Lipid Raft, Regulator of Plasmodesmal Callose Homeostasis.
Abstract: The specialized plasma membrane microdomains known as lipid rafts are enriched by sterols and sphingolipids. Lipid rafts facilitate cellular signal transduction by controlling the assembly of signaling molecules and membrane protein trafficking. Another specialized compartment of plant cells, the plasmodesmata (PD), which regulates the symplasmic intercellular movement of certain molecules between adjacent cells, also contains a phospholipid bilayer membrane. The dynamic permeability of plasmodesmata (PDs) is highly controlled by plasmodesmata callose (PDC), which is synthesized by callose synthases (CalS) and degraded by β-1,3-glucanases (BGs). In recent studies, remarkable observations regarding the correlation between lipid raft formation and symplasmic intracellular trafficking have been reported, and the PDC has been suggested to be the regulator of the size exclusion limit of PDs. It has been suggested that the alteration of lipid raft substances impairs PDC homeostasis, subsequently affecting PD functions. In this review, we discuss the substantial role of membrane lipid rafts in PDC homeostasis and provide avenues for understanding the fundamental behavior of the lipid raft-processed PDC.


Efficacy and Safety of Tocilizumab Treatment COVID-19 Patients: A Case-Control Study and Meta-Analysis.
As the pandemic progresses, the pathophysiology of COVID-19 is becoming more apparent, and the potential for tocilizumab is increasing. However, the clinical efficacy and safety of tocilizumab in the treatment of COVID-19 patients remain unclear. To assess the efficacy and safety of tocilizumab treatment in COVID-19 patients, we performed a retrospective case-control study. The study was conducted, including 95 patients treated with tocilizumab plus standard treatment and matched controls with 95 patients treated with standard treatment therapy by propensity score from February to April 2020. We searched some databases using the search terms for studies published from January 1, 2020, to June 1, 2021. Our case-control study found a lower mortality rate in the tocilizumab treatment group than in the standard treatment group (9.47% versus 16.84%, P = 0.134), but the results were not statistically significant. We also found that the mortality rate in tocilizumab treatment groups was significantly lower than in the standard treatment group in the stratified ICU analysis (OR 0.52, 95% CI 0.44-0.61, P = 0.048 and OR 0.31, 95% CI 0.10-0.99, P = 0.044). We selected 49 studies (including 6568 cases and 11,660 controls) that met the inclusion criteria in the meta-analysis. In the overall analysis, we performed a meta-analysis that showed significantly decreased mortality after patients received tocilizumab (OR 0.81, 95% CI 0.69-0.95, P = 0.008). We also revealed significant associations within some subgroups. The sequential trial analysis showed a true-positive result. No significant associations were observed between tocilizumab and elevated secondary infection risk, discharge, adverse events, and mechanical ventilation in the overall analysis. Tocilizumab significantly decreased mortality in COVID-19 patients with no increased discharge, secondary infection risk, adverse events, and mechanical ventilation in a meta-analysis. Our data suggest that clinicians should pay attention to tocilizumab therapy as an effective and safe treatment for COVID-19 patients.


Risk assessment: the perspective and experience of U.S. environmentalists.
Risk assessment is a set of decision rules widely used in the United States for identifying and quantifying the risks of chemicals and other events for adverse effects to human health, usually cancer. Scientific criticism has been directed toward the default assumptions and test methods used in risk assessment by regulatory agencies. This paper evaluates the contribution of risk assessment as an instrument of public policy toward the timely and efficient resolution of controversial issues in environmental and occupational health. Experience with risk assessment during the past decade does not support its utility in this regard. Alternatives to risk assessment in its current formulation are discussed.


Generation and characterization of human kidney cell lines stably expressing recombinant human PTH/PTHrP receptor: lack of interaction with a C-terminal human PTH peptide.
Parathyroid hormone (PTH) exerts its biological action by binding to membrane-bound, G-protein coupled receptors expressed predominantly in bone and kidney. In this study, we describe the production and characterization of a panel of cell lines, derived from a human embryonic kidney cell line (HEK-293), each of which stably express different amounts of the recombinant human PTH/parathyroid hormone-related protein (PTHrP) receptor (Rc). A total of 52 distinct clones displaying different levels of PTH-responsive cAMP production were analyzed; three clones were chosen for more detailed evaluation. These clones (and the receptor-lacking parental cell line) were examined for PTH binding, PTH-stimulated cyclic AMP accumulation and PTH/PTHrP Rc mRNA expression. Receptor-positive clones display a spectrum of PTH-responsiveness that correlates with receptor number/cell and level of receptor mRNA present. The interaction of a C-terminal hPTH-(52-84) peptide with the stably expressed human receptor was examined in cells expressing the highest amount of Rc (> 400,000 Rc/cell). There was no direct binding of hPTH-(52-84) or specific competition versus radiolabeled PTH-(1-34). However, competition versus radiolabeled PTH-(1-34) was observed with bPTH-(1-34), hPTH-(1-84) and hPTHrP-(1-34). These data suggest that hPTH-(52-84) does not interact with the only known form of the human PTH/PTHrP Rc. Therefore, the reported effects of PTH-(52-84) in other systems must be via an alternate (as yet unidentified) mechanism(s). The expression of various amounts of the human PTH/PTHrP Rc in a human target cell background should facilitate characterization of the ligand-binding properties and physiological signal transduction mechanism of the Rc.


Halocuprate(I) zigzag chain structures with N-methylated DABCO cations--bright metal-centered luminescence and thermally activated color shifts.
Two compounds 1,4-dimethyl-1,4-diazoniabicyclo[2.2.2]octane catena-tetra-μ-halo-dicuprate(I) with DABCOMe2 Cu2X4 (1: X = Br, 2: X = I) were synthesized by hydrothermal reaction of copper(I) halides with the corresponding 1,4-diazoniabicyclo[2.2.2]octane (DABCO) dihydrohalides in an acetonitrile/methanol mixture. Both compounds crystallize monoclinically, 1 with a = 9.169(4) Å, b = 10.916(6) Å, c = 15.349(6) Å, β = 93.93(2)°, V = 1533(1) Å(3), Z = 4, space group P2(1)/n (no. 14) and 2 with a = 15.826(9) Å, b = 9.476(5) Å, c = 22.90(2) Å, β = 90.56(5)°, V = 3434(5) Å(3), Z = 8, space group P2(1) (no. 4), respectively (lattice constants refined from powder diffraction data measured at 293 K). The cations in both compounds are formed by in situ N-methylation of DABCOH2(2+) cations by methanol in a S(N)2 reaction. Both compounds contain an anionic copper(I) halide chain structure consisting of trans edge-sharing CuX4 tetrahedra. The chains are strongly kinked at every 2(nd) junction thus forming a zigzag structure. The shortest halide-halide distances are observed between the halide ions of adjacent tetrahedra which are approaching each other due to the kinking. This structure type shows a specific luminescence behavior. Under optical excitation, the compounds exhibit yellow (1) and green (2) emission with photoluminescence quantum yields of Φ(PL) = 52 and 4%, respectively, at ambient temperature. According to DFT and TDDFT calculations, the emission is assigned to be a phosphorescence essentially involving a metal centered transition between the HOMO consisting mainly of copper 3d and halide p orbitals and the LUMO consisting mainly of copper 4s and 4p orbitals. The temperature dependence of the emission spectra, decay times, and quantum yields has been investigated in detail, especially for 1. From the resulting trends it can be concluded that the emission for T≤ 100 K stems from energetically lower lying copper halide segments. Such segments represent the structural motif of the halocuprate(I) chains. With increasing temperature energetically higher lying segments are populated which also emit, but open the pathway for thermally activated energy transfer to quenching defects.


Mechanical ventilation in patients with acute respiratory distress syndrome: current status and future perspectives.
Although there has been extensive research on mechanical ventilation for acute respiratory distress syndrome (ARDS), treatment remains mainly supportive. Recent studies and new ventilatory modes have been proposed to manage patients with ARDS; however, the clinical impact of these strategies remains uncertain and not clearly supported by guidelines. The aim of this narrative review is to provide an overview and update on ventilatory management for patients with ARDS. This article reviews the literature regarding mechanical ventilation in ARDS. A comprehensive overview of the principal settings for the ventilator parameters involved is provided as well as a report on the differences between controlled and assisted ventilation. Additionally, new modes of assisted ventilation are presented and discussed. The evidence concerning rescue strategies, including recruitment maneuvers and extracorporeal membrane oxygenation support, is analyzed. PubMed, EBSCO, and the Cochrane Library were searched up until June 2023, for relevant literature. Available evidence for mechanical ventilation in cases of ARDS suggests the use of a personalized mechanical ventilation strategy. Although promising, new modes of assisted mechanical ventilation are still under investigation and guidelines do not recommend rescue strategies as the standard of care. Further research on this topic is required.


Tumefactive demyelination: Clinical outcomes, lesion evolution and treatments.
Large demyelinating lesions with possible mass effect (tumefactive multiple sclerosis or tumefactive demyelination) can be mistaken for tumour-like space-occupying lesions suggesting a malignant outcome. We reviewed our own experience of multiple sclerosis subjects (n = 28) with tumefactive demyelination to determine the relationship between clinical outcomes and lesion evolution, clinical outcomes and their relationship to different therapies. Patients with central nervous system demyelinating disease were identified from our database over the last 10 years. No patient increased in extended disability status scale (EDSS). Overall, lesion regression was associated with improved EDSS. Lesion regression was also associated with therapy versus no therapy. No specific therapy or corticosteroid infusions improved EDSS over the long term. The absence of enhancement on follow up on magnetic resonance imaging portended lesion regression. Tumefactive demyelination may predict a more benign overall course and is susceptible to traditional immunomodulatory treatments.


Design of a label-free aptasensor for electrochemical determination of hemoglobin: investigation of the peroxidase-like activity of hemoglobin for the sensing of different substrates.
The unbalanced hemoglobin level in biological fluids can cause several diseases; hence it can be used as a biomarker for diagnosis. We aim, in the present study, to construct a label-free electrochemical aptasensor for the quantification of hemoglobin. For that, a conjugate of L-cysteine and gold nanoparticles was used for the aptamer immobilization on screen printed carbon electrodes. Using square wave voltammetry, the calibration plot was obtained and it was linear in the range of 50 ng ml-1 to 36 000 ng ml-1 while the detection limit was 1.2 ng ml-1. After the binding of Hb on the modified screen-printed carbon electrode surface, the peroxidase-like activity of the bound hemoglobin was explored in the quantification of different substrates. Hydrogen peroxide and nitrite were chosen as model analytes. Amperometric measurements showed wide linear ranges: 0.2 μM-7.7 mM and 3.6 nM-1.3 mM for H2O2 and nitrite, respectively, with detection limits of 0.044 μM and 0.55 nM. In the proposed strategy, the aptamer provides excellent orientation and a biocompatible environment for hemoglobin whose catalytic activity plays a key role in H2O2 and nitrite analysis.


