Medical Emergency Triage and Treatment System (METTS): a new protocol in primary triage and secondary priority decision in emergency medicine.
In many Emergency Department (ED) triage scoring systems, vital signs are not included as an assessment parameter. To evaluate the validity of a new protocol for Emergency Medicine in a large cohort of patients referred to in-hospital care. From January 1 to June 30, 2006, 22,934 patients were admitted to the ED at Sahlgrenska University Hospital. Of those, 8695 were referred to in-hospital care and included in the study. A new five-level triage tool, combining vital signs, symptoms, and signs in the triage decision, was used. A small control of the inter-rater disagreement was also performed in 132 parallel, single-blinded observations. Fifty percent of the patients were admitted by ambulance and the other 50% by walk-in. Hospital stay was significantly (p < 0.001) longer in those admitted by ambulance (9.3 ± 14 days) as compared with walk-in patients (6.2 ± 10 days). In-hospital mortality incidence was higher (8.1%) in patients admitted by ambulance, as compared with walk-in patients (2.4%). Hospital stay and in-hospital mortality increased with higher level of priority. In the highest priority groups, 32-53% of the patients were downgraded to a lower priority level after primary treatment. In the present study, the METTS protocol was shown to be a reliable triage method and a sensitive tool for secondary re-evaluation of the patient in the ED.


A serological test for leprosy based on competitive inhibition of monoclonal antibody binding to the MY2a determinant of Mycobacterium leprae.
A novel serological assay for leprosy has been devised on the basis of serum inhibition of binding of 125I-labelled ML04 monoclonal antibody to Mycobacterium leprae sonicate-coated microtitre plates. Antibodies were detected in 93% of lepromatous leprosy patients, whereas controls from the endemic area, including leprosy contacts and patients with tuberculosis, were serologically negative. The specificity and efficacy of the test may offer an advantage over previously used techniques.


Further experimental results on modelling and algebraic control of a delayed looped heating-cooling process under uncertainties.
The aim of this research is to revise and substantially extend experimental modelling and control of a looped heating-cooling laboratory process with long input-output and internal delays under uncertainties. This research follows and extends the authors' recent results. As several significant improvements regarding robust modelling and control have been reached, the obtained results are provided with a link and comparison to the previous findings. First, an infinite-dimensional model based on mathematical-physical heat and mass transfer principles is developed. All important heat-fluid transport and control-signal delays are considered when assembling the model structure and relations of quantities. Model parameter values optimization based on the measurement data follows. When determining static model parameter values, all variations in steady-state measured data are taken into account simultaneously, which enhances previously obtained models. Values of dynamic model parameters and delays are further obtained by least mean square optimization. This innovative model is compared to two recently developed process models and to the best-fit model that ignores the measured variations. Controller structures are designed using algebraic tools for all four models. The designed controllers are robust in the sense of robust stability and performance. Both concepts are rigorously assessed, and the obtained conditions serve for controller parameter tuning. Two different control systems are assumed: the standard closed-loop feedback loop and the two-feedback-controllers control system. Numerous experimental measurements for nominal conditions and selected perturbations are performed. Obtained results are further analyzed via several criteria on manipulated input and controlled temperature. The designed controllers are compared to the Smith predictor structure that is well-established for time-delay systems control. An essential drawback of the predictor regarding disturbance rejection is highlighted.


Priapism in children: an experience of the modified Winter procedure.
Priapism in children is a rare disease, which seldom presents during the pediatric surgery practice. It is, however, a surgical and urological emergency. Early diagnosis and prompt management can prevent the devastating sequelae of this potentially fatal condition. A prospective study was conducted between March 1st, 2007 and February 28th, 2019 at the Department of Pediatric Surgery, Khyber Teaching hospital, Peshawar. All the patients between 3 and 15 years of age, with the diagnosis of priapism, were enrolled in the study with ethical approval. A total of ten patients were enrolled in the study period from March 1st, 2007 to February 28th, 2019. The age ranged between 3 and 15 years and the mean age of presentation was 8 years. The mean duration of symptoms was 4 h. The mean hospital stay was 4 days. The modified Winter procedure by creating a corporoglanular shunt was performed in all cases. Successful detumescence was achieved in eight patients, while two patients needed further detumescence and manual evacuation. Symptomatic relief was achieved in all the children. Priparism in children is a rare urological emergency that can lead to permanent erectile dysfunction if prompt medical intervention is not done. The modified Winter procedure technically is a less invasive procedure to achieve satisfactory clinical outcome in terms of achieving good erectile functions.


Advantages of milling versus broaching the proximal femur.
Femoral canal preparation in cementless total hip arthroplasty requires either broaching or milling of the proximal femur to create an osseous envelope for component implantation. The purpose of this article is to discuss the merits of milling the proximal femur for implant placement in primary or revision total hip arthroplasty.


RNA-mediated virus resistance.
Post-transcriptional gene silencing is an RNA degradation mechanism that can be induced by viruses. Recent evidence indicates that silencing may also be involved in virus synergism, tissue limitation of virus spread, non-host resistance, virus transmission through seeds and in more general mechanisms of defense such as that mediated by salicylic acid. The analysis of Arabidopsis mutants, and of viruses carrying silencing suppressors, has led to a greater understanding of post-transcriptional gene silencing pathways. Much still remains to be discovered, however, not least to allow the successful exploitation of gene silencing in conferring pathogen resistance to transgenic plants.


Transient Versus Two-Dimensional Shear-Wave Elastography in a Multistep Strategy to Detect Advanced Fibrosis in NAFLD.
The combination of laboratory and elastography tests allows the accurate diagnosis of advanced liver fibrosis in patients with NAFLD. In this study, we compared the diagnostic performances of a two-step strategy (laboratory tests and vibration-controlled transient elastography [VCTE] or two-dimensional shear-wave elastography with SuperSonic Imagine [2D-SWE-SSI]) and the added value of a three-step strategy (laboratory tests and two elastography methods). From a prospective registry, we retrospectively selected 577 consecutive patients with suspicion of NAFLD who underwent laboratory tests to calculate the Fibrosis-4 (FIB-4) score, liver stiffness evaluation by VCTE (M and XL probes) and 2D-SWE-SSI, and liver biopsy. The diagnostic performances and need for liver biopsy in unclassified patients for the diagnosis of advanced fibrosis (F ≥ 3) in multistep strategies were compared. The area under the curve of FIB-4, VCTE, and 2D-SWE-SSI was 0.74, 0.82, and 0.88, respectively. Using the same thresholds, the FIB-4/2D-SWE-SSI and FIB-4/VCTE diagnostic performances were comparable (sensitivity, 71.4% and 66%; specificity, 91.4% and 91.5%; and accuracy, 83.7% and 81.4%; all P = not significant). Conversely, more patients required liver biopsy after 2D-SWE-SSI (24.6% versus 15.3%, P < 0.001). Performing a second elastography technique in patients with unreliable or gray zone (between 8 and 10 kPa) results greatly decreased the need for liver biopsy (42/577, 7.3%). The diagnostic performances (accuracy, sensitivity, and specificity) of FIB-4/2D-SWE-SSI/VCTE and FIB-4/VCTE/2D-SWE-SSI were comparable (81.1%, 71.5%, and 87.9% versus 81.3%, 69.7%, and 89.5%, respectively; all P = not significant). Using the same cutoff values, 2D-SWE-SSI is as accurate as VCTE for advanced liver fibrosis diagnosis in NAFLD. The three-step strategy in selected patients strongly decreased the need for liver biopsy while maintaining excellent accuracy.


Tubular network formation by adriamycin-resistant MCF-7 breast cancer cells is closely linked to MMP-9 and VEGFR-2/VEGFR-3 over-expressions.
We have previously demonstrated that matrix metalloproteinase-9 (MMP-9) is critical for breast cancer cell migration and is necessary but not sufficient for tubular network formation. Given the important angiogenic activity of vascular endothelial growth factor (VEGF), we investigate here its possible contribution in tubular network formation and its link with MMP-9. Exposure of resistant epithelial breast cancer cells (rMCF-7) to Avastin, a VEGF neutralising antibody, suppresses tubular network formation but not cell migration. However, their exposure to MMP-9 inhibitor markedly decreases both parameters. Besides, the addition of exogenous VEGF or MMP-9 alone or in combination to sensitive parental cells (sMCF-7) or rMCF-7 cells enhances tubular network formation by rMCF-7 cells but not by sMCF-7 cells. The evaluation of the expression levels of VEGF receptor (VEGFR) subtypes shows that sMCF-7 cells express only small quantities of VEGFR-2 and VEGFR-3 compared with rMCF-7 cells that express strong quantities. However, treatment of sMCF-7 cells by phorbol 12-myristate 13-acetate (PMA), a PKC activator, induces both tubular network formation and VEGFR-2/VEGFR-3 over-expressions. Interestingly, exposure of rMCF-7 cells or PMA-treated sMCF-7 cells to the specific inhibitors of VEGFR-2 and VEGFR-3 reduces markedly the tubular network formation. Together, our results demonstrate that the proteolytic enzyme MMP-9 promotes rMCF-7 cell migration and, consequently, tubular network formation through VEGFR-2/ VEGFR-3 activation. Understanding of mechanisms involved in vasculogenic mimicry and cell migration related to MMP-9 and VEGF may open new opportunities to improve cancer therapy.


Retention of chromosome arm 5q in stage II colon cancers identifies 83% of liver metastasis occurrences.
The decision to use chemotherapy in the treatment of colon cancer patients depends on the risk of developing metastases, as estimated by clinicopathological staging combining body imaging and pathological findings. The aim of this study was to identify all chromosome arms that, when allelotyped, correlate with the metastatic process, add prognostic information to pathology, and are of relevance for predicting metachronous metastases. A 5-year follow-up survey enrolled 401 MSS (microsatellite stable) colon cancer patients who were divided into three groups. Staging was performed with and without imaging data (called tumor and patient staging, respectively). The first 192 patients were used to construct a model prognosticating metastases. The subsequent 146 patients were used to validate this model. The third group evaluated its consistency by comparing the status of the relevant chromosome arms in 63 liver metastases and primary tumors that did or did not metastasize. The first group identified three factors: tumor staging (P < 0.0001), 5q status (P = 0.003), and gender (P = 0.02). The second group confirmed 5q as a marker of metastasis occurrence (P = 0.004). Merged data predicted that, when both 5q arms are retained, metastatic risk increases 4.3-fold in stage II patients. The third group corroborated these findings, with a 5q retention rate in metastases comparable to that of primary tumors that metastasize, but significantly higher than that observed in nonmetastatic tumors (one-tail, P = 0.0005). Long arm of chromosome 5 allelotyping detects high-risk stage II tumors. This simple, easily implemented, and inexpensive test increases the power of randomized studies that evaluate chemotherapy.


