Stakeholders in nursing education: their role and involvement.
In literature, there is evidence that all stakeholders need to be involved in the curricula building process to make sure that health professionals are "educated" to meet the stakeholders' "demands". In Italy, the involvement of stakeholders in the definition of university curricula is ratified by various regulations. To describe the major experiences of stakeholder involvement in nursing education, identify the main stakeholders for nursing education, and the processes in which they are involved. The search strategy included an electronic exploration of the relevant databases. The search terms were: Stakeholders, Curriculum, Nursing Education combined with Boolean operators. The references of the retrieved articles were hand searched for additional related studies. Most of the studies identified were from the United Kingdom, Australia, and the USA. In Italy, no relevant studies were found. The most frequently identified stakeholders were: students, clinicians, educators, nurse managers. They were mainly involved during profound changes in the curricula and the implementation of new educational approaches. Stakeholders are mostly involved in countries with a private funding system for universities. Such funding systems have probably developed in the academia a greater propensity to involve stakeholders, to provide recognition of success when starting new programs, and are perceived more as marketing research. This seems contrary to the spirit of the Italian and European regulatory interventions, which instead, provide a structured commitment to consolidating and expanding the collaboration among universities, users, and the world of labor. This latter collaboration should facilitate internship activities, lifelong learning, and employability of the newly-graduated professionals.


An Inactivation Switch Enables Rhythms in a Neurospora Clock Model.
Autonomous endogenous time-keeping is ubiquitous across many living organisms, known as the circadian clock when it has a period of about 24 h. Interestingly, the fundamental design principle with a network of interconnected negative and positive feedback loops is conserved through evolution, although the molecular components differ. Filamentous fungus Neurospora crassa is a well-established chrono-genetics model organism to investigate the underlying mechanisms. The core negative feedback loop of the clock of Neurospora is composed of the transcription activator White Collar Complex (WCC) (heterodimer of WC1 and WC2) and the inhibitory element called FFC complex, which is made of FRQ (Frequency protein), FRH (Frequency interacting RNA Helicase) and CK1a (Casein kinase 1a). While exploring their temporal dynamics, we investigate how limit cycle oscillations arise and how molecular switches support self-sustained rhythms. We develop a mathematical model of 10 variables with 26 parameters to understand the interactions and feedback among WC1 and FFC elements in nuclear and cytoplasmic compartments. We performed control and bifurcation analysis to show that our novel model produces robust oscillations with a wild-type period of 22.5 h. Our model reveals a switch between WC1-induced transcription and FFC-assisted inactivation of WC1. Using the new model, we also study the possible mechanisms of glucose compensation. A fairly simple model with just three nonlinearities helps to elucidate clock dynamics, revealing a mechanism of rhythms' production. The model can further be utilized to study entrainment and temperature compensation.


Zosteriform Collagen Nevus in an Infant.
Connective tissue nevi (CTN) are dermal hamartomas characterized by an imbalance in the amount and distribution of the normal components of the extracellular dermal matrix, specifically collagen, elastin, and/or proteoglicans. The term "CTN" was first mentioned by Lewandowsky in 1921 (1), although it was not accepted until the review by Gutmann in 1926 (2). Classification of CTN was established by Uitto et al. (3) in 1980 according to clinical, genetic, and histopathological features. But this classification did not include zosteriform nevi. The more recent Pierard and Lapiere (4) classification seems to be a more suitable method of classification for zosteriform nevi. They classified CTN into two groups: (1) reticular and (2) adventitial. Zosteriform nevus is a rare form of reticular CTN that is diagnosed according to its clinical distribution. Here we report a collagen nevus in an infant that followed a zosteriform pattern. An 8-month-old girl presented with flesh-colored plaques on the right buttock in a zosteriform distribution, which had been present since birth. The plaques appeared to be well-defined cobblestone-like nodules on palpation (Figure 1). Systemic examination, laboratory tests and radiologic examinations did not reveal any abnormalities. The patient had no associated disease and no history of similar skin findings among family members. A skin punch biopsy was performed from one of the nodules. The histopathologic examination showed significantly increased density of thickened collagen fibers in the lower dermis and subcutaneous tissue. Verhoeff-van Gieson and orcein stains demonstrated the presence of dense collagen fibers with diminished elastic fibers (Figure 2). Four subtypes of collagen tissue nevus have been described: (I) familial cutaneous collagenoma, (II) shagreen patches in tuberous sclerosis, (III) eruptive collagenoma, (IV) and isolated collagenoma (5). Isolated collagenoma with lack of family history is fairly rare. It is sporadic, localized to only one body region, and not associated with any disease. In confluent plaques it has the appearance of "peau de chagrin" or a cobblestone-like pattern. The reported presentations include paving stone nevi, plantar fibromatosis, papulolinear lesions, and zosteriform lesions (5). Zosteriform distribution is an extremely rare variety of connective tissue nevus. Steiner (6) was the first to describe the condition in 1944, in a 5-year-old girl who presented with nevi in a zosteriform distribution. The histopathology of the lesion revealed an abnormality in both collagen and elastin fibers. Only 11 other cases have been reported as zosteriform CTN in dermatological literature. To the best of our knowledge, only 3 collagen nevi in a zosteriform distribution have been previously described in the literature. De et al. (7) described the first case in a 25-year-old man presenting a collagen tissue nevus with zosteriform distribution located over the lower back. Subsequently, Kumari et al. (8) described the second case in a 20-year-old man presenting a large, flesh-colored, well-defined plaque in a zosteriform distribution on his right buttock since birth. Topal et al. (9) reported another case of a 10-year-old boy with a zosteriform collagen tissue nevus on his right arm as sclerotic papules and plaques. Clinically, zosteriform CTN has similar morphology and distribution to nevus lipomatosus superficialis (NLS) or segmental neurofibromatosis. The latter differential possibility needs to be excluded due to its association with gliomas. The histopathologic findings of NLS make it easy to differentiate from zosteriform CTN. The peculiar finding of ectopic fat in the dermis is considered to be almost pathognomonic of NLS (10). In conclusion, the zosteriform distribution of CTN is very rare, especially in the variety with collagen predominance. As the lesion remains asymptomatic, with only cosmetic effects, the condition needs no specific treatment. The present case is a rare type of isolated collagenoma with zosteriform distribution presenting over the right buttock with no associated abnormalities and family history.


Public Health Data for Individual Patient Care: Mapping Poison Control Center Data to the C-CDA Consultation Note.
We are developing a new process of health information exchange supported collaboration that leverages the HL7 consolidated CDA standard through four document types (consultation note, history and physical, progress note and discharge summary). The focus of the present study is the C-CDA consultation note template that will be submitted from poison control centers (PCC)s to emergency departments (EDs) with treatment recommendations. Specifically, we aimed to (i) create computable mappings between a poison control center database and the C-CDA consultation note template; and (ii) assess the extent and nature of information types that successfully map to discrete data elements in a poison control center database. The resulting template and mappings can be used to implement standards-based health information exchange between PCCs and EDs in the U.S. This is a part of the first formal effort to leverage health information exchange standards to support PCC-ED collaboration.


High-resolution laser Doppler perfusion imaging aids in differentiating between benign and malignant melanocytic skin tumours.
Malignant melanomas are characterized by heterogeneity and asymmetry as well as by a higher density of blood vessels than benign pigmented tumours. The aim of this study was to evaluate the benefit of high-resolution laser Doppler perfusion imaging (LDPI) in the differential diagnosis of pigmented skin tumours. One-hundred-and-eighty-nine patients were examined with the LDPI, 22 with malignant melanomas, 39 with clinically suspicious dysplastic melanocytic naevi and 27 with basal cell carcinomas. Following examination, the tumours were excised and examined histologically. A control group of 101 melanocytic naevi showed clinically and, with epiluminescence microscopy, definitely benign criteria. These naevi were not excised. In malignant melanomas there was a 3.6+/-1.5 times higher perfusion than in healthy skin. The corresponding figures for clinically suspicious melanocytic naevi and basal cell carcinomas were 2.2+/-1.1 and 2.0+/-0.7, respectively. The increase in flow in malignant melanomas was significantly higher than in clinically suspicious melanocytic naevi and basal cell carcinomas (p < 0.001). All malignant melanomas showed at least 1.8 times higher flow values than healthy skin. When this value is taken as the basis for the diagnosis "benign or malignant", the LDPI proved a sensitivity of 100% and a specificity of 85%. If only the distinction between malignant melanomas and clinically suspicious naevi is considered, the specificity is reduced to 48%. There was no correlation between tumour thickness and increase in the mean perfusion of malignant melanomas (r = 0.14; p = 0.5). High-resolution LDPI can be used as an additional automatic screening method.


Substance use and associated factors among high school students in Northwest Ethiopia.
substance abuse is the use of a drug that affects both the function and the structure of the brain by altering the activity neurotransmitters of particular pathways in the central nervous system that affect the mood, perception, and consciousness of the person. a cross-sectional study design was employed among 422 high school students. Study participants were selected by simple random sampling from all five high school students. A self-reported questionnaire was used that included alcohol, smoking, and substance involvement screening test, Oslo-3 social support, and other instruments. Data were checked, coded, and entered into Epi-Data version 4.6.2 then exported to the statistical package for social sciences version 20 for analysis. Bi-variable and multi-variable logistic regression analyses were used to identify factors associated with substance use. Adjusted odds ratios with 95% confidence intervals were determined and predictors with a p-value of <0.05 were counted as significantly associated. a total of 406 students have participated with an overall response rate of 96.2% (n=406). Of the participants 235 were female and 171 were male. The mean age was 17.51 with a standard deviation of ±1.42. The prevalence of substance use among study participants was 52.5%. Being male aOR: 1.77, 95% CI 1.11-2.77, family history of substance use aOR: 3.07, 95% CI 1.57-6.01, and having close friends´ pressure aOR: 5.77, 95% CI 2.39-13.89 were significantly associated with substances use among high school students. the prevalence of substance use among high school students was high. Being male, family history of substance use, and having peer pressures were strongly associated with substance use.


