Do Acute Myocardial Infarction and Heart Failure Readmissions Flagged as Potentially Preventable by the 3M Potentially Preventable Readmissions Software Have More Process-of-Care Problems?
The 3M Potentially Preventable Readmissions (3M-PPR) software matches clinically related index admission and readmission diagnoses that may signify in-hospital or postdischarge quality problems. To assess whether the PPR algorithm identifies preventable readmissions, we compared processes of care between PPR software-flagged and nonflagged cases. Using 2006 to 2010 national VA administrative data, we identified acute myocardial infarction and heart failure discharges associated with 30-day all-cause readmissions, then flagged cases (PPR-Yes/PPR-No) using the 3M-PPR software. To assess care quality, we abstracted medical records of 100 readmissions per condition using tools containing explicit processes organized into admission work-up, in-hospital evaluation/treatment, discharge readiness, postdischarge period. We derived quality scores, scaled to a maximum of 25 per section (maximum total score=100) and compared cases on total and section-specific mean scores. For acute myocardial infarction, 77 of 100 cases were flagged as PPR-Yes. Section quality scores were highest for in-hospital evaluation/treatment (20.5±2.8) and lowest for postdischarge care (6.8±9.1). Total and section-related mean scores did not differ by PPR status; respective PPR-Yes versus PPR-No total scores were 61.6±11.1 and 60.4±9.4; P=0.98. For heart failure, 86 of 100 cases were flagged as PPR-Yes. Section scores were highest for discharge readiness (18.8±2.4) and lowest for postdischarge care (7.3±8.1). Like acute myocardial infarction, total and section-related mean scores did not differ by PPR status; PPR-Yes versus PPR-No total scores were 61.2±10.8 and 63.4±7.0, respectively; P=0.47. Among VA acute myocardial infarction and heart failure readmissions, the 3M-PPR software does not distinguish differences in case-level quality of care. Whether 3M-PPR software better identifies preventable readmissions by using other methods to capture poorly documented processes or performing different comparisons requires further study.


Sutureless coronary anastomoses: revival of old concepts.
Surgical environment is becoming increasingly challenging for the cardiac surgeon since off-pump coronary arteries bypass grafts and minimally invasive approach came up. The suture technique for coronary anastomosis construction is becoming inadequate to meet new surgeons' demand. Therefore, there is an increasing need for alternative ways to perform coronary bypasses. This article reviews the most recent devices developed for cardiac surgery (Q-Cab and distal connector from St. Jude Medical, CoreLink from Ethicon, GraftConnector from Jomed Int.), and demonstrates that the new anastomotic technologies are based on concepts expressed by Payr and other authors in the 19th century. We propose to consider three aspects to evaluate a sutureless anastomotic device: the device-vessel wall connection, the graft preparation and the anastomosis' biomechanical properties. Pins, wall eversion on an anvil and squeezing are the three systems used to anchor the connector to the graft and to the native artery. The graft preparation and anastomotic biomechanics are analysed with respect to the possibility of affecting graft patency rate. Finally, we trace the profile of the ideal anastomotic device: minimal graft manipulation, no limitation in anastomotic timing, no material in the vessel lumen and optimal anastomotic angle and compliance. The evidence of long-term graft patency is fundamental for any anastomotic device to become widely acceptable.


[Action of proteinase inhibitors. 4. Effect of short-term application of chymostatin on nitrogen metabolism in the digestive tract and protein metabolism in tissue].
Chymostatin is an effective inhibitor of intracellular proteinases in vitro. In the present experiment male rats were injected intraperitonealy during a 3 days period twice daily with a solution containing 0,9 mg Chymostatin per 100 g live weight. Reference animals received a control injection containing the same solvents but no chymostatin. During this period a daily nitrogen balance was made and metabolic faecal nitrogen and true digestibility of nitrogen were estimated using 15N-labelled animals. Furthermore, apparent biological half lives of proteins in liver and intestinal tissues were determined following the decay curves for radioactivity in proteins 48 hours after injection of L-[5-3H]-arginine und L-[guanido-14C]-arginine. The fractional rate of protein synthesis in tissues was measured by a 6 hours continuous infusion technique with L-[U-14C]-tyrosine and L-[U-14C]-leucine. Among the parameters estimated only the apparent biological half lives of proteins in liver and intestinal tissues were influenced by chymostatin. However, the prolonged half lives seemed to be rather an effect of an increased reutilisation of amino acids resulting from the intracellular protein breakdown than a decreased rate of protein degradation. The in vivo effect of the proteinase inhibitor was by far inferior compared with the action in vitro. Factors like distribution, degradation and excretion of the inhibitor could be responsible for the moderate in vivo action of chymostatin.


FRET-Modulated Fluorescence Lifetime-Traceable Nanocarriers for Multidrug Release Monitoring and Synergistic Therapy.
In situ monitoring multidrug release in complex cellular microenvironments is significant, and currently, it is still a great challenge. In this work, a smart nanocarrier with the capability of codelivery of small molecules and gene materials as well as with Förster resonance energy transfer (FRET)-modulated fluorescence lifetime is fabricated by integrating gold nanoparticles (the acceptor) into dual-mesoporous silica loaded with multiple drugs (the donor). Once internalized into tumor cells, in weakly acidic environments, the conformation switch of the polymer grafted on nanocarriers causes its shedding from the mesopores, triggering the release of drugs. Simultaneously, based on the strong overlap between the emission spectrum of donors and the absorption spectrum of the acceptors, any slight fluctuation of the dissociation of the drugs from nanocarriers can result in a change in the FRET-modulated lifetime signal due to the extraordinarily sensitive FRET signal to the separation distance between donors and acceptors. All these implied the potential applications of this nanoplatform in various biomedical fields that require the codelivery and real-time monitoring of multidrug-based synergistic therapy.


Efficacy of Low-Dose Trimethoprim/Sulfamethoxazole for the Treatment of Pneumocystis jirovecii Pneumonia in Deceased Donor Kidney Recipients.
Trimethoprim/sulfamethoxazole (TMP-SMX) is considered the first-choice treatment for Pneumocystis jirovecii pneumonia (PJP) in recipients of solid organ transplantation. However, this treatment is associated with various severe adverse events that might not be tolerable for some renal transplant recipients, and the optimal dose remains elusive. The present study assessed the efficacy of low-dose TMP-SMX in recipients of a deceased donor kidney. A total of 37 adult deceased donor kidney recipients who suffered PJP between January 2015 and June 2020 were included. The survival rates of the patients and grafts, the rate of invasive ventilation, and adverse events, including gastrointestinal discomfort, hematologic side effects, hyperkalemia, and renal function impairments, were assessed. The patient and graft survival rates were both 100%. Two patients (5.4%) required invasive ventilation. Eight patients (21.6%) reported gastrointestinal discomfort, but none required dose reduction or discontinued treatment. The frequencies of hematologic side effects, hyperkalemia and impaired kidney function were 5.4% (2/37), 2.7% (1/37), and 2.7% (1/37), respectively. Optimization of TMP-SMX dose may reduce the risk of adverse events without compromising efficacy for the treatment of PJP in deceased donor kidney recipients.


Gamete and immune cell recognition revisited.
Fertilization is the result of a series of successful recognition and binding events mediated by gamete surface molecules. Recent advances in the identification and characterization of some of these recognition molecules provide extremely valuable information necessary to understand sperm-egg recognition and subsequent egg activation. We discuss these new data in the context of the model of gamete recognition first proposed by F.R. Lillie in the early part of the 20th century, and revisited periodically in the subsequent literature, which relates fertilization events to those of immune cell recognition and activation events. Here we discuss the principles underlying the molecular recognition and activation mechanisms of gametes and immune cells.


Narrow linewidth swept laser source based on cascaded multi-wavelength injection of DFB lasers.
A linearly swept laser source over broadband with a fast sweep rate and narrow linewidth is realized using a novel optoelectronic scheme based on a multi-wavelengths (mutually coherent) injected distributed feedback (DFB) laser. Under the condition of multi-wavelengths injection, the injection-locking and four-wave mixing (FWM) process can occur simultaneously in the DFB laser, inducing a swept laser source with a sweep range of 100 GHz and sweep rate of 10 THz/s. Furthermore, with the phase noise character analyzation of the swept laser source, the phase noise deterioration due to the radio frequency (RF) signal is studied quantitatively. Besides the influence of the RF signal noise, the phase noise deterioration in the FWM process can be suppressed completely with the phase-locked pump beam and signal beam based on the injection-locking principle. This low phase noise swept laser source with sub-kilohertz linewidth could have wide applications in lidar.


Adverse motor effects induced by antiepileptic drugs.
Cognitive effects of anti-epileptic drugs (AEDs) have been already extensively reported. In contrast, motor disturbances, frequently induced by these drugs, have not received similar attention. We review subjective and objective adverse motor effects of traditional and new AEDs. We discuss the methodological issues caused by the heterogeneous sources of information on drug adverse effects (controlled clinical studies, open studies, and case reports). We describe specific disturbances (vestibulocerebellar, dyskinesias, parkinsonism, tics, myoclonus, and tremor) as the effects of different AEDs on distinct motor circuitries. Finally, we summarize the role of sophisticated technical studies which provide a valuable insight into the specific or subtle effects of AEDs on the central nervous system.


Antinociceptive mechanisms of platycodin D administered intracerebroventricularly in the mouse.
Platycodin D administered intracerebroventricularly (i.c.v.) showed an antinociceptive effect in a dose-dependent manner as measured by the tail-flick assay. The antinociception induced by platycodin D was maintained at least 1 h. MK-801 [(+/-)-5-methyl-10,11-dihydro-5 H-dibenzo[ a,d]cyclohepten-5,10-imine maleate], a competitive N-methyl- D-aspartic acid (NMDA) receptor antagonist, or CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), a non-NMDA receptor antagonist, muscimol (a GABA(A) receptor agonist), or baclofen (a GABA(B) receptor antagonist), or sulfated cholecystokinin (CCK-8 s; CCK A receptor agonist), injected i.c.v. significantly reduced the inhibition of the tail-flick response induced by platycodin D administered i.c.v. Additionally, intrathecal (i.t.) pretreatment with yohimbine (an alpha 2 -adrenergic receptor antagonist) or methysergide (a serotonin receptor antagonist) dose-dependently attenuated inhibition of the tail-flick response induced by i.c.v. administered platycodin D. However, naloxone (an opioid receptor antagonist) did not affect the inhibition of the tail-flick response induced by platycodin D. Our results suggest that platycodin D has an antinociceptive effect when it is administered supraspinally, and supraspinal GABA(A), GABA(B), NMDA and non-NMDA receptors are involved in platycodin D-induced antinociception. Furthermore, platycodin D administered supraspinally produces antinociception by stimulating descending noradrenergic and serotonergic, but not opioidergic, pathways.


