Simultaneous pain intensity rating and quantification of ischemia throughout exercise and recovery in proximal versus distal arterial claudication.
Data on simultaneous hemodynamic changes and pain rating estimation in arterial claudication while walking are lacking. This study was conducted to determine if a difference in transcutaneous oxygen pressure (tc pO2) exists between proximal and distal localization at pain appearance (PAINapp), maximal pain (PAINmax) and pain relief (PAINrel) in proximal or distal claudication and if a relationship exists between tc pO2 changes and pain intensity. We analyzed the pain rating (Visual Analog Scale (VAS)) to lower limb ischemia, measured with the decrease from rest of oxygen pressure (DROP) tc pO2 index during constant-load treadmill tests in patients with calf ( n = 41) or buttock ( n = 19) claudication. Calves versus buttocks results were analyzed with ANOVA tests. The R2 correlation coefficient between individual VAS versus DROP was calculated. Ischemia intensity versus pain rating changes were correlated. Significant ischemia was required for pain appearance, but pain disappeared despite the persistence of ischemia. We observed no statistical difference for DROP at PAINapp, PAINmax or PAINrel between proximal or distal claudication. A significant correlation between pain rating versus DROP was found: from PAINapp to PAINmax, R2 = 0.750 (calves) and 0.829 (buttocks), and from PAINmax to PAINrel, R2 = 0.608 (calves) and 0.560 (buttocks); p<0.05. Pain appeared after a significant decrease of hemodynamic parameters but disappeared while parameters were not normalized. No difference in pain rating was found in proximal versus distal claudication.


Cholangitis due to Blastomyces dermatitidis.
A 70-yr-old woman presented with nonspecific complaints and had findings of a cholestatic liver enzyme pattern and a dilated left intrahepatic ductal system by radiographic imaging. Endoscopic retrograde cholangiopancreatography revealed multiple irregular flat stones and a fixed filling defect of the left hepatic duct. At the time of surgery a stonelike lesion of this ductal orifice was found along with a miliary pattern of infection of the left liver lobe. Histologic and microbiologic studies confirmed an infection by Blastomyces dermatitidis. Therapy with amphotericin B resulted in eradication of this infection. Despite their rarity, fungal infections of the biliary tree need to be considered in the differential diagnosis of biliary tract disease in the elderly and immunocompromised patient.


A forecasting framework for predicting perceived fatigue: Using time series methods to forecast ratings of perceived exertion with features from wearable sensors.
Advancements in sensing and network technologies have increased the amount of data being collected to monitor the worker conditions. In this study, we consider the use of time series methods to forecast physical fatigue using subjective ratings of perceived exertion (RPE) and gait data from wearable sensors captured during a simulated in-lab manual material handling task (Lab Study 1) and a fatiguing squatting with intermittent walking cycle (Lab Study 2). To determine whether time series models can accurately forecast individual response and for how many time periods ahead, five models were compared: naïve method, autoregression (AR), autoregressive integrated moving average (ARIMA), vector autoregression (VAR), and the vector error correction model (VECM). For forecasts of three or more time periods ahead, the VECM model that incorporates historical RPE and wearable sensor data outperformed the other models with median mean absolute error (MAE) <1.24 and median MAE <1.22 across all participants for Lab Study 1 and Lab Study 2, respectively. These results suggest that wearable sensor data can support forecasting a worker's condition and the forecasts obtained are as good as current state-of-the-art models using multiple sensors for current time prediction.


Effects of electron cutouts on absorbed dose in and outside Varian-20 electron fields.
Electron beam outputs in the presence of beam shaping cutouts were measured for 6, 9, 12, 16, and 20 MeV electrons from a Varian-20 linear accelerator. This machine was provided with a new model of electron cones, for which photon jaw sizes were set differently from those of old cones. The effects of different photon jaw sizes on the electron outputs were studied. Also measured was the absorbed dose under a cutout, which was presumably contributed by scattered electrons and bremsstrahlung photons.


Tuberculosis in pediatric patients treated with anti-TNFα drugs: a cohort study.
Adult patients receiving anti-TNFα drugs are at increased risk of tuberculosis (TB), but studies in pediatric populations are limited, and the best strategy for latent tuberculosis infection (LTBI) screening in this population remains controversial. We describe the prevalence of LTBI prior to anti-TNFα therapy and the long-term follow-up after biological treatment initiation in a cohort of children and adolescents. Cohort observational study in children and adolescents receiving anti-TNFα agents in a tertiary-care pediatric hospital. LTBI was ruled out prior to the implementation of anti-TNFα drugs by tuberculin skin test (TST), and, from March 2012 on, QuantiFERON Gold-In Tube test (QTF-G). During anti-TNFα treatment, patients were evaluated every 6 months for TB with history and physical examination. TST/QTF-G were not repeated unless signs or symptoms consistent with TB arose or there was proven TB contact. The final cohort consisted of 221 patients (56.1% female; 261 treatments), of whom 51.7%/30.0%/17.3% were treated with etanercept/adalimumab/infliximab, respectively, for a variety of rheumatic diseases (75.6%), inflammatory bowel disease (20.8%), and inflammatory eye diseases (3.6%). The median (IQR) age at diagnosis of the primary condition was 6.8 years (2.7-11.0) and the duration of the disease before implementing the anti-TNFα agent was 1.8 years (0.6-4.2). LTBI was diagnosed in 3 adolescent girls (prevalence rate: 1.4%; 95% CI: 0.4-4.2) affected with juvenile idiopathic arthritis: TST tested positive in only 1, while QTF-G was positive in all cases (including 2 patients already on etanercept). They all received antiTB chemoprophylaxis and were later (re)treated with etanercept for 24-29 months, without incidences. No incident cases of TB disease were observed during the follow-up period under anti-TNFα treatment of 641 patients-year, with a median (IQR) time per patient of 2.3 years (1.4-4.3). In our study, the prevalence of LTBI (1.4%) was similar to that reported in population screening studies in Spain; no incident cases of TB disease were observed. In low-burden TB settings, initial screening for TB in children prior to anti-TNFα treatment should include both TST and an IGRA test, but systematic repetition of LTBI immunodiagnostic tests seems unnecessary in the absence of symptoms or known TB contact.


Antiviral efficacy of cerium oxide nanoparticles.
Nanomaterials are prospective candidates for the elimination of viruses due to their multimodal mechanisms of action. Here, we tested the antiviral potential of a largely unexplored nanoparticle of cerium dioxide (CeO2). Two nano-CeO2 with opposing surface charge, (+) and (-), were assessed for their capability to decrease the plaque forming units (PFU) of four enveloped and two non-enveloped viruses during 1-h exposure. Statistically significant antiviral activity towards enveloped coronavirus SARS-CoV-2 and influenza virus was registered already at 20 mg Ce/l. For other two enveloped viruses, transmissible gastroenteritis virus and bacteriophage φ6, antiviral activity was evidenced at 200 mg Ce/l. As expected, the sensitivity of non-enveloped viruses towards nano-CeO2 was significantly lower. EMCV picornavirus showed no decrease in PFU until the highest tested concentration, 2000 mg Ce/l and MS2 bacteriophage showed slight non-monotonic response to high concentrations of nano-CeO2(-). Parallel testing of antiviral activity of Ce3+ ions and SiO2 nanoparticles allows to conclude that nano-CeO2 activity was neither due to released Ce-ions nor nonspecific effects of nanoparticulates. Moreover, we evidenced higher antiviral efficacy of nano-CeO2 compared with Ag nanoparticles. This result along with low antibacterial activity and non-existent cytotoxicity of nano-CeO2 allow us to propose CeO2 nanoparticles for specific antiviral applications.


Reference intervals established using indirect method for serum ferritin assayed on Abbott Architect i2000SR analyzer in Chinese adults.
Serum ferritin (SF) test has been widely used in clinical practice. However, its reference intervals (RIs) vary depending on the analytical method and ethnic origin. This study was to establish the RIs using indirect method for SF in Chinese adults. SF was assayed on Abbott i2000SR analyzer. The SF test results of all health examinees (8913 males aged 18-93 years and 5397 females aged 18-90 years) between December 2010 and April 2019 were obtained from our laboratory information system. After Box-Cox transformation of raw data and exclusion of outliers, parametric and non-parametric approaches were used to calculate 95% RIs. The correlation between SF levels and ages, and the differences in SF levels between subgroups were also analyzed. SF levels in females were significantly different from those in males (Z = 88.96, Z* = 23.17; Z > Z*) and showed a weak positive correlation with age (r = .466, P < .0001). The RIs based on parametric approach in males were 66.12-561.58 µg/L, whereas in all females were 3.59-269.59 µg/L, females aged <50 years 3.26-148.02 µg/L and those aged ≥50 years 17.28-303.27 µg/L. The RIs based on non-parametric approach in males were 65.00-571.37 µg/L whereas in all females were 4.00-254.00 µg/L, females aged <50 years 4.00-152.00 µg/L and those aged ≥50 years 16.00-304.05 µg/L. Our indirect RIs for SF were markedly different from the manufacturer's recommended RIs and might be more suitable for Chinese adults, which would be helpful in interpreting laboratory data and clinical decision-making.


[Secretion of plasminogen activators and their inhibitors in corneal fibroblasts. Modification of this secretion in Schnyder's lens corneal dystrophy].
In this study, we have shown that the secretion of plasminogen activators (PA) by corneal fibroblasts from Schnyder dystrophy is much lower than that secreted by normal corneal fibroblasts. This defective secretion of PA was noted both in the supernatant of cell culture and on the cell surface. This anomaly is found in cultured fibroblasts and therefore is not related to environment modification. Since PA was implicated in remodeling of extracellular matrix, we hypothesized that this anomaly should be responsible for the corneal dystrophy.


Evaluation of the prevalence of the most common psychiatric disorders in patients with type 2 diabetes mellitus using the patient health questionnaire: results of the cross-sectional "DIA2PSI" study.
Common Psychiatric Disorders (CPDs) are associated with the development of overweight and obesity, the strongest risk factors for the onset and maintenance of Type 2 Diabetes mellitus (T2D). To the best of our knowledge, this is the first study to assess the prevalence of CPDs in patients with T2D in Italy. This is a monocentric cross-sectional study; n = 184 T2D patients were screened for CPDs using the Patient Health Questionnaire (PHQ). Primary outcome was to evaluate the prevalence of CPDs. To assess association between CPDs and risk factors, we have utilized univariable logistic regression models. 64.1% were men, median age was 67 (59-64) and median BMI 27 (25-30) kg/m2. The 42.9% tested positive for one or more mental disorders, 25.6% for depression. Patients with higher BMI (p = 0.04) had an increased likelihood of testing positive to the PHQ. Patients who had implemented lifestyle changes (p < 0.01) and were aware that mental health is linked to body health (p = 0.07) had a reduction in the likelihood of testing positive. Prevalence of CPDs in T2D patients is higher than in the general population. Since CPDs favor the onset and subsistence of T2D, integrated diabetic-psychiatric therapy is required for improvement or remission of T2D in patients with comorbid CPDs.