Natural Language Processing for Adjudication of Heart Failure Hospitalizations in a Multi-Center Clinical Trial.
The gold standard for outcome adjudication in clinical trials is chart review by a physician clinical events committee (CEC), which requires substantial time and expertise. Automated adjudication by natural language processing (NLP) may offer a more resource-efficient alternative. We previously showed that the Community Care Cohort Project (C3PO) NLP model adjudicates heart failure (HF) hospitalizations accurately within one healthcare system. This study externally validated the C3PO NLP model against CEC adjudication in the INVESTED trial. INVESTED compared influenza vaccination formulations in 5260 patients with cardiovascular disease at 157 North American sites. A central CEC adjudicated the cause of hospitalizations from medical records. We applied the C3PO NLP model to medical records from 4060 INVESTED hospitalizations and evaluated agreement between the NLP and final consensus CEC HF adjudications. We then fine-tuned the C3PO NLP model (C3PO+INVESTED) and trained a de novo model using half the INVESTED hospitalizations, and evaluated these models in the other half. NLP performance was benchmarked to CEC reviewer inter-rater reproducibility. 1074 hospitalizations (26%) were adjudicated as HF by the CEC. There was high agreement between the C3PO NLP and CEC HF adjudications (agreement 87%, kappa statistic 0.69). C3PO NLP model sensitivity was 94% and specificity was 84%. The fine-tuned C3PO and de novo NLP models demonstrated agreement of 93% and kappa of 0.82 and 0.83, respectively. CEC reviewer inter-rater reproducibility was 94% (kappa 0.85). Our NLP model developed within a single healthcare system accurately identified HF events relative to the gold-standard CEC in an external multi-center clinical trial. Fine-tuning the model improved agreement and approximated human reproducibility. NLP may improve the efficiency of future multi-center clinical trials by accurately identifying clinical events at scale.


Complement-mediated inhibition of immune precipitation. II. Analysis by sucrose density gradient ultracentrifugation.
The factors influencing the ultracentrifugation characteristics of immune complexes generated in the presence of fresh normal human serum have been analysed. In the absence of alternative pathway factors B, D or Properdin, the size of complexes was increased. When classical pathway function was blocked, in C1q deficient serum or in the presence of Mg EGTA, although the proportion of complexes remaining in solution were reduced their size was similar to those formed in normal human serum. In C2 deficient serum, a heterogeneous population of complexes was generated. In all instances repletion with the appropriate missing complement component reversed the abnormality. We conclude that there is normally a rapid sequential process of classical followed by alternative pathway activation leading to stable soluble complexes. In the absence of C1 activation the alternative pathway process requires precipitation of the antigen-antibody aggregates whereas in normal serum these events occur in the fluid phase. We suggest that in C2 deficient serum the C1 and/or C4 reacted complexes fail to activate the alternative pathway efficiently.


Glucose transporter protein responses to selective hyperglycemia or hyperinsulinemia in fetal sheep.
The acute effect of selective hyperglycemia or hyperinsulinemia on late gestation fetal ovine glucose transporter protein (GLUT-1, GLUT-3, and GLUT-4) concentrations was examined in insulin-insensitive (brain and liver) and insulin-sensitive (myocardium and fat) tissues at 1, 2.5, and 24 h. Hyperglycemia with euinsulinemia caused a two- to threefold increase in brain GLUT-3, liver GLUT-1, and myocardial GLUT-1 concentrations only at 1 h. There was no change in GLUT-4 protein amounts at any time during the selective hyperglycemia. In contrast, selective hyperinsulinemia with euglycemia led to an immediate and persistent twofold increase in liver GLUT-1, which lasted from 1 until 24 h with a concomitant decline in myocardial tissue GLUT-4 amounts, reaching statistical significance at 24 h. No other significant change in response to hyperinsulinemia was noted in any of the other isoforms in any of the other tissues. Simultaneous assessment of total fetal glucose utilization rate (GURf) during selective hyperglycemia demonstrated a transient 40% increase at 1 and 2.5 h, corresponding temporally with a transient increase in brain GLUT-3 and liver and myocardial GLUT-1 protein amounts. In contrast, selective hyperinsulinemia led to a sustained increase in GURf, corresponding temporally with the persistent increase in hepatic GLUT-1 concentrations. We conclude that excess substrate acutely increases GURf associated with an increase in various tissues of the transporter isoforms GLUT-1 and GLUT-3 that mediate fetal basal glucose transport without an effect on the GLUT-4 isoform that mediates insulin action. This contrasts with the tissue-specific effects of selective hyperinsulinemia with a sustained increase in GURf associated with a sustained increase in hepatic basal glucose transporter (GLUT-1) amounts and a myocardial-specific emergence of mild insulin resistance associated with a downregulation of GLUT-4.


[Symptomatic hypersomnia due to orexin deficiency in hypothalamic lesions].
Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy and other abnormal manifestations of REM sleep. Recently, it was discovered that the pathophysiology of idiopathic narcolepsy-cataplexy is linked to orexin ligand deficiency in the brain and cerebrospinal fluid. Orexin neurons localize in the posterior hypothalamic area, which was previously described as "waking center" by von Economo in 1920s. Hypersomnia due to orexin ligand deficiency can also occur during the course of other neurological conditions, such as hypothalamic tumor, encephalopathy and demyelinating disorder (i.e. symptomatic hypersomnia). We experienced 8 pediatric cases with symptomatic hypersomnia. These cases were diagnosed as brain tumor (n = 2), head trauma (n = 1), encephalopathy (n = 1), demyelinating disorder (n = 3) and infarction (n = 1). Six pediatric cases with orexin measurements from the literatures were additionally included and total 14 cases were studied. Although it is difficult to rule out the comorbidity of idiopathic narcolepsy in some cases, a review of the case histories reveals numerous unquestionable cases of symptomatic hypersomnia. In these cases, the occurrences of the hypersomnia run parallel with the rise and fall of the causative diseases. Most of symptomatic hypersomnia cases show both extended nocturnal sleep time and EDS consisting of prolonged sleep episodes of NREM sleep. The features of nocturnal sleep and EDS in symptomatic hypersomnia are more similar to idiopathic hypersomnia than to narcolepsy.


Efficient fiber-to-waveguide coupling through the vertical leakage from a microring.
A fiber-to-waveguide coupler is proposed to efficiently couple light from a single-mode fiber into a submicrometer semiconductor waveguide for integration with optoelectronic circuits. A microring with a specific refractive index is designed on the top of the semiconductor waveguide. The gradual vertical leakage from the microring forms steady coupling into the semiconductor waveguide. Coupling efficiency up to 93% is demonstrated using the three-dimensional finite-difference time-domain method. A tapered-waveguide or microring structure can be used to convert the lateral-mode size for coupling light into a single-mode semiconductor waveguide.


Novel point mutation in the NKX2-5 gene in a Moroccan family with atrioventricular conduction disturbance and an atrial septal defect in the oval fossa.
Defects of the oval fossa usually occur as isolated malformations, but can show an autosomal dominant pedigree in familial cases. Several mutations have been described for the transcription factor NKX2-5, and co-segregate with varied cardiac anomalies. We have identified by sequence analysis a novel missense heterozygous mutation in the NKX2-5 gene, specifically a substitution of glutamine for proline at codon 160, in a Moroccan family, the affected members having a deficiency of the floor of the oval fossa and atrioventricular block.


Enhanced antitumor effect of combination therapy with interleukin-2 and polyribonucleotides against adenocarcinoma 755.
Human recombinant interleukin-2 (IL-2) and interferon (IFN) inducers in combination were evaluated for their in vivo antitumor efficacy in relation to s.c.-implanted adenocarcinoma 755 in C57BL/6 mice. Two IFN inducers, polyinosinic-polycytidylic acid [poly(I)poly(C)] and polyadenylic-polyuridylic acid [poly(A)poly(U)], induced high IFN production in various tissues for a long time compared to treatment with murine interferon-beta. Especially, poly(I)poly(C) at 5 mg/kg, the maximum tolerated dose, produced the highest level of IFN in the tumor, but the tumor did not show regression. Poly(I)poly(C), however, brought about marked regression of the tumor when administered together with IL-2. This combination resulted in cure of some mice when both drugs were administered intraperitoneally. Intraperitoneal injection of IL-2 in combination with poly(I)poly(C) was more effective than intravenous injection of IL-2. The combination of IL-2 and poly(A)poly(U) also showed an enhanced antitumor effect. Thus, endogenous IFN produced by IFN inducers as well as exogenous IFN as reported previously potentiated the antitumor effect when administered together with IL-2. The degree of potentiation by combination of IL-2 and IFN inducers may depend on the level of IL-2 and IFN at the injection site.


Trauma severity scoring systems as predictors of nosocomial infection.
To describe the patterns of nosocomial infections in patients with traumatic injuries and to compare the associations between injury severity, derived from various severity scoring systems, and subsequent nosocomial infections. Prospective observational study. A 750-bed university hospital serving as a medical school and referral center for the southern part of Thailand. All trauma patients admitted to the hospital for more than 3 days during 1996 to 1999 were eligible for this study. The severity of injuries was measured in terms of injury severity score (ISS), revised trauma score (RTS), new injury severity score (NISS), and trauma injury severity score (TRISS). Infections acquired during hospitalization were categorized using Centers for Disease Control and Prevention criteria. The association between severity of injury and nosocomial infection was examined with Poisson regression models. There were 222 nosocomial infections identified among 146 patients, yielding an infection rate of 0.8 infections per 100 patient-days. Surgical-site infection was the most common site-specific infection, accounting for 31.1% of all infections. The incidence of intravenous catheter-related bloodstream infection was 1.6 infections per 100 catheter-days. The bladder catheter-related urinary tract infection rate was 2.8 infections per 100 catheter-days. The rate of ventilator-associated pneumonia was 3.2 infections per 100 ventilator-days. The incidence of infection correlated well with injury severity. The infection incidence rate ratios for one severity category increment of ISS, NISS, RTS, and TRISS were 1.65 (95% confidence interval [CI95], 1.42 to 1.92), 1.79 (CI95, 1.55 to 2.05), 1.64 (CI95 1.43 to 1.88), and 1.32 (CI95, 1.14 to 1.52), respectively. Surgical-site infection was the most common site-specific nosocomial infection. The NISS might be the most appropriate severity scoring system for adjustment of infection rates in trauma patients.


