic factors when studied both individually and in combination. Glioblastomas were excluded. Nine morphologic parameters and 25 clinicotherapeutic factors were correlated with survival. Cell density, endothelial hyperplasia, number of mitoses X 10 high-power field (HPF), and vessel frequency appeared to be highly significant prognostic factors (P less than 0.001). Nuclear polymorphism, microcysts, and vessel size were significant moderately (P less than 0.01). Microcysts, vessel size, endothelial hyperplasia, and number of mitoses X 10 HPF remained significant statistically after a multivariate analysis that also included clinicotherapeutic factors. Survival was similar for astrocytomas with "extensive malignancy" and astrocytomas with only "slight and localized malignancy." Multivariate analysis showed that the presence or absence of malignancy was more important prognostically than the clinical variables (i.e., postoperative Karnofsky status or extent of surgical removal).


Receptor alterations in manganese intoxicated monkeys.
The density of four different receptors and one marker of dopamine uptake sites were analyzed in monkey brains after manganese exposure (0.1 g manganese per month during 26 months, a dose comparable to that workers might inhale in dusty environments) by means of quantitative receptor autoradiography. The binding of 3H-mazindol to the dopamine uptake sites was reduced by 75% in both the head of the caudate nucleus and putamen, while it remained unchanged in the other regions analyzed. The binding of the D1 receptor ligand 3H-SCH 23,390 was reduced about 45% in the same areas as mazindol binding, while the density of D2 receptors was unaffected. The muscarinic acetylcholine receptors as well as GABAA receptors remained also unchanged in all brain areas analyzed after manganese exposure. Thus the dopaminergic neurons must be considered to be vulnerable to manganese concentrations attainable in the work environment. Our results also indicate that postsynaptic structures containing D1 receptors are sensitive while cells containing D2 receptors are either spared or compensated for by up-regulation of the number of receptors on remaining sites.


Development of quality evaluation sensor for fish freshness control based on KI value.
Recently, raw fish, sashimi, is becoming a popular dish in countries other than Japan. Therefore, in order to assure that the raw fish and shellfish are safe for human consumption, a quality evaluation sensor, which shows, at a glance, the quality of sashimi, was developed. The proposed sensor is based on the principle that the freshness of sashimi, which is judged from the KI value, can be determined from the degree of color change of thiazole blue (MTT: 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) due to the redox reaction of MTT accompanying the oxidation of hypoxanthine (Hx) by xanthine oxidase (XOD). The proposed sensor consists of 5 ml of 80% ethanol-1 M Tris-HCl buffer (pH 7.8) containing 2.0 mg of Hx, 2.0 mg of MTT and 0.38 unit of XOD. The proposed sensor and fish were kept together at 5, -10 and -20 degrees C, and the freshness of sashimi stored at each temperature was determined from the color change of the sensor. The concept "freshness of sashimi" can be expressed as remaining of validity (RDV), which is described in our previous study. A good relationship was obtained between the KI value and the RDV determined by the proposed sensor. From these results, the proposed sensor system can be used to non-destructively determine the fish freshness and RDV.


Effect of radiotherapy on the DNA cargo and cellular uptake mechanisms of extracellular vesicles.
In the past decades, plenty of evidence has gathered pointing to the role of extracellular vesicles (EVs) secreted by irradiated cells in the development of radiation-induced non-targeted effects. EVs are complex natural structures composed of a phospholipid bilayer which are secreted by virtually all cells and carry bioactive molecules. They can travel certain distances in the body before being taken up by recipient cells. In this review we discuss the role and fate of EVs in tumor cells and highlight the importance of DNA specimens in EVs cargo in the context of radiotherapy. The effect of EVs depends on their cargo, which reflects physiological and pathological conditions of donor cell types, but also depends on the mode of EV uptake and mechanisms involved in the route of EV internalization. While the secretion and cargo of EVs from irradiated cells has been extensively studied in recent years, their uptake is much less understood. In this review, we will focus on recent knowledge regarding the EV uptake of cancer cells and the effect of radiation in this process.


Difficult decisions in endoscopic sinus surgery.
Sinus disease, like many other problems in otolaryngology, may run the gamut of being either easily correctable with a clear-cut treatment or completely resistant to any form of treatment. Fortunately, many patients have problems somewhere between these two extremes. Clearly there is no one correct approach for treatment of many problems. Two, three, or even four approaches may be equally effective in some cases. In other cases, one approach may be successful in the hands of one surgeon whereas another approach is more appropriate for a different surgeon. This article presents nine cases that do not have clear-cut solutions. In some, the consultants clearly disagreed, whereas in others there was some uniformity in treatment plans. This flexibility in surgery in general and specifically with a technique that is relatively new is what makes it so exciting and so promising for continued success in treating sinus disease.