Ex vivo magnifying endoscopic observation of bile duct mucosa using narrowband imaging.
Detailed endoscopic findings of the bile duct mucosa have not been fully established. This fundamental ex vivo study assesses the relationship between magnified endoscopic findings and pathological findings of the bile duct mucosa. Forty-one surgically resected common bile duct mucosae were investigated. Each common bile duct was cut open longitudinally for ex vivo endoscopic observation. A magnifying endoscope commonly used for the gastrointestinal tract was used, using both white light imaging and narrowband imaging. After pathological diagnosis, the association between the magnifying endoscopic findings and histopathology was evaluated. Totally, 39 non-neoplastic mucosae and 13 neoplastic mucosae were evaluated. In 13 non-neoplastic mucosae without inflammation, an oval-shaped depressed area and a fine, regular network of microvessels were observed. These findings were not clearly seen or not seen at all in the non-neoplastic mucosae with inflammation. Although vessels with loop-like structure were observed on all eight papillary tumors of 13 neoplastic mucosae, no characteristic vessels were seen on the other five. Ishida and colleagues assessed the association between magnifying endoscopic findings and histopathological findings of the bile duct mucosa ex vivo. Oval-shaped, depressed areas and a fine, regular network of microvessels are characteristic features of normal bile duct mucosa, while loop structures may be indicative of a type of tumor vessel.


Current knowledge and clinical perspectives for a unique new phylum: Nanaorchaeota.
Nanoarchaea measuring less than 500 nm and encasing an average 600-kb compact genome have been studied for twenty years, after an estimated 4193-million-year evolution. Comprising only four co-cultured representatives, these symbiotic organisms initially detected in deep-sea hydrothermal vents and geothermal springs, have been further distributed in various environmental ecosystems worldwide. Recent isolation by co-culture of Nanopusillus massiliensis from the unique ecosystem of the human oral cavity, prompted us to review the evolutionary diversity of nanaorchaea resulting in a rapidly evolving taxonomiy. Regardless of their ecological niche, all nanoarchaea share limited metabolic capacities correlating with an obligate ectosymbiotic or parasitic lifestyle; focusing on the dynamics of nanoarchaea-bacteria nanoarchaea-archaea interactions at the morphological and metabolic levels; highlighting proteins involved in nanoarchaea attachment to the hosts, as well metabolic exchanges between both organisms; and highlighting clinical nanoarchaeology, an emerging field of research in the frame of the recent discovery of Candidate Phyla radiation (CPR) in human microbiota. Future studies in clinical nanobiology will expand knowledge of the nanaorchaea repertoire associated with human microbiota and diseases, to improve our understanding of the diversity of these nanoorganims and their intreactions with microbiota and host tissues.


Relationship Between Hair Cell Loss and Hearing Loss in Fishes.
Exposure to intense sound or ototoxic chemicals can damage the auditory hair cells of vertebrates, resulting in hearing loss. Although the relationship between such hair cell damage and auditory function is fairly established for terrestrial vertebrates, there are limited data available to understand this relationship in fishes. Although investigators have measured either the morphological damage of the inner ear or the functional deficits in the hearing of fishes, very few have directly measured both in an attempt to find a relationship between the two. Those studies that have examined both auditory hair cell damage in the inner ear and the resulting hearing loss in fishes are reviewed here. In general, there is a significant linear relationship between the number of hair cells lost and the severity of hearing threshold shifts, although this varies between species and different hair cell-damaging stimuli. After trauma to the fish ear, auditory hair cells are able to regenerate to control level densities. With this regeneration also comes a restoration of hearing. Thus there is also a significant relationship between hair cell recovery and hearing recovery in fishes.


Patterns of metal soil contamination and changes in terrestrial cryptogamic communities.
Correlations between terricolous bryophyte- and lichen- vegetation and edaphic parameters (pH, organic matter, nitrogen, Carbon/nitrogen ratio, Cation Exchange Capacity, and Cd, Pb and Zn soil contents) of soils submitted to a gradient of metal contamination in northern France were performed using statistical analysis. Six classes can be distinguished according to the low-, intermediate- and high-trace metal levels respectively, leading to the conclusion that bryophyte- and lichen-groupings have a strong bioindicative value of the heavy metal pollution of soils.


Direct anti-inflammatory effects of angiotensin-(1-7) on microglia.
Much evidence indicates that pro-inflammatory effects of the renin-angiotensin system within the hypothalamus, including microglial activation and production of pro-inflammatory cytokines, play a role in chronic neurogenic hypertension. Our objective here was to examine whether angiotensin-(1-7) [Ang-(1-7)], a protective component of the renin-angiotensin system, exerts direct actions at microglia to counteract these pro-inflammatory effects. Mas, the Ang-(1-7) receptor, was shown to be present on cultured hypothalamic microglia. Treatment of these cells with Ang-(1-7) (100-1000 nM, 3-12 h) elicited significant decreases in basal levels of mRNAs for the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor-necrosis factor α (TNFα) and of the microglia-macrophage marker CD11b, and increases in basal levels of the anti-inflammatory cytokine interleukin-10. Incubation of microglial cultures with (pro)renin (PRO) (10-50 nM; 6 h) elicited significant increases in mRNAs for IL-1β, TNFα and CD11b. The effects of PRO (10 nM) on IL-1β and TNFα mRNAs, and TNFα protein, were significantly attenuated by co-treatment with Ang-(1-7) (100 nM). Lastly, these actions of Ang-(1-7) were abolished by the Mas antagonist A-779, and were associated with reductions in NF-κB subunit expression. Collectively, these data provide the first evidence that Ang-(1-7) can exert direct effects at microglia to lower baseline and counteract PRO-induced increases in pro-inflammatory cytokines. Renin-Angiotensin system mediated microglial activation and pro-inflammatory cytokine production within the hypothalamus are components of the chronic neuroinflammation associated with 'neurogenic' hypertension. We demonstrated that angiotension-(1-7) acting via its receptor Mas on hypothalamic microglia lessens baseline and (pro)renin-induced increases in pro-inflammatory cytokine production by these cells. This is the first evidence that angiotensin-(1-7) has direct anti-inflammatory effects via microglia.


Evaluation of DNA adduct damage using G-quadruplex-based DNAzyme.
Toxicity assessment is a major problem in pharmaceutical candidates and industry chemicals development. However, due to the lack of practical analytical methods for DNA adduct analysis, the safety evaluation of drug and industry chemicals was severely limited. Here, we develop a DNAzyme-based method to detect DNA adduct damage for toxicity assessment of drugs and chemicals. Among 18 structural variants of G4 DNAzyme, EA2 DNAzyme exhibits an obvious DNA damaging effect of styrene oxide (SO) due to its unstable structure. The covalent binding of SO to DNAzyme disrupts the Hoogsteen hydrogen bonding sites of G-plane guanines and affects the formation of the G4 quadruplex. DNA damage chemicals reduce the peroxidase activity of the G4 DNAzyme to monitor the DNA adduct damage by disrupting the structural integrity of the G4 DNAzyme. Our method for genotoxic assessment of pharmaceutical candidates and industrial chemicals can elucidate the complex chemical pathways leading to toxicity, predict toxic effects of chemicals, and evaluate possible risks to human health.


Healing of leg ulcers associated with transjugular intrahepatic portosystemic shunt in decompensated cirrhosis: case series of a possible hepatodermal syndrome.
The occurrence of leg ulcers in patients with cirrhosis is not well documented in the literature. In this case series, we describe 4 patients with cirrhosis complicated by leg ulceration that failed all conventional therapy, yet healed completely following the placement of transjugular intrahepatic portosystemic shunt. The course of disease and the possibility of a hepatodermal syndrome underlying this observation are discussed.


National validation of the nursing Intensive-Care satisfaction scale: Research protocol.
Validate the Nursing Intensive-Care Satisfaction Scale in ICUs throughout Spain. Identify the improvement strategies recommended by the patients and professionals. Quantitative psychometric methodology and a cross-sectional descriptive correlational design. The study population will be all patients discharged from 19 participating ICUs in Spain. Consecutive sampling (n = 564). Once discharged from the ICUs, they will receive the questionnaire and then, after 48 hours it will be given to them again to analyse the temporal stability. To validate the questionnaire, the internal consistency (Cronbach's Alpha) and temporal stability (test-retest) will be analysed. Improve the quality of nursing care by modifying, changing or strengthening behaviours, skills, attitudes or areas for improvement involved in the process.


Modulation of the immune response by plasma protease inhibitors III. Alpha 1-antichymotrypsin inhibits human natural killing and antibody-dependent cell-mediated cytotoxicity.
The effects of alpha 1-antichymotrypsin (AChy), a serum protease inhibitor, on two parameters of the cellular immune response, natural killing (NK) and antibody-dependent cell-mediated cytotoxicity (ADCC), were tested. Both NK and ADCC were inhibited by the protein in a dose-dependent fashion. Our results suggest that this protease inhibitor binds to the surface of NK and ADCC target cells and neutralizes the lytic signal passed between the effector and target.


Effect of obesity and weight loss on ventricular repolarization: a systematic review and meta-analysis.
We performed a systematic review and meta-analysis of the effects of obesity ± overweight and weight loss on the corrected QT interval (QTc) and QT or QTc dispersion (indices of ventricular repolarization). Mean difference for both QTc and QT or QTc dispersion with 95% confidence intervals (CIs) was calculated comparing obese ± overweight subjects and normal weight controls and QTc and QT or QTc dispersion before and after weight loss from diet ± exercise or bariatric surgery. A total of 22 studies fulfilled the selection criteria. Compared with normal weight controls, there was a significantly longer QTc in obese ± overweight subjects (mean difference of 21.74 msec, 95% CI: 18.76 to 22.32) and significantly longer QT or QTc dispersion (mean difference of 15.17 msec, 95% CI: 13.59 to 16.74). Weight loss was associated with a significant decrease in QTc (mean difference -25.77 msec, 95% CI: -28.33-23.21) and QT or QTc dispersion (mean difference of -13.46 msec, 95% CI: -15.60 to -11.32 in obese ± overweight subjects. Thus, obesity ± overweight is associated with significant prolongation of QTc and QT or QTC dispersion. Weight loss in obese ± overweight subjects produces significant decreases in these variables. © 2016 World Obesity.