Genetics of growth habit and development of new coleus (Solenostemon scutellarioides (L.) Codd) varieties with trailing habit and bright color.
A high level of genetic variability for growth habit types is observed in tetraploid, cultivated coleus (Solenostemon scutellarioides (L.) Codd). Very few cultivars with trailing habit exist, and those that are available generally have dark green or purple foliage color. Coleus with trailing growth habit is desirable as it increases its utility for use in hanging baskets, mixed containers, and as ground cover. There is a lack of published information on the genetic mechanism controlling growth habit and the development of new trailing types with orange colors. Two commercial cultivars, "Red Trailing Queen" (RQ) with trailing habit and "Sedona" (S) with upright stature, were selfed and crossed (RQ x S) to produce self and F(1) populations. F(2) populations were produced by selfing plants in the F(1) population. For each population analyzed, growth habit was rated on a visual 1-5 phenotypic scale, where 1 = upright, 2 = semi-upright, 3 = prostrate, 4 = semitrailing, and 5 = trailing. Genotypes were assigned to each phenotype, assuming that upright was dominant to trailing. In this study, growth habit was observed to be controlled by a single gene (U) with additive effects, with upright growth habit designated with a UUUU genotype and trailing growth habit designated with a uuuu genotype. In addition, foliage color was rated on a visual 1-5 phenotypic scale, and purple foliage color was found to be dominant to yellow-orange color. Several new coleus selections with trailing growth habit and orange foliage color were successfully developed.


Effects of age and gender on toe flexor muscle strength.
Toe flexor muscle strength determines the anterior limit of the functional base of support, thereby affecting a standing individual's maximum forward reach or lean capacity. We developed a method for measuring toe flexor muscle strength in order to test the null hypotheses that it is neither affected by age nor gender. Gender-balanced groups of 20 healthy young adults (YA) (average age 22.8 years) and 20 healthy older adults (OA) (average age 73.2 years) participated in the study. Toe flexor isometric muscle strength, calculated as the maximum volitional moment developed simultaneously in the sagittal plane by the toe flexor muscles about a reference axis through the first metatarsophalangeal joint, was measured in three trials while subjects reached forward as far as possible while standing on a force plate. Significant age (p <.005) and gender (p <.0005) differences were found in maximum toe flexor muscle strength. OA were 28.9% less strong than the YA [mean (SD) 13.5 (5.7) Nm and 19.0 (6.8) Nm, respectively]. The men developed 39.1% greater strength than the women [20.2 (7.1) Nm and 12.3 (3.7) Nm, respectively]. However, when normalized by body size (body weight x height), the gender difference in strength no longer reached statistical significance. Across all subjects, the anterior limit of the functional base of support was significantly correlated with toe flexor strength (coefficient of determination: 0.84). Toe flexor muscle strength decreased significantly with age. This decrement underlies the known age-related reduction in the functional base of support.


Ischemic preconditioning elevates cardiac stress protein but does not limit infarct size 24 or 48 h later in rabbits.
We investigated whether ischemic preconditioning (PC) produced a second window of protection by delayed synthesis of cardioprotective proteins. Anesthetized open-chest rabbits were subjected to 30 min of coronary occlusion and 3 h of reperfusion. PC was elicited by 5 min of ischemia and was separated from sustained ischemia by 5 min, 2 h, or 24 h of reperfusion. Infarct size (% area at risk) was markedly limited by PC with 5 min of reperfusion when compared with controls (13.3 +/- 2.5 vs. 46.8 +/- 7.0%; P < 0.05). This protective effect was lost when the interval between PC and sustained ischemia was extended to 2 h (47.8 +/- 4.8%; P = NS vs. control) and did not reoccur even when it was extended to 24 h (44.2 +/- 6.5%; P = NS vs. sham-operated control). To potentiate induction of heat shock proteins (HSPs), a PC protocol involving four 5-min episodes of ischemia and reperfusion was also used and was separated from sustained ischemia by 24 or 48 h of reperfusion. However, neither of these protocols was protective, and limitation of infarct size was not observed (55.5 +/- 5.9 and 53.4 +/- 6.5% in 24 and 48 h of reperfusion, respectively; P = NS vs. corresponding sham-operated control). Myocardial expression of HSPs was examined using a monoclonal antibody against 72- to 73-kDa HSP in additional rabbits. Immunoreactivity was observed in the myocardium at 24 and 48 h after PC, but not immediately after PC.(ABSTRACT TRUNCATED AT 250 WORDS)


Deaths from Alzheimer's Disease - United States, 1999-2014.
Alzheimer's disease (Alzheimer's), an ultimately fatal form of dementia, is the sixth leading cause of death in the United States, accounting for 3.6% of all deaths in 2014 (1,2). Alzheimer's deaths can be an indicator of paid and unpaid caregiver burden because nearly everyone in the final stages of Alzheimer's needs constant care, regardless of the setting, as the result of functional and cognitive declines (2). To examine deaths with Alzheimer's as the underlying cause, state-level and county-level death certificate data from the National Vital Statistics System for the period 1999-2014 were analyzed. A total of 93,541 Alzheimer's deaths occurred in the United States in 2014 at an age-adjusted (to the 2000 standard population) rate of 25.4 deaths per 100,000 population, a 54.5% increase compared with the 1999 rate of 16.5 deaths per 100,000. Most deaths occurred in a nursing home or long-term care facility. The percentage of Alzheimer's decedents who died in a medical facility (e.g., hospital) declined from 14.7% in 1999 to 6.6% in 2014, whereas the percentage who died at home increased from 13.9% in 1999 to 24.9% in 2014. Significant increases in Alzheimer's deaths coupled with an increase in the number of persons with Alzheimer's dying at home have likely added to the burden on family members or other unpaid caregivers. Caregivers might benefit from interventions such as education, respite care, and case management that can lessen the potential burden of caregiving and can improve the care received by persons with Alzheimer's.


Cost-effectiveness of a community-based integrated care model compared with usual care for older adults with complex needs: a stepped-wedge cluster-randomised trial.
To assess the cost of implementation, delivery and cost-effectiveness (CE) of a flagship community-based integrated care model (OPEN ARCH) against the usual primary care. A 9-month stepped-wedge cluster-randomised trial. Community-dwelling older adults with chronic conditions and complex care needs were recruited from primary care (14 general practices) in Far North Queensland, Australia. Costs and outcomes were measured at 3-month windows from the healthcare system and patient's out-of-pocket perspectives for the analysis. Outcomes included functional status (Functional Independence Measure (FIM)) and health-related quality of life (EQ-5D-3L and AQoL-8D). Bayesian CE analysis with 10 000 Monte Carlo simulations was performed using the BCEA package in R (V.3.6.1). The OPEN ARCH model of care had an average cost of $A1354 per participant. The average age of participants was 81, and 55% of the cohort were men. Within-trial multilevel regression models adjusted for time, general practitioner cluster and baseline confounders showed no significant differences in costs, resource use or effect measures regardless of the analytical perspective. Probabilistic sensitivity analysis with 10 000 simulations showed that OPEN ARCH could be recommended over usual care for improving functional independence at a willing to pay above $A600 (US$440) per improvement of one point on the FIM Scale and for avoiding or reducing inpatient stay for any willingness-to-pay threshold up to $A50 000 (US$36 500). OPEN ARCH was associated with a favourable Bayesian CE profile in improving functional status and dependency levels, avoiding or reducing inpatient stay compared with usual primary care in the Australian context. ACTRN12617000198325.


Printable Bioelectronics To Investigate Functional Biological Interfaces.
Thin-film transistors can be used as high-performance bioelectronic devices to accomplish tasks such as sensing or controlling the release of biological species as well as transducing the electrical activity of cells or even organs, such as the brain. Organic, graphene, or zinc oxide are used as convenient printable semiconducting layers and can lead to high-performance low-cost bioelectronic sensing devices that are potentially very useful for point-of-care applications. Among others, electrolyte-gated transistors are of interest as they can be operated as capacitance-modulated devices, because of the high capacitance of their charge double layers. Specifically, it is the capacitance of the biolayer, being lowest in a series of capacitors, which controls the output current of the device. Such an occurrence allows for extremely high sensitivity towards very weak interactions. All the aspects governing these processes are reviewed here.


Heat Capacity and Thermodynamic Functions of Titanium-Manganites of Lanthanum, Lithium and Sodium of LaLi2TiMnO6 and LaNa2TiMnO6.
Titanium-manganites of LaLi2TiMnO6 and LaNa2TiMnO6 were synthesized by the methods of ceramic technology from the oxides of lanthanum, titanium (IV), manganese (III), and the carbonates of lithium and sodium. The types of their syngony and the parameters of their gratings were determined radiographically. The isobaric heat capacities of titanium-manganites were measured with experimental calorimetry in the range of 298.15-673 K. It was found that on the dependence curve of heat capacity versus temperature of C°p~f(T), for LaLi2TiMnO6 at 348 K and 598 K, and LaNa2TiMnO6 at 348 K, there are abnormal jumps in heat capacity, probably related to phase transitions of the second kind. Taking into account the temperatures of the phase transitions, the equations of the temperature dependence of the heat capacity of titanium-manganites were derived. Their standard entropies were calculated by the ion increments method. Temperature dependences of the thermodynamic functions of S°(T), H°(T)-H°(298.15), and Φxx(T) were calculated using the experimental data on heat capacities and the calculated values of the standard entropies. The standard heat capacities of the studied compounds were calculated by the independent methods of ion increments and Debye, the values of which were in satisfactory agreement with the experimental data. The standard enthalpy of the formation of LaLi2TiMnO6 and LaNa2TiMnO6 was calculated according to the methodology developed by the authors. The conducted electrophysical studies determined the nature of the second-order phase transition and the semiconductor features of their conductivity. Thus, all the above-mentioned data on the experimental and calculated studies of the temperature dependence of heat capacity, the thermodynamic functions to determine a standard enthalpy of formation of LaLi2TiMnO6 and LaNa2TiMnO6, and the investigation of their electrical properties are absolutely new, and they have no analogues.


Bone demineralization, biochemical indices of bone remodeling, and estrogen replacement therapy in adults with Turner's syndrome.
The study centered on a controversy about whether long-term estrogen replacement therapy may ameliorate the osteoporosis seen in patients with Turner's syndrome. This study comprised 26 adult patients with Turner's syndrome (9 treated and 17 untreated or insufficiently treated) and 12 adult women with pure gonadal dysgenesis (8 untreated and 4 treated). A low bone density below -2 standard deviations from the age- and sex-matched predicted normal mean was documented by dual-photon absorptiometry of the lumbar spine in all the untreated and insufficiently treated patients, but only in 6 treated patients. The biochemical indices of bone resorption (urinary hydroxyproline excretion and plasma tartrate-resistant acid phosphatase activity), as well as osteoblastic function (serum osteocalcin and bone alkaline phosphatase isoenzyme), were significantly increased in untreated and insufficiently treated patients compared with treated patients. A significant negative correlation was found between biochemically documented osteoresorption and spinal bone mineral density corrected for age of the patients. Significant positive correlations were found between serum osteocalcin and bone alkaline phosphatase isoenzyme and between biochemical indices of bone resorption and formation. Although in the patients there was an evidence of a high bone remodeling rate, the rate of bone mass loss seemed to be low, comparable with that seen in oophorectomized women who had already passed their accelerated phase of bone loss. The results indicate that long-term hormonal replacement therapy is justified in gonadal dysgenesis, regardless of the karyotype of the patient, to prevent further bone mass loss.


