Granulosa cells from emerged antral follicles of the bovine ovary initiate inflammation in response to bacterial pathogen-associated molecular patterns via Toll-like receptor pathways.
Bacterial infections of the uterus or mammary gland commonly perturb ovarian antral follicle growth and function, causing infertility in cattle. Cells of the innate immune system use Toll-like receptors (TLRs) TLR2, TLR4, and TLR5 to recognize pathogen-associated molecular patterns (PAMPs) of bacteria, leading to production of inflammatory mediators, such as IL-1beta, IL-6, and IL-8. The present study examined whether granulosa cells from emerged antral follicles have functional responses to typical bacterial PAMPs. Granulosa cells from emerged bovine antral follicles expressed mRNA for all 10 TLRs. Cellular expression of mRNA for the cytokines IL1B, IL6, IL10, and TNF, and chemokines IL8 and CCL5, increased after treatment with synthetic bacterial lipoprotein binding TLR2, lipopolysaccharide binding TLR4, or flagellin binding TLR5. Supernatants of granulosa cells accumulated IL-1beta, IL-6, and IL-8 protein in a concentration-dependent manner when treated with lipoprotein or lipopolysaccharide, but not flagellin. Accumulation of IL6 in response to lipoprotein and lipopolysaccharide was attenuated using siRNA targeting TLR2 and TLR4, respectively. Granulosa cells increased phosphorylation of mitogen-activated protein kinase (MAPK) 14 and MAPK3/1 within 30 min of treatment with lipopolysaccharide or lipoprotein, and inhibitors targeting MAPK14 reduced the accumulation of IL-6 in response to the PAMPs. Treatment with hormones follicle-stimulating hormone, luteinizing hormone, estradiol, or progesterone did not significantly affect granulosa cell responses to PAMPs. However, epidermal growth factor enhanced IL-6 accumulation in response to lipoprotein and inhibiting epidermal growth factor receptor (EGFR) abrogated the effect, whereas lipoprotein increased granulosa cell EGFR mRNA expression. In conclusion, bovine granulosa cells from emerged follicles sense bacterial PAMPs and initiate inflammatory responses via TLR2 and TLR4 pathways.


Temperature increases on the external root surface during endodontic treatment using single file systems.
The aim of this study is to evaluate increases in temperature on the external root surface during endodontic treatment with different rotary systems. Fifty human mandibular incisors with a single root canal were selected. All root canals were instrumented using a size 20 Hedstrom file, and the canals were irrigated with 5% sodium hypochlorite solution. The samples were randomly divided into the following three groups of 15 teeth: Group 1: The OneShape Endodontic File no.: 25; Group 2: The Reciproc Endodontic File no.: 25; Group 3: The WaveOne Endodontic File no.: 25. During the preparation, the temperature changes were measured in the middle third of the roots using a noncontact infrared thermometer. The temperature data were transferred from the thermometer to the computer and were observed graphically. Statistical analysis was performed using the Kruskal-Wallis analysis of variance at a significance level of 0.05. The increases in temperature caused by the OneShape file system were lower than those of the other files (P < 0.05). The WaveOne file showed the highest temperature increases. However, there were no significant differences between the Reciproc and WaveOne files. The single file rotary systems used in this study may be recommended for clinical use.


Effects of Stress and Task Difficulty on Working Memory and Cortical Networking.
This study investigated interactive effects of stress and task difficulty on working memory and cortico-cortical communication during memory encoding. Thirty-eight adolescent participants (mean age of 15.7 ± 1.5 years) completed easy and hard working memory tasks under low- and high-stress conditions. We analyzed the accuracy and reaction time (RT) of working memory performance and inter- and intrahemispheric electroencephalogram coherences during memory encoding. Working memory accuracy was higher, and RT shorter, in the easy versus the hard task. RT was shorter under the high-stress (TENS) versus low-stress (no-TENS) condition, while there was no difference in memory accuracy between the two stress conditions. For electroencephalogram coherence, we found higher interhemispheric coherence in all bands but only at frontal electrode sites in the easy versus the hard task. On the other hand, intrahemispheric coherence was higher in the left hemisphere in the easy (versus hard task) and higher in the right hemisphere (with one exception) in the hard (versus easy task). Inter- and intracoherences were higher in the low- versus high-stress condition. Significant interactions between task difficulty and stress condition were observed in coherences of the beta frequency band. The difference in coherence between low- and high-stress conditions was greater in the hard compared with the easy task, with lower coherence under the high-stress condition relative to the low-stress condition. Stress seemed to cause a decrease in cortical network communications between memory-relevant cortical areas as task difficulty increased.


Curli, fibrous surface proteins of Escherichia coli, interact with major histocompatibility complex class I molecules.
Curli are thin, coiled fibers expressed on the surface of Escherichia coli that bind several matrix and plasma proteins such as fibronectin, laminin, plasminogen, tissue plasminogen activator, and H-kininogen. In this work, we examined the interactions between curli-expressing E. coli and human major histocompatibility complex class I (MHC-I) and class II (MHC-II) molecules. Curliated E. coli was found to interact with an MHC-I-expressing lymphoma cell line as shown by scanning electron microscopy, whereas the binding to a mutant variant of this cell line expressing small amounts of MHC-I molecules was significantly lower. Moreover, curli-expressing E. coli bound purified radiolabeled MHC-I but not MHC-II molecules, whereas an isogenic curli-deficient mutant strain showed no affinity for either MHC-I or MHC-II. Purified insoluble curli could also bind 125I-labeled MHC-I molecules, and in Western blot experiments the 15-kDa curlin subunit protein bound intact MHC-I molecules as well as beta2-microglobulin, the light chain of MHC-I molecules. A direct interaction between monomeric MHC-I molecules and a bacterial surface protein has previously not been reported. The binding of curli to MHC-I molecules, which are present on virtually all cells in higher vertebrates, will provide curliated E. coli with ample opportunities to interact with a great variety of hosts and host cells. This should facilitate the adaptation of E. coli to different ecological niches, and in human infections the interaction between curli and MHC-I molecules could contribute to adherence and colonization.


Monorail snare technique for the retrieval of an adherent microcatheter from an onyx cast: technical case report.
Microcatheters retained after Onyx (eV3 Neurovascular, Inc., Irvine, CA) embolization represent a potential source of thromboembolic complications. Catheter retention depends on the degree of Onyx reflux and vessel tortuosity. To overcome this problem, we have adapted a previously described monorail snare technique for stretched coils to remove an adherent microcatheter from the occipital artery during Onyx embolization of a dural arteriovenous fistula. We used this technique successfully in a 62-year-old man with a posterior fossa dural arteriovenous fistula. An Echelon-10 microcatheter (eV3 Neurovascular, Inc.) system became adherent in the right occipital artery because of reflux and vessel tortuosity. Significant stretching of the microcatheter was observed during attempted removal. A 2-mm Amplatz Goose Neck microsnare (Microvena Corp., White Bear Lake, MN) was placed through a Rapid Transit microcatheter (Cordis Corp., Miami, FL). The hub of the indwelling Echelon microcatheter was cut off and the snare advanced over the outside of the microcatheter. The snare and Rapid Transit microcatheter were then advanced into the guiding catheter (6-French) as a unit over the indwelling Echelon microcatheter. Using the adherent Echelon as a "monorail" guide, the snare and Rapid Transit microcatheter were advanced distally into the occipital artery and the snare was retracted to engage the microcatheter. The microcatheters and snare were then easily removed because of the second vector of force placed by the snare system on the adherent microcatheter very close to the point of adherence. The monorail snare technique represents a simple and safe way to remove an adherent microcatheter from an Onyx cast during the embolization of dural arteriovenous fistulas. Prospective knowledge of this technique will facilitate more aggressive embolization without the reservation that a retained microcatheter could require surgical removal or anticoagulation.


Creating better doctors: exploring the value of learning medicine in primary care.
Across the UK, 13% of undergraduate medical education is undertaken in primary care (PC). Students value their experiences in this setting but uncertainty remains about the extent to which these placements influence their future practice. To explore the impact of PC based undergraduate medical education on the development of medical students and new doctors as clinicians, and on students' preparedness for practice. Mixed method study across two UK medical schools. Focus groups and individual interviews with Year 5 medical students, Foundation Year 2 doctors and GP Specialty Trainees; online surveys of Year 5 medical students and Foundation Year 2 doctors. PC placements play an important part in the development of all 'apprentice' doctors, not just those wanting to become GPs. They provide a high quality learning environment, where students can: gradually take on responsibility; build confidence; develop empathy in their approach to patient care; and gain understanding of the social context of health and illness. The study suggests that for these results to be achieved, PC placements have to be high quality, with strong links between practice-based learning and teaching/assessment in medical school. GP tutors need to be enthusiastic and students actively involved in consultations.


The immunotherapy of prostate and bladder cancer.
The role of the immune system in controlling the growth of tumour cells is highly complex and has been extensively debated. It is well documented that the immune system controls virally induced cancers, and there is evidence for a role of specific immunity in other types of tumours. The greater understanding of the regulation and optimization of adoptive, specific immune responses, and the better characterization of tumour-associated antigens indicate the way for active specific vaccination and cell therapy in urological tumours. Currently, bacille Calmette Guerin immunotherapy is established for localized bladder cancer and many experimental immunotherapies are under evaluation. Here we review some timely aspects of tumour immunology, and describe the current status and development of immunotherapy in prostate and bladder cancer.


Structure determination of the coincidence phase of graphene on Ru(0001).
The structure of the commensurate (23x23) phase of graphene on Ru(0001) has been analyzed by quantitative low-energy electron diffraction (LEED)-I(V) analysis and density-functional theory calculations. The I(V) analysis uses Fourier components as fitting parameters to determine the vertical corrugation and the lateral relaxation of graphene and the top Ru layers. Graphene is shown to be strongly corrugated by 1.5 A with a minimum C-Ru distance of 2.1 A. Additionally, lateral displacements of C atoms and a significant buckling in the underlying Ru layers are observed, indicative for strong local C-Ru interactions.


