Forty-year psychiatric outcomes following assessment for internalizing disorder in adolescence.
The aim of this study was to define the long-term psychiatric outcomes of adolescent internalizing disorder in the general population, using data collected over 40 years from a national birth cohort. A total of 3,279 members of the Medical Research Council National Survey of Health and Development (the 1946 British birth cohort) underwent assessments of psychiatric symptoms, primarily anxiety and depression, at ages 13 and 15. Adolescents who had internalizing disorder at both ages 13 and 15 and those who had internalizing disorder at one of the two ages were compared with mentally healthy adolescents on various psychiatric outcomes in adulthood (ages 26-53), including the prevalence of mental disorders, self-reported trouble with "nerves," suicidal ideation, and treatment for psychiatric disorders. About 70% of adolescents who had internalizing disorder at both ages 13 and 15 had mental disorder at age 36, 43, or 53, compared with about 25% of the mentally healthy adolescents. They were also more likely than healthy adolescents to have self-reported "nervous trouble" and to have been treated for psychiatric disorder during adulthood. None of these effects was apparent among subjects who had internalizing disorder at only one of the two adolescent assessments. The long-term psychiatric outcome for adolescents with persistent or recurrent internalizing disorder was poor, whereas the outcome for those who had a single episode was better than expected. The association between adolescent internalizing disorder and poor psychiatric outcomes in adulthood may be mediated by persistence or severity of symptoms in adolescence.


Mutation of rpiA in Enterobacter cloacae decreases seed and root colonization and biocontrol of damping-off caused by Pythium ultimum on cucumber.
Strains of Enterobacter cloacae show promise as biocontrol agents for Pythium ultimum-induced damping-off on cucumber and other crops. E. cloacae A145 is a mini-Tn5 Km transposon mutant of strain 501R3 that was significantly reduced in suppression of damping-off on cucumber caused by P. ultimum. Strain A145 was deficient in colonization of cucumber, sunflower, and wheat seeds and significantly reduced in colonization of corn and cowpea seeds relative to strain 501R3. Populations of strain A145 were also significantly lower than those of strain 501R3 at all sampling times in cucumber, wheat, and sunflower rhizosphere. Populations of strain A145 were not detectable in any rhizosphere after 42 days, while populations of strain 501R3 remained at substantial levels throughout all experiments. Molecular characterization of strain A145 indicated mini-Tn5 Km was inserted in a region of the E. cloacae genome with a high degree of DNA and amino acid sequence similarity to rpiA, which encodes ribose-5-phosphate isomerase. In Escherichia coli, RpiA catalyzes the interconversion of ribose-5-phosphate and ribulose-5-phosphate and is a key enzyme in the pentose phosphate pathway. Ribose-5-phosphate isomerase activity in cell lysates from strain A145 was approximately 3.5% of that from strain 501R3. In addition, strain A145 was a ribose auxotroph, as expected for an rpiA mutant. Introduction of a 1.0-kb DNA fragment containing only the rpiA homologue into strain A145 restored ribose phosphate isomerase activity, prototrophy, seedling colonization, and disease suppression to levels similar to those associated with strain 501R3. Experiments reported here indicate a key role for rpiA and possibly the pentose phosphate pathway in suppression of damping-off and colonization of subterranean portions of plants by E. cloacae.


Determining the Clinical Value of Routine Post Operative follow up in Common Paediatric Surgical Conditions: A Prospective Observational Study.
The traditional postoperative visit consists of an in-person hospital visit at a predetermined date which requires the investment of time and resources. This implies a need to prioritize visits rather than mandating them, which can be assessed by the requirement of clinical intervention at the time of follow-up. The purpose of this study is to determine the clinical value of routine postoperative physical follow-up in common pediatric surgery conditions, to identify factors determining follow-up, and to estimate the cost of routine follow-up. Surgical data of 226 patients admitted for routine pediatric surgical procedures were collected. The postoperative period was documented in detail and interventions done either physically or telephonically at the time of follow-up were used as a proxy measure of clinical value. There were 226 patients enrolled, of which 64.60% followed up physically in outpatient department and 35.40% followed up telephonically. Maximum percentage of patients with postoperative complications belonged to the group of laparotomy at 22.22%, followed by complicated appendicitis at 15.62%. 13.27% of patients required clinical intervention at the time of follow-up. Patients undergoing simpler procedures such as inguinal hernia, hydrocele, and orchidopexy have lesser rate of complications which translates to requirement of fewer clinic visits, whereas those undergoing procedures such as appendectomy and laparotomy require a physical visit after discharge since they are more susceptible to develop complications requiring interventions. By selecting patients for physical visit, we can potentially eliminate unnecessary visits in patients who have low chance of developing complications.


[Importance of an Aldehyde Dehydrogenase 2 Polymorphism in Preventive Medicine].
Unlike genetic alterations in other aldehyde dehydrogenase (ALDH) isozymes, a defective ALDH2 polymorphism (rs671), which is carried by almost half of East Asians, does not show a clear phenotype such as a shortened life span. However, impacts of a defective ALDH2 allele, ALDH2*2, on various disease risks have been reported. As ALDH2 is responsible for the detoxification of endogenous aldehydes, a negative effect of this polymorphism is predicted, but bidirectional effects have been actually observed and the mechanisms underlying such influences are often complex. One reason for this complexity may be the existence of compensatory aldehyde detoxification systems and the secondary effects of these systems. There are many issues to be addressed with regard to the ALDH2 polymorphism in the field of preventive medicine, including the following concerns. First, ALDH2 in the fetal stage plays a role in aldehyde detoxification; therefore, prenatal health effects of environmental aldehyde exposure are of concern for ALDH2*2-carrying fetuses. Second, ALDH2*2 carriers are at high risk of drinking-related cancers. However, their drinking habits result in less worsening of physiological findings, such as energy metabolism index and liver functions, compared with non-ALDH2*2 carriers, and therefore opportunities to detect excessive drinking can be lost. Third, personalized medicine such as personalized prescriptions for ALDH2*2 carriers will be required in the clinical setting, and accumulation of evidence is awaited. Lastly, since the ALDH2 polymorphism is not considered in workers' limits of exposure to aldehydes and their precursors, efforts to lower exposure levels beyond legal standards are required.


[Exposition of the operator's eye lens and efficacy of radiation shielding in fluoroscopically guided interventions].
Efficacy of radiation protection tools for the eye lens dose of the radiologist in fluoroscopic interventions. A patient phantom was exposed using a fluoroscopic system. Dose measurements were made at the eye location of the radiologist using an ionization chamber. The setting followed typical fluoroscopic interventions. The reduction of scattered radiation by the equipment-mounted shielding (undercouch drapes and overcouch top) was evaluated. The ceiling-suspended lead acrylic glass screen was tested in scattered radiation generated by a slab phantom. The protective properties of different lead glass goggles and lead acrylic visors were evaluated by thermoluminescence measurements on a head phantom in the primary beam. The exposition of the lens of about 110 to 550 μSv during radiologic interventions is only slightly reduced by the undercouch drapes. Applying the top in addition to the drapes reduces the lens dose by a factor of 2 for PA projections. In 25°LAO the dose is reduced by a factor between 1.2 and 5. The highest doses were measured for AP angulations furthermore the efficacy of the equipment-mounted shielding is minimal. The ceiling-suspended lead screen reduced scatter by a factor of about 30. The lead glass goggles and visors reduced the lens dose up to a factor of 8 to 10. Depending on the specific design, the tested models are less effective especially for radiation from lateral with cranial angulation of the beam. Occasionally the visors even caused an increase of dose. The exposition of the eye lens can be kept below the new occupational limit recommended by the ICRP if the radiation shielding equipment is used consistently.


Primary causes of neonatal deaths in a tertiary care hospital in Delhi: an autopsy study of 331 cases.
Of a total of 755 neonates who died between 1972 and 1988, 331 (43.9%) were subjected to necropsy examination. The ranking of major primary causes of neonatal death was as follows: infections 27.2%, hyaline membrane disease 20.2%, congenital malformations 19.6%, perinatal anoxia 14.5%, immaturity 5.1% and birth trauma 2.7%. Over the years, the prevalence of infections as the cause of death has consistently declined. Compared with that in other contemporary Indian studies, the prevalence of hyaline membrane disease is higher and that of infections and perinatal anoxia relatively lower.


Plasminogen activator and prostaglandin E2 levels in human synovial fibroblasts. Differential stimulation by synovial activator and other cytokines.
Interaction between cells of the immune system and of the synovial tissue may be contributing to the pathogenesis of rheumatoid arthritis. Cytokines, produced by PBMC, were tested for their effects on plasminogen activator activity and PGE2 levels of a number of human synovial fibroblast-like cell lines. Evidence was obtained for a human monocyte polypeptide, synovial activator, which can stimulate synovial cell plasminogen activator activity but not PGE2 levels. Purified human rIL-1 alpha and IL-1 beta increased the levels of both products in the supernatants of the synovial cells; TNF-alpha raised the PGE2 levels but raised the plasminogen activator activity only weakly and inconsistently. Synovial activator was further distinguished from IL-1 alpha and IL-1 beta (and TNF-alpha) on biochemical, immunologic, and functional criteria. No other purified native or recombinant human cytokine tested was active on the synovial cells when judged by the criteria in question. Synovial activator could therefore be a novel monokine. The differences in the type of response elicited by the various cytokines in the synovial fibroblast-like cells could have implications for the understanding of the cellular interactions occurring in rheumatoid lesions.


Ionic polymer-metal composite actuators obtained from radiation-grafted cation- and anion-exchange membranes.
Two series of ionic polymer-metal composites (IPMCs), one cationic and one anionic, are designed and prepared from radiation-grafted ion-exchange membranes. Through examination of the properties of the membranes synthesized from the two grafting monomers and the two base polymers, acrylic acid-grafted poly(vinylidene fluoride-co-hexafluoropropylene) and quarternized 4-vinylpyridine-grafted poly(ethylene-co-tetrafluoroethylene) with the appropriate amount of ionic groups are employed for the fabrication of cation and anion IPMCs, respectively. The bending displacement of the cation IPMC is comparable to Nafion-based IPMC under direct- and alternating-current voltage, but back-relaxation is not observed. The actuation performance of the anion IPMC is highly improved over those reported earlier in the literature for the other anion IPMCs.