The Relationship Between Magnet Designation, Electronic Health Record Adoption, and Medicare Meaningful Use Payments.
The objective of this study was to examine the relationship between nursing excellence and electronic health record adoption. Of 6582 US hospitals, 4939 were eligible for the Medicare Electronic Health Record Incentive Program, and 6419 were eligible for evaluation on the HIMSS Analytics Electronic Medical Record Adoption Model. Of 399 Magnet hospitals, 330 were eligible for the Medicare Electronic Health Record Incentive Program, and 393 were eligible for evaluation in the HIMSS Analytics Electronic Medical Record Adoption Model. Meaningful use attestation was defined as receipt of a Medicare Electronic Health Record Incentive Program payment. The adoption electronic health record was defined as Level 6 and/or 7 on the HIMSS Analytics Electronic Medical Record Adoption Model. Logistic regression showed that Magnet-designated hospitals were more likely attest to Meaningful Use than non-Magnet hospitals (odds ratio = 3.58, P < .001) and were more likely to adopt electronic health records than non-Magnet hospitals (Level 6 only: odds ratio = 3.68, P < .001; Level 6 or 7: odds ratio = 4.02, P < .001). This study suggested a positive relationship between Magnet status and electronic health record use, which involves earning financial incentives for successful adoption. Continued investigation is needed to examine the relationships between the quality of nursing care, electronic health record usage, financial implications, and patient outcomes.


Evidence for Mannitol as an Effective Agent Against Intracranial Hypertension: An Individual Patient Data Meta-analysis.
Mannitol is currently used to reduce intracranial pressure (ICP), but the evidence supporting its usefulness has been questioned. We aim to meta-analyze the effectiveness of mannitol in reducing ICP in adult patients with cerebral injuries and its dependency on baseline ICP values, comparing findings from individual patient data (IPD) and aggregated data (AD) meta-analysis performed on the same studies. We searched the Medline database, with no time limitation, through March 1, 2019. We selected studies for which IPD were available, with a before-after design, concerning adult patients with traumatic cerebral hemorrhages, subarachnoid hemorrhages, or hemorrhagic and ischemic stroke, treated with mannitol for increased intracranial hypertension. We extracted ICP values at baseline and at different time-points, and mannitol doses. We used a multilevel approach to account for multiple measurements on the same patient and for center variability. The AD meta-analysis and meta-regression were conducted using random-effects models. Three studies published IPD, and four authors shared their datasets. Two authors did not own their datasets anymore. Eight authors were unreachable, while 14 did not answer to our request. Overall, 7 studies provided IPD for 98 patients. The linear mixed-effects model showed that ICP decreased significantly after mannitol administration from an average baseline value of 22.1 mmHg to 16.8, 12.8, and 9.7 mmHg at 60, 120, and 180 min after mannitol administration. ICP reduction was proportional to baseline values with a 0.64 mmHg decrease for each unitary increment of the initial ICP value. Dose did not influence ICP reduction. The AD meta-analysis, based on data collected between 30 and 60 min from mannitol administration not accounting for multiple time-point measurements, overestimated ICP reduction (10 mmHg), while meta-regression provided similar results (0.66 mmHg decrease for each unitary increase of initial ICP). Mannitol is effective in reducing pathological ICP, proportionally to the degree of intracranial hypertension. IPD meta-analysis provided a more precise quantification of ICP variation than the AD approach.


Induced sputum methodology: Validity and reproducibility of total glutathione measurement in supernatant of healthy and asthmatic individuals.
Glutathione (GSH), a major antioxidant, has repeatedly been linked to the pathogenesis of pulmonary disease. The measurement of GSH in induced sputum (IS) offers a noninvasive tool for the study and monitoring of oxidative stress in airway diseases. In this study we assessed the validity and reproducibility of GSH quantification in IS from healthy subjects and individuals with mild asthma. We spectrophotometrically quantified total GSH in the IS of 31 healthy nonsmoking volunteers and 12 individuals with mild asthma. IS was processed with varying concentrations of dithiothreitol (DTT) in an effort to evaluate the effect of DTT on GSH measurements. We performed spiking experiments with defined concentrations of GSH and quantified the percentage of recovery and also analyzed the effect of induction time on GSH levels through sequential sampling of sputum portions (15, 30, and 45 minutes' induction). Finally we tested the reproducibility of GSH measurements at 2 separate time points (0 and 72 hours) and expressed it as an intraclass correlation coefficient (R(i)) with a coefficient of reliability (CR). Processing with DTT increased GSH values in IS (P <.05 for each DTT concentration > 0.001%). Recovery of GSH after spiking was complete, with a mean recovery of 102% +/- 4.8%. Increasing duration of induction led to an increase in sputum GSH (15 minutes, 10.2 +/- 2.3 micromol/L; 30 minutes, 18.4 +/- 3.5 micromol/L; 45 minutes, 26.1 +/- 4 micromol/L; P <.05 for all comparisons). Reproducibility of sputum GSH both in healthy subjects and asthmatic individuals was good (R(i) =.78, P <.001; and R(i) =.51, P =.003, respectively). With the use of standardized protocols for duration of induction and sample processing, sputum GSH measurement in healthy subjects and asthmatic individuals is valid and reproducible.


Systematic Analysis of Smooth Muscle and Cartilage Ring Formation during Mouse Tracheal Tubulogenesis.
The trachea tube is the exclusive route to allow gas exchange between the external environment and the lungs. Recent studies have shown the critical role of mesenchymal cells in tracheal tubulogenesis. Improved methods for studying the dynamics of the tracheal mesenchyme development are needed to investigate the cellular and molecular mechanisms during tracheal tubulogenesis. Here, we describe a detailed protocol for a systematic analysis of tracheal tube development to enable observing tracheal smooth muscle (SM) and cartilage ring formation. We describe immunostaining, confocal and stereomicroscopy imaging, and quantitative methods to study the process of tracheal SM and cartilage ring development, including SM cell alignment, polarization, and changes in cell shape as well as mesenchymal condensation. The technologies and approaches described here not only improve analysis of the patterning of the developing trachea but also help uncover the mechanisms underlying airway disease. This protocol also provides a useful technique to analyze cell organization, polarity, and nuclear shape in other organ systems.


A GABAergic projection from the zona incerta to cortex promotes cortical neuron development.
γ-Aminobutyric acid (GABA) is the major inhibitory transmitter in the mature brain but is excitatory in the developing cortex. We found that mouse zona incerta (ZI) projection neurons form a GABAergic axon plexus in neonatal cortical layer 1, making synapses with neurons in both deep and superficial layers. A similar depolarizing GABAergic plexus exists in the developing human cortex. Selectively silencing mouse ZI GABAergic neurons at birth decreased synaptic activity and apical dendritic complexity of cortical neurons. The ZI GABAergic projection becomes inhibitory with maturation and can block epileptiform activity in the adult brain. These data reveal an early-developing GABAergic projection from the ZI to cortical layer 1 that is essential for proper development of cortical neurons and balances excitation with inhibition in the adult cortex.


Fetal cardiac interventions: clinical and experimental research.
Fetal cardiac interventions for congenital heart diseases may alleviate heart dysfunction, prevent them evolving into hypoplastic left heart syndrome, achieve biventricular outcome and improve fetal survival. Candidates for clinical fetal cardiac interventions are now restricted to cases of critical aortic valve stenosis with evolving hypoplastic left heart syndrome, pulmonary atresia with an intact ventricular septum and evolving hypoplastic right heart syndrome, and hypoplastic left heart syndrome with an intact or highly restrictive atrial septum as well as fetal heart block. The therapeutic options are advocated as prenatal aortic valvuloplasty, pulmonary valvuloplasty, creation of interatrial communication and fetal cardiac pacing. Experimental research on fetal cardiac intervention involves technical modifications of catheter-based cardiac clinical interventions and open fetal cardiac bypass that cannot be applied in human fetuses for the time being. Clinical fetal cardiac interventions are plausible for midgestation fetuses with the above-mentioned congenital heart defects. The technical success, biventricular outcome and fetal survival are continuously being improved in the conditions of the sophisticated multidisciplinary team, equipment, techniques and postnatal care. Experimental research is laying the foundations and may open new fields for catheter-based clinical techniques. In the present article, the clinical therapeutic options and experimental fetal cardiac interventions are described.


Nitric Oxide Orchestrates a Power-Law Modulation of Sympathetic Firing Behaviors in Neonatal Rat Spinal Cords.
Nitric oxide (NO) is a diffusible gas and has multifarious effects on both pre- and postsynaptic events. As a consequence of complex excitatory and inhibitory integrations, NO effects on neuronal activities are heterogeneous. Using in vitro preparations of neonatal rats that retain the splanchnic sympathetic nerves and the thoracic spinal cord as an experimental model, we report here that either enhancement or attenuation of NO production in the neonatal rat spinal cords could increase, decrease, or not change the spontaneous firing behaviors recorded from splanchnic sympathetic single fibers. To elucidate the mathematical features of NO-mediated heterogeneous responses, the ratios of changes in firing were plotted against their original firing rates. In log-log plots, a linear data distribution demonstrated that NO-mediated heterogeneity in sympathetic firing responses was well described by a power function. Selective antagonists were applied to test if glycinergic, GABAergic, glutamatergic, and cholinergic neurotransmission in the spinal cord are involved in NO-mediated power-law firing modulations (plFM). NO-mediated plFM diminished in the presence of mecamylamine (an open-channel blocker of nicotinic cholinergic receptors), indicating that endogenous nicotinic receptor activities were essential for plFM. Applications of strychnine (a glycine receptor blocker), gabazine (a GABAA receptor blocker), or kynurenate (a broad-spectrum ionotropic glutamate receptor blocker) also caused plFM. However, strychnine- or kynurenate-induced plFM was diminished by L-NAME (an NO synthase inhibitor) pretreatments, indicating that the involvements of glycine or ionotropic glutamate receptor activities in plFM were secondary to NO signaling. To recapitulate the arithmetic natures of the plFM, the plFM were simulated by firing changes in two components: a step increment and a fractional reduction of their basal firing activities. Ionotropic glutamate receptor activities were found to participate in plFM by both components. In contrast, GABAA receptor activities are involved in the component of fractional reduction only. These findings suggest that NO orchestrates a repertoire of excitatory and inhibitory neurotransmissions, incurs a shunting effect on postsynaptic membrane properties, and thus, alters sympathetic firing in a manner of plFM. We propose that the plFM mediated by NO forms a basic scheme of differential controls for heterogeneous sympathetic regulation of visceral functions.


