Effects of the morphology of nanostructured ZnO and interface modification on the device configuration and charge transport of ZnO/polymer hybrid solar cells.
In an organic-based solar cell, the short exciton diffusion length of organic materials requires effective donor-acceptor heterojunction at the nanoscale. In this work, hybrid inorganic/polymer solar cells based on ZnO nanostructures and poly(3-hexylthiophene) (P3HT) are constructed to study the effects of ZnO morphologies and wettability of the surface on the P3HT infiltration ability and charge transport mechanisms. The P3HT infiltrates the ZnO nanorod (NR) more remarkably than ZnO nanoparticle (NP) substrates. Although surface modification with indoline D205 dye molecules improves the wettability (viz. enlarges the contact angle) of NP surface, the P3HT infiltration distance decreases in comparison with the pristine NP case. This leads to relatively low short-circuit current density (Jsc) of the NP devices in comparison with that of the NR devices, even though the surface area of NP layers is larger than that of NR ones. Moreover, surface modification with squaraine dye onto the NR surface shows more significant improvement in Jsc than the NP case. This is due to the well-aligned morphology of the NRs, which facilitates dye modification, P3HT infiltration, and charge transport processes. These indicate that the NRs are more qualified as electron accepting substrates and transport pathway in hybrid solar cells than NPs.


3,5-Dicaffeoylquinic acid isolated from Artemisia argyi and its ester derivatives exert anti-leucyl-tRNA synthetase of Giardia lamblia (GlLeuRS) and potential anti-giardial effects.
An aqueous ethanol extract of Artemisia argyi inhibited the aminoacylation activity of LeuRS from Giardia lamblia (GlLeuRS). The bioassay-guided fractionation of the extract led to the isolation of 3,5-dicaffeoylquinic acid (1), with an IC₅₀ of 5.82 μg/mL. The ester derivatives of 1 were also found to possess strong anti-GlLeuRS effects, with IC₅₀ values of 1.79, 5.51 and 2.56 μg/mL respectively. Anti-giardial assay showed that the derivatives, especially 3,5-dicaffeoylquinic acid propyl ester (4) (IC₅₀=4.62 μg/mL), were effective at killing G. lamblia.


Immolation of p-Aminobenzyl Ether Linker and Payload Potency and Stability Determine the Cell-Killing Activity of Antibody-Drug Conjugates with Phenol-Containing Payloads.
The valine-citrulline (Val-Cit) dipeptide and p-aminobenzyl (PAB) spacer have been commonly used as a cleavable self-immolating linker in ADC design including in the clinically approved ADC, brentuximab vedotin (Adcetris). When the same linker was used to connect to the phenol of the cyclopropabenzindolone (CBI) (P1), the resulting ADC1 showed loss of potency in CD22 target-expressing cancer cell lines (e.g., BJAB, WSU-DLCL2). In comparison, the conjugate (ADC2) of a cyclopropapyrroloindolone (CPI) (P2) was potent despite the two corresponding free drugs having similar picomolar cell-killing activity. Although the corresponding spirocyclization products of P1 and P2, responsible for DNA alkylation, are a prominent component in buffer, the linker immolation was slow when the PAB was connected as an ether (PABE) to the phenol in P1 compared to that in P2. Additional immolation studies with two other PABE-linked substituted phenol compounds showed that electron-withdrawing groups accelerated the immolation to release an acidic phenol-containing payload (to delocalize the negative charge on the anticipated anionic phenol oxygen during immolation). In contrast, efficient immolation of LD4 did not result in an active ADC4 because the payload (P4) had a low potency to kill cells. In addition, nonimmolation of LD5 did not affect the cell-killing potency of its ADC5 since immolation is not required for DNA alkylation by the center-linked pyrrolobenzodiazepine. Therefore, careful evaluation needs to be conducted when the Val-Cit-PAB linker is used to connect antibodies to a phenol-containing drug as the linker immolation, as well as payload potency and stability, affects the cell-killing activity of an ADC.


Theory and modeling of light-matter interactions in chemistry: current and future.
Light-matter interaction not only plays an instrumental role in characterizing materials' properties via various spectroscopic techniques but also provides a general strategy to manipulate material properties via the design of novel nanostructures. This perspective summarizes recent theoretical advances in modeling light-matter interactions in chemistry, mainly focusing on plasmon and polariton chemistry. The former utilizes the highly localized photon, plasmonic hot electrons, and local heat to drive chemical reactions. In contrast, polariton chemistry modifies the potential energy curvatures of bare electronic systems, and hence their chemistry, via forming light-matter hybrid states, so-called polaritons. The perspective starts with the basic background of light-matter interactions, molecular quantum electrodynamics theory, and the challenges of modeling light-matter interactions in chemistry. Then, the recent advances in modeling plasmon and polariton chemistry are described, and future directions toward multiscale simulations of light-matter interaction-mediated chemistry are discussed.


Recombinant human BMP-2 for the treatment of open tibial fractures.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) improves healing of open tibial fractures treated with intramedullary nail fixation. However, routine use has not occurred. The purposes of the current study were to provide a systematic review of the literature using rhBMP-2 in the treatment of acute open tibial fractures treated with intramedullary nail fixation and to provide a meta-analysis of the randomized, controlled trials. Multiple databases, reference lists of relative articles, and main orthopedic journals were searched. The basic information and major results were compared. Four studies with a total of 609 patients were included.The secondary intervention rate in the standard-of-care (SOC) group was significantly higher than in the rhBMP-2 combined with absorbable collagen sponge (rhBMP-2/ACS) group (27.1% vs 17.5%, respectively; P<.01). The treatment failure rate in the SOC group was significantly higher (34.3% vs. 21.4%, respectively; P<.01). No significant differences were found in infection rate, hardware failure rate, fracture healing rate at 20 weeks, and postoperative pain level. For patients treated with reamed intramedullary nail fixation, only the treatment failure rate in the SOC group was significantly higher (21.5% vs 14.2%, respectively; P=.02); no other significant difference was observed. Adding rhBMP-2 to the treatment of Gustilo-Anderson grade IIIA and B open tibial fractures led to net savings of approximately $6000 per case.Recombinant human bone morphogenetic protein-2 added to intramedullary nail fixation of open tibial fractures could reduce the frequency of secondary interventions and total health care costs. For reamed patients, adding rhBMP-2 reduced treatment failure. This analysis supports the clinical efficacy of rhBMP-2/ACS for the treatment of these severe fractures.


Clinical aspects of Reiter's disease.
The clinical manifestations and results of investigations in a series of 221 patients diagnosed as suffering from Reiter's disease are described in detail. Attention is drawn to the very varied natural history of the disease, the relapse rate of 60% and the development of serious complications and disability in young people. The failure to establish the cause of the condition or to unravel its relationship to nonspecific urethritis and bacillary dysentery contrasts with the reported presence of the human leucocyte antigen HLA-B27 in 76% of patients. There is no curative treatment but symptomatic treatment will relieve pain and stiffness and may shorten the duration of individual attacks. Prolonged follow-up of established cases, monitoring of activity of the disease by regular measurements of the erythrocyte sedimentation test and prompt treatment of relapses may prevent the development of serious locomotor disability.


Does host plant richness explain diversity of ectomycorrhizal fungi? Re-evaluation of Gao et al. (2013) data sets reveals sampling effects.
The generally positive relationship between biodiversity of groups of directly or indirectly interacting organisms is one of the most important ecological concepts (Gaston, 2000 Nature, 405, 220-227; Scherber C, Eisenhauer N, Weisser WW et al., 2010 Nature, 468, 553-556). In a recent issue of Molecular Ecology, Gao C, Shi N-N, Liu Y-X et al. (2013: 22, 3403-3414) reported that the richness of plants and ectomycorrhizal fungi is positively correlated both at local and at global scales. Here, we challenge these findings by re-analysis of data and ascribe the reported results to sampling effect and poor data compilation.


Lyme nephritis.
To review what is known and highlight knowledge gaps regarding Lyme nephritis (LN). Publications identified via PubMed using the keywords "Borrelia burgdorferi," "Borreliosis," "glomerulonephritis," "protein-losing nephropathy," "autoimmunity," and "retriever," and as generated by investigators working in the fields of Borreliosis and immune-mediated glomerulonephritis. Postborrelial immune-mediated glomerulonephritis was described recently in 6 people; 3 responded to antimicrobials/steroids, 1 to antimicrobials/angiotensin-converting enzyme inhibitor/warfarin, 1 required hemodialysis but became hemodialysis independent after 5 months and treatment with antimicrobials, steroids, plasmapheresis, immunoglobulin, and 1 did not respond to steroids and angiotensin-converting enzyme inhibitor and still requires hemodialysis. Lyme nephritis is seen in <1-2% of Lyme seropositive dogs, with an average onset at 5-6 years. Labrador and Golden Retrievers are predisposed to this condition. Prior or concurrent lameness is described in 9-28% cases. Historical presentations include acute progressive protein-losing nephropathy with membranoproliferative glomerulonephritis, tubular necrosis/regeneration, and interstitial nephritis, but possibly milder forms exist. Complications include thromboembolic events, hypertension, effusive disease, and oliguric/anuric renal failure. Diagnostic tests help stage disease and rule out other causes. Renal biopsy is advocated early, when intervention may help, and to prove if immune-complex disease exists. Treatment includes standard therapy for protein-losing nephropathy, long-term antimicrobials, and perhaps immunosuppressive therapy. There is no experimental model of LN to study predisposing factors, pathogenesis, onset, progression, treatment, or prevention. There are no predictive tests to identify the few individuals at highest risk, therefore all seropositive dogs should be screened and monitored for proteinuria. Lyme nephritis mimics other forms of protein-losing nephropathy and sometimes Leptospirosis. Renal biopsy helps show if immune-complex disease exists, but may not prove LN specifically. More studies are warranted on dogs with Lyme-specific immune-complex deposition to evaluate risk factors, understand pathogenesis, variability of expression, and to validate treatment and prevention protocols.