Effect of EU electrical stunning conditions on breast meat quality of broiler chickens.
Electrical stunning is still the main stunning method used worldwide in commercial poultry plants. The stunning procedures in water bath stunners affect both bird welfare and meat quality attributes. The European Union (EU) Council Regulation 1099/2009 on the protection of the animal at the time of killing established the minimum current flow through an individual bird at a specified frequency to assure an effective stun that must last until the bird's death. The aim of this study was to compare the effect of the application of different stunning current flows on the prevalence of hemorrhages (classified as 1 = no lesion, 2 = moderate, and 3 = severe lesion) and some quality traits (pHu, color, drip and cooking losses, and shear force) of chicken breast meat. A total of 12 flocks of broiler chickens, each equally divided into light, medium, and heavy sizes, was submitted either to the stunning condition usually adopted before the entry into force of the current EU regulation (90 mA/bird, 400 Hz) (OLD) or to that enforced by it (150 mA/bird, 400 Hz) (NEW). Overall, the prevalence of severe hemorrhages dramatically increased in the NEW group in comparison with the OLD one (55 vs. 27%; P < 0.001) and particularly in heavy-sized birds (72 vs. 25%; P < 0.001). In general, meat quality attributes were not affected by the stunning conditions with the exception of drip loss that resulted lower in NEW than OLD birds (1.01 vs. 1.27; P < 0.001). In conclusion, the adoption of a higher current flow, as suggested by the EU regulation to protect animals at the time of killing, increases the prevalence of breast hemorrhages while maintaining meat quality traits with a possible beneficial effect on water holding capacity of fresh meat.


The benefits of index telephone consultations in patients referred on the two-week wait colorectal cancer pathway.
The coronavirus disease 2019 (COVID-19) pandemic led to hospitals in the UK substituting face-to-face (FtF) clinics with virtual clinic (VC) appointments. We evaluated the use of virtual two-week wait (2-ww) lower gastrointestinal (LGI) clinic appointments, conducted using telephone calls at a district general hospital in England. Patients undergoing index outpatient 2-ww LGI clinic assessment between 1 June 2019 and 31 October 2019 (FtF group) and 1 June 2020 and 31 October 2020 (VC group) were identified. Relevant data were obtained using electronic patient records. Compliance with national cancer waiting time targets was assessed. Environmental and financial impact analyses were performed. In total, 1,531 patients were analysed (median age=70, male=852, 55.6%). Of these, 757 (49.4%) were assessed virtually via telephone; the remainder were seen FtF (n=774, 50.6%). Ninety-two (6%, VC=44, FtF=48) patients had malignant pathology and 64 (4.2%) had colorectal cancer (CRC); of these, 46 (71.9%, VC=26, FtF=20) underwent treatment with curative intent. The median waiting times to index appointment, investigation and diagnosis were significantly lower following VC assessment (p<0.001). The cancer detection rates (p=0.749), treatments received (p=0.785) and median time to index treatment for CRC patients (p=0.156) were similar. A significantly higher proportion of patients were seen within two weeks of referral in the VC group (p<0.001). VC appointments saved patients a total of 9,288 miles, 0.7 metric tonnes of CO2 emissions and £7,482.97. Taxpayers saved £80,242.00 from VCs. No formal complaints were received from patients or staff in the VC group. Virtual 2-ww LGI clinics were effective, safe and were associated with tangible environmental and financial benefits.


The Effect of Increasing Topsoil Disturbance on Surface-Active Invertebrate Composition and Abundance under Grazing and Cropping Regimes on Vertisols in North-West New South Wales, Australia.
Agricultural intensification practices involve varying degrees of disturbance to the soil ecosystem. This study evaluated six agricultural management regimes with increasing levels of topsoil disturbance, on the composition and abundance of surface-active invertebrates on Vertisols at a sub-catchment scale. Two grazing (native and introduced pastures), and four cropping (combining short and long fallow, with zero and conventional tillage) management regimes were examined. Surface-active invertebrates were collected seasonally with pitfall traps over 2 years (8 seasons), and identified to order, while ants (Formicidae) that comprised 47% of total invertebrates collected, were identified to genera. Season had a significant effect on ant abundance and number of genera recorded with higher abundance and twice the number of genera in summer than all other seasons. Ants, particularly Iridomyrmex, were mainly active in summer, while other invertebrates especially Coleoptera, were more active in winter. Surface-active invertebrates were 30% more abundant in grazing than cropping land use types. Native pasture, with little surface soil disturbance, recorded the highest number of invertebrates, mainly ants, compared to other agricultural management regimes. Coleoptera and Dermaptera were higher in abundance under conventional tillage compared with those agricultural management regimes that disturb the topsoil less. Optimizing surface-active invertebrate activity on Vertisols for most taxa will require reducing topsoil disturbance. However, the research findings also suggest that the impact of agricultural management regimes on invertebrate activity was difficult to predict with any certainty as the three main ant genera, and most abundant invertebrate collected, did not respond in a consistent manner.


Modified Frailty Index Predicts Postoperative Complications Following Parastomal Hernia Repair.
The 5-factor frailty index (5-mFI), validated frailty index with Spearmen rho correlation of .95 and C statistic >.7 for predicting postoperative complications, can be preoperatively used to stratify patients prior to parastomal hernia repairs. Retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database identified patients from 2015 to 2020. 5-mFI scores were calculated by adding one point for each comorbidity present: diabetes mellitus, congestive heart failure (CHF), hypertension requiring medication, severe chronic obstructive pulmonary disease (COPD), non-independent functional status. Primary endpoint was 30-day overall complications; secondary endpoints were 30-day readmission, reoperation, and discharge to care facility. 2924 (52.2% female) patients underwent elective parastomal hernia repair. Univariate analysis showed 5-mFI > 2 had higher rates of overall (P = .008), pulmonary (P = .002), cardiovascular (P = .003)), hematologic (P = .003), and renal (P = .002) complications and higher rates of readmission (P = .009), reoperation (P = .001), discharge to care facility (P < .001), and death (P < .001). Multivariate analysis identified a 5-mFI of 2 or more as an independent risk factor for overall complications [OR: 1.40, 1.03-1.78; P = .032], pulmonary complications [2.97, 1.63-5.39; P < .001], hematological complications [1.60, 1.03-2.47; P = .035], renal complications [2.04, 1.19-3.46; P = .009], readmission [1.54, 1.19-1.99; P < .001], and discharge to facility [2.50, 1.66-3.77; P < .001]. Reoperation was not signification on multivariate analysis. Parastomal hernia repair patients with 5-mFI score of >2 had higher risk of renal, cardiovascular, pulmonary, and hematologic complications, readmissions, longer hospitalization, discharge to care facility, and mortality, and can be useful during preoperative risk stratification.


Trabeculae in the basilar venous plexus: anatomical and histological study with application to intravascular procedures.
Few studies have examined the basilar venous plexus (BVP) and to our knowledge, no previous study has described its histology. The present anatomical study was performed to better elucidate these structures. In ten cadavers, the BVP was dissected. The anatomical and histological evaluation of the intraluminal trabeculae within this sinus were evaluated. Once all gross measurements were made, the clivus and overlying BVP were harvested and submitted for histological analysis. A BVP was identified in all specimens and in each of these, intraluminal trabeculae were identified. The mean number of trabeculae per plexus was five. These were most concentrated in the upper half of the clivus and were more often centrally located. These septations traveled in a posterior to anterior direction and usually, from inferiorly to superiorly however some were noted to travel horizontally. In a few specimens the trabeculae had wider bases, especially on the posterior attachment to the meningeal layer of dura mater. More commonly, the trabeculae ended in a denticulate form at their two terminal ends. The trabeculae were on average were 0.85 mm in length. The mean width of the trabeculae was 0.35 mm. These septations were consistent with the cords of Willis as are found in the lumen of some of the other intradural venous sinuses. An understanding of the internal anatomy of the BVP can aid in our understanding of venous pathology. Furthermore, this knowledge will benefit patients undergoing interventional treatments that involve the BVP.


Effects of prenatal androgenization, melengestrol acetate, and Synovex-H on feedlot performance, carcass, and sensory traits of once-calved heifers.
Three studies were designed using a 2 x 2 factorial arrangement of treatments within each experiment to evaluate the effects of various management techniques on growth and carcass traits of once-calved heifers. In Exp. 1, 33 yearling (16 control [C] and 17 prenatally androgenized [PA]) and 39 once-calved (20 C and 19 PA) nonpregnant heifers were used to evaluate the effects of age and PA. Once-calved heifers were approximately 31 kg heavier (P < .03) on-test, initially consumed 11% more (P < .01) DM, and gained 11% faster (P < .08), but had similar (P = .44) gain to feed ratios (.138 vs. .131) as yearlings. Growth performance was not affected by PA. The yearling and once-calved heifers were then slaughtered at approximately 707 and 1,080 d of age, respectively. Despite maturity differences (P < .01), marbling scores (P = .26) and percentage of choice carcasses (P = .27) were similar. However, on the basis of newly accepted grading changes, percentage of once-calved heifer carcasses grading choice decreased from 57.3 to 34.4%. Organoleptic properties did not differ. Experiments 2 and 3 were then conducted to evaluate effects of commercially available products (melengestrol acetate [MGA] and Synovex-H) on feedlot characteristics of heifers following weaning of their first calf. In Exp. 2, 48 once-calved Simmental-based heifers were fed during the summer to a constant compositional fat thickness of .8 cm. Experiment 3 was conducted in the late fall and early winter, during which 52 moderately sized heifers were fed for 116 d postweaning and slaughtered. Performance of heifers in Exp. 2 was not affected by MGA. However, heifers fed MGA in Exp. 3 gained 9% faster (P < .05) than controls. In Exp. 2, Synovex-H tended to improve ADG (P < .09) and feed efficiency (P < .07), but did not affect performance in Exp. 3. Most carcass traits were not affected by either treatment. Nonpregnant, once-calved heifers seem to have a large capacity for efficient weight gain as compared with yearling heifers. However, hormonal compounds, such as testosterone propionate provided pre- or postnatally (Synovex-H), and MGA do not appear to provide the consistent, positive responses often seen with younger, more typical feedlot heifers.


[The topological structure of the genetic code].
On the basis of the topological concept of the vicinity of the point, graphs of connectedness for four nitrous bases (L and D tetrahedra) and the topological patterns of doublet and triplet genetic codes were constructed. These topological patterns were isomorphic to Boolean hypercubes B4 and B6, respectively. The resultant structures of the genetic code resembled those obtained earlier in terms of the rhombic variant of the genetic code table, which was constructed on the basis of complementarity of the coding doublets. Specifically, both models assumed the following: (1) when two groups of doublets and quartets of triplets that coded for one amino acid or two amino acids each were transformed into each other according to Rumer's rule (C <--> A, G <--> U), they retained C2 symmetry, and (2) single transitions of nitrous bases changed the structures of the encoded amino acids to the minimum possible extent. A possible mechanism for the origin of the genetic code and the possibility of using the characteristics of the obtained structures to develop the algorithm of prediction of the supermolecular protein structure, read genetic "texts", and refine the functions of amino acids as molecular modules are discussed in terms of the results obtained.