[Social inequality in home care].
Social inequality in Germany is discussed primarily with regard to educational or social welfare issues. There is a political consensus that more action should be taken to ensure equality of chances and fulfillment of basic needs for everyone. In long-term care these considerations have not yet taken place and there are hardly any research studies in this field. However, the startling rise of the need for long-term care will definitely require a discussion of social inequality in various care arrangements. To learn more about social inequality in home care, a qualitative approach was used and 16 home care nurses were interviewed. Our study shows that many care recipients face numerous problems they cannot handle on their own, which may even worsen their situation. In addition, the results reveal that facing social inequalities place a burden on nurses and influence their work performance.


Designing a bioadjuvant candidate vaccine targeting infectious bursal disease virus (IBDV) using viral VP2 fusion and chicken IL-2 antigenic epitope: A bioinformatics approach.
Infectious Bursal Disease (IBD) is a common and contagious viral infection that significantly affects the poultry industry. This severely suppresses the immune system in chickens, thereby threating their health and well-being. Vaccination is the most effective strategy for preventing and controlling this infectious agent. The development of VP2-based DNA vaccines combined with biological adjuvants has recently received considerable attention due to their effectiveness in eliciting both humoral and cellular immune responses. In this study, we applied bioinformatics tools to design a fused bioadjuvant candidate vaccine from the full-length sequence of the VP2 protein of IBDV isolated in Iran using the antigenic epitope of chicken IL-2 (chiIL-2). Furthermore, to improve the antigenic epitope presentation and to maintain the three-dimensional structure of the chimeric gene construct, the P2A linker (L) was used to fuse the two fragments. Our in-silico analysis for the design of a candidate vaccine indicates that a continuous sequence of amino acid residues ranging from 105 to 129 in chiIL-2 is proposed as a B cell epitope by epitope prediction servers. The final 3D structure of the VP2-L-chiIL-2105-129 was subjected to physicochemical property determination, molecular dynamic simulation, and antigenic site determination. The results of these analyses led to the development of a stable candidate vaccine that is non-allergenic and has the potential for antigenic surface display potential and adjuvant activity. Finally, it is necessary to investigate the immune response induced by our proposed vaccine in avian hosts. Notably, increasing the immunogenicity of DNA vaccines can be achieved by combining antigenic proteins with molecular adjuvants using the principle of rational vaccine design.


Comprehensive analysis of the expression, prognosis and biological significance of FSCN family in clear cell renal cell carcinoma.
Fascin (FSCN) is an actin-binding protein that serves a critical role in cell migration and invasion, contributing to tumor metastasis. However, there is little known about the function of FSCN family in kidney renal clear cell carcinoma (KIRC). The present study used the UALCAN, gene expression profiling interactive analysis, The Cancer Genome Atlas, cBioPortal, STRING and The Tumor Immune Estimation Resource databases to investigate the transcription level, genetic alteration and biological function of FSCNs in KIRC and their association with the prognosis value and immune cell infiltration in patients with KIRC. Results showed that the expression of FSCN1 and FSCN3 was markedly upregulated in patients with KIRC, while the expression of FSCN2 showed an opposite trend, which was the same as the experiments. Furthermore, the expression levels of FSCNs were associated with pathological stage, molecular subtypes and tumor grade. The expression levels of FSCNs were statistically correlated with the immune cell infiltration in KIRC. Higher expression levels of FSCN1 and FSCN3 were associated with worse overall survival (OS) and progression-free interval of patients bearing KIRC. Univariate and multivariate analysis demonstrated that FSCN2 was an independent risk factor for OS time in KIRC. Furthermore, mutations in FSCNs were significantly associated with poor OS and progression-free survival in patients with KIRC. The FSCNs were involved in pathways including focal adhesion, endocytosis, hypertrophic cardiomyopathy, regulation of actin cytoskeleton. The results indicated that FSCN2 might serve as an independent prognostic factor for OS of KIRC and that FSCN1 and FSCN3 can be used as favorable biomarkers for predicting clinical outcomes in KIRC.


Music, rhythm, rise time perception and developmental dyslexia: perception of musical meter predicts reading and phonology.
Rhythm organises musical events into patterns and forms, and rhythm perception in music is usually studied by using metrical tasks. Metrical structure also plays an organisational function in the phonology of language, via speech prosody, and there is evidence for rhythmic perceptual difficulties in developmental dyslexia. Here we investigate the hypothesis that the accurate perception of musical metrical structure is related to basic auditory perception of rise time, and also to phonological and literacy development in children. A battery of behavioural tasks was devised to explore relations between musical metrical perception, auditory perception of amplitude envelope structure, phonological awareness (PA) and reading in a sample of 64 typically-developing children and children with developmental dyslexia. We show that individual differences in the perception of amplitude envelope rise time are linked to musical metrical sensitivity, and that musical metrical sensitivity predicts PA and reading development, accounting for over 60% of variance in reading along with age and I.Q. Even the simplest metrical task, based on a duple metrical structure, was performed significantly more poorly by the children with dyslexia. The accurate perception of metrical structure may be critical for phonological development and consequently for the development of literacy. Difficulties in metrical processing are associated with basic auditory rise time processing difficulties, suggesting a primary sensory impairment in developmental dyslexia in tracking the lower-frequency modulations in the speech envelope.


Particulate emboli retained by the Intersept (R) transfusion filter; a sem study.
The Intersept (R) transfusion filter is the transfusion filter developed by Johnson and Johnson. Filtration is performed by both adsorption and mechanical retention. Not only microaggregates, but damaged and injured cells are likely to be trapped and/or adsorbed. Such a filter is not injurious to the blood components, but thrombotic material accumulation can occur with fresh blood.


[Premature immunosenescence in catecholamines syntesis deficient mice. Effect of social environment].
Healthy state depends on the appropriate function of the homeostatic systems (nervous, endocrine and immune systems) and the correct communication between them. The functional and redox state of the immune system is an excellent marker of health, and animals with premature immunosenescence show a shorter lifespan. Since catecholamines modulate the function of immune cells, the alteration in their synthesis could provoke immunosenescence. The social environment could be a strategy for modulating this immunosenescence. To determine if an haploinsufficiency of tyrosine hydroxylase (TH), the limiting enzyme of synthesis of catecholamines, may produce a premature immunosenescence and if this immunosenescence could be modulated by the social environment. Adult (9±1 months) male ICR-CD1 mice with deletion of a single allele (hemi-zygotic: HZ) of the tyrosine hydroxylase enzyme (TH-HZ) and wild-type (WT) mice were used. Animals were housed in four subgroups: WT>50% (in the cage, the proportion of WT mice was higher than 50% in relation to TH-HZ), WT<50%, TH-HZ<50% and TH-HZ>50%. Peritoneal leukocytes were collected and phagocytosis, chemotaxis and proliferation of lymphocytes in the presence of lipopolysaccharide were analyzed. Glutathione reductase and glutathione peroxidase activities as well as oxidized/reduced glutathione ratio were studied. TH-HZ>50% mice showed a deteriorated function and redox state in leukocytes respect to WT>50% and similar to old mice. However, TH-HZ<50% animals had similar values to those found in WT<50% mice. The haploinsufficiency of TH generates premature immunosenescence, which appears to be compensated by living together with an appropriate number of WT animals.


A survey of primary care patients' readiness to engage in the de-adoption practices recommended by Choosing Wisely Canada.
Strategies such as Choosing Wisely have been established to identify the overuse of interventions considered as low-value. Reduction of low-value practices will require patients to understand why certain interventions are no longer recommended. The objective of this study was to determine whether older adults accept the rationale for and perceive themselves ready to de-adopt annual electrocardiogram testing, imaging for low back pain, the use of antibiotics for sinusitis, the use of sedative-hypnotics for insomnia, and the use of antipsychotics to treat behavioural symptoms of dementia. A self-administered iPad survey was distributed to consecutive patients aged 50 years and older, presenting to three primary care outpatient practices in Ontario, Canada. Data from patients who were able and willing to complete the survey while waiting to see their physician were included. The survey queried knowledge, attitudes and behaviours around the targeted low-value interventions, before and after exposure to a Choosing Wisely Canada patient educational brochure on one of these five topics. A subset of patients agreed to participate in a semi-structured interview after their clinic visit. Three-hundred and forty-four patients (mean age 63, range 50-88, 59 % female) read the materials and completed the survey. Forty-eight percent (95 % CI 43-53 %) intended to discuss the information with a healthcare provider. Forty-five percent (95 % CI 40-51 %) expressed a desire to change current low-value practices. Approximately two-thirds of those who indicated they would not change future behaviours explained that it was because they were already espousing the Choosing Wisely values. After reading the Choosing Wisely brochures, knowledge improved independent of age, sex and education in 48 % (95 % CI 38-57 %) of participants about electrocardiogram testing, in 74 % (95 % CI 65-82 %) about use of antipsychotics, in 66 % (95 % CI 52-78 %) about use of antibiotics for sinusitis, in 60 % (95 % CI 46-72 %) about imaging for low back pain, and in 40 % (95 % CI 26-55 %) about sedative-hypnotic use in the elderly. The majority of primary care patients seem ready to de-adopt low-value practices. Provision of education in clinic waiting rooms can help improve knowledge around unnecessary care.


2-Alkylamino- and alkoxy-substituted 2-amino-1,3,4-oxadiazoles-O-Alkyl benzohydroxamate esters replacements retain the desired inhibition and selectivity against MEK (MAP ERK kinase).
This paper reports a second generation MEK inhibitor. The previously reported potent and efficacious MEK inhibitor, PD-184352 (CI-1040), contains an integral hydroxamate moiety. This compound suffered from less than ideal solubility and metabolic stability. An oxadiazole moiety behaves as a bioisostere for the hydroxamate group, leading to a more metabolically stable and efficacious MEK inhibitor.


Vertebrobasilar occlusive disease and childhood migraine.
A nine-year-old girl developed a cerebellar infarct documented by computed tomography. This infarct occurred in association with a typical migrainous attack. Vertebrobasilar occlusive disease has been reported in adult migraineurs but has not been previously reported in children.


A body-worn gait analysis system for evaluating hemiplegic gait.
This paper describes a system for measuring the temporal parameters of hemiplegic gait. This system uses shoe insoles with sensors, acting as switches, placed under the heel, head of the first metatarsal, head of the fifth metatarsal and the big toe. This system is able to monitor gait for up to 10 min and can be used by the patient over any surface. Parameters for evaluating hemiplegic gait are defined, including scuffing during swing and the degree of inversion during stance.