[A case of prostatic tuberculosis: usefulness of transrectal ultrasound in diagnosis].
A case of prostatic tuberculosis is reported. A 61-year-old male visited our clinic complaining of urinary retention. On digital rectal examination, the prostate was found to be enlarged, hard, and uneven. Transrectal ultrasound revealed a large hypoechoic lesion in the posterior aspect of the prostate. Transrectal ultrasound guided systematic biopsies of the prostate were performed. The specimens obtained from the hypoechoic lesion, were diagnosed histopathologically as prostatitis with epithelioid granuloma, Langhans' type giant cells, and caseous necrosis. Mycobacterium tuberculosis was detected in the physiological saline solution injected into the urethra after prostatic massage. The patient was diagnosed as having prostatic tuberculosis and underwent antituberculotic therapy with INH and RFP. Transrectal ultrasound seemed to be useful in detecting histopathological changes associated with tuberculosis in the prostate.


Crystalline Neutral Allenic Diborene.
A zwitterionic boraalkenyl boronium 3 was synthesized by reduction of cyclic (alkyl)(amino)carbene (cAAC) and trimethylphosphine (PMe3 )-coordinated tetrabromodiborane 2 with KC8 in the presence of PMe3 . Further reduction of 3 led to the formation of neutral allenic diborene 4. X-ray diffraction and computational studies revealed that 4 features the cumulated C=B and B=B double bonds. The reaction of 4 with four isonitrile molecules afforded a heterocycle 5 with the B2 C3 five-membered ring, via a complete scission of the B=B bond of 4.


Response to changing contingencies in infants at high and low risk for autism spectrum disorder.
One recently proposed theory of autism spectrum disorder (ASD) hypothesizes that individuals with the disorder may have difficulty using prior experiences to predict future events [Hellendoorn et al., 2015; Northrup, 2016; Sinha et al., 2014]. To date, this theory has not been tested in infancy. The current study analyzed how young infants at heightened (HR; older sibling with ASD) vs. low risk (LR; no first degree relatives with ASD) for ASD responded to changing contingencies when interacting with two visually identical rattles-one that produced sounds during shaking (Sound), and one that did not (Silent). Infants were given the rattles in a Sound-Silent-Sound order at 6 and 10 months, and shaking behavior was coded. Results indicated that LR and HR infants (regardless of ASD diagnosis) did not differ from each other in shaking behavior at 6 months. However, by 10 months, LR infants demonstrated high initial shaking with all three rattles, indicating expectations for rattle affordances, while HR infants did not. Significantly, HR infants, and particularly those with an eventual ASD diagnosis, did not demonstrate an "extinction burst"-or high level of shaking-in the first 10 sec with the "silent" rattle, indicating that they may have difficulty generalizing learning from one interaction to the next. Further, individual differences in the strength of this "extinction burst" predicted cognitive development in toddlerhood among HR infants. Difficulty forming expectations for new interactions based on previous experiences could impact learning and behavior in a number of domains. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1239-1248. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.


The influence of the electrolyte on chemical and morphological modifications of an iron sulfide thin film negative electrode.
The chemical and morphological modifications of FeS thin film as anode material for LiBs have been studied in detail in two classical electrolytes usually used in Li-ion batteries: 1 M LiClO4-PC and 1 M LiPF6-EC/DMC. The X-ray photoelectron spectroscopic (XPS) analysis evidenced the formation of a solid electrolyte interphase (SEI) that contains a more significant amount of inorganic salt residues formed in LiPF6-EC/DMC than in LiClO4-PC, which is likely to increase the ionic resistivity of the SEI, thus impeding the lithiation-delithiation in the first cycles while improving its reversibility. Ion depth profiles performed by time-of-flight secondary ion mass spectrometry (ToF-SIMS) show volume expansion-shrinkage of the thin film leading to cracking and pulverization of the electrode material, which is also confirmed by scanning electron microscopy (SEM) analysis. The prolonged cycling results in penetration and accumulation of the electrolyte in a bulk electrode with accumulation of the inorganic species in the inner part of the SEI enhanced in a fluoride-containing electrolyte. Cycling in these two different electrolytes leads also to formation of two different electrode morphologies: with a compact electrode structure formed in LiClO4-PC and a foam-like, porous structure in LiPF6-EC/DMC. A model of this conversion-type thin film electrode modification based on these thorough spectroscopic and microscopic analyses induced by cycling in two different electrolytes is proposed.


Bayesian inference of spreading processes on networks.
Infectious diseases are studied to understand their spreading mechanisms, to evaluate control strategies and to predict the risk and course of future outbreaks. Because people only interact with few other individuals, and the structure of these interactions influence spreading processes, the pairwise relationships between individuals can be usefully represented by a network. Although the underlying transmission processes are different, the network approach can be used to study the spread of pathogens in a contact network or the spread of rumours in a social network. We study simulated simple and complex epidemics on synthetic networks and on two empirical networks, a social/contact network in an Indian village and an online social network. Our goal is to learn simultaneously the spreading process parameters and the first infected node, given a fixed network structure and the observed state of nodes at several time points. Our inference scheme is based on approximate Bayesian computation, a likelihood-free inference technique. Our method is agnostic about the network topology and the spreading process. It generally performs well and, somewhat counter-intuitively, the inference problem appears to be easier on more heterogeneous network topologies, which enhances its future applicability to real-world settings where few networks have homogeneous topologies.


Bifunctional LaMn0.3Co0.7O3 Perovskite Oxide Catalyst for Oxygen Reduction and Evolution Reactions: The Optimized eg Electronic Structures by Manganese Dopant.
Perovskite oxides as bifunctional electrocatalysts toward oxygen reduction (ORR) and oxygen evolution reactions (OER) have been investigated for decades because of the flexible and adjustable electronic structures. For example, by optimizing the strength of the Co-O bond, the ORR and OER activity of a typical perovskite oxide, LaCoO3, can be improved, but they are still unsatisfying. The insufficient insights into the effects of secondary metal dopants at the B-site on the electronic structure and activity, especially for ORR, significantly limit the R&D of bifunctional perovskite oxide catalysts. In this work, a series of LaMnxCo1-xO3 (x = 0, 0.25, 0.3, 0.35, 0.5, 1) catalysts are prepared by a polyol-assisted solvothermal method to investigate the structure-property relationships between the B-site metal substitution and the electrochemical performance of perovskite oxides catalysts. The optimized LaMn0.3Co0.7O3 catalyst demonstrates an enhanced half-wave potential of 0.72 V for ORR, 52 mV higher than that of the pristine LaCoO3 (0.668 V). Meanwhile, the OER overpotential of LaMn0.3Co0.7O3 catalyst is 416 mV, which is reduced by 64 mV compared to LaCoO3 (480 mV). It is revealed that the appropriate Mn dopant efficiently optimizes the covalency of Co-O bonds and significantly reduces the eg orbit-filling electron from 1.23 of pristine LaCoO3 to 1.02 in LaMn0.3Co0.7O3 (very close to theoretical value 1). This work paves a new way to design and synthesize bifunctional perovskite oxide electrocatalyst for ORR and OER.


Contrasted impact of maternal rat food restriction on the fetal endocrine pancreas.
The effects of food restriction of the mother (65% restriction of ad libitum food intake) on fetal and maternal insulin secretion and islet function were studied at 21 days gestation in three different rat populations: 1) undernourished from 0-7 days gestation, 2) undernourished from 7-14 days gestation, and 3) undernourished from 14-21 days gestation. The body weights of mothers were decreased in groups 2 and 3 vs. those in control fed pregnant animals, and no changes in basal parameters were found in any group. A glucose tolerance test in mothers from group 3 showed a mild intolerance to glucose and a decreased islet insulin content, although islet stimulation in vitro with glucose alone or plus arginine showed a normal insulin secretory response. Body weight was decreased in fetuses from the three groups (P < 0.01), and pancreas weight was reduced only in group 3. Insulinemia was increased in groups 2 and 3, and pancreatic insulin content increased only in group 3. However, fetuses from mothers of group 3 showed increased islet insulin content, increased response of insulin in vitro to glucose or glucose plus arginine, and hypertrophy of beta-cell mass. These results indicate, first, that the development of the fetal pancreas depends on a balanced maternal glucose homeostasis and, second, that adaptive maternal changes to undernutrition seem to induce alterations on the fetal endocrine pancreas, especially when food restriction is applied during the last week of gestation.


Bioavailability of two L-thyroxine formulations after oral administration to healthy dogs.
To describe the pharmacokinetics of two veterinary formulations of L-thyroxine available in Australia. A two-phase randomised, crossover, open-label trial followed by a third-phase parallel-dosing trial was conducted in 11 healthy dogs with an investigative oral L-thyroxine liquid formulation and a reference tablet formulation. Blood sampling was done at defined intervals and serum total L-thyroxine concentrations were measured by radioimmunoassay. The post-dose concentrations were plotted as a function of time for each period and the relative bioavailability of the two formulations were compared using a general linear model with factors for dog, phase, sequence and formulation. Following oral administration of the reference tablet at the dose of 100 μg/kg, a maximum plasma concentration of approximately 96.2 nmol/L (baseline endogenous corrected) was reached within 3.77 h. For the investigative liquid preparation at a dose of 50 μg/kg, the maximum plasma concentration was 60.1 nmol/L (baseline endogenous corrected), which was reached within 3.59 h. The geometric mean of the relative bioavailability for the liquid/tablet product was 1.1, which suggests that the relative bioavailability of thyroxine following administration of tablet or liquid formulation is similar.