Reactions to Standardized Cigarette Packs With Varying Structural Designs, and the Association With Smoking Susceptibility: A Postimplementation Cross-Sectional Survey With Never-Smoking Adolescents in Scotland.
From May 20, 2017, cigarettes in the United Kingdom must be sold in standardized (plain) packaging. We explore postimplementation reactions to standardized cigarette packaging among never-smokers in Scotland, whether reactions vary in relation to permitted variations in pack structure, and whether reactions are associated with susceptibility. A cross-sectional survey with 12-17-year-old never-smokers (n = 507) in Scotland, conducted November 2017-November 2018. Participants were shown one "regular" standardized cigarette pack (flip-top lid and straight-edged pack, similar to designs in Australia) and three standardized packs with varied pack structures (beveled-edges, slim pack, and shoulder box), which are permitted postimplementation in the United Kingdom. Participants rated each pack on eight five-point reaction measures (eg, attractiveness). Participants also indicated which pack, if any, they would choose. Smoking susceptibility was the outcome. The mean reaction scores for all four packs were mostly negative, however the shoulder box was consistently rated less negatively than the regular, slim, or beveled-edge packs. Most participants (87%) said they would not select any of the four packs, although susceptible participants were more likely to select one than nonsusceptible participants (25% vs. 7%; χ 2 = 29.70; p < .001). For all four packs, not finding them off-putting was associated with susceptibility (Adjusted Odds Ratio range: 2.73-3.69), albeit only a minority of adolescents did not find each pack off-putting. Adolescents have negative reactions to the standardized cigarette packs implemented in the United Kingdom, albeit permitted variations in structure can reduce the extent of negativity. Most reactions to standardized packaging had no association with susceptibility. We provide the first empirical evidence that adolescents find the standardized cigarette packs implemented in the United Kingdom unappealing and that most pack reactions have no association with susceptibility among never-smokers, with the exception of the minority who did not think that they would put them off smoking. This suggests that the legislation is achieving one of its primary aims, to reduce the appeal of packaging. That permitted variations in pack structure (eg, shoulder boxes) somewhat reduce negative reactions suggests that the United Kingdom, and other countries introducing similar legislation, should ensure that all aspects of pack design are fully standardized.


The molecular basis of the evolution of sex.
Traditionally, sexual reproduction has been explained as an adaptation for producing genetic variation through allelic recombination. Serious difficulties with this explanation have led many workers to conclude that the benefit of sex is a major unsolved problem in evolutionary biology. A recent informational approach to this problem has led to the view that the two fundamental aspects of sex, recombination and outcrossing, are adaptive responses to the two major sources of noise in transmitting genetic information, DNA damage and replication errors. We refer to this view as the repair hypothesis, to distinguish it from the traditional variation hypothesis. On the repair hypothesis, recombination is a process for repairing damaged DNA. In dealing with damage, recombination produces a form of informational noise, allelic recombination, as a by-product. Recombinational repair is the only repair process known which can overcome double-strand damages in DNA, and such damages are common in nature. Recombinational repair is prevalent from the simplest to the most complex organisms. It is effective against many different types of DNA-damaging agents, and, in particular, is highly efficient in overcoming double-strand damages. Current understanding of the mechanisms of recombination during meiosis suggests that meiosis is designed for repairing DNA. These considerations form the basis for the first part of the repair hypothesis, that recombination is an adaptation for dealing with DNA damage. The evolution of sex can be viewed as a continuum on the repair hypothesis. Sex is presumed to have arisen in primitive RNA-containing protocells whose sexual process was similar to that of recombinational repair in extent segmented, single-stranded RNA viruses, which are among the simplest known organisms. Although this early form of repair occurred by nonenzymatic reassortment of replicas of undamaged RNA segments, it evolved into enzyme-mediated breakage and exchange between long DNA molecules. As some lines of descent became more complex, their genome information increased, leading to increased vulnerability to mutation. The diploid stage of the sexual cycle, which was at first transient, became the predominant stage in some lines of descent because it allowed complementation, the masking of deleterious recessive mutations. Out-crossing, the second fundamental aspect of sex, is also maintained by the advantage of masking mutations. However, outcrossing can be abandoned in favor of parthenogenesis or selfing under conditions in which the costs of mating are very high.(ABSTRACT TRUNCATED AT 400 WORDS)


Ethanol Consumption Induces Nonspecific Inflammation and Functional Defects in Alveolar Macrophages.
Chronic alcohol drinking is associated with increased susceptibility to viral and bacterial respiratory pathogens. In this study, we use a rhesus macaque model of voluntary ethanol self-administration to study the effects of long-term alcohol drinking on the immunological landscape of the lung. We report a heightened inflammatory state in alveolar macrophages (AMs) obtained from ethanol (EtOH)-drinking animals that is accompanied by increased chromatin accessibility in intergenic regions that regulate inflammatory genes and contain binding motifs for transcription factors AP-1, IRF8, and NFKB p-65. In line with these transcriptional and epigenetic changes at the basal state, AMs from EtOH-drinking animals generate elevated inflammatory mediator responses to lipopolysaccharides and respiratory syncytial virus. However, the transcriptional analysis revealed an inefficient induction of interferon-stimulated genes with EtOH in response to the respiratory syncytial virus, suggesting disruption of antimicrobial defenses. Correspondingly, AMs from EtOH-drinking animals exhibited transcriptional shifts indicative of increased oxidative stress and oxidative phosphorylation, which was coupled with higher cytosolic reactive oxygen species and mitochondrial potential. This heightened oxidative stress state was accompanied by decreased ability to phagocytose bacteria. Bulk RNA and assay for transposase-accessible chromatin sequencing data further revealed reduced expression and chromatin accessibility of loci associated with tissue repair and maintenance with chronic EtOH drinking. Similarly, analysis of single-cell RNA sequencing data revealed shifts in cell states from tissue maintenance to inflammatory responses with EtOH. Collectively, these data provide novel insight into mechanisms by which chronic EtOH drinking increases susceptibility to infection in patients with alcohol use disorders.


Mutations in the erythrocyte chemokine receptor (Duffy) gene: the molecular basis of the Fya/Fyb antigens and identification of a deletion in the Duffy gene of an apparently healthy individual with the Fy(a-b-) phenotype.
The erythrocyte chemokine receptor, a receptor for Plasmodium vivax, carries the antigens of the Duffy blood group system. Sequence analysis of reticulocyte RNA from individuals of known Duffy phenotype showed that the Fya antigen differs from the Fyb antigen as a result of a single nucleotide difference (A131 or G) encoding amino acid Gly44 (Fya) or Asp (Fyb) in the N-terminal extracellular domain of the glycoprotein. Evidence is presented for two different genetic backgrounds giving rise to the Fy(a-b-) phenotype. The most likely genetic mechanism in most individuals of the Fy(a-b-) phenotype is down-regulation of Duffy glycoprotein mRNA. However, the Duffy gene from a very rare Caucasian individual (AZ) with the Fy(a-b-) phenotype has a 14 base-pair deletion (nucleotides 287-301) resulting in a frameshift which introduces a stop codon and produces a putative truncated 118 amino acid protein. The occurrence of this mutation in an apparently healthy individual raises questions about the functional importance of the Duffy glycoprotein not only in normal erythrocytes but also in all human cells and tissues.