Ataxia: an early indicator in high altitude cerebral edema.
Wu, Tianyi, Shouquan Ding, Jinliang Liu, Jianhou Jia, Ruichen Dai, Baozhu Liang, Jizhui Zhao, and Detang Qi. Ataxia: an early indicator in high altitude cerebral edema. High Alt. Med. Biol. 7:275-280, 2006.--As a result of industrial development in the western region of China, in 2001 the Chinese government decided to build Qinghai-Tibetan Railway. The new railroad stretches 1118 km from Golmud (2808 m) to Lhasa (3658 m), with more than three-quarter of the distance above 4000 m, through the Mt. Kun Lun and Tanggula ranges. From the beginning of the project on June, 29, 2001, to the end of the year of 2003, about 74,735 construction workers worked in the harsh climate, in adverse circumstances and a low-barometric-pressure environment. The construction provided an opportunity for the investigation and study of acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE). These altitude illnesses were very common in the construction workers. From July 1, 2001, to October 31, 2003, the overall incidence of AMS, HAPE, and HACE in the total workers was approximately 45%-95%, 0.49%, and 0.26%, respectively. Altitude illnesses were studied at two hospitals near the construction site. One hospital is located on the Fenghuoshan (Mt. Wind-gap) at an altitude of 4779 m (PB 428 torr), and the second hospital is situated in the Kekexili area at an altitude of 4505 m (PB 440 torr). Kekexili is a sparsely populated zone because the weather conditions are very bad all year round. These two hospitals received patients from the construction sites, where workers were working at altitudes between 4464 and 4905 m. A total of 8014 workers were treated at Fenghuoshan and 5488 were in Kekexili over the past 3 years. According to local guidance about proper medical care, workers ascending to high altitude should be examined physically, complete an AMS questionnaire, and be monitored for ataxia as an early warning sign of the impending, more serious aspects of HACE. The onset of HACE is frequently characterized by an ataxic gait, as reported since the middle of the 20th century (Gray et al., 1971; Wilson, 1973; Houston and Dickinson, 1975; Dickinson, 1979; Clarke, 1988; Hackett and Oelz, 1992; Hackett, 2002; Hackett and Roach, 2004). However, there are no detailed analyses of ataxia in HACE. This paper considers the relation between ataxia and HACE and its frequency, significance, and importance.


Two Nucleoporin98 homologous genes jointly participate in the regulation of starch degradation to repress senescence in Arabidopsis.
Starch is synthesized during daylight for temporary storage in leaves and then degraded during the subsequent night to support plant growth and development. Impairment of starch degradation leads to stunted growth, even senescence and death. The nuclear pore complex is involved in many cellular processes, but its relationship with starch degradation has been unclear until now. We previously identified that two Nucleoporin98 genes (Nup98a and Nup98b) redundantly regulate flowering via the CONSTANS (CO)-independent pathway in Arabidopsis thaliana. The double mutant also shows severe senescence phenotypes. We find that Nucleoporin 98 participates in the regulation of sugar metabolism in leaves and is also involved in senescence regulation in Arabidopsis. We show that Nup98a and Nup98b function redundantly at different stages of starch degradation. The nup98a-1 nup98b-1 double mutant accumulates more starch, showing a severe early senescence phenotype compared to wild type plants. The expression of marker genes related to starch degradation is impaired in the nup98a-1 nup98b-1 double mutant, and marker genes of carbon starvation and senescence express their products earlier and in higher abundance than in wild type plants, suggesting that abnormalities in energy metabolism are the main cause of senescence in the double mutant. Addition of sucrose to the growth medium rescues early senescence phenotypes of the nup98a-1 nup98b-1 mutant. Our results provide evidence for a novel role of the nuclear pore complex in energy metabolism related to growth and development, in which Nup98 functions in starch degradation to control growth regulation in Arabidopsis.


Bhlhe40 limits early IL-10 production from CD4+ T cells during Plasmodium yoelii 17X infection.
The cytokine IL-10 suppresses T-cell-mediated immunity, which is required to control infection with Plasmodium yoelii. Consequently, IL-10 can delay the time needed to resolve this infection, leading to a higher parasite burden. While the pathways that lead to IL-10 production by CD4+ T cells are well defined, much less is known about the mediators that suppress the expression of this potent anti-inflammatory cytokine. Here, we show that the transcription factor basic helix-loop-helix family member e40 (Bhlhe40) contributes to controlling parasite burden in response to P. yoelii infection in mice. Loss of Bhlhe40 expression in mice results in higher Il10 expression, higher peak parasitemia, and a delay in parasite clearance. The observed phenotype was not due to defects in T-cell activation and proliferation or the humoral response. Nor was it due to changes in regulatory T-cell numbers. However, blocking IL-10 signaling reversed the outcome in Bhlhe40-/ - mice, suggesting that excess IL-10 production limits their ability to control the infection properly. In addition to suppressing Il10 expression in CD4+ T cells, Bhlhe40 can promote Ifng expression. Indeed, IFN-γ production by CD4+ T cells isolated from the liver was significantly affected by the loss of Bhlhe40. Lastly, Bhlhe40 deletion in T cells resulted in a phenotype similar to that observed in the Bhlhe40-/ - mice, indicating that Bhlhe40 expression in T cells contributes to the ability of mice to control infection with P. yoelii.


Combined -omics framework reveals how ant symbionts benefit the Neotropical ant-plant Tococa quadrialata at different levels.
Ant-plant defensive mutualism is a widely studied phenomenon, where ants protect their host plants (myrmecophytes) against herbivores in return for the provision of nesting sites and food. However, few studies addressed the influence of ant colonization and herbivory on the plant's metabolism. We chose the Amazonian plant Tococa quadrialata, living in association with Azteca cf. tonduzi ants for an ant-exclusion study to reveal the chemistry behind this symbiosis. We found that colonized plants did not only benefit from protection but also from increased amino acid and nitrogen content, enabling better performance even in an herbivore-free environment. In contrast, ant-deprived T. quadrialata plants accumulated more ellagitannins, a major class of constitutive defense compounds. Moreover, herbivory-induced jasmonate-mediated defense responses, including the upregulation of signaling and defense genes and the emission of volatiles irrespective of colonization status. Altogether, we show how ant-colonization can influence the general and defense-related metabolism and performance of myrmecophytes.


Environment vs. Plant Ontogeny: Arthropod Herbivory Patterns on European Beech Leaves along the Vertical Gradient of Temperate Forests in Central Germany.
Environmental and leaf trait effects on herbivory are supposed to vary among different feeding guilds. Herbivores also show variability in their preferences for plant ontogenetic stages. Along the vertical forest gradient, environmental conditions change, and trees represent juvenile and adult individuals in the understorey and canopy, respectively. This study was conducted in ten forests sites in Central Germany for the enrichment of canopy research in temperate forests. Arthropod herbivory of different feeding traces was surveyed on leaves of Fagus sylvatica Linnaeus (European beech; Fagaceae) in three strata. Effects of microclimate, leaf traits, and plant ontogenetic stage were analyzed as determining parameters for herbivory. The highest herbivory was caused by exophagous feeding traces. Herbivore attack levels varied along the vertical forest gradient for most feeding traces with distinct patterns. If differences of herbivory levels were present, they only occurred between juvenile and adult F. sylvatica individuals, but not between the lower and upper canopy. In contrast, differences of microclimate and important leaf traits were present between the lower and upper canopy. In conclusion, the plant ontogenetic stage had a stronger effect on herbivory than microclimate or leaf traits along the vertical forest gradient.


The proteasome: a macromolecular assembly designed to confine proteolysis to a nanocompartment.
Significant progress has been made over the past few years in elucidating the structural principles and the enzymatic mechanism of the 20S proteasome. As a result, the proteasome has become the prototype of a new family of enzymes, the Ntn hydrolases, as well as a paradigm for macromolecular assemblies that confine their proteolytic activity to an inner nanocompartment. Since access to this nanocompartment is restricted to unfolded substrate polypeptides, the 20S proteasome must be functionally linked to a substrate recognition and unfolding machinery. In eukaryotes this is provided by the 19S 'cap' complex, which associates with the 20S core to form the 26S proteasome, a protease capable of degrading ubiquitinated proteins in an ATP-dependent manner.


High Performance Epoxy Composites Containing Nanofiller Modified by Plasma Bubbles.
The thermal conductivity of polymer materials is a fundamental parameter in the field of high-voltage electrical insulation. When the operating frequency and power for electrical equipment or electronic devices increase significantly, the internal heat will increase dramatically, and the accumulation of heat will further lead to insulation failure and serious damage of the whole system. The addition of filler with high thermal conductivity into polymer is a common solution. However, the interfacial thermal resistance between filler and bulk materials is the major obstacle to improve thermal conductivity. Herein, in order to reduce the interfacial thermal resistance, nanofillers are modified by plasma technology. The surface modification of nano-Al2O3 is carried out using plasma bubbles with three atmospheres (Ar, Ar+O2, air) as well as coupling agent. The situation of surface grafting before and after the modification is characterized using FTIR, XPS, and SEM. The effect of the mechanism of modification on the thermal conductivity and reaction pathway is investigated. The results showed that the thermal conductivity after plasma modification is increased significantly. Especially, the thermal conductivity is increased by 35% for the sample modified by Ar+O2 atmosphere. This results because more hydroxyl is introduced on the filler surface by the plasma bubbles, which enhance the interface compatibility between filler and epoxy. In addition, surface insulation performance for the modified samples also is enhanced by 14%. This is associated with the change of surface resistance and trap distribution. These results provide potential support for the development of fabrication for high performance epoxy composites.


[Laryngeal cancer in immunosuppressive therapy with cyclosporin A].
As a serious side effect of immunosuppressive therapy following organ transplantation, the incidence of malignancies shows a significant threefold increase compared with the age-matched general population. Under treatment with conventional immunosuppressive drugs (azathioprine, steroids and antilymphocyte globulin) patients are supposed to be susceptible to skin and lip cancers (40%) whereas the recently introduced new immunosuppressive drug cyclosporine A shows a comparable incidence of non-Hodgkin lymphomas (41%) and the patients seem to develop more potentially life threatening tumours of internal organs. In the present paper we report on a case of laryngeal carcinoma following immunosuppressive treatment with cyclosporine A 10 months after heart transplantation.


