Microbiological water quality in a large irrigation system: El Valle del Yaqui, Sonora México.
The primary objective of this study was to determine the microbial water quality of a large irrigation system and how this quality varies with respect to canal size, impact of near-by communities, and the travel distance from the source in the El Valle del Yaqui, Sonora, México. In this arid region, 220,000 hectares are irrigated with 80% of the irrigation water being supplied from an extensive irrigation system including three dams on the Yaqui River watershed. The stored water flows to the irrigated fields through two main canal systems (severing the upper and lower Yaqui Valley) and then through smaller lateral canals that deliver the water to the fields. A total of 146 irrigation water samples were collected from 52 sample sites during three sampling events. Not all sites could be accessed on each occasion. All of the samples contained coliform bacteria ranging from 1,140 to 68,670 MPN/100 mL with an arithmetic mean of 11,416. Ninety-eight percent of the samples contained less than 1,000 MPN/100 mL Escherichia coli, with an arithmetic mean of 291 MPN/100 mL. Coliphage were detected in less than 30% of the samples with an arithmetic average equal to 141 PFU/100 mL. Enteroviruses, Cryptosporidium oocysts, and Giardia cysts were also detected in the canal systems. No significant difference was found in the water quality due to canal system (upper or lower Yaqui Valley), canal-size (main vs. lateral), distance from source, and the vicinity of human habitation (presence of various villages and towns along the length of the canals). There was a significant decrease in coliforms (p < 0.011) and E. coli (< 0.022) concentrations as travel distance increased from the City of Obregón.


Integrating research and practice.
The opinion that research is not a legitimate activity for nurses has support in and outside the profession. It has been argued that nursing is a simple art that is not enhanced by science, and that research hinders rather than facilitates the provision of quality nursing services. This paper will examine these arguments and relate them to current controversies in nursing theory, education, research and practice.


Complete genome sequences of Methylophaga sp. strain JAM1 and Methylophaga sp. strain JAM7.
Methylophaga sp. strains JAM1 and JAM7 have been isolated from a denitrification system. Strain JAM1 was the first Methylophaga strain reported to be able to grow under denitrifying conditions. Here, we report the complete genome sequences of the two strains, which allowed prediction of gene clusters involved in denitrification in strain JAM1.


Fluoride and calcium release from peppermint-flavored fluoride varnish containing dicalcium-phosphate-dihydrate coated with xylitol.
Bakground: Fluoride varnish with high initial fluoride and calcium release can help patients with high-risk caries. Ample quantities of free fluoride and calcium ions in the oral cavity can enhance enamel remineralization. This study aimed to investigate the effect of dicalcium phosphate dihydrate coated with xylitol (DCPD-xylitol), in fluoride varnish, on the release of fluoride and calcium ions in the oral cavity. DCPD powder with xylitol was synthesized by preparing a 60% xylitol solution and mixed it with DCPD solution. The mixture was stirred for 1 h at room temperature and dried at 80 °C for 18 h to reduce the water content. Then, the powder was used in the formulation of peppermint-flavored fluoride varnish as an active agent. The amounts of fluoride and calcium ion released in deionized water at 37 °C for 6 h were assessed with an ion-selective electrode. The cumulative fluoride and calcium ion release data were analyzed using one-way analysis of variance (ANOVA) and the post hoc Tukey test with α = 0.05. The results showed that the addition of DCPD coated with xylitol provided better bioavailability of the ions than DCPD without coating. Peppermint-flavored fluoride varnish (PFFV) with DCPD-xylitol 1% gave the highest fluoride ion release (296.90 mg/L) compared to the varnishes with other xylitol concentrations and the positive control. In contrast, PFFV DCPD-xylitol 5% afforded the highest calcium ion release at 111.20 mg/L. This study concluded that xylitol affects the bioavailability of free fluoride and calcium ions in varnishes. However, the efficacy of fluoride and calcium uptake in enamel and under different in vitro media conditions requires further investigation.


TGA2 signaling in response to reactive electrophile species is not dependent on cysteine modification of TGA2.
Reactive electrophile species (RES), including prostaglandins, phytoprostanes and 12-oxo phytodienoic acid (OPDA), activate detoxification responses in plants and animals. However, the pathways leading to the activation of defense reactions related to abiotic or biotic stress as a function of RES formation, accumulation or treatment are poorly understood in plants. Here, the thiol-modification of proteins, including the RES-activated basic region/leucine zipper transcription factor TGA2, was studied. TGA2 contains a single cysteine residue (Cys186) that was covalently modified by reactive cyclopentenones but not required for induction of detoxification genes in response to OPDA or prostaglandin A1. Activation of the glutathione-S-transferase 6 (GST6) promoter was responsive to cyclopentenones but not to unreactive cyclopentanones, including jasmonic acid suggesting that thiol reactivity of RES is important to activate the TGA2-dependent signaling pathway resulting in GST6 activation We show that RES modify thiols in numerous proteins in vivo, however, thiol reactivity alone appears not to be sufficient for biological activity as demonstrated by the failure of several membrane permeable thiol reactive reagents to activate the GST6 promoter.


Exploring the biomechanical properties of brain malignancies and their pathologic determinants in vivo with magnetic resonance elastography.
Malignant tumors are typically associated with altered rigidity relative to normal host tissue. Magnetic resonance elastography (MRE) enables the noninvasive quantitation of the mechanical properties of deep-seated tissue following application of an external vibrational mechanical stress to that tissue. In this preclinical study, we used MRE to quantify (kPa) the elasticity modulus Gd and viscosity modulus Gl of three intracranially implanted glioma and breast metastatic tumor models. In all these brain tumors, we found a notable softness characterized by lower elasticity and viscosity than normal brain parenchyma, enabling their detection on Gd and Gl parametric maps. The most circumscribed tumor (U-87 MG glioma) was the stiffest, whereas the most infiltrative tumor (MDA-MB-231 metastatic breast carcinoma) was the softest. Tumor cell density and microvessel density correlated significantly and positively with elasticity and viscosity, whereas there was no association with the extent of collagen deposition or myelin fiber entrapment. In conclusion, although malignant tumors tend to exhibit increased rigidity, intracranial tumors presented as remarkably softer than normal brain parenchyma. Our findings reinforce the case for MRE use in diagnosing and staging brain malignancies, based on the association of different tumor phenotypes with different mechanical properties.


Synthetic polyion-counterion transport systems in polymersomes and gels.
Transport across the membranes of polymersomes remains difficult in part due to the great thickness of the polymer bilayers. Here, we report that dynamic polyion-counterion transport systems are active in fluorogenic polymersomes composed of poly(dimethylsiloxane)-b-poly(2-methyloxazoline) (PDMS-PMOXA). These results suggest that counterion-activated calf-thymus DNA can act as cation carrier that moves not only across lipid bilayer and bulk chloroform membranes but also across the "plastic" membranes of polymersomes. Compared to egg yolk phosophatidylcholine (EYPC) lipsosomes, activities and activator scope in PDMS-PMOXA polymersomes are clearly reduced. Embedded in agar gel matrices, fluorogenic PDMS-PMOXA polymersomes respond reliably to polyion-counterion transporters, with high contrast, high stability and preserved selectivity. Compared to standard EYPC liposomes, it cannot be said that PDMS-PMOXA polymersomes are better. However, they are different, and this difference could be interesting for the development of sensing devices.


A Non-invasive Method for Assessment of Intravascular Fluid Status: Inferior Vena Cava Diameters and Collapsibility Index.
To evaluate the correlation between central venous pressure (CVP) and inferior vena cava (IVC) diameters measured by ultrasonography (Ultrasound) in critically ill patients. Intubated critically ill patients were enrolled. The CVP values were measured using a U-tube manometer and were compared to the IVC diameters and collapsibility index, which were measured by bedside Ultrasound. Patients younger than 18 years old, who were not intubated, who had an abdominal pressure greater than 12 mmHg, and/or who were admitted for trauma were excluded from the study. Eighty three patients with a mean age of 73.6±11.2 years were enrolled. The most common diagnosis was sepsis (21 patients, 25.30%). IVC inspiration measurements were statistically significantly correlated with CVP measurements (p0.05, r: 0.1). IVC collapsibility measurements showed a negative correlation with CVP measurements (p<0.01, r: 0.68). There is a strong correlation between CVP and IVC diameters and the collapsibility index. This is a new formula for evaluating CVP, based on our statistical analyses.


Two-stage arthrodesis for complex, failed, infected total knee arthroplasty.
Arthrodesis is rarely used as a salvage procedure for patients with a chronically infected total knee arthroplasty (TKA), and little information is available about the outcome. The aim of this study was to assess the reliability, durability, and safety of this procedure as the definitive treatment for complex, chronically infected TKA, in a current series of patients. We retrospectively identified 41 patients (41 TKAs) with a complex infected TKA, who were treated between 2002 and 2016 using a deliberate, two-stage knee arthrodesis. Their mean age was 64 years (34 to 88) and their mean body mass index (BMI) was 39 kg/m2 (25 to 79). The mean follow-up was four years (2 to 9). The extensor mechanism (EM) was deficient in 27 patients (66%) and flap cover was required in 14 (34%). Most patients were host grade B (56%) or C (29%), and limb grade 3 (71%), according to the classification of McPherson et al. A total of 12 patients (29%) had polymicrobial infections and 20 (49%) had multi-drug resistant organisms; fixation involved an intramedullary nail in 25 (61%), an external fixator in ten (24%), and dual plates in six (15%). Survivorship free from amputation, persistent infection, and reoperation, other than removal of an external fixator, at five years was 95% (95% confidence interval (CI) 89% to 100%), 85% (95% CI 75% to 95%), and 64% (95% CI 46% to 82%), respectively. Reoperation, other than removal of an external fixator, occurred in 13 patients (32%). After the initial treatment, radiological nonunion developed in ten knees (24%). Nonunion was significantly correlated with persistent infection (p = 0.006) and external fixation (p = 0.005). Of those patients who achieved limb salvage, 34 (87%) remained mobile and 31 (79%) had 'absent' or 'minimal' pain ratings. Knee arthrodesis using a two-stage protocol achieved a survivorship free from amputation for persistent infection of 95% at five years with 87% of patients were mobile at final follow-up. However, early reoperation was common (32%). This is not surprising as this series included worst-case infected TKAs in which two-thirds of the patients had a disrupted EM, one-third required flap cover, and most had polymicrobial or multi-drug resistant organisms. Cite this article: Bone Joint J 2020;102-B(6 Supple A):170-175.