Deconvolution of Gene Expression Noise into Spatial Dynamics of Transcription Factor-Promoter Interplay.
Gene expression noise is not only the mere consequence of stochasticity, but also a signal that reflects the upstream physical dynamics of the cognate molecular machinery. Soil bacteria facing recalcitrant pollutants exploit noise of catabolic promoters to deploy beneficial phenotypes such as metabolic bet-hedging and/or division of biochemical labor. Although the role of upstream promoter-regulator interplay in the origin of this noise is little understood, its specifications are probably ciphered in flow cytometry data patterns. We studied Pm promoter activity of the environmental bacterium Pseudomonas putida and its cognate regulator XylS by following expression of Pm-gfp fusions in single cells. Using mathematical modeling and computational simulations, we determined the kinetic properties of the system and used them as a baseline code to interpret promoter activity in terms of upstream regulator dynamics. Transcriptional noise was predicted to depend on the intracellular physical distance between regulator source (where XylS is produced) and the target promoter. Experiments with engineered bacteria in which this distance is minimized or enlarged confirmed the predicted effects of source/target proximity on noise patterns. This approach allowed deconvolution of cytometry data into mechanistic information on gene expression flow. It also provided a basis for selecting programmable noise levels in synthetic regulatory circuits.


Fertility Preservation in 2016: Where Are We?
This review focuses on advances in the field of fertility preservation achieved over the past few decades. The main purpose of fertility preservation is to help young cancer survivors retain their fertility by restoring either their ability to procreate or simply their reproductive endocrine function. Although different options are available in this regard, successful fertility preservation is yet to reach its full potential. Herein, we review the most significant work conducted over the past five decades and present new methodologies.


[The Appointment of Paediatric Professorships in the Soviet Occupation Zone and the early GDR. The Impact of the Political System Change after 1945].
This paper examines the impact of the political system change after 1945 on the appointment of paediatric professorships in the Soviet Occupation Zone and the GDR up until the time the Wall was built in 1961. It can be demonstrated that the political purge in the post-war period had only minor impact on the appointment of professorships and the National Socialist past no longer mattered after the conclusion of denazification. In 1957, the proportion of former NSDAP members among East German university professors of paediatrics was 100 per cent. When it came to new appointments, both members of the "bourgeois" academic non-professorial teaching staff from the GDR as well as paediatricians from West Germany, who had largely gained their scientifically qualifications under National Socialism, were in the running. A politically-controlled elite exchange did not take place until the construction of the Wall. State and party organs generally followed the personnel proposals of the universities since an insufficient number of qualified candidates was available for the systematic appointment of ,,progressive" paediatricians. Given the lack of staff, the SED personnel policy was aimed at the integration of previous elites, as long as they behaved loyally towards the new state. Since the East German faculties continued to make the questioning of the professionally competent professors in West Germany and East Germany the basis for their appointment lists, West German university paediatricians were able to exert considerable influence on the appointment of East German paediatric professorship until 1960s.


X-Ray absorption spectra of microsolvated metal cations.
Core excited states in clusters or bulk medium are known to undergo a process of internal ionisation, whereby the excited electron delocalises throughout the medium. This delocalisation is visible in the shifting and broadening of lines in X-ray absorption spectra, and it impacts the electronic decay initiated by photoabsorption. In this paper we study the delocalisation of electrons excited from the 1s core orbital of Na(+) and Mg(2+) ions in microsolvated Na(+)(H2O)m and Mg(2+)(H2O)m clusters (m = 1-6) by computing the X-ray absorption spectra and electron distributions in different core excited states. We show that addition of water ligands to the ion leads to more and more pronounced delocalisation of the core-to-valence 1s → 3p and core-to-Rydberg 1s → 4p excitations. Even for the compact 1s → 3p excitation the excited electron is mostly located on the water molecules when the solvation shell is complete. We also found that the degree of delocalisation strongly depends on the cluster geometry and the ionic charge. These results indicate that even in small microsolvated clusters delocalisation of core excited electrons is substantial and will affect the following electronic decay. The accuracy and transferability of our results are corroborated by the good agreement between our XAS spectra of microsolvated Na(+) and experimental X-ray absorption spectra of dilute NaCl solutions.


Characteristics and abstinence outcomes among tobacco quitline enrollees using varenicline or nicotine replacement therapy.
Telephone counseling through quitlines combined with cessation medication is an effective strategy to support tobacco cessation. This study assessed the characteristics of quitline enrollees selecting varenicline (Chantix) compared with nicotine replacement therapy (NRT) medication and evaluated the cessation outcomes (7-day point prevalence) among these enrollees at 3 and 6 months after program completion. A retrospective study analyzed demographic, tobacco use history, and abstinence outcome information of participants who enrolled in the Montana Tobacco Quit Line program and selected varenicline (n = 3,116) or NRT (n = 3,697). Participants selecting varenicline had significantly different demographic characteristics and tobacco use histories compared with enrollees selecting NRT. In the bivariate analyses, the odds of abstinence were greater among persons using varenicline compared with NRT at 3 months (22% and 13%; odds ratio [OR] = 1.85 95% CI 1.50-2.29) and 6 months (17% and 11%; OR = 1.66 95% CI 1.23-2.24). Independently, varenicline use, increasing age, having health insurance, and a greater number of counseling sessions were associated with tobacco use abstinence at 3 months. Only increasing age and a greater number of counseling sessions were independently associated with 6-month abstinence. Organizations providing varenicline as part of their quitline services should anticipate that participants selecting this medication have different demographic characteristics and tobacco use histories. The findings suggest that the addition of varenicline enhances 3-month abstinence rates and that the tobacco user's commitment to quit may be the most important predictor of successfully quitting.


Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches.
In addition to deoxynivalenol (DON), acetylated derivatives, i.e., 3-acetyl and 15-acetyldexynivalenol (or 3/15ADON), are present in cereals leading to exposure to these mycotoxins. Animal and human studies suggest that 3/15ADON are converted into DON after their ingestion through hydrolysis of the acetyl moiety, the site(s) of such deacetylation being still uncharacterized. We used in vitro and ex vivo approaches to study the deacetylation of 3/15ADON by enzymes and cells/tissues present on their way from the food matrix to the blood in humans. We found that luminal deacetylation by digestive enzymes and bacteria is limited. Using human cells, tissues and S9 fractions, we were able to demonstrate that small intestine and liver possess strong deacetylation capacity compared to colon and kidneys. Interestingly, in most cases, deacetylation was more efficient for 3ADON than 15ADON. Although we initially thought that carboxylesterases (CES) could be responsible for the deacetylation of 3/15ADON, the use of pure human CES1/2 and of CES inhibitor demonstrated that CES are not involved. Taken together, our original model system allowed us to identify the small intestine and the liver as the main site of deacetylation of ingested 3/15ADON in humans.


Hypoxia Mimetic Agents for Ischemic Stroke.
Every year stroke claims more than 6 million lives worldwide. The majority of them are ischemic stroke. Small molecule-based therapeutics for ischemic stroke has attracted a lot of attention, but none has been shown to be clinically useful so far. Hypoxia-inducible factor-1 (HIF-1) plays a crucial role in the transcriptional adaptation of cells to hypoxia. Small molecule-based hypoxia-mimetic agents either stabilize HIF-1α via HIF-prolyl hydroxylases (PHDs) inhibition or through other mechanisms. In both the cases, these agents have been shown to confer ischemic neuroprotection in vitro and in vivo. The agents which act via PHD inhibition are mainly classified into iron chelators, iron competitors, and 2 oxoglutarate (2OG) analogs. This review discusses HIF structure and key players in the HIF-1 degradation pathway as well as the genes, proteins and chemical molecules that are connected to HIF-1 and how they affect cell survival following ischemic injury. Furthermore, this review gives a summary of studies that used PHD inhibitors and other HIF-1α stabilizers as hypoxia-mimetic agents for the treatment of ischemic injury.


Mutual neoplastic promotion by instillation of mitomycin C and cauterization on rat bladder urothelium.
The authors studied the effect of bladder instillation of mitomycin C (MMC), a potential carcinogen, on the duration and severity of the hyperplasia induced by transurethral fulguration. This experimental system may simulate closely the intravesical chemoprophylaxis of MMC after transurethral resection of bladder cancer. Physiologic saline or MMC was instilled into the rat bladder once on the day of, or 3 or 7 days after cauterization. In all groups instilled with physiologic saline the changes were reversed by day 14. On the other hand, five of nine MMC-instilled rats developed papillary lesions, and three of these had mild dysplastic epithelium on day 84. Under the scanning electron microscope, the animals of these groups showed pleomorphic microvilli on the luminal surface of the regenerative cells on days 10 and 14 after cauterization. These results may indicate the mutual neoplastic promotion by instillation of MMC and cauterization to a certain extent.


Intracellular dynamic response characteristics of pineal photoreceptors.
The dynamic properties of single pineal photoreceptors of Lampetra japonica were measured intracellularly by sinusoidal modulated light stimuli. According to the Bode plots the response amplitude and phase characteristic of pineal photoreceptors could be simulated by a linear model with 4th-order transfer function. A similarity to the receptor response of the vertebrate lateral eye was observed.


Are They Just Two Children COVID-19 Cases Confused With Flu?
COVID-19, an emerging infectious disease, has quickly spread all over the world. All human populations are susceptible to this disease. Here we present two pediatric COVID-19 cases, both of whom exhibited negative SARS-CoV-2 nucleic acid tests upon nasopharyngeal swab and were initially diagnosed with influenza A infection. COVID-19 was later confirmed in both patients by serum antibodies of SARS-CoV-2 and nucleic acid test on stool samples. Because children are susceptible to many respiratory pathogens, especially influenza, we concluded that children can be coinfected with multiple pathogens, and more attention should be paid to the exploration of SARS-CoV-2 during the pandemic of COVID-19. This report shows the possibility of misdiagnosis or missed diagnosis of children with COVID-19. We suggest that highly suspected pediatric COVID-19 cases with negative nucleic acid tests on nasopharyngeal swabs should be further checked by performing a nucleic acid test on stool samples and testing serum for antibodies against SARS-CoV-2.


AZD6244 and doxorubicin induce growth suppression and apoptosis in mouse models of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, with no effective treatment for most individuals who succumb to this neoplasm. We report that treatment of primary HCC cells with the mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase 1/2 inhibitor AZD6244 (ARRY-142886) plus doxorubicin led to synergistic growth inhibition and apoptosis. In vivo administration of AZD6244, doxorubicin, or the combination of AZD6244 and doxorubicin in mice bearing 5-1318 HCC xenografts resulted in approximately 52% +/- 15%, 12% +/- 9%, and 76% +/- 7% growth inhibition, respectively. AZD6244-inhibited tumor growth was associated with increased apoptosis, inactivation of ERK1/2, inhibition of cell proliferation, and down-regulation of cell cycle regulators, including cyclin D1, cdc-2, cyclin-dependent kinases 2 and 4, cyclin B1, and c-Myc. The AZD6244-doxorubicin combined protocol not only promoted apoptosis but also induced a synergistic effect not seen in single-agent-treated tumors, including increased expression of the p130 RB tumor suppressor gene. Our study provides a strong rationale for clinical investigation of combination therapy with the mitogen-activated protein/ERK kinase 1/2 inhibitor AZD6244 and doxorubicin in patients with HCC.