Responding to JCAHO standards: everybody's business.
At this stage, JCAHO [Joint Commission on Accreditation of Healthcare Organizations] site visitors simply want to know how the institution plans to respond to the organization ethics standard. In the near future, however, they will expect data on how ethical issues have been addressed that faced the organization in marketing, billing, managed care contracts, and so on. Pointing to an organizational code of ethics will not be enough. Examples of leadership utilizing the processes of the committee or an appropriate consultant or group, to the ends of education, policy studies, and consultation on specific choices will meet the standard. Organizations that evade or choose not to supply data along these lines will presumably be negatively evaluated. Noncompliance presumably means a risk to accreditation. The message to the clinical ethics committee is a serious one. We must engage in the regional planning and organization needed to provide education and training needed by ethics committees for these two tasks, within the constraints of realism, that is, that these are requirements that are primarily expected of the clinical community and the organizations that provide care to patients.


The neurochemical basis of the contextual interference effect.
Efficient practice organization maximizes learning outcome. Although randomization of practice as compared to blocked practice damages training performance, it boosts retention performance, an effect called contextual interference. Motor learning modulates the GABAergic (gamma-aminobutyric acid) system within the sensorimotor cortex (SM); however, it is unclear whether different practice regimes differentially modulate this system and whether this is impacted by aging. Young and older participants were trained on 3 variations of a visuomotor task over 3 days, following either blocked or random practice schedule and retested 6 days later. Using magnetic resonance spectroscopy, SM and occipital cortex GABA+ levels were measured before and after training during the first and last training days. We found that (1) behavioral data confirmed the contextual interference effects, (2) within-day occipital cortex GABA+ levels decreased in random and increased in blocked group. This effect was more pronounced in older adults; and (3) baseline SM GABA+ levels predicted initial performance. These findings indicate a differential modulation of GABA levels across practice groups that is amplified by aging.


Improving care of chronic pain patients with spinal cord stimulator therapy amidst the opioid epidemic.
The US government and other key stakeholders including professional medical bodies have amended recommendations in recent years to emphasize using no opioids or the lowest effective dose of opioids needed for treatment of chronic pain. However, there remains an unmet need for pain treatments that can both relieve the pain of patients and reduce the doses of opioids they require. The Center for Medicare and Medicaid Services (CMS) is currently considering such treatments through the SUPPORT ACT and has recently conferred with the Health and Human Services (HHS) Inter-agency Pain Management Task Force to consider such therapies. We reviewed literature evidence in PubMed on pain relief and opioid reduction following spinal cord stimulation (SCS) treatment. SCS presents an effective non-pharmacologic pain treatment modality that has been used for decades to reduce chronic pain from trauma or neuropathy and has been shown to either stabilize or reduce opioid use in some patients with painful conditions. A more recently developed high-frequency SCS modality, 10 kHz SCS, has the advantage of being paresthesia-independent. It has been shown to be associated with significant reductions in opioid consumption after stimulation therapy was initiated, and many patients even taking high doses of opioids (> 90 mg morphine equivalent dose per day) were able to reduce their opioid intake to levels associated with less risk. The evidence shows that reduction of opioids as early in the treatment process as possible is desirable to reduce patient risk and improve pain relief from stimulation therapy.


Public Views on Medicaid Work Requirements and Mandatory Premiums in Kentucky.
Federal and state policymakers continue to pursue work requirements and premiums as conditions of Medicaid participation. Opinion polling should distinguish between general policy preferences and specific views on quotas, penalties, and other elements. To identify views of adults in Kentucky regarding the design of Medicaid work requirements and premiums. A cross-sectional survey was conducted via telephone and the internet from June 27 through July 11, 2019, of 1203 Kentucky residents 9 months before the state intended to implement Medicaid work requirements and mandatory premiums. Statistical analysis was performed from October 2019 to August 2023. Agreement, disagreement, or neutral views on policy components were the main outcomes. Recruitment for the survey used statewide random-digit dialing and an internet panel to recruit residents aged 18 years or older. Findings were weighted to reflect state demographics. Of 39 110 landlines called, 209 reached an eligible person (of whom 150 participated), 8654 were of unknown eligibility, and 30 247 were ineligible. Of 55 305 cell phone lines called, 617 reached an eligible person (of whom 451 participated), 29 951 were of unknown eligibility, and 24 737 were ineligible. Internet recruitment (602 participants) used a panel of adult Kentucky residents maintained by an external data collector. Percentages were weighted to resemble the adult population of Kentucky residents. Of the participants in the study, 52% (95% CI, 48%-55%) were women, 80% (95% CI, 77%-82%) were younger than 65 years, 41% (95% CI, 38%-45%) were enrolled in Medicaid, 36% (95% CI, 32%-39%) were Republican voters, 32% (95% CI, 29%-36%) were Democratic voters, 14% (95% CI, 11%-16%) were members of racial and ethnic minority groups (including but not limited to American Indian or Alaska Native, Asian, Black, Hispanic or Latinx, and Native Hawaiian or Pacific Islander), and 48% (95% CI, 44%-52%) were employed. Most participants supported work requirements generally (69% [95% CI, 66%-72%]) but did not support terminating benefits due to noncompliance (43% [95% CI, 39%-46%]) or requiring quotas of 20 or more hours per week (34% [95% CI, 31%-38%]). Support for monthly premiums (34% [95% CI, 31%-38%]) and exclusion penalties for premium nonpayment (22% [95% CI, 19%-25%]) was limited. Medicaid enrollees were significantly less supportive of these policies than nonenrollees. For instance, regarding work requirements, agreement was lower (64% [95% CI, 59%-69%] vs 72% [95% CI, 68%-77%]) and disagreement higher (26% [95% CI, 21%-31%] vs 20% [95% CI, 16%-24%]) among current Medicaid enrollees compared with nonenrollees (P = .04). Among Medicaid enrollees, some beliefs about work requirements varied significantly by employment status but not by political affiliation. Among nonenrollees, beliefs about work requirements, premiums, and Medicaid varied significantly by political affiliation but not by employment. This study suggests that even when public constituencies express general support for Medicaid work requirements or premiums, they may oppose central design features, such as quotas and termination of benefits. Program participants may also hold significantly different beliefs than nonparticipants, which should be understood before policies are changed.


Retrospective study of perioperative cardiac arrest from a Chinese tertiary hospital.
Studies on perioperative cardiac arrest in Chinese hospitals have rarely been retrieved from international journals. This survey evaluated the incidence, causes, and outcomes of perioperative cardiac arrests in a Chinese tertiary general hospital between July 2013 and December 2020. The incidence of cardiac arrest within 24 hours of anesthesia administration was retrospectively identified using an anesthesia database in Liaocheng People's Hospital. During the study period, there were 118,152 anesthetics. Data collected included patient characteristics, surgical procedures (elective or emergency), American Society of Anesthesiologists (ASA) physical status score, type of surgery, anesthesia technique, and outcome. Cardiac arrests were grouped into one of 3 groups: totally anesthesia-related, partially anesthesia-related, or anesthesia-unrelated. In total, 41 cardiac arrests (3.5:10,000) and 26 deaths (2.2:10,000) were found. Major risk factors for cardiac arrest were children under 1 year, adults between 19 and 65 years, and the elderly (>80 years) (P < .001), male patients (P = .02), emergency surgery (P < .001), and ASA grade V patients without anesthesia (P = .009). There were 19 anesthesia-related cardiac arrests (1.6:10,000) - 2 were totally related, and 17 were partially related to anesthesia. There were 9 anesthesia-related deaths (0.8:10,000), all of which were partially related to anesthesia. Perioperative cardiac arrests were correlated with age, gender, ASA grade and surgical procedures. The 2 most important patient factors leading to cardiac arrest were hemorrhagic shock from trauma and septic shock, respectively.


Hybrid PbS Quantum Dot/Nanoporous NiO Film Nanostructure: Preparation, Characterization, and Application for a Self-Powered Cathodic Photoelectrochemical Biosensor.
This work reports the first preparation and characterization of a hybrid PbS quantum dot (QD)/nanoporous NiO film nanostructure as well as its application for novel self-powered cathodic photoelectrochemical (PEC) sensing. Specifically, we synthesized the thioglycolic acid-capped PbS QDs and then assembled them onto the hydrothermally fabricated three-dimensional (3D) NiO nanostructured films on the transparent indium tin oxide-coated glass substrates, followed by the subsequent conjugation with the glucose oxidase as a model biocatalyst. Favorable alignment existed between the NiO and PbS QDs, and the as-obtained p-type heterostructure was characterized by various techniques and found to have good PEC activities. In the self-powered PEC biosensing of glucose, the system exhibited high sensitivity toward the presence of dissolved oxygen in the electrolyte, and thereby, a novel PEC enzymatic sensor was developed. With a PbS QD/3D NiO nanofilm, this work manifested the great promise of a heterostructure photocathode for a self-powered PEC biosensor that to the best of our knowledge has not been reported. We believe that it could inspire more interest in the design and development of numerous other p-type heterostructures for advanced self-powered PEC biosensors.


Effectiveness of interventions aimed at reducing HIV acquisition and transmission among gay and bisexual men who have sex with men (GBMSM) in high income settings: A systematic review.
HIV transmission continues among gay and bisexual men who have sex with men (GBMSM), with those who are younger, or recent migrants, or of minority ethnicity or who are gender diverse remaining at increased risk. We aimed to identify and describe recent studies evaluating the effectiveness of HIV prevention interventions for GBMSM in high income countries. We searched ten electronic databases for randomized controlled trials (RCTs), conducted in high income settings, and published since 2013 to update a previous systematic review (Stromdahl et al, 2015). We predefined four outcome measures of interest: 1) HIV incidence 2) STI incidence 3) condomless anal intercourse (CLAI) (or measure of CLAI) and 4) number of sexual partners. We used the National Institute for Health and Care Excellence (UK) Quality Appraisal of Intervention Studies tool to assess the quality of papers included in the review. As the trials contained a range of effect measures (e.g. odds ratio, risk difference) comparing the arms in the RCTs, we converted them into standardized effect sizes (SES) with 95% confidence intervals (CI). We identified 39 original papers reporting 37 studies. Five intervention types were identified: one-to-one counselling (15 papers), group interventions (7 papers), online interventions (9 papers), Contingency Management for substance use (2 papers) and Pre-exposure Prophylaxis (PrEP) (6 papers). The quality of the studies was mixed with over a third of studies rated as high quality and 11% rated as poor quality. There was some evidence that one-to-one counselling, group interventions (4-10 participants per group) and online (individual) interventions could be effective for reducing HIV transmission risk behaviours such as condomless anal intercourse. PrEP was the only intervention that was consistently effective at reducing HIV incidence. Our systematic review of the recent evidence that we were able to analyse indicates that PrEP is the most effective intervention for reducing HIV acquisition among GBMSM. Targeted and culturally tailored behavioural interventions for sub-populations of GBMSM vulnerable to HIV infection and other STIs should also be considered, particularly for GBMSM who cannot access or decline to use PrEP.