Relationships between C3b receptor (CR1) activity of erythrocytes and positive Coombs' tests.
Although positive direct Coombs' tests occur in most patients with active systemic lupus erythematosus (SLE), haemolytic anaemic associated with antibody to erythrocytes (E) occurs in less than 10%. Our studies show an association between positive direct Coombs' tests and both the presence of circulating immune complexes and diminished activity of the C3b receptor (CR1) of E. Data presented in this report suggest that in vivo binding of immune complexes and complement by the CR1 of E results in positive direct Coombs' tests in the absence of antibody to E. These observations explain the low frequency of haemolytic anaemia compared with the high frequency of direct positive Coombs' tests in patients with SLE.


Value of HAVOC and Brown ESUS-AF scores for atrial fibrillation on implantable cardiac monitors after embolic stroke of undetermined source.
Up to 20 % of ischemic strokes are associated with overt atrial fibrillation (AF). Furthermore, silent AF was detected by an implantable cardiac monitor (ICM) in 1 in 3 cryptogenic strokes in the CRYSTAL AF study. An ESC position paper has suggested a HAVOC score ≥ 4 or a Brown ESUS-AF score ≥ 2 as criteria for ICM implantation after cryptogenic stroke, but neither of these criteria has been developed or validated in ICM populations. We assessed the performance of HAVOC and Brown ESUS-AF scores in a cohort of ICM patients implanted after embolic stroke of undetermined source (ESUS). All patients implanted with an ICM for ESUS between February 2016 and February 2022 at two French University Hospitals were retrospectively included. Demographic data, cardiovascular risk factors, and clinical and biological data were collected after a review of electronic medical records. HAVOC and Brown ESUS-AF scores were calculated for all patients. Among the 384 patients included, 106 (27 %) developed AF during a mean follow-up of 33 months. The scores performances for predicting AF during follow-up were: HAVOC= AUC: 68.5 %, C-Index: 0.662, and Brown ESUS-AF=AUC: 72.9 %, C-index 0.712. Compared with the CHA2DS2-VASc score, only the Brown ESUS-AF score showed significant improvement in NRI/IDI. Furthermore, classifying patients according to the suggested HAVOC and Brown ESUS-AF thresholds, only 24 % and 31 % of the cohort, respectively, would have received an ICM, and 58 (55 %) and 47 (44 %) of the AF patients, respectively, would not have been implanted with an ICM. HAVOC and Brown ESUS-AF scores showed close and moderate performance in predicting AF on ICM after cryptogenic stroke, with a significant lack of sensitivity. Specific risk scores should be developed and validated in large ICM cohorts.


Rasmussen encephalitis: a clinicopathologic and immunohistochemical study of seven patients.
We retrospectively reviewed the clinicopathologic features and immunohistochemical profiles of 7 patients with Rasmussen encephalitis (age range, 3.5-15 years at surgery). All had medically intractable seizures (6 months' to 7 years' duration); all but 1 developed unilateral hemiparesis. Histologically, all cases were characterized by leptomeningeal and parenchymal perivascular chronic inflammation consisting primarily of T lymphocytes (CD3+, CD5+, CD7+). In all but 1 case, a predominance of CD8+ T-cytotoxic/suppressor lymphoid cells over CD4+ cells was observed. All cases had rare B lymphocytes (CD79a+, CD20+). Rare CD10+ and no CD56+ cells were noted. All cases were marked by diffuse proliferation of microglial cells, highlighted on CD68 immunostaining. Focal microglial nodule formations were observed in 4 cases and focal cortical atrophy in 5 cases. Viral inclusions were not noted. There was no evidence of Epstein-Barr virus by LMP-1 antibody immunostaining. The histologic findings of Rasmussen encephalitis resemble those of viral meningoencephalitis. The pathologicfindings may be only focally present, and missed, if diagnosis is made or confirmed with biopsy alone. Most lymphoid cells have a T-cell immunophenotype, with a predominance of CD8+ cells in most cases.


The National Research Council report on the Colleges of Agriculture at the Land Grant Universities: some issues of interest to poultry science.
The recently released National Research Council report, Colleges of Agriculture at the Land Grant Universities: Public Service and Public Policy (NRC 1996), may be of particular interest to poultry scientists. The dramatic changes in U.S. agriculture, which were among the factors that spawned the NRC's interest in a study of the land grant colleges, are probably nowhere more evident than in the poultry industry. Furthermore, there is considerable discussion in the report about the value of multi-state and multi-disciplinary efforts in teaching, research, and extension. The need to attract nontraditional students to poultry science curricula and to produce graduates well-suited for modern, vertically integrated agricultural enterprises, such as poultry, are a high priority.


Renal effects of the angiotensin receptor neprilysin inhibitor LCZ696 in patients with heart failure and preserved ejection fraction.
Increases in serum creatinine with renin-angiotensin-aldosterone system (RAAS) inhibitors can lead to unnecessary discontinuation of these agents. The dual-acting angiotensin receptor neprilysin inhibitor LCZ696 improves clinical outcome patients with heart failure with reduced ejection fraction, and pilot data suggest potential benefit in heart failure with preserved ejection fraction (HFpEF). The effects of LCZ696 on renal function have not been assessed. A total of 301 HFpEF patients were randomly assigned to LCZ696 or valsartan in the PARAMOUNT trial. We studied renal function [creatinine, estimated glomerular filtration rate (eGFR), cystatin C, and urinary albumin to creatinine ratio (UACR)] at baseline, 12 weeks, and after 36 weeks of treatment. Worsening renal function (WRF) was determined as an serum creatinine increase of >0.3 mg/dL and/or >25% between two time-points. Mean eGFR at baseline was 65.4 ± 20.4 mL/min per 1.73 m(2) . The eGFR declined less in the LCZ696 group than in the valsartan group (-1.5 vs. -5.2 mL/min per 1.73 m(2) ; P = 0.002). The incidence of WRF was lower in the LCZ696 group (12%) than in the valsartan group (18%) at any time-point, but this difference was not statistically significant (P = 0.18). Over 36 weeks, the geometric mean of UACR increased in the LCZ696 group (2.4-2.9 mg/mmol), whereas it remained stable in the valsartan group (2.1-2.0 mg/mmol; P for difference between groups = 0.016). In patients with HFpEF, therapy with LCZ696 for 36 weeks was associated with preservation of eGFR compared with valsartan therapy, but an increase in UACR.


Health benefits of exercise in an aging society.
The effects of regular aerobic exercise are important to an aging society increasingly preoccupied with exercise. Traditionally, most attention has been directed to the relationship between a physically active life-style and cardiovascular mortality. In an aging society, however, active life expectancy and maintenance of independence may be as important as effects of regular exercise on longevity. Regular exercise results in increased maximum aerobic capacity due to peripheral changes in muscle (increased capacity for aerobic metabolism and improved substrate and oxygen extraction with a widened arteriovenous oxygen difference) and also due to cardiovascular changes with increased stroke volume and cardiac output in normal persons. "Therapeutic benefits" of conditioning probably occur at submaximal work loads common to everyday activity, when cardiac work and myocardial oxygen consumption are less for any given work load, muscles are more efficient, and relative oxygen requirements are less. Aging is associated with a linear decline in maximum aerobic capacity. The rate of decline is twofold greater when comparing sedentary with physically active middle-aged men. Thus, regular exercise could conceivably lower functional aerobic age by slowing this functional decline. Exercise, particularly excessive exercise, is also associated with serious hazards, including sudden death, nonfatal myocardial infarction, excessive fatigue, hyperthermia, and significant musculoskeletal problems. Accounts of the health effects of exercise should consider a wide range of risks and benefits, especially those related to improving function, minimizing disability, and prolonging independent living.


Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study.
The ATHENA study was designed to assess the performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping compared with liquid-based cytology for cervical cancer screening in a large US population aged 21 years and older. We did a subanalysis of this population to compare the screening performance of the cobas HPV test versus liquid-based cytology in women aged 25 years and older, and assess management strategies for HPV-positive women. Women aged 25 years or older who were attending routine cervical screening were enrolled from 61 clinical centres in 23 US states. Cervical specimens were obtained for liquid-based cytology and HPV DNA testing with two first-generation assays (Amplicor HPV test and Linear Array HPV genotyping test) and the second-generation cobas HPV test (with individual HPV16 and HPV18 detection). Colposcopy and diagnostic biopsies were done on women with atypical squamous cells of undetermined significance (ASC-US) or worse cytology, those who tested positive with either first-generation HPV test, and a random sample of women who tested negative for HPV and cytology. All women not selected for colposcopy received their results and exited the study. Participants and colposcopists were masked to cytology and HPV test results until the colposcopy visit was completed. The primary endpoint for this substudy was histologically confirmed cervical intraepithelial neoplasia grade 3 (CIN3) or worse. This study is registered with ClinicalTrials.gov, number NCT00709891; the study is in the follow-up phase, which is due to be completed in December, 2012. From May 27, 2008, to Aug 27, 2009, 47,208 women were enrolled, of whom 41,955 met our eligibility criteria. Valid cobas HPV and liquid-based cytology test results were available for 40,901 women (97%), who were included in this analysis. Of these, 4275 women (10%) tested cobas HPV positive and 2617 (6%) had abnormal cytology. 431 women were diagnosed with CIN2 or worse and 274 with CIN3 or worse. In women who had colposcopy, the cobas HPV test was more sensitive than liquid-based cytology for detection of CIN3 or worse (252/274 [92·0%, 95% CI 88·1-94·6] vs 146/274 [53·3%, 95% CI 47·4-59·1]; difference 38·7%, 95% CI 31·9-45·5; p<0·0001). Addition of liquid-based cytology to HPV testing increased sensitivity for CIN3 or worse to 96·7% (265/274, 95% CI 93·9-98·3), but increased the number of screen positives by 35·2% (5783/40,901 vs 4275/40,901) compared with HPV testing alone. As a triage test to identify CIN3 or worse in HPV-positive women, detection of HPV16, HPV18, or both alone was equivalent to detection of ASC-US or worse alone in terms of sensitivity (150/252 [59·5%] vs 133/252 [52·8%]; p=0·11) and positive predictive value (PPV) (150/966 [15·5%] vs 133/940 [14·1%]; p=0·20). Among HPV-positive women, detection of HPV16, HPV18, or both or low-grade squamous intraepithelial lesion or worse cytology had better sensitivity (182/252 [72·2%]; p<0·0001) and similar PPV (182/1314 [13·9%]; p=0·70) for detection of CIN3 or worse than ASC-US or worse cytology alone. Furthermore, detection of HPV16, HPV18, or both or high-grade squamous intraepithelial lesion or worse cytology had higher sensitivity (165/252 [65·5%]; p=0·0011) and PPV (165/1013 [16·3%]; p=0·031) for detection of CIN3 or worse than ASC-US or worse cytology alone. HPV testing with separate HPV16 and HPV18 detection could provide an alternative, more sensitive, and efficient strategy for cervical cancer screening than do methods based solely on cytology. Roche Molecular Systems.