In Search of Congenital Chagas Disease in the Sierra Nevada de Santa Marta, Colombia.
Chagas disease remains a major impediment to sustainable socioeconomic development in Latin America. Transplacental transmission explains the persistence of transmission in urban areas, in non-endemic regions, and in areas with an established interrupted vectorial transmission. One of every five cases of congenital Chagas disease in the world occurs in Colombia and Venezuela. The massive migration of impoverished populations from neighboring Venezuela has worsened the situation creating a humanitarian crisis in Northeastern Colombia, including the Sierra Nevada de Santa Marta. The prevalence of Chagas infection among pregnant women in these areas is higher than the national average, and the public health resources are insufficient. This perspective discusses the associated increased morbidity and mortality of congenital Chagas in this region, where stigmatization contributes to the impression among health authorities and the general population that it affects indigenous communities only. The monitoring and control of congenital Chagas disease in the Sierra Nevada of Santa Marta is a public health necessity that demands urgent and effective interventions.


Aicardi syndrome.
Aicardi syndrome is a rare neurodevelopmental disease characterised by congenital chorioretinal lacunae, corpus callosum dysgenesis, seizures, polymicrogyria, cerebral callosum, chorioretinopathy and electroencephalogram abnormality. We present a case of Aicardi syndrome with callosal hypogenesis in a 4.5-month-old baby who presented with infantile spasms. Ophthalmoscopy revealed chorioretinal lacunae. The clinical and magnetic resonance imaging features were diagnostic of Aicardi syndrome.


Social amplification of risks and the clean energy transformation: Elaborating on the four attributes of information.
The social amplification of risk framework (SARF) was developed to help comprehend how emerging contributions about the psychological, social, and cultural dimensions of risk could work in unison to impact decision making about risk. The framework proposed that risks are amplified or attenuated by interested parties employing different rhetorical strategies to give information about risk a certain "spin." The original literature identified four "attributes of information." However, despite the longevity of the framework, these have not been explicated in detail. Here we add depth and clarity by examining how amplification stations send risk signals that amplify or attenuate risk by emphasizing these different attributes of information. Drawing on a wealth of qualitative data from two case studies of offshore wind turbine siting off the coasts of Maryland and Delaware and guided by an extensive literature review, we reveal the strategies interested parties are using to influence siting decisions and risk management. The paper explores the usefulness of SARF in organizing qualitative information and sharpening insights on participatory risk governance and the nuances of public responses to a relatively new low-carbon technology. The authors conclude that the framework is valuable for analyzing stakeholder information while also recognizing limitations that may be addressed with some targeted future research.


lhCLIP reveals the in vivo RNA-RNA interactions recognized by hnRNPK.
RNA-RNA interactions play a crucial role in regulating gene expression and various biological processes, but identifying these interactions on a transcriptomic scale remains a challenge. To address this, we have developed a new biochemical technique called pCp-biotin labelled RNA hybrid and ultraviolet crosslinking and immunoprecipitation (lhCLIP) that enables the transcriptome-wide identification of intra- and intermolecular RNA-RNA interactions mediated by a specific RNA-binding protein (RBP). Using lhCLIP, we have uncovered a diverse landscape of intermolecular RNA interactions recognized by hnRNPK in human cells, involving all major classes of noncoding RNAs (ncRNAs) and mRNA. Notably, hnRNPK selectively binds with snRNA U4, U11, and U12, and shapes the secondary structure of these snRNAs, which may impact RNA splicing. Our study demonstrates the potential of lhCLIP as a user-friendly and widely applicable method for discovering RNA-RNA interactions mediated by a particular protein of interest and provides a valuable tool for further investigating the role of RBPs in gene expression and biological processes.


Within-person association of volitional factors and physical activity: Insights from an ecological momentary assessment study.
Current health behavior models of physical activity (PA) suggest that not all PA intentions are translated into actual PA behavior, resulting in a significant intention-behavior gap (IBG) of almost 50%. These models further suggest that higher self-efficacy and specific planning can aid in decreasing this gap. However, as most evidence stems from between-person (trait level), questionnaire-based research, it is unclear how large short-term IBGs are, how self-efficacy and planning covary within-persons across time and whether they similarly predict smaller IBGs. It is likely that day-to-day changes in circumstances and barriers affect these variables thus the applicability of theoretical models is uncertain. Here, within-person prospective analyses of ecological momentary assessment (EMA) data can provide insights. 35 healthy participants (aged 23-67) completed four EMA-based questionnaires every day for three weeks. Each prompt assessed PA (retrospectively, "since the last EMA prompt"); PA intentions, planning specificity, self-efficacy, and intrinsic motivation (prospectively, "until the next EMA prompt") and momentary affect. Generalized logistic mixed-effect modeling was used to test predictors of PA. Across the 2341 answered EMA prompts, PA intentions were not enacted in 25% of the episodes (IBG). In episodes with given intentions, PA likelihood increased with higher levels of self-efficacy, planning specificity, and intrinsic motivation. The latter two also positively predicted PA duration and intensity. Short-term intention behavior gaps seem to be smaller than what is known from more long-term studies, most likely as individuals can anticipate the actual circumstances of PA. Further, current health behavior models show validity in explaining within-person dynamics in IBGs across time. Knowing the relevance of planning specificity, self-efficacy and intrinsic motivation for day-to-day variations in PA enactment can inform respective real-time mHealth interventions for facilitating PA.


Radioprotective action of caffeine: use of Saccharomyces cerevisiae as a test system.
Mechanism of radioprotective action of caffeine by studying the gamma radiation -induced killing of yeast, S. cerevisae is reported. The results reveal that caffeine specifically protects aerobically (oxic) grown cells from gamma - radiation and sensitizes anaerobically (hypoxic) grown cells to some extent. Using radiation sensitive strains which lack recombinational pathway, it was found that protection by caffeine was solely brought about by reducing DNA damage, rather than by interfering with DNA repair process.


Effect of task length on remembered and predicted duration.
Vierordt's (1868) law states that when estimating the duration of a previous task, people overestimate short durations and underestimate long ones. We examine whether this same pattern holds for remembered and predicted duration for tasks lasting between 1 and 15 min. In support of Vierordt's law and its extension to future duration estimates, task duration tended to be overestimated for short tasks (less than 2 min) and underestimated for long tasks for both remembered and predicted duration.


Nitrate Bioreduction under Cr(VI) Stress: Crossroads of Denitrification and Dissimilatory Nitrate Reduction to Ammonium.
This study explored the response of NO3--N bioreduction to Cr(VI) stress, including reduction efficiency and the pathways involved (denitrification and dissimilatory nitrate reduction to ammonium (DNRA)). Different response patterns of NO3--N conversion were proposed under Cr(VI) suppress (0, 0.5, 5, 15, 30, 50, and 80 mg/L) by evaluating Cr(VI) dose dependence, toxicity accumulation, bioelectron behavior, and microbial community structure. Cr(VI) concentrations of >30 mg/L rapidly inhibited NO3--N removal and immediately induced DNRA. However, denitrification completely dominated the NO3--N reduction pathway at Cr(VI) concentrations of <15 mg/L. Therefore, 30 and 80 mg/L Cr(VI) (R4 and R6) were selected to explore the selection of the different NO3--N removal pathways. The pathway of NO3--N reduction at 30 mg/L Cr(VI) exhibited continuous adaptation, wherein the coexistence of denitrification (51.7%) and DNRA (13.6%) was achieved by regulating the distribution of denitrifiers (37.6%) and DNRA bacteria (32.8%). Comparatively, DNRA gradually replaced denitrification at 80 mg/L Cr(VI). The intracellular Cr(III) accumulation in R6 was 6.60-fold greater than in R4, causing more severe oxidant injury and cell death. The activated NO3--N reduction pathway depended on the value of nitrite reductase activity/nitrate reductase activity, with 0.84-1.08 associated with DNRA activation and 1.48-1.57 with DNRA predominance. Although Cr(VI) increased microbial community richness and improved community structure stability, the inhibition or death of nitrogen-reducing microorganisms caused by Cr(VI) decreased NO3--N reduction efficiency.


Risk and protective factors in the clinical rehabilitation of chronic back pain.
Chronic back pain (CBP) can lead to disability and burden. In addition to its medical causes, its development is influenced by psychosocial risk factors, the so-called flag factors, which are categorized and integrated into many treatment guidelines. Currently, most studies investigate single flag factors, which limit the estimation of individual factor significance in the development of chronic pain. Furthermore, factors concerning patients' lifestyle, biography and treatment history are often neglected. Therefore, the objectives of the present study are to identify commonly neglected factors of CBP and integrate them into an analysis model comparing their significance with established flag factors. A total of 24 patients and therapists were cross-sectionally interviewed to identify commonly neglected factors of CBP. Subsequently, the impact of these factors was surveyed in a longitudinal study. In two rehabilitation clinics, CBP patients (n = 145) were examined before and 6 months after a 3-week inpatient rehabilitation. Outcome variables, chronification factor pain experience (CF-PE) and chronification factor disability (CF-D), were ascertained with confirmatory factor analysis (CFA) of standardized questionnaires. Predictors were evaluated using stepwise calculations of simple and multiple regression models. Through interviews, medical history, iatrogenic factors, poor compliance, critical life events (LEs), social support (SS) type and effort-reward were identified as commonly neglected factors. However, only the final three held significance in comparison to established factors such as depression and pain-related cognitions. Longitudinally, lifestyle factors found to influence future pain were initial pain, physically demanding work, nicotine consumption, gender and rehabilitation clinic. LEs were unexpectedly found to be a strong predictor of future pain, as were the protective factors, reward at work and perceived SS. These findings shed insight regarding often overlooked factors in the development of CBP, suggesting that more detailed operationalization and superordinate frameworks would be beneficial to further research. In particular, LEs should be taken into account in future research. Protective factors should be integrated in therapeutic settings.


