The Financial Costs, Behaviour and Psychology of Obesity: A One Health Analysis.
People who are overweight or have obesity are estimated to comprise 30% of the global population and up to 59% of companion dogs and cats are estimated to be above their optimal body weight. The prevalence of human and companion obesity is increasing. The direct and indirect costs of obesity and associated comorbidities are significant for human and veterinary healthcare. There are numerous similarities between obesity in people and companion animals, likely related to the shared environmental and lifestyle elements of this multifactorial disease. While the study of human obesity is relatively robust, research conducted in pets is generally limited to small studies, studies with cross-sectional designs or reports that have yet to be replicated. Greater understanding of human obesity may elucidate some of the factors driving the more recent rise in pet obesity. In particular, there are overlapping features of obesity in children and pets that are, in part, related to dependency on their 'parents' for care and feeding. When feeding is used in a coercive and controlling fashion, it may lead to undesirable feeding behaviour and increase the risk for obesity. A 'responsive parenting' intervention teaches parents to respond appropriately to hunger-satiety cues and to recognize and respond to others' distress. Such interventions may impact on childhood overweight and obesity and have the potential to be adapted for use with companion animals. Social behaviour towards people with obesity or owners of pets with obesity is often driven by beliefs about the cause of the obesity. Educating healthcare professionals and the public about the multifactorial nature of this complex disease process is a fundamental step in reducing the bias and stigma associated with obesity. Children living in low-income households have particularly high rates of obesity and as household income falls, rates of obesity also rise in pets and their owners. There are risk regulators (i.e. dynamic components of interconnected systems that influence obesity-related behaviours) and internal factors (i.e. biological determinants of obesity) that may influence the development of both childhood and pet obesity, and poverty may intersect with these variables to exacerbate obesity in low-income environments. This review discusses the costs, behaviours and psychology related to obesity in people and pets, and also proposes potential techniques that can be considered for prevention and treatment of this disease in pets. A 'One Health' approach to obesity suggests that an understanding of human obesity may elucidate some of the factors driving the more recent rise in pet obesity.


Sample size justifications in Gait & Posture.
Context regarding how researchers determine the sample size of their experiments is important for interpreting the results and determining their value and meaning. Between 2018 and 2019, the journal Gait & Posture introduced a requirement for sample size justification in their author guidelines. How frequently and in what ways are sample sizes justified in Gait & Posture research articles and was the inclusion of a guideline requiring sample size justification associated with a change in practice? The guideline was not in place prior to May 2018 and was in place from 25th July 2019. All articles in the three most recent volumes of the journal (84-86) and the three most recent, pre-guideline volumes (60-62) at time of preregistration were included in this analysis. This provided an initial sample of 324 articles (176 pre-guideline and 148 post-guideline). Articles were screened by two authors to extract author data, article metadata and sample size justification data. Specifically, screeners identified if (yes or no) and how sample sizes were justified. Six potential justification types (Measure Entire Population, Resource Constraints, Accuracy, A priori Power Analysis, Heuristics, No Justification) and an additional option of Other/Unsure/Unclear were used. In most cases, authors of Gait & Posture articles did not provide a justification for their study's sample size. The inclusion of the guideline was associated with a modest increase in the percentage of articles providing a justification (16.6-28.1%). A priori power calculations were the dominant type of justification, but many were not reported in enough detail to allow replication. Gait & Posture researchers should be more transparent in how they determine their sample sizes and carefully consider if they are suitable. Editors and journals may consider adding a similar guideline as a low-resource way to improve sample size justification reporting.


Inflammation But Not Biliary Obstruction Is Associated With Carbohydrate Antigen 19-9 Levels in Patients With Primary Sclerosing Cholangitis.
Assays that measure the serum level of carbohydrate antigen 19-9 (CA19-9) are used to screen patients with primary sclerosing cholangitis (PSC) for malignancies. However, in patients with PSC, cholestasis, and bacterial cholangitis, the CA19-9 level can be affected by variants in the fucosyltransferases 2 and 3 genes (FUT2 and FUT3), which regulate the production of CA19-9. We investigated how these genotypes affect cancer screening in these patients. We performed a retrospective analysis of data from 209 patients with PSC (19 patients with biliary malignancy, 23 patients with cholestasis and bacterial cholangitis) treated at the University Hospital Heidelberg from 1987 through 2014. We collected data on the maximum serum level of CA19-9; laboratory measures of cholestasis or inflammation; the presence of dominant stenosis, cholestasis, and bacterial cholangitis; and FUT2 and FUT3 genotypes. Patients were assigned to intermediate (n = 161) or high (n = 48) CA19-9 biosynthesis groups, based on FUT2 and FUT3 genotypes. Patients incapable of CA19-9 biosynthesis, based on genetic features, were excluded. The median level of CA19-9 was 31.1 U/mL in cancer-free patients. The CA19-9 level correlated with the level of C-reactive protein (P < .001); high CA19-9 biosynthesis correlated with high leukocyte counts (P = .037), but not intermediate CA19-9 biosynthesis. There was no correlation between the level of CA19-9 and laboratory markers of cholestasis. The level of CA19-9 was the lowest in patients without biliary obstruction, cholestasis, or bacterial cholangitis (7.8 U/mL), followed by patients with only obstruction (28.0 U/mL), and then patients with cholestasis and bacterial cholangitis (77.0 U/mL and 205.4 U/mL in patients without or with concomitant obstruction, respectively). The greatest increase in CA19-9 as a result of cholestasis and bacterial cholangitis was observed in patients in the high CA19-9 biosynthesis group. In patients with PSC, cholestasis has little effect on the level of CA19-9, but cholestasis and bacterial cholangitis increase the level. Their effects on CA19-9 level depend on the FUT2 and FUT3 genotype. These findings support the analysis of FUT2 and FUT3 genotype during follow-up evaluation of patients with PSC.


Surgical oncology of the pelvis: ostomy planning and management.
Advanced pelvic surgery may result in the formation of a colostomy, ileostomy, urostomy, or multiples of these stomas. Stomas may be created because of a planned therapeutic attack to eradicate cancer or manage complications arising from treatments or they may be constructed to palliate severe symptoms or life-threatening problems. In some instances, fistulae between various organs and the skin may occur. Special skills are required to meet the needs of patients with ostomies or fistulae. The often complex care presents critical challenges to nurses, particularly in today's cost-conscious health care environment where prompt hospital discharges, brief clinic appointments, and valuable but limited home care visits are the norm. The skills of the enterostomal therapy nurse are valuable in all phases of care of these patients, from preoperative to outpatient care.


Discovery of T cell epitopes implementing HLA-peptidomics into a reverse immunology approach.
T cell recognition of minor histocompatibility Ags (MiHA) plays an important role in the graft-versus-tumor effect of allogeneic stem cell transplantation. Selective infusion of T cells reactive for hematopoiesis-restricted MiHA presented in the context of HLA class I or II molecules may help to separate the graft-versus-tumor effects from graft-versus-host disease effects after allogeneic stem cell transplantation. Over the years, increasing numbers of MiHA have been identified by forward immunology approaches, and the relevance of these MiHA has been illustrated by correlation with clinical outcome. As the tissue distribution of MiHA affects the clinical outcome of T cell responses against these Ags, it would be beneficial to identify additional predefined MiHA that are exclusively expressed on hematopoietic cells. Therefore, several reverse immunology approaches have been explored for the prediction of MiHA. Thus far, these approaches frequently resulted in the identification of T cells directed against epitopes that are not naturally processed and presented. In this study we established a method for the identification of biologically relevant MiHA, implementing mass spectrometry-based HLA-peptidomics into a reverse immunology approach. For this purpose, HLA class I binding peptides were eluted from transformed B cells, analyzed by mass spectrometry, and matched with a database dedicated to identifying polymorphic peptides. This process resulted in a set of 40 MiHA candidates that were evaluated in multiple selection steps. The identification of LB-NISCH-1A demonstrated the technical feasibility of our approach. On the basis of these results, we present an approach that can be of value for the efficient identification of MiHA or other T cell epitopes.


Options of partners improve carbon for phosphorus trade in the arbuscular mycorrhizal mutualism.
The mutualism between plants and arbuscular mycorrhizal fungi (AMF) is widespread and has persisted for over 400 million years. Although this mutualism depends on fair resource exchange between plants and fungi, inequality exists among partners despite mechanisms that regulate trade. Here, we use (33) P and (14) C isotopes and a split-root system to test for preferential allocation and reciprocal rewards in the plant-AMF symbiosis by presenting a plant with two AMF that differ in cooperativeness. We found that plants received more (33) P from less cooperative AMF in the presence of another AMF species. This increase in (33) P resulted in a reduced (14) C cost per unit of (33) P from less cooperative AMF when alternative options were available. Our results indicate that AMF diversity promotes cooperation between plants and AMF, which may be an important mechanism maintaining the evolutionary persistence of and diversity within the plant-AMF mutualism.


Effects of cardiac overexpression of type 6 adenylyl cyclase affects on the response to chronic pressure overload.
Adenylyl cyclase (AC) type 5 (AC5) and AC type 6 (AC6) are the two major AC isoforms in the heart. Cardiac overexpression of AC6 has been shown to be protective in response to several interventions. In this investigation, we examined the effects of chronic pressure overload in AC6 transgenic (TG) mice. In the absence of any stress, AC6 TG mice exhibited enhanced contractile function compared with their wild-type (WT) littermates, i.e., increased (P < 0.05) left ventricular (LV) ejection fraction (EF) (75 +/- 0.9 vs. 71 +/- 0.5%) and LV dP/dt (7,850 +/- 526 vs. 6,374 +/- 315 mmHg/s). Forskolin (25 microg x kg(-1) x min(-1) for 5 min) increased LVEF more (P < 0.05) in AC6 TG mice (14.8 +/- 1.0%) than in WT mice (7.7 +/- 1.0%). Also, isoproterenol (0.04 microg x kg(-1) x min(-1) for 5 min) increased LVEF more (P < 0.05) in AC6 TG mice (18.0 +/- 1.2%) than in WT mice (11.6 +/- 2.1%). Pressure overload, induced by 4 wk of transverse aortic constriction (TAC), increased the LV weight-to-body weight ratio and myocyte cross-sectional area similarly in both groups, but reduced LVEF more in AC6 TG mice (22%) compared with WT mice (9%), despite the higher starting level of LVEF in AC6 TG mice. LV systolic wall stress increased more in AC6 TG mice than in WT mice, which could be responsible for the reduced LVEF in AC6 TG mice with chronic pressure overload. In addition, LV dP/dt was no longer elevated in AC6 TG mice after TAC compared with WT mice. LV end-diastolic diameter was also greater (P < 0.05) in AC6 TG mice (3.8 +/- 0.07 mm) than in WT mice (3.6 +/- 0.05 mm) after TAC. Thus, in contrast to other interventions previously reported to be salutary with cardiac AC6 overpression, the response to chronic pressure overload was not; actually, AC6 TG mice fared worse than WT mice. The mechanism may be due to the increased LV systolic wall stress in AC6 TG mice with chronic pressure overload.