Lack of association between MTHFR A1298C variant and Alzheimer's disease: evidence from a systematic review and cumulative meta-analysis.
Previous studies have investigated the association between MTHFR A1298C (rs1801131) polymorphism and susceptibility to Alzheimer's disease (AD). Nevertheless, an ultimate conclusion remains obscure. We then executed this meta-analysis to estimate this association more precisely. Related studies were systematically searched on PubMed, Embase, China National Knowledge Infrastructure, Google scholar, and AlzGene databases. The association was evaluated by reviewing the odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Publication bias, sensitivity analysis, and cumulative meta-analysis were performed to help draw a more definite conclusion. Ten eligible studies were finally enrolled in this meta-analysis. Lack of association between MTHFR A1298C polymorphism and AD risk was observed in five genetic models (allelic: OR = 1.17, 95% CI: 0.88-1.56; homozygous: OR = 1.15, 95% CI: 0.87-1.53; heterozygous: OR = 1.19, 95% CI: 0.76-1.86; dominant: OR = 1.23, 95% CI: 0.81-1.87; recessive: OR = 1.16, 95% CI: 0.89-1.52). The result of cumulative meta-analysis sorted by publication year was also detected a dynamic tendency of no correlation between MTHFR A1298C polymorphism and AD. This meta-analysis reveals that MTHFR A1298C polymorphism may not be associated with AD risk.


Smoking cessation interventions and older adults.
Older adults suffer a large proportion of the health consequences from smoking and can greatly benefit their health by quitting smoking. This article examines the current state of research and practice for older adults and smoking cessation interventions. For over 17 years, the health care literature has mandated that people of all ages be provided with smoking cessation interventions. However, smoking cessation interventions are offered to older adults at suboptimal rates. Nurses, especially those caring for clients in the inpatient setting, have an opportunity to provide smoking cessation interventions to older smokers. Recent research has shown that older smokers, particularly those hospitalized with cardiovascular disease, can quit at high rates when provided an intervention. Furthermore, use of nicotine replacement therapy has been shown to be safe and efficacious among older smokers with cardiovascular disease.


Otocephaly Complex: Case Report, Literature Review, and Ethical Considerations.
Otocephaly complex is a rare and usually lethal syndrome characterized by a set of malformations consisting of microstomia, mandibular hypoplasia/agnathia, and ventromedial malposition of the ears. Those cases that have been diagnosed prenatally have used an ex utero intrapartum treatment procedure to establish a definitive airway. However, prenatal diagnosis continues to be challenging, primarily because of poor diagnostic sensitivity associated with ultrasonography. We present a case of a newborn with an unanticipated otocephaly complex requiring emergent airway management. In this report, we discuss the medical and ethical issues related to the care of a newborn with this frequently fatal condition.


Emerging treatment strategies for adrenocortical carcinoma: a new hope.
Adrenocortical carcinoma (ACC) is a rare cancer but one that has devastating consequences for affected patients. Surgery is the mainstay of therapy, although the high frequency of metastatic disease implies that it is frequently noncurative. Traditional cytotoxic chemotherapy for ACC has generally produced disappointing responses, implying the need for the new therapies for this disease. Review articles and primary literature were identified by extensive PubMed searching to obtain papers evaluating the current state of knowledge regarding ACC, as well as assessing the development of new therapeutic modalities for the treatment of cancer. When needed, additional articles were identified from the reference lists of the papers obtained from the primary screen. Multiple new modalities that may enhance the future treatment of ACC were identified. They include the following: combating drug resistance, targeting tumor vasculature, inhibiting signaling pathways with small molecules, and using gene and/or immunotherapy. This review provides a brief summary of the progress and prospects of each of these modalities and focuses on emerging data and treatments that may alter the course of this disease within the next few years. Despite the current grim outlook, the recent applications of emerging technology to the study of ACC and the development of newer, "targeted" therapies for cancer suggest the possibility of a new hope for patients with this disease, although these therapies will need to be evaluated by rigorous clinical trials to verify their effectiveness.


Disentangling the effects of trait and state worry on error-related brain activity: Results from a randomized controlled trial using worry manipulations.
Enhanced amplitudes of the error-related negativity (ERN) have been suggested to be a transdiagnostic neural risk marker for internalizing psychopathology. Previous studies propose worry to be an underlying mechanism driving the association between enhanced ERN and anxiety. The present preregistered study focused on disentangling possible effects of trait and state worry on the ERN by utilizing a cross sectional observational and a longitudinal randomized controlled experimental design. To this end, we examined the ERN of n = 90 students during a flanker task (T0), which were then randomly assigned to one of three groups (worry induction, worry reduction, passive control group). Following the intervention, participants performed another flanker task (T1) to determine potential alterations of their ERN. Manipulation checks revealed that compared to the control group, state worry increased in the induction but also in the reduction group. ERN amplitudes did not vary as a function of state worry. An association of trait worry with larger ERN amplitudes was only observed in females. Furthermore, we found larger ERN amplitudes in participants with a current or lifetime diagnosis of internalizing disorders. In summary, our findings suggest that the ERN seems to be insensitive to variations in state worry, but that an elevated ERN is associated with the trait-like tendency to worry and internalizing psychopathology, which is consistent with the notion that the ERN likely represents a trait-like neural risk associated with anxiety.


[Coronary bypass with arteries].
The internal mammary artery (IMA) and the right gastroepiploic artery are increasingly used for myocardial revascularization. The postoperative results are much better than those of the saphenous vein regarding mortality, patency rate, and relief of symptoms. The IMA can be used as an in-situ-graft or as a free transplant, either as a single graft or using sequential anastomoses. Ten years postoperative 90% of the IMA-bypasses are patent and risk of reoperation is significantly lower in patients with IMA-grafts. From August 10, 1989 until January 31, 1991, 1515 patients were operated for coronary artery disease in our center. There were 1219 men and 296 woman with a mean age of 58.9 years (26-83 years). In 1050 patients (69.3%), either one or both IMA-arteries were used. 75% of the men and 47.7% of the women received an IMA-graft. 981 patients had an in-situ-graft, and in 69 patients the IMA was used as a free transplant. In 74 cases both IMAs were used. In 315 patients sequential anastomoses with one IMA and several coronary arteries were performed. According to our experience, the IMA is an ideal bypass conduit and should be used predominantly.


A new approach for endoscopic neurolysis of the suprascapular nerve at the spinoglenoid notch: A preliminary cadaver study.
The suprascapular nerve (SSN) can become compressed at its 2 scapular attachments: the suprascapular and the spinoglenoid notch. The objective of this study was to describe a new arthroscopic approach for SSN neurolysis at the spinoglenoid notch. Ten cadaver shoulders were used. Two were dissected to simulate the "classical" arthroscopic approach and to help in the creation of a new "direct medial retrospinal" approach. Eight other shoulders were used to validate this new approach, with control of the whole juxta-glenoid course of the SSN as criterion of success. The retrospinal posterior approach allowed the entire juxta-glenoid segment of the SSN to be explored in 6 cases out of 8. One exploration was incomplete, another not feasible. SSN neurolysis at the spinoglenoid notch was feasible in cadavers on a retrospinal approach.


Pharmacokinetics of aminoglycoside antibiotics in blood, inner-ear fluids and tissues and their relationship to ototoxicity.
This review critically evaluates the literature on aminoglycoside pharmacokinetics in order to answer the question how fluid and tissue levels of the drugs relate to the development of ototoxic and nephrotoxic side effects. We will summarize the evidence that: (1) aminoglycosides do not accumulate in inner-ear fluids; (2) aminoglycoside levels in fluids do not correlate with the ototoxic potential of a drug, and (3) selective toxicity cannot be explained by selective tissue penetration of the drugs. We suggest that studies of drug disposition at the cellular level after chronic aminoglycoside treatment be conducted to establish whether a cell-specific uptake contributes to the selective toxicity of the aminoglycoside antibiotics. A sequence of biochemical events that may lead to the development of toxicity at the molecular level is briefly described.


[A prospective and randomized study of the complete response, index of recurrences and progression in superficial bladder carcinoma treated with mitomycin C alone versus mitomycin C and BCG alternatively].
The results of a comparative randomized study on intravesical chemoprophylaxis are presented. The study comprised 66 patients; one group of 29 patients received mitomycin C alone, while another group of 37 patients received mitomycin C and alternating BCG therapy. This latter treatment modality was found to achieve a slightly higher complete response rate and a much lower tumor progression rate. Although these results were not statistically significant (p > 0.05), they indicate that if the study were comprised of a larger series, the combined modality may be shown to achieve better results than the other modalities currently used.


The nurse educator as teacher: exploring the construction of the 'reluctant instructor'.
This paper explores the discursive construction of the category of teacher identified as the 'reluctant instructor'. Data are drawn from my doctoral study, an ethnography of a school of nursing located in the higher education sector in which I was employed. This study explored the question: What shapes nurse educators and what do they, in turn, shape? Participants included nurse educators who taught a pre-registration programme. Data were gathered through interview and observations of classroom teaching. Analysis focused on the discursive constitution of participants' sense of being a nurse educator and on the implications of their ways of 'knowing and doing' for students. The analysis suggests that the dominant subject positions adopted by participants were those of 'academic' and 'victim'. They employed an ideal/real dichotomy to give a sense of coherence to the inconsistencies or contradications that they saw as structuring their daily activities. Being an academic entailed being an educator, specifically a facilitator, as being competent and having some degree of autonomy. However, participants saw the reality of their situation as markedly different from their ideal; as exhibiting traits of the 'outmoded', oppressive, hospital system of nurse training. Within this context most participants positioned themselves as a 'reluctant instructor'. The implications of their practices for the creation of the 'passive student' are suggested in the paper. In this analysis the nurse educator is viewed as implicated in the formation and maintenance of the context in which she or he is located. Such a view challenges the neutrality that is implicated in understandings of the nurse educator that inform nursing texts and that helped constitute participants' sense of self.


An interaction of endogenous and exogenous opiates in the guinea-pig isolated ileum.
In the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum an interaction of exogenously applied opiates with posttetanic inhibition was studied. The electric tetanic stimulation (30 Hz) evoking the release of endogenous opioids resulted in an inhibition of neurogenic cholinergic twitch contractions (0.1 Hz) of the same preparation. This posttetanic inhibition was largely attenuated or even reversed into potentiation if tested in the presence of ketocyclazocine (40 nmol/l) or pentazocine (0.3 and 3 mumol/l) and also methionine-enkephalin (0.2 and 2 mumol/l) or morphine (1 mumol/l) while it was not affected in the presence of leucine-enkephalin (2 mumol/l) or D-Ala2-D-Leu5-enkephalin (40 and 400 nmol/l). An involvement of kappa- and mu-opiate receptors in the action of the endogenous mediator(s) of posttetanic inhibition is suggested.