Differential clot stabilising effects of rFVIIa and rFXIII-A2 in whole blood from thrombocytopenic patients and healthy volunteers.
The haemostatic effect of recombinant activated factor VII (rFVIIa;NovoSeven) in thrombocytopenic patients has been a matter of controversy. Haemostasis by rFVIIa occurs via FVIIa-mediated thrombin generation in a platelet-dependent manner and may therefore be suboptimal in patients without functional platelets. Under such conditions, a clot-stabilizing agent, such as factor XIII (FXIII), may supplement the effect ofrFVIIa and improve haemostasis. Recombinant factor XIII (rFXIII-A2) is produced as an A2 homodimer of the FXIII A subunit and is equivalent to cellular FXIII normally found in platelets. The combined effects of rFVIIa andrFXIII-A2 were evaluated in clot lysis assays using factor XIII-deficient plasma and by whole blood thrombelastography (TEG) analysis from normal donors and thrombocytopenic stem cell transplantation patients. Clotting time was shortened by rFVIIa (0.6-10 microg/ml). rFVIIa only modestly improved anti-fibrinolysis,whereas rFXIII-A2 (0-20 microg/ml) enhanced anti-fibrinolysis without effect on clotting time. TEG analysis showed rFVIIa shortened the clotting time, and enhanced clot development, maximal mechanical strength and resistance to fibrinolysis, whereas, rFXIII-A2 enhanced clot development,maximal mechanical strength and markedly enhanced resistance to fibrinolysis. These data illustrate that rFVIIa and rFXIII-A2 contribute to clot formation and stability by different mechanisms suggesting enhanced haemostatic efficacy by combining these agents.


Gender differences in activity of daily living of the elderly in rural China: evidence from Chaohu.
Using data from a sample survey, Well-being of the elderly in Anhui province, China, this paper studies the effects of health, economic and family factors on the activities of daily living (ADLs) as measures of disability for elderly men and women. The objective is to explore reasons for gender differences in ADLs in rural China. Our results suggest that higher incidence rates of chronic diseases, lower cognitive ability, as well as heavier household and daily care burdens of females, are the main factors leading to a higher prevalence of ADL disability for the female elderly.


Abscess of allantoic duct remnant.
A recently submitted placenta was found to be histopathologically unique. Funicitis was present at the early gestational age of 22 1/7 weeks, and an abscessed allantoic duct remnant was present. The latter finding had not previously been seen at this pathology department, nor could reference to it be found in the literature.


Maternity waiting homes in Liberia: Results of a countrywide multi-sector scale-up.
Descriptions of maternity waiting homes (MWHs) as an intervention to increase facility delivery for women living in remote geographic areas dates back to the 1950s, yet there is limited information on the scale-up and sustainability of MWHs. The objective of this study was to describe the evolutionary scale-up of MWHs as a component of health system strengthening efforts and document the successes, challenges, and barriers to sustainability in Liberia. Data were collected from a national sample of 119 MWHs in Liberia established between 2010-2018. The study used a mixed method design that included focus group discussions, individual interviews, logbook reviews, and geographic information systems. Qualitative data were grouped into themes using Glaser's constant comparative method. Quantitative data were analyzed using negative binomial regression to measure the differences in the counts of monthly stays at facilities with different funding sources and presence of advisory committee. Additionally, each MWH was geo-located for purposes of geo-visualization. In the years since the original construction of five MWHs, an additional 114 MWHs were constructed in 14 of the 15 counties in Liberia. Monthly stays at facilities funded by community were 2·5 times those funded by NGOs (IRR, 2·46, 95% CI 1·33-4·54). Attributes of sustainability included strong local leadership/active community engagement and community ownership and governance. Success factors for scale-up and sustainability included strong government support through development of public policy, local and county leadership, early and sustained engagement with communities, and self-governance. A multi-pronged approach with strong community engagement is key to the scale-up and sustainability of MWHs as an intervention to increase facility delivery for women living the farthest from a healthcare facility.


Improving the Performance of Continuous-Variable Measurement-Device-Independent Quantum Key Distribution via a Noiseless Linear Amplifier.
In the continuous variable measurement-device-independent quantum key distribution (CV-MDI-QKD) protocol, both Alice and Bob send quantum states to an untrusted third party, Charlie, for detection through the quantum channel. In this paper, we mainly study the performance of the CV-MDI-QKD system using the noiseless linear amplifier (NLA). The NLA is added to the output of the detector at Charlie's side. The research results show that NLA can increase the communication distance and secret key rate of the CV-MDI-QKD protocol. Moreover, we find that the more powerful the improvement of the performance with the longer gain of NLA and the optimum gain is given under different conditions.


Accuracy and precision of cap thickness in small incision lenticule extraction.
To report and compare the cap thickness predictability of small incision lenticule extraction (SMILE) and flap thickness of femtosecond laser-assisted in situ keratomileusis (femto-LASIK). Beyoglu Eye Training and Research Hospital, Refractive Surgery Department, Istanbul, Turkey. Retrospective pilot study. Medical records of patients who had SMILE in one eye and femto-LASIK in the other eye were reviewed. Visante corneal Optical Coherence Tomography (OCT) images at 1 week and 1 month post-surgery were analyzed. Both cap and flap thickness at the temporal edge and the nasal edge were measured and compared to each other. STATISTICAL ANALYSES USED: PAWS Statistics 18 and unpaired student t-test were used to compare the groups. The study included 66 eyes of 33 patients (24.7 ± 3.8 years, 20 females and 13 males). Mean flap thickness was 114.88 μm ± 4.96 μm, and mean cap thickness was 114.63 μm ± 5.18 μm. In group 1 (SMILE), cap thickness values were 115.84 μm ± 6.84 μm, 114.75 μm ± 7.36 μm, 113.66 μm ± 6.88 μm, and 114.27 μm ± 6.90 μm in measurement zones 1, 2, 3, and 4, respectively. In group 2 (FemtoLASIK), flap corneal thickness values were 115.96 mmHg ± 7.01 mmHg, 114.72 mmHg ± 7.17 mmHg, 113.54 mmHg ± 6.45 mmHg, and 115.30 mmHg ± 6.64 mmHg in measurement zones 1, 2, 3, and 4, respectively. In both groups, no statistically significant change within the measurement zones was observed. The predictability of cap thickness in SMILE surgery does not differ from the femto-LASIK flaps created using the same femtosecond laser platform.


Efficient multitask learning with an embodied predictive model for door opening and entry with whole-body control.
Robots need robust models to effectively perform tasks that humans do on a daily basis. These models often require substantial developmental costs to maintain because they need to be adjusted and adapted over time. Deep reinforcement learning is a powerful approach for acquiring complex real-world models because there is no need for a human to design the model manually. Furthermore, a robot can establish new motions and optimal trajectories that may not have been considered by a human. However, the cost of learning is an issue because it requires a huge amount of trial and error in the real world. Here, we report a method for realizing complicated tasks in the real world with low design and teaching costs based on the principle of prediction error minimization. We devised a module integration method by introducing a mechanism that switches modules based on the prediction error of multiple modules. The robot generates appropriate motions according to the door's position, color, and pattern with a low teaching cost. We also show that by calculating the prediction error of each module in real time, it is possible to execute a sequence of tasks (opening door outward and passing through) by linking multiple modules and responding to sudden changes in the situation and operating procedures. The experimental results show that the method is effective at enabling a robot to operate autonomously in the real world in response to changes in the environment.


Strengthening scientific credibility against misinformation and disinformation: Where do we stand now?
Health behaviors related to COVID-19 prevention measures, especially vaccination, are used to exemplify mechanisms whereby misinformation and disinformation can spark an "infodemic": a situation in which false information can spread more rapidly and widely than its truthful, science-based counterpart. We define key terminologies and identify potential sources that led to the pandemic infodemic, and highlight the harmful implications of such events. Issues related to scientific communication, how the public perceives information, and factors influencing individuals' decision-making are also discussed. This is the first in a series of two perspective articles on this topic.


Frequent Emergency Department Visits and Hospitalizations Among Homeless People With Medicaid: Implications for Medicaid Expansion.
We examined factors associated with frequent hospitalizations and emergency department (ED) visits among Medicaid members who were homeless. We included 6494 Massachusetts Medicaid members who received services from a health care for the homeless program in 2010. We used negative binomial regression to examine variables associated with frequent utilization. Approximately one third of the study population had at least 1 hospitalization and two thirds had 1 or more ED visits. More than 70% of hospitalizations and ED visits were incurred by only 12% and 21% of these members, respectively. Homeless individuals with co-occurring mental illness and substance use disorders were at greatest risk for frequent hospitalizations and ED visits (e.g., incidence rate ratios [IRRs] = 2.9-13.8 for hospitalizations). Individuals living on the streets also had significantly higher utilization (IRR = 1.5). Despite having insurance coverage, homeless Medicaid members experienced frequent hospitalizations and ED visits. States could consider provisions under the Patient Protection and Affordable Care Act (e.g., Medicaid expansion and Health Homes) jointly with housing programs to meet the needs of homeless individuals, which may improve the quality and cost effectiveness of care.


Extramedullary hematopoiesis of the middle ear.
A 22-year-old man with sickle cell disease developed a conductive hearing loss as a result of extramedullary hematopoiesis in the right middle ear. This is the first reported case of conductive hearing loss from extramedullary hematopoiesis and only the second report of extramedullary hematopoiesis in the middle ear.


Functional assessment of rabbit alveolar macrophages following intermittent inhalation exposures to sulfuric acid mist.
Sulfuric acid (H2SO4) aerosols are common in both ambient and occupational environments. This study examined the numbers and selected in vitro functional properties of alveolar macrophages recovered from rabbits undergoing inhalation exposure to 0.5 mg/m3 submicrometer (0.3 micron) H2SO4 for 2 hr/day. Bronchoalveolar lavage was performed on Days 3, 7, and 14 during the exposure period (specifically, 24 hr after either 2, 6, or 13 exposures). Total cell numbers and macrophage counts were increased on Day 3, but returned to control levels by Day 7; no change in polymorphonuclear leukocytes was observed at any time point. Macrophage substrate attachment was not affected by exposures to H2SO4, but random mobility was severely depressed at Days 7 and 14. The numbers of phagocytically active macrophages and the level of such activity were increased on Day 3, but became depressed by Day 14. These results demonstrate significant alterations in important functional properties of alveolar macrophages due to short-term intermittent exposures to H2SO4 aerosols; these changes have implications for the ability of the lungs to maintain adequate defense against deposited viable and nonviable particles.