Some immunochemical and chemical aspects of S and R Shigella dysenteriae 1 endotoxins.
Endotoxins of S and R forms of Shigella dysenteriae 1 were prepared by NaCl-Na citrate extraction, purified by gel chromatography on Sephadex G 200 and on Sepharose 4B and subjected to immunochemical and chemical analysis. The toxins contained 25--30% of lipids, 40--50% of carbohydrates and 14--24% of protein. The lipid and protein moieties of the lipopolysaccharide-protein complexes exhibited no significant difference, whereas the sugar moieties differed markedly (both qualitatively and quantitatively), in relation to the growth form of the culture. The lipid moiety, which consists at least of 22 fatty acids, has the greatest relative content (approx. 50%) of behenic acid, 22:0, and palmitic acid, 16:0 (approx. 11%). In the protein moiety, at least 16 amino acids were determined; these amino acids were identical in both endotoxin types, but their total content was higher in the R form, giving an R:S ratio of 1.7 +/- 0.2. The sugar moiety consists of galactose, glucosamine and either rhamnose (in S endotoxin) or aldoheptose (in R endotoxin). The difference of the chemical composition of the sugar moiety is believed to account for the diametric difference in the immunochemical character, in particular the different behaviour in the electric field, of both endotoxin types. The average content of 3-deoxy-D-manno-2-octulosonic acid was determined as 0.5% for both S and R endotoxin. Trace amounts of O-phosphorylethanolamine were found. Individual aspects of the chemical and immunochemical analysis are discussed in detail.


The Conjugated Double Bond of Coniferyl Aldehyde Is Essential for Heat Shock Factor 1 Mediated Cytotoprotection.
Coniferyl aldehyde (1) is previously reported as a potent inducer of heat shock factor 1 (HSF1). Here, we further examined the active pharmacophore of 1 for activation of HSF1 using the derivatives coniferyl alcohol (2), 4-hydroxy-3-methoxyphenylpropanal (3), and 4-hydroxy-3-methoxyphenylpropanol (4). Both 1 and 2 resulted in increased survival days after a lethal radiation (IR) dose. The decrease in bone marrow (BM) cellularity and Ki67-positive BM cells by IR was also significantly restored by 1 or 2 in mice. These results suggested that the vinyl moiety of 1 and 2 is necessary for inducing HSF1, which may be useful for developing small molecules for cytoprotection of normal cells against damage by cytotoxic drugs and radiation.


Hydrofluorination of Alkynes: From (E) to (Z).
The hydrofluorination of alkynes is an efficient synthetic route to monofluoroalkenes or difluoroalkanes. Both fluorinated motifs have found applications in medicinal chemistry and beyond. This review explores the recent advances in the hydrofluorination of diverse alkynes through various activation methods, from classical coinage metal catalysis to metal-free conditions. The range of alkynes goes from the simplest unactivated alkynes to activated ones (ynones and derivatives, ynamides, alkynyl sulfides and sulfones as much as haloalkynes). Regio- and stereoselective methods exists, but there is still room for improvement depending on the type of alkyne.


Chiral separation performance of micrometer-sized monodispersed silica spheres with high protein loading.
Micrometer-sized monodispersed silica spheres (approximately 360 microm) with high loading of bovine serum albumin (BSA) (approximately 450 mg/g) were prepared as an adsorbent for large-scale chiral separation. The new adsorbent was characterized with scanning electron microscopy (SEM), nitrogen adsorption-desorption isotherms, the mercury intrusion method, infrared spectroscopic analysis, and elementary analysis. The extent of chiral separation was tested with rac-tryptophan (rac-Trp) and rac-phenylalanine (rac-Phe) as solutes. The results showed that the absorbent exhibited a high surface area, large pore volume, and bimodal macromesoporous structures, enabling fast mass transfer and high separation efficiency. A fast adsorption rate, reaching equilibrium in less than 6 min, and a high degree of chiral separation, with the enantiomer excess (e.e.) value reaching as high as 100% in the first 10 min, was observed in a small (5 cm in height, 0.46 cm in internal diameter) packed column that could be regenerated with a pH 5.0 HAc-NaAc buffer. The results show that monodispersed silica spheres with a high BSA loading have great potential for applications in large-scale chiral separation processes.


Analysis by rotavirus gene 6 reverse transcriptase-polymerase chain reaction assay of rotavirus-positive gastroenteritis cases observed during the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST).
During the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST), the period between the administration of dose 1 through 13 days after the administration of dose 3, there were more wild-type rotavirus gastroenteritis (RVGE) cases among vaccine recipients compared with placebo recipients using the protocol-specified microbiological plaque assay in the clinical-efficacy cohort, a subset of subjects where vaccine efficacy against RVGE of any severity was assessed. In this study, a rotavirus genome segment 6-based reverse transcriptase-polymerase chain reaction assay was applied post hoc to clarify the accuracy of type categorization of all these RVGE cases in vaccine recipients during the vaccination phase of REST. The assay characterized 147 (90%) of 163 re-assayed RVGE cases or rotavirus-associated health care contacts as type-determinable: either wild-type or vaccine-type rotavirus strains. In the clinical-efficacy cohort (N = 5673), 19 (18.8%) of 101 samples from RVGE cases contained wild-type rotavirus, 70 (69.3%) vaccine virus, and 12 (11.9%) were indeterminable. In the large-scale cohort (N = 68,038), 10 (34.5%) of 29 samples from RVGE-related health care contacts contained wild-type rotavirus strains, 15 (51.7%) vaccine-type rotavirus strains, and 4 (13.8%) were indeterminable. Of the 33 samples from RVGE cases in placebo recipients, all were confirmed to contain wild-type rotaviruses. Altogether, this post-hoc re-evaluation showed that the majority (75%) of type-determinable RVGE cases or health care contacts that occurred during the vaccination phase of REST in vaccine recipients were associated with vaccine-type rotavirus strains rather than wild-type rotavirus strains.


Independent premotor encoding of the sequence and structure of birdsong in avian cortex.
How the brain coordinates rapid sequences of learned behavior, such as human speech, remains a fundamental problem in neuroscience. Birdsong is a model of such behavior, which is learned and controlled by a neural circuit that spans avian cortex, basal ganglia, and thalamus. The songs of adult male zebra finches (Taeniopygia guttata), produced as rapid sequences of vocal gestures (syllables), are encoded by the cortical premotor region HVC (proper name). While the motor encoding of song within HVC has traditionally been viewed as unitary and distributed, we used an ablation technique to ask whether the sequence and structure of song are processed independently within HVC. Results revealed a functional topography across the medial-lateral axis of HVC. Bilateral ablation of medial HVC induced a positive disruption of song (increase in atypical syllable sequences), whereas bilateral ablation of lateral HVC induced a negative disruption (omission of individual syllables). Bilateral ablation of central HVC either had no effect on song or induced syllable omission, similar to lateral HVC ablation. We then investigated HVC connectivity and found parallel afferent and efferent pathways that transit medial and lateral HVC and converge at vocal motor cortex. In light of recent evidence that syntactic and lexical components of human speech are processed independently by neighboring regions of cortex (Menenti et al., 2012), our demonstration of anatomically distinct pathways that differentially process the sequence and structure of birdsong in parallel suggests that the vertebrate brain relies on a common approach to encode rapid sequences of vocal gestures.


Hepatitis B virus RNA is measurable in serum and can be a new marker for monitoring lamivudine therapy.
Changes in the serum hepatitis B virus (HBV) RNA level during lamivudine therapy were compared to those in the serum HBV DNA and HBV core-related antigen (HBVcrAg) levels in 24 patients with chronic hepatitis B. For measurement of HBV RNA, total nucleic acid was extracted from serum samples and treated with RNase-free DNase I. After cDNA synthesis from extracted RNA, HBV RNA was measured by real-time detection polymerase chain reaction. The peak fraction of HBV RNA in serum samples was consistent with peak fractions of HBV DNA and HBV core protein in a sucrose gradient analysis, indicating that HBV RNA was incorporated into virus particles. All levels of HBV DNA, HBV RNA, and HBVcrAg decreased gradually during lamivudine therapy (P < 0.001 for all). The amount of decrease from the start of lamivudine therapy was significantly higher for HBV DNA than for HBV RNA or HBVcrAg during 6 months of lamivudine therapy (P < 0.001 for all). However, a similar difference was not seen between HBV RNA and HBVcrAg levels during that period. The HBV RNA level was significantly correlated (P < 0.001 for all) with levels of HBV DNA and HBVcrAg both at the beginning and 2 months after the start of lamivudine therapy. HBV RNA is detectable in serum in a form indicating incorporation into virus particles, and its serum level might serve as a new viral marker with a significance different from that of HBV DNA in lamivudine therapy.


Compatibilization of All-Conjugated Polymer Blends for Organic Photovoltaics.
Compatibilization of an immiscible binary blend comprising a conjugated electron donor and a conjugated electron acceptor polymer with suitable electronic properties upon addition of a block copolymer (BCP) composed of the same building blocks is demonstrated. Efficient compatibilization during melt-annealing is feasible when the two polymers are immiscible in the melt, i.e. above the melting point of ∼250 °C of the semicrystalline donor polymer P3HT. To generate immiscibility at these high temperatures, the acceptor polymer PCDTBT is equipped with fluorinated side chains leading to an increased Flory-Huggins interaction parameter. Compatibilization in bulk and thin films is demonstrated, showing that the photovoltaic performance of pristine microphase separated and nanostructured BCPs can also be obtained for compatibilized blend films containing low contents of 10-20 wt % BCP. Thermodynamically stable domain sizes range between several tens of microns for pure blends and ∼10 nm for pure block copolymers. In addition to controlling domain size, the amount of block copolymer added dictates the ratio of edge-on and face-on P3HT crystals, with compatibilized films showing an increasing amount of face-on P3HT crystals with increasing amount of compatibilizer. This study demonstrates the prerequisites and benefits of compatibilizing all-conjugated semicrystalline polymer blends for organic photovoltaics.


