Deciphering the Mrr1/Mdr1 Pathway in Azole Resistance of Candida auris.
Candida auris is an emerging yeast pathogen with a remarkable ability to develop antifungal resistance, in particular to fluconazole and other azoles. Azole resistance in C. auris was shown to result from different mechanisms, such as mutations in the target gene ERG11 or gain-of-function (GOF) mutations in the transcription factor TAC1b and overexpression of the drug transporter Cdr1. The roles of the transcription factor Mrr1 and of the drug transporter Mdr1 in azole resistance is still unclear. Previous works showed that deletion of MRR1 or MDR1 had no or little impact on azole susceptibility of C. auris. However, an amino acid substitution in Mrr1 (N647T) was identified in most C. auris isolates of clade III that were fluconazole resistant. This study aimed at investigating the role of the transcription factor Mrr1 in azole resistance of C. auris. While the MRR1N647T mutation was always concomitant to hot spot ERG11 mutations, MRR1 deletion in one of these isolates only resulted in a modest decrease of azole MICs. However, introduction of the MRR1N647T mutation in an azole-susceptible C. auris isolate from another clade with wild-type MRR1 and ERG11 alleles resulted in significant increase of fluconazole and voriconazole MICs. We demonstrated that this MRR1 mutation resulted in reduced azole susceptibility via upregulation of the drug transporter MDR1 and not CDR1. In conclusion, this work demonstrates that the Mrr1-Mdr1 axis may contribute to C. auris azole resistance by mechanisms that are independent from ERG11 mutations and from CDR1 upregulation.


Preclinical investigations that subserve efforts to employ bone marrow transplantation for rheumatoid or autoimmune diseases.
Bone marrow transplantation (BMT) results in the replacement of host immunohematopoiesis with that of the donor. This procedure may be appropriate for patients with severe combined immunodeficiency disease, Wiskott-Aldrich syndrome, and after lethal myeloablation for treatment of leukemia. Preclinical studies in experimental mice with autoimmune disorders indicate that BMT may successfully prevent the development or induce remission of disease. In some experimental models both marrow and stroma must be transplanted for a successful outcome. Allogeneic, rather than syngeneic, transplants are required for successful outcome in these genetically based spontaneous models of autoimmune disease. However, remissions of relapsing forms of demyelinating autoimmune (acquired) central nervous system diseases can be achieved with both syngeneic and allogeneic marrow transplantation. These preclinical studies form part of the rationale for considering BMT as treatment for severe autoimmune diseases.


Prone Positioning in Postoperative Cardiac Surgery Patients: A Narrative Review.
Limited data are available on the use of the prone position in cardiac surgery. Concerns in performing this maneuver in open cardiac surgery due to the risk of post-sternotomy wound infections and hemodynamic instability do not seem to be supported by existing evidence. Indeed, available data show that prone positioning may improve gas exchange in cardiac surgery patients as well. However, previous studies of prone positioning in this setting were heterogeneous in patient characteristics and outcomes evaluated. As a result, whether prone positioning also may be effective in reducing mortality in patients with postoperative acute respiratory failure, particularly in those who underwent surgery under extracorporeal circulation, remains to be clearly elucidated. The aim of this article is to provide an overview of available literature, which seems to suggest the efficacy of prone positioning, and to make an in-depth analysis of the studies on this topic by evaluating the efficacy of this maneuver on hard endpoints.


Metabolic Surgery on Patients With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.
Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease that is closely related to obesity. Metabolic surgery ameliorates a series of clinical manifestations and related comorbidities of PCOS. However, the overall efficacy of metabolic surgery on PCOS remains uncertain. This systematic review and meta-analysis aimed to evaluate the therapeutic effects of metabolic surgery on obese patients with PCOS. A systematic literature search for relevant studies was conducted on PubMed, Embase, Web of Science, and the Cochrane Library from inception to June 2021. Data extraction and quality evaluation were performed by three researchers, and RevMan 5.4 software was used to conduct the meta-analysis. A total of 14 studies involving 501 obese patients with PCOS were included. Incidence of PCOS in obese women ranged from 5.5% to 63.5% among the included studies. The results showed the incidence of abnormal menstruation decreased from 81% to 15% (OR=0.03, 95% confidence interval (CI): 0.01-0.08), while the incidence of hirsutism dropped from 71% to 38% (OR=0.21, 95% CI: 0.06-0.74). Serum total testosterone and free testosterone levels decreased by 25.92 ng/dL (MD = -25.92, 95% CI: -28.90- -22.93) and 2.28 ng/dL (SMD = -2.28, 95% CI: -3.67- -0.89), respectively. Sex hormone-binding globulin (SHBG) levels increased by 26.46 nmol/L (MD = 26.46, 95% CI: 12.97-39.95). Serum anti-Mullerian hormone (AMH) levels decreased by 1.29 ng/mL (MD = -1.29, 95% CI: -1.92- -0.66). Small sample size studies revealed that pregnancy rates ranged from 95.2% to 100% postoperatively. Metabolic surgery contributed to marked improvement of abnormal menstruation, hirsutism, and levels of free testosterone, total testosterone, SHBG, and AMH in patients with PCOS. Our findings indicate that patients with PCOS are expected to benefit from metabolic surgery, and could help potentially improve their reproductive outcomes. Metabolic surgery could thus be a new viable option for the clinical treatment of PCOS. PROSPERO https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021251524.


Quantum spin correlations through the superconducting-to-normal phase transition in electron-doped superconducting Pr0.88LaCe0.12CuO4-delta.
The quantum spin fluctuations of the S = 1/2 Cu ions are important in determining the physical properties of high-transition-temperature (high T(c)) copper oxide superconductors, but their possible role in the electron pairing of superconductivity remains an open question. The principal feature of the spin fluctuations in optimally doped high-T(c) superconductors is a well defined magnetic resonance whose energy (E(R)) tracks T(c) (as the composition is varied) and whose intensity develops like an order parameter in the superconducting state. We show that the suppression of superconductivity and its associated condensation energy by a magnetic field in the electron-doped high-T(c) superconductor Pr(0.88)LaCe(0.12)CuO(4-delta) (T(c) = 24 K), is accompanied by the complete suppression of the resonance and the concomitant emergence of static antiferromagnetic order. Our results demonstrate that the resonance is intimately related to the superconducting condensation energy, and thus suggest that it plays a role in the electron pairing and superconductivity.


Theoretical prediction of HRgCO(+) ion (Rg=He, Ne, Ar, Kr, and Xe).
Ab initio quantum chemical methods have been employed to investigate the structure, stability, charge redistribution, and harmonic vibrational frequencies of rare gas (Rg=He, Ne, Ar, Kr, and Xe) containing HRgCO(+) ion. The Rg atoms are inserted in between the H and C atoms of HCO(+) ion and the geometries are optimized for minima as well as transition state using second order Moller-Plesset perturbation theory, density functional theory, and coupled-cluster theory [CCSD(T)] methods. The HRgCO(+) ions are found to be metastable and exhibit a linear structure at the minima position and show a nonlinear structure at the transition state. The predicted ion is unstable with respect to the two-body dissociation channel leading to the global minima (HCO(+)+Rg) on the singlet potential surface. The binding energies corresponding to this channel are -406.4, -669.3, -192.3, -115.4, and -52.2 kJ mol(-1) for HHeCO(+), HNeCO(+), HArCO(+), HKrCO(+), and HXeCO(+) ions, respectively, at CCSD(T) method. However, with respect to other two-body dissociation channel, HRg(+)+CO, the ions are found to be stable and have positive energies except for HNeCO(+) at the same level of theory. The computed binding energies for this channel are 15.0, 28.8, 29.5, and 29.1 kJ mol(-1) for HHeCO(+), HArCO(+), HKrCO(+), and HXeCO(+) ions, respectively. Very high positive three-body dissociation energies are found for H+Rg+CO(+) and H(+)+Rg+CO dissociation channels. It indicates the existence of a very strong bonding between Rg and H atoms in HRgCO(+) ions. The predicted ions dissociate into global minima, HCO(+)+Rg, via a transition state involving H-Rg-C bending mode. The barrier heights for the transition states are 22.7, 10.1, 13.1, and 15.0 kJ mol(-1) for He, Ar, Kr, and Xe containing ions, respectively. The computed two-body dissociation energies are comparable to that of the experimentally observed mixed cations such as ArHKr(+), ArHXe(+), and KrHXe(+) in an electron bombardment matrix isolation technique. Thus HRgCO(+) cations may also be possible to prepare and characterize similar to the mixed cations (RgHRg('))(+) in low temperature matrix isolation technique.


Self-directed care: participants' service utilization and outcomes.
Self-directed care (SDC) is a mental health service delivery model in which participants budget the state dollars allotted for their care to purchase the goods and services they deem most appropriate for achieving their recovery goals. This study examines the demographic characteristics, service utilization patterns, and outcomes of individuals enrolled in the Florida Self-Directed Care (FloridaSDC) program, which is the oldest and most established SDC program in the United States for individuals diagnosed with a severe and persistent mental illness. This is a naturalistic descriptive study in which demographic, service utilization, and outcome data (i.e., Functional Assessment Rating Scale (FARS) scores, days in the community, days worked, monthly income, discharge status) were collected from the clinical and fiscal records of 136 FloridaSDC participants. Key findings suggest that FloridaSDC participants had very little income and largely utilized their budgets to subsidize their living expenses. Though most participants did not work or earn income and very few left the program due to employment, participants' FARS scores improved modestly and nearly all participants remained in the community throughout the study period. Participants' service purchases were rational given the poverty in which they live, and their outcomes did not suffer when they controlled decisions regarding their service needs. These findings highlight the utility and value of the personalized budgeting and individualized planning components of SDC. Findings also point to the need for practitioners to implement innovative strategies to enhance participants' employment readiness and supported employment opportunities. (PsycINFO Database Record


Enumerating outdoor aeromycota in suburban West Bengal, India, with reference to respiratory allergy and meteorological factors.
Aeromycota may act as a reservoir of aeroallergens and upon inhalation may induce IgE-mediated Type I hypersensitivity reaction in pre-sensitized individuals. The total aerospora of an outdoor occupational setting (agricultural farm) in suburban West Bengal was sampled for two years (2002-2004) by a Burkard sampler. Concurrently, the cultivable aeromycota were trapped by an Andersen 2-stage sampler, cultured and tested for allergenic potential by skin prick test. The relationships between various climatic factors (temperature, relative humidity, rainfall and wind speed) and the distribution of aerospora were explored by Spearman correlation test. The antigenic extracts of 15 fungal species belonging to Alternaria, Aspergilli/Penicilli, Cladosporium, Curvularia, Drechslera, and Nigrospora evoked 10.8-54.8% skin reactivity in subjects with clinical history of respiratory allergy. The aerospora with skin sensitizing potential collectively represented a considerable fraction (52.3-58.4%) of the total aeromycota. The airborne concentration of Alternaria spores was higher than its borderline value of 100 spores m(-3) in May and June, whereas Cladosporium spore count exceeded its threshold limit value (3,000 spores m(-3)) in December, suggesting that this particular time of the year poses allergenic risk for individuals sensitive to these aerospora. Daily minimum temperature and rainfall appeared to be the most important meteorological factors to affect the concentration of aerospora in the study area.