Localized gene expression changes during adventitious root formation in black walnut (Juglans nigra L.).
Cutting propagation plays a large role in the forestry and horticulture industries where superior genotypes need to be clonally multiplied. Integral to this process is the ability of cuttings to form adventitious roots. Recalcitrance to adventitious root development is a serious hurdle for many woody plant propagation systems including black walnut (Juglans nigra L.), an economically valuable species. The inability of black walnut to reliably form adventitious roots limits propagation of superior genotypes. Adventitious roots originate from different locations, and root induction is controlled by many environmental and endogenous factors. At the molecular level, however, the regulation of adventitious root formation is still poorly understood. In order to elucidate the transcriptional changes during adventitious root development in black walnut, we used quantitative real-time polymerase chain reaction to measure the expression of nine key genes regulating root formation in other species. Using our previously developed spatially explicit timeline of adventitious root development in black walnut softwood cuttings, we optimized a laser capture microdissection protocol to isolate RNA from cortical, phloem fiber and phloem parenchyma cells throughout adventitious root formation. Laser capture microdissection permitted high-resolution, site-specific analysis of gene expression that differentiated between participatory and non-participatory root progenitor cells. Results indicated mRNA abundance was altered in all nine rooting-related genes in response to auxin treatment in both juvenile and mature cuttings. SCARECROW LIKE-1 (SCL) had the greatest change in expression in juvenile rooting-competent cells at days 16 and 18, with a 24- and 23-fold increase relative to day 0, respectively. Tissues not linked to root organogenesis had little change in SCL expression at similar time points. AUXIN RESPONSE FACTOR (ARF)6 and ARF8 as well as SHORTROOT expression also increased 2- to 4-fold in rooting-competent tissue. The greatest transcript abundance in rooting-competent cuttings was restricted to root progenitor cells, while recalcitrant cuttings had a diffuse mRNA signal among tissue types.


Self-powered water splitting using flowing kinetic energy.
By utilizing a water-flow-driven triboelectric nanogenerator, a fully self-powered water-splitting process is demonstrated using the electricity converted from a water flow without additional energy costs. Considering the extremely low costs, the demonstrated approach is universally applicable and practically usable for future water electrolysis, which may initiate a research direction in the field of triboelectrolysis and possibly impacts energy science in general.


The immune system in pregnancy: a unique complexity.
Placental immune response and its tropism for specific viruses and pathogens affect the outcome of the pregnant woman's susceptibility to and severity of certain infectious diseases. The generalization of pregnancy as a condition of immune suppression or increased risk is misleading and prevents the determination of adequate guidelines for treating pregnant women during pandemics. There is a need to evaluate the interaction of each specific pathogen with the fetal/placental unit and its responses to design the adequate prophylaxis or therapy. The complexity of the immunology of pregnancy and the focus, for many years, on the concept of immunology of pregnancy as an organ transplantation have complicated the field and delayed the development of new guidelines with clinical implications that could help to answer these and other relevant questions. Our challenge as scientists and clinicians interested in the field of reproductive immunology is to evaluate many of the 'classical concepts' to define new approaches for a better understanding of the immunology of pregnancy that will benefit mothers and fetuses in different clinical scenarios.


Nutrition rehabilitation and the importance of the perception of malnutrition in the follow-up of rehabilitated children.
Nutrition rehabilitation of malnourished children remains a challenge for health services. This paper reports the results of an evaluation of the nutrition component of a mother and child health program in Nepal. The treatment of severely malnourished children was very satisfactory: case fatality rate varied from 4 to 9 % between projects. Follow-up, however, was found to be very poor: only one percent of the discharged children came for a follow-up visit after the first two weeks. The perception of malnutrition within the communities was identified as one of the possible determinants for a successful follow-up and small scale qualitative investigations were organized to gain insight in the topic. Results are quite revealing regarding the perception of nutrition problems. If for severe cases (kwashiorkor and marasmus) awareness of malnutrition did exist in the community, chronic malnutrition seems to be considered as a normal state of being. When a problem is perceived (in severe cases) people will seldom think of it as a nutrition related disease. Results show that the aetiology used by the people differs significantly from the western paradigm, and that traditional convictions put the causes at natural, supra-natural or social levels. The striking point is that no relation is established in the traditional framework between malnutrition (either severe or mild) and food intake of the children. Perception of malnutrition and of its causes influences health seeking behaviour in terms of prevention and treatment. Traditional healers play an important curative role and will often be the first to be contacted. The absence of perception of the links between the shape of the body and nutrients is put forward as one of the possible explaining mechanisms for low follow-up rates observed. An implication of this study would be to revise the health messages delivered to the communities in order to make them culturally more appropriate and relevant.


Use of a Phosphorylation Site Mutant To Identify Distinct Modes of Gene Repression by the Control of Virulence Regulator (CovR) in Streptococcus pyogenes.
Control of the virulence regulator/sensor kinase (CovRS) two-component system (TCS) serves as a model for investigating the impact of signaling pathways on the pathogenesis of Gram-positive bacteria. However, the molecular mechanisms by which CovR, an OmpR/PhoB family response regulator, controls virulence gene expression are poorly defined, partly due to the labile nature of its aspartate phosphorylation site. To better understand the regulatory effect of phosphorylated CovR, we generated the phosphorylation site mutant strain 10870-CovR-D53E, which we predicted to have a constitutive CovR phosphorylation phenotype. Interestingly, this strain showed CovR activity only for a subset of the CovR regulon, which allowed for classification of CovR-influenced genes into D53E-regulated and D53E-nonregulated groups. Inspection of the promoter sequences of genes belonging to each group revealed distinct promoter architectures with respect to the location and number of putative CovR-binding sites. Electrophoretic mobility shift analysis demonstrated that recombinant CovR-D53E protein retains its ability to bind promoter DNA from both CovR-D53E-regulated and -nonregulated groups, implying that factors other than mere DNA binding are crucial for gene regulation. In fact, we found that CovR-D53E is incapable of dimerization, a process thought to be critical to OmpR/PhoB family regulator function. Thus, our global analysis of CovR-D53E indicates dimerization-dependent and dimerization-independent modes of CovR-mediated repression, thereby establishing distinct mechanisms by which this critical regulator coordinates virulence gene expression.IMPORTANCEStreptococcus pyogenes causes a wide variety of diseases, ranging from superficial skin and throat infections to life-threatening invasive infections. To establish these various disease manifestations, Streptococcus pyogenes requires tightly coordinated production of its virulence factor repertoire. Here, the response regulator CovR plays a crucial role. As an OmpR/PhoB family member, CovR is activated by phosphorylation on a conserved aspartate residue, leading to protein dimerization and subsequent binding to operator sites. Our transcriptome analysis using the monomeric phosphorylation mimic mutant CovR-D53E broadens this general notion by revealing dimerization-independent repression of a subset of CovR-regulated genes. Combined with promoter analyses, these data suggest distinct mechanisms of CovR transcriptional control, which allow for differential expression of virulence genes in response to environmental cues.


Extracorporeal circulation models in small animals: beyond the limits of preclinical research.
Extracorporeal membrane oxygenation (ECMO) use has remarkably increased in recent years. Although ECMO has become essential for patients with refractory cardiac and respiratory failure, extracorporeal circulation (ECC) is associated with significant complications. Small-animal models of ECC have been developed and widely used to better understand ECC-induced pathophysiology. This review article summarizes the development of small-animal ECC models, including the animal species, circuit configuration, priming, perioperative procedures, cannulation, and future perspectives of small-animal ECMO models.


Analytical methods of antibody surface coverage and orientation on bio-functionalized magnetic beads: application to immunocapture of TNF-α.
The use of magnetic beads bio-functionalized by antibodies (Ab) is constantly increasing with a wide range of biomedical applications. However, despite an urgent need for current methods to monitor Ab's grafting process and orientation, existing methods are still either cumbersome and/or limited. In this work, we propose a new simple and rapid analytical approach to evaluate antibody orientation and density on magnetic beads. This approach relies on the cleavage by IdeS, a highly specific protease for human immunoglobulin G (hIgG), of immobilized antibodies. The F(ab)2 and Fc fragments could be then accurately quantified by size exclusion chromatography (SEC)-coupled to fluorescent detection (FLD), and the ratio of these fragments was used to give insight on the IgG orientation at the bead surface. Four different commercially available magnetic beads, bearing carboxyl groups, tosyl groups, streptavidin, or protein G on their surface have been used in this study. Results obtained showed that this approach ensures reliable information on hIgG orientation and bead surface coverage. Protein G magnetic beads demonstrated an optimal orientation of antibodies for antigen capture (75% of accessible F(ab)2 fragment) compared to tosylactivated, carboxylated, and streptavidin ones. Capture efficiency of the different functionalized beads towards human TNF-α immunocapture, a biomarker of inflammation, has been also compared. Protein G beads provided a more efficient capture compared to other beads. In the future, this approach could be applied to any type of surface and beads to assess hIgG coverage and orientation after any type of immobilization. A rapid and simple approach to evaluate orientation and density of antibodies immobilized on magnetic beads.


A fusion of the EBV latent membrane protein-1 (LMP1) transmembrane domains to the CD40 cytoplasmic domain is similar to LMP1 in constitutive activation of epidermal growth factor receptor expression, nuclear factor-kappa B, and stress-activated protein kinase.
The EBV latent infection transforming protein, LMP1, has six hydrophobic transmembrane domains that enable it to aggregate in the plasma membrane and a 200-amino acid carboxyl-terminal cytoplasmic domain (CT) that activates nuclear factor-kappaB and induces many of the phenotypic changes in B lymphocytes that accompany CD40 activation. Since the phenotypic effects of LMP1 are similar to those of activated CD40, we now compare signaling from the LMP1 CT with that from the CD40 CT fused to the LMP1 transmembrane domains. The LMPCD40 chimera was similar to LMP1 in nuclear factor-kappaB activation and in up-regulation of epidermal growth factor receptor expression. CD40 ligation was known to activate the stress-activated protein kinase, and both LMPCD40 and LMP1 are now shown to induce stress-activated protein kinase activity in the absence of ligand. Deletion of the first four transmembrane domains of LMP1 abrogated LMP1 aggregation in the plasma membrane and nearly abolished signaling from LMP1 or the LMPCD40 chimera. These results highlight the role of LMP1 as a constitutively active receptor similar to CD40 and provide a novel approach for the generation of ligand-independent receptors.