[The dependence of the osmotic properties of Escherichia coli bacteria on temperature].
The influence of water solutions of NaCl on the osmoresistance and reproduction of E. coli B/r and E. coli Bs-1 at different temperatures was studied. The increase in cell resistance was studied. The increase in cell resistance to NaCl hypertonia was noticed after the temperature rise from 20 to 37 degrees C. In this case the concentration of NaCl in the medium, which made this medium isotonic, was seen to increase too. On the contrary, when the temperature decreased to 0 degrees, the cell resistance to high concentrations of NaCl was found suppressed. In this case the concentration of NaCl in the medium, which made this medium isotonic, was seen to decrease. The salt tolerance of bacteria reproduction was found to depend on the temperature: the tolerance increased with the temperature rise, and vice versa. It is concluded that the solution temperature was to be considered as one of the major factors governing the osmotic bacterial cell homeostasis.


New physics searches at kaon and hyperon factories.
Rare meson decays are among the most sensitive probes of both heavy and light new physics. Among them, new physics searches using kaons benefit from their small total decay widths and the availability of very large datasets. On the other hand, useful complementary information is provided by hyperon decay measurements. We summarize the relevant phenomenological models and the status of the searches in a comprehensive list of kaon and hyperon decay channels. We identify new search strategies for under-explored signatures, and demonstrate that the improved sensitivities from current and next-generation experiments could lead to a qualitative leap in the exploration of light dark sectors.


Clostridium septicum Bacteremia As the Presenting Sign of Colon Cancer.
Colon cancer is one of the leading causes of morbidity and mortality throughout the world. Some of the most common presenting signs are a change in bowel habits, alteration of fecal contour or consistency, blood in stool, fatigue, and weight loss. However, it may present insidiously. This is the case of an 81-year-old female with Clostridium septicum bacteremia as the primary presenting sign of metastatic colon cancer. In further literature review, we discuss the genomic associations that contribute to the severity of the disease and explore the potential links between the gut microbiome and colorectal carcinoma. This article highlights risk factor modifications and lab abnormalities that may be useful for the primary care provider and acute care practitioner.


[Subfulminant hepatitis A treated by hepatic transplant].
A case of subfulminant hepatitis A in a 3 1/2 year-old boy is reported. This child is alive after a liver transplantation. Such a procedure should modify the prognosis of severe hepatic failure whatever its origin, viral or toxic. Some practical problems concerning this new management of fulminant hepatitis are considered.


Optomagnetic read-out enables easy, rapid, and cost-efficient qualitative biplex detection of bacterial DNA sequences.
There is an increasing need to develop novel bioassay methods for low-cost, rapid, and easy-to-use multiplex detection of pathogens in various fields ranging from human infectious disease diagnosis, drinking water quality control, to food safety applications. Due to their unique advantages, magnetic and optomagnetic bioassay principles are particularly promising for biodetection platforms that will be used in developing countries. In this paper, an optomagnetic method for rapid and cost-efficient qualitative biplex detection of bacterial DNA sequences is demonstrated. Within less than two hours, the assay gives an answer to whether none, both, or only one of the bacterial DNA sequences is present in the sample. The assay relies on hybridization of oligonucleotide-functionalized magnetic nanobeads of two different sizes to rolling circle amplification (RCA) products originating from two different bacterial targets. The different bead sizes are equipped with different oligonucleotide probes, complementary to only one of the RCA products, and the read-out is carried out in the same sample volume. In an optomagnetic setup, the frequency modulation of transmitted laser light in response to an applied AC magnetic field is measured. The presented methodology is potentially interesting for low-cost screening of pathogens relating to both human and veterinary medicine in resource-poor regions of the world.


α-Aminoalkyl Radical Addition to Maleimides via Electron Donor-Acceptor Complexes.
A catalyst-free, photochemical oxidative annulation reaction between dialkylanilines and maleimides to generate tetrahydroquinolines is presented. The reaction is driven by the photochemical activity of an electron donor-acceptor (EDA) complex and has a broad substrate scope with the corresponding products isolated in good to excellent yields. Photochemical characterization of the EDA complex and a mechanistic rational is provided.


Echocardiographic aortic valve calcification and outcomes in women and men with aortic stenosis.
Sex differences in risk factors of aortic valve calcification (AVC) by echocardiography have not been reported from a large prospective study in aortic stenosis (AS). AVC was assessed using a prognostically validated visual score and grouped into none/mild or moderate/severe AVC in 1725 men and women with asymptomatic AS in the Simvastatin Ezetimibe in Aortic Stenosis study. The severity of AS was assessed by the energy loss index (ELI) taking pressure recovery in the aortic root into account. More men than women had moderate/severe AVC at baseline despite less severe AS by ELI (p<0.01). Moderate/severe AVC at baseline was independently associated with lower aortic compliance and more severe AS in both sexes, and with increased high-sensitive C reactive protein (hs-CRP) only in men (all p<0.01). In Cox regression analyses, moderate/severe AVC at baseline was associated with a 2.5-fold (95% CI 1.64 to 3.80) higher hazard rate of major cardiovascular events in women, and a 2.2-fold higher hazard rate in men (95% CI 1.54 to 3.17) (both p<0.001), after adjustment for age, hypertension, study treatment, aortic compliance, left ventricular (LV) mass and systolic function, AS severity and hs-CRP. Moderate/severe AVC at baseline also predicted a 1.8-fold higher hazard rate of all-cause mortality in men (95% CI 1.04 to 3.06, p<0.05) independent of age, AS severity, LV mass and aortic compliance, but not in women. In conclusion, AVC scored by echocardiography has sex-specific characteristics in AS. Moderate/severe AVC is associated with higher cardiovascular morbidity in both sexes, and with higher all-cause mortality in men. ClinicalTrials.gov identifier: NCT00092677.


Noiseless Performance of Prussian Blue Based (Bio)sensors through Power Generation.
In contrast to "self-powered" (bio)sensors aiming to generate maximum energy output, we propose the systems with the lowest potential difference between the working and the counter electrodes, which in galvanic mode would provide achievement of the best analytical performance characteristics. Prussian Blue based (bio)sensors known to operate at 0.00 V versus Ag|AgCl reference, in the short-circuit regime generate the current proportional to analyte concentration. Sensitivity and dynamic range of Prussian Blue based (bio)sensors in power generation mode are, respectively, even slightly higher and wider compared to the same (bio)sensors operated in the conventional three-electrode regime powered by a potentiostat. Selectivity of the (bio)sensors in power generation mode is similarly high relative to both oxygen, allowing H2O2 detection by its reduction, and reductants. Among the most important advantages of the proposed power generation mode is an order of magnitude decreased noise compared to performance in a conventional three-electrode setup powered by a potentiostat. Noiseless performances of Prussian Blue based (bio)sensors would open new horizons for electrochemical analysis.


Cloning, expression and immunization of the new antigen gene Sj-Ts4 of Schistosoma japonicum.
In order to explore the molecular mechanism of high immune protection against schistosomes infection in animals infected with Trichinella spiralis, and to provide several cross-protective antigen genes for developing anti-schistosomiasis vaccine, a Schistosoma japonicum adult worm cDNA library was immunoscreened using sera taken from mice infected with Trichinella spiralis. Nine positive clones were obtained after 3 rounds of immunoscreening. Among them, Sj-Ts4 represents a novel gene of S. japonicum, which coding for a novel protein of 210 amino acids. The protein has a deduced molecular mass of 23 kD and isoelectric point of 7.72. Sj-Ts4 was expressed as a glutathione-S-transferase (GST) fusion protein by cloning into the prokaryotic expression vector pGEX-5X-3. The recombinant Sj-Ts4 protein (rSj-Ts4) was purified and could be recognized by sera of mice infected with S.japonicum. Vaccination of several groups of mice with rSj-Ts4 or rSj-Ts4 incorporated into Freund's complete adjuvant induced high titers of specific IgG antibodies. Two vaccination groups all obtained significant reduction in worm burden (31.36%, 36.80%, P<0.01), compared with the control groups.


The impact of mirror therapy on body schema perception in patients with complex regional pain syndrome after distal radius fractures.
Mirror therapy requires a minimum of equipment, is relatively simple to perform and effective for various pathological conditions. The effect of mirror therapy on body schema disturbances registered in complex regional pain syndrome type I (CRPS I) patients has not yet been determined. The study is based on the analysis of the treatment results of 30 patients with CRPS I, developed as a result of the distal radius fractures, with help of mirror therapy together with exercise therapy and medications. The control group consisted of 20 patients with CRPS I developed as a result of the distal radius fractures treated only with exercise therapy and medications. We evaluated the results before the treatment, after 3 days and after 6 weeks of treatment according to The Bath CRPS Body Perception Disturbance Scale. A total of 83.33% patients experienced the positive effect of mirror therapy on the perception of the 'body schema' after 6 weeks of treatment, and 35% underwent standard treatment without mirror therapy. The positive effect was statistically significant for the first five points of the Bath scale after 6 weeks of treatment compared to the control group. Improvements observed in some patients after 3 days of treatment were less pronounced and statistically insignificant. Mirror therapy can improve the perception of the body schema as an element of integrated treatment of CRPS I developed after fractures of the distal radius less than 3 years duration.


Nitric oxide promotes proliferation and plasminogen activator production by coronary venular endothelium through endogenous bFGF.
We reported previously that NO is responsible for the angiogenesis produced by endothelium-dependent vasodilating peptides. To investigate the mechanisms by which NO controls angiogenesis, NO was assessed for the ability to affect cell proliferation and upregulation of urokinase-type plasminogen activator (uPA) induced by basic fibroblast growth factor (bFGF) when added exogenously to or when produced endogenously by coronary venular endothelial cells (CVECs). The treatment of the cells with the NO donor sodium nitroprusside (NaNp) induced uPA upregulation and cell proliferation, which were prevented by anti-bFGF antibodies. Similarly, the NO-dependent mitogenic activity of the vasodilating peptide substance P (SP) was blocked by anti-bFGF antibodies, thus implicating endogenous bFGF in the NO-induced response. NaNp and SP induced bFGF expression as measured by Western blot analysis of CVEC extracts and by differential reverse transcriptase-polymerase chain reaction of bFGF mRNA. SP-induced upregulation of bFGF was prevented by the NO synthase inhibitor N omega-monomethyl-L-arginine. We conclude that NO promotes cell proliferation and uPA upregulation in CVECs by inducing endogenous bFGF and that this pathway mediates the angiogenetic response to the vasoactive neuropeptide SP. This signaling paradigm may provide an important link between shear rate, NO, bFGF, and coronary angiogenesis.