Anaerobic meningitis and bacteremia caused by Fusobacterium species.
In the two cases of anaerobic meningitis and bacteremia caused by Fusobacterium species described, upper respiratory tract infection preceded the onset of meningitis. Isolation of the causative organism and appropriate antibiotic therapy resulted in cures in both patients. Although extremely rare, these organisms should be considered as possible causative agents in meningitis when routine cultures are negative, and appropriate anaerobic culture techniques should be employed, especially when sinus, otitic, or mastoid symptoms precede or accompany the onset of meningitis. Susceptibility testing of these organisms is necessary to ensure proper therapy because of the resistance of some anaerobes to antibiotics commonly employed in meningitis. In this regard, metronidazole, which provides excellent cerebrospinal fluid levels, may prove to be an effective agent in anaerobic infections of the central nervous system.


LYSTO: The Lymphocyte Assessment Hackathon and Benchmark Dataset.
We introduce LYSTO, the Lymphocyte Assessment Hackathon, which was held in conjunction with the MICCAI 2019 Conference in Shenzhen (China). The competition required participants to automatically assess the number of lymphocytes, in particular T-cells, in images of colon, breast, and prostate cancer stained with CD3 and CD8 immunohistochemistry. Differently from other challenges setup in medical image analysis, LYSTO participants were solely given a few hours to address this problem. In this paper, we describe the goal and the multi-phase organization of the hackathon; we describe the proposed methods and the on-site results. Additionally, we present post-competition results where we show how the presented methods perform on an independent set of lung cancer slides, which was not part of the initial competition, as well as a comparison on lymphocyte assessment between presented methods and a panel of pathologists. We show that some of the participants were capable to achieve pathologist-level performance at lymphocyte assessment. After the hackathon, LYSTO was left as a lightweight plug-and-play benchmark dataset on grand-challenge website, together with an automatic evaluation platform. LYSTO has supported a number of research in lymphocyte assessment in oncology. LYSTO will be a long-lasting educational challenge for deep learning and digital pathology, it is available at https://lysto.grand-challenge.org/.


Factors of nocturnal sleep and daytime nap durations in community-dwelling elderly: a longitudinal population-based study.
Durations of nocturnal sleep and daytime nap influence the well-being of older adults. It is thus essential to understand their determinants. However, much previous research did not assess sleep duration and nap duration individually, and longitudinal data is lacking. This study aimed at examining the impact of demographic, psychosocial, and health factors, including ethnicity, social networks outside the household, smoking and physical exercise on sleep duration and nap duration among community-dwelling elderly. Our study involved over 2,600 older adults (≥60 years) from a longitudinal, nationally representative survey - the Panel on Health and Ageing of Singaporean Elderly. Sleep and nap durations at Time 2 (two years later) were regressed on predictors measured at Time 1. Time 2 short nocturnal sleep duration was predicted by Malay ethnicity (relative to Chinese and Indian), older age, lower education level, more depressive symptoms, and obesity, whereas future long nocturnal sleep duration was predicted by weaker social networks, older age, and more chronic diseases. Furthermore, smoking, obesity, Malay or Indian (relative to Chinese), older age, male gender, and cognitive impairment predicted longer daytime nap duration in the future. Older adults' nocturnal sleep and daytime nap durations may be affected by different demographic, psychosocial, and health factors. Thus, it is important to differentiate these two attributes in this age group.


The plasma membrane ferrireductase activity of Saccharomyces cerevisiae is partially controlled by cyclic AMP.
The plasma-membrane-bound ferrireductase activity of ras1 and ras2 mutants of Saccharomyces cerevisiae is not induced in response to iron limitation. This phenotype was suppressed by the bcy1 mutation in ras2 but not in ras1 mutants. The cellular haem content of ras-1-bearing strains decreased dramatically when cells were grown in semi-synthetic medium (low yeast extract content), which could account for their very low ferrireductase activity. The ferrireductase activity of cdc25 and cdc35 mutants dropped when the cells were shifted to a non-permissive temperature. This drop was prevented in the double mutant cdc35 sra5 by adding cyclic AMP to the growth medium. We propose that ferrireductase activity is under the control of a cyclic AMP-dependent protein phosphorylation.


Breakdown and rebuilding of myofibrils in cultured adult cardiac muscle cells.
The myofibrils of adult rat cardiac muscle cells in culture break down and later reorganize into mature myofibrils. The myofibrillar breakdown and reorganization processes have been investigated with electron microscopical and immunocytochemical studies. The immunocytochemical studies included antibodies to actin, myosin, titin, and alpha-actinin. In addition, rhodamine-labeled phalloidin has been used. These studies revealed that the myofibrils were disorganized into amorphous and/or other forms during breakdown process. Some of these myofibrils undergo degradation and finally extrusion through exocytosis. The reorganization of myofibrils takes place mainly with the participation of the existing myofibrillar proteins in myocytes. This remyofibrillogenesis showed the emergence of punctate alpha-actinin from the existing amorphous alpha-actinin along with the differentiation of titin periodicities, which remained attached to the alpha-actinin structures. The punctate alpha-actinin later differentiated into periodicities, forming Z-lines. The periodicities of actin were differentiated from the amorphous actin and associated with the Z-lines, giving rise to titin, alpha-actinin, and actin complexes. Later, myosin filaments became associated with these complexes, forming sarcomeres where other myofibrillar proteins participated in the formation of mature myofibrils. The temporal sequence of differentiation of periodicities of certain myofibrillar proteins varied among different myocytes and within a single myocyte. The dynamic role of adult cardiac myocytes in the reconstruction of myofibrils is a remarkable phenomenon, which stabilizes adult cardiac muscle cells in long-term culture.


Fucoidan from Macrocystis pyrifera has powerful immune-modulatory effects compared to three other fucoidans.
Fucoidan, a sulfated polysaccharide purified from brown algae, has a variety of immune-modulation effects, such as promoting activation of dendritic cells (DCs), natural killer (NK) cells and T cells, and enhancing anti-viral and anti-tumor responses. However, the immune-modulatory effect of fucoidan from different seaweed extracts has not been thoroughly analyzed and compared. We analyzed fucoidans obtained from Ascophyllum nodosum (A. nodosum), Macrocystis pyrifera (M. pyrifera), Undaria pinnatifida (U. pinnatifida) and Fucus vesiculosus (F. vesiculosus) for their effect on the apoptosis of human neutrophils, activation of mouse NK cells, maturation of spleen DCs, proliferation and activation of T cells, and the adjuvant effect in vivo. Fucoidans from M. pyrifera and U. pinnatifida strongly delayed human neutrophil apoptosis at low concentration, whereas fucoidans from A. nodosum and F. vesiculosus delayed human neutrophil apoptosis at higher concentration. Moreover, fucoidan from M. pyrifera promoted NK cell activation and cytotoxic activity against YAC-1 cells. In addition, M. pyrifera fucoidan induced the strongest activation of spleen DCs and T cells and ovalbumin (OVA) specific immune responses compared to other fucoidans. These data suggest that fucoidan from M. pyrifera can be potentially useful as a therapeutic agent for infectious diseases, cancer and an effective adjuvant for vaccine.


Astaxanthin Protects OTA-Induced Lung Injury in Mice through the Nrf2/NF-κB Pathway.
The aim of this research was to evaluate the potential protective mechanism of astaxanthin (ASTA) against oxidative damage and inflammation caused by ochratoxin (OTA) in mouse lung. We divided mice into a control group (CG), an OTA group (PG), an astaxanthin group (AG), and an OTA+ASTA group (JG). Oxidative indices (malondialdehyde (MDA), total superoxide dismutase (T-SOD), and reduced glutathione (GSH)) and inflammatory markers (interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α)) were assayed in the lung, and the lung-weight-to-body-weight ratio was calculated. Apoptosis was detected in pathological sections by the TdT-mediated dUTP nick-end labeling (TUNEL) assay. Oxidative damage and inflammation were detected in the lung of mice after exposure to OTA. Besides, Nrf2- and NF-κB-pathway-associated proteins were detected by Western blot. In contrast with OTA, ASTA significantly raised the expression of Nrf2, HO-1, and MnSOD, while the expression of other proteins (Keap1, TLR4, and NF-κB) was significantly decreased. These results indicate that ASTA exerted protective effects against OTA-induced oxidative damage and inflammation in the lung by regulating the Nrf2 and NF-κB pathways.


In vivo IL-4 prevents allo-antigen driven CD8+ CTL development.
IL-4 has been shown to suppress acute graft vs. host disease (GVHD) in irradiated hosts. Here we evaluated whether IL-4 suppresses acute GVHD in the un-irradiated parent-into-F1 GVHD model with relevance to renal allograft rejection. IL-4 completely suppressed CD8 CTL when administered with donor cells however this effect was lost if its administration was delayed 3days. IL-4 did not inhibit donor CD8+ T cell homing to the host spleen but rather prevented donor CD8+ T cell differentiation into CTLs. Studies with IL-4Rα-deficient donor cells or recipient mice demonstrated that IL-4 effects on the host, rather than, or in addition to IL-4 effects on donor cells, were critical for suppression of CTL. Because IL-4 decreased all splenic dendritic cell populations and increased neutrophil and CD8+ T cells, IL-4 may suppress donor CD8+ CTL by decreasing Ag presentation and/or increasing host myeloid and CD8+ T cell suppression of donor T cells.


Validation of a new prognostic model to easily predict outcome in renal cell carcinoma: the GRANT score applied to the ASSURE trial population.
Prognostic scores have been developed to estimate the risk of recurrence and the probability of survival after nephrectomy for renal cell carcinoma (RCC). The use of these tools, despite being helpful to plan a customized schedule of follow-up, to the patient's tailored counselling and to select individuals who could potentially benefit from adjuvant treatment, currently is not routine, due to their relative complexity and to the lack of histological data (i.e. necrosis). We developed a simple score called GRade, Age, Nodes and Tumor (GRANT) based on four easily obtained parameters: Fuhrman grade, age, pathological nodal status and pathological tumor size. Patients with 0 or 1 factor are classified as favorable risk, whereas patients with two or more risk factors as unfavorable risk. The large population of RCC patients from the ASSURE adjuvant trial was used as independent dataset for this external validation, to investigate the prognostic value of the new score in terms of disease-free survival and overall survival and to evaluate its possible application as predictive tool. Statistical analyses were carried out by the Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute (Boston, USA) for the ASSURE trial patients' population. The performance of the new model is similar to that of the already validated score systems, but its strength, compared with the others already available, is the ease and clarity of its calculation, with great speed of use during the clinical practice. Limitations are the use of the Fuhrman nuclear grade, not valid for rare histologies, and the TNM classification modifications over time. The GRANT score demonstrated its potential usefulness for clinical practice. NCT00326898.