[Calcification of the intervertebral disk in children].
Authors present two cases of calcification of the intervertebral disc. They provide an analysis of etiology, symptoms, and roentgenographic clinic course, as well as a review of cases which have been reported in literature.


Giant Parapharyngeal Space Pleomorphic Adenoma Causing Acute Airway Obstruction.
Primary parapharyngeal space (PPS) tumors are rare, representing only 0.5% of all head and neck neoplasms. About 80% of tumors of this space are benign, and 20% are malignant. They often pose therapeutic and diagnostic problems due to variable non-specific symptoms and the complex anatomy of this space. Pleomorphic adenoma is the most common benign tumor of this space. It presents as an asymptomatic mass causing mild bulging in the soft palate or tonsillar region, or fullness near the angle of the mandible in the neck. We report the case of a 60-year-old male admitted to the emergency department with breathing difficulty and acute stridor. He was unable to maintain oxygen saturation, and an emergency tracheostomy was performed. Radiological and cytological evaluation were performed, and the patient was diagnosed as having primary PPS pleomorphic adenoma. The tumor was excised via the transcervical approach. The rarity of tumor in this space and unusual life-threatening presentation prompted the authors to report this case. To our knowledge, this is the third case reported worldwide of a pleomorphic adenoma causing upper airway obstruction and acute respiratory failure.


Paroxysmal nocturnal hemoglobinuria: analysis of 40 cases.
Forty cases of paroxysmal nocturnal hemoglobinuria (PNH) were studied from 1978 to 1988. Thirty patients were male and 10 were female. Their ages ranged from 15 to 58 years with a median of 32 years. Symptoms related to anemia (85%) and dark colored urine (45%) were the most frequent clinical manifestations. Seven patients (17.5%) had a previous history of aplastic anemia. The interval between the diagnosis of aplastic anemia and PNH ranged from 11 months to 26 years. All the patients had anemia with varying combinations of cytopenia. In 36 patients, bone marrow examinations were performed, and 32 were hypercellular, one normocellular and 3 hypocellular. Documented thrombosis was noted in 3 patients, involving the intra-abdominal, cerebral and renal veins, respectively. The patient with intra-abdominal venous thrombosis subsequently died of E. coli septicemia. The remaining two patients achieved complete recovery. All 40 patients were treated with corticosteroids and/or anabolic agents, 32 (80%) patients improved and 4 (10%) achieved normal hemoglobin levels. Our studies demonstrate that there is a male predominance in Chinese PNH patients and the incidence of thrombotic complications is much lower than that reported by Western countries.


Cerebral Blood Flow Measurement in Healthy Children and Children Suffering Severe Traumatic Brain Injury-What Do We Know?
Traumatic brain injury is the leading cause of death in children. Children with severe TBI are in need of neurointensive care where the goal is to prevent secondary brain injury by avoiding secondary insults. Monitoring of cerebral blood flow (CBF) and autoregulation in the injured brain is crucial. However, there are limited studies performed in children to investigate this. Current studies report on age dependent increase in CBF with narrow age range. Low initial CBF following TBI has been correlated to poor outcome and may be more prevalent than hyperemia as previously suggested. Impaired cerebral pressure autoregulation is also detected and correlated with poor outcome but it remains to be elucidated if there is a causal relationship. Current studies are few and mainly based on small number of patients between the age of 0-18 years. Considering the changes of CBF and cerebral pressure autoregulation with increasing age, larger studies with more narrow age ranges and multimodality monitoring are required in order to generate data that can optimize the therapy and clinical management of children suffering TBI.


Impact of individualized pharmaceutical care on efficacy and safety of opioid-tolerant outpatients with cancer pain: a multicenter randomized controlled trial.
Managing cancer pain is a growing challenge. Individualized pharmaceutical care is particularly important for opioid-tolerant outpatients due to variation in terms of their knowledge about pain, treatment adherence, and risk of experiencing inadequate analgesia and severe adverse events. This study aimed to determine the influence of individualized pharmaceutical care on outcomes in opioid-tolerant outpatients with cancer pain. A multicenter, open-label, randomized, controlled study was carried out. Opioid-tolerant outpatients experiencing chronic cancer pain and receiving sustained-release opioids were randomly assigned to the intervention group and the control group with a 1:1 ratio. The intervention group received individualized pharmaceutical care, while the control group received conventional care during 4-week period. The primary endpoint was medication adherence on the intention-to-treat (ITT) population. Secondary outcomes included the patients' knowledge of cancer pain and pain medications, pain score, frequency of breakthrough pain, quality of life (QoL) which were assessed on the ITT population. Adverse events were evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 4.0 on the per-protocol (PP) population. A total of 118 patients were enrolled, and 102 patients (51 in each group) completed the 30-day follow-up from six oncology centers in China. The proportion of patients adhering to opioid medication increased to similar levels in the two groups during the 4 weeks (P=0.149). The intervention group had a significantly lower pain score at 4 weeks compared to the control group (P=0.015), and the proportion of participants without breakthrough pain was significantly higher at 4 weeks than at baseline in the intervention group (P=0.029), but not in the control group (P=0.322). The two groups did not differ significantly in terms of QoL or adverse events. Our results suggest that individualized pharmaceutical care can markedly reduce patient-related problems and significantly improve pain control in opioid-tolerant outpatients. These findings validate the recommendations to include clinical pharmacists in the management of cancer pain. ClinicalTrials.gov identifier: NCT03439904.


SLE: translating lessons from model systems to human disease.
Systemic lupus erythematosus (SLE, lupus) results from immune-mediated damage to multiple organs. Its pathogenesis should be viewed as a series of steps, beginning with impaired immune regulation that permits self-reactive T-B-cell activation, which results in the production of autoantibodies. Activated T and B cells then infiltrate tissues, which along with autoantibody and immune complex deposition, triggering local events that ultimately cause organ damage. Although improved understanding of early autoimmune events might open up avenues for disease prevention, future investigations must focus on the mechanisms of end-organ damage in model systems and how to translate this knowledge into human disease. Understanding the mechanisms of each pathogenetic step would provide a rational basis for the development of disease stage-specific diagnostic markers and treatments.


Are communication activities shaped by environmental constraints in reverberating and absorbing forest habitats?
In the dense vegetation of temperate or tropical forests, communication processes are constrained by propagation-induced modifications of the transmitted sounds. The presence of leaves, trunks and branches induces important sound reverberation and absorption leading to diminution of the signal energy as well as qualitative modifications. The aim of this paper is to briefly review the different strategies used by birds to manage with these constraints. At the emitter's level, an adapted emission behavior which takes into account both the physical heterogeneities of the forest environment and the temporal variations of the acoustic constraints, is especially useful to control the active space of signaling. The coding of information into acoustic parameters that have different susceptibility to propagation constraints is also of great interest. At the receiver's level, an adaptive reception behavior (listening post) and a great tolerance to sound degradation during the decoding process are the keys to an optimal communication process.


Maternal lineages of Pinus densata, a diploid hybrid.
Previous morphological, allozyme and chloroplast DNA data have suggested that Pinus densata originated through hybridization between P. tabuliformis and P. yunnanensis. In the present study, sequence and restriction site analyses of maternally inherited mitochondrial nad1 intron were used to detect variation patterns in 19 populations of P. tabuliformis, P. yunnanensis and P. densata. A total of three mitotypes (A, B, C) were detected. All but one of the populations of P. yunnanensis possessed mitotype B while all populations of P. tabuliformis had mitotype A. Pinus densata populations, on the other hand, harboured both mitotypes A and B, which are characteristic of P. tabuliformis and P. yunnanensis, respectively. This result gives strong additional evidence supporting the hybrid origin of this diploid pine. The distribution of mitotypes indicated very different mating compositions and evolutionary history among P. densata populations. It seems that local founder populations and backcrosses may have played important roles in the early establishment of P. densata populations. The uplift of the Tibetan Plateau had a significant impact on the distribution of maternal lineages of P. densata populations.


Chiral discrimination between thalidomide enantiomers using a solid surface with two-dimensional chirality.
Chiral discrimination between thalidomide enantiomers was achieved using the self-assembled monolayer (SAM) of an atropisomeric compound, 1,1'-binaphthalene-2,2'-dithiol (BNSH), which takes a two-dimensional chiral arrangement on gold(111) surface. Interestingly, an "all-or-none" type enantioselectivity appears; one enantiomeric form of BNSH SAM allows the adsorption of only one enantiomer of thalidomide. In addition, the response of a racemic SAM of BNSH was revealed to be one-half of that caused by pure enantiomeric SAM.


Professional Stereotypes of Interprofessional Education Naive Pharmacy and Nursing Students.
Objective. To assess and compare interprofessional education (IPE) naive pharmacy and nursing student stereotypes prior to completion of an IPE activity. Methods. Three hundred and twenty-three pharmacy students and 275 nursing students at Mercer University completed the Student Stereotypes Rating Questionnaire. Responses from pharmacy and nursing students were compared, and responses from different level learners within the same profession also were compared. Results. Three hundred and fifty-six (59.5%) students completed the survey. Pharmacy students viewed pharmacists more favorably than nursing students viewed pharmacists for all attributes except the ability to work independently. Additionally, nursing students viewed nurses less favorably than pharmacy students viewed nurses for academic ability and practical skills. There was some variability in stereotypes between professional years. Conclusion. This study confirms the existence of professional stereotypes, although overall student perceptions of their own profession and the other were generally positive.