Enhancing Daily Affect in Youth Experiencing High-Conflict Parental Divorce: A Multiple Baseline Trial of an Online Prevention Program.
This study investigated the effects of a highly interactive, online cognitive-behavioral youth coping program: Children of Divorce-Coping with Divorce (CoD-CoD; Boring et al., 2015) on children exposed to high levels of interparental conflict (IPC). A multiple-baseline experimental design (N = 9) evaluated within-subject intervention effects on change in daily positive and negative affect before, during, and after the intervention (nobservations = 462). Participants were youth ages 11-16 who reported high exposure to IPC and whose parents had filed for divorce or parenting plan determinations in the prior year. A significant interaction effect indicated change in positive affect, but not negative affect, between the intervention and baseline phases. Positive affect linearly decreased during the baseline phase and flattened during the intervention phase. Results indicate that CoD-CoD was effective in interrupting a decline in youth-reported positive affect in a high-IPC sample, which may indicate a buffering effect against depression. Critical future directions include conducting large-scale randomized trials with children from high-IPC families to assess for whom the program is effective and assess long-term effects across a broad range of important outcomes.


Photocatalytic Oxidative Coupling of Ethane to n-Butane Using CO2 as a Soft Oxidant over NiTi-Layered Double Hydroxide.
Selective conversion of ethane (C2 H6 ) to high-value-added chemicals is a very important chemical process, yet it remains challenging owing to the difficulty of ethane activation. Here, a NiTi-layered double hydroxide (NiTi-LDH) photocatalyst is reported for oxidative coupling of ethane to n-butane (n-C4 H10 ) by using CO2 as an oxidant. Remarkably, the as-prepared NiTi-LDH exhibits a high selectivity for n-C4 H10 (92.35%) with a production rate of 62.06 µmol g-1 h-1 when the feed gas (CO2 /C2 H6 ) ratio is 2:8. The X-ray absorption fine structure (XAFS) and photoelectron characterizations demonstrate that NiTi-LDH possesses rich vacancies and high electron-hole separation efficiency, which can promote the coupling of C2 H6 to n-C4 H10 . More importantly, density functional theory (DFT) calculations reveal that ethane is first activated on the oxygen vacancies of the catalyst surface, and the C─C coupling pathway is more favorable than the C─H cleavage to C2 H4 or CH4 , resulting in the high production rate and selectivity for n-C4 H10 .


[Pilot study of The Child and Adolescent Health Survey: methodological aspects and procedure].
In the pilot study of the National Health Survey for Children and Adolescents which has been conducted under the responsibility of the Robert Koch Institute from March 12th 2001 to March 15th 2002, 1,630 children and adolescents from 0 to 17 years as well as their parents have been included. Methodological issues have been very prominent. Questionnaires regarding properties, indicators (for example for psychic well-being) were developed and evaluated, different methods of access to the study participants as well as methods to increase the motivation to participate in the study were tested, and the property for generalisation or validity of the obtained information was investigated. The conduct of the pilot study resulted in a number of experiences and findings that will contribute to an optimised approach in the main course of the survey.


2D crystallization of membrane proteins: rationales and examples.
The difficulty in crystallizing channel proteins in three dimensions limits the use of X-ray crystallography in solving their structures. In contrast, the amphiphilic character of integral membrane proteins promotes their integration into artificial lipid bilayers. Protein-protein interactions may lead to ordering of the proteins within the lipid bilayer into two-dimensional crystals that are amenable to structural studies by electron crystallography and atomic force microscopy. While reconstitution of membrane proteins with lipids is readily achieved, the mechanisms for crystal formation during or after reconstitution are not well understood. The nature of the detergent and lipid as well as pH and counter-ions is known to influence the crystal type and quality. Protein-protein interactions may also promote crystal stacking and aggregation of the sheet-like crystals, posing problems in data collection. Although highly promising, the number of well-studied examples is still too small to draw conclusions that would be applicable to any membrane protein of interest. Here we discuss parameters influencing the outcome of two-dimensional crystallization trials using prominent examples of channel protein crystals and highlight areas where further improvements to crystallization protocols can be made.


A survey of chronic kidney disease in a large hospital in China.
Chronic kidney disease (CKD) has emerged as a serious public health problem worldwide. How a CKD program should be organized, though, is still unknown. Therefore, we conducted a study to investigate the burden of CKD in a large university hospital and explore the possible approaches to care CKD appropriately in China. This is a retrospective cohort study of all new cases of CKD in a large hospital determined by a persistently increased serum creatinine (SCr) level (>1.47 mg/dL, >130 umol/L for more than three months) measured in the hospital laboratory. An abbreviate MDRD equation was used to estimate GFR from initial SCr values. There was a large CKD population in the hospital. In all, 1,006 cases had definite chronic kidney disease. Excepting the nephrology department, CKD patients were distributed in 18 disciplines and departments, with the focus on outpatient department and emergency department. In total, 1,257 cases were suspicious of CKD, who had only one or two tests of serum creatinine without detailed follow-up data. Furthermore, when SCr level is higher than 442 umol/L, there were 129 cases with only one test result. CKD is a great burden in the hospital. Multidiscipline cooperation based on outpatient, emergency department, and good follow-up system establishments are necessary for appropriate CKD care. Future work is needed to explore how to organize a good CKD management program to advance the care of patients with CKD.


[Study on spectroscopy of alpha, alpha'-dioxoketene cyclic s, s-acetals].
The rule of infrared spectroscopic characteristics of the five alpha, alpha'-dioxoketene cyclic s, s-acetals was studied, and the influence of the molecular structure on the IR was indicated. All 1H and 13C NMR chemical shifts of the five compounds were assigned, and the effects of structures on the chemical shifts of 1H and 13C NMR were discussed. The rule of change is the same as that of IR. The study offers a method of elicitation for studies on the structure and the spectroscopy of this kind of compounds.


Long-term immune recovery of patients undergoing allogeneic stem cell transplantation: a comparison with their respective sibling donors.
We have addressed whether patients' immune system status after allogeneic stem cell transplantation, assessed more than 1 year after the procedure, recovers normal function as compared with that of their respective donors. An additional aim was to compare the status of the immune system between patients receiving reduced-intensity conditioning regimens and those undergoing myeloablative transplantations. For this purpose, we analyzed not only the different subsets of peripheral blood (PB) lymphocytes, but also circulating dendritic cell (DC) subpopulations, together with cytokine production by PB T cells, in a series of 38 patients undergoing allogeneic stem cell transplantation. We compared these patients with their respective HLA-matched donors by performing a simultaneous patient/donor paired study. Complete bone marrow chimerism status and normal PB cell counts were demonstrated in all recipients. The most relevant numeric differences found between patients and donors were related to the distribution of the distinct subsets of PB DCs (CD16+ DCs were increased, whereas myeloid and plasmacytoid DC subsets were decreased in the patient group). This was associated with an increased number of B cells, an inverted CD4/CD8 T-cell ratio, and a decrease in CD4+/CD8+ double-positive T cells in the patient group. In addition, a predominance of a T-helper 1 pattern of cytokine production (interferon gamma and tumor necrosis factor alpha) with decreased secretion of T-helper 2-associated cytokines (interleukin 5 and interleukin 10) was also observed at the single-cell level. No significant differences were found in any of the parameters analyzed between patients receiving reduced-intensity conditioning regimens and those undergoing myeloablative transplantations.


Thermoluminescence Characteristics of Copper and Terbium Co-Doped Lithium Tetraborate Glass.
In this study, the preparation and characterization of copper (Cu) and terbium (Tb) co-doped lithium borate glass using spectroscopic and thermoluminescence techniques are reported. A thermal treatment was introduced to increase the degree of crystallinity. The thermoluminescence glow curve signal of the samples displayed upon exposure to beta radiation was measured and analyzed. It was found that the samples doped with 0.1% of copper and co-doped with 0.3% terbium showed the highest thermoluminescent (TL) signal in response to the irradiated dose. The analyses revealed that the glow curves of the doped samples were composed of nine overlapping glow peaks with activation energies between 0.73 and 2.78 eV. As a whole area under the glow curve, the TL signals displayed a linear dose response in the range from 110 mGy to 55 Gy. The minimum detectible dose of the samples was found to be 10.39 µGy. It was found that peaks 1 and 2 disappear after one day of storage. The rest of the peaks (3-9) remain almost constant up to 74 days of storage.


Combined treatment of myo-inositol and d-chiro-inositol (80:1) as a therapeutic approach to restore inositol eumetabolism in patients with bipolar disorder taking lithium and valproic acid.
Patients with bipolar disorder (BD) experience a poor quality of life (QoL) and a weak adherence to the therapy due to the various side effects occurring during the pharmacological therapy. To date clinicians have no tools to intervene on such effects, considering them as an unavoidable part of the therapy. This review paves the way for a step forward in the management of patients with BD bridging the therapeutic gap in clinical practice. We reviewed the literature, searching through different databases (MEDLINE, Scopus, Google Scholar). We used different keywords, including bipolar disorder, lithium and valproic acid, inositol role in bipolar disorder, side effects, inositol depletion, supplementation of inositols under lithium treatment, inositol role in metabolism, hypothyroidism, renal and cardiac functionality. In particular, we narrowed the search down to English literature, excluding works before 1980s. Regarding clinical studies, we included case reports and both preclinical and clinical studies, especially only those exhibiting a control group. The outcome of the database search was to highlight the threat of side effects and the relationship with inositol lower levels, paving the way for a step forward in the management of patients with BD. Based on the collected evidence, the combined administration of myo-inositol (myo-ins) and d-chiro-inositol (d-chiro-ins) is strongly recommended in order to restore levels and metabolism of inositols. Previous studies pointed out the beneficial effects of inositols in recovering pathological conditions, like polycystic ovary syndrome (PCOS), hypothyroidism, weight gain, cardiac functionality, being all these conditions related to the depletion of inositols. Furthermore, a controlled dosage of inositols, up to 6 grams/daily, may reduce the side effects caused by lithium therapy, without hindering its central therapeutic role on patients' mood. Considering the iatrogenic depletion of inositols, the tailored ratio 80:1 in favour of myo-ins, may become a safe and effective strategy to counteract side effects, by providing a large amount of myo-ins and an adequate one of d-chiro-ins. The clinical dosage of inositols used as dietary supplementation is 4 grams/daily, and it may allow the recovery of the side effects and improve patients' QoL, without reducing the central therapeutic effect of the pharmacological therapy.