Community Health Teams: a qualitative study about the factors influencing the decision-making process.
The purpose of this study was to explore the factors influencing how individual Community Health Teams (CHTs) make decisions about what services to offer and how to allocate their resources. We conducted thirteen semi-structured interviews with all 13 CHTs program managers between January and March, 2021. We analyzed interviewees descriptions of their service offerings, resources allocation, and decision-making process to identify themes. Four major themes emerged from the interview data as factors influencing community health team program managers' decision-making process: commitment to offering high-quality care coordination, Blueprint's stable and flexible structure, use of data in priority setting, and leveraging community partnerships and local resources. Community-based CHTs with flexible funding allowed programs to tailor service offerings in response to community needs. It is important for teams to have access to community-level data. Teams are cultivating and leveraging community partners to increase their care coordination capacity, which is focus of their work. CHTs are a model for leveraging community partnerships to increase service capacity and pubic engagement in health services for other states to replicate.


Application of the ERICA Integrated Approach to the Drigg coastal sand dunes.
The EC-funded project 'Environmental Risks from Ionising Contaminants: Assessment and Management' (ERICA) developed an 'Integrated Approach' for assessing the impact of ionising radiation on ecosystems. This paper presents the application of the ERICA Integrated Approach, supported by a software programme (the ERICA Tool) and guidance documentation, to an assessment of the Drigg coastal sand dunes (Cumbria, UK). Targeted sampling provided site-specific data for sand dune biota, including amphibians and reptiles. Radionuclides reported included (90)Sr, (99)Tc, (137)Cs, (238)Pu, (239+240)Pu and (241)Am. Site-specific data were compared to predictions derived using the ERICA Tool. Some under- and over-predictions of biota activity concentrations were identified but can be explained by the specific ecological characteristics and contamination mechanism of the dunes. Overall, the results indicated no significant impact of ionising radiation on the sand dune biota and the Integrated Approach was found to be a flexible and effective means of conducting a radiation impact assessment.


Evaluation of metal pollution-induced biological effects in Chinese shrimp Fenneropenaeus chinensis by NMR-based metabolomics.
Metal pollution in Laizhou Bay along the Bohai Sea in China has been posing a risk on fishery species and hence may affect seafood quality. In this work, shrimps Fenneropenaeus chinensis were sampled from three sites, namely, a reference (site 6334) and two metal-polluted (sites 6262 and 7262) sites, located in Laizhou Bay. The metal concentrations in shrimp muscle tissues were tested using the ICP-MS technique. The Cr and Cu concentrations were the highest in the shrimp samples from site 7262, exceeding the national seafood safety standard Ⅱ, and the As concentration was much higher than the national seafood safety standard Ⅲ. NMR-based metabolomics indicated that metal pollution induced oxidative and immune stresses, damaged the muscular structure, and disrupted energy metabolism in shrimps at sites 6262 and 7262, in particular disturbed osmotic regulation in shrimps at site 7262. Glycine and serine could serve as biomarkers for Cd in F. chinensis.


Individual chitin synthase enzymes synthesize microfibrils of differing structure at specific locations in the Candida albicans cell wall.
The shape and integrity of fungal cells is dependent on the skeletal polysaccharides in their cell walls of which beta(1,3)-glucan and chitin are of principle importance. The human pathogenic fungus Candida albicans has four genes, CHS1, CHS2, CHS3 and CHS8, which encode chitin synthase isoenzymes with different biochemical properties and physiological functions. Analysis of the morphology of chitin in cell wall ghosts revealed two distinct forms of chitin microfibrils: short microcrystalline rodlets that comprised the bulk of the cell wall; and a network of longer interlaced microfibrils in the bud scars and primary septa. Analysis of chitin ghosts of chs mutant strains by shadow-cast transmission electron microscopy showed that the long-chitin microfibrils were absent in chs8 mutants and the short-chitin rodlets were absent in chs3 mutants. The inferred site of chitin microfibril synthesis of these Chs enzymes was corroborated by their localization determined in Chsp-YFP-expressing strains. These results suggest that Chs8p synthesizes the long-chitin microfibrils, and Chs3p synthesizes the short-chitin rodlets at the same cellular location. Therefore the architecture of the chitin skeleton of C. albicans is shaped by the action of more than one chitin synthase at the site of cell wall synthesis.


Shift in Rayleigh matches after adaptation to monochromatic light of various intensities.
The action spectrum for inducing a long-lasting protan shift in colour matches was investigated. Rayleigh matches were measured before and after 30 min adaptation to monochromatic light of 520, 550, 580 or 620 nm. For each wavelength, seven retinal illuminances, ranging from 3.0 to 5.0 log td, were chosen in random order. Results for one colour-normal observer show that the shift in Rayleigh match after adaptation increases monotonically as a function of the luminance of the adapting light. The dynamic response range is from 3.3 to 4.7 log td. The wavelength of the adapting light had no systematic influence on the form of the response function. The results imply that the effect is triggered by light absorbed in the photopigments themselves.


Decreased calcineurin and increased phosphothreonine-DARPP-32 in the striatum of rats behaviorally sensitized to methamphetamine.
We investigated changes in signal transduction via calcineurin (CaN) in the striatum of rats behaviorally sensitized to methamphetamine (Meth). The rats were injected with Meth (4 mg/kg, s.c.) five times a week for 3 weeks and then were given a challenge dose of Meth (2 mg/kg, s.c.). Seven days after the challenge test, we determined the levels of CaN Aalpha and Abeta by Western blotting. We further immunoquantified DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, mw 32,000) and phosphothreonine-DARPP-32, which can be dephosphorylated at threonine sites by CaN. We found that both CaN Aalpha and Abeta were significantly decreased in the particulate fractions but were not changed in the soluble fractions from the striatum of Meth-sensitized rats as compared with control rats. The same findings were observed in the striatum of rats 6 h after the injection of PCP (10 mg/kg, s.c.). In the striatum of Meth-sensitized rats, phosphothreonine-DARPP-32 immunoreactivities significantly increased, but DARPP-32 immunoreactivities were not significantly different from those of the control rats. These results indicate that the activity of signal transduction via CaN is functionally decreased in the striatum of Meth-sensitized rats.


[Production of surfactants by Acinetobacter calcoaceticus K-4 grown on ethanol with organic acids].
The effect of fumarate (C4-dicarboxylic acid, a gluconeogenesis precursor) and citrate (a lipid synthesis regulator) on the production of surfactants by Acinetobacter calcoaceticus K-4 grown on ethanol has been studied. Simultaneous addition of fumarate and citrate to concentrations of 0.01-0.02% at the end of the log phase of K-4 growth in a medium with 2 vol% ethanol increases the nominal surfactant concentration by 45-55% in comparison with a culture without organic acids. The increased level of surfactant production in the presence of fumarate and citrate is determined by the increase in the activities of enzymes involved in the production of glycolipids (phosphoenolpyruvate synthase and trehalose phosphate synthase) and aminolipids (NADP(+)-dependent glutamate dehydrogenase) by factors of 1.7-7, as well as by the simultaneous operation of two anaplerotic pathways: the glyoxylate cycle and the reaction catalyzed by phosphoenolpyruvate carboxylase.


The protective influence of progestogen only contraception against vaginal moniliasis.
The incidence of Candida albicans (C.A.) infection of the vagina was evaluated in vaginal discharges obtained from 85 subjects using a large battery of culture media and confirmatory tests. Twenty women using DMPA 150 mg i.m. contraceptive injections for more than one year (long-term users) were compared with forty 2nd trimester pregnant cases with respect to vaginal candidiasis. The basis of comparison was the presence of amenorrhea and high hormonal levels in both groups. However, pregnant subjects showed a 60% prevalence while none of the DMPA cases had a positive culture or smear. Another group of 25 cases was similarly studied once before DMPA injection and again three months following drug administration (short-term use). The pre-therapy samples demonstrated a 32% incidence which was reduced to 8% after three months of use. It therefore appears that progestogen only contraceptives have the advantage of some protective influence against monilial vaginitis. Moreover, the use of these drugs may carry the beneficial potential of use in resistant cases of monilial vaginitis, either as a single approach or better as a supplementary procedure to known antifungal agents.


Bmi1 Is a Key Epigenetic Barrier to Direct Cardiac Reprogramming.
Direct reprogramming of induced cardiomyocytes (iCMs) suffers from low efficiency and requires extensive epigenetic repatterning, although the underlying mechanisms are largely unknown. To address these issues, we screened for epigenetic regulators of iCM reprogramming and found that reducing levels of the polycomb complex gene Bmi1 significantly enhanced induction of beating iCMs from neonatal and adult mouse fibroblasts. The inhibitory role of Bmi1 in iCM reprogramming is mediated through direct interactions with regulatory regions of cardiogenic genes, rather than regulation of cell proliferation. Reduced Bmi1 expression corresponded with increased levels of the active histone mark H3K4me3 and reduced levels of repressive H2AK119ub at cardiogenic loci, and de-repression of cardiogenic gene expression during iCM conversion. Furthermore, Bmi1 deletion could substitute for Gata4 during iCM reprogramming. Thus, Bmi1 acts as a critical epigenetic barrier to iCM production. Bypassing this barrier simplifies iCM generation and increases yield, potentially streamlining iCM production for therapeutic purposes.


Comparative Analysis of Infection by Rickettsia rickettsii Sheila Smith and Taiaçu Strains in a Murine Model.
Rocky Mountain spotted fever (RMSF) is a life-threatening tick-borne disease caused by Rickettsia rickettsii, which is widely distributed throughout the Americas. Over 4000 cases of RMSF are recorded annually in the United States, while only around 100 cases are reported in Brazil. Conversely, while case fatality rates in the United States oscillate around 5%, in Brazil they can surpass 70%, suggesting that differences in tick vectoring capacity, population sensitivity, and/or variability in virulence of the rickettsial strains may exist. In this study, we compared the susceptibility of C3H/HeN mice to two highly virulent strains of R. rickettsii, one from the United States (Sheila Smith) and the other from Brazil (Taiaçu). Animals inoculated with the Taiaçu strain succumbed to infection earlier and exhibited severe histological lesions in both liver and spleen sooner than mice infected with the Sheila Smith strain. These differences in survival and signs of the disease are not related to a greater proliferation of the Taiaçu strain, as there were no significant differences in the rickettsial load in mice tissues inoculated with either strain. The present study is the first step to experimentally assess differences in fatality rates of RMSF in two different regions of the American continent.


