The evolution of mindfulness-based physical interventions in breast cancer survivors.
Survivors of breast cancer are faced with a multitude of medical and psychological impairments during and after treatment and throughout their lifespan. Physical exercise has been shown to improve survival and recurrence in this population. Mind-body interventions combine a light-moderate intensity physical exercise with mindfulness, thus having the potential to improve both physical and psychological sequelae of breast cancer treatments. We conducted a review of mindfulness-based physical exercise interventions which included yoga, tai chi chuan, Pilates, and qigong, in breast cancer survivors. Among the mindfulness-based interventions, yoga was significantly more studied in this population as compared to tai chi chuan, Pilates, and qigong. The participants and the outcomes of the majority of the studies reviewed were heterogeneous, and the population included was generally not selected for symptoms. Yoga was shown to improve fatigue in a few methodologically strong studies, providing reasonable evidence for benefit in this population. Improvements were also seen in sleep, anxiety, depression, distress, quality of life, and postchemotherapy nausea and vomiting in the yoga studies. Tai chi chuan, Pilates, and qigong were not studied sufficiently in breast cancer survivors in order to be implemented in clinical practice.


The use of remotely sensed environmental data in the study of malaria.
Mapping and anticipating risk is a major issue in the fight against malaria, a disease causing an estimated one million deaths each year. Approximately half the world's population is at risk and it is of prime importance to evaluate the burden of malaria at the spatial as well as the temporal level. The role of the environment with regard to the determinants of transmission and burden of the disease are described followed by a discussion of special issues such as urban malaria, human population mapping and the detection of changes at the temporal scale. Risk maps at appropriate scales can provide valuable information for targeted control and the present review discusses the essentials of principles, methods, advantages and limitations of remote sensing along with a presentation of ecological, meteorological and climatologic data which rule the distribution of malaria. The panel of commonly used analytic methods is examined and the methodological limitations are highlighted. A review of the literature details the increasing interest in the use of remotely sensed data in the study of malaria, by mapping or modeling several malariometric indices such as prevalence, morbidity and mortality, which are discussed with reference to vector breeding, vector density and entomological inoculation rate, estimates of which constitute the foundation for understanding endemicity and epidemics.


First Report of Stem Blight Caused by Calonectria colhounii (Anamorph Cylindrocladium colhounii) on Greenhouse-Grown Blueberries in the United States.
Necrotic stems and leaves were observed on 2- to 4-month-old, rooted microshoot plants (Vaccinium corymbosum L. 'Liberty' and 'Bluecrop', V. angustifolium Aiton 'Putte', and V. corymbosum × V. angustifolium 'Polaris') in a Michigan greenhouse in 2008 and 2009. As the disease progressed, leaves fell off and 80 to 100% of the plants died in some cases. Root rot symptoms were also observed. A fungus was isolated from stem lesions. On potato dextrose agar (PDA), cultures first appeared light tan to orange, then rusty brown and zonate with irregular margins. Chains of orange-brown chlamydospores were abundant in the medium. Macroconidiophores were penicillately branched and had a stipe extension of 220 to 275 × 2.5 μm with a narrowly clavate vesicle, 3 to 4 μm wide at the tip. Conidia were hyaline and cylindrical with rounded ends, (1-)3-septate, 48 to 73 × 5 to 7 (average 60 × 5.5) μm and were held together in parallel clusters. Perithecia were globose to subglobose, yellow, 290 to 320 μm high, and 255 to 295 μm in diameter. Ascospores were hyaline, 2- to 3-septate, guttulate, fusoid with rounded ends, slightly curved, and 30 to 88 × 5 to 7.5 (average 57 × 5.3) μm. On the basis of morphology, the fungus was identified as Calonectria colhounii Peerally (anamorph Cylindrocladium colhounii Peerally) (1,2). The internal transcribed spacer region (ITS1 and ITS2) of the ribosomal DNA and the β-tubulin gene were sequenced (GenBank Accession Nos. HQ909028 and JF826867, respectively) and compared with existing sequences using BLASTn. The ITS sequence shared 99% maximum identity with that of Ca. colhounii CBS 293.79 (GQ280565) from Java, Indonesia, and the β-tubulin sequence shared 97% maximum identity with that of Ca. colhounii CBS 114036 (DQ190560) isolated from leaf spots on Rhododendron sp. in North Carolina. The isolate was submitted to the Centraalbureau voor Schimmelcultures in the Netherlands (CBS 129628). To confirm pathogenicity, 5 ml of a conidial suspension (1 × 105/ml) were applied as a foliar spray or soil drench to four healthy 'Bluecrop' plants each in 10-cm plastic pots. Two water-sprayed and two water-drenched plants served as controls. Plants were misted intermittently for 2 days after inoculation. After 7 days at 25 ± 3°C, drench-inoculated plants developed necrotic, sporulating stem lesions at the soil line, while spray-inoculated plants showed reddish brown leaf and stem lesions. At 28 days, three drench-inoculated and one spray-inoculated plant had died, while others showed stem necrosis and wilting. No symptoms were observed on control plants. Fungal colonies reisolated from surface-disinfested symptomatic stem, leaf, and root segments appeared identical to the original isolate. Cy. colhounii was reported to cause a leaf spot on blueberry plants in nurseries in China (3), while Ca. crotalariae (Loos) D.K. Bell & Sobers (= Ca. ilicicola Boedijn & Reitsma) causes stem and root rot of blueberries in North Carolina (4). To our knowledge, this is the first report of Ca. colhounii causing a disease of blueberry in Michigan or the United States. Because of its destructive potential, this pathogen may pose a significant threat in blueberry nurseries. References: (1) P. W. Crous. Taxonomy and Pathology of Cylindrocladium (Calonectria) and Allied Genera. The American Phytopathological Society, St. Paul, MN, 2002. (2) L. Lombard et al. Stud. Mycol. 66:31, 2010. (3) Y. S. Luan et al. Plant Dis. 90:1553, 2006. (4) R. D. Milholland. Phytopathology 64:831, 1974.


Phosphate determination in seawater: toward an autonomous electrochemical method.
Initial steps to create an autonomous in situ electrochemical sensor for orthophosphate determination in seawater are presented. First, the optimal conditions to form the molybdophosphate complex in artificial seawater medium were determined by addition of sulphuric acid and sodium molybdate to the solution containing orthophosphate. Secondly, the anodic oxidation of molybdenum to form molybdate ions and protons was used to create the molybdophosphate complex without addition of any liquid reagents. The molybdophosphate complex is detectable by amperometry with an average precision of 2.2% for the concentration range found in the open ocean and the detection limit is 0.12 μM. Three solutions are proposed to address the silicate interferences issue and one of these methods is used for the natural samples collected in the coastal waters offshore Peru during the Pelagico 1011-12-BIC OLAYA cruise in November-December 2010. Results showed a good precision with an average of 2.5% and a reasonable deviation of the amperometric analysis as compared with colorimetric measurements (4.9%).


The functional requirement of two structural domains within telomerase RNA emerged early in eukaryotes.
Telomerase emerged during evolution as a prominent solution to the eukaryotic linear chromosome end-replication problem. Telomerase minimally comprises the catalytic telomerase reverse transcriptase (TERT) and telomerase RNA (TR) that provides the template for telomeric DNA synthesis. While the TERT protein is well-conserved across taxa, TR is highly divergent amongst distinct groups of species. Herein, we have identified the essential functional domains of TR from the basal eukaryotic species Trypanosoma brucei, revealing the ancestry of TR comprising two distinct structural core domains that can assemble in trans with TERT and reconstitute active telomerase enzyme in vitro The upstream essential domain of T. brucei TR, termed the template core, constitutes three short helices in addition to the 11-nt template. Interestingly, the trypanosome template core domain lacks the ubiquitous pseudoknot found in all known TRs, suggesting later evolution of this critical structural element. The template-distal domain is a short stem-loop, termed equivalent CR4/5 (eCR4/5). While functionally similar to vertebrate and fungal CR4/5, trypanosome eCR4/5 is structurally distinctive, lacking the essential P6.1 stem-loop. Our functional study of trypanosome TR core domains suggests that the functional requirement of two discrete structural domains is a common feature of TRs and emerged early in telomerase evolution.


Fresnel coefficients in materials with magnetic monopoles.
Recent experiments have found entities in crystals whose behavior is equivalent to magnetic monopoles. In this paper, we explain some optical properties based on the reformulated "Maxwell" equations in material media in which there are equivalent magnetic charges. We calculate the coefficients of reflection and transmission of an electromagnetic wave in a plane interface between the vacuum and a medium with magnetic charges. These results can give a more extended vision of the properties of the materials with magnetic monopoles, since the phase and the amplitudes of the reflected and transmitted waves, differ with and without these magnetic entities.


Microbial Ecology and Water Chemistry Impact Regrowth of Opportunistic Pathogens in Full-Scale Reclaimed Water Distribution Systems.
Need for global water security has spurred growing interest in wastewater reuse to offset demand for municipal water. While reclaimed (i.e., nonpotable) microbial water quality regulations target fecal indicator bacteria, opportunistic pathogens (OPs), which are subject to regrowth in distribution systems and spread via aerosol inhalation and other noningestion routes, may be more relevant. This study compares the occurrences of five OP gene markers ( Acanthamoeba spp., Legionella spp., Mycobacterium spp., Naegleria fowleri, Pseudomonas aeruginosa) in reclaimed versus potable water distribution systems and characterizes factors potentially contributing to their regrowth. Samples were collected over four sampling events at the point of compliance for water exiting treatment plants and at five points of use at four U.S. utilities bearing both reclaimed and potable water distribution systems. Reclaimed water systems harbored unique water chemistry (e.g., elevated nutrients), microbial community composition, and OP occurrence patterns compared to potable systems examined here and reported in the literature. Legionella spp. genes, Mycobacterium spp. genes, and total bacteria, represented by 16S rRNA genes, were more abundant in reclaimed than potable water distribution system samples ( p ≤ 0.0001). This work suggests that further consideration should be given to managing reclaimed water distribution systems with respect to nonpotable exposures to OPs.


