Using a multiplex serological assay to estimate time since SARS-CoV-2 infection and past clinical presentation in malagasy patients.
The world is facing a 2019 coronavirus (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, efficient serological assays are needed to accurately describe the humoral responses against the virus. These tools could potentially provide temporal and clinical characteristics and are thus paramount in developing-countries lacking sufficient ongoing COVID-19 epidemic descriptions. We developed and validated a Luminex xMAP® multiplex serological assay targeting specific IgM and IgG antibodies against the SARS-CoV-2 Spike subunit 1 (S1), Spike subunit 2 (S2), Spike Receptor Binding Domain (RBD) and the Nucleocapsid protein (N). Blood samples collected periodically for 12 months from 43 patients diagnosed with COVID-19 in Madagascar were tested for these antibodies. A random forest algorithm was used to build a predictive model of time since infection and symptom presentation. The performance of the multiplex serological assay was evaluated for the detection of SARS-CoV-2 anti-IgG and anti-IgM antibodies. Both sensitivity and specificity were equal to 100% (89.85-100) for S1, RBD and N (S2 had a lower specificity = 95%) for IgG at day 14 after enrolment. This multiplex assay compared with two commercialized ELISA kits, showed a higher sensitivity. Principal Component Analysis was performed on serologic data to group patients according to time of sample collection and clinical presentations. The random forest algorithm built by this approach predicted symptom presentation and time since infection with an accuracy of 87.1% (95% CI = 70.17-96.37, p-value = 0.0016), and 80% (95% CI = 61.43-92.29, p-value = 0.0001) respectively. This study demonstrates that the statistical model predicts time since infection and previous symptom presentation using IgM and IgG response to SARS-CoV2. This tool may be useful for global surveillance, discriminating recent- and past- SARS-CoV-2 infection, and assessing disease severity. This study was funded by the French Ministry for Europe and Foreign Affairs through the REPAIR COVID-19-Africa project coordinated by the Pasteur International Network association. WANTAI reagents were provided by WHO AFRO as part of a Sero-epidemiological "Unity" Study Grant/Award Number: 2020/1,019,828-0 P·O 202546047 and Initiative 5% grant n°AP-5PC-2018-03-RO.


An efficient process for co-production of γ-aminobutyric acid and probiotic Bacillus subtilis cells.
This study was to establish an integrated process for the co-production of γ-aminobutyric acid (GABA) and live probiotics. Six probiotic bacteria were screened and Bacillus subtilis ATCC 6051 showed the highest GABA-producing capacity. The optimal temperature and initial pH value for GABA production in B. subtilis were found to be 30 °C and 8.0, respectively. A variety of carbon and nitrogen sources were tested, and potato starch and peptone were the preferred carbon and nitrogen sources for GABA production, respectively. The concentrations of carbon source, nitrogen source and substrate (sodium l-glutamate) were then optimized using the response surface methodology. The GABA titer and concentration of viable cells of B. subtilis reached 19.74 g/L and 6.0 × 108 cfu/mL at 120 h. The GABA titer represents the highest production of GABA in B. subtilis. This work thus demonstrates a highly efficient co-production process for GABA and probiotic B. subtilis cells.


Poly(m6A) tails stabilize transcripts.
Viegas et al. (2022) discover that in Trypanosoma brucei the poly(A) tails of the variant surface glycoprotein (VSG) transcripts are methylated, a mechanism that stabilizes these transcripts and ensures protection against the immune response in mammals.


The influence of toxic working environment on the urothelial bladder tumors characteristics, the experience of "Sf. Ioan" Clinical Emergency Hospital on selected series.
A correlation between urothelial bladder tumor incidence and exposure to various occupational toxic factors was established for more than a century. The aim of our study was to establish the relationship between these two features. We analyzed one hundred consecutive bladder tumor patients treated in "Sf. Ioan" Clinical Emergency Hospital, Department of Urology. These cases were studied concerning their occupation and pathological findings. We identified 58 patients having potential urothelial bladder tumors inducing occupations: dye industry, motor vehicle drivers and miners. Among these patients, the incidence of muscle invasive tumors was of 33%, of the high-grade tumors was of 69%, of the multiple tumors was of 60% and of the associated CIS lesions was of 38%. All these rates were significantly lower in the non-occupational hazard group: 12%, 26%, 29% and 14% respectively. Exposure to occupational toxic factors seems to influence the evolution of urothelial bladder tumor into more aggressive patterns. Further studies in this regard are necessary.


Stress and salicylic acid induce the expression of PnFT2 in the regulation of the stress-induced flowering of Pharbitis nil.
Poor nutrition and low temperature stress treatments induced flowering in the Japanese morning glory Pharbitis nil (synonym Ipomoea nil) cv. Violet. The expression of PnFT2, one of two homologs of the floral pathway integrator gene FLOWERING LOCUS T (FT), was induced by stress, whereas the expression of both PnFT1 and PnFT2 was induced by a short-day treatment. There was no positive correlation between the flowering response and the homolog expression of another floral pathway integrator gene SUPPRESSOR OF OVEREXPRESSION OF CO1 and genes upstream of PnFT, such as CONSTANS. In another cultivar, Tendan, flowering and PnFT2 expression were not induced by poor nutrition stress. Aminooxyacetic acid (AOA), a phenylalanine ammonia-lyase inhibitor, inhibited the flowering and PnFT2 expression induced by poor nutrition stress in Violet. Salicylic acid (SA) eliminated the inhibitory effects of AOA. SA enhanced PnFT2 expression under the poor nutrition stress but not under non-stress conditions. These results suggest that SA induces PnFT2 expression, which in turn induces flowering; SA on its own, however, may not be sufficient for induction.


Preparation of a Microspherical Silver-Reduced Graphene Oxide-Bismuth Vanadate Composite and Evaluation of Its Photocatalytic Activity.
A novel Ag-reduced graphene oxide (rGO)-bismuth vanadate (BiVO₄) (AgGB) ternary composite was successfully synthesized via a one-step method. The prepared composite was characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), Brunauer-Emmett-Teller (BET) surface area measurement, Raman scattering spectroscopy, and ultraviolet-visible diffuse-reflection spectroscopy (UV-vis DRS). The results showed that bulk monoclinic needle-like BiVO₄ and Ag nanoparticles with a diameter of approximately 40 nm formed microspheres (diameter, 5-8 μm) with a uniform size distribution that could be loaded on rGO sheets to facilitate the transport of electrons photogenerated in BiVO₄, thereby reducing the rate of recombination of photogenerated charge carriers in the coupled AgGB composite system. Ag nanoparticles were dispersed on the surface of the rGO sheets, which exhibited a localized surface plasmon resonance phenomenon and enhanced visible light absorption. The removal efficiency of rhodamine B dye by AgGB (80.2%) was much higher than that of pure BiVO₄ (51.6%) and rGO-BiVO₄ (58.3%) under visible light irradiation. Recycle experiments showed that the AgGB composite still presented significant photocatalytic activity after five successive cycles. Finally, we propose a possible pathway and mechanism for the photocatalytic degradation of rhodamine B dye using the composite photocatalyst under visible light irradiation.


Peroxynitrite decomposition with FeTMPyP improves plasma-induced vascular dysfunction and infarction during mild but not severe hyperglycemic stroke.
We investigated mechanisms by which circulating factors during hyperglycemic (HG) stroke affect cerebrovascular function and the role of peroxynitrite in stroke outcome. Middle cerebral arteries (MCAs) were isolated from male Wistar rats and perfused with plasma from rats that were hyperglycemic for 5 to 6 days by streptozotocin and underwent either MCA occlusion (HG MCAO) or Sham surgery (HG Sham) compared with MCA perfused with physiologic saline (No plasma). Myogenic responses and endothelial function were compared in untreated MCA (n=8/group) or with inhibitors of NADPH oxidase (apocynin; n=8), peroxynitrite (FeTMPyP; n=8) or endothelin-1 (ET-1)(A) (BQ-123; n=8). Finally, animals were treated in vivo before reperfusion after mild (<68% cerebral blood flow (CBF) decrease) or severe (>68% CBF decrease) MCAO with FeTMPyP (n=12) or vehicle (n=12) and CBF and infarction measured. The HG MCAO plasma increased tone in MCA versus No plasma (P<0.05) that was reversed by FeTMPyP, but not by apocynin or BQ-123. The HG Sham plasma also increased tone in MCA (P<0.05) that was reversed by BQ-123 only. In vivo, FeTMPyP was neuroprotective during mild, but not severe ischemia. These results show that circulating factors in plasma can affect cerebrovascular function through peroxynitrite generation and ET-1. In addition, peroxynitrite decomposition improves stroke outcome acutely during mild, but not severe HG ischemia.


Chitosan nanocarrier for FTY720 enhanced delivery retards Parkinson's disease via PP2A-EzH2 signaling in vitro and ex vivo.
Parkinson's disease (PD) develops due to oxidative stress, mitochondrial aberrations, posttranslational modification, and α-Synuclein (α-Syn) aggregation. The α-synucleinopathy is attributed to phosphorylation and aggregation of α-Syn. A strategy to degrade or reduce phosphorylated protein paves the way to develop PD therapy. Hence, the neuroprotective efficiency of PP2A (Protein phosphatase 2) activator FTY720, loaded chitosan nanoformulation has been evaluated in vitro and ex vivo experimental PD models. Bio-compatible chitosan-based nanocarriers have been utilized to enhance the bio-availability and neuroprotective effect of FTY720. The neuroprotective effect of characterized nanoformulation was determined by the downregulation of PD hallmark phospho-serine 129 (pSer129) α-Syn, with anti-oxidative and anti-inflammatory potentials. The neuroprotective mechanism uncovered novel physical interaction of PP2A and polycomb group of protein Enhancer of zeste homolog 2 to mediate ubiquitination and degradation of agglomerated pSer129 α-Syn. Indeed, this study establishes the neuroprotective potential of chitosan based FTY720 nanoformulations by PP2A mediated epigenetic regulation for PD prevention.


The endocrine cells in the gut of Mugil saliens Risso, 1810 (Teleostei): an immunocytochemical and ultrastructural study.
The endocrine cells in the gut of Mugil saliens Risso, 1810 (leaping grey mullet) were investigated by immunocytochemical and electron microscopic techniques. Gastrin-, glucagon-, and somatostatin-immunoreactive cells were identified in the cardiac and cecal stomach regions, located mainly in the lower part of the gastric folds and in the upper part of the glands. Substance P-, somatostatin-, and pancreatic polypeptide (PP)-immunoreactive cells were found between epithelial cells in the pyloric stomach region. Gastrin-, cholecystokinin (CCK)-, gastric inhibitory polypeptide (GIP)-, substance P-, Met-enkephalin- and PP-immunoreactive cells were observed throughout the intestine while only the last three of these appeared in the posterior intestine. Nine types of gastroenteroendocrine cells were ultrastructurally characterized; some of them were related to the cell types immunocytochemically identified.