Laryngeal T regulatory cells in the setting of smoking and reflux.
The larynx is a mucosal organ rich in lymphatic tissue that is regularly exposed to a multitude of inhaled, ingested, and refluxed microorganisms and irritants. The first line of mucosal immune defense is the barrier, including resident immune cells. T regulatory (Treg) cells are a specialized subset of CD4+ T cells that suppress or dampen immune responses to prevent damaging immunopathology. As Treg cells have been shown to preferentially accumulate at sites of infection, and Treg responses may contribute to persistence of infection by impairing antibacterial immunity, we sought to quantify these cells in laryngeal tissue exposed to smoking and reflux. Cross-sectional study. Using an epigenetic assay, we quantified Treg and T cells and calculated the ratio of Treg to T cells (i.e., cellular ratio of immune tolerance [ImmunoCRIT]) in disease-free laryngeal biopsies representing four inflammatory states: 1) tobacco-exposed tissue, 2) refluxate and tobacco-exposed tissue, 3) refluxate-exposed tissue, and 4) unexposed tissue. There was epigenetic evidence of Treg cells in all tissues, and we found no differences in Treg cell frequency relative to smoking and reflux in laryngeal tissue collected from 42 non-treatment-seeking participants. There was a decrease in total T cell frequency and an increase in ImmunoCRIT values in smokers regardless of reflux status. In this study, laryngeal tissue from smokers show decreased overall T cells and increased ImmunoCRIT values. Our findings indicate that laryngeal inflammation is not directly mediated by loss of Treg cells in response to smoking and reflux in local tissue and increased ImmunoCRIT values in smokers implicate a role for this environmental exposure in modulating laryngeal immune homeostasis. More studies are indicated to explore Treg cell dysfunction in the pathophysiology of laryngeal disease. NA Laryngoscope, 127:882-887, 2017.


The Northwestern University Twin Study. XV: Rationales for a standard of care in compromised twin pregnancies.
Current antenatal technologies have improved the obstetrician's ability to assess fetal well-being as well as to diagnose fetal compromise. These technologies have given rise to very difficult ethical issues in the management of compromised twin pregnancies: for example, a choice must be made between putting a healthy twin at risk due to preterm delivery for the sake of a compromised cotwin or of allowing the compromised twin to die in order to buy time for the healthy twin. Though each case is unique, good medical practice requires a standard of care by which consistent patient management can be proposed. In the pluralistic environment of Northwestern Memorial Hospital, our staff has favored a standard of care based on patient autonomy. This approach demands: 1) a practitioner who offers a thorough explanation of the diagnosis and possible treatment approaches; 2) time for the patient and her partner to assimilate this information and test treatment options against their personal value system; 3) a third, but disinterested, party to facilitate patient understanding and value clarification; 4) a practitioner either willing to support the patient's decisions or refer her to another practitioner who will.


Traumatic Neck and Skull Base Injuries.
Patients with blunt and penetrating traumatic injuries to the skull base and soft tissues of the neck present to the emergency department every day. Fortunately, truly life-threatening injuries to these regions are relatively uncommon. However, when encountered and not correctly diagnosed, these entities may result in severe morbidity or mortality. The radiologist plays a critical role recognizing these injuries, in which findings may often be subtle and the anatomy potentially challenging to identify. Multisection CT and CT angiography are commonly performed to assess these injuries in the emergency department. Vascular injury to the neck may result in dissection, occlusion, pseudoaneurysm formation, or frank extravasation resulting in stroke or death. Airway compromise may result from laryngotracheal injury. Injuries to the pharynx and esophagus may result in perforation. Injuries to the temporal bone may result in vascular injury to the internal carotid artery or facial nerve injury, which would require immediate surgery or intervention to prevent paralysis.©RSNA, 2019.


The evaluation of three comorbidity indices in predicting postoperative complications and readmissions in pediatric urology.
The surgical comorbidity assessment is important for patient risk stratification, counseling, and research. In adults, risk assessment indices, such as the Charlson Co-morbidity Score (CCS) or Van Walraven Index (VWI), are well established. In pediatrics, however, risk assessment indices are scarce. Recently, a pediatric-specific risk assessment index, the Rhee index, was developed to discriminate mortality for pediatric general surgery patients. Currently, there is no validated risk assessment tool in pediatric urology. We compared the performance of the CCS, VWI, and Rhee Index in discriminating postoperative complications and readmissions to the emergency room/inpatient unit after pediatric urological procedures. We analyzed the Nationwide Readmissions Database (NRD), State Inpatient Databases (SID), and State Emergency Department Databases (SEDD). We included patients (<18 years) who underwent the following urological procedures: ureteroneocystostomy, ureteroureterostomy, radical/partial nephrectomy, pyeloplasty, appendicovesicostomy, enterocystoplasty, vesicostomy, and bladder neck sling. Complications were identified based on definitions in the National Surgical Quality Improvement Program (NSQIP). Thirty-day emergency room admission and inpatient readmissions were extracted. Comorbidity scores were calculated using each of the three indices. We compared the performance of each index in discriminate primarily postoperative complications in the NRD and both admission types in the SID/SEDD by constructing a receiver operating characteristics (ROC). AUCs were compared using the Delong method. This protocol was reviewed by our Institutional Review Board and deemed to be exempt. We identified a total of 8006 patients in NRD and 6236 patients in SID/SEDD. The Rhee index had the best performance for discriminating postoperative complications (AUC = 0.67, 95% CI 0.64-0.70) compared to CCS (AUC = 0.62, 95% CI 0.60-0.65) and VWI (AUC = 0.62, 95% CI 0.59-0.65); p < 0.01. The CCS had the best performance for discriminating 30-day inpatient readmissions (AUC = 0.63, 95% CI 0.61-0.66) than VWI (AUC = 0.54, 95% CI 0.52-0.57), and Rhee Index (AUC = 0.56, 95% CI 0.54-0.59); p < 0.0001. All three indices had similarly poor discrimination for 30-day ER admissions: CCS (AUC = 0.52), VWI (AUC = 0.51), and Rhee Index (AUC = 0.50); p = 0.5 (see Table). The Rhee Index had the best performance for discriminating postoperative complications, while the CCS was superior for discriminating inpatient readmissions among the three indices. Limitations to our study include inpatient-only procedures, inability to identify complications managed in clinics, omission of secondary operations, accounting for parental anxiety, and the generalizability of SID. The three comorbidity indices evaluated are poor discriminators for postoperative complications, 30-day inpatient readmissions or 30-day ER admissions. A new index is needed for pediatric urology patients.


Prevalence of unrecognized myocardial infarction in a low-intermediate risk asymptomatic cohort and its relation to systemic atherosclerosis.
Unrecognized myocardial infarctions (UMIs) have been described in 19-30% of the general population using late gadolinium enhancement (LGE) on cardiac magnetic resonance. However, these studies have focused on an unselected cohort including those with known cardiovascular disease (CVD). The aim of the current study was to ascertain the prevalence of UMIs in a non-high-risk population using magnetic resonance imaging (MRI). A total of 5000 volunteers aged >40 years with no history of CVD and a 10-year risk of CVD of <20%, as assessed by the ATP-III risk score, were recruited to the Tayside Screening for Cardiac Events study. Those with a B-type natriuretic peptide (BNP) level greater than their gender-specific median were invited for a whole-body MR angiogram and cardiac MR including LGE assessment. LGE was classed as absent, UMI, or non-specific. A total of 1529 volunteers completed the imaging study; of these, 53 (3.6%) were excluded because of either missing data or inadequate LGE image quality. Ten of the remaining 1476 (0.67%) displayed LGE. Of these, three (0.2%) were consistent with UMI, whereas seven were non-specific occurring in the mid-myocardium (n = 4), epicardium (n = 1), or right ventricular insertion points (n = 2). Those with UMI had a significantly higher BNP [median 116 (range 31-133) vs. 22.6 (5-175) pg/mL, P = 0.015], lower ejection fraction [54.6 (36-62) vs. 68.9 (38-89)%, P = 0.007], and larger end-systolic volume [36.3 (27-61) vs. 21.7 (5-65) mL/m2, P = 0.014]. Those with non-specific LGE had lower diastolic blood pressure [68 (54-70) vs. 72 (46-98) mmHg, P = 0.013] but no differences in their cardiac function. Despite previous reports describing high prevalence of UMI in older populations, in a predominantly middle-aged cohort, those who are of intermediate or low cardiovascular risk have a very low risk of having an unrecognized myocardial infarct.


Development of Cholesterol-Lowering and Detox Formulations Using Bentonite and Herbal Ingredients.
Detoxification enzymes involved in human metabolism works to minimize the potential xenobiotic-induced damage constantly. Studies have revealed that toxin accumulation plays an important role in the etiology of cardiovascular disease. This study has been designed to provide evidence of medicinal use of bentonite, turmeric (Curcuma longa L.), grape (Vitis vinifera L.) seed, flaxseed (Linum usitatissimum L.), and psyllium (Plantago ovata L.) as detoxification and cholesterol-lowering agents using a hypercholesterolemic model in mice. The potential hypocholesterolemic effects and detoxification ability of these ingredients were evaluated at the same time: Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, glucose, aspartate aminotransferase, alanine aminotransferase, malondialdehyde, plasma total antioxidant activity, nitric acid, leptin levels and glutathione, glutathione peroxidase, lipid peroxidation, superoxide dismutase and catalase values were measured. It was determined that GBTF group (grape seed extract, bentonite, turmeric, and flaxseed), GBTP group (grape seed extract, bentonite, turmeric, and psyllium), and GBT group (grape seed extract, bentonite, and turmeric) of the tested materials decreased the serum total cholesterol concentration by 64.8, 57.5, and 48.9%, respectively, in mice fed a high cholesterol diet. In addition, it was determined that some detoxification parameters such as superoxide dismutase, catalase, glutathione, and glutathione peroxidase were statistically significantly reversed in GBTF, GBTP, and GBT groups. Flaxseed, psyllium, and bentonite clay did not show significant effects in reducing total cholesterol; however, GBTF, GBTP, and GBT groups interventions had a significant effect in reducing total cholesterol levels. Moreover, it was observed that adding flaxseed or psyllium to the GBT group increased the cholesterol-lowering effect. Therefore, it can be thought that this significant effect is due to the synergistic effect of the raw materials. When the results obtained were evaluated, it was seen that the cholesterol-lowering and detoxification effects of the combinations were higher than from the effect of natural material used alone. As a result, combinations of some of these ingredients have a positive effect on reducing the risk of cardiovascular disease.