Presentation of Various Tactile Sensations Using Micro-Needle Electrotactile Display.
Tactile displays provoke tactile sensations by artificially stimulating tactile receptors. While many types of tactile displays have been developed, electrotactile displays that exploit electric stimulation can be designed to be thin, light, flexible and thus, wearable. However, the high voltages required to stimulate tactile receptors and limited varieties of possible sensations pose problems. In our previous work, we developed an electrotactile display using a micro-needle electrode array that can drastically reduce the required voltage by penetrating through the high-impedance stratum corneum painlessly, but displaying various tactile sensations was still a challenge. In this work, we demonstrate presentation of tactile sensation of different roughness to the subjects, which is enabled by the arrangement of the electrodes; the needle electrodes are on the fingertip and the ground electrode is on the fingernail. With this arrangement, the display can stimulate the tactile receptors that are located not only in the shallow regions of the finger but also those in the deep regions. It was experimentally revealed that the required voltage was further reduced compared to previous devices and that the roughness presented by the display was controlled by the pulse frequency and the switching time, or the stimulation flow rate. The proposed electrotactile display is readily applicable as a new wearable haptic device for advanced information communication technology.


Silicosis and lung cancer among workers in North Carolina dusty trades.
In 1940-1983, 760 cases of silicosis were identified among male North Carolina (NC) workers in dusty trades. Vital status was ascertained through 1983 for 714 silicotics, and death certificates were obtained for 546 of the 550 decedents. The standardized mortality ratio (SMR) for lung cancer based on United States rates was 2.6 [95% confidence interval (95% CI) 1.8-3.6] for whites, 2.3 (95% CI 1.5-3.4) for whites unexposed to other known occupational carcinogens, and 2.4 (95% CI 1.5-3.6) for whites with no other exposure and diagnosed with silicosis while still employed in dusty trades. In addition, the age- and smoking-adjusted rate for silicotics was 3.9 times higher (95% CI 2.4-6.4) than that of nonsilicotic metal miners. This analysis effectively controlled for confounding by age, cigarette smoking, exposure to other occupational carcinogens, and detection bias. The results congrue with the hypothesis of an association between silicosis and lung cancer.


Neighborhood Deprivation and Unmet Health Care Needs: A Multilevel Analysis of Older Individuals in South Korea.
In this study the relationship between neighborhood deprivation and the unmet health care needs of elderly individuals (≥ 65 years) was examined. Some previous studies suggested that neighborhood characteristics affect access to health care, yet research on the unmet needs of older individuals is limited. Multilevel logistic regression analysis was used to assess the relationship of neighborhood-level factors with unmet health care needs due to costs, adjusting for individual-level factors, in individuals ≥ 65 years in the 2017 Korean Community Health Survey (n = 63,388). There were 2.6% of elderly individuals who experienced unmet health care needs due to costs. Following adjustment for individual and neighborhood characteristics, the neighborhood deprivation in urban areas was found to have an inverse association with unmet needs (odds ratio = 0.50; 95% confidence interval = 0.24-1.06) for the most deprived quartile versus the least deprived quartile). However, in rural areas neighborhood deprivation was not a significant variable. Among the individual-level variables, household income was one of the strongest correlates with unmet needs in both urban and rural areas. The present findings suggest that targeted policy interventions reflecting both neighborhood and individual characteristics, should be implemented to reduce the unmet health care needs of elderly individuals.


Standardised Tool for the Assessment of Bruxism.
This paper aims to present and describe the Standardised Tool for the Assessment of Bruxism (STAB), an instrument that was developed to provide a multidimensional evaluation of bruxism status, comorbid conditions, aetiology and consequences. The rationale for creating the tool and the road map that led to the selection of items included in the STAB has been discussed in previous publications. The tool consists of two axes, specifically dedicated to the evaluation of bruxism status and consequences (Axis A) and of bruxism risk and etiological factors and comorbid conditions (Axis B). The tool includes 14 domains, accounting for a total of 66 items. Axis A includes the self-reported information on bruxism status and possible consequences (subject-based report) together with the clinical (examiner report) and instrumental (technology report) assessment. The Subject-Based Assessment (SBA) includes domains on Sleep Bruxism (A1), Awake Bruxism (A2) and Patient's Complaints (A3), with information based on patients' self-report. The Clinically Based Assessment (CBA) includes domains on Joints and Muscles (A4), Intra- and Extra-Oral Tissues (A5) and Teeth and Restorations (A6), based on information collected by an examiner. The Instrumentally Based Assessment (IBA) includes domains on Sleep Bruxism (A7), Awake Bruxism (A8) and the use of Additional Instruments (A9), based on the information gathered with the use of technological devices. Axis B includes the self-reported information (subject-based report) on factors and conditions that may have an etiological or comorbid association with bruxism. It includes domains on Psychosocial Assessment (B1), Concurrent Sleep-related Conditions Assessment (B2), Concurrent Non-Sleep Conditions Assessment (B3), Prescribed Medications and Use of Substances Assessment (B4) and Additional Factors Assessment (B5). As a rule, whenever possible, existing instruments, either in full or partial form (i.e. specific subscales), are included. A user's guide for scoring the different items is also provided to ease administration. The instrument is now ready for on-field testing and further refinement. It can be anticipated that it will help in collecting data on bruxism in such a comprehensive way to have an impact on several clinical and research fields.


A Cross-Sectional Study of SARS-CoV-2 Antibodies and Risk Factors for Seropositivity in Staff in Day Care Facilities and Preschools in Denmark.
The aim of this study was to provide information about immunity against COVID-19 along with risk factors and behavior among employees in day care facilities and preschools (DCS) in Denmark. In collaboration with the Danish Union of Pedagogues, during February and March 2021, 47,810 members were offered a point-of-care rapid SARS-CoV-2 antibody test (POCT) at work and were invited to fill in an electronic questionnaire covering COVID-19 exposure. Seroprevalence data from Danish blood donors (total Ig enzyme-linked immunosorbent assay [ELISA]) were used as a proxy for the Danish population. A total of 21,018 (45%) DCS employees completed the questionnaire and reported their POCT result {median age, 44.3 years (interquartile range [IQR], [32.7 to 53.6]); females, 84.1%}, of which 20,267 (96.4%) were unvaccinated and included in analysis. A total of 1,857 (9.2%) participants tested seropositive, significantly higher than a seroprevalence at 7.6% (risk ratio [RR], 1.2; 95% confidence interval [CI], 1.14 to 1.27) among 40,541 healthy blood donors (median age, 42 years [IQR, 28 to 53]; males, 51.3%). Exposure at work (RR, 2.9; 95% CI, 2.3 to 3.6) was less of a risk factor than exposure within the household (RR, 12.7; 95% CI, 10.2 to 15.8). Less than 25% of participants reported wearing face protection at work. Most of the participants expressed some degree of fear of contracting COVID-19 both at work and outside work. SARS-CoV-2 seroprevalence was slightly higher in DCS staff than in blood donors, but possible exposure at home was associated with a higher risk than at work. DCS staff expressed fear of contracting COVID-19, though there was limited use of face protection at work. IMPORTANCE Identifying at-risk groups and evaluating preventive interventions in at-risk groups is imperative for the ongoing pandemic as well as for the control of future epidemics. Although DCS staff have a much higher risk of being infected within their own household than at their workplace, most are fearful of being infected with COVID-19 or bringing COVID-19 to work. This represents an interesting dilemma and an important issue which should be addressed by public health authorities for risk communication and pandemic planning. This study design can be used in a strategy for ongoing surveillance of COVID-19 immunity or other infections in the population. The findings of this study can be used to assess the need for future preventive interventions in DCS, such as the use of personal protective equipment.


The vitamin D axis in the lung: a key role for vitamin D-binding protein.
There has been much recent interest in the role of the vitamin D axis in lung disease, which includes vitamin D, vitamin D receptor (VDR) and vitamin D-binding protein (VDBP; also known as Gc-globulin). VDBP is a serum protein which has immunomodulatory functions relevant in the lung, predominantly relating to macrophage activation and neutrophil chemotaxis. Variations within its gene are also associated with airways disease, implying a role for the protein product in pathogenesis. Thus far the majority of evidence relates to chronic obstructive pulmonary disease (COPD), but is scant in other airways diseases, such as asthma and bronchiectasis. VDBP also acts as a scavenger protein to clear extracellular G-actin released from necrotic cells, which may be of relevance in severe lung infections and acute lung injury. Vitamin D protects against the development of cancer and tuberculosis, although optimal levels are unknown. The majority of circulating vitamin D is bound to VDBP, and its uptake into cells occurs in both bound and unbound forms, which suggests the role of VDBP warrants further study in these conditions as well. This article reviews the evidence of the role VDBP and its gene (GC) in a range of lung diseases, including asthma, COPD and tuberculosis.