In vivo evaluation of skin of children with LC-OCT: An objective assessment.
Several non-invasive skin imaging methods have been developed in recent years. Line-field confocal optical coherence tomography (LC-OCT) is one of them, leading to the best compromise in terms of resolution and penetration depth. Skin biopsies are an essential technique in paediatric dermatology, but they are a major stressful event for the child and their parents. Current LC-OCT studies have not been dedicated to a paediatric population. If, however, LC-OCT proves to be helpful in children, it may help guide and decrease a certain number of skin biopsies. (1) To evaluate the feasibility of using LC-OCT in paediatric patients, and (2) to assess the maturation of skin structures in children over time with this method. In vivo LC-OCT images were collected on six specific body regions (forehead, forearm, chest, back, dorsum of the hand and palmar surface) and in six age groups (between the ages of 0 and 16 years). In all body areas and age groups assessed, 9 of 10 images were rated as good-to-excellent, the only exception were the images acquired on the palmar surface. LC-OCT allowed visualizing very well the skin structures up to a penetration of 500 μm. We observed that the body regions located on the upper extremities of the body (forearm, dorsum of the hand and palmar surface) showed both a maturation on their structure and differences in thickness with respect to the other regions evaluated. LC-OCT can easily be used for non-invasive imaging of children's skin and allows to document progressive skin changes in the different age groups. It may be a useful asset for imaging and diagnosing superficial skin disorders and as such reducing the number of invasive procedures while increasing the speed of diagnosis in the paediatric population.


Effects of prolonged retinal ganglion cell inactivity on superior colliculus glucose metabolism in the mature hooded rat.
Previous work utilizing the 2-deoxyglucose (2-DG) technique demonstrated that denervation, both direct (enucleation) or indirect (retinal receptor destruction, leaving ganglion cells intact), resulted in a depression followed by an increase in glucose metabolism in the superior colliculus (SC) of the mature hooded rat. Both enucleation and receptor loss result in (1) cessation of ganglion cell activity and (2) disruption of connections between visual system neurons. To examine the relative importance of these two factors to the metabolic depression-"recovery" sequence, retinal ganglion cells were silenced without denervation for periods ranging from 24 h to 2 months by means of repeated intraocular tetrodotoxin (TTX) injections. SC metabolic activity fell to levels comparable to those seen after enucleation or receptor damage, but no recovery was detected. A more sensitive within-animal comparison was carried out to detect any small shifts in metabolic activity which might have occurred during retinal blockade; after 1 or 2 months of monocular TTX treatment, either binocular enucleation or binocular TTX injections were performed 24 h before 2-DG, depriving both sides of the SC of retinal input. Metabolic activity was slightly higher in the SC that had received no retinal input for 1 or 2 months, indicating that physiological changes had occurred within the SC during the afferent blockade. A second group of rats was allowed to recover from the effects of long-term TTX for from 1 to 12 days and binocularly exposed to visual stimuli during 2-DG uptake to determine whether damage had resulted from the TTX injections and to assess the time course of the effects of retinal blockade on SC functional activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Confinement of molecular liquids: consequences on thermodynamic, static and dynamical properties of benzene and toluene.
We relate the dynamical behavior of molecular liquids confined in mesoscopic cylindrical pores to the thermodynamic properties, heat capacity and density and to the static structure by combining different experimental methods (H-NMR, calorimetry, elastic and inelastic neutron scattering, numerical simulations). The crystallization process is greatly reduced or avoided by confinement under standard cooling conditions, instead a glass transition temperature T(g) at the 1000s time scale can be observed. The pore averaged local structure of the confined liquid is not noticeably affected when "excluded-volume" corrections are carefully applied, but follows the density changes reflected by the Bragg peak intensities of the porous matrices. The pore size dependence of T(g) is dominated by two factors, surface interaction and finite-size effect. For the smallest pores ([Formula: see text], [Formula: see text] being the van der Waals radius of a molecule), one observes an increase of T(g) and a broadening of the transition region, related to the interaction with the surface that induces a slowing-down of the molecules close to the wall. This is confirmed by neutron scattering experiments and molecular-dynamics simulations at shorter time scales and higher temperatures, which indicate a remaining fraction of frozen molecules. For larger pore sizes, taking the decrease of density under confinement conditions into account, a decrease of T(g) is observed. This could be related to finite-size effects onto the putative cooperativity length that is often invoked to explain glass formation. However, no quantitative determination of this length (not to mention its T-dependence) can be extracted, since the interaction with the wall itself introduces an additional length that adds to the complexity of the problem.


brlA is necessary and sufficient to direct conidiophore development in Aspergillus nidulans.
The brlA gene of A. nidulans mediates the developmental switch from the indeterminate, apical growth pattern of vegetative cells to the budding growth pattern of conidiophores. brlA encodes a 432 amino acid polypeptide containing two directly repeated motifs resembling the Zn(II) coordination sites first recognized in Xenopus TFIIIA. Misscheduled expression of brlA in vegetative cells results in transcriptional activation of developmentally regulated genes, cessation of unidirectional hyphal growth, initiation of cellular transformations resembling those that occur during normal conidiophore development, and production of viable conidiospores. We propose that BRLA is a nucleic acid-binding protein whose expression in vegetative cells is sufficient to induce sporulation through its role in regulating expression of conidiation-specific genes.


Surface-based integration approach for fNIRS-fMRI reliability assessment.
Studies integrating functional near-infrared spectroscopy (fNIRS) with functional MRI (fMRI) employ heterogeneous methods in defining common regions of interest in which similarities are assessed. Therefore, spatial agreement and temporal correlation may not be reproducible across studies. In the present work, we address this issue by proposing a novel method for integration and analysis of fNIRS and fMRI over the cortical surface. Eighteen healthy volunteers (age mean±SD 30.55 ± 4.7, 7 males) performed a motor task during non-simultaneous fMRI and fNIRS acquisitions. First, fNIRS and fMRI data were integrated by projecting subject- and group-level source maps over the cortical surface mesh to define anatomically constrained functional ROIs (acfROI). Next, spatial agreement and temporal correlation were quantified as Dice Coefficient (DC) and Pearson's correlation coefficient between fNIRS-fMRI in the acfROIs. Subject-level results revealed moderate to substantial spatial agreement (DC range 0.43 - 0.64), confirmed at the group-level only for blood oxygenation level-dependent (BOLD) signal vs. HbO2 (0.44 - 0.69), while lack of agreement was found for BOLD vs. HbR in some instances (0.05 - 0.49). Subject-level temporal correlation was moderate to strong (0.79 - 0.85 for BOLD vs. HbO2 and -0.62 to -0.72 for BOLD vs. HbR), while an overall strong correlation was found for group-level results (0.95 - 0.98 for BOLD vs. HbO2 and -0.91 to -0.94 for BOLD vs. HbR). The proposed method directly compares fNIRS and fMRI by projecting individual source maps to the cortical surface. Our results indicate spatial and temporal correspondence between fNIRS and fMRI, and promotes the use of fNIRS when more ecological acquision settings are required, such as longitudinal monitoring of brain activity before and after rehabilitation.


Adherence to Cervical Cancer Screening Guidelines Among Women Aged 66-68 Years in a Large Community-Based Practice.
The 2012 national cervical cancer screening guidelines recommended cessation of screening after age 65 years in women with adequate prior screening. In this retrospective cohort study, adherence to these screening exit guidelines was examined. Women who turned age 66 years in 2012-2013 at Kaiser Permanente Southern California were followed through age 68 years for cervical cancer screening uptake. Adequacy of prior screening was assessed between age 56 and 65 years using electronic medical records. Guideline adherence was determined based on screening pattern between age 66 and 68 years. Patient- and physician-level correlates for guideline adherence were examined using multivariable logistic regression. Data collection and analyses were conducted in 2018. A total of 14,778 women were included; 24% did not have adequate prior screening by age 65 years. Among those without adequate prior screening, the proportion screened after age 65 years ranged from 71% (177 of 249) in those whose most recent test was abnormal to 3% (34 of 1,330) in those who did not have any testing in 10 years. Prior screening pattern was the only factor associated with screening after age 65 years. Of those with adequate prior screening, 10% (1,135 of 11,295) continued to receive screening after age 65 years. Frequent office visits and having a male primary care physician were associated with continuing screening after age 65 years. A considerable proportion of women did not have adequate prior screening by age 65 years. Of these, a large proportion did not receive screening after age 65 years, except those who had a recent abnormal screening result. Further research is needed to understand barriers for guideline adherence and rationales for clinical decision making.


[Suicide among the French National Police forces: Implication of life events and life trajectories].
Research indicates that suicide rates are high among members of law enforcement. Our objectives were: (1) to determine life events implicated in suicide mortality among French law enforcement; and (2) to describe the different life trajectories of police officers who deceased by suicide. All suicides of police officers which occurred during 2008 (n=49) were explored using the psychological autopsy method. Key informants were: a supervisor, a colleague and a member of the family or a close friend. Each of them were interviewed by trained psychologists using standardized questionnaires exploring: sociodemographic characteristics, life events, social integration and support, health service use, mental health with the Composite International Diagnostic Interview short form (CIDI-SF), occupational stress with the Spielberger Inventory, impulsiveness with the Barratt Impulsiveness Scale and aggressiveness with the Brown-Goodwin Lifetime Aggression Scale. Information was then summarized in a timetable life trajectory of all life areas. All cases were finally appraised by at least two experts in order to identify the determinants of the suicide and to determine psychiatric diagnoses. For each period of time, a burdensomeness score was determined, from 6 (no adversity) to 1 (adversities in each sphere of life). Of the 49 cases of suicide, two were excluded and 39 were investigated and appraised (response rate: 39/47=83%). Eighty-two percent of the suicide cases were men and the mean age at death was 35years. In more than half of the cases, police officers used their service weapon to commit suicide. All deceased police officers were suffering from mental health symptoms (primarily depression). Of them, two thirds had used healthcare for this distress. The main other cause of suicide was problems in the married life (70% of the cases). Four distinct types of life trajectories of adversities could be identified by a qualitative analysis. It is the first time such a study was performed in France, and results are concordant with those of the literature. This study showed that all deceased police officers were suffering from mental disorders and that there was not one single profile of life trajectory: screening and support of police officers in distress need to be prioritized. Moreover, results suggested that the availability of the service weapon during off-duty periods should be reconsidered. This study helped the Home ministry to elaborate and improve strategies to prevent suicide among police officers.