Fast phasic release properties of dopamine studied with a channel biosensor.
Few other neurotransmitters are of as intense interest to neuropsychiatry and neurology as dopamine, yet existing techniques to monitor dopamine release leave an important spatiotemporal gap in our understanding. Electrochemistry and fluorescence imaging tools have been developed to fill the gap, but these methods have important limitations. We circumvent these limitations by introducing a dopamine-gated chloride channel into rat dorsal striatal medium spiny neurons, targets of strong dopamine innervation, thereby transforming dopamine from a slow transmitter into a fast transmitter and revealing new opportunities for studying moment-to-moment regulation of dopamine release. We demonstrate pharmacological and biophysical properties of the channel that make it suitable for fast, local dopamine measurements, and we demonstrate for the first time spontaneous and evoked responses to vesicular dopamine release in the dorsal striatum. Evoked dopamine currents were separated into a fast, monosynaptic component and a slower-rising and decaying disynaptic component mediated by nicotinic receptor activation. In summary, LGC-53 represents a dopamine biosensor with properties suitable for temporal separation of distinct dopamine signals in targets of dopamine innervation.


Activation of p53 transcriptional activity by SMRT: a histone deacetylase 3-independent function of a transcriptional corepressor.
The silencing mediator of retinoic acid and thyroid hormone receptors (SMRT) is an established histone deacetylase 3 (HDAC3)-dependent transcriptional corepressor. Microarray analyses of MCF-7 cells transfected with control or SMRT small interfering RNA revealed SMRT regulation of genes involved in DNA damage responses, and the levels of the DNA damage marker γH2AX as well as poly(ADP-ribose) polymerase cleavage were elevated in SMRT-depleted cells treated with doxorubicin. A number of these genes are established p53 targets. SMRT knockdown decreased the activity of two p53-dependent reporter genes as well as the expression of p53 target genes, such as CDKN1A (which encodes p21). SMRT bound directly to p53 and was recruited to p53 binding sites within the p21 promoter. Depletion of GPS2 and TBL1, components of the SMRT corepressor complex, but not histone deacetylase 3 (HDAC3) decreased p21-luciferase activity. p53 bound to the SMRT deacetylase activation domain (DAD), which mediates HDAC3 binding and activation, and HDAC3 could attenuate p53 binding to the DAD region of SMRT. Moreover, an HDAC3 binding-deficient SMRT DAD mutant coactivated p53 transcriptional activity. Collectively, these data highlight a biological role for SMRT in mediating DNA damage responses and suggest a model where p53 binding to the DAD limits HDAC3 interaction with this coregulator, thereby facilitating SMRT coactivation of p53-dependent gene expression.


Leishmania RNA virus-1 is similarly detected among metastatic and non-metastatic phenotypes in a prospective cohort of American Tegumentary Leishmaniasis.
American Tegumentary Leishmaniasis (ATL) is an endemic and neglected disease of South America. Here, mucosal leishmaniasis (ML) disproportionately affects up to 20% of subjects with current or previous localised cutaneous leishmaniasis (LCL). Preclinical and clinical reports have implicated the Leishmania RNA virus-1 (LRV1) as a possible determinant of progression to ML and other severe manifestations such as extensive cutaneous and mucosal disease and treatment failure and relapse. However, these associations were not consistently found in other observational studies and are exclusively based on cross-sectional designs. In the present study, 56 subjects with confirmed ATL were assessed and followed out for 24-months post-treatment. Lesion biopsy specimens were processed for molecular detection and quantification of Leishmania parasites, species identification, and LRV1 detection. Among individuals presenting LRV1 positive lesions, 40% harboured metastatic phenotypes; comparatively 58.1% of patients with LRV1 negative lesions harboured metastatic phenotypes (p = 0.299). We found treatment failure (p = 0.575) and frequency of severe metastatic phenotypes (p = 0.667) to be similarly independent of the LRV1. Parasite loads did not differ according to the LRV1 status (p = 0.330), nor did Leishmanin skin induration size (p = 0.907) or histopathologic patterns (p = 0.780). This study did not find clinical, parasitological, or immunological evidence supporting the hypothesis that LRV1 is a significant determinant of the pathobiology of ATL.


Extraction of Natural Gum from Cold-Pressed Chia Seed, Flaxseed, and Rocket Seed Oil By-Product and Application in Low Fat Vegan Mayonnaise.
This study involves the modeling of rheological behavior of the gum solution obtained from cold-pressed chia seed (CSG), flaxseed (FSG), and rocket seed (RSG) oil by-products and the application of these gums in a low-fat vegan mayonnaise formulation as fat replacers and emulsifier. CSG, FSG, and RSG solutions showed shear-thinning flow behavior at all concentrations. The K values ranged between 0.209 and 49.028 Pa·sn for CSG, FSG, and RSG solutions and significantly increased with increased gum concentration. The percentage recovery for the G' was significantly affected by gum type and concentrations. CSG, FSG, and RSG showed a solid-like structure, and the storage modulus (G') was higher than the loss modulus (G″) in all frequency ranges. The rheological characterization indicated that CSG, FSG, and RSG could be evaluated as thickeners and gelling agents in the food industry. In addition, the rheological properties, zeta potential, and particle size and oxidative stability (at 90 °C) of low-fat vegan mayonnaise samples prepared with CSG, FSG, and RSG were compared to samples prepared with guar gum (GG), Arabic gum (AG), and xanthan gum (XG). As a result, CSG, FSG, and RSG could be utilized for low-fat vegan mayonnaise as fat and egg replacers, stabilizers, and oxidative agents. The results of this study indicated that this study could offer a new perspective in adding value to flaxseed, chia seed, and rocket seed cold-press oil by-product.


The cytokine-adhesion molecule cascade in ischemia/reperfusion injury of the rat kidney. Inhibition by a soluble P-selectin ligand.
Ischemia/reperfusion (I/R) injury associated with renal transplantation may influence both early graft function and late changes. The initial (</= 7 d) events of warm and in situ perfused cold ischemia of native kidneys in uninephrectomized rats were examined. mRNA expression of the early adhesion molecule, E-selectin, peaked within 6 h; PMNs infiltrated in parallel. T cells and macrophages entered the injured kidney by 2-5 d; the associated upregulation of MHC class II antigen expression suggested increased immunogenicity of the organ. Th1 products (IL-2, TNFalpha, IFNgamma) and macrophage-associated products (IL-1, IL-6, TGFbeta) remained highly expressed after 2 d. To examine directly the effects of selectins in I/R injury, a soluble P-selectin glycoprotein ligand (sPSGL) was used. Ischemic kidneys were perfused in situ with 5 microg of sPSGL in UW solution; 50 microg was administered intravenously 3 h after reperfusion. E-selectin mRNA remained at baseline, leukocytes did not infiltrate the injured organs throughout the 7-d period, and their associated products were markedly inhibited. Class II expression did not increase. No renal dysfunction secondary to I/R occurred. The early changes of I/R injury may be prevented by treatment with soluble P- and E-selectin ligand. This may reduce subsequent host inflammatory responses after transplantation.


Effects of formalin-inactivated respiratory syncytial virus (FI-RSV) in the perinatal lamb model of RSV.
Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis in infants and children worldwide. There are currently no licensed vaccines or effective antivirals. The lack of a vaccine is partly due to increased caution following the aftermath of a failed clinical trial of a formalin-inactivated RSV vaccine (FI-RSV) conducted in the 1960's that led to enhanced disease, necessitating hospitalization of 80% of vaccine recipients and resulting in two fatalities. Perinatal lamb lungs are similar in size, structure and physiology to those of human infants and are susceptible to human strains of RSV that induce similar lesions as those observed in infected human infants. We sought to determine if perinatal lambs immunized with FI-RSV would develop key features of vaccine-enhanced disease. This was tested in colostrum-deprived lambs immunized at 3-5 days of age with FI-RSV followed two weeks later by RSV infection. The FI-RSV-vaccinated lambs exhibited several key features of RSV vaccine-enhanced disease, including reduced RSV titers in bronchoalveolar lavage fluid and lung, and increased infiltration of peribronchiolar and perivascular lymphocytes compared to lambs either undergoing an acute RSV infection or naïve controls; all features of RSV vaccine-enhanced disease. These results represent a first step proof-of-principle demonstration that the lamb can develop altered responses to RSV following FI-RSV vaccination. The lamb model may be useful for future mechanistic studies as well as the assessment of RSV vaccines designed for infants.


Arachidonic and docosahexaenoic acid supplementation and brain maturation in preterm infants; a double blind RCT.
Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important structural components of neural cellular membranes and possess anti-inflammatory properties. Very preterm infants are deprived of the enhanced placental supply of these fatty acids, but the benefit of postnatal supplementation on brain development is uncertain. The aim of this study was to test the hypothesis that early enteral supplementation with ARA and DHA in preterm infants improves white matter (WM) microstructure assessed by diffusion-weighted MRI at term equivalent age. In this double-blind, randomized controlled trial, infants born before 29 weeks gestational age were allocated to either 100 mg/kg ARA and 50 mg/kg DHA (ARA:DHA group) or medium chain triglycerides (control). Supplements were started on the second day of life and provided until 36 weeks postmenstrual age. The primary outcome was brain maturation assessed by diffusion tensor imaging (DTI) using Tract-Based Spatial Statistics (TBSS) analysis. We included 120 infants (60 per group) in the trial; mean (range) gestational age was 26+3 (22+6 - 28+6) weeks and postmenstrual age at scan was 41+3 (39+1 - 47+0) weeks. Ninety-two infants underwent MRI imaging, and of these, 90 had successful T1/T2 weighted MR images and 74 had DTI data of acceptable quality. TBSS did not show significant differences in mean or axial diffusivity between the groups, but demonstrated significantly higher fractional anisotropy in several large WM tracts in the ARA:DHA group, including corpus callosum, the anterior and posterior limb of the internal capsula, inferior occipitofrontal fasciculus, uncinate fasciculus, and the inferior longitudinal fasciculus. Radial diffusivity was also significantly lower in several of the same WM tracts in the ARA:DHA group. This study suggests that supplementation with ARA and DHA at doses matching estimated fetal accretion rates improves WM maturation compared to control treatment, but further studies are needed to ascertain any functional benefit. www. gov; ID:NCT03555019.