Development and characterization of a novel fluorescent indicator protein PMCA4-GCaMP2 in cardiomyocytes.
Isoform 4 of the plasma membrane calcium/calmodulin dependent ATPase (PMCA4) has recently emerged as an important regulator of several key pathophysiological processes in the heart, such as contractility and hypertrophy. However, direct monitoring of PMCA4 activity and assessment of calcium dynamics in its vicinity in cardiomyocytes are difficult due to the lack of molecular tools. In this study, we developed novel calcium fluorescent indicators by fusing the GCaMP2 calcium sensor to the N-terminus of PMCA4 to generate the PMCA4-GCaMP2 fusion molecule. We also identified a novel specific inhibitor of PMCA4, which might be useful for studying the role of this molecule in cardiomyocytes and other cell types. Using an adenoviral system we successfully expressed PMCA4-GCaMP2 in both neonatal and adult rat cardiomyocytes. This fusion molecule was correctly targeted to the plasma membrane and co-localised with caveolin-3. It could monitor signal oscillations in electrically stimulated cardiomyocytes. The PMCA4-GCaMP2 generated a higher signal amplitude and faster signal decay rate compared to a mutant inactive PMCA4(mut)GCaMP2 fusion protein, in electrically stimulated neonatal and adult rat cardiomyocytes. A small molecule library screen enabled us to identify a novel selective inhibitor for PMCA4, which we found to reduce signal amplitude of PMCA4-GCaMP2 and prolong the time of signal decay (Tau) to a level comparable with the signal generated by PMCA4(mut)GCaMP2. In addition, PMCA4-GCaMP2 but not the mutant form produced an enhanced signal in response to β-adrenergic stimulation. Together, the PMCA4-GCaMP2 and PMCA4(mut)GCaMP2 demonstrate calcium dynamics in the vicinity of the pump under active or inactive conditions, respectively. In summary, the PMCA4-GCaMP2 together with the novel specific inhibitor provides new means with which to monitor calcium dynamics in the vicinity of a calcium transporter in cardiomyocytes and may become a useful tool to further study the biological functions of PMCA4. In addition, similar approaches could be useful for studying the activity of other calcium transporters during excitation-contraction coupling in the heart.


Antigenic divergence between Bordetella pertussis clinical isolates from Moscow, Russia, and vaccine strains.
We analyzed temporal changes in the frequencies of the ptxA, prn, fim2, and fim3 alleles in Bordetella pertussis strains isolated from pertussis patients in Moscow, Russia, from 1948 to 2004. The three strains used for the whole-cell vaccine harbored the alleles ptxA2, ptxA4, prn1, fim2-1, and fim3A. Vaccine-type alleles of ptxA (ptxA2 and ptxA4) were characteristic for all prevaccination strains and for 96% of the strains isolated in the 1960s and 1970s. At the beginning of the 1970s, ptxA2 and ptxA4 were replaced by the ptxA1 allele. In the 1980s and to the present, strains with ptxA1 were predominant in the B. pertussis population. All prevaccination strains harbored the prn1 allele, which corresponds to the vaccine-type allele. In subsequent years, the proportion of strains with the prn1 allele decreased and the proportion of prn3 and prn2 strains increased. From 2002 to 2004 strains with prn2 or prn3 were predominant in the B. pertussis population. The vaccine-type alleles fim2-1 and fim3A were found in all prevaccination strains and in 92% of the strains isolated from 1960 to 1989. The fim2-2 and fim3B alleles were first observed at the beginning of the 1980s. In subsequent years, these strains became predominant. Together with waning immunity, the antigenic divergence between vaccine strains and clinical isolates observed in the Moscow area may explain the persistence of pertussis, despite the high rates of vaccine coverage. The results demonstrate that the selection of B. pertussis strains for vaccine manufacturing must be based on a thorough study of the B. pertussis population.


Phenoxazinone synthetase from Streptomyces antibioticus: multiple activities of the enzyme.
A procedure for the preparation of relatively large quantities of highly purified phenoxazinone synthetase from Streptomyces antibioticus is described. Enzyme preparations consisted of multiple forms, as determined by polyacrylamide gel electrophoresis. Each of the electrophoretically separable forms catalyzed the oxidation of catechols, ferrocyanide, and ethylenic thiols, in addition to o-aminophenols.


Progress Toward Measles Elimination - Bangladesh, 2000-2016.
In 2013, at the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR), a regional goal was established to eliminate measles and control rubella and congenital rubella syndrome* by 2020 (1). WHO-recommended measles elimination strategies in SEAR countries include 1) achieving and maintaining ≥95% coverage with 2 doses of measles-containing vaccine (MCV) in every district, delivered through the routine immunization program or through supplementary immunization activities (SIAs)†; 2) developing and sustaining a sensitive and timely measles case-based surveillance system that meets targets for recommended performance indicators; and 3) developing and maintaining an accredited measles laboratory network (2). In 2014, Bangladesh, one of 11 countries in SEAR, adopted a national goal for measles elimination by 2018 (2,3). This report describes progress and challenges toward measles elimination in Bangladesh during 2000-2016. Estimated coverage with the first MCV dose (MCV1) increased from 74% in 2000 to 94% in 2016. The second MCV dose (MCV2) was introduced in 2012, and MCV2 coverage increased from 35% in 2013 to 93% in 2016. During 2000-2016, approximately 108.9 million children received MCV during three nationwide SIAs conducted in phases. During 2000-2016, reported confirmed measles incidence decreased 82%, from 34.2 to 6.1 per million population. However, in 2016, 56% of districts did not meet the surveillance performance target of ≥2 discarded nonmeasles, nonrubella cases§ per 100,000 population. Additional measures that include increasing MCV1 and MCV2 coverage to ≥95% in all districts with additional strategies for hard-to-reach populations, increasing sensitivity of measles case-based surveillance, and ensuring timely transport of specimens to the national laboratory will help achieve measles elimination.


A Visit to the Pediatrician as a Part of Comprehensive Prenatal Care?
The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists recommend that expectant parents receive a preventive visit with a pediatrician in the prenatal period (a pediatric prenatal visit, or PPV). Discussing newborn health topics in the prenatal period tends to be more effective than immediately postpartum, and research suggests, for example, that the PPV increases timely childhood immunizations. However, only 22% of expectant parents have these visits, and there are significant disparities by race and income. A 2-min online survey with open-ended questions was emailed to 304 eligible obstetrics providers in Rochester, NY. Simple descriptive statistics and chisquare analysis were applied to survey responses. Responses were organized within the framework of knowledge, attitudes, and practices to identify barriers to guideline adherence resulting in chronic under-utilization of the PPV. Ninety obstetric providers completed the survey. 66 reported awareness of the PPV, and 45 reported referring patients for a PPV. However, in open-ended questions, respondents expressed confusion between the PPV and a "meet and greet" visit with a pediatrician. Some respondents believed that the PPV is not covered by insurance, even though these visits are covered by Medicaid and marketplace insurance. Providers who had personally received one as a parent expressed positive attitudes. These findings indicate that unfamiliarity with the PPV is one barrier to referral. Educating providers about the guideline recommendations, evidence base, and insurance coverage could overcome this barrier. Doing so could reduce disparities in utilization of the pediatric prenatal visit.


Stroke 20 20: Implementation goals for intravenous thrombolysis.
Knowledge of the implementation gap would facilitate the use of intravenous thrombolysis in stroke, which is still low in many countries. The study was conducted to identify national implementation targets for the utilisation and logistics of intravenous thrombolysis. Multicomponent interventions by stakeholders in health care to optimise prehospital and hospital management with the goal of fast and accessible intravenous thrombolysis for every candidate. Implementation results were documented from prospectively collected cases in all 45 stroke centres nationally. The thrombolytic rate was calculated from the total number of all ischemic strokes in the population of the Czech Republic since 2004. Thrombolytic rates of 1.3 (95%CI 1.1 to 1.4), 5.4 (95%CI 5.1 to 5.7), 13.6 (95%CI 13.1 to 14.0), 23.3 (95%CI 22.8 to 23.9), and 23.5% (95%CI 23.0 to 24.1%) were achieved in 2005, 2009, 2014, 2017, and 2018, respectively. National median door-to-needle times were 60-70 minutes before 2012 and then decreased progressively every year to 25 minutes (IQR 17 to 36) in 2018. In 2018, 33% of both university and non-university hospitals achieved median door-to-needle time ≤20 minutes. In 2018, door-to-needle times ≤20, ≤45, and ≤60 minutes were achieved in 39, 85, and 93% of patients. Thrombolysis can be provided to ≥ 20% of all ischemic strokes nationwide and it is realistic to achieve median door-to-needle time 20 minutes. Stroke 20-20 could serve as national implementation target for intravenous thrombolysis and country specific implementation policies should be applied to achieve such target.


Fasudil reduces monocrotaline-induced pulmonary arterial hypertension: comparison with bosentan and sildenafil.
Pulmonary arterial hypertension (PAH) still cannot be cured, warranting the search for novel treatments. Fasudil (a Rho kinase inhibitor) was compared with bosentan (an endothelin receptor blocker) and sildenafil (a phosphodiesterase 5 inhibitor), with emphasis on right ventricular (RV) function, in a reversal rat model of monocrotaline (MCT)-induced PAH. In addition, the effects of combining bosentan or sildenafil with fasudil were studied. MCT (40 mg·kg body weight(-1)) induced clear PAH in male Wistar rats (n = 9). After 28 days, echocardiography, RV catheterisation and histochemistry showed that cardiac frequency, stroke volume and RV contractility had deteriorated, accompanied by RV dilatation and hypertrophy, and marked pulmonary arterial wall thickening. Mean pulmonary arterial pressure and pulmonary vascular resistance increased significantly compared to healthy rats (n = 9). After 14 days, MCT-treated rats received a 14-day oral treatment with bosentan, sildenafil, fasudil or a combination of fasudil with either bosentan or sildenafil (all n = 9). All treatments preserved cardiac frequency, stroke volume and RV contractility, and reduced pulmonary vascular resistance and RV dilatation. Fasudil lowered RV systolic pressure and mean pulmonary arterial pressure significantly, by reducing pulmonary arterial remodelling, which reduced RV hypertrophy. Combining bosentan or sildenafil with fasudil had no synergistic effect. Fasudil significantly improved PAH, to a greater degree than did bosentan and sildenafil.