YAP promotes cell-autonomous immune responses to tackle intracellular Staphylococcus aureus in vitro.
Transcriptional cofactors YAP/TAZ have recently been found to support autophagy and inflammation, which are part of cell-autonomous immunity and are critical in antibacterial defense. Here, we studied the role of YAP against Staphylococcus aureus using CRISPR/Cas9-mutated HEK293 cells and a primary cell-based organoid model. We found that S. aureus infection increases YAP transcriptional activity, which is required to reduce intracellular S. aureus replication. A 770-gene targeted transcriptomic analysis revealed that YAP upregulates genes involved in autophagy/lysosome and inflammation pathways in both infected and uninfected conditions. The YAP-TEAD transcriptional activity promotes autophagic flux and lysosomal acidification, which are then important for defense against intracellular S. aureus. Furthermore, the staphylococcal toxin C3 exoenzyme EDIN-B was found effective in preventing YAP-mediated cell-autonomous immune response. This study provides key insights on the anti-S. aureus activity of YAP, which could be conserved for defense against other intracellular bacteria.


Effects of ultraviolet radiation produced from artificial lights on serum 25-hydroxyvitamin D concentration in captive domestic rabbits (Oryctolagus cuniculi).
To determine the effects of UVB radiation produced by artificial lights on serum 25-hydroxyvitamin D concentrations in domestic rabbits (Oryctolagus cuniculi). 9 juvenile domestic rabbits. After an acclimation period, rabbits were anesthetized with isoflurane, and an initial blood sample was collected for determination of serum 25-hydroxyvitamin D concentration. Rabbits were randomly assigned to receive 12-hour exposure to UVB radiation produced by 2 compact fluorescent lights daily (n = 5) or no UVB supplementation (4) commencing on day 1. The UVB radiation emitted into the cage was measured at 9 points approximately 34 cm from the surface of the UVB light sources (representing the position of the rabbits in the cage) after 10 hours of exposure on days 1, 8, and 14. On day 14, another blood sample was collected from anesthetized rabbits for determination of serum 25-hydroxyvitamin D concentration. The UVB radiation level was 8.3 to 58.1 μW/cm² for the exposed rabbits and consistently < 0.001 μW/cm² for the control rabbits. Mean ± SD serum 25-hydroxyvitamin D concentrations in the rabbits that were or were not provided supplemental UVB radiation for 14 days differed significantly (66.4 ± 14.3 nmol/L and 31.7 ± 9.9 nmol/L, respectively). Exposure to UVB radiation produced by artificial light significantly increased serum 25-hydroxyvitamin D concentration in juvenile rabbits. Because vitamin D is an essential hormone in vertebrates, these findings suggested that the provision of supplemental UVB radiation to captive rabbits may be important.


Surgical management of isolated acromion fractures: technical tricks and clinical experience.
Acromion fractures of the scapula are rare and most often occur with concomitant fractures of the ipsilateral glenoid, neck and body of the scapula as sequelae of high-energy injuries. Indications for operative management include symptomatic nonunion, displaced fractures, or acromion fractures associated with other lesions of the superior shoulder suspensory complex. Less displaced acromion fractures resulting in decreased subacromial space may also warrant surgery. Although surgical indications have been reported, the literature regarding surgical approaches and fixation techniques for management of these factures is limited. Acromion fractures can generally be addressed with a direct posterior approach using either tension band or low-profile plating in combination with cortical lag screws to obtain a stable construct. This technique is both effective in achieving fracture union and safe to the patient. When associated with a more complex fracture of the glenoid and/or scapula body, the surgical approach and fixation strategy should be dictated by the optimal approach to other displaced elements of a scapula fracture. The purpose of this study was to describe a step-wise approach to the surgical management of isolated acromion fractures, describe surgical tips and techniques, and to present the early clinical outcomes in 13 patients after surgical treatment with this approach.


An animal model of chronic inflammatory pain: pharmacological and temporal differentiation from acute models.
Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic.


Light-based solution for the dominating set problem.
In this paper, an optical solution for the dominating set problem is provided. The solution is based on long ribbon-shaped optical filters, on which some operations can be optically applied efficiently. The provided solution requires polynomial time, exponential length of filters, and exponential number of photons to solve the dominating set problem. The provided solution is implemented experimentally using lithographic sheets, on a graph with six vertices, to find all dominating sets with two vertices.


Alemtuzumab induction in renal transplantation.
There are few comparisons of antibody induction therapy allowing early glucocorticoid withdrawal in renal-transplant recipients. The purpose of the present study was to compare induction therapy involving alemtuzumab with the most commonly used induction regimens in patient populations at either high immunologic risk or low immunologic risk. In this prospective study, we randomly assigned patients to receive alemtuzumab or conventional induction therapy (basiliximab or rabbit antithymocyte globulin). Patients were stratified according to acute rejection risk, with a high risk defined by a repeat transplant, a peak or current value of panel-reactive antibodies of 20% or more, or black race. The 139 high-risk patients received alemtuzumab (one dose of 30 mg, in 70 patients) or rabbit antithymocyte globulin (a total of 6 mg per kilogram of body weight given over 4 days, in 69 patients). The 335 low-risk patients received alemtuzumab (one dose of 30 mg, in 164 patients) or basiliximab (a total of 40 mg over 4 days, in 171 patients). All patients received tacrolimus and mycophenolate mofetil and underwent a 5-day glucocorticoid taper in a regimen of early steroid withdrawal. The primary end point was biopsy-confirmed acute rejection at 6 months and 12 months. Patients were followed for 3 years for safety and efficacy end points. The rate of biopsy-confirmed acute rejection was significantly lower in the alemtuzumab group than in the conventional-therapy group at both 6 months (3% vs. 15%, P<0.001) and 12 months (5% vs. 17%, P<0.001). At 3 years, the rate of biopsy-confirmed acute rejection in low-risk patients was lower with alemtuzumab than with basiliximab (10% vs. 22%, P=0.003), but among high-risk patients, no significant difference was seen between alemtuzumab and rabbit antithymocyte globulin (18% vs. 15%, P=0.63). Adverse-event rates were similar among all four treatment groups. By the first year after transplantation, biopsy-confirmed acute rejection was less frequent with alemtuzumab than with conventional therapy. The apparent superiority of alemtuzumab with respect to early biopsy-confirmed acute rejection was restricted to patients at low risk for transplant rejection; among high-risk patients, alemtuzumab and rabbit antithymocyte globulin had similar efficacy. (Funded by Astellas Pharma Global Development; INTAC ClinicalTrials.gov number, NCT00113269.).


Accuracy of electromyometrial imaging of uterine contractions in clinical environment.
Clinically, uterine contractions are monitored with tocodynamometers or intrauterine pressure catheters. In the research setting, electromyography (EMG), which detects electrical activity of the uterus from a few electrodes on the abdomen, is feasible, can provide more accurate data than these other methods, and may be useful for predicting preterm birth. However, EMG lacks sufficient spatial resolution and coverage to reveal where uterine contractions originate, how they propagate, and whether preterm contractions differ between women who do and do not progress to preterm delivery. To address those limitations, electromyometrial imaging (EMMI) was recently developed and validated to non-invasively assess three-dimensional (3D) electrical activation patterns on the entire uterine surface in pregnant sheep. EMMI uses magnetic resonance imaging to obtain subject-specific body-uterus geometry and collects uterine EMG data from up to 256 electrodes on the body surface. EMMI software then solves an ill-posed inverse computation to combine the two datasets and generate maps of electrical activity on the entire 3D uterine surface. Here, we assessed the feasibility to clinically translate EMMI by evaluating EMMI's accuracy under the unavoidable geometrical alterations and electrical noise contamination in a clinical environment. We developed a hybrid experimental-simulation platform to model the effects of fetal kicks, contractions, fetal/maternal movements, and noise contamination caused by maternal respiration and environmental electrical activity. Our data indicate that EMMI can accurately image uterine electrical activity in the presence of geometrical deformations and electrical noise, suggesting that EMMI can be reliably translated to non-invasively image 3D uterine electrical activation in pregnant women.


Tetanus. A clinical review.
Although tetanus is now uncommon in Oman (The Expanded Program on Immunization was introduced in 1981), patients continue to present from time to time at an average rate of 6 cases per year. Worldwide, the mortality rate for tetanus remains high (ranging from 15-20% in developed countries). At the Sultan Qaboos University Hospital, Muscat, Oman, prolonged Intensive Care Unit treatment and multi-disciplinary management is invariably required for tetanus patients. This study was carried out to evaluate our results over the past decade. All tetanus patients admitted to the Sultan Qaboos University Hospital from 1991 up to the end of 1999 were retrospectively reviewed. Patients were diagnosed early, and aggressive treatment in the Intensive Care Unit was instituted, with a coordinated multidisciplinary management. Ten cases were identified and included in the review, comprising 9 adults and one infant aged 2 weeks. Adult patients were aged 36-75 years (mean 59 years), and the average Intensive Care Unit stay of the 9 surviving patients was 5.5 weeks (range 3-7 weeks). All patients presented with severe generalized tetanus. Two patients with traditional cautery marks developed tetanus. A focus of infection could not be found in 2 patients. All patients had early tracheostomy and assisted ventilation with appropriate sedation. One patient required almost 45 gm of diazepam throughout his Intensive Care Unit stay. One adult patient died on the 6th day of admission following myocardial infarction. The neonatal case survived after 35 days care in the Intensive Care Unit. The mortality rate for our patients was therefore 10%. Tetanus in Oman remains an infrequent but important disease requiring costly and prolonged Intensive Care Unit treatment. We attribute the comparatively low mortality rate (10%) in this study, to early diagnosis, institution of aggressive treatment, good nursing as well as a well-coordinated multi-disciplinary management.