Body talk among college men: content, correlates, and effects.
Though researchers are beginning to examine body-related talk in women (often referred to as fat talk), little work has examined how men talk about their bodies with peers. The two studies presented in this article explore body talk among U.S. college men. First, an online survey examined the frequency with which college men engage in negative body talk, the content of these conversations, and the body image variables associated with engaging in this type of talk. Negative body talk in men was associated with drive for muscularity, eating disordered behavior, and appearance investment. Study 2 experimentally examined the effects of hearing male peers engage in negative body talk. Hearing muscle talk or fat talk caused decreased state appearance self-esteem and increased state body dissatisfaction. The correlates and consequences of negative body talk among men appear no less troubling than those identified among women.


Elucidating Peptide and Protein Structure and Dynamics: UV Resonance Raman Spectroscopy.
UV resonance Raman spectroscopy (UVRR) is a powerful method that has the requisite selectivity and sensitivity to incisively monitor biomolecular structure and dynamics in solution. In this perspective, we highlight applications of UVRR for studying peptide and protein structure and the dynamics of protein and peptide folding. UVRR spectral monitors of protein secondary structure, such as the Amide III(3) band and the C(α)-H band frequencies and intensities can be used to determine Ramachandran Ψ angle distributions for peptide bonds. These incisive, quantitative glimpses into conformation can be combined with kinetic T-jump methodologies to monitor the dynamics of biomolecular conformational transitions. The resulting UVRR structural insight is impressive in that it allows differentiation of, for example, different α-helix-like states that enable differentiating π- and 3(10)- states from pure α-helices. These approaches can be used to determine the Gibbs free energy landscape of individual peptide bonds along the most important protein (un)folding coordinate. Future work will find spectral monitors that probe peptide bond activation barriers that control protein (un)folding mechanisms. In addition, UVRR studies of sidechain vibrations will probe the role of side chains in determining protein secondary, tertiary and quaternary structures.


Preoperative anxiety in children risk factors and non-pharmacological management.
It is important for anesthesiologists to appreciate the impact of preoperative anxiety in children. Not only does it cause suffering in many children prior to their surgical experience, it has a negative impact on their postoperative recovery and possibly long afterwards. Because of these concerns, continued research is warranted to seek ways of minimizing their fears in the perioperative setting. In this review, we will examine the risk factors for preoperative anxiety, tools for quantifying children and parent's anxiety, and strategies that may play a part in decreasing preoperative anxiety. Variables, which influence preoperative anxiety in children, include their age, temperament, prior hospital experience and parent coping abilities. This review will also explore issues surrounding parental presence during a child's anesthesia induction and how understanding child development can enhance their cooperativeness during the preoperative period, especially during anesthesia induction. Non-pharmacological interventions as a means of decreasing pediatric anxiety will be explored. Finally recent trends and new directions will be touched upon.


A qualitative case study examining intervention tailoring for minorities.
To explore issues of intervention tailoring for ethnic minorities based on information and experiences shared by researchers affiliated with the Health Maintenance Consortium (HMC). A qualitative case study methodology was used with the administration of a survey (n = 17 principal investigators) and follow-up telephone interviews. Descriptive and content analyses were conducted, and a synthesis of the findings was developed. A majority of the HMC projects used individual tailoring strategies regardless of the ethnic background of participants. Follow-up interview findings indicated that key considerations in the process of intervention tailoring for minorities included formative research; individually oriented adaptations; and intervention components that were congruent with participants' demographics, cultural norms, and social context. Future research should examine the extent to which culturally tailoring long-term maintenance interventions for ethnic minorities is efficacious and should be pursued as an effective methodology to reduce health disparities.


Pre-assembly of the extracellular domains of CD40 is not necessary for rescue of mouse B cells from anti-immunoglobulin M-induced apoptosis.
CD40 is a tumour necrosis factor receptor (TNFR) family member of central importance for the adaptive immune system. To elucidate the functional role of the different extracellular domains of CD40, we have created a set of truncated CD40 molecules where domains, or parts of domains, have been removed. These CD40 proteins, which contain a peptide tag in the N-terminal end, have been expressed in a murine B-cell line, WEHI 231. It was found that ligation of these engineered CD40 proteins via the peptide tag, was sufficient to rescue as well as to promote proliferation of apoptotic WEHI 231 cells, even when all the extracellular domains of CD40 were absent. Our results suggest that pre association of CD40 in the cell membrane plays no critical role for the CD40 signalling pathway. Furthermore, our data imply that conformational changes initiated in the extracellular domains of CD40 are not essential for signal transduction.


The IRONy in Athletic Performance.
Iron is an essential micronutrient for athletes, intricately linked to their performance, by regulating cellular respiration and metabolism. Impaired iron levels in the body can significantly hinder athletic performance. The increased demand for iron due to exercise, coupled with potential dietary iron insufficiencies, particularly among endurance athletes, amplifies the risk of iron deficiency. Moreover, prolonged exercise can impact iron absorption, utilization, storage, and overall iron concentrations in an athlete. On the contrary, iron overload may initially lead to enhanced performance; however, chronic excess iron intake or underlying genetic conditions can lead to detrimental health consequences and may negatively impact athletic performance. Excess iron induces oxidative damage, not only compromising muscle function and recovery, but also affecting various tissues and organs in the body. This narrative review delineates the complex relationship between exercise and iron metabolism, and its profound effects on athletic performance. The article also provides guidance on managing iron intake through dietary adjustments, oral iron supplementation for performance enhancement in cases of deficiency, and strategies for addressing iron overload in athletes. Current research is focused on augmenting iron absorption by standardizing the route of administration while minimizing side effects. Additionally, there is ongoing work to identify inhibitors and activators that affect iron absorption, aiming to optimize the body's iron levels from dietary sources, supplements, and chelators. In summary, by refining the athletic diet, considering the timing and dosage of iron supplements for deficiency, and implementing chelation therapies for iron overload, we can effectively enhance athletic performance and overall well-being.


Cardiopulmonary and anesthetic effects of medetomidine-ketamine-butorphanol and antagonism with atipamezole in servals (Felis serval).
Seven (three male and four female) 4-7-yr old captive servals (Felis serval) weighing 13.7 +/- 2.3 kg were used to evaluate the cardiopulmonary and anesthetic effects of combined intramuscular injections of medetomidine (47.4 +/- 10.3 microg/kg), ketamine (1.0 +/- 0.2 mg/kg), and butorphanol (0.2 +/- 0.03 mg/kg). Inductions were smooth and rapid (11.7 +/- 4.3 min) and resulted in good muscle relaxation. Significant decreases in heart rate (85 +/- 12 beats/min) at 10 min after injection and respiratory rate (27 +/- 10 breaths/min) at 5 min after injection continued throughout the immobilization period. Rectal temperature and arterial blood pressure did not change significantly. The PaO2 decreased significantly, and PaCO2 increased significantly during immobilization but remained within clinically acceptable limits. Hypoxemia (PaO2 < 60 mm Hg) was not noted, and arterial blood oxygen saturation (SaO2) was greater than 90% at all times. Relative arterial oxygen saturation (SpO2) values, indicated by pulse oximetry, were lower than SaO2 values. All animals could be safely handled while sedated. Administration of atipamezole (236.8 +/- 51.2 microg/kg half i.v. and half s.c.), an alpha2 antagonist, resulted in rapid (4.1 +/- 3 min to standing) and smooth recoveries.


Emotion word comprehension from 4 to 16 years old: a developmental survey.
Whilst previous studies have examined comprehension of the emotional lexicon at different ages in typically developing children, no survey has been conducted looking at this across different ages from childhood to adolescence. To report how the emotion lexicon grows with age. Comprehension of 336 emotion words was tested in n = 377 children and adolescents, aged 4-16 years old, divided into 6 age-bands. Parents or teachers of children under 12, or adolescents themselves, were asked to indicate which words they knew the meaning of. Between 4 and 11 years old, the size of the emotional lexicon doubled every 2 years, but between 12 and 16 years old, developmental rate of growth of the emotional lexicon leveled off. This survey also allows emotion words to be ordered in terms of difficulty. Studies using emotion terms in English need to be developmentally sensitive, since during childhood there is considerable change. The absence of change after adolescence may be an artifact of the words included in this study. This normative developmental data-set for emotion vocabulary comprehension may be useful when testing for delays in this ability, as might arise for environmental or neurodevelopmental reasons.


Entropy production in non-equilibrium fluctuating hydrodynamics.
Fluctuating entropy production is studied for a set of linearly coupled complex fields. The general result is applied to non-equilibrium fluctuating hydrodynamic equations for coarse-grained fields (density, temperature, and velocity), in the framework of model granular fluids. We find that the average entropy production, obtained from the microscopic stochastic description, can be expressed in terms of macroscopic quantities, in analogy with linear non-equilibrium thermodynamics. We consider the specific cases of driven granular fluids with two different kinds of thermostat and the homogeneous cooling regime. In all cases, the average entropy production turns out to be the product of a thermodynamic force and a current: the former depends on the specific energy injection mechanism, the latter takes always the form of a static correlation between fluctuations of density and temperature time-derivative. Both vanish in the elastic limit. The behavior of the entropy production is studied at different length scales and the qualitative differences arising for the different granular models are discussed.