Review of clinical applications of radiation-enhancing nanoparticles.
Clinical evidence of the radiation-enhancing effects of nanoparticles has emerged. We searched the literature in English and French on PubMed up to October 2019. The search term was "nanoparticle" AND "radiotherapy", yielding 1270 results. The two main NP used in clinical trials were hafnium oxide and gadolinium involving a total of 229 patients. Hafnium oxide NP were used in three phase 1/2 trials on sarcoma, head and neck squamous cell carcinoma or liver cancer and one phase 2/3 trial. There are six ongoing phase 1/2 clinical trials to evaluate the combination of gadolinium-based NP and RT for the treatment of brain metastases and cervical cancer. So far, intratumoral hafnium oxide nanoparticles were safe and improved efficacy in locally advanced sarcoma.


Interferon-gamma is a therapeutic target molecule for prevention of postoperative adhesion formation.
Intestinal adhesions are bands of fibrous tissue that connect the loops of the intestine to each other, to other abdominal organs or to the abdominal wall. Fibrous tissue formation is regulated by the balance between plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (tPA), which reciprocally regulate fibrin deposition. Several components of the inflammatory system, including cytokines, chemokines, cell adhesion molecules and neuropeptide substance P, have been reported to participate in adhesion formation. We have used cecal cauterization to develop a unique experimental mouse model of intestinal adhesion. Mice developed severe intestinal adhesion after this treatment. Adhesion development depended upon the interferon-gamma (IFN-gamma) and signal transducer and activator of transcription-1 (STAT1) system. Natural killer T (NKT) cell-deficient mice developed adhesion poorly, whereas they developed severe adhesion after reconstitution with NKT cells from wild-type mice, suggesting that NKT cell IFN-gamma production is indispensable for adhesion formation. This response does not depend on STAT4, STAT6, interleukin-12 (IL-12), IL-18, tumor necrosis factor-alpha, Toll-like receptor 4 or myeloid differentiation factor-88-mediated signals. Wild-type mice increased the ratio of PAI-1 to tPA after cecal cauterization, whereas Ifng(-/-) or Stat1(-/-) mice did not, suggesting that IFN-gamma has a crucial role in the differential regulation of PAI-1 and tPA. Additionally, hepatocyte growth factor, a potent mitogenic factor for hepatocytes, strongly inhibited intestinal adhesion by diminishing IFN-gamma production, providing a potential new way to prevent postoperative adhesions.


Parotid retention cysts as a complication of rhytidectomy. Case report.
We present an unusual complication of rhytidectomy in which several salivary cyst formed in the region of one parotid duct. Treatment with drainage and presure resolved the problem.


Receptor-mediated endocytosis for drug delivery in African trypanosomes: fulfilling Paul Ehrlich's vision of chemotherapy.
Bloodstream-form cells of Trypanosoma brucei exhibit massively increased endocytic activity relative to the insect midgut stage, enabling rapid recycling of variant surface glycoprotein and antibody clearance from the surface. In addition, recent advances have identified a role for receptor-mediated endocytosis in the uptake of the antitrypanosomal drug, suramin, via invariant surface glycoprotein 75, and in the uptake of trypanosome lytic factor 1 via haptoglobin-haemoglobin receptor. Here, we argue that receptor-mediated endocytosis represents both a validated drug target and a promising route for the delivery of novel therapeutics into trypanosomes.


Increased affinity predominates in insulin stimulation of glucose transport in the adipocyte.
The kinetics for transport of glucose and 3-O-methylglucose (MeGlc) were determined in preparations of rat adipocytes characterized by low basal rates which could be increased consistently more than 30-fold by addition of insulin (10 nM). In basal cells, the Km of [14C]glucose uptake was about 75 mM. The Ki for glucose inhibition of [14C]MeGlc uptake was similarly high (105 mM). These results were further confirmed by studies of basal glucose consumption which remained linear up to the highest glucose concentration used (30 mM) and by measurements of MeGlc transport kinetics (net and equilibrium exchange Km were both about 35 mM). Basal glucose uptake was determined to be stereospecific and cytochalasin sensitive (greater than 90%) and thus could not be dismissed as nonmediated diffusion. Insulin treatment decreased the transport Km for glucose and MeGlc to one-tenth the values measured in basal cells. The Vmax for glucose was doubled and that for MeGlc quadrupled. We conclude that insulin brings about a great reduction in the Km of hexose transport in adipocytes. This can only be perceived if activation of basal cells by experimental manipulations is avoided. The decrease in Km is the major kinetic factor involved in the stimulation of glucose transport by insulin.


[Degranulation test of basophils with scalar concentrations of 3% carbocaine. Evaluation of clinical cases with test over 40%].
On the basis of 3 clinical cases, the diagnostic contribution of the basophil degranulation test in the screening of allergical pathologies of dental interest is evaluated.


Genetics of phenotypic plasticity: QTL analysis in barley, Hordeum vulgare.
Phenotypic plasticity is the variation in phenotypic traits produced by a genotype in different environments. In contrast, environmental canalization is defined as the insensitivity of a genotype's phenotype to variation in environments. Despite the extensive literature on the evolutionary significance and potential genetic mechanisms driving plasticity and canalization, few studies tried to unravel the genetic basis of this phenomenon. Using both simulations and real data from barley (Hordeum vulgare), we used QTL mapping to obtain insights into the genetics of phenotypic plasticity. We explored two ways of quantifying phenotypic plasticity, namely the phenotypic variance across environments and the Finlay-Wilkinson's regression slope. Each relates to a different concept of stability. Through QTL detection with real and simulated data, we show that each measure of plasticity detects specific types of plasticity QTL. Most of the plasticity QTLs were detected in the data set with the lowest number of environments. All plasticity QTL co-located with loci showing QTL x E interaction and there were no QTL that only affected plasticity. The number of environments that are considered and their homogeneity is a key to interpret the genetic control of phenotypic plasticity. Regulatory pathways of plasticity may vary from one set of environments to another due to unique features of each environment. Therefore, with an increasing number of environments, it may become impossible to detect a single 'consistent' regulatory pathway for all environments.


[Clinical aspects, diagnosis and surgical treatment in injuries of the iliofemoral venous segment in children].
In 1985-1991 forty patients aged from 12 days to 14 years were treated for sequelae of iatrogenic injury to the iliofemoral venous segment. Twenty-five various operations for autovenous shunting were performed: cross shunt after Palma in 15, autovenous shunt in the anatomical projection in 3, phlebolysis and ligation of the collaterals in 5 cases, extravasal correction with A. N. Vedensky's casing spiral in one case, and direct anastomosis in a newborn infant.


Iridoid glycosides isolated from Nardostachys chinensis batal with NO production inhibitory activity.
Investigation into the chemical diversity of Nardostachys chinensis Batal led to the discovery of three new (1-3) and one known (4) iridoid glycosides. Their structures were established through spectroscopic methods including 1 D and 2 D NMR experiments and HRESIMS analysis. Inhibitory effects of 1-4 on nitric oxide production were investigated in lipopolysaccaride (LPS)-mediated RAW 264.7 cells, and they displayed IC50 values in the range 7.8-15.2 μM.


Urokinase as a multidomain protein and polyfunctional cell regulator.
The urokinase type plasminogen activator (urokinase) plays a pivotal role in the regulation of cell adhesion and migration during tissue remodeling. Urokinase not only specifically cleaves plasminogen and converts it into plasmin but also activates intracellular signaling upon binding to certain receptors on the cell surface. The polyfunctional properties of this protein are associated with its three-domain structure as follows: the C-terminal proteolytic domain containing the serine protease active center, the central kringle domain, and the N-terminal domain homologous to epidermal growth factor. This review considers functional properties of urokinase and of its fragments generated on the cell surface as a result of proteolytic processing. This review will discuss the mechanisms of urokinase-mediated regulation of cellular function upon binding to membrane receptors.


Adult dystonic lipidosis: clinical, histologic, and biochemical findings of a neurovisceral storage disease.
A 43-year-old man presented with splenomegaly and a 20-year history of a neurologic disorder that included vertical supranuclear ophthalmoplegia, mild dementia, and a movement disorder. Adult dystonic lipidosis was diagnosed from the clinical picture and demonstration of foamy and sea-blue histiocytes in bone marrow. Ultrastructural patterns in cytolysosomes suggested accumulation of neutral fat and phospholipids. Liver content of bis-(monoacylglycerol) phosphate was increased, probably because the number of lysosomes had increased. Sphingomyelinase activity was normal in cultured skin fibroblasts. Juvenile and adult dystonic lipidosis form a clinically, histologically, and biochemically distinct neurovisceral storage disease that differs from Niemann-Pick disease.


Controversy of TMEM230 Associated with Parkinson's Disease.
Parkinson's disease (PD) is a common neurodegenerative disease with movement disorders including resting tremor, bradykinesia, rigidity, and postural instability. The key pathological features of PD are selective loss of dopaminergic (DA) neurons in substantial nigra and the presence of Lewy bodies (LBs). Mutations in TMEM230 (transmembrane protein 230) have been recently reported to play a pathological role and contribute to PD pathogenesis. TMEM230 gene encodes two isoforms of TMEM230 proteins, isoform I (183 amino acids) and isoform II (120 amino acids). The function of TMEM230 is not clear, but it may be involved in vesicle trafficking and recycling, autophagy, protein aggregation, and cell toxicity. There are four reported PD-linked TMEM230 mutations (p.Y92C, p.R141L, p.*184Wext*5, p.*184PGext*5). TMEM230-linked PD cases exhibit late-onset, good-response to levodopa, and typical clinical features of sporadic PD with DA neuronal loss in substantial nigra and Lewy body pathology. In this mini review, we recap the current literature of TMEM230 in genetic, neurobiological, and pathological studies in order to further understand the potential roles of TMEM230 in PD pathogenesis.