Exacerbation of epileptic seizures by carbamazepine: report of 10 cases.
Carbamazepine (CBZ) is an effective anticonvulsant agent. Current literature reports describe several cases of seizure exacerbation and/or EEG worsening due to CBZ with a high prevalence in children and adolescents; we report 10 new cases. Nine patients had epilepsy; one showed delayed psychomotor development and frequent EEG paroxysmal abnormalities. Four patients were on monotherapy, six on polytherapy. All but one had therapeutic CBZ plasma concentrations. Seizures increased in frequency in nine, and in eight patients new seizure types appeared, mostly absences. Cognitive functions/behaviour worsened in eight; EEG recordings showed slowing background activity and increased paroxysmal abnormalities, in six cases diffuse/generalized spike waves were seen and in two continuous spike wave discharges. The mean time of clinical EEG worsening was 1-2 days after introduction of CBZ at therapeutic doses. After CBZ withdrawal clinical EEG improvement was evident in a few days. The underlying pathogenetic mechanism is not yet understood. However, the pathophysiology of seizure exacerbation might be related to the interaction between age-related alterations in the balance of excitation and inhibition in the developing thalamocortical circuitry and the essential activity of CBZ that tends to induce interictal discharges.


Technological approaches to in-room CBCT imaging.
The use of Cone-Beam Computed Tomography (CBCT) in Image-Guided Radiation Therapy (IGRT) has become increasingly feasible and popular in recent years. Advances and developments in Flat-Panel Imager (FPI) technology and image reconstruction software allow for linac-mounted 3D CBCT imaging. Taking CBCT images on a daily/weekly basis, offers the possibility to guide the treatment beam according to tumour motion and to apply changes to the treatment plan if necessary. This however raises the issue of additional imaging dose and thus increases in secondary cancer risk. The performance characteristics of kV-CBCT and MV-CBCT solutions currently offered by Elekta, Siemens and Varian are compared in this paper in terms of additional imaging dose and image quality. The review also outlines applications of CBCT for IGRT and Adaptive Radiotherapy (ART). As CBCT is not the only in-room IGRT platform, helical MV-CT (Tomotherapy) and in-room CT designs are also presented.


An Enzyme-Free Sandwich Amperometry-Type Immunosensor Based on Au/Pt Nanoparticle-Functionalized Graphene for the Rapid Detection of Avian Influenza Virus H9 Subtype.
Avian influenza virus H9 subtype (AIV H9) has contributed to enormous economic losses. Effective diagnosis is key to controlling the spread of AIV H9. In this study, a nonenzymatic highly electrocatalytic material was prepared using chitosan (Chi)-modified graphene sheet (GS)-functionalized Au/Pt nanoparticles (GS-Chi-Au/Pt), followed by the construction of a novel enzyme-free sandwich electrochemical immunosensor for the detection of AIV H9 using GS-Chi-Au/Pt and graphene-chitosan (GS-Chi) nanocomposites as a nonenzymatic highly electrocatalytic material and a substrate material to immobilize capture antibodies (avian influenza virus H9-monoclonal antibody, AIV H9/MAb), respectively. GS, which has a large specific surface area and many accessible active sites, permitted multiple Au/Pt nanoparticles to be attached to its surface, resulting in substantially improved conductivity and catalytic ability. Au/Pt nanoparticles can provide modified active sites for avian influenza virus H9-polyclonal antibody (AIV H9/PAb) immobilization as signal labels. Upon establishing the electrocatalytic activity of Au/Pt nanoparticles on graphene towards hydrogen peroxide (H2O2) reduction for signal amplification and optimizing the experimental parameters, we developed an AIV H9 electrochemical immunosensor, which showed a wide linear range from 101.37 EID50 mL-1 to 106.37 EID50 mL-1 and a detection limit of 100.82 EID50 mL-1. This sandwich electrochemical immunosensor also exhibited high selectivity, reproducibility and stability.


Peer navigation for individuals with serious mental illness leaving jail: a pilot randomized trial study protocol.
Serious mental illness (SMI) is a prevalent public health problem affecting 25% of individuals in jail. Re-entry to the community following incarceration is a vulnerable time for justice-involved individuals with SMI. SMI requires prompt and ongoing access to mental health and other healthcare services. The study will (1) develop a Mentoring And Peer Support (MAPS) intervention for post-release mental health and other service connection among jailed individuals with SMI and (2) pilot test the MAPS intervention to determine its feasibility and acceptability. The primary outcomes will be to evaluate the feasibility and acceptability of the proposed recruitment methods and research design, of the intervention training methods, and of delivering the enhanced peer-navigator and control interventions. Study samples include focus groups (n=36), open trial (n=15), and a randomized pilot trial in a sample of 40 individuals with SMI re-entering the community after jail release. Secondary outcomes will include post-release enrollment in mental health, medical care, and substance use services. We will also evaluate reduction in psychiatric symptoms, improvements in functioning, adherence to psychiatric medications, fewer substance using days, fewer hospitalizations and suicide attempts, nights unstably housed, and time until rearrest. This pilot study will evaluate the feasibility and acceptability of a peer navigation intervention for individuals with serious mental illness leaving jails. The study will serve as a formative work for a larger randomized controlled trial assessing the effectiveness of peer navigator intervention for (include the primary outcome) in this population.


Preparation a Recombinant Form of Pneumolysin Protein from Streptococcus pneumoniae.
A recombinant form of pneumolysin from Streptococcus pneumoniae was obtained. By using Vector NTI Advance 11.0 bioinformatic analysis software, specific primers were designed in order to amplify the genome fragment of strain No. 3358 S. pneumoniae serotype 19F containing the nucleotide sequence encoding the full-length pneumolysin protein. A PCR product with a molecular weight corresponding to the nucleotide sequence of the S. pneumoniae genome fragment encoding the full-length pneumolysin was obtained. An expression system for recombinant pneumolysin in E. coli was constructed. Sequencing confirmed the identity of the inserted nucleotide sequence encoding the full-length recombinant pneumolysin synthesized in E. coli M15 strain. Purification of the recombinant protein was performed by affinity chromatography using Ni-Sepharose in 8 M urea buffer solution. Confirmation of the recombinant protein was performed by immunoblotting with monoclonal antibodies to pneumolysin.


Oxygen consumption rate of tumour cells as a function of their proliferative status.
The oxygen consumption rate (QO2) of EMT6/Ro-cells cultured as monolayers was investigated as a function of their proliferative status. The transition of these cells from the exponential to the plateau growth phase was associated with a continuous decrease in QO2 per single cell. This decrease can partially be attributed to a corresponding decline in cellular volume. In addition, the QO2 per cell volume was also reduced during the passage of the cells through the growth phase described. The results lead to the conclusion that a reduction in cellular volume and factors which are still unknown may contribute to the metabolic changes observed.


Detection of a new kappa-casein variant in cow's milk.
In German Simmental cattle a new kappa-casein variant was detected by isoelectric focusing, which cannot be distinguished from kappa-casein A by polyacrylamide and starch gel electrophoresis. It was named kappa-casein D. The frequencies of kappa-casein alleles were kappa-Cn A 0.75, kappa-Cn B 0.24, kappa-Cn D 0.01.


Cell sheet transplantation for heart tissue repair.
Cell transplantation is attracting considerable attention as the next-generation therapy for treatment of cardiovascular diseases. We have developed cell sheet engineering as a type of scaffold-less tissue engineering for application in myocardial tissue engineering and the repair of injured heart tissue by cell transplantation. Various types of cell sheet transplantation have improved cardiac function in animal models and clinical settings. Furthermore, cell-based tissue engineering with human induced pluripotent stem cell technology is about to create thick vascularized cardiac tissue for cardiac grafts and heart tissue models. In this review, we summarize the current cardiac cell therapies for treating heart failure with cell sheet technology and cell sheet-based tissue engineering.


A phase 1/2 of carfilzomib and melphalan conditioning for autologous stem cell transplantation for multiple myeloma (CARAMEL).
In this phase 1/2 study, carfilzomib was added to high-dose melphalan conditioning prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma that had been treated with ≤2 prior lines of therapy. Carfilzomib was escalated at doses of 27, 36, 45, and 56 mg/m2 on days -6, -5, -2, and -1 before ASCT in the phase 1 component of the study. In addition, all the patients received melphalan 100 mg/m2 on days -4 and -3. The primary endpoint of the phase 1 component was to identify the maximum tolerated dose, and the primary endpoint of the phase 2 component was the rates of complete response (≥CR) at 1 year after ASCT. The phase 1 dose escalation cohort included 14 patients, and 35 patients were included in the phase 2 cohort. The maximum tested dose was 56 mg/m2 (MTD). The median time from diagnosis to study enrollment was 5.8 (range 3.4-88.4) months, and 16% of patients had obtained a ≥CR prior to ASCT. The best response within 1 year after ASCT was a ≥ CR rate in 22% for the entire cohort, and 22% for patients treated at the MTD. The ≥VGPR rates improved from 41% before ASCT to 77% by 1 year after ASCT. One patient had a grade 3 renal adverse event, and renal function returned to baseline with supportive care. The rate of grade 3-4 cardiovascular toxicity was 16%. The addition of carfilzomib to melphalan conditioning was safe and resulted in deep responses after ASCT.


Adhesive properties of the arolium of a lantern-fly, Lycorma delicatula (Auchenorrhyncha, Fulgoridae).
The arolium in Lycorma delicatula is shaped as a truncated pyramid, tapering proximally. The base or the terminal area is corrugated, forming parasagittal wrinkles (period 1.5-5.0 microm), which are supported from inside by cuticular dendrites. Side faces of the arolium are made up of sclerotized dorsolateral plates. When claws slip on a smooth substrate and pronate, the dorsolateral plates diverge and expand the sticky terminal area. The real contact area with the glass plate was recognized by light reflection on its periphery. This area was measured and shown to be smaller when the leg was pressed perpendicularly to the substrate (0.02 mm(2)) than when it was sheared in a direction parallel to the substrate (0.05 mm(2)). Attachment forces were measured with the aid of dynamometric platforms during pulling of active insects from horizontal or vertical glass surfaces. Normal adhesive force (about 9-12 mN) was much less than friction force during sliding with velocity of 6-17 mm/s (50-100 mN); however, when expressed in tenacity per unit contact area the difference was less pronounced: 170 and 375-625 mN/mm(2), respectively. Sliding of the arolium during shear displacement was shown to be oscillatory in frame-by-frame video analysis. Relaxative oscillations consisted of periodical sticks-slips of the arolium along the glass surface.