Consistency of Renal Stone Volume Measurements Across CT Scanner Model and Reconstruction Algorithm Configurations.
The objective of this prospective study is to evaluate the consistency of renal stone volume estimation using dual-energy CT across scanner model and reconstruction algorithm configurations. Patients underwent scanning with routine kidney stone composition protocols on both second- and third-generation dual-source CT scanners. Images were reconstructed using filtered back projection and iterative reconstruction (IR). In addition, a modified IR kernel on the third-generation CT scanner was evaluated. Individual kidney stone volumes were determined and compared. No significant difference was noted in measured volumes between filtered back-projection data, IR data from the second-generation scanner, and the modified IR kernel data (p > 0.05). The third-generation commercially available IR kernel yielded lower volumes than did the other configurations (p < 0.0001). With the use of a modified kernel for the third-generation scanner, patients being monitored for changes in kidney stone volume can undergo scanning performed with second- or third-generation dual-energy CT scanners, and the images obtained can be reconstructed with either filtered back projection or IR without the introduction of bias into kidney stone volume measurements.


Magneto-mechanical mixing and manipulation of picoliter volumes in vesicles.
Superparamagnetic beads in giant unilamellar vesicles are used to facilitate magnetic manipulation, positioning, agitation and mixing of ultrasmall liquid volumes. Vesicles act as leakproof picoliter reaction vessels in an aqueous bulk solution and can be deliberately conveyed by an external magnetic field to a designated position. Upon application of an external magnetic field the beads align to form extended chains. In a rotating magnetic field chains break up into smaller fragments caused by the interplay of viscous friction and magnetic attraction. This process obeys a simple relationship and can be exploited to enhance mixing of the vesicle content and the outer solution or adjacent vesicle volumes exactly at the position of release.


[Variations in management of suspected scaphoid fractures].
This study evaluated the daily clinical practice for management of patients with suspected scaphoid fractures in hospitals in the Netherlands and compared it with recommendations from the current literature. Questionnaire-based investigation. Doctors working in emergency departments in hospitals in the Netherlands were asked to complete an 8-question survey including questions on diagnostic strategies, treatment type and the time between different steps in the management policy. Doctors from 90 of the 100 hospitals approached completed the questionnaire. A total of 71 of these 90 hospitals had an established protocol. In the other 19 it depended on the preference of the treating doctor. In 75 hospitals a follow-up outpatient clinic appointment was made for within 10 days. In 70 hospitals X-rays were repeated before additional imaging investigation. CT was the most frequently used additional investigation in 35 hospitals, followed by bone scintigraphy (12) and MRI (2). No additional investigation was carried out in 11 hospitals and when X-rays showed no abnormalities treatment was implemented on the basis of clinical evaluation. In 72 hospitals the wrist was immobilised with a lower-arm plaster cast including the thumb. Lower-arm plaster cast not including the thumb was used in 1 hospital. There is a great deal of variation in diagnosis and treatment of patients with a suspected scaphoid fracture within hospitals in the Netherlands. Furthermore, management policy in most hospitals is not in keeping with the most recent recommendations. Evidence-based guidelines are required in order to limit over-diagnosis and unnecessary immobilisation.


Frequency layered color indexing for content-based image retrieval.
Image patches of different spatial frequencies are likely to have different perceptual significance as well as reflect different physical properties. Incorporating such concept is helpful to the development of more effective image retrieval techniques. We introduce a method which separates an image into layers, each of which retains only pixels in areas with similar spatial frequency characteristics and uses simple low-level features to index the layers individually. The scheme associates indexing features with perceptual and physical significance thus implicitly incorporating high level knowledge into low level features. We present a computationally efficient implementation of the method, which enhances the power and at the same time retains the simplicity and elegance of basic color indexing. Experimental results are presented to demonstrate the effectiveness of the method.


Antioxidant Activities of Streptomyces sp. strain MUSC 14 from Mangrove Forest Soil in Malaysia.
The mangrove ecosystem of Malaysia remains yet to be fully explored for potential microbes that produce biologically active metabolites. In the present study, a mangrove-derived Streptomyces sp. strain MUSC 14 previously isolated from the state of Pahang, Malaysia Peninsula, was studied for its potential in producing antioxidant metabolites. The identity of Streptomyces sp. strain MUSC14 was consistent with the genotypic and phenotypic characteristics of the Streptomyces genus. The antioxidant potential of Streptomyces sp. strain MUSC 14 was determined through screening of its methanolic extract against sets of antioxidant assays. The results were indicative of Streptomyces sp. strain MUSC 14 displaying strong antioxidant activity against ABTS, DPPH free radicals and metal chelating activity of 62.71 ± 3.30%, 24.71 ± 2.22%, and 55.82 ± 2.35%, respectively. The result of ferric reducing activity measured in terms of dose was equivalent to 2.35-2.45 μg of positive control ascorbic acid. Furthermore, there was a high correlation between the total phenolic content and the antioxidant activities with r = 0.979, r = 0.858, and r = 0.983 representing ABTS, DPPH, and metal chelation, respectively. Overall, the present study suggests that Streptomyces sp. strain MUSC 14 from mangrove forest soil has potential to produce antioxidant metabolites that can be further exploited for therapeutic application.


Use of automatic computerised pump to maintain constant intragastric pH.
We used continuous variable rate infusions of famotidine in eight normal volunteers under fasting conditions to raise intragastric pH to 5.0. An intragastric glass electrode continuously monitored acidity and this information was automatically computed to regulate an intravenous infusion system (GastroJet). The computer was programmed to aim for pH 6.0, increasing and lowering infusion rates accordingly. Two regimens were compared with placebo (10 mg bolus followed by infusion or infusion of famotidine alone). Volunteers were admitted to an investigation ward and each study was preceded by a standard normal meal. Hydration was maintained with intravenous fluids. During placebo treatment the median pH was 1.5 and the pH was less than 5.0 for 98% of the time. All volunteers responded to famotidine but dosage requirements varied (range 41 mg to 126 mg). The median pH rose to 6.5 when infusions of famotidine followed boluses and to 6.6 when infusions alone were used - the pH was less than 5.0 for 20% and 16% of the time respectively (p less than 0.05 Wilcoxon compared with placebo). Mean drug use was greater with boluses (98 mg v 87 mg p = 0.03: paired Student's t test) and onset was not apparently faster. Blood famotidine concentrations followed infusion rate changes. Famotidine infused by GastroJet maintains a high fasting intragastric pH and priming boluses are probably unnecessary.


Experimental reproduction of postweaning multisystemic wasting syndrome in pigs by dual infection with Mycoplasma hyopneumoniae and porcine circovirus type 2.
The objectives of this study were to investigate the interactions between Mycoplasma hyopneumoniae and porcine circovirus type 2 (PCV2) and to establish a model for studying the pathogenesis of and testing intervention strategies for the control of PCV2-associated porcine respiratory disease complex (PRDC). Sixty-seven pigs were randomly assigned to four groups. Group 1 (n=17) pigs served as controls, group 2 (n=17) pigs were inoculated with M. hyopneumoniae, group 3 (n=17) pigs were dual infected with M. hyopneumoniae and PCV2, and group 4 (n=16) pigs were inoculated with PCV2. Pigs were inoculated intratracheally with M. hyopneumoniae at 4 weeks of age followed by intranasal inoculation with PCV2 at 6 weeks of age. Dual-infected pigs had moderate dyspnea, lethargy, and reduced weight gain. The overall severity of macroscopic lung lesions, PCV2-associated microscopic lesions in lung and lymphoid tissues, and the amount of PCV2-antigen associated with these lesions were significantly (P <0.05) higher in dual-infected pigs compared with all other groups. Four of 17 (23.5%) dual-infected pigs had decreased growth rate and severe lymphoid depletion and granulomatous lymphadenitis associated with high amounts of PCV2-antigen consistent with postweaning multisystemic wasting syndrome (PMWS). PCV2-antigen in lung tissue was most often associated with M. hyopneumoniae-induced peribronchial lymphoid hyperplasia, suggesting that this is an important site for PCV2 replication in the lung. This study indicates that M. hyopneumoniae potentiates the severity of PCV2-associated lung and lymphoid lesions, increases the amount and prolongs the presence of PCV2-antigen, and increases the incidence of PMWS in pigs.


[Successful endoscopic removal of pancreatic catheter after Whipple resection being effective for improving repeated pancreatitis-a case report].
A 54-year-old man had repeated pancreatitis since three years after pylorus-preserving pancreatoduodenectomy (PpPD) and reconstruction by the modified Child method. Since abdominal pain appeared after meals, a pancreatic duct tube was removed endoscopically, which resulted in an improvement. It has been postulated that a pancreatic duct tube, used at the anastomosis between the pancreas and gastrointestinal tract, is spontaneously dislodged or creates a spatial gap with the wall of the main pancreatic duct enough to let the pancreatic juice outflow. However, endoscopic removal of the tube remained in place was significantly effective. We here discussed this case with reference of previous published reports.


MDMA-induced neurotoxicity of serotonin neurons involves autophagy and rilmenidine is protective against its pathobiology.
Toxicity of 3,4-methylenedioxymethamphetamine (MDMA) towards biogenic amine neurons is well documented and in primate brain predominantly affects serotonin (5-HT) neurons. MDMA induces damage of 5-HT axons and nerve fibres and intracytoplasmic inclusions. Whilst its pathobiology involves mitochondrially-mediated oxidative stress, we hypothesised MDMA possessed the capacity to activate autophagy, a proteostatic mechanism for degradation of cellular debris. We established a culture of ventral pons from embryonic murine brain enriched in 5-HT neurons to explore mechanisms of MDMA neurotoxicity and recruitment of autophagy, and evaluated possible neuroprotective actions of the clinically approved agent rilmenidine. MDMA (100 μM-1 mM) reduced cell viability, like rapamycin (RM) and hydrogen peroxide (H2O2), in a concentration- and time-dependent manner. Immunocytochemistry revealed dieback of 5-HT arbour: MDMA-induced injury was slower than for RM and H2O2, neuritic blebbing occurred at 48 and 72 h and Hoechst labelling revealed nuclear fragmentation with 100 μM MDMA. MDMA effected concentration-dependent inhibition of [3H]5-HT uptake with 500 μM MDMA totally blocking transport. Western immunoblotting for microtubule associated protein light chain 3 (LC3) revealed autophagosome formation after treatment with MDMA. Confocal analyses and immunocytochemistry for 5-HT, Hoechst and LC3 confirmed MDMA induced autophagy with abundant LC3-positive puncta within 5-HT neurons. Rilmenidine (1 μM) protected against MDMA-induced injury and image analysis showed full preservation of 5-HT arbours. MDMA had no effect on GABA neurons, indicating specificity of action at 5-HT neurons. MDMA-induced neurotoxicity involves autophagy induction in 5-HT neurons, and rilmenidine via beneficial actions against toxic intracellular events represents a potential treatment for its pathobiology in sustained usage.