Subchronic liver injuries caused by microcystins.
The subchronic effects of cyanobacterial lyophilizate (CL) containing microcystins on liver were investigated in female New Zealand rabbits. Sterilised CL containing microcystins was injected i.p. Liver toxicity was assessed by histological examination of liver samples. Non-invasive magnetic resonance imaging (MRI) of liver was also performed in order to assess changes in the homogeneity of liver tissue. Subchronical intoxication with microcystins caused morphological changes of liver tissue that were also detected by use of MRI. Histological analysis showed that changes seen on MRI represent liver injury characterised with fatty infiltration and periportal fibrosis. This demonstrates that subchronic exposure to microcystins can lead to liver degeneration, which can easily be detected in vivo by use of MRI.


mRNA stability and polysome loss in hibernating Arctic ground squirrels (Spermophilus parryii).
All small mammalian hibernators periodically rewarm from torpor to high, euthermic body temperatures for brief intervals throughout the hibernating season. The functional significance of these arousal episodes is unknown, but one suggestion is that rewarming may be related to replacement of gene products lost during torpor due to degradation of mRNA. To assess the stability of mRNA as a function of the hibernation state, we examined the poly(A) tail lengths of liver mRNA from arctic ground squirrels sacrificed during four hibernation states (early and late during a torpor bout and early and late following arousal from torpor) and from active ground squirrels sacrificed in the summer. Poly(A) tail lengths were not altered during torpor, suggesting either that mRNA is stabilized or that transcription continues during torpor. In mRNA isolated from torpid ground squirrels, we observed a pattern of 12 poly(A) residues at greater densities approximately every 27 nucleotides along the poly(A) tail, which is a pattern consistent with binding of poly(A)-binding protein. The intensity of this pattern was significantly reduced following arousal from torpor and undetectable in mRNA obtained from summer ground squirrels. Analyses of polysome profiles revealed a significant reduction in polyribosomes in torpid animals, indicating that translation is depressed during torpor.


Distinct Physiological Maturation of Parvalbumin-Positive Neuron Subtypes in Mouse Prefrontal Cortex.
Parvalbumin-positive (PV+) neurons control the timing of pyramidal cell output in cortical neuron networks. In the prefrontal cortex (PFC), PV+ neuron activity is involved in cognitive function, suggesting that PV+ neuron maturation is critical for cognitive development. The two major PV+ neuron subtypes found in the PFC, chandelier cells (ChCs) and basket cells (BCs), are thought to play different roles in cortical circuits, but the trajectories of their physiological maturation have not been compared. Using two separate mouse lines, we found that in the mature PFC, both ChCs and BCs are abundant in superficial layer 2, but only BCs are present in deeper laminar locations. This distinctive laminar distribution was observed by postnatal day 12 (P12), when we first identified ChCs by the presence of axon cartridges. Electrophysiology analysis of excitatory synapse development, starting at P12, showed that excitatory drive remains low throughout development in ChCs, but increases rapidly before puberty in BCs, with an earlier time course in deeper-layer BCs. Consistent with a role of excitatory synaptic drive in the maturation of PV+ neuron firing properties, the fast-spiking phenotype showed different maturation trajectories between ChCs and BCs, and between superficial versus deep-layer BCs. ChC and BC maturation was nearly completed, via different trajectories, before the onset of puberty. These findings suggest that ChC and BC maturation may contribute differentially to the emergence of cognitive function, primarily during prepubertal development.SIGNIFICANCE STATEMENT Parvalbumin-positive (PV+) neurons tightly control pyramidal cell output. Thus PV+ neuron maturation in the prefrontal cortex (PFC) is crucial for cognitive development. However, the relative physiological maturation of the two major subtypes of PV+ neurons, chandelier cells (ChCs) and basket cells (BCs), has not been determined. We assessed the maturation of ChCs and BCs in different layers of the mouse PFC, and found that, from early postnatal age, ChCs and BCs differ in laminar location. Excitatory synapses and fast-spiking properties matured before the onset of puberty in both cell types, but following cell type-specific developmental trajectories. Hence, the physiological maturation of ChCs and BCs may contribute to the emergence of cognitive function differentially, and predominantly during prepubertal development.


Arteriovenous fistula between descending aorta and left inferior pulmonary vein: Closure with vascular plugs.
Echocardiography revealed systemic artery to pulmonary venous fistula, a rare vascular anomaly, in a 20-month-old girl, and multislice computed tomography angiography (CTA) was performed to rule out congenital heart disease. Normal bronchial connection and pulmonary vasculature were observed in the lung. The fistula drained through the left inferior pulmonary vein to the left atrium leading to a left-to-left shunt. Percutaneous intervention was performed in 2 stages using Amplatzer vascular plugs to close successfully.


A novel role for the integrin-binding III-10 module in fibronectin matrix assembly.
Fibronectin matrix assembly is a cell-dependent process which is upregulated in tissues at various times during development and wound repair to support the functions of cell adhesion, migration, and differentiation. Previous studies have demonstrated that the alpha 5 beta 1 integrin and fibronectin's amino terminus and III-1 module are important in fibronectin polymerization. We have recently shown that fibronectin's III-1 module contains a conformationally sensitive binding site for fibronectin's amino terminus (Hocking, D.C., J. Sottile, and P.J. McKeown-Longo. 1994. J. Biol. Chem. 269: 19183-19191). The present study was undertaken to define the relationship between the alpha 5 beta 1 integrin and fibronectin polymerization. Solid phase binding assays using recombinant III-10 and III-1 modules of human plasma fibronectin indicated that the III-10 module contains a conformation-dependent binding site for the III-1 module of fibronectin. Unfolded III-10 could support the formation of a ternary complex containing both III-1 and the amino-terminal 70-kD fragment, suggesting that the III-1 module can support the simultaneous binding of III-10 and 70 kD. Both unfolded III-10 and unfolded III-1 could support fibronectin binding, but only III-10 could promote the formation of disulfide-bonded multimers of fibronectin in the absence of cells. III-10-dependent multimer formation was inhibited by both the anti-III-1 monoclonal antibody, 9D2, and amino-terminal fragments of fibronectin. A fragment of III-10, termed III-10/A, was able to block matrix assembly in fibroblast monolayers. Similar results were obtained using the III-10A/RGE fragment, in which the RGD site had been mutated to RGE, indicating that III-I0/A was blocking matrix assembly by a mechanism distinct from disruption of integrin binding. Texas red-conjugated recombinant III-1,2 localized to beta 1-containing sites of focal adhesions on cells plated on fibronectin or the III-9,10 modules of fibronectin. Monoclonal antibodies against the III-1 or the III-9,10 modules of fibronectin blocked binding of III-1,2 to cells without disrupting focal adhesions. These data suggest that a role of the alpha 5 beta 1 integrin in matrix assembly is to regulate a series of sequential self-interactions which result in the polymerization of fibronectin.


[Current periodontal therapy].
Current periodontal therapy consists of a multitude of categories for study and concern. Therapy for Disease, Esthetics and Implant obligates the clinician to truly become a scientist, therapist and artist to fulfill these categories of therapy. Excellent technical skills must be combined with sound biologic knowledge for a successful, predictable and lasting outcome.


Effects of Memory Load and Test Position on Short-Duration Sustained Attention Tasks.
The current study applies a dual-task working memory and vigilance task to examine sustained attention performance and perceived workload in a multi-instrument battery. In Experiment 1 we modified a task developed by Helton and Russell (2011) to examine declines in performance and to assess the effects of its position within a larger battery. Experiment 1 failed to reveal a sensitivity decrement, and test position revealed only spurious influence. Workload scores derived from the NASA-TLX fell at the high end of the scale, with mental and temporal demand receiving the highest ratings. In Experiment 2, we modified the dual task to place more emphasis on attention rather than working memory. Results revealed a significant decline in performance across the vigil for the perceptual sensitivity index A'. Test position (early vs. late) effects appeared with the reaction time variability measure, with performance becoming more variable when the task appeared in the latter half of the battery. Workload scores varied according to position in the battery: Workload scores were higher when the vigilance task appeared in the latter half of the battery. Practical and theoretical implications are discussed.


[Adenylate deaminase of the liver mitochondria in normal state and in alcoholic intoxication].
AMP-deaminases were isolated and partially purified from subfractions of soluble mitochondrial proteins of rat liver under normal conditions and in ethanol intoxication. Repeated freezing and thawing of the mitochondrial fractions from liver of rats, which were treated with ethanol (1 ml of 32% solution daily for 7 days, intraperitoneally), liberated into the subfraction of soluble mitochondrial proteins significantly less AMP-deaminases, as compared with the control animals. The enzyme preparations obtained from intoxicated and intact animals were quite similarly inactivated by controlled heating, deaminated at similar rates AMP, ADP, FAD and some other nitrogenous compounds (but did not deaminate adenosine and some structural analogues of AMP). However, an inhibitory effect of the structural analogues of AMP and of nucleosides was significantly higher towards the AMP-deaminase from healthy rats as compared with the corresponding enzyme preparations obtained from the ethanol-treated animals. The increase in velocity of enzymatic AMP deamination in the subfraction of soluble mitochondrial proteins apparently does not represent a suitable target for possible therapeutic approaches to control the phenomenon, observed in the experimental ethanol intoxication, of stimulation of the deaminating activity in total mitochondrial fraction of rat liver.