Comparison of granulocyte-macrophage colony-stimulating factor and sucralfate mouthwashes in the prevention of radiation-induced mucositis: a double-blind prospective randomized phase III study.
To compare granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwashes with sucralfate mouthwashes in the prevention of radiation-induced mucositis. Forty patients with radically operated head-and-neck cancer were randomly allocated to use either GM-CSF (n = 21) or sucralfate (n = 19) mouthwashes during postoperative radiotherapy (RT). All patients received conventionally fractionated RT to a total dose of 50-60 Gy in 2-Gy daily fractions during 5-6 weeks to the primary site and regional lymphatics. A minimum of 50% of the oral cavity and oropharyngeal mucosa was included in the clinical target volume. GM-CSF mouthwashes consisted of 37.5 microg GM-CSF and sucralfate mouthwashes of 1.0 g of sucralfate distilled in water. Both washes were used 4 times daily, beginning after the first week of RT and continued to the end of the RT course. Symptoms related to radiation mucositis and body weight, serum prealbumin level, and blood cell counts were monitored weekly. Oral mucositis tended to be less severe in the GM-CSF group (p = 0.072). Complete (n = 1) or partial (n = 4) healing of mucositis occurred during the RT course in 5 patients (24%) in the GM-CSF group and in none of the patients in the sucralfate group (p = 0.049). Patients who received GM-CSF had less mucosal pain (p = 0.058) and were less often prescribed opioids for pain (p = 0.042). Three patients in the sucralfate group needed hospitalization for mucositis during RT compared with none in the GM-CSF group. Four patients (21%) in the sucralfate group and none in the GM-CSF group required an interruption in the RT course (p = 0.042). No significant differences in weight, prealbumin level, or blood cell count were found between the groups, and both mouthwashes were well tolerated. GM-CSF mouthwashes may be moderately more effective than sucralfate mouthwashes in preventing radiation-induced mucositis and mucositis-related pain, and their use may lead to less frequent RT course interruptions from mucositis. The present findings need to be confirmed before adopting GM-CSF mouthwashes in routine clinical use.


Mechanistic Studies of the Catalytic Reduction of CO2 to CO: Efficient CO-Releasing Si- and Ge-Based Catalysts.
Besides its significant challenges, efficient catalytic conversion of CO2 to value-added chemicals is highly desired. Herein, we report efficient silicon- and germanium-based catalysts for CO2 activation and its reduction to CO studied using B3LYP-GD3/6-31++G(d,p)/tetrahydrofuran (THF) and M06-2X/6-311++g(d,p)/THF density functional theory methods. The catalysts were systematically designed based on the previously reported silicon- and germanium-based compounds. The germanium-based catalysts are reported for the first time in this study. The calculated transition state energy barriers (5.7-15.8 kcal/mol) indicate that all the catalysts can easily activate CO2. Among all the B3LYP-GD3-calculated transition-state energy barriers, the highest energy barrier found (27.2-28.3 kcal/mol) is for the protonation of the carboxylic acid group of the silacarboxylic and germacarboxylic acids. Once the silacarboxylic and germacarboxylic acids are protonated, the water molecule can easily dehydrate and leave the catalysts with CO. The electrochemical reduction of the M-CO (M = Si and Ge) complexes further enhances the complexes to easily release CO, with all transition state energy barriers being lower than 10 kcal/mol. The results show that both CO2 activation and its reduction to CO using the studied catalysts are thermodynamically and kinetically favorable. This work provides an important insight for CO2 activation and its reduction to CO using earth-abundant and nontoxic main group element-based catalysts.


Coping strategy enhancement for the treatment of distressing voices in young people: A service evaluation within routine clinical practice.
Hearing voices is a common experience in young people, irrespective of diagnosis. This experience can be associated with distress, self-harm and an increased risk of attempting suicide. However, there are currently no evidence-based interventions which specifically target distressing voice hearing experiences in young people. This was a service evaluation exploring the engagement, outcomes and experiences of young people who were offered a brief 4-session intervention for distressing voices within a Child and Adolescent Mental Health Service (CAMHS) in the UK's National Health Service. The intervention was based on the principles of Coping Strategy Enhancement (CSE). A total of 24 young people were offered the CSE intervention over a 20-month period. The intervention was completed by 15 young people. Pre-post outcomes suggested clinically meaningful reductions in the negative impact of voices for the majority of the young people. Qualitative feedback was positive and highlighted the value of both a space to talk about voice hearing experiences and a focus upon coping strategies. The findings from this service evaluation suggest that CSE can be a brief, acceptable and helpful way for young people within a CAMHS context to start a therapeutic conversation about their distressing voice hearing experiences.


Superficial Femoral Artery Pseudoaneurysm and Arterial Wall Destruction After Drug-Coated Balloon Treatment.
Drug-coated balloon angioplasty may present an efficient alternative to traditional balloon angioplasty and stenting, which suffer from high rates of restenosis and increased risk of stent fractures in the anatomically unfavorable regions, such as the superficial femoral artery in the adductor canal. Although pseudoaneurysms are the most common vascular access site complications, they are considerably rarer at the site of the endovascular treatment. They can be caused by several mechanisms, including stent fractures, usage of oversized balloons, high-pressure inflations, and infections. In addition, paclitaxel, the drug released from drug-coated balloons, may also play a significant role in the formation and exacerbation of pseudoaneurysms. The exact pathophysiology remains unclear, but it may be due to a combination of paclitaxel's suppression of neointimal healing and immune response, cytotoxic properties, and hypersensitivity-related inflammation.


The impact of cognitive delay on pediatric heart transplant outcomes.
The presence of CD may be viewed as a relative contraindication to transplantation; however, its impact on pediatric HTx outcomes is poorly characterized. The aim of this study was to assess the impact of CD on pediatric HTx outcomes using academic progress as a surrogate measure of cognitive performance. The OPTN database was queried for all pediatric HTx recipients (2004-2014) with reported academic progress. Multivariable analysis assessed the impact of DGL and the need for SE on post-HTx graft survival. A total of 2245 children were included: 1707 (76%) within grade level, 269 (12%) with DGL, and 269 (12%) who required SE. The need for SE was not a risk factor for post-HTx mortality; however, DGL was an independent risk factor for worse post-HTx outcomes (AHR 1.4, 95% CI 1.02, 1.79, P=.03). Patients who require SE have similar outcomes compared to those without CD, likely secondary to significant parental involvement. Children with DGL demonstrate inferior post-HTx survival, which could result from less parental oversight in children perceived to maintain compliance. Ensuring adequate social support for patients with evidence of CD may help to improve outcomes.


The telephone survey method: a discussion paper.
The telephone survey method is discussed in the light of the experiences of one research team investigating case management practices among nurses working in the community using a multiple-method design. An account is given of the strategies employed to recruit a study sample, minimize non-response and bias and ensure the use of sound practices during data collection. The findings highlight the benefits of using the telephone survey method when recruiting respondents across a wide geographical area and/or working within a continually changing environment. However, the findings also highlight the challenge of non-response caused by non-contact and the resource implications of 'doing more' to recruit key informants via the telephone.


Proteus, Matrine, and Pyridalyl Toxicity and Their Sublethal Effects on Orius laevigatus (Hemiptera: Anthocoridae).
Proteus, matrine, and pyridalyl were tested in the laboratory for their effects upon Orius laevigatus (Fieber), which is a polyphagous predator used for IPM programs of Frankliniella occidentalis (Pergande). Against female adults, the most toxic insecticide was Proteus (LC50 = 44.3 µl L-1), followed by pyridalyl (LC50 = 83.8 µl L-1) and matrine (LC50 = 102.7 µl L-1). The mortality of female adults was checked 24, 48, 72, and 96 h after exposure to 14-d residues of the treatments on strawberry leaves. The residual of Proteus was less toxic; the remaining products caused the lowest mortality at different times after exposure. Sublethal treatments (LC25) significantly prolonged the developmental duration of total immature stages from 17.6 d in control to 21.6 and 20.0 d in Proteus and pyridalyl treatments, respectively. Also, the fecundity of O. laevigatus treated with Proteus, pyridalyl, and matrine decreased to 58.8%, 75.6%, and 96.7%, respectively, in comparison to the control. Compared with the control population (0.118 d-1), the intrinsic rate of increase (r) of F1 generation decreased by 0.053, 0.095, and 0.110 d-1 in Proteus, pyridalyl, and matrine treatments, respectively. The consumption rate of control bugs reached 14.0 thrips during 24 h. The adults fed on Proteus treatment had the lowest consumption rate in this period (9.4 preys). Overall, matrine proved to be harmless with reproductive capacity and r similar to what was recorded in control bugs. We concluded that matrine can be used as an alternative for the synthetic insecticide to integrate with O. laevigatus.


Compressive-Sensing-Based Structure Identification for Multilayer Networks.
The coexistence of multiple types of interactions within social, technological, and biological networks has motivated the study of the multilayer nature of real-world networks. Meanwhile, identifying network structures from dynamical observations is an essential issue pervading over the current research on complex networks. This paper addresses the problem of structure identification for multilayer networks, which is an important topic but involves a challenging inverse problem. To clearly reveal the formalism, the simplest two-layer network model is considered and a new approach to identifying the structure of one layer is proposed. Specifically, if the interested layer is sparsely connected and the node behaviors of the other layer are observable at a few time points, then a theoretical framework is established based on compressive sensing and regularization. Some numerical examples illustrate the effectiveness of the identification scheme, its requirement of a relatively small number of observations, as well as its robustness against small noise. It is noteworthy that the framework can be straightforwardly extended to multilayer networks, thus applicable to a variety of real-world complex systems.


A twisting electronic nanoswitch made of DNA.
Single-stranded DNAs and RNAs that are rich in the nucleobase guanine form four-stranded G-quadruplexes, which are held together by hydrogen-bonded guanine quartets. In aqueous solution, both DNA duplexes and G-quadruplexes are modest conductors of electrical charge. A tight, topologically constrained DNA construct called twDNA is now reported, in which a core of four guanine-rich single strands structurally and electronically links together four DNA double helices. The addition and removal of K(+) or Sr(2+) cations promote alternative conformers of twDNA, which have strikingly distinct electronic properties. Unlike DNA mechano-electronic switches that require large conformational changes, twDNA requires only modest twisting/untwisting structural attenuations to achieve electronic switching.


