Adjuvant intraperitoneal chemotherapy for the treatment of colorectal cancer at risk for peritoneal carcinomatosis: a systematic review.
The peritoneal surface is the second most common site of disease recurrence, after the liver, following definitive surgery for colorectal cancer. Adjuvant intraperitoneal (IP) chemotherapy delivered at time of surgical resection has the potential to delay or prevent future spread to the peritoneal surface and improve clinical outcome. The exact role of adjuvant IP chemotherapy in colorectal cancer, including its associated morbidity and mortality, is not well defined. Systematic review and pooled random effect analysis of comparative trials examining the addition of adjuvant IP chemotherapy compared to surgery alone in colorectal cancer. The primary outcome was overall survival, and the secondary outcomes were of post-operative morbidity and mortality. In nine colorectal cancer studies identified, seven were two-arm trials comparing adjuvant IP chemotherapy to surgery alone. Of these, four trials had outcome reporting and met criteria that allowed inclusion into a random effects model. Heterogeneity was measured by Cochran's Q-test (Q = 13.9; p = 0.01) and random effect models were utilised. Pooling eligible trials together revealed a 0.55 odds ratio of death associated with the administration of IP chemotherapy compared to surgery alone (CI = 0.31, 0.98; p = 0.04). Trials selecting patients at elevated risk for the development of peritoneal carcinomatosis by clinicopathological biomarkers for administration of adjuvant IP chemotherapy reported more favourable overall outcomes. There was no increase in mortalities or IP chemotherapy-related abdominal complication rates among patients undergoing IP chemotherapy (OR = 1.4; CI = 0.52, 3.8; p = 0.5). This systematic review supports the use of adjuvant IP chemotherapy in resectable colorectal cancer at risk for peritoneal spread. Future trials should seek to standardise inclusion criteria and IP chemotherapy modalities to better define the role of this treatment in patients with resectable colorectal cancer.


Urinary tract infection in women over the age of 65: is age alone a marker of complication?
We were interested to know if our older female patients with urinary tract infections (UTIs) might have differing pathogens or rates of Escherichia coli antibiotic sensitivity and if our physicians managed them in a manner similar or dissimilar to the care provided to younger patients with no complications. This was a secondary analysis from patients excluded from a previous retrospective study regarding uncomplicated UTIs. Twenty-six percent of total patients with UTIs were older than 65 and otherwise medically uncomplicated whereas 21% were older patients who did have complicating factors. E. coli was a pathogen in 81% of uncomplicated elders' and 54% of complicated elders' cultures. E. coli sensitivity rate to sulfamethoxazole-trimethoprim (SMX/TMP) in both groups was 86%. Physicians were significantly less likely to prescribe SMX/TMP for complicated older patients with complications than for young patients with an uncomplicated UTI (P = .017); there was a significant trend of physicians to be less likely to prescribe SMX/TMP with advancing age in a patient and complications across all 3 groups (P = .011). Antibiotics rarely needed to be changed after cultures. The presence of E. coli on culture in patients with a UTI changes based on medical complications, not age. Being medically complex did not result in reduced sensitivity of E. coli to SMX/TMP but was associated with increased rates of the presence of other pathogens. In our setting, treatment employed with SMX/TMP and without the use of culture and sensitivity may be effective for appropriately selected older women. Prospective studies are needed to determine the optimal approach to management.


Morning glory syndrome in children. Association with endocrine and central nervous system anomalies.
To identify morning glory syndrome, an uncommon optic disc anomaly. Generally, it is an isolated ocular abnormality; however, some cranial facial and neurologic associations have been reported. We herein report two patients with morning glory syndrome and associated pituitary dwarfism. In one patient, the pituitary insufficiency was secondary to compression of the pituitary gland by a basal encephalocele; in the second patient, causative factors were not identified. Patients with morning glory syndrome should have a complete general physical examination and growth evaluation so that early recognition and treatment of the patient with pituitary dwarfism can occur.


[Displacement and resection of the ascending colon in the horse: a literature review on the basis of 2 cases].
A review of displacements and surgery of the large colon is given on the basis of two cases. A four-year-old Dutch Warmblood mare was referred, one week before foaling, for colic of twelve hours duration. At rectal palpation a large uterus was found, but no cause for the colic. Laparotomy revealed a colonic volvulus and resection of about 75% of the large colon was necessary. A dead foal was born five days postoperatively, but the mare recovered well. A nine year-old Dutch Warmblood stallion with a history of frequent colic had been treated for nephrosplenic entrapment three times. Resection of the left part of the colon was performed successfully to prevent another entrapment.


Systematic review and meta-analysis of randomized controlled trials for the management of limited vertical height in the posterior region: short implants (5 to 8 mm) vs longer implants (> 8 mm) in vertically augmented sites.
The aim of this study was to undertake a systematic review with meta-analysis on randomized controlled trials (RCTs) to compare the rates of survival, success, and complications of short implants to those of longer implants in the posterior regions. Electronic literature searches were conducted through the MEDLINE (PubMed) and EMBASE databases to locate all relevant articles published between January 1, 1990, and April 30, 2013. Eligible studies were selected based on inclusion criteria, and quality assessments were conducted. After data extraction, meta-analyses were performed. In total, 539 dental implants (265 short implants [length 5 to 8 mm] and 274 control implants [length > 8 mm]) from four RCTs were included. The fixed prostheses of multiple short and control implants were all splinted. The mean follow-up period was 2.1 years. The 1-year and 5-year cumulative survival rates (CSR) were 98.7% (95% confidence interval [CI], 97.8% to 99.5%) and 93.6% (95% CI, 89.8% to 97.5%), respectively, for the short implant group and 98.0% (95% CI, 96.9% to 99.1%) and 90.3% (95% CI, 85.2% to 95.4%), respectively, for the control implant group. The CSRs of the two groups did not demonstrate a statistically significant difference. There were also no statistically significant differences in success rates, failure rates, or complications between the two groups. Placement of short dental implants could be a predictable alternative to longer implants to reduce surgical complications and patient morbidity in situations where vertical augmentation procedures are needed. However, only four studies with potential risk of bias were selected in this meta-analysis. Within the limitations of this meta-analysis, these results should be confirmed with robust methodology and RCTs with longer follow-up duration.


Sorption of palladium(II), rhodium(III), and platinum(IV) on Fe(3)O(4) nanoparticles.
The adsorption of palladium(II), rhodium(III), and platinum(IV) from diluted hydrochloric acid solutions onto Fe(3)O(4) nanoparticles has been investigated. The parameters studied include the contact time and the concentrations of metals and other solutes such as H(+) and chloride. The equilibrium time was reached in less than 20 min for all metals. The maximum loading capacity of Fe(3)O(4) nanoparticles for Pd(II), Rh(III), and Pt(IV) was determined to be 0.103, 0.149, and 0.068 mmol g(-1), respectively. A sorption mechanism for Pd(II), Rh(III), and Pt(IV) has been proposed and their conditional adsorption equilibrium constants have been determined to be logK=1.72, 1.69, and 1.84, respectively. Different compositions of eluting solution were tested for the recovery of Pt(IV), Pd(II), and Rh(III) from Fe(3)O(4) nanoparticles. It was found that 0.5 mol L(-1) HNO(3) can elute all of the metal ions simultaneously, while 1 mol L(-1) NaHSO(3) was an effective eluting solution for Rh(III), and 0.5 mol L(-1) NaClO(4) for Pt(IV). In competitive adsorption, the nanoparticles showed stronger affinity for Rh(III) than for Pd(II) and Pt(IV).


Nerve growth factor protects the ischemic heart via attenuation of the endoplasmic reticulum stress induced apoptosis by activation of phosphatidylinositol 3-kinase.
Increased expression of nerve growth factor (NGF) has been found in the myocardium suffered from ischemia and reperfusion (I/R). The pro-survival activity of NGF on ischemic heart has been supposed to be mediated by phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Endoplasmic reticulum (ER) stress, which is activated initially as a defensive response to eliminate the accumulated unfolded proteins, has shown a critical involvement in the ischemia induced myocardial apoptosis. This study was aimed to investigate whether NGF induced heart protection against I/R injury includes a mechanism of attenuation of ER stress-induced myocardial apoptosis by activation of PI3K/Akt pathway. Isolated adult rat hearts were perfused with a Langendörff perfusion system. Hearts in the Sham group were subjected to 225 min of continuous Krebs-Henseleit buffer (KHB) perfusion without ischemia. Hearts in I/R group were perfused with KHB for a 75-min of equilibration period followed by 30 min of global ischemia and 120 min of KHB reperfusion. Hearts in the NGF group accepted 45 min of euilibration perfusion and 30 min of NGF pretreatment (with a final concentration of 100 ng/ml in the KHB) before 30 min of global ischemia and 120 min of reperfusion. Hearts in K252a and LY294002 groups were pretreated with either a TrkA inhibitor, K252a or a phosphatidyl inositol 3-kinase inhibitor, LY294002 for 30 min before NGF (100 ng/ml) administration. Cardiac hemodynamics were measured from the beginning of the perfusion. Cardiac enzymes and cardiac troponin I (cTnI) were assayed before ischemia and at the end of reperfusion. Myocardial apoptosis rate was measured by TUNEL staining, and expression of glucose-related protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, total- and phospho-(Ser473)-Akt were assessed by Western blot analyses. NGF pretreatment significantly improved the recovery of post-ischemia cardiac hemodynamics. Reduced creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) activity and cTnI levels, as well as decreased myocardial apoptosis ratio were observed in the NGF group. The improvement of NGF on recovery of cardiac function and alleviation of myocardial injury were completely abolished by K252a or LY294002. GRP78, caspase-12 and CHOP were highly expressed in ischemic myocardium, while NGF significantly inhibited the overexpression of these proteins which were involved in ER stress-induced myocardial apoptosis. NGF pretreatment also induced phosphorylation of Akt. When the activation of PI3K/Akt pathway is blocked by LY294002, the NGF induced suppression of the apoptosis-related proteins expression was reversed. NGF pretreatment may protect the ischemic heart via inhibition of the ER stress-induced apoptosis; this pro-survival effect is mediated by PI3K/Akt pathway.