NaBr-Assisted Sintering of Na3Zr2Si2PO12 Ceramic Electrolyte Stabilizes a Rechargeable Solid-state Sodium Metal Battery.
Solid-state metal batteries with nonflammable solid-state electrolytes are regarded as the next generation of energy storage technology on account of their high safety and energy density. However, as for most solid electrolytes, low room temperature ionic conductivity and interfacial issues hinder their practical application. In this work, Na super ionic conductor (NASICON)-type Na3Zr2Si2PO12 (NZSP) electrolytes with improved ionic conductivity are synthesized by the NaBr-assisted sintering method. The effects of the NaBr sintering aid on the crystalline phase, microstructure, densification degree, and electrical performance as well as the electrochemical performances of the NZSP ceramic electrolyte are investigated in detail. Specifically, the NZSP-7%NaBr-1150 ceramic electrolyte has an ionic conductivity of 1.2 × 10-3 S cm-1 (at 25 °C) together with an activation energy of 0.28 eV. A low interfacial resistance of 35 Ω cm2 is achieved with the Na/NZSP-7%NaBr-1150 interface. Furthermore, the Na/NZSP-7%NaBr-1150/Na3V2(PO4)3 battery manifests excellent cycling stability with a capacity retention of 98% after 400 cycles at 1 C and 25 °C.


Open-access microfluidic patch-clamp array with raised lateral cell trapping sites.
A novel open-access microfluidic patch-clamp array chip with lateral cell trapping sites raised above the bottom plane of the chip was developed by combining both a microscale soft-lithography and a macroscale polymer fabrication method. This paper demonstrates the capability of using such an open-access fluidic system for patch-clamp measurements. The surface of the open-access patch-clamp sites prepared by the macroscale hole patterning method of soft-state elastic polydimethylsiloxane (PDMS) is examined; the seal resistances are characterized and correlated with the aperture dimensions. Whole cell patch-clamp measurements are carried out with CHO cells expressing Kv2.1 ion channels. Kv2.1 ion channel blocker (TEA) dosage response is characterized and the binding activity is examined. The results demonstrate that the system is capable of performing whole cell measurements and drug profiling in a more efficient manner than the traditional patch-clamp set-up.


Improvement of nutritional status in patients receiving maintenance hemodialysis after correction of renal anemia with recombinant human erythropoietin.
Despite a large body of evidence showing the beneficial effects of successful treatment of anemia with recombinant human erythropoietin (EPO) in patients with end-stage renal disease, controversy remains as to whether EPO treatment of anemia can improve the nutritional status in patients on maintenance hemodialysis. This prompted us to conduct a prospective study in 41 hemodialysis patients with basal hemoglobin less than 9 g/dl. The dose of EPO was increased for 12 weeks to achieve the target hemoglobin concentration of 10 g/dl and then titrated in the following 12 weeks to maintain the target value. Nutritional status was assessed at baseline and after 6 months of follow-up, using the global protein-calorie malnutrition (PCM) index proposed by Bilbrey and Cohen. A low global PCM score indicates better nutrition. The results showed that hemoglobin values significantly increased from 8.7 +/- 0.8 g/dl at baseline to 10.7 +/- 0.5 g/dl in the 6th month (p < 0.001). No significant changes were observed in the normalized protein catabolic rate and Kt/V during the study period. Global PCM scores improved from 30.0 +/- 7.5 to 23.6 +/- 3.1 (p < 0.001) and paralleled the correction of anemia by EPO treatment. The data were consistent with a major improvement in the nutritional markers of relative body weight, triceps skinfold, midarm circumference, midarm muscle circumference, serum albumin, serum transferrin and total lymphocyte count in the 6th month as compared to baseline. The percentages of mild and moderate-severe PCM at baseline were 32 and 58%, respectively. These percentages were significantly reduced during the 6th month to 20 and 30%, respectively (p = 0.0004). In summary, correction of renal anemia with EPO improves the nutritional status in hemodialysis patients. A postulated mechanism is that EPO may exhibit anabolic effects, with a better utilization of ingested protein.


Magnetic annihilation of the dark mode in a strongly coupled bright-dark terahertz metamaterial.
Dark mode in metamaterials has become a vital component in determining the merit of the Fano type of interference in the system. Its strength dictates the enhancement and suppression in the amplitude and Q-factors of resulting resonance features. In this work, we experimentally probe the effect of strong near-field coupling on the strength of the dark mode in a concentrically aligned bright resonator and a dark split ring resonator (SRR) system exhibiting the classical analog of the electromagnetically induced transparency effect. An enhanced strong magnetic field between the bright-dark resonators destructively interferes with the inherent magnetic field of the dark mode to completely annihilate its effect in the coupled system. Moreover, the observed annihilation effect in the dark mode has a direct consequence on the disappearance of the SRR effect in the proposed system, wherein under the strong magnetic interactions, the LC resonance feature of the split ring resonator becomes invisible to the incident terahertz wave.


Quantization of collagen organization in the stroma with a new order coefficient.
Many optical and biomechanical properties of the cornea, specifically the transparency of the stroma and its stiffness, can be traced to the degree of order and direction of the constituent collagen fibers. To measure the degree of order inside the cornea, a new metric, the order coefficient, was introduced to quantify the organization of the collagen fibers from images of the stroma produced with a custom-developed second harmonic generation microscope. The order coefficient method gave a quantitative assessment of the differences in stromal collagen arrangement across the cornea depths and between untreated stroma and cross-linked stroma.


An accurate full-dimensional potential energy surface for H-Au(111): Importance of nonadiabatic electronic excitation in energy transfer and adsorption.
We have constructed a potential energy surface (PES) for H-atoms interacting with fcc Au(111) based on fitting the analytic form of the energy from Effective Medium Theory (EMT) to ab initio energy values calculated with density functional theory. The fit used input from configurations of the H-Au system with Au atoms at their lattice positions as well as configurations with the Au atoms displaced from their lattice positions. It reproduces the energy, in full dimension, not only for the configurations used as input but also for a large number of additional configurations derived from ab initio molecular dynamics (AIMD) trajectories at finite temperature. Adiabatic molecular dynamics simulations on this PES reproduce the energy loss behavior of AIMD. EMT also provides expressions for the embedding electron density, which enabled us to develop a self-consistent approach to simulate nonadiabatic electron-hole pair excitation and their effect on the motion of the incident H-atoms. For H atoms with an energy of 2.7 eV colliding with Au, electron-hole pair excitation is by far the most important energy loss pathway, giving an average energy loss ≈3 times that of the adiabatic case. This increased energy loss enhances the probability of the H-atom remaining on or in the Au slab by a factor of 2. The most likely outcome for H-atoms that are not scattered also depends prodigiously on the energy transfer mechanism; for the nonadiabatic case, more than 50% of the H-atoms which do not scatter are adsorbed on the surface, while for the adiabatic case more than 50% pass entirely through the 4 layer simulation slab.


The Swedish marine nematologist Carl Allgén (1886-1960): a bio-bibliography and his collection.
The Swedish marine nematologist Carl Allgén (1886-1960) published 185 scientific papers on parasitic, terrestrial, limnic and especially marine nematodes between 1921 and 1960. Among them are also some papers on species of suctorians found mostly on desmodorid nematodes. He described about 70 new genera and over 800 new species and subspecies of nematodes. Allgén left a large collection of nematodes to the Swedish Museum of Natural History in Stockholm and it is now deposited in the invertebrate collection of the Zoology department. The collection comprises about 4500 slides in total, with about 310 slides containing type specimens collected from the Arctic to Antarctica. Allgén's publications have to a large extent been ignored by scientists working on marine nematodes, likely because of the poor quality of many of his species descriptions. The authors want to remind the scientific community about the existence of Allgén's collection, its availability for study and its importance for nematode taxonomy and systematics. A complete list of Allgén's publications, a list of all species described by him, and a list of type material available is presented.


Central control of bone remodelling.
The discovery that the brain controls bone remodelling has provided a new paradigm for our understanding of bone biology. This review summarises the genetic, molecular and physiological bases for the central control of bone remodelling and discusses the future directions of this new research field of neuroskeletal biology.


Power calculations for genetic association studies using estimated probability distributions.
The determination of the power of-or of an appropriate sample size for-genetic association studies that exploit linkage disequilibrium requires many assumptions. Some of the more important assumptions include the linkage-disequilibrium strength among alleles at the observed marker-locus sites and a potential trait-influencing locus, the frequencies of the marker locus and trait-influencing alleles, and the ultimate density of the marker locus "map" (i.e., the number of bases between marker loci) necessary in order to identify, with some confidence, trait-influencing alleles. I consider an approach to assessment of the power and sample-size requirements of genetic case-control association study designs that makes use of empirically derived estimates of the distributions of important parameters often assumed to take on arbitrary values. My proposed methodology is extremely general and flexible and ultimately can provide realistic answers to questions such as "How many markers and/or how many individuals might it take to identify, with confidence, a disease gene, via linkage-disequilibrium and association methods from a candidate region or whole genome perspective?" I showcase aspects of the proposed methodology, using information abstracted from the literature.


Crystal structures of medium-chain acyl-CoA dehydrogenase from pig liver mitochondria with and without substrate.
The three-dimensional structure of medium-chain acyl-CoA dehydrogenase from pig mitochondria in the native form and that of a complex of the enzyme and a substrate (product) have been solved and refined by x-ray crystallographic methods at 2.4-A resolution to R factors of 0.172 and 0.173, respectively. The overall polypeptide folding and the quaternary structure of the tetramer are essentially unchanged upon binding of the ligand, octanoyl (octenoyl)-CoA. The ligand binds to the enzyme at the rectus (re) face of the FAD in the crevice between the two alpha-helix domains and the beta-sheet domain of the enzyme. The fatty acyl chain of the thioester substrate is buried inside of the polypeptide and the 3'-AMP moiety is close to the surface of the tetrameric enzyme molecule. The alkyl chain displaces the tightly bound water molecules found in the native enzyme and the carbonyl oxygen of the thioester interacts with the ribityl 2'-hydroxyl group of the FAD and the main-chain carbonyl oxygen of Glu-376. The C alpha--C beta of the fatty acyl moiety lies between the flavin and the gamma-carboxylate of Glu-376, supporting the role of Glu-376 as the base that abstracts the alpha proton in the alpha--beta dehydrogenation reaction catalyzed by the enzyme. Trp-166 and Met-165 are located at the sinister (si) side of the flavin ring at the surface of the enzyme, suggesting that they might be involved in the interactions with electron transferring flavoprotein. Lys-304, the prevalent mutation site found in patients with medium-chain acyl-CoA dehydrogenase deficiency, is located approximately 20 A away from the active site of the enzyme.