Temporal and Spatial Evolution of Vegetation Coverage in the Mianyuan River Basin Influenced by Strong Earthquake Disturbance.
The 2008 Wenchuan earthquake caused significant economic losses and degradation of regional ecosystems, including the terrestrial vegetation. Since the vegetation root system can enhance the soil's anti-erosion capacity and therefore mitigate the occurrence of slope instabilities, it is beneficial to study the spatial and temporal evolution of vegetation for a long-term assessment of co-seismic secondary disasters. The Mianyuan River Basin, an uninhabited area passing through an active fault located in the earthquake-affected region, was selected as the study area. The Normal Difference Vegetation Index (NDVI) was calculated using remote sensing images from 1994 to 2017 to analyze the process of vegetation growth, loss, fluctuation and recovery. Statistical results suggest that the area in the middle and lower reaches, near the river network, and with a slope of 30 to 40 degrees were variable regions, showing more significant vegetation destruction during the earthquake and faster repair after the seismic event. Besides, vegetation near the fault was damaged more severely after the earthquake, but the active fault did not play an essential role in the vegetation recovery period. In the Mianyuan River Basin, vegetation experienced a volatility period (5 plus or minus one year) before entering the recovery period. In 8 to 9 years after the earthquake, the surficial vegetation could recover to the state before the earthquake.


[Variability of the relay neurons in the corpus geniculatum laterale, pars dorsalis in the albino rat].
38 Golgi-impregnated relay cells from the Wistar rat's dLGN were investigated considering their possible differentiation into 2 types using camera lucida drawings with a magnification of 800. The following criteria were taken into account: 1. size of neurons (perikarya, size of dendritic domains) 2. structure of dendrites (number of dendrites, branching points, distribution of dendritic density in relation to the perikaryon, surface structures of dendrites). It was tried to correlate the investigated parameters quantitatively and qualitatively. The results showed that inspite of a missing clear subdivision into 2 types there exists a trend towards developing a second type of relay cells.


A deep-learning framework for metacarpal-head cartilage-thickness estimation in ultrasound rheumatological images.
Rheumatoid arthritis (RA) is a chronic disease characterized by erosive symmetrical polyarthritis. Bone and cartilage are the main joint targets of this disease. Cartilage damage is one of the most relevant determinants of physical disability in RA patients. Cartilage damage is nowadays assessed by clinicians, which manually measure cartilage thickness in ultrasound (US) imaging. This poses issues relevant to intra-and inter-observer variability. Relying on the acquisition of metacarpal-head US images from 38 subjects, this work addresses the problem of automatic cartilage-thickness measurement by designing a new deep-learning (DL) framework. The framework consists of a Convolutional Neural Network (CNN), responsible for regressing cartilage-interface distance fields, followed by a post-processing step to delineate the two cartilage interfaces from the predicted distance fields and compute the cartilage thickness. Our framework achieved encouraging results with a mean absolute difference (ADF) of 0.032 (±0.026) mm against manual thickness annotation by an expert clinician. When evaluating the intra-observer variability, we obtained an ADF = 0.036 (±0.028) mm. The proposed framework achieved an ADF against manual annotation that was comparable to the intra-observer variability, proving the potential of DL in the field. This work is the first to address the problem of automatic cartilage-thickness estimation in US rheumatological images with DL, paving the way for future research in the field. From a clinical perspective, the proposed framework proved to be a valuable tool to support the clinical routine increasing the reproducibility of cartilage thickness measurements.


Gram-positive bacterial sepsis in rat and tissue lipolytic activity on commercial parenteral fat emulsions.
To study the influence of a gram-positive sepsis on the metabolism of circulating lipids, fasted rats were injected with saline (control group) or with a suspension of heat-killed or live Staphylococcus aureus. 18 h later, body temperature was increased, while albuminemia and ketonemia were decreased in the group injected with heat-killed bacteria, as opposed to the control group. Passing from these groups to the group injected with live bacteria, more differences appeared: increase of triglyceridemia and free cholesterolemia; decrease of esterified cholesterol levels and especially of the in vitro activity of diaphragm, heart and adipose tissue lipoprotein lipase and of hepatic lipase. The decrease of lipolytic activities occurred whether they were measured on a fat emulsion containing long-chain or medium- and long-chain triglycerides. The fact that for the latter the activity was always higher than for the former suggests that the host infected with gram-positive bacteria would clear exogenous fat more easily in the case of medium-chain triglycerides.


High serum carotenoids are inversely associated with serum gamma-glutamyltransferase in alcohol drinkers within normal liver function.
Many studies have reported that the consumption of alcohol induces the generation of free radicals. Moreover, recent studies suggest that serum gamma-glutamyltransferase (gamma-GTP) within its normal range might be an early marker of oxidative stress. In this study, we tested the hypothesis that serum antioxidant carotenoids would be inversely associated with serum gamma-GTP in alcohol drinkers within normal liver function. A total of 266 Japanese men who had received health examination in 2003 participated in the study. The associations of serum gamma-GTP and serum-carotenoid concentrations stratified by alcohol intake levels were evaluated cross-sectionally. The participants were divided into three groups according to their ethanol intake level (non-drinker, less than 1 g/day; light drinker, 1-25 g/day; and moderate and heavy drinkers, 25+ g/day). The multivariate-adjusted geometric means of the serum gamma-GTP concentrations in each tertile of the serum-carotenoid concentrations were calculated after adjustment for ethanol intake, age, body mass index, total cholesterol, triacylglycerols, current tobacco use, and habitual exercise. The serum gamma-GTP concentrations were significantly high in accordance with the ethanol intake level. In moderate and heavy drinkers, the multivariate-adjusted geometric means of serum gamma-GTP concentrations were significantly low in accordance with the tertiles of the serum lycopene, alpha-carotene, beta-carotene, and beta-cryptoxanthin concentrations. The serum antioxidant carotenoids were inversely associated with alcohol-induced increases of serum gamma-GTP in moderate and heavy drinkers within normal liver function.