Physicians' view of primary care-based case management for patients with heart failure: a qualitative study.
As part of a trial aiming to improve care for patients with chronic (systolic) heart failure, a standardized, multifaceted case management approach was evaluated in German general practices. It consisted of regular telephone monitoring, home visits, health counselling, diagnostic screening and booklets for patients. Practice-based doctors' assistants (equivalent to a nursing role) adopted these new tasks and reported regularly to the employing general practitioner (GP). To explore GPs' perceptions of case management, subsequent changes in relationships within the practice team and the potential future role. Twenty-four GPs participated in five moderated, semi-structured, audio-taped focus groups. Full transcription and thematic content analysis was undertaken. GPs rated all elements and instruments of case management conducted by doctors' assistants feasible, except for the geriatric assessment as patients had not been at risk. GPs perceived difficulties in their own role in delivering health behaviour counselling. Relationships between doctors' assistants and patients and between GPs and patients or doctors' assistants remained stable or improved. All GPs perceived a variety of role changes in doctors' assistants including more in-depth medical knowledge and higher responsibilities yielding more recognition by patients and GPs. Some GPs suggested transferring the case management programme to other chronic conditions and that it should form part of a further education curriculum for doctors' assistants. This primary care-based case management model characterized by the orchestrated delegation of tasks to doctors' assistants offers a promising strategy of enhanced chronic illness care, but it needs further adaptation and evaluation.


Bone disease in alcohol abuse.
We evaluated bone disease in eight white men between the ages of 49 and 61 years who had been abusing alcohol for at least 10 years. The mean density of vertebral cancellous bone was 58% of normal, whereas the mean density of appendicular cortical bone was 90% of normal. Marked reduction in active bone resorption and bone formation was seen without evidence of osteomalacia. Serum levels of calcium and magnesium were in the lower range of normal; serum levels of phosphorus, calcifediol, and calcitriol were normal; and serum levels of parathyroid hormone and nephrogenous cyclic adenosine monophosphate were in the higher range of normal. These data suggest that bone disease in these subjects is not due to inhibition of parathyroid hormone secretion or function, or abnormal vitamin D metabolism, but to an inhibition of bone remodeling by a mechanism independent of the calciotropic hormones.


Predicting Alcohol Pre-Drinking in Australian Undergraduate Students Using an Integrated Theoretical Model.
The aim of the present study was to examine the social-cognitive and motivational factors associated with pre-drinking based on a model integrating motivational constructs from self-determination theory and belief-based constructs from the theory of planned behaviour. A prospective correlational design was used. Participants (N = 286; 66.4% female) completed self-report measures of past alcohol consumption, autonomous and controlled forms of motivation from self-determination theory, and attitudes, subjective norms, perceived behavioural control, and behavioural intentions from the theory of planned behaviour at baseline. Participants reported pre-drinking frequency four weeks later. Variance-based structural equation modelling showed that the hypothesised model predicted 54 per cent of the variance in pre-drinking intentions at baseline, and 20 per cent of the variance in pre-drinking behaviour at follow-up. Mediation analyses indicated strong, statistically significant effects of autonomous motivation on intentions to pre-drink, partially mediated by attitudes and subjective norms. Intention and perceived behavioural control significantly predicted pre-drinking frequency. Results provide support for the hypothesised model relationships. Autonomous motivation, attitude, subjective norm, and perceived behavioural control were influential in forming students' intentions to pre-drink. However, consistent with previous findings, the intention-behaviour relationship was relatively weak. Future research should look to non-intentional and volitional processes that may influence pre-drinking in undergraduates.


HLA-DRB1*04:05 allele is associated with intracortical lesions on three-dimensional double inversion recovery images in Japanese patients with multiple sclerosis.
Cortical lesions (CLs) frequently observed in Caucasian patients with multiple sclerosis (MS) contribute to disability. However, it remains unclear whether CLs are associated with clinical features and genetic risk factors, such as HLA-DRB1*15:01 and -DRB1*04:05 in Asian MS patients. To elucidate the frequency of CLs and their association with HLA-DRB1 and DPB1 alleles in Japanese MS patients. Three-dimensional double inversion recovery imaging and clinical information were retrospectively obtained from 92 Japanese MS patients. CLs of any type, intracortical lesions (ICLs), and leukocortical lesions (LCLs) were detected in 39.1%, 26.1%, and 28.3% of patients, respectively. MS patients with ICLs had a significantly higher frequency of secondary progression and greater Expanded Disability Status Scale (EDSS) scores than those without ICLs. Similar trends were observed with CLs and LCLs. The number of all three lesion types positively correlated with EDSS scores. The frequency and number of ICLs were significantly higher in HLA-DRB1*15:01 carriers than in HLA-DRB1*15:01 non-carriers, but significantly lower in HLA-DRB1*04:05 carriers than in HLA-DRB1*04:05 non-carriers. Multivariate logistic regression analysis revealed a negative association of HLA-DRB1*04:05 with ICLs. ICLs are associated with greater disease severity in Japanese MS patients and are partly suppressed by the HLA-DRB1*04:05 allele.


Incidence of lung cancer and air pollution in boroughs of Chile: an ecological study.
Lung cancer frequency has been progressively increasing; this has been linked to the use of inhaled tobacco and air pollution. In Chile, air pollution has reached alarming levels due to motor vehicle traffic, firewood burning for heating and minerals in urban areas; for this reason, our objective was to evaluate the association between the incidence of lung cancer and the concentration of the main air pollutants monitored in the country. We carried out a cross-sectional ecological study that evaluated the association between the average incidence of lung cancer in a 5-year period (2015-2019) with the average annual concentration of six atmospheric pollutants in the 5 years prior in 14 Chilean boroughs, using the population of beneficiaries of the Fundación Arturo-López-Pérez Cancer Institute. The annualised incidence of lung cancer was 9.77 per 100,000 and it varied significantly within the boroughs studied. When evaluating the relationship between lung-cancer incidence and the average concentration of atmospheric pollutants, we only found a direct and significant correlation between the level of respirable particulates 2.5 and the incidence of adenocarcinomas (β: 0.16; p: 0.023).


Vasomodulation of tumor blood flow: effect on perfusion and thermal ablation size.
Blood flow is a key factor in the efficacy of radiofrequency (RF) ablation treatment of solid tumors. We hypothesized that vasoactive drugs can modulate tumor blood flow and thereby improve the outcome of this thermal ablation approach. To verify this hypothesis, we measured the tumor perfusion changes in response to phenylephrine (PE) and hydralazine (HYZ) using a CT perfusion method in a rat subcutaneous tumor model. The coagulation sizes induced by RF ablation alone, RF ablation with PE and RF ablation with HYZ were compared. Results demonstrated that HYZ produced a marked decrease in entire tumor and tumor rim blood flow of 31.1 and 29.1%; while PE insignificantly change tumor blood flow (5.1% decrease in whole tumor and 6.0% decrease in tumor rim). A markedly greater coagulation area (0.59 cm2 +/- 0.24) was observed when HYZ was administered before RF ablation. No difference was noted in the coagulation area induced by RF ablation alone or the combination of PE injection followed by RF ablation (0.29 cm2 +/- 0.13 vs. 0.30 cm2 +/- 0.18). Results suggest that HYZ decreases subcutaneous tumor blood flow and enhances the coagulation size induced by RF ablation. PE has little influence on tumor blood flow and does not improve ablation.


Unique Contributors to the Curriculum: From Research to Practice for Speech-Language Pathologists in Schools.
This lead article of the Clinical Forum focuses on the research that supports why speech-language pathologists (SLPs) are an integral part of the overarching curriculum for all students in schools. Focus on education has shifted to student performance in our global world, specifically in college and career readiness standards. This article reviews recommendations on best practice from the American Speech-Language-Hearing Association on SLPs' roles in schools, as well as data on school-based services. Implementation of these practices as it is applicable to school initiatives will be explored. Methods of interventions available in schools, from general education to special education, will be discussed based on national guidelines for a Response to Intervention and Multi-Tiered System of Support. Research regarding teacher knowledge of the linguistic principles of reading instruction will be explored, as well as correlation between teacher knowledge and student performance. The implications for how SLPs as the linguistic experts offer unique roles in curriculum and the evidence available to support this role will be explored. Implications for future research needs will be discussed. The demands of a highly rigorous curriculum allow SLPs a unique opportunity to apply their knowledge in linguistic principles to increase student performance and achievement. With the increased focus on student achievement, growth outcome measures, and value-added incentives, it is critical that SLPs become contributors to the curriculum for all students and that data to support this role are gathered through focused research initiatives.


Preparing medical students for the world: service learning and global health justice.
In this article, we discuss the growth of international service learning in undergraduate medical education and tie it to a burgeoning interest among students and educators in global health justice. The process of experience, reflection, and action is the cornerstone of cultivating a sense of social justice among students. Finally, we examine both risks and benefits to international service learning for medical students. We define "service learning," distinguish it from service and volunteerism, and offer praxis as a manifestation of professionalism.


Changes in segmentation and setation along the anterior/posterior axis of the homonomous trunk limbs of a remipede (Crustacea, Arthropoda).
This study describes the segmentation and setation at different developmental stages of the homonomous trunk limbs of the remipede Speleonectes tulumensis Yager, 1987 collected in anchialine caves of the Yucatan Peninsula. Most homonomous trunk limbs originate ventrolaterally and are composed of two protopodal segments, three exopodal segments and four endopodal segments; contralateral limb pairs are united by a sternal bar. However, the last few posterior limbs originate ventrally, are smaller sized, and have regressively fewer segments, suggesting that limb development passes through several intermediate steps beginning with a limb bud. A terminal stage of development is proposed for specimens on which the posterior somite bears a simple bilobate limb bud, and the adjacent somite bears a limb with a protopod comprised of a coxapod and basipod, and with three exopodal and four endopodal segments. On each trunk limb there are 20 serially homologous groups of setae, and the numbers of setae on different limbs usually varies. These groups of setae are arranged linearly and are identified based on the morphology of the setae and their position on the segments. The number of setae in these groups increases gradually from the anterior homonomous limb to a maximum between limbs 8-12; the number then decreases sharply on the more posterior limbs. Changes in the number of setae, which reach a maximum between trunk limbs 8-12, differ from changes in segmentation which vary only over the last few posterior trunk limbs. Following a vector analysis that identified a spatial pattern for these 20 groups of setae among the different homonomous limbs, the hypothesis was confirmed that the number of setae in any given group and any given limb is correlated with the group, with the position of the somite along the body axis, and with the number of somites present on the specimens. This is the first vector analysis used to analyze a pattern of developmental changes in serially homologs of an arthropod. Development of remipede limbs are compared and contrasted with similar copepod limbs. Architecture, particularly the sternal bar uniting contralateral limb pairs, proposed as homologous, and development of trunk limb segmentation of the remipede is generally similar to that of copepods, but the remipede limb differs in several ways including an additional endopodal segment, the proximal, that appears simultaneously with the protopod during development.