Early diagnosis of avascular necrosis of the femoral head.
Early diagnosis is important because it leads to early treatment and a better chance of saving the femoral head. The first, and perhaps the most important step, in making an early diagnosis is a heightened clinical awareness of this condition. The physician must be familiar with the nonspecific symptoms, physical findings, and laboratory tests, as well as with the various predisposing factors associated with avascular necrosis. Other causes of hip abnormality or symptoms must be ruled out, as AVN is in part a diagnosis of exclusion. Imaging techniques, which are extremely useful in the early diagnosis of this condition, include good-quality plain radiographs, technetium bone scans, and especially MRI. Technetium bone scans and MRI are quite sensitive, although not entirely specific, and must be used in conjunction with a comprehensive clinical evaluation of the patient.


Frequency of leisure-time physical activity and serum 25-hydroxyvitamin D levels in the US population: results from the Third National Health and Nutrition Examination Survey.
The decline in vitamin D status among older people is probably due to decreased synthesis of vitamin D by sun-exposed skin and/or decreased outdoor activity. The authors examined the association between outdoor leisure physical activity and serum 25-hydroxyvitamin D in the Third National Health and Nutrition Examination Survey (1988-1994) (n = 15,148 aged >/=20 years). The mean 25-hydroxyvitamin D concentration declined with increasing age, with 79, 73, and 68 nmol/liter for persons aged 20-39, 40-59, and 60 or more years. The proportion that engaged in outdoor activity in the past month was 80% for persons aged 20-39 and 40-59 years but 71% for those aged 60 or more years. In contrast, the mean difference in 25-hydroxyvitamin D between those who participated in outdoor activities daily compared with those who did not participate in the past month was similar for the youngest and oldest age groups: 13 and 16 nmol/liter, respectively. Those persons aged 60 or more years who participated in daily outdoor activities had a mean 25-hydroxyvitamin D concentration similar to that of persons aged 20-39 years: 77 versus 79 nmol/liter, respectively. These nationally representative data suggest that persons aged 60 or more years can synthesize enough vitamin D from daily outdoor activities to maintain vitamin D levels similar to those of young adults.


Changes in algal community structure via density- and trait-mediated indirect interactions in a marine ecosystem.
In various terrestrial and aquatic ecosystems, predators affect resources indirectly via intermediate prey. Such indirect interactions involve reducing the density of the prey (density-mediated indirect interactions, DMIIs) or changing the behavioral, morphological, or life history traits of the prey (trait-mediated indirect interactions, TMIIs). Although the importance of TMIIs has been highlighted recently, the strengths of both DMIIs and TMIIs under natural conditions have rarely been evaluated, especially in the context of resource community structure. We studied a three-level marine food chain involving the carnivorous snail Thais clavigera, its limpet prey Siphonaria sirius, and the limpet's food sources, the algae Lithoderma sp. and Ulva sp. We measured the strengths of DMIIs and TMIIs and observed how the algal community changes under the pressure of natural predation by T. clavigera on S. sirius. Neither DMIIs nor TMIIs affected the total algal cover or chlorophyll content per unit area. However, both types of indirect interactions caused similar changes in algal composition by increasing the cover of Ulva and decreasing the cover of Lithoderma. This change in the algal community was caused by a reduction in the limpet's preferential consumption of the competitively dominant Ulva over Lithoderma. These results suggest that both DMIIs and TMIIs have similar effects on the changes in resource community structure under natural conditions.


Cognitive-behavioral therapy for anxiety disorders: an update on the empirical evidence.
A large amount of research has accumulated on the efficacy and effectiveness of cognitive-behavioral therapy (CBT) for anxiety disorders including posttraumatic stress disorder, obsessive-compulsive disorder, panic disorder, generalized anxiety disorder, social anxiety disorder, and specific phobia. The purpose of the current article is to provide an overview of two of the most commonly used CBT methods used to treat anxiety disorders (exposure and cognitive therapy) and to summarize and discuss the current empirical research regarding the usefulness of these techniques for each anxiety disorder. Additionally, we discuss the difficulties that arise when comparing active CBT treatments, and we suggest directions for future research. Overall, CBT appears to be both efficacious and effective in the treatment of anxiety disorders, but dismantling studies are needed to determine which specific treatment components lead to beneficial outcomes and which patients are most likely to benefit from these treatment components.


The amino-terminal module of the C4b-binding protein alpha-chain is crucial for C4b binding and factor I-cofactor function.
C4b-binding protein (C4BP) regulates the classical pathway C3-convertase of the complement system. Human C4BP is composed of seven identical subunits (alpha-chains) and one unique one (beta-chain). Both types of chains contain homologous repeats called complement control proteins (CCPs); the alpha-chain contains eight CCPs and the beta-chain three. Each alpha-chain contains a binding site for C4b although the detailed localization of this binding site is not known. We have used three different chimeric proteins, originally designed to localize the protein S-binding site on C4BP, to demonstrate the importance of the amino-terminal part of the alpha-chain for the complement-regulatory functions of C4BP. These recombinant proteins were composed of C4BP alpha-chains with one, two or three of the amino-terminal CCPs replaced by corresponding CCPs from the C4BP beta-chain. Furthermore, seven different monoclonal antibodies were raised against C4BP and characterized using the recombinant chimeric proteins. Whereas all three recombinant chimeras bind protein S with the same affinity as plasma-purified C4BP, none of them bound to C4b. Three of the antibodies, which were found to bind to alpha-chain CCP 1 and CCP 2, completely inhibited the binding of plasma-purified C4BP to immobilized C4b. In addition, two of these antibodies totally blocked the factor I-cofactor activity of C4BP in a C4b-degradation assay. The binding site for one of the monoclonal antibodies was also studied using electron microscopy where it was confirmed that this antibody bound to the amino-terminal tip of the alpha-chain. These results show that the amino-terminal CCP of the C4BP alpha-chain (CCP 1) is crucial for the C4b binding and factor I-cofactor activity.


Isolation and characterization of a genetic variant of bovine proinsulin.
A genetic variant of bovine proinsulin has been isolated using preparative reverse-phase HPLC. The new proinsulin (bovine proinsulin II) differs from the known proinsulin (bovine proinsulin I) by a single amino acid residue at position C-48 in the connecting peptide. The amino acid replacement is a leucine substitution for proline. The two proinsulins were found in a ratio of approximately 9:1, proinsulin I: proinsulin II. No chemical or biological differences were observed for the two proinsulins other than their different elution times on reverse-phase HPLC.


Assessment of primary health care facilities' service readiness in Nigeria.
Effective delivery of healthcare services requires availability of adequate infrastructure, diagnostic medical equipment, drugs and well-trained medical personnel. In Nigeria, poor funding and mismanagement often characterize healthcare service delivery thereby affecting coverage and quality of healthcare services. Therefore, the state of service delivery in Nigeria's health sector has come under some persistent criticisms. This paper analyzed service readiness of Primary Health Care (PHC) facilities in Nigeria with focus on availability of some essential drugs and medical equipment. Service Delivery Indicator (SDI) data for PHC in Nigeria were used. The data were collected from 2480 healthcare facilities from 12 states in the Nigeria's 6 geopolitical zones between 2013 and 2014. Data were analyzed with descriptive statistics, Principal Component Analysis (PCA) and Ordinary Least Square regression. Medical disposables such as hand gloves and male condoms were reported to be available in 77.18 and 44.03% of all the healthcare facilities respectively, while immunization services were provided by 86.57%. Functional stethoscopes were reported by 77.22% of the healthcare facilities, while only 68.10% had sphygmomanometers. In the combined healthcare facilities, availability of some basic drugs such as Azithromycin, Nifedipine, Dexamethasone and Misoprostol was low with 10.48, 25.20, 21.94 and 17.06%, respectively, while paracetamol and folic acid both had high availability with 74.31%. Regression results showed that indices of drug and medical equipment availability increased significantly (p < 0.05) among states in southern Nigeria and with presence of some power sources (electricity, generators, batteries and solar), but decreased among dispensaries/health posts. Travel time to headquarters and rural facilities significantly reduced indices of equipment availability (p < 0.05). It was concluded that for Nigeria to ensure better equity in access to healthcare facilities, which would facilitate achievement of some health-related sustainable development goals (SDGs), quality of services at its healthcare facilities should be improved. Given some differences between availability of basic medical equipment and their functionality, and lack of some basic drugs, proper inventory of medical services should be taken with effort put in place to increase funding and ensure proper management of healthcare resources.


Psychosocial biomarker research: integrating social, emotional and economic factors into population studies of aging and health.
There are complex reciprocal relationships between health and social, emotional and economic factors in aging populations. Social and affective neurosciences are rapidly developing an understanding of the mechanisms underlying these phenomena using sophisticated behavioural, neuroimaging and psychophysiological methods. These techniques are often complex and expensive, so are generally used in relatively small selected samples rather than in large-scale cohort studies. However, an understanding of the significance of these processes in health and well-being depends on integrating findings from social and affective neuroscience into population-level studies. The aim of this article is to describe how a population perspective on the determinants of health and well-being in old age articulates with the agenda of social, affective and economic neuroscience, particularly through the application of psychosocial biomarker research. Social and affective neuroscience and epidemiological approaches provide complementary research strategies for understanding the mechanisms linking social, emotional and economic factors with health risk. This will be illustrated primarily from findings from two studies conducted at University College London, the Whitehall II Study and the English Longitudinal Study of Ageing.


A comparative study of epithelialization of subcutaneous fascial flaps and muscle-only flaps in the oral cavity. A rabbit model.
Epithelialization of subcutaneous fascial flaps and muscle-only flaps used for reconstruction of the oral mucosa were studied in a rabbit model. Angiography was performed to help to design a subcutaneous cervical fascial flap and a cleidomastoid muscle-only flap. These flaps were transferred into a mucoperiosteal defect on the mandibular alveolus. The flaps were gradually infiltrated by acute inflammatory cells from the periphery and then replaced by granulation tissue originating from the oral mucosa. The epithelialization was by secondary intention. An epithelial tongue from the surrounding epithelium migrated onto the granulating flaps with eventual coverage after three weeks. After two months, the muscle-only flap was covered by a poorly organized epithelium, different from the highly uniform epithelium in the fascial flap. The granulation tissue which replaced the muscle-only flap matured to fibrous tissue, associated with severe contraction. This was characterized by dense regular collagen fibers, no elastic fibers, and few capillaries, while the fibrous tissue which replaced the fascial flap was characterized by random collagen and elastic fiber morphology and numerous dilated blood vessels, and was associated with mild contraction. This experiment supports the view that the different extracellular matrices of these flaps may play a role in epithelial configuration and contraction.