[Focal nodular liver lesions associated with a congenital portocaval shunt in an adult woman].
The Abernethy malformation is a rare anomaly with partial or complete congenital absence of the portal vein and subsequent development of extrahepatic portocaval shunts. Diagnosis is usually made in childhood following the finding of liver neoplasms combined with slightly increased liver enzymes. There is a female predominance. Further findings are malformations of the heart, skeletal system and kidneys. Short-term follow-up of the liver lesions is recommended. Progressive disease can be treated by partial liver resection or transplantation. Diagnosis of the Abernethy malformation is based on various imaging modalities. We report the MRI and MRA findings of an Abernethy malformation in a 35-year-old woman with multiple liver cell adenomas and review the 32 previously published cases.


The architecture of a water-selective pore in the lipid bilayer visualized by electron crystallography in vitreous ice.
The water-selective pathway through aquaporin 1 (AQP1) membrane channel has been visualized by fitting an atomic model to a 3.7 A resolution three-dimensional density map. This map was determined by analysing images and electron diffraction patterns of lipid-reconstituted two-dimensional crystals of AQP1 preserved in vitrified buffer in the absence of any additive. The aqueous pathway in a monomer is characterized by a size-selective, to approximately 4.0 +/- 0.5 A wide pore that spans a length of to approximately 18 and bends by to approximately 25 degrees as it traverses the bilayer. This narrow pore is connected by wide, funnel-shaped openings at the extracellular and cytoplasmic faces, and is outlined mostly by hydrophobic residues interspersed with short stretches of polar amino acids, which results in relatively inert pathway conducive to diffusion-limited water flow. Although not visible at the current resolution, the 3D structure suggests putative binding sites for water molecules in the size-selective pore.


Humoral immune responses within the lung of bone marrow transplant recipients studied by bronchoalveolar lavage.
We investigated 20 bone marrow transplant recipients with pneumonitis using bronchoalveolar lavage (BAL) to assess the humoral immune response in the lung. We measured the levels of total IgG, IgM and IgA in bronchoalveolar lavage fluid and serum, and albumin measurements were used to correct for simple diffusion of immunoglobulins from serum into the lung. We found evidence for the local production of immunoglobulins G, M and A in 15 patients. This was independent of the cause of the pneumonitis. We also found that, although seven patients who recovered from their pulmonary problem had evidence of considerable local production of immunoglobulin, eight patients who died were also producing immunoglobulins in the lung. Death due to pneumonitis in BMT recipients cannot, therefore, be ascribed to a failure of the local humoral immune response.


Composite polymer nanoarchitectures from a one-pot hydrothermal route.
Exploitation of facile and versatile synthetic approaches to polymeric nanoarchitectures is of great interest in polymer science and engineering. Herein, we show that a simple hydrothermal route using double-solvents as reaction media has the ability to generate polymer nanospheres with tunable morphologies and components. In this one-pot approach, condensation polymerization of a resol precursor and radical polymerization of styrene are allowed to occur simultaneously under hydrothermal treatment. The synergistic self-organization of phenol-formaldehyde crosslinked networks and polystyrene chains leads to the formation of well-defined hollow nanospheres with adjustable shell thickness or even Janus particles comprising a solid hemisphere and a hollow hemisphere. Furthermore, control over the composition of the hollow polymer nanospheres can be easily achieved by introducing a third monomer into the hydrothermal system.


Ten-Step Minimally Invasive Treatment of Lumbar Giant Disc Herniation via Unilateral Tubular Laminotomy for Bilateral Decompression: 2-Dimensional Operative Video.
Giant disc herniation (GDH) is generally defined as a lumbar disc herniation that obstructs 50% or more of the space in the spinal canal.1-3 Common treatment options for GDH include unilateral interlaminar approach, bilateral approach, or open full laminectomy.4,5 Surgical treatment of GDH may be challenging because severe bilateral compression of neural elements in the spinal canal increases the risk of iatrogenic injury to nerve roots and dura. The surgical approach can be further complicated by calcification, hardening, and dehydration of the GDH tissue. The prevailing opinion in the literature is that giant disc herniations cannot safely be treated via tubular minimally invasive approaches.5-7 In this video, we present a case of a 52-yr-old male patient with a history of progressive low back pain that radiates bilaterally from the buttocks toward the posterior legs and knees for 2 yr because of a GDH at the L4-5 level. The patient was treated via a tubular "over-the-top" minimally invasive decompression in order to first provide generous bilateral decompression of neural elements and dura.8,9 After sufficient decompression at the surgical level, the discectomy was performed via an ipsilateral piecemeal resection of the GDH. The "over-the-top" contralateral mobilization of disc herniation was also achieved with this approach, which facilitated the removal of the entire disc fragment. Patient consent was obtained prior to performing the procedure. Therefore, GDH should not be considered as a contraindication for tubular decompression when this modified technique is performed.


Silica-Derived Hydrophobic Colloidal Nano-Si for Lithium-Ion Batteries.
Silica can be converted to silicon by magnesium reduction. Here, this classical reaction is renovated for more efficient preparation of silicon nanoparticles (nano-Si). By reducing the particle size of the starting materials, the reaction can be completed within 10 min by mechanical milling at ambient temperature. The obtained nano-Si with high surface reactivity are directly reacted with 1-pentanol to form an alkoxyl-functionalized hydrophobic colloid, which significantly simplifies the separation process and minimizes the loss of small Si particles. Nano-Si in 5 g scale can be obtained in one single batch with laboratory scale setups with very high yield of 89%. Utilizing the excellent dispersion in ethanol of the alkoxyl-functionalized nano-Si, surface carbon coating can be readily achieved by using ethanol soluble oligomeric phenolic resin as the precursor. The nano-Si after carbon coating exhibit excellent lithium storage performance comparable to the state of the art Si-based anode materials, featured for the high reversible capacity of 1756 mAh·g-1 after 500 cycles at a current density of 2.1 A·g-1. The preparation approach will effectively promote the development of nano-Si-based anode materials for lithium-ion batteries.


Traditional Chinese medicine for lipid metabolism disorders.
Dyslipidemia significantly contributes to the development of cardiovascular disease (CVD), which is the most common cause of morbidity and mortality in China. Statins are the first-line therapy for reducing LDL-C serum levels. However, they have adverse effects, which restrict their clinical application. Traditional Chinese medicine (TCM) preparations have been increasingly described for their beneficial effects in hyperlipidemic patients. Existing data show that the lipid-regulating effects of TCM may be related to: (1) inhibiting intestinal absorption of lipids; (2) reducing endogenous cholesterol synthesis; (3) regulating cholesterol transport; (4) promoting the excretion of cholesterol in the liver; (5) regulating transcription factors related to lipid metabolism. This study provides an overview of recent studies and elaborates the underlying mechanisms of lipid-regulation by TCM.


Higher maternal education is associated with favourable growth of young children in different countries.
Childhood growth affects long-term health and could contribute to health inequalities that persist throughout life. We compared growth data of 4-year-old to 6-year-old children born 1997-2002 in UK (n=15,168), Sweden (n=6749) and rural China (n=10,327). SD scores (SDS) were calculated against the WHO Growth Standard. Obesity and overweight were defined by the International Obesity Taskforce cut-offs, and stunting, underweight and thinness by height, weight or body mass index (BMI)<-2 SDS. Associations with maternal education were standardised by calculating the Slope Index of Inequality (SII). Mean SDS height, weight and BMI in the UK (-0.01, 0.42, 0.62, respectively) and Sweden (0.45, 0.59, 0.45) were higher than in China (-0.98, -0.82, -0.29). Higher maternal education was consistently associated with taller offspring height SDS (SII: UK 0.25; Sweden 0.17; China 1.06). Underweight and stunting were less common in the UK (prevalence: 0.6% and 2.2%, respectively) and Sweden (0.3% and 0.6%) than in China (9.5% and 16.4%), where these outcomes were inversely associated with maternal education (SII: -25.8% and -12.7%). Obesity prevalence in the UK, Sweden and China was 4.8%, 3.7% and 0.4%, respectively. Maternal education was inversely associated with offspring obesity in the UK (SII: -3.3%) and Sweden (-2.8%), but not in China (+0.3%). Higher maternal education was associated with more favourable growth in young children: lower obesity and overweight in the UK and Sweden, and lower stunting and underweight in rural China. Public health strategies to optimise growth in early childhood need to acknowledge socioeconomic factors, but possibly with a different emphasis in different settings.


Imaging Brain Function with Functional Near-Infrared Spectroscopy in Unconstrained Environments.
Assessing the neural correlates of motor and cognitive processes under naturalistic experimentation is challenging due to the movement constraints of traditional brain imaging technologies. The recent advent of portable technologies that are less sensitive to motion artifacts such as Functional Near Infrared Spectroscopy (fNIRS) have been made possible the study of brain function in freely-moving participants. In this paper, we describe a series of proof-of-concept experiments examining the potential of fNIRS in assessing the neural correlates of cognitive and motor processes in unconstrained environments. We show illustrative applications for practicing a sport (i.e., table tennis), playing a musical instrument (i.e., piano and violin) alone or in duo and performing daily activities for many hours (i.e., continuous monitoring). Our results expand upon previous research on the feasibility and robustness of fNIRS to monitor brain hemodynamic changes in different real life settings. We believe that these preliminary results showing the flexibility and robustness of fNIRS measurements may contribute by inspiring future work in the field of applied neuroscience.


An Exercise Health Simulation Method Based on Integrated Human Thermophysiological Model.
Research of healthy exercise has garnered a keen research for the past few years. It is known that participation in a regular exercise program can help improve various aspects of cardiovascular function and reduce the risk of suffering from illness. But some exercise accidents like dehydration, exertional heatstroke, and even sudden death need to be brought to attention. If these exercise accidents can be analyzed and predicted before they happened, it will be beneficial to alleviate or avoid disease or mortality. To achieve this objective, an exercise health simulation approach is proposed, in which an integrated human thermophysiological model consisting of human thermal regulation model and a nonlinear heart rate regulation model is reported. The human thermoregulatory mechanism as well as the heart rate response mechanism during exercise can be simulated. On the basis of the simulated physiological indicators, a fuzzy finite state machine is constructed to obtain the possible health transition sequence and predict the exercise health status. The experiment results show that our integrated exercise thermophysiological model can numerically simulate the thermal and physiological processes of the human body during exercise and the predicted exercise health transition sequence from finite state machine can be used in healthcare.