Updated methodological guidance for the conduct of scoping reviews.
The objective of this paper is to describe the updated methodological guidance for conducting a JBI scoping review, with a focus on new updates to the approach and development of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (the PRISMA-ScR). Scoping reviews are an increasingly common approach to informing decision-making and research based on the identification and examination of the literature on a given topic or issue. Scoping reviews draw on evidence from any research methodology and may also include evidence from non-research sources, such as policy. In this manner, scoping reviews provide a comprehensive overview to address broader review questions than traditionally more specific systematic reviews of effectiveness or qualitative evidence. The increasing popularity of scoping reviews has been accompanied by the development of a reporting guideline: the PRISMA-ScR. In 2014, the JBI Scoping Review Methodology Group developed guidance for scoping reviews that received minor updates in 2017 and was most recently updated in 2020. The updates reflect ongoing and substantial developments in approaches to scoping review conduct and reporting. As such, the JBI Scoping Review Methodology Group recognized the need to revise the guidance to align with the current state of knowledge and reporting standards in evidence synthesis. Between 2015 and 2020, the JBI Scoping Review Methodology Group expanded its membership; extensively reviewed the literature; engaged via annual face-to-face meetings, regular teleconferences, and email correspondence; sought advice from methodological experts; facilitated workshops; and presented at scientific conferences. This process led to updated guidance for scoping reviews published in the JBI Manual for Evidence Synthesis. The updated chapter was endorsed by JBI's International Scientific Committee in 2020. The updated JBI guidance for scoping reviews includes additional guidance on several methodological issues, such as when a scoping review is (or is not) appropriate, and how to extract, analyze, and present results, and provides clarification for implications for practice and research. Furthermore, it is aligned with the PRISMA-ScR to ensure consistent reporting. The latest JBI guidance for scoping reviews provides up-to-date guidance that can be used by authors when conducting a scoping review. Furthermore, it aligns with the PRISMA-ScR, which can be used to report the conduct of a scoping review. A series of ongoing and future methodological projects identified by the JBI Scoping Review Methodology Group to further refine the methodology are planned.


Differential Expression of miR-4520a Associated With Pyrin Mutations in Familial Mediterranean Fever (FMF).
Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent, acute, and self-limiting attacks of fever. Mutations in MEFV gene encoding pyrin account for FMF, but the high number of heterozygote patients with typical symptoms of the disease has driven a number of alternative aetiopathogenic hypotheses. The MEFV gene was knocked down in human myelomonocytic cells that express endogenous pyrin to identify deregulated microRNAs (miRNAs). Microarray analyses revealed 29 significantly differentially expressed miRNAs implicated in pathways associated with cellular integrity and survival. Implementation of in silico gene network prediction algorithms and bioinformatics analyses showed that miR-4520a is predicted to target genes implicated in autophagy through regulation of RHEB/mTOR signaling. Differential expression levels of RHEB were confirmed by luciferase reporter gene assays providing further evidence that is directly targeted by miR-4520a. Although the relative expression levels of miR-4520a were variable among FMF patients, the statistical expression of miR-4520a was different between FMF mutation carriers and controls (P = 0.0061), indicating an association between miR-4520a expression and MEFV mutations. Comparison between FMF patients bearing the M694V mutation, associated with severe disease, and healthy controls showed a significant increase in miR-4520a expression levels (P = 0.00545). These data suggest that RHEB, the main activator of mTOR signaling, is a valid target of miR-4520a with the relative expression levels of the latter being significantly deregulated in FMF patients and highly dependent on the presence of pyrin mutations, especially of the M694V type. These results suggest a role of deregulated autophagy in the pathogenesis of FMF. J. Cell. Physiol. 232: 1326-1336, 2017. © 2016 Wiley Periodicals, Inc.


Modulation of Macrophages Differentiation by Nanoscale-Engineered Geometric and Chemical Features.
Macrophage differentiation into M1 (inflammatory) and M2 (healing) phenotypes plays a vital role in determining the fate of biomaterials. The biophysical properties of the extracellular matrix are known to affect macrophage behavior. Mimicking these special biophysical properties of the extracellular matrix has led to increasing interest in biomaterial constructs with tailor-engineered surface nanotopographical and chemical properties. However, a significant gap of knowledge exists in the role played by the combinational effect of surface nanotopography and chemistry. To address this gap, we have fabricated nanoporous surfaces of controlled pore size (30, 65, and 200 nm) and lateral spacing with uniform outermost surface chemistry tailored with amines (NH2), carboxyl (COOH-) and hydrocarbon (CH3-) functionalities. We show that the combinatory effects of surface properties can direct the differentiation of macrophages to the pro-healing M2 phenotype. This is most evident on the surface featuring nanopores of 200 nm and -COOH functionality. Overall, the concentration of pro-inflammatory cytokines significantly decreases, while the concentration of anti-inflammatory cytokines increases many folds on nanotopographically, and chemically, modified surfaces compared to their planar counterparts. Our data provide pioneering knowledge that could provide pathways to tuning inflammatory and foreign body responses and instruct the design of tailor-engineered biomaterial implants to enable better clinical outcomes.


Assessment of oxygen saturation in retinal vessels of normal subjects and diabetic patients with and without retinopathy using Flow Oximetry System.
To assess oxygen saturation (StO2) in retinal vessels of normal subjects and diabetic patients with and without retinopathy using the modified version of the Flow Oximetry System (FOS) and a novel assessment software. The FOS and novel assessment software were used to determine StO2 levels in arteries and veins located between 1 and 2 mm from the margin of the optic disc and in the macular area. Eighteen normal subjects, 15 diabetics without diabetic retinopathy (DM no DR), and 11 with non-proliferative diabetic retinopathy (NPDR) were included in final analysis. The mean [± standard deviation (SD)] StO2 in retinal arteries was 96.9%±3.8% in normal subjects; 97.4%±3.7% in DM no DR; and 98.4%±2.0% in NPDR. The mean venous StO2 was 57.5%±6.8% in normal subjects; 57.4%±7.5% in DM no DR; and 51.8%±6.8% in NPDR. The mean arterial and venous StO2 across the three groups were not statistically different (P=0.498 and P=0.071, respectively). The arterio-venous differences between the three study groups, however, were found to be statistically significant (P=0.015). Pairwise comparisons have demonstrated significant differences when comparing the A-V difference in the NPDR group to either normal subjects (P=0.02) or diabetic patients without DR (P=0.04). The arterio-venous difference was greater, and statistically significant, in patients with NPDR when compared to normal subjects and to patients with diabetes and no retinopathy. The mean venous StO2 was lower, but not statistically significant, in NPDR compared with diabetics without retinopathy and with normal subjects.


Silage or limit-fed grain growing diets for steers: II. Empty body and carcass composition.
The influence of energy source (silage- or grain-based) on empty body and carcass composition and adipocyte cellularity independent of rate of gain was tested. Sixty-four Angus steers were allotted to either a forage (ad libitum) or grain (limit-fed) diet for a growing phase (145 d) followed by 45, 75, or 105 d of ad libitum access to a grain-based diet. Eight steers were slaughtered initially and eight from each treatment were slaughtered at the end of the growing phase, and at each of the termination dates. The silage growing diet consisted (DM basis) of 55% sorghum silage (approximately 24% dry matter), 22% alfalfa hay, 11% ground shelled corn, and 11% soybean meal. The grain-based growing diet was composed of 77% ground shelled corn, 5% soybean meal, 14% cottonseed hulls, 3% molasses, and 1% salt and mineral; it was limit-fed to produce the same rate of gain as the silage diet. No implants or ionophores were used. At the end of the growing phase, the steers fed grain were heavier and had a higher percentage of fat in the empty body (24 vs 19% fat) and the carcass (26 vs 21% fat) than did steers fed forage. Rate of gain during the growth phase was related positively to percentage of carcass fat; when corrected for fill, data for both diets fit one regression line for fat vs rate of gain. When adjusted for gain during the growing phase, fat content was not different in empty body or carcass, but internal fat was higher (P < .10) for steers fed grain. After 45 d on the finishing diet, carcass fat remained low (23%), but after 75 and 105 d, fat content reached 27%. Source of energy did not detectably affect carcass composition independent of rate of gain. Cell size of adipocytes from four adipose depots increased with time on feed but were not affected by diet during the growing phase. Lean Choice beef can be produced in only 45 d in the feedlot with medium-framed Angus cattle.


Urinary prolactin is correlated with mothering and allo-mothering in squirrel monkeys.
The hormone prolactin is implicated in infant care-giving by parents and allo-parents in a variety of species. Adult female squirrel monkeys (Saimiri spp.) engage in allo-mothering behavior, which includes carrying and nursing infants, but communal care of offspring has not been investigated from an endocrine standpoint in this taxon. We attempted to fill this gap by examining prolactin levels in squirrel monkeys (Saimiri sciureus) as a function of parental responsiveness. Subjects were housed at the National Institutes of Health Animal Center and assays were performed at the Wisconsin National Primate Research Center. To test for the presence of prolactin in squirrel monkey, saliva, blood and saliva were simultaneously collected from anesthetized subjects during routine health examinations. Prolactin was detectable in serum but not in saliva samples. In the core investigation, behavioral data were collected by focal animal sampling on three 1-male multi-female groups, and individually identified urine was collected non-invasively from foil containers underneath group cages on a daily basis throughout the behavioral study. Changes in urinary prolactin over time reflected changes in the reproductive state of a female who was pregnant, gave birth and lactated during the study. Mean urinary prolactin levels in non-lactating females and a male housed with infants in one group were higher than in adults from 2 groups without infants. In the group with infants, mean urinary prolactin levels in adults increased with the amount of infant contact and care-giving. The squirrel monkey may represent a new primate model for investigating the endocrinology of infant care-giving.