Nuptial feeding of spermless spermatophores in the Hawaiian swordtail cricket, Laupala pacifica (Gryllidae: Triginodiinae).
Crickets in the genus Laupala (subfamily Trigonidiinae) have an elaborate courtship system, defined by a highly ritualized serial transfer of multiple spermatophores. Males produce multiple "micro" spermatophores followed by a final "macro" spermatophore during a single mating bout. Remarkably, the microspermatophores of L. cerasina, the first species whose mating system was studied in detail, were discovered to be spermless. However, in a study of another species, L. pacifica, sperm transfer was reported after every copulation suggesting that L. pacifica microspermatophores contain sperm. The presence or absence of sperm in the microspermatophore has important implications for the evolution of this exaggerated courtship system and the origin of nuptial gifts. In this study, we systematically examined L. pacifica spermatophore contents for sperm using a fluorescent nuclear stain. We detected sperm only in macrospermatophores. This finding suggests that spermless microspermatophores are typical for Laupala; thus, to determine the origin of this highly modified phenotype will require comparative analyses with closely related outgroups that exhibit less exaggerated courtship systems.


Influence of the surface properties on bactericidal and fungicidal activity of magnetron sputtered Ti-Ag and Nb-Ag thin films.
In this study the comparative investigations of structural, surface and bactericidal properties of Ti-Ag and Nb-Ag thin films have been carried out. Ti-Ag and Nb-Ag coatings were deposited on silicon and fused silica substrates by magnetron co-sputtering method using innovative multi-target apparatus. The physicochemical properties of prepared thin films were examined with the aid of X-ray diffraction, grazing incidence X-ray diffraction, scanning electron microscopy, atomic force microscopy and X-ray photoelectron spectroscopy methods. Moreover, the wettability of the surface was determined. It was found that both, Ti-Ag and Nb-Ag thin films were nanocrystalline. In the case of Ag-Ti film presence of AgTi3 and Ag phases was identified, while in the structure of Nb-Ag only silver occurred in a crystal form. In both cases the average size of crystallites was ca. 11 nm. Moreover, according to scanning electron microscopy and atomic force microscopy investigations the surface of Nb-Ag thin films was covered with Ag-agglomerates, while Ti-Ag surface was smooth and devoid of silver particles. Studies of biological activity of deposited coatings in contact with Bacillus subtilis, Pseudomonas aeruginosa, Enterococcus hirae, Klebisiella pneumoniae, Escherichia coli, Staphylococcus aureus and Candida albicans were performed. It was found that prepared coatings were bactericidal and fungicidal even in a short term-contact, i.e. after 2 h.


Development and Validation of a Predictive Model of the Risk of Pediatric Septic Shock Using Data Known at the Time of Hospital Arrival.
To derive and validate a model of risk of septic shock among children with suspected sepsis, using data known in the electronic health record at hospital arrival. This observational cohort study at 6 pediatric emergency department and urgent care sites used a training dataset (5 sites, April 1, 2013, to December 31, 2016), a temporal test set (5 sites, January 1, 2017 to June 30, 2018), and a geographic test set (a sixth site, April 1, 2013, to December 31, 2018). Patients 60 days to 18 years of age in whom clinicians suspected sepsis were included; patients with septic shock on arrival were excluded. The outcome, septic shock, was systolic hypotension with vasoactive medication or ≥30 mL/kg of isotonic crystalloid within 24 hours of arrival. Elastic net regularization, a penalized regression technique, was used to develop a model in the training set. Of 2464 included visits, septic shock occurred in 282 (11.4%). The model had an area under the curve of 0.79 (0.76-0.83) in the training set, 0.75 (0.69-0.81) in the temporal test set, and 0.87 (0.73-1.00) in the geographic test set. With a threshold set to 90% sensitivity in the training set, the model yielded 82% (72%-90%) sensitivity and 48% (44%-52%) specificity in the temporal test set, and 90% (55%-100%) sensitivity and 32% (21%-46%) specificity in the geographic test set. This model estimated the risk of septic shock in children at hospital arrival earlier than existing models. It leveraged the predictive value of routine electronic health record data through a modern predictive algorithm and has the potential to enhance clinical risk stratification in the critical moments before deterioration.


The deafferentation syndrome in the rat: effects of intraventricular neurotensin and cholecystokinin.
A deafferentation syndrome can be produced in rats by dorsal root ganglionectomies. This syndrome consists of scratching and/or biting of the anesthetic limb to the point of amputation. This behavior may serve as an experimental model to study certain aspects of chronic dysesthesias and/or pain caused by deafferentation in man. In this study, we made behavioral observations on the deafferentation syndrome and examined the possibility that intraventricular neurotensin and cholecystokinin alter the course of this syndrome. We found that neurotensin accelerated the scratching component without affecting the biting behavior. Cholecystokinin, however, attenuated the release of both components of the syndrome.