Creating standard treatment protocols: an analysis of pharmacy charges as an aid in their development.
A method for selecting DRG categories that have the potential for greatest pharmacy cost savings is described for a 400-bed, urban medical center. Seven variables describing the overall hospital costs and the specific pharmacy charges for 252 patients categorized under the four most prevalent DRGs observed over a 7-month period were examined. The DRG for chronic obstructive pulmonary disease was found to have the highest mean value for four of the seven variables and thus was selected as the first DRG for which to develop a standard treatment protocol. Preliminary progress in the design of pharmacy services within the standard treatment protocol are discussed.


Pneumococcal serotypes from acute otitis media in rural Kentucky.
Acute otitis media (AOM) accounts for most infections caused by, but few data are available regarding the incidence of pneumococcal serotypes recovered from children with AOM in the United States. Between January 1992 and March 1998, 777 middle ear pathogens from AOM were obtained from 701 patients by tympanocentesis (84.6%) or by culture of otorrhea (15.4%) from spontaneous perforation or draining tubes. The ambulatory patient population was mostly white and cared for by a sole private pediatric practice in rural Kentucky. Penicillin-nonsusceptible (penicillin MIC > or = 0.1 microg/ml) (PNSP) isolates accounted for 18% [6% resistant PNSP (rPNSP) and 12% intermediate resistant PNSP], and penicillin-susceptible strains accounted for 35% of the pathogens recovered from children with culture-proved AOM. Comparing the frequency of isolates between 1992 and 1993 with those between 1994 and 1998, overall rates of PNSP strains remained remarkably stable (32.2% 37.3%), but intermediate resistant PNSP strains doubled from 14% to 27% ( < 0.01), whereas rPNSP strains fell by one-third. Serotypes 19F (34%), 23F (30%), 6B (26%) and 14 (8%) accounted for nearly all rPNSP isolates. Two cross-reactive serotypes (6A and 19A) not included in the available pneumococcal conjugate vaccine comprised 8.4 and 15% of all serotypes and PNSP serotypes, respectively. Nearly all PNSP strains recovered in children < or =24 months are included in the vaccine serogroups. Depending on rates of efficacy and serotype cross-protection, the current pneumococcal conjugate vaccine could potentially protect against most PNSP strains in all ages, particularly in those < or =24 months.


Calcineurin binds the transcription factor NFAT1 and reversibly regulates its activity.
NFAT1 (previously termed NFATp) is a cytoplasmic transcription factor involved in the induction of cytokine genes. We have previously shown that the dephosphorylation of NFAT1, accompanied by its nuclear translocation and increased DNA binding activity, is regulated by calcium- and calcineurin-dependent mechanisms, as each of these hallmarks of NFAT1 activation is elicited by ionomycin and blocked by the immunosuppressive drugs cyclosporin A and FK506 (Shaw, K.T.-Y., Ho, A.M., Raghavan, A., Kim, J., Jain, J., Park, J., Sharma, S., Rao, A., and Hogan, P.G. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 11205-11209). Here we show that the activation state of NFAT1 in T cells is remarkably sensitive to the level of calcineurin activity. Addition of cyclosporin A, even in the presence of ongoing ionomycin stimulation, results in rephosphorylation of NFAT1, its reappearance in the cytoplasm, and a return of its DNA binding activity to low levels. Similar effects are observed upon removal of ionomycin or addition of EGTA. We also demonstrate a direct interaction between calcineurin and NFAT1 that is consistent with a direct enzyme-substrate relation between these two proteins and that may underlie the sensitivity of NFAT1 activation to the level of calcineurin activity. The NFAT1-calcineurin interaction, which involves an N-terminal region of NFAT1 conserved in other NFAT family proteins, may provide a target for the design of novel immunosuppressive drugs.


Chlorophyll-Protein Complexes from the Red-Tide Dinoflagellate, Gonyaulax polyedra Stein : Isolation, Characterization, and the Effect of Growth Irradiance on Chlorophyll Distribution.
A comparision of high (330 microeinsteins per meter squared per second) and low (80 microeinsteins per meter squared per second) light grown Gonyaulax polyedra indicated a change in the distribution of chlorophyll a, chlorophyll c(2), and peridinin among detergent-soluble chlorophyll-protein complexes. Thylakoid fractions were prepared by sonication and centrifugation. Chlorophyll-protein complexes were solubilized from the membranes with sodium dodecyl sulfate and resolved by Deriphat electrophoresis. Low light cells yielded five distinct chlorophyll-protein complexes (I to V), while only four (I' to IV') were evident in preparations of high light cells. Both high molecular weight complexes I and I' were dominated by chlorophyll a absorption and associated with minor amounts of chlorophyll c. Both complexes II and II' were chlorophyll a-chlorophyll c(2)-protein complexes devoid of peridinin and unique to dinoflagellates. The chlorophyll a:c(2) molar ratio of both complexes was 1:3, indicating significant chlorophyll c enrichment over thylakoid membrane chlorophyll a:c ratios of 1.8 to 2:1. Low light complex III differed from all other high or low light complexes in that it possessed peridinin and had a chlorophyll a:c(2) ratio of 1:1. Low light complexes IV and V and high light complexes III' and IV' were spectrally similar, had high chlorophyll a:c(2) ratios (4:1), and were associated with peridinin. The effects of growth irradiance on the composition of chlorophyll-protein complexes in Gonyaulax polyedra differed from those described for other chlorophyll c-containing plant species.


Large unidentified open reading frame in plastid DNA (ORF2280) is expressed in chloroplasts.
The chloroplast DNA encodes genes for components of photosynthesis and the transcription-translation machinery; a number of unidentified open reading frames (ORFs) are also present. To determine whether a large ORF in the inverted repeat of chloroplast DNA of tobacco (ORF2280) encodes a chloroplast protein, a conserved region of the ORF was expressed in Escherichia coli. An antibody against the ORF protein was prepared using the purified fusion protein as an antigen. When incubated with proteins from the soluble fraction of tobacco, spinach and Oenothera chloroplasts, the antiserum detects relatively labile polypeptides, which have apparent molecular weights of 170 to 180 kDa. The ORF in tobacco and spinach is large enough to encode a protein of 240-250 kDa, thus it is possible that post-transcriptional or post-translational processing reduces the size of the expression product. Analysis of Oenothera chloroplasts representing four different plastome types revealed endonuclease restriction fragment length polymorphisms in chloroplast DNA indicative of insertion/deletion events in a region of the chloroplast DNA that shared significant sequence similarity with ORF2280. The ORF2280 antiserum was used to demonstrate that there are qualitative differences in the ORF proteins from different Oenothera plastome types.


Measuring Enzymatic Stability by Isothermal Titration Calorimetry.
This work demonstrates a new method for measuring the stability of enzyme activity by isothermal titration calorimetry (ITC). The peak heat rate observed after a single injection of the substrate solution into an enzyme solution is correlated with enzyme activity. Multiple injections of the substrate into the same enzyme solution over time show the loss of enzyme activity. The assay is autonomous, requiring very little personnel time, and is applicable to most media and enzymes.


Buffers of Racial Discrimination: Links with Depression among Rural African American Mothers.
The current study examines racial discrimination as a predictor of depression in a sample of 414 rural, low-income African American mothers of young children. The potential moderating role of optimism and church-based social support was also examined. Mothers completed questionnaires when their child was 24-months-old. Hierarchical regression revealed that mothers' perception of racism was a significant predictor of depression even after controlling for a variety of distal demographic characteristics and environmental stressors. Significant interactions suggested the importance of psychological and social characteristics in understanding maternal depression. Specifically, high levels of optimism and church-based social support buffered mothers from increased depressive symptomology due to perceived racism.


Effects of chlorpromazine on excitation-contraction coupling events in fast-twitch skeletal muscle fibres of the rat.
1. Single mechanically skinned fibres from the rat extensor digitorum longus muscle, which allow access to intracellular compartments, were used to examine the effects of 0.5-100 microM chlorpromazine hydrochloride (CPZ) on the major steps of the excitation-contraction (E-C) coupling to elucidate the involvement of skeletal muscle in the neuroleptic malignant syndrome (NMS). 2. At 1 microM, CPZ caused a 20-30% increase in the force response induced by t-system depolarisation and a marked increase in the rate of caffeine-induced SR Ca(2+) release. At [CPZ]> or =2.5 microM, there was an initial increase followed by a marked decrease of the t-system depolarisation-induced force responses, while the potentiating effect on the caffeine-induced SR Ca(2+) release remained. These effects were reversible. 3. CPZ had no effect on the maximum Ca(2+)-activated force, but caused reversible, concentration-dependent increases in the Ca(2+) sensitivity of the contractile apparatus at [CPZ] > or =10 microM, with a 50% predicted shift of 0.11 pCa (-log [Ca(2+)]) units at 82.3 microM CPZ. 4. CPZ did not alter the rate of SR-Ca(2+) loading at 1 and 10 microM, but reversibly reduced it by approximately 40% at 100 microM by reducing the SR Ca(2+) pump. Nevertheless, the SR Ca(2+) content was greater when fibres became unresponsive to t-system-induced depolarisation in the presence than in the absence of 100 microM CPZ. 5. The results show that CPZ has concentration-dependent stimulatory and inhibitory effects on various steps of the E-C coupling, which can explain the involvement of skeletal muscle in NMS and reconcile previous divergent data on CPZ effects on muscle.


Case Report of a Neonate Born to a Mother with Severe SARS-CoV-2 Infection under ECMO.
Neonatal SARS-CoV-2 infections are rare and although there is some evidence of vertical transmission, most newborns show no clinical signs or present with only mild clinical symptoms. Fetal survival is reported around 70% in mothers submitted to extracorporeal membrane oxygenation. We present a case of a male newborn born at 29 weeks from a mother under extracorporeal membrane oxygenation due to SARS-CoV-2 infection. There was no evidence of vertical transmission, polymerase chain reaction testing of nasopharyngeal/throat swab and polymerase chain reaction testing of blood sample for SARS-CoV-2 were both negative. On day 2, he developed signs of osteomyelitis of the distal femur extremity, which resolved after six weeks of antibiotic therapy, with no other significant events during admission. This case report depicts the favorable outcome of a live infant born to a mother with severe SARS-CoV-2infection under extracorporeal membrane oxygenation.


Prenatal care and the prevention of preterm delivery.
This paper reports the methods and results of an innovative program of prenatal care, designed to prevent preterm delivery in Clamart, France, during 1976-1981. Rates of preterm delivery among women who entered the prenatal care program early in pregnancy (and, thus, could derive full benefit of the program) were compared with those among two comparison groups: (1) women who entered the same program later in pregnancy; and (2) women who delivered in Paris. In the first comparison, women who entered the program early had significantly lower rates of preterm delivery than did women who entered later, even when stratified by various risk factors, and when high-risk women were eliminated altogether. In the second comparison, the early care group in Clamart did not exhibit the usual inverse relationship between socioeconomic status and rates of preterm delivery. The usual significant inverse relationship was found in the Clamart population as a whole, and in the Paris series.