Adolescent coarctation of aorta treated with subclavian-descending aorta bypass grafting.
Aortic coarctation in older children most frequently represents cases of re-coarctation following previous transcatheter or surgical therapy or missed cases of native coarctation. We describe three cases of adolescents – two girls and one boy – with aortic coarctation, operated between January, 2012 and December, 2013. Computed tomography angiography was performed as an essential diagnostic procedure. Hypertension was detected, and weaker arterial pulses in the lower limbs were noted in all cases. All operations were performed via left posterolateral thoracotomy. Aortic coarctation was treated surgically, with left subclavian-lower descending thoracic aorta bypass grafting. Postoperative course was uneventful in all cases. No residual brachial-ankle pressure gradient was observed, and all patients have remained in good condition after the operation. Surgical treatment of aortic coarctation in adolescent patients can be achieved by resection with end-to-end anastomosis, interposition of a graft or bypass graft across the area of coarctation when the distance to be bridged is too long for end-to-end repair. The extra-anatomic subclavian-descending aortic bypass grafting provides good results in adolescent patients, particularly in those with complex coarctation.


An interdisciplinary educational trial for adolescent health and development in urbanising China.
To evaluate the effects on master student participants of an intensive interdisciplinary educational programme aiming at improving adolescent health and development services in urbanising China. There is a need for interdisciplinary education and collaborative practice in health, but few educational programmes have been reported. Experimental design including a qualitative component. Purposive sampling was used to identify master students in relevant disciplinary areas for the four-day classroom learning, four-day field learning and a half-day reflection, focusing on key aspects of adolescent health and development in the face of rapid urbanisation. Data about family function, cognitive development, adolescent health and development competency, and difficulties caused by health conditions were collected using quantitative and qualitative methods. Master student participants reported positive outcomes in adolescent health and development competency, and cognitive development. Six themes were identified about the programme and its impact: 'programme evaluation', 'programme characteristics', 'changed views about nursing and nurses', 'lessons learned', 'participation benefits' and 'suggestions for future action'. Interdisciplinary educational programmes are possible and beneficial at masters level but may be very challenging given the need for administrative, financial and human resources. Interdisciplinary educational programmes require to start with small health sector trials to accumulate evidence and skills. Faculty development is a prerequisite for such programmes towards collaborative practice.


[Urological illnesses in the elderly].
Urological illnesses in the elderly are a growing clinical problem because as life expectancy increases so does the prevalence of such illnesses. However, sufficient data for judging the various possible therapies are lacking for patients over the age of 70. Age itself does not have enough predictive value for the determination of the best treatment. It seems more important to estimate the functional and socio-economic status, comorbidity, and the cognitive and emotional abilities of elderly patients as well as their nutritional intake.


Children's history of speech-language difficulties: genetic influences and associations with reading-related measures.
This study examined (a) the extent of genetic and environmental influences on children's articulation and language difficulties and (b) the phenotypic associations between such difficulties and direct assessments of reading-related skills during early school-age years. Behavioral genetic analyses focused on parent-report data regarding the speech-language skills of 248 twin pairs (M = 6.08 years) from the Western Reserve Reading Project. In addition, phenotypic associations between children's speech-language status and direct assessments of early reading-related abilities were examined through hierarchical linear modeling (HLM). Probandwise concordance rates and intraclass tetrachoric correlations indicated high heritability for children's difficulties in expressive language and articulation, with estimates of .54 and .97 accordingly. HLM results indicated that children with histories of speech-language difficulties scored significantly lower than unaffected children on various measures of early reading-related abilities. Results from the parent-report survey provided converging evidence of genetic effects on children's speech and language difficulties and suggest that children with a history of speech-language difficulties are at risk for lower performance on early reading-related measures. The extent of risk differed across measures and appeared greatest for children who demonstrated a history of difficulties across articulation, expressive language, and receptive language. Implications for future genetic research and clinical practice are discussed.


Effect of nurse staffing and education on the outcomes of surgical patients with comorbid serious mental illness.
This study of surgical patients compared outcomes of those with and those without serious mental illness and examined effects of patient-to-nurse ratios and nurses' education levels on outcomes, including death within 30 days of admission, failure to rescue (death resulting from surgery complication), and length of stay. Cross-sectional data from a nurse survey and from patient and administrative records were linked. Data for 9,989 nurses and 228,433 surgical patients discharged from 157 Pennsylvania hospitals were analyzed by using generalized estimating equations. Records indicated that 4.7% (N=10,666) of the sample had a diagnosis of serious mental illness. A higher level of nurse staffing had a stronger effect on prevention of death among patients with serious mental illness than among those without it. Length of stay for patients with serious mental illness was shorter in hospitals with higher proportions of baccalaureate-prepared nurses. Better nurse staffing and higher education level mitigated poor patient outcomes among highly vulnerable patients with serious mental illness.


Molecular Dynamics Simulations of the Host Defense Peptide Temporin L and Its Q3K Derivative: An Atomic Level View from Aggregation in Water to Bilayer Perturbation.
Temporin L (TempL) is a 13 residue Host Defense Peptide (HDP) isolated from the skin of frogs. It has a strong affinity for lipopolysaccharides (LPS), which is related to its high activity against Gram-negative bacteria and also to its strong tendency to neutralize the pro-inflammatory response caused by LPS release from inactivated bacteria. A designed analog with the Q3K substitution shows an enhancement in both these activities. In the present paper, Molecular Dynamics (MD) simulations have been used to investigate the origin of these improved properties. To this end, we have studied the behavior of the peptides both in water solution and in the presence of LPS lipid-A bilayers, demonstrating that the main effect through which the Q3K substitution improves the peptide activities is the destabilization of peptide aggregates in water.


Bacterial profile and their antimicrobial resistance patterns among patients with community-acquired pneumonia in southwestern Iran.
Community-acquired pneumonia (CAP) is one of the most common life-threatening infections, occurring in the community or within the first 48 hours of a patient's hospitalization. The present study aimed to investigate the frequency of pathogenic bacteria and their antibiotic resistance pattern in the sputum of patients with community-acquired pneumonia in Yasuj from 2018 to 2019. In the present study, 128 patients with CAP were included. Under aseptic conditions clinical samples including sputum collected from each patient were sent to the Microbiology Laboratory. Specific culture media and biochemical tests were used to identify the bacteria. Antimicrobial resistance patterns of the isolates were examined by disc diffusion. DNA was extracted from sputum using the phenol-chloroform method. The PCR method was used for the molecular detection of bacteria. Data were analyzed using SPSS software version 22 and the chi-square test. The most common clinical symptoms in patients were sputum (68.8%), fever (64.1%), shortness of breath (60.2%), cough (50.8%), and chest pain (24.2%). A total of 133 bacteria were identified by culture and 117 bacteria by PCR. In the current study, the most prevalent organisms were Streptococcus pneumoniae (24.1%), Hemophilus influenzae (18%), Staphylococcus aureus (13.5%), and Moraxella catarrhalis (11.4%). Antibiogram test showed that most of the Gram-negative bacteria were resistant to levofloxacin (22.6%), rifampin (20.8%) and ceftriaxone (17%), and the highest resistance rate to clindamycin (43.1%), ciprofloxacin (43.1%) and amoxicillin (41.4%) were detected in the Gram-positive bacteria. Cefepime was the most effective antibiotic against Gram negative bacteria. S. pneumoniae was the most prevalent bacteria identified by culture and PCR methods in patients with CAP, indicating an important role of this bacterium in the pathogenesis of CAP. According to the results, cefepime can be used to treat patients with CAP with Gram-negative bacteria. In the present study, S. pneumoniae, S. aureus, P. aeruginosa, H. influenzae, M. catarrhalis, and K. pneumoniae have been isolated from the CAP patient population with varying frequencies. This is consistent with various studies in different parts of the world.


Using a state-and-transition approach to manage endangered Eucalyptus albens (White Box) woodlands.
Eucalyptus albens (White Box) woodlands are among the most poorly conserved and threatened communities in Australia. Remnants are under further threat from stock grazing, deteriorating soil conditions, weed invasion, and salinity. There is an urgent need to restore degraded White Box and other woodland ecosystems to improve landscape function. However, there is still a poor understanding of the ecology of degraded woodland ecosystems in fragmented agricultural landscapes, and consequently a lack of precise scientific guidelines to manage these ecosystems in a conservation context. State and Transition Models (STMs) have received a great deal of attention, mainly in rangeland applications, as a suitable framework for understanding the ecology of complex ecosystems and to guide management. We have developed a STM for endangered White Box woodlands and discuss the merits of using this approach for land managers of other endangered ecosystems. An STM approach provides a greater understanding of the range of states, transitions, and thresholds possible in an ecosystem, and provides a summary of processes driving the system. Importantly, our proposed STM could be used to clarify the level of "intactness" of degraded White Box woodland sites, and provide the impetus to manage different states in complementary ways, rather than attempting to restore ecosystems to one pristine stable state. We suggest that this approach has considerable potential to integrate researcher and land manager knowledge, focus future experimental studies, and ultimately serve as a decision support tool in setting realistic and achievable conservation and restoration goals.


Isolating primary melanocyte-like cells from the mouse heart.
We identified a novel population of melanocyte-like cells (also known as cardiac melanocytes) in the hearts of mice and humans that contribute to atrial arrhythmia triggers in mice. To investigate the electrical and biological properties of cardiac melanocytes we developed a procedure to isolate them from mouse hearts that we derived from those designed to isolate neonatal murine cardiomyocytes. In order to obtain healthier cardiac melanocytes suitable for more extensive patch clamp or biochemical studies, we developed a refined procedure for isolating and plating cardiac melanocytes based on those originally designed to isolate cutaneous melanocytes. The refined procedure is demonstrated in this review and produces larger numbers of healthy melanocyte-like cells that can be plated as a pure population or with cardiomyocytes.


Iron Acquisition Systems of Gram-negative Bacterial Pathogens Define TonB-Dependent Pathways to Novel Antibiotics.
Iron is an indispensable metabolic cofactor in both pro- and eukaryotes, which engenders a natural competition for the metal between bacterial pathogens and their human or animal hosts. Bacteria secrete siderophores that extract Fe3+ from tissues, fluids, cells, and proteins; the ligand gated porins of the Gram-negative bacterial outer membrane actively acquire the resulting ferric siderophores, as well as other iron-containing molecules like heme. Conversely, eukaryotic hosts combat bacterial iron scavenging by sequestering Fe3+ in binding proteins and ferritin. The variety of iron uptake systems in Gram-negative bacterial pathogens illustrates a range of chemical and biochemical mechanisms that facilitate microbial pathogenesis. This document attempts to summarize and understand these processes, to guide discovery of immunological or chemical interventions that may thwart infectious disease.