Two sensitive immunometric assays for serum thyroid stimulating hormone evaluated.
This study was conducted to evaluate the analytical performance (functional sensitivity, reproducibility, parallelism, and accuracy) of two recent commercial kits marketed as third generation immunometric assays for measuring serum thyroid stimulating hormone (TSH). One assay is automated; the other is manual. Accuracy by method comparisons was evaluated using 86 patient samples assayed by an established third generation immunometric assay as the comparative method. The new assays met the third generation criterion for functional sensitivity (CV < or = 20 percent at TSH < or = 0.02 mIU/L), were reproducible (CVs < 11 percent), and measured serum TSH in parallel with the calibrator curves. Linear regression analysis of the intermethod comparison data showed highly correlated (R > .095) results; however, the regression slopes were non-unity, indicating patient sample results were not transferable between methods. Clinical laboratories choosing a third generation TSH assay should validate the performance characteristics of the selected method to ensure reliable results for patient care.


Hypoxic brain injury with motor apraxia following an anaphylactic reaction to hymenoptera venom.
Hypoxic brain injury can be a complication following several well known situations or disorders. The neurological and neuropsychological characteristics of patients who suffer hypoxic brain injury depend on the mechanism of injury and the structures of the brain that are particularly vulnerable to hypoxia. Injury to the hippocampus with resultant memory impairment is a well described clinical feature. Motor apraxia has not been described as a common feature following hypoxic injury. This paper describes an unusual case of hypoxic brain injury that resulted from an anaphylactic reaction to hymenoptera venom. The patient presented with severe ideomotor apraxia as he emerged from coma after cardiorespiratory arrest. Surprisingly, the patients memory was relatively preserved in relation to other cognitive impairments. A brief discussion of the pathophysiology of hypoxic brain injury and the patient's rehabilitation outcome is presented.


Assessment of nutritional habits and preferences among secondary school students
Appropriate nutrition is one of the most important factors affecting the proper development of man, nutritional status and maintaining good health. Adolescence is a period of development of skills of self-determination and self-realization, also in the case of nutrition. Children and school-age youth are the group most vulnerable to the effects of incorrect nutrition. The way of nutrition during this period determines psychophysical and emotional development, effectiveness in learning process and has influence on health in adulthood. The aim of this study was to evaluate the habits and nutrition preferences in secondary school students from Rzeszów and Krosno age 16-19 years and to identify the differences between their eating behaviours. The study involved 300 secondary school students from Rzeszów and Krosno. The research material was the Authors' questionnaire containing questions examining the eating habits of surveyed students. The statistical analysis was performed using the program StatSoft, Inc. STATISTICA version 12.0. To evaluate the differences between the two examined qualities there was used the Chi2 test of independence. As the statistically significant level there was assumed the level of p ≤ 0.05. In the surveyed group of high school students, more than half (59.66%) ate 4-5 meals a day. Snacking between meals declared 95% of high school students. Between meals the youth most frequently consumed fruits and vegetables (72.99%) and sweets (59.66%). Daily consumption of first breakfast before leaving the home declared more than half (62.33%) of the surveyed youth. Consuming products containing complete protein several times a week was declared by 49%. Whole wheat bread was daily consumed by 10.33% of the respondents, and grain products are daily consumed by 52.66% of the youth. 43.33% every day drank milk and milk products, while fruits and vegetables several times a day were consumed by 59.66% of the surveyed students. Consumption of products of "fast-food" type several times a month was declared by 49.66%, while irregular consumption of meals was declared by 20.33% of high school students. Physical activity was declared by 93.99%, and 3-5 times a week by only 21.66% of the surveyed students. The conducted research shows that eating habits of most of the surveyed secondary school students both from Rzeszów and Krosno are satisfactory. The comparison of dietary habits among secondary school students showed no significant differences. Both groups committed similar errors: sweets snacking between meals, irregular meals and insufficient physical activity. A positive phenomenon was snacking of fruit and vegetables between meals and selection of mineral water and juices as the most frequently consumed beverages.


Clinical Aspects Of Sclerodermatous Type Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation.
We aimed to evaluate the clinical features of sclerodermatous chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (AHSCT). We retrospectively analyzed 423 patients who underwent AHSCT. We assessed age, sex, pre-transplant diagnosis, conditioning regimen, GVHD prophylaxis, and occurrence of acute GVHD (aGVHD), chronic lichenoid and chronic systemic GVHD, and clinical properties of sclerodermatous GVHD. Sclerotic skin lesions developed in 22 patients after a mean of 752±647 days (median 480). aGVHD appeared in 17 patients, with hepatic involvement in 2, gastrointestinal tract involvement in 2 and skin involvement in 13 of these patients. Extensive chronic GVHD (liver, pulmonary, skin and oral mucosa) developed in 12 patients. Sclerosis was generalized in 19 patients (86.4%) and localized in 3 patients (13.6%). Leopard skin eruption appeared in 8 (36.4%) of the 19 patients with generalized sclerodermatous changes. In most cases, sclerotic lesions appeared on the trunk, and distal parts of the extremities were spared. Eight patients (36.4%) progressed from lichenoid to sclerodermatous lesions, 2 (9.1%) with lichenoid and sclerodermatous phases together and 12 (55.5%) with de novo sclerodermatous lesions. Five patients died because of late transplant-related complications. Sclerodermatous GVHD has a late onset and may be quite disabling. Unlike scleroderma, acral involvement is seen rarely. Although most lesions do not disappear in the course of the disease, most patients have a good prognosis.


Interrogation of surfaces for the quantification of adsorbed species on electrodes: oxygen on gold and platinum in neutral media.
We introduce a new in situ electrochemical technique based on the scanning electrochemical microscope (SECM) operating in a transient feedback mode for the detection and direct quantification of adsorbed species on the surface of electrodes. A SECM tip generates a titrant from a reversible redox mediator that reacts chemically with an electrogenerated or chemically adsorbed species at a substrate of about the same size as the tip, which is positioned at a short distance from it (ca.1 microm). The reaction between the titrant and the adsorbate provides a transient positive feedback loop until the adsorbate is consumed completely. The sensing mechanism is provided by the contrast between positive and negative feedback, which allows a direct quantification of the charge neutralized at the substrate. The proposed technique allows quantification of the adsorbed species generated at the substrate at a given potential under open circuit conditions, a feature not attainable with conventional electrochemical methods. Moreover, the feedback mode allows the tip to be both the titrant generator and detector, simplifying notably the experimental setup. The surface interrogation technique we introduce was tested for the quantification of electrogenerated oxides (adsorbed oxygen species) on gold and platinum electrodes at neutral pH in phosphate and TRIS buffers and with two different mediator systems. Good agreement is found with cyclic voltammetry at the substrate and with previous results in the literature, but we also find evidence for the formation of "incipient oxides" which are not revealed by conventional voltammetry. The mode of operation of the technique is supported by digital simulations, which show good agreement with the experimental results.


Balloon valvuloplasty for fungal endocarditis induced stenosis of a bioprosthetic tricuspid valve.
Palliative treatment was provided without complications by double balloon valvuloplasty of a stenotic porcine tricuspid valve in a patient with fungal endocarditis. With two 15 mm diameter valvulotomy balloons the peak tricuspid gradient decreased from 21 to 7 mm Hg and valve area increased from 0.3 to 1.2 cm2. After the procedure the patient clinically improved; however, valve replacement was not performed as planned because the patient developed an intracranial hemorrhage. She subsequently died of complications of fungemia. The present report demonstrates the possible use of valvuloplasty as a palliative procedure in selected patients with valvular stenosis involved with endocarditis.


Programmable snapping composites with bio-inspired architecture.
The development of programmable self-shaping materials enables the onset of new and innovative functionalities in many application fields. Commonly, shape adaptation is achieved by exploiting diffusion-driven swelling or nano-scale phase transition, limiting the change of shape to slow motion predominantly determined by the environmental conditions and/or the materials specificity. To address these shortcomings, we report shape adaptable programmable shells that undergo morphing via a snap-through mechanism inspired by the Dionaea muscipula leaf, known as the Venus fly trap. The presented shells are composite materials made of epoxy reinforced by stiff anisotropic alumina micro-platelets oriented in specific directions. By tailoring the microstructure via magnetically-driven alignment of the platelets, we locally tune the pre-strain and stiffness anisotropy of the composite. This novel approach enables the fabrication of complex shapes showing non-orthotropic curvatures and stiffness gradients, radically extending the design space when compared to conventional long-fibre reinforced multi-stable composites. The rare combination of large stresses, short actuation times and complex shapes, results in hinge-free artificial shape adaptable systems with large design freedom for a variety of morphing applications.


Stunting among children under 3 years of age in Côte d'Ivoire: spatial and temporal variations between 1994 and 2011.
To investigate spatial heterogeneity of stunting prevalence among children in Côte d'Ivoire and examine changes in stunting between 1994 and 2011, to assess the impact of the 2002-2011 civil war that led to temporary partitioning of the country. Data from 1994, 1998 and 2011 Côte d'Ivoire Demographic and Health Surveys (DHS) were analysed using a geostatistical approach taking into account spatial autocorrelation. Stunting data were interpolated using ordinary kriging; spatial clusters with high and low stunting prevalence were identified using Kulldorff spatial scan statistics. Multilevel multivariable logistic regression was then carried out, with year of survey as the main independent variable and an interaction term for time by geographic zone (Abidjan, South, North). Côte d'Ivoire, West Africa. Children aged 0-35 months included in three DHS (n 6709). Overall stunting prevalence was 30·7, 28·7 and 27·8 % in 1994, 1998 and 2011, respectively (P=0·32). Clusters with high prevalence were found in 1994 (in the West region, P<0·001) and 1998 (in the West and North-West regions, P<0·01 and P=0·01, respectively), but not in 2011. Abidjan was included in a cluster with low prevalence in all surveys (P<0·05). Risk of stunting did not change between 1994 and 2011 at national level (adjusted OR; 95 % CI: 1·39; 0·72, 2·64), but decreased in the South (0·74; 0·58, 0·94) and increased from 1998 to 2011 in Abidjan (1·96; 1·06, 3·64). In Côte d'Ivoire, significant changes in stunting prevalence were observed at the sub-national level between 1994 and 2011.