Social Information Processing in Dating Conflicts: Reciprocal Relationships With Dating Aggression in a One-Year Prospective Study.
The aim of this study was to assess the reciprocal associations among social information processing (SIP) in dating conflicts and the perpetration of dating aggression. A first step involved the development of a measure (The Social Information Processing Questionnaire in Dating Conflicts, SIPQ-DC) to assess social information in scenarios of conflict with dating partners. A sample of 1,272 adolescents (653 girls, 619 boys; Mage = 14.74 years, SD = 1.21) completed measures of SIP and dating aggression perpetration in two different times, which were spaced 1 year apart. Confirmatory factor analyses provided support for a model with five correlated factors for the SIPQ-DC, namely, hostile attribution, anger, aggressive response access, anticipation of positive consequences for oneself, and anticipation of negative consequences for partners. Although the perpetration of dating aggression at T1 was cross-sectionally associated with all the SIP components, anger was the only component that predicted the residual increase in dating aggression behavior over time. The perpetration of dating aggression predicted a worsening of cognitive-emotional processes involved in dating conflicts. Some longitudinal paths were significant only in male adolescents. In conclusion, relationships among SIP and aggression are reciprocal. Gender differences in longitudinal paths can contribute to explaining men's higher perpetration of violence in adulthood.


Cloning and characterization of Neisseria meningitidis genes encoding the transferrin-binding proteins Tbp1 and Tbp2.
Genes tbp1 and tbp2, encoding the transferrin-binding proteins Tbp1 and Tbp2, have been isolated from two strains of Neisseria meningitidis. The tbp2 and tbp1 open reading frames are tandemly arranged in the genome with an 87-bp intergenic region, and the DNA region upstream from the tbp2-coding sequence contains domains homologous to Escherichia coli promoter consensus motives. Nucleotide sequence analysis suggests the existence of a Tbp1 precursor carrying an N-terminal signal peptide with a peptidase I cleavage site and of a Tbp2 precursor with N-terminal homology to lipoproteins, including a peptidase II cleavage site. Comparison of the Tbp1 deduced amino acid (aa) sequences from both strains showed about 76% aa homology, while those of Tbp2 revealed only about 47% aa homology. These comparisons should be extended to other Neisseria strains in order to evaluate further this genetic divergence further.


Decaspirones F-I, bioactive secondary metabolites from the saprophytic fungus Helicoma viridis.
Decaspirones F-H (1-3), three new spirobisnaphthalene derivatives, and one new non-spirobisnaphthalene, decaspirone I (4), have been isolated from cultures of an isolate of the saprophytic fungus Helicoma viridis. The structures of these compounds were determined mainly by analysis of their NMR spectroscopic data. The absolute configuration of decaspirone F (1) was established by X-ray crystallographic analysis of its mono-bromobenzoate derivative. In standard disk assays, compounds 1-4 showed modest activity against Pseudomonas aeruginosa (multiple antibiotic-resistant strain, ATCC 27853), and decaspirone G (2) also displayed activity against Lactococcus lacti (PCM 2379).


Statistical injury prediction for professional sumo wrestlers: Modeling and perspectives.
In sumo wrestling, a traditional sport in Japan, many wrestlers suffer from injuries through bouts. In 2019, an average of 5.2 out of 42 wrestlers in the top division of professional sumo wrestling were absent in each grand sumo tournament due to injury. As the number of injury occurrences increases, professional sumo wrestling becomes less interesting for sumo fans, requiring systems to prevent future occurrences. Statistical injury prediction is a useful way to communicate the risk of injuries for wrestlers and their coaches. However, the existing statistical methods of injury prediction are not always accurate because they do not consider the long-term effects of injuries. Here, we propose a statistical model of injury occurrences for sumo wrestlers. The proposed model provides the estimated probability of the next potential injury occurrence for a wrestler. In addition, it can support making a risk-based injury prevention scenario for wrestlers. While a previous study modeled injury occurrences by using the Poisson process, we model it by using the Hawkes process to consider the long-term effect of injuries. The proposed model can also be applied to injury prediction for athletes of other sports.


Social Media in Professional Medicine: New Resident Perceptions and Practices.
For younger generations, unconstrained online social activity is the norm. Little data are available about perceptions among young medical practitioners who enter the professional clinical arena, while the impact of existing social media policy on these perceptions is unclear. The objective of this study was to investigate the existing perceptions about social media and professionalism among new physicians entering in professional clinical practice; and to determine the effects of formal social media instruction and policy on young professionals' ability to navigate case-based scenarios about online behavior in the context of professional medicine. This was a prospective observational study involving the new resident physicians at a large academic medical center. Medical residents from 9 specialties were invited to participate and answer an anonymous questionnaire about social media in clinical medicine. Data were analyzed using SAS 9.4 (Cary, NC), chi-square or Fisher's exact test was used as appropriate, and the correct responses were compared between different groups using the Kruskal-Wallis analysis of variance. Familiarity with current institutional policy was associated with an average of 2.2 more correct responses (P=.01). Instruction on social media use during medical school was related to correct responses for 2 additional questions (P=.03). On dividing the groups into no policy exposure, single policy exposure, or both exposures, the mean differences were found to be statistically significant (3.5, 7.5, and 9.4, respectively) (P=.03). In this study, a number of young physicians demonstrated a casual approach to social media activity in the context of professional medical practice. Several areas of potential educational opportunity and focus were identified: (1) online privacy, (2) maintaining digital professionalism, (3) safeguarding the protected health information of patients, and (4) the impact of existing social media policies. Prior social media instruction and/or familiarity with a social media policy are associated with an improved performance on case-based questions regarding online professionalism. This suggests a correlation between an instruction about online professionalism and more cautious online behavior. Improving the content and delivery of social media policy may assist in preserving institutional priorities, protecting patient information, and safeguarding young professionals from online misadventure.


Influence of consultation on ethical decision making: an analogue study.
Participants (62 students from 6 doctoral programs in professional psychology) were given 3 ethical dilemmas, asked to generate their own solutions, and asked to make judgments about a number of provided alternatives. Students were asked either to make decisions after seeking consultation or to make decisions independently of consultation. There were few significant between-group differences along a number of dimensions including participants' ratings of acceptability of provided alternatives and levels of certainty, justification, and satisfaction with personally generated solutions. For one of the vignettes, individuals using consultation, when compared with the control group, were significantly more likely to prefer their own solution to that of provided alternatives. The study was viewed as a needed first step in investigating a cherished assumption in clinical practice.


Maladaptive Beliefs of Young Adults in Interpersonal Relationships: A Systematic Literature Review.
Beliefs that are too rigid and misadjusted may legitimize interpersonal relationships marked by verbal, physical, or sexual violence. A systematic literature review was performed to identify the existence of maladaptive beliefs (MBs) in interpersonal relationships of young adults and their association with problematic behaviors. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, studies were obtained through a search in multiple databases: EBSCOhost, PubMed, and Web of Science. Of the 1,280 articles retrieved, 42 were retained for further analysis and 15 were considered eligible for inclusion. In addition, seven studies were added through manual search, leading to a final sample of 15 articles, published between 1964 and 2021. Only empirical studies with quantitative methodologies were included. Objectives, sample (age in years), sample type, country of origin of studies, instruments, control group, and results and main conclusions were extracted from each study. Results suggest the existence of MBs that may legitimize antisocial behavior and violence, whether physical, sexual, gender, domestic, or in intimate relationships. Some intervention programs were also identified, with different approaches with a reasonable degree of efficacy in changing these beliefs or in reducing the rates of recidivism by the aggressors.


Effect of Malaria and Geohelminth Infection on Birth Outcomes in Kumasi, Ghana.
In 2005, the Ghana Health Service mandated malaria and helminths chemoprophylaxis during antenatal care visits. The aim of this study was to investigate the prevalence of malaria and helminth infections and their relationship with adverse birth outcomes (low birth weight, stillbirth, and preterm) following the implementation of these treatments. A quantitative cross-sectional study. The study was conducted on 630 women presenting for delivery in the Komfo Anokye Teaching Hospital and the Manhyia District Hospital from July to November 2011. Socio-demographic information and medical and obstetric history were collected. Laboratory analyses for the presence of malaria and helminths were performed. Association of malaria and helminths with birth outcomes was assessed using logistic regression to obtain odds ratios (ORs) and 95% confidence intervals. The prevalence of malaria, helminths and adverse birth outcomes was 9.0%, 5.0% and 22.2%, respectively. Compared with women who received malaria prophylaxis, women without malaria prophylaxis were two times more likely to have malaria infection (aOR = 2.1; 95% CI = 1.06-4.17). Women who were not screened for helminths were twice as likely to be infected with helminths (aOR = 2.4; 95% CI = 1.15-5.12) than women who were screened for helminths. For women infected with hookworm or Schistosoma mansoni, the odds of having an adverse birth outcome (aOR = 3.9; 95% CI = 1.09-14.20) and stillbirth (aOR = 7.7; 95% CI = 1.21-36.38) were greater than for women who were not infected. The prevalence of malaria, helminths and adverse birth outcomes was lower than previously reported 9.0% vs. 36.3, 5.0% vs. 25.7 and 22.2% vs. 44.6, respectively. Helminth but not malaria infection was found to be significantly associated with adverse birth outcomes.


The potential for radiation sensitizers and possible strategy for use.
The search for radiation sensitzers for use in radiotherapy is based on the assumption that proper use of these compounds will provide a differential sensitization of tumor and normal tissue. Based on the evidence that hypoxic cells exist within human tumors but not within normal cell populations, there is reason to believe that specific sensitizers of hypoxic cells might provide useful therapeutic benefit. This paper discusses the possible advantages of such sensitizers, over reliance on the phenomenon of reoxygenation, and describes very briefly the current status of hypoxic cell sensitizers. Finally a proposal is made concerning the way in which such sensitizers might be tested for their efficacy in human radiotherapy.