Health poverty among people with type 2 diabetes mellitus (T2DM) in Malaysia.
In the context of the escalating burden of diabetes in low and middle-income countries (LMICs), there is a pressing concern about the widening disparities in care and outcomes across socioeconomic groups. This paper estimates health poverty measures among individuals with type 2 diabetes mellitus (T2DM) in Malaysia. Using data from the National Diabetes Registry between 2009 and 2018, the study linked 932,855 people with T2DM aged 40-75 to death records. Cox proportional hazards models were used to estimate the 5-year survival probabilities for each patient, stratified by age and sex, while controlling for comorbidities and area-based indicators of socio-economic status (SES), such as district-level asset-based indices and night-time luminosity. Measures of health poverty, based on the Foster-Greer-Thorbecke (FGT) measures, were employed to capture excessive risk of premature mortality. Two poverty line thresholds were used, namely a 5% and 10% reduction in survival probability compared to age and sex-adjusted survival probability of the general population. Counterfactual simulations estimated the extent to which comorbidities contribute to health poverty. 43.5% of the sample experienced health poverty using the 5% threshold, and 8.9% were health poor using the 10% threshold. Comorbidities contribute 2.9% for males and 5.4% for females, at the 5% threshold. At the 10% threshold, they contribute 7.4% for males and 3.4% for females. If all patients lived in areas of highest night-light intensity, poverty would fall by 5.8% for males and 4.6% for females at the 5% threshold, and 4.1% for males and 0.8% for females at the 10% threshold. In Malaysia, there is a high incidence of health poverty among people with diabetes, and it is strongly associated with comorbidities and area-based measures of SES. Expanding the application of health poverty measurement, through a combination of clinical registries and open spatial data, can facilitate simulations for health poverty alleviation.


Association between lumbar discectomy and subsequent cervical discectomy.
Lumbar discectomy (LD) is one of the most common spinal surgical procedures. However, the remote effect of the cervical spine has seldom been discussed. The comparative incidence of cervical discectomy with or without a previous LD is an essential feature in predicting this effect. A cohort comparative study was conducted from the National Health Research Institute, Taiwan, over the period from 1996 to 2010. Patients who received LDs and patients who did not receive LDs in the same period were randomly selected to serve as samples for comparison. A total of 14 480 patients who did not undergo LD surgery and 3620 patients who received LDs were enrolled in this study. The incidence rates of discectomy-cervical in both groups were calculated from the follow-up period until the end of 2010. The baseline comorbidity history was determined for each patient. Comorbidities included facture and osteoporosis. During the follow-up period, the overall incidence rate of CD was significantly higher in patients who were treated with LD than in those who were not (24.7 vs. 2.73 per 10 000 person years). The risk of CD in the LD-treated cohort was ∼9-fold greater than that of the non-LD-treated cohort (HRs = 8.58, 95% CI = 5.38-13.7). Patients who have undergone LDs are at A greater risk of subsequent CDs, an increased risk that is evident in all patients regardless of demographics or the presence of fracture or osteoporosis.


IFAP syndrome "plus" seizures, mental retardation, and callosal hypoplasia.
Ichthyosis follicularis, congenital alopecia, and photophobia are typical features of a rare X-linked recessive disorder termed ichthyosis follicularis with atrichia and photophobia syndrome. A 3-year-old male with these findings and severe growth failure, mental retardation, generalized seizures, vascularizing keratitis, nail anomalies, inguinal hernia, and a normal chromosome constitution is presented. Two maternal male relatives were affected by the same condition. Magnetic resonance imaging revealed corpus callosum hypoplasia not described at present. Syndromes with alopecia, seizures, and mental retardation are analyzed on the basis of genetic and clinical results.


Patient safety and sociotechnical considerations for electronic handover tools in an Australian ehealth landscape.
The Australian Commission for Safety and Quality in Health Care (ACSQHC) coordinates national improvements in a range of complex health system problems including clinical handover, and has funded a range of handover improvement projects in Australia. One of these, the SafeTECH project in South Australia has developed guidelines for safe use of electronic handover tools. These guidelines were developed using evidence from three hospital case studies into the use of an electronic tool to support different types of shift-to-shift handover. This paper provides an overview of the project, and highlights challenges for patient safety in the design and use of electronic tools to support clinical handover in a busy clinical environment. The paper then considers these challenges within the broader context of the Australian ehealth landscape. Australia's National eHealth Transition Authority (NEHTA) is actively developing ehealth standards and infrastructure requirements for the electronic collection and secure exchange of health information. The paper argues for flexible standardisation in the design and implementation of electronic handover tools to ensure that all key dimensions of the challenges faced in ensuring patient safety are addressed.


Clinical effect of human-fibroblast-derived (Beta) interferon in treatment of adeno-virus epidemic keratoconjunctivitis and its complications.
The clinical studies reviewed here indicated the usefulness of topical application of Human-fibroblast-derived (Beta) interferon (Hu1FN-B) in treatment of Adeno-8 Epidemic-keratoconjunctivitis. A week treatment with 2-5 x 10(5) reference units daily doses, starting early as possible, reduced the length of the disease from 22 day to a week, and almost totally prevented the appearance of subepithelial keratitis which occurred in 57% of the control group. Possibly interferon should be given also prophylactically to individuals exposed to contagion. Our results encourage further investigation on the Hu1 FN-B use as a drug for treatment and prevention of viral infection.


A Systematic Review of Telehealth and Sport-Related Concussion: Baseline Testing, Diagnosis, and Management.
Background: The use of telehealth has increased as a result of the COVID-19 pandemic. As sports at all levels resume, sports medicine physicians may be interested in how telehealth can be used for concussion care. Questions/Purpose: We sought to assess how telehealth has been used in the baseline testing, diagnosis, and/or management of concussion. Secondarily, we sought to assess the strengths and weaknesses of telehealth for concussion care and identify aspects of concussion care for which telehealth has not yet been studied. Methods: A systematic review was performed in September 2020 of PubMed and Embase using the following terms: concuss*, "mild traumatic brain," "head injur*," telehealth, telemedicine, telecare, "mobile health," m-health, virtual. Studies included were original research articles investigating the use of telehealth in the care of concussion (including baseline testing, diagnosis, and management), published in English, and had full text available. Results: A total of 356 articles were screened, of which 5 were determined to meet inclusion criteria. These articles described the use of telehealth for managing concussion in military and rural settings. No articles involved the use of telehealth for baseline concussion testing of athletes or for sideline evaluation. Conclusion: Despite the limited original research on the use of telehealth for concussion care, the articles identified provide a foundation for exploring the potential value of telehealth in the office practice and sports team setting. Telehealth may expand the ability of a sports medicine physician to provide timely and effective concussion care to athletes during the COVID-19 pandemic and beyond. More rigorous research is needed.


A new and facile method to prepare uniform hollow MnO/functionalized mSiO₂ core/shell nanocomposites.
Trifunctional uniform nanoparticles comprising a manganese nanocrystal core and a functionalized mesoporous silica shell (MnO@mSiO(2)(Ir)@PEG, where Ir is an emissive iridium complex and PEG is polyethylene glycol) have been strategically designed and synthesized. The T(1) signal can be optimized by forming hollow core (H-MnO@mSiO(2)(Ir)@PEG) via a novel and facile etching process, for which the mechanism has been discussed in detail. Systematic investigation on correlation for longitudinal relaxation (T(1)) versus core shapes and shell silica porosity of the nanocomposites (MnO, H-MnO, MnO@SiO(2), MnO@mSiO(2), H-MnO@mSiO(2)) has been carried out. The results show that the worm-like nanochannels in the mesoporous silica shell not only increase water permeability to the interior hollow manganese oxide core for T(1) signal but also enhance photodynamic therapy (PDT) efficacy by enabling the free diffusion of oxygen. Notably, the H-MnO@mSiO(2)(Ir)@PEG nanocomposite with promising r(1) relaxivity demonstrates its versatility, in which the magnetic core provides the capability for magnetic resonance imaging, while the simultaneous red phosphorescence and singlet oxygen generation from the Ir complex are capable of providing optical imaging and inducing apoptosis, respectively.


[Collagen implant in refractory glaucoma surgery].
The problem of surgical treatment of refractory glaucoma (RG) in patients with corneal disease is studied. Glaucoma prior to penetrating keratoplasty is a significant risk factor for postkeratoplastic glaucoma that results in graft failure. The main tendency of RG surgery is implantation of draining devices. The aim of our study was to evaluate the efficacy of glaucoma surgery with collagen implant in patients with RG associated with severe corneal disease. 42 operations were analyzed. This operation technique let us achieve persistent hipotensive effect and corneal improvement. The insertion of collagen implant is absolutely safe in terms of corneal graft survival and it prevents scaring in surgery zone.


Metabolic and Anti-Inflammatory Protective Properties of Human Enriched Serum Following Artichoke Leaf Extract Absorption: Results from an Innovative Ex Vivo Clinical Trial.
The aging of our population is accompanied by an increased prevalence of chronic diseases. Among those, liver, joint and adipose tissue-related pathologies have a major socio-economic impact. They share common origins as they result from a dysregulation of the inflammatory and metabolic status. Plant-derived nutrients and especially polyphenols, exert a large range of beneficial effects in the prevention of chronic diseases but require clinically validated approaches for optimized care management. In this study, we designed an innovative clinical approach considering the metabolites produced by the digestive tract following the ingestion of an artichoke leaf extract. Human serum, enriched with metabolites deriving from the extract, was collected and incubated with human hepatocytes, human primary chondrocytes and adipocytes to determine the biological activity of the extract. Changes in cellular behavior demonstrated that the artichoke leaf extract protects hepatocytes from lipotoxic stress, prevents adipocytes differentiation and hyperplasia, and exerts chondroprotective properties in an inflammatory context. These data validate the beneficial health properties of an artichoke leaf extract at the clinical level and provide both insights and further evidence that plant-derived nutrients and especially polyphenols from artichoke may represent a relevant alternative for nutritional strategies addressing chronic disease issues.


[Switching sickness funds and risk compensation mechanisms in the statutory health insurance system in Germany--empirical results from the cooperative health research in the region of Augsburg (KORA)].
Since 1996, all citizens of the Federal Republic of Germany who are insured in the statutory health insurance system are entitled to switch their sickness fund. The rationale of this regulation was to strengthen elements of competition in this system in order to stimulate the sickness funds to improve the efficiency of health care and to respond to consumers' preferences. Simultaneously, to avoid the implicit incentives for sickness funds to engage in risk selection, a risk compensation mechanism was introduced, including as morbidity-related risk adjusters age, sex and incapacity to work. Based on the KORA survey S4 (1999/2001) we take the case of switching behaviour in the region of Augsburg, and analyse whether this risk adjustment scheme was working effectively. The results show that persons changing their sickness fund were characterised by a comparatively smaller burden of chronic diseases and by a less frequent utilization of inpatient health care. Under these conditions, differences in the contribution rates do not accurately reflect differences in the performance and efficiency of sickness funds. Moreover, the migration of good risk to sickness funds with favourable contribution rates threatens the principle of financial solidarity. Therefore, the system of risk equalisation has to be developed towards measuring the risk volume borne by the sickness funds more precisely than hitherto.