Brightness induction: unequal spatial integration with increments and decrements.
Modern theories of brightness induction include an influence from regions that do not share a border with the target. This study tested whether the spatial range of neural integration is the same with incremental versus decremental contrast edges in relatively remote parts of the background. Using an asymmetric matching task, observers set the brightness of a comparison ring, within its own uniform surround, to match the brightness of a test ring within a contiguous surround and a noncontiguous background. The measurements showed that the area of integration depended on the incremental versus decremental contrast polarity at the edge between the surround and background. This implies that brightness induction from an inhomogeneous background must consider the polarity of contrast edges within the whole scene.


Inhibition of Rho-kinase is involved in the therapeutic effects of atorvastatin in heart ischemia/reperfusion.
The aim of the present study was to investigate the effects of atorvastatin against heart ischemia/reperfusion (I/R) injury and its potential underlying mechanism. Rats were allocated into the following groups: Sham, I/R, atorvastatin (10 mg/kg daily), fasudil (10 mg/kg daily) and atorvastatin + fasudil in combination. Drugs were administered for 2 weeks prior to I/R injury. I/R was established by ligating the left anterior descending branch (LAD) for 30 min and releasing the ligature for 180 min. The I/R group was found to have increased myocardial infarct size, cardiomyocyte apoptosis, levels of plasma interleukin (IL)-6 and tumor necrosis factor (TNF)-α, superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels and Rho-kinase activity compared with the other treatment groups (P<0.05). Moreover, pretreatment with atorvastatin significantly attenuated Rho-kinase activity, myocardial infarct size, cardiomyocyte apoptosis, levels of plasma IL-6 and TNF-α, SOD activity and MDA levels, and upregulated nitric oxide production. It was also indicated that the specific Rho-kinase inhibitor, fasudil, had the same effects as atorvastatin in I/R. Therefore, the present results suggested atorvastatin may lead to cardiovascular protection, which may be mediated by Rho-kinase inhibition in heart I/R injury.


Translation attenuation by minocycline enhances longevity and proteostasis in old post-stress-responsive organisms.
Aging impairs the activation of stress signaling pathways (SSPs), preventing the induction of longevity mechanisms late in life. Here, we show that the antibiotic minocycline increases lifespan and reduces protein aggregation even in old, SSP-deficient Caenorhabditis elegans by targeting cytoplasmic ribosomes, preferentially attenuating translation of highly translated mRNAs. In contrast to most other longevity paradigms, minocycline inhibits rather than activates all major SSPs and extends lifespan in mutants deficient in the activation of SSPs, lysosomal or autophagic pathways. We propose that minocycline lowers the concentration of newly synthesized aggregation-prone proteins, resulting in a relative increase in protein-folding capacity without the necessity to induce protein-folding pathways. Our study suggests that in old individuals with incapacitated SSPs or autophagic pathways, pharmacological attenuation of cytoplasmic translation is a promising strategy to reduce protein aggregation. Altogether, it provides a geroprotecive mechanism for the many beneficial effects of tetracyclines in models of neurodegenerative disease. This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).


Epidemiological profile of tuberculosis cases with HIV coinfection in Porto Alegre city, Brazil.
To describe and compare the epidemiological profile of cases of tuberculosis and HIV coinfection of the District Administration Health Units of Porto Alegre, Brazil, from 2009 to 2013. Retrospective cohort with data from national health information systems. Sociodemographic, clinical and follow-up variables were investigated through association tests. 2,419 cases of tuberculosis and HIV coinfection were reported, with a mean age of 38 ± 9.91 years, predominantly white and with up to 7 years of study. The comparison between the District Administration Health Units was significant in terms of race/color (p<0.001), gender (p<0.001), schooling (p<0.004), age (p<0.003), place of origin (p<0.001), (p<0.001), alcoholism (p<0.001), indication and performance of Directly Observed Therapy (p<0.001), closure (p<0.001). Socioeconomic and treatment variables influence the occurrence of coinfection in different areas of Porto Alegre, reinforcing that the sum of different factors explains the indicators of the disease.


Expressing the sunflower transcription factor HaHB11 in maize improves waterlogging and defoliation tolerance.
The sunflower (Helianthus annuus) transcription factor HaHB11 (H. annuus Homeobox 11) belongs to the homeodomain-leucine zipper family and confers improved yield to maize (Zea mays) hybrids (HiII × B73) and lines. Here we report that transgenic maize lines expressing HaHB11 exhibited better performance under waterlogging, both in greenhouse and field trials carried out during three growth cycles. Transgenic plants had increased chlorophyll content, wider stems, more nodal roots, greater total aerial biomass, a higher harvest index, and increased plant grain yield. Under severe defoliation caused by a windstorm during flowering, transgenic genotypes were able to set more grains than controls. This response was confirmed in controlled defoliation assays. Hybrids generated by crossing B73 HaHB11 lines with the contrasting Mo17 lines were also tested in the field and exhibited the same beneficial traits as the parental lines, compared with their respective controls. Moreover, they were less penalized by stress than commercial hybrids. Waterlogging tolerance increased via improvement of the root system, including more xylem vessels, reduced tissue damage, less superoxide accumulation, and altered carbohydrate metabolism. Multivariate analyses corroborated the robustness of the differential traits observed. Furthermore, canopy spectral reflectance data, computing 29 vegetation indices associated with biomass, chlorophyll, and abiotic stress, helped to distinguish genotypes as well as their growing conditions. Altogether the results reported here indicate that this sunflower gene constitutes a suitable tool to improve maize plants for environments prone to waterlogging and/or wind defoliation.


[Variety systematization and research progress of Mongolian medicine "Bashaga"].
Mongolian medicine is the traditional drug with the theory of Mongolian medicine and pharmacy as a guide, which made a great contribution to the survival and development of the Mongolian people. Mongolian medicine "Bashaga" faced the situations of origin is unclear, and clinical therapy is confused and so on. This paper summarizes the original plants and studies the species textual research and ethnopharmacology of Mongolian medicine "Bashaga". This paper intends to ensure authentic plant and provide comprehensive insight into the chemical constituents, pharmacology and application status of Mongolian medicine "Bashaga" to discuss the rationality of the confirmation in "Bashaga" authentic plant.


[Study on soluble and insoluble lens proteins in contusion cataract of rat model].
To study the water soluble and insoluble lens proteins in contusion cataract of rat model, and to study the influence of heat shock (thermotolerance) or quercetin (heat shock protein inhibitor) on the lens proteins. Sprague-Dawley (SD) rats were randomized into four groups (6 in each group): (1) A group, control group. (2) B group, contusion group. (3) C group, heat shock group. (4) D group, quercetin group. In contusion group, contusion of eyes was induced by dropping steel ball against the eyeball (20 g ball dropped from 20 cm height for 100 times each week for 5 weeks). In heat shock group, heat shock was induced by raising the body temperature to 40.5 - 41.5 degrees Celsius for 8 min, 2 - 3 h before the eye contusion (as previously described). Heat shock and contusion was given each week for 5 weeks. In quercetin group, rats were fed with quercetin (100 mg/kg weight) 2-3 h before the contusion. Quercetin and contusion was given each week for 5 weeks. Amount of proteins was measured by using Bradford methods. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used for the separation and analysis of lens proteins. Five weeks after contusion, the mean water soluble protein of heat shock group was 22.71 + or - 1.99, increased significantly than that of the other three groups. The mean insoluble protein of contusion group was 2.60 + or - 0.48, increased than that of the other three groups. From the analysis of SDS-PAGE, we found that there was a high molecular band near 66 KD in opaque lens and the band became more prominent with the growing opacification of the lens. In contusion cataract, water insoluble lens protein is increased and water soluble lens protein is decreased. SDS-PAGE showed that lens injury resulted in lens proteins moving toward high molecular band.


Frequency-spatial domain joint optimization for improving super-resolution images of nonlinear structured illumination microscopy.
Introducing nonlinear fluorophore excitation into structured illumination microscopy (SIM) can further extend its spatial resolution without theoretical limitation. However, it is a great challenge to recover the weak higher-order harmonic signal and reconstruct high-fidelity super-resolution (SR) images. Here, we proposed a joint optimization strategy in both the frequency and spatial domains to reconstruct high-quality nonlinear SIM (NL-SIM) images. We demonstrate that our method can reconstruct SR images with fewer artifacts and higher fidelity on the BioSR dataset with patterned-activation NL-SIM. This method could robustly overcome one of the long-lived obstacles on NL-SIM imaging, thereby promoting its wide application in biology.


Oncologic applications of diffusion-weighted MRI in the body.
Diffusion-weighted MRI (DWI) allows the detection of malignancies in the abdomen and pelvis. Lesion detection and characterization using DWI largely depends on the increased cellularity of solid or cystic lesions compared with the surrounding tissue. This increased cellularity leads results in restricted diffusion as indicated by reduction in the apparent diffusion coefficient (ADC). Low pretreatment ADC values of several malignancies have been shown to be predictive of better outcome. DWI can assess response to systemic or regional treatment of cancer at a cellular level and will therefore detect successful treatment earlier than anatomical measures. In this review, we provide a brief technical overview of DWI, discuss quantitative image analysis approaches, and review studies which have used DWI for the purpose of detection and characterization of malignancies as well as the early prediction of treatment response.


A role for pref-1 and HES-1 in thymocyte development.
T lymphocyte development requires a series of interactions between developing thymocytes and thymic epithelial (TE) cells. In this paper we show that TE cells in the developing thymus express Pref-1, a Delta-like cell-surface molecule. In fetal thymus organ cultures (FTOC), thymocyte cellularity was increased by the exogenous dimeric Pref-1 fusion protein, but was reduced by the soluble Pref-1 monomer or anti-Pref-1 Ab. Dimeric Pref-1 in FTOC also increased thymocyte expression of the HES-1 transcription factor. Thymocyte cellularity was increased in FTOC repopulated with immature thymocytes overexpressing HES-1, whereas FTOC from HES-1-deficient mice were hypocellular and unresponsive to the Pref-1 dimer. We detected no effects of either Pref-1 or HES-1 on developmental choice among thymocyte lineages. These results indicate that Pref-1 expressed by TE cells and HES-1 expressed by thymocytes are critically involved in supporting thymocyte cellularity.


Evaluation on Elongation Factor 1 Alpha of Entamoeba histolytica Interaction with the Intermediate Subunit of the Gal/GalNAc Lectin and Actin in Phagocytosis.
Entamoeba histolytica is the causative agent of amoebiasis. This disease results in 40,000 to 100,000 deaths annually. The pathogenic molecules involved in the invasion of trophozoites had been constantly being clarified. This study explored the role of elongation factor 1 alpha (EF1a) in E. histolytica pathogenicity. Biolayer interferometry binding and pull-down assays suggest that EF1a and intermediate subunit of lectin (Igl) binding are specific. Submembranous distribution of EF1a closely aligns with the localization of Igl, which appear in abundance on membranes of trophozoites. Messenger RNA (mRNA) expression of EF1a is positively correlated with trends in Igl levels after co-incubation with Chinese hamster ovary (CHO) cells in vitro, suggesting a regulatory linkage between these proteins. Erythrophagocytosis assays also imply a role for EF1a in phagocytosis. Finally, EF1a and actin are collocated in trophozoites. These results indicated elongation factor 1a is associated with E. histolytica phagocytosis, and the relationships between EF1a, Igl, and actin are worth further study to better understand the pathogenic process.


[Molecular genetic analysis for myoclonus epilepsy associated with ragged-red fibers (MERRF)].
Two mutations in tRNA(Lys) gene of mitochondrial DNA were detected as the causes of this disease. We reviewed our previous studies and the recent literatures. We analyzed the mtDNA nucleotide sequence of a MERRF patient, the original case of MERRF described by Fukuhara et al., and identified a point mutation of 8,344 in tRNA(Lys) gene. This mutation detected in all 8 MERRF patients from 6 independent families, and not detected in 15 controls by polymerase chain reaction using a mismatched primer. We also quantitated the degrees of heteroplasmy of the point mutation at nt 8,344 of tRNA(Lys) in various postmortem tissues from two patients with MERRF. The percentages of the mutant mtDNA were similar in both clinically affected and unaffected tissues.


Stimulation of bone formation by electrical current on spinal fusion.
An experimental double-blind study to evaluate the effectiveness of a constant current stimulator was performed on 30 young pigs that underwent a spinal fusion at the level of L5-L6. The group of animals with an active bone-growth stimulator showed a statistically significant increase of osteoblastic activity with bone formation.


Glycan Profile Analysis of Engineered Trastuzumab with Rationally Added Glycosylation Sequons Presents Significantly Increased Glycan Complexity.
Protein aggregation constitutes a recurring complication in the manufacture and clinical use of therapeutic monoclonal antibodies (mAb) and mAb derivatives. Antibody aggregates can reduce production yield, cause immunogenic reactions, decrease the shelf-life of the pharmaceutical product and impair the capacity of the antibody monomer to bind to its cognate antigen. A common strategy to tackle protein aggregation involves the identification of surface-exposed aggregation-prone regions (APR) for replacement through protein engineering. It was shown that the insertion of N-glycosylation sequons on amino acids proximal to an aggregation-prone region can increase the physical stability of the protein by shielding the APR, thus preventing self-association of antibody monomers. We recently implemented this approach in the Fab region of full-size adalimumab and demonstrated that the thermodynamic stability of the Fab domain increases upon N-glycosite addition. Previous experimental data reported for this technique have lacked appropriate confirmation of glycan occupancy and structural characterization of the ensuing glycan profile. Herein, we mutated previously identified candidate positions on the Fab domain of Trastuzumab and employed tandem mass spectrometry to confirm attachment and obtain a detailed N-glycosylation profile of the mutants. The Trastuzumab glycomutants displayed a glycan profile with significantly higher structural heterogeneity compared to the HEK Trastuzumab antibody, which contains a single N-glycosylation site per heavy chain located in the CH2 domain of the Fc region. These findings suggest that Fab N-glycosites have higher accessibility to enzymes responsible for glycan maturation. Further, we have studied effects on additional glycosylation on protein stability via accelerated studies by following protein folding and aggregation propensities and observed that additional glycosylation indeed enhances physical stability and prevent protein aggregation. Our findings shed light into mAb glycobiology and potential implications in the application of this technique for the development of "biobetter" antibodies.


Hospital outbreak caused by linezolid resistant Enterococcus faecium in Upper Austria.
Enterococcus faecium is part of the human gastrointestinal flora but may act as opportunistic pathogen. Environmental persistence, high colonization capability and diverse intrinsic and acquired resistance mechanisms make it especially successful in nosocomial high-risk settings. In March 2014, an outbreak of Linezolid resistant Enterococcus faecium (LREfm) was observed at the hematooncology department of a tertiary care center in Upper Austria. We report on the outbreak investigation together with the whole genome sequencing (WGS)-based typing results including also non-outbreak LREfm and susceptible isolates. The 54 investigated isolates could be divided in six clusters based on cgMLST. Cluster one comprised LREfm isolates of genotype ST117 and CT24, which was identified as the causative clone of the outbreak. In addition, the detection of four other clusters comprising isolates originating from hematooncology patients but also at other hospitals, pointed to LREfm transmission between local healthcare facilities. LREfm patients (n = 36) were typically at risk for acquisition of nosocomial pathogens because of immunosuppression, frequent hospitalization and antibiotic therapies. Seven of these 36 patients developed LREfm infection but were successfully treated. After termination of the initial outbreak, sporadic cases occurred despite a bundle of applied outbreak control interventions. WGS proved to be an effective tool to differentiate several LREfm clusters in an outbreak. Active screening for LREfm is important in a high-risk setting such as hematooncology, where multiple introductions are possible and occur despite intensified infection control measures.


Treatment of Parkinson's disease.
Early stage Parkinson's disease may be better left untreated if it does not limit motor function. Once limitation of function is present levodopa-dopa decarboxylase inhibitor combinations are the most effective therapy, although amantadine may be satisfactory for a time in milder cases. The optimal independent roles of the ergot derivatives bromocriptine and pergolide, and the MAOb inhibitor selegiline, are not yet generally agreed although they are accepted as useful in supplementing the effects of levodopa. With prolonged levodopa use various late-stage treatment problems may appear. The pathogenesis of these is poorly understood and no completely satisfactory ways of managing them are available.


[The role of nicotine in regulation of lymphocyte proliferation].
The effect of nicotine on both the expression of nicotinic acetylcholine receptors (nAChRs) and proliferation of hybridoma cells and normal mouse lymphocytes has been investigated. By means of immunoenzyme assay, nicotine was shown to regulate the number of nAChRs in both hybridoma cells and normal rat splenocytes. According to the data of triazolyl blue inclusion and ELISpot assay, nicotine stimulated proliferation of both hybridoma cells and normal plasma cells generated in the course of immune response in vivo. The cell sensitivity to nicotine depended on the number of nAChRs expressed on the membrane, as well as on their functional activity affected, in particular, by adhesive contacts. The use of the open channel blocker benzohexonium revealed that proliferative signal through nAChR in hybridoma cells was mediated by ion channel opening. The data obtained demonstrate the proproliferative role of nicotine for B lymphocytes, and may account for the development of lymphoproliferative disorders in tobacco smokers.


Isolation and characterization of cloned DNA sequences containing ribosomal protein genes of Drosophila melanogaster.
Ribosomal (r) proteins encoded by polyadenylated RNA were specifically precipitated in vitro from polysomes by using antibodies raised against characterized Drosophila melanogaster r proteins. The immuno-purified mRNA in the polysome complex was used to prepare cDNA with which to probe a D. melanogaster genomic library. Selected recombinant phages were used to hybrid select mRNAs, which were analyzed by in vitro translation. Three clones containing the genes for r proteins 7/8, S18, and L12 were positively identified by electrophoresis of the translation products in one-dimensional and two-dimensional polyacrylamide gels. Sequences encoding r proteins S18 and L12 were found to be present in the genome in single copies. In contrast, the polynucleotide containing the region encoding 7/8 may be repeated or may contain or be flanked by short repeated sequences. The sizes of mRNAs that hybridized to the recombinant clone containing 7/8 were significantly larger than would be expected from the molecular weight of protein 7/8, implying that there were unusually long 5' and 3' noncoding sequences. The mRNAs for r proteins S18 and L12 were however, only about 10% larger. In situ hybridizations to salivary gland polytene chromosomes, using the recombinant phage, revealed that the recombinant clone containing the gene for r protein 7/8 hybridized to 5D on the X chromosome; the recombinant clone containing the gene for S18 hybridized to 15B on the same chromosome, and the recombinant phage containing the gene for L12 hybridized to 62E on chromosome 3L. It is of interest that the genomic locations of all three r protein clones were within the chromosomal intervals known to contain the Minute mutations [M(1)0, M(1)30, and M(3)LS2]. Although each clone contained sequences specifying two to four proteins, none had more than one identifiable r protein gene, suggesting that different D. melanogaster r protein genes may not be closely linked.


Beta-blocker brain concentrations in man.
Patients with subarachnoid haemorrhage (SAH) have been shown to benefit from beta-blockade. SAH patients who came to surgery were investigated if they had been receiving chronic (approximately one week) oral treatment with either hydrophilic atenolol (100 mg/day) or one of the following lipophilic beta-blockers: propranolol (80 mg b.i.d.), oxprenolol (80 mg b.i.d.), or metoprolol (100 mg b.i.d.). Cerebrospinal fluid concentrations of beta-blockers did not reflect their concentrations in the brain. Brain concentrations of the three lipophilic beta-blockers were 10-20 times higher than those of atenolol. The approximate brain/plasma concentration ratios were 26 for propranolol, 50 for oxprenolol, 12 for metoprolol, and 0.2 for atenolol. The brain is thus buffered from peak blood concentrations of atenolol, and this may account for the low incidence of CNS-related side-effects with this hydrophilic beta-blocker.


Novel Technologies for Isolated Lung Perfusion: Beyond Lung Transplant.
Isolated lung perfusion (ILP) has been examined and developed in lung transplantation and thoracic oncology research. In lung transplantation, ILP has been used to assess physiologic integrity of donor lungs after removal from the donor, and it has also been proposed as a method for active treatment and repair of injured unsuitable donor organs ex vivo. ILP is attractive as a concept to deliver high-dose chemotherapy to treat pulmonary metastatic disease, referred to as in vivo lung perfusion. This article focuses on the rationale, technical aspects, and experimental and clinical experience of in vivo lung perfusion. A perspective on the future application of these techniques is described.


Patient issues in breast reconstruction.
Breast reconstruction is not a new idea. Techniques have been developing since the late 1800s. The state of the art is such that the knowledge of its availability and success has significant effect on the willingness of women to seek earlier diagnosis and treatment. However, reconstruction is not for everyone. This paper examines the issues about knowledge, attitudes, and practices that either result in electing for or against reconstruction. Some issues involved are financial, others have to do with cosmetic appearance, and still others involve the medical and psychological affects. Identifying and understanding the issues from the point of view of the patient is important in providing support for the patient with breast cancer.


Mechanisms of drug eruptions: Part I.
The pathogenetic mechanisms underlying common, and less common but severe, adverse cutaneous drug reactions are reviewed. Pharmacogenetic variability may account for a susceptibility to serious drug reactions to sulphonamides and anticonvulsants, as well as to lupus erythematosus (LE)-like syndrome. Exanthematous drug reactions may have an immunological basis. Cell mediated cutaneous drug reactions, including lichenoid reactions, LE-like syndrome, fixed drug eruption, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis, will inevitably involve elements of the skin immune system. Graft-versus-host disease provides a useful model for aspects of these drug-induced disorders. Urticaria, angioedema, anaphylaxis and anaphylactoid reactions may involve Type I immunoglobulin (Ig)-mediated or Type III hypersensitivity, or may be caused by pharmacological, non-allergic means. Drug-induced vasculitis, serum sickness and the Arthus phenomenon are manifestations of the immune complex disease. Drug-induced pemphigus may involve immune dysregulation, but several thiol-containing drugs are able to cause antibody-independent acantholysis directly.


[Molecular diversity and physiological roles of the NMDA-receptor channel].
Molecular cloning has elucidated the molecular diversity of the N-methyl-D-aspartate (NMDA)-receptor channel and has provided a solid basis for extensive studies of the structure and function of the NMDA-receptor channel. Mutational analyses have assigned functional domains and the transmembrane topology of the channel subunits. Identification of the multiple subunits with distinct distribution, properties, and regulation has suggested that NMDA-receptor channels are distinct in molecular architecture and functional characteristics in various brain regions at different developmental stages. The physiological significance of the NMDA-receptor channel diversity is presently under investigation by various techniques including gene targeting.


One-Step In Situ Self-Assembly of Biodegradable Films for Long-Term Intravesical Bladder Cancer Therapy.
Intravesical instillation therapy is increasingly recognized as one of the most common clinical treatment strategies for bladder cancer. However, the antitumor efficacy of chemotherapy drugs is still limited due to their rapid clearance by periodic urination. To circumvent this issue, a drug-loaded thin film comprising the self-assembly of tannic acid (TA) and ferric ions (Fe3+) was in situ fabricated on the bladder wall in vivo. As expected, the TA@Fe film with adjustable thickness could effectively prolong the residence time of anticancer drugs in the bladder and realize sustained release of anticancer drugs. Together with the antibacterial properties, the TA@Fe film enabled improved chemotherapeutic efficacy. Moreover, the TA@Fe film caused no adverse effects on bladder function, demonstrating the in vivo biocompatibility. In addition, the T2 contrast effect of Fe3+ was employed to real-time monitor the disassembly of the TA@Fe film and the ensuing drug release process by magnetic resonance imaging. We believe that the TA@Fe-based drug delivery platform with enhanced retention in the bladder would be of great potential for treating various bladder diseases.


Distributions of HLA class II alleles in autoantibody subsets among Norwegian patients with systemic lupus erythematosus.
In order to find potential correlations between HLA class II alleles and anti-SS-A, -SS-B, -Sm and anti-snRNP responses among Norwegian patients with systemic lupus erythematosus (SLE), HLA-DRB1, -DRB3*0101, -DQA1 and -DQB1 alleles were determined by DNA typing 50 patients and 108 controls. HLA distributions were analysed in the following autoantibody subgroups: anti-SS-A with -SS-B, anti-SS-A without -SS-B, anti-snRNP without -Sm, anti-SS-A without -snRNP and anti-snRNP without -SS-A. The autoantibodies were detected by EIA (enzyme immunuassay). Patients with anti-SS-A and -SS-B had significantly increased frequencies of DRB1*03, DRB3*0101, DQA1*0501, DQB1*0201 (in linkage disequilibrium) versus controls and versus patients without anti-SS-A and -SS-B. No differences in HLA distribution were found when the group with anti-SS-A alone was compared to the group with anti-SS-A and concomitant -SS-B. Comparing the groups with and without anti-SS-A and -SS-B, the highest RR were found for the alleles DRB1*03, DRB3*0101, DQB1*0501, DQB1*0201 (in linkage disequilibrium) with RR: 16.8, 5.0, 19.6, 10.3, respectively, P < 0.05). RR for DQw2/DQw6 heterozygotes was 3.5 (Ns.), and RR for cases having DQ alpha molecules with glutamine in position 34 and DQ beta molecules with leucine in position 26 on both chains was 6.3 (P < 0.05). No HLA associations were observed in the group with anti-snRNP without concomitant -Sm or without concomitant -SS-A. These results show that production of anti-SS-A and -SS-B is associated to the HLA alleles DRB1*03, DRB3*0101, DQA1*0501, DQB1*0201, and that this haplotype shows stronger correlation to these responses than DQw2/DQw6 heterozygosity or HLA molecules having glutamine in position 34 (DQ alpha) and leucine in position 26 (DQ beta). The failure to observe any correlation with DRBI*15,16 (DR2) in the group with anti-SS-A alone may demonstrate ethnic differences concerning this response. The failure to identify any HLA associations for the anti-snRNP response may reflect the heterogeneity of the molecules that constitute this antigen.


Kikuchi-Fujimoto Disease Post COVID-19 Vaccination: Case Report and Review of Literature.
With the rapid development of various coronavirus disease 2019 (COVID-19) vaccines in a bid to counter and contain the COVID-19 pandemic, unusual and uncommon side effects of COVID-19 vaccination have been increasingly reported in the literature. Ipsilateral lymphadenopathy is a fairly common side effect of vaccination of any kind, with its etiology most commonly related to reactive lymphadenopathy. However, Kikuchi-Fujimoto Disease (KFD) or necrotizing histiocytic lymphadenitis is rarely observed post-vaccination, with only one other case of KFD post COVID-19 vaccination reported to date. We report two more cases of KFD post COVID-19 vaccination in the Asian population, highlighting the clinical course and salient clinical, radiological and histologic findings. In addition, we provide a literature review of the existing cases of lymphadenopathy post COVID-19 vaccination with cytologic and/or histologic correlation.


[Prenatal diagnosis of omphalopagus conjoined twins at 13 weeks of amenorrhea].
Conjoined twins are a rare occurrence. We present a case of conjoined twins at 13 weeks' gestation. This case demonstrated the possibility of making an accurate diagnosis of conjoined twins and delineating the extent of organ sharing in the first trimester. This analysis and the discover of another anomalies can help the parents with the option for pregnancy termination. Early diagnosis and precise delineation of the shared organs of conjoined twins are essential for optimal obstetric and postnatal management.


Ultrastructure of the synovial sensory peptidergic fibers is distinctively altered in different phases of adjuvant induced arthritis in rats: ultramorphological characterization combined with morphometric and immunohistochemical study for substance P, calcitonin gene related peptide, and protein gene product 9.5.
To characterize sequential ultramorphological changes in synovial sensory peptidergic fibers in different phases of adjuvant induced arthritis. Topographically defined regions of the tarsal joints from arthritic rats were evaluated 7, 10, 14, and 21 days after inoculation with Freund's adjuvant. Peptidergic fibers were identified by high resolution video microscope, then fibers containing calcitonin gene related peptide (CGRP) were visualized by electron microscopy. Morphometric quantification of synovial fibers immunohistochemically stained for CGRP, substance P (SP), and protein gene product 9.5 (PGP 9.5) was done at this time. The control synovial lining contained numerous ramified axon terminals, whereas the sublining contained mostly nerve fiber bundles, except for axon terminals visible around the blood vessels. In arthritis, on Day 14, there were few immunoreactive nerve fibers and terminals. Instead, electron microscopy disclosed numerous activated and/or degenerated axons [CGRP: 2973 +/- 345 vs 495 +/- 288; SP: 657 +/- 344 vs 199 +/- 60; PGP 9.5: 4473 +/- 944 vs 886 +/- 299, all p < 0.05 (units: microm/mm2)]. On Day 21 CGRP and PGP 9.5 immunoreactive fibers were numerous again (4892 +/- 551 and 3613 +/- 1350, respectively), but SP immunoreactive nerve fibers did not seem to regenerate (126 +/- 44). Regenerating nerve fibers had a distinctive ultrastructure and they were always seen in association to Schwann cells. The healthy synovial lining is innervated by peptidergic nerve terminals. During the inflammatory phase of arthritis neuropeptides are locally released due to stimulation and degeneration of the axons. The apparently unaffected Schwann cells seem to play a pivotal role in subsequent regeneration of peptidergic axons. However, the ultrastructure and the neuropeptide content (and probably the function) of the regenerating axons are different from those of the normal synovial nerve fibers.


Prediction of Oral Pharmacokinetics Using a Combination of In Silico Descriptors and In Vitro ADME Properties.
Accurate prediction of oral pharmacokinetics remains challenging. This study investigated quantitative approaches for the prediction of the area under the plasma concentration-time curve after oral administration (AUCp,oral) to rats using the in vitro-in vivo extrapolation (IVIVE), in silico model using machine learning approaches and the combination of the in silico model and in vitro data. A set of 595 structurally diverse compounds with determined AUCp,oral at 1 mg/kg, in vitro intrinsic clearance (CLint), an unbound fraction in plasma (fu,p) in rats, and kinetic solubility at pH 6.8 was used for this assessment. Prediction models developed by two different types of machine learning techniques (i.e., random forest regression and Gaussian processes) were evaluated using three validation methods implementing the time and cluster-split training and test set and fivefold cross-validation. The developed machine learning models have a square of correlation coefficient (R2) in the range of 0.381-0.685 with 33-45% of the compounds being predicted within 2-fold of the observed AUCp,oral value. The predictivity was improved by incorporating CLint, fu,p, and solubility as explanatory variables with R2 = 0.554-0.743. In cases where extraction by the liver is the main elimination pathway and intestinal extraction is negligible, AUCp,oral can be expressed by dose, CLint, and fu,p based on a well-stirred model. By using this conventional IVIVE approach, only 1.7-5.0% of compounds were predicted within the 2-fold error with R2 = 0.354-0.487. Two empirical scaling factors (ESFs) determined by linear regression analysis and machine learning approaches improved the predictivity of AUCp,oral with 33-44% predicted within twofold variability. The IVIVE using ESF predicted by random forest regression showed better predictivity of AUCp,oral with R2 = 0.471-0.618, while it still showed lower predictivity than machine learning approaches applied directly to AUCp,oral prediction. This study demonstrated that the combination of in silico and in vitro parameters is useful to improve the predictivity of the machine learning model for rat AUCp,oral and supports consideration for predicting AUCp,oral for human and other non-clinical species in a similar manner.


Prospect of mesenchymal stem cells in therapy of osteoporosis: A review.
Osteoporosis is a systemic skeletal disease associated with reduced bone strong point that results in raised fracture risk, with decreased bone strength, leading to reduced bone mineral density and poor bone quality. It is the most common in older females but some men are also at high risk. Although considered as a predictable result of aging, it is can be avoidable and treatable. The existing treatment of osteoporosis mainly contains antiresorptive and anabolic agents. In spite of these improvements, concerns around unusual side-effects of antiresorptive drugs, and the lack of perfect confirmation in maintenance of their long-standing effectiveness is bring about many patients not receiving these drugs. Over the years, the stem cell-based therapy has attained substantial clinical consideration because of its potential to treat numerous diseases. The stem cell therapy has been recommended as a probable therapeutic approach for patients with osteoporosis. Even though the concept of stem cell-based therapy for osteoporosis has caught substantial attention, no clinical trial has been published on humans. The cell studies based on osteoporosis are primarily focused on osteoclastic activity and bone resorption procedures. Earlier, it was on osteoblastogenesis and in recent times, on the differentiation probable of mesenchymal stem cells. In this review, we have summarized the therapeutic role of stem cell-based strategy in osteoporosis.


Epithelial plasma cell granuloma-like tumors of the lungs. A hitherto unrecognized tumor.
We present two cases of benign pulmonary epithelial tumors located in the middle lobes of the lungs. The patients were women of 56 and 36 years of age. The tumors were morphologically similar to plasma cell granuloma. At the tumor periphery, the lesion cells formed thin organoid rows of cells and vague trabeculae, disclosing morphologically their epithelial nature. In addition, the tumors strongly stained immunohistochemically with antibodies to cytokeratins, TTF-1 and EMA, and they were negative for immunoglobulin kappa and lambda light chains. We are not aware of similar tumors described in the literature, and we suggest the name "epithelial plasma cell granuloma-like tumors" for these lesions.


Reversible solvatomagnetic switching in a spongelike manganese(II)-copper(II) 3D open framework with a pillared square/octagonal layer architecture.
The concept of "molecular magnetic sponges" was introduced for the first time in 1999 by the creative imagination of the late Olivier Kahn. It refers to the exotic spongelike behavior of certain molecule-based materials that undergo a dramatic change of their magnetic properties upon reversible dehydration/rehydration processes. Here we report a unique example of a manganese(II)-copper(II) mixed-metal-organic framework of formula [Na(H(2)O)(4)](4)[Mn(4){Cu(2)(mpba)(2)(H(2)O)(4)}(3)]·56.5H(2)O (1) (mpba=N,N'-1,3-phenylenebis(oxamate)). Compound 1 possesses a 3D Mn(II)(4)Cu(II)(6) pillared layer structure with mixed square and octagonal pores of approximate dimensions 1.2×1.2 nm and 2.1×3.0 nm, respectively, hosting a large amount of crystallization H(2)O molecules and hydrated Na(I) countercations as guests. It reversibly switches from a crystalline hydrated phase with long-range ferromagnetic ordering at a rather high critical temperature (T(c)) of 22.5 K to an amorphous dehydrated phase with T(c) as low as 2.3 K, which is accompanied by a breathing-type dynamic effect involving a large crystal volume (ca. 45%) and color changes after water desorption/adsorption. The combination of both the open-framework structure and the spongelike optical, mechanical, and magnetic switching behavior in this new class of oxamato-based porous magnets offers fascinating possibilities in designing multifunctional materials for host-guest molecular sensing.


Improving Surgical Safety and Nontechnical Skills in Variable-Resource Contexts: A Novel Educational Curriculum.
A substantial proportion of adverse intraoperative events are attributed to failures in nontechnical skills. To strengthen these skills and improve surgical safety, the Non-Technical Skills for Surgeons (NOTSS) taxonomy was developed as a common framework. The NOTSS taxonomy was adapted for low- and middle-income countries, where variable resources pose a significant challenge to safe surgery. The NOTSS for variable-resource contexts (VRC) curriculum was developed and implemented in Rwanda, with the aim of enhancing knowledge and attitudes about nontechnical skills and promoting surgical safety. The NOTSS-VRC curriculum was developed through a rigorous process of integrating contextually appropriate values. It was implemented as a 1-day training course for surgical and anesthesia postgraduate trainees. The curriculum comprises lectures, videos, and group discussions. A pretraining and posttraining questionnaire was administered to compare knowledge and attitudes regarding nontechnical skills, and their potential to improve surgical safety. The setting of this study was in the tertiary teaching hospital of Kigali, Rwanda. Participants were residents of the University of Kigali. A total of 55 residents participated from general surgery (31.4%), obstetrics (25.5%), anesthesia (17.6%), and other surgical specialties (25.5%). In a paired analysis, understanding of NOTSS improved significantly (55.6% precourse, 80.9% postcourse, p<0.01). All residents reported that the course would improve their ability to provide safer patient care, and 97.4% believed developing nontechnical skills would improve patient outcomes. Nontechnical skills must be highlighted in surgical training in low- and middle-income countries. The NOTSS-VRC curriculum can be implemented without additional technology or significant financial cost. Its deliberate design for resource-constrained settings allows it to be used both as an educational course and a quality improvement strategy. Our research demonstrates it is feasible to improve knowledge and attitudes about NOTSS through a 1-day course, and represents a novel approach to improving global surgical safety.


[HTLV-I antibody screening of blood donors].
Routine screening of 344,266 blood donations of approximately 200,000 donors for anti-HTLV-I was done by enzyme immuno assay (EIA). Repeatedly reactive samples were confirmed by Western Blot (WB) and radio immuno precipitation assay (RIPA). The prevalence of anti-HTLV-I in Bavarian blood donors is 0.02-0.026%. The specificity of HTLV-I-EIA is 99.95%.


Regional and ultrastructural immunolocalization of copper-zinc superoxide dismutase in rat central nervous system.
We examined the distribution of copper-zinc superoxide dismutase (CuZnSOD) in adult rat central nervous system by light and electron microscopic immunocytochemistry, using an affinity-purified polyclonal antibody. The enzyme appeared to be exclusively localized in neurons. No immunoreactivity was seen in non-neuronal cells. The staining intensity was variable, depending on the brain region and, within the same region, on the neuron type. Highly immunoreactive elements included cortical neurons evenly distributed in the different layers, hippocampal interneurons, neurons of the reticular thalamic nucleus, and Golgi, stellate, and basket cells of the cerebellar cortex. Other neurons, i.e., pyramidal cells of the neocortex and hippocampus, Purkinje and granule cells of the cerebellar cortex, and the majority of thalamic neurons, showed much weaker staining. In the spinal cord, intense CuZnSOD immunoreactivity was present in many neurons, including motor neurons. Pre-embedding immunoelectron microscopy of the neocortex, hippocampus, reticular thalamic nucleus, and cerebellar cortex showed cytosolic and nucleoplasmic labeling. Moreover, single membrane-limited immunoreactive organelles identified as peroxisomes were often found, even in neurons that appeared weakly stained at the light microscopic level. In double immunogold labeling experiments, particulate CuZnSOD immunoreactivity co-localized with catalase, a marker enzyme for peroxisomes, thus demonstrating that in neural tissue CuZnSOD is also present in peroxisomes.


Clinicopathological significance and diagnostic accuracy of HER2 immunohistochemistry in colorectal cancer: a meta-analysis.
The aim of this study was to elucidate the clinicopathological significance of HER2 expression and the diagnostic accuracy of HER2 immunohistochemistry (IHC) in colorectal cancer (CRC). A total of 2,573 CRC cases from 13 eligible studies were included. We performed a meta-analysis to examine the correlations between HER2 expression and clinicopathological characteristics in CRC. Concordance analysis between HER2 IHC and in situ hybridization (ISH) and diagnostic test accuracy review was conducted. The estimated rate of HER2 IHC overexpression was 0.162 (95% confidence interval [CI] 0.106-0.240). HER2 IHC overexpression was significantly correlated with lymph node metastasis and distant metastasis but not tumor depth. HER2 IHC overexpression was not correlated with overall survival. The concordance rates between IHC and ISH were 0.968 (95% CI 0.881-0.992), 0.377 (95% CI 0.225-0.557) and 0.780 (95% CI 0.390-0.952) for HER2 IHC scores of 0/1+, 2+ and 3+, respectively. The diagnostic test accuracy review of HER2 IHC revealed that the pooled sensitivity and specificity were 0.71 (95% CI 0.58-0.82) and 0.96 (95% CI 0.94-0.97), respectively. The diagnostic odds ratio and area under the summary receiver operating characteristic curve were 51.34 (95% CI 3.82-690.54) and 0.9704, respectively. HER2 IHC overexpression was significantly correlated with lymph node metastasis and distant metastasis. CRC cases with HER2 IHC scores of 0/1+ exhibited good agreement with the ISH data. However, additional ISH analysis is needed to confirm HER2 status in cases with IHC scores of 2+ or 3+.


Indonesian Medicinal Plants. XIV. Characterization of 3'-O-Caffeoylsweroside, a new secoiridoid glucoside, and kelampayosides A and B, two new phenolic apioglucosides, from the bark of Anthocephalus chinensis (Rubiaceae).
A new secoiridoid glucoside named 3'-O-caffeoylsweroside (1), and two new phenolic apioglucosides, named kelampayoside A (4) and kelampayoside B (6), together with eleven known compounds (five iridoids and six alkaloids), were isolated from the bark of Anthocephalus chinensis (Rubiaceae), an Indonesian medicinal plant from Sumatra Island, Indonesia. The chemical structures of 1, 4 and 6 have been elucidated respectively as 3'-O-caffeoylsweroside (1), antiarol 1-O-beta-D-apiofuranosyl (1 --> 6)-beta-D-glucopyranoside (4), and antiarol 1-O-beta-D-5"-O-caffeoylapiofuransoyl (1 --> 6)-beta-D-glucopyranoside (6) on the bases of their chemical and physiochemical properties. Among fourteen constituents characterized, cadambine (13), one of the major indole alkaloid constituents of A. chinensis, was shown to exhibit moderate growth-inhibitory activity against the malarial parasite Plasmodium falciparum (a chloroquine-resistant K1 strain) cultured in human erythrocytes.


Effects of fish species composition on Diphyllobothrium spp. infections in brown trout - is three-spined stickleback a key species?
Subarctic populations of brown trout (Salmo trutta) are often heavily infected with cestodes of the genus Diphyllobothrium, assumedly because of their piscivorous behaviour. This study explores possible associations between availability of fish prey and Diphyllobothrium spp. infections in lacustrine trout populations. Trout in (i) allopatry (group T); (ii) sympatry with Arctic charr (Salvelinus alpinus) (group TC); and (iii) sympatry with charr and three-spined stickleback (Gasterosteus aculeatus) (group TCS) were contrasted. Mean abundance and intensity of Diphyllobothrium spp. were higher in group TCS compared to groups TC and T. Prevalence, however, was similarly higher in groups TCS and TC compared to group T. Zero-altered negative binomial modelling identified the lowest probability of infection in group T and similar probabilities of infection in groups TC and TCS, whereas the highest intensity was predicted in group TCS. The most infected trout were from the group co-occurring with stickleback (TCS), possibly due to a higher availability of fish prey. In conclusion, our study demonstrates elevated Diphyllobothrium spp. infections in lacustrine trout populations where fish prey are available and suggests that highly available and easily caught stickleback prey may play a key role in the transmission of Diphyllobothrium spp. parasite larvae.


Facilitating emotional coping during treatment.
Patient resources for coping with breast cancer can be enhanced by attention to cognitive, affective, psychosomatic, and social components of the illness. The diagnosis and treatment of breast cancer constitutes an immediate confrontation with mortality, and sympathetic but direct examination of the patient's vulnerability and means of coping with it will reduce rather than amplify death anxiety. The development and pursuit of realistic goals influenced by the prognosis can help patients adjust constructively. Extremes of emotion are to be expected at times, but persistent depression and/or anxiety should be vigorously treated, including the use of appropriate psychoactive medication when the symptoms are primarily somatic (e.g., sleep disturbance and reductions in energy). Physical symptoms such as pain, nausea, and vomiting can be controlled by teaching patients such techniques as self-hypnosis, biofeedback, and systemic desensitization. Finally, a feeling of social isolation is the rule, not the exception, with cancer patients. Group and family treatment can effectively counter this. Systematic studies of such treatment interventions have shown favorable results, including significant reductions in mood disturbance and pain.


A pragmatic study exploring the prevention of delirium among hospitalized older hip fracture patients: Applying evidence to routine clinical practice using clinical decision support.
Delirium occurs in up to 65% of older hip fracture patients. Developing delirium in hospital has been associated with a variety of adverse outcomes. Trials have shown that multi-component preventive interventions can lower delirium rates. The objective of this study was to implement and evaluate the effectiveness of an evidence-based electronic care pathway, which incorporates multi-component delirium strategies, among older hip fracture patients. We conducted a pragmatic study using an interrupted time series design in order to evaluate the use and impact of the intervention. The target population was all consenting patients aged 65 years or older admitted with an acute hip fracture to the orthopedic units at two Calgary, Alberta hospitals. The primary outcome was delirium rates. Secondary outcomes included length of hospital stay, in-hospital falls, in-hospital mortality, new discharges to long-term care, and readmissions. A Durbin Watson test was conducted to test for serial correlation and, because no correlation was found, Chi-square statistics, Wilcoxon test and logistic regression analyses were conducted as appropriate. At study completion, focus groups were conducted at each hospital to explore issues around the use of the order set. During the 40-week study period, 134 patients were enrolled. The intervention had no effect on the overall delirium rate (33% pre versus 31% post; p = 0.84). However, there was a significant interaction between study phase and hospital (p = 0.03). Although one hospital did not experience a decline in delirium rate, the delirium rate at the other hospital declined from 42% to 19% (p = 0.08). This difference by hospital was mirrored in focus group feedback. The hospital that experienced a decline in delirium rates was more supportive of the intervention. Overall, post-intervention there were no significant differences in mean length of stay (12 days post versus 14 days pre; p = 0.74), falls (6% post versus 10% pre; p = 0.43) or discharges to long-term care (6% post versus 13% pre; p = 0.20). Translation of evidence-based multi-component delirium prevention strategies into everyday clinical care, using the electronic medical record, was not found to be effective at decreasing delirium rates among hip facture patients.


Evaluation of Breast Cancer Size Measurement by Computer-Aided Diagnosis (CAD) and a Radiologist on Breast MRI.
Purpose: This study aimed to evaluate cancer size measurement by computer-aided diagnosis (CAD) and radiologist on breast magnetic resonance imaging (MRI) relative to histopathology and to determine clinicopathologic and MRI factors that may affect measurements. Methods: Preoperative MRI of 208 breast cancers taken between January 2017 and March 2021 were included. We evaluated correlation between CAD-generated size and pathologic size as well as that between radiologist-measured size and pathologic size. We classified size discrepancies into accurate and inaccurate groups. For both CAD and radiologist, clinicopathologic and imaging factors were compared between accurate and inaccurate groups. Results: The mean sizes as predicted by CAD, radiologist and pathology were 2.66 ± 1.68 cm, 2.54 ± 1.68 cm, and 2.30 ± 1.61 cm, with significant difference (p < 0.001). Correlation coefficients of cancer size measurement by radiologist and CAD in reference to pathology were 0.898 and 0.823. Radiologist's measurement was more accurate than CAD, with statistical significance (p < 0.001). CAD-generated measurement was significantly more inaccurate for cancers of larger pathologic size (>2 cm), in the presence of an extensive intraductal component (EIC), with positive progesterone receptor (PR), and of non-mass enhancement (p = 0.045, 0.045, 0.03 and 0.002). Radiologist-measured size was significantly more inaccurate for cancers in presence of an in situ component, EIC, positive human epidermal growth factor receptor 2 (HER2), and non-mass enhancement (p = 0.017, 0.008, 0.003 and <0.001). Conclusion: Breast cancer size measurement showed a very strong correlation between CAD and pathology and radiologist and pathology. Radiologist-measured size was significantly more accurate than CAD size. Cancer size measurement by CAD and radiologist can both be inaccurate for cancers with EIC or non-mass enhancement.


Prion diseases, blood and the immune system: concerns and reality.
There is a great amount of uncertainty about the nature of the agent which causes spongiform encephalopathies. In recent years the occurrence of bovine spongiform encephalopathy and of new variant-Creutzfeldt Jakob disease, has raised concerns that prions may, under certain circumstances, contaminate the blood supply. This review article illustrates the problems with which research in this field is fraught, and presents some of the arguments which are controversially discussed in the field.


Emerging biologics in inflammatory bowel disease.
Early biologic therapy is recommended in patients with inflammatory bowel disease and poor prognostic factors and in those refractory to conventional medications. Anti-tumor necrosis factor (anti-TNF) agents are the most commonly used biologic agents. However, some patients may not have an initial response to anti-TNF therapy, and one-third will develop loss of response over time. Anti-TNF drugs can also be associated with side effects. In addition, the use of biologics is currently limited by their cost, especially in developing countries. A number of new therapeutic targets, including novel small molecules, and cellular therapy are available or under investigation. These novel molecules include oral Janus kinase (JAK) inhibitor (tofacitinib), interleukin inhibitor (ustekinumab), oral SMAD7 antisense oligonucleotide (mongersen), and anti-integrin inhibitors (vedolizumab). Here, we review the mechanisms of action, the efficacy, and the safety data of these novel agents. Biological products that are highly similar to reference biologic products whose patents have expired-also known as "biosimilars"-can be produced at lower cost with similar efficacy, and are also available for the treatment of IBD. We review the efficacy data for such agents as well.


Seed longevity and fire: germination responses of an exotic perennial herb in NW Patagonian grasslands (Argentina).
Fire affects grassland composition by selectively influencing recruitment. Some exotic species can increase their abundance as a consequence of fire-stimulated seed germination, but response may depend on seed age. Rumex acetosella L. (Polygonaceae, sheep's sorrel) is a cosmopolitan herb that has invaded NW Patagonia's grasslands. This species forms persistent soil seed banks and increases after disturbances, particularly fire. We studied how fire and seed longevity influence R. acetosella germination. In 2008, we conducted laboratory experiments where we exposed different-aged seeds (up to 19 years old) to heat, smoke, charcoal, ash and control treatments. Total percentage germination and mean germination time depended on both seed age and fire treatment. Germination of younger seeds decreased with increasing temperature. There was no general pattern in germination responses of different-aged seeds to smoke, charcoal and ash. While smoke improved the germination of fresh seeds, charcoal decreased germination. Germination of untreated seeds was negatively correlated with seed age, and mean germination time increased with seed age. In most treatments, fresh seeds had lower germination than 1-5-year-old seeds, indicating an after-ripening requirement. Smoke stimulates R. acetosella germination, causing successful recruitment during post-fire conditions. Fresh seeds are particularly responsive to fire factors, possibly because they have not experienced physical degradation and are more receptive to environmental stimuli. Knowing the colonisation potential from the soil seed bank of this species during post-fire conditions will allow us to predict their impact on native communities.


Synthesis of hybrid dendrimer-star polymers by the RAFT process.
A first generation phosphorus-containing dendrimer with twelve terminal benzyl dithiobenzoate functions was designed and subsequently used as a multifunctional agent to derive hybrid star copolymers consisting of a dendritic core surrounded by twelve polystyrene branches by reversible addition-fragmentation chain transfer (RAFT).


Darifenacin: a novel M3 muscarinic selective receptor antagonist for the treatment of overactive bladder.
Darifenacin is a novel M3 muscarinic selective receptor antagonist for once-daily treatment of overactive bladder (OAB), a highly prevalent, chronic and debilitating disease defined by urinary urgency with or without urge incontinence, usually with increased frequency of micturition and nocturia. In vitro, darifenacin is a potent and specific muscarinic receptor antagonist with </= 59-fold higher selectivity for muscarinic M3 receptors relative to other muscarinic receptor subtypes. This profile may, therefore, confer clinical efficacy in the treatment of OAB, with a lower propensity for adverse effects and safety issues related to blockade of other muscarinic receptor subtypes. Indeed, consistent with its low relative affinity for M1 and M2 receptors, no effects on cognitive function and heart-rate variability, respectively, have been observed with darifenacin. Subsequent large-scale clinical trials have confirmed that darifenacin (at doses of 7.5 and 15 mg/day) results in central nervous system and cardiac adverse events comparable to placebo, and provides early and meaningful improvement across a range of OAB symptoms including incontinence episodes, urgency and urinary frequency. On the basis of such findings, darifenacin would appear to meet the current need for an effective OAB pharmacotherapy that is efficacious, well-tolerated and, more importantly, minimises the risk of safety-related adverse effects.