[Problems to be solved in the development from the perspective of future application scenarios of telesurgery].
Telemedicine, which integrates medicine, communication, engineering, information and other disciplines, is a hot emerging cross field in recent years. With the development of telecommunication technology and surgical robot, telesurgery is regarded as the "crown pearl" in telemedicine and has attracted more and more attention. As an extension of traditional surgery, telesurgery greatly extends the connotation and concept of surgery and embodies the great leap forward development of surgical technology. Despite the current limitations such as network delay, transparency of remote robot operation and team construction of surgeons, telesurgery has still formed a variety of innovative application scenarios and achieved rapid development in China in recent years. In view of the uneven distribution of medical resources in China and the epidemic of COVID-19 in the world, this paper puts forward the possible problems and solutions in the development of telesurgery, and looks forward to the feasibility of telesurgery technology in process of shifting the focus of medical and health care down to the community level, channeling resources accordingly.


Lewandowsky's Rosaceiform Eruption: a Form of Cutaneous Tuberculosis Confirmed by PCR in Two Patients.
Cutaneous tuberculosis (TBC) is a chronic disease caused by Mycobacterium tuberculosis, and is present in less than 1-2% of all TBC cases. The current problem with diagnosis is the demonstration of bacillus in the skin, especially paucibacillar forms, where sources like polymerase chain reaction (PCR) have improved diagnostic capacity. Two cases of cutaneous TBC are reported. The first patient was 52-year-old woman with facial erythematous papulo-nodular lesions which had been developing for 4 months, and had previously been treated as acne rosacea, with partial response. Histopathological studies showed chronic granulomatous inflammation. TBC was suspected, so PCR was performed, which showed positive for M. tuberculosis. The second case was a 43-year-old woman with a facial rosaceiform plaque which began 6 months previously, and was treated as rosacea without any change for 5 months. Skin biopsy and PCR were positive for TBC. Both cases were treated using primary schedule for TBC, and both presented a favorable response. A clinical profile called Lewandowsky's rosacea-like eruption has been previously described. The condition has been questioned for years and was later removed from the spectrum of tuberculids and cutaneous TBC for not being able to isolate microorganisms in skin samples, a situation that might now change. In paucibacillar forms, when culture and staining are negative and TBC is still suspected, it is recommended to use DNA amplification by PCR for an accurate diagnosis. Both cases bring up the concern about once again bringing Lewandowsky's rosaceiform eruption into the spectrum of cutaneous TBC, and the discussion about the current definition of tuberculid.


Flow characteristics of Luer and non-Luer spinal needles.
We investigated the flow rates of 25-G and 27-G spinal needles, of 90-mm and 120-mm lengths, from Vygon, BD, B. Braun and Pajunk; the needles had either a Luer connector, or a Surety® or UniVia® non-Luer connector. We used a bench-top model of entering the spinal space, pressurised to 35 cmH2 O to simulate cerebrospinal fluid pressure in the sitting position. We examined the time to first appearance of simulated cerebrospinal fluid in the needle hub, as well as the amount of fluid collected over 120 s after the needle was introduced. The mean (SD) times to first appearance of fluid in the needle hub of Luer spinal needles varied from 0.36 (0.22) s for the 25-G 90-mm BD to 3.14 (0.72) s for the 27-G 120-mm B. Braun, and in the non-Luer spinal needles from 0.22 (0.17) s for the 25-G 90-mm B. Braun to 2.99 (0.71) s for the 27-G 120-mm Pajunk. There was a significant difference in the time to first appearance of fluid in the needle hub between Luer and non-Luer needles of the same type for seven of 14 comparisons made, of which four showed slower appearance of fluid in the non-Luer version. In some of these cases, the time to appearance of fluid was nearly twice as long with the non-Luer counterpart. The mean (SD) weight of fluid collected in 120 s using the Luer spinal needles varied from 0.21 (0.05) g for the 27-G 120-mm Pajunk to 1.21 (0.18) g for the 25-G 90-mm Vygon, and using the non-Luer spinal needles from 0.25 (0.05) g for the 27-G 120-mm Pajunk to 1.55 (0.05) g for the 25-G 90-mm B. Braun. All of the needle types showed a greater weight of fluid collected using the non-Luer compared with the Luer version, with six of the 14 needle types showing a significant difference. Significant variations in flow were also seen between the same needle type from different manufacturers. We conclude that changing from Luer to non-Luer versions of spinal needles does not merely change the hub design and connection, but may introduce important differences in function.


[Condition of patients who require heart surgery during treatment for advanced digestive cancer and early recurrence after surgery- an assessment from the viewpoint of digestive surgeons].
The need for cardiac surgery among patients undergoing treatment for advanced digestive cancer is limited to the following situations:(i) heart diseases that can be life threatening if left untreated and that cannot be cured by medicinal treatment alone (e.g., cardiac tumors) and (ii) heart diseases (e.g., infectious endocarditis and pulmonary thromboembolism) occurring after digestive cancer surgery that need emergency treatment and that are resistant to medicinal treatment. We encountered 2 cases that required cardiac surgery.( Case 1) A 68-year-old woman with advanced gastric carcinoma accompanied by pyloric stenosis and left atrial myxoma underwent radical surgery for gastric cancer( Stage IIIA). Subsequently, the left atrial myxoma was resected before adjuvant chemotherapy for the treatment of gastric cancer was administered. One month after the surgery, multiple liver metastases appeared. However, they disappeared after chemotherapy was completed, and the patient survived for more than 3 years with complete response. (Case 2) A 67-year-old woman who underwent a Hartmann operation for obstructive rectal cancer (Stage II) experienced infectious endocarditis after the surgery. Because the endocarditis was resistant to medicinal treatment and acute heart failure was anticipated, cardiac surgery was performed. Approximately 2 months after the surgery, the bacilli( methicillin-resistant Staphylococcus aureus [MRSA]) were not found in blood culture. However, multiple liver metastases appeared immediately after the disappearance of the bacilli, and the patient died 3 months after the surgery. In both cases, cancer recurrence occurred early after cardiac surgery. Excessive surgical stress due to cardiac surgery may have promoted cancer recurrence. A decision pertaining to the timing of cardiac surgery is difficult in cases of patients with advanced digestive cancer and co-existing heart disease, which cannot be cured by medicinal treatment.


[The knowledge about mental disorders and the attitudes towards treatment among students--preliminary results].
Public image of psychiatry and psychiatrists is filled with stigmatizing stereotypes. Psychiatric patients also suffer from stigma. Mental illness is one of the most socially excluding stigmata. The aim of the study was to present state of knowledge about mental disorders among medical students and to assess students' attitudes to psychiatric treatment. The study involved 60 students from the Medical University of Lodz, a medical faculty (n = 30) and emergency medical services faculty (n = 30). The study used a questionnaire constructed by the authors, consisting of three parts: 1. socio-demographic variables, 2. attitudes towards psychiatric treatment, 3. knowledge about mental disorders. According to the majority of respondents (95%) specialization in psychiatry is necessary. Only 40% of respondents know that to hold a first visit to a psychiatrist a referral is not necessary. Over 90% of the students did not treat visiting the psychiatrist as a reason for shame. A small percentage of them would approach this appointment at the instigation (26.6%). Respondents demonstrated a knowledge of the causes of mental disorders, but confirmed the negative stereotypes about aggression of psychiatric patients and electroconvulsive therapy (only 22 students are aware of its use in modem psychiatry). According to the majority of respondents, mental illness does not begin suddenly (78.33%), hereditary factors play a dominant role in their development (48.33%), and stress significantly increases the risk of their occurrence. Only 26 of the respondents did not agree with the finding of increased aggressiveness of psychiatric patients. The image a mentally ill person in the eyes of medical students does not differ from the stereotypical thinking of the general population. The results of this study suggest necessity of spread the knowledge of psychiatry among medical students.


[Sexual violence in urban environments: example in the city of Lubumbashi, Democratic Republic of the Congo].
Introduction: Sexual violence, which is becoming increasingly recurrent in the Democratic Republic of the Congo, is a public health problem in Lubumbashi.Objective: The objective of this study was to determine the prevalence of sexual violence, the circumstances of occurrence and risk environments.Method: This was a retrospective, cross-sectional, descriptive study based on a document review of 116 female victims between the ages of 2 to 34 years attending the Kampemba General Hospital in Lubumbashi in 2013, generally for forensic examination.Results: The prevalence of sexual violence in Lubumbashi was 127 per 100,000 in the absence of any armed conflict. The frequency of sexual violence in Kampemba General Hospital was 3.35%. Victims of sexual violence were mostly young people (94%) aged 14 to 17 years (over 60% of cases), while the perpetrators of sexual violence were predominantly male (100%), civilians (98%) and adults (86.2%). 24% of pregnancies were observed among the victims and nearly 72% of cases of mental distress. Only 19.18% of cases of sexual violence were reported to the police.Conclusion: Gender-based sexual violence, which constitutes a denial of human rights and health remains a real public health problem in the DRC in general and especially in Lubumbashi.


Presence of radionuclides in sludge from conventional drinking water treatment plants. A review.
The analysis of sludge samples generated during water treatment processes show that different radioisotopes of uranium, thorium and radium, among others can accumulate in that kind of samples, even the good removal rates obtained in the aqueous phase (by comparison of influent and effluent water concentrations). Inconsequence, drinking water treatment plants are included in the group of Naturally Occurring Radioactive Material (NORM) industries. The accumulation of radionuclides can be a serious problem especially when this sludge is going to be reused, so more exhaustive information is required to prevent the possible radiological impact of these samples in the environment and also on the people. The main aim of this review is to outline the current situation regarding the different studies reported in the literature up to date focused on the analysis of the radiological content of these sludge samples from drinking water treatment plants. In this sense, special attention is given to the recent approaches for their determination. Another important aim is to discuss about the final disposal of these samples and in this regard, sludge reuse (including for example direct agricultural application or also as building materials) are together with landfilling the main reported strategies.