Conventional and unconventional secretory proteins expressed with silkworm bombyxin signal peptide display functional fidelity.
Growth factors are signaling molecules which orchestrate cell growth, proliferation and differentiation. The majority are secreted proteins, exported through the classical endoplasmic reticulum (ER)/Golgi-dependent pathway, but a few are released by unconventional ER/Golgi-independent means. Human fibroblast growth factor 2 (FGF2) and insulin-like growth factor 1 (IGF1), are canonical prototypes secreted by the unconventional and conventional pathway, respectively. We herein examined whether expression of these two growth factors in the Bombyx mori nucleopolyhedrovirus (BmNPV)-based silkworm expression system with its innate signal peptide, bombyxin, secures structural homogeneity at the signal peptide cleavage site regardless of the native secretory route. Proteomic analysis mapped structural microheterogeneity of signal peptide cleavage at the amino terminus of FGF2, whereas IGF1 displayed homogeneous amino-terminal cleavage with complete removal of the bombyxin signal peptide. A cell proliferation assay revealed potent functional activity of both FGF2 and IGF1, suggesting that FGF2 amino-terminal microheterogeneity does not alter mitogenic activity. These findings demonstrate that the occurrence of amino-terminal structural homogeneity may be associated with the original secretion mechanism of a particular growth factor. Furthermore, our results highlight the bombyxin signal peptide as a reliable secretion sequence applicable to mass production of functionally active secretory proteins in a silkworm-based expression platform.


Histopathological findings in the iris of dapsone treated leprosy patients.
From 43 Nepalese leprosy patients skin smear negative, and treated with dapsone (diamino diphenyl sulphone), and without any sign of active leprosy or iritis, specimens from iridectomy during cataract surgery were studied histopathologically. Of 49 iris specimens only six (12%) were found to be without any histopathological change. Atrophy of the iris stroma was seen in 63% and neovascularisation in 6% of all cases. In 16% in which the dilator muscle could be detected, it was atrophic, and in 11% the pigmented epithelium was thinned and atrophic. Cellular inflammatory infiltrations were seen in 88% of all specimens. They were mostly slight in eyes which before operation had been without posterior synechiae of the iris. In most of the eyes in which posterior synechiae had been present moderate or heavy inflammatory cell infiltrates composed of lymphocytes and plasma cells, often associated with macrophages, neutrophils, or eosinophils, were found. In five iris specimens acid fast bacilli were present. This raises the question whether these can survive systemically despite dapsone chemotherapy in the iris, thus leading to dapsone-resistant leprosy and to recurrent iritis.


Viral promoters can initiate expression of toxin genes introduced into Escherichia coli.
The expression of recombinant proteins in eukaryotic cells requires the fusion of the coding region to a promoter functional in the eukaryotic cell line. Viral promoters are very often used for this purpose. The preceding cloning procedures are usually performed in Escherichia coli and it is therefore of interest if the foreign promoter results in an expression of the gene in bacteria. In the case molecules toxic for humans are to be expressed, this knowledge is indispensable for the specification of safety measures. We selected five frequently used viral promoters and quantified their activity in E. coli with a reporter system. Only the promoter from the thymidine kinase gene from HSV1 showed no activity, while the polyhedrin promoter from baculovirus, the early immediate CMV promoter, the early SV40 promoter and the 5' LTR promoter from HIV-1 directed gene expression in E. coli. The determination of transcription start sites in the immediate early CMV promoter and the polyhedrin promoter confirmed the existence of bacterial -10 and -35 consensus sequences. The importance of this heterologous gene expression for safety considerations was further supported by analysing fusions between the aforementioned promoters and a promoter-less cytotoxin gene. According to our results a high percentage of viral promoters have the ability of initiating gene expression in E. coli. The degree of such heterologous gene expression can be sufficient for the expression of toxin genes and must therefore be considered when defining safety measures for the handling of corresponding genetically modified organisms.


Exploring Dementia Care Systems Across the African Caribbean Diaspora: A Scoping Review and Consultation Exercise.
Understanding the influences of marginalized cultural and social identities as experienced by the African Caribbean diaspora within the context of dementia care is essential to minimize the gaps in current practice and policy in the health care setting. This study explores the impact of marginalized identities upon the meaning-making process, access to services and experience of care provisions through a scoping review and consultancy exercises with key stakeholders. Fourteen databases were searched using key terms. Primary studies in English, any year, study design, and country of origin were eligible. Titles, abstracts, and full texts were screened for inclusion and data were extracted in stages. Thematic analysis was performed and the findings were discussed in a series of consultation meetings with people with dementia, carers, and health care professionals in Manchester (United Kingdom) and Jamaica. The scoping review retrieved n = 1,989 research articles. Nineteen were included, most were qualitative (n = 14), 3 quantitative, and 2 mixed-method. The findings revealed limited insight into cultural and multiple individual identities in explaining conceptualization and service access. Consultation meetings confirmed these findings and highlighted differences in health care services and systems in the United Kingdom and Jamaica. This study suggests there is a complex interaction of sociocultural processes that marginalize African Caribbean persons in and across various national settings within the context of dementia care. The study highlights the importance of acknowledging and addressing how prevalent racialized- and class-based divides and related marginalized social locations are reflected in inequities in access to and use of dementia services.


Results of a multicentre clinical trial of the solid-phase enzyme immunoassay for hepatitis B surface antigen.
The results obtained in a multicentre clinical trial of an enzyme immunoassay (EIA) method for hepatitis B surface antigen (HBsAg) (65,451 sera tested) have demonstrated that this new test has a significantly higher sensitivity than a reversed haemagglutination test (rHA). In a part of the trial, EIA was also compared with radioimmunoassay (RIA). Only a small number of discrepant results was obtained with these two tests, indicating similar sensitivities. No definite conclusion about a difference in sensitivities could be drawn from these results. Although the specificity of the EIA screening test is lower than that of rHA and RIA, the mean percentage of false positives was 2.2% of the total number of donor samples screened. Presumptive positives in EIA were subjected to a confirmatory test based on neutralization with human antibodies to HBsAg. After elimination of false positives in EIA screening, there was excellent agreement between EIA and RIA results.


Role of ooplasm in nuclear and nucleolar remodeling of intergeneric somatic cell nuclear transfer embryos during the first cell cycle.
Initially, development of the zygote is under control of the oocyte ooplasm. However, it is presently unknown if and to what extent is the ooplasm able to interact with a transferred somatic cell from another species in the context of interspecies somatic cell nuclear transfer (SCNT). Here, one-cell stage embryos were processed at different points in time post activation (2 hpa, 4 hpa, 8 hpa, and 12 hpa) for detailed nuclear and nucleolar analysis by TEM, and immunofluorescence for visualization of nucleolar proteins related to transcription (UBF) and processing (fibrillarin). Bovine and porcine intergeneric SCNT embryos were compared to their parthenogenetic counterparts to assess the effects of the introduced somatic cell. Despite the absence of morphological remodeling (premature chromatin condensation, nuclear envelope breakdown), reconstructed embryos showed nuclear and nucleolar precursor body (NPB) morphology similar to the host ooplasm, which, together with detected posttranslational activity of somatic cell introduced into the bovine ooplasm, suggests a universal function of ooplasmic factors. However, the lack of distinct UBF localization in intergeneric embryos indicates failures in sequence-specific interactions between the ooplasm and chromatin of another genus. In conclusion, the results demonstrate a possible reason why the intergeneric SCNT embryos never reached the full term.


Role of a rat membrane inhibitor of complement in anti-basement membrane antibody-induced renal injury.
In the kidneys of anti-glomerular basement membrane (anti-GBM) antibody disease, binding of antibodies to tubular basement membrane (TBM) is often observed. The present work was performed to explore the mechanisms of binding of anti-GBM antibodies to TBM in vivo with special reference to 5I2Ag, a rat membrane inhibitor of complement which regulates complement activation at C3 convertase level. To suppress functions of renal 5I2Ag, F(ab')2 fragment of 5I2 (a neutralizing mAb against 5I2Ag) was perfused in the left kidney and then blood circulation was restored. Mild proteinuria ( < 10 mg/16 hr) was observed during first several days. Five days later, there were tubulointerstitial injuries defined by tubular vimentin staining and leukocyte infiltration. Significant deposition of C3 was observed in the capillaries and in TBM. In rats intravenously injected with rabbit anti-rat GBM antibodies five minutes after kidney perfusion with 5I2, strong binding of rabbit IgG to TBM was observed at one and five days after injection. Although these rats showed mild proteinuria comparable to those perfused with 5I2 and those injected with normal rabbit serum, tubulointerstitial injury was significantly enhanced at Day 5. In contrast, rats perfused with irrelevant mAb and injected with anti-GBM antibodies did not show any significant binding of antibodies to TBM nor tubulointerstitial injury. Furthermore, rats which were made proteinuric by puromycin aminonucleoside and injected with anti-GBM antibodies did not show any significant binding of rabbit IgG to TBM. These results indicate that 5I2Ag, a rat membrane inhibitor of complement at the C3 convertase level, regulates vascular permeability in the living kidney, and that dysfunction or decreased expression of this molecule leads to increased accessibility of anti-GBM antibodies to TBM.


Two cases of duodenal obstruction due to a congenital web.
We present two cases of windsock deformity; both were rare in location and one had a rare associated anomaly. In the first case, the windsock was observed in the fourth part of duodenum, causing partial intestinal obstruction. In the second case, the windsock was located in the third part of the duodenum.


Processing of different types of social threat in shyness: Preliminary findings of distinct functional neural connectivity.
Current theory suggests that the processing of different types of threat is supported by distinct neural networks. Here we tested whether there are distinct neural correlates associated with different types of threat processing in shyness. Using fMRI and multivariate techniques, we compared neural responses and functional connectivity during the processing of imminent (i.e., congruent angry/angry face pairs) and ambiguous (i.e., incongruent angry/neutral face pairs) social threat in young adults selected for high and low shyness. To both types of threat processing, non-shy adults recruited a right medial prefrontal cortex (mPFC) network encompassing nodes of the default mode network involved in automatic emotion regulation, whereas shy adults recruited a right dorsal anterior cingulate cortex (dACC) network encompassing nodes of the frontoparietal network that instantiate active attentional and cognitive control. Furthermore, in shy adults, the mPFC interacted with the dACC network for ambiguous threat, but with a distinct network encompassing nodes of the salience network for imminent threat. These preliminary results expand our understanding of right mPFC function associated with temperamental shyness. They also provide initial evidence for differential neural networks associated with shy and non-shy profiles in the context of different types of social threat processing.