Beta-peptidic peptidomimetics.
For more than a decade now, a search for answers to the following two questions has taken us on a new and exciting journey into the world of beta- and gamma-peptides: What happens if the oxygen atoms in a 3i-helix of a polymeric chain composed of (R)-3-hydroxybutanoic acid are replaced by NH units? What happens if one or two CH2 groups are introduced into each amino acid building block in the chain of a peptide or protein, thereby providing homologues of the proteinogenic alpha-amino acids? Our journey has repeatedly thrown up surprises, continually expanding the potential of these classes of compound and deepening our understanding of the structures, properties, and multifaceted functions of the natural "models" to which they are related. Beta-peptides differ from their natural counterparts, the alpha-peptides, by having CH2 groups inserted into every amino acid residue, either between the C=O groups and the alpha-carbon atoms (beta(3)) or between the alpha-carbon and nitrogen atoms (beta(2)). The synthesis of these homologated proteinogenic amino acids and their assembly into beta-peptides can be performed using known methods. Despite the increased number of possible conformers, the beta-peptides form secondary structures (helices, turns, sheets) even when the chain lengths are as short as four residues. Furthermore, they are stable toward degrading and metabolizing enzymes in living organisms. Linear, helical, and hairpin-type structures of beta-peptides can now be designed in such a way that they resemble the characteristic and activity-related structural features ("epitopes") of corresponding natural peptides or protein sections. This Account presents examples of beta-peptidic compounds binding, as agonists or antagonists (inhibitors), to (i) major histocompatibility complex (MHC) proteins (immune response), (ii) the lipid-transport protein SR-B1 (cholesterol uptake from the small intestine), (iii) the core (1-60) of interleukin-8 (inflammation), (iv) the oncoprotein RDM2, (v) the HIVgp41 fusion protein, (vi) G-protein-coupled somatostatin hsst receptors, (vii) the TNF immune response receptor CD40 (apoptosis), and (viii) DNA. Short-chain beta-peptides may be orally bioavailable and excreted from the body of mammals; long-chain beta-peptides may require intravenous administration but will have longer half-lives of clearance. It has been said that an interesting field of research distinguishes itself in that the results always throw up new questions; in this sense, the structural and biological investigation of beta-peptides has been a gold mine. We expect that these peptidic peptidomimetics will play an increasing role in biomedical research and drug development in the near future.


Effects of probiotics on gastrointestinal complications and nutritional status of postoperative patients with esophageal cancer: A protocol of randomized controlled trial.
Gastrointestinal complications and malnutrition are common problems that affect postoperative rehabilitation and survival of patients with esophageal cancer. Evidence has shown that probiotics have a positive effect on improving gastrointestinal complications and nutritional status of patients with esophageal cancer after surgery, but there is a lack of prospective studies on this topic. We designed this prospective randomized controlled trial to evaluate the effects of probiotics on gastrointestinal complications and nutritional status in patients with postoperative esophageal cancer. This is a prospective, randomized, double-blind, placebo-controlled trial. It was approved by the Clinical Research Ethics Committee of our hospital. 192 patients will be randomly divided into probiotics group and the placebo group in a 1:1 ratio. After operation, probiotics and placebo will be given orally for 8 weeks. The indexes of nutritional status and incidence of digestive tract complications will be recorded and the data will be analyzed by SPSS 18.0 software. This study will evaluate the effect of probiotics on gastrointestinal complications and nutritional status of postoperative patients with esophageal cancer. The results of this study will provide clinical basis for the use of probiotics in postoperative treatment of esophageal cancer. OSF Registration number: D DOI 10.17605/OSF.IO/QHW86.


Lung adenocarcinoma patients with malignant pleural effusions in hot adaptive immunity status have a longer overall survival.
Malignant pleural effusion (MPE) is a common complication of lung adenocarcinoma (LADC) which is associated with a dismal prognosis. We investigated the prognostic role of PD-L1 and other immunomodulators expression in the immune compartment of MPE immune composition. MPE cytologic cell blocks of 83 LADC patients were analysed for the mRNA expression of 770 cancer-immune genes by the NanoString nCounter platform. The expression of relevant immune cell lineage markers was validated by immunohistochemistry (IHC) using quantitative pathology. The mRNA immune profiling identified four MPE patient clusters (C). C1/2 (adaptive+, hot) showed better overall survival (OS) than C3/4 (adaptive-, cold). Additionally, cold immunity profiles (adaptive-), C4 (innate+) were associated with worse OS than C3 (innate-). High PD-L1 expression was linked to the regulation of T cell activation and interferon signalling pathways. Genes of pattern recognition receptor and type I interferon signalling pathways were specifically upregulated in the long-survival (≥90 days) patient group. Moreover, immunomodulators were co-activated and highly expressed in hot adaptive immunity patient clusters, whereas CD274 (PD-L1), TNFRSF9 (4-1BB), VEGFA (VEGF-A) and CD276 (B7-H3) were upregulated in the groups referred as cold. The patient cluster, age and PD-L1 expression were independent prognosticators for LADC MPE patients (p-value < 0.05). Our study sheds light on the variances of immune contexture regarding different PD-L1 expression and survival conditions. It revealed four distinct prognostic patient clusters with specific immune cell components and immunomodulator expression profiles, which, collectively, is supportive for future therapeutic and prognosis for cancer management.


Nursing care in the evaluation of the epilepsy surgery candidate.
The Epilepsy Surgery Program at the Veterans' Administration Medical Center is designed to surgically treat specific individuals with intractable epilepsy. A thorough workup encompassing several months ensures the appropriateness of each candidate. Members of the evaluating health team include nursing, neurology, neurosurgery, neuropsychology, psychiatry, and neuroradiology. In order to progress to surgery, the candidate must be physically, psychologically, and socially healthy within the limits of a developed criteria.


[Diseases and the diseased--scientific and alternative medicine].
Exposing alternative medicine as quackery and unscientific is necessary, but one should be aware of the limitations of scientific medicine as far as the care of individual patients is concerned. Medicine is primarily about people, not about science. Current regular medicine uses a rational approach and carries out actions of which the effectiveness has been demonstrated in controlled trials. But some questions cannot be translated into a testable hypothesis, e.g., what is the best treatment for the individual incurable cancer patient sitting in my surgery right now? However, this question is a relevant one, especially for the patient involved. In daily clinical practice, there is no clear distinction between scientifically-based and not-scientifically-based acts. The task of medicine is to cure, but also to encourage and to console. When exposing alternative medicine, one should be able to offer the patient a different approach; otherwise the exposure is nothing more than a nihilistic exercise. Alternative medicine does not cure diseases, but it sometimes helps diseased people.


Intraventricular infusion of epidermal growth factor restores dopaminergic pathway in hemiparkinsonian rats.
We assessed the effect of a 35-day delayed intracerebroventricular (ICV) infusion of epidermal growth factor (EGF) on the survival and function of the substantia nigra (SN) dopaminergic neurons after a unilateral mechanical transection of rat nigrostriatal pathway. EGF infusion for 28 days resulted in a twofold increase in the number of surviving tyrosine-hydroxylase (TH)-positive SN neurons and a significant increase in ipsilateral striatal TH-positive fiber staining compared to controls at 200 days following the injury. In addition, there was a persistent enhancement of behavioral recovery, as indicated by a reduction in amphetamine-induced rotations. We conclude that EGF exerts a neurotrophic effect on the dopaminergic neurons in this experimental model of parkinsonism.


Photosynthesis and chlorophyll fluorescence of Iranian licorice (Glycyrrhiza glabra l.) accessions under salinity stress.
While salinity is increasingly becoming a prominent concern in arable farms around the globe, various treatments can be used for the mitigation of salt stress. Here, the effective presence of Azotobacter sp. inoculation (A1) and absence of inoculation (A0) was evaluated on Iranian licorice plants under NaCl stress (0 and 200 mM) (S0 and S1, respectively). In this regard, 16 Iranian licorice (Glycyrrhiza glabra L.) accessions were evaluated for the effects on photosynthesis and chlorophyll fluorescence. Leaf samples were measured for photosynthetic pigments (via a spectrophotometer), stomatal and trichome-related features (via SEM), along with several other morphological and biochemical features. The results revealed an increase in the amount of carotenoids that was caused by bacterial inoculation, which was 28.3% higher than the non-inoculated treatment. Maximum initial fluorescence intensity (F0) (86.7) was observed in the 'Bardsir' accession. Meanwhile, the highest variable fluorescence (Fv), maximal fluorescence intensity (Fm), and maximum quantum yield (Fv/Fm) (0.3, 0.4, and 0.8, respectively) were observed in the 'Eghlid' accession. Regarding anatomical observations of the leaf structure, salinity reduced stomatal density but increased trichome density. Under the effect of bacterial inoculation, salinity stress was mitigated. With the effect of bacterial inoculation under salinity stress, stomatal length and width increased, compared to the condition of no bacterial inoculation. Minimum malondialdehyde content was observed in 'Mahabad' accession (17.8 μmol/g FW). Principle component analysis (PCA) showed that 'Kashmar', 'Sepidan', 'Bajgah', 'Kermanshah', and 'Taft' accessions were categorized in the same group while being characterized by better performance in the aerial parts of plants. Taken together, the present results generally indicated that selecting the best genotypes, along with exogenous applications of Azotobacter, can improve the outcomes of licorice cultivation for industrial purposes under harsh environments.


Extended X-ray absorption fine structure of copper in CuA-depleted, p-(hydroxymercuri)benzoate-modified, and native cytochrome c oxidase.
Cytochrome c oxidase contains four redox-active metal centers: two heme irons, cytochromes a and a3, and two copper ions, CuA and CuB. Due to the paucity of spectroscopic signatures for both copper sites in cytochrome c oxidase, the ligands and structures for these sites have remained ambiguous. The specific depletion of CuA from the p-(hydroxymercuri)benzoate- (pHMB-) modified cytochrome c oxidase recently reported [Gelles, J., & Chan, S. I. (1985) Biochemistry 24, 3963-3972] is herein described. Characterization of this enzyme shows that the structures of the remaining metal centers are essentially unperturbed by the CuA modification and depletion (P. M. Li, J. Gelles, and S. I. Chan, unpublished results). Copper extended X-ray absorption fine structure (EXAFS) measurements on the CuA-depleted cytochrome c oxidase reveal coordination of three (N, O) ligands and one (S, Cl) ligand at the CuB site. Comparison of EXAFS results obtained for the CuA-depleted, pHMB-modified, and "unmodified control" enzymes has allowed the deconvolution of the EXAFS in terms of the inner coordination spheres for CuA as well as CuB. On the basis of these data, it is found that the structure for the CuA site is consistent with two (N, O) ligands and two S ligands.