The comparison of sharps injuries reported by doctors versus nurses from surgical wards in the context of the prevalence of HBV, HCV and HIV infections.
The aim of the study was to evaluate the nature and frequency of sharps injuries among doctors and nurses from the same surgical/gynecological wards and the prevalence of HBV/HCV/HIV infection. An anonymous cross-sectional sero-survey, with ELISA system used to detect anti-HBc, anti-HCV, anti-HIV, was conducted among 89 doctors and 414 nurses from 16 randomly selected hospitals in West Pomerania, Poland, between January-June 2009. During the preceding 12 months, 82% doctors and 44.4% nurses (p<0.0001) had sustained at least one sharps injury; 12.3% doctors vs 2.2% nurses (p<0.003) sustained more than 10 injuries. The multivariable regression model revealed that being a doctor was associated with a greater odds (OR 4.2) of being injured with sharps. Sixty nine percent of nurses sustained a hollow-bore needle injury vs 8.9% doctors; p<0.001. Anti-HBc were found in 16.4% of doctors and 11.2% of nurses, p>0.28; anti-HCV - in 1.1% of doctors vs 1.4% of nurses, p>0.79; no anti-HIV positive cases were found. The analysis of potential risk factors for contracting a HBV revealed that for both job categories only length of employment was associated with an increased odds of being infected. Although the prevalence of HBV/HCV infection between doctors and nurses does not differ significantly, modifiable risk factors for contracting a BBI such as frequency and nature of sharps injuries may differ, which call for tailoring preventive measures to specific job categories. Long lasting exposure to injury events should be taken into consideration while assessing the risk for accuiring an occupational infection with HBV, HCV or HIV.


Impulsivity but not sensation seeking is associated with opioid analgesic misuse risk in patients with chronic pain.
Impulsivity and sensation seeking have been associated with substance use disorders, including opioid use disorders. This pilot study sought to examine whether impulsivity and sensation seeking, as measured by the Barratt Impulsiveness Scale (BIS) and Sensation Seeking Scale (SSS), were associated with opioid analgesic misuse risk in chronic, low-back pain patients prescribed opioid analgesics. Participants were 42 chronic, low-back pain patients enrolled in a larger study examining problematic opioid analgesic use. Impulsivity was assessed using the BIS, sensation seeking was measured using the SSS, and opioid analgesic misuse risk was assessed using the Current Opioid Misuse Measure (COMM). Significant bivariate associations were found between the COMM and the following predictor variables: age and the three BIS subscales: Attentional Impulsiveness, Non-planning Impulsiveness, and Motor Impulsiveness. Using a multivariate linear regression, after controlling for age, the BIS subscales accounted for 29.0% of the variance in the COMM. Attentional Impulsiveness was the only significant BIS subscale. These results suggest a potential relationship between impulsivity, but not sensation seeking, and risk for opioid analgesic misuse. Impulsivity is not a prominent trait observed in chronic pain patients; however, it may be an important risk factor for opioid analgesic misuse for a subset of individuals with chronic pain. As such, these findings suggest that additional exploration of this potential risk factor is warranted.


Activation of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway overcomes cisplatin resistance in ovarian carcinoma cells.
This study was aimed to elucidate the roles of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3'-kinase (PI3K)/Akt pathways in regulating cytotoxicity induced by cisplatin (CDDP) in ovarian carcinoma cells. We treated 7 ovarian cancer cell lines with CDDP alone or with CDDP and either a PI3K inhibitor (LY294002), a MEK inhibitor (PD98059), or a MEK/ERK activator (phorbol 12-myristate 13-acetate [PMA]) and assessed cell viability, expression of MEK/ERK and PI3K/Akt, cell cycle distribution, and apoptosis. We also investigated the effect of combination treatment on survival in a xenograft model. The cell lines showed half-maximal inhibitory concentrations (IC50) of CDDP from 2.4 to 26.9 μmol/L. KFr, a CDDP-resistant cell line developed from KF cells, showed an IC50 of CDDP of 9.6 μmol/L. Five of the cell lines with IC50 values of 9.6 μmol/L or greater were defined as CDDP-resistant. Cisplatin and LY294002 had an additive effect on inhibiting cell growth, and CDDP and PD98059 had and antagonistic effect on cell growth in all cell lines. In CDDP-resistant cells, CDDP and PMA dramatically suppressed the cell growth, up-regulated the expression of phosphorylated ERK and cleaved caspase-9, down-regulated the expression of checkpoint kinases, and increased the proportion of cells in the synthesis-phase fraction and apoptotic cells. The treatment of nude mice with CDDP and PMA prolonged survival in an ovarian cancer xenograft model. The present study indicates that further study is warranted to determine the effectiveness of combination treatment with CDDP and PMA for platinum-resistant ovarian carcinoma.


[Early complications and their causes in prosthetic hip joint replacement for coxarthrosis or median femoral neck fracture. Retrospective study of 3613 implanted hip joints].
In this retrospective descriptive study--including 3613 patients--type, frequency, and causes of early postoperative complications after total hip replacement are analysed. Operations were indicated in the majority of all cases by degenerative hip-joint diseases (n = 3214) and 399 cases by medial collum femoris fracture from adduction type (Garden III and IV). The frequency of early postoperative complications in total amount to 14.3%, the postoperative mortality was 2.3%. Total hip replacement in medial collum femoris fracture showed a significantly higher frequency of postoperative complications (4 times) and mortality (17 times). Complications in detail (cardiac, pulmonic, thromboembolic, early luxation, wound infection etc.) are represented and discussed in literature.


CE determination of quinolones in the presence of bovine serum albumin.
This article describes the influence of bovine serum albumin (BSA) as an additive on the capillary electrophoresis-potential gradient determination of five quinolones, enoxacin, norfloxacin, ofloxacin, fleroxacin, and pazufloxacin. With 10 mg/L of BSA present in the buffer of 30 mM Tris and 3 mM phosphoric acid at pH 9, the detection limits of the five quinolones were in the range of 0.24-0.68 mg/L, i. e. 5.8-16.5-fold lower than those obtained with the buffer devoid of BSA, and the analysis time was shortened. We suggest that the inner wall-adsorbed BSA suppresses the adsorption of quinolones and simultaneously enhances the electroosmotic flow rate. Our experiments indicated that adopting the potential gradient detection technique could eliminate the interference of the UV-active proteins on the detection of quinolones that would occur with conventional optical detection, and therefore offer high detection sensitivity. As a demonstration, the method was applied to the determination of QNs in fortified chicken muscle sample with satisfactory results.


New Reports on the Portuguese Endemic Species, Santolina impressa: Secretory Structures, Essential Oil Composition and Antiviral Activity.
Santolina impressa is an aromatic Asteraceae species endemic to Portugal, traditionally used for its anti-inflammatory properties. The aim of this study was to characterize S. impressa secretory structures, analyze the essential oil (EO) from the aerial organs, and evaluate its antiviral activity against herpes simplex viruses HSV-1 and HSV-2. Secretory structures were investigated by light and scanning microscopy, and the secretion was histochemically characterized. The EO from the aerial organs in full blooming was analyzed by gas chromatography with flame ionization detection and gas chromatography-mass spectrometry. Antiviral assays were performed by direct contact with viral suspensions (virucidal effect), and in infected Vero E6 cells, at different time periods during the viral replication cycle. Two types of secretory structures were described, biseriate glandular trichomes and secretory ducts, producing an oleoresin and a resin rich in flavonoids, respectively. Fifty compounds were identified in S. impressa EO, accounting for 87% of the total constituents. Monoterpenes constituted the main EO fraction (82%), with β-pinene (13%) and β-phellandrene (10%) being their major components. The EO interacted with HSV-1 and HSV-2 in a dose-dependent manner, thereby inactivating both viral infections. The EO did not evidence a virucidal effect but inhibited the HSV-1 and HSV-2 infection in Vero cells in a dose-dependent manner. However, further studies are needed to investigate the mode of action in the replication cycle.


[Diagnostic significance of immunophenotyping and detection of gene rearrangement in subcutaneous panniculitis-like T-cell lymphoma].
To explore the diagnostic implication of immunophenotyping and gene rearrangement in subcutaneous panniculitis-like T-cell lymphoma (SPTL). According to the selection criteria of 2005 WHO-EORTC classification for cutaneous lymphomas, 20 SPTL patients were enrolled in this study. A 10-antibody panel was used for immunophenotyping and in addition, polymerase chain reaction for TCR gamma and IgH gene rearrangement and in situ hybridization for EBER1/2 were also employed. There were 9 males and 11 female with a mean age of 29.5 years. Immunophenotypic study showed that all the patients expressed one to three T-cell associated antigens (CD2, CD3 or CD45RO), 18 patients were positive for beta F1, 18 for CD8, 20 for TIA-1 and 16 for granzyme B. None of the patients expressed CD4, CD20 and CD56. TCR gamma gene rearrangement was found in 16 of 20 cases (80.0%) and none for IgH gene rearrangement. The positive rate of EBER1/2 was 25.0% (5/20). Since the majority of SPTL patients show clonal TCR gene rearrangements, correlations among clinical presentation, histological features, immunophenotype and gene rearrangement data are considered important in confirming a diagnosis of SPTL.


Autism Insurance Mandates in the US: Comparison of Mandated Commercial Insurance Benefits Across States.
Autism mandates are laws that require commercial insurers to cover certain evidence-based treatments for Autism Spectrum Disorder (ASD). The purpose of this study was to review state variability in autism insurance mandates and the benefits they cover and to discuss recommendations for research and policy to improve ASD services across states. Data were extracted from 2001 to 2020 from all 50 states plus the District of Columbia (N = 51) from policy text. News articles and websites of ASD advocacy organizations were also reviewed to ensure inclusion of the most recent policy changes. Descriptive statistics and heatmaps were used to characterize the autism mandate landscape and visualize variability in benefit parameters across states. Autism mandates vary greatly in benefit parameters across US states, but there is a common set of benefits that most states have adopted. These include coverage of provider-recommended ASD services except for medical equipment, coverage up to an age limit of 18 to 21, an annual dollar limit of $36,000 with no restriction on the number of hours or visits, no lifetime cap on benefits, and requirement of BCBA® certification or its equivalent for providers of ABA. There is a need for continued research evaluating the impact of autism mandates and benefit parameters on access to care, service utilization, and clinical outcomes for the ASD population. Stakeholder engagement and understanding the impact of autism mandates on clinical and patient-centered outcomes may provide direction for policy advocacy and public health initiatives.