Differential eye movements in mild traumatic brain injury versus normal controls.
Objective measures to diagnose and to monitor improvement of symptoms following mild traumatic brain injury (mTBI) are lacking. Computerized eye tracking has been advocated as a rapid, user friendly, and field-ready technique to meet this need. Eye-tracking data collected via a head-mounted, video-based binocular eye tracker was used to examine saccades, fixations, and smooth pursuit movement in military Service Members with postconcussive syndrome (PCS) and asymptomatic control subjects in an effort to determine if eye movement differences could be found and quantified. Sixty Military Service Members with PCS and 26 asymptomatic controls. The diagnosis of mTBI was confirmed by the study physiatrist's history, physical examination, and a review of any medical records. Various features of saccades, fixation and smooth pursuit eye movements were analyzed. Subjects with symptomatic mTBI had statistically larger position errors, smaller saccadic amplitudes, smaller predicted peak velocities, smaller peak accelerations, and longer durations. Subjects with symptomatic mTBI were also less likely to follow a target movement (less primary saccades). In general, symptomatic mTBI tracked the stepwise moving targets less accurately, revealing possible brain dysfunction. A reliable, standardized protocol that appears to differentiate mTBI from normals was developed for use in future research. This investigation represents a step toward objective identification of those with PCS. Future studies focused on increasing the specificity of eye movement differences in those with PCS are needed.


The Role of Dopamine in Value-Based Attentional Orienting.
Reward learning gives rise to strong attentional biases. Stimuli previously associated with reward automatically capture visual attention regardless of intention. Dopamine signaling within the ventral striatum plays an important role in reward learning, representing the expected reward initiated by a cue. How dopamine and the striatum may be involved in maintaining behaviors that have been shaped by reward learning, even after reward expectancies have changed, is less well understood. Nonspecific measures of brain activity have implicated the striatum in value-based attention. However, the neurochemical mechanisms underlying the attentional priority of learned reward cues remain unexplored. Here, we investigated the contribution of dopamine to value-based attention using positron emission tomography (PET) with [(11)C]raclopride. We show that, in the explicit absence of reward, the magnitude of attentional capture by previously reward-associated but currently task-irrelevant distractors is correlated across individuals with changes in available D2/D3 dopamine receptors (presumably due to intrasynaptic dopamine) linked to distractor processing within the right caudate and posterior putamen. Our findings provide direct evidence linking dopamine signaling within the striatum to the involuntary orienting of attention, and specifically to the attention-grabbing quality of learned reward cues. These findings also shed light on the neurochemical basis of individual susceptibility to value-driven attentional capture, which is known to play a role in addiction. More broadly, the present study highlights the value and feasibility of using PET to relate changes in the release of a neurotransmitter to learning-dependent changes in healthy adults.


c-Myc represses and Miz-1 activates the murine natural resistance-associated protein 1 promoter.
Iron is essential for growth, and impaired iron homoeostasis through a non-conserved mutation within murine Nramp1, also termed Slc11a1, contributes to susceptibility to infection. Nramp1 depletes the macrophage cytosol of iron, with effects on iron-regulated gene expression and iron-dependent processes. Wu and colleagues (Wu, K.-J., Polack, A., and Dalla-Favera, R. (1999) Science 283, 676-679) showed converse control of iron regulatory protein expression (IRP2) and H-ferritin by c-Myc, suggesting a role for c-Myc in enhancing cytoplasmic iron levels for growth. We investigated if c-Myc also regulates Nramp1 expression. We show an inverse correlation with cell growth, and in co-transfection experiments c-Myc represses the Nramp1 promoter. Within the Nramp1 promoter we identified six non-canonical E boxes, which are not important for c-Myc repression. By deletion analysis the repressor site maps to one or more initiator elements flanking the transcriptional initiation site. Co-transfections with the c-Myc interacting zinc finger protein (Miz-1) show that Miz-1 can overcome c-Myc repression of Nramp1, and, from a deletion construct lacking E box sites, Miz-1 activates the Nramp1 promoter. These studies reinforce the link between c-Myc and iron regulation and provide further evidence that c-Myc negatively regulates genes that decrease the iron content of the cytosol. The results provide further support for a divalent cation antiporter function for Nramp1.


Vitamin D Deficiency as It Relates to Oral Immunity and Chronic Periodontitis.
The biologically active form of vitamin D, 1,25 dihydroxyvitamin D (1,25(OH)2D) and its receptor, the vitamin D receptor (VDR), play roles in maintaining oral immunity and the integrity of the periodontium. Results of observational cross-sectional clinical studies investigating the association between vitamin D serum level and the incidence and severity of chronic periodontitis indicate that, perhaps owing to the immunomodulatory, anti-inflammatory, and antibacterial properties of 1,25(OH)2 D/VDR signalling, a sufficient serum level of vitamin D is necessary for the maintenance of periodontal health. In cases of established chronic periodontitis, vitamin D supplementation is associated with reduction in the severity of periodontitis. As cross-sectional studies provide only weak evidence for any causal association and therefore are of questionable value, either longitudinal cohort studies, case controlled studies, or randomized control trials are needed to determine whether or not deficiency of vitamin D is a risk factor for chronic periodontitis, and whether or not vitamin D supplementation adjunctive to standard periodontal treatment is in any way beneficial. In this article, we discuss the relationship between vitamin D, oral immunity and periodontal disease and review the rationale for using vitamin D supplementation to help maintain periodontal health and as an adjunct to standard periodontal treatment.


Clustering of Janus particles in an optical potential driven by hydrodynamic fluxes.
Self-organisation is driven by the interactions between the individual components of a system mediated by the environment, and is one of the most important strategies used by many biological systems to develop complex and functional structures. Furthermore, biologically-inspired self-organisation offers opportunities to develop the next generation of materials and devices for electronics, photonics and nanotechnology. In this work, we demonstrate experimentally that a system of Janus particles (silica microspheres half-coated with gold) aggregates into clusters in the presence of a Gaussian optical potential and disaggregates when the optical potential is switched off. We show that the underlying mechanism is the existence of a hydrodynamic flow induced by a temperature gradient generated by the light absorption at the metallic patches on the Janus particles. We also perform simulations, which agree well with the experiments and whose results permit us to clarify the underlying mechanism. The possibility of hydrodynamic-flux-induced reversible clustering may have applications in the fields of drug delivery, cargo transport, bioremediation and biopatterning.


Numerical model of fluid flow and oxygen transport in a radial-flow microchannel containing hepatocytes.
The incorporation of monolayers of cultured hepatocytes into an extracorporeal perfusion system has become a promising approach for the development of a temporary bioartificial liver (BAL) support system. In this paper we present a numerical investigation of the oxygen tension, shear stress, and pressure drop in a bioreactor for a BAL composed of plasma-perfused chambers containing monolayers of porcine hepatocytes. The chambers consist of microfabricated parallel disks with center-to-edge radial flow. The oxygen uptake rate (OUR), measured in vitro for porcine hepatocytes, was curve-fitted using Michaelis-Menten kinetics for simulation of the oxygen concentration profile. The effect of different parameters that may influence the oxygen transport inside the chambers, such as the plasma flow rate, the chamber height, the initial oxygen tension in the perfused plasma, the OUR, and K(m) was investigated. We found that both the plasma flow rate and the initial oxygen tension may have an important effect upon oxygen transport. Increasing the flow rate and/or the inlet oxygen tension resulted in improved oxygen transport to cells in the radial-flow microchannels, and allowed significantly greater diameter reactor without oxygen limitation to the hepatocytes. In the range investigated in this paper (10 microns < H < 100 microns), and for a constant plasma flow rate, the chamber height, H, had a negligible effect on the oxygen transport to hepatocytes. On the contrary, it strongly affected the mechanical stress on the cells that is also crucial for the successful design of the BAL reactors. A twofold decrease in chamber height from 50 to 25 microns produced approximately a fivefold increase in maximal shear stress at the inlet of the reactor from 2 to 10 dyn/cm2. Further decrease in chamber height resulted in shear stress values that are physiologically unrealistic. Therefore, the channel height needs to be carefully chosen in a BAL design to avoid deleterious hydrodynamic effects on hepatocytes.


A repeated short educational intervention improves asthma control and quality of life.
We assessed the effectiveness of an asthma educational programme based on a repeated short intervention (AEP-RSI) to improve asthma control (symptom control and future risk) and quality of life. A total of 230 adults with mild-to-moderate persistent uncontrolled asthma participated in a 1-year cluster randomised controlled multicentre study. The AEP-RSI was given in four face-to-face sessions at 3-month intervals, and included administration of a written personalised action plan and training on inhaler technique. Centres were randomised to the AEP-RSI (intervention) group or usual clinical practice group. Specialised centres using a standard educational programme were the gold standard group. A significant improvement in the Asthma Control Test score was observed in all three groups (p<0.001), but improvements were higher in the intervention and gold standard groups than in the usual clinical practice group (p=0.042), which also showed fewer exacerbations (mean±sd; 1.20±2.02 and 0.56±1.5 versus 2.04±2.72, respectively) and greater increases in the Mini Asthma Quality of Life Questionnaire scores (0.95±1.04 and 0.89±0.84 versus 0.52±0.97, respectively). The AEP-RSI was effective in improving asthma symptom control, future risk and quality of life.