A novel high-yield volume-reduction method for the cryopreservation of UC blood units.
For the application of umbilical cord blood (UCB) units as hematopoietic grafts, a dose of 3.7 x 10(7) nucleated cells (NC)/kg body weight is required. NC can be lost during volume-reduction processing and during thawing. A novel modification of the double-processing protocol with the aim of minimizing NC loss is described and evaluated. One-hundred and fifty UCB were collected. The volume was reduced by a centrifugation step following double-processing in the presence of 2% HES 200/0.5. Pre- and post-processing cell counts and platelet parameters were measured with an automatic counter. The number of viable CD34+ hemopoietic stem cells was measured by flow cytometry. In 25 of the samples, colony-forming units (CFU) were also determined. The same samples were thawed 6 months after cryopreservation and re-evaluated. The volume was reduced to 6 +/- 1.5 mL. The recovery of NC, MNC, CD34+ hemopoietic stem cells, RBC depletion and CFU following double-processing was 93.6 +/- 3.2%, 95.8 +/- 2.2%, 98.4 +/- 1.5%, 96.8 +/- 1.1% and 107.1 +/- 6.1% (for 25 samples), respectively. The post-thaw recoveries of NC, MNC, CD34+ hemopoietic stem cells and CFU (for 25 samples) were 78.6 +/- 5.4%, 90.8 +/- 4.4%, 96.4 +/- 2.5%, 89.1 +/- 4.1%, respectively. No post-thaw cell aggregation was observed. A significant (P<0.05) post-thaw loss of platelets and signs of platelet activation was observed. The protocol uses non-expensive equipment and clinically approved materials and results in samples that can be used in patients with a mean weight of 32.7 kg.


Relapse after allogeneic bone marrow transplantation for Philadelphia chromosome positive chronic myeloid leukemia: cytogenetic analysis of 24 patients.
One hundred patients with chronic myeloid leukemia (CML) submitted to bone marrow transplantation (BMT) were included in a cooperative cytogenetic study. Relapse (defined on the basis of hematological and cytogenetic findings) occurred in 24 (24%) patients at different intervals after BMT. In 18 of these patients (studied on average 3.3 times between BMT and relapse) no Ph-positive metaphases were detected before relapse. Sixteen (75%) of the patients relapsed with the same chromosomal pattern as that seen before BMT; eight patients, of whom five relapsed in blast crisis, showed additional chromosomal abnormalities resembling those seen in non-transplanted patients. One of these patients relapsed in cells of donor origin. After recognition of relapse, various hematological and cytogenetic patterns were observed. Four patients showed spontaneous reversion to normal (donor-type) chromosomes and hematology. Two other patients were followed for prolonged periods with hypercellular marrows with more than 50% Ph-positive cells but with normal peripheral blood values. The majority of patients proceeded to clinical relapse and required treatment with chemotherapy. We conclude that the isolated finding of a minority of Ph-positive metaphases after BMT should not be classified as relapse; for patients who do relapse, the sequence of cytogenetic and hematological events thereafter is variable.


Inhibitory control and verb inflection in Italian preschool children.
The study investigates whether Italian verbal inflectional morphology is associated with inhibitory control skills after controlling for receptive vocabulary and verbal working memory. A sample of Italian preschoolers aged 4;0 to 6;0 was assessed using a standardized inhibitory control task tapping two different inhibitory skills (response inhibition and interference suppression), and a morphological task requiring simple and complex inflections of verbs. The hierarchical multiple regression analyses showed that working memory and the interference suppression scores were significantly associated with complex inflections but not with simple inflections of the verbs.


The Effect of Metabolic Syndrome on the Outcome of Hepatitis B-Associated Hepatocellular Carcinoma Patients After Hepatectomy: A Multicenter Study.
With changes in dietary patterns and modern lifestyles, the prevalence of metabolic syndrome (MetS) in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients is increasing. The purpose of our study is to explore the impact of MetS on the prognosis of HBV-associated HCC patients following radical hepatectomy. Data on consecutive HCC patients who underwent radical hepatectomy were prospectively obtained and retrospectively analyzed from seven medical centers in west areas of China. Propensity score matching (PSM) analysis was conducted to balance the heterogeneity between MetS-HBV-HCC group and HBV-HCC group. Surgical outcomes have been contrasted between the two groups. In 984 patients, 179 (18.19%) were diagnosed with MetS. Patients in the MetS-HBV-HCC group had higher CCI score (8.7 [0.0, 12.2] vs. 0.0 [0.0, 8.7], p = 0.048) and a higher rate of severe complications (Clavien-Dindo ≥3, 7.82% vs. 4.10%, p = 0.035), to be more precise: postoperative liver failure, hydrothorax, and hyperglycemia. Patients in the MetS-HBV-HCC group tended to have worse 5-year overall survival (OS) rate (61.45% vs. 69.94%, p = 0.027) and recurrence-free survival (RFS) rate (62.57% vs. 53.66%, p = 0.030), consistent with the results of the competing risk models. Last, MetS was identified to be an independent unfavorable prognostic factor in the multivariate analysis. The involvement of MetS increased the risk of postoperative complications and worsens the overall survival and recurrence-free survival time, reminding us to be more prudent to face metabolic disorder among tumor patients.


Situational factors associated with road traffic crashes: a case-control study on the Yaoundé-Douala road section, Cameroon.
Our aim was to identify situational factors associated with road traffic crash sites on a heavy traffic 243 km road section in Cameroon. We conducted a case-control study on Yaounde-Douala road section. Cases were sites where an injury crash was reported to one of the 13 police stations on this road section over a period from 2004 to 2007. Control sites were randomly selected on same road section where no crash was reported. A total of 474 crash sites and 509 control sites were included. Results showed statistically significant associations with injury crash risk for flat road profile (adjusted odds ratio (aOR) = 1.52, 95% confidence interval (CI) = 1.15-2.01), irregular road surface conditions (aOR = 1.43, 95% CI = 1.04-1.99), roadside obstacle situated less than 4 m from the road edge (aOR = 1.99, 95% CI = 1.09-3.63), three-legged intersections (aOR = 3.11, 95% CI = 1.15-8.39) and four-legged intersections (aOR = 3.23, 95% CI = 1.15-6.92). Built-up areas were significantly associated with injury crash sites where verge depth was 0 m (aOR = 2.33; 95% CI = 1.97-2.77). Our results suggest that traffic calming and speed enforcement measures in built-up areas, intersections and on flat sections of this road should be strongly encouraged.


The aging of the red blood cell. A multifactor process.
Red blood cell (rbc) senescence is associated with loss of surface sialic acid, which is the principal carrier of surface negative charge and determines the electrokinetic behavior of old rbcs. Loss of sialic acid in an old rbc is demonstrated in its decreased electric mobility and lower negative charge density, determined topographically with cationic particle labeling. Surface sialic acid determines also the mutual attraction--repulsion forces, as demonstrated in enhanced aggluinability with cationic molecules, lectins, and blood group antibodies. Loss of sialic acid accompanies ATP-depletion in vitro; thus, a T-antigen site is unmasked. Macrophages have specific receptors to the site as to newly exposed galactose and N-acetyl galactosamine sugars. Furthermore, the involvement of complement molecules in the recognition of old RBCs by macrophages has been shown. This is possibly due to loss of sialic acid or at least a regrouping--relocation of surface anionic sites due to cell shape changes from discocytes to crenated forms, which accompany both in vivo and in vitro rbc aging. In turn, shape changes are apparently controlled by the cytoskeletal network underlying the rbc membrane, which undergoes structural alteration with physiologic aging in changing the dimensions of oligomeric spectrin and the thickness of the spectrin-actin cytoskeletal assembly.


Genetic markers of children asthma: predisposition to disease course variants.
Asthma is a heterogeneous and often difficult to treat condition that results in a disproportionate cost to healthcare systems. Children with severe asthma are at increased risk for adverse outcomes including medication-related side effects, life-threatening exacerbations, and impaired quality of life. An important therapeutic focus is to achieve disease control, which is supposed to involve a personalized approach to treatment of asthma of any severity. Asthma is a multifactorial disease with a significant genetic determinant, however, the inheritance of asthma has not been fully elucidated. Polymorphic genes of inflammatory mediators, including cytokines, play an important role in developing various disease forms. In the current study, large-scale original data on the prevalence of cytokine gene genotypes (IL2, IL4, IL5, IL6, IL10, IL12, IL13, IL17A, IL31, IL33, IFNG, TNFA) among Russian children with asthma in Krasnoyarsk region have been obtained. Genotyping was carried out using real-time PCR. We identified markers predisposing to the development of different variants of the course of childhood asthma: the CT genotype and T allele of IL4 rs2243250 are associated with asthma (p < 0.05), especially in mild asthma and in controlled asthma. The TT genotype and allele T of IL13 rs1800925 are associated with severe and uncontrolled asthma (p < 0.05). The AA genotype of IL17A rs2275913, the TT genotype of IFNG rs2069705 and allelic A variants of TNFA rs1800629 are associated with mild asthma, and the TT genotype of IFNG rs2069705 is additionally associated with controlled asthma. The results obtained will supplement information on the prevalence of polymorphic variants of the cytokine genes in the Russian population and in asthma patients with different disease courses, which is likely to be used in order to shape a plan for Public Health Authority to prevent the development of severe uncontrolled asthma and to optimize personalized therapy.


In Vivo Survival of Mesenchymal Stromal Cell-Enhanced Decellularized Nerve Grafts for Segmental Peripheral Nerve Reconstruction.
Adipose-derived mesenchymal stromal cells (MSCs) have emerged as promising tools for peripheral nerve reconstruction. There is a paucity of information regarding the ultimate survivorship of implanted MSCs or whether these cells remain where they are placed. The aim of the present study was to track the in vivo distribution and survival of MSCs seeded on a decellularized nerve allograft reconstruction of a peripheral nerve defect using luciferase-based bioluminescence imaging (BLI). To determine the in vivo survivability of MSCs, autologous Lewis rat MSCs were stably labeled with luciferase by lentiviral particles. Labeled cells were dynamically seeded onto a Sprague Dawley decellularized rat nerve allograft and used to bridge a 10-mm sciatic nerve defect. The MSC survival was determined by performing in vivo BLI to detect living cells. Twelve animals were examined at 24 hours after implantation, 3, 7, 9, 11, and 14 days, and at daily intervals thereafter if signals were still present. Labeled MSCs could be detected for up to 29 days. Gradually diminishing BLI signals were observed within the first week following implantation. Implanted MSCs were not detected anywhere other than the site of surgery. The MSCs seeded on decellularized nerve allografts can survive in vivo but have finite survival after implantation. There was no evidence of migration of MSCs to surrounding tissues. The findings support a therapeutic approach that combines MSCs with a biological scaffold for peripheral nerve surgery. It provides understanding of the viability and distribution of implanted MSCs, which is a prerequisite before clinical translation can be considered.