A generalized smith predictor for unstable time-delay SISO systems.
In this work, a generalization of the Smith Predictor (SP) is proposed to control linear time-invariant (LTI) time-delay single-input single-output (SISO) systems. Similarly to the SP, the combination of any stabilizing output-feedback controller for the delay-free system with the proposed predictor leads to a stabilizing controller for the delayed system. Furthermore, the tracking performance and the steady-state disturbance rejection capabilities of the equivalent delay-free loop are preserved. In order to place this contribution in context, some modifications of the SP are revisited and recast under the same structure. The features of the proposed scheme are illustrated through simulations, showing a comparison with respect to the corresponding delay-free loop, which is here considered to be the ideal scenario. In order to emphasize the feasibility of this approach, a successful experimental implementation in a laboratory platform is also reported.


Predicting busulfan exposure in patients undergoing hematopoietic stem cell transplantation using machine learning techniques.
This study aimed to establish an optimal model to predict the busulfan (BU) area under the curve at steady state (AUCss) by using machine learning (ML). Seventy-nine adult patients (age ≥18 years) who received BU intravenously and underwent therapeutic drug monitoring from 2013 to 2021 at Fujian Medical University Union Hospital were enrolled in this retrospective study. The whole dataset was divided into a training group and test group at the ratio of 8:2. BU AUCss were considered as the target variable. Nine different ML algorithms and one population pharmacokinetic (pop PK) model were developed and validated, and their predictive performance was compared. All ML models were superior to the pop PK model (R2 = 0.751, MSE = 0.722, 14 and RMSE = 0.830) in model fitting and had better predictive accuracy. The ML model of BU AUCss established through support vector regression (SVR) and gradient boosted regression trees (GBRT) had the best predictive ability (R2 = 0.953 and 0.953, MSE = 0.323 and 0.326, and RMSE = 0.423 and 0.425). All the ML models can potentially be used to estimate BU AUCss with the aim of facilitating rational use of BU on the individualized level, especially models built by SVR and GBRT algorithms.


Cilostazol preserves CA1 hippocampus and enhances generation of immature neuroblasts in dentate gyrus after transient forebrain ischemia in rats.
In the present study, cerebral ischemia was induced by a 10 min transient bilateral common carotid artery occlusion in rats combined with arterial blood pressure lowering to 37-42 mm Hg during occlusion. When histologically evaluated at 7 and 28 days after the forebrain ischemia (DAI) by staining with cresyl violet and Fluoro-Jade, the hippocampal CA1 region was most prominently damaged. At 7 DAI, treatment with cilostazol (60 mg/kg/day, orally) significantly reduced the neuronal damage in the CA1 region. The number of surviving neurons, visualized by NeuN immunostaining, in the CA1 region significantly increased at 7 and 28 DAI in the cilostazol-treated groups. To elucidate whether cilostazol enhances hippocampal neurogenesis after ischemia, we planned a co-labeling study using 5-bromo-2'-deoxyuridine (BrdU), NeuN (a marker for mature neurons) and doublecortin (DCX) (a marker for immature migratory neuroblasts). Double immunofluorescence staining at 7 DAI showed that cilostazol significantly increased the immunoreactivities of both DCX and phosphorylated cAMP-response element-binding protein (CREB) in the dentate gyrus that was co-expressed with BrdU. These results suggest that cilostazol has dual beneficial effects preserving the CA1 hippocampal region and promoting the generation of immature migratory neuroblasts in the dentate gyrus by upregulation of CREB phosphorylation after transient forebrain ischemia.


A recent outbreak of rinderpest in East Africa.
Rinderpest was brought under control in Kenya in 1976 but in April 1986 an outbreak of the disease occurred in cattle in Western Kenya, five kilometres from the Kenya-Uganda border. This was the first confirmed field outbreak of the disease in Kenya after a lull of over 10 years. Clinical disease was confined to unvaccinated zebu calves aged six to eight months from which rinderpest virus was isolated. High titres of antibodies to rinderpest virus were demonstrated in sera collected from sheep and goats that were grazing together with the affected cattle herds; there was, however, no evidence of clinical disease in these small ruminants and wildlife species in the affected area. The disease outbreak was rapidly stamped out by quarantine and vaccination.


Comorbidity between DSM-IV alcohol and specific drug use disorders in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions.
To date, there have been no published data on 12-month comorbidity of DSM-IV alcohol and drug use disorders in the general U.S. population. The purposes of the present study were to examine the prevalence and comorbidity of alcohol and specific drug use disorders, and to identify sociodemographic and psychopathologic correlates and treatment seeking among three groups of respondents: (1) those with alcohol use disorders only; (2) those with drug use disorders only; (3) those with comorbid alcohol and drug use disorders. Information on 12-month alcohol and specific drug use disorders in the United States was derived from face-to-face interviews in the National Institute on Alcohol Abuse and Alcoholism's (NIAAA) 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC: n = 43,093). Prevalences were 7.35% for alcohol use disorders only, 0.90% for drug use disorder only and 1.10% for comorbid alcohol and drug use disorders. Sociodemographic and psychopathologic correlates of these three groups were quite different, with the drug use disorder and comorbid groups significantly more likely to be young, male, never married and of lower socioeconomic status than the alcohol use disorder only group. Associations between current alcohol use disorders and 25 specific drug use disorders were generally positive and statistically significant. The 12-month prevalence of treatment seeking significantly increased from 6.06% for those with an alcohol use disorder only to 15.63% for those with a drug use disorder only, and to 21.76% for those with comorbid alcohol and drug use disorders. This study provides detailed data on the homotypic comorbidity of alcohol use disorders and 25 different drug use disorders and confirms the high levels of association seen in previous studies based on lifetime measures. Implications of this study are discussed in terms of integrating alcohol and drug treatment services and refining prevention and intervention efforts.


Variation in surfperch diets between allopatry and sympatry: circumstantial evidence for competition.
Characteristics of the diet of black surfperch, Embiotoca jacksoni (Embiotocidae), were compared between islands where it occurs with and without a congener, the striped surfperch, Embiotoca lateralis. Several hypotheses were considered to explain observed dietary differences between allopatric and sympatric populations of black surfperch. Some differences could be readily attributed to interisland differences in the availability of prey items. Remaining dietary differences were examined in view of optimal foraging and competition hypotheses. Observations did not conform to predictions of optimal foraging theory, but did fit predictions regarding interspecific competition. There was a shift in the types and sizes of gammarid amphipods consumed between allpatric and sympatric populations of black surfperch. Gammarid amphipods are the most important prey taxon to both Embiotoca species, comprising more than 70% by number of all prey items in the diet. Further, allopatric E. jacksoni displayed patterns of selectivity for prey of various sizes that were qualitatively different from those displayed by black surfperch sympatric with E. lateralis. The prey size selectivity of allopatric black surfperch was qualitatively very similar to that found for E. lateralis. The differences in black surfperch diet that were not explained by differences in resource bases among islands were in the direction predicted by competition theory. The dietary breadth of E. jacksoni was also broader in allopatry than in sympatry. As a result of these dietary differences, there was an apparant divergence in prey use by co-occurring Embiotoca species.


Shinsplints.
Shinsplints is not a specific diagnosis; it is a general term encompassing several conditions that result in chronic leg pain. Some recent advances, particularly the use of bone scan, have improved the diagnosis of shinsplints. Physicians dealing with these problems should refer to specific anatomic and etiologic conditions rather than use the term shinsplints. This will not only improve communication but also permit more accurate direction of therapy.


The ethics of publishing in medical journals.
Ethics has been defined as the way we ought to behave. Medical publishing essentially exists to broadcast current and new medical knowledge to aid in the practice of medicine. In this review article we consider many of the aspects of medical publishing with regard to 'what we ought to do' and, equally, 'what we ought not to do' from the perspective of various ethical frameworks. Although ethics is not the law or a set of rules, nor a code of conduct, an ethical lens can be useful when developing good general guidelines for medical publishing.


Lipid profile and future risk of exudative age-related macular degeneration development: a nationwide cohort study from South Korea.
This nationwide population-based cohort study evaluated the association between lipid profiles and the future risk of exudative age-related macular degeneration (AMD) using authorized clinical data provided by the Korean National Health Insurance Service. A total of 6,129,616 subjects over 50 years of age who participated in the Korean National Health Screening Program in 2013 or 2014 were included. Data on risk factors, including age, sex, comorbidities, behavioral factors, and baseline lipid profiles, including total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels were collected. Patients were followed-up patients until December 2018, and incident cases of exudative AMD were identified using registered diagnostic codes. During an average follow-up period of 4.91 years, 18,803 patients were newly diagnosed with exudative AMD. Compared to the lowest HDL cholesterol quartile group, the highest HDL cholesterol quartile group had a greater risk of future exudative AMD development with a hazard ratio (95% confidence interval) of 1.13 (1.08-1.18) in the fully adjusted model. The highest TG quartile group had a lower risk of exudative AMD than the lowest TG quartile group, with a hazard ratio (95% confidence interval) of 0.84 (0.81-0.88). High HDL cholesterol and low TG levels were prospectively associated with exudative AMD incidence.


Gene therapy restores adipose tissue and metabolic health in a pre-clinical mouse model of lipodystrophy.
Congenital generalized lipodystrophy type 2 is a serious multisystem disorder with limited treatment options. It is caused by mutations affecting the BSCL2 gene, which encodes the protein seipin. Patients with congenital generalized lipodystrophy type 2 lack both metabolic and mechanical adipose tissue and develop severe metabolic complications including hepatic steatosis, lipoatrophic diabetes, and cardiovascular disease. Gene therapies are becoming viable treatments, helping to alleviate inherited and acquired human disorders. We aimed to determine whether gene therapy could offer an effective form of medical intervention for lipodystrophy. We examined whether systemic adeno-associated virus delivery of human BSCL2 could reverse metabolic disease in seipin knockout mice, where white adipose tissue is absent. We reveal that adeno-associated virus gene therapy targets adipose progenitor cells in vivo and substantially restores white adipose tissue development in adult seipin knockout mice. This resulted in both rapid and prolonged beneficial effects to metabolic health in this pre-clinical mouse model of congenital generalized lipodystrophy type 2. Hyperglycemia was normalized within 2 weeks post-treatment together with normalization of severe insulin resistance. We propose that gene therapy offers great potential as a therapeutic strategy to correct multiple metabolic complications in patients with congenital lipodystrophy.