Application of "OTSU"-an image segmentation method for differentiation of snow and ice regions of glaciers and assessment of mass budget in Chandra basin, Western Himalaya using Remote Sensing and GIS techniques.
In this study, an image segmentation algorithm ("OTSU") is applied for differentiation of snow/ice regions followed by interpretation of snowlines and estimation of mass budget of glaciers in Chandra basin, Western Himalaya, India between 2014 and 2020. The observations strongly suggest that the OTSU method can be used to differentiate the snow and ice regions on a glacier accurately from any satellite image, irrespective of the sensor characteristics. Also, this method suits well to delineate the snowlines for large sample of glaciers, other than the manual interpretation and semi-automated methods. The estimates of mass budget of the glaciers are observed varying from - 1.20 ± 0.51 m w.e to almost 0.64 ± 0.51 m w.e, with a total loss of - 61.91 ± 6.70 m w.e of ice mass at basin scale during the observation period. Based on this study, it is highly recommended the application of OTSU method for the differentiation of snow/ice zones of glaciers and snowline demarcation at a large spatial scale in the harsh weather rugged terrain of the Western Himalaya.


Systematic analysis of expression profiles and prognostic significance for MMDS-related iron-sulfur proteins in renal clear cell carcinoma.
Mitochondrial metabolism disorders play an important role in the occurrence and development of tumors, and iron-sulfur protein is an important molecule for maintaining the normal function of mitochondria. However, the relationship between the expression, prognostic value, and immune infiltration of MMDS-related iron-sulfur protein genes in kidney renal clear cell carcinoma (KIRC) remains unclear. Based on online databases bioinformatics analysis was performed to evaluate the expression differences, survival impacts, immune infiltration, and prognostic significance of multiple mitochondrial dysfunction syndrome (MMDS)-related iron-sulfur protein genes in KIRC patients. For example, the protein-protein interaction (PPI) network was constructed using STRING and GEPIA database; Survival impacts were constructed by TCGA database; Immune infiltration was analyzed using TIMER database. There were significant differences in the mRNA expression levels of ISCA1, ISCA2, C1ORF69 and NFU1 in KIRC among different tumor grades and individual cancer stages. Furthermore, KIRC with high transcription levels of ISCA1, ISCA2, C1ORF69 and NFU1 (p < 0.01) was significantly associated with long overall survival (OS) and disease-free survival (DFS). In addition, overexpression of four genes, NFU1, ISCA1, ISCA2, and C1ORF69 in KIRC indicated a better prognosis. Further studies showed that immune cells had a significantly positive correlation with iron-sulfur protein family genes, including CD8+ T cells, CD4+ T cells and B cells. More importantly, the results of immunohistochemistry showed that the expression of NFU1, ISCA1, ISCA2 and C1ORF69 in normal tissues was higher than that in renal clear cell carcinoma tissues. In this study, we systematically analyzed the expression and prognostic value of iron-sulfur protein family genes in KIRC. More importantly, NFU1, ISCA1, ISCA2, and C1ORF69 are expected to become potential therapeutic targets for KIRC, as well as potential prognostic markers for improving the survival rate and prognostic accuracy of KIRC.


Radionuclide ventriculography (equilibrium gated blood pool scanning)--its present clinical position and recent developments.
Myocardial scanning (MS) and radionuclide ventriculography (RNV) are the foundation of nuclear cardiology. These procedures aim in two completely different directions: RNV tries to image heart motion, that is, mechanical (pump) function, and therefore belongs to the group of first-order functional imaging (FI, imaging mechanical function), whereas MS is based on myocardial metabolism, and therefore can be attributed to third-order functional imaging (metabolism). This statement is relevant for the assessment of the clinical position of RNV: Third-order (metabolism) functional imaging is the domain of nuclear medicine (NM), whereas first-order FI has to face the competition of alternative noninvasive procedures such as ultrasound (US), digital subtraction angiography (DSA), computer tomography (CT), and nuclear magnetic resonance (NMR). The domain of RNV includes stages two (acute infarction) and three (postinfarction period) of coronary arterial disease (CAD). The advantageous combination of quantitative data on global, left ventricular (LV) function and imaging of regional motion ensures the superiority of RNV over US. However, RNV is inferior to MS in physical examinations in the preinfarction stage of CAD, whereas US is clearly inferior to both NM procedures. Recent progress could be attained by gated SPECT (GASPECT). A proposal is presented for simplification of this time-consuming procedure. Technetium-labeled isonitriles offer the chance for the combination of "perfusion-motion" imaging of the myocardium. However, even standard RNV offers new possibilities. The multitude of parameters produced by quantitation has not yet been exploited completely. This can be done by discriminant analysis. The computer finds out an optimal subset from the whole set of parameters for the solution of a significant clinical problem. The software "learns" to find the "label" of a special pathognomonic entity. This computer work is supported by a relational data bank (Oracle) and an optical disk. Two examples for the effectiveness of the computer in problem solving are presented. It is concluded that RNV, even in the very competitive class of first-order functional imaging, enjoys a preferred position. The future indeed seems brighter because labeled isonitriles offer the chance for the combination of perfusion-motion imaging of the myocardium.