Linking supportive leadership to satisfaction with care: proposing and testing a service-profit chain inspired model in the context of elderly care.
As marketization has gained ground in elderly care, satisfaction with care has come to play a crucial role in designing for high-quality care. Inspired by the service-profit chain (SPC) model, the authors aimed to gain a deeper understanding of the intricate interplay between supportive leadership practices, organizational climate, job satisfaction and service quality by predicting satisfaction with care. A Swedish sample of frontline elderly care staff (n = 1,342) participated in a cross-sectional questionnaire study. Mediation analyses were conducted to test the proposed model. As predicted, engaging in supportive leadership practices was directly and positively associated with satisfaction with care. In addition, as predicted, this relationship was partially mediated by organizational climate and job satisfaction. Moreover, job satisfaction predicted satisfaction with care with service quality explaining a statistically significant part of this relationship. Managers in elderly care services may improve satisfaction with care in multiple ways but primarily by showing that they care about the staff and ensuring that they are satisfied with their working conditions. Employee job satisfaction seems to be particularly crucial for satisfaction with care, beyond what can be accounted for by care service quality. The authors proposed a novel service-outcome model. Adding to the original SPC model, the model in this study suggested and validated previously unexplored relationships including a direct path between leadership practices and satisfaction with service and a multiple-mediator model explaining this relationship. Also, new measures of organizational climate and supportive leadership were developed for which satisfactory reliability estimates were obtained.


Chiral Plasma Pharmacokinetics and Urinary Excretion of Bupropion and Metabolites in Healthy Volunteers.
Bupropion, widely used as an antidepressant and smoking cessation aid, undergoes complex metabolism to yield numerous metabolites with unique disposition, effect, and drug-drug interactions (DDIs) in humans. The stereoselective plasma and urinary pharmacokinetics of bupropion and its metabolites were evaluated to understand their potential contributions to bupropion effects. Healthy human volunteers (n = 15) were administered a single oral dose of racemic bupropion (100 mg), which was followed by collection of plasma and urine samples and determination of bupropion and metabolite concentrations using novel liquid chromatography-tandem mass spectrometry assays. Time-dependent, elimination rate-limited, stereoselective pharmacokinetics were observed for all bupropion metabolites. Area under the plasma concentration-time curve from zero to infinity ratios were on average approximately 65, 6, 6, and 4 and Cmax ratios were approximately 35, 6, 3, and 0.5 for (2R,3R)-/(2S,3S)-hydroxybupropion, R-/S-bupropion, (1S,2R)-/(1R,2S)-erythrohydrobupropion, and (1R,2R)-/(1S,2S)-threohydrobupropion, respectively. The R-/S-bupropion and (1R,2R)-/(1S,2S)-threohydrobupropion ratios are likely indicative of higher presystemic metabolism of S- versus R-bupropion by carbonyl reductases. Interestingly, the apparent renal clearance of (2S,3S)-hydroxybupropion was almost 10-fold higher than that of (2R,3R)-hydroxybupropion. The prediction of steady-state pharmacokinetics demonstrated differential stereospecific accumulation [partial area under the plasma concentration-time curve after the final simulated bupropion dose (300-312 hours) from 185 to 37,447 nM⋅h] and elimination [terminal half-life of approximately 7-46 hours] of bupropion metabolites, which may explain observed stereoselective differences in bupropion effect and DDI risk with CYP2D6 at steady state. Further elucidation of bupropion and metabolite disposition suggests that bupropion is not a reliable in vivo marker of CYP2B6 activity. In summary, to our knowledge, this is the first comprehensive report to provide novel insight into mechanisms underlying bupropion disposition by detailing the stereoselective pharmacokinetics of individual bupropion metabolites, which will enhance clinical understanding of bupropion's effects and DDIs with CYP2D6.


Apicoectomy of Perforated Root Canal Using Bioceramic Cement and Photodynamic Therapy.
Root perforation is a common endodontic accident. Its management depends mainly on root canal disinfection and sealing the perforation area by preventing any communication with the periodontium to prevent recontamination. A patient was referred to treat root perforation due to a previous treatment of tooth #22. The diagnosis was symptomatic periapical periodontitis, and the treatment plan was to retreat the root canal of #22 and make a surgical intervention (apicoectomy) associated with antimicrobial photodynamic therapy as a complementary technique. Five mineral oxides (5MO) cement was used as a root-end filling material. The procedures were performed in two sessions and controlled in two visits (after 30 days and 12 months). A bone neoformation was observed at the periapical area of tooth #22. 5MO bioceramic cement was effective in inducing the repair of the periapical lesion and had the ability to seal the exposed periapical area of the tooth. Its success depended mainly on root canal and surgical site disinfection.


Lysosomal localization of the neuronal ceroid lipofuscinosis CLN5 protein.
The Finnish variant late infantile neuronal ceroid lipofuscinosis (vLINCL) belongs to the neuronal ceroid lipofuscinosis group of common recessively inherited neurodegenerative disorders. The CLN 5 gene responsible for this brain disorder codes for a novel protein with no homology to previously reported proteins. In this study, we have investigated the biosynthesis and intracellular localization of this protein in transiently transfected BHK-21 cells using a CLN5-specific peptide antibody. Confocal immunofluorescence microscopy showed that wild-type CLN5 is predominantly targeted to lysosomes and immunoprecipitation analysis recognized a 60 kDa polypeptide. The molecular weight of this protein was reduced to 40 kDa by deglycosylation with Endo H and to 38 kDa with PNGase F. The same-sized glycosylated polypeptides were also observed in the media, suggesting that the 60 kDa glycosylated CLN5 polypeptide represents a soluble lysosomal glycoprotein, not an integral transmembrane protein as predicted earlier. The most common human vLINCL mutation blocked the lysosomal targeting of expressed polypeptides. This would imply that the pathogenesis of vLINCL would be associated with the defective lysosomal trafficking, preventing the normal biological function of the corresponding polypeptide.


[Advances in molecular nutrition: nutrigenomics and/or nutrigenetics].
The application of molecular biology techniques and the success of the Human Genome Project have opened a new era for both Medicine and Nutrition. To date, at least 1,000 human genes causing disease have been identified and partially characterized, 97% of which we now know that are the cause of monogenic diseases. However, other diseases such as obesity, cardiovascular disease, diabetes, and cancer are due to complex interactions between several genes and environmental factors. In spite of the many association studies, over 600 published since 2002, the molecular base of chronic diseases is still uncertain. Information about nucleotide polymorphisms and haplotypes maps is an additional resource for identifying genes implicated in diseases. Genomic development gets close, however we frequently do not accurately know the dietary components and their mechanisms that importantly influence on genetic information expression and its pathologic impairments. The food industry has the opportunity for utilizing the bioactive components of foods to improve health and prevent diseases while considering the consumers' genetic constitution. This new era of molecular nutrition--gene-nutrient interactions--may evolve in several ways, although two of them are essential. On the one hand, the study of the influence of nutrients on gene expression (nutrigenomics) and, on the other hand, to know the influence of genetic variations in the organism response to nutrients (nutrigenetics).


Influence of body fatness distribution and total lean mass on aortic stiffness in nonobese individuals.
Subjects with normal body mass index but high body fat percentage have higher cardiovascular risk than subjects with normal weight and low fat mass. However, the association of fat distribution and lean mass with carotid-femoral pulse wave velocity (cfPWV) among nonobese apparently healthy individuals has never been assessed. In 136 nonobese volunteers (mean age = 45±9 years; 57% women) without manifest cardiovascular disease, cfPWV was measured by applanation tonometry. Fat and lean mass were measured by dual-energy x-ray absorptiometry. In univariate analysis, total fat (r = 0.17; P < 0.01), trunk fat (r = 0.27; P < 0.01), and trunk/total fat ratio (r = 0.32; P < 0.01) were correlated with cfPWV. After adjustment for age and mean arterial pressure, only central fat distribution (trunk/total fat ratio) was significantly associated with cfPWV. In the fully adjustment model, there was a significant interaction between fat distribution and lean mass. When the study sample was grouped by fat distribution and total lean mass medians, subjects with central fat distribution and low lean mass (group 4) had higher log-transformed cfPWV than the noncentral fat/low lean mass group (group 2) (0.89, 95% confidence interval (CI) = 0.86-0.92 vs. 0.85, 95% CI = 0.83-0.87; P < 0.01) or the noncentral fat/high lean mass group (group 1) (0.89, 95% CI = 0.86-0.92 vs. 0.84, 95% CI = 0.81-0.87; P < 0.01) after adjustments. Aortic stiffness increased from group 1 to group 4 (P for linear trend < 0.001). Among normal weight individuals without manifest cardiovascular disease, the combination of central fat distribution and low lean mass is associated with higher cfPWV. These factors are more closely related to cfPWV than total fat mass.


Binocular Alignment Changes Between Sitting and Supine Positions in Patients with Dizziness.
Vertical and torsional ocular misalignment can occur from mild traumatic brain injury or inner ear pathology, which may vary depending on head position. Here, we evaluate differences in a behavioral measure of binocular alignment in both upright and supine head position. Ocular perception of vertical and torsional alignment was measured using the torsional and vertical alignment nulling (TAN, VAN) task in N = 52 veterans with dizziness (N = 38 with traumatic brain injury), N = 41 civilians with vestibular schwannoma resection (UVD), and N = 33 healthy controls for both positions. The interquartile range within each group, regardless of head position, was greater for torsional compared to vertical misalignment. We use generalized estimating equations to compare average TAN (torsional) scores and VAN (vertical) scores between groups and test position. Compared to the healthy controls, TAN was significantly increased by + 0.4186° in veterans (P = 0.030) and by + 0.5747° in UVD (P = 0.010), but there was no difference with head position. For VAN, no difference was found between the three groups, but the misalignment did worsen by 0.0888° (P = 0.0070) as the head position moved from upright to supine. Head position had negligible effects on this behavioral measure of vertical and torsional binocular misalignment, and torsional misalignments were worse than controls in both veterans with dizziness and patients with vestibular nerve resection although neither reported torsional diplopia. Our data suggests that the tolerance for roll misalignment may be abnormally large in patients with dizziness. Alternatively, perceptual roll misalignments may be a manifest cause for dizziness, and therefore a useful proxy for distinguishing differences in putative otolith function in veterans with dizziness.