Prevalence, Characteristics, and Associated Risk Factors of the Elderly with Hip Fractures: A Cross-Sectional Analysis of NHANES 2005-2010.
This cross-sectional study was aimed to update the assessment of prevalence, characteristics, and risk factors of the elderly with hip fractures in a non-institutionalized American population. This current study included a total of 31,034 participants from the existing National Health and Nutritional Examination Survey (NHANES) database from 2005 to 2010, and 4,265 participants aged 65 years and older were ultimately identified. Their condition of hip fractures was determined by method of questionnaires according to the orthopedic surgeons' diagnosis, and related epidemiological and demographic data were further collected. The univariate analysis was used to screen the risk factors of hip fractures in the elderly, and the logistic regression model was established to conduct the multivariate analysis. Of the total 4,265 participants with clear information of hip fractures in elderly, 127 individuals with hip fractures were identified according to results of questionnaires, exhibiting a prevalence of 28.49 per 1,000 (95% confidence interval [CI]=21.38-35.60) for males and 31.03 per 1,000 (95% CI=23.72-38.35) for females. The mean age of the elderly with hip fractures was 77.12±5.88 years and tumble (48.0%) was the primary factor. In univariate analysis, age, race, smoking, drinking alcohol, and combined with osteoporosis were regarded as risk factors. Multivariate analysis showed that age (80 years and older), living alone, smoking, combined with diabetes and osteoporosis were the independent risk factors. Our nationwide data indicate the prevalence of hip fractures in the elderly is generally on the rise, and the female occupies a higher proportion. Age (especially aged 80 years and older), race (mainly Non-Hispanic white), smoking, drinking alcohol, living alone, combined with diabetes and osteoporosis may be closely linked to the occurrence of hip fractures in the elderly, although these variables still need to be verified in further prospective investigations.


Mammalian wax biosynthesis. II. Expression cloning of wax synthase cDNAs encoding a member of the acyltransferase enzyme family.
Wax monoesters are synthesized by the esterification of fatty alcohols and fatty acids. A mammalian enzyme that catalyzes this reaction has not been isolated. We used expression cloning to identify cDNAs encoding a wax synthase in the mouse preputial gland. The wax synthase gene is located on the X chromosome and encodes a member of the acyltransferase family of enzymes that synthesize neutral lipids. Expression of wax synthase in cultured cells led to the formation of wax monoesters from straight chain saturated, unsaturated, and polyunsaturated fatty alcohols and acids. Polyisoprenols also were incorporated into wax monoesters by the enzyme. The wax synthase had little or no ability to synthesize cholesteryl esters, diacylglycerols, or triacylglycerols, whereas other acyltransferases, including the acyl-CoA:monoacylglycerol acyltransferase 1 and 2 enzymes and the acyl-CoA:diacylglycerol acyltransferase 1 and 2 enzymes, exhibited modest wax monoester synthesis activities. Confocal light microscopy indicated that the wax synthase was localized in membranes of the endoplasmic reticulum. Wax synthase mRNA was abundant in tissues rich in sebaceous glands such as the preputial gland and eyelid and was present at lower levels in other tissues. Coexpression of cDNAs specifying fatty acyl-CoA reductase 1 and wax synthase led to the synthesis of wax monoesters. The data suggest that wax monoester synthesis in mammals involves a two step biosynthetic pathway catalyzed by fatty acyl-CoA reductase and wax synthase enzymes.


Comparison of fast flow and initial slope index values for cerebral blood flow following subarachnoid haemorrhage.
Forty five patients with subarachnoid haemorrhage proved by lumbar puncture underwent serial measurements of cerebral blood flow and central conduction time. When the initial slope index (ISI) value for cerebral blood flow is considered there is a clear relationship between reduction of cerebral blood flow and deteriorating clinical grade. This relationship is not so clearly demonstrated using the fast flow (f1) value for cerebral blood flow. When cerebral blood flow is compared to central conduction time those patients with a central conduction time longer than 6 X 4 ms have a significantly lower CBFisi but not a significant lower CBFf1. Furthermore, using the ISI value, there is a linear relationship between the fall in cerebral blood flow and the lengthening of CCT below a threshold blood flow of about 35 ml/100 g/min. This relationship is not demonstrated with the CBFf1 value. It therefore appears that the ISI value for cerebral blood flow shows a greater correlation between clinical and electrophysiological events than the f1 value.


Multifrequency InSAR height reconstruction through maximum likelihood estimation of local planes parameters.
In this paper, a technique that is able to reconstruct highly sloped and discontinuous terrain height profiles, starting from multifrequency wrapped phase acquired by interferometric synthetic aperture radar (SAR) systems, is presented. We propose an innovative unwrapping method, based on a maximum likelihood estimation technique, which uses multifrequency independent phase data, obtained by filtering the interferometric SAR raw data pair through nonoverlapping band-pass filters, and approximating the unknown surface by means of local planes. Since the method does not exploit the phase gradient, it assures the uniqueness of the solution, even in the case of highly sloped or piecewise continuous elevation patterns with strong discontinuities.


Wnt-1 signal induces phosphorylation and degradation of c-Myb protein via TAK1, HIPK2, and NLK.
The c-myb proto-oncogene product (c-Myb) regulates both the proliferation and apoptosis of hematopoietic cells by inducing the transcription of a group of target genes. However, the biologically relevant molecular mechanisms that regulate c-Myb activity remain unclear. Here we report that c-Myb protein is phosphorylated and degraded by Wnt-1 signal via the pathway involving TAK1 (TGF-beta-activated kinase), HIPK2 (homeodomain-interacting protein kinase 2), and NLK (Nemo-like kinase). Wnt-1 signal causes the nuclear entry of TAK1, which then activates HIPK2 and the mitogen-activated protein (MAP) kinase-like kinase NLK. NLK binds directly to c-Myb together with HIPK2, which results in the phosphorylation of c-Myb at multiple sites, followed by its ubiquitination and proteasome-dependent degradation. Furthermore, overexpression of NLK in M1 cells abrogates the ability of c-Myb to maintain the undifferentiated state of these cells. The down-regulation of Myb by Wnt-1 signal may play an important role in a variety of developmental steps.


Tetraspanin CD81-regulated cell motility plays a critical role in intrahepatic metastasis of hepatocellular carcinoma.
Human hepatocellular carcinoma (HCC) can invade the portal vein and metastasize to other parts of the liver. Currently, the molecular and cellular mechanisms underlying intrahepatic metastasis of HCC are poorly understood. Tumor invasiveness could be considered an aspect of dysregulated motility, and the mechanisms that inhibit cell movement are considered to counteract the spreading of cancer cells through the liver. Accumulating observations suggest that the CD81 tetraspanin may have an inhibitory effect on cell movement. In the present study using both loss- and gain-of-gene function approaches, we verified that the functional interaction of tetraspanin CD81 with type II phosphoinositide 4-kinase (PI4KII) suppressed HCC cell motility by promoting the formation of CD81-enriched vesicles, non-endosomal intracellular structures, that sequestered actinin-4 with consequent remodeling of actin cytoskeleton. We reported that HCC cells expressing CD81 showed an inability to metastasize compared with HCC cells with undetectable levels of CD81. Taken together, these findings indicate that CD81 functions as a molecular organizer of membrane microdomains, whereby proteins such as PI4KII control actin remodeling and cell motility, establishing a role for these genes as negative modifiers of oncogenicity and HCC progression.


Motion compensation for ultrasound thermal imaging using motion-mapped reference model: an in vivo mouse study.
Ultrasound (US)-based thermal imaging is very sensitive to tissue motion, which is a major obstacle to apply US temperature monitoring to noninvasive thermal therapies of in vivo subjects. In this study, we aim to develop a motion compensation method for stable US thermal imaging in in vivo subjects. Based on the assumption that the major tissue motion is approximately periodic caused by respiration, we propose a motion compensation method for change in backscattered energy (CBE) with multiple reference frames. Among the reference frames, the most similar reference to the current frame is selected to subtract the respiratory-induced motions. Since exhaustive reference searching in all stored reference frames can impede real-time thermal imaging, we improve the reference searching by using a motion-mapped reference model. We tested our method in six tumor-bearing mice with high intensity focused ultrasound (HIFU) sonication in the tumor volume until the temperature had increased by 7°C. The proposed motion compensation was evaluated by root-mean-square-error (RMSE) analysis between the estimated temperature by CBE and the measured temperature by thermocouple. As a result, the mean ±SD RMSE in the heating range was 1.1±0.1°C with the proposed method, while the corresponding result without motion compensation was 4.3±2.6°C. In addition, with the idea of motion-mapped reference frame, total processing time to produce a frame of thermal image was reduced in comparison with the exhaustive reference searching, which enabled the motion-compensated thermal imaging in 15 frames per second with 150 reference frames under 50% HIFU duty ratio.


Gastrodin protects against MPP(+)-induced oxidative stress by up regulates heme oxygenase-1 expression through p38 MAPK/Nrf2 pathway in human dopaminergic cells.
Although the etiology of PD remains unclear, increasing evidence has shown that oxidative stress plays an important role in its pathogenesis and that of other neurodegenerative disorders. The phenolic glucoside gastrodin, a main constituent of a Chinese herbal medicine Gastrodia elata (GE) Blume, has been known to display antioxidant activity. The present study aimed to investigate the protective effects of gastrodin on 1-methyl-4-phenylpyridinium (MPP(+))-induced oxidative cytotoxicity in human dopaminergic SH-SY5Y cells and the underlying mechanism for this neuroprotection. Results indicate that pre-treatment with gastrodin for 1h significantly reduced the MPP(+)-induced viability loss, apoptotic rate and attenuated MPP(+)-mediated ROS production. In addition, gastrodin inhibited MPP(+)-induced lowered membrane potential, decreased Bcl-2/Bax ratio. Moreover, we have revealed the gastrodin increased Nrf2 nuclear translocation, which is upstream of heme oxygenase-1 (HO-1) expression and for the first time revealed gastrodin could increased antioxidant enzyme HO-1 expression in concentration-dependent and time-dependent manners. HO-1 siRNA transfection was employed, and confirmed gastrodin could active the expression of HO-1. And the increase in HO-1 expression was correlated with the protective effect of gastrodin against MPP(+)-induced injury. Because the inhibitor of HO-1 activity, ZnPP reversed the protective effect of gastrodin against MPP(+)-induced cell death. We also demonstrated that the specific p38 MAPK inhibitor, SB203580, concentration-dependently blocked on gastrodin-induced HO-1 expression, and meanwhile SB203580 reversed the protective effect of gastrodin against MPP(+)-induced cell death. Taken together, these findings suggest that gastrodin can induce HO-1 expression through activation of p38 MAPK/Nrf2 signaling pathway, thereby protecting the SH-SY5Y cells from MPP(+)-induced oxidative cell death. Thus our study indicates that gastrodin has a partial cytoprotective role in dopaminergic cell culture systems and could be of importance for the treatment of PD and other oxidative stress-related diseases.