A Fourier reconstruction algorithm with constant attenuation compensation using 180 degrees acquisition data for SPECT.
In this paper, we develop an approximate analytical reconstruction algorithm that compensates for uniform attenuation in 2D parallel-beam SPECT with a 180-degree acquisition. This new algorithm is in the form of a direct Fourier reconstruction. The complex variable central slice theorem is used to derive this algorithm. The image is reconstructed with the following steps: first, the attenuated projection data acquired over 180 degrees are extended to 360 degrees and the value for the uniform attenuator is changed to a negative value. The Fourier transform (FT) of the image in polar coordinates is obtained from the Fourier transform of an analytic function interpolated from an extension of the projection data according to the complex central slice theorem. Finally, the image is obtained by performing a 2D inverse Fourier transform. Computer simulations and comparison studies with a 360-degree full-scan algorithm are provided.


Inexpensive, safe and simple nasoenteral intubation--an alternative for the cost conscious.
The efficacy and safety of nasoenteral feedings via small bore, flexible tubes have been extensively studied and reported. Most of the tubes currently used have similar characteristics including a high price ($7.00-$17.30 per tube). Our study using inexpensive ($0.55 each), polyvinyl pediatric feeding tubes and reusable guide wires in 21 patients shows that a weighted tip is not necessary for the passage of tubes into the duodenum (19/27 tubes passed) and that with proper nursing care and patient cooperation, the tubes can remain in place and patent for periods up to 71 days. The cost savings using the ubiquitous pediatric feeding tube and a reusable guide wire are significant (between $6.25 and $16.55 per tube used) and make this a more cost conscious alternative.


[Drug interactions of lithium. Review of the literature].
The authors have reviewed the literature regarding interactions of lithium and other drugs. The hypothetical physiopathogenic mechanisms of these interactions are discussed even if in some cases the mechanisms are not understood. The interactions of diuretic and anti-inflammatory drugs with lithium will mainly affect renal function and ionic exchange across cell membranes. Other drugs become toxic when associated to lithium because of the addition of their adverse effects. The beneficial effects of some drugs associations are also discussed.


Cytotoxic effects and apoptosis induction of enrofloxacin in hepatic cell line of grass carp (Ctenopharyngodon idellus).
We determined the effect of enrofloxacin on the lactate dehydrogenase (LDH) release, reactive oxygen species (ROS), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), malondialdehyde (MDA), mitochondria membrane potential (ΔΨm) and apoptosis in the hepatic cell line of grass carp (Ctenopharyngodon idellus). Cultured cells were treated with different concentrations of enrofloxacin (12.5-200 ug/mL) for 24 h. We found that the cytotoxic effect of enrofloxacin was mediated by apoptosis, and that this apoptosis occurred in a dose-dependent manner. The doses of 50,100 and 200 μg/mL enrofloxacin increased the LDH release and MDA concentration, induced cell apoptosis and reduced the ΔΨm compared to the control. The highest dose of 200 ug/mL enrofloxacin also significantly induced apoptosis accompanied by ΔΨm disruption and ROS generation and significantly reduced T-AOC and increased MDA concentration compared to the control. Our results suggest that the dose of 200 ug/mL enrofloxacin exerts its cytotoxic effect and produced ROS via apoptosis by affecting the mitochondria of the hepatic cells of grass carp.


Early versus late spinal decompression surgery in treatment of traumatic spinal cord injuries; a systematic review and meta-analysis.
Despite the vast number of surveys, no consensus has been reached on the optimum timing of spinal decompression surgery. This systematic review and meta-analysis aimed to compare the effects of early and latespinal decompression surgery on neurologic improvement and post-surgical complications in patients with traumatic spinal cord injuries. Two independent reviewers carried out an extended search in electronic databases. Data of neurological outcome and post-surgery complication were extracted. Finally, pooled relative risk (RR) with a 95% confidence interval (CI) was reported for comparing of efficacy of early and late surgical decompression. Eventually 22 studies were included. The pooled RRwas 0.77 (95% CI: 0.68-0.89)for at least one grade neurological improvement, and 0.84 (95% CI: 0.77-0.92)for at least two grade improvement. Pooled RR for surgical decompression performed within 12 hours after the injury was 0.26 (95% CI: 0.13-0.52; p<0.001), while it was 0.75 (95% CI: 0.63-0.90; p=0.002) when the procedure was performed within 24 hours, and 0.93 (95% CI: 0.76-1.14; p=0.48) when it was carried out in the first 72 hours after the injury. Surgical decompression performed within 24 hours after injury was found to be associated with significantly lower rates of post-surgical complications (RR=0.77; 95% CI: 0.68-0.86; p<0.001). The findings of this study indicate that early spinal decompression surgery can improve neurologic recovery and is associated with less post-surgical complications. The optimum efficacy is observed when the procedure is performed within 12 hours of the injury.


The chromosome 9q subtelomere deletion syndrome.
The chromosome 9q subtelomere deletion syndrome (9qSTDS) is among the first and most common clinically recognizable syndromes to arise from widespread testing by fluorescent in situ hybridization (FISH) of subtelomere deletions. There are about 50 reported cases worldwide. Affected individuals invariably have severe hypotonia with speech and gross motor delay. The facial gestalt is distinct and features absolute or relative micro- or brachycephaly, hypertelorism, synophrys, and/or arched eyebrows, mid-face hypoplasia, a short nose with upturned nares, a protruding tongue with everted lower lip and down-turned corners of the mouth. Approximately half of affected individuals have congenital heart defects (primarily ASD or VSD). A significant minority have epilepsy and/or behavioral and sleep disturbances. A variety of other major and minor eye, ear, genital, and limb anomalies have been reported. Most patients have sub-microscopic deletions of the subtelomere region of chromosome 9q34.3 that range from <400 kb to >3 Mb. The 9qSTDS is caused by haplo-insufficiency of EHMT1, a gene whose protein product (Eu-HMTase1) is a histone H3 Lys 9 (H3-K9) methyltransferase. This was established by identification of three patients with features of the syndrome and either mutations or a balanced translocation in EHMT1. H3-K9 histone methylation is restricted to the euchromatin of mammals and functions to silence individual genes. Deletion size does not correlate with the severity of the 9qSTDS since patients with mutations in EHMT1 are as severely affected as those with submicroscopic deletions. Patients clinically suspected of having the 9qSTDS but with normal subtelomere deletion testing by FISH or MLPA should be considered for detailed 9q MLPA analysis and/or sequencing of EHMT1. EHMT1 is another example in the growing list of genes responsible for brain development that appear to play a role in chromatin remodeling. Published 2007 Wiley-Liss, Inc.


Anti-D and Intravenous Immunoglobulin Treatments in Chronic Idiopathic Thrombocytopenic Purpura.
The aim of this prospective study was to evaluate the data from 29 patients diagnosed as chronic refractory idiopathic thrombocytopenic purpura (ITP) treated with anti-D immunoglobulin and intravenous immunoglobulin G (IVIG). We used anti-D and IVIG in 11 and 18 patients respectively in whom the previous treatments including corticosteroids and splenectomy had been unsuccessful. The complete response rates were significantly higher in IVIG arm (55.5% to 18.1%) with a duration of 8 weeks. The overall efficacy of IVIG in the chronic ITP is similar to previous data, however we found lower platelet responses in patients treated with anti-D that can be attributed to the lower sucess in the splenectomized patients.


The genus Sicoderus Vanin 1986 (Coleoptera: Curculionidae: Curculioninae: Erodiscini) in the West Indies.
The genus Sicoderus Vanin is revised for the West Indies. A total of 32 species are known with 18 new species described herein as follows: Sicoderus aeneus (Haiti), S. alternatus (Dominican Republic), S. bautistai (Dominican Republic, Haiti), S. beatyi (Cuba), S. bipunctiventris (Cuba), S. caladeler (Cuba), S. detonnancouri (Dominican Republic), S. franzi (Puerto Rico), S. guanyangi (Dominican Republic), S. humeralis (Dominican Republic), S. lucidus (Dominica), S. medranae (Dominican Republic, Haiti), S. perezi (Dominican Republic), S. pseudostriatolateralis (Dominican Republic, Haiti), S. striatolateralis (Dominican Republic), S. thomasi (Haiti), S. turnbowi (Dominican Republic), and S. woodruffi (Grenada). All species are described or redescribed, natural history information is summarized and a listing of locality data from all specimens examined is included. A key is provided to all West Indian species of the genus. All species distributions are mapped and all (excepting S. propinquus Vanin) are represented by habitus images and images of male genitalia.


Individually experienced heat stress among elderly residents of an urban slum and rural village in India.
The elderly are one of the most vulnerable groups to heat-related illnesses and mortality. In tropical countries like India, where heat waves have increased in frequency and severity, few studies have focused on the level of stress experienced by the elderly. The study presented here included 130 elderly residents of Kolkata slums and 180 elderly residents of rural villages about 75 km south of Kolkata. It used miniature monitoring devices to continuously measure temperature, humidity, and heat index experienced during everyday activities over 24-h study periods, during hot summer months. In the Kolkata slum, construction materials and the urban heat island effect combined to create hotter indoor than outdoor conditions throughout the day, and particularly at night. As a result, elderly slum residents were 4.3 times more likely to experience dangerous heat index levels (≥ 45°C) compared to rural village elderly. In both locations, the median 24-h heat indexes of active elderly were up to 2°C higher than inactive/sedentary elderly (F = 25.479, p < 0.001). Among Kolkata slums residents, there were no significant gender differences in heat exposure during the day or night, but in the rural village, elderly women were 4 times more likely to experience dangerous heat index levels during the hottest times of the day compared to elderly men. Given the decline in thermoregulatory capacity associated with aging and the increasing severity of extreme summer heat in India, these results forecast a growing public health challenge that will require both scientific and government attention.