Radiofrequency ablation zones in ex vivo bovine and in vivo porcine livers: comparison of the use of internally cooled electrodes and internally cooled wet electrodes.
This experimental study was undertaken to compare radiofrequency (RF) ablation zones created by internally cooled (IC) and internally cooled wet (ICW) electrodes. IC and ICW electrodes with a 2-cm exposed active tip were used to induce 30 ablation zones in 10 explanted bovine livers with a 12-min ablation time, respectively. In addition, two kinds of electrodes produced 16 ablation zones in five living porcine livers, respectively. In explanted bovine livers using IC and ICW electrodes, the mean long-axis diameter, short-axis diameter, volume, and variable coefficient of long-axis diameters of the ablation zones were 3.01 cm, 2.62 cm, 11.08 cm3, 10%, 5.28 cm, 5.07 cm, 73.48 cm3, and 14%, respectively. In living porcine livers using IC and ICW electrodes, the corresponding values were 2.62 cm, 2.00 cm, 5.76 cm3, 15%, 3.84 cm, 2.89 cm, 18.50 cm3, and 25%, respectively. In both ex vivo and in vivo livers, long-axis diameters, short-axis diameters, volumes, and variable coefficients for the use of ICW electrodes were significantly greater than for the use of IC electrodes (each p<0.05). ICW electrodes produced significantly larger ablation zones than IC electrodes in both ex vivo and in vivo livers, but the ablation zones induced by IC electrodes were more reproducible.


Fast hierarchical Bayesian analysis of population structure.
We present fastbaps, a fast solution to the genetic clustering problem. Fastbaps rapidly identifies an approximate fit to a Dirichlet process mixture model (DPM) for clustering multilocus genotype data. Our efficient model-based clustering approach is able to cluster datasets 10-100 times larger than the existing model-based methods, which we demonstrate by analyzing an alignment of over 110 000 sequences of HIV-1 pol genes. We also provide a method for rapidly partitioning an existing hierarchy in order to maximize the DPM model marginal likelihood, allowing us to split phylogenetic trees into clades and subclades using a population genomic model. Extensive tests on simulated data as well as a diverse set of real bacterial and viral datasets show that fastbaps provides comparable or improved solutions to previous model-based methods, while being significantly faster. The method is made freely available under an open source MIT licence as an easy to use R package at https://github.com/gtonkinhill/fastbaps.


Rapid solid-phase extraction/derivatization system for sample preparation and gas chromatographic/mass spectrometric determination of drugs in human urine.
A novel automatic system has been developed for the rapid solid-extraction and derivatization of different drugs and their metabolites from urine, prior to further analysis. Manual injection of underivatized/derivatized drugs in a GC/MS system, in which the quadrupole mass filter was operated conventionally, provided high sensitivity and selectivity at the selected m/z value. The precision (2.1-6.8%) is acceptable and the overall recovery from urine was determined to be ca. 95%. The effectiveness of this approach is demonstrated with data obtained from different urine samples which had tested positively.


Population structure and virulence gene profiles of Streptococcus agalactiae collected from different hosts worldwide.
Streptococcus agalactiae is a leading cause of morbidity and mortality among neonates and causes severe infections in pregnant women and nonpregnant predisposed adults, in addition to various animal species worldwide. Still, information on the population structure of S. agalactiae and the geographical distribution of different clones is limited. Further data are urgently needed to identify particularly successful clones and obtain insights into possible routes of transmission within one host species and across species borders. We aimed to determine the population structure and virulence gene profiles of S. agalactiae strains from a diverse set of sources and geographical origins. To this end, 373 S. agalactiae isolates obtained from humans and animals from five different continents were typed by DNA microarray profiling. A total of 242 different S. agalactiae strains were identified and further analyzed. Particularly successful clonal lineages, hybridization patterns, and strains were identified that were spread across different continents and/or were present in more than one host species. In particular, several strains were detected in both humans and cattle, and several canine strains were also detected in samples from human, bovine, and porcine hosts. The findings of our study suggest that although S. agalactiae is well adapted to various hosts including humans, cattle, dogs, rodents, and fish, interspecies transmission is possible and occurs between humans and cows, dogs, and rabbits. The virulence and resistance gene profiles presented enable new insights into interspecies transmission and make a crucial contribution to the identification of suitable targets for therapeutic agents and vaccines.


Bioinformatic and enzymatic characterization of the MAPEG superfamily.
The membrane associated proteins in eicosanoid and glutathione metabolism (MAPEG) superfamily includes structurally related membrane proteins with diverse functions of widespread origin. A total of 136 proteins belonging to the MAPEG superfamily were found in database and genome screenings. The members were found in prokaryotes and eukaryotes, but not in any archaeal organism. Multiple sequence alignments and calculations of evolutionary trees revealed a clear subdivision of the eukaryotic MAPEG members, corresponding to the six families of microsomal glutathione transferases (MGST) 1, 2 and 3, leukotriene C4 synthase (LTC4), 5-lipoxygenase activating protein (FLAP), and prostaglandin E synthase. Prokaryotes contain at least two distinct potential ancestral subfamilies, of which one is unique, whereas the other most closely resembles enzymes that belong to the MGST2/FLAP/LTC4 synthase families. The insect members are most similar to MGST1/prostaglandin E synthase. With the new data available, we observe that fish enzymes are present in all six families, showing an early origin for MAPEG family differentiation. Thus, the evolutionary origins and relationships of the MAPEG superfamily can be defined, including distinct sequence patterns characteristic for each of the subfamilies. We have further investigated and functionally characterized representative gene products from Escherichia coli, Synechocystis sp., Arabidopsis thaliana and Drosophila melanogaster, and the fish liver enzyme, purified from pike (Esox lucius). Protein overexpression and enzyme activity analysis demonstrated that all proteins catalyzed the conjugation of 1-chloro-2,4-dinitrobenzene with reduced glutathione. The E. coli protein displayed glutathione transferase activity of 0.11 micromol.min(-1).mg(-1) in the membrane fraction from bacteria overexpressing the protein. Partial purification of the Synechocystis sp. protein yielded an enzyme of the expected molecular mass and an N-terminal amino acid sequence that was at least 50% pure, with a specific activity towards 1-chloro-2,4-dinitrobenzene of 11 micromol.min(-1).mg(-1). Yeast microsomes expressing the Arabidopsis enzyme showed an activity of 0.02 micromol.min(-1).mg(-1), whereas the Drosophila enzyme expressed in E. coli was highly active at 3.6 micromol.min(-1).mg(-1). The purified pike enzyme is the most active MGST described so far with a specific activity of 285 micromol.min(-1).mg(-1). Drosophila and pike enzymes also displayed glutathione peroxidase activity towards cumene hydroperoxide (0.4 and 2.2 micromol.min(-1).mg(-1), respectively). Glutathione transferase activity can thus be regarded as a common denominator for a majority of MAPEG members throughout the kingdoms of life whereas glutathione peroxidase activity occurs in representatives from the MGST1, 2 and 3 and PGES subfamilies.


Emotion regulation mediates the relationship between ACES and physical and mental health.
Adverse Childhood Experiences (ACEs) have consistently been associated with a range of negative psychological and physical outcomes in adulthood. Despite the strength of this association, no studies to date have investigated psychological processes that might underlie this relationship. The current study evaluated emotion regulation as a potential mediator between ACEs and three outcomes: PTSD symptoms, depression and poor physical health, all of which are frequently co-occurring among women with ACEs. Mediational analyses were conducted with baseline data from a sample of 290 women enrolled in a clinical trial for PTSD. Emotion regulation was assessed with the Difficulties in Emotional Regulation Scale (DERS), PTSD with the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), depression with the Brief Symptom Inventory Depression subscale (BSI-D) and physical health with a shortened version of Medical Outcomes Study Short Form (SF-8). Emotion regulation significantly mediated the relationship between ACEs and all three outcomes. The estimates of the standardized indirect effects of ACEs on the health outcomes as mediated through DERS scores were as follows: PTSD β = 0.1, p < .001; depression β = 0.16, p < .001; physical health β = 0.07, p = .002. Interventions that focus on improving emotion regulation skills might provide an efficient "transdiagnostic" treatment strategy for both psychological and physical health problems. The study successfully tested a mediational model that identified a common pathway influencing both mental and physical health symptoms. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Leishmania chagasi: genotypically similar parasites from Honduras cause both visceral and cutaneous leishmaniasis in humans.
In the Mediterranean region Leishmania infantum causes both visceral and cutaneous leishmaniasis. These two pathologies tend to be caused by distinct parasite zymodemes. We have studied 33 isolates of Leishmania, 2 from sandflies, 5 from visceral cases, and 26 from cutaneous cases in Honduras, to determine if there is a correlation between pathology and parasite type in the New World similar to that in the Mediterranean region. Nine of the 26 cutaneous cases were caused by L. mexicana parasites, which have not been previously reported from Honduras; the remaining 17 cutaneous cases were due to L. chagasi. Only minor differences were found between the Honduran L. chagasi parasites by random amplified polymorphic DNA, differential display, pulsed-field gel electrophoresis, and schizodemes. This suggests that in Honduras the parasite type may not be the only factor determining the clinical outcome of L. chagasi infections.


Vector competence of sterile male Glossina fuscipes fuscipes for Trypanosoma brucei brucei: implications for the implementation of the sterile insect technique in a sleeping sickness focus in Chad.
Human African trypanosomiasis (HAT) is a neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by tsetse flies in sub-Saharan West Africa. In southern Chad the most active and persistent focus is the Mandoul focus, with 98% of the reported human cases, and where African animal trypanosomosis (AAT) is also present. Recently, a control project to eliminate tsetse flies (Glossina fuscipes fuscipes) in this focus using the sterile insect technique (SIT) was initiated. However, the release of large numbers of sterile males of G. f. fuscipes might result in a potential temporary increase in transmission of trypanosomes since male tsetse flies are also able to transmit the parasite. The objective of this work was therefore to experimentally assess the vector competence of sterile males treated with isometamidium for Trypanosoma brucei brucei. An experimental infection was set up in the laboratory, mimicking field conditions: the same tsetse species that is present in Mandoul was used. A T. b. brucei strain close to T. b. gambiense was used, and the ability of the sterile male tsetse flies fed on blood with and without a trypanocide to acquire and transmit trypanosomes was measured. Only 2% of the experimentally infected flies developed an immature infection (midgut) while none of the flies developed a metacyclic infection of T. b. brucei in the salivary glands. We did not observe any effect of the trypanocide used (isometamidium chloride at 100 mg/l) on the development of infection in the flies. Our results indicate that sterile males of the tested strain of G. f. fuscipes were unable to cyclically transmit T. b. brucei and might even be refractory to the infection. The data of the research indicate that the risk of cyclical transmission of T. brucei by sterile male G. f. fuscipes of the strain colonized at IAEA for almost 40 years appears to be small.