Fore-aft asymmetric flocking.
We show that fore-aft asymmetry, a generic feature of living organisms and some active matter systems, can have a strong influence on the collective properties of even the simplest flocking models. Specifically, an arbitrarily weak asymmetry favoring front neighbors changes qualitatively the phase diagram of the Vicsek model. A region where many sharp traveling band solutions coexist is present at low noise strength, below the Toner-Tu liquid, at odds with the phase-separation scenario well describing the usual isotropic model. Inside this region, a "banded-liquid" phase with algebraic density distribution coexists with band solutions. Linear stability analysis at the hydrodynamic level suggests that these results are generic and not specific to the Vicsek model.


Metal-Free Oxidative Formation of Aryl Esters by Catalytic Coupling of Acyl and Sulfonyl Chlorides with Arylboronic Acids.
A practical and efficient synthesis of aryl esters was developed through metal-free oxidation. This reaction employs stable and readily available acyl or sulfonyl chlorides and arylboronic acids as the starting materials and proceeds under mild reaction conditions without additional precious metal catalysts. This new strategy exhibits broad substrate tolerance and operational simplicity and gives diverse aryl esters in moderate to high yields.


Sleep and dreaming are for important matters.
Recent studies in sleep and dreaming have described an activation of emotional and reward systems, as well as the processing of internal information during these states. Specifically, increased activity in the amygdala and across mesolimbic dopaminergic regions during REM sleep is likely to promote the consolidation of memory traces with high emotional/motivational value. Moreover, coordinated hippocampal-striatal replay during NREM sleep may contribute to the selective strengthening of memories for important events. In this review, we suggest that, via the activation of emotional/motivational circuits, sleep and dreaming may offer a neurobehavioral substrate for the offline reprocessing of emotions, associative learning, and exploratory behaviors, resulting in improved memory organization, waking emotion regulation, social skills, and creativity. Dysregulation of such motivational/emotional processes due to sleep disturbances (e.g., insomnia, sleep deprivation) would predispose to reward-related disorders, such as mood disorders, increased risk-taking and compulsive behaviors, and may have major health implications, especially in vulnerable populations.


Capillary Forces Lead to Pendant Crystals at the Liquid-Air Interface of Evaporating Salt Solutions.
We investigated the nucleation and growth processes of individual NaCl crystals from an evaporating salt solution that is supersaturated. We find that crystals nucleate at the liquid/vapor interface, resulting in distinct "pendant" crystals, which reach millimeter dimensions. The substantial size of the crystals induces deformation of the interface. This process and the evaporation rate, in turn, determine the final crystal shape, which features a deep central cavity. Our findings reveal that a delicate balance exists between gravity, buoyancy, and the surface tension of the liquid/vapor interface that allows the crystal to remain pendant. When the contact angle of the crystal with the meniscus reaches 90°, the crystal disconnects from the interface and falls into the solution. We quantitatively predict the critical mass at which this occurs.


A model to predict long-term performance of vapor-phase bioreactors: a cellular automaton approach.
A novel numerical model was constructed to predict performance of vapor-phase bioreactors (VPBs) operated over extended periods. This model incorporates two unique features to simulate changes in pollutant removal efficiency and biomass accumulation: (1) total biomass is divided into two microbial components, active and inactive biomass, and (2) biomass growth and biofilm thickness changes are simulated by means of a cellular automaton (CA) approach. The CA approach, a differential-discrete algorithm, numerically allows the excess quantity of biomass in each numerical element to move toward the biofilm surface as biomass accumulates. One set of experimental bioreactor data was used to estimate unknown model parameters. A 90-day simulation using the estimated parameters agreed with pollutant removal and biomass accumulation profiles determined experimentally. Four additional model simulations using the same estimated model parameters were generally consistent with experimental data collected from a series of toluene-degrading VPBs operated over a range of conditions. Model predictions imply that the decline in bioreactor performance observed over extended operation was caused by a decline in the active biomass fraction and a decrease in the biofilm specific surface area. This CA model provides insight into biomass accumulation during complex bioreactor operation and improves our capability to predict long-term VPB performance.


Development of a variable focal length concave mirror for on-shot thermal lens correction in rod amplifiers.
An optical surface of variable concave parabolic shape and a clear aperture of 30 mm was created using two rings to deform a flat 50.8 mm diameter mirror. The deformable mirror assembly was modeled using finite element analysis software as well as analytical solutions. Measured parabolic surface deformation showed good agreement with those models. Mirror performance was quantitatively studied using an interferometer and focal lengths from hundreds of meters down to the meter scale have been achieved. In this publication, the deformable mirror has been applied to compensate on shot thermal lensing in 16 mm diameter and 25 mm diameter Nd:Phosphate glass rod amplifiers by using only a single actuator. The possibility to rapidly change focal lengths across two to three orders of magnitude has applications for remote sensing, such as laser induced breakdown spectroscopy, LIDAR, and control of laser filament formation.


Prevalence of adenocarcinoma at esophagectomy for Barrett's esophagus with high grade dysplasia.
Barrett's esophagus with high grade dysplasia (HGD) may require surgical resection because of the risk of concomitant adenocarcinoma. The prevalence of invasive, occult carcinoma (≥stage 1B) in this setting has varied. We investigated the association of adenocarcinoma at operative resection for high grade dysplasia. Using an electronic medical record, we identified patients who underwent esophagectomy for high grade dysplasia at the University of Pittsburgh Medical Center between 1993 and 2007. Preoperative diagnosis was confirmed by reviewing endoscopic, radiologic and pathology reports. Postoperative pathology reports were compared to the preoperative diagnosis. 68 patients (12 females and 56 males) with a preoperative diagnosis of high grade dysplasia underwent operative resection. The mean age was 64 years (range 36 to 86 years). Of 68 patients, 12 (17.6%) had adenocarcinoma, 2 (2.9%) were downgraded to low grade dysplasia, and 54 (79.4%) were confirmed as HGD. Of the 12 patients with adenocarcinoma, 4 (5.9% of total cohort) had intramucosal cancer (Stage 1A) and 8 (11.7% of total cohort) had invasive cancer with submucosal invasion or more advanced disease. Of the 8 patients with invasive adenocarcinoma, 4 did not have preoperative endoscopic or radiologic testing suggestive of advanced disease. The overall prevalence of adenocarcinoma in association with a preoperative diagnosis of HGD was 17.6%. Invasive adenocarcinoma was present in 11.7% of subjects and was clinically occult in 5.9%.


Longitudinal changes and variation in human DNA methylation analysed with the Illumina MethylationEPIC BeadChip assay and their implications on forensic age prediction.
DNA methylation, a pivotal epigenetic modification, plays a crucial role in regulating gene expression and is known to undergo dynamic changes with age. The present study investigated epigenome-wide methylation profiles in 64 individuals over two time points, 15 years apart, using the Illumina EPIC850k arrays. A mixed-effects model identified 2821 age-associated differentially methylated CpG positions (aDMPs) with a median rate of change of 0.18% per year, consistent with a 10-15% change during a human lifespan. Significant variation in the baseline DNA methylation levels between individuals of similar ages as well as inconsistent direction of change with time across individuals were observed for all the aDMPs. Twenty-three of the 2821 aDMPs were previously incorporated into forensic age prediction models. These markers displayed larger changes in DNA methylation with age compared to all the aDMPs and less variation among individuals. Nevertheless, the forensic aDMPs also showed inter-individual variations in the direction of DNA methylation changes. Only cg16867657 in ELOVL2 exhibited a uniform direction of the age-related change among the investigated individuals, which supports the current knowledge that CpG sites in ELOVL2 are the best markers for age prediction.


A selective thyroid hormone β receptor agonist enhances human and rodent oligodendrocyte differentiation.
Nerve conduction within the mammalian central nervous system is made efficient by oligodendrocyte-derived myelin. Historically, thyroid hormones have a well described role in regulating oligodendrocyte differentiation and myelination during development; however, it remains unclear which thyroid hormone receptors are required to drive these effects. This is a question with clinical relevance since nonspecific thyroid receptor stimulation can produce deleterious side-effects. Here we report that GC-1, a thyromimetic with selective thyroid receptor β action and a potentially limited side-effect profile, promotes in vitro oligodendrogenesis from both rodent and human oligodendrocyte progenitor cells. In addition, we used in vivo genetic fate tracing of oligodendrocyte progenitor cells via PDGFαR-CreER;Rosa26-eYFP double-transgenic mice to examine the effect of GC-1 on cellular fate and find that treatment with GC-1 during developmental myelination promotes oligodendrogenesis within the corpus callosum, occipital cortex and optic nerve. GC-1 was also observed to enhance the expression of the myelin proteins MBP, CNP and MAG within the same regions. These results indicate that a β receptor selective thyromimetic can enhance oligodendrocyte differentiation in vitro and during developmental myelination in vivo and warrants further study as a therapeutic agent for demyelinating models.


Cytogenetics of extramedullary manifestations in multiple myeloma.
Extramedullary disease in patients with multiple myeloma is a rare event, occurring mostly in advanced disease or relapse. Outcome is poor and prognostic factors predicting the development of extramedullary disease have not been defined. We investigated cytogenetic alterations of myeloma cells in different extramedullary manifestations by adapting the fluorescence in situ hybridization (FISH) technique in combination with cytoplasmic immunoglobulin staining to study the cytogenetics of plasma cell tumours on paraffin embedded material. Thirty six patients were investigated: 19 with extramedullary disease, 11 with skeletal extramedullary disease and six with solitary extramedullary plasmacytoma. The first two groups showed the following results: del(17p13) 32% vs. 27%, del(13q14) 35% vs. 27%, MYC-overrepresentation 28% vs. 18% and t(4;14) 37% vs. 18%. We detected an overall higher incidence of del(17p13) in both groups compared to data from bone marrow samples of multiple myeloma reported to date (range 7-16%). The solitary extramedullary plasmacytomas presented overall less cytogenetic aberrations than the other groups. Most important, three patients with extramedullary disease and one with skeletal extramedullary disease presented different FISH findings in the extramedullary tumour compared to their bone marrow plasma cells. del(17p13), occurring additional in three of four cases, seems a strong marker for extramedullary progression of myeloma.