Prevalence of oropharyngeal antibiotic-resistant flora among residents of aged care facilities: a pilot study.
Residents in 11 long-term care facilities, and presenting to a single tertiary hospital site, were sampled to estimate prevalence of oropharyngeal colonization with resistant Gram-negative bacteria. From 124 residents, only one isolate (0.8%; 95% confidence interval 0.0%, 4.4) was multi-resistant (an extended-spectrum β-lactamase producing Escherichia coli) indicating that different treatment recommendations for respiratory infections in this population may not be justified.


Combined lifestyle factors on mortality among the elder population: evidence from a Chinese cohort study.
Numerous studies have suggested that lifestyle-related factors are associated with mortality, however limited evidence is available for the Chinese elder population. The data of this study was obtained from the Chinese Longitudinal Health Survey (CLHLS) during 2008 - 2018, lifestyle-related factors including body mass index (BMI), smoking, drinking, consumption of vegetables and fruits, physical activity and sleep duration were included as dependent variables in the analysis. A lifestyle risk score was created using six unhealthy behaviors: smoking, drinking, unhealthy weight, physical inactivity, not eat vegetables or fruits and short or prolonged sleep. The Kaplan-Meier curves were used to illustrate the cumulative effect of lifestyle factors on mortality and cox regression models were conducted to estimate the combined effects of lifestyle-related factors on total mortality. The results illustrated that low BMI, smoking, no fruit eating, and no physical inactivity were risk factors for total mortality. KM curves showed significant cumulative effect of unhealthy lifestyle factors on mortality. Compared with participants without any unhealthy factors, the hazard ratio (HR) for participants with six unhealthy factors was 1.335 (1.015,1.757) for all-cause mortality. This study demonstrated poor adherence to a healthy lifestyle may increase all-cause mortality and specific combinations of lifestyle related factors have different effects on mortality among Chinese elderly population.


Two cases of untoward sequelae associated with thiopentone.
Two cases of adverse sequelae associated with the use of 2.5% thiopentone are reported: one involved extensive local venous thrombosis at the site of the injection causing great distress to the patient; the other involved a histaminoid reaction in a patient who, like others who have been reported with this type of reaction, had a history of allergy.


Effects of socio-demographic variables on performance on the Cambridge neuropsychological automated tests for the assessment of dementia and Portuguese norms for older adults living in retirement homes.
This study aimed to analyze the effects of age, education, gender, computer experience, institutionalization time, and psychotropic drug use on performance on four tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) which are recommended for the assessment of dementia (Rapid Visual Information Processing [RVP], Paired Associates Learning [PAL], Spatial Working Memory [SWM], and Reaction Time [RTI]), and to provide norms for Portuguese older persons without neuropsychiatric diagnoses who are living in retirement homes. The normative sample included 128 adults aged 69-96 years who had no neuropsychiatric diagnosis and who had lived in retirement homes for 3-232 months. The CANTAB was administered, at the latest, one week after a screening session that comprised an interview and the administration of pencil-and-paper tests. The simultaneous multiple linear regression models were significant (p < .05) for all tests except the RTI five-choice movement time measure. The total variance explained by the socio-demographic variables was smaller for the CANTAB measures (4-14%) than for the pencil-and-paper tests (10-33%). Significant effects involving age or gender were observed for RVP, PAL, and SWM. A marginally significant computer experience effect was found for the RTI simple movement time measure. We additionally observed significant effects of education, age, gender, and computer experience on several pencil-and-paper tests. Our findings suggest that different socio-demographic variables influence distinct tests and measures of the same test, and that the associations between computer experience and several pencil-and-paper tests may be mediated by possible cognitive skills developed through computer use.


Crystallization and preliminary X-ray analysis of recombinant histone HPhA from the hyperthermophilic archaeon Pyrococcus horikoshii OT3.
Recombinant archaeal histone from the hyperthermophile Pyrococcus horikoshii OT3 (HPhA) was crystallized by the hanging-drop vapour-diffusion method. Crystals grew at 291 K in 200 mM (NH(4))(2)SO(4), 100 mM sodium acetate buffer pH 4.6, 19% PEG 4000. Diffraction data were obtained to a resolution of 2.3 A from a single frozen crystal, which belonged to space group P2(1) with unit-cell parameters a = 34.99, b = 46.89, c = 35.02 A, alpha = gamma = 90, beta = 104 degrees. The asymmetric unit contained two molecules and had a solvent content of approximately 35%.


Increased clastogenicity and decreased inhibition of DNA synthesis by neocarzinostatin and tallysomycin in ataxia telangiectasia lymphoid cells.
Cytogenetic damage in cells cultured from normal individuals and patients with ataxia telangiectasia (A-T) and xeroderma pigmentosum (XP) was induced by the chemotherapeutic antibiotics neocarzinostatin (NCS), tallysomycin (TLM) and bleomycin (BLM). Chromosomal breakage was specifically elevated in A-T cells when compared to the other genotypes tested. Similar results were not observed with the clastogens mitomycin C (MMC) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as all cells responded similarly. All 5 chemical agents caused a marked suppression of de novo DNA synthesis in normal and XP long-term lymphoid cell lines while the A-T cells seemed resistant to this effect of NCS, TLM and BLM.


Toxicological classification of urine samples using pattern recognition techniques and capillary electrophoresis.
In toxicology, hazardous substances detected in organisms may often lead to different pathological conditions depending on the type of exposure and level of dosage; hence, further analysis on this can suggest the best cure. Urine profiling may serve the purpose because samples typically contain hundreds of compounds representing an effective metabolic fingerprint. This paper proposes a pattern recognition procedure for determining the type of cadmium dosage, acute or chronic, administrated to laboratory rats, where urinary profiles are detected using capillary electrophoresis. The procedure is based on the composition of a sample data matrix consisting of areas of common peaks, with appropriate pre-processing aimed at reducing the lack of reproducibility and enhancing the potential contribution of low-level metabolites in discrimination. The matrix is then used for pattern recognition including principal components analysis, cluster analysis, discriminant analysis and support vector machines. Attention is particularly focussed on the last of these techniques, because of its novelty and some attractive features such as its suitability to work with datasets that are small and/or have low samples/variable ratios. The type of cadmium administration is detected as a relevant feature that contributes to the structure of the sample matrix, and samples are classified according to the class membership, with discriminant analysis and support vector machines performing complementarily on a training and on a test set.


Oxygen uptake rate optimization with nitrogen regulation for erythromycin production and scale-up from 50 L to 372 m3 scale.
Effects of different nitrogen sources on the erythromycin production were investigated in 50 l fermenter with multi-parameter monitoring system firstly. With the increase of soybean flour concentration from 27 g/l to 37 g/l to the culture medium, the erythromycin production had no obvious increase. Whereas adding corn steep liquor 15 g/l in the medium was beneficial for the production of erythromycin, the maximum erythromycin production was 22.2% higher than that of the control. It was found that corn steep liquor can regulate and enhance the oxygen uptake rate (OUR) which characterizes the activity of the microbial metabolism by inter-scale observation and data association. Both Intracellular and extracellular organic acids of central metabolism were analyzed, and it was found that the whole levels of lactic acid, pyruvic acid, citric acid, and propionic acid were higher than those of control before 64th h. The consumption amount of amino acids, which could be transformed into the precursors for erythromycin synthesis (i.e. threonine, serine, alanine, glycine and phenylalanine), were elevated compared with the control in erythromycin biosynthesis phase. The results indicated that corn steep liquor can regulate OUR to certain level in the early phase of fermentation, and enhance the metabolic flux of erythromycin biosynthesis. Erythromycin production was successfully scaled up from a laboratory scale (50 l fermenter) to an industrial scale (132 m(3) and 372 m(3)) using OUR as the scale-up parameter. Erythromycin production on industrial scale was similar to that at laboratory scale.


Comparative Clinical Study of Two Tooth Whitening Protocols.
This study aimed to clinically evaluate the effectiveness of two different at-home whitening protocols and to determine which is more effective: applying the whitening gel (16% carbamide peroxide) every 24 hours (Group A) or every 48 hours (Group B) for 2 weeks. Group C received a placebo gel (glycerin) without peroxide, which was applied every 24 hours for 2 weeks. The differences in terms of tooth sensitivity were also analyzed. A sample of 60 patients was divided into three groups of 20 patients. To compare the groups, color measurements were made using a spectrophotometer, and Student t test was used for independent samples. The confidence level was set at 95% (P ≤ .05). No statistically significant differences were found between Groups A and B (P > .05). The study concluded that 16% carbamide peroxide was equally effective when applied with either protocol and obtained the same results, but the 48-hour application protocol produced less sensitivity than the 24-hour application protocol.


The absolute configuration of chrysomelidial: a widely distributed defensive component among oribotririid mites (Acari: Oribatida).
The absolute configuration of the iridoid monoterpene chrysomelidial from the oribatid mite, Austrotritia dentate Aoki, was elucidated by the GC-MS and GC comparisons with four synthetic stereoisomers of this well-known natural product. This identification was made possible by asymmetric synthesis of the known alcohol, (5S,8S)-chrysomelidiol. The GC retention time of diol derived from the natural oribatid dial agreed with that of the synthetic (5S,8S)-chrysomelidiol, confirming that the absolute configurations at C5 and C8 positions of the natural chrysomelidial are both S. Chrysomelidial was detected as a single or a major component in nine oribatid mites examined; thus, this compound is considered to be commonly distributed in Oribotririidae where it serves a defensive role.