Bridging molecular simulation models and elastic theories for amphiphilic membranes.
The Single Chain Mean Field theory is used to link coarse-grained models of amphiphilic molecules with analytical models for membrane elasticity, where phenomenological parameters are deduced from explicit molecular models and force fields. We estimate the elastic constants based on the free energy of the amphiphilic bilayer in planar and cylindrical geometries on the example of four amphiphilic molecules that differ in length and stiffness. We study how these variations affect the equilibrium bilayer structure, the equilibrium free energy, and the elastic constants. Bending rigidities are obtained within the typical range of experimental values for phospholipid membranes in a liquid state.


Household food insecurity, coping strategies, and nutritional status of pregnant women in rural areas of Northern Ghana.
There is limited information on the magnitude and determinants of household food insecurity (HFI) and how it relates to the nutritional status of pregnant women in Northern Ghana. The magnitude, determinants of HFI, and how it relates to the nutritional status of pregnant women were evaluated in the Africa RISING West Africa project intervention communities in Northern Ghana. The prevalence of moderate and severe household hunger was 25.9% (95% CI: 19.0, 34.3) and 6.8% (95% CI: 4.2, 10.9) respectively. The independent predictors of maternal thinness were region of residence, gestational age and maternal age. Compared to women in the first trimester, women in the third trimester were 2.2 times more likely of being underweight adjusted odds ratio (AOR = 2.19, CI: 1.02, 4.70). Women who were under 20 years of age were 11.9 times more likely of being thin compared to women aged more than 35 years (AOR = 11.97, CI: 2.55, 5. 67). Food insecurity was highly prevalent but it was not associated with maternal thinness of pregnant women. The risk of maternal thinness increased as the gestational age increased and this has a great potential of adversely influencing pregnancy outcomes and overall quality of life.


Anti-HIV potency of T-cell responses elicited by dendritic cell therapeutic vaccination.
Identification and characterization of CD8+ and CD4+ T-cell epitopes elicited by HIV therapeutic vaccination is key for elucidating the nature of protective cellular responses and mechanism of the immune evasion of HIV. Here, we report the characterization of HIV-specific T-cell responses in cART (combination antiretroviral therapy) treated HIV-1 infected patients after vaccination with ex vivo-generated IFNα Dendritic Cells (DCs) loaded with LIPO-5 (HIV-1 Nef 66-97, Nef 116-145, Gag 17-35, Gag 253-284 and Pol 325-355 lipopeptides). Vaccination induced and/or expanded HIV-specific CD8+ T cells producing IFNγ, perforin, granzyme A and granzyme B, and also CD4+ T cells secreting IFNγ, IL-2 and IL-13. These responses were directed against dominant and subdominant epitopes representing all vaccine regions; Gag, Pol and Nef. Interestingly, IL-2 and IL-13 produced by CD4+ T cells were negatively correlated with the peak of viral replication following analytic treatment interruption (ATI). Epitope mapping confirmed that vaccination elicited responses against predicted T-cell epitopes, but also allowed to identify a set of 8 new HIV-1 HLA-DR-restricted CD4+ T-cell epitopes. These results may help to better design future DC therapeutic vaccines and underscore the role of vaccine-elicited CD4+ T-cell responses to achieve control of HIV replication.


Effect of ouabain on tone, membrane potential and sodium efflux compared with [3H]ouabain binding in rat resistance vessels.
To investigate the mechanism by which ouabain causes acute increase in peripheral resistance, the effect of ouabain on vessel tone, 22Na efflux and membrane potential has been compared with the binding of [3H]ouabain in rat isolated mesenteric resistance vessels (lumen diameter approximately 200 microns). Ouabain at concentrations between 1 X 10(-8) and 1 X 10(-3) M had no effect on the tone of resting vessels but caused potentiation of the tone of vessels which were submaximally contracted with noradrenaline. In the entire concentration range, these acute potentiating effects of ouabain on vessel tone correlated well with an acute inhibitory effect on 22Na efflux and with acute [3H]ouabain binding, consistent with the vasoconstrictor effect of ouabain being associated with inhibition of the Na-K pump. At all concentrations, in both resting and activated vessels, ouabain exposure caused an acute concentration-dependent depolarization of the membrane. At low ouabain concentrations (1 X 10(-6) and 1 X 10(-5) M) the potentiating effect on vessel tone and the inhibitory effect on 22Na efflux were transient, so that after 10 min no effect of ouabain was seen. This was consistent with these ouabain concentrations failing to cause a measurable increase in the intracellular Na concentration ([Na]i) after longer term (up to 2 h) exposure. The recovery of 22Na efflux was due to a recovery of the ouabain-sensitive part of the 22Na efflux, suggesting that the transitory nature of these effects is due to stimulation of uninhibited Na-K pumps. The transient effects of low ouabain concentrations contrasted with binding experiments where, with 1 X 10(-6) M-ouabain, the binding first peaked after 30 min with only a small decline thereafter. With higher concentrations of ouabain (1 X 10(-4) and 1 X 10(-3) M), the potentiating effect was also transitory, but 22Na efflux was permanently inhibited and the [Na]i rose. The possibility of there being two populations of ouabain binding sites having different affinities, was supported by the observation of shoulders in the ouabain concentration-effect characteristics obtained with respect to the mechanical potentiation of noradrenaline responses, the 22Na efflux and the acute ouabain binding. In all cases a shoulder was seen between 1 X 10(-6) and 1 X 10(-5) M-ouabain. The results are consistent with the vasoconstrictor effect of ouabain being due to depolarization of the membrane as a consequence of inhibition of the Na-K pump.


Reducing Time to Discovery: Materials and Molecular Modeling, Imaging, Informatics, and Integration.
Multiscale and multimodal imaging of material structures and properties provides solid ground on which materials theory and design can flourish. Recently, KAIST announced 10 flagship research fields, which include KAIST Materials Revolution: Materials and Molecular Modeling, Imaging, Informatics and Integration (M3I3). The M3I3 initiative aims to reduce the time for the discovery, design and development of materials based on elucidating multiscale processing-structure-property relationship and materials hierarchy, which are to be quantified and understood through a combination of machine learning and scientific insights. In this review, we begin by introducing recent progress on related initiatives around the globe, such as the Materials Genome Initiative (U.S.), Materials Informatics (U.S.), the Materials Project (U.S.), the Open Quantum Materials Database (U.S.), Materials Research by Information Integration Initiative (Japan), Novel Materials Discovery (E.U.), the NOMAD repository (E.U.), Materials Scientific Data Sharing Network (China), Vom Materials Zur Innovation (Germany), and Creative Materials Discovery (Korea), and discuss the role of multiscale materials and molecular imaging combined with machine learning in realizing the vision of M3I3. Specifically, microscopies using photons, electrons, and physical probes will be revisited with a focus on the multiscale structural hierarchy, as well as structure-property relationships. Additionally, data mining from the literature combined with machine learning will be shown to be more efficient in finding the future direction of materials structures with improved properties than the classical approach. Examples of materials for applications in energy and information will be reviewed and discussed. A case study on the development of a Ni-Co-Mn cathode materials illustrates M3I3's approach to creating libraries of multiscale structure-property-processing relationships. We end with a future outlook toward recent developments in the field of M3I3.


Reconsidering a science of psychology built on laws.
At one time, psychologists aspired to build a science composed of interrelated descriptive laws and the theories that explain them--a nomothetic science. For various reasons this goal was abandoned. In its place, we have a collection of theories that, for the most part, are organized by topic and subdiscipline or by themes and shared language (e.g., characterization of cognition in terms of information processing, which is neither a law nor a rigorous theory but a viewpoint or approach). As things stand, although our theories and research are scientific, we have failed to create a coherent science. In this article the nomothetic goal is reconsidered, and an example of how we might begin to achieve it is described.


Alveolar epithelium transport of albumin and sucrose: concentration difference effect.
Isolated Ringer-perfused rabbit lungs were used to study albumin and sucrose transport across the blood-gas barrier. Lungs were filled to about 20% total lung capacity (TLC) ith Ringer solution containing radioactive albumin and sucrose, and their rate of appearance in the recirculating perfusate was monitored. From this the product permeability x area (PA) was calculated. In the middle of the 180-min experiments, some alveolar fluid was removed. In control experiments, the same fluid was reinstilled, in other experiments new fluid with higher test molecule concentrations was infused. In all experiments the results for both molecules were similar: PA for the second half of the experiment was 80% of that in the first half. The reduction was probably due to a decrease in exchange area. We thus find the albumin and sucrose permeabilities to be proportional to their concentration difference. In addition, the PA for sucrose was roughly four times that of albumin. These results can possibly be explained by a two-compartment model with two parallel pathways across the alveolar epithelium. One pathway would be small pores, whereas the other would involve a bulk flow or pinocytosis process.


Thioridazine dose-related effects on biomechanical force platform measures of sway in young and old men.
Thioridazine (TDZ) is associated with an increased risk of falls. The purpose of this study was to determine whether (1) thioridazine increases Biomechanics Force Platform (BFP) measures of sway in a dose-related manner, (2) there is a difference in sway between young and old men, (3) there is a correlation between sway and orthostatic changes in BP and HR. Seven younger (aged 20-42) and five older (aged 70-76) healthy male volunteers received, in a randomized order double-blind design, a single oral dose of 0, 25, and 50 mg of TDZ on three separate days at least 7 days apart and 75 mg on the fourth day of the study. Sway and blood pressure were measured for 24 hours. A general clinical research center. Biomechanics force platform measures of postural sway were measured as the movement of the center of pressure. The elliptical area (EA) and average velocity (AV) were calculated with eyes open and eyes closed. Blood pressure and heart rate were measured for 5 minutes supine and 5 minutes standing. Thioridazine increases BFP sway in a dose-dependent manner. EA increased from 0.56 (SD = .51) cm2 for placebo to 0.88 (SD = 1.09) cm2 for 75 mg TDZ. AV increased from 1.07 (SD = .27) cm/sec, placebo, to 1.43 (SD = .55) cm/sec, 75 mg TDZ. Older men swayed more than younger men. Changes followed the expected time course for TDZ. EA and AV were associated with HR and BP, e.g., SBP versus ln(EA) and ln(AV) (r = -0.21 and r = -0.22, respectively; P < .0001). Thioridazine increases validated measures of fall risk dose dependently in young and old men. This may explain the effects of neuroleptic drugs on fall risk in older people.