Trauma-focused cognitive-behavioral therapy for posttraumatic stress disorder in three-through six year-old children: a randomized clinical trial.
The evidence base for trauma-focused cognitive behavioral therapy (TF-CBT) to treat posttraumatic stress disorder (PTSD) in youth is compelling, but the number of controlled trials in very young children is few and limited to sexual abuse victims. These considerations plus theoretical limitations have led to doubts about the feasibility of TF-CBT techniques in very young children. This study examined the efficacy and feasibility of TF-CBT for treating PTSD in three- through six-year-old children exposed to heterogeneous types of traumas. Procedures and feasibilities of the protocol were refined in Phase 1 with 11 children. Then 64 children were randomly assigned in Phase 2 to either 12-session manualized TF-CBT or 12-weeks wait list. In the randomized design the intervention group improved significantly more on symptoms of PTSD, but not on depression, separation anxiety, oppositional defiant, or attention deficit/hyperactivity disorders. After the waiting period, all participants were offered treatment. Effect sizes were large for PTSD, depression, separation anxiety, and oppositional defiant disorders, but not attention-deficit/hyperactivity disorder. At six-month follow-up, the effect size increased for PTSD, while remaining fairly constant for the comorbid disorders. The frequencies with which children were able to understand and complete specific techniques documented the feasibility of TF-CBT across this age span. The majority were minority race (Black/African-American) and without a biological father in the home, in contrast to most prior efficacy studies. These preliminary findings suggest that TF-CBT is feasible and more effective than a wait list condition for PTSD symptoms, and the effect appears lasting. There may also be benefits for reducing symptoms of several comorbid disorders. Multiple factors may explain the unusually high attrition, and future studies ought to oversample on these demographics to better understand this understudied population.


E-therapies in England for stress, anxiety or depression: what is being used in the NHS? A survey of mental health services.
To document the range of web and smartphone apps used and recommended for stress, anxiety or depression by the National Health Service (NHS) in England. The study was conducted using Freedom of Information (FOI) requests and systematic website searches. Data were collected via FOI requests to NHS services between 13 February 2015 and 31 March 2015, and searches conducted on NHS apps library websites between 26 March 2015 and 2 November 2015. Data were compiled from responses to: (1) FOI requests sent to all Improving Access to Psychological Therapies (IAPT) services and NHS Mental Health Trusts in England and (2) NHS apps library search results. A total of 61 (54.95%) out of the then 111 IAPT service providers responded, accounting for 191 IAPT services, and all 51 of the then NHS Mental Health Trusts responded. The results were that 13 different web apps and 35 different smartphone apps for depression, anxiety or stress were available through either referral services or the online NHS Apps Libraries. The apps used and recommended vary by area and by point of access (online library/IAPT/trust). Future research is required to establish the evidence base for the apps that are being used in the NHS in England. There is a need for service provision to be based on evidence and established guidelines.


An applied simulation model for estimating the supply of and requirements for registered nurses based on population health needs.
Aging populations, limited budgets, changing public expectations, new technologies, and the emergence of new diseases create challenges for health care systems as ways to meet needs and protect, promote, and restore health are considered. Traditional planning methods for the professionals required to provide these services have given little consideration to changes in the needs of the populations they serve or to changes in the amount/types of services offered and the way they are delivered. In the absence of dynamic planning models that simulate alternative policies and test policy mixes for their relative effectiveness, planners have tended to rely on projecting prevailing or arbitrarily determined target provider-population ratios. A simulation model has been developed that addresses each of these shortcomings by simultaneously estimating the supply of and requirements for registered nurses based on the identification and interaction of the determinants. The model's use is illustrated using data for Nova Scotia, Canada.


Nrf2 modulates contractile and metabolic properties of skeletal muscle in streptozotocin-induced diabetic atrophy.
The role of Nrf2 in disease prevention and treatment is well documented; however the specific role of Nrf2 in skeletal muscle is not well described. The current study investigated whether Nrf2 plays a protective role in an STZ-induced model of skeletal muscle atrophy. Modulation of Nrf2 through siRNA resulted in a more robust differentiation of C2C12s, whereas increasing Nrf2 with sulforaphane treatment inhibited differentiation. Diabetic muscle atrophy was not dramatically influenced by Nrf2 genotype, since no differences were observed in total atrophy (all fiber types combined) between WT+STZ and KO+STZ animals. Nrf2-KO animals however illustrated alterations in muscle size of Fast, Type II myosin expressing fibers. KO+STZ animals show significant alterations in myosin isoform expression in the GAST. Similarly, KO controls mimic both WT+STZ and KO+STZ muscle alterations in mitochondrial subunit expression. PGC-1α, a well-established player in mitochondrial biogenesis and myosin isoform expression, was decreased in KO control, WT+STZ and KO+STZ SOL muscle. Similarly, PGC-1α protein levels are correlated with Nrf2 levels in C2C12s after modulation by Nrf2 siRNA or sulforaphane treatment. We provide experimental evidence indicating Nrf2 plays a role in myocyte differentiation and governs molecular alterations in contractile and metabolic properties in an STZ-induced model of muscle atrophy.


Insulin-like growth factor-1 regulates the mechanosensitivity of chondrocytes by modulating TRPV4.
Both mechanical and biochemical stimulation are required for maintaining the integrity of articular cartilage. However, chondrocytes respond differently to mechanical stimuli in osteoarthritic cartilage when biochemical signaling pathways, such as Insulin-like Growth Factor-1 (IGF-1), are altered. The Transient Receptor Potential Vanilloid 4 (TRPV4) channel is central to chondrocyte mechanotransduction and regulation of cartilage homeostasis. Here, we propose that changes in IGF-1 can modulate TRPV4 channel activity. We demonstrate that physiologic levels of IGF-1 suppress hypotonic-induced TRPV4 currents and intracellular calcium flux by increasing apparent cell stiffness that correlates with actin stress fiber formation. Disruption of F-actin following IGF-1 treatment results in the return of the intracellular calcium response to hypotonic swelling. Using point mutations of the TRPV4 channel at the microtubule-associated protein 7 (MAP-7) site shows that regulation of TRPV4 by actin is mediated via the interaction of actin with the MAP-7 domain of TRPV4. We further highlight that ATP release, a down-stream response to mechanical stimulation in chondrocytes, is mediated by TRPV4 during hypotonic challenge. This response is significantly abrogated with IGF-1 treatment. As chondrocyte mechanosensitivity is greatly altered during osteoarthritis progression, IGF-1 presents as a promising candidate for prevention and treatment of articular cartilage damage.


Ethics in research with human beings: from knowledge to practice.
In Brazil, resolution 196/96 and its amendments regulate the preservation of rights, respect and dignity of human beings involved in research. To analyze the adequacy of Free Communications (FC) presented during the XVIII Congresso Pernambucano de Cardiologia to resolution 196/96. During a cross-sectional study, interviews were carried out with the authors of the FC presented at the Congress and the abstracts of the studies were assessed in order to identify the need for previous approval by a Research Ethics Committee (REC). A total of 90 FC were presented and, in most of them (86.8%), medical files were the most commonly used source of data. Only 23.1% of the FC were submitted to the assessment of a REC and 15.4% of them used a Free and Informed Consent Form (FICF). Among the authors whose studies were not assessed by a REC, 65.6% stated that this conduct was not necessary and 18% of them were unaware of the need to submit the study to such assessment. The written authorization given by the institution where the FC were carried out was not obtained in 56.6% of the studies. Most of the authors (80.0%) stated that they had never read Resolution 196/96. The proportion of FC submitted to a REC was significantly higher among authors that had read Resolution 196/96 (p = 0.005). The FC design influenced the non-submission of the studies to a REC (p < 0.001). Most of the FC that were authorized by the institution where they were carried out were submitted to a REC (p < 0.001). Most of the FC presented at the Congress did not follow the Brazilian regulations concerning the ethics in research.


On the nature of long range electronic coupling in a medium: distance and orientational dependence for chromophores in molecular aggregates.
The electronic coupling that mediates energy transfer in molecular aggregates is theoretically investigated using the principles of quantum electrodynamics (QED). In this context, both the electromagnetic tensor and rate equation relating to these couplings are re-examined with a focus on the role of the relative distance and orientation of transition dipole moment pairs, considering near-, intermediate-, and far-zone contributions to the coupling. The QED based coupling terms are investigated both analytically and numerically, and they are physically interpreted in terms of the character of the mediating (virtual) photons. The spatial dependence of the couplings for a two-dimensional molecular aggregate of ordered and isotropic transition dipole moments is numerically calculated. Further, Pauli Master Equations are employed for a one-dimensional chain of molecules and donor-acceptor pairs, to investigate the importance of intermediate- and far-zone contributions to the electronic coupling on electronic energy transfer dynamics. The results indicate that although Förster theory is often qualitatively and quantitatively correct for describing electronic energy transfer (EET) processes, intermediate- and far-zone coupling terms could sometimes be non-negligible for correctly describing EET in natural and artificial, mesoscopic, solar energy harvesting systems. In particular, the results indicate that these terms are non-negligible when using Förster resonance energy transfer spectroscopic ruler techniques for distances >10 nm.


Intraoperative lactate measurements are not predictive of death in high risk surgical patients.
An increased lactate level is classically considered a marker for poorer prognosis, however little information is available on intraoperative lactate's kinetics and its connection with prognosis. This study aimed to evaluate the time when perioperative lactate is most relevant for prognosis. This was an observational prospective study conducted in a tertiary hospital. Patients with requested intensive care unit postoperative stay, aged > 18 years, undergoing major surgery were included. Palliative surgery patients and those with heart and/or severe liver failure were excluded. Arterial lactate levels were measured immediately before the surgery start (T0), after anesthesia induction (T1), 3 hours after the surgery start (T2), intensive care unit admission (T3) and 6 hours after the intensive care unit admission (T4). Sixty seven patients were included. The mean lactate values for the patients' T0, T1, T2 and T4 were 1.5 ± 0.8 mmol/L, 1.5 ± 0.7 mmol/L, 1.8 ± 1.2 mmol/L, 2.7 ± 1.7 mmol/L and 3.1 ± 2.0 mmol/L, respectively. The hospital mortality rate was 25.8%, and surviving and non-surviving patients lactate values in the intensive care unit were 2.5 ± 1. and 4.8 ± 2.8 mmol/L (P < 0.0001), respectively. The other times measurements showed no statistically significant differences between the groups. In surgical patients, intraoperative arterial lactate levels failed to show a predictive value; however during the postoperative period, this assessment was shown to be useful for hospital mortality prediction.