Choice of reference area in studies of Alzheimer's disease using positron emission tomography with fluorodeoxyglucose-F18.
At present, there is still no consensus on the choice of the reference area in positron emission tomography (PET) studies of Alzheimer's disease (AD). In this study, PET scans with fluorodeoxyglucose-F18 were carried out in the following groups of subjects: 47 patients with probable AD, 8 patients with mild cognitive impairment, and 15 age-similar healthy subjects. Scans normalized to the cerebral global mean (CGM), cerebellum (CBL), and the primary sensorimotor cortex (SMC). We evaluated the effect of the different count normalization procedures on the accuracy of (18)F-FDG PET to detect AD-specific metabolic abnormalities (voxel-based group comparison) and to differentiate between patients and healthy subjects (ROI-based discriminant analysis) with regard to the degree of clinical deterioration. Metabolic reductions in groups of very mildly, mildly and moderate-to-severely affected patients appeared, respectively, 2.2, 2.6, and 2.7 times greater in spatial extent when tracer uptake was normalized to SMC rather than to CGM. The overall accuracy of discrimination was 94%, 91%, and 80% after normalization to SMC, CBL, and CGM, respectively. In general, normalization to SMC was somewhat superior to cerebellar normalization, allowing the detection of more pronounced metabolic deficits and the more accurate discrimination of patients from non-patients. Normalization to CGM should be used with great caution not only in advanced stages of dementia, but also in very mild AD cases.


Spectroscopic coherent Raman imaging of Caenorhabditis elegans reveals lipid particle diversity.
Caenorhabditis elegans serves as a model for understanding adiposity and its connections to aging. Current methodologies do not distinguish between fats serving the energy needs of the parent, akin to mammalian adiposity, from those that are distributed to the progeny, making it difficult to accurately interpret the physiological implications of fat content changes induced by external perturbations. Using spectroscopic coherent Raman imaging, we determine the protein content, chemical profiles and dynamics of lipid particles in live animals. We find fat particles in the adult intestine to be diverse, with most destined for the developing progeny. In contrast, the skin-like epidermis contains fats that are the least heterogeneous, the least dynamic and have high triglyceride content. These attributes are most consistent with stored somatic energy reservoirs. These results challenge the prevailing practice of assessing C. elegans adiposity by measurements that are dominated by the intestinal fat content.


Graphene as efficient and robust catalysts for catalytic wet peroxide oxidation of phenol in a continuous fixed-bed reactor.
Monolayer graphene film (Gr) as a metal-free catalyst was synthesized on the paper-like sintered stainless steel fibers (PSSF) with three-dimensional net structure by chemical vapor deposition (CVD) technique. The prepared PSSF-Gr was characterized by SEM, EDS, XRD, AFM, TEM, and Raman spectroscopy. Then, the optimum reaction conditions for catalytic wet peroxide oxidation (CWPO) of phenol in a continuous reactor using PSSF-Gr catalysts were explored by analyzing the effects of reaction temperature, feed flow rate, and catalyst bed height on catalytic performance. Moreover, the long-term stability of PSSF-Gr catalyst was investigated and demonstrated complete phenol oxidation and dramatic TOC removal (values ranging between 80.7% and 91.0%) after continuously operating for 72 h under optimum condition. Finally, a reasonable reaction mechanism for CWPO of phenol was proposed by analyzing the HPLC results and evolution of aromatic intermediates content. From these results, seldom toxic aromatic intermediates were observed on account of the production of short-chain organic acids by opening of aromatic ring, which subsequently mineralized to CO2 and H2O. The simple preparation method, unique structure, extraordinary catalytic activity and stability of the graphene-based material would provide a new potential catalyst for environmental catalysis.


From Microurchins to V2O5 Nanowalls: Improved Synthesis through Vanadium Powder and Fast, Selective Adsorption of Methylene Blue.
Research on synthesizing micro- and nanosized materials directly from metals has attracted considerable attention because of its simplicity, ability to synthesize in large quantities, and high uniformity. This study proposes a simple method to synthesize high-uniformity or high-density V2O5 microurchins and nanowalls directly from vanadium powder. Remarkably, the synthesis condition of 60 °C for 1 h is considered to be an optimal condition to convert metals into micro- or nano-oxides. The as-synthesized V2O5 nanowalls can adsorb nearly 90% of methylene blue in the dark in 3 min. The adsorption selectivity of these samples with several pigments is investigated.


Comparison of sexual function in infertile women with polycystic ovary syndrome and endometriosis: A cross-sectional study.
Infertility is one of the issues affecting sexual function (SF). Infertility is also one of the complications of polycystic ovary syndrome (PCOS) and endometriosis. This research seeks to assess and compare SF and the prevalence of sexual dysfunction in infertile women with PCOS and endometriosis. A cross-sectional study was carried out with a sample of 630 (210 infertile women with endometriosis, 210 infertile women with PCOS, and 210 healthy women of childbearing age as the control group). SF was assessed by the female sexual function index (FSFI). Descriptive statistics and inferential statistics were used to analyze the data. The primary outcome measured was FSFI score. Secondary outcome was hospital anxiety and depression scale score. The results showed that the mean score of the total FSFI in the 2 groups of PCOS and endometriosis was lower than the control group (p < 0.001). In addition, women with higher education (university education) had a higher total FSFI. Sexual dysfunction rates are high in infertile women with endometriosis and PCOS. Infertility service providers in infertility centers need to pay attention to this issue.


Suicide attempt in mental disorders (MeDi): Association with 5-HTT, IL-10 and TNF-alpha polymorphisms.
Mental disorders (MeDi) and suicide attempts (SA) are influenced by environmental and genetic factors. Genetic polymorphism studies have identified some candidate genes for suicidal behaviour in people with MeDi. To evaluate MeDi and SA in relation to the presence of rs2020933 (5-HTT), rs1800871 (IL-10) and rs1800629 (TNF-α) polymorphisms. A questionnaire for identification and general data, a brief quality of life assessment (WHOQOL-brief), the scale of suicide ideation by Beck and the MINI International Neuropsychiatric Interview were used in this study. DNA was obtained using buccal mucosa swab samples, and genotyping was performed using real-time polymerase chain reaction. A total of 306 patients were assessed with MeDi; 161 patients had MeDi and a history of SA, and 145 patients had MeDi and no history of SA. The study had 175 subjects in the control group. The TNF-α rs1800629 -308A/G genotype was significantly associated with function as a protection factor in the control group compared with MeDi without SA. The TNF-α rs1800629 -308G allele appeared as risk factor for MeDi compared to the control group, for female gender. Additionally, the -308A/G + A/A genotype appeared as protection factor for the control group compared to the group with MeDi. For TNF-α, the -308G allele appeared as risk factor for the number of SA (1 time) compared to the control group. The IL-10 (rs1800871) and 5-HTT (rs2020933) SNPs were considered to have inadequate statistical power. The rs1800629 (TNF-α) polymorphism may be associated with MeDi without SA, MeDi in females and the number of SA (1 time) in the studied group.


Halitosis associated volatile sulphur compound levels in patients with laryngopharyngeal reflux.
Previous reports have suggested that laryngopharyngeal reflux (LPR) may cause halitosis. However, it remains unclear if LPR is a risk factor for halitosis. The aim of this study was to investigate if patients diagnosed with LPR have an increased probability of halitosis compared to a normal population. Fifty-eight patients complaining of LPR symptoms and 35 healthy subjects were included in the study. A LPR diagnosis was made using an ambulatory 24-h double pH-probe monitor, which is the gold standard diagnostic tool for LPR. Additionally, halitosis was evaluated by measuring the levels of volatile sulphur compounds using OralChroma™ and an organoleptic test score. The result of the final diagnosis of the 58 patients after the 24 h ambulatory pH monitoring was that 42 patients had LPR. Significant correlations were observed between the organoleptic test score and hydrogen sulfide (H2S) and methyl mercaptan (CH3SH) levels. These were also significantly correlated with LPR. We found a strong positive association between LPR and volatile sulphur compound levels. The H2S and CH3SH levels differed significantly between the LPR and control groups (p < 0.0001 and p < 0.0001, respectively). Halitosis was significantly associated with the occurrence and severity of LPR. The present study provides clear evidence for an association between halitosis and LPR. Halitosis has a high frequency in patients with LPR and reflux characteristics are directly related to their severity and therefore could be considered as a manifestation of LPR.


The dynamin A ring complex: molecular organization and nucleotide-dependent conformational changes.
Here we show that Dictyostelium discoideum dynamin A is a fast GTPase, binds to negatively charged lipids, and self-assembles into rings and helices in a nucleotide-dependent manner, similar to human dynamin-1. Chemical modification of two cysteine residues, positioned in the middle domain and GTPase effector domain (GED), leads to altered assembly properties and the stabilization of a highly regular ring complex. Single particle analysis of this dynamin A* ring complex led to a three-dimensional map, which shows that the nucleotide-free complex consists of two layers with 11-fold symmetry. Our results reveal the molecular organization of the complex and indicate the importance of the middle domain and GED for the assembly of dynamin family proteins. Nucleotide-dependent changes observed with the unmodified and modified protein support a mechanochemical action of dynamin, in which tightening and stretching of a helix contribute to membrane fission.


Development and validation of a new multivariable prediction model to estimate risk of abnormal vault.
To develop and validate a new multivariable prediction model to estimate risk of abnormal vault after EVO Implantable Collamer Lens (EVO-ICL) implantation using the preoperative parameters. This retrospective study comprised 282 eyes of 143patients who underwent EVO-ICL surgery between May 2021 and April 2022. We measured preoperative parameters before surgery and vaults in 1 week after the operation using swept-source optical coherence tomography (SS-OCT). Risk factors for abnormal vault were determined by univariate and multivariate logistic regression analyses, and a nomogram was developed to forecast the risk of abnormal vault after EVO-ICL implantation. We assessed the performance of nomogram in terms of discrimination and calibration, including concordance index (C-index), receiver operating characteristic curve (ROC), area under the ROC curve (AUC), and decision curve analysis (DCA). Bootstrap resampling was used as an internal verification method. The logistic regression analysis revealed the independent risk factors for abnormal vault were white-to-white(WTW), anterior chamber angle(ACA), pupil size, and ICL-size, all of them were used to establish a nomogram based on multivariate logistic regression to predict the risk of abnormal vault. The C-indexes and AUC were 0.669 (95%CI, 0.605, 0.733). The calibration curves of the nomogram showed relatively small bias from the reference line, implicating an acceptable degree of confidence. The DCA indicates the potential clinical significance of the nomogram. We developed a new multivariable prediction model to estimate risk of abnormal vault. The model shows good prediction effect and can provide assistance for clinical decision of ICL size.


The synthesis of novel matrix metalloproteinase inhibitors employing the Ireland-Claisen rearrangement.
Matrix metalloproteinase inhibitors of general formula (1) were synthesised by a route involving an Ireland-Claisen rearrangement which enables systematic modification of the substituent alpha to the hydroxamic acid. An analogue (12c) possessing an alpha-cyclopentyl group is a potent broad spectrum inhibitor that displays high and sustained blood levels following oral dosing in both the rat and marmoset ex-vivo bioassays. This compound and analogues are also potent inhibitors of TNF alpha release.