Isolation of S9 fractions from mouse and rat with increased enzyme activities after repeated administration of cytochrome P-450 and P-448 inducers.
Cytochrome P-450 (cyt P-450), NADPH cytochrome P-450 reductase and various microsomal monooxygenase activities [e.g. aminopyrine N-demethylase, p-nitroanisole O-demethylase, dinemorphan N-demethylase, ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase (ERD)], were determined in hepatic post-mitochondrial supernatant from mice and rats. Experiments were performed on male and female animals treated with a combination of sodium phenobarbital and beta-naphthoflavone according to the standard protocol schedule for short-term genotoxicity testing. A second inductive treatment after 2, 3, 4 or 5 weeks was provided. The increase in cyt P-450 and in all enzymatic activities measured was enhanced in both species by a second induction treatment, particularly when given after 4 weeks. ERD activity was the only monooxygenase activity which was sex-dependent, being more active in female than in male animals. To extend the biochemical data, experiments were performed with the proposed S9 fractions on styrene, which previously has proved difficult to detect in short-term in vitro mutagenicity tests. Using the new induction conditions positive results were obtained with the D7 strain of Saccharomyces cerevisiae. It was concluded that a simple pre-induction of the animals 3-4 weeks before the main induction treatment leads to a more active S9 fraction for in vitro genotoxicity studies.


Students' performance in accounting: differential effect of field dependence-independence as a learning style.
This study examined the differential moderating effects associated with field dependence-independence and perceptions of stress on students' performance after controlling for SAT Mathematics and Verbal scores as well as students' actual effort on homework. The average performance of 178 third-year accounting majors over three examinations was used to evaluate their understanding of financial accounting. The students also took the Group Embedded Figures Test. While the data indicate that the most significant variables were students' effort, SAT Verbal scores, and their perceptions of stress, these variables were differentially associated with students' performance depending upon whether the student was classified as a field-independent or field-dependent learner.


LSD1: biologic roles and therapeutic targeting.
LSD1 (KDM1A; BHC110; AOF2) was the first protein reported to exhibit histone demethylase activity and has since been shown to have multiple essential roles in mammalian biology. Given its enzymatic activity and its high-level expression in many human malignancies, a significant recent focus has been the development of pharmacologic inhibitors. Here we summarize structural and biochemical knowledge of this important epigenetic regulator, with a particular emphasis on the functional and preclinical studies in oncology that have provided justification for the evaluation of tranylcypromine derivative LSD1 inhibitors in early phase clinical trials.


Monitoring mycophenolic acid.
The immunosuppressive agent mycophenolate mofetil is a prodrug for the active compound mycophenolic acid. Following organ transplantation, it is used mostly in combination with other immunosuppressive drugs, but it has also been used as primary therapy. Although in the pivotal clinical studies the drug was given in fixed doses, there has been substantial interest in the measurement of mycophenolic acid in plasma as a guide to optimizing therapy. Data have emerged which indicate that the metabolism of the compound is more complex than was originally thought and that variability in exposure to the drug, assessed by area under the time-concentration curve, is an important determinant of efficacy. This article highlights basic pharmacokinetic and pharmacodynamic data for mycophenolic acid, which underlie the rationale for its measurement. These data are then set in the context of providing a routine service for the measurement of the drug with either of the analytical techniques currently available--immunoassay or high-performance liquid chromatography. There are a number of issues regarding the clinical interpretation of mycophenolic acid measurements which are yet to be resolved. Centres contemplating the introduction of such a service will need to keep abreast of a rapidly evolving literature.


Treatment modalities for surgical management of anterior palatal fistula: Comparison of various techniques, their outcomes, and the factors governing treatment plan: A retrospective study.
Aim of this retrospective study was to access the various surgical treatment options available for repair of Anterior palatal fistula depending upon their size and presenting age, and also to anticipate the treatment outcome. The series include study report of forty patients with secondary anterior palatal fistula post cleft palate repair, reported in a single unit during a duration of 3 years. All the cases were managed surgically under general anesthesia. The patients were classified depending upon the location of anterior palatal fistula (APF), the quality of tissue and age of patients to chalk out a justified treatment option outlay. Forty cases were split for surgical correction into various options depending on their size, site, and quality of the tissue. Most of the cases were operated with a Bardach's Redo for fistula closure (n = 16) (40%) and crevicular flap technique (n = 13) (32.5%). Our overall success (satisfactory results) was 77.5% as observed in 31 out of 40 cases with individual success rates for Bardach's and crevicular being 75% and 77%, respectively. There was reduction in size of fistula in three cases (7.5%) and a remnant pinpoint hole in four cases (10%) among all the operated cases. Management of post palatoplasty fistulas of the hard palate presents a challenging situation for a clinician following the surgical correction of cleft palate. Current paper describes the diagnosis and clinical management of forty cases reporting with unilateral APF following cleft palate surgery, over 3 years. Authors have attempted to propose different treatment modalities for surgical management of unilateral APF. It was concluded in the primary review that the size of fistula was irrelevant in determining the clinical outcome. Instead, the quality and condition of the adjacent tissue appear to be the major governing factors for selecting treatment modality as well as the surgical consequences.


Educational Inequalities in Self-Rated Health in Europe and South Korea.
While numerous comparative works on the magnitude of health inequalities in Europe have been conducted, there is a paucity of research that encompasses non-European nations such as Asian countries. This study was conducted to compare Europe and Korea in terms of educational health inequalities, with poor self-rated health (SRH) as the outcome variable. The European Union Statistics on Income and Living Conditions and the Korea National Health and Nutrition Examination Survey in 2017 were used (31 countries). Adult men and women aged 20+ years were included (207,245 men and 238,007 women). The age-standardized, sex-specific prevalence of poor SRH by educational level was computed. The slope index of inequality (SII) and relative index of inequality (RII) were calculated. The prevalence of poor SRH was higher in Korea than in other countries for both low/middle- and highly educated individuals. Among highly educated Koreans, the proportion of less healthy women was higher than that of less healthy men. Korea's SII was the highest for men (15.7%) and the ninth-highest for women (10.4%). In contrast, Korea's RII was the third-lowest for men (3.27), and the lowest among women (1.98). This high-SII-low-RII mix seems to have been generated by the high level of baseline poor SRH.


REINFORCEMENT: A NEW PERSPECTIVE ON AN OLD CONTROVERSY.
A critical component of the reinforcement model, incomplete postzygotic reproductive isolation, has been overlooked in the many selection experiments designed to test this model. Many field observations are consistent with the reinforcement model, but theoretical work predicts that reinforcement should only work when nearly complete postzygotic reproductive isolation has developed. The experiments described here used four levels of postzygotic reproductive isolation: complete, strong, moderate, and none. A significant decrease in heterotypic matings occurred over 25 generations in the complete postzygotic reproductive isolation treatment. No evidence for reinforcement was found in any of the other treatments using incomplete postzygotic reproductive isolation.


Impact of early rise of intraocular pressure on visual outcome following diabetic vitrectomy.
The objective was to study the incidence and risk factors for an early rise in intraocular pressure (IOP) following pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) and to correlate its impact on visual outcome. This was a longitudinal prospective study. IOP and best corrected visual acuity (BCVA) for 73 cases of PDR (52 males and 21 females) who underwent PPV were recorded at day 1, week 1, and months 1, 3, and 6. Risk factors for the early IOP rise, defined as IOP ≥ 30 mmHg at day 1, were evaluated using cross-tabulation and the t-test. Mean IOP at day 1 was 21.8 ± 9.8 mmHg with 15 cases (20.5%) having an early rise in IOP. Risk factors for the early IOP rise included intraoperative fibrovascular frond removal (P = 0.003), lens removal (P = 0.043), and intraoperative vitreous bleed (P = 0.008). The early rise in IOP was also associated with consistently raised IOP (P = 0.02), defined as IOP > 21 mmHg during first three consecutive follow-up visits. Further, difference in BCVA at 6 months among the two groups, i.e., with and without an early IOP rise was statistically significant (3.11 ± 1.52 logMAR vs. 2.11 ± 1.49 logMAR; P = 0.025). An early rise in IOP is a significant risk factor which compromises the visual outcome of patients undergoing diabetic vitrectomy.


Inverting the power dynamic: The process of first sessions of psychotherapy with therapists of color and non-Latino white patients.
The present study is the first to apply Trawalter, Richeson, and Shelton's (2009) stress and coping framework to qualitatively examine interracial interactions in initial sessions of psychotherapy. The sample included 22 dyads: 15 therapists of color administering various treatment modalities to 15 treatment-seeking non-Latino White (NLW) patients and a comparison group of 7 intraracial (NLW-NLW) dyads. In Phase 1, videorecordings of the first session of treatment were analyzed using inductive thematic analysis (TA) to describe patient and therapist behaviors. In Phase 2, a deductive TA approach was used to interpret and cluster those dyadic behaviors according to Trawalter et al.'s (2009) framework. NLW patients paired with therapists of color made more efforts to bridge differences and more often questioned the therapist's professional qualifications compared with those matched with NLW therapists. Therapists of color made more self-disclosures than NLW therapists and maintained a more formal stance, compared with NLW therapists. The deductive TA operationalized 4 of Trawalter and colleagues' (2009) coping responses within a therapeutic framework. Findings highlight the ability of therapists' of color to engage positively with their NLW patients even in the face of challenges to their expertise and credibility. (PsycINFO Database Record


A Surgeon Scorecard Is Associated with Improved Value in Elective Primary Hip and Knee Arthroplasty.
Despite increasing interest in total joint arthroplasty registries, evidence of the impact of physician-level performance on the value of care provided to patients undergoing hip and knee arthroplasty is lacking. The purpose of this study was to examine the effectiveness of an unblinded orthopaedic surgeon-specific value scorecard in improving patient outcomes and reducing hospital costs. We retrospectively analyzed patient outcomes and hospital costs associated with total joint arthroplasties before and 9 months after the introduction of a Surgeon Value Scorecard at an urban tertiary care center. From August 2016 to May 2017, orthopaedic surgeons received an unblinded monthly Surgeon Value Scorecard summarizing a rolling 6-month view of results by surgeon for patients attributed to Diagnosis Related Group 470 (major lower-extremity arthroplasty without comorbidity or complication). Prior to implementation, surgeons were educated on the scorecard and participated in the development of a document outlining the definition and calculation of included metrics. Scorecard metrics were grouped into 5 categories: patient demographic characteristics, patient outcomes (for example, length of stay, discharge disposition, readmissions), patient experience, financial, and operational (for example, operative times). Financial (cost) measures and patient outcomes were selected as the key performance indicators analyzed in this study. Continuous variables were analyzed using the t test when a normal distribution was assumed and using Mann-Whitney tests when a non-normal distribution was assumed. Categorical variables were compared using chi-square tests. Significance was defined as p < 0.05. After 9 months of unblinded Surgeon Value Scorecard distribution, the mean total costs for total joint arthroplasties decreased by 8.7%, from $17,996 to $16,426 (p < 0.001). The mean total direct variable costs decreased by 17.1% from $10,945 to $9,070 (p < 0.001), and implant costs decreased by 5.3% (p < 0.001). Length of stay also decreased by 0.2 day to 1.7 days (p < 0.001), and, although there was improvement in the home-discharge rate, 30-day readmission rate, and 90-day readmission rate, the differences were not significant (p > 0.05). The implementation of a surgeon-specific value scorecard for lower-extremity joint arthroplasties was associated with reduced total and direct variable hospital costs, reduced implant costs, decreased variation in costs, and reduced postoperative length of stay, without compromising clinical outcomes. Sharing unblinded clinical and financial outcomes with surgeons may promote a culture of shared accountability and may empower surgeons to improve value-based decision-making in care delivery.