New Isotopes for the Treatment of Pancreatic Cancer in Collaboration With CERN: A Mini Review.
The use of radioactivity in medicine has been developed over a century. The discovery of radioisotopes and their interactions with living cells and tissue has led to the emergence of new diagnostic and therapeutic modalities. The CERN-MEDICIS infrastructure, recently inaugurated at the European Center for Nuclear Research (CERN), provides a wide range of radioisotopes of interest for diagnosis and treatment in oncology. Our objective is to draw attention to the progress made in nuclear medicine in collaboration with CERN and potential future applications, in particular for the treatment of aggressive tumors such as pancreatic adenocarcinoma, through an extensive review of literature. Fifty seven out of two hundred and ten articles, published between 1997 and 2020, were selected based on relevancy. Meetings were held with a multi-disciplinary team, including specialists in physics, biological engineering, chemistry, oncology and surgery, all actively involved in the CERN-MEDICIS project. In summary, new diagnostic, and therapeutic modalities are emerging for the treatment of pancreatic adenocarcinoma. Targeted radiotherapy or brachytherapy could be combined with existing therapies to improve the quality of life and survival of these patients. Many studies are still in the pre-clinical stage but open new paths for patients with poor prognosis.


[The importance of HRT II (Heidelberg retina tomography) and perimeter Octopus 101 in glaucoma diseases].
To follow up and statistically evaluate the importance of HRT II (Heidelberg retina tomograph) and perimeter Octopus 101 in glaucoma diseases. There were 154 eyes (77 patients) enrolled into prospective study. The follow up period was 3 years, from January 2003 to December 2005. Patients were divided into 3 groups: (1) the primary open angle glaucoma (PGOU) group and the preperimetric form of PGOU group (88 eyes), (2) the ocular hypertension (OH) group with medical therapy and without medical therapy (44 eyes) and (3) the group of persons with large optic disc areas (22 eyes). The structural optic nerve head (ONH) changes were interpreted by means of HRT II equipment and the functional changes were evaluated by means of perimeter Octopus 101 every 6 months. The statistic analysis was performed with the program Statgraphics plus. HRT II is a reproducible method to follow up the structural changes of the ONH for its low variability of achieved results in all evaluated groups. Low correlation between MD (mean defect) and CLV (corrected lose variance) parameters in the first and the third groups occurred. The standard automated perimetry was accompanied by greater long-term variability, making it less reproducible, but it is useful method comparing to HRT II. In the group of PGOU patients, significant correlations between MD perimetric parameter and the mean RNFL (retinal nerve fibre layer) thickness parameters were observed by means of HRT II. HRT II is not able to replace visual field examination with perimetry, both methods are important in the evaluation of glaucoma patients.


High Glucose-Induced Podocyte Injury Involves Activation of Mammalian Target of Rapamycin (mTOR)-Induced Endoplasmic Reticulum (ER) Stress.
The mechanisms by which high glucose (HG) results in podocyte damage remains unclear. We investigated the potential role of endoplasmic reticulum (ER) stress and mTOR signaling in HG injured podocyte. In cultured mouse podocytes, cellular apoptosis was assessed using FITC-Annexin V and propidium iodide staining followed by flow cytometry analysis. Apoptosis-related proteins as well as the ER stress and the mTOR signals were evaluated using immunoblot assay. Compared to normal glucose (NG) and osmotic mannitol (MN) control, the percentage of apoptotic cells was increased significantly in HG-treated podocytes. The levels of CHOP, Grp78, phospho-PERKThr982, and caspase-12 were increased significantly following HG treatment. The downstream effects of ER stress were obtained in HG-treated podocytes, showing upregulation of Bax, Bak and cytochrome c, and downregulation of Bcl-2. HG-induced increase of cytochrome c, Bax and active caspase-3 was prevented by both ER inhibitor sodium 4-phenylbultyrate (PBA) and CHOP siRNA (siCHOP). PBA and CHOP knockdown remarkably decreased HG-induced apoptosis. In addition, the levels of phospho-mTORSer2448 and phospho- p70S6kThr389 as well as phospho-AMPKα (a sensor of energy consumption) were increased significantly in HG-treated cells. Moreover, the Erk inhibitor U0126 prevented HG-induced mTOR activation. Increased phospho-AMPKα, CHOP and Grp78 as well as cellular apoptosis were prevented by mTOR inhibitor rapamycin in HG-treated podocytes. Our data demonstrate that the activated mTOR by Erk1/2 results in energy consumption, which in turn leads to ER stress signaling and thus induces apoptosis in HG-treated podocytes.


Evaluation of target angular position algorithms for multi-beam fishery sonars.
Two methods for measuring the angular position of a reference target when observed with a horizontally transmitting, multi-beam fishery sonar are described. The theory behind realizations of both a Split-Beam (SB) algorithm and an Interpolated Neighbouring Beam (INB) algorithm is described for a cylindrical transducer array. The algorithms were implemented on both simulated and real data collected during field calibrations. The estimated precision was ±0.2 to ±0.25°, for both algorithms when the target was within the central part of the beam. The precision was reduced for targets with large inclination angles, or in the beam-overlap region of the SB's two half-transducer arrays. The SB algorithm provides an accurate target location within the entire main lobe of the acoustic beam. For the INB method, the accuracy is only good within a small sector close to the acoustic axis, or within ±1.5°-±2.5° depending on the sonar operating frequency. Repeated calibration trials have shown that the SB algorithm can be used to track the reference-target position in real-time with adequate accuracy for use on fishery acoustic surveys.


Insect herbivores associated with Ludwigia species, Oligospermum section, in their Argentine distribution.
The South American water primroses, Ludwigia grandiflora (Michx.) Greuter & Burdet, L. grandiflora subsp. hexapetala (Hook. & Arn.) G.L. Nesom & Kartesz, Ludwigia peploides (Kunth) P.H. Raven, and L. p. subsp. montevidensis (Spreng.) P.H. Raven (Onagraceae, Section Oligospermum), have become invasive in several watersheds of the United States and Europe. Surveys were carried out in center-east of Argentina to find insect species that might serve as biological control agents for L. g. subsp. hexapetala in California and elsewhere. Stems (0.5-0.6 m) of Ludwigia species, Sect. Oligospermum, were collected in 41 sites and analyzed in the laboratory; immature insects were reared to adults. The plant species found in the area were L. grandiflora (2 sites), L. g. subsp. hexapetala (33 sites), and L. p. subsp. montevidensis (4 sites). There was a variety of insect guilds feeding on L. g. subsp. hexapetala, including six species with stem-borer larvae, one species with fruit-feeding larvae, four species with defoliating larvae, two species with defoliating larvae on young leaves and axil meristems, one species of cell content feeder, and three species of sap feeders. Nine of these species also have defoliating adults. Biological information on most of them is provided. Of these insect herbivores, only two species were also found on L. grandiflora, and one on L. peploides. Several of the species found on L. g. hexapetala, such as the cell-content feeder Liothrips ludwigi (Thysanoptera), the stem-borers Merocnemus binotatus (Boheman) and Tyloderma spp. (Coleoptera), are promising candidates for biocontrol agents.


Variations in transrenal DNA and comparison with plasma DNA as a diagnostic marker for colorectal cancer.
Transrenal DNA can potentially be useful in the disease management of colorectal cancer (CRC) and has potential diagnostic utility. Our study aimed to conduct preoperative and postoperative analysis of KRAS-positive patients, using transrenal DNA compared with plasma DNA. This is critically needed for disease diagnostics and treatment response monitoring. CRC patients at different stages of the disease and with different molecular profiles were recruited for serial time-point analysis. Preoperative and postoperative urine specimens were extracted and compared with tumor tissues and plasma DNA. Our analysis demonstrated that transrenal DNA offered comparable sensitivity and specificity to plasma DNA analysis. Collection of transrenal DNA, being noninvasive, is an attractive assay and easily allows serial monitoring of the disease. Results from preoperative detection showed a close correlation to tumor tissue profiling and demonstrated close associations to the disease. We also observed significant decreases in mutant KRAS DNA concentration after surgery, which confirmed transrenal DNA's sensitivity to treatment response. The use of transrenal DNA offers a possible alternative method of disease profiling, detection and tracking. Our study is one of the first to systematically analyze a relatively large number of different CRC patients using transrenal DNA. The positive correlation with disease demonstrates the assay's viability in the clinical setting, and our method further opens up the possibility to use transrenal DNA for clinical intervention investigations.


Intraocular lens explantation technique for one-piece acrylic lenses.
To present a simple technique to remove a one-piece, acrylic AcrySof (Alcon Laboratories Inc) intraocular lens (IOL) via the original incision. The AcrySof IOL is removed via the original (2.75-mm) incision, without cutting or folding the IOL or widening the incision. After the IOL is viscodissected from the capsular bag and brought into the anterior chamber, toothed forceps hold the optic through the incision while the manipulator enters the side-port incision and hooks onto the optic 180° away. With the forceps pulling and the lens manipulator pushing the IOL toward the incision, the IOL will fold and be delivered. A one-piece, acrylic (Acrysof) IOL can be removed without cutting or folding the lens and without widening the original 2.75-mm incision.


Physical Therapy Considerations for Chronic Kidney Disease and Secondary Sarcopenia.
Chronic kidney disease (CKD) is a progressive condition that may negatively affect musculoskeletal health. These comorbidities may include malnutrition, osteoporosis, and decreased lean body mass. Secondary sarcopenia due to CKD may be associated with mobility limitations and elevated fall risk. Physical therapists are well-positioned among the health care team to screen for secondary sarcopenia in those with CKD and for the treatment of musculoskeletal comorbid conditions that may affect functional performance. Given the consequences of both low muscle mass and low bone mineral density, appropriate and timely physical therapy is important for fall risk assessment and intervention to minimize the susceptibility to bone fracture. While strength training has been studied less frequently than aerobic training for the management of secondary CKD conditions, evidence suggests that this patient population benefits from participation in strength training programs. However, the provision of a formal exercise prescription by a health care professional, along with formal implementation of an exercise program, may need to be more fully integrated into the standard plan of care for individuals with CKD.


Combination chemotherapy used prior to radiation therapy for locally advanced squamous cell carcinoma of the head and neck.
Thirty-three patients with locally advanced squamous cell carcinoma of the head and neck were scheduled to receive two courses of chemotherapy prior to radical radiotherapy. Chemotherapy consisted of moderate-dose methotrexate with leucovorin rescue, bleomycin by infusion, and cisplatin. Loss of body weight and the duration of membrane formation at a specified region of the oral cavity during radiation therapy were used as indices of radiation toxicity: there was no excessive loss of body weight or mucosal reaction in patients who received combined treatment compared to patients in a nonrandomized control group who received radiotherapy alone. Twenty patients (60%) had a greater than or equal to 50% decrease of measurable disease prior to starting irradiation, but only eight patients (24%) are alive and disease-free at a median followup of 16 months. Aggressive chemotherapy does not prevent delivery of subsequent full-dose radiotherapy for squamous cell carcinoma of the head and neck, but this study does not suggest that chemotherapy has a great beneficial effect on long-term survival.