Deploying two-stage anaerobic process to co-digest greasy sludge and waste activated sludge for effective waste treatment and biogas recovery.
High-strength waste activated sludge (WAS) and greasy sludge (GS) were largely generated from canned tuna processing. This study reports the performance of the two-stage anaerobic process for co-digesting WAS and GS. Various WAS:GS mixing ratios of 0:100, 10:90, 20:80, 30:70, 40:60, 50:50, 60:40, 70:30, 80:20, 90:10, and 100:00 (volatile solids (VS) basis) were investigated in batch acidogenic stage at ambient (30 °C ± 3 °C), 55 °C, and 60 °C temperatures. Subsequently, the effluents from the first stage were used to produce methane in the second methanogenic stage at an ambient temperature. The highest methane yield of 609 mL CH4/g-VSadded was achieved using acidogenic effluents generated from a WAS:GS mixing ratio of 40:60 at an ambient temperature. The first-order kinetic constants (k) for the first (k1) and second (k2) stages were subsequently estimated to be 0.457 d-1 and 0.139 d-1, respectively. The obtained k constants were further used to predict the hydraulic retention time (HRT) for the two continuously stirred tank reactors (CSTR) in series. Consequently, the calculated 4-day HRT and 20-day HRT for 50-L CSTR1 and 250-L CSTR2, respectively, were used to operate the continuous two-stage process at an ambient temperature by feeding with a 40:60-WAS:GS mixing ratio. A satisfactory methane yield of 470-mL CH4/g-VS along with 75% chemical oxygen demand (COD) removal was generated. Furthermore, the predicted methane yield of 450-mL CH4/g-VS obtained from the simple kinetic CSTR model resembled the experimental yield with 96% accuracy. The obtained experimental results demonstrate that WAS and GS co-digestion could be successfully accomplished using a practical two-stage anaerobic process operated at an ambient temperature.


Auditory Processing Intervention Program for school-aged children - development and content validation.
The study aimed at the development and content validation of an Auditory Processing Intervention Program for school-aged European Portuguese speaking children with Auditory Processing Disorder. The first step was the program's development and its instructions manual, which includes objectives, activities, procedures, materials, reinforcement, instructions, and verbal stimuli used, for the following auditory skills: auditory discrimination, auditory attention; auditory memory; auditory closure; figure-ground; auditory separation; auditory integration; binaural fusion; content validation was performed next, with two expert panels analyzing the program, through the use of a questionnaire. Content validity was calculated using the content validity index. Program evaluation shows an excellent content validity. Some items were modified after analyzing the experts' comments and suggestions (e.g. instructions, intensity differences, main character). This work allowed the development and content validation of an auditory processing intervention program, with verbal stimuli, selected according to strict linguistic criteria. In the future, the acceptability and efficacy of this program with the target population should be analyzed.


Application of CRISPR/Cas9-based genome editing in ecotoxicology.
Chemicals are widely used and released into the environment, and their degradation, accumulation, migration, and transformation processes in the environment can pose a threat to the ecosystem. The advancement in analytical methods with high-throughput screening of biomolecules has revolutionized the way toxicologists used to explore the effects of chemicals on organisms. CRISPR/Cas is a newly developed tool, widely used in the exploration of basic science and biologically engineered products given its high efficiency and low cost. For example, it can edit target genes efficiently, and save loss of the crop yield caused by environmental pollution as well as gain a better understanding of the toxicity mechanisms from various chemicals. This review briefly introduces the development history of CRISPR/Cas and summarizes the current application of CRISPR/Cas in ecotoxicology, including its application on improving crop yield and drug resistance towards agricultural pollution, antibiotic pollution and other threats. The benefits by applying the CRISPR/Cas9 system in conventional toxicity mechanism studies are fully demonstrated here together with its foreseeable expansions in other area of ecotoxicology. Finally, the prospects and disadvantages of CRISPR/Cas system in the field of ecotoxicology are also discussed.


The relationship between serum water proton T1 and protein content in the P388 leukemic mouse and the effect of chemotherapy by cis-diamminedichloroplatinum(II).
Proton NMR longitudinal relaxation times (T1; 10.7 MHz; 37 degrees C) were measured in the kidneys and blood serum of mice inoculated with P388 leukemia, and/or treated with the chemotherapeutic drug cis-diamminedichloroplatinum(II) (cis-Pt). In parallel, serum total protein content, urea and creatinine levels were determined and protein fractions were separated electrophoretically. Serum T1 was found to be 1518 +/- 73 ms (1 SD) in control mice, 1670 +/- 69 ms in leukemic mice, and 1380 +/- 71 ms in the healthy and the leukemic cis-Pt treated mice. The T1 increase in leukemic serum and T1 decrease in the serum of cis-Pt injected mice are attributed to decreased and increased protein contents respectively. A detailed analysis in terms of electrophoretic fractions of serum proteins reveals that the serum relaxation rate 1/T1 is a multilinear function of the mass concentrations of the main serum protein fractions, explaining all serum T1 effects. This makes T1 a non-specific blood parameter. The kidney T1 was found to be 311 +/- 12 ms in normal mice and 334 +/- 20 ms in leukemic mice. A dramatic T1 increase is observed when the mice are injected with cis-Pt; the values are 400 +/- 38 ms and 407 +/- 39 ms for healthy and leukemic mice, respectively. This effect is related to the nephrotoxicity of the drug, as evidenced by serum urea and creatinine levels and protein content being higher than normal.


A simple technique for the fabrication of P(St-BA-AA) colloidal crystal microdots on ink-jet paper.
The generation of three-dimensional superb packages of compact hexagonal periodic assembly with multifaceted layers was demonstrated using Poly (styrene-butylcrylate-acrylic acid) on glass substrates. The synthesized P(St-BA-AA) microspheres were used to formulate a fast drying UV curable terpolymer microspheres printing ink for the generation of colloidal crystal microdots on ink-jet paper with remarkable colours. The terpolymer microspheres and their formulated terpolymer ink undergo self-assembly to form blue monochromatic and viewing angle dependent tunable colours, thus affirming the photonic nature of the generated colloidal crystal films. Unlike other printing techniques which usually make use of specialized tools, this study generated a well ordered coloured tunable assembly of spherical shaped core-shell colloidal crystal microdots on the surface of an inkjet-paper by manually writing the as-synthesized P(St-BA-AA) UV curable printing ink microdots on it. The TEM analysis showed core and shell sizes of 198/50nm and 176/30nm for P(St-BA-AA)1 and P(St- BA-AA)2 respectively. Whenever the prepared terpolymer microspheres are used within the heating and transition temperatures of 383 °C and 110 °C, their thermal stability is retained. This simple technique of generating crystals microdots on inkjet paper may find use in optical devices, security applications and other colour coating applications.