[Minimally invasive therapy of obstruction of the kidney pelvis].
We report on 109 patients with ureteropelvic junction obstruction (UPJO) treated according to the following algorithm: intrinsic stenoses were treated by laser endopyelotomy (LEP). We used retroperitoneoscopy with ureterolysis to manage significant extrinsic UPJO due to a crossing vessel and either non-dismembered pyeloplasty in cases of an anterior vessel or dismembered pyeloplasty in cases of a posterior crossing vessel. Children were mostly treated by open dismembered pyeloplasty. Analysis of the factors that influence the postoperative results in the group of 64 patients treated by LEP showed significance for the presence of extrinsic causes of UPJO and the underlying grade of hydronephrosis. Based on our own results and the review of the literature, minimally invasive approaches for the management of UPJO have been proven safe and effective with results comparable to open surgery.


Relationship between gait variables and domains of neurologic dysfunction in multiple sclerosis using six-minute walk test.
Most multiple sclerosis (MS) patients eventually suffer from mobility impairment, and thus it is critical that walking disability in MS be accurately assessed. The six-minute walk test (6MWT), a reliable MS measure, is traditionally used to determine the distance covered in six minutes using a standard protocol. With the availability of body sensor networks (BSNs), researchers are interested in leveraging BSN data for finding new gait assessment anchors for improved separability performance. Further, current methods for gait assessments are insufficient since assessments are absolute, performed by comparing outcomes to the statistical norms established from diverse patient data despite natural inter-patient variability. For example, walking at a slower pace may be a personal trait rather than a fatigue-induced impact in MS. Thus instead of using actual values, changes in gait features during a 6MWT can be used to draw clinical conclusions and remove inter-subject variability. We use 6MWT gait time series BSN data of MS subjects to determine changes in their gait speed and gait cycle length variance over six minutes. We also determine the relationships between these variables and three subjective assessments, namely functional systems scores, modified fatigue impact scale, and multiple sclerosis walking scale. These relationships are important in order to validate features and make them clinically meaningful for a doctor. In MS, feelings of fatigue can occur more often, and have a greater impact on a subject's daily life. The results show that MS patients who reported high motor-related fatigue slowed down and had high gait cycle length variance in the last minute of the test, in contrast to those on whom fatigue had minimal impact, enhancing the separability between MS subjects of varied disabilities based on their scores. It is also observed that FSS components related to coordination, balance, and physical activities show strong correlation with gait parameters.


Brachial artery diameter and the right ventricle: the Multi-Ethnic Study of Atherosclerosis-right ventricle study.
Endothelial dysfunction is associated with left ventricular morphology and long-term cardiovascular outcomes. The purpose of this study was to assess the relationship between both baseline brachial artery diameter and peripheral endothelial function (assessed by brachial artery ultrasonography) and right ventricular (RV) mass, RV end-diastolic volume (RVEDV), and RV ejection fraction (RVEF). The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI and brachial artery ultrasonography on participants without clinical cardiovascular disease. Baseline brachial artery diameter and flow-mediated dilation were assessed. The mean age was 60.9 years, and 49.4% of subjects were men (n = 2,425). In adjusted models, larger brachial artery diameter was strongly associated with greater RV mass (β = 0.55 g, P < .001), larger RVEDV (β = 3.99 mL, P < .001), and decreased RVEF (β = -0.46%, P = .03). These relationships persisted after further adjustment for the respective left ventricular parameters. Flow-mediated dilation was not associated with RV mass or RVEF and was only weakly associated with RVEDV. Brachial artery diameter is associated with greater RV mass and RVEDV, as well as lower RVEF. Changes in the systemic arterial circulation may have pathophysiologic links to pulmonary vascular dysfunction or abnormalities in RV perfusion.


Bibliometric analysis of the scientific production in implantology (2009-2013).
To quantify, using bibliometric indicators, the scientific productivity of researchers, organizations, and countries, publishing articles on implantology in dental journals indexed in Journal Citation Reports between 2009 and 2013. Published texts were identified by applying the truncated search term "implant*." Document type was limited to "Article." Records were manually refined and normalized to unify terms and to remove typographical, transcription, and/or indexing errors. A total of 6088 articles were located. A progressive increase in the rate of publication was observed, especially between 2010 and 2012. This increase was clearly linked to increased collaboration between authors, institutions, and countries. Keywords appeared at a frequency of 3.1 per document. The journals Clinical Oral Implants Research and International Journal of Oral & Maxillofacial Implants published the highest numbers of articles. This study revealed a significant growth in implant dentistry literature in terms of the total number of journals, number of authors, organizations, and author collaborations. Most key bibliometric indicators demonstrated upward trends.


Factors Contributing to the Link between Physical Well-Being and Chronic Pain in Young People from Galicia, Northwest Spain.
Introduction: The relation between physical well-being and chronic pain is complex and involves several subjective and objective covariates. We aimed to assess the role of mediator, confounder, or interactor played by covariates, including sleep quality, physical activity, perceived stress, smoking, and alcohol drinking in the relation between physical well-being and chronic pain. Method: We used Poisson regression to obtain incidence rate ratios (IRR) of the association between physical well-being and chronic pain in a cohort study carried out among university students. We applied General Structural Equation Modeling (GSEM) to assess mediation and stratum-specific analyses to distinguish confounding from interaction. We computed Relative Excess Risks due to Interaction (RERI), Attributable Proportion (AP), and the Synergy index (S) to measure additive interaction. Results: High physical well-being is related to a large decrease in the risk of chronic pain (IRRTotal Effect = 0.58; 95% CI: 0.50-0.81). Perceived stress mediates 12.5% of the total effect of physical well-being on chronic pain. The stratum-specific IRRs of current smokers and non-current smokers were different from each other and were larger than the crude IRR (IRR = 1.49; 95% CI: 1.24-1.80), which indicates that smoking could be both confounder and interactor. Interaction analyses showed that physical activity could act as a potential interactor (RERI = 0.25; 95% CI: 0.13, 0.60). Conclusions: Perceived stress is an important mediator of the relation between physical well-being and chronic pain, while smoking is both a confounder and an interactor. Our findings may prove useful in distinguishing high-risk groups from low-risk groups, in the interventions aimed at reducing chronic pain.


[Chemotherapy of malignant brain tumors in childhood].
The best conventional care for medulloblastoma and malignant ependymoma in children consists of surgery and radiotherapy. The preliminary observations of some authors suggested that chemotherapy could be useful in treating these tumors. The two major experiences in this field are those from SIOP and CCSG -RTOG trials which used chemotherapy as adjuvant to surgery and radiotherapy. In such studies chemotherapy appears to be effective mostly in high-risk patients. A study performed by Italian Child's Neurooncology Group ( ICNG ) confirms the preceding results.


Impact of silk fibroin-based scaffold structures on human osteoblast MG63 cell attachment and proliferation.
The present study was carried out to investigate the impact of various types of silk fibroin (SF) scaffolds on human osteoblast-like cell (MG63) attachment and proliferation. SF was isolated from Bombyx mori silk worm cocoons after degumming. Protein concentration in the degummed SF solution was estimated using Bradford method. Aqueous SF solution was used to fabricate three different types of scaffolds, viz, electrospun nanofiber mat, sponge, and porous film. The structures of the prepared scaffolds were characterized using optical microscopy and field emission scanning electron microscopy. The changes in the secondary structure of the proteins and the thermal behavior of the scaffolds were determined by Fourier transform infrared spectroscopy and thermo-gravimetric analysis, respectively. The biodegradation rate of scaffolds was determined by incubating the scaffolds in simulated body fluid for 4 weeks. MG63 cells were seeded on the scaffolds and their attachment and proliferation onto the scaffolds were studied. The MTT assay was carried out to deduce the toxicity of the developed scaffolds. All the scaffolds were found to be biocompatible. The amount of collagen produced by the osteoblast-like cells growing on different scaffolds was estimated.


Repair activity and crystal adhesion inhibition of polysaccharides with different molecular weights from red algae Porphyra yezoensis against oxalate-induced oxidative damage in renal epithelial cells.
Renal epithelial cell injury is a key step in inducing kidney stone formation. However, research on the role of cell repair in the prevention and treatment of kidney stones is limited. In this study, the repair effect of degraded Porphyra yezoensis polysaccharide (PYP) on oxidative stress-mediated intracellular damage triggered by oxalate in human kidney proximal tubular epithelial (HK-2) cells was investigated, and the influence of molecular weight (Mw) on the repair ability of PYP was elucidated. Polysaccharides with different Mws were prepared by degrading PYP with hydrogen peroxide. Four degraded fractions, namely, PYP1, PYP2, PYP3, and PYP4, were successfully obtained with Mws of 576.2, 49.54, 12.65, and 4.020 kDa, respectively. A damaged cell model was established using 2.6 mmol L-1 oxalate to injure HK-2 cells. Various Mws of PYPs were used to repair the damaged cells. The repair mechanism of PYPs against oxalate-induced oxidative stress was examined by evaluating cell proliferation and physiological function recovery. Our study revealed that PYPs increased the viability of oxalate-injured HK-2 cells and restored their morphological characteristics and cytoskeleton. PYPs reduced the levels of oxalate-mediated lactase dehydrogenase release, reactive oxygen species generation, and intracellular Ca2+, the loss of mitochondrial membrane potential, the number of cells arrested in S phase, the expression of 8-hydroxy-desoxyguanosine and poly ADP ribose polymerase, lysosomal damage, and the number of apoptotic cells. The PYP fraction with low Mw presented an increased repair activity against cellular damage induced by oxalate. The resistance of the repaired renal cells to crystal adhesion and aggregation was stronger than that of the damaged cells. PYPs might inhibit the formation of kidney stones by repairing damaged cells and inhibiting crystal adhesion and aggregation. We concluded that PYP with low Mw could be used as a potential therapeutic agent against renal stone formation and recurrence.