Improving Gene Annotation of the Peanut Genome by Integrated Proteogenomics Workflow.
Peanut (Arachis hypogaea L.) is a staple crop in semiarid tropical and subtropical regions. Although the genome of peanut has been fully sequenced, the current gene annotations are still incomplete. New technologies in genomics and proteomics have resulted in the emergence of proteogenomics, which can integrate genomic, transcriptomic, and proteomic data for improving gene annotation. In the present study, we collected RNA-seq and proteomic data from multiple tissues such as seed, shell, and gynophore of peanut and utilized a proteogenomic approach to improve the gene annotation of peanut based on these data. A total of 1 935 655 904 RNA-seq reads and 7 490 280 MS/MS spectra were collected. Ultimately, 13 767 annotated genes were found with evidence at the protein level, and seven novel protein-coding genes were found with both RNA-seq and proteomics evidence. In addition, 35 gene models were updated based on proteomics data. Proteogenomic approaches improved the gene annotation in certain aspects by integrating both RNA-seq and proteomic data. We expect that these approaches could help improve existing genome annotations of other species.


Metabolic syndrome, diabetes and atherosclerosis: influence of gene-environment interaction.
Despite remarkable progress in diagnosis and understanding of risk factors, cardiovascular disease (CVD) remains still the leading cause of morbidity and mortality in the world's developed countries. The metabolic syndrome, a cluster of risk factors (visceral obesity, insulin resistance, dyslipidaemia, and hypertension), is increasingly being recognized as a new risk factor for type 2 diabetes and atherosclerotic cardiovascular disease. Nevertheless, there is wide variation in both the occurrence of disease and age of onset, even in individuals who display very similar risk profiles. There is now compelling evidence that a complex interplay between genetic determinants and environmental factors (still largely unknown) is the reason for this large inter-individual variation in disease susceptibility. The purpose of the present review is to describe the current status of our knowledge concerning the gene-environment interactions potentially implicated in the pathogenesis of metabolic syndrome, diabetes and cardiovascular disease. It focuses predominantly on studies of genes (peroxisome proliferator-activated receptor-gamma, alcohol dehydrogenase type 1C, apolipoprotein E, glutathione S-transferases T1 and M1) that are known to be modified by dietary and lifestyle habits (fat diet, intake of alcohol and smoking habit). It also describes the limited current understanding of the role of genetic variants of xenobiotic metabolizing enzymes and their interactions with environmental toxicants. Additional studies are needed in order to clarify whether inter-individual differences in detoxification of environmental toxicants may have an essential role in the development of CVD and contribute to the emerging field of "environmental cardiology". Such knowledge may be particularly relevant for improving cardiovascular risk stratification and conceiving the development of "personalized intervention program".


The value of fluorine-18 fluorodeoxyglucose PET/MRI in the diagnosis of head and neck carcinoma: a meta-analysis.
Fluorine-18 fluorodeoxyglucose (18F-FDG) PET/MRI has been used in the diagnosis of head and neck carcinoma. The aim of this study was to systematically review and perform a meta-analysis of published data on the performance of F-PET/MRI in the diagnosis of head and neck carcinoma. We conducted a comprehensive review of the literature on the role of soft-based fusion and integrated 18F-FDG PET/MRI in the diagnosis of head and neck carcinoma. Pooled sensitivity, specificity, and area under the receiver-operating characteristic curve of soft-based fusion and integrated 18F-FDG PET/MRI in the diagnosis of head and neck carcinoma were calculated. Ten studies comprising 421 patients, which included 1879 head and neck primary carcinoma and metastatic lesions, were included in this meta-analysis. 18F-FDG PET/MRI had a pooled sensitivity of 91%, a pooled specificity of 63%, and an area under the receiver-operating characteristic curve of 0.96 on a per lesion-based analysis in detecting head and neck carcinoma lesions. Soft-based fusion and integrated 18F-FDG PET/MRI had a pooled sensitivity of 92 and 90%, a pooled specificity of 53 and 87%, and an area under the receiver-operating characteristic curve of 0.95 and 0.96, respectively, on a per lesion-based analysis in detecting head and neck carcinoma lesions. 18F-FDG PET/MRI demonstrated high sensitivity and moderate specificity in the diagnosis of head and neck carcinoma lesions. 18F-FDG PET/MRI is an accurate method in the diagnosis of head and neck carcinoma.


The effects of an undergraduate nursing informatics curriculum on students' knowledge and attitudes.
This paper describes the fourth stage of a process to design, implement and evaluate the nursing informatics courses incorporated into a baccalaureate nursing program. The challenge is to structure the nursing informatics curriculum so as to provide the nursing professional with the basis with which to impact health care delivery. The basic components of the framework are information, technology, and clinical care process. Students in the fourth course worked closely with agency personnel to design, implement and evaluate clinical application projects.


Differences in prevalence and extent of coronary artery calcium detected by ultrafast computed tomography in asymptomatic men and women.
Coronary artery calcium is a marker of atherosclerosis in asymptomatic subjects. Ultrafast computed tomography (CT) can detect and quantify coronary calcium, simply and noninvasively, with greater sensitivity than can other techniques. The prevalence and extent of coronary calcium in a large population of asymptomatic men and women were measured and compared. Coronary calcium studies were performed in an asymptomatic population of 1,396 male and 502 female subjects (age range 14 to 88 years). The prevalence of calcium, and the distribution of total calcium scores (which reflect the amount of calcium present) were determined and compared for men and women at 5- and 10-year intervals. The prevalence of calcium in women was half that of men, until the age of 60 years when the difference diminished. The mean total calcium score distributions of men between the ages of 40 and 69 years were virtually identical to those of women between the ages of 50 and 79. The quantitative data obtained by Ultrafast CT showed very close agreement with autopsy studies of coronary calcium. Ultrafast CT is a sensitive technique to measure coronary calcium in both men and women. The differences in prevalence and extent of coronary calcium appear to be parallel to those observed in the clinical incidence of coronary artery disease in men and women. Ultrafast CT may have a greater impact on the treatment of women than of men, because it can be used to provide objective evidence of coronary atherosclerosis.


Phase I/II study of intermitted erlotinib in combination with docetaxel in patients with recurrent non-small cell lung cancer (WJOG4708L).
Preclinical data suggest sequential administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) following chemotherapy may improve efficacy. We hypothesized that intermittent delivery of EGFR-TKI following chemotherapy may increase efficacy. This was a multicenter, single-arm phase I/II study to evaluate the efficacy of intermitted erlotinib in combination with docetaxel in patients with EGFR-negative NSCLC who failed one prior chemotherapy. The phase I primary objectives were to determine the maximum tolerated dose (MTD) and recommended dose (RD) of erlotinib. Erlotinib was administered orally once per day on days 2-16 in combination with 60 mg/m2 docetaxel on day1 for 21 days. A standard 3 + 3 dose escalation design was employed for erlotinib from 100 to 150 mg/dose. The phase II primary endpoint was the objective response rate (ORR). The ORR and 95% confidence interval (CI) were calculated using a binomial distribution. This study required 45 patients. In the phase I part, the planned dose escalation was completed without reaching MTD. The RD of erlotinib was determined as 150 mg/dose. In the phase II part, the ORR and disease control rate were 17.1% (95%CI: 7.2-32.1%) and 53.7% (95%CI: 37.4-69.3%), respectively. Median progression-free survival and overall survival were 3.5 (95%CI: 3.1-4.5) and 11.3 (95%CI: 8.6-16.6) months, respectively. The common non-hematological adverse event was febrile neutropenia (grade 3-4:19.6%). Two treatment-related deaths were occurred because of interstitial lung disease and pleural infection. Intermittent dosing of erlotinib plus docetaxel is clinically feasible in phase I part but did not significantly improve ORR in phase II part.


Comprehensive Genetic Analysis of Tuberculosis and Identification of Candidate Biomarkers.
Purpose: The purpose of this study is to use the data in the GEO database to analyze, screen biomarkers that can diagnose tuberculosis, and verification of candidate biomarkers. Materials and methods: GSE158767 dataset were used to process WGCNA analysis, differential gene analysis, Gene ontology and KEGG analysis, protein-protein network analysis and hub genes analysis. Based on our previous study, the intersect between WGCNA and differential gene analysis could be used as candidate biomarkers. Then, the enzyme-linked immunosorbent assay was used to validate candidate biomarkers, and receiver operating characteristic was used to assess diagnose ability of candidate biomarkers. Results: A total of 412 differential genes were screened. And we obtained 105 overlapping genes between DEGs and WGCNA. GO and KEGG analysis showed that most of the differential genes were significantly enriched in innate immunity. A total of 15 hub genes were screened, and four of them were verified by Enzyme-linked immunosorbent assay. CCL5 performed well in distinguishing the healthy group from the TB group (AUC = 0.723). And CCL19 performed well in distinguishing the TB group from the ORD groups (AUC = 0.811). Conclusion: CCL19, C1Qb, CCL5 and HLA-DMB may play important role in tuberculosis, which indicated four genes may become effective biomarkers and could be conveniently used to facilitate the individual tuberculosis diagnosis in Chinese people.


Structure revision of aspergicin by the crystal structure of aspergicine, a co-occurring isomer produced by co-culture of two mangrove epiphytic fungi.
The structure of aspergicin (1), an antibacterial alkaloid produced by co-culture of two marine-derived mangrove epiphytic fungi, were revised by the co-occurring isomer named as aspergicine (2), whose structure was determined on the basis of spectroscopic analysis and X-ray crystallography.


Hearing impairment, emotions and audiological rehabilitation: a sociological perspective.
Encounters are one of the basic dynamics of society, although this does not imply that macro-phenomena do not have ontological status. Encounters involve interaction and hence communication, and interaction and communication generate emotions. Emotions are of great significance to our well-being. Disturbed communication is by far the most commonly reported effect of hearing loss and many handicaps resulting from hearing impairment are of an emotional character. Following Goffman and Scheff I argue that fear of losing face is crucial in interaction, and that shame is an important emotion. Shame is often hidden, misnamed or avoided. But if shame is acknowledged, it is discharged. In traditional audiological rehabilitation, the focus is aural perception, visual perception and speech. I contend that emotional problems, like shame and embarrassment, have to be brought to the fore, the focus less on the compensatory side of rehabilitation and more on the acceptance and coping sides.