Detailed analysis of prognostic factors in primary esophageal small cell carcinoma.
Primary small cell carcinoma of the esophagus (SCCE) is characterized as highly aggressive with a poor prognosis. To identify potential prognostic factors and to assess the role of surgical procedures, chemotherapy, and radiotherapy for SCCE, we retrospectively analyzed patients with SCCE from three large institutions in China. All of the SCCE patients between 1998 and 2012 were identified from three clinical databases of the Sun Yat-Sen University Cancer Center, Peking Union Cancer Hospital and Shantou Cancer Hospital. Potential prognostic factors were analyzed with univariate analysis and a Cox regression model. Subgroup analysis based on the 2002 American Joint Committee on Cancer staging system for esophageal cancer was applied to examine the effect of treatment on survival. In patients with stage I/II SCCE, 85% underwent operations and showed improved survival (median survival time [MST] 29 vs 17.4 months, p = 0.082). However, chemotherapy did not further improve survival. In patients with stage IIB/III SCCE, chemotherapy, instead of operation, improved survival (MST 13.0 vs 6.1 months, p = 0.003), and radiotherapy resulted in improved survival. In stage IV patients, chemotherapy improved survival (MST 12.5 vs 4.0 months, p < 0.001), and chemotherapy combined with radiotherapy was superior to chemotherapy alone (MST 13.2 vs 8.9 months, p = 0.014). Surgical procedures alone can be recommended for stage I/IIA patients. In patients with stage IIB disease or above, chemotherapy should be the main treatment approach, and chemotherapy combined with radiotherapy tended to improve survival.


Directed use of the Cincinnati Prehospital Stroke Scale by laypersons.
The Cincinnati Prehospital Stroke Scale (CPSS) is a three-item examination that has been effective in the identification of stroke victims by health care professionals. However, assessment of the patient earlier in the chain of care, specifically by a 9-1-1 telecommunicator, may improve stroke outcomes. To modify the CPSS for over-the-phone administration and to assess whether untrained adults can follow the CPSS instructions, identify deficits in stroke survivors, and return these findings to an investigator. One hundred nonpatient visitors to an academic tertiary care emergency department were recruited. Each participant was brought to a room with a stroke survivor possessing unresolved symptoms from a previous stroke. The participant was telephoned by an investigator and led through administering the CPSS to the stroke survivor. The investigator noted whether the participant accurately administered CPSS instructions and whether normal or abnormal findings were returned. Participants correctly administered CPSS directions 98% of the time. For facial weakness, the sensitivity of the participants' assessments was 74% and the specificity was 94%. For arm weakness, the sensitivity was 97% and the specificity was 72%. For speech deficits, the sensitivity was 96% and the specificity was 96%. Untrained adults can use the CPSS to accurately identify stroke symptoms and can relay these findings to an investigator. Telecommunicator administration of the CPSS may allow for expedited prehospital triage of the stroke patient and delivery of resources in a timely manner and, given the limited time window for efficacious treatment, may lead to improved patient outcome.


A new approach to the problem of retinal neovascularization.
Tumor cells introduced into the rabbit vitreous produced a form of retinal neovascularization, but only when the tumor cells were in direct contact with the vascularized retina. This contrasted with the production of neovascularization at a distance of several millimeters in other angiogenesis models. An extract of adult rabbit vitreous was found to inhibit the growth of limbal neovascularization induced by tumors implanted in the rabbit corneal stroma. The experimental model of retrolental fibroplasia provides a bioassay to investigate further the apparent inhibitory substances in the vitreous.


The effect of feeding rats with partially hydrogenated marine oil or rapeseed oil on the chain shortening of erucic acid in perfused heart.
1. The metabolism of [14(-14)C]erucic acid and [U-14C]palmitic acid was studied in perfused hearts from rats fed diets containing hydrogenated marine oil, rapeseed oil or peanut oil for three weeks. 2. [14C]Erucic acid was shortened to [14C]eicosenoic acid (20 : 1, n -- 9) and [14C]oleic acid (18 : 1, n -- 9) in perfused rat hearts from all diet groups. The rapeseed oil diet caused a three-fold increase and the marine oil diet a four-fold increase in the amount of chain-shortened products recovered in heart lipids at the end of perfusion, compared to peanut oil diet. 3. The content of C16:1, C18:1 and C20:1 fatty acids was increased in heart lipids of rats fed hydrogenated marine oil or rapseed oil diet, compared to peanut oil diet. 4. Feeding hydrogenated marine oil or rapeseed oil to the rats induced a 85% increase in catalase activity, a 20% increase in the activity of cytochrome oxidase and a 30--40% increase in the content of total CoA in the heart compared to rats fed peanut oil diet. 5. It is suggested that [14(-14)C]erucic acid is shortened by the beta-oxidation system of peroxisomes in the heart. The increased chain shortening in the hearts from animals fed rapeseed oil or partially hydrogenated marine oil for three weeks may be an important part of an adaptation process.


Splenic infarction associated with transient anti-prothrombin antibodies is a rare manifestation of acute Mycoplasma pneumoniae infection.
We report the first paediatric case of splenic infarction following acute Mycoplasma pneumoniae infection with induction of anti-prothrombin (aPT) antibodies. A 12-year-old boy was admitted to the paediatric emergency department for a left pleuropneumonia and a splenic infarction. aPT antibodies were transitorily detected. The patient recovered fully after antibiotic therapy and a 3-month course of anticoagulation treatment. Antiphospholipid (aPL) antibodies induced by acute infections have already been reported but cases of clinically relevant thrombosis remain rare. The pathogenicity of aPT antibodies is discussed here. We hypothesize that these antibodies were involved in this symptomatic hypercoagulable state.


YKT6 expression, exosome release, and survival in non-small cell lung cancer.
Cancer-derived exosomes are involved in metastasis. YKT6 is a SNARE protein that participates in the regulation of exosome production and release, but its role in non-small cell lung cancer (NSCLC) has not been examined. Ultracentrifugation-purified exosomes from the A549 cell line were studied by CRYO-TEM, nanoparticle tracking analysis and western blot (TSG101 marker). YKT6 was inhibited using a DsiRNA and selected pre-microRNAs. MicroRNAs targeting YKT6 were validated by Renilla/Luciferase assay and western blot. YKT6 expression and its prognostic impact were analyzed in 98 tissue specimens from resected NSCLC patients. Membranous nanosized vesicles (mode size: 128nm) with TSG101 protein were purified from A549 cells. YKT6 inhibition reduced exosome release by 80.9%. We validated miR-134 and miR-135b as miRNAs targeting YKT6, and transfection with the pre-miRNAs also produced a significant reduction in exosome release. The analysis of YKT6 in tumor samples showed that patients with high levels had shorter disease-free and overall survival. YKT6 is a key molecule in the regulation of exosome release in lung cancer cells and is in turn precisely regulated by miR-134 and miR-135b. Moreover, YKT6 levels impact prognosis of resected NSCLC patients.


Specific anosmia in the laboratory mouse.
As an approach to a general theory of olfaction, different specific anosmia phenotypes characterized by different profiles of odorant sensitivities have been proposed for humans. In the present experiments, male inbred mice were tested for relative odorant sensitivity using a conditioned aversion technique and odors classified as primary or complex for humans. C57BL/6J and C57BL/10J mice appeared to be less sensitive to the primary odorant isovaleric acid than were males of seven other inbred strains (A/J, AKR/J, BALB/cJ,C3HeB/FeJ, DBA/2J, SJL/J, and SWR/J). In comparisons of C57BL/6J and AKR/J strains, the relative insensitivity of C57 to isovaleric acid did not generalize to the musklike primary odor of pentadecalactone or to the complex odor of amyl acetate. The C57BL/6J genotype may provide an animal model of a specific anosmia as characterized among humans.


Delayed post-traumatic diaphragmatic rupture complicated by total hepato-thorax: A case report.
Intra-thoracic herniation of abdominal organs following diaphragmatic rupture represents an unusual clinical occurrence that poses great diagnostic difficulty. We report a rare case of delayed total hepatothorax caused by a right sided post-traumatic diaphragmatic rupture in a 67 year old male. Reduction of the liver in the abdominal cavity and repair of the diaphragm was feasible via a thoraco-abdominal approach. Postoperative chest radiography showed normal position of the right diaphragmatic border. Characteristics of right diaphragmatic rupture and subsequent complications are reviewed with the aim to reinforce physicians' awareness of this uncommon clinical condition in order to establish a timely diagnosis and reduce the mortality related burden. Surgeons should consider this entity in the differential diagnosis of injured patients experiencing sudden respiratory distress during hospitalization as well as days or months after discharge.


The OptimaMed intervention to reduce medication burden in nursing home residents with severe dementia: results from a pragmatic, controlled study.
Nursing home (NH) residents with severe dementia use many medications, sometimes inappropriately within a comfort care approach. Medications should be regularly reviewed and eventually deprescribed. This pragmatic, controlled trial assessed the effect of an interprofessional knowledge exchange (KE) intervention to decrease medication load and the use of medications of questionable benefit among these residents. A 6-month intervention was performed in 4 NHs in the Quebec City area, while 3 NHs, with comparable admissions criteria, served as controls. Published lists of "mostly", "sometimes" or "exceptionally" appropriate medications, tailored for NH residents with severe dementia, were used. The intervention included 1) information for participants' families about medication use in severe dementia; 2) a 90-min KE session for NH nurses, pharmacists, and physicians; 3) medication reviews by NH pharmacists using the lists; 4) discussions on recommended changes with nurses and physicians. Participants' levels of agitation and pain were evaluated using validated scales at baseline and the end of follow-up. Seven (7) NHs and 123 participants were included for study. The mean number of regular medications per participant decreased from 7.1 to 6.6 in the intervention, and from 7.7 to 5.9 in the control NHs (p-value for the difference in differences test: < 0.05). Levels of agitation decreased by 8.3% in the intervention, and by 1.4% in the control NHs (p = 0.026); pain levels decreased by 12.6% in the intervention and increased by 7% in the control NHs (p = 0.049). Proportions of participants receiving regular medications deemed only exceptionally appropriate decreased from 19 to 17% (p = 0.43) in the intervention and from 28 to 21% (p = 0.007) in the control NHs (p = 0.22). The mean numbers of regular daily antipsychotics per participant fell from 0.64 to 0.58 in the intervention and from 0.39 to 0.30 in the control NHs (p = 0.27). This interprofessional intervention to reduce inappropriate medication use in NH residents with severe dementia decreased medication load in both intervention and control NHs, without important concomitant increase in agitation, but mixed effects on pain levels. Practice changes and heterogeneity within these 7 NHs, and a ceiling effect in medication optimization likely interfered with the intervention. The study is registered at ClinicalTrials.gov: # NCT05155748 (first registration 03-10-2017).


Induction of DNA double strand breaks in cultured mammalian cells exposed to hydrogen peroxide and histidine.
The amino acid histidine was found to increase the toxicity of H(2)O(2) in cultured mammalian cells. Histidine also augmented the level of DNA single strand breaks (SSB) detectable in cells exposed to the oxidant and, in addition, resulted in the appearance of DNA double strand breaks (DSB), a lesion which is not produced by H(2)O(2) alone.