Enhanced asynchronous Ca(2+) oscillations associated with impaired glutamate transport in cortical astrocytes expressing Fmr1 gene premutation expansion.
FMR1 CGG expansion repeats in the premutation range have not been linked to astrocyte pathophysiology. Premutation cortical astrocytes display decreased Glu transporter expression/activity and enhanced asynchronous Ca(2+) oscillations. Glu transport and Ca(2+) signaling defects in premutation astrocytes could contribute to FXTAS neuropathology. Premutation astrocytes may have an etiological role in FXTAS neuropathology. Premutation CGG repeat expansions (55-200 CGG repeats; preCGG) within the fragile X mental retardation 1 (FMR1) gene can cause fragile X-associated tremor/ataxia syndrome. Defects in early neuronal migration and morphology, electrophysiological activity, and mitochondria trafficking have been described in a premutation mouse model, but whether preCGG mutations also affect astrocyte function remains unknown. PreCGG cortical astrocytes (∼170 CGG repeats) displayed 3-fold higher Fmr1 mRNA and 30% lower FMR1 protein (FMRP) when compared with WT. PreCGG astrocytes showed modest reductions in expression of glutamate (Glu) transporters GLT-1 and GLAST and attenuated Glu uptake (p < 0.01). Consistent with astrocyte cultures in vitro, aged preCGG mice cerebral cortex also displayed reduced GLAST and GLT-1 expression. Approximately 65% of the WT and preCGG cortical astrocytes displayed spontaneous asynchronous Ca(2+) oscillations. PreCGG astrocytes exhibited nearly 50% higher frequency of asynchronous Ca(2+) oscillations (p < 0.01) than WT, a difference mimicked by chronic exposure of WT astrocytes to l-trans-pyrrolidine-2,4-dicarboxylic acid (l-trans-PDC) or by partial suppression of GLAST using siRNA interference. Acute challenge with Glu augmented the frequency of Ca(2+) oscillations in both genotypes. Additionally, 10 μm Glu elicited a sustained intracellular Ca(2+) rise in a higher portion of preCGG astrocytes when compared with WT. Pharmacological studies showed that mGluR5, but not NMDA receptor, contributed to Glu hypersensitivity in preCGG astrocytes. These functional defects in preCGG astrocytes, especially in Glu signaling, may contribute to fragile X-associated tremor/ataxia syndrome neuropathology.


Altered myosin isozyme patterns from pressure-overloaded and thyrotoxic hypertrophied rabbit hearts.
Cardiac hypertrophy, induced by pressure overload, leads to a depression in the rate of force development, velocity of shortening, tension-dependent heat generation, and myosin ATPase activity, whereas cardiac hypertrophy, induced by thyroxine administration, leads to an increase in these parameters. These changes have been attributed, in part, to structural changes in myosin. In this study, we have investigated changes in the relative content of myosin isozymes and differences in primary structure of the isozymes in pressure-overloaded and thyrotoxic cardiac hypertrophy in the rabbit. Three myosin isozymic forms (V1 = fastest, V2 = intermediate, V3 = slowest mobility) were observed in pyrophosphate polyacrylamide gels from normal hearts with the V3 component being the predominant species. In the pressure-overloaded model, the V1 and V2 components disappeared or were present in reduced amounts leaving the V3 more predominant. The most striking difference was the isozymic profile produced in thyrotoxic hearts where the V1 became the predominant component and V2 and V3 the minor components. alpha-Chymotryptic digestion of myosin heavy chains produced characteristic, reproducible peptide patterns for each of the animal models, as did fluorographic analyses of alpha-chymotryptic digests of 14C-iodoacetamide (IAA)-labeled SH1 peptides of myosin. Our results suggest that altered proportions of myosin isozymes may be responsible for altered cardiac performance.


Evaluation and Comparison of Anatomical Landmark Detection Methods for Cephalometric X-Ray Images: A Grand Challenge.
Cephalometric analysis is an essential clinical and research tool in orthodontics for the orthodontic analysis and treatment planning. This paper presents the evaluation of the methods submitted to the Automatic Cephalometric X-Ray Landmark Detection Challenge, held at the IEEE International Symposium on Biomedical Imaging 2014 with an on-site competition. The challenge was set to explore and compare automatic landmark detection methods in application to cephalometric X-ray images. Methods were evaluated on a common database including cephalograms of 300 patients aged six to 60 years, collected from the Dental Department, Tri-Service General Hospital, Taiwan, and manually marked anatomical landmarks as the ground truth data, generated by two experienced medical doctors. Quantitative evaluation was performed to compare the results of a representative selection of current methods submitted to the challenge. Experimental results show that three methods are able to achieve detection rates greater than 80% using the 4 mm precision range, but only one method achieves a detection rate greater than 70% using the 2 mm precision range, which is the acceptable precision range in clinical practice. The study provides insights into the performance of different landmark detection approaches under real-world conditions and highlights achievements and limitations of current image analysis techniques.


Effects of transportation and delay in processing on the stability of nutritional and metabolic biomarkers.
The effects of transportation and delay in processing of blood samples on the concentration of biomarkers are significant in epidemiological studies for which specimens are collected from participants at locations other than a designated center or laboratory. These sources of variability in measurement were studied by collecting two sets of blood samples from 51 men between 26 and 50 years of age. The first set was sent immediately to the laboratory for processing. The second set was transported by car for one hour and then returned to the laboratory for processing. Both sets were stored together at -80 degrees C until the end of the study. Several blood constituents were evaluated. Vitamins, liver enzymes, and electrolytes showed no changes in concentration after transport by car for one hour. There were decreases in the concentrations of red and white blood cells, high-density-lipoprotein cholesterol, glucose, and creatinine after transportation. The transported total cholesterol, total testosterone, free testosterone, alkaline phosphatase, total bilirubin, and thiobarbituric acid-reactive substances increased in concentration. Although transportation and delay in processing of blood samples do not appear to greatly impact relative risk estimates, epidemiologists should be aware of these potential sources of variability in measurement and consider the consequences in their particular study.


High resolution studies of the Afa/Dr adhesin DraE and its interaction with chloramphenicol.
Pathogenic Escherichia coli expressing Afa/Dr adhesins are able to cause both urinary tract and diarrheal infections. The Afa/Dr adhesins confer adherence to epithelial cells via interactions with the human complement regulating protein, decay accelerating factor (DAF or CD55). Two of the Afa/Dr adhesions, AfaE-III and DraE, differ from each other by only three residues but are reported to have several different properties. One such difference is disruption of the interaction between DraE and CD55 by chloramphenicol, whereas binding of AfaE-III to CD55 is unaffected. Here we present a crystal structure of a strand-swapped trimer of wild type DraE. We also present a crystal structure of this trimer in complex with chloramphenicol, as well as NMR data supporting the binding position of chloramphenicol within the crystal. The crystal structure reveals the precise atomic basis for the sensitivity of DraE-CD55 binding to chloramphenicol and demonstrates that in contrast to other chloramphenicol-protein complexes, drug binding is mediated via recognition of the chlorine "tail" rather than via intercalation of the benzene rings into a hydrophobic pocket.


The formation of diglutathionyl dithiocarbonate as a metabolite of chloroform, bromotrichloromethane, and carbon tetrachloride.
One hour after the intraperitoneal administration of CHCl3, CBrCl3, or CCl4 to phenobarbital (PB)-treated rats, hepatic GSH levels decreased to 30, 59, and 88% of control levels, respectively; after 4 hr, the GSH levels had returned to 46, 65, 99%, respectively, of control levels. When incubated for 15 min in air with rat liver microsomes from PB-treated rats, a NADPH-generating system, and GSH (5 mM), all of the compounds were converted to diglutathionyl dithiocarbonate (GSCOSG). The rate of conversion of CHCl3, CBrCl3, and CCl4 to GSCOSG was 180, 58, and 8 nmol per mg of protein per 15 min, respectively. The GSCOSG was also identified in bile by 13C-NMR spectroscopy and HPLC as an in vivo metabolite of CHCl(3), CBrCl3, and CCl4. After the administration of CHCl3, CBrCl3, and CCl4, 2.89, 0.64, or 0.11 mumol of GSCOSG, respectively, was excreted in 6 hr. These results suggest that CHCl3, CBrCl3, and CCl4 are metabolized in vitro and in vivo to phosgene (COCl2), which reacts with GSH to produce GSCOSG. The reaction of GSH with COCl2 may be responsible at least in part for the GSH-depleting properties of CHCl3, CBrCl3, and CCl4, inasmuch as the relative amounts of formation of GSCOSG in vitro and in vivo paralleled their relative GSH-depleting activities.


Ribosome-binding proteins Mdm38 and Mba1 display overlapping functions for regulation of mitochondrial translation.
Biogenesis of respiratory chain complexes depends on the expression of mitochondrial-encoded subunits. Their synthesis occurs on membrane-associated ribosomes and is probably coupled to their membrane insertion. Defects in expression of mitochondrial translation products are among the major causes of mitochondrial disorders. Mdm38 is related to Letm1, a protein affected in Wolf-Hirschhorn syndrome patients. Like Mba1 and Oxa1, Mdm38 is an inner membrane protein that interacts with ribosomes and is involved in respiratory chain biogenesis. We find that simultaneous loss of Mba1 and Mdm38 causes severe synthetic defects in the biogenesis of cytochrome reductase and cytochrome oxidase. These defects are not due to a compromised membrane binding of ribosomes but the consequence of a mis-regulation in the synthesis of Cox1 and cytochrome b. Cox1 expression is restored by replacing Cox1-specific regulatory regions in the mRNA. We conclude, that Mdm38 and Mba1 exhibit overlapping regulatory functions in translation of selected mitochondrial mRNAs.