Blastocyst Cell Number and Allocation Affect the Developmental Potential and Transcriptome of Bovine Somatic Cell Nuclear Transfer Embryos.
Cloning cattle using somatic cell nuclear transfer (SCNT) is inefficient. Although the rate of development of SCNT embryos in vitro is similar to that of fertilized embryos, most fail to develop into healthy calves. In this study, we aimed to identify developmentally competent embryos according to blastocyst cell composition and perform transcriptome analysis of single embryos. Transgenic SCNT embryos expressing nuclear-localized HcRed gene at day 7 of development were imaged by confocal microscopy for cell counting and individually transferred to recipient heifers. Pregnancy rates were determined by ultrasonography. Embryos capable of establishing pregnancy by day 35 had an average of 117 ± 6 total cells, whereas embryos with an average of 128 ± 5 cells did not establish pregnancy (P < 0.05). A lesser average number of 41 ± 3 cells in the inner cell mass (ICM) also resulted in pregnancies (<0.05) than a greater number of 48 ± 2 cells in the ICM. Single embryos were then subjected to RNA sequencing for transcriptome analysis. Using weighted gene coexpression network analysis, we identified clusters of genes in which gene expression correlated with the number of total cells or ICM cells. Gene ontology analysis of these clusters revealed enriched biological processes in coenzyme metabolic process, intracellular signaling cascade, and glucose catabolic process, among others. We concluded that SCNT embryos with fewer total and ICM cell numbers resulted in greater pregnancy establishment rates and that these differences are reflected in the transcriptome of such embryos.


Synthesis of Novel Blue and Green Light Emitting 4-Nitrophenol Luminophors for Optoelectronics.
The number of anthracene (AN) and anthracene-tetracene (AN-TN) doped 4-nitrophenol (4-NP) luminophors (AN/4-NP and AN-TN/4-NP) were prepared at different proportion by conventional technique called solid state reaction. Excitation energy transfer was observed by fluorescence spectroscopy and cyclic voltammetry. 4-NP acts as an outstanding light emitting matrix. The effect of the donor emission was perceived by changing the dopant concentration; this showed that AN/4-NP and TN-AN/4-NP exhibit fluorescence emission ranging from blue to green i.e. in the range from 400 to 525 nm and 535-550 nm, respectively. Structural properties and thermal stability was studied by XRD, SEM and TGA-DSC techniques. The study reveals that the prepared materials show excellent properties which can meet the demands of optoelectronic devices as well as for light emitting devices.


Responsive Exosome Nano-bioconjugates for Synergistic Cancer Therapy.
Exosomes hold great potential in therapeutic development. However, native exosomes usually induce insufficient effects in vivo and simply act as drug delivery vehicles. Herein, we synthesize responsive exosome nano-bioconjugates for cancer therapy. Azide-modified exosomes derived from M1 macrophages are conjugated with dibenzocyclooctyne-modified antibodies of CD47 and SIRPα (aCD47 and aSIRPα) through pH-sensitive linkers. After systemic administration, the nano-bioconjugates can actively target tumors through the specific recognition between aCD47 and CD47 on the tumor cell surface. In the acidic tumor microenvironment, the benzoic-imine bonds of the nano-bioconjugates are cleaved to release aSIRPα and aCD47 that can, respectively, block SIRPα on macrophages and CD47, leading to abolished "don't eat me" signaling and improved phagocytosis of macrophages. Meanwhile, the native M1 exosomes effectively reprogram the macrophages from pro-tumoral M2 to anti-tumoral M1.


Competition between the Sendai virus N mRNA start site and the genome 3'-end promoter for viral RNA polymerase.
The genomic and antigenomic 3'-end replication promoters of Sendai virus are bipartite in nature and symmetrical, composed of le or tr sequences; a gene start or gene end site, respectively; and a simple hexameric repeat. The relative strengths of these 3'-end promoters determines the ratios of genomes and antigenomes formed during infection and whether model mini-genomes can be rescued from DNA by nondefective helper viruses. Using these tests of promoter strength, we have confirmed that tr is stronger than le in this respect. We have also found that the presence of a gene start site within either 3'-end promoter strongly reduces 3'-end promoter strength. The negative effects of the gene start site on the 3'-end promoter suggest that these closely spaced RNA start sites compete with each other for a common pool of viral RNA polymerase. The manner in which this competition could occur for polymerase off the template (in trans) and polymerase on the template (in cis) adds insight into how the viral RNA polymerase switches between its dual functions as transcriptase and replicase.


Shared neuroanatomical substrates of impaired phonological working memory across reading disability and autism.
Individuals with reading disability or individuals with autism spectrum disorder (ASD) are characterized, respectively, by their difficulties in reading or social communication, but both groups often have impaired phonological working memory (PWM). It is not known whether the impaired PWM reflects distinct or shared neuroanatomical abnormalities in these two diagnostic groups. White-matter structural connectivity via diffusion weighted imaging was examined in sixty-four children, ages 5-17 years, with reading disability, ASD, or typical development (TD), who were matched in age, gender, intelligence, and diffusion data quality. Children with reading disability and children with ASD exhibited reduced PWM compared to children with TD. The two diagnostic groups showed altered white-matter microstructure in the temporo-parietal portion of the left arcuate fasciculus (AF) and in the temporo-occipital portion of the right inferior longitudinal fasciculus (ILF), as indexed by reduced fractional anisotropy and increased radial diffusivity. Moreover, the structural integrity of the right ILF was positively correlated with PWM ability in the two diagnostic groups, but not in the TD group. These findings suggest that impaired PWM is transdiagnostically associated with shared neuroanatomical abnormalities in ASD and reading disability. Microstructural characteristics in left AF and right ILF may play important roles in the development of PWM. The right ILF may support a compensatory mechanism for children with impaired PWM.


Alterations in mitochondrial aconitase activity and respiration, and in concentration of citrate in some organs of mice with experimental or genetic diabetes.
Mouse islets (not used for respiration), kidneys and liver were studied in early and manifest alloxan diabetes, and in genetic diabetes. In these organs the mitochondrial aconitase activity was lower, state 3 respiration with citrate or pyruvate plus malate (but not with succinate) was decreased, and the concentration of citrate was increased, compared with non-diabetic control mice. The alterations suggest a role of lowered activity of mitochondrial aconitase in alloxan diabetes, and probably also in genetic diabetes.


Path Forward for RAF Therapies: Inhibition of Monomers and Dimers.
Current BRAF inhibitors block signaling from monomeric BRAF(V600E), but not from oncogenic RAS, which requires RAF dimerization. In this issue of Cancer Cell, Yao and colleagues investigate why current drugs are ineffective against RAF dimers, while Peng and colleagues describe a pan-RAF inhibitor targeting both monomeric and dimeric RAF.


Salivary gland choristoma of the middle ear and mastoid.
We report a choristoma larger than those previously reported. Its possible causes are discussed.


"Love Can't Be Taken to the Hospital. If It Were Possible, It Would Be Better": Patients' Experiences of Being Cared for in an Intensive Care Unit.
In this study, we aimed to explore the experiences of being cared for in an intensive care unit (ICU) through patients' memories. We adopted a convergent parallel mixed-method design. We interviewed 100 patients shortly after their ICU discharge. Content analysis revealed 14 categories and 49 codes grouped according to themes corresponding to ICU Memory tool core components (factual events, feelings, delusions). The most critical patients reported mostly fragmented or delusional memories, the less critically-ill more factual memories. All experiences were recounted with strong feelings. ICU was identified as a hostile, stressful environment. Positive experiences were mainly associated with a sense of safety promoted by the nurses. Negative experiences were related to privacy and dignity violations, lack of empathy, not being understood, delays/lack of obtaining support, and total control by the health care staff. Removing any avoidable sources of stress and ensuring personalized, dignified care represent a key aim for ICU interprofessional teams.


Draft Genome Sequence of Pseudenhygromyxa sp. Strain WMMC2535, a Marine Ascidian-Associated Bacterium.
Pseudenhygromyxa WMMC2535, a representative of the myxobacteria (family Nannocystaceae), was isolated from a ragged sea hare in the Florida Keys, and its genome was sequenced using PacBio technology. The WMMC2535 genome sequence is the first of this genus and validates the notion that myxobacteria represent outstanding sources of structurally diverse natural products.


Does Preoperative Weight Loss Within 6 Months or 1 Year Change the Risk of Adverse Outcomes in Total Knee Arthroplasty by Initial Body Mass Index Classification?
High body mass index (BMI) is associated with adverse outcomes after total knee arthroplasty (TKA). Thus, many patients are advised to lose weight before TKA. This study examined how weight loss before TKA is associated with adverse outcomes depending on patients' initial BMI. This was a retrospective study of 2,110 primary TKAs at a single academic center. Data on preoperative BMIs, demographics, comorbidities, and incidences of revision or prosthetic joint infection (PJI) were obtained. Multivariable logistic regressions segmented by patients' initial (1-year preoperative) BMI classifications were performed to determine if a > 5% BMI decrease from 1 year or 6 months preoperatively predicted PJI and revision controlling for patient age, race, sex, and Elixhauser comorbidity index. Preoperative weight loss did not predict adverse outcomes for patients who had Obesity Class II or III. 6-month weight loss had greater odds of adverse outcomes than 1-year weight loss and most significantly predicted the occurrence of 1-year PJI (adjusted odds ratio: 6.55, P < .001) for patients who had Obesity Class 1 or lower. This study does not show a statistically significant effect to patients who had Obesity Class II and III losing weight preoperatively with respect to PJI or revision. For patients who have Obesity Class I or lower pursuing TKA, future research should consider potential risks associated with weight loss. Further study is needed to determine if weight loss can be implemented as a safe and effective risk reduction strategy for specific BMI classes of TKA patients.


A comparison of student outcomes following problem-based learning instruction versus traditional lecture learning in a graduate pharmacology course.
To determine if there would be a difference in students' performance and level of satisfaction when taught pharmacology in a problem-based learning format as compared to traditional lecture format. Control (n = 12) and experimental (n = 10) group means for middle-of-term examinations, final examinations, end-of-course numerical averages, and numerical scores of satisfaction were analyzed with a t test for statistically significant differences. There was no significant difference between groups for any of the items measured, suggesting that problem-based learning and traditional lecture format may be equally effective course delivery methods. Replication with a larger sample is recommended. The small sample size precludes generalizing results to the entire population, but outcomes of this pilot study suggest that problem-based learning may be at least as effective as traditional lecture and should be explored in larger studies.