Heats of Formation of Medium-Sized Organic Compounds from Contemporary Electronic Structure Methods.
Computational electronic structure calculations are routinely undertaken to predict thermodynamic properties of various species. However, the application of highly accurate wave function theory methods, such as the "gold standard" coupled cluster approach including single, double, and partly triple excitations in perturbative fashion, CCSD(T), to large molecules is limited due to high computational cost. In this work, the promising domain based local pair natural orbital coupled cluster approach, DLPNO-CCSD(T), has been tested to reproduce 113 accurate formation enthalpies of medium-sized molecules (few dozens heavy atoms) important for bio- and combustion chemistry via the reaction based Feller-Peterson-Dixon approach. For comparison, eight density functional theory (B3LYP, B3LYP-D3, PBE0, PBE0-D3, M06, M06-2X, ωB97X-D3, and ωB97M-V) and MP2-based (B2PLYP-D3, PWPB95-D3, B2T-PLYP, B2T-PLYP-D, B2GP-PLYP, DSD-PBEP86-D3, SCS-MP2, and OO-SCS-MP2) methods have been tested. The worst performance has been obtained for the standard hybrid DFT functionals, PBE0 (mean unsigned error (MUE)/mean signed error (MSE) = 9.1/6.0 kcal/mol) and B3LYP (MUE/MSE = 13.5/-13.3 kcal/mol). The influence of an empirical dispersion correction term on these functionals' performance is not homogeneous: B3LYP performance is improved (B3LYP-D3 (MUE/MSE = 6.0/0.8 kcal/mol)); meanwhile PBE0 performance is worse (PBE0-D3 (MUE/MSE = 14.1/13.6 kcal/mol)). The Minnesota functionals, M06 (MUE/MSE = 3.8/-2.0 kcal/mol) and M06-2X (MUE/MSE = 3.5/3.0 kcal/mol), and recently developed ωB97X-D3 (MUE/MSE = 3.2/0.2 kcal/mol) and ωB97M-V (MUE/MSE = 2.2/1.3 kcal/mol) methods provided significantly better formation enthalpies. Enthalpies of similar quality can also be obtained from some double hybrid methods (B2PLYP-D3 (MUE/MSE = 4.7/2.0 kcal/mol), PWPB95-D3 (MUE/MSE = 4.3/3.2 kcal/mol), B2T-PLYP (MUE/MSE = 4.1/-3.0 kcal/mol), and B2T-PLYP-D (MUE/MSE = 3.3/1.7 kcal/mol)). The two spin component scaled (SCS) MP2 methods resulted in even smaller errors (SCS-MP2 (MUE/MSE = 1.9/1.2 kcal/mol) and OO-SCS-MP2 (MUE/MSE = 1.6/0.1 kcal/mol)). The best performance was found for the frozen core (FC) DLPNO-CCSD(T) method with a MUE/MSE of 1.6/-1.2 kcal/mol. The performance of the DLPNO-CCSD(T) method can be further improved by running the post-SCF calculations on the B3LYP orbitals: the MUE/MSE for the DLPNO-CCSD(T,B3LYP) approximation is 1.2/-0.4 kcal/mol. We recommend the DLPNO-CCSD(T,B3LYP) method for black box applications in thermodynamics of medium-sized organic molecules when the canonical CCSD(T) calculations with basis sets of reasonable quality are prohibitively expensive.


Kinetic isotope effects on the rate-limiting step of heme oxygenase catalysis indicate concerted proton transfer/heme hydroxylation.
Heme oxygenase (HO) catalyzes the O2 and NADPH/cytochrome P450 reductase-dependent conversion of heme to biliverdin, free iron ion, and CO through a process in which the heme participates as both dioxygen-activating prosthetic group and substrate. We earlier confirmed that the first step of HO catalysis is a monooxygenation in which the addition of one electron and two protons to the HO oxy-ferroheme produces ferric-alpha-meso-hydroxyheme (h). Cryoreduction/EPR and ENDOR measurements further showed that hydroperoxo-ferri-HO converts directly to h in a single kinetic step without formation of a Compound I. We here report details of that rate-limiting step. One-electron 77 K cryoreduction of human oxy-HO and annealing at 200 K generates a structurally relaxed hydroperoxo-ferri-HO species, denoted R. We here report the cryoreduction/annealing experiments that directly measure solvent and secondary kinetic isotope effects (KIEs) of the rate-limiting R --> h conversion, using enzyme prepared with meso-deuterated heme and in H2O/D2O buffers to measure the solvent KIE (solv-KIE), and the secondary KIE (sec-KIE) associated with the conversion. This approach is unique in that KIEs measured by monitoring the rate-limiting step are not susceptible to masking by KIEs of other processes, and these results represent the first direct measurement of the KIEs of product formation by a kinetically competent reaction intermediate in any dioxygen-activating heme enzyme.The observation of both solv-KIE(298) = 1.8 and sec-KIE(298) = 0.8 (inverse) indicates that the rate-limiting step for formation of h by HO is a concerted process: proton transfer to the hydroperoxo-ferri-heme through the distal-pocket H-bond network, likely from a carboxyl group acting as a general acid catalyst, occurring in synchrony with bond formation between the terminal hydroperoxo-oxygen atom and the alpha-meso carbon to form a tetrahedral hydroxylated-heme intermediate. Subsequent rearrangement and loss of H2O then generates h.


Dural sinus thrombosis: value of venous MR angiography for diagnosis and follow-up.
The purpose of this study was to determine the value of venous MR angiography as the sole procedure for the diagnosis and follow-up of dural sinus thrombosis. Forty-two patients with clinical findings suggestive of dural sinus thrombosis were examined with venous MR angiography and spin-echo MR imaging. Maximum-intensity-projection reconstructions and individual sections of the MR angiograms were examined for direct and indirect signs of dural sinus thrombosis by assessing flow signal from the major sinuses, the jugular bulb, upper jugular veins, ascending cortical veins (occlusion or increased flow due to formation of collaterals), diploe (emissary) veins and extracranial veins, and the deep subcortical veins (Galen's and internal cerebral veins). Direct signs of dural sinus thrombosis on MR angiograms included lack of typical high flow signal from a sinus that did not appear aplastic or hypoplastic on single sections from MR angiography and the frayed appearance of the flow signal from a sinus after recanalization. Indirect signs of dural sinus thrombosis included evidence of formation of collaterals, unusually prominent flow signal from deeper medullary veins, cerebral hemorrhage, visualization of emissary veins, and signs of increased intracranial pressure. When available, conventional angiograms were evaluated by analogous criteria as appropriate. Digital subtraction or cut-film angiograms were available for correlation in nine patients. In nine patients, MR angiography was repeated up to eight times during the course of follow-up. The results of MR angiography for all patients were compared with results in 10 control subjects. Confirmation of the diagnosis of dural sinus thrombosis was based either on conventional angiographic findings or on the changes seen in follow-up examinations. Dural sinus thrombosis could be ruled out in 25 of the 42 patients on the basis of clinical and MR angiographic findings. In 17 patients with MR angiographic findings that indicated dural sinus thrombosis, conventional angiography confirmed the diagnosis in nine patients, and changes seen on repeat MR angiograms during follow-up confirmed the diagnosis in nine patients as well (one patient's diagnosis was confirmed by both techniques). Individual frames from two-dimensional fast low-angle shot sequences allowed direct visualization of thrombus. Limited spin-echo sequences as performed here provided inconsistent findings and were insufficient for diagnosis. In the 10 control subjects, attenuation of flow signal was seen in the torcular Herophili in all studies; one subject had a nonpathologic variant of the sinojugular system. MR angiography is the technique of choice for diagnostic evaluation and follow-up of dural sinus thrombosis, and it is reliable as the sole examination for this condition. When MR angiographic findings are unremarkable and other abnormalities must be ruled out, routine spin-echo MR imaging should be performed.


Noise suppression of a dipole source by tensioned membrane with side-branch cavities.
Reducing the ducted-fan noise at the low frequency range remains a big technical challenge. This study presents a passive approach to directly suppress the dipole sound radiation from an axial-flow fan housed by a tensioned membrane with cavity backing. The method aims at achieving control of low frequency noise with an appreciable bandwidth. The use of the membrane not only eliminates the aerodynamic loss of flow, but also provides flexibility in controlling the range of the stopband with high insertion loss by varying its tension and mass. A three-dimensional model is presented which allows the performance of the proposed device to be explored analytically. With the proper design, this device can achieve a noise reduction of 5 dB higher than the empty expansion cavity recently proposed by Huang et al. [J. Acoust. Soc. Am. 128, 152-163 (2010)]. Through the detailed modal analysis, even in vacuo modes of the membrane vibration are found to play an important role in the suppression of sound radiation from the dipole source. Experimental validation is conducted with a loudspeaker as the dipole source and good agreement between the predicted and measured insertion loss is achieved.


Racial disparities in COVID-19 outcomes exist despite comparable Elixhauser comorbidity indices between Blacks, Hispanics, Native Americans, and Whites.
Factors contributing to racial inequities in outcomes from coronavirus disease 2019 (COVID-19) remain poorly understood. We compared by race the risk of 4 COVID-19 health outcomes--maximum length of hospital stay (LOS), invasive ventilation, hospitalization exceeding 24 h, and death--stratified by Elixhauser comorbidity index (ECI) ranking. Outcomes and ECI scores were constructed from retrospective data obtained from the Cerner COVID-19 De-Identified Data cohort. We hypothesized that racial disparities in COVID-19 outcomes would exist despite comparable ECI scores among non-Hispanic (NH) Blacks, Hispanics, American Indians/Alaska Natives (AI/ANs), and NH Whites. Compared with NH Whites, NH Blacks had longer hospital LOS, higher rates of ventilator dependence, and a higher mortality rate; AI/ANs, higher odds of hospitalization for ECI = 0 but lower for ECI ≥ 5, longer LOS for ECI = 0, a higher risk of death across all ECI categories except ECI ≥ 5, and higher odds of ventilator dependence; Hispanics, a lower risk of death across all ECI categories except ECI = 0, lower odds of hospitalization, shorter LOS for ECI ≥ 5, and higher odds of ventilator dependence for ECI = 0 but lower for ECI = 1-4. Our findings contest arguments that higher comorbidity levels explain elevated COVID-19 death rates among NH Blacks and AI/ANs compared with Hispanics and NH Whites.