Evaluation of right ventricular function in operated tetralogy of Fallot patients with tissue Doppler imaging before and after pulmonary valve replacement.
This study aims to investigate the efficacy of tissue Doppler echocardiography for the diagnosis of right ventricular dysfunction and for the evaluation of the response to pulmonary valve replacement. Between December 2008 and December 2010, a total of 15 patients (8 males, 7 females; mean age: 14.5±4.5 years; range, 7 to 22 years) with pulmonary valve insufficiency in the follow-up of total correction of tetralogy of Fallot who underwent pulmonary valve replacement were included in the study. Echocardiographic imaging was performed before and one, three, and six months after replacement. Using pulse wave Doppler, early diastolic E and late diastolic A waves were measured in the flow velocity curve of tricuspid valve. Tissue Doppler measurements were made from the basal segment of right ventricular free wall and interventricular septum. S, e, and a myocardial velocities, isometric contraction time, isovolumetric relaxation time and ejection time were measured. Myocardial performance index was calculated for each patient. In pre-pulmonary valve replacement phase, s, e, a velocities and ejection time were lower in the interventricular septum compared to the basal segment of right ventricular free wall, while isometric contraction time, isovolumetric relaxation time and myocardial performance index values were higher. In the first post-replacement month, there was a significant decrease in the s value of interventricular septum, compared to pre-pulmonary valve replacement period; isometric contraction time decreased and myocardial performance index increased in the first postpulmonary valve replacement month in the free wall of right ventricle, while isovolumetric relaxation time decreased in the postoperative third month, and s velocity, isometric contraction time and myocardial performance index increased in the postoperative sixth month. Pre-pulmonary valve replacement tissue Doppler values at the septum showed that myocardial systolic and diastolic dysfunction developed earlier than the basal segment of right ventricular free wall. This result showed that right ventricular recovery was not complete in the sixth post-pulmonary valve replacement month. Tissue Doppler can show right ventricular dysfunction before replacement, but it may be insufficient to visualize right ventricular recovery until six months after treatment.


Kidney function on admission predicts in-hospital mortality in COVID-19.
Recent data have suggested the presence of a reciprocal relationship between COVID-19 and kidney function. To date, most studies have focused on the effect of COVID-19 on kidney function, whereas data regarding kidney function on the COVID-19 prognosis is scarce. Therefore, in this study, we aimed to investigate the association between eGFR on admission and the mortality rate of COVID-19. We recruited 336 adult consecutive patients (male: 57.1%, mean age: 55.0±16.0 years) that were hospitalized with the diagnosis of COVID-19 in a tertiary care university hospital. Data were collected from the electronic health records of the hospital. On admission, eGFR was calculated using the CKD-EPI formula. Acute kidney injury was defined according to the KDIGO criteria. Binary logistic regression and Cox regression analyses were used to assess the relationship between eGFR on admission and in-hospital mortality of COVID-19. Baseline eGFR was under 60 mL/min/1.73m2 in 61 patients (18.2%). Acute kidney injury occurred in 29.2% of the patients. In-hospital mortality rate was calculated as 12.8%. Age-adjusted and multivariate logistic regression analysis (p: 0.005, odds ratio: 0.974, CI: 0.956-0.992) showed that baseline eGFR was independently associated with mortality. Additionally, age-adjusted Cox regression analysis revealed a higher mortality rate in patients with an eGFR under 60 mL/min/1.73m2. On admission eGFR seems to be a prognostic marker for mortality in patients with COVID-19. We recommend that eGFR be measured in all patients on admission and used as an additional tool for risk stratification. Close follow-up should be warranted in patients with a reduced eGFR.


DnaG interacts with a linker region that joins the N- and C-domains of DnaB and induces the formation of 3-fold symmetric rings.
Loading of the replicative ring helicase onto the origin of replication (oriC) is the final outcome of a well coordinated series of events that collectively constitute a primosomal cascade. Once the ring helicase is loaded, it recruits the primase and signals the switch to the polymerization mode. The transient nature of the helicase-primase (DnaB-DnaG) interaction in the Escherichia coli system has hindered our efforts to elucidate its structure and function. Taking advantage of the stable DnaB-DnaG complex in Bacillus stearothermophilus, we have reviewed conflicting mutagenic data from other bacterial systems and shown that DnaG interacts with the flexible linker that connects the N- and C-terminal domains of DnaB. Furthermore, atomic force microscopy (AFM) imaging experiments show that binding of the primase to the helicase induces predominantly a 3-fold symmetric morphology to the hexameric ring. Overall, three DnaG molecules appear to interact with the hexameric ring helicase but a small number of complexes with two and even one DnaG molecule bound to DnaB were also detected. The structural/functional significance of these data is discussed and a speculative structural model for this complex is suggested.


A model-based approach to predict muscle synergies using optimization: application to feedback control.
This paper presents a new model-based method to define muscle synergies. Unlike the conventional factorization approach, which extracts synergies from electromyographic data, the proposed method employs a biomechanical model and formally defines the synergies as the solution of an optimal control problem. As a result, the number of required synergies is directly related to the dimensions of the operational space. The estimated synergies are posture-dependent, which correlate well with the results of standard factorization methods. Two examples are used to showcase this method: a two-dimensional forearm model, and a three-dimensional driver arm model. It has been shown here that the synergies need to be task-specific (i.e., they are defined for the specific operational spaces: the elbow angle and the steering wheel angle in the two systems). This functional definition of synergies results in a low-dimensional control space, in which every force in the operational space is accurately created by a unique combination of synergies. As such, there is no need for extra criteria (e.g., minimizing effort) in the process of motion control. This approach is motivated by the need for fast and bio-plausible feedback control of musculoskeletal systems, and can have important implications in engineering, motor control, and biomechanics.


PPARs in the Renal Regulation of Systemic Blood Pressure.
Recent research has revealed roles for the peroxisome proliferator activated receptor (PPAR) family of transcription factors in blood pressure regulation, expanding the possible therapeutic use of PPAR ligands. PPARalpha and PPARgamma modulate the renin-angiotensin-aldosterone system (RAAS), a major regulator of systemic blood pressure and interstitial fluid volume by transcriptional control of renin, angiotensinogen, angiotensin converting enzyme (ACE) and angiotensin II receptor 1 (AT-R1). Blockade of RAAS is an important therapeutic target in hypertension management and attenuates microvascular damage, glomerular inflammation and left ventricular hypertrophy in hypertensive patients and also show antidiabetic effects. The mechanisms underlying the benefits of RAAS inhibition appear to involve PPARgamma-regulated pathways. This review summarizes current knowledge on the role of PPARs in the transcriptional control of the RAAS and the possible use of PPAR ligands in the treatment of RAAS dependent hypertension.


Neuromuscular adaptations to 4 weeks of intensive drop jump training in well-trained athletes.
This study examined the effects of 4 weeks of intensive drop jump training in well-trained athletes on jumping performance and underlying changes in biomechanics and neuromuscular adaptations. Nine well-trained athletes at high national competition level within sprinting and jumping disciplines participated in the study. The training was supervised and augmented feedback on performance was used to ensure maximal training intensity. The drop jumps were performed with minimal contact time and maximal jumping height. Assessment of performance during training showed effects of motor learning. Before and after the training intervention maximal isometric muscle strength, the biomechanics, muscle activity pattern of the lower extremities and the soleus H-reflex and V-wave during drop jumping were measured. Maximal jump height and performance index (PI) defined as jumping height divided by contact time improved significantly by 11.9% (P = 0.024) and 16.2% (P = 0.009), respectively. Combined ankle and knee joint peak power was significantly increased by 7% after training (P = 0.047). The preactivity in the soleus muscle decreased 16% (P = 0.015). The soleus H-reflex was unchanged after training, while the soleus V-wave increased significantly at 45 msec after touchdown. This may indicate an increased drive to the α-motor neuron pool following training. Muscle strength parameters were unaffected by the training. The results demonstrate that 4 weeks of intensive drop jump training can improve jumping performance also in well-trained athletes without concomitant changes in muscle strength. It is suggested that the behavioral improvement is primarily due to neural factors regulating the activation pattern controlling the drop jump movement.


Repeated Neonatal Isoflurane Exposure is Associated with Higher Susceptibility to Chronic Variable Stress-induced Behavioural and Neuro-inflammatory Alterations.
Numerous studies have reported that prolonged or multiple exposures to anaesthetics in early life lead to detrimental effects on brain function, most having focused on neurocognitive function, and relatively few on long term neuropsychiatric performance. The present study investigated the impact of repeated neonatal isoflurane exposure on chronic variable stress (CVS)-induced psychiatric and behavioural outcomes together with CVS-related neuronal activity and neuro-inflammatory reactivity in relevant brain circuits. In the present study, C57BL/6J mice received either three exposures to isoflurane at postnatal days 7, 8, and 9 or a control exposure. From postnatal day 45, mice were exposed to a mild, 3-week, CVS paradigm or none and the CVS-related neuropsychiatric performance was evaluated using a series of behavioural tests. The neuronal activity in relevant brain regions was measured by ΔFosB immunopositivity and CVS-related neuroinflammation was assessed by analysing levels of pro-inflammatory cytokines IL-1α, IL-1β, IL-6, and TNF-α. In mice experiencing serial neonatal isoflurane exposure, we detected a significant enhancement in anxiety levels following CVS procedures, together with enhanced neuronal activity, and exacerbated neuroinflammation in the basolateral amygdaloid nuclei (BLA) and hippocampal dentate gyrus (DG) regions. No such change was found in control mice. These results indicate an association between early multiple isoflurane exposures in infant mice and susceptibility to a CVS-evoked anxious phenotype accompanied by enhanced neuronal activity in BLA and DG regions and high inflammatory reactivity in response to CVS.