Mobilization of contaminants: Potential for soil remediation and unintended consequences.
Land treatment has become an essential waste management practice. Therefore, soil becomes a major source of contaminants including organic chemicals and potentially toxic elements (PTEs) which enter the food chain, primarily through leaching to potable water sources, plant uptake, and animal transfer. A range of soil amendments are used to manage the mobility of contaminants and subsequently their bioavailability. Various soil amendments, like desorbing agents, surfactants, and chelating agents, have been applied to increase contaminant mobility and bioavailability. These mobilizing agents are applied to increase the contaminant removal though phytoremediation, bioremediation, and soil washing. However, possible leaching of the mobilized pollutants during soil washing is a major limitation, particularly when there is no active plant uptake. This leads to groundwater contamination and toxicity to plants and soil biota. In this context, the present review provides an overview on various soil amendments used to enhance the bioavailability and mobility of organic and inorganic contaminants, thereby facilitating increased risk when soil is remediated in polluted areas. The unintended consequences of the mobilization methods, when used to remediate polluted sites, are discussed in relation to the leaching of mobilized contaminants when active plant growth is absent. The toxicity of targeted and non-targeted contaminants to microbial communities and higher plants is also discussed. Finally, this review work summarizes the existing research gaps in various contaminant mobilization approaches, and prospects for future research.


Notes on the models of cadmium kinetics.
This paper identifies several drawbacks in the models of absorption and desorption of cadmium presented by [Garcia-Gomez, C., Carbonell, G., 2004. Modelling the absorption and desorption of cadmium on paper pulp using kinetic approaches. Chemosphere 55, 869-878]. It then provides suggestions on improving the effectiveness of the model.


Human papillomavirus and cervical disease in adolescents.
The addition of the human papillomavirus vaccination and the 2006 national guidelines for the management of abnormal cervical cytology have led to significant changes in the management of cervical disease among adolescents. This article reviews recommendations for prevention, screening, diagnosis, and management of cervical disease.


Developmental outcome in newborn infants treated for acute respiratory failure with extracorporeal membrane oxygenation: present experience.
To describe the later health status of newborn infants who received extracorporeal membrane oxygenation (ECMO) for acute respiratory failure in the era after the UK ECMO trial. Prospective follow up study of newborn infants who received ECMO at a single centre between January 1997 and January 2001. Departments of ECMO and Paediatric Intensive Care, University Hospitals of Leicester. All babies who received ECMO within 14 days of birth. Neurodevelopment screening using the schedule for growing skills-II (SGS-II) assessment tool. Survival at 12 months of age by disease and functional development at follow up. A total of 145 neonates received ECMO for treatment of respiratory failure. Of these, 108 (75%) were alive at 1 year of age. There were no deaths in children treated for respiratory failure secondary to meconium aspiration syndrome (73/145). Ninety three (86% of survivors) infants attended a follow up visit at 11-19 months postnatal age. Eighty two were classed as normal, seven as having "impairment", and four as having "severe disability". Most newborn infants with acute respiratory failure treated with ECMO will have a normal neurodevelopment screening assessment at 11-19 months of postnatal age. There is no evidence to suggest that changes in neonatal practice since the UK ECMO trial have led to changes in outcome of infants undergoing ECMO therapy.


A year in the thermal life of a free-ranging herd of springbok Antidorcas marsupialis.
We used miniature data loggers implanted in the abdominal cavity to measure core body temperatures at 30 min intervals in eight (three males, five females) adult free-ranging springbok Antidorcas marsupialis in their natural habitat, over a period of 11-13 months. The animals were subjected to a nychthemeral range of air temperature that often exceeded 20 degrees C, with an absolute minimum temperature of -6 degrees C and a maximum of 34 degrees C. Abdominal temperature exhibited a low amplitude (approximately 1.2 degrees C) nychthemeral rhythm, with a temperature peak near sunset and a trough shortly after sunrise. The amplitude of the nychthemeral rhythm of body temperature was not correlated with the 24 h range of air temperature. Although mean 24 h body temperatures were positively correlated with corresponding air temperatures, mean daily body temperature increased, on average, by only 0.02 degrees C per 1 degrees C increase in air temperature, so that it was only approximately 0.3 degrees C higher in summer than in winter. Mean monthly body temperatures were strongly positively correlated with photoperiod and, in parallel with changes in the time of sunrise, the times at which the minimum and maximum body temperatures occurred were shifted approximately 1.2 h earlier in summer than in winter. Annual and daily variations in body temperature of springbok, like those of other free-living African ungulates, therefore appear to reflect an endogenous rhythm, entrained by the light:dark cycle, but largely independent of fluctuations in the environmental thermal load. Springbok exhibit remarkable homeothermy and do not employ adaptive heterothermy to survive in their natural environment.