The Incidence of Allergic Disorders in First Degree Relatives of Neonates with Transient Tachypnea of Neonate.
The role of maternal allergic disorders to increase the risk of Transient Tachypnea of Neonate (TTN) in neonates remained unclear. We determined the incidence of allergic disorders in first degree relatives of neonates suffered from TTN to clear role of these allergic disorders to predispose TTN in neonates. In a cross-sectional study carried out at Fatemieh hospital between September 2010 and September 2011, all consecutive neonates with the diagnosis of TTN were included into the study. Those neonates were not treated after 5 days of hospitalization were excluded. Baseline information with regard to the history of allergic diseases among first degree relatives of neonates were charted from family members using a structured questionnaire at enrolment by interviewing and examination if required. The two groups were matched for baseline data including neonate gender, birth weight, and type of delivery. In the TTN group, one of first degree relatives (2.9%) suffered from bronchial asthma and two of them (5.7) had atopic dermatitis. In total, allergic diseases was revealed in 8.6% of first degree relatives of neonates with TTN. Besides, none of the first degree relatives of neonates in healthy neonates group experienced bronchial asthma or atopic dermatitis. Allergic rhinitis was not also found in the relatives of the two study neonates groups. Comparing incidence of allergic diseases in first degree relatives of neonates in TTN and healthy groups showed no significant difference (8.6% in TTN group versus 0.0% in healthy group, p = 0.076). Our study showed that the incidence of allergic disorders in first degree relatives of neonates suffered from TTN is higher than healthy newborns, but these differences are not statistically significant.


Acinic cell carcinoma of the sublingual gland accompanied by bone formation.
A rare case of acinic cell carcinoma of the sublingual gland accompanied by bone formation is reported. The patient is a 79-year-old male who was referred to Yokohama Minami Kyosai Hospital with sublingual swelling. A tumor mass, 20 x 10 mm in diameter, was detected on the right side of the floor of the mouth. Computed tomography (CT) revealed a mass lesion with calcification in the sublingual gland. The patient underwent total sialadenectomy of the sublingual gland with conservation of the lingual nerve. Histologically, the lesion showed amylase-positive atypical cells with thyroid gland-like arrangement, and mature bone tissue in the stroma. Based on these findings, the tumor was diagnosed as acinic cell carcinoma accompanied by bone formation. Postoperative recovery was uneventful, and two years after surgery, there are no signs of distant metastases or recurrence.


[Mechanism of puerarin reversing SH-SY5Y cell injury induced by Aβ_(1-42) based on proteomics].
Puerarin has the anti-Alzheimer's disease (AD) activity,which can reverse nerve injury induced by Aβand inhibit neuronal apoptosis.However,its potential pharmacodynamic mechanism still needs to be further researched.The occurrence and development of AD is due to the change of multiple metabolic links in the body,which leads to the destruction of balance.Puerarin may act on multiple targets and multiple metabolic processes to achieve therapeutic purposes.Quantitative proteomic analysis provides a new choice to understand the mechanism as completely as possible.This research adopted SH-SY5Y cells induced by Aβ_(1-42)to establish AD cell model,and Aβimmunofluorescence detection showed that Aβdecreased significantly after puerarin intervention.The mechanism of puerarin reversing SH-SY5Y cell injured by Aβ_(1-42)was further explored by using label-free non-labeled quantitative technology and Western blot detection based on bioinformatics analysis result.The results showed that most of the differential proteins were related to biological processes such as cellular component organization or biogenesis,cellular component organization and cellular component biogenesis,and they mainly participated in the top ten pathways of P value such as pathogenic Escherichia coli infection,m TOR signaling pathway,regulation of autophagy,regulation of actin cytoskeleton,spliceosome,hepatocellular carcinoma,tight junction,non-small cell lung cancer,apoptosis and gap junction.Annexin V/PI flow cytometry and TUNEL were used to detect apoptosis,and the results showed that Aβdecreased significantly and the rate of apoptosis decreased significantly after puerarin intervention.Western blot analysis found that the protein expression level of autophagy related protein LC3Ⅱwas up-regulated after Aβinduction,and the degree of this up-regulation was further enhanced in puerarin intervention group.The trend of the ratio of LC3Ⅱ/LC3Ⅰamong groups was the same as the protein expression level of LC3Ⅱ,the protein expression level of p62 in the control group,AD model group and puerarin intervention group decreased successively.Protein interaction network analysis showed that CAP1 was correlated with TUBA1B,HSP90AB2P,DNM1L,TUBA1A and ERK1/2,and the correlation between CAP1 and ERK1/2 was the highest among them.Western blot showed that the expressions of p-ERK1/2,Bax and CAP1 were significantly down-regulated and the protein expression level of Bcl-2 was significantly up-regulated after puerarin intervention.Therefore,puerarin might improve the SH-SY5Y cells injured by Aβ_(1-42)through the interaction of multiple biological processes and pathways in cells multiple locations,and CAP1 might play an important role among them.


Phosphorylation and activation of Bub1 on unattached chromosomes facilitate the spindle checkpoint.
The spindle checkpoint inhibits anaphase until all kinetochores have attached properly to spindle microtubules. The protein kinase Bub1 is an essential checkpoint component that resides at kinetochores during mitosis. It is shown herein that Xenopus Bub1 becomes hyperphosphorylated and the kinase is activated on unattached chromosomes. MAP kinase (MAPK) contributes to this phosphorylation, as inhibiting MAPK or altering MAPK consensus sites in Bub1 to alanine or valine (Bub1(5AV)) abolishes the phosphorylation and activation on chromosomes. Both Bub1 and Bub1(5AV) support the checkpoint under an optimal condition for spindle checkpoint activation. However, Bub1, but not Bub1(5AV), supports the checkpoint at a relatively low concentration of nuclei or the microtubule inhibitor nocodazole. Similar to Bub1(5AV), Bub1 without the kinase domain (Bub1(deltaKD)) is also partially compromised in its checkpoint function and in its ability to recruit other checkpoint proteins to kinetochores. This study suggests that activation of Bub1 at kinetochores enhances the efficiency of the spindle checkpoint and is probably important in maintaining the checkpoint toward late prometaphase when the cell contains only a few or a single unattached kinetochore.


[Anterior crucial ligament reconstruction with allograft hamstring fixed by Rigidfix and Intrafix anchorages].
To explore an improved reconstruction of the anterior crucial ligament (ACL) with the allograft hamstring fixed by the Rigidfix and Intrafix anchorages and to evaluate its therapeutic effectiveness in a short term. The ACL reconstruction was performed under the arthroscope on 21 patients' knees from Janaury 2006 to December 2006. There were 13 males and 8 females aged from 18 to 53 years. The injuries were caused by a traffic accident in 7 patients, a movement damage in 11, and other factors in 3. The medial collateral ligament(MCL) and the medial meniscus were injured in 10 patients, the medial meniscus and the lateral meniscus were injured in 3, the lateral meniscus was injured in 6, and only the ACL was injured in 2. The operations were performed 7 days to 3 months after the injuries. The graft used was the four-stranded allograft hamstring, which was fixed by the Rigidfix and Intrafix anchorages. The therapeutic effect was evaluated according to the Lysholm rating scale. The follow-up of all the 21 patients for 3-9 months (average, 5.8 months) revealed that the knees of 19 patients could move beyond 120 degrees after operation. In 1 patient who had the MCL injury, the range of genuflex was limited to 80 degrees at 3 months after operation, and so the operation of lysis was performed under the arthroscope again. In 1 patient, the rejection against the allograft was treated by the irrigating under the arthroscope but had little effect. The anterior drawer test and the pivot shift test were negative in the 21 patients. During the Lanchman test, 1 patient had a positive result (Degree I ). The Lysholm scores were significantly increased from 56.73 +/- 6.58 to 88.14 +/- 7.02 (P < 0.01). The surgical approach to reconstruction of ACL with the four-stranded allograft hamstring fixed by the Rigidfix and Intrafix anchorages is feasible and safe. The resulting fixation is reliable. The patients can begin their postoperative rehabilitation exercise earlier and their movement function can be restored earlier.


SIOP-PODC recommendations for graduated-intensity treatment of retinoblastoma in developing countries.
Retinoblastoma remains incurable in many regions of the world. The major obstacles to cure are delayed diagnosis, poor treatment compliance, and lack of evidence-based recommendations for clinical management. Although enucleation is curative for intraocular disease, in developing countries retinoblastoma is often diagnosed after the disease has disseminated beyond the eye. A SIOP-PODC committee generated guidelines for the clinical management of retinoblastoma in developing countries and developed a classification system based on the resources available in those settings. Recommendations are provided for staging and treatment of unilateral and bilateral retinoblastoma and counseling of families for whom compliance is an issue.


Combined Use of Neutrophil to Lymphocyte Ratio and C-Reactive Protein Level to Predict Clinical Outcomes in Acute Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention.
Both neutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP) are biomarkers associated with poor prognosis of patients with acute myocardial infarction (AMI). However, the combined usefulness of NLR and CRP in predicting adverse outcomes has not been investigated. We analyzed 381 consecutive AMI patients who underwent percutaneous coronary intervention (PCI) from January 2012 to January 2014. The endpoints were all-cause mortality, recurrent myocardial infarction (MI), stent thrombosis, repeat revascularization, stroke, and major adverse cardiac and cerebrovascular events (MACCE) at 2-year follow-up. Included patients were divided into 4 groups according to the optimal cut-off values for NLR and CRP on receiver operating characteristic analysis predicting mortality. Patients with both high NLR (>6.30) and high CRP (>0.76) had significantly greater risk of all-cause death and MACCE at 24 months, with no significant increase in the risk of recurrent MI, stent thrombosis, or stroke compared with patients with either low NLR or low CRP, as well as those with low NLR and low CRP. Kaplan-Meier analysis revealed significantly lower survival in patients with high NLR-CRP. On Cox multivariate analysis, high NLR-CRP (hazard ratio 23.172, 95% confidence interval 6.575 to 81.671, p<0.001) was an independent predictor of all-cause death. Elevated levels of both NLR and CRP are associated with increased risk of long-term mortality in AMI patients who have undergone PCI.


Postprandial elevation of remnant lipoprotein leads to endothelial dysfunction.
Recent studies have demonstrated that elevated levels of cholesterol in the form of remnant-like particles (RLP-C) induce deterioration of endothelial function during the fasting state, but it is not known whether postprandial RLP-C elevation has the same effect. The objective of this study was to assess the effect of postprandial RLP-C elevation on endothelial function in 24 fasting normolipidemic subjects. Flow-mediated dilatation (FMD) during reactive hyperemia in the brachial artery was investigated. Serum lipids and lipoproteins during fasting and 4h after regular fat-loading were measured. Subjects were divided into 2 groups: the high responders (postprandial RLP-C level >7.5mg/dl, n=8) and the normal responders (postprandial RLP-C level < or =7.5mg/dl, n=16). Significant increases in the level of both triglycerides and RLP-C were observed in the high responders. Basal FMD in the high responders (4.3+/-3.0%) was significantly lower than that in the normal responders (8.3+/-2.4%) (p<0.01), but FMD after the fat-loading in both groups did not change significantly. The change in RLP-C levels during the fat-loading test correlated significantly with basal FMD (r=-0.588, p<0.01). Multiple regression analysis showed a significant correlation between basal FMD and the change in RLP-C levels (r=-0.488, p<0.02). The results of this study suggest that postprandial RLP-C elevation could be associated with atherosclerotic progression even in normolipidemic subjects.