Seasonal Monitoring of Volatiles and Antioxidant Activity of Brown Alga Cladostephus spongiosus.
Cladostephus spongiosus was harvested once a month during its growing season (from May to August) from the Adriatic Sea. Algal volatile organic compounds (VOCs) were obtained by headspace solid-phase microextraction (HS-SPME) and hydrodistillation (HD) and analysed by gas chromatography and mass spectrometry (GC-MS). The effects of air drying and growing season on VOCs were determined. Two different extraction methods (ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE)) were used to obtain ethanolic extracts of C. spongiosus. In addition, the seasonal antioxidant potential of the extracts was determined, and non-volatile compounds were identified from the most potent antioxidant extract. Aliphatic compounds (e.g., pentadecane) were predominantly found by HS-SPME/GC-MS. Hydrocarbons were more than twice as abundant in the dry samples (except in May). Aliphatic alcohols (e.g., hexan-1-ol, octan-1-ol, and oct-1-en-3-ol) were present in high percentages and were more abundant in the fresh samples. Hexanal, heptanal, nonanal, and tridecanal were also found. Aliphatic ketones (octan-3-one, 6-methylhept-5-en-2-one, and (E,Z)-octa-3,5-dien-2-one) were more abundant in the fresh samples. Benzene derivatives (e.g., benzyl alcohol and benzaldehyde) were dominant in the fresh samples from May and August. (E)-Verbenol and p-cymen-8-ol were the most abundant in dry samples in May. HD revealed aliphatic compounds (e.g., heptadecane, pentadecanal, (E)-heptadec-8-ene, (Z)-heptadec-3-ene), sesquiterpenes (germacrene D, epi-bicyclosesquiphellandrene, gleenol), diterpenes (phytol, pachydictyol A, (E)-geranyl geraniol, cembra-4,7,11,15-tetraen-3-ol), and others. Among them, terpenes were the most abundant (except for July). Seasonal variations in the antioxidant activity of the ethanolic extracts were evaluated via different assays. MAE extracts showed higher peroxyl radical inhibition activity from 55.1 to 74.2 µM TE (Trolox equivalents). The highest reducing activity (293.8 µM TE) was observed for the May sample. Therefore, the May MAE extract was analysed via high-performance liquid chromatography with high-resolution mass spectrometry and electrospray ionisation (UHPLC-ESI-HRMS). In total, 17 fatty acid derivatives, 9 pigments and derivatives, and 2 steroid derivatives were found. The highest content of pheophorbide a and fucoxanthin, as well as the presence of other pigment derivatives, could be related to the observed antioxidant activity.


An exploration of differences between Japan and two European countries in the self-reporting and valuation of pain and discomfort on the EQ-5D.
To investigate the systematic differences in the self-reporting and valuation of overall health and, in particular, pain/discomfort between three countries (England/UK, Japan, and Spain) on the EQ-5D. Existing datasets were used to explore differences in responses on the EQ-5D descriptive system between Japan (3L and 5L), the UK (3L), England (5L), and Spain (5L), particularly on the dimension of pain/discomfort. The role of different EQ dimensions in determining self-reported overall health scores for the EuroQol visual analog scale (EQ-VAS) was investigated using ordinary least squares regression. Time trade-off (TTO) results from Japanese and UK respondents for the EQ-5D-3L as well as Japanese and English respondents for the EQ-5D-5L were compared using t tests. For the EQ-5D-3L, a higher percentage of respondents in Japan than in the UK reported 'no pain/discomfort' (81.6 vs 67.0%, respectively); for the EQ-5D-5L, the proportions were 79.2% in Spain, 73.2% in Japan, and 63-64% in England, after adjusting for age differences in samples. The 'pain/discomfort' dimension had the largest impact on respondents' self-reported EQ-VAS only for EQ-5D-3L in Japan. Using the EQ-5D-3L, Japanese respondents were considerably less willing to trade off time to avoid pain/discomfort than the UK respondents; for example, moving from health state, 11121 (some problems with pain/discomfort) to 11131 (extreme pain/discomfort) represented a decrement of 0.65 on the observed TTO value in the UK compared with 0.15 in Japan. Using the EQ-5D-5L, Japanese respondents were also less willing to trade off time to avoid pain/discomfort than respondents in England; however, the difference in values was much smaller than that observed using EQ-5D-3L data. This study provides evidence of between-country differences in the self-reporting and valuation of health, including pain/discomfort, when using EQ-5D in general population samples. The results suggest a need for caution when comparing or aggregating EQ-5D self-reported data in multi-country studies.


Depression in informal caregivers of persons with dementia.
Worldwide, there are more than 35 million individuals diagnosed with Alzheimer's disease. Many of these individuals are cared for at home by unpaid caregivers who often report high levels of depressive symptoms and depression. The majority of studies conducted to predict which caregivers are at risk for depression have examined non-modifiable risk factors. Therefore, it is important to discover modifiable factors that may be associated with risk for depression in caregivers. The aims of this research were to identify a set of factors that are modifiable and known to be associated with high levels of depression/depressive symptomology (D/DS) in other populations and to determine whether these factors are predictive of D/DS after controlling for non-modifiable, demographic, and clinical factors. Secondary data analysis. Fifty-three participants provided direct care to a person with dementia with night-time activity. Inclusion criteria included not undergoing treatment for sleep disorders; living with the care recipient; and a Mini-Mental Status Exam score > 27. Baseline data collected by questionnaires, sleep diary and actigraphy. In multivariate analyses of the modifiable factors, only high levels of negative affect predicted higher levels of depressive symptomatology. When non-modifiable factors were included in the model, negative affect and high levels of perceived caregiver burden predicted 52.6% of the variance in depressive symptomology. In secondary analyses, wake after sleep onset misperception was associated with higher depression scores. While negative affect had a moderate effect on depressive symptoms, modifiable factors often associated with depressive symptoms in other studies were not associated with caregiver depression in this study. Possibly caregivers' overall poor sleep causes a floor effect and masks a potential relationship. Both caregivers' affect and perceived burden are strongly related to depressive symptoms, so healthcare practitioners need to frequently assess both so as to provide timely interventions.


Superoxide is a potential culprit of caspase-3 dependent endothelial cell death induced by lysophosphatidylcholine.
Oxidative stress in the vascular wall has intimately been implicated in the apoptosis of human umbilical vein endothelial cells (HUVECs) by lysophosphatidylcholine (LPC). However, the major type of reactive oxygen species (ROS) in this apoptotic signaling pathway remains to be clarified. In this study, we report that superoxide mediate LPC-induced caspase-3 dependent apoptosis in cultured HUVECs. The stimulation of HUVECs with LPC evoked apoptosis and ROS generation, and inhibited nitric oxide (NO) production in a dose-dependent manner. The classical caspase-3 dependent apoptosis was determined after 16 hours treatment by Western blotting using an antibody against cleaved caspase-3. The caspase-3 activation induced by LPC was prominently inhibited by antioxidants or NO donors and enhanced by NO inhibitors. Especially, LPC-induced caspase-3 activation was inhibited by superoxide dismutase (SOD) and enhanced by ammonium tetrathiomolybdate, SOD inhibitor. Additionally, xanthine/xanthine oxidase mixture increased the caspase-3 activation but catalase failed to reduce this superoxide-induced caspase-3 activation. These findings indicate that the superoxide generation caused by LPC activates the caspase-3 which results in HUVECs death. This study reveals some evidences linking superoxide with caspase-3 activation and provides a new dimension to superoxide-mediated caspase-3 activation in developing the endothelial dysfunction and atherosclerosis.


Aprotinin revisited: formulation, characterization, biodistribution and therapeutic potential of new aprotinin microemulsion in acute pancreatitis.
The aim of this study was to develop aprotinin-loaded microemulsion (MA) for intravenous administration and evaluate the biodistribution and therapeutic potential of developed formulation in acute pancreatitis models in rats. Phase diagrams were constructed to identify microemulsion region and the optimal microemulsion was evaluated for physicochemical properties and treatment effect in rats, and comparisons made with the solution of aprotinin (SA). To evaluate the biodistribution of the drug by gamma scintigraphy aprotinin was radiolabeled with (99m)Tc radionuclide. Mild and severe acute pancreatitis was induced in rats by subcutaneous injections of cerulein and introductal infusion of 3% sodium taurocholate into the bile-pancreatic duct, respectively. In addition, serum amylase and pancreatic tissue myeloperoxidase activities were measured to evaluate the pancreatic damage. According to gamma scintigraphy and biodistribution studies, accumulation times and distribution of (99m)Tc-MA and SA were different. While MA was highly uptake by reticuloendothelial system, SA was mostly excreted by kidneys and bladder. Compared with the mild acute pancreatitis group, treatment with MA significantly decreased the serum amylase activity and pancreas myeloperoxidase activity. Furthermore, the protease inhibitor molecule aprotinin has therapeutic potential in acute pancreatitis. Finally, MA may be suggested as a promising alternative for treatment of acute pancreatitis.


Perceptions of Tennessee cattle producers regarding the Veterinary Feed Directive.
Since January 1, 2017, the United States Food and Drug Administration (FDA) has fully implemented the Veterinary Feed Directive (VFD) final rule aimed at facilitating the judicious use of medically important antimicrobials in food-producing animals. The objective of this study was to identify the common perceptions of Tennessee (TN) cattle producers regarding the VFD. We used a combination of focus groups and survey questionnaires to explore TN cattle producers' perceptions regarding the VFD. Preliminary findings from seven focus groups of 62 producers were used in the development of the questionnaire sent both online and in-print to rest of cattle producers in TN. The beef focus group participants perceived the VFD: to be a top-down policy; to have led to unregulated access to in-feed antimicrobials; a regulation that has limited the producers' ability to prevent disease and leading to economic losses; to negatively affect small producers; and to be affected by challenges related to prescription writing and disposal of un-used medicines. The dairy focus group participants perceived the VFD as unnecessary and burdensome, to have affected small producers, and introduced additional costs. Among the survey questionnaire respondents, 35 (15.4%) beef producers and 6 (13.6%) dairy producers respectively were not familiar at all with the VFD. Forty-eight (21.1%) beef producers and 11 (25%) dairy producers were slightly familiar with VFD. Gender was significantly associated (P = 0.02) with the beef producers' belief in the usefulness of the VFD. Similarly, for dairy producers, herd size was significantly associated (P = 0.002) with their perceptions regarding the usefulness of the VFD. The findings of this study could inform future VFD policy review processes. More awareness regarding the VFD and its benefits is needed among both beef and dairy producers in TN.