Molecular cloning into Tn5 and integration in the Pseudomonas aeruginosa chromosome: a tool for heterologous gene expression.
The DNA primase gene of the promiscuous IncP-1 conjugative plasmid RP1, encoding two polypeptides of 118 and 80 kDa, was inserted into the transposon Tn5 in Escherichia coli. The derivative transposon, Tn2523, was then transposed to a temperature-sensitive replication mutant of the promiscuous IncP-1 conjugative plasmid R68 at permissive temperature and the plasmid transferred to Pseudomonas aeruginosa strain PAO. The latter strain was then grown at non-permissive temperature to identify transposition of Tn2523 into the P. aeruginosa chromosome. Immunological and enzymic analysis showed the expression of functional primase polypeptides in the constructed P. aeruginosa strain. This strain also restored wild-type conjugational transfer proficiency, by complementation, to mutants of the IncP-1 plasmid R18 affected in transfer from P. aeruginosa to P. stutzeri or to Acinetobacter calcoaceticus due to transposon Tn7 insertion mutations in the primase gene. This strategy of cloning into a transposon and integration into the bacterial chromosome should facilitate genetic manipulation and studies of gene expression in a range of Gram-negative bacteria.


Extensor carpi radialis brevis. An anatomical analysis of its origin.
We studied the origin of extensor carpi radialis brevis using 40 fresh frozen human cadaver specimens. Ten were stained with haematoxylin and eosin and trichrome which showed the collagenous structure of the extensor tendons at their origin. Gross anatomical observation showed that there was no definitive separation between brevis and communis at the osseotendinous junction. The histological findings confirmed the lack of separation between the two tendons. The extensor tendons were in close proximity to the joint capsule but trichrome staining showed no interdigitation of the tendon with the capsule. The validity of ascribing the pain of lateral epicondylitis to extensor carpi radialis brevis must be questioned. It appears to arise more from the 'common extensor' origin.


Acoustic and Physiologic Correlates of Vocal Effort in Individuals With and Without Primary Muscle Tension Dysphonia.
The aims of this study were to determine relationships between vocal effort and (a) acoustic correlates of vocal output and (b) supraglottic compression in individuals with primary muscle tension dysphonia (pMTD) and without voice disorders (controls) in the context of a vocal load challenge. Twenty-six individuals with pMTD and 35 vocally healthy controls participated in a 30-min vocal load challenge. The pre- and postload relationships among self-ratings of vocal effort, various acoustic voice measures, and supraglottic compression (mediolateral and anteroposterior) were tested with multiple regression models and post hoc Pearson's correlations. Acoustic measures included cepstral peak prominence (CPP), low-to-high spectral ratio, difference in intensity between the first two harmonics, fundamental frequency, and sound pressure level (dB SPL). Regression models for CPP and mediolateral compression were statistically significant. Vocal effort, diagnosis of pMTD, and vocal demand were each significant variables influencing CPP measures. CPP was lower in the pMTD group across stages. There was no statistical change in CPP following the vocal load challenge within either group, but both groups had an increase in vocal effort postload. Vocal effort and diagnosis influenced the mediolateral compression model. Mediolateral compression was higher in the pMTD group across stages and had a negative relationship with vocal effort, but it did not differ after vocal loading. CPP and mediolateral supraglottic compression were influenced by vocal effort and diagnosis of pMTD. Increased vocal effort was associated with lower CPP, particularly after vocal load, and decreased mediolateral supraglottic compression in the pMTD group.


Role of cardiovascular intervention as a bridge to liver transplantation.
End stage liver disease (ESLD) is associated with many specific derangements in cardiovascular physiology, which influence perioperative outcomes and may profoundly influence diagnostic and management strategies in the preoperative period. This review focuses on evidence-based diagnosis and management of coronary, hemodynamic and pulmonary vascular disease in this population with an emphasis on specific strategies that may provide a bridge to transplantation. Specifically, we address the underlying prevalence of cardiovascular disease states in the ESLD population, and relevant diagnostic criteria thereof. We highlight traditional and non-traditional predictors of cardiovascular outcomes following liver transplant, as well as data to guide risk-factor based diagnostic strategies. We go on to discuss the alterations in cardiovascular physiology which influence positive- and negative-predictive values of standard noninvasive testing modalities in the ESLD population, and review the data regarding the safety and efficacy of invasive testing in the face of ESLD and its co-morbidities. Finally, based upon the totality of available data, we outline an evidence-based approach for the management of ischemia, heart failure and pulmonary vascular disease in this population. It is our hope that such evidence-driven strategies can be employed to more safely bridge appropriate candidates to liver transplant, and to improve their cardiovascular health and outcomes in the peri-operative period.


Patients-people-place: developing a framework for researching organizational culture during health service redesign and change.
Organizational culture is considered by policy-makers, clinicians, health service managers and researchers to be a crucial mediator in the success of implementing health service redesign. It is a challenge to find a method to capture cultural issues that is both theoretically robust and meaningful to those working in the organizations concerned. As part of a comparative study of service redesign in three acute hospital organizations in England, UK, a framework for collecting data reflective of culture was developed that was informed by previous work in the field and social and cultural theory. As part of a larger mixed method comparative case study of hospital service redesign, informed by realist evaluation, the authors developed a framework for researching organisational culture during health service redesign and change. This article documents the development of the model, which involved an iterative process of data analysis, critical interdisciplinary discussion in the research team, and feedback from staff in the partner organisations. Data from semi-structured interviews with 77 key informants are used to illustrate the model. In workshops with NHS partners to share and debate the early findings of the study, organizational culture was identified as a key concept to explore because it was perceived to underpin the whole redesign process. The Patients-People-Place framework for studying culture focuses on three thematic areas ('domains') and three levels of culture in which the data could be organised. The framework can be used to help explain the relationship between observable behaviours and cultural artefacts, the values and habits of social actors and the basic assumptions underpinning an organization's culture in each domain. This paper makes a methodological contribution to the study of culture in health care organizations. It offers guidance and a practical approach to investigating the inherently complex phenomenon of culture in hospital organizations. The Patients-People-Place framework could be applied in other settings as a means of ensuring the three domains and three levels that are important to an organization's culture are addressed in future health service research.


Long-chain n-3 fatty acids and inflammation: potential application in surgical and trauma patients.
Lipids used in nutritional support of surgical or critically ill patients have been based on soybean oil, which is rich in the n-6 fatty acid linoleic acid (18:2n-6). Linoleic acid is the precursor of arachidonic acid (20:4n-6). In turn, arachidonic acid in cell membrane phospholipids is the substrate for the synthesis of a range of biologically active compounds (eicosanoids) including prostaglandins, thromboxanes, and leukotrienes. These compounds can act as mediators in their own right and can also act as regulators of other processes, such as platelet aggregation, blood clotting, smooth muscle contraction, leukocyte chemotaxis, inflammatory cytokine production, and immune function. There is a view that an excess of n-6 fatty acids should be avoided since this could contribute to a state where physiological processes become dysregulated. One alternative is the use of fish oil. The rationale of this latter approach is that fish oil contains long chain n-3 fatty acids, such as eicosapentaenoic acid. When fish oil is provided, eicosapentaenoic acid is incorporated into cell membrane phospholipids, partly at the expense of arachidonic acid. Thus, there is less arachidonic acid available for eicosanoid synthesis. Hence, fish oil decreases production of prostaglandins like PGE2 and of leukotrienes like LTB4. Thus, n-3 fatty acids can potentially reduce platelet aggregation, blood clotting, smooth muscle contraction, and leukocyte chemotaxis, and can modulate inflammatory cytokine production and immune function. These effects have been demonstrated in cell culture, animal feeding and healthy volunteer studies. Fish oil decreases the host metabolic response and improves survival to endotoxin in laboratory animals. Recently clinical studies performed in various patient groups have indicated benefit from this approach.


Acquired hemophilia in association with ANCA-associated vasculitis: response to rituximab.
We describe a patient with end-stage renal disease secondary to antineutrophil cytoplasmic antibody-associated vasculitis who subsequently developed acquired hemophilia A with autoantibodies to factor VIII. This is a novel association. Previous vasculitis therapy with the anti-CD52 monoclonal antibody Campath-1H may have contributed to the development of a second autoimmune disease in this patient by inadvertent depletion of regulatory T cells. The hemophilia followed a relapsing course under oral corticosteroid therapy, but B-cell depletion with anti-CD20 monoclonal antibody (rituximab) was effective in inducing a prolonged remission.


Clinicopathologic features of endometrial cancer with mismatch repair deficiency.
The inclusion of DNA mismatch repair (MMR) evaluation as a standard of care for endometrial cancer management will result in a growing population of patients with MMR deficiency and negative germline Lynch syndrome testing (MMR-deficient). In this systematic review and study, the clinicopathologic features of endometrial cancer in patients with MMR-intact, MLH1 methylation positive, MMR-deficient or Lynch syndrome are evaluated. A systematic search of online databases between 1990 and 2018 identified studies of endometrial cancer patients with tumour testing (MMR protein immunohistochemistry or microsatellite instability) and germline assessment for Lynch syndrome. Extracted data included tumour testing, germline genetic testing, age, body mass index (BMI), family history, tumour stage, grade and histologic type. Associations between MMR-intact, MLH1 methylation positive, MMR-deficient and Lynch syndrome groups were analysed using descriptive statistics. The comprehensive search produced 4,400 publications, 29 met inclusion criteria. A total of 7,057 endometrial cancer cases were identified, 1,612 with abnormal immunohistochemistry, 977 with microsatellite instability. Nine-hundred patients underwent germline genetic testing, identifying 212 patients with Lynch syndrome. Patients in the Lynch syndrome and MMR-deficient groups were significantly younger than patients in the MMR-intact and MLH1 methylation positive groups. Patients with MMR-intact tumours had the highest BMI, followed by MMR-deficient, then Lynch syndrome. MMR-intact tumours were more likely to be grade I at diagnosis than other groups. Patients with Lynch syndrome and MMR-deficient tumours were less likely to have stage I disease as compared to patients with MMR-intact tumours. Endometrial cancer patients with MMR-deficient tumours have similar features to those with germline Lynch syndrome mutations, including age, grade, histology and stage. Even in the absence of a germline mutation, tumour evaluation for MMR status may have important clinical implications.