Vital Signs: Increased Medicaid Prescriptions for Preexposure Prophylaxis Against HIV infection--New York, 2012-2015.
Approximately 3,000 incident cases of human immunodeficiency virus (HIV) infection occur in New York state each year. Daily HIV preexposure prophylaxis (PrEP) with the oral antiretroviral medication Truvada is a key component of New York's plan to end HIV/acquired immunodeficiency syndrome (AIDS) as an epidemic in the state by 2020. Prescription data from the New York state Medicaid program from July 2012 through June 2015 were analyzed with an algorithm using medication and diagnoses codes to identify continuous use of Truvada for >30 days, after excluding use for postexposure prophylaxis or treatment of HIV or chronic hepatitis B infection. During July 2012-June 2013, a total of 259 persons filled prescriptions for PrEP in the Medicaid program. During July 2013-June 2014, a total of 303 persons filled prescriptions for PrEP. During July 2014-June 2015, a total of 1,330 persons filled prescriptions for PrEP, a substantial increase over the previous 12 months. Across all periods studied, 1,708 Medicaid recipients filled at least one prescription for PrEP, most of whom were New York City (NYC) residents, male, aged <50 years, and, for those with available data on race, white. PrEP use by Medicaid-insured persons increased substantially in the years following statewide efforts to increase knowledge of PrEP among potential prescribers and candidates for PrEP. Other jurisdictions can follow New York state's example by taking similar steps to remove the financial and knowledge barriers experienced by both potential users and prescribers of PrEP. Although both state and local health department efforts contribute to the availability and use of PrEP, their collaboration enhances the successful implementation of strategies to increase PrEP use. In addition, the decision by the state Medicaid agency to cover PrEP recognizes the long-term benefits of preventing HIV infections.


Risk factors for severe nonsteroidal anti-inflammatory drug-induced small intestinal damage.
Few studies have assessed the risk factors associated with nonsteroidal anti-inflammatory drugs (NSAIDs)-induced small intestinal damage. To evaluate the risk factors for NSAID-induced enteropathy in patients with rheumatoid arthritis. A cross-sectional study using capsule endoscopy was conducted. A total of 113 patients who took NSAIDs for over 3 months underwent capsule endoscopies. Endoscopic findings were scored as (0) normal, (1) red spots, (2) 1-4 erosions, (3) >4 erosions, or (4) large erosions/ulcers. Initial scores were grouped into 3 categories: No damage (0-1), mild damage (2), and severe damage (3-4), and the potential risk factors for damage development were assessed. Five patients were excluded because of incomplete visualization of the entire small intestine. Fifty-two (47.2%) and 27 (25%) patients had no damage and mild damage, respectively, while the remaining 30 patients (27.8%) had severe damage and significantly decreased hemoglobin levels. In a multivariate logistic regression analysis, ages of 65 years or more (odds ratio [OR], 4.16; 95% confidence interval [CI], 1.51-11.47), proton pump inhibitor usage (OR, 5.22; 95% CI, 1.36-20.11), and histamine H2 receptor antagonist usage (OR, 3.95; 95% CI, 1.28-12.25) were independent risk factors for severe damage. Elderly patients and acid suppressant users are more likely to develop severe NSAID-induced enteropathy.


How inclusive leadership paves way for psychological well-being of employees during trauma and crisis: A three-wave longitudinal mediation study.
Nurses are at the forefront of public health emergencies facing psychological pressures ensuing from the loss of patients and potential risk of infection while treating the infected. This study examines whether inclusive leadership has a causal relationship with psychological distress and to assess the mediation effect of psychological safety on this relationship in the long run. The hypotheses are developed and interpreted with the help of theoretical underpinnings from job demands resources theory and the theory of shattered assumptions. Three-wave longitudinal study. Questionnaire was used to carry out three waves of data collection from 405 nurses employed at five hospitals in Wuhan during the COVID-19 outbreak between the months of January-April 2020. Partial least square structural equation modelling (PLS-SEM) was used to analyze data while controlling for age, gender, education, experience, and working hours. Results supported the hypothesized relationships where inclusive leadership indicated significant inverse causal relationship with psychological distress and a positive causal relationship with psychological safety. Mediation effect of psychological safety was found significant, while the model explained 73.9% variance in psychological distress. Inclusive leadership, through its positive and supportive characteristics, can pave way for such mechanisms that improve the psychological safety of employees in the long run and curbs psychological distress. This is the first longitudinal study to examine the relationship between inclusive leadership and psychological distress in health care and also examines the mediating mechanism of psychology safety. There is scarcity of empirical research on factors that determine and affect behavioural mechanism of healthcare workers during traumatic events and crisis. Clinical leaders and healthcare policy makers must invest in and promote inclusive and supportive environment characterized with open and accessible leaders at workplace to improve psychological safety; it helps reduce levels of psychological distress.


Discovery of a novel Coumarin-Dihydroquinoxalone derivative MY-673 as a tubulin polymerization inhibitor capable of inhibiting the ERK pathway with potent anti-gastric cancer activities.
As a class of microtubule targeting agents, colchicine binding site inhibitors (CBSIs) are considered as promising drug candidates for cancer therapy. However, due to adverse reactions, there are currently no CBSIs approved by FDA for cancer treatment. Therefore, extensive efforts are still encouraged to find novel CBSIs with different chemical structures and better anticancer efficacies. In this work, we designed and synthesized a new coumarin-dihydroquinoxalone derivative, MY-673, and evaluated its anticancer potency in vitro and in vivo. We confirmed that MY-673 was a potent CBSI that it not only inhibited tubulin polymerization, but also exhibited significant inhibitory potency on the growth of 13 cancer cells with IC50 values from 11.7 nM to 395.9 nM. Based on the results of kinase panel screening, MY-673 could inhibit ERK (extracellular regulated protein kinases) pathways-related kinases. We further confirmed that MY-673 could inhibit ERK signaling pathway in MGC-803 and HGC-27 cells, and then affected the expression level of SMAD4 protein in TGF-β (transforming growth factor β) /SMAD (small mother against decapentaplegic) signaling pathway using the western blotting assay. In addition, compound MY-673 could effectively inhibit cell proliferation, migration and induce cell apoptosis. We also further confirmed the in vivo efficacy of MY-673 in inhibiting tumor growth using the MGC-803 xenograft tumor model. At 20 mg/kg, the TGI rate was 85.9%, and it did not cause obvious toxicity to the main organs of mice. Together, the results we report here indicated that MY-673 was a promising CBSI for cancer treatment, which was capable of inhibiting the ERK pathway with potent antiproliferative activities in vitro and in vivo.