Applying decision analysis to pharmacy management and practice decisions.
Decision analysis, a structured approach to decision making, is presented and applied to a typical management situation. Decision analysis is an explicit, quantitative, and prescriptive approach to choosing among alternative outcomes. It engenders in the decision maker an analytical viewpoint, the need to structure the various courses of action and the resultant consequences of the actions, to assess the degree of uncertainty of the actions occurring, and to value the preferences for the alternative outcomes. Literature examples of using pharmacy-related decision analysis are provided, including its use in formulary additions, cost-effectiveness analysis, drug therapy evaluation, therapeutic drug monitoring, and health policy issues.


Media Source Characteristics Regarding Food Fraud Misinformation According to the Health Information National Trends Survey (HINTS) in China: Comparative Study.
Ongoing rumors and fake news regarding food fraud, adulteration, and contamination are highly visible. Health risk information circulating through media and interpersonal communication channels has made health crisis an important research agenda. This study explored the issue of food fraud and the effect of misinformation. Further, it assessed whether and how these issues have provided evidence-based interventions for food handlers and regulators to mitigate fraud misinformation. The Health Information National Trends Survey (HINTS) was adopted for a collaborative study in China, after which a cross-sectional survey with door-to-door interviews was performed. Participants from Beijing and Hefei were selected using multistage sampling of adults in May 2017. Based on 4 government surveillance reports on food rumors and safety incidents, a descriptive analysis, correlation analysis, and analysis of variance were performed on the data. A total of 3090 results were gathered and analyzed. Among the respondents, 83.6% (2584/3090) heard at least one food rumor. Learning about food fraud was correlated with interpersonal connections (eg, doctors or health specialists) for accessing food health information. Overall, Chinese citizens with a higher level of interpersonal connection were more likely to be concerned about food incidents with a statistical difference (P<.001). Interpersonal connection was the most frequent communication source (698/1253, 55.7%), followed by traditional media (325/1253, 25.9%) and internet portals (144/1253, 11.5%). There was a significant relationship between media use and media category in Beijing (P<.001) and Hefei (P<.001). Overall, responses to food fraud and incident risks were lower in Beijing than in Hefei (P=.006). The respondents in Beijing were confronted more frequently by food rumors (range 346-1253) than those in Hefei (range 155-946). The urban dwellers in Beijing and their rural counterparts in Hefei also differed in terms of perceiving different levels of food risks from different media sources. The food rumor narratives that examined the conspiracy belief showed that social media played more important roles in influencing attitudes against misinformation for users in Hefei than in Beijing. This study shows that consumers have to be on guard against not only fake food, but also spreading fake information and rumors, as well as conspiracy beliefs involving fake food. This study focused on characterizing media sources, types of food fraud misinformation, and risk perceptions of food safety, which mix urgency and suspicion, and attempted to provide evidence-based interventions for risk management guidance, with the hypothesis of significant correlations between media types and sources, and consumer exposure and perception levels of food rumors and risks.


Stochastic modelling of Listeria monocytogenes single cell growth in cottage cheese with mesophilic lactic acid bacteria from aroma producing cultures.
A stochastic model was developed for simultaneous growth of low numbers of Listeria monocytogenes and populations of lactic acid bacteria from the aroma producing cultures applied in cottage cheese. During more than two years, different batches of cottage cheese with aroma culture were analysed for pH, lactic acid concentration and initial concentration of lactic acid bacteria. These data and bootstrap sampling were used to represent product variability in the stochastic model. Lag time data were estimated from observed growth data (lactic acid bacteria) and from literature on L. monocytogenes single cells. These lag time data were expressed as relative lag times and included in growth models. A stochastic model was developed from an existing deterministic growth model including the effect of five environmental factors and inter-bacterial interaction [Østergaard, N.B, Eklöw, A and Dalgaard, P. 2014. Modelling the effect of lactic acid bacteria from starter- and aroma culture on growth of Listeria monocytogenes in cottage cheese. International Journal of Food Microbiology. 188, 15-25]. Growth of L. monocytogenes single cells, using lag time distributions corresponding to three different stress levels, was simulated. The simulated growth was subsequently compared to growth of low concentrations (0.4-1.0 CFU/g) of L. monocytogenes in cottage cheese, exposed to similar stresses, and in general a good agreement was observed. In addition, growth simulations were performed using population relative lag time distributions for L. monocytogenes as reported in literature. Comparably good predictions were obtained as for the simulations performed using lag time data for individual cells of L. monocytogenes. Therefore, when lag time data for individual cells are not available, it was suggested that relative lag time distributions for L. monocytogenes can be used as a qualified default assumption when simulating growth of low concentrations of L. monocytogenes.


Influence of combined therapy with mevinolin and interruption of bile-acid reabsorption on low density lipoproteins in heterozygous familial hypercholesterolemia.
Patients with heterozygous familial hypercholesterolemia have a 50% deficiency of receptors for plasma low density lipoproteins (LDL) that induces a marked increase in plasma LDL levels. Two therapeutic measures that seem to increase the synthesis of LDL receptors are interruption of the enterohepatic circulation of bile acids with either bile-acid sequestrants or the ileal-exclusion operation, and competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase with mevinolin or compactin. To determine the effectiveness of this combination and the mechanisms of lowering LDL levels, we measured turnover rates of LDL apoprotein (apo-LDL) before and during treatment with mevinolin and colestipol in eight patients with heterozygous familial hypercholesterolemia. Drug therapy reduced LDL cholesterol levels by an average of 52%; this response was due to a 40% increase in fractional catabolic rate of apo-LDL and a 26% decrease in its production rate. A similar response was obtained in two patients who had previously had an ileal-exclusion operation for severe hypercholesterolemia and who were treated with mevinolin.


Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors.
Recent studies have investigated the risks associated with BRCA1 gene mutations using various functional assessment methods such as fluorescent reporter assays, embryonic stem cell viability assays, and therapeutic drug-based sensitivity assays. Although they have clarified a lot of BRCA1 variants, these assays involving the use of exogenously expressed BRCA1 variants are associated with overexpression issues and cannot be applied to post-transcriptional regulation. To resolve these limitations, we previously reported a method for functional analysis of BRCA1 variants via CRISPR-mediated cytosine base editor that induce targeted nucleotide substitution in living cells. Using this method, we identified variants whose functions remain ambiguous, including c.-97C>T, c.154C>T, c.3847C>T, c.5056C>T, and c.4986+5G>A, and confirmed that CRISPR-mediated base editors are useful tools for reclassifying the variants of uncertain significance in BRCA1. Here, we describe a protocol for functional analysis of BRCA1 variants using CRISPR-based cytosine base editor. This protocol provides guidelines for the selection of target sites, functional analysis and evaluation of BRCA1 variants.


Ensemble of Convolutional Neural Networks Improves Automated Segmentation of Acute Ischemic Lesions Using Multiparametric Diffusion-Weighted MRI.
Accurate automated infarct segmentation is needed for acute ischemic stroke studies relying on infarct volumes as an imaging phenotype or biomarker that require large numbers of subjects. This study investigated whether an ensemble of convolutional neural networks trained on multiparametric DWI maps outperforms single networks trained on solo DWI parametric maps. Convolutional neural networks were trained on combinations of DWI, ADC, and low b-value-weighted images from 116 subjects. The performances of the networks (measured by the Dice score, sensitivity, and precision) were compared with one another and with ensembles of 5 networks. To assess the generalizability of the approach, we applied the best-performing model to an independent Evaluation Cohort of 151 subjects. Agreement between manual and automated segmentations for identifying patients with large lesion volumes was calculated across multiple thresholds (21, 31, 51, and 70 cm3). An ensemble of convolutional neural networks trained on DWI, ADC, and low b-value-weighted images produced the most accurate acute infarct segmentation over individual networks (P < .001). Automated volumes correlated with manually measured volumes (Spearman ρ = 0.91, P < .001) for the independent cohort. For the task of identifying patients with large lesion volumes, agreement between manual outlines and automated outlines was high (Cohen κ, 0.86-0.90; P < .001). Acute infarcts are more accurately segmented using ensembles of convolutional neural networks trained with multiparametric maps than by using a single model trained with a solo map. Automated lesion segmentation has high agreement with manual techniques for identifying patients with large lesion volumes.


Highly Successful Hepatitis C Virus (HCV) Treatment Outcomes in Human Immunodeficiency Virus/HCV-Coinfected Patients at a Large, Urban, Ryan White Clinic.
The introduction of direct-acting antivirals (DAAs) created a major paradigm shift in the treatment of chronic hepatitis C. Currently, there is little "real-world" data regarding hepatitis C virus (HCV) treatment outcomes in the human immunodeficiency virus (HIV)/HCV-coinfected population. This retrospective cohort study examined HCV treatment outcomes of HIV/HCV-coinfected patients at a large, urban, Ryan White-funded clinic caring for an underserved population. All HIV patients initiating HCV treatment from January 1, 2013 to November 30, 2015 were included in the analysis. The primary end point was sustained virologic response 12 weeks after the end of therapy (SVR12). A total of 172 patients initiated HCV treatment within the study period: 79% were male, 83% were black, 95% were HCV genotype 1, 79% were HCV treatment naive, and 16% had cirrhosis. At baseline, median CD4 was 494 cells/μL (interquartile range, 316-722) and 92% had HIV ribonucleic acid less than 40 copies/mL. The most common DAA initiated was ledipasvir/sofosbuvir (LDV/SOF) (85%), with 92% receiving 12 weeks of treatment. Overall, SVR12 was 93% by intention-to-treat analysis and 98% by per-protocol analysis. The majority of patients on LDV/SOF did not report any adverse effect. One patient in the ribavirin plus SOF group discontinued treatment due to adverse effect. In a cohort of mainly black, male, HIV/HCV-coinfected patients at a large, urban, Ryan White clinic, HCV treatment with DAAs resulted in high SVR12 rates and was well tolerated despite real-world challenges including medication access barriers and drug interaction concerns.