Acute Portal Vein Thrombosis as an Initial Presentation of Protein C Deficiency: A Case Report.
Protein C (PC) is an essential vitamin K-dependent protein that regulates thrombosis and hemostasis in the body. A mutation in the PROC gene on chromosome 2q14.3 results in PC deficiency. The clinical presentation of PC deficiency can vary, ranging from a single vein thrombosis to disseminated intravascular coagulation, purpura fulminans, or even life-threatening complications such as sepsis. Here, we present a case of a 37-year-old female who was found to have acute portal vein thrombosis as an initial presentation of PC deficiency. She presented to the hospital with acute onset of abdominal pain associated with nausea, blood-streaked emesis, and bloody bowel movement.


Takayasu arteritis: surgical interventions.
Open and endovascular surgery remains important in the management of Takayasu arteritis. This review summarizes the indications and approaches available, the evidence for them and recent advances. The outlook in Takayasu arteritis has improved over the last decade, reflecting earlier diagnosis, increased use of noninvasive imaging and combination immunotherapy. This is likely to be reflected in a reduced requirement for vascular intervention in the next decade. An important role remains for open surgery, which is effective, well tolerated and improves long-term survival in those with severe disease. Primary angioplasty offers a less invasive option for specific arterial sites, although restenosis rates are higher. Interventional outcomes are significantly improved by adequate pre and postoperative immunosuppression to render arteritis inactive. Stent placement should be reserved predominantly for primary and secondary angioplasty failures. The role of drug-eluting stents is not yet established. Preliminary evidence suggests that stent grafts represent an important noninvasive option. Vascular intervention remains important for the treatment of stenosed and occluded arteries leading to organ ischaemia or hypertension, and for aneurysmal disease. Endovascular stent grafts are likely to be increasingly deployed, and targeted biologic therapies may reduce the need for vascular intervention.


Predicting Multiple Facets of School Functioning in Pediatric Chronic Pain: Examining the Direct Impact of Anxiety.
The relationships among chronic pain, anxiety, and school functioning are complex, and school functioning is often negatively impacted in youth with chronic pain. The objective of this study was to empirically test a model of associations between constructs predicting school functioning in youth with chronic pain to examine the direct effect of anxiety on school attendance and other indicators of school-related disability. Participants included 349 youth and their parents (311 mothers and 162 fathers) who attended a multidisciplinary pain clinic. Youth, mothers, fathers, and clinicians completed assessments of clinical outcomes important to family and clinician perceptions of school functioning; youth, mothers, and fathers completed an assessment of youth anxiety. Structural equation modeling was used to examine interrelations among predictors. Measurement and structural models for predicting youth school functioning provided a very good fit of the data to the conceptual model. Anxiety was directly related to problems with school attendance and avoidance, concentration, and keeping up with schoolwork. Anxiety was a robust predictor of school functioning across a range of domains. Evaluating anxiety symptoms in pediatric chronic pain will likely facilitate case conceptualization and treatment planning. This study supports a shift in focus from pain to anxiety as the driving force of school impairment in youth with chronic pain.


Association of citalopram with congenital anomalies: A meta-analysis.
The antenatal use of citalopram, a widely prescribed selective serotonin reuptake inhibitor, has been suspected to be associated with congenital, particularly cardiac, anomalies. This study aimed to prove the association between citalopram use and congenital anomalies. We searched the English literature from July 1998 to July 2015, by using the search terms ' citalopram', ' pregnancy', ' birth defects', ' congenital anomalies', and ' malformations' in PubMed, Embase, Web of Science, and the Cochrane Library. Eight eligible articles were analyzed including a total of 1,507,896 participants. The odds ratio (OR) of major malformations associated with citalopram use during pregnancy was 1.07 (95% confidence interval [CI], 0.98 to 1.17). Concerning cardiac malformations, the OR for all included studies was 1.31 (95% CI, 0.88 to 1.93). The analysis of cardiac malformations was repeated to reduce heterogeneity after excluding one outlier study (OR, 1.03; 95% CI, 0.84 to 1.26). From our data, it can be concluded that citalopram use is not associated with major birth defects. However, physicians should carefully weigh the benefits against the potential risks of citalopram use, and counsel patients accordingly.


Role of Substrate Binding Interactions on DNA Repair by Photolyase.
The repair of the cyclobutane pyrimidine dimer (CPD) lesion in DNA by photolyase is determined by its initial recognition, and the catalytic efficiency depends on a series of intermolecular electron-transfer (ET) processes. Here, we investigated the repair of a CPD structural isomer, replacing the deoxyribose with a pyranose sugar on the 5' site, and found a loss in binding efficiency and repair quantum yield. Using femtosecond spectroscopy, we characterized all elementary repair steps and observed a systemic slowdown of the four intermolecular ET reactions and the second bond splitting. Our observations and molecular dynamics simulations suggest that the sugar replacement disrupts the lesion binding configuration, weakening the electronic coupling between the cofactor and lesion and altering the stability of lesion intermediates. These findings highlight how the CPD photolyases have utilized the structural features of the CPD lesion and optimized its interactions with the cofactor and key active-site residues to maximize repair yields.


Non-invasive Transcranial Electrical Stimulation in Movement Disorders.
Dysfunction within large-scale brain networks as the basis for movement disorders is an accepted hypothesis. The treatment options for restoring network function are limited. Non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation are now being studied to modify the network. Transcranial electrical stimulation (tES) is also a portable, cost-effective, and non-invasive way of network modulation. Transcranial direct current stimulation and transcranial alternating current stimulation have been studied in Parkinson's disease, dystonia, tremor, and ataxia. Transcranial pulsed current stimulation and transcranial random noise stimulation are not yet studied enough. The literature in the use of these techniques is intriguing, yet many unanswered questions remain. In this review, we highlight the studies using these four potential tES techniques and their electrophysiological basis and consider the therapeutic implication in the field of movement disorders. The objectives are to consolidate the current literature, demonstrate that these methods are feasible, and encourage the application of such techniques in the near future.


Strain differences in arsenic-induced oxidative lesion via arsenic biomethylation between C57BL/6J and 129X1/SvJ mice.
Arsenic is a common environmental and occupational toxicant with dramatic species differences in its susceptibility and metabolism. Mouse strain variability may provide a better understanding of the arsenic pathological profile but is largely unknown. Here we investigated oxidative lesion induced by acute arsenic exposure in the two frequently used mouse strains C57BL/6J and 129X1/SvJ in classical gene targeting technique. A dose of 5 mg/kg body weight arsenic led to a significant alteration of blood glutathione towards oxidized redox potential and increased hepatic malondialdehyde content in C57BL/6J mice, but not in 129X1/SvJ mice. Hepatic antioxidant enzymes were induced by arsenic in transcription in both strains and many were higher in C57BL/6J than 129X1/SvJ mice. Arsenic profiles in the liver, blood and urine and transcription of genes encoding enzymes involved in arsenic biomethylation all indicate a higher arsenic methylation capacity, which contributes to a faster hepatic arsenic excretion, in 129X1/SvJ mice than C57BL/6J mice. Taken together, C57BL/6J mice are more susceptible to oxidative hepatic injury compared with 129X1/SvJ mice after acute arsenic exposure, which is closely associated with arsenic methylation pattern of the two strains.


Is the preferential use of polytetrafluoroethylene grafts for below-knee femoropopliteal bypass justified?
The usefulness of polytetrafluoroethylene graft (PTFE) for primary below-knee femoropopliteal bypass was examined. Forty-five primary femoropopliteal bypasses with PTFE were performed in 35 patients during a 7-year period. Patients were divided into two groups: above-knee (A-K group, n = 20) and below-knee (B-K group, n = 25) bypass. Differences in intergroup patient demographics were not significant. The primary patency rate in the A-K group at 3 and 5 years was 83.6% and 50.2%, respectively, and was 76.2% at both 3 and 5 years in the B-K group. These differences were not significant. Cause of graft failure, 3 grafts in the A-K group and 5 grafts in the B-K group, was kinking or thrombus formation associated with intimal hyperplasia at the distal anastomosis. All grafts in the A-K group with more than 10% stenosis in the early postoperative period had more than 50% stenosis in the late postoperative period. On the other hand, the one graft in the B-K group with 25% stenosis in the early postoperative period had 50% stenosis in the late postoperative period. We concluded that the use of PTFE for primary below-knee femoropopliteal artery is reasonable when atherosclerosis in the proximal popliteal artery is slight. However, close follow-up is necessary to detect and treat graft stenosis early.


DNA lesion recognition by the bacterial repair enzyme MutM.
MutM is a bacterial DNA glycosylase that removes the mutagenic lesion 8-oxoguanine (oxoG) from duplex DNA. The means of oxoG recognition by MutM (also known as Fpg) is of fundamental interest, in light of the vast excess of normal guanine bases present in genomic DNA. The crystal structure of a recognition-competent but catalytically inactive version of MutM in complex with oxoG-containing DNA reveals the structural basis for recognition. MutM binds the oxoG nucleoside in the syn glycosidic configuration and distinguishes oxoG from guanine by reading out the protonation state of the N7 atom. The segment of MutM principally responsible for oxoG recognition is a flexible loop, suggesting that conformational mobility influences lesion recognition and catalysis. Furthermore, the structure of MutM in complex with DNA containing an alternative substrate, dihydrouracil, demonstrates how MutM is able to recognize lesions other than oxoG.


Confocal endomicroscopy and cyst fluid molecular analysis: Comprehensive evaluation of pancreatic cysts.
Increases in the quality as well as utilization of cross-sectional imaging have led to rising diagnoses of pancreatic cystic lesions (PCL). Accurate presurgical diagnosis enables appropriate triage of PCLs. Unfortunately, current diagnostic approaches have suboptimal accuracy and may lead to unnecessary surgical resections or missed diagnoses of advanced neoplasia. Additionally, early detection represents an opportunity for intervention to prevent the progression to pancreatic adenocarcinoma. Our aim for this review is to systematically review the current literature on confocal endomicroscopy and molecular biomarkers in the evaluation of PCLs. Confocal laser endomicroscopy is a novel technology that allows for real-time in vivo microscopic imaging with multiple clinical trials identifying characteristic endomicroscopy findings of various pancreatic cystic lesions. DNA-based molecular markers have also emerged as another diagnostic modality as the pattern of genetic alternations present in cyst fluid can provide both diagnostic and prognostic data. We propose that both techniques can be utilized to improve patient outcomes.