Catalytic molecular motors: fuelling autonomous movement by a surface bound synthetic manganese catalase.
A molecular approach to the powering of multi-component nano-devices capable of autonomous translational and rotational motion through the conversion of chemical to kinetic energy is reported.


Renal denervation in hypertension: An updated meta-analysis of the randomized controlled trials.
Radiofrequency or ultrasound renal denervation (RDN) has shown conflicting results when used as an adjunctive option for hypertension management in randomized controlled trials (RCTs). We searched Pubmed, MEDLINE, and other online databases for RCTs comparing RDN versus sham-control procedures in patients with uncontrolled or resistant hypertension. The endpoints of interest were 24-h ambulatory (AMB) blood pressure (BP), daytime AMB BP, and office BP. We performed a random-effects meta-analysis using the inverse variance method to estimate mean difference (MD) with a 95% confidence interval (CI). Nine studies with 1643 patients were included in the final analysis. The mean follow-up was 5 months. As compared with the sham-controlled group, RDN was associated with a significant decrease in 24-h AMB BP (systolic [MD -4.20; 95% CI -5.36 to -3.03; p < 0.00001], diastolic [-2.38; -3.42 to -1.35]), and daytime AMB BP (systolic: -5.11; -6.75 to -3.47, diastolic: -2.88; -3.91 to -1.85). Similarly, office BP was reduced with RDN (systolic: -5.46; -7.12 to -3.81; diastolic: -3.17; -4.23 to -2.12) when compared with placebo. Our meta-analysis shows that RDN is associated with a significant reduction in the 24-h AMB BP, daytime AMB BP, and office BP.


Diverging stereochemical pathways in an intramolecular Diels-Alder reaction determined by dienophile structure.
[reaction: see text] Intramolecular Diels-Alder cycloaddition of tolylsulfonyl alkynone 5a and vinyl ketone 19 led to single isomers with opposite diastereoselectivity. Decalin 20 incorporates the correct C(9)-C(11) stereochemical array for a projected synthesis of HMP-Y1 (1).


A case of progressive supranuclear palsy--neurotological findings and etiology.
The eye movements of a case of progressive supranuclear palsy were recorded over a period of time with the aid of electronystagmography. The etiology of this syndrome is not clearly understood as yet. In this case, however, we cannot neglect the influence of solvent intoxication.


Impact of shifting from laparoscopic to robotic surgery during 600 minimally invasive pancreatic and liver resections.
Many centers worldwide are shifting from laparoscopic to robotic minimally invasive hepato-pancreato-biliary resections (MIS-HPB) but large single center series assessing this process are lacking. We hypothesized that the introduction of robot-assisted surgery was safe and feasible in a high-volume center. Single center, post-hoc assessment of prospectively collected data including all consecutive MIS-HPB resections (January 2010-February 2022). As of December 2018, all MIS pancreatoduodenectomy and liver resections were robot-assisted. All surgeons had participated in dedicated training programs for laparoscopic and robotic MIS-HPB. Primary outcomes were in-hospital/30-day mortality and Clavien-Dindo ≥ 3 complications. Among 1875 pancreatic and liver resections, 600 (32%) were MIS-HPB resections. The overall rate of conversion was 4.3%, Clavien-Dindo ≥ 3 complications 25.7%, and in-hospital/30-day mortality 1.8% (n = 11). When comparing the period before and after the introduction of robotic MIS-HPB (Dec 2018), the overall use of MIS-HPB increased from 25.3 to 43.8% (P < 0.001) and blood loss decreased from 250 ml [IQR 100-500] to 150 ml [IQR 50-300] (P < 0.001). The 291 MIS pancreatic resections included 163 MIS pancreatoduodenectomies (52 laparoscopic, 111 robotic) with 4.3% conversion rate. The implementation of robotic pancreatoduodenectomy was associated with reduced operation time (450 vs 361 min; P < 0.001), reduced blood loss (350 vs 200 ml; P < 0.001), and a decreased rate of delayed gastric emptying (28.8% vs 9.9%; P = 0.009). The 309 MIS liver resections included 198 laparoscopic and 111 robotic procedures with a 3.6% conversion rate. The implementation of robotic liver resection was associated with less overall complications (24.7% vs 10.8%; P = 0.003) and shorter hospital stay (4 vs 3 days; P < 0.001). The introduction of robotic surgery was associated with greater implementation of MIS-HPB in up to nearly half of all pancreatic and liver resections. Although mortality and major morbidity were not affected, robotic surgery was associated with improvements in some selected outcomes. Ultimately, randomized studies and high-quality registries should determine its added value.


On-line dialysis solid-phase extraction coupled to capillary electrophoresis.
A fully automated dialysis solid-phase extraction (SPE) sample preparation procedure is coupled on-line to capillary electrophoresis (CE) for the first time. The system is used to determine sulfonamides in serum and urine. The dialysis unit serves to remove proteins and particulate matter. Reconcentration of the analytes is performed with a small SPE column while (in)organic salts and other interferences are removed simultaneously. Finally, the analytes are desorbed and injected, via a homemade interface, into the CE system. Limits of detection (LOD) of 0.05-0.1 and 0.05-0.3 microg/mL are obtained in urine and serum, respectively. The within-day and between-day precisions are in the range of 2-6% and 3-8%, respectively, for a concentration of five times the LOD. The dialysis SPE-CE system was used over a period of six months for the analysis of over 500 serum and urine samples without problems such as clogging of the CE capillary or SPE column.


Roles of soluble minerals in Cd sorption onto rice straw biochar.
Transforming to biochar provides an environmentally friendly approach for crop residue reutilization, which are usually applied as sorbent for heavy metal removal. As typical silicon-rich material, the specific sorptive mechanisms of rice straw derived biochar (RSBC) are concerned, especially at the low concentration range which is more environmentally relevant. In the present study, Cd sorption onto RSBCs at the concentration of ≤ 5 mg/L was investigated. The sorptive capacity was positively correlated with the pyrolytic temperature of the biochar and the environmental pH value. Water soluble minerals of the RSBCs played the dominant roles in Cd sorption, contributing 29.2%, 62.5% and 82.9% of the total sorption for RSBCs derived under 300°C, 500°C and 700°C, respectively. Increased number of cations, dominantly K+, were exchanged during the sorption. Coprecipitation with cations and carbonates may also be contributive to the sorption. The dissolution of silicon-containing minerals was found to be declined during sorption, suggesting its involvement in the sorption process, possibly through precipitation. Whilst, the sparingly soluble silicate crystals may impose ignorable role in the sorption. Complexation with organic groups is only a minor mechanism in Cd sorption, compared to the much more dominant roles of the inorganic ashes.


On the use of extreme value tail modeling for generalized pairwise comparisons with censored outcomes.
In randomized clinical trials, methods of pairwise comparisons such as the 'Net Benefit' or the 'win ratio' have recently gained much attention when interests lies in assessing the effect of a treatment as compared to a standard of care. Among other advantages, these methods are usually praised for delivering a treatment measure that can easily handle multiple outcomes of different nature, while keeping a meaningful interpretation for patients and clinicians. For time-to-event outcomes, a recent suggestion emerged in the literature for estimating these treatment measures by providing a natural handling of censored outcomes. However, this estimation procedure may lead to biased estimates when tails of survival functions cannot be reliably estimated using Kaplan-Meier estimators. The problem then extrapolates to the other outcomes incorporated in the pairwise comparison construction. In this work, we suggest to extend the procedure by the consideration of a hybrid survival function estimator that relies on an extreme value tail model through the Generalized Pareto distribution. We provide an estimator of treatment effect measures that notably improves on bias and remains easily apprehended for practical implementation. This is illustrated in an extensive simulation study as well as in an actual trial of a new cancer immunotherapy.


The Impact of Syringe Age Prior to Filling on Migration of Subvisible Silicone-Oil Particles into Drug Product.
Silicone oil is often applied to the inner surface of glass syringes and cartridges to reduce friction between the glass surface and elastomeric plunger stopper. This oil can appear as intrinsic and non-proteinaceous particles in the ejected fluid or drug product. Limited data is available to understand the impact of age (time between syringe manufacture and filling) on silicone oil migration into the drug product. This study compares subvisible particle count and extrusion force of siliconized syringes from two different manufacturers stored at ambient condition for 2-3 (fresh syringes) and 13-14 (aged syringes) months then filled and placed at 40°C for an additional three months. The fresh syringes exhibit a 2.5-fold increase in subvisible particle count compared to those aged ones. Moreover, the fresh syringes exhibit up to a 2-fold increase in extrusion force. These findings suggest the degree and amount of silicone oil migration is influenced by the time in storage of the glass syringe prior to filling. This rapid communication highlights syringe storage time prior to filling as a factor to be considered during development.


Ankle-brachial index in relation to the natriuretic peptide system polymorphisms and urinary sodium excretion in Chinese.
Recent studies have demonstrated that the natriuretic pepetides induce endothelial regeneration and angiogenesis after vascular injury through the autocrine or paracrine action, and might have an inhibitory effect on atherosclerosis. We therefore systematically investigated single nucleotide polymorphisms (SNPs) in the natriuretic peptide system in relation to ankle-brachial index (ABI) in a Chinese population. The study population was recruited from a mountainous area 500 km south of Shanghai from 2003 to 2009. Using the SNapShot method, we first genotyped 951 subjects enrolled in 2005 for 16 SNPs and then the remaining 1355 subjects as validation for 5 SNPs selected from the primary study. ABI and plasma proBNP were measured using the Omron VP-2000/1000 device and the Elecsys proBNP immunoassay, respectively. Overall, the genetic associations were not significant (P ≥ 0.07). However, in the primary study, there was significant (Pint ≤ 0.045) interaction between 3 SNPs (rs6668352, rs198388, and rs198389) at the NPPA-NPPB locus and urinary sodium excretion in relation to ABI, and the rs6668352 polymorphism had the strongest association (Pint = 0.018). In the primary combined with the validation study populations, the interaction between the rs6668352 polymorphism and urinary sodium excretion in relation to ABI remained statistically significant (Pint = 0.0036). After adjustment for covariates, the rs6668352 A allele carriers, compared with GG homozygotes, had a higher ABI (mean ± standard error, 1.103 ± 0.006 vs. 1.084 ± 0.004, P = 0.009) and lower risk of peripheral arterial disease (PAD, defined as an ABI < 0.90, odds ratio 0.37, 95% confidence interval: 0.14-0.98, P = 0.04) in the subjects of high sodium intake. The minor alleles of 3 SNPs at the NPPA-NPPB locus are associated with a lower risk of PAD, especially in the subjects of high sodium intake.