Off-label use of biologics for the treatment of refractory and/or relapsing granulomatosis with polyangiitis.
To describe the efficacy and safety of off-label use of biologics for refractory and/or relapsing granulomatosis with polyangiitis (GPA). We conducted a French retrospective study including GPA patients who received off-label biologics for refractory and/or relapsing disease after failure of conventional immunosuppressive regimens. Among 26 patients included, 18 received infliximab (IFX), 2 adalimumab (ADA) and 6 abatacept (ABA). Biologics were initiated in median as 4th-line therapy (IQR 3-6) for relapsing and/or refractory disease in 23 (88%) and/or significant glucocorticoid-dependency in 8 cases (31%). At biologics initiation, median (IQR) BVAS and prednisone dose in anti- TNF-α and ABA recipients were 7 (3-8) and 2 (1-6), and 20 (13-30) mg/day and 20 (15-25) mg/day, respectively. Clinical manifestations requiring biologics were mainly pulmonary and ENT manifestations in 58% each. Anti-TNF-α and ABA were continued for a median duration of 8 months (IQR 6-13) and 11 months (IQR 6-18) respectively. Anti-TNF-α recipients showed remission, partial response and treatment failure in 10%, 30% and 60% at 6 months, and 25%, 20% and 55% at 12 months, respectively. ABA recipients showed remission, partial response and treatment failure in 17%, 33% and 50% at 6 months and 17%, 33% and 50% at 12 months. One patient treated with IFX experienced life-threatening reaction while one patient treated with ABA experienced a severe infection. This real-life study suggests that off-label use of anti-TNF-α and abatacept shows efficacy in less than 50% of refractory and/or relapsing GPA.


Biochar: An environmentally friendly platform for construction of a SARS-CoV-2 electrochemical immunosensor.
Waste management is a key feature to ensure sustainable consumption and production patterns, and to combat the impacts of climate change. In this scenario, the production of biochar from different biomasses results in environmental and economic advantages. In this study, biochar was produced from sugarcane bagasse pyrolysis, to immobilize biomolecules, in order to assemble an electrochemical immunosensor to detect antibodies against SARS-CoV-2. For this, screen-printed carbon electrodes (SPCE) were modified with a dispersion of biochar and used to immobilize the receptor-binding-domain (RBD) against virus S-protein, through EDC/NHS crosslinking reaction. Under the best set of experimental conditions, negative and positive serum samples responses distinguished based on a cutoff value of 82.3 %, at a 95 % confidence level. The immunosensor showed selective behavior to antibodies against yellow fever and its performance was stable up to 7 days of storage. Therefore, biochar yielded from sugarcane bagasse is an ecofriendly material that can be used as a platform to immobilize biomolecules for construction of electrochemical biosensors.


Is preoperative anxiety associated with postoperative delirium in older persons undergoing cardiac surgery? Secondary data analysis of a randomized controlled trial.
Although many studies have reported numerous risk factors for postoperative delirium, data are scarce about preoperative anxiety as a risk factor. The study aimed to investigate the association between preoperative anxiety and postoperative delirium in older patients undergoing cardiac surgery. Secondary data analysis of a randomized, observer-blind, controlled trial. A total of 190 patients 65 years or older and admitted to the intensive care unit and cardiac surgery unit of a university hospital scheduled for elective on-pump cardiac surgery were included. State anxiety was measured preoperatively using the Amsterdam Preoperative Anxiety and Information Scale and the Visual Analogue Scale for anxiety. Incidence of delirium was measured during the first 5 postoperative days using the Confusion Assessment Method for Intensive Care Unit (when ventilated), or the 3 Minute Diagnostic Interview for Confusion Assessment Method (when extubated) and by daily chart review. Preoperative state anxiety was reported by 31% of the patients and 41% had postoperative delirium. A multiple step logistic regression analyses revealed no association between preoperative anxiety and postoperative delirium. Significant risk factors for postoperative delirium were age (OR = 1.10, 95% CI (1.03-1.18)), activities of daily living (0.69, 95% CI (0.50-0.96)), diabetes mellitus (OR = 3.15, 95% CI (1.42-7.00)) and time on cardiopulmonary bypass (OR = 1.01, 95% CI (1.00 to 1.02)). No relationship could be found between preoperative anxiety and postoperative delirium.


[Immunomodulating effect of cyclophosphamide on cytotoxic activity of rats and mice splenocytes].
This study examines the immunomodulating effect of cytostatic drug--cyclophosphamide (Cy)--on natural cytotoxic activity of rats and mice splenocytes. The cytotoxicity of the effector cells against the confluent monolayer cell lines of rat hepatoma Zajdela and HTC and mice hepatoma MH-22a was estimated by means the morphometric analysis. It was shown, that 48 h after single intraperitoneal injection of Cy produced a immunomodulating effect on the activity of splenocytes--suppressor action on cells of Zajdela hepatoma and immunopotentiating action on the target cells of HTC and MH-22a hepatomas. The possible mechanisms of immunopotentiating effect of Cy are discussed.


Long-Term Phytoplankton Dynamics in a Complex Temporal Realm.
Faced with an environment of accelerated change, the long-term dynamics of biotic communities can be approached to build a consistent and causal picture of the communities' life. We have undertaken a 25-year monthly-sampling study on the phytoplankton of a meso-oligotrophic lake, paying attention to controlling factors of overall biomass (TB) and taxonomical group biomass (TGBs). Long-term series included decreased trends of TB and TGBs, and multi-scale periodicity. A decadal TB periodicity emerged related to nitrogen concentration and Cryptophytes. Annual periodicities were mainly related to air and water temperature controlling the abundance of Chlorophytes or Dinoflagellates. Intra-annual cycles could arise from autogenic processes. The analysis by periods revealed relevant dynamics (for example, Diatom periodicities), hidden in the analysis of the complete series. These results allow us to establish that: i) two organizational levels of phytoplankton change differently in time scales from months to decades; ii) controlling factors (climate, water physics and chemistry) act at different time scales and on different TGBs, and iii) different combinations of the "taxonomical group-control factor-trend and periodicity" set throughout the studied time explain total biomass dynamics. A holistic approach (multiple complementary analyses) is necessary to disentangle the different actors and relationships that explain non-stationary long-term phytoplankton dynamics.


Design and analysis of experiments.
This chapter is primarily devoted to experiments that compare 2 treatments with respect to an outcome measure. Six design scenarios are discussed: (a) completely randomized designs (treatments are assigned completely at random); (b) randomized block designs (experimental units are subdivided into blocks of like subjects, with one subject in each block randomly assigned to each treatment); (c) stratified designs (subjects are categorized into subpopulations called strata, and within each stratum, a completely randomized design is conducted); (d) crossover designs (each subject gets both treatments, but order is completely at random); (e) 2 x 2 factorial designs [design can be in any of the formats (a)-(d) but there are 4 not 2 treatments representing 2 types of treatment interventions, each with 2 levels]; and (f) randomized designs with "random" effects. This is much like the stratified design, except there is only 1 sample, at least conceptually, from the strata. Examples might be litters of laboratory animals, surgical practices, or batches of a therapeutic agent. The desire is to make inferences about treatments in the population as a whole, not just in the strata that were actually sampled.


Interaction of methylene blue with transfer RNA--a spectroscopic study.
The binding of methylene blue (MB) with tRNA was studied using absorption, fluorescence and circular dichroic spectroscopy. In the spectral titration of MB with tRNA, hypochromism was observed in the absorption maximum of the dye in the visible region till P/D = 4 and thereafter the intensity increased with a red shift at P/D > 9, indicating electrostatic and intercalative binding at low and high P/D ratios, respectively. Analysis of absorption data, following Schwarz's procedure, showed that the electrostatic binding is cooperative in nature (cooperatively parameter q = 50) with a binding constant K = 7.77 x 10(3) M-1. A non-linear Scatchard plot was observed for the intercalative binding (at P/D > 4), probably due to a difference in the spectral characteristics of the dye intercalated between the base pairs and that between the bases in the single stranded domains. Quenching of fluorescence was observed for both the binding processes. In the circular dichroism spectra of tRNA-MB complexes at high P/D (approximately 30), nonconservative positive ICD bands were seen at 620 and 680 nm while at low P/D (approximately 2), two conservative negative CD bands at 300 and 660 nm and two bisignate bands with cross overs at 565 and 605 nm were observed. The short wavelength component of the bisignate band at 565 nm is negative while that of the 605-nm band is positive, indicating that the former arises from left handed and the latter from the right handed helical disposition of dye molecules along the tRNA backbone. The changes in the CD spectrum of tRNA on dye binding could be due to a conformational change of the nucleic acid or a negative CD being induced at that region.


Neural dynamics of cross-modal and cross-temporal associations.
We have studied a neurodynamic model of cross-modal and cross-temporal associations. We show that a network of integrate-and-fire neurons can generate spiking activity with realistic dynamics during the delay period of a paired associates task. In particular, the activity of the model resembles reported data from single-cell recordings in the prefrontal cortex.


Regulation of human natural cytotoxicity by IgG--I. Characterization of the structural site on monomeric IgG responsible for inhibiting natural killer cell activity.
Inhibition of human natural killer (NK) cell activity upon exposure of peripheral blood lymphocytes (PBL) to IgG in monomeric form (mIgG) was found to be dose-, time- and temp-dependent. PBL incubated for 2 hr at 37 degrees C in the presence of myeloma protein of a certain class or subclass had a significant reduction of their NK activity when exposed to IgG, but not to IgM or IgD, and the IgG-induced inhibition of NK cells was observed only when IgG1 or IgG3 paraproteins were used. IgG3 isolated from normal serum had a higher inhibitory property than that of total mIgG. The cytophilic activity of the IgG molecules was confined entirely to the Fc region and seemed to be localized in the CH3 domain, since human and rabbit Facb fragments had a reduced ability to inhibit NK activity. When synthetic peptides representing various sequences of the human gamma-chain were tested for inhibition of NK activity, only treatment of effector cells with a peptide comprising the sequence Tyr407-Arg416 of the CH3 domain showed a reduction of NK cell function comparable to the inhibition obtained following incubation of cells in the presence of mIgG. However, on a molar basis, this peptide was 20 times less active than mIgG. In contrast, peptides derived from sequences in the CH2 domain lacked this inhibitory capacity. Our data indicate that the structural site responsible for inhibiting NK cell activity is located in the C-terminal domain of the IgG molecule.