Synthesis and structural characterizations of multi-crystalline La0.5Ba0.5MnO3 nanowires: a "multi-nuclei" growth mode.
Multi-crystalline La0.5Ba0.5MnO3 Nanowires have been synthesized with cationic surfactant at 220 degrees C. The structure, composition and physical property of the as-prepared nanowires have been characterized by a series of techniques including XRD, SEM, HRTEM, electron energy-loss spectroscopy (EELS) and magnetic measurements. It is found that the La0.5Ba0.5MnO3 nanowire has the typical cubic perovskite structure, each nanowire is composed of many small crystalline grains with different orientations. Valance state of manganese ion in La0.5Ba0.5MnO3 nanowires is determined by EELS technique. A "multi-nuclei" growth mode is proposed based on the microstructure analysis. The temperature dependence of magnetization has been briefly discussed.


High L-Carnitine Levels Impede Viral Control in Chronic Hepatitis B Virus Infection.
Persistent antigen exposure during chronic hepatitis B infection leads to exhausted immune responses, thus impeding viral control. In recent years, immunometabolism opens new therapeutic possibilities for the modulation of immune responses. Herein, we investigated the immunomodulatory effect of L-carnitine (L-Cn) on immune cells in chronic HBV infection. In this study, 141 treatment-naïve patients with chronic HBV infection, 38 patients who achieved HBsAg loss following antiviral treatment, and 47 patients who suffered from HBV-related HCC from real-life clinical practice were recruited. The plasma L-Cn levels were measured by ELISA. RNA sequencing was conducted to define the transcriptional profiles of peripheral blood mononuclear cells after L-Cn stimulation. In vitro assays were performed to assess the effect of L-Cn on immune cells; the frequencies and function of immune cells were analyzed by flow cytometry. We found that compared with patients with HBsAg loss, patients with HBsAg positivity and patients who suffered from HBV-related HCC had higher levels of L-Cn, and the plasma levels of L-Cn in the HBeAg-positive chronic hepatitis patients who had elevated ALT were significantly higher than that of HBeAg-negative chronic infection and HBsAg loss groups. Moreover, a positive correlation between plasma levels of L-Cn and HBsAg levels was found. Additionally, RNA sequencing analysis demonstrated that L-Cn altered the transcriptional profiles related to immune response. In vitro assays revealed that L-Cn suppressed the proliferation of and IFN-γ production by CD4+ and CD8+ T cells. It also down-regulated the proliferation and IgG production of B cells. Notably, L-Cn enhanced IL-10 secretion from regulatory T cells and up-regulated the expression of inhibitory receptors on T cells. Moreover, a variant in CPT2 (rs1799821) was confirmed to be associated with L-Cn levels as well as complete response in CHB patients following Peg-IFNα antiviral therapy. Taken together, the immunosuppressive properties of L-Cn may hinder the control of HBV in chronic HBV infection, implicating that L-Cn manipulation might influence the prognosis of patients with HBV infection.


Reducing effect of aerobic exercise on blood pressure of essential hypertensive patients: A meta-analysis.
The comprehensive meta-analysis aimed to explore the reductive effect of aerobic exercise on blood pressure of hypertensive patients. The related researches were selected from PubMed and Embase databases up to June 2016. Based on specific inclusive criteria, the eligible studies were selected, and the heterogeneities in their results were estimated by χ-based Q-test and I statistics. Quantitative meta-analysis was assessed by R 3.12 software, and results were presented by standardized mean difference (SMD) and their 95% confidence intervals (CIs). Outcome indicators were systolic blood pressure (SBP) and diastolic blood pressure (DBP). The publication biases were estimated by Egger test. Besides, the "leave one out" method was used for sensitivity evaluations. As a result, a total of 13 papers with 802 samples were included. Based on the meta-analysis results, there were no significant differences in SBP and DBP between aerobic and control groups before exercise (SMD = 0.15, 95%CI: -0.16-0.46; SMD = 0.16, 95% CI: -0.23-0.55). However, significant reductions were obviously in aerobic group after aerobics, compared with control (SMD = -0.79, 95% CI: -1.29 to -0.28; SMD = -0.63, 95% CI: -1.14 to -0.12). A significant publication bias was detected in SBP (t = -2.2314, P = 0.04549) but not in DBP (t = -1.4962, P = 0.1604). Additionally, the DBP result would be altered after the exclusion of 2 individual papers. Aerobic exercise may be a potential nonpharmacological treatment for blood pressure improvement in essential hypertensive patients.


Family nursing assessment: meeting the challenge of health promotion.
Family nursing assessment has traditionally followed an illness-care model. This paper proposes a re-evaluation of traditional family assessment and suggests an approach which is fundamentally based in health promotion. The paper includes a discussion of varying perspectives of health and health care, the health promotion perspective adopted by the World Health Organization, and the relevance of these perspectives for family nursing practice. Central elements of health promotion are outlined and serve as the guiding principles for family nursing assessment. Two inherent aspects of health-promoting family nursing practice are proposed and described. These include an emphasis on a human caring nursing ontology, and a framework for guiding family nursing assessment. This health-promoting assessment framework contains four essential components: (a) listening to the family; (b) participatory dialogue; (c) recognizing patterns; and (d) envisaging action and positive change. These components are described, together with the strategic elements inherent in each. Based on this health-promoting family nursing assessment, implications for nursing practice are discussed, and recommendations are made for research into this assessment framework.


How selective are 3-year-olds in imitating novel linguistic material?
In 3 studies we explored when 3-year-olds would imitate novel words in utterances produced by adult speakers. Child and experimenter took turns in requesting objects from a game master. The experimenter always went first and always preceded the object's familiar name with a novel adjective (e.g., "the dilsige duck"). In the first 2 experiments, we found that children were more likely to reproduce the adjective when there were 2 different instances of the same object present in the situation than when there was only 1 or when there were 2 objects of different types present. Thus, children seemed to be sensitive to the descriptive and contrastive function of the adjectives in determining which parts of the utterances to reproduce. Nonetheless, replication of even redundant material was over 50%, suggesting a strategy of somewhat blind copying. In the 3rd experiment, we found that children were less likely to reproduce a redundant adjective when the speaker indicated gesturally that he did not intend to produce it than when he clearly produced it intentionally. We distinguish insightful imitation (the copying of a speaker's goal and means when motivated by insight into why those particular means were chosen) and blind imitation (the copying of a speaker's goal and means with no awareness of why those specific means were chosen) from mimicry. We explore the roles that these modes of imitation might play in language development.


Reevaluation of the protein requirement in young men with the indicator amino acid oxidation technique.
The current estimated protein requirements are based on the nitrogen balance method, which has many limitations. An alternate approach is needed to permit a reevaluation of protein requirements. The objective was to determine protein requirements in men by using the indicator amino acid oxidation technique. Eight healthy men randomly received graded protein intakes (0.10, 0.30, 0.60, 0.90, 1.2, 1.5 and 1.8 g kg(-1) d(-1)) as a crystalline amino acid mixture along with L-[1-(13)C]phenylalanine. The mean protein requirement was determined by applying a biphase linear regression crossover analysis on F(13)CO(2) data, which identified a breakpoint at the minimal rate of appearance of (13)CO(2) to graded protein intakes. The mean and population-safe (recommended dietary allowance; RDA) protein requirements were found to be 0.93 and 1.2 g kg(-1) d(-1), respectively. These requirements are comparable with those estimated by the application of a biphase linear regression model to the data from nitrogen balance studies (0.91 and 1.0 g kg(-1) d(-1), respectively). These requirements are 41% and 50% higher than the current recommendations for the estimated average requirement (EAR) of 0.66 g kg(-1) d(-1) and the RDA of 0.80 g kg(-1) d(-1), as determined by applying a linear regression model where it intersects the zero balance line. The indicator amino acid oxidation technique defined a protein requirement that is comparable with that estimated by the application of a biphase linear regression model to nitrogen balance data in the literature. Our data and the reanalysis of the preexisting nitrogen balance data suggest that the current recommended protein requirements are too low and require reassessment.


Morphine, nortriptyline and their combination vs. placebo in patients with chronic lumbar root pain.
Although lumbar radicular pain is the most common chronic neuropathic pain syndrome, there have been few randomized studies of drug treatments. We compared the efficacy of morphine (15-90 mg), nortriptyline (25-100 mg), their combination, and a benztropine "active placebo" (0.25-1 mg) in patients with chronic sciatica. Each period consisted of 5 weeks of dose escalation, 2 weeks of maintenance at the highest tolerated doses, and 2 weeks of dose tapering. The primary outcome was the mean daily leg pain score on a 0-10 scale during the maintenance period. Secondary outcomes included a 6-point ordinal global pain relief scale, the Beck Depression Inventory (BDI), the Oswestry Back Pain Disability Index (ODI) and the SF-36. In the 28 out of 61 patients who completed the study, none of the treatments produced significant reductions in average leg pain or other leg or back pain scores. Pain reduction, relative to placebo treatment was, 14% for nortriptyline (95% CI=[-2%, 30%]), 7% for morphine (95% CI=[-8%, 22%]), and 7% for the combination treatment (95% CI=[-4%, 18%]). Mean doses were: nortriptyline alone, 84+/-24.44 (SD) mg/day; morphine alone, 62+/-29 mg/day; and combination, morphine, 49+/-27 mg/day plus nortriptyline, 55 mg+/-33.18 mg/day. Over half of the study completers reported some adverse effect with morphine, nortriptyline or their combination. Within the limitations of the modest sample size and high dropout rate, these results suggest that nortriptyline, morphine and their combination may have limited effectiveness in the treatment of chronic sciatica.