Context-dependent kernels for object classification.
Kernels are functions designed in order to capture resemblance between data and they are used in a wide range of machine learning techniques, including support vector machines (SVMs). In their standard version, commonly used kernels such as the Gaussian one show reasonably good performance in many classification and recognition tasks in computer vision, bioinformatics, and text processing. In the particular task of object recognition, the main deficiency of standard kernels such as the convolution one resides in the lack in capturing the right geometric structure of objects while also being invariant. We focus in this paper on object recognition using a new type of kernel referred to as "context dependent." Objects, seen as constellations of interest points, are matched by minimizing an energy function mixing 1) a fidelity term which measures the quality of feature matching, 2) a neighborhood criterion which captures the object geometry, and 3) a regularization term. We will show that the fixed point of this energy is a context-dependent kernel which is also positive definite. Experiments conducted on object recognition show that when plugging our kernel into SVMs, we clearly outperform SVMs with context-free kernels.


Hyoid and laryngeal excursion kinematics - magnitude, duration and velocity - changes following successful exercise-based dysphagia rehabilitation: MDTP.
Variability in magnitude of deglutitional hyolaryngeal excursion in patients with dysphagia suggests that it does not adequately represent the kinematics of swallowing difficulties or recovery following rehabilitation. On the other hand, reduced hyolaryngeal excursion velocity has been reported in patients with dysphagia. While increased movement velocity often accompanies clinical and functional recovery in many diseases, velocity changes in swallowing-related movement following dysphagia therapy have not been well studied. This study evaluated changes in hyoid and laryngeal excursion (magnitude, duration and velocity) before and following successful dysphagia therapy to provide a more comprehensive representation of improvement to swallowing kinematics in patients who have experienced successful rehabilitation. A secondary analysis of case series data was completed. Eight patients with severe, chronic dysphagia completed a standard course of an exercise-based dysphagia treatment programme (McNeill dysphagia therapy program, MDTP). Pre- and post-treatment, kinematic aspects of swallowing were evaluated for thin liquid, thick liquid and pudding swallows. Maximum hyoid and laryngeal excursion magnitude and excursion duration were measured. Excursion velocities were calculated from excursion magnitude and duration measures. Successful treatment for dysphagia facilitated increased hyolaryngeal excursion magnitude, duration and velocity. These changes were most prominent for the hyoid and most often observed with thin liquids. By examining hyoid and laryngeal excursion velocity in patients who have experienced successful dysphagia rehabilitation, this study demonstrated the value of evaluating spatial and temporal aspects of swallowing kinematics in a single measure for a more comprehensive representation of positive changes underlying functional recovery.


Healthy elderly French women living at home have secondary hyperparathyroidism and high bone turnover in winter. EPIDOS Study Group.
It was recently demonstrated that calcium and vitamin D supplements were capable of decreasing the incidence of hip fractures in institutionalized elderly subjects through a reduction of senile secondary hyperparathyroidism. As there are no appropriate data to recommend such a supplement to the elderly living at home, the aim of this study was to determine the incidence of senile secondary hyperparathyroidism in old French women from the general community, its relation to vitamin D status, and its contribution to bone turnover. Four hundred and forty women, aged 75-90 yr, were randomly selected from the general community by mailing from electoral listing in 5 French cities whose latitude varies from 49 degrees 9N to 43 degrees 6N. At the end of the winter, with previous hip fractures or those who were institutionalized were excluded. The results obtained in these women were compared to those obtained in 59 institutionalized old women and 54 younger healthy women. In the five cities for the women living at home, we found a mean PTH value greater than that obtained in young women (63 +/- 28 vs. 43 +/- 15 pg/ml; P = 0.001), but lower that that found in institutionalized women (76 +/- 49 pg/mL; P = 0.05). The mean 25-hydroxyvitamin D (25OHD) level was not different in subjects from the 5 cities, but in all of them it was significantly greater than that found in 59 institutionalized women (42.5 +/- 25.0 vs. 15.5 +/- 6.5 nmol/L; P = 0.0001) but lower than that in young adults (P < 0.001). The main determinants of PTH were in equal ratio, i.e. age (r = 0.19; P < 0.001), 25OHD, and, to a lesser degree, creatinine clearance (r = 0.10; P = 0.03). For 25OHD, the main determinant was the personal outdoor score and, to a lesser extent, the amount of daily sunlight in the city. The mean values of biochemical markers of bone turnover, bone alkaline phosphatase, osteocalcin, and Crosslaps, were significantly increased compared with the results obtained in young women, and significant negative correlations were found between these markers and hip bone mineral density. These results show that vitamin D status of a French aged population in good health and living at home depends mainly on lifestyle. Like institutionalized women, old women living at home exhibit clear evidence of senile hyperparathyroidism in the winter, secondary in part to a reduced 25OHD level and associated with biological signs of increased bone turnover. The maintenance of PTH within the normal range for healthy adults by vitamin D and calcium treatment might constitute an approach for the prevention of bone loss in the entire aged population.


[Risk-based analysis in the handling of sensitive data in the health sector].
This contribution delves into the EU Regulation 2016/679 that defines the accountability of data controllers, with regard to the processing of personal data, and imposes the adoption of technological and organizational measures demonstrating a full commitment to European data protection laws. A risk-based analysis and an impact-based approach are recommended for all personal data, and especially those concerning health, in order to safeguard the rights and freedoms of the data subjects. The article also describes the processes that should be put in place to avoid errors and violations in the handling of personal data, which can result in physical, material or non-material damage to natural persons. The controller, in fact, needs to evaluate the situation carefully and follow a series of compulsory steps to assess any potential weaknesses in the system. A balancing act between public health concerns and privacy protection is necessary; this can be obtained through a detailed analysis of the norms and their careful implementation.


A phase 2 study to evaluate the safety and immunogenicity of a recombinant HIV type 1 vaccine based on adeno-associated virus.
The recombinant vaccine, tgAAC09, based on an adeno-associated virus serotype 2 (AAV2) vector encoding HIV-1 subtype C Gag, protease, and part of reverse transcriptase, induced robust T cell and antibody responses in nonhuman primates. In a previous phase I study in 80 healthy HIV-seronegative European and Indian adults, the vaccine was generally safe, well tolerated, and modestly immunogenic when administered once at doses up to 3 x 10(11) DRP. This phase II double-blind, randomized, placebo-controlled trial tested two administrations and a higher dosage of tgAAC009. Ninety-one healthy HIV-seronegative adults from three African countries were given one of three dosage levels of tgAAC09 (3 x 10(10), 3 x 10(11), or 3 x 10(12) DRP) intramuscularly, either at a 6- or 12-month interval; follow-up was 18 months. Overall, 65% and 57% of vaccine recipients experienced local and systemic signs and symptoms, respectively, most being mild. Frequency and severity were not dose related and were similar to those in placebo recipients. No vaccine-related serious adverse events were reported. Overall, HIV-specific T cell responses were detected by IFN-gamma ELISPOT in 17/69 (25%) vaccine recipients with 38% (10/26) responders in the highest dosage group. The response rate improved significantly with boosting at 6, but not 12 months, in the 3 x 10(11) and 3 x 10(12) dosage groups only. Neutralizing antibody titers to the AAV2 did not alter the frequency of immune responses to HIV. Two doses of tgAAC09 were well tolerated at the dosage levels given. Fewer than half the recipients of the highest vaccine dosage, 3 x 10(12) DRP, had T cell responses to HIV.


Ligand-independent activation of the sevenless receptor tyrosine kinase changes the fate of cells in the developing Drosophila eye.
Cell fate in the developing eye is determined by a cascade of inductive interactions. In this process, the sevenless protein--a receptor tyrosine kinase--is required for the specification of the R7 photoreceptor cell fate. We have constructed a gain-of-function sevenless mutation (SevS11) by overexpressing a truncated sevenless protein in the cells where sevenless is normally expressed. In SevS11 mutant flies, all sevenless-expressing cells initiate neural development. This results in the formation of multiple R7-like photoreceptors per ommatidium. Therefore, sevenless activity appears to be necessary and sufficient for the determination of R7 cell fate. These results illustrate the central role receptor tyrosine kinases can play in the specification of cell fate during development.


Study on Direct Synthesis of Energy Efficient Multifunctional Polyaniline-Graphene Oxide Nanocomposite and Its Application in Aqueous Symmetric Supercapacitor Devices.
The synthesis of promising nanocomposite materials can always be tricky and depends a lot on the method of synthesis itself. Developing such synthesis routes, which are not only simple but also can effectively catch up the synergy of the compositing material, is definitely a worthy contribution towards nanomaterial science. Carbon-based materials, such as graphene oxide, and conjugative polymers, such as conductive polyaniline, are considered materials of the 21st century. This study involves a simple one pot synthesis route for obtaining a nanocomposite of polyaniline and graphene oxide with synergistic effects. The study was carried out in a systematic way by gradually changing the composition of the ingredients in the reaction bath until the formation of nanocomposite took place at some particular reaction parameters. These nanocomposites were then utilized for the fabrication of electrodes for aqueous symmetric supercapacitor devices utilizing gold or copper as current collectors. The device manifested a good capacitance value of 264 F/g at 1 A/g, magnificent rate performance, and capacitance retention of 84.09% at a high current density (10 A/g) when gold sheet electrodes were used as the current collectors. It also showed a capacitance retention of 79.83% and columbic efficiency of 99.83% after 2000 cycles.