N160 of Aiolos Determines its DNA-Binding Activity.
Aiolos is a transcription factor of the Ikaros family. It is expressed in lymphocytes and plays a vital role in the development of lymphatic system. Recently, Aiolos has been found to be ectopically expressed in lung cancer cells and promotes cancer metastasis through repression of p66Shc expression. Blocking DNA-binding activity of Aiolos may benefit cancer patients by preventing further metastasis. However, it is not clear which sequence is essential for its DNA binding. In this study, we found that N160 is a key amino acid to determine the DNA-binding activity of Aiolos. Mutation of N160A resulted in loss of peripheral heterochromatin localization and dissociation with its target gene. Accordingly, Aiolos with N160A could not change the expression of its target genes. Thus, we identified the amino acid (N160) that is essential for Aiolos binding to DNA. Anat Rec, 302:2014-2019, 2019. © 2019 American Association for Anatomy.


Up-to-date Critical Review of the Classification of Epilepsies and Epileptic Seizures.
The classification of epileptic seizures and epilepsies is a subject of interest in various medical disciplines (such as neurology, pediatric neurology, molecular biology and genetics, neurosurgery, pharmacology, radiology, histopathology), and each of them requires a different approach in their practice. In last 15 years, enormous amount of debate in which irrelevant to actual level of knowledge, were ongoing in the literature. Epilepsy classification is a fundamental tool that impacts not only daily clinical practice but also research era and education. The current lack of consensus in this field causes a serious obstacle in patient management, student and resident education, and information sharing among different scientific interest groups. The comparison of different classification proposals by means of positive and negative aspects is beyond the scope of discussion in this article; therefore, I will try to give a brief summary of our current level of understanding. Main issues regarding the classifications proposal are as follows: Concepts of epileptic seizure/epilepsy/syndromeFocal & generalized epilepsy conceptIdiopathic, genetic, cryptogenic, and symptomatic (structural/metabolic) concepts.


Research interests: a study of proposals submitted for approval.
The purpose of this paper is to attempt a simple classification of research interests of nurses and midwives in order to describe the main areas and themes. Caring for the Future( 1 ), previously The Welsh Office Strategic Intent and Direction for Health Services in Wales ( 2 ), is used as a framework for some parts of the classification as it is argued that Caring for the Future should now form the agenda for research and development activity of all disciplines. Common areas for failure in obtaining approval to proceed with research projects are discussed in order to suggest ways in which the researcher can speed the process by anticipating problems.


Safety and efficacy of sirolimus-eluting stent in patients with acute coronary syndrome undergoing emergency procedure.
Sirolimus-eluting stents (SES) reduce restenosis and revascularization rates, compared with bare-metal stents (BMS), in elective percutaneous coronary intervention (PCI). This study investigated the safety and efficacy of SES for emergency PCI in acute coronary syndrome (ACS) patients. The 154 consecutive patients (SES: n=77, BMS: n=77) admitted to hospital with ACS were enrolled in this study. Procedural success (%DS <50%, Thrombolysis In Myocardial Infarction grade 3), major adverse cardiac events (MACE) at 30 days and 8 months, and the incidence of stent thrombosis were evaluated. There was no difference between the groups regarding procedural success. Patients treated with SES had smaller stent diameter (SES 3.04 mm vs BMS 3.24 mm; p=0.01) and longer stent length (25.7 mm vs 21.2 mm; p=0.01). At 30 days, there was no difference between the groups in the incidence of cardiovascular events. At 8 months, patients treated with the SES had a lower rate of repeat PCI (5.6% vs 18.6%; p=0.04) and MACE (9.7% vs 27.1%; p=0.01). Stent thrombosis was no different between groups (1.4% vs 2.9%). In emergency PCI for ACS patients, SES implantation significantly reduced cardiovascular events, compared with BMS, by decreasing the incidence of repeat PCI. The safety profile of SES is equal to that of BMS.


Antisense-induced knockdown of cAMP response element-binding protein downregulates Per1 gene expression in the shell region of nucleus accumbens resulting in reduced alcohol consumption in mice.
We recently showed that circadian genes expressed in the shell region of nucleus accumbens (NAcSh) play a key role in alcohol consumption, though, the molecular mechanism of those effects is unclear. Because CREB-binding protein (CBP) promotes Per1 gene expression, we hypothesized that alcohol consumption would increase CBP expression in the NAcSh and antisense-induced knockdown of CBP would reduce Per1 expression and result in a reduction in alcohol consumption. To test our hypothesis, we performed two experiments. The Drinking-in-the-dark (DID) paradigm was used to evaluate alcohol consumption in male C57BL/6J mice. In Experiment 1 we examined the effects of alcohol consumption on CBP gene expression in the NAcSh. Control animals were exposed to, sucrose [10% (w/v) taste and calorie] and water (consummatory behavior). In Experiment 2 examined the effects of CBP gene silencing on the expression of the Per1 gene in the NAcSh and alcohol consumption in mice exposed to alcohol using the DID paradigm. CBP gene silencing was achieved by local infusion of two doses of either CBP antisense oligodeoxynucleotides (AS-ODNs; Antisense group) or nonsense ODNs (NS-ODNs; Nonsense group) bilaterally microinjected into the NAcSh within 24 h before alcohol consumption on Day 4 of the DID paradigm. The microinfusion sites were verified by cresyl violet staining. Compared to sucrose, alcohol consumption, under the DID paradigm, significantly increased the expression of CBP in the NAcSh. Compared to Controls, bilateral infusion of CBP AS-ODNs significantly reduced the expression of Per1 in the NAcSh and alcohol consumption without affecting the amount of sucrose consumed. Our results suggest that CBP is an upstream regulator of Per1 expression in the NAcSh and may act via Per1 to modulate alcohol consumption.


Weaning of epoprostenol in a small infant receiving concomitant bosentan for severe pulmonary arterial hypertension secondary to bronchopulmonary dysplasia.
Endothelin receptor antagonism is an important therapeutic tool of pulmonary arterial hypertension (PAH). Bosentan was the first orally active, dual antagonist of endothelin receptors in human adults, and has been recently considered for children as well. However, little is known about bosentan treatment in children weighing less than 10 kg. We describe the use of bosentan concomitantly to epoprostenol in an infant weighing 3.5 kg and affected with severe bronchopulmonary dysplasia (BPD) and PAH. At 5 months old, when she presented subsystemic PAH secondary to severe BPD, she was treated with oxygen, digoxin and diuretics. At 8 months old, due to severe PAH not responsive to 100% oxygen, high frequency oscillatory ventilation (HFOV) and nitric oxide (NO), we started epoprostenol and bosentan. Bosentan dose was doubled at 9 months old, when HFOV and NO were slowly discontinued due to improved oxygenation index. Regular echocardiographic measurements of systolic right ventricular pressure were recorded by the method of tricuspidal atrio-ventricular gradient. A four-month combined epoprostenol and bosentan treatment decreased systolic right ventricular pressure from 68% to 40% of the systemic level, till its normalization at 11 months old. Later, when bosentan and epoprostenol were discontinued and sildenafil was started, severe PAH was reported again. Our patient died due to septic shock and refractory hypoxia at 14 months old.


Lipid Nanodisc-Templated Self-Assembly of Gold Nanoparticles into Strings and Rings.
Gold nanoparticles (AuNPs) exhibit strong fluorescent and electromagnetic properties, which can be enhanced upon clustering and used in therapeutic, imaging, and sensing applications. A combination of gold nanoparticles with lipid nanodiscs can be attractive for AuNP self-assembly and useful in biomedical applications. Using molecular dynamics simulations we show that lipid nanodiscs can serve as templates for AuNP clustering into rings and string-like structures. We demonstrate that equilibrium encapsulation of 1 nm hydrophobically modified AuNPs into lipid nanodiscs composed of a mixture of dipalmitoylphosphatidylcholine (DPPC) and dihexanoylphosphatidylcholine (DHPC) lipids occurs at the rim and results in formation of a ring of gold. The interior of the nanodisc is inaccessible to AuNPs due to the DPPC liquid crystalline order. With temperature increase the lipid order diminishes, initiating the nanodisc transformation into a vesicle, upon which encapsulated AuNPs cluster into a close-packed string or nanoring, thereby stalling the vesiculation process at a "round vase" or cup-like stage depending on the AuNP concentration. In contrast, encapsulation of AuNPs by an equilibrium lipid vesicle results in its deformation with randomly clustered AuNPs, in agreement with experimental observations. We characterize the AuNP cluster size and surface-to-surface pair distribution, both of which impact the AuNP luminescent properties. We investigate the effect of alkane tether length on the nanodisc stability and AuNP clustering inside the nanodiscs and vesicles. Our results show that lipid nanodiscs can enhance gold cluster formation, which can be further exploited in imaging applications.


Risk stratification and long-term risk prediction of E6 oncoprotein in a prospective screening cohort in China.
E6 oncoprotein is a necessary agent of HPV driven oncogenic transformation. This study is aimed at evaluating the risk stratification potency of HPV 16/18 E6 oncoprotein (E6) as a triage method for HPV positivity. Moreover, it also acts as a predictor of cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The screening cohort of 1,997 women was followed for a 15 year period in approximate five-year intervals. Participants were concurrently screened by HPV DNA testing (HC2), liquid based cytology (LBC), visual inspection with acetic acid (VIA) and were referred to colposcopy and biopsy if any tests reflected positive. E6 was performed on cervical samples collected from this cohort in 2005 and 2014. The ability of E6 to predict CIN3+ risk after the five- and ten-year interval was evaluated. Among HPV positive women in 2005, E6 indicated the lowest positive rate (9.9%) compared to LBC (48.4%) and VIA (28.0%), however, a higher prevalence rate (10.3%) and 10-year cumulative incidence rate (53.0%) of CIN3+ were detected among women who were E6 positive. Meanwhile, only 4.2% and 2.9% of women with abnormal LBC and positive VIA were diagnosed as prevalent CIN3+ in 2005, 23.0% and 16.5% developed to CIN3+ after year 10, respectively. Strong associations were found between precedent and subsequent HPV persistence and E6 oncoprotein expression (ORadjusted = 40.0 and 21.2, respectively). E6 oncoprotein could serve as a low-cost, highly specific, strongly indicative point-of-care method in the triage and treatment of HPV positive women.