Does repair of pectus excavatum improve cardiopulmonary function?
A best evidence topic was written according to a structured protocol. The question addressed was 'Does repair of pectus excavatum (PE) improve cardiopulmonary function?' One hundred and sixty-eight papers were found using the reported search, 19 level III evidence papers and three meta-analyses were relevant. Studies were divided into four groups based on the surgical technique applied and pulmonary and cardiac functions in these groups were analysed. The meta-analyses show conflicting results for improvements in pulmonary and cardiac functions when comparing surgical techniques, while four more recent studies show improved long-term results using the Nuss technique. The best evidence of papers studying the PE repair using the minimally invasive Nuss technique demonstrates a decrease in pulmonary function during the early postoperative period, however, there is a small but significant improvement during the late postoperative period and after bar removal. The best evidence for cardiac function in this group suggests an early improvement that is sustained during further follow-up. The best evidence of papers studying the PE repair using the Ravitch technique shows that pulmonary function decreased during the early postoperative period, however, there is a small but significant improvement during the late postoperative period. The best evidence for cardiac function in this group suggests an early improvement that is sustained during further follow-up. The best evidence of papers studying the PE repair using other techniques (modified Daniel's technique, modified Baronofsky's technique, sterno-costal turn-over technique and sterno-costal elevation technique) or where surgical techniques used were not described (preceding year 1985) suggests that there is no improvement in pulmonary function after surgery. There is some evidence that certain aspects of cardiac function improved after surgery in this group.


Galactosaminoglycan composition in chicken eggshell.
Galactosaminoglycans, isolated from decalcified chicken eggshell by papain digestion and ion-exchange chromatography, were fractionated by selective precipitation at varying concentrations of ethanol and characterized by chemical and enzymatic methods. The eggshell contained 0.15 microg galactosaminoglycan uronic acid/mg dry weight. Most (to approximately 87% of total) galactosaminoglycans were found to be chondroitin sulfate-dermatan sulfate copolymers with iduronic acid contents being approximately 20 to 30% of uronic acid. The remaining (to approximately 12% of total) galactosaminoglycans were chondroitin sulfate-dermatan sulfate copolymers with higher iduronic acid contents averaging 59% of uronic acid. Results of chondroitinase-ABC digestion demonstrated 4-sulfated disaccharides to be the major repeating units in the chicken eggshell galactosaminoglycans.


Fat jets for a light higgs boson.
At the LHC associated top quark and Higgs boson production with a Higgs boson decay to bottom quarks has long been a heavily disputed search channel. Recently, it has been found not to be viable. We show how it can be observed by tagging massive Higgs bosons and top jets. For this purpose we construct boosted top and Higgs taggers for standard-model processes in a complex QCD environment.


Nutrition policy reforms to address the double burden of malnutrition in Zambia: a prospective policy analysis.
The evolution of nutrition patterns in Zambia has resulted in the coexistence of undernutrition and overnutrition in the same population, the double burden of malnutrition. While Zambia has strong policies addressing undernutrition and stunting, these do not adequately address food environment drivers of the double burden of malnutrition and the adolescent age group and hence the need for nutrition policy reforms. We conducted a theory-based qualitative prospective policy analysis involving in-depth interviews with nutrition policy stakeholders and policy document review to examine the feasibility of introducing nutrition policy options that address the double burden of malnutrition among adolescents to identify barriers and facilitators to such policy reforms. Using the multiple streams theory, we categorized the barriers and facilitators to prospective policy reforms into those related to the problem, policy solutions and politics stream. The use of a life-course approach in nutrition programming could facilitate policy reforms, as adolescence is one of the critical invention points in a person's lifecycle. Another key facilitator of policy reform was the availability of institutional infrastructure that could be leveraged to deliver adolescent-focused policies. However, the lack of evidence on the burden and long-term impacts of adolescent nutrition problems, the food industry's strong influence over governments' policy agenda setting and the lack of public awareness to demand better nutrition were perceived as critical barriers to policy reforms. In addition, the use of the individual responsibility framing for nutrition problems was dominant among stakeholders. As a result, stakeholders did not perceive legislative nutrition policy options that effectively address food environment drivers of the double burden of malnutrition to be feasible for the Zambian context. Policy entrepreneurs are required to broker policy reforms that will get legislative policy options on the government's agenda as they can help raise public support and re-engineer the framing of nutrition problems and their solutions in Zambia.


Corticocortical connections predict patches of stimulus-evoked metabolic activity in monkey somatosensory cortex.
Stimulus-evoked metabolic activity in the anterior parietal cortex (areas 3a, 3b, 1, and 2) occurs in the form of column-like patches. Similar patches characterize the connections to, within, and from these fields. The relation of the patches elicited metabolically to those formed by retrograde or anterograde transport, however, is not clear. If a type of projection connecting areas 3a, 3b, 1, and 2 transmits sensory information among these cortical fields, the resultant projection pattern may directly contribute to the definition of somatosensory metabolic "columns." To test this possibility, electrophysiological recordings in areas 3b and 1 of Macaca fascicularis monkeys characterized stimuli that elicited the best neuronal response at a specific cortical site. Iontophoretic injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were subsequently made into the identified cortical sites. Two days later, the animals were injected with 2-deoxyglucose (2DG) and received the somatic stimulus previously determined to best activate the neurons isolated at the injected cortical site. After injections of WGA-HRP into physiologically defined loci in area 3b, the patches of transported label within areas 3b and 1 were colocalized with evoked metabolic activity. Injections of WGA-HRP into area 1 produced anterogradely labeled terminals in areas 1 and 2 that also overlapped with patches of evoked metabolic activity, as did patches of retrogradely labeled cells located in area 3b. Patches of anterograde label found in area 3b after area 1 injections, however, were not coincident with the metabolically activated patches. These findings suggest that excitatory information is transmitted from area 3b to area 1 in a way that connects clusters of cells with similar response properties.


Donepezil augmentation of clozapine monotherapy in schizophrenia patients: a double blind cross-over study.
Increasing evidence suggests that the cholinergic system is involved in the pathogenesis of schizophrenia. Donepezil, a central cholinesterase inhibitor, improves psychotic symptomatology in demented patients, however, evidence for its role in the management of active psychosis in schizophrenia remains limited. An 18-week double blind cross-over study was conducted in which eight patients were randomly assigned to either donepezil (5 mg/day for the first 4 weeks and 10 mg/day for the following 4 weeks) or placebo as augmentation treatment to clozapine. After this initial phase, there was a 2-week washout period of the study medication after which the same regimen was crossed over at the same dose and for the same period (8 weeks). No significant difference was noted in the total positive and negative symptom scale scores when donepezil was compared with placebo (16.7%+12.97% vs 3.20%+13.94% respectively, p = 0.18). However, three patients improved (>15%) in the total PANSS scores (37.03%, 16.6% and 25.33%) during the donepezil treatment phase, while only one patient improved (20.87%) during the placebo phase. No differences were noted in the Calgary depression scale (p = 0.305), Simpson Angus scale (p = 0.374), clinical global impression-improvement scale (p = 0.23) and clinical global impression-severity of illness scores (p = 0.116). Although this preliminary study failed to demonstrate a clear effect of donepezil augmentation in clozapine treated chronic schizophrenia patients, it seems that the subtle positive effect of donepezil observed in some of our patients should encourage further investigation in a larger sample of this patient subpopulation.


Clinical study of falls among inpatients with hematological diseases and exploration of risk prediction models.
Falls are serious health events that can cause life-threatening injuries, especially among specific populations. This study assessed the risk factors associated with falls among inpatients with hematological diseases and explored the predictive value of fall risk assessment models. Clinical data from 275 eligible hematology disease patients who visited Mianyang Central Hospital with or without falls from September 2019 to August 2022 were retrospectively analyzed. Fall risk scores were determined in all included patients. Clinical characteristics were compared between patients with and without falls. Binary logistic regression models were used to screen for potential fall-specific risk factors among hospitalized patients with hematology diseases. Falls occurred in 79 cases. Patients in the fall group had a higher Charlson Comorbidity Index (CCI), a higher incidence of diabetes mellitus, visual impairment, hematological malignancies, and maintenance of stable disease stage, higher glucose levels, and a greater proportion of dizziness, nocturnal defecation, and receipt of intensive chemotherapy than those in the non-fall group (all P < 0.05). Fall patients were also more likely to have used diuretics, laxatives, sedative-sleeping drugs, analgesics, albumin, and calcium, and to have had catheters placed. The Barthel Index, grade of nursing care, support of chaperones, body temperature, nutrition score, and pain score also differed significantly between the two groups (all P < 0.05). Multivariable logistic regression analysis showed that the maintenance of stable disease stage (OR = 4.40, 95% CI 2.11-9.18, P < 0.001), use of sedative and sleeping drugs (OR = 4.84, 95% CI 1.09-21.49, P = 0.038), use of diuretics (OR = 5.23, 95% CI 2.40-11.41, P < 0.001), and intensive chemotherapy (OR = 10.41, 95% CI 3.11-34.87, P < 0.001) were independent risk factors for falls. A high Barthel Index (OR = 0.95, 95% CI 0.93-0.97, P < 0.001), a high level of nursing care (OR = 0.19, 95% CI 0.04-0.98, P = 0.047), and availability of family accompaniment (OR = 0.15, 95% CI 0.06-0.34, P < 0.001) were protective factors for falls. A ROC curve analysis was used to evaluate the predictive value of different fall-specific risk scales among inpatients with hematological diseases. The Johns Hopkins Fall Risk Rating Scale had high sensibility and specificity with an area under the curve of 0.73 (95% CI 0.66-0.80, P < 0.001). The Johns Hopkins Fall Risk Scale had a strong predictive value for falls among hospitalized patients with hematology diseases and can be recommended as a valid tool for clinical use.


ARMC5 mutations in familial and sporadic primary bilateral macronodular adrenal hyperplasia.
To investigate Armadillo repeat-containing 5 (ARMC5) mutations in Chinese patients with familial and sporadic primary bilateral macronodular adrenal hyperplasia (PBMAH), we performed clinical data collection and ARMC5 sequencing for three PBMAH families and 23 sporadic PBMAH patients. ARMC5 pathogenic germline mutations were identified in all 3 PBMAH families. Secondary ARMC5 somatic mutations were found in two adrenal nodules from two PBMAH family members with ARMC5 germline mutations. PBMAH family members with ARMC5 pathogenic germline mutations displayed various clinical manifestations. ARMC5 pathogenic germline mutations were identified in 5 sporadic PBMAH patients among whom one patient displayed both hypercortisolism and primary aldosteronism. We detected a total of 10 ARMC5 pathogenic mutations, of which 8 had not been previously reported. Our results suggest that ARMC5 pathogenic germline mutations are common in familial and sporadic Chinese PBMAH patients, and demonstrate the importance of ARMC5 screening in PBMAH family members to detect patients with insidious PBMAH.