Simple high-performance liquid chromatography method for the simultaneous determination of ketoconazole and piperine in rat plasma and hepatocyte culture.
Piperine, a major alkaloid of black and long peppers has been reported to act as bioavailability enhancer of several drugs by inhibiting drug metabolising enzymes and/or by increasing oral absorption. Ketoconazole is a well established potent inhibitor of CYP 3A4 and P-glycoprotein. A simple and rapid HPLC method has been developed for the simultaneous analysis of ketoconazole and piperine in rat plasma and hepatocyte culture. Analysis was performed using a Symmetry C18 column (150x4.6 mm, 5 microm) and isocratic elution with 25 mM KH2PO4 (pH 4.5)-acetonitrile (50:50) with a flow-rate of 1 ml/min. Photodiode array detection was used to simultaneously monitor piperine at 340 nm and ketoconazole at 231 nm in a single sample. Calibration plots in spiked plasma, hepatocytes and William's medium E were linear over the range studied (10-2000 ng for both drugs). The detection limits for piperine and ketoconazole are 2 and 4 ng, respectively, and the limits of quantitation are 10 and 12 ng, respectively. Intra- and inter-assay variations were less than 8%.


Invited Commentary: Heterogeneity of Cardiovascular Diseases Among Populations-Recognition and Seminal Explanations.
Kuller and Reisler's 1971 publication (Am J Epidemiol. 1971;93(1):1-9) was an important contribution to the understanding of the epidemiology of cardiovascular diseases, particularly stroke. The authors synthesized pathological and risk-factor evidence to theorize why rates of various subtypes of arterial disease might vary across populations. Specifically, they suggested that different population levels of blood pressure, lipids, and glucose led to population differences in the location and extent of arterial disease. The publication is an excellent model of how to integrate data on person, place, and time of a major public health problem, together with information on pathology and factors that determine individual risk, to derive a coherent explanation for population patterns in cardiovascular disease. The authors' basic theory has proven solid for the past 5 decades.


SFKs/p38 Pathway is Involved in Radicular Pain by Promoting Spinal Expression of Pro-Inflammatory Cytokines in a Rat Model of Lumbar Disc Herniation.
A controlled, randomized, animal study. The aim of this study was to investigate the role of src-family kinases/p38 pathway in a rat model of lumbar disc herniation (LDH). LDH always generates radicular pain, and the mechanism remains unclear. We have reported that spinal src-family kinases (SFKs) may be involved in the process, but the downstream mechanism needs further investigation. LDH was induced by implantation of autologous nucleus pulposus (NP), harvest from the tail, in lumbar 4/5 spinal nerve roots of rat. Von Frey filaments and radiant heat tests were performed to determine mechanical and thermal pain threshold respectively. Basso, Beattie, and Bresnahan (BBB) scale was assessed to test the locomotor function. The protein level of p-SFKs, t-SFKs, p-p38, t-p38 in spinal cord was examined by western blotting analysis. Cellular location of p-p38 was determined by immunochemistry staining. Spinal tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 levels were detected by enzyme-linked immunosorbent assay (ELISA). Rats with NP implantation showed persistent ipsilateral mechanical allodynia and thermal hyperalgesia, which manifested as obvious decrease of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). BBB scale indicated the locomotor function of hindpaws in rats with NP implantation kept intact. Western blotting and immunohistochemistry staining revealed that phosphorylated SFKs (p-SFKs) and phosphorylated p38 MAPK (p-p38) were sequentially upregulated in ipsilateral spinal dorsal horn, but not in contralateral side of rats with NP. Intrathecal delivery of SFKs inhibitor reduced spinal p-p38 expression. Both SFKs and p38 inhibitors alleviated pain behaviors in a dose-responsive manner without disturbing locomotor function and reduced spinal expression of TNF-α, IL-1β, and IL-6 in rats with NP. Spinal SFKs contribute to radicular pain by activation of p38 MAPK and increasing pro-inflammatory cytokines expression in rats with NP implantation. Targeting SFKs/p38 pathway may be helpful for alleviating radicular pain. N/A.


Discharge of elongated grains in silos under rotational shear.
The discharge of elongated particles from a silo with rotating bottom is investigated numerically. The introduction of a slight transverse shear reduces the flow rate Q by up to 70% compared with stationary bottom, but the flow rate shows a modest increase by further increasing the external shear. Focusing on the dependency of flow rate Q on orifice diameter D, the spheres and rods show two distinct trends. For rods, in the small-aperture limit Q seems to follow an exponential trend, deviating from the classical power-law dependence. These macroscopic observations are in good agreement with our earlier experimental findings [Phys. Rev. E 103, 062905 (2021)2470-004510.1103/PhysRevE.103.062905]. With the help of the coarse-graining methodology we obtain the spatial distribution of the macroscopic density, velocity, kinetic pressure, and orientation fields. This allows us detecting a transition from funnel to mass flow pattern caused by the external shear. Additionally, averaging these fields in the region of the orifice reveals that the strong initial decrease in Q is mostly attributed to changes in the flow velocity, while the weakly increasing trend at higher rotation rates is related to increasing packing fraction. Similar analysis of the grain orientation at the orifice suggests a correlation of the flow rate magnitude with the vertical orientation and the packing fraction at the orifice with the order of the grains. Lastly, the vertical profile of mean acceleration at the center of the silo denotes that the region where the acceleration is not negligible shrinks significantly due to the strong perturbation induced by the moving wall.


Treatment of symptom clusters: pain, depression, and fatigue.
There is not yet sufficient evidence-based experience for the coordinated treatment of three symptoms that cluster in cancer: pain, depression, and fatigue. Each symptom taken individually has accepted treatment modalities. With some overlap between these symptoms, established treatments for one symptom may "cross-over" and reduce the burden of one, or both of the others. To optimize patient care in advance of the evidence basis, attention to these symptoms is value-added for patients and their families. Standardized screening using the Distress Thermometer for physical, practical, emotional, or spiritual symptoms helps effectively identify patients whose symptoms warrant attention. Cancer Supportive Services, an innovative program at the Continuum Cancer Centers of New York at Beth Israel and St. Luke's-Roosevelt, provides comprehensive intervention throughout the trajectory of care for pain, depression, and fatigue. These services are provided in tandem with efforts to cure or contain the cancer. Cancer Supportive Services sets up a natural entry point to survivors' follow-up or end-of-life care. Such an effort reinforces a basic principle that active symptom management is integral to each patient encounter in the cancer treatment setting.


Mucilaginibacter aquaedulcis sp. nov., isolated from fresh water.
An aerobic, Gram-stain-negative, rod-shaped bacterium, designated strain PGW1-R01(T), was isolated from fresh water from the Yeongju in the Republic of Korea. The strain grew optimally at 30 °C and at pH 6-8 on R2A agar. The major cellular fatty acids were summed feature 3 [comprising C16 : 1ω7c and/or C16 : 1ω6c (50.2 %) and iso-C15 : 0 (24.8 %)]. The major respiratory quinone was MK-7. The G+C contents were 39.4 mol% and the predominant respiratory quinone was MK-7. Based on 16S rRNA gene phylogeny, the strain belongs to the genus Mucilaginibacter. The strain PGW1-R01(T) was closely related to 'Mucilaginibacter ginsenosidivorax' (96.6 % sequence similarity), Mucilaginibacter lappiensis (96.4 %) and Mucilaginibacter flavus (96.4 %). On the basis of the evidence presented in this study, strain PGW1-R01(T) represents a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacter http://dx.doi.org/10.1601/nm.11437aquaedulcis sp. nov., is proposed. The type strain is PGW1-R01(T)( = KCTC 23942(T) = CECT 8102(T)).


Topical, residual and ovicidal contact toxicity of three reduced-risk insecticides against the European corn borer, Ostrinia nubilalis (Lepidoptera: Crambidae), on potato.
The goal of the research was to gather efficacy data required to introduce reduced-risk insecticides in sustainable control programs for European corn borer, Ostrinia nubilalis Hubner, on potato. Laboratory tests confirmed that sprays of indoxacarb and novaluron at recommended field rates are as effective as spinosad against neonate larvae of O. nubilalis. However, there is evidence that higher rates would enhance the inhibition of chitin synthesis by novaluron. The three insecticides showed ovilarvicidal activity when applied to O. nubilalis egg masses 2 days prior to black head stage. The ovicidal activity of spinosad and novaluron was almost twice that of indoxacarb. At the recommended field rates, the residues of the three insecticides displayed contact toxicity to O. nubilalis larvae. Spinosad residues 16 h old or less provided the highest immediate (24 h after exposure) contact mortality, followed by indoxacarb and then by novaluron. Also, residues of spinosad had faster contact efficacy than indoxacarb, which had faster efficacy than novaluron. Spinosad, indoxacarb and novaluron have ovicidal properties, which could enhance O. nubilalis management programs. However, the contact residual toxicity is limited in duration and would likely only play a minor role in O. nubilalis control.


Interleukin 2 regulates antigen-specific immunoglobulin response of naive murine B cells.
Activation of mouse B cells with lipopolysaccharide in conjunction with anti-immunoglobulin (Ig) antibodies results in interleukin 2 (IL2) receptor (IL2-R) expression and IL2 responsiveness. In most studies on the effect of IL2 on antibody production by B cells, polyclonally activated normal B cells or B cell lines established in vitro have been used as indicator cells, thus allowing no direct correlation between the experimental findings and the actual physiological mechanism of IL2 action in antigen-specific B cell response. We employed the splenic fragment culture technique, which measures antibody response on the clonal level, to analyze the effect of purified human recombinant IL2 (rIL2) on the primary antigen-specific Ig response of mouse B cells. Here we report that rIL2 increased the frequency of dinitrophenyl (DNP)-responsive splenic B cells and the amount of Ig secreted per clone. The anti-DNP antibody response was dependent upon interaction of naive B cells with carrier-primed T cells, which apparently provided the signal for IL2-R expression. Recombinant IL2 also facilitated Ig isotype switching by individual clones, suggesting a role for IL2 in activation, maturation, and differentiation of antigen-specific naive B cells in their response to T-dependent antigens.