Abnormalities of nonvisually-guided eye movements in Parkinson's disease.
Rapid eye movements (saccades) were examined in 7 patients with idiopathic Parkinson's disease (PD) and a matched group of normal control subjects. The effect of instructional and stimulus conditions used to elicit saccades was examined using 3 experimental paradigms. Eye movements directly elicited by a novel peripheral target were unimpaired in patients with PD as compared with control subjects. Saccades to a remembered target location, however, were dysmetric in the PD group and showed a characteristic multistepping pattern. The PD impairment was not caused by a loss of information on target location since their final eye position was close to the target at all eccentricities. Peak velocity, duration, and latency did not distinguish between PD patients and controls. These results support the view that for saccades which are not directly elicited by a visual target there is a neural pathway that can be distinguished from structures involved in the generation of visually elicited (or 'reflexive') saccades. The finding that in PD saccades to a remembered target are selectively impaired suggests that structures in the basal ganglia play a crucial role in this alternative pathway.


Intrinsic H(+) ion mobility in the rabbit ventricular myocyte.
The intrinsic mobility of intracellular H(+) ions was investigated by confocally imaging the longitudinal movement of acid inside rabbit ventricular myocytes loaded with the acetoxymethyl ester (AM) form of carboxy-seminaphthorhodafluor-1 (carboxy-SNARF-1). Acid was diffused into one end of the cell through a patch pipette filled with an isotonic KCl solution of pH 3.0. Intracellular H(+) mobility was low, acid taking 20-30 s to move 40 microm down the cell. Inhibiting sarcolemmal Na(+)-H(+) exchange with 1 mM amiloride had no effect on this time delay. Net H(+)(i) movement was associated with a longitudinal intracellular pH (pH(i)) gradient of up to 0.4 pH units. H(+)(i) movement could be modelled using the equations for diffusion, assuming an apparent diffusion coefficient for H(+) ions (D(H)(app)) of 3.78 x 10(-7) cm(2) s(-1), a value more than 300-fold lower than the H(+) diffusion coefficient in a dilute, unbuffered solution. Measurement of the intracellular concentration of SNARF (approximately 400 microM) and its intracellular diffusion coefficient (0.9 x 10(-7) cm(2) s(-1)) indicated that the fluorophore itself exerted an insignificant effect (between 0.6 and 3.3 %) on the longitudinal movement of H(+) equivalents inside the cell. The longitudinal movement of intracellular H(+) is discussed in terms of a diffusive shuttling of H(+) equivalents on high capacity mobile buffers which comprise about half (approximately 11 mM) of the total intrinsic buffering capacity within the myocyte (the other half being fixed buffer sites on low mobility, intracellular proteins). Intrinsic H(+)(i) mobility is consistent with an average diffusion coefficient for the intracellular mobile buffers (D(mob)) of ~9 x 10(-7) cm(2) s(-1).


Variability of the needle essential oils of Pinus peuce from different populations in Montenegro and Serbia.
The essential-oil composition of Pinus peuce Griseb. is reported at the population level. Macedonian pine is endemic high-mountain Balkan pine relict of an anthropogenically reduced area, with large morphological diversity and insufficiently clear taxonomic position. In the pine-needle terpene profile of two populations from Montenegro and one from Serbia, 78 compounds were detected, 56 of which are identified (Table 3). The dominant constituents were alpha-pinene (36.5%) and germacrene D (11.4%). The following 20 additional components were found to be present in medium-to-high amounts (0.5-10%): camphene (8.5%), bornyl acetate (6.8%), beta-pinene (6.8%), beta-caryophyllene (5.2%), beta-phellandrene (4.7%), terpinen-4-ol acetate (1.6%), (E)-hex-2-enal (1.5%), alpha-muurolene (1.2%), beta-gurjunene (1.1%), beta-myrcene (1.0%), alpha-terpinyl acetate (0.9%), alpha-phellandrene (0.8%), delta-cadinene (0.8%), alpha-humulene (0.8%), sabinene (0.7%), aromadendrene (0.6%), alpha-thujene (0.6%), gamma-muurolene (0.6%), gamma-cadinene (0.6%), alpha-terpinolene (0.5%), and one unknown component (0.5%). The similarity of the populations and the within-population variability were visualized by principle-component analysis (PCA) and genetic analysis of selected terpenes in 90 tree samples. Our study suggests a closer connection between populations II and III compared to population I. Based on the profile of the main terpene components, the studied populations are more similar to populations from Kosovo and Greece than to the population from Mt. Mokra (Montenegro) and the population in France.


Exact Solutions of Coupled Multispecies Linear Reaction-Diffusion Equations on a Uniformly Growing Domain.
Embryonic development involves diffusion and proliferation of cells, as well as diffusion and reaction of molecules, within growing tissues. Mathematical models of these processes often involve reaction-diffusion equations on growing domains that have been primarily studied using approximate numerical solutions. Recently, we have shown how to obtain an exact solution to a single, uncoupled, linear reaction-diffusion equation on a growing domain, 0 < x < L(t), where L(t) is the domain length. The present work is an extension of our previous study, and we illustrate how to solve a system of coupled reaction-diffusion equations on a growing domain. This system of equations can be used to study the spatial and temporal distributions of different generations of cells within a population that diffuses and proliferates within a growing tissue. The exact solution is obtained by applying an uncoupling transformation, and the uncoupled equations are solved separately before applying the inverse uncoupling transformation to give the coupled solution. We present several example calculations to illustrate different types of behaviour. The first example calculation corresponds to a situation where the initially-confined population diffuses sufficiently slowly that it is unable to reach the moving boundary at x = L(t). In contrast, the second example calculation corresponds to a situation where the initially-confined population is able to overcome the domain growth and reach the moving boundary at x = L(t). In its basic format, the uncoupling transformation at first appears to be restricted to deal only with the case where each generation of cells has a distinct proliferation rate. However, we also demonstrate how the uncoupling transformation can be used when each generation has the same proliferation rate by evaluating the exact solutions as an appropriate limit.


Cooperation dynamics in networked geometric Brownian motion.
Recent works suggest that pooling and sharing may constitute a fundamental mechanism for the evolution of cooperation in well-mixed fluctuating environments. The rationale is that, by reducing the amplitude of fluctuations, pooling and sharing increases the steady-state growth rate at which individuals self-reproduce. However, in reality interactions are seldom realized in a well-mixed structure, and the underlying topology is in general described by a complex network. Motivated by this observation, we investigate the role of the network structure on the cooperative dynamics in fluctuating environments, by developing a model for networked pooling and sharing of resources undergoing a geometric Brownian motion. The study reveals that, while in general cooperation increases the individual steady state growth rates (i.e., is evolutionary advantageous), the interplay with the network structure may yield large discrepancies in the observed individual resource endowments. We comment possible biological and social implications and discuss relations to econophysics.


Noninvasive prenatal diagnosis of duchenne muscular dystrophy: comprehensive genetic diagnosis in carrier, proband, and fetus.
Noninvasive prenatal diagnosis of monogenic disorders using maternal plasma and targeted massively parallel sequencing is being investigated actively. We previously demonstrated that comprehensive genetic diagnosis of a Duchenne muscular dystrophy (DMD) patient is feasible using a single targeted sequencing platform. Here we demonstrate the applicability of this approach to carrier detection and noninvasive prenatal diagnosis. Custom solution-based target enrichment was designed to cover the entire dystrophin (DMD) gene region. Targeted massively parallel sequencing was performed using genomic DNA from 4 mother and proband pairs to test whether carrier status could be detected reliably. Maternal plasma DNA at varying gestational weeks was collected from the same families and sequenced using the same targeted platform to predict the inheritance of the DMD mutation by their fetus. Overrepresentation of an inherited allele was determined by comparing the allele fraction of 2 phased haplotypes after examining and correcting for the recombination event. The carrier status of deletion/duplication and point mutations was detected reliably through using a single targeted massively parallel sequencing platform. Whether the fetus had inherited the DMD mutation was predicted correctly in all 4 families as early as 6 weeks and 5 days of gestation. In one of these, detection of the recombination event and reconstruction of the phased haplotype produced a correct diagnosis. Noninvasive prenatal diagnosis of DMD is feasible using a single targeted massively parallel sequencing platform with tiling design.


Relationship between changes in bone mineral density and vertebral fracture risk associated with risedronate: greater increases in bone mineral density do not relate to greater decreases in fracture risk.
Low bone mineral density (BMD) is correlated with increased fracture risk. Whether greater BMD increases induced by osteoporosis drugs are related to greater decreases in fracture risk is controversial. We analyzed the relationship between BMD change and fracture risk in postmenopausal osteoporotic women receiving antiresorptive treatment. The analysis combined data from three pivotal risedronate fracture end-point trials. Women received risedronate (n = 2047) or placebo (n = 1177) daily for up to 3 yr. The BMD and vertebral radiographs were assessed periodically during 3 yr. The estimated risk of new vertebral fracture was compared between patients whose BMD increased and those whose BMD decreased. Risedronate-treated patients whose BMD decreased were at a significantly greater risk (p = 0.003) of sustaining a vertebral fracture than patients whose BMD increased. The fracture risk was similar (about 10%) in risedronate-treated patients whose increases in BMD were < 5% (the median change from baseline) and in those whose increases were >/= 5% (p = 0.453). The changes in lumbar spine BMD explained only 18% (95% confidence interval [CI], 10%, 26%; p < 0.001) of risedronate's vertebral fracture efficacy. Although patients showing an increase in BMD had a lower fracture risk than patients showing a decrease in BMD, