A qualitative systematic review of internal and external influences on shared decision-making in all health care settings.
The objective of this review is to identify and synthesize the best available evidence related to the meaningfulness of internal and external influences on shared-decision making for adult patients and health care providers in all health care settings.The specific questions to be answered are: BACKGROUND: Patient-centered care is emphasized in today's healthcare arena. This emphasis is seen in the works of the International Alliance of Patients' Organizations (IAOP) who describe patient-centered healthcare as care that is aimed at addressing the needs and preferences of patients. The IAOP presents five principles which are foundational to the achievement of patient-centered healthcare: respect, choice, policy, access and support, as well as information. These five principles are further described as:Within the description of these five principles the idea of shared decision-making is clearly evident.The concept of shared decision-making began to appear in the literature in the 1990s. It is defined as a "process jointly shared by patients and their health care provider. It aims at helping patients play an active role in decisions concerning their health, which is the ultimate goal of patient-centered care." The details of the shared decision-making process are complex and consist of a series of steps including:Three overall representative decision-making models are noted in contemporary literature. These three models include: paternalistic, informed decision-making, and shared decision-making. The paternalistic model is an autocratic style of decision-making where the healthcare provider carries out the care from the perspective of knowing what is best for the patient and therefore makes all decisions. The informed decision-making model takes place as the information needed to make decisions is conveyed to the patient and the patient makes the decisions without the healthcare provider involvement. Finally, the shared decision-making model is representative of a sharing and a negotiation towards treatment decisions. Thus, these models represent a range with patient non-participation at one end of the continuum to informed decision making or a high level of patient power at the other end. Several shared decision-making models focus on the process of shared decision-making previously noted. A discussion of several process models follows below.Charles et al. depicts a process model of shared decision-making that identifies key characteristics that must be in evidence. The patient shares in the responsibility with the healthcare provider in this model. The key characteristics included:This model illustrates that there must be at least two individuals participating, however, family and friends may be involved in a variety of roles such as the collector of information, the interpreter of this information, coach, advisor, negotiator, and caretaker. This model also depicts the need to take steps to participate in the shared decision-making process. To take steps means that there is an agreement between and among all involved that shared decision-making is necessary and preferred. Research about patient preferences, however, offers divergent views. The link between patient preferences for shared decision-making and the actuality of shared decision-making in practice is not strong. Research concerning patients and patient preferences on shared decision-making points to variations depending on age, education, socio-economic status, culture, and diagnosis. Healthcare providers may also hold preferences for shared decision-making; however, research in this area is not as comprehensive as is patient focused research. Elwyn et al. explored the views of general practice providers on involving patients in decisions. Both positive and negative views were identified ranging from receptive, noting potential benefits, to concern for the unrealistic nature of participation and sharing in the decision-making process. An example of this potential difficulty, from a healthcare provider perspective, is identifying the potential conflict that may develop when a patient's preference is different from clinical practice guidelines. This is further exemplified in healthcare encounters when a situation may not yield itself to a clear answer but rather lies in a grey area. These situations are challenging for healthcare providers.The notion of information sharing as a prerequisite to shared decision-making offers insight into another process. The healthcare provider must provide the patient the information that they need to know and understand in order to even consider and participate in the shared decision-making process. This information may include the disease, potential treatments, consequences of those treatments, and any alternatives, which may include the decision to do nothing. Without knowing this information the patient will not be able to participate in the shared decision-making process. The complexity of this step is realized if one considers what the healthcare provider needs to know in order to first assess what the patient knows and does not know, the readiness of the patient to participate in this educational process and learn the information, as well as, the individual learning styles of the patient taking into consideration the patient's ideas, values, beliefs, education, culture, literacy, and age. Depending on the results of this assessment the health care provider then must communicate the information to the patient. This is also a complex process that must take into consideration the relationship, comfort level, and trust between the healthcare provider and the patient.Finally, the treatment decision is reached between both the healthcare provider and the patient. Charles et al. portrays shared decision-making as a process with the end product, the shared decision, as the outcome. This outcome may be a decision as to the agreement of a treatment decision, no agreement reached as to a treatment decision, and disagreement as to a treatment decision. Negotiation is a part of the process as the "test of a shared decision (as distinct from the decision-making process) is if both parties agree on the treatment option."Towle and Godolphin developed a process model that further exemplifies the role of the healthcare provider and the patient in the shared decision-making process as mutual partners with mutual responsibilities. The capacity to engage in this shared decision-making rests, therefore, on competencies including knowledge, skills, and abilities for both the healthcare provider and the patient. This mutual partnership and the corresponding competencies are presented for both the healthcare provider and the patient in this model. The competencies noted for the healthcare provider for shared decision making include:Patient competencies include:This model illustrates the shared decision-making process with emphasis on the role of the healthcare provider and the patient very similar to the prior model. This model, however, gives greater emphasis to the process of the co-participation of the healthcare provider and the patient. The co-participation depicts a mutual partnership with mutual responsibilities that can be seen as "reciprocal relationships of dialogue." For this to take place the relationship between and among the participants of the shared decision-making process is important along with other internal and external influences such as communication, trust, mutual respect, honesty, time, continuity, and commitment. Cultural, social, and age group differences; evidence; and team and family are considered within this model.Elwyn et al. presents yet another model that depicts the shared decision-making process; however, this model offers a view where the healthcare provider holds greater responsibility in this process. In this particular model the process focuses on the healthcare provider and the essential skills needed to engage the patient in shard decisions. The competencies outlined in this model include:The healthcare provider must demonstrate knowledge, competencies, and skills as a communicator. The skills for communication competency require the healthcare provider to be able to elicit the patient's thoughts and input regarding treatment management throughout the consultation. The healthcare provider must also demonstrate competencies in assessment skills beyond physical assessment that includes the ability to assess the patient's perceptions and readiness to participate. In addition, the healthcare provider must be able to assess the patient's readiness to learn the information that the patient needs to know in order to fully engage in the shared decision-making process, assess what the patient already knows, what the patient does not know, and whether or not the information that the patient knows is accurate. Once this assessment is completed the healthcare provider then must draw on his/her knowledge, competencies, and skills necessary to teach the patient what the patient needs to know to be informed. This facilitates the notion of the tailor-made information noted previously. The healthcare provider also requires competencies in how to check and evaluate the entire process to ensure that the patient does understand and accept with comfort not only the plan being negotiated but the entire process of sharing in decision-making. In addition to the above, there are further competencies such as competence in working with groups and teams, competencies in terms of cultural knowledge, competencies with regard to negotiation skills, as well as, competencies when faced with ethical challenges.Shared decision-making has been associated with autonomy, empowerment, and effectiveness and efficiency. Both patients and health care providers have noted improvement in relationships and improved interactions when shared decision-making is in evidence. Along with this improved relationship and interaction enhanced compliance is noted. Additional research points to patient satisfaction and enhanced quality of life. There is some evidence to suggest that shared decision-making does facilitate positive health outcomes.In today's healthcare environment there is greater emphasis on patient-centered care that exemplifies patient engagement, participation, partnership, and shared decision-making. Given the shift from the more autocratic delivery of care to the shared approach there is a need to more fully understand the what of shared decision-making as well as how shared decision-making takes place along with what internal and external influences may encourage, support, and facilitate the shared decision-making process. These influences are intervening variables that may be of significance for the successful development of practice-based strategies that may foster shared decision-making in practice. The purpose of this qualitative systematic review is to identify internal and external influences on shared decision-making in all health care settings.A preliminary search of the Joanna Briggs Library of Systematic Reviews, MEDLINE, CINAHL, and PROSPERO did not identify any previously conducted qualitative systematic reviews on the meaningfulness of internal and external influences on shared decision-making.


Effect of metal strengthener length on stress distribution in acrylic denture bases: a finite element study.
This study investigated the influence of metal strengthener length on stress created in acrylic denture bases in relation to location of the vertical support to the dentures. Finite element analysis was conducted to calculate stress generated in the straps of 2 mm-thickness and 18 mm-width that were reinforced with metal strengtheners of five different lengths. A vertical biting force of 60 N was directed on one end of each strap, while the other end was fixed. Vertical movements were restricted at one of the three support locations between the centre of the strap and the loading site. When the straps were vertically supported near the loading site, greater maximum tensile stresses were seen in the straps with relatively short strengtheners than those shown in the straps with longer strengtheners. The metal strengtheners with sufficient length may provide a preventive denture design against the acrylic fractures.


[Effect of phospholipase A2 inhibitor on substance P-induced histamine release from rat peritoneal mast cells].
Rat peritoneal mast cells purified on a Percoll gradient were challenged with substance P and effect of phospholipase A2 inhibitor ONO-RS-082 on substance P-induced histamine release from the cells were investigated. Substance P at the concentration of 10(-5) M caused a significant histamine release and the amount of histamine release reached to its submaximum at 1 min after the challenge and then slowly increased. ONO-RS-082 inhibited the substance P-induced histamine release in a concentration-dependent manner at the concentration from 10(-6) to 10(-4) M, suggesting that phospholipase A2 may play some roles in the process of substance P-induced histamine release from rat peritoneal mast cells.


Effect of WS₂ Inorganic Nanotubes on Isothermal Crystallization Behavior and Kinetics of Poly(3-Hydroxybutyrate-co-3-hydroxyvalerate).
Nanocomposites of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and tungsten disulfide inorganic nanotubes (INT-WS₂) were prepared by blending in solution, and the effects of INT-WS₂ on the isothermal crystallization behavior and kinetics of PHBV were investigated for the first time. The isothermal crystallization process was studied in detail using various techniques, with emphasis on the role of INT-WS₂ concentration. Differential scanning calorimetry (DSC) and polarized optical microscopy (POM) showed that, in the nucleation-controlled regime, crystallization rates of PHBV in the nanocomposites are influenced by the INT-WS₂ loading. Our results demonstrated that low loadings of INT-WS₂ (0.1⁻1.0 wt %) increased the crystallization rates of PHBV, reducing the fold surface free energy by up to 24%. This is ascribed to the high nucleation efficiency of INT-WS₂ on the crystallization of PHBV. These observations facilitate a deeper understanding of the structure-property relationships in PHBV biopolymer nanocomposites and are useful for their practical applications.


The involvement of extracellular calcium in the formation of 5-lipoxygenase metabolites by human polymorphonuclear leukocytes.
We have addressed the question why in the presence of a Ca2+ ionophore human polymorphonuclear leukocytes generate leukotrienes in high yields, but in only low amounts after stimulation by receptor agonists like fMLF (fM, formylmethionine), leukotriene B4 or platelet-activating factor (PAF), although a significant release of intracellular calcium can be measured. Using ionomycin we can show that from the two enzymes involved, phospholipase A2 and 5-lipoxygenase, the first requires a threshold level of about 350-400 nM calcium whereas 5-lipoxygenase shows a linear dependence on calcium and saturates at this concentration. Our data indicate that the Ca2+ requirement of phospholipase A2 can only be met by an additional influx of extracellular calcium, whereas 5-lipoxygenase will operate already at levels provided by intracellular stores. Consequently, the complexing of extracellular calcium by EGTA stops phospholipase A2 activity immediately, whereas added arachidonate can be still adequately metabolized by intracellular Ca2+ release triggered by fMLF or PAF. Interestingly, PAF shows a stronger extracellular component in its Ca2+ transient than fMLF, and also generates more 5-lipoxygenase metabolites. However, a clear correlation between the amount of 5-lipoxygenase metabolites and the extracellular Ca2+ signal was lacking, since maximal activity was achieved before the bulk of the extracellular calcium was monitored. Ca2+ influx after PAF stimulation could be blocked after 2 min by EGTA, but a further increase in the formation of 5-lipoxygenase metabolites was observed. In contrast ionomycin-elicited 5-lipoxygenase activity could be stopped at any time shortly after EGTA addition.


Whistle blowing and research integrity: Potential remedy for research misconduct in Malaysian institutions of higher education.
This study found that less than half of the respondents are willing to blow the whistle. The results reveal that a lack of protection with regard to the whistleblower's identity, the tedious investigative process, and the notion of avoiding confrontation, which is more apparent in Asian cultures as compared to the West, are among the reasons why individuals who witnessed misconduct chose to remain silent. Adhering to the Asian cultural upbringing where the young must respect the old, those of lower rank must obey those with higher authority, and subordinates do not question the actions of their superior, has become a norm even in the working environment. Therefore, emphasize the need for better protection for whistleblowers including using experienced individuals with a research ethics background to handle allegations from whistleblowers. In addition, established guidelines and procedures for whistleblowers with regard to voicing their allegations against colleagues engaged in research misconduct is still lacking or, to a certain extent, is still unknown to researchers. Thus, the concern indicates a need for institutions to create awareness among researchers regarding the existing platform for whistleblowers, or to develop a systematic and clear procedure which is reliable and independent to promote professionalism in academia.


Post-Doc: satisfying the information needs of general practitioners in continuing medical education and daily practice.
The learning needs of General Practitioners (GPs) are not optimally covered by traditional ways of Continuing Medical Education (CME). The European-funded Post-Doc project sets up a model for a European internet-based infra-structure and learning environment to support GPs' individual CME activities, focusing on problems of daily work. It integrates education, information and communication for both daily work and learning at home. Based upon a user requirements analysis, the service includes multimedia training applications, selections of relevant information sources, a calendar of events, and communication facilities. The service is intended to fit in existing health care structures and accreditation systems. Because of different languages and user requirements in Post-Doc's regions each region builds an own website. The regional prototypes are built and evaluated in cooperation with small core user groups. This regional approach proved feasible and also influenced the network structure with regional demonstrator websites and one master website including central functionality.


Combined tetrahydrobiopterin-phenylalanine loading test in the detection of partially defective biopterin synthesis.
Deficiency in the synthesis of biopterin causes neonatal hyperphenylalaninemia. We report a 10-year-old girl of normal appearance with a partial defect in biopterin synthesis, normal intelligence and normal serum phenylalanine levels (95 mumol/l) (1.6 mg/dl). During her 1st year of life serum phenylalanine levels were 250 mumol/l (4 mg/dl) and phenylalanine loading performed at 6 months and 1 year of age was not followed by an increase in serum tyrosine. At 9 years of age she had developed a severely abnormal EEG with focal spike activity but no observable clinical abnormalities. Determination of urinary pterins showed abnormal low levels of biopterin and high levels of neopterin. Phenylalanine loading combined with oral administration of tetrahydrobiopterin (BH4) was followed by a normal increase in serum tyrosine and a normal decrease in serum phenylalanine. Considering the importance of BH4 for the synthesis of dopamine, catecholamines, and serotonin we suggest that these cases should be followed carefully. If neurological symptoms appear, e.g., epilepsy, it may be worthwhile to consider treatment with BH4 and neurotransmitter precursors.


Impact of a multidisciplinary team review of potential outpatient parenteral antimicrobial therapy prior to discharge from an academic medical center.
Outpatient parenteral antimicrobial therapy (OPAT) is frequently prescribed at hospital discharge, often without infectious diseases (ID) clinician oversight. We developed a multidisciplinary team, including an ID pharmacist, to review OPAT care plans at hospital discharge to improve safety, clinical efficacy, practicality, and appropriateness of the proposed antimicrobial regimen. To evaluate the impact of the OPAT team on regimen safety, efficacy, and complexity; calculate the economic benefits of the service by avoiding hospital discharge delay, central venous catheter placement, or need for OPAT; and evaluate the discharge environment among OPAT referrals. In an observational design, we analyzed the impact of an OPAT team from July 2009 through June 2010 at a large academic tertiary care hospital. All patients with plans for continued parenteral therapy after discharge referred to the OPAT team were included in the analysis. Patients were excluded if OPAT was cancelled prior to processing of the referral. During the 1-year study period, 569 of 644 consecutive referrals to the OPAT team met inclusion criteria, resulting in 494 OPAT courses. Interventions by an ID pharmacist were made for safety (56%), regimen complexity (41%), and efficacy (29%). Lack of formal ID physician consultation resulted in more interventions for safety (64% vs 48%, p < 0.001) and efficacy (36% vs 21%, p < 0.001). Discharge delays were avoided for 35 referrals, resulting in 228 hospital days avoided and approximately $366,000 in hospital bed cost savings. Use of OPAT was avoided in 75 referrals (13.2%), preventing central venous catheter placement in 48 patients (8.4%), resulting in an additional $58,080 in cost savings. The OPAT team optimized safety, efficacy, and convenience of OPAT while providing substantial cost savings. Further studies are needed to confirm the program's cost-effectiveness.


Peripartum Infections Among Women With Inflammatory Bowel Disease.
Pregnant patients with inflammatory bowel diseases (IBDs) are frequently treated with immunomodulatory agents and may be at increased risk of adverse outcomes, including peripartum infections. We sought to examine the risk for peripartum infections in patients with IBD compared with control subjects and identify potential risk factors associated with peripartum infections in these patients. This retrospective cohort study compared peripartum infection rates and associated risk factors between pregnant women with and without IBD. The study population included women attending a dedicated joint maternal-fetal medicine and gastroenterology clinic for pregnant women with IBD between 2012 and 2019 at the Rabin Medical Center in Israel, a major referral center for patients with IBD. For each patient, 5 women without IBD were matched according to the newborn's birth date (±2 years), age, parity, and body mass index. Peripartum infection was defined as any 1 of the following: chorioamnionitis, maternal fever (>38°C) detected during labor or postpartum hospitalization, and positive culture taken during the hospitalization. Overall, 195 pregnant women with IBD (72 [37%] with ulcerative colitis, 123 [63%] with Crohn's disease) were matched with 888 control subjects. The mean disease duration was 8.4 ± 7.02 years. IBD therapy, used by 81%, included most frequently 5-aminosalicylic acid (44%) and tumor necrosis factor inhibitors (27%). Peripartum infections were observed in 15 (7.7%) patients and 49 (5.5%) control subjects (P = 1.00). No medication significantly increased the likelihood of peripartum infection. Cesarean delivery was more likely among women with IBD but was not associated with an increased risk of peripartum infection. Peripartum infections were comparable in patients with IBD and control subjects. These reassuring data augment existing knowledge of obstetrical outcomes in IBD patients and contribute to the discussion between caregivers and patients.


[Temporal prediction of the dengue epidemic in Colombia: the epidemic's probabilistic dynamics].
Studying geometric dynamics for annual cases of dengue recorded in Colombia from 19902006 by making an analogy with a probabilistic random walk. The geometric dynamics for the number of annual cases of dengue registered in Colombia for 1990-2006 was mathematically analyzed as a probabilistic random walk, building the total probability space for the dynamics in order to analyze the probabilistic behavior of consecutive increases and decreases and the probabilistic behavior of cases during ranges of serial years and thus calculate the temporary prediction of annual cases. The extreme values predicted for the number of infected people during 2007 were 57 581 and 20 008; the predicted value was refined by analysing annual variations, giving a 48 188 predicted value for the number of infected people in 2007. This prediction was then corroborated by using Colombian National Institute of Health data having a 43 564 recorded real infected value on December 31st; the real value corresponded to 90,4 % regarding predicted value. A mathematical and acausal order for the dengue epidemic in Colombia was found from the probabilistic random walk; thus led to carrying out temporary, simple and useful predictions in the public health decision-making.


First Steps in the Analysis of Prokaryotic Pan-Genomes.
Pan-genome is defined as the set of orthologous and unique genes of a specific group of organisms. The pan-genome is composed by the core genome, accessory genome, and species- or strain-specific genes. The pan-genome is considered open or closed based on the alpha value of the Heap law. In an open pan-genome, the number of gene families will continuously increase with the addition of new genomes to the analysis, while in a closed pan-genome, the number of gene families will not increase considerably. The first step of a pan-genome analysis is the homogenization of genome annotation. The same software should be used to annotate genomes, such as GeneMark or RAST. Subsequently, several software are used to calculate the pan-genome such as BPGA, GET_HOMOLOGUES, PGAP, among others. This review presents all these initial steps for those who want to perform a pan-genome analysis, explaining key concepts of the area. Furthermore, we present the pan-genomic analysis of 9 bacterial species. These are the species with the highest number of genomes deposited in GenBank. We also show the influence of the identity and coverage parameters on the prediction of orthologous and paralogous genes. Finally, we cite the perspectives of several research areas where pan-genome analysis can be used to answer important issues.


Multiplexed holographic Fabry-Perot étalons.
We discuss a multiplexed holographic Fabry-Perot étalon that includes a multiplexed hologram in a novel holographic Fabry-Perot étalon. Two unique advantages can be achieved by using the multiplexed holographic Fabry-Perot étalon: coherently coupled fabrication of holographic Fabry-Perot mirrors significantly reduces the need to have the nearly flat surfaces typically required in conventional Fabry-Perot etalons, and the angular-wavelength multiplexing capability of a multiplexed hologram can be added to the tunable narrow-band filtering capability of Fabry-Perot étalons. Several types of multiplexed holographic Fabry-Perot étalon are experimentally demonstrated.


Total Synthesis of Paenibacterin and Its Analogues.
Paenibacterin is a recently discovered cyclic lipodepsipeptide antibiotic produced by the soil bacterium Paenibacillus thiaminolyticus. It is produced as a mixture of three compounds with isomeric 15-carbon acyl lipids, designated P-A1 (linear lipid), P-A2 (anteiso lipid), and P-A3 (iso lipid). Here, we report the total synthesis of P-A1 and P-A2, as well as two analogues of P-A1 in which the threonine residue in P-A1 was replaced with l-2,3-diaminopropionic acid (P-A1-Dapa) and (2 S,3 R)-2,3-diaminobutyric acid (P-A1-Daba), converting the ring-closing ester bond to an amide bond. Solid phase peptide chemistry was used to prepare branched precursors which were cyclized off-resin to obtain the target peptides in good to excellent overall yields. The use of a pseudoproline dipeptide building block was found to be important for obtaining good yields. The antibacterial activity of the peptides was determined against Escherichia coli K-12 (G-) and Bacillus subtilis 1046 (G+). The minimum inhibitory concentrations of P-A1 and P-A2 were the same despite the variation in the structure of the acyl tail. Replacing the ring-closing ester bond with an amide bond had little or no effect on activity. The synthetic routes developed here should prove to be useful for creating new antibiotics based on the structure of paenibacterin.


Functional analysis of the early development of self-injurious behavior: incorporating gene-environment interactions.
The analysis of the early development of self-injurious behavior (SIB) has, to date, reflected the wider distinction between nature and nurture. Despite the status of genetic factors as risk markers for the later development of SIB, a model that accounts for their influence on early behavior-environment relations is lacking. In the current paper we argue that the investigation of gene-environment interactions (GxE) and other forms of gene-environment interplay could potentially enhance current approaches to the study of self-injury. A conceptual model of the early development of SIB based explicitly on such relations is presented. The model is consistent with the basic tenets of functional analysis. Implications for research and the assessment, treatment, and prevention of SIB are discussed.


A low-molecular-weight (25-kDa) IGF-binding protein is increased with growth inhibition in the fasting striped bass, Morone saxatilis.
The effect of fasting on circulating IGFBPs in the striped bass was assessed in relation to changes in growth and metabolism. Thirty-day-fasted (30DF) and 60-day-fasted (60DF) fish, and 60DF fish refed for 14 additional days (REFED), were compared with control, fed fish. Growth and metabolic status of each animal were assessed by determining body length (BL) and body weight (BW) changes, hepatosomatic index (HSI), condition factor (CF), and serum glucose concentration, and by assaying for incorporation of [35S]sulfate (proteoglycan synthetic activity) and [3H]thymidine (mitotic activity) in ceratobranchial cartilage explants in vitro. Serum IGFBP concentrations were assessed by a Western ligand blot procedure using 125I-labeled human IGF-I tracer. Both 30DF and 60DF fish exhibited hypoglycemia and reduced HSI and CF, and their BL and BW growth rates were significantly inhibited. Strongly correlated with the inhibited body growth indices were significantly depressed levels of cartilage [35S]sulfate incorporation in both 30DF and 60DF animals. The 60DF group also exhibited reduced [3H]thymidine incorporation. Associated with this growth inhibition was a dramatic increase in the serum levels of a 25-kDa IGFBP (sbIGFBP-1). A 35-kDa IGFBP (sbIGFBP-3), on the other hand, was not significantly altered with fasting. All fasting-induced changes in growth, metabolism, and IGFBP levels were restored in the REFED group. These results demonstrate that an IGFBP of low molecular weight is increased with growth inhibition in the fasting striped bass, suggesting that a teleost fish counterpart to mammalian IGFBP-1 may exist.


Preparation of Biocolorant and Eco-Dyeing Derived from Polyphenols Based on Laccase-Catalyzed Oxidative Polymerization.
Natural products have been believed to be a promising source to obtain ecological dyes and pigments. Plant polyphenol is a kind of significant natural compound, and tea provides a rich source of polyphenols. In this study, biocolorant derived from phenolic compounds was generated based on laccase-catalyzed oxidative polymerization, and eco-dyeing of silk and wool fabrics with pigments derived from tea was investigated under the influence of pH variation. This work demonstrated that the dyeing property was better under acidic conditions compared to alkalinity, and fixation rate was the best when pH value was 3. Furthermore, breaking strength of dyed fabrics sharply reduced under the condition of pH 11. Eventually, the dyeing method was an eco-friendly process, which was based on bioconversion, and no mordant was added during the process of dyeing.


Cleaning with Bulk Nanobubbles.
The electrolysis of aqueous solutions produces solutions that are supersaturated in oxygen and hydrogen gas. This results in the formation of gas bubbles, including nanobubbles ∼100 nm in size that are stable for ∼24 h. These aqueous solutions containing bubbles have been evaluated for cleaning efficacy in the removal of model contaminants bovine serum albumin and lysozyme from surfaces and in the prevention of the fouling of surfaces by these same proteins. Hydrophilic and hydrophobic surfaces were investigated. It is shown that nanobubbles can prevent the fouling of surfaces and that they can also clean already fouled surfaces. It is also argued that in practical applications where cleaning is carried out rapidly using a high degree of mechanical agitation the role of cleaning agents is not primarily in assisting the removal of soil but in suspending the soil that is removed by mechanical action and preventing it from redepositing onto surfaces. This may also be the primary mode of action of nanobubbles during cleaning.


A possible role for ferritin during inflammation.
Inflammation induces the hepatic synthesis of the iron storage protein (apo)ferritin, which is released into the circulation, and behaves as an acute phase protein. The biological significance of the extracellular rise in serum (apo)ferritin is unknown. We have observed that (apo)ferritin will stimulate superoxide production from neutrophils in the presence of cytochalasin B across a physiologically appropriate concentration range. We therefore propose that extracellular ferritin has an important role in host defence against bacteraemia by stimulating oxidative metabolism.


Treatment of enlarged pores with the quasi long-pulsed versus Q-switched 1064 nm Nd:YAG lasers: A split-face, comparative, controlled study.
A variety of treatment modalities have been used to reduce the size of en-larged pores. The 1064 nm Nd:YAG laser, in addition to its role in removal of tattoos and age-related dyschromia, depilation and skin rejuvenation, may also play a role in reducing the size of enlarged pores. The present split-face controlled study assessed and compared the efficacy between the quasi long-pulsed (micropulsed) and the Q-switched modes of the Nd:YAG laser in the treatment of enlarged pores. Twenty subjects with enlarged pores were recruited for the micropulsed vs Q-switched study, all treated with the same 1064 nm Nd:YAG laser system. Ten subjects were treated with the 300 µs micropulsed mode and the other ten subjects were treated with the 5 ns Q-switched mode. All subjects were treated on the right half of the face, the left half serving as an untreated control. Five laser sessions were performed. The pore sizes were measured using an image analysis program and the sebum level was measured with a Sebumeter(®) before and after the treatments. The pore size and sebum level significantly decreased with treatment on the treated side (right cheek and right half of nose) in both the micropulsed and Q-switched modes compared to the control side (p<0.05), but without any statistically significant difference between the modes. The micropulsed and Q-switched Nd:YAG laser treatments reduced pore size and sebum levels with more or less equal efficacy and with no adverse side effects.


A minimum version of log-rank test for testing the existence of cancer cure using relative survival data.
Cancer survival is one of the most important measures to evaluate the effectiveness of treatment and early diagnosis. The ultimate goal of cancer research and patient care is the cure of cancer. As cancer treatments progress, cure becomes a reality for many cancers if patients are diagnosed early and get effective treatment. If a cure does exist for a certain type of cancer, it is useful to estimate the time of cure. For cancers that impose excess risk of mortality, it is informative to understand the difference in survival between cancer patients and the general cancer-free population. In population-based cancer survival studies, relative survival is the standard measure of excess mortality due to cancer. Cure is achieved when the survival of cancer patients is equivalent to that of the general population. This definition of cure is usually called the statistical cure, which is an important measure of burden due to cancer. In this paper, a minimum version of the log-rank test is proposed to test the equivalence of cancer patients' survival using the relative survival data. Performance of the proposed test is evaluated by simulation. Relative survival data from population-based cancer registries in SEER Program are used to examine patients' survival after diagnosis for various major cancer sites.


Lack of serologic immunity against vaccine-preventable diseases in children after thoracic transplantation.
We investigated whether children after heart- (HTx) or heart-lung transplantation (HLTx) show protective antibody levels against recommended vaccinations, whether vaccination schedules are completed and which factors influence serologic immunity. We performed a cross sectional ELISA - quantification of specific antibodies in 46 patients after pediatric thoracic Tx. Findings were correlated to vaccination history, age at Tx, clinical course and immunosuppressive regimen. We found protective antibody levels against diphtheria in 74% of patients, against tetanus in 22%, against Haemophilus influenzae type b in 30% and against Streptococcus pneumoniae in 59%. Antibody concentrations against live attenuated vaccines were significantly lower in children transplanted in the first 2 years of life. Antibodies were absent for measles in 55% of late - and 81% of early transplanted children, for mumps in 66%/94%, for rubella in 30%/56% and for Varicella in 34%/63%. We found significant correlation of low antibody concentrations and age at Tx. Patients without protective antibody concentrations had significantly longer use of steroids. Vaccination schedules were incomplete or delayed in the majority of patients associated with more days in hospital pre-Tx. Our study shows that closer adherence to pretransplantation vaccination schedules and also post-transplantation monitoring of antibody levels are required in transplant patients.


[Immune system and hypophysis].
The immune system does not function in isolation from either nervous or endocrine system. Recent advances in biology have made it clear that there are many connections between immune system and hypothalamo-pituitary axis. Among them, relationship of cytokines to hypothalamus is of great interest. We reviewed functions of the cytokines such as interleukin, interferon and tumour necrosis factor. For example, IL-1 releases ACTH from the hypophysis being mediated by corticotropin releasing hormone in the hypothalamus. ACTH shows inhibitory effect on the immune system. Interferons, as well as interleukins bring fever and anorexia via opioid receptors in the hypothalamus. There are some evidences which show effect of IL-1 on the posterior hypophysis which secretes vasopressin and oxytocin. There are, however, many unknown mechanisms in this field. The resolution of the specific interactions between the immune system and the hypothalamo-pituitary axis is subject to further investigations.


Efficacy of aliskiren, compared with angiotensin II blockade, in slowing the progression of diabetic nephropathy in db/db mice: should the combination therapy be a focus?
Although the intensive use of angiotensin II blockade (ACEI or ARB), progression of diabetic nephropathy is common. A feedback increase in renin production often accompanies angiotensin II blockade. We therefore examined whether aliskiren, a direct renin inhibitor, confers better renoprotection than angiotensin II blockade and whether the addition of aliskiren to an ACEI or ARB would enhance the efficacy in slowing the progression of glomerulosclerosis in diabetes. Untreated db/db mice developed progressive mesangial matrix expansion and albuminuria between weeks 18 and 22, associated with reduction of WT-1 immunopositive podocytes and nephrin and podocin production and induction of desmin and B7-1 generation and renal expression of TGFß1, PAI-1, fibronectin and type IV collagen. Treatment with aliskiren at 30 mg/kg/d inhibited the increases in albuminuria and markers of renal fibrosis and the changes that are indicative of podocyte injury seen in the db/db mice. Notably, the therapeutic effect of aliskiren was similar to that of either enalapril or valsartan given alone at maximally effective doses. Combined therapy caused the loss of 10% ~ 16.6% of db/db mice, yielded no further reduction in renal fibrosis and podocyte injury but further reduced albuminuria and renal production of TNFα, Nox2 and p47phox and urine MCP-1 and malondialdehyde levels, the markers of renal inflammation and oxidative stress. These results suggest that aliskiren, enalapril and valsartan are equally effective in slowing the progression of diabetic nephropathy. The use of combination therapy with aliskiren and ACEI/ARB may not be strongly supported.


Chemosensitivity of IDH1-Mutated Gliomas Due to an Impairment in PARP1-Mediated DNA Repair.
Mutations in isocitrate dehydrogenase (IDH) are the most prevalent genetic abnormalities in lower grade gliomas. The presence of these mutations in glioma is prognostic for better clinical outcomes with longer patient survival. In the present study, we found that defects in oxidative metabolism and 2-HG production confer chemosensitization in IDH1-mutated glioma cells. In addition, temozolomide (TMZ) treatment induced greater DNA damage and apoptotic changes in mutant glioma cells. The PARP1-associated DNA repair pathway was extensively compromised in mutant cells due to decreased NAD+ availability. Targeting the PARP DNA repair pathway extensively sensitized IDH1-mutated glioma cells to TMZ. Our findings demonstrate a novel molecular mechanism that defines chemosensitivity in IDH-mutated gliomas. Targeting PARP-associated DNA repair may represent a novel therapeutic strategy for gliomas. Cancer Res; 77(7); 1709-18. ©2017 AACR.


Parents' perceptual preferences between compensatory articulation and nasal escape of air in children with cleft palate.
Two groups of parents (27 parents of children with cleft palate and 25 parents of normal children) listened to 14 pairs of tape-recorded words produced by two children with cleft palate. In each pair, one word was produced with compensatory articulation and the other with audible nasal escape of air. The parents indicated their preference by selecting from each pair the word that sounded better. Parents considered single words produced with compensatory articulation to be better than single words produced with nasal escape of air. Results are interpreted in terms of existing hypotheses and information concerning the acquisition of speech by children with cleft palate.


In situ Raman characterization of minerals and degradation processes in a variety of cultural and geological heritage sites.
We test the capabilities of in situ Raman spectroscopy for non-destructive analysis of degradation processes in invaluable masterpieces, as well as for the characterization of minerals and prehistoric rock-art in caves. To this end, we have studied the mechanism of decay suffered by the 15th-century limestone sculptures that decorate the retro-choir of Burgos Cathedral (N Spain). In situ Raman probe detected hydrated sulfate and nitrate minerals on the sculptures, which are responsible for the decay of the original limestone. In addition, in situ Raman analyses were performed on unique speleothems in El Soplao Cave (Cantabria, N Spain) and in the Gruta de las Maravillas (Aracena, SW Spain). Unusual cave minerals were detected in El Soplao Cave, such as hydromagnesite (Mg5(CO3)4(OH)2·4H2O), as well as ferromanganese oxides in the black biogenic speleothems recently discovered in this cavern. In the Gruta de las Maravillas, gypsum (CaSO4·2H2O) was identified for the first time, as part of the oldest cave materials, so providing additional evidence of hypogenic mechanisms that occurred in this cave during earlier stages of its formation. Finally, we present preliminary analyses of several cave paintings in the renowned "Polychrome Hall" of Altamira Cave (Cantabria, N. Spain). Hematite (Fe2O3) is the most abundant mineral phase, which provides the characteristic ochre-reddish color to the Altamira bison and deer paintings. Thus, portable Raman spectroscopy is demonstrated to be an analytical technique compatible with preserving our cultural and natural heritage, since the analysis does not require physical contact between the Raman head and the analyzed items.


Thrombocytopenia-Related Problems in Patients with Concomitant Atrial Fibrillation Requiring Antithrombotic Prevention: A Retrospective Cohort Study.
Low-dose edoxaban and enoxaparin sodium have been the subject of a retrospective comparison implemented with the propensity score technique in order to mitigate the effects of the differences in the basal clinical features of two cohorts and minimize the risk of bias. Subsequently, using a Cox proportional-hazards model, the association of each type of therapy with the risk of the composite of all-cause death, stroke/transient ischemic attack, hospitalizations and major bleeding events was assessed. For this analysis, a p-value < 0.05 was considered statistically significant. Therapy with enoxaparin and liver cirrhosis as causing thrombocytopenia were associated with increased risk of the composite endpoint (enoxaparin: hazard ratio (HR): 3.31; 95% CI: 1.54 to 7.13; p = 0.0023; liver cirrhosis, HR: 1.04; 95% CI: 1.002 to 1.089; p = 0.0410). Conversely, edoxaban therapy was significantly associated with decreased risk of the composite endpoint (HR: 0.071; 95% CI: 0.013 to 0.373; p = 0.0019). Based on this retrospective analysis, edoxaban at low doses would appear as an effective and safe pharmacological tool for the prophylaxis of cardioembolic events in patients with AF and thrombocytopenia.


HiFun: homology independent protein function prediction by a novel protein-language self-attention model.
Protein function prediction based on amino acid sequence alone is an extremely challenging but important task, especially in metagenomics/metatranscriptomics field, in which novel proteins have been uncovered exponentially from new microorganisms. Many of them are extremely low homology to known proteins and cannot be annotated with homology-based or information integrative methods. To overcome this problem, we proposed a Homology Independent protein Function annotation method (HiFun) based on a unified deep-learning model by reassembling the sequence as protein language. The robustness of HiFun was evaluated using the benchmark datasets and metrics in the CAFA3 challenge. To navigate the utility of HiFun, we annotated 2 212 663 unknown proteins and discovered novel motifs in the UHGP-50 catalog. We proved that HiFun can extract latent function related structure features which empowers it ability to achieve function annotation for non-homology proteins. HiFun can substantially improve newly proteins annotation and expand our understanding of microorganisms' adaptation in various ecological niches. Moreover, we provided a free and accessible webservice at http://www.unimd.org/HiFun, requiring only protein sequences as input, offering researchers an efficient and practical platform for predicting protein functions.


'Are you sure you're going to have another one of those?': A qualitative analysis of the social control and social support models in type 2 diabetes.
While there is evidence that spouses can impact the self-management of adults with type 2 diabetes mellitus, less is known about the influence of the wider social network. This qualitative study explored the perceived impact of the family as well as friends and work colleagues on type 2 diabetes mellitus self-management. A total of 25 adults with type 2 diabetes mellitus participated in semi-structured interviews regarding their social experiences of living with diabetes. Deductive thematic analysis was applied to the data. Pre-existing themes of health-related social control and social support were identified in the wider social network, with additional themes of non-involvement and unintentional undermining also emerging.


Harpacticoid copepods-their symbiotic associations and biogenic substrata: a review.
Members of the order Harpacticoida are primarily free-living and benthic but some lineages have adopted alternative modes of life which involve a major habitat shift or dependence on a host. Since the first discovery of a harpacticoid associated with an invertebrate host about 150 years ago, a total of 172 species, representing 84 genera and 17 families, have been shown to live in symbiotic partnership with other organisms. The steady addition of new taxa during the last 35 years testifies to the widespread and previously underestimated occurrence of symbiosis in the group. Harpacticoids have entered into associations with Cyanobacteria, Protozoa, macroalgae, grasses, fish hosts, marine tetrapods (including whales, sea turtles and manatees) and at least eleven invertebrate phyla. At present, 86 independent colonizations of marine and freshwater host organisms can be identified but this number is a minimum estimate and is expected to increase as certain host groups will be more properly sampled. In contrast to the Cyclopoida and Siphonostomatoida, which have been extremely successful in developing associations with cnidarians, sponges, echinoderms and ascidiaceans, members of the Harpacticoida have a marked predilection for crustacean hosts. Except for a few species that can be classified as genuine parasites, the precise nature of the relationship between most associated harpacticoids and their hosts has yet to be elucidated but can probably be defined as commensalistic, where the benefit to the copepod may be nutritional or protective. Most are ectosymbiotic but some live as endocommensals in microhabitats which provide considerable protection from predation. The success of symbiotic harpacticoids in freshwater is limited with the few species known to be associated with freshwater hosts typically representing isolated forays into a symbiotic lifestyle from an otherwise free-living lineage. The scattered literature on symbiotic harpacticoids is compiled and presented by host group. Dichotomous keys are provided for the identification of most species while accidental and doubtful records are discussed where appropriate.The genus Idomenella T. Scott, 1906a (Pseudotachidiidae), previously a junior subjective synonym of Dactylopodella Sars, 1905a, is reinstated to accommodate Dactylopodella rostrata (T. Scott, 1893), D. janetae Hicks, 1989, Xouthous coronatus (T. Scott, 1894b), X. antarcticus (Giesbrecht, 1902), X. intermedius (Lang, 1934) and Idomenella paracoronata sp. nov. Kioloaria Harris, 1994 (Porcellidiidae) is adopted as the valid replacement name for the preoccupied Acutiramus Harris, 2014a. The name of a second porcellidiid genus, Murramia Harris, 1994, lacks the mandatory type fixation and is made available here by adopting the original name but taking the present authorship and date. The generic name Ellucana Sewell, 1940 is currently unavailable and must instead be attributed to Coull (1971b). Laophonte commensalis Raibaut, 1962a is fixed as the type of Raibautius gen. nov. in the family Laophontidae, Tegastes cnidicus Humes, 1981b as the type of Aglaogastes gen. nov. in the Tegastidae, and Canuella (Canuella) indica Krishnaswamy, 1957 as the type of Indicanuella gen. nov.A number of new names are proposed for species that had previously been misidentified: Diarthrodes septemtrionalis sp. nov. for D. roscoffensis (Monard, 1935b) sensu Kornev & Chertoprud (2008), Kioloaria jejuensis sp. nov. for Porcellidium brevicaudatum Thompson & Scott, 1903 sensu Kim & Kim (1996), Xouthous andamanensis sp. nov. for X. maldivae [sic] Sewell, 1940 sensu Wells & Rao (1987), X. wellsi sp. nov. for X. laticaudatus (Thompson & Scott, 1903) sensu Wells (1967), X. namibiensis sp. nov. for X. pectinatus (Scott & Scott, 1898) sensu Kunz (1963), and Idomenella paracoronata sp. nov. for Idomene coronata (T. Scott, 1894b) sensu Sars (1909a). The inadequately described Amenophia ovalis Brady, 1910 is relegated to a species inquirenda in Amenophia Boeck, 1865. Idomene australis Brady, 1910, I. pusilla Brady, 1910, Dactylopusia ferrieri T. Scott, 1912 and I. kabylica Monard, 1936 are ranked species incertae sedis in the Pseudotachidiidae. Dactylopus bahamensis Edwards, 1891 is tentatively considered as species incertae sedis in the Dactylopusiidae. Canuellina onchophora Por, 1967 and C. nicobaris Wells & Rao, 1987 are transferred to the genus Ellucana Coull, 1971b while Ellucana secunda Coull, 1971b is assigned to the genus Canuellina Gurney, 1927. Xylora calyptogenae Willen, 2006 is sunk as a junior subjective synonym of X. bathyalis Hicks, 1988a. The incorrect original spellings of Parathalestris pacificus Chislenko, 1971, P. infestus Ho & Hong, 1988, Tripartisoma ovalis Avdeev, 1983, T. trapezoidalis Avdeev, 1983, Amplipedicola pectinatus Avdeev, 2010 and Sunaristes japonicus Ho, 1986a are amended to reflect agreement in gender with their respective generic names.


TMEM16A/B associated CaCC: structural and functional insights.
Calcium-activated chloride channels (CaCCs) play fundamental roles in numerous physiological processes. Transmembrane proteins 16A and 16B (TMEM16A/B) were identified to be the best molecular identities of CaCCs to date. This makes molecular investigation of CaCCs become possible. This review discusses the latest findings of TMEM16A/B associated CaCCs, the calcium and voltage dual dependence,the reorganization of Ca(2+)-binding site, the mechanisms of direct or indirect activation, the structure-functional relationship, and the possible stereoscopic structure. TMEM16A and other members of the family are associated with several kinds of cancers and other chloride channelopathies. An understanding of TMEM16 associated channel proteins will shed some light on their role in oncology and in pharmacology development.


Parental decisions regarding a prenatally detected fetal chromosomal abnormality and the impact of genetic counseling: an analysis of 38 cases with aneuploidy in Southeast Turkey.
This study investigated parental decision-making to terminate or continue a pregnancy after prenatal diagnosis of a chromosomal abnormality among a sample of patients in Southeast Turkey. Between 2004 and 2007, 1068 amniocentesis tests were performed in the Medical Biology and Genetic Department Laboratory at Dicle University. Aneuploidy was found in 38 cases (3.56%). Genetic counseling was provided for the couples that received abnormal results, and they were later interviewed and asked if they had continued or interrupted the pregnancy after the diagnosis. When confronted with autosomal aneuploidy in which a severe prognosis was expected, 85% of cases decided to terminate the pregnancy. When confronted with sex chromosome aneuploidy with a low risk of an abnormal clinical phenotype 60% of cases decided to continue the pregnancy. Among the diagnoses with aneuploidy, pregnancy was continued in 21.1% of cases due to religious beliefs regardless of whether there was a low or severe risk of an abnormal clinical phenotype. These findings indicate that both severity of abnormality and religiosity play an important role in genetic counseling patients' decision-making processes and outcomes in Turkey. In addition, the findings suggest the need for legislation that reduces the differences in approaches between the physicians and institutions regarding parental decision-making to terminate or continue a pregnancy in our country.


HapCUT: an efficient and accurate algorithm for the haplotype assembly problem.
The goal of the haplotype assembly problem is to reconstruct the two haplotypes (chromosomes) for an individual using a mix of sequenced fragments from the two chromosomes. This problem has been shown to be computationally intractable for various optimization criteria. Polynomial time algorithms have been proposed for restricted versions of the problem. In this article, we consider the haplotype assembly problem in the most general setting, i.e. fragments of any length and with an arbitrary number of gaps. We describe a novel combinatorial approach for the haplotype assembly problem based on computing max-cuts in certain graphs derived from the sequenced fragments. Levy et al. have sequenced the complete genome of a human individual and used a greedy heuristic to assemble the haplotypes for this individual. We have applied our method HapCUTto infer haplotypes from this data and demonstrate that the haplotypes inferred using HapCUT are significantly more accurate (20-25% lower maximum error correction scores for all chromosomes) than the greedy heuristic and a previously published method, Fast Hare. We also describe a maximum likelihood based estimator of the absolute accuracy of the sequence-based haplotypes using population haplotypes from the International HapMap project. A program implementing HapCUT is available on request.


Esophageal contraction pressures are not affected by normal menstrual cycles.
Previous studies of lower esophageal sphincter pressures during the menstrual cycle and pregnancy have suggested that the smooth muscle relaxing effect of progesterone depresses sphincter tone. Results, however, have been contradictory and limited to a small number of patients. We studied lower esophageal sphincter and distal peristaltic pressures during the follicular (days 2-8) and luteal (days 20-28) phases of the menstrual cycle. Twenty normal menstruating women (mean age 31 yr) not using oral contraceptives were evaluated. A low compliance pneumohydraulic infusion system was used for all studies. Lower esophageal sphincter pressure was determined by both rapid and station pull-through techniques. Distal peristaltic pressures were recorded 2 and 7 cm above the sphincter in response to 10 wet swallows (5 cc of H2O). Mean amplitude and duration in the distal esophagus were evaluated. Plasma progesterone and estrogen concentrations were obtained and correlated with changes in esophageal pressures. The results were as follows: (a) unlike prior investigations, we found the menstrual cycle had no effect on lower esophageal sphincter pressure and (b) likewise, no change in esophageal contractions in the distal esophagus was found during the cycle. We concluded that changes in female sex hormone concentrations that characterize the menstrual cycle are not associated with changes in parameters of esophageal motor function.


[Demographic aspects of a regional socioeconomic survey].
"The Demographic Data Base (DDB) automated information system is discussed in the article. The system was developed recently at the Department of Social Problems of the Institute for Economics and Organization of Industrial Production at the Siberian Department of the Academy of Sciences of the USSR. Shown are the basic operation modes for automated DDB, as well as the basic stages of the development," (SUMMARY IN ENG AND RUS)


Single Nucleotide Polymorphism in Patients with Moyamoya Disease.
Moyamoya disease (MMD) is a chronic, progressive, cerebrovascular occlusive disorder that displays various clinical features and results in cerebral infarct or hemorrhagic stroke. Specific genes associated with the disease have not yet been identified, making identification of at-risk patients difficult before clinical manifestation. Familial MMD is not uncommon, with as many as 15% of MMD patients having a family history of the disease, suggesting a genetic etiology. Studies of single nucleotide polymorphisms (SNPs) in MMD have mostly focused on mechanical stress on vessels, endothelium, and the relationship to atherosclerosis. In this review, we discuss SNPs studies targeting the genetic etiology of MMD. Genetic analyses in familial MMD and genome-wide association studies represent promising strategies for elucidating the pathophysiology of this condition. This review also discusses future research directions, not only to offer new insights into the origin of MMD, but also to enhance our understanding of the genetic aspects of MMD. There have been several SNP studies of MMD. Current SNP studies suggest a genetic contribution to MMD, but further reliable and replicable data are needed. A large cohort or family-based design would be important. Modern SNP studies of MMD depend on novel genetic, experimental, and database methods that will hopefully hasten the arrival of a consensus conclusion.


A possible mechanism in interaction of a partial agonist with beta-adrenoceptor in guinea-pig taenia caecum: effects of Gpp(NH)p on its two different binding sites.
The mechanisms of the actions of the beta-adrenergic partial agonist (befunolol) were studied in isolated guinea-pig taenia caecum. Befunolol, 2-acetyl-7-(2-hydroxy-3-isopropylaminopropoxy)benzofuran hydrochloride was found to be a typical partial agonist in guinea-pig taenia caecum. The pD2-value of befunolol was in agreement with its pKA-value obtained with photoaffinity labeling, but was different from its pA2-value against isoprenaline and pKI-value obtained from the inhibition of specific [3H]-dihydroalprenolol binding. The Scatchard plot of the specific [3H]-befunolol binding showed two affinity sites of the receptor in the absence of Gpp(NH)p, but the low affinity site was reduced while the high affinity site was not affected in the presence of Gpp(NH)p. The pKD-value of the high affinity site of befunolol was in agreement with its pA2-value, and the pKD-value of the low affinity site was in agreement with its pD2-value or pKA-value. These results suggest that the beta-adrenergic partial agonist may interact with two different sites: an agonist binding site and an antagonist binding site.


Nanopore formation and phosphatidylserine externalization in a phospholipid bilayer at high transmembrane potential.
Atomic-resolution molecular dynamics simulations of lipid bilayers containing 7% phosphatidylserine (PS) on one leaflet are consistent with experimental observations of membrane poration and PS externalization in living cells exposed to nanosecond, megavolt-per-meter electric pulses. Nanometer-diameter aqueous pores develop within nanoseconds after application of an electric field of 450 mV/nm, and electrophoretic transport of the anionic PS headgroup along the newly constructed hydrophilic pore surface commences even while pore formation is still in progress.


Space charge characteristics of an insulating thin film negatively charged by a low-energy electron beam.
In this study, based on a comprehensive numerical simulation of self-consistent charging, we investigate the formation, evolution and influencing factors of space charge distributions for a grounded insulating thin film of SiO(2) negatively charged by a keV non-penetrating focused electron beam. The simulated space charge presents first positive distributions and then negative ones along both the radial and depth directions because of the difference between electron and hole transports. The variations in distribution occur within a range of the minimum potential acting as a potential barrier for carrier transport. The negative space charge is distributed more widely and deeply, though its peak value in density is usually lower than that of the positive one. Electrons trapped outside the minimum potential range dominate the strength of negative charging. With the increase in potential barrier and the occurrence of leakage current, the space charge eventually reaches equilibrium and exhibits an approximately one-dimensional axial distribution outside the minimum potential range. Distribution features of the space charge density in the equilibrium state correlate with the film and beam parameters via transients of the leakage current. These results and analyses provide new insights into the negative charging effects involved in various electron-beam-based surface microscopic methods, analyses and fabrication techniques.


A model for linking networks in social work practice with the institutionalized elderly.
The authors describe a demonstration project that used network theory as a framework for a broad-range ecological approach to social work practice in long-term care facilities for the elderly. The importance of developing and maintaining social supports and the reciprocal benefits in linking kinship, friendship, formal caregiving, and mutual-aid networks are examined. Examples of the practical applications of network theory are presented also.


2D Bi2Se3 van der Waals Epitaxy on Mica for Optoelectronics Applications.
Bi2Se3 possesses a two-dimensional layered rhombohedral crystal structure, where the quintuple layers (QLs) are covalently bonded within the layers but weakly held together by van der Waals forces between the adjacent QLs. It is also pointed out that Bi2Se3 is a topological insulator, making it a promising candidate for a wide range of electronic and optoelectronic applications. In this study, we investigate the growth of high-quality Bi2Se3 thin films on mica by the molecular beam epitaxy technique. The films exhibited a layered structure and highly c-axis-preferred growth orientation with an XRD rocking curve full-width at half-maximum (FWHM) of 0.088°, clearly demonstrating excellent crystallinity for the Bi2Se3 deposited on the mica substrate. The growth mechanism was studied by using an interface model associated with the coincidence site lattice unit (CSLU) developed for van der Waals epitaxies. This high (001) texture favors electron transport in the material. Hall measurements revealed a mobility of 726 cm2/(Vs) at room temperature and up to 1469 cm2/(Vs) at 12 K. The results illustrate excellent electron mobility arising from the superior crystallinity of the films with significant implications for applications in conducting electrodes in optoelectronic devices on flexible substrates.


Laparoscopic versus open appendectomy: an analysis of outcomes in 17,199 patients using ACS/NSQIP.
The current study was undertaken to evaluate the outcomes for open and laparoscopic appendectomy using the 2008 American College of Surgeons: National Surgical Quality Improvement Program (ACS/NSQIP) Participant Use File (PUF). We hypothesized that laparoscopic appendectomy would have fewer infectious complications, superior perioperative outcomes, and decreased morbidity and mortality when compared to open appendectomy. Using the Current Procedural Technology (CPT) codes for open (44950) and laparoscopic (44970) appendectomy, 17, 199 patients were identified from the ACS/NSQIP PUF file that underwent appendectomy in 2008. Univariate analysis with chi-squared tests for categorical data and t tests or ANOVA tests for continuous data was used. Binary logistic regression models were used to evaluate outcomes for independent association by multivariable analysis. Of the patients, 3,025 underwent open appendectomy and 14,174 underwent laparoscopic appendectomy. Patients undergoing laparoscopic appendectomy had significantly shorter operative times and hospital length of stay. They also had a significantly lower incidence of superficial and deep surgical site infections, wound disruptions, fewer complications, and lower perioperative mortality when compared to patients undergoing open appendectomy. Using the ACS/NSQIP PUF file, we demonstrate that laparoscopic appendectomy has better outcomes than open appendectomy for the treatment of appendicitis. While the operative treatment of appendicitis is surgeon specific, this study lends support to the laparoscopic approach for patients requiring appendectomy.


Modification of cardiac subcellular remodeling due to pressure overload by captopril and losartan.
In view of the activation of renin-angiotensin system under conditions associated with pressure overload on the heart, we examined the effects of captopril, an angiotensin converting enzyme inhibitor, and losartan, an angiotensin II receptor antagonist, on cardiac function, myofibrillar ATPase and sarcoplasmic reticular (SR) Ca2+-pump (SERCA2) activities, as well as myosin and SERCA2 gene expression in hypertrophied hearts. Cardiac hypertrophy was induced in rats treated with or without captopril or losartan by banding the abdominal aorta for 8 weeks; sham operated animals served as control. Decrease in left ventricular developed pressure, +dP/dt and -dP/dt as well as increase in left ventricular end diastolic pressure and increased muscle mass due to pressure overload were prevented by captopril or losartan. Treatment of animals with captopril or losartan also attenuated the pressure overload-induced depression in myofibrillar Ca2+-stimulated ATPase, myosin ATPase, SR Ca2+-uptake and SR Ca2+-release activities. An increase in beta-myosin heavy chain mRNA and a decrease in alpha-myosin heavy chain mRNA as well as depressed SERCA2 protein and SERCA2 mRNA levels were prevented by captopril or losartan. These results suggest that both captopril and losartan improve myocardial function in cardiac hypertrophy by preventing changes in gene expression and subsequent subcellular remodeling due to pressure overload.


Levels of evidence for the outcome of endodontic retreatment.
The purpose of this investigation was 2-fold: (a) to complete a thorough search of published literature related to clinical studies on the success and failure of nonsurgical retreatment, and (b) to assign levels of evidence to these publications. Clinical studies related to success and failure of retreatment since 1970 were identified using both electronic and manual literature searches. After identification of pertinent literature, each article received a level of evidence (LOE) from one (high) to five (low). Thirty-one clinical studies and six review articles related to this subject were identified. There was no LOE 1 Randomized Control Trials (RCT). There were three LOE 2 RCTs, one LOE 2 Cohort, and two LOE 3 Case Control Studies. Thirteen Case Series (LOE 4), which comprise the most highly quoted success and failure data, were found. Twelve Case Reports (LOE 5) and six review articles (LOE 5) were found. Based on these findings, it appears that few high level studies have been published in the past 34 yr related to the success and failure of endodontic retreatment.


Heterogeneity within Corynebacterium minutissimum strains is explained by misidentified Corynebacterium amycolatum strains.
Forty-eight clinical strains that were tentatively identified as Corynebacterium minutissimum on the basis of standard biochemical reactions (Hollis-Weaver tables) as well as by the use of the API (RAPID) Coryne system were examined further. Two different groups of strains were observed. The first group (including the type strain of C minutissimum) contained 27 strains showing creamy colonies. These strains grew homogeneously in 6.5% NaCl broth, exhibited DNase activity, were susceptible to the vibriocidal compound O/129, produced succinic acid, and contained mycolic acids. The second group comprised 21 strains with dry colonies. They grew in clumps at the surface of 6.5% NaCl broth, DNase activity was not detected, they were resistant against O/129, produced large amounts of propionic acid, and mycolic acids were not detected. In combination with quantitative DNA-DNA hybridizations, it was demonstrated that strains of the second cluster belonged, in fact, to C amycolatum. Furthermore, it was observed that a few C minutissimum strains may also ferment mannitol. These data indicate that the clinical microbiologist must be careful not to misidentify C amycolatum strains as C minutissimum.


Mechanical Properties of Sprinting in Elite Rugby Union and Rugby League.
To compare mechanical properties of overground sprint running in elite rugby union and rugby league athletes. Thirty elite rugby code (15 rugby union and 15 rugby league) athletes participated in this cross-sectional analysis. Radar was used to measure maximal overground sprint performance over 20 or 30 m (forwards and backs, respectively). In addition to time at 2, 5, 10, 20, and 30 m, velocity-time signals were analyzed to derive external horizontal force-velocity relationships with a recently validated method. From this relationship, the maximal theoretical velocity, external relative and absolute horizontal force, horizontal power, and optimal horizontal force for peak power production were determined. While differences in maximal velocity were unclear between codes, rugby union backs produced moderately faster split times, with the most substantial differences occurring at 2 and 5 m (ES 0.95 and 0.86, respectively). In addition, rugby union backs produced moderately larger relative horizontal force, optimal force, and peak power capabilities than rugby league backs (ES 0.73-0.77). Rugby union forwards had a higher absolute force (ES 0.77) despite having ~12% more body weight than rugby league forwards. In this elite sample, rugby union athletes typically displayed greater short-distance sprint performance, which may be linked to an ability to generate high levels of horizontal force and power. The acceleration characteristics presented in this study could be a result of the individual movement and positional demands of each code.


E2F1-dependent miR-421 regulates mitochondrial fragmentation and myocardial infarction by targeting Pink1.
Mitochondrial fragmentation plays an important role in the progression of cardiac diseases, such as myocardial infarction and heart failure. Mitochondrial network is controlled by many factors in different cell types. Here we show that the interplay between E2F1, miR-421 and Pink1 regulates mitochondrial morphology and cardiomyocyte cell death. Pink1 reduces mitochondrial fragmentation and protects cardiomyocyte from apoptosis. On the other hand, miR-421 promotes cardiomyocyte mitochondrial fragmentation, apoptosis and myocardial infarction by suppressing Pink1 translation. Finally, we show that transcription factor E2F1 activates miR-421 expression. Knocking down E2F1 suppresses mitochondrial fragmentation, apoptosis and myocardial infarction by affecting miR-421 levels. Collectively, these data identify the E2F1/miR-421/Pink axis as a regulator of mitochondrial fragmentation and cardiomyocyte apoptosis, and suggest potential therapeutic targets in treatment of cardiac diseases.


Increase in Ceftriaxone Resistance and Widespread Extended-Spectrum β-Lactamases Genes Among Salmonella enterica from Human and Nonhuman Sources.
Salmonella producing β-lactamases has spread rapidly worldwide and poses a serious threat to human and animal health. In this study, we characterized 220 ceftriaxone (CRO)-resistant isolates identified among 3153 Salmonella from humans, animals, food, and water collected in Shanghai, China. They were assessed for antimicrobial susceptibility, phenotypic identification of extended-spectrum β-lactamases (ESBLs), and β-lactamase genes and integrons. CRO resistance in Salmonella increased from 5.0% in 2011 to 8.4% in 2013. Salmonella Enteritidis (45.5%), Salmonella Typhimurium (20.9%) from humans, and Salmonella Indiana (14.5%) from poultry represented the majority of the CRO-resistant isolates. Many isolates were also resistant to other antimicrobials, including nalidixic acid (84.5%), sulfisoxazole (70.5%), and tetracycline (61.8%). Resistance to ciprofloxacin was also found in 33.6% of the isolates. Most isolates (98.2%) were confirmed as ESBL producers. Resistance genes such as blaCTX-M, blaTEM, and blaOXA were detected in 207 (94.1%), 99 (45%), and 53 (24.1%) isolates, respectively. Three types of integron I and one type of integron II were identified in 13 (5.9%) and 2 (0.9%) isolates, respectively. The integrons encompassed 10 different genes: dfrA1/12/17/25, aadA1/2/5, sat2, orfF, and ybeA. Our study underscores concern for increasing CRO resistance, and highlights the widespread ESBL genes in Salmonella enterica.


Effect of auditory cortex lesions on NADPH-diaphorase staining in the inferior colliculus of rat.
Projections from the auditory cortex (AC) in the rat terminate in the dorsal cortex (DC) and in the external cortex (EC) of the inferior colliculus (IC), areas which exhibit a moderate number of nicotinamide-adenine dinucleotide phosphate-diaphorase (NADPH-d) positive neurons. NADPH-d co-localizes with nitric oxide synthase, which is responsible for the production of the transcellular messenger, nitric oxide. Changes in NADPH-d staining in the IC were found after unilateral lesions of the AC. Lesions resulted in a reduction in NADPH-d staining in neurons and neuropil within the ipsilateral DC and EC with the maximum reduction occurring 3-4 days after lesion. The reduction in NADPH-d staining in the contralateral IC was less pronounced. Lesions affecting auditory areas Te 1 and Te 3 produced the largest decrease in NADPH-d staining in neurons and neuropil. This finding may be related to the abolition of the influence of glutamatergic corticocollicular and commissural pathways.


[Arterial hypertension and pregnancy].
Hypertension is observed in 10 to 15% of pregnancies, but only 10% of affected women will suffer preeclampsia. The pathophysiology of preeclampsia is based on an early anomaly of placental implantation, leading to a cascade of events (secretion of vasopressive prostaglandins, anomalies of hemostatis) which can cause disseminated intravascular coagulation. The diagnosis of preeclampsia is based on hypertension and significant proteinuria (above 0.5 g/24 h), and paraclinical maternal and fetal examinations to follow the evolution and detect the appearance of maternal complications (retroplacental haematoma, Hellp syndrome and eclampsia) and (or) fetal complications (delayed growth, in utero fetal death, perinatal death). The aim of hypertensive treatment is to normalise blood pressure and to avoid maternal complications. Preventive treatment with aspirin reduces the frequency of recurrent preeclampsia and delayed growth of the fetus.


Correlation of DEFA1 gene copy number variation with intestinal involvement in Behcet's disease.
Copy number variation has been associated with various autoimmune diseases. We investigated the copy number (CN) of the DEFA1 gene encoding α-defensin-1 in samples from Korean individuals with Behcet's disease (BD) compared to healthy controls (HC). We recruited 55 BD patients and 35 HC. A duplex Taqman® real-time PCR assay was used to assess CN. Most samples (31.1%) had a CN of 5 with a mean CN of 5.4 ± 0.2. There was no significant difference in the CN of the DEFA1 gene between BD patients and HC. A high DEFA1 gene CN was significantly associated with intestinal involvement in BD patients. Variable DEFA1 gene CNs were observed in both BD patients and HC and a high DEFA1 gene CN may be associated with susceptibility to intestinal involvement in BD.


Sunscreens. Update and review.
The awareness of sun-induced skin damage has increased in both the lay public and physician. Coincidentally, there has been progress in the development of new ultraviolet-(UV) radiation protecting sunscreens. In this review and update on sunscreens, sunscreen classification, UVB and UVA protection, sunscreen vehicle, and substantivity will be addressed.


PARENTAL DEATH IN THE LIVES OF PEOPLE WITH SERIOUS MENTAL ILLNESS.
Nearly a fourth (22%) of the participants within a research sample of 148 individuals with serious mental illness reported the death of a loved one as a significant loss, and two thirds of these deaths involved the loss of one or both parents. The key determinant of the severity and duration of grief in response to the death of a parent was whether or not there were extenuating circumstances that complicated the death event, such as co-residence with the deceased at the time of death or a lack of regular social contact with anyone other than the deceased. In all instances of severe or prolonged grief, there was no preparation for the parental death, either through preparatory counseling or practical plans for funeral arrangements, financial repercussions, life-style changes, or residential relocation. Mental health agencies serving people with serious mental illness should begin to incorporate financial and emotional preparation for parental deaths and bereavement counseling as essential services.


Common forms of dementia.
Dementia occurs in various forms and may be associated with other conditions (secondary dementias). Each type has a different impact on the brain, leading to a variety of cognitive losses and behaviour problems. Appropriate identification is vital so that the most suitable treatment can be instigated.


Adsorption of Cu(II), Co(II), and Ni(II) ions by modified magnetic chitosan chelating resin.
Cross-linked magnetic chitosan-isatin Schiff's base resin (CSIS) was prepared for adsorption of metal ions. CSIS obtained was investigated by means of FTIR, (1)H NMR, wide-angle X-ray diffraction (WAXRD), magnetic properties and thermogravimetric analysis (TGA). The adsorption properties of cross-linked magnetic CSIS resin toward Cu(2+), Co(2+) and Ni(2+) ions were evaluated. Various factors affecting the uptake behavior such as contact time, temperature, pH and initial concentration of the metal ions were investigated. The kinetic parameters were evaluated utilizing the pseudo-first-order and pseudo-second-order. The equilibrium data were analyzed using the Langmuir, Freundlich, and Tempkin isotherm models. The adsorption kinetics followed the mechanism of the pseudo-second-order equation for all systems studied, evidencing chemical sorption as the rate-limiting step of adsorption mechanism and not involving a mass transfer in solution. The best interpretation for the equilibrium data was given by Langmuir isotherm, and the maximum adsorption capacities were 103.16, 53.51, and 40.15mg/g for Cu(2+), Co(2+) and Ni(2+) ions, respectively. Cross-linked magnetic CSIS displayed higher adsorption capacity for Cu(2+) in all pH ranges studied. The adsorption capacity of the metal ions decreased with increasing temperature. The metal ion-loaded cross-linked magnetic CSIS were regenerated with an efficiency of greater than 88% using 0.01-0.1M ethylendiamine tetraacetic acid (EDTA).


Influence of Caretakers' Health Literacy on Delays to Traumatic Brain Injury Care in Uganda.
Traumatic brain injury (TBI) is a life-altering condition, and delays to care can significantly impact outcomes. In Uganda, where nurse shortages are prevalent, patients' family members are the primary caretakers of these patients and play an important role in ensuring patients' access to timely care. However, caretakers often have little or no knowledge of appropriate patient care. Caretakers' ability to navigate the healthcare system and find and use health information to support their patients can impact delays in seeking, reaching, and receiving care. This study seeks to determine the factors that impact TBI patient caretakers' health literacy and examine how these factors influence delays in care. This study was carried out in the Mulago National Referral Hospital neurosurgical ward, where 27 adult caretakers were interviewed using semi-structured, in-depth, qualitative interviews. "The Three Delay Framework" was utilized to understand participants' experiences in seeking, reaching, and receiving care for TBI patients. Thematic content analysis and manual coding was used to analyze interview transcripts and identify overarching themes in participant responses. The main health literacy themes identified were Extrinsic, Intrinsic and Health System Factors. Nine sub-themes were identified: Government Support, Community Support, Financial Burdens, Lack of Medical Resources, Access to Health Information, Physician Support, Emotional Challenges, Navigational Skills, and Understanding of Health Information. These components were found to influence the delays to care to varying degrees. Financial Burdens, Government Support, Emotional Challenges, Physician Support and Lack of Medical Resources were recurring factors across the three delays. The health literacy factors identified in this study influence caretakers' functional health literacy and delays to care in a co-dependent manner. A better understanding of how these factors impact patient outcomes is necessary for the development of interventions targeted at improving a caretaker's ability to maneuver the healthcare system and support patients in resource-poor settings.


[Effects of nitrogen supplementation on forage yield and quality of a degraded grassland in Hulunbuir, China.]
Long-term overuse of grasslands results in quantitative and qualitative decline of forage yield. Nutrient supplementation is a key strategy to improve forage yield. While mounting evidence showed that nitrogen (N) supplementation can increase forage yield, little is known about its impacts on forage quality. To understand the effects of N supplementation on forage quality at the community level, we carried out a field experiment in the meadow steppe of Hulunbuir. Our results showed that N supplementation significantly increased forage yield by 23%, which was mainly due to positive responses of perennial rhizomatous grass. The yield of other plant functional groups showed neutral response to N supplementation. The concentrations of crude protein, crude fat, and crude fiber varied significantly among different plant functional groups. Nitrogen supplementation significantly enhanced the concentration of crude protein in rhizomatous grass, bunchgrass, legume, and sedge. It enhanced the content of crude fat in rhizomatous grass but with no effect on other functional groups. Nitrogen supplementation had no effect on the concentration of crude fibre in all functional groups. At the community level, N supplementation significantly increased the concentrations of crude protein and crude fat. Our results are important for understanding the responses of forage production in meadow steppe under the scenarios of N enrichment.


The organic mercury compounds, methylmercury and ethylmercury, inhibited ciliary movement of ventricular ependymal cells in the mouse brain around the concentrations reported for human poisoning.
Functions of the nervous system are supported by the flow of cerebrospinal fluid (CSF), which is driven by the ciliary beating of ventricular ependymal cells. The aim of the present study was to examine whether methylmercury (MeHg), a substance with potent neurotoxicity in humans, affects the ciliary movement. The effects of another organic mercury compound, ethylmercury (EtHg), were also assessed for comparison. Toxicity of MeHg or EtHg was evaluated by measuring alterations in the ciliary beat frequency of ependymal cells lining the third ventricle of mouse brain slices. The obtained results were: (1) Both MeHg and EtHg started to inhibit ciliary motility between 1 and 3μM, the reported threshold limit of MeHg in humans. (2) An abrupt increase was observed in the inhibitory curves from 3 to 6μM for MeHg and EtHg. (3) The "give-in" concentration, i.e., concentration at which the cilia lose the ability to recover, for MeHg and EtHg was 6μM and 12μM, respectively. (4) Ciliary beating was irreversibly halted by MeHg and EtHg at concentrations above 12μM and 30μM, respectively. (5) The estimated half-maximal inhibitory concentration (IC50) for MeHg and EtHg was 5.53μM and 5.80μM, respectively. Based on these findings, we conclude that: (a) Ependymal cell cilia movement in mice was inhibited by MeHg in a concentration-dependent manner around concentrations reported to cause poisoning in humans; EtHg inhibited ciliary motility to a less extent. (b) Inhibition of CSF flow by suppression of ciliary movement is suggested to be an additional route for MeHg poisoning in humans, especially in prenatal exposure than in adult exposure.


[Levels of T-Lymphocyte Subsets, IL-17, IL-35 and IFN-γ in Peripheral Blood and Their Clinical Significance in Patients with Multiple Myeloma].
To explore the levels of T-lymphocyte subsets and IL-17, IL-35, IFN-γ in peripheral blood of patients with multiple myeloma(MM) and their clinical significance. A total of 86 MM patients in our hospital from January 2014 to January 2017 were enrolled in MM group and 30 healthy persons were enrolled in control group, the CD4+/CD8+ T cells ratio, CD4+CD25high/+ CD127low/- Treg level in peripheral blood were detected by flow cytometer. The levels of IL-17, IL-35 and IFN-γ in peripheral serum were detected by ELISA, and the differences of detected indicators between different groups were compared. Compared with control group, the proportion of CD4+ T cells and CD4+/CD8+ T cells ratio decreased, the proportion of CD8+ T cells and Treg increased in MM group. The differences of T lymphocyte subsets level between group III stage of MM and control group were statistically significant (P<0.05). With enhancing of clinical stages, Treg level showed a increasing trend, especially in III stage (P<0.05), the serum level of IL-17 as followed in turn: III stage>II stage>I stage>control, the serum level of IL-35 and IFN-γ as followed in turn: control>I stage>II stage>III stage (P<0.05). In terms of disease status, the propurtion of Treg cells as fllowed in turn: disease progression stage>stable stage>control (P<0.05), the serum level of IL-17 as followed in turn also: disease progression stage>stable stage (P<0.05), while the serum level of IL-35 and IFN-γ as followed in turn: control>disease table stage>progression stage (P<0.05). The abnomal level of T-lymphocyte subsets, Treg, IL-17, IL-35 and IFN-γ are related with progression and prognosis of MM patients.


Iron-based layered superconductor: LaOFeP.
We report superconductivity in an iron-based layered oxy-pnictide LaOFeP. LaOFeP is composed of an alternate stack of lanthanum oxide (La3+O2-) and iron pnictide (Fe2+P3-) layers. Magnetic and electrical resistivity measurements verify the occurrence of the superconducting transition at approximately 4 K.


Severe thrombophilic diathesis starting with hepatic vein thrombosis (BUDD-CHIARI syndrome) in a family with a new Protein S gene mutation.
We report the case of a 26-year-old man with a chronic Budd-Chiari syndrome with ascites, caused by a hereditary Protein S deficiency, in a Turkish family with consanguinity. In this family, the father, the two sisters and the young brother suffered from severe venous thrombosis of the limbs, with pulmonary embolism in two of them. Those thrombotic events are caused by a hitherto not reported mutation in the PROS 1 gene on chromosome 3, resulting in a severe familial Protein S deficiency. No other thrombophilic defect was detected in the family, despite extensive investigation. Furthermore, we observe hereditary twenty-nail dystrophy in this family, the two genes probably segregating independently. Prophylaxis is discussed.


Effect of alsD deletion and overexpression of nox and alsS on diacetyl and acetoin production by Lacticaseibacillus casei during milk fermentation.
Diacetyl and acetoin are key aroma components of fermented milk but are produced in low concentrations by starter cultures. In this study, we expressed NADH oxidase, acetolactate synthase, and inactivated acetolactate decarboxylase in Lacticaseibacillus casei TCS to generate recombinant L. casei strains, and investigated the effects of the genes encoding these enzymes on diacetyl and acetoin production during milk fermentation. In the single-gene recombinant strains tested, diacetyl concentrations were highest in milk fermented by L. casei TCSI-nox (nox gene overexpressed, 3.68 mg/kg), whereas acetoin concentrations were highest in milk fermented by L. casei TCS-ΔalsD (alsD gene deleted, 32.94 mg/kg). Moreover, diacetyl and acetoin concentrations were higher in the inducible strains than in the corresponding constitutive strains (e.g., TCSI-nox vs. TCSC-nox, and TCSI-ΔalsD-nox vs. TCSC-ΔalsD-nox). This phenomenon was also reflected in the protein expression levels and enzyme activities. In the double-gene recombinant strains tested, the highest concentrations of diacetyl and acetoin were produced by L. casei TCSI-ΔalsD-nox (nox overexpressed and alsD deleted, 4.66 mg/kg, 69.62 mg/kg, respectively). The triple-gene recombinant L. casei TCS-ΔalsD-nox-alsS produced the highest concentrations of diacetyl and acetoin, which were 2.38 and 11.19 times, respectively, the concentrations produced by the original strain. These results show that the nox, alsS, and alsD genes make key contributions to the biosynthesis of diacetyl and acetoin by L. casei. The modification of multiple genes had a synergistic effect, leading to greatly increased synthesis of diacetyl and acetoin by L. casei during its fermentation of milk.


X-prolyl dipeptidyl aminopeptidase gene (pepX) is part of the glnRA operon in Lactobacillus rhamnosus.
A peptidase gene expressing X-prolyl dipeptidyl aminopeptidase (PepX) activity was cloned from Lactobacillus rhamnosus 1/6 by using the chromogenic substrate L-glycyl-L-prolyl-beta-naphthylamide for screening of a genomic library in Escherichia coli. The nucleotide sequence of a 3.5-kb HindIII fragment expressing the peptidase activity revealed one complete open reading frame (ORF) of 2,391 nucleotides. The 797-amino-acid protein encoded by this ORF was shown to be 40, 39, and 36% identical with PepXs from Lactobacillus helveticus, Lactobacillus delbrueckii, and Lactococcus lactis, respectively. By Northern analysis with a pepX-specific probe, transcripts of 4.5 and 7.0 kb were detected, indicating that pepX is part of a polycistronic operon in L. rhamnosus. Cloning and sequencing of the upstream region of pepX revealed the presence of two ORFs of 360 and 1,338 bp that were shown to be able to encode proteins with high homology to GlnR and GlnA proteins, respectively. By multiple primer extension analyses, the only functional promoter in the pepX region was located 25 nucleotides upstream of glnR. Northern analysis with glnA- and pepX-specific probes indicated that transcription from glnR promoter results in a 2.0-kb dicistronic glnR-glnA transcript and also in a longer read-through polycistronic transcript of 7.0 kb that was detected with both probes in samples from cells in exponential growth phase. The glnA gene was disrupted by a single-crossover recombinant event using a nonreplicative plasmid carrying an internal part of glnA. In the disruption mutant, glnRA-specific transcription was derepressed 10-fold compared to the wild type, but the 7.0-kb transcript was no longer detectable with either the glnA- or pepX-specific probe, demonstrating that pepX is indeed part of glnRA operon in L. rhamnosus. Reverse transcription-PCR analysis further supported this operon structure. An extended stem-loop structure was identified immediately upstream of pepX in the glnA-pepX intergenic region, a sequence that showed homology to a 23S-5S intergenic spacer and to several other L. rhamnosus-related entries in data banks.


Development and application of ab initio QM/MM methods for mechanistic simulation of reactions in solution and in enzymes.
Determining the free energies and mechanisms of chemical reactions in solution and enzymes is a major challenge. For such complex reaction processes, combined quantum mechanics/molecular mechanics (QM/MM) method is the most effective simulation method to provide an accurate and efficient theoretical description of the molecular system. The computational costs of ab initio QM methods, however, have limited the application of ab initio QM/MM methods. Recent advances in ab initio QM/MM methods allowed the accurate simulation of the free energies for reactions in solution and in enzymes and thus paved the way for broader application of the ab initio QM/MM methods. We review here the theoretical developments and applications of the ab initio QM/MM methods, focusing on the determination of reaction path and the free energies of the reaction processes in solution and enzymes.


A complicated multisystem flare of systemic lupus erythematosus during pregnancy.
We report a case of systemic lupus erythematosus (SLE) in a young woman who became pregnant amid a severe flare. She continued to have active disease in the face of aggressive treatments complicated by several side effects of immunosuppressive drugs including recurrent sepsis and gestational diabetes. Her fetus was at risk for congenital heart block during the second and third trimesters. Despite an extremely guarded prognosis, she delivered a healthy baby girl. This case highlights the complexities of SLE management during pregnancy. We discuss the therapeutic options available in pregnancy, and highlight the importance of cross-specialty multidisciplinary care in these women.