Determinants of Under-Five Pneumonia at Gondar University Hospital, Northwest Ethiopia: An Unmatched Case-Control Study.
Pneumonia causes about two million under-five deaths each year, accounting for nearly one in five child deaths globally. Knowing the determinants of under-five pneumonia is useful for prevention and intervention programs that are aimed to control the disease. Thus, the main aim of this study was to assess the determinants of under-five pneumonia at Gondar University Hospital, Ethiopia. An institution-based unmatched case-control study was carried out from April 1 to April 30, 2015, taking a sample size of 435 study participants (145 cases and 290 controls). The researchers used a systematic random sampling technique for selecting cases and controls. Data were entered and cleaned using Epi Info version 7 and exported to SPSS version 20 for analysis. Bivariable analysis was performed, and variables with a p value less than 0.2 were entered into multivariable logistic regression. Determinant factors were identified based on p value less than 0.05 and adjusted odds ratio with 95% confidence interval (AOR with 95% CI). An increased odds of pneumonia was associated with children who had diarrhea in the past fifteen days of data collection (AOR = 6.183; 95% CI: 3.482, 10.977), children's mothers who did not hear about how to handle domestic smoking (AOR = 5.814; 95% CI: 2.757, 12.261), and children of mothers who did not follow proper handwashing practice (AOR = 3.469; 95% CI: 1.753, 6.863). Being infected with diarrhea, not knowing how to handle domestic smoking, and poor compliance with proper handwashing practice were identified as determinants of pneumonia. Dedicated, coordinated, and integrated intervention needs to be taken to enhance proper handwashing practice by mothers/caregivers, improve the indoor air quality, and prevent diarrheal diseases at the community level.


Thermally stable access to microresonator solitons via slow pump modulation.
Temporal dissipative Kerr solitons (DKSs) in microresonators provide ultra-short optical pulses and low-noise frequency combs with gigahertz to terahertz repetition rates. Owing to their unique properties, they have found application in fields, including optical communications, rapid laser ranging, and optical precision spectroscopy. However, due to the thermal instability encountered when entering the DKS regime, the stable generation of solitons remains challenging for many systems and usually requires rapid actuation of the pump laser detuning, pulsed driving, additional lasers, a particular mode structure and/or active feedback loops to stabilize the system. Here we show that slow pump modulation can remove the thermal instability and enable passively stable soliton states that can be readily accessed via arbitrarily slow laser tuning, thereby greatly reducing the technical complexity of stable DKS generation.


Regulation of hepatic cholesterol biosynthesis. Effects of a cytochrome P-450 inhibitor on the formation and metabolism of oxygenated sterol products of lanosterol.
The involvement of oxygenated cholesterol precursors in the regulation of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was studied by examining the effect of ketoconazole on the metabolism of mevalonic acid, lanosterol and the lanosterol metabolites, lanost-8-ene-3 beta,32-diol,3 beta-hydroxylanost-8-en-32-al and 4,4-dimethylcholesta-8,14-dien-3 beta-ol, in liver subcellular fractions and hepatocyte cultures. Inhibition of cholesterol synthesis from mevalonate by ketoconazole at concentrations up to 30 microM was due exclusively to a suppression of cytochrome P-450LDM (LDM = lanosterol demethylase) activity, resulting in a decreased rate of lanosterol 14 alpha-demethylation. No enzyme after the 14 alpha-demethylase step was affected. When [14C]mevalonate was the cholesterol precursor, inhibition of cytochrome P450LDM was accompanied by the accumulation of several labelled oxygenated sterols, quantitatively the most important of which was the C-32 aldehyde derivative of lanosterol. There was no accumulation of the 24,25-oxide derivative of lanosterol, nor of the C-32 alcohol. Under these conditions the activity of HMG-CoA reductase declined. The C-32 aldehyde accumulated to a far greater extent when lanost-8-ene-3 beta,32-diol rather than mevalonate was used as the cholesterol precursor in the presence of ketoconazole. With both precursors, this accumulation was reversed at higher concentrations of ketoconazole in liver subcellular fractions. A similar reversal was not observed in hepatocyte cultures.


Coffee, tea, and plasma cholesterol: the Jerusalem Lipid Research Clinic prevalence study.
The association of intake of coffee and tea, assessed by 24 hour dietary recall, with plasma cholesterol and its lipoprotein fractions was studied in a sample of 1007 men and 589 women aged 35-64 resident in Jerusalem. These cross sectional data showed a significant linear association (p less than 0.001) between consumption of coffee in men and plasma cholesterol and low density lipoprotein cholesterol concentrations. Men who drank five cups of coffee or more had plasma cholesterol concentrations about 0.5 mmol/l (20 mg/100 ml) higher than non-drinkers after controlling for age, ethnicity, body mass, education, season of year, smoking, tea drinking, and dietary intake of fat and carbohydrates. In women adjusted mean plasma cholesterol concentration was 0.34 mmol/l (13 mg/100 ml) higher in coffee drinkers grouped together (p less than 0.01). The test for a linear trend was not significant. The association in both sexes was largely with the low density lipoprotein cholesterol fraction. High density lipoprotein cholesterol concentrations were somewhat increased in women who drank coffee (p less than 0.01 for a linear trend) but not in men. Tea drinking was not associated with unadjusted plasma cholesterol concentrations in either sex. Male tea drinkers, but not female, had slightly higher adjusted plasma cholesterol concentrations than non-drinkers (0.15 mmol/l (6 mg/100 ml), p = 0.04). No dose response relation was evident. In this population, characterised by a low intake of saturated fatty acids and relatively low mean plasma cholesterol concentrations, coffee drinking may be a determinant of low density lipoprotein cholesterol concentrations.


Orotate decreases the inhibitory effect of ethanol on galactose elimination in the perfused rat liver.
1. The galactose-elimination rate in perfused livers from starved rats was decreased in the presence of ethanol (2-28mM) to one-third of the control values. Orotate injections partly reversed the effect of ethanol, so that the galactose-elimination rate was about two-thirds of the control values. Orotate alone had no effect on the galactose-elimination rate. 2. Ethanol increased [galactose 1-phosphate] and [UDP-galactose], and decreased (UDP-glucose] and [UTP], both with and without orotate. Orotate increased [UTP], [UDP-galactose], both with and without ethanol. The increase of [galactose 1-phosphate] in the presence of ethanol was inhibited by orotate. Orotate alone had no appreciable effect on [galactose 1-phosphate]. 3. Both the effect of ethanol and that of orotate on the galactose-elimination rate can be accounted for by assuming inhibition of galactokinase by galactose 1-phosphate with Ki about 0.2mM, the inhibition being either non-competitive or uncompetitive. 4. The primary effect of ethanol seems to be inhibition of UDP-glucose epimerase (EC 220.127.116.11), followed by accumulation of UDP-galactose, trapping of UDP-glucose and increase of [galactose 1-phosphate]. Orotate decreased the effect of ethanol, probably by increasing [UDP-glucose].


Serum creatinine and cystatin C provide conflicting evidence of acute kidney injury following acute ingestion of potassium permanganate and oxalic acid.
Acute kidney injury (AKI) is common following deliberate self-poisoning with a combination washing powder containing oxalic acid (H2C2O4) and potassium permanganate (KMnO4). Early and rapid increases in serum creatinine (sCr) follow severe poisoning. We investigated the relationship of these increases with direct nephrotoxicity in an ongoing multicenter prospective cohort study in Sri Lanka exploring AKI following poisoning. Multiple measures of change in kidney function were evaluated in 48 consenting patients who had serial sCr and serum cystatin C (sCysC) data available. Thirty-eight (38/48, 79%) patients developed AKI (AKIN criteria). Twenty-eight (58%) had AKIN stage 2 or 3. Initial increases in urine creatinine (uCr) excretion were followed by a substantial loss of renal function. The AKIN stage 2 and 3 (AKIN2/3) group had very rapid rises in sCr (a median of 118% at 24 h and by 400% at 72 h post ingestion). We excluded the possibility that the rapid rise resulted from the assay used or muscle damage. In contrast, the average sCysC increase was 65% by 72 h. In most AKI, sCysC increases to the same extent but more rapidly than sCr, as sCysC has a shorter half-life. This suggests either a reduction in Cystatin C production or, conversely, that the rapid early rise of sCr results from increased production of creatine and creatinine to meet energy demands following severe oxidative stress mediated by H2C2O4 and KMnO4. Increased early creatinine excretion supports the latter explanation, since creatinine excretion usually decreases transiently in AKIN2/3 from other causes.


Perceived Family Climate and Self-Esteem in Adolescents With ADHD: A Study With a Control Group.
Objective: In this study, our objective is to assess the perception of family environments by adolescents with ADHD based on perceived expressed emotion (EE) and the self-esteem of the adolescents. Method: Uludag University Medical Faculty Hospital completed this study with 41 adolescents with ADHD and 35 control group participants who were matched based on age and gender. Results: The total scores of perceived EE, described as a lack of emotional support, irritability, and intrusiveness, were significantly higher in ADHD group than in the control group. The group with ADHD also showed significantly lower self-esteem. There was a negative correlation between self-esteem scores and total perceived EE scores in the ADHD group and the control group. Conclusion: This study showed that the adolescents with ADHD perceive less emotional support and higher levels of intrusiveness, with patients also describing their families as more irritating. Other results in this study show that adolescents with less emotional support possess lower self-esteem, as do adolescents with more irritable parents.


Ultrastructural study of ehrlichial organisms in the large colons of ponies infected with Potomac horse fever.
Potomac horse fever is characterized by fever, anorexia, leukopenia, profuse watery diarrhea, dehydration, and high mortality. An ultrastructural investigation was made to search for any unusual microorganisms in the digestive system, lymphatic organs, and blood cells of ponies that had developed clinical signs after transfusion with whole blood from horses naturally infected with Potomac horse fever. A consistent finding was the presence of rickettsial organisms in the wall of the intestinal tract of these ponies. The organisms were found mostly in the wall of the large colon, but fewer organisms were found in the small colon, jejunum, and cecum. The organisms were also detected in cultured blood monocytes. In the intestinal wall, many microorganisms were intracytoplasmic in deep glandular epithelial cells and mast cells. Microorganisms were also found in macrophages migrating between glandular epithelial cells in the lamina propria and submucosa. The microorganisms were round, very pleomorphic, and surrounded by a host membrane. They contained fine strands of DNA and ribosomes and were surrounded by double bileaflet membranes. Their ultrastructure was very similar to that of the genus Ehrlichia, a member of the family Rickettsiaceae. The high frequency of detection of the organism in the wall of the intestinal tract, especially in the large colon, indicates the presence of organotrophism in this organism. Infected blood monocytes may be the vehicle for transmission between organs and between animals. The characteristic severe diarrhea may be induced by the organism directly by impairing epithelial cell functions or indirectly by perturbing infected macrophages and mast cells in the intestinal wall or by both.