A primary estimate of global PCDD/F release based on the quantity and quality of national economic and social activities.
The correlations between polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) releases and factors relevant to human social-economic activities (HSEAs) were analyzed. The multiple linear regression model was successfully developed to estimate the total global PCDD/F release. The PCDD/F releases significantly correlated with population, area, GDP and GNI, suggesting that "quantity" of HSEAs have significantly contributed to the PCDD/F releases. On another aspect, advanced technologies are usually adopted in developed countries/regions, and hence reduce the PCDD/F release. The significant correlation between PCDD/F release and CO2 emission implies the potential of simultaneous reduction of CO2 emission and PCDD/F release. The total global PCDD/F release from 196 countries/regions was estimated to be 100.4 kg-TEQ yr(-1). The estimated annual PCDD/F release per unit area ranged from 0.007 to 28 mg-TEQ km(-2). Asia is estimated to have the highest PCDD/F release of 47.1 kg-TEQ yr(-1), almost half of the total world release. Oceania is estimated to have the smallest total release but the largest per-capita release. For the developed areas, such as Europe and North America, the PCDD/F release per unit GDP is lower, while for Africa, it is much higher.


The role of quantitative sensory testing in the evaluation of musculoskeletal pain conditions.
Quantitative sensory testing (QST) is a noninvasive method of assessing sensory and pain perception that has been used in the past 30 years primarily for analysis of cutaneous and mucosal perception. In recent years, several published studies have demonstrated that QST may be useful in the analysis of painful musculoskeletal disorders as well. Based on the results of these studies, it can be postulated that QST may be useful in the analysis of the pathogenesis, classification, and differential diagnosis of musculoskeletal disorders. However, due to the diverse ethiopathogenetic basis of these disorders, a broad range of QST test batteries may be necessary to analyze the various musculoskeletal disease entities. This review analyzes published studies on this subject and summarizes current information on altered sensory and pain perception available for some of the most common musculoskeletal disorders. At present, QST remains primarily a research tool but may be useful in differential diagnosis in indicating the presence of central sensitization and for clinical monitoring of disease progression or treatment response.


Health needs assessment in a regional community pharmacy using the PRECEDE-PROCEED model.
Community pharmacies have capacity to provide a variety of professional pharmacy services. However, planning models are underutilised when guiding pharmacists in assessing local health and social needs for providing tailored services to meet community needs and priorities. The objective of this was to utilize the PRECEDE-PROCEED model to perform a health needs assessment to identify health concerns in a regional Australian community for guiding professional pharmacy service development. A health needs assessment using the PRECEDE-PROCEED model was conducted in November 2019 using a convergent mixed-methods design through: (1) convenience sampling of pharmacy customers with a survey, (2) purposive sampling of a sole community pharmacist with a semi-structured interview, and (3) collection of regional health and social data from online databases. The community survey response rate was 44.8%. Of 113 participants, the majority were female (71.7%) and town dwellers (89.4%), representing 6.4% of the town's population. Mental illness was cited by 35.3% of community survey participants to be impacting local health and wellbeing, with depression/anxiety the most prevalent self-reported condition (44.2%), predominantly affecting women (72%). The community pharmacist and regional secondary data provided additional support for the prioritization of mental illness. Depression/anxiety was associated with delays/avoidance of prescription medicine due to cost (p = .002), poor self-rated health (p = .012), worsening health over the past year (p < .001), seeking advice from a pharmacist about health or medicines (p = .03), and receipt of emergency care in the past year (p = .001). The lack of a local general practitioner, social isolation, and environmental issues also impacted health and wellbeing. The PRECEDE-PROCEED model identified mental health as the greatest health priority in the community, using multiple data sources and participatory methods. Using this model provides insight into the development of tailored community pharmacy interventions that address health priorities such as mental health needs in a community.


Composition and variation in vitamin C, carotenoids, protein, nitrate and oxalate contents in Celosia leaves.
Twenty two lines/accessions belonging to 5 species of Celosia were analysed for their nutritional and antinutritional composition. The nutrient contents, vitamin C varied from 18.8 to 53.6 mg/100 g, carotenoids 9.1 to 15.1 mg/100g, protein 2.1 to 5.9%, while the antinutritional factors, nitrate 0.18 to 0.46% and oxalate 0.98 to 3.93%. Moisture ranged 81 to 89%. Variation of these parameters with leaf position and the amino acids profile of some promising lines was also evaluated.


Support vector machine for classification of walking conditions using miniature kinematic sensors.
A portable gait analysis and activity-monitoring system for the evaluation of activities of daily life could facilitate clinical and research studies. This current study developed a small sensor unit comprising an accelerometer and a gyroscope in order to detect shank and foot segment motion and orientation during different walking conditions. The kinematic data obtained in the pre-swing phase were used to classify five walking conditions: stair ascent, stair descent, level ground, upslope and downslope. The kinematic data consisted of anterior-posterior acceleration and angular velocity measured from the shank and foot segments. A machine learning technique known as support vector machine (SVM) was applied to classify the walking conditions. SVM was also compared with other machine learning methods such as artificial neural network (ANN), radial basis function network (RBF) and Bayesian belief network (BBN). The SVM technique was shown to have a higher performance in classification than the other three methods. The results using SVM showed that stair ascent and stair descent could be distinguished from each other and from the other walking conditions with 100% accuracy by using a single sensor unit attached to the shank segment. For classification results in the five walking conditions, performance improved from 78% using the kinematic signals from the shank sensor unit to 84% by adding signals from the foot sensor unit. The SVM technique with the portable kinematic sensor unit could automatically recognize the walking condition for quantitative analysis of the activity pattern.


Diffusion during dehydrogenase reactions: the effects of intermediate electron acceptors.
A hamster cheek pouch model has been used to study the diffusion of reactants from the epithelium into adjacent muscle and connective tissue during the histochemical demonstration of glucose-6-phosphate dehydrogenase activity. The effects of the addition of intermediate electron acceptors to the incubation medium varied considerably from one acceptor to another, but were independent of the grade of polyvinyl alcohol incorporated into the medium. Menadione was the least effective intermediate both in transferring reducing equivalents from the primary dehydrogenase to Neotetrazolium chloride and in preventing diffusion. Phenazine methosulphate, Methylene Blue and Thionin were more efficient intermediates. Nevertheless, considerable diffusion occurred in the presence of Phenazine methosulphate, although very little diffusion was detectable with either of the thiazine dyes. It is suggested that these differences are related to different modes and sites of action of the carriers.


Photocatalytic degradation of reactive dyes using natural photo-smart pigment-A novel approach for waste water re-usability.
The present study is aimed at an efficient photocatalytic degradation of industrially important reactive dyes using phycocyanin extract as a photocatalyst. The percentage of dye degradation was evidenced by a UV-visible spectrophotometer and FT-IR analysis. The degraded water was checked for its complete degradation by varying pH from 3 to 12. Furthermore, the degraded water was also analyzed for water quality parameters and was found to meet industrial wastewater standards. The calculated irrigation parameters like magnesium hazard ratio, soluble sodium percentage, and Kelly's ratio of degraded water were within the permissible limits, which enables its reusability in irrigation, aquaculture, as industrial coolants, and domestic applications. The calculated correlation matrix shows that the metal influences various macro-, micro-, and non-essential elements. These results suggest that the non-essential element lead can be effectively reduced by increasing all the other micronutrients and macronutrients under study except sodium metal.


Selective uptake of single-walled carbon nanotubes by circulating monocytes for enhanced tumour delivery.
In cancer imaging, nanoparticle biodistribution is typically visualized in living subjects using 'bulk' imaging modalities such as magnetic resonance imaging, computerized tomography and whole-body fluorescence. Accordingly, nanoparticle influx is observed only macroscopically, and the mechanisms by which they target cancer remain elusive. Nanoparticles are assumed to accumulate via several targeting mechanisms, particularly extravasation (leakage into tumour). Here, we show that, in addition to conventional nanoparticle-uptake mechanisms, single-walled carbon nanotubes are almost exclusively taken up by a single immune cell subset, Ly-6C(hi) monocytes (almost 100% uptake in Ly-6C(hi) monocytes, below 3% in all other circulating cells), and delivered to the tumour in mice. We also demonstrate that a targeting ligand (RGD) conjugated to nanotubes significantly enhances the number of single-walled carbon nanotube-loaded monocytes reaching the tumour (P < 0.001, day 7 post-injection). The remarkable selectivity of this tumour-targeting mechanism demonstrates an advanced immune-based delivery strategy for enhancing specific tumour delivery with substantial penetration.


Mechanism of death and prevalence of myocardial ischemic symptoms in the terminal event after acute myocardial infarction.
A prospective study to determine prognostic factors for risk stratification in 867 patients surviving the coronary care unit phase of acute myocardial infarction (AMI) is reported. During a 48-month follow-up, 144 patients (17%) died. The deaths were examined for the chronology, cause, mechanism, location and presence of myocardial ischemia in the terminal event. A classification previously proposed by Hinkle and Thaler was used to define the mechanism of cardiac death and the presence of ischemia. There were 113 deaths due to coronary atherosclerotic coronary artery disease, including 5 due to complications of coronary artery bypass graft surgery. Of the remaining 108 of these deaths, 74% were classified as due to an arrhythmic mechanism and 26% as myocardial failure. Of the deaths due to an arrhythmia or to myocardial failure, 56 (52%) occurred out of hospital. The ratio of arrhythmic: myocardial failure deaths was not different for the patients who died within 3 months after the index AMI compared with later deaths. Sudden death (less than or equal to 1 hour of new symptoms) was strongly associated with arrhythmic death but 32 (54%) of patients who died greater than 1 hour after the onset of symptoms were also classified as having an arrhythmic cause of death. Previously described risk factors, including an ejection fraction less than 0.40 and greater than or equal to 10 ventricular premature complexes/hour, were independent predictors of mortality but did not differentially predict the mechanism of cardiac death. Evidence of myocardial ischemia before the terminal event was found in about 50 (60%) patients whose deaths were witnessed and who died from an arrhythmia or myocardial failure.