Moyamoya disease.
Moyamoya disease is a rare cerebrovascular condition of uncertain aetiology commonly affecting young persons. The disease is mainly seen in Japanese patients. We report two cases of moyamoya disease in Caucasian women and review the postulated aetiological factors and associated conditions as well as the spectrum of invasive and non-invasive imaging modalities useful in the diagnosis and follow-up of the disease, with particular reference to the developing role of magnetic resonance imaging and angiography.


Prevalence and Impact of Hyponatremia in Patients With Coronavirus Disease 2019 in New York City.
Hyponatremia occurs in up to 30% of patients with pneumonia and is associated with increased morbidity and mortality. The prevalence of hyponatremia associated with coronavirus disease 2019 and the impact on outcome is unknown. We aimed to identify the prevalence, predictors, and impact on outcome of mild, moderate, and severe admission hyponatremia compared with normonatremia among coronavirus disease 2019 patients. Retrospective, multicenter, observational cohort study. Four New York City hospitals that are part of the same health network. Hospitalized, laboratory-confirmed adult coronavirus disease 2019 patients admitted between March 1, 2020, and May 13, 2020. None. Hyponatremia was categorized as mild (sodium: 130-134 mmol/L), moderate (sodium: 121-129 mmol/L), or severe (sodium: ≤ 120 mmol/L) versus normonatremia (135-145 mmol/L). The primary outcome was the association of increasing severity of hyponatremia and in-hospital mortality assessed using multivariable logistic regression analysis. Secondary outcomes included encephalopathy, acute renal failure, mechanical ventilation, and discharge home compared across sodium levels using Kruskal-Wallis and chi-square tests. In exploratory analysis, the association of sodium levels and interleukin-6 levels (which has been linked to nonosmotic release of vasopressin) was assessed. Among 4,645 patient encounters, hyponatremia (sodium < 135 mmol/L) occurred in 1,373 (30%) and 374 of 1,373 (27%) required invasive mechanical ventilation. Mild, moderate, and severe hyponatremia occurred in 1,032 (22%), 305 (7%), and 36 (1%) patients, respectively. Each level of worsening hyponatremia conferred 43% increased odds of in-hospital death after adjusting for age, gender, race, body mass index, past medical history, admission laboratory abnormalities, admission Sequential Organ Failure Assessment score, renal failure, encephalopathy, and mechanical ventilation (adjusted odds ratio, 1.43; 95% CI, 1.08-1.88; p = 0.012). Increasing severity of hyponatremia was associated with encephalopathy, mechanical ventilation, and decreased probability of discharge home (all p < 0.001). Higher interleukin-6 levels correlated with lower sodium levels (p = 0.017). Hyponatremia occurred in nearly a third of coronavirus disease 2019 patients, was an independent predictor of in-hospital mortality, and was associated with increased risk of encephalopathy and mechanical ventilation.


Age at menarche and the menstrual pattern of Igbo women of southeast Nigeria.
This study determines the age at menarche and menstrual pattern of an Igbo population in 12 randomly selected rural communities of Ebonyi State. Information on recalled ages at menarche, menstrual flow duration and cycle length was collected using a semi structured questionnaire over three months. 1209 women of reproductive age were interviewed. The mean age at menarche was 15.0 years and this declined over the years. The mean menstrual flow duration and cycle lengths were 3.3 days and 29.7 days respectively. Only 10.2% had a menstrual cycle length of 28 days. Account should be taken of the average length of 29-30 days in the rural Igbo population when calculating the expected date of delivery and in the family planning clinics.


Pyoderma gangrenosum: skin grafting after preparation with hyperbaric oxygen.
Four patients with pyoderma gangrenosum were treated with hyperbaric oxygen to prepare the wounds for skin grafting. Each wound responded to a course of daily hyperbaric oxygen with reduction of infection and increased capillary angiogenesis. During follow-up periods of 12 to 30 months, all wounds remained healed. Although the exact etiology of pyoderma gangrenosum is unknown, vasculitis with wound ischemia and infection are prominent components. Inspired oxygen partial pressures of 1100 to 1300 mmHg elevate wound oxygen tension despite relative ischemia. The impaired intracellular bacterial killing of hypoxic leukocytes is corrected during each day's 2-hour bolus of hyperbaric oxygen. Daily wound oxygenation increases collagen production by fibroblasts to support capillary angiogenesis.


Effects of dietary concentration of wet distillers grains on performance by newly received beef cattle, in vitro gas production and volatile fatty acid concentrations, and in vitro dry matter disappearance.
Three studies were designed to evaluate effects of wet distillers grains with solubles (WDGS) on health and performance of newly received beef cattle, in vitro gas production, molar proportions and total concentrations of VFA, and IVDMD. In Exp. 1 and 2, 219 (BW = 209 kg, SE = 2.2 kg; Exp. 1) and 200 beef steers (BW = 186 kg, SE = 3.2 kg; Exp. 2) were used in randomized complete block design receiving studies. The 4 dietary treatments (DM basis) were a 65% concentrate, steam-flaked corn (SFC)-based receiving diet without WDGS (CON) or diets that contained 12.5, 25.0, or 37.5% WDGS. There were no differences among the 4 receiving diets in BW (P ≥ 0.61), ADG (P ≥ 0.75), DMI (P ≥ 0.27), and G:F (P ≥ 0.35), or in the proportion of cattle treated for morbidity from bovine respiratory disease in either of the 2 experiments. In Exp. 3, in vitro methods were used to determine the effects of WDGS on IVDMD, total gas production, and molar proportions and total concentrations of VFA. Substrates used for the incubations contained the same major components as the diets used in Exp. 1, with ruminal fluid obtained from steers fed a 60% concentrate diet. Total gas production was less (P = 0.03) for the average of the 3 WDGS substrates than for CON, with a linear decrease (P = 0.01) in total gas production as WDGS concentration increased in the substrates. In contrast to gas production, IVDMD was greater for the average of the 3 WDGS concentrations vs. CON (P ≤ 0.05) at 6 and 12 h and increased (P ≤ 0.02) with increasing WDGS concentration at 6 (linear and quadratic) and 12 h (linear) of incubation. At 48 h, there was a quadratic effect (P = 0.05) on IVDMD, with the greatest value for 25% WDGS. Molar proportion of butyrate increased linearly (P < 0.01) as the concentration of WDGS increased in the substrate, and the average of the 3 substrates containing WDGS had a greater proportion of butyrate (P = 0.03) than CON. Performance data from Exp. 1 and 2 indicate that including WDGS in the SFC-based diets for newly received cattle can be an effective at concentrations up to 37.5% of the DM. In vivo measurements are needed to corroborate the in vitro fermentation changes noted with addition of WDGS.


Sample sizes for clinical trials using sputum eosinophils as a primary outcome.
Clinical trials do not report sputum eosinophil data in a consistent method and this makes it difficult to compare across studies and to evaluate the sample sizes estimated in these studies. The objectives of the paper are: 1) to systematically review reporting of effect size and sample calculations in randomised controlled trials using sputum eosinophil count as a primary outcome and 2) to illustrate sample size estimation under different methods of data representation using data from an effective anti-eosinophil treatment strategy (mepolizumab). Randomised controlled trials in adults (excluding allergen provocation models) of treatment of asthma and chronic obstructive pulmonary disease for the past 10 years were searched in Ovid MEDLINE and 20 studies were identified that met all the inclusion criteria. Only nine studies discussed sample size calculation. Change from baseline was used as an outcome in 11 studies and was expressed as change in absolute percentage count, percentage change from baseline or as fold changes. Assuming a minimal clinically important reduction of 15% in absolute terms, 18 subjects in each arm will be required to achieve 80% power using an ANCOVA analysis, which we recommend, to detect significance with an alpha error of 0.05.


The impact of lying about a traumatic virtual reality experience on memory.
The goal of the present experiment was to examine the effect of certain (deceptive) strategies (e.g., false denial) on memory. Specifically, participants were shown a traumatic virtual reality (VR) video of an airplane crash. Following this, participants (N= 94) received questions concerning details from the VR scene in a baseline memory task. Then, participants could choose from 3 options how to cope in response to having experienced the VR scene: tell the truth, falsely deny, or fabricate. The majority opted to tell the truth (n = 81). A subsample of truth tellers were instructed to falsely deny having seen certain details. One week later, all participants received a source monitoring task in which they were asked (1) whether they remembered talking about these details during an interview, and (2) whether they remembered seeing certain details during the VR experience the week before. Participants had to tell the truth during this task. Participants who were instructed to falsely deny showed impaired memory for presented details that had previously been discussed (i.e., denial-induced forgetting) and seen in the VR scene. Also, the presentation of certain details in the baseline memory task seemed to inoculate participants who were instructed to falsely deny from experiencing memory impairment. The current experiment suggests that false denials can have adverse ramifications for memory for what is discussed and seen.


Simulium dermatitis in man--clinical and biological features in South Africa. A case report.
Simulium bite reaction is described; the lesions were present mainly on the lower legs as palpable purpura, which persisted for 2 weeks with marked oedema and considerable discomfort. Simuliids are tiny bloodsucking flies, popularly known as blackflies or buffalo flies, belonging to the dipterous family Simuliidae. They occur world-wide, breed in fast-flowing streams, and are a major animal pest. This is the first description of blackfly bites in man in the South African literature.


Understanding pain and coping in women with interstitial cystitis/bladder pain syndrome.
To examine a self-regulation and coping model for interstitial cystitis/bladder pain syndrome (IC/BPS) that may help us understand the pain experience of patients with chronic IC/BPS. The model tested illness perceptions, illness-focused coping, emotional regulation, mental health and disability in a stepwise method using factor analysis and structural equation modelling. Step 1, explored the underlying constructs. Step 2, confirmed the measurement models to determine the structure/composition of the main constructs. Step 3, evaluated the model fit and specified pathways in the proposed IC/BPS self-regulation model. In all, 217 female patients with urologist diagnosed IC/BPS were recruited and diagnosed across tertiary care centres in North America. The data were collected through self-report questionnaires. An IC/BPS self-regulation model was supported. Physical disability was worsened by patient's negative perception of their illness, attempts to cope using illness-focused coping and poorer emotional regulation. Mental health was supported by perceptions that individuals could do something about their illness, using wellness-focused behavioural strategies and adaptive emotion regulation. The results clarify the complex and unique process of self-regulation in women with IC/BPS, implicating cognitive and coping targets, and highlighting emotional regulation. This knowledge should help clinicians understand and manage these patients' distress and disability.