A hyperactive piggyBac transposon system is an easy-to-implement method for introducing foreign genes into mouse preimplantation embryos.
Transgenic mice are important tools for genetic analysis. A current prominent method for producing transgenic mice involves pronuclear microinjection into 1-cell embryos. However, the total transgenic efficiency obtained using this method is less than 10%. Here, we demonstrate that highly efficient transgenesis in mice can be achieved by cytoplasmic microinjection using a hyperactive piggyBac system. In embryos in which hyPBase mRNA and pPB-CAG-TagRFP DNA were co-injected into the cytoplasm, TagRFP fluorescence was observed after the 2-cell stage; when 30 ng/µl pPB-CAG-TagRFP DNA and 30 ng/µl hyPBase mRNA were co-injected, 94.4% of blastocysts were TagRFP positive. Furthermore, a high concentration of hyPBase mRNA resulted in creation of mosaic embryos in which the TagRFP signals partially disappeared. However, suitable concentrations of injected DNA and hyPBase mRNA produced embryos in which almost all blastomeres were TagRFP positive. Thus, the hyperactive piggyBac transposon system is an easy-to-implement and highly effective method that can contribute to production of transgenic mice.


Natural transfer of helminths of marine origin to freshwater fishes with observations on the development of Diphyllobothrium alascense.
Infective stages of helminths of 5 species that occur as adults in marine mammals were found in burbot, Lota lota (L.) (Gadidae), from the lower Kuskokwim River (southwestern Alaska): Diphyllobothrium alascense Rausch et Williamson, 1958; Pyramicocephalus phocarum (Fabricius, 1780); Corynosoma strumosum (Rudolphi, 1801); Corynosoma semerme (Forsell, 1904); and Pseudoterranova decipiens (Krabbe, 1878). Some larval stages were obtained also from smelt, Osmerus mordax dentex Steindachner, an anadromous fish important as prey of burbot. Burbot, which are freshwater fish, could become paratenic hosts of those helminths by means of at least 3 interactions: by consuming marine fishes in brackish waters at river mouths, by feeding on marine fishes that enter lower reaches of rivers, or by preying on anadromous fishes as they migrate up rivers. Consumption of burbot by people may result in infection by helminths of marine origin; of those recorded, only P. decipiens may be significantly pathogenic. Attempts to rear P. phocarum in dogs were unsuccessful. Plerocercoids of D. alascense, of very small size and found only in the gastric lumen of burbot, readily infected dogs. For study of their development, strobilae were obtained at intervals of 48 hr to 32 days postinfection. In heavy infections, some strobilae developed slowly, while others underwent rapid development.


Intracranial MR-guided laser-induced thermal therapy: single-center experience with the Visualase thermal therapy system.
OBJECTIVE MR-guided laser-induced thermal therapy (MRgLITT) can be used to treat intracranial tumors, epilepsy, and chronic pain syndromes. Here, the authors report their single-center experience with 102 patients, the largest series to date in which the Visualase thermal therapy system was used. METHODS A retrospective analysis of all patients who underwent MRgLITT between 2010 and 2014 was performed. Pathologies included glioma, recurrent metastasis, radiation necrosis, chronic pain, and epilepsy. Laser catheters were placed stereotactically, and ablation was performed in the MRI suite. Demographics, operative parameters, length of hospital stay, and complications were recorded. Thirty-day readmission rates were calculated by using the standard method according to America's Health Insurance Plans Center for Policy and Research guidelines. RESULTS A total of 133 lasers were placed in 102 patients who required intervention for intracranial tumors (87 patients), chronic pain syndrome (cingulotomy, 5 patients), or epilepsy (10 patients). The procedure was completed in 98% (100) of these patients. Ninety-two patients (90.2%) had undergone previous treatment for their intracranial tumors. The average (± SD) total procedural time was 170.5 ± 34.4 minutes, and the mean laser-on time was 8.7 ± 6.8 minutes. The average intensive care unit (ICU) and hospital stays were 1.8 and 3.6 days, respectively, and the median length of stay for both the ICU and the hospital was 1 day. By postoperative Day 1, 54% of the patients (n = 55) were neurologically stable for discharge. There were 27 cases of morbidity, including new-onset neurological deficits, and 2 perioperative deaths. Fourteen patients (13.7%) developed new deficits after the MRgLITT procedure, and of those 14 patients, 64.3% (n = 9) had complete resolution of deficits within 1 month, 7.1% (n = 1) had partial resolution of symptoms within 1 month, 14.3% (n = 2) had not had resolution of symptoms at the most recent follow-up, and 14.3% (n = 2) died without resolution of symptoms. The 30-day readmission rate was 5.6% CONCLUSIONS MRgLITT, although minimally invasive, must be used with caution. Thermal damage to critical and eloquent structures can occur despite MRI guidance. Once the learning curve is overcome, the overall procedural complication rate is low, and most patients can be discharged within 24 hours, with a relatively low readmission rate. In cases in which they occurred, most neurological deficits were temporary. The therapeutic role of MRgLITT in various intracranial diseases will require larger and more rigorous studies.


Seeking the Optimal Descriptor for SN2 Reactions through Statistical Analysis of Density Functional Theory Results.
Bimolecular nucleophilic substitution is one of the fundamental reactions in organic chemistry, yet there is still knowledge to be gained on the role of the nucleophile and the substrate. A statistical treatment of over 600 density functional theory (DFT)-computed barriers for bimolecular nucleophilic substitution at methyl derivatives (SN2@C) leads to the identification of numerical descriptors that best represent the entering and leaving ability of 26 different nucleophiles. The treatment is based on singular value decomposition (SVD) of a matrix of computed energy barriers. The current work represents the extension to a problem of reactivity of the hidden descriptor methodology that we had previously developed for the thermodynamic problem of bond dissociation energies in transition-metal complexes. The analysis of the results shows that a single descriptor is sufficient. This hidden descriptor has different values for nucleophilic and leaving abilities and, contrary to expectation, does not correlate especially well with either frontier molecular orbital descriptors or solvation descriptors. In contrast, it correlates with other thermodynamic and geometric parameters. This statistical procedure can be in principle extended to additional chemical fragments and other reactions.


Exploring Young Adults' Beliefs About Cigar Smoking by Susceptibility: A Belief Elicitation Study.
Young adults are at risk for cigar smoking, which is associated with cancers and pulmonary and cardiovascular diseases. Little is known about young adults' beliefs about smoking cigarillos, little filtered cigars, and large cigars, and how these beliefs may vary across cigar types and by cigar susceptibility. The larger study surveyed a U.S. sample of young adults (18-30 years old) who never used tobacco products (n = 948) through Qualtrics online panel services in August 2021-January 2022. We assessed participants' susceptibility to using different cigar types. Participants were randomly assigned to open-ended questions about one of the three cigar types to elicit behavioral, normative, and control beliefs. We conducted thematic analysis to code emergent themes within each belief and examined the frequency of reported themes at the intersection of cigar type and cigar susceptibility. Cigar susceptible participants reported positive behavioral beliefs (eg, anticipated relaxation, mood regulation, being cool), friends as supportive referents, and easy-to-smoke control beliefs (eg, high accessibility, low cost) more frequently than non-susceptible participants. Varied frequency by cigar type also emerged. For example, cigarillo and little filtered cigar features were mentioned more frequently as easy-to-smoke control beliefs, while low accessibility was reported more frequently as a hard-to-smoke control belief for large cigars. Findings identify salient beliefs about cigarillo, little filtered cigar, and large cigar smoking among young adult tobacco never-users. Future research should investigate the potential importance of these beliefs in cigar smoking susceptibility and initiation among young adults, and their potential utility in prevention research. This thematic analysis identified salient beliefs about cigarillos, little filtered cigars, and large cigars among a U.S. young adult sample, and differentiated emergent beliefs by cigar susceptibility status and by cigar type. Given the lack of cigar smoking prevention media campaigns, identifying these beliefs is the one of the first steps in developing effective cigar smoking prevention strategies. Future quantitative studies are needed to confirm the relationships between these beliefs and smoking initiation of each cigar type to further inform the types of beliefs to be targeted in strategic communication and help prevent cigar smoking initiation among susceptible young adults.


Cyberbullying Victimization and Adolescent Mental Health: Evidence of Differential Effects by Sex and Mental Health Problem Type.
The use of electronic communication technologies has become a core method for adolescent communication. While there are many benefits to such technologies, cyberbullying has emerged as a potential harm. This study examines the association between cyberbullying and adolescent mental health problems and the extent to which this association differs by sex and mental health problem type. A clustered sample of 31,148 students in grades 6-12 (Female = 51.9%; 56.5% Caucasian, 10.2% South Asian) completed an anonymous survey asking their frequency of exposure to traditional forms of bullying, cyberbullying, and experiences of mental health problems over the past 6 months. Multilevel structural equation modelling was used to examine the associations. Controlling for age and traditional forms of bullying, cyberbullying was a significant predictor of adolescents' emotional and behavioral problems. Cyberbullying was more strongly associated with emotional problems for females and with behavioral problems for males. This evidence identifies unique adverse effects associated with cyberbullying on both emotional and behavioural problems and sex differences in the strength of these associations.


The Dutch Birth Centre Study: study design of a programmatic evaluation of the effect of birth centre care in the Netherlands.
Birth centres are regarded as settings where women with uncomplicated pregnancies can give birth, assisted by a midwife and a maternity care assistant. In case of (threatening) complications referral to a maternity unit of a hospital is necessary. In the last decade up to 20 different birth centres have been instituted in the Netherlands. This increase in birth centres is attributed to various reasons such as a safe and easy accessible place of birth, organizational efficiency in integration of care and direct access to obstetric hospital care if needed, and better use of maternity care assistance. Birth centres are assumed to offer increased integration and quality of care and thus to contribute to better perinatal and maternal outcomes. So far there is no evidence for this assumption as no previous studies of birth centres have been carried out in the Netherlands. The aims are 1) Identification of birth centres and measuring integration of organization and care 2) Measuring the quality of birth centre care 3) Effects of introducing a birth centre on regional quality and provision of care 4) Cost-effectiveness analysis 5) In depth longitudinal analysis of the organization and processes in birth centres. Different qualitative and quantitative methods will be used in the different sub studies. The design is a multi-centre, multi-method study, including surveys, interviews, observations, and analysis of registration data and documents. The results of this study will enable users of maternity care, professionals, policy makers and health care financers to make an informed choice about the kind of birth location that is appropriate for their needs and wishes.