Sigmund Freud and money.
I have tried to clarify Sigmund Freud's attitude toward money during the different time periods of his life. Most biographers have written that Freud was born into a poor family that later was elevated to the socioeconomic middle class in Vienna. This traditional viewpoint can be supported by various of Freud's letters and writings. A very different viewpoint has been proposed by the well-known American economist, Peter Drucker. As has been noted, his parents knew the Freud family in Vienna where Drucker actually met Freud. Drucker contends that Freud unconsciously misrepresented his parents' financial situation by creating the myth that they lived in poverty. Furthermore, Freud also developed another myth that it was because of the strong anti-Semitism in Vienna that he was so delayed in being appointed a professor of psychiatry. Drucker points out that the majority of the Viennese physicians were Jewish and that Freud's becoming a professor did not entail a delay and was not affected by any anti-Semitism in Vienna. Another area of conflict between Freud and the other Viennese physicians was Freud's refusal to treat any of his psychoanalytic patients without a fee. Freud believed that treating a patient in analysis for free created a transference-countertransference problem that might doom the treatment to failure. Freud's transference explanation for not taking on charity patients did not satisfy many of his Viennese physician colleagues. They believed that Freud was given an opportunity to accept their traditional standards and turned it down. In their eyes, Freud rejected them, they did not reject him. The same reasoning applied to the Viennese physicians' request for some scientific proof of the efficacy of psychoanalysis. Freud could only provide them with anecdotal or testimonial evidence to support psychoanalytic treatment. This placed psychoanalysis in the category of a belief system and not a scientific treatment. Drucker explains Freud's "obsession" with having lived in poverty as a manifestation of his "poorhouse neurosis." According to Drucker this syndrome was frequently found among Viennese during the last quarter of the 19th century. It was an irrational and deep-seated fear that an individual and his family were on the verge of being placed in the poorhouse because they lacked any funds. Freud does not specifically mention his having this irrational fear or obsession, but he made several statements quoted here indicating such a dread. At a recent psychoanalytic meeting I asked Freud scholar John Gedo of Chicago if he thought Freud experienced a "poorhouse neurosis."(ABSTRACT TRUNCATED AT 400 WORDS)


Improving the catalytic and mechanical performance of alginate catalyst through functionalization by aminopolycarboxylic acids.
Biomass-based aerogel catalysts have attracted extensive attention due to their high surface aera, continuous porous and environmental friendliness. However, their catalytic activity and mechanical strength are not satisfied for industrial applications. In this work, to solve the above two issues, a new kind of graphene oxide enhancediminodiacetic acid-functionalized Cu-cross-linked alginate (GO-Cu-SA-IDA) aerogel composites were prepared. The physicochemical property of the prepared alginate aerogel composites was characterized systematically, and their catalytic activities were studied in the hydroxylation of phenol. Results illustrated that compared with Cu-SA aerogels (∼16 %), the amount of loaded copper ion which played as the active sites in GO-Cu-SA-IDA aerogel composite was increased by 2 times (32.2 %). In addition, the mechanical strength of GO-Cu-SA-IDA was increased by 10 times. After functionalization, both the catalytic activity and mechanical strength of prepared alginate aerogel composites were enhanced successfully. In addition, the catalyst had been recycled five times with only 5.8 % loss of its catalytic activity, which provided a desirable material for next generation of catalysts.


A patient with recurrent hepatic encephalopathy and chronic renal failure treated successfully with long-term hemodialysis.
A 38-year-old man suffering from chronic recurrent hepatic enchephalopathy due to liver cirrhosis complicated with chronic renal failure had been maintained well by regular hemodialysis treatment for 14 months. Only four episodes of hepatic encephalopathy occurred in that period. Each of four episodes of disturbed consciousness was accompanied by slightly elevated blood ammonia levels. Energetic serial dialysis for 5-7 days was necessary for its recovery. The factors causing hepatic encephalopathy did not appear to be easily dialysable as compared with those of uremic coma. It is concluded that the hemodialysis is quite an effective treatment for the recurrent type of hepatic encephalopathy.


Computed tomography and spinal dysraphism: clinical and phantom studies.
Two cases illustrating the value of CT in the assessment of spinal dysraphic tissue are presented. In one case, the configuration and origins of two osseous diastematomyelic spurs were shown well; in the second case, the CT recognition of a sacral lipoma led to air myelographic confirmation of the tumor and tethered cord. CT phantom studies indicated that dysraphic tissues, such as fat, cartilage, and fibrous tissue, are better identified and quantitated in the spinal canal when surrounded by air. Varying degrees of image degradation occur with water (simulating CSF) or metrizamide.


Comparison of the contents of phenolic compounds including flavonoids and antioxidant activity of rice (Oryza sativa) and Chinese wild rice (Zizania latifolia).
The contents of phenolic compounds, especially flavonoids, and antioxidant activity of rice (Oryza sativa, Os) and Chinese wild rice (Zizania latifolia, Zl) harvested in China were compared. Zl possessed significantly higher contents of total phenolics, flavonoids, and proanthocyanidins and exhibited higher antioxidant activity than in the Os Xian group, the Os Geng group, and red rice. The flavonoid contents of Os and Zl were compared using a UHPLC-QqQ-MS-based metabolomics approach. A total of 159 flavonoids were identified, among which 78 showed differential expression (72 up-regulated and six down-regulated in the Zl group). The Kyoto Encyclopaedia of Genes and Genomes annotation and classification indicated that the differentially expressed flavonoids were mainly related to anthocyanin biosynthesis. Moreover, candidate genes for flavonoid biosynthesis in Os and Zl were identified in this study. Compared with non-pigmented and red rice, Zl may be more nutritious and is thus considered a better source of natural antioxidants.


Are There Real-world Benefits to Bimodal Listening?
To assess the benefits of bimodal listening (i.e., addition of contralateral hearing aid) for cochlear implant (CI) users on real-world tasks involving high-talker variability speech materials, environmental sounds, and self-reported quality of life (quality of hearing) in listeners' own best-aided conditions. Cross-sectional study between groups. Outpatient hearing clinic. Fifty experienced adult CI users divided into groups based on normal daily listening conditions (i.e., best-aided conditions): unilateral CI (CI), unilateral CI with contralateral HA (bimodal listening; CIHA), or bilateral CI (CICI). Task-specific measures of speech recognition with low (Harvard Standard Sentences) and high (Perceptually Robust English Sentence Test Open-set corpus) talker variability, environmental sound recognition (Familiar Environmental Sounds Test-Identification), and hearing-related quality of life (Nijmegen Cochlear Implant Questionnaire). Test group differences among CI, CIHA, and CICI conditions. No group effect was observed for speech recognition with low or high-talker variability, or hearing-related quality of life. Bimodal listeners demonstrated a benefit in environmental sound recognition compared with unilateral CI listeners, with a trend of greater benefit than the bilateral CI group. There was also a visual trend for benefit on high-talker variability speech recognition. Findings provide evidence that bimodal listeners demonstrate stronger environmental sound recognition compared with unilateral CI listeners, and support the idea that there are additional advantages to bimodal listening after implantation other than speech recognition measures, which are at risk of being lost if considering bilateral implantation.


Single-fiber electromyography of the laryngeal muscles.
Single-fiber electromyography (SFEMG) is useful in the evaluation of disorders of neuromuscular transmission and the assessment of motor unit morphology. Standard EMG techniques are used routinely in the evaluation of laryngeal dysfunction, but the feasibility of laryngeal SFEMG has not been established. We, therefore, performed laryngeal SFEMG in 10 normal individuals to demonstrate the feasibility of the technique and generate preliminary normative data. We also studied 2 patients with amyotrophic lateral sclerosis and 1 patient previously treated with botulinum toxin for comparative purposes.


Extracorporeal shock-wave therapy in the treatment of pseudoarthrosis: a case report.
We describe the case of a of a 23 year old man (european) with a complicated fibular-tibial shaft fracture with subsequent pseudoarthrosis formation, which was unable to be corrected by surgery, but which we were finally able to heal using Extracorporeal shock-wave therapy.


Association between Early Menopause, Gynecological Cancer, and Tobacco Smoking: A Cross-Sectional Study.
The rates of smoking among women are rising. Previous studies have shown that smoking is associated with early menopause. However, the association of gynecological cancer, including breast and cervical cancer, with early menopause and smoking, remains unclear. Therefore, this study aimed to determine the association between smoking and early menopause, breast cancer, and cervical cancer. This cross-sectional study used data from the Korean National Health and Nutritional Survey Examination (KHANES) (2016-2018). Early menopause was defined as menopause before 50 years of age. A total of 4,481 participants were included in the analysis. There was no association between early menopause and cervical cancer (adjusted odds ratio [aOR]: 1.435, 95% confidence interval [CI]: 0.730-2.821), but women who had experienced early menopause had a significantly higher risk of breast cancer than women who had experienced normal menopause (aOR: 1.683, 95% CI: 1.089-2.602, p=0.019). Early menopause was not associated with an increased risk of breast cancer in ever-smoker (aOR: 0.475, 95% CI: 0.039-5.748), but was associated with a significantly increased risk of breast cancer in never-smokers (aOR: 1.828, 95% CI: 1.171-2.852). Early menopause was associated with an increased risk of breast cancer in women who had never smoked, but not in women who had ever smoked.


Therapy of mantle cell lymphoma: current standards and future strategies.
Mantle cell lymphoma is characterized clinically by an aggressive clinical course and is relatively resistant to conventional chemotherapies. When in its advanced stages, currently available immunochemotherapy regimens remain noncurative despite high initial response rates. In contrast, consolidating high-dose therapy with autologous stem cell retransfusion significantly extends progression-free survival of young patients. Currently, allogenic bone marrow transplantation represents the only therapy with the potential for a curative approach, although associated with a high rate of complications. New concepts of therapy are urgently warranted, including new molecular approaches, such as bortezomib, thalidomide, lenalidomide, and temsirolimus.


Morphology and chemical characteristics of subepithelial laminar nerve endings in the rat epiglottic mucosa.
The laminar nerve endings are distributed in the laryngeal mucosa, and described as sensory receptors evoked by laryngeal pressure changes. The present study aimed to determine detailed morphological characteristics of the laryngeal laminar endings of the rat. Immunohistochemistry for Na(+)-K(+)-ATPase, α(3) subunit, showed that laminar endings were distributed in the entire laryngeal surface of the epiglottis. The parent axons of the endings were thick in diameter, and they were branched and continued to the endings. In some cases, several endings from different parent axons fused into a large complex structure of 500 μm in width. The laminar endings were also immunoreactive for vesicular glutamate transporter 1 (vGLUT1) and vGLUT2, but not for P2X(3) purinoceptor. Around the laminar endings, terminal Schwann cells with immunoreactivity for S-100 protein were closely associated with axon terminals. Use of scanning electron microscopy with alkaline maceration method showed that the terminal Schwann cells consisted of a rounded perinuclear region and lamellar cytoplasmic processes. Ultrastructurally, axon terminals with numerous mitochondria were partly covered with Schwann cell sheath, and some terminals intruded into the epithelial layer. Clear vesicles of 50 nm in diameter were also observed especially in small cytoplasmic processes of 400 nm to 1 μm in size. The results in the present study suggested that the laminar endings in epiglottic mucosa have morphological characteristics of slowly adapting mechanoreceptors and contribute to sensation of laryngeal pressure via mucosal tension.


Increased consumption of diazepam during continuous amphetamine administration.
Previous investigations in our laboratory have demonstrated that after implantation of slow-release d-amphetamine pellets, rats with free access to water and a 10% ethanol solution selectively increase their consumption of the ethanol solution. We now report that this d-amphetamine treatment produces a similar increase in drinking of a benzodiazepine (diazepam) solution. Female albino rats were given free access to water and a 0.060 mg/ml diazepam solution and fluid intake was recorded every two days. The baseline consumption of diazepam averaged 25% of the total daily fluid intake. After d-amphetamine pellet implantation, rats increased their diazepam consumption to an average of 48% of total fluid intake, whereas rats implanted with control pellets containing vehicle only showed no change in diazepam drinking.


Health-care utilization for sinusitis after pneumococcal vaccination in patients with low antibody titers.
Pneumococcal antibody deficiency has been the subject of limited study in chronic rhinosinusitis (CRS) and has not been studied in recurrent acute rhinosinusitis (RARS). The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is considered for patients with nonprotective Streptococcus pneumoniae titers. We hypothesized that both RARS and CRS patients with deficient S pneumoniae titers and subsequent PPSV23 vaccination would have reduced health-care encounters for sinusitis and fewer prescriptions for antibiotics or steroids. A retrospective cohort study was performed of patient encounters between January 2011 and December 2019. All patients included were ≥18 and ≤65 years old with a diagnosis of CRS or RARS and pneumococcal titer data. Patients with immunodeficiency and comorbid conditions requiring PPSV23 vaccination before 65 years of age were excluded. A total of 938 patients were included in the study. Nonprotective antibody titers were present in 75.8% of CRS and 74.8% of RARS patients. A total of 306 patients with deficient antibody titers received the PPSV23 vaccine. Eighty-nine percent of CRS and 90.1% of RARS patients had protective responses. Among the 217 patients with continuous data from 2 years before through 2 years after PPSV23 vaccination, a decrease in the number of encounter diagnoses of CRS (p < 0.0001) and RARS (p = 0.0006) was observed. Decreases in the frequency of antibiotic (p = 0.002) and corticosteroid (p = 0.04) prescriptions were also appreciated. Most patients with CRS and RARS have nonprotective antibody titers. PPSV23 administration significantly decreases health-care utilization.


Lucifer yellow uptake in developing rat retina: selective staining of horizontal cells.
We have examined the uptake of Lucifer yellow CH by developing rat retina. We find that selective dye uptake occurs in retina incubated in vitro in the absence of external Ca2+. The pattern of uptake appears to depend on the developmental stage examined. Although little uptake is seen before postnatal day 5, between days 6 and 9, the dye selectively stains putative horizontal cell bodies and their process. Later, other cell bodies located deeper in the INL begin to show staining until day 21, when the uptake pattern becomes analogous to that seen in adult retina. By nearest neighbor analysis of labeled cell bodies in wholemounts of D-9 retina, we have shown that the labeled cells are distributed in a quasi-regular mosaic in the retina. Upon proteolytic dissociation of labeled retina, individual cells with Lucifer yellow fluorescence could be readily identified in the cell suspensions.


BrabA.11339.a: anomalous diffraction and ligand binding guide towards the elucidation of the function of a 'putative β-lactamase-like protein' from Brucella melitensis.
The crystal structure of a β-lactamase-like protein from Brucella melitensis was initially solved by SAD phasing from an in-house data set collected on a crystal soaked with iodide. A high-resolution data set was collected at a synchroton at the Se edge wavelength, which also provided an independent source of phasing using a small anomalous signal from metal ions in the active site. Comparisons of anomalous peak heights at various wavelengths allowed the identification of the active-site metal ions as manganese. In the native data set a partially occupied GMP could be identified. When co-crystallized with AMPPNP or GMPPNP, clear density for the hydrolyzed analogs was observed, providing hints to the function of the protein.


Glucocorticoid-induced reduction of prostanoid synthesis in TPA-differentiated U937 cells is mainly due to a reduced cyclooxygenase activity.
The molecular mechanism of the glucocorticoid-induced inhibition of prostanoid synthesis was investigated in human monoblastoid U937 tumor cells and phorbol ester (TPA)-differentiated U937 cells. Prostanoid synthesis was inhibited in TPA-differentiated U937 cells by glucocorticoids such as dexamethasone and prednisolone, whereas aldosterone and progesterone showed no inhibitory effect. None of these methods had any influence on prostanoid secretion of undifferentiated U937 cells. Receptor binding studies revealed the presence of glucocorticoid receptors in both undifferentiated and TPA-differentiated U937 cells (Kp approximately 5 x 10(-9)M), however, the number of receptors per cell was increased 10-fold in TPA-differentiated U937 cells. Expression of lipocortin I and II as measured by Western blot analysis was not affected by dexamethasone. In TPA-differentiated cells, dexamethasone decreased the activities of two enzymes essential for prostanoid synthesis, cyclooxygenase and phospholipase A2, by 60-70% and 30%, respectively. Cells pretreated with the translation inhibitor cyclohexmide and dexamethasone showed similar cyclooxygenase and phospholipase A2 activities as cells treated with cycloheximide alone. Western blot analysis demonstrated that the significantly decreased cyclooxygenase activity correlated with an inhibited protein synthesis. In this human macrophage-like model glucocorticoids thus interfere at least at two levels with prostanoid synthesis by inhibiting the activities of phospholipase A2 as well as cyclooxygenase.


Experience with the surgical treatment of radial polydactyly in adults.
The aim of this study is to investigate the functional and cosmetic outcome after surgical reconstruction in adult patients. Eleven hands of the 10 adult patients with radial polydactyly were treated surgically. Clinical and radiologic examination was performed and cases were classified according to the Wassel system. The outcome was evaluated according to the Modified Wood criteria. Average age of the patients was 20 years (range, 19-23 years) and all patients were male. All of the patients were admitted with the social consequences of the cosmetic problems resulting from the anomaly. Cosmetic and functional results were excellent in 9 cases and good in 2 cases. The findings of this study revealed that radial polydactyly can be surgically reconstructed satisfactorily in adulthood. However, the fact that these patients were mainly admitted as a result of the psychosocial consequences of the cosmetic aspect of the anomaly, we concluded that regardless of age, surgery should not be delayed after diagnosis.


Effects of attention on visual experience during monocular rivalry.
There is a long-running debate over the extent to which volitional attention can modulate the appearance of visual stimuli. Here we use monocular rivalry between afterimages to explore the effects of attention on the contents of visual experience. In three experiments, we demonstrate that attended afterimages are seen for longer periods, on average, than unattended afterimages. This occurs both when a feature of the afterimage is attended directly and when a frame surrounding the afterimage is attended. The results of these experiments show that volitional attention can dramatically influence the contents of visual experience.


Conjugating 4β-NH-(5-Aminoindazole)-podophyllotoxin and Galectin-1-Targeted Aptamer for Synergistic Chemo-Immunotherapy of Hepatocellular Carcinoma.
By conjugating a chemotherapeutic candidate drug 4β-NH-(5-aminoindazole)-podophyllotoxin (βIZP) and an immunosuppressive protein galectin-1 targeted aptamer AP74, a chemo-immunotherapy molecule (AP74-βIZP) is developed against liver cancer. AP74-βIZP can target galectin-1 and enrich the tumor microenvironment to improve the tumor inhibition ratio by 6.3%, higher than that of βIZP in a HepG2 xenograft model. In safety evaluation, βIZP cannot be released from AP74-βIZP in normal tissues with low glutathione level. Therefore, the degrees of organs injury and myelosuppression after the treatment with AP74-βIZP are lower than those with βIZP. After 21 d treatment at a drug dose of 5 mg kg-1 , AP74-βIZP does not cause weight loss in mice, while the weight is significantly reduced by 24% and 14% from oxaliplatin and βIZP, respectively. In immune synergy, AP74-IZP enhances CD4/CD8 cell infiltration to promote the expression of cell factor (i.e., IL-2, TNF-α, and IFN-γ), which further improves the antitumor activity. The tumor inhibition ratio of AP74-βIZP is 70.2%, which is higher than that of AP74 (35.2%) and βIZP (48.8%). Because of the dual effects of chemotherapy and immunotherapy, AP74-βIZP exhibits superior activity and lower toxicity. The approach developed in this work could be applicable to other chemotherapy drugs.


Multiple forms of urease in cytoplasmic fractions of Ureaplasma urealyticum.
The urease activity of Ureaplasma urealyticum was found to be located in the cytoplasmic fraction and consisted of multiple stable enzyme forms representing at least four biotypes.


Beyond the Typical Syndrome: Understanding Non-motor Features in Niemann-Pick Type C Disease.
Niemann-Pick type C (NPC) is a rare autosomal recessive disorder characterized by storage of unesterified glycolipids and cholesterol in lysosome. NPC's clinical presentation is highly heterogeneous, depending on the time of onset. It encompasses visceral, neurological, and/or psychiatric manifestations. As the motor findings are so important and devastating in this disease, there is a lack of description about non-motor symptoms, even though they play important role in quality of life of NPC patients. We described the most common non-motor findings in NPC like cognitive dysfunction, neuroimaging, psychiatric symptoms, sleep disorders, seizures, hearing problems, respiratory and other systemic features, bladder and fecal dysfunction, hypersalivation, and malnutrition. In this review, we highlighted the importance of these undervalued symptoms and their management. Specific measures of all aforementioned clinical features may work as relevant biomarkers in order to evaluate successful therapies in future clinical trials.


Stability criterion for controlling standing in able-bodied subjects.
A new stability criterion that can be used to assess the standing condition of a subject from center of pressure (CoP) measurements is presented. This criterion can be applied, for example, to control a standing prosthesis, which should allow a paraplegic subject to stand up, sit down and stand safely without using hands for support. Experiments conducted with able-bodied subjects enabled us to establish a relationship between its stability and the subject's CoP position. Four CoP stability zones were identified: high preference, low preference, undesirable and unstable zones. The high preference zone is defined as the area where the CoP is found 99% of the time during quiet standing. The area where the CoP is found during the remaining 1% of the time is called the low preference zone. The undesirable zone is defined as the CoP area where the subject is forced to change posture in order to maintain balance, and the unstable zone is defined as the CoP area in which the subject is forced to step forward, backward or sideways to maintain stability. A general model of the proposed four stability zones was derived, which can be used to compute stability zones a priori for any subject and thus allows one to assess the subject's stability condition from the CoP measurements.


Comparison of Resident, Advanced Practice Clinician, and Hospitalist Teams in an Academic Medical Center: Association With Clinical Outcomes and Resource Utilization.
Academic medical centers have expanded their inpatient medicine services with advanced practice clinicians (APCs) or nonteaching hospitalists in response to patient volumes, residency work hour restrictions, and recently, COVID-19. Reports of clinical outcomes, cost, and resource utilization differ among inpatient team structures. Directly compare outcomes among resident, APC, and solo hospitalist inpatient general medicine teams. Retrospective cohort study using multivariable analysis adjusted for time of admission, interhospital transfer, and comorbidities that compares clinical outcomes, cost, and resource utilization. Patients 18 years or older discharged from an inpatient medicine service between July 2015 and July 2018 (N = 12,716). Length of stay (LOS), 30-day readmission, inpatient mortality, normalized total direct cost, discharge time, and consultation utilization. Resident teams admitted fewer patients at night (32.0%; P < .001) than did APC (49.5%) and hospitalist (48.6%) teams. APCs received nearly 4% more outside transfer patients (P = .015). Hospitalists discharged patients 26 minutes earlier than did residents (mean hours after midnight [95% CI], 14.58 [14.44-14.72] vs 15.02 [14.97-15.08]). Adjusted consult utilization was 15% higher for APCs (adjusted mean consults per admission [95% CI], 1.00 [0.96-1.03]) and 8% higher for residents (0.93 [0.90-0.95]) than it was for hospitalists (0.85 [0.80-0.90]). No differences in LOS, readmission, mortality, or cost were observed between the teams. We observed similar costs, LOS, 30-day readmission, and mortality among hospitalist, APC, and resident teams. Our results suggest clinical outcomes are not significantly affected by team structure. The addition of APC or hospitalist teams represent safe and effective alternatives to traditional inpatient resident teams.


Foreign body removal using flexible bronchoscopy in terminal cancer: A case report.
Pulmonary foreign body aspiration is a serious medical problem. The risk of foreign body aspiration into the airways increases considerably in patients with end stage cancer with reduced consciousness and impaired airway reflexes. However, few studies have reported on foreign body aspiration in the airways in patients with terminal cancer or receiving end-of-life care. Herein, we report the use of flexible bronchoscopy in patients with end-of-life cancer with pulmonary aspiration. A 71-year-old man with neuroendocrine carcinoma was admitted to a palliative care unit for end-of-life care. He accidentally aspirated implant teeth into the airway with decreased consciousness and death rattle. On chest x-ray, the foreign material was observed in the left main bronchus. Despite concerns regarding the use of bronchoscopy given the deterioration of the overall organ function, flexible bronchoscopy was performed. Eventually, the foreign body was removed using a basket in the nasal cavity without major complications. The patient died comfortably after 7 days. The possibility of patients in the palliative care unit with reduced consciousness and death rattle to aspirate foreign bodies into the airways must be carefully considered. Flexible bronchoscopy should be considered to carefully remove aspirated foreign bodies in the airway without any side effects, even in patients with terminal cancer or receiving end-of-life care.


Lead contamination in food consumed and produced in Brazil: Systematic review and meta-analysis.
This systematic review (SR) evaluated evidence of lead (Pb) levels in foods consumed or produced in Brazil. Seventy-seven publications were included in this review, corresponding to a total of 8466 food samples that were grouped into 12 food categories with similar characteristics (infant food; sugar; beverages; meat and meat products; nuts, cocoa and products; fruits and fruit products; grains, cereals and products; milk and milk products; eggs; oil and fat spreads; vegetables and vegetable products and other foods). The random model was used to establish levels of Pb in food categories. We used the software R® to perform the meta-analysis. The overall occurrence of Pb was estimated at 0.0541 mg/kg, and ranged from 0.0004 mg/kg to 0.4842 mg/kg. The SR and meta-analysis presented relevant results about Pb contamination on foods, despite the high heterogeneity. They were understood as a viable strategy to answer questions regarding prevalence of Pb which is necessary for the risk assessment of Pb intake in foods.


Pregnancy duration and the ratio of long-chain n-3 fatty acids to arachidonic acid in erythrocytes from Faroese women.
Dietary long-chain n-3 fatty acids (FA) may prolong gestation by inhibiting formation of prostaglandins from arachidonic acid. FA were quantified in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and total lipids (TL) of red cells sampled during pregnancy from 29 Faroese women. The ratio of long-chain n-3 FA to arachidonic acid (the (3/6) ratio) was used as the most relevant single measure of exposure. In 18 women with certain gestational age and with spontaneous onset of delivery, gestational age was significantly associated with the (3/6) ratio quantified in PC (correlation coefficient 0.50, P = 0.035), but not with the (3/6) ratio in PE (correlation coefficient 0.21, P = 0.40) or TL (correlation coefficient 0.29, P = 0.26). The association with the (3/6) ratio in PC could not be attributed to confounding by maternal age, weight, marital status or smoking.


Membrane fusion in vesicles of oligomerizable lipids.
Membrane fusion has been examined in a model system of small unilamellar vesicles of synthetic lipids that can be oligomerized through the lipid headgroups. The oligomerization can be induced either in both bilayer leaflets or in the inner leaflet exclusively. Oligomerization leads to denser lipid headgroup packing, with concomitant reduction of lipid lateral diffusion and membrane permeability. As evidenced by lipid mixing assays, electron microscopy, and light scattering, calcium-induced fusion of the bilayer vesicles is strongly retarded and inhibited by oligomerization. Remarkably, oligomerization of only the inner leaflet of the bilayer is already sufficient to affect fusion. The efficiency of inhibition and retardation of fusion critically depend on the relative amount of oligomeric lipid present, on the concentration of calcium ions, and on temperature. Implications for the mechanism of bilayer membrane fusion are discussed in terms of lipid lateral diffusion and membrane curvature effects.


Risk factors of cerebrospinal fluid rhinorrhea following transsphenoidal surgery.
Cerebrospinal fluid (CSF) rhinorrhea is a potentially life-threatening complication following transsphenoidal surgery (TSS). To elucidate the risk factors that may affect the incidence of postoperative CSF rhinorrhea, we retrospectively reviewed 200 consecutive cases of TSS performed by a single surgeon for 168 adenomas and 32 other sellar and parasellar lesions. Intra-operative CSF leakage was encountered in 38 cases (19.0%). Its incidence did not correlate to tumor size. Among 4 microadenoma cases with CSF leak, 3 were ACTH adenomas. In contrast, postoperative CSF rhinorrhea was observed in 5 cases (2.5%), all following TSS for adenomas. It was frequently noted in cases with prior TSS (3/40, 7.5%, p = 0.0235) and prior radiotherapy (2/7, 28.6%, p < 0.0001). Two cases who required surgical intervention had received TSS and radiotherapy previously. The risk of postoperative CSF rhinorrhea is significantly increased in cases with prior TSS or radiotherapy or both. In addition, these cases tended to show delayed CSF leaks and require sellar reconstruction for its treatment. When a CSF leak was encountered during TSS in these high-risk cases, thorough sellar reconstruction and long-term follow-up is necessary.


Construction and evaluation of PAMAM-DOX conjugates with superior tumor recognition and intracellular acid-triggered drug release properties.
An ideal drug delivery system for cancer therapy should be equipped with extended circulation, improved tumor targeting and controlled drug release, as well as low toxicity from the carrier. In this study, a multifunctional drug delivery system based on the PEGylated poly(amidoamine) (PAMAM) dendrimer was designed, and folate-PEGylation was applied to modify the dendrimer in order to enhance tumor selectivity. A series of acid-labile PAMAM-DOX conjugates (FPP-hyd-DOX) with different FA ligand ratios were successfully constructed. (1)H NMR, FTIR, DLS and TEM were used to describe the physicochemical characterization of PAMAM-DOX conjugates. Both in vitro drug release assay and subcellular localization, the conjugates exhibited an obvious pH-triggered drug release. The FPP-hyd-DOX 16/1 displayed much lower IC50 value than that of non-targeted PP-hyd-DOX. Through fluorescence microscopy and flow cytometry investigations, the cellular uptake of FPP-hyd-DOX 16/1 was obviously enhanced, compared with that of PP-hyd-DOX. The cellular uptake mechanism and subcellular localization study revealed that the conjugates were internalized by KB cells via FA receptor and clathrin co-mediated endocytosis, delivered to acidic lysosomes and triggered the release of DOX into nuclei to exert its cytotoxicity. These obtained results showed that FPP-hyd-DOX conjugations would be a promising drug delivery carrier for targeted cancer therapy.


[Social support as a way of reforging links].
Refugees suffer from a lack of institutional and administrative continuity and experience a succession of separations. Compassionate and sustained links with a single institution, whatever ups and downs they encounter on their journey in Europe, can encourage integration and support the individual therapeutic work. The care can thereby become a factor in a more collective transmission within the population supported by the same institution.


Purine and pyrimidine transport and permeation in human erythrocytes.
Time courses of the uptake of radiolabeled hypoxanthine, adenine and uracil were measured by rapid kinetic techniques over substrate ranges from 0.02 to 5000 microM in suspensions of human erythrocytes at 25 or 30 degrees C. At concentrations above 25 microM, the rate of intracellular phosphoribosylation of hypoxanthine and adenine was insignificant relative to their rates of entry into the cell and time courses of transmembrane equilibration of the substrates could be measured and analyzed by integrated rate analysis. Hypoxanthine and uracil are transported by simple facilitated carriers with directional symmetry, high capacity and Michaelis-Menten constants of about 0.2 and 5 mM, respectively. Adenine is probably transported by a carrier with similar properties but no saturability was detectable up to a concentration of 5 mM. Cytosine entered the cells much more slowly than the other three nucleobases, and its entry seems not to be mediated by a carrier. The hypoxanthine transporter resembles that of one group of mammalian cell lines, which does not exhibit any overlap with the nucleoside transporter and is resistant to inhibitors of nucleoside transport. Results from studies on the effects of the nucleobases on the influx and countertransport of each other were complex and did not allow unequivocal conclusions as to the number of independent carriers involved. At concentrations below 5 microM, radiolabel from adenine and hypoxanthine accumulated intracellularly to higher than equilibrium levels. Part of this accumulation reflected metabolic trapping, especially when the medium contained 50 mM phosphate. But part was due to an apparent concentrative accumulation of free adenine and hypoxanthine up to 3-fold at medium concentrations much less than 1 microM and when cells were incubated in phosphate-free medium. This concentrative accumulation could be due to the functioning of additional high-affinity, low-capacity, active transport systems for adenine and hypoxanthine, but other factors could be responsible, such as saturable binding to intracellular components.


In search of social support in the NICU: features, benefits and antecedents of parents' tendency to share with others the premature birth of their baby.
To investigate social sharing among 40 parents (20 couples) of hospitalized premature newborns, the social network of addressees with whom they shared their experience, the perceived benefits of this activity and the sources of individual differences. Emotional reaction and attachment status were assessed within 7 days and between 30 and 45 days from birth, respectively. At 3 months of infant's corrected age, parents completed a self-report assessing retrospectively their social sharing. Over 80% of the parents felt the need to share the event and actually did within a week; one's own partner was the most preferred addressee. The extent of father's social sharing was mainly related to the newborn's medical risk, while mother's to her own emotional reaction. Guilt and anger were found to lengthen the latency of sharing in mothers and fathers, respectively. Secure attachment status, compared to insecure ones, was found to be the most effective in promoting social sharing. These findings help to understand why parents differ from each other in their use of social support in the NICU; from a practical standpoint, they highlight important factors which require attention when implementing intervention program in the NICU directed to parents of premature newborns.


Linkage to Care Following an HIV Diagnosis in Three Public Sector Clinics in eThekwini (Durban), South Africa: Findings from a Prospective Cohort Study.
Linkage to care following an HIV diagnosis remains an important HIV care continuum milestone, even in the era of universal ART eligibility. In an 8-month prospective cohort study among 459 (309 women, 150 men) newly-diagnosed HIV-positive individuals in three public-sector clinics in Durban metropolitan region, South Africa, from 2010 to 2013, median time to return to clinic for CD4+ results (linkage) was 10.71 weeks (95% CI 8.52-12.91), with 54.1% 3-month cumulative incidence of linkage. At study completion (9.23 months median follow-up), 26.2% had not linked. Holding more positive outcome-beliefs about enrolling in care was associated with more rapid linkage [adjusted hazard ratio (AHR)each additional belief 1.31; 95% CI 1.05-1.64] and lower odds of never linking [adjusted odds ratio (AOR) 0.50; 95% CI 0.33-0.75]. Holding positive ARV beliefs was strongly protective against never linking to care. Age over 30 years (AHR 1.59; 95% CI 1.29-1.97) and disclosing one's HIV-positive status within 30 days of diagnosis (AHR 1.52; 95% CI 1.10-2.10) were associated with higher linkage rates and lower odds of never linking. Gender was not associated with linkage and did not alter the effect of other predictors. Although expanded access to ART has reduced some linkage barriers, these findings demonstrate that people's beliefs and social relations also matter. In addition to structural interventions, consistent ART education and disclosure support, and targeting younger individuals for linkage are high priorities.


Wnt signaling in the niche.
There is much interest in understanding the signals in the bone marrow niche that keep hematopoietic stem cells (HSCs) in a quiescent state. In the current issue of Cell Stem Cell, Fleming et al. (2008) report that blocking Wnt signaling in the niche increases the number of proliferating HSCs and reduces their ability to reconstitute the hematopoietic system of irradiated recipient mice. These findings show that Wnt/beta-catenin activity is crucial for the maintenance of HSC quiescence in the bone marrow niche.


Determinants of prognosis in patients with oral squamous cell carcinoma metastasizing to a single cervical lymph node.
Metastasis in a single lymph node without adverse tumour factors and perineural invasion has been assigned to a lower risk category by the ASCO recommendations of 2019. We analyzed patients with a single positive node with a view to identifying high risk features and their impact on prognosis within this subgroup. The study retrospectively analyzed 707 patients with OSCC. Descriptive statistics were used to compare distribution of clinicopathologic risk features between 323 N0 and 121 single node positive (Ns) patients. The Ns group was further analyzed for the impact of clinicopathologic factors on disease free (DFS) and overall survival (OS) using univariate and multivariate models. The Ns group exhibited greater depth of invasion compared to the N0 group and significantly higher proportion of lymphovascular invasion (LVI), perineural invasion (PNI) and poorly differentiated tumors. Within the Ns group, primary tumor localised to the gingivobuccal subsite (HR 2.55, 1.18-5.52 95%CI, p = 0.02) and PNI (HR 2.55, 1.14-5.62, 95%CI p = 0.02) exhibited poor DFS. PNI also contributed to poor OS (HR 2.86, 1.27-6.47 95%CI, p = 0.01). Uninvolved margins (HR 0.46, 0.22-0.96 95%CI, p = 0.04) and chemoradiation (HR 0.18,0.05-0.68 95% CI, p = 0.01) improved OS. Significant differences are noted in the prevalence of pathologic risk factors between the single node positive and node negative groups. Within the single node positive group, tumour factors like the gingivobuccal subsite, PNI and margin positivity impacted survival. Among nodal factors, deposit size of 12 mm or more and presence of ENE are pointers to poor prognosis. These patients would benefit from adjuvant treatment.


Sleep in the chronic fatigue syndrome.
Chronic fatigue syndrome (CFS) is a disabling condition characterized by severe fatigue lasting for more than six months and the presence of at least four out of eight minor criteria. Sleep disturbance presenting as unrefreshing or nonrestorative sleep is one of these criteria and is very common in CFS patients. Biologically disturbed sleep is a known cause of fatigue and could play a role in the pathogenesis of CFS. However, the nature of presumed sleep impairment in CFS remains unclear. Whilst complaints of NRS persist over time, there is no demonstrable neurophysiological correlate to substantiate a basic deficit in sleep function in CFS. Polysomnographic findings have not shown to be significantly different between subjects with CFS and normal controls. Discrepancies between subjectively poor and objectively normal sleep suggest a role for psychosocial factors negatively affecting perception of sleep quality. Primary sleep disorders are often detected in patients who otherwise qualify for a CFS diagnosis. These disorders could contribute to the presence of daytime dysfunctioning. There is currently insufficient evidence to indicate that treatment of primary sleep disorders sufficiently improves the fatigue associated with CFS. Therefore, primary sleep disorders may be a comorbid rather than an exclusionary condition with respect to CFS.


Forebrain noradrenaline depletion blocks the release by chlordiazepoxide of behavioral extinction in the rat.
The interaction between chlordiazepoxide (CDP) and forebrain noradrenaline (NA) was investigated in rats with bilateral radiofrequency lesions of the noradrenergic dorsal tegmental bundle (DTB). Forebrain NA was reduced to 35% of control by the DTB lesions; hypothalamic NA and dopamine were unchanged. Rats were trained on a straight alley runway task for food reward. During extinction of the runway task, CDP significantly increased extinction responding in sham lesion animals but not in DTB lesion animals. Thus, CDP was ineffective in increasing resistance to extinction responding in the runway task in animals with significant depletion of forebrain NA.


Pediatric ECMO: unfavorable outcomes are associated with inflammation and endothelial activation.
Inflammatory and endothelial activation responses during extracorporeal membrane oxygenation (ECMO) support in children are poorly understood. In this study, we aimed to determine if circulating inflammatory, endothelial activation, and fibrinolytic markers are associated with mortality and with neurologic outcomes in children on ECMO. We conducted a secondary analysis of a two-center prospective observational study of 99 neonatal and pediatric ECMO patients. Inflammatory (interferon gamma [IFNγ], interleukin-6 [IL-6], IL-1β, tumor necrosis factor alpha [TNFα]), endothelial activation (E-selectin, P-selectin, intercellular adhesion molecule-3 [ICAM-3], thrombomodulin [TM]), and fibrinolytic markers (tissue plasminogen activator [tPA], plasminogen activator inhibitor-1 [PAI-1]) were measured in plasma on days 1, 2, 3, 5, 7, and every third day thereafter during the ECMO course. All ECMO day 1 inflammatory biomarkers were significantly elevated in children with abnormal vs. normal neuroimaging. ECMO day 1 and peak levels of IL-6 and PAI-1 were significantly elevated in children who died compared to those who survived to hospital discharge. Tested biomarkers showed no significant association with long-term neurobehavioral outcomes measured using the Vineland Adaptive Behavioral Scales, Second Edition. High levels of circulating inflammatory, endothelial activation, and fibrinolytic markers are associated with mortality and abnormal neuroimaging in children on ECMO. The inflammatory, endothelial activation, and fibrinolytic profile of children on ECMO differs by primary indication for extracorporeal support. Proinflammatory biomarkers on ECMO day 1 are associated with abnormal neurologic imaging in children on ECMO in univariable but not multivariable models. In multivariable models, a pronounced proinflammatory and prothrombotic biomarker profile on ECMO day 1 and longitudinally was significantly associated with mortality. Further studies are needed to identify inflammatory, endothelial, and fibrinolytic profiles associated with increased risk for neurologic injury and mortality through potential mediation of bleeding and thrombosis.


The geriatric patient and general hospital psychiatry.
The geriatric population in the United States is large and growing. General hospital psychiatrists need to be especially knowledgeable about the issues presented by elderly patients because of their high proportion on medical and surgical services. The special problems involved in treating such patients on inpatient psychiatric units are also discussed.