Active Participation in Outpatient Cardiac Rehabilitation Is Associated With Better Prognosis After Coronary Artery Bypass Graft Surgery - J-REHAB CABG Study.
There is little evidence regarding the effect of outpatient cardiac rehabilitation (CR) on exercise capacity or the long-term prognosis in patients after coronary artery bypass graft surgery (CABG). This study aimed to determine whether participation in outpatient CR improves exercise capacity and long-term prognosis in post-CABG Japanese patients in a multicenter cohort.Methods and Results:We enrolled 346 post-CABG patients who underwent cardiopulmonary exercise testing during early (2-3 weeks) and late (3-6 months) time points after surgery. They formed the Active (n=240) and Non-Active (n=106) CR participation groups and were followed for 3.5 years. Primary endpoint was a major adverse cardiac event (MACE): all-cause death or rehospitalization for acute myocardial infarction/unstable angina/worsening heart failure. Peak oxygen uptake at 3-5 months from baseline was significantly more increased in Active than in Non-Active patients (+26±24% vs. +19±20%, respectively; P<0.05), and the MACE rate was significantly lower in Active than Non-Active patients (3.4% vs. 10.5%, respectively; P=0.02). Multivariate Cox proportional hazard analysis showed that participation in outpatient CR was a significant prognostic determinant of MACE (P=0.03). This unique study showed that a multicenter cohort of patients who underwent CABG and actively participated in outpatient CR exhibited greater improvement in exercise capacity and better survival without cardiovascular events than their counterparts who did not participate.


Health and Ecological Aspects of Stray Cats in Old San Juan, Puerto Rico: Baseline Information to Develop an Effective Control Program.
The overpopulation of stray cats in urban areas represents a potential risk for humans, as stray cats may carry diseases, such as toxoplasmosis, and virus such as rabies, the feline immunodeficiency, and the feline leukemia. In Old San Juan, a historic neighborhood and one of the most touristic places in Puerto Rico, there is an overpopulation of stray cats. In this study, we generated baseline information fundamental to developing a successful control program by estimating the stray cat population size, density, and spatial distribution. Furthermore, we quantified the number of neutered cats and developed a spatial database to include information about the external physical condition of each individual. We estimated a population of 178 (±21) cats, with a density of 3.6 cats/ha. Overall, we observed 209 cats, from which 149 (71%) were identified as new and 60 (29%) were recaptured. We found stray cats had a significant non-random and clustered spatial distribution (z-score = -19.39 SD; ratio = 0.29; p<0.0001), with an observable larger abundance in residential zones where food was provided. A total of 105 (70%) cats were neutered, and 32 (21%) individuals exhibited very poor physical conditions, including skin problems, scars, underweight, and blindness. We concluded that the ecological and descriptive data generated in this study are essential for an effective control of stray cats and their potential impacts on humans living in this neighborhood.


WOCN 2016 Guideline for Prevention and Management of Pressure Injuries (Ulcers): An Executive Summary.
This article provides an executive summary of recommendations from the 2016 Guideline for Prevention and Management of Pressure Ulcers (Injuries) published by the Wound, Ostomy and Continence Nurses Society (WOCN). It presents an overview of the process used to update and develop the guideline, and lists the specific recommendations from the guideline for assessment, prevention, and treatment of pressure injuries. The guideline is a resource for physicians, nurses, therapists, and other healthcare professionals who work with adults who have/or are at risk for pressure injuries. The full text of the published guideline, which includes the available evidence supporting the recommendations and a complete reference list, is available from the Wound, Ostomy and Continence Nurses Society, 1120 Rt 73, Ste 200, Mount Laurel, NJ 08054; Web site: www.wocn.org. Refer to the Supplemental Digital Content (http://links.lww.com/JWOCN/A38) associated with this article for a complete reference list for the guideline. The guideline has been accepted for inclusion in the National Guideline Clearinghouse (www.guideline.gov/).


Fut2-null mice display an altered glycosylation profile and impaired BabA-mediated Helicobacter pylori adhesion to gastric mucosa.
Glycoconjugates expressed on gastric mucosa play a crucial role in host-pathogen interactions. The FUT2 enzyme catalyzes the addition of terminal alpha(1,2)fucose residues, producing the H type 1 structure expressed on the surface of epithelial cells and in mucosal secretions of secretor individuals. Inactivating mutations in the human FUT2 gene are associated with reduced susceptibility to Helicobacter pylori infection. H. pylori infects over half the world's population and causes diverse gastric lesions, from gastritis to gastric cancer. H. pylori adhesion constitutes a crucial step in the establishment of a successful infection. The BabA adhesin binds the Le(b) and H type 1 structures expressed on gastric mucins, while SabA binds to sialylated carbohydrates mediating the adherence to inflamed gastric mucosa. In this study, we have used an animal model of nonsecretors, Fut2-null mice, to characterize the glycosylation profile and evaluate the effect of the observed glycan expression modifications in the process of H. pylori adhesion. We have demonstrated expression of terminal difucosylated glycan structures in C57Bl/6 mice gastric mucosa and that Fut2-null mice showed marked alteration in gastric mucosa glycosylation, characterized by diminished expression of alpha(1,2)fucosylated structures as indicated by lectin and antibody staining and further confirmed by mass spectrometry analysis. This altered glycosylation profile was further confirmed by the absence of Fucalpha(1,2)-dependent binding of calicivirus virus-like particles. Finally, using a panel of H. pylori strains, with different adhesin expression profiles, we have demonstated an impairment of BabA-dependent adhesion of H. pylori to Fut2-null mice gastric mucosa, whereas SabA-mediated binding was not affected.


Generalizability of demographically corrected Zambian neuropsychological norms to South African women.
Objective: Demographically corrected norms typically account for the effects of age, education, and in some cases, sex and other factors (e.g. race/ethnicity). However, generalizability of normative standards to different countries and ethnic groups is not universal. This study sought to determine whether demographically specific Zambian neuropsychological norms would generalize to a group of South African women.Method: 212 English-Xhosa bilingual, South African (SA) women were administered a comprehensive neuropsychological (NP) test battery in either English or Xhosa. We examined rates of "impairment" using Global Deficit Scores (GDS) based upon published, demographically corrected norms from a nearby African country (Zambia). Using multiple regression, we examined the extent to which Zambian norms "corrected" for the effects of age and education in this SA sample.Results: Compared to the normative standards from Zambia, the South African women performed somewhat worse than expected on a few test measures and better than expected on others, but their GDS and associated "impairment" rates were close to what was seen in Zambia. Demographically corrected Zambian norms adequately adjusted for the effects of age and years of education in this sample of SA women, with the exception that Zambian norms appeared to "under correct" for the positive effects of years of education on tests of information processing speed.Conclusions: Demographically corrected norms developed for Zambia may adequately adjust for the effects of age in SA women. Further research is needed to determine whether additional corrections for education are needed in SA, especially for tests of information processing speed.


Costs, effectiveness, and workload impact of management strategies for women with an adnexal mass.
We compared the estimated clinical outcomes, costs, and physician workload resulting from available strategies for deciding which women with an adnexal mass should be referred to a gynecologic oncologist. We used a microsimulation model to compare five referral strategies: 1) American Congress of Obstetricians and Gynecologists (ACOG) guidelines, 2) Multivariate Index Assay (MIA) algorithm, 3) Risk of Malignancy Algorithm (ROMA), 4) CA125 alone with lowered cutoff values to prioritize test sensitivity over specificity, 5) referral of all women (Refer All). Test characteristics and relative survival were obtained from the literature and data from a biomarker validation study. Medical costs were estimated using Medicare reimbursements. Travel costs were estimated using discharge data from Surveillance, Epidemiology and End Results-Medicare and State Inpatient Databases. Analyses were performed separately for pre- and postmenopausal women (60 000 "subjects" in each), repeated 10 000 times. Refer All was cost-effective compared with less expensive strategies in both postmenopausal (incremental cost-effectiveness ratio [ICER] $9423/year of life saved (LYS) compared with CA125) and premenopausal women (ICER $10 644/YLS compared with CA125), but would result in an additional 73 cases/year/subspecialist. MIA was more expensive and less effective than Refer All in pre- and postmenopausal women. If Refer All is not a viable option, CA125 is an optimal strategy in postmenopausal women. Referral of all women to a subspecialist is an efficient strategy for managing women with adnexal masses requiring surgery, assuming sufficient capacity for additional surgical volume. If a test-based triage strategy is needed, CA125 with lowered cutoff values is a cost-effective strategy.


The behavioural response of Australian fur seals to motor boat noise.
Australian fur seals breed on thirteen islands located in the Bass Strait, Australia. Land access to these islands is restricted, minimising human presence but boat access is still permissible with limitations on approach distances. Thirty-two controlled noise exposure experiments were conducted on breeding Australian fur seals to determine their behavioural response to controlled in-air motor boat noise on Kanowna Island (39°10'S, 146°18'E). Our results show there were significant differences in the seals' behaviour at low (64-70 dB) versus high (75-85 dB) sound levels, with seals orientating themselves towards or physically moving away from the louder boat noise at three different sound levels. Furthermore, seals responded more aggressively with one another and were more alert when they heard louder boat noise. Australian fur seals demonstrated plasticity in their vocal responses to boat noise with calls being significantly different between the various sound intensities and barks tending to get faster as the boat noise got louder. These results suggest that Australian fur seals on Kanowna Island show behavioural disturbance to high level boat noise. Consequently, it is recommended that an appropriate level of received boat sound emissions at breeding fur seal colonies be below 74 dB and that these findings be taken into account when evaluating appropriate approach distances and speed limits for boats.


Biofortification: a new tool to reduce micronutrient malnutrition.
The density of minerals and vitamins in food staples eaten widely by the poor may be increased either through conventional plant breeding or through the use of transgenic techniques, a process known as biofortification. HarvestPlus seeks to develop and distribute varieties of food staples (rice, wheat, maize, cassava, pearl millet, beans, and sweet potato) that are high in iron, zinc, and provitamin A through an interdisciplinary, global alliance of scientific institutions and implementing agencies in developing and developed countries. In broad terms, three things must happen for biofortification to be successful. First, the breeding must be successful--high nutrient density must be combined with high yields and high profitability. Second, efficacy must be demonstrated--the micronutrient status of human subjects must be shown to improve when they are consuming the biofortified varieties as normally eaten. Thus, sufficient nutrients must be retained in processing and cooking and these nutrients must be sufficiently bioavailable. Third, the biofortified crops must be adopted by farmers and consumed by those suffering from micronutrient malnutrition in significant numbers. Biofortified crops offer a rural-based intervention that, by design, initially reaches these more remote populations, which comprise a majority of the undernourished in many countries, and then penetrates to urban populations as production surpluses are marketed. In this way, biofortification complements fortification and supplementation programs, which work best in centralized urban areas and then reach into rural areas with good infrastructure. Initial investments in agricultural research at a central location can generate high recurrent benefits at low cost as adapted, biofortified varieties become available in country after country across time at low recurrent costs.


Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell-depleted stem cell transplantation.
We evaluated the efficacy, toxicity, and outcome of preemptive ganciclovir (GCV) therapy in 80 cytomegalovirus (CMV)-seropositive patients allografted between 1991 and 1996 and compared their outcome to 35 seronegative patients allografted during the same period. Both cohorts were comparable with respect to diagnosis and distribution of high- versus standard-risk patients. All patients received a stem cell graft from an HLA-identical sibling donor, and grafts were partially depleted of T cells in 109 patients. Patients were monitored for CMV antigenemia by leukocyte expression of the CMV-pp65 antigen. Fifty-two periods of CMV reactivation occurring in 30 patients were treated preemptively with GCV. A favorable response was observed in 48 of 50 periods, and only 2 patients developed CMV disease: 1 with esophagitis and 1 with pneumonia. Ten of 30 treated patients developed GCV-related neutropenia (less than 0.5 x 10(9)/L), which was associated with a high bilirubin at the start of GCV therapy. Overall survival at 5 years was 64% in the CMV-seronegative cohort and 40% in the CMV-seropositive cohort (P =.01). Increased treatment-related mortality accounted for inferior survival. CMV seropositivity proved an independent risk factor for developing acute graft-versus-host disease, and acute graft-versus-host disease predicted for higher treatment-related mortality and worse overall survival in a time-dependent analysis. We conclude that, although CMV disease can effectively be prevented by preemptive GCV therapy, CMV seropositivity remains a strong adverse risk factor for survival following partial T-cell-depleted allogeneic stem cell transplantation.


Bone marrow stromal cells generate muscle cells and repair muscle degeneration.
Bone marrow stromal cells (MSCs) have great potential as therapeutic agents. We report a method for inducing skeletal muscle lineage cells from human and rat general adherent MSCs with an efficiency of 89%. Induced cells differentiated into muscle fibers upon transplantation into degenerated muscles of rats and mdx-nude mice. The induced population contained Pax7-positive cells that contributed to subsequent regeneration of muscle upon repetitive damage without additional transplantation of cells. These MSCs represent a more ready supply of myogenic cells than do the rare myogenic stem cells normally found in muscle and bone marrow.


One-pot conversions of raffinose into furfural derivatives and sugar alcohols by using heterogeneous catalysts.
Inedible and/or waste biomass reserves are being strongly focused upon as a suitable new energy and chemical source. Raffinose, which is an indigestible trisaccharide composed of glucose, galactose, and fructose, is found abundantly in beet molasses, sugar cane, and seeds of many leguminous plants. Herein, we demonstrate the one-pot synthesis of furan derivatives and sugar alcohols from raffinose by using heterogeneous acid, base, and/or metal-supported catalysts. The combination of Amberlyst-15 and hydrotalcite (HT) showed a high activity (37% yield) for 5-hydroxymethyl-2-furaldehyde (HMF) through continuous hydrolysis, isomerization, and dehydration reactions. In addition, the use of a hydrotalcite-supported ruthenium catalyst (Ru/HT) successfully afforded 2,5-diformylfuran (DFF, 27% yield) from HMF produced by raffinose, directly. Moreover, the hydrogenation of hexoses obtained by raffinose hydrolysis into sugar alcohols (galactitol, mannitol, sorbitol) was also achieved in a high yield (91%) with Amberlyst-15 and Ru/HT catalysts. Thus, we suggest that raffinose has great potential for the synthesis of important industrial intermediates under mild reaction conditions.


Linker region of a halobacterial transducer protein interacts directly with its sensor retinal protein.
pHtrII, a pharaonis halobacterial transducer protein, possesses two transmembrane helices and forms a signaling complex with pharaonis phoborhodopsin (ppR, also called pharaonis sensory rhodopsin II, NpSRII) within the halobacterial membrane. This complex transmits a light signal to the sensory system located in the cytoplasm. It has been suggested that the linker region connecting the transmembrane region and the methylation region of pHtrII is important for binding to ppR and subsequent photosignal transduction. In this study, we present evidence to suggest that the linker region itself interacts directly with ppR in addition to the interaction in the membrane region. An in vitro pull-down assay revealed that the linker region bound to ppR, and its dissociation constant (K(D)) was estimated to be approximately 10 microM using isothermal titration calorimetry (ITC). Solution NMR analyses showed that ppR interacted with the linker region of pHtrII (pHtrII(G83)(-)(Q149)) and resulted in the broadening of many peaks, indicating structural changes within this region. These results suggest that the pHtrII linker region interacts directly with ppR. There was no demonstrable interaction between the C-terminal region of ppR (ppR(Gly224)(-)(His247)) and either the linker region (pHtrII(G83)(-)(Q149)) or the transmembrane region (pHtrII(M1)(-)(E114)) of pHtrII. On the basis of the NMR, CD, and photochemical data, we discuss the structural changes and role of the linker region of pHtrII in relation to photosignal transduction.


Elongation and gene expression in bovine cloned embryos transferred to temporary recipients.
SummaryElongated embryos provide a unique source of information about trophoblastic differentiation, gene expression and maternal-embryonic interactions; however they are difficult and costly to obtain, especially elongated cloned embryos. One alternative is their production in heterologous temporary recipients such as sheep and goats. We aimed to produce elongated bovine cloned embryos using heterologous transfer to temporary recipients. Day-7 cloned cattle blastocysts were transferred to the uteri of ewes and goats and recovered as elongated structures at day 17. We evaluated elongation, length, presence of embryonic disc and expression of several important genes for embryonic development. We also produced homologous (cloned cattle embryos transferred into cattle uteri). Cloned bovine blastocysts were able to proceed with preimplantation development through elongation with high efficiency despite the species to which they were transferred. In qualitative and quantitative RT-PCR experiments we found differences in the pattern of gene expression among embryos recovered from different species. Sox2, Nanog and FGF-4 were markedly deregulated. No previous reports about the expression pattern of the studied genes had been published for elongated bovine cloned embryos produced in intermediate recipients, furthermore, the pattern of expression of Nanog, Oct4, Eomes, Cdx2, IFN-tau, Dicer, FGF-4 and Sox2 shown here are novel for elongated cloned bovine embryos created by hand-made cloning. Our data confirmed that sheep and goats can be used as temporary recipients. This model could serve as a basis for further research on gene expression and cellular changes during bovine peri-implantation development.


Neural substrates of envisioning the future.
The ability to envision specific future episodes is a ubiquitous mental phenomenon that has seldom been discussed in the neuroscience literature. In this study, subjects underwent functional MRI while using event cues (e.g., Birthday) as a guide to vividly envision a personal future event, remember a personal memory, or imagine an event involving a familiar individual. Two basic patterns of data emerged. One set of regions (e.g., within left lateral premotor cortex; left precuneus; right posterior cerebellum) was more active while envisioning the future than while recollecting the past (and more active in both of these conditions than in the task involving imagining another person). These regions appear similar to those emerging from the literature on imagined (simulated) bodily movements. A second set of regions (e.g., bilateral posterior cingulate; bilateral parahippocampal gyrus; left occipital cortex) demonstrated indistinguishable activity during the future and past tasks (but greater activity in both tasks than the imagery control task); similar regions have been shown to be important for remembering previously encountered visual-spatial contexts. Hence, differences between the future and past tasks are attributed to differences in the demands placed on regions that underlie motor imagery of bodily movements, and similarities in activity for these two tasks are attributed to the reactivation of previously experienced visual-spatial contexts. That is, subjects appear to place their future scenarios in well known visual-spatial contexts. Our results offer insight into the fundamental and little-studied capacity of vivid mental projection of oneself in the future.


Bias in Radiology: The How and Why of Misses and Misinterpretations.
Medical errors are a leading cause of morbidity and mortality in the medical field and are substantial contributors to medical costs. Radiologists play an integral role in the diagnosis and care of patients and, given that those in this field interpret millions of examinations annually, may therefore contribute to diagnostic errors. Errors can be categorized as a "miss" when a primary or critical finding is not observed or as a "misinterpretation" when errors in interpretation lead to an incorrect diagnosis. In this article, the authors describe the cognitive causes of such errors in diagnostic medicine, specifically in radiology. Recognizing the cognitive processes that radiologists use while interpreting images should improve one's awareness of the inherent biases that can impact decision making. The authors review the common biases that impact clinical decisions, as well as strategies to counteract or minimize the potential for misdiagnosis. System-level processes that can be implemented to minimize cognitive errors are reviewed, as well as ways to implement personal changes to minimize cognitive errors in daily practice. ©RSNA, 2017.


A Complement-Optimized EGFR Antibody Improves Cytotoxic Functions of Polymorphonuclear Cells against Tumor Cells.
Complement-dependent cytotoxicity (CDC) has been suggested to be an important mechanism of action of tumor-targeting Abs. However, single unmodified epidermal growth factor receptor (EGFR)-targeting IgG1 Abs fail to trigger efficient CDC. For the current study, we generated a CDC-optimized variant of the EGFR Ab matuzumab (H425 wt) by introducing amino acid substitutions K326A/E333A (H425 mt). This Ab was then used to elucidate the impact of complement activation on the capacity of effector cells such as mononuclear cells (MNC) and polymorphonuclear cells (PMN) to exert Ab-dependent cell-mediated cytotoxicity (ADCC). H425 mt, but not H425 wt, significantly induced complement deposition, release of anaphylatoxins, and CDC against distinct tumor cell lines, whereas no differences in ADCC by MNC or PMN were detected. Notably, stronger cytotoxicity was induced by H425 mt than by H425 wt in whole blood assays and in experiments in which MNC or PMN were combined with serum. Although MNC-ADCC was not affected by C5 cleavage, the cytotoxic activity of PMN in the presence of serum strongly depended on C5 cleavage, pointing to a direct interaction between complement and PMN. Strong cell surface expression of C5a receptors was detected on PMN, whereas NK cells completely lacked expression. Stimulation of PMN with C5a led to upregulation of activated complement receptor 3, resulting in enhanced complement receptor 3-dependent PMN-ADCC against tumor cells. In conclusion, complement-optimized EGFR Abs may constitute a promising strategy to improve tumor cell killing by enhancing the interaction between humoral and cellular effector functions in Ab-based tumor therapy.