Long-Term Outcomes of Coronary Stenting With and Without Use of Intravascular Ultrasound.
This study sought to explore if intravascular ultrasound (IVUS) use in real-world patients is associated with improved long-term outcomes of percutaneous coronary intervention (PCI). The benefit of IVUS use with PCI in real world is uncertain. We identified Medicare patients who underwent PCI from 2009 to 2017 and evaluated the association of IVUS use with long-term risk of mortality, myocardial infarction (MI), and repeat revascularization. We used propensity score matching and inverse probability weighting to adjust for baseline characteristics. To account for hospital effects, patients undergoing IVUS-guided PCI were matched to non-IVUS patients in the same hospital and year. Sensitivity analyses comparing outcomes with and without IVUS in stable coronary artery disease and acute coronary syndrome, PCI with bare-metal stents and drug-eluting stents, complex and noncomplex PCI, and facilities with 1% to 5%, 5% to 10%, and >10% IVUS use were performed. Overall, IVUS was used in 5.6% of all PCI patients (105,787 out of 1,877,177 patients). Patients with IVUS-guided PCI had a higher prevalence of most comorbidities. In the propensity matched analysis, IVUS-guided PCI was associated with lower 1-year mortality (11.5% vs. 12.3%), MI (4.9% vs. 5.2%), and repeat revascularization (6.1% vs. 6.7%) (p < 0.001 for all). In inverse probability weighting analysis with a median follow-up of 3.7 years (interquartile range: 1.7 to 6.4 years), IVUS-guided PCI was associated with a lower risk of mortality (adjusted hazard ratio [aHR]: 0.903; 95% confidence interval [CI]: 0.885 to 0.922), MI (aHR: 0.899; 95% CI: 0.893 to 0.904), and repeat revascularization (aHR: 0.893; 95% CI: 0.887 to 0.898) (p < 0.001 for all). These findings were consistent in all subgroups in sensitivity analyses. In this contemporary U.S. Medicare cohort, the use of IVUS guidance in PCI remains low. Use of IVUS is associated with lower long-term mortality, MI, and repeat revascularization.


Training cardiovascular specialists in imaging: a curriculum based on fundamental concepts required for multimodal imaging.
Training cardiovascular (CV) imaging specialists is becoming increasingly complex owing to rapidly emerging technological advances and the growing recognition that single modality training is inefficient and results in suboptimal education and practice. The purpose of this document was to propose a multimodality CV imaging curriculum to improve training of future CV imaging specialists. Relevant national standards relating to aiming training, competence, and quality were reviewed, including current training recommendations from the American College of Cardiology and requirements from the Accreditation Council for Graduate Medical Education. Experts from all imaging modalities identified areas of commonality that could create efficiencies in training. Finally, the proposed curriculum was placed within the context of a standard 3-year fellowship training program with optional advanced imaging training. Multimodality imaging training can be accomplished efficiently and effectively for most trainees by introducing a curriculum of imaging didactic content broadly based on understanding basic cardiovascular anatomy and physiology, principles of performing quality CV imaging, and imaging in the broader health care environment. A curriculum and training program are proposed that satisfy level 2 training in 2 to 3 modalities and level 3 training in 1 modality in a traditional 3-year fellowship. Training cardiovascular specialists to be competent in multimodality imaging is possible based on the proposed curriculum and training program within a traditional 3-year cardiovascular fellowship. Imaging specialists may require additional training.


Serine metabolism during differentiation of human iPSC-derived astrocytes.
Astrocytes are essential players in development and functions, being particularly relevant as regulators of brain energy metabolism, ionic homeostasis and synaptic transmission. They are also the major source of l-serine in the brain, which is synthesized from the glycolytic intermediate 3-phosphoglycerate through the phosphorylated pathway. l-Serine is the precursor of the two main co-agonists of the N-methyl-d-aspartate receptor, glycine and d-serine. Strikingly, dysfunctions in both l- and d-serine metabolism are associated with neurological and psychiatric disorders. Here, we exploited a differentiation protocol, based on the generation of human mature astrocytes from neural stem cells, and investigated the modification of the proteomic and metabolomic profile during the differentiation process. We show that differentiated astrocytes are more similar to mature rather than to reactive ones, and that axogenesis and pyrimidine metabolism increase up to 30 days along with the folate cycle and sphingolipid metabolism. Consistent with the proliferation and cellular maturation processes that are taking place, also the intracellular levels of l-serine, glycine, threonine, l- and d-aspartate (which level is unexpectedly higher than that of d-serine) show the same biosynthetic time course. A significant utilization of l-serine from the medium is apparent while glycine is first consumed and then released with a peak at 30 days, parallel to its intracellular level. These results underline how metabolism changes during astrocyte differentiation, highlight that d-serine synthesis is restricted in differentiated astrocytes and provide a valuable model for developing potential novel therapeutic approaches to address brain diseases, especially the ones related to serine metabolism alterations.


The operating room case-mix problem under uncertainty and nurses capacity constraints.
Surgery is one of the key functions in hospitals; it generates significant revenue and admissions to hospitals. In this paper we address the decision of choosing a case-mix for a surgery department. The objective of this study is to generate an optimal case-mix plan of surgery patients with uncertain surgery operations, which includes uncertainty in surgery durations, length of stay, surgery demand and the availability of nurses. In order to obtain an optimal case-mix plan, a stochastic optimization model is proposed and the sample average approximation method is applied. The proposed model is used to determine the number of surgery cases to be weekly served, the amount of operating rooms' time dedicated to each specialty and the number of ward beds dedicated to each specialty. The optimal case-mix selection criterion is based upon a weighted score taking into account both the waiting list and the historical demand of each patient category. The score aims to maximizing the service level of the operating rooms by increasing the total number of surgery cases that could be served. A computational experiment is presented to demonstrate the performance of the proposed method. The results show that the stochastic model solution outperforms the expected value problem solution. Additional analysis is conducted to study the effect of varying the number of ORs and nurses capacity on the overall ORs' performance.


Aneurysm and pseudoaneurysm of the left ventricle.
The severity of myocardial infarction lies in its complications. Certainly, there was a significant decrease in their impact thanks to the improvement of medical care and advent of early reperfusion methods, but there is still a considerable rate of complications that pose diagnostic and therapeutic problems. Among them, there are left ventricular aneurysm and pseudoaneurysm. These two complications are relatively rare, their diagnosis and treatment are often difficult. We have attempted to review the existing literature and discuss the characteristic findings of each entity.


An invasive beetle-fungus complex is maintained by fungal nutritional-compensation mediated by bacterial volatiles.
Mutualisms between symbiotic microbes and animals have been well documented, and nutritional relationships provide the foundation for maintaining beneficial associations. The well-studied mutualism between bark beetles and their fungi has become a classic model system in the study of symbioses. Despite the nutritional competition between bark beetles and beneficial fungi in the same niche due to poor nutritional feeding substrates, bark beetles still maintain mutualistic associations with beneficial fungi over time. The mechanism behind this phenomenon, however, remains largely unknown. Here, we demonstrated the bark beetle Dendroctonus valens LeConte relies on the symbiotic bacterial volatile ammonia, as a nitrogen source, to regulate carbohydrate metabolism of its mutualistic fungus Leptographium procerum to alleviate nutritional competition, thereby maintaining the stability of the bark beetle-fungus mutualism. Ammonia significantly reduces competition of L. procerum for carbon resources for D. valens larval growth and increases fungal growth. Using stable isotope analysis, we show the fungus breakdown of phloem starch into D-glucose by switching on amylase genes only in the presence of ammonia. Deletion of amylase genes interferes with the conversion of starch to glucose. The acceleration of carbohydrate consumption and the conversion of starch into glucose benefit this invasive beetle-fungus complex. The nutrient consumption-compensation strategy mediated by tripartite beetle-fungus-bacterium aids the maintenance of this invasive mutualism under limited nutritional conditions, exacerbating its invasiveness with this competitive nutritional edge.


Vascular trainee perceptions of diversity, equity, and inclusion within United States vascular surgery training programs.
Vascular surgery training programs face multiple pressures, including attracting and retaining trainees. Current knowledge of trainees' views with respect to diversity and equity in vascular training programs is limited. We sought to understand United States vascular surgery trainees' perceptions and expectations regarding diversity, equity, and inclusion (DEI). The Association of Program Directors in Vascular Surgery designed and administered the Annual Training Survey to specifically address DEI and administered it to all trainees (Integrated Residents/Fellows; n = 637) at 122 institutions in August 2020. Of the 637 vascular trainees, 227 (35%) responded. The respondents included 115 male and 62 female trainees, with 50 not disclosing or not answering the question. The majority of respondents (96.9%) believed their programs incorporated a diverse background of trainees. Of the trainees, 89.8% felt that the faculty were similarly comprised of a diverse background. The majority of respondents (63.6%) felt that their training program was both more diverse and focused on inclusion compared with other training programs at their institution. However, 20% of respondents had experienced discrimination. Seventy-three percent (n = 143) of trainees felt empowered to disagree or engage in a discussion should they observe a faculty member make a disparaging remark about a patient's background/race/gender, although 27% (n = 35) trainees expressed fear of retaliation as a reason to not engage. Trainees view their program director (82.6%), faculty mentor (60.9%), and Graduate Medical Education office (52.7%) as potential resources for support. Overall, 83.7% (n = 160) of trainees believe that their program has been open to discussion of race relations within the medical community. Trainees are committed to multifaceted diversity and inclusion. The perception of trainees regarding DEI issues within vascular surgery training programs appears to be positive; however, trainees did describe discrimination and gender biases in their institutions. This data has the potential to improve institutional education of faculty and trainees about the multidimensional levels of diversity and increased awareness and incorporation of this philosophy can assist in the recruitment of diverse vascular surgeons.


The SAFE-trial: Safe surgery for glioblastoma multiforme: Awake craniotomy versus surgery under general anesthesia. Study protocol for a multicenter prospective randomized controlled trial.
Surgery of GBM nowadays is usually performed under general anesthesia (GA) and resections are often not as aggressive as possible, due to the chance of seriously damaging the patient with a rather low life expectancy. A surgical technique optimizing resection of the tumor in eloquent areas but preventing neurological deficits is necessary to improve survival and quality of life in these patients. Awake craniotomy (AC) with the use of cortical and subcortical stimulation has been widely implemented for low-grade glioma resections (LGG), but not yet for GBM. AC has shown to increase resection percentage and preserve quality of life in LGG and could thus be of important value in GBM surgery. This study is a prospective, multicenter, randomized controlled trial (RCT). Consecutive patients with a glioblastoma in or near eloquent areas (Sawaya grading II/III) will be 1:1 randomized to awake craniotomy or craniotomy under general anesthesia. 246 patients will be included in neurosurgical centers in the Netherlands and Belgium. Primary end-points are: 1) Postoperative neurological morbidity and 2) Proportion of patients with gross-total resections. Secondary end-points are: 1) Health-related quality of life; 2) Progression-free survival (PFS); 3) Overall survival (OS) and 4) Frequency and severity of Serious Adverse Effects in each group. Also, a cost-benefit analysis will be performed. All patients will receive standard adjuvant treatment with concomitant chemoradiotherapy. This RCT should demonstrate whether AC is superior to craniotomy under GA on neurological morbidity, extent of resection and survival for glioblastoma resections in or near eloquent areas. Clinicaltrials.gov: NCT03861299 Netherlands Trial Register (NTR): NL7589.


Efficacy of vitamin D in treating multiple sclerosis-like neuroinflammation depends on developmental stage.
The association of vitamin D deficiency with higher prevalence, relapse rate and progression of multiple sclerosis (MS) has stimulated great interest in using vitamin D supplementation as a preventative measure and even a therapy for established MS. However, there is a considerable lack of evidence when it comes to an age/developmental stage-dependent efficacy of vitamin D action and a time-window for the most effective prophylactic treatment remains unclear. We studied the effect of vitamin D supplementation in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), an animal model of MS, at three different developmental stages in rats. Supplementation treatment was initiated: i) prior to gestation and maintained throughout pre- and early postnatal development (gestation and lactation); ii) after weaning, throughout juvenile/adolescence period and iii) in adult age. We observed a marked attenuation of EAE in juvenile/adolescent rats reflected in a less severe CNS inflammation and demyelination, accompanied by a lower amount of IFN-γ producing MOG-specific T cells. Moreover, the cytokine expression pattern in these rats reflected a more anti-inflammatory phenotype of their peripheral immune response. However, the same supplementation regimen failed to improve the disease outcome both in adult rats and in rats treated during pre- and early post-natal development. Our data demonstrate a developmental stage-dependent efficiency of vitamin D to ameliorate neuroinflammation, suggesting that childhood and adolescence should be the target for the most effective preventive treatment.


[The influence of a controlled active motion splint on proprioception after anterior cruciate ligament plasty. A prospective randomized study].
A ruptured anterior cruciate ligament (ACL) leads to both mechanical and functional instability. Functional instability is caused by proprioceptive deficit. The aim of this study was to determine whether the proprioceptive deficit can be reduced by using a controlled active motion (CAM) splint postoperatively. A total of 50 patients with ACL rupture were randomized into two groups. After ACL plasty the PT group received postoperative physiotherapy, while the CAM group were managed with a CAM splint and physiotherapy. Proprioceptive ability was measured with a passive angle-reproduction test. On the day of discharge 80% of the patients in the CAM group and 25% in the PT group had a reduced proprioceptive deficit. Overall the main measured value in the CAM group improved by 83.7%, but deteriorated by 39.3% in the PT group. There was no significant difference between the CAM group and a healthy control group. Using a CAM splint in addition to physiotherapy after ACL plasty in comparison to physiotherapy alone decreases the proprioceptive deficit significantly. We recommend the use of a CAM splint in the postoperative management following ACL plasty.


Multimodal Assessments of Altered Sensation after Transoral Endoscopic Thyroidectomy.
Transoral endoscopic thyroidectomy, a novel technique, uses oral vestibule as the entry point and leaves no scar on the body surface. However, because the incisions are close to the mental nerve, nerve damage and the associated sensory impairment are concerning. Herein, we evaluated sensory alteration after transoral endoscopic thyroidectomy and determined factors associated with the prolonged sensory alteration. Patients who underwent transoral endoscopic thyroidectomy were enrolled. Sensation over the lower lip, chin, and neck was evaluated before and after the surgery. A self-assessment questionnaire, Semmes-Weinstein monofilament test, and two-point discrimination test were used to subjectively and objectively evaluate sensory changes. Fifty-one patients were enrolled; most of them reported altered sensation, with chin (72.5%) being the most common site, followed by lower lip (52.9%), upper neck (33.3%), and lower neck (5.9%) on postoperative day 2. The sensory disturbance resolved within 3 months. Factors associated with prolonged sensory alteration are male sex and old age. Fourteen patients (27.5%) experienced mild drooling from the mouth, which was usually self-limiting in 1 month. Sensory impairments in light touch pressure threshold and two-point discrimination were significant in the chin and neck on postoperative day 2 and at 1 week. The ability to discern two-point was also compromised in the lower lip on postoperative day 2. All these significant changes normalized to preoperative baseline at 1 month. There was an altered sensation after transoral endoscopic thyroidectomy with the most common and disturbed in the chin. Sensory impairment was usually transient and recovered in 3 months.


Comparison of cardiac stem cells and mesenchymal stem cells transplantation on the cardiac electrophysiology in rats with myocardial infarction.
Whether transplanted cardiac stem cells (CSCs) and mesenchymal stem cells (MSCs) improved ventricular fibrillation threshold (VFT) similarly is still unclear. We sought to compare the effects of the CSC and MSC transplantation on the electrophysiological characteristics and VFT in rats with myocardial infarction (MI). MI was induced in 30 male Sprague-Dawley rats. Two weeks later, animals were randomized to receive 5 × 10(6) CSCs labeled with PKH26 in PBS or 5 × 10(6) MSCs labeled with PKH26 in phosphate buffer solution(PBS) or PBS alone injection into the infarcted anterior ventricular free wall. Six weeks after the injection, electrophysiological characteristics and VFT were measured. Labeled CSCs and MSCs were observed in 5 μm cryostat sections from each heart. Malignant ventricular arrhythmias were significantly (P = 0.0055) less inducible in the CSC group than the MSC group. The VFTs were improved in the CSC group compared with the MSC group. Labeled CSCs and MSCs were identified in the infarct zone and infarct marginal zone. Labeled CSCs expressed Connexin-43, von Willebrand factor, α-smooth muscle actin and α-sarcomeric actin,while the Labeled MSCs expressed von Willebrand factor, α-smooth muscle actin and α-sarcomeric actin in vivo. After 6 weeks of cell transplantation, CSCs are superior to MSCs in modulating the electrophysiological abnormality and improving the VFT in rats with MI. CSCs and MSCs express markers that suggest muscle, endothelium and vascular smooth muscle phenotypes in vivo, but MSCs rarely express Connexin-43.


Thorium in the workplace: results from a European-based measurement comparison project.
A Series of comparisons were conducted to test the capabilities of a range of metrological techniques and analytical laboratories engaged in the assay of thorium in the workplace. The results of these exercises are presented together with the decision criteria used to determine whether results are significantly different from the true value. The discussion highlights those aspects which warrant closer and further attention.


Embryonic signature in breast cancers; Pluripotency roots of cancer stem cells.
Drug discovery programs for preclinical oncology typically select compounds which have a predilection for inducing cytotoxic effects in cancer cell lines and subsequently, for inhibiting the growth of the transplanted cancer cells in vivo (Winquist et al., 2010). Unfortunately, the cytotoxic effect in vitro and inhibition of tumor growth in animal models are not the end story for curing cancer in preclinical models. The reason behind that is the exciting of small sub type of cells that are relatively resistance to therapy and able to repopulate in vivo, called cancer stem cells (CSCs). O leis et al. recently reported that the pluripotency gene Sox2 but not Oct4 or Nanog is expressed in early stage of breast tumor. Furthermore, the authors demonstrated that Sox2 downregulation, inhibited mammosphere formation and delayed tumor formation in xenograft tumor initiation models (Leis et al., 2012). In this review, we will shed the light on the importance of Sox2 in breast and other tissue tumorigenesis and associated aggressiveness.


Driving forces linking microbial community structure and functions to enhanced carbon stability in biochar-amended soil.
Biochar induces various priming effects on native soil organic carbon (nSOC), whereas the underlying mechanisms linking these to soil microbial community structure and functions remain unclear. To investigate soil microbial community structure and functions associated with priming effects, rice straw (RS) and the derived biochar samples (RS400 and RS700, pyrolyzed at 400 °C and 700 °C, respectively) were applied to a sandy loam soil for a 33- and 200-day incubation. Using stable C isotopic ratios, CO2-C emissions from biochar/feedstock and nSOC were quantitatively identified and indicated an enhanced C stability of RS700 over that of RS and RS400. A decreased soil pH and increased dissolved organic carbon and NH4+-N concentrations with the RS amendment are driving forces that lead to an enhanced soil microbial activity and a higher abundance of heterotrophic microbes, especially Proteobacteria and Acidobacteria, which contribute to high CO2 emissions. The enhanced C stability of biochar and nSOC over that of pristine feedstock was primarily attributable to a stable and high soil pH, which minimized the disturbance of soil heterotrophic microbial community structure and functions, favoring the growth of Actinobacteria, Proteobacteria, and Ascomycota. The biochar amendment in soil enriched the metabolic pathways of biosynthesis and the decomposition of secondary metabolites, polycyclic aromatic hydrocarbons (PAHs) degradation, and electron transfer carriers.


Purification from Deinococcus radiodurans of a 66 kDa ABC transporter acting on peptides containing at least 3 amino acids.
Deinococcus radiodurans is a Gram positive bacterium the capability of which to withstand high doses of ionizing radiations is well known. Physiologically speaking, D. radiodurans is a proteolytic prokaryote able to express and secrete quite a number of proteases, and to use amino acids as an energy source. When considering this, it is surprising that little information is available on the biochemical components responsible for the uptake of peptides in D. radiodurans. Here we report on the purification and characterization of an ABC peptide transporter, isolated from D. radiodurans cells grown in tryptone-glucose-yeast extract (TGY) medium. In particular, we show here that the action of this transporter (denoted DR1571, SwissProt data bank accession number Q9RU24 UF71_DEIRA) is exerted on peptides containing at least 3 amino acids. Further, using tetra-peptides as model systems, we were able to observe that the DR1571 protein does not bind to peptides containing phenylalanine or valine, but associates with high efficiency to tetra-glycine, and with moderate affinity to tetra-peptides containing arginine or aspartate.


Stain intensity of human nucleolus organizer region reflects incorporation of uridine into mature ribosomal RNA.
The stain intensity of the nucleolus organizer regions (NORs) of acrocentric chromosomes was correlated positively with incorporation of [3H]uridine into 18S rRNA and 28S rRNA from cultured diploid human skin fibroblasts. An analysis of these data from twins by a path model indicated that no other common genetic or environmental parameters were required to explain the relationship between NOR scores and uptake of [3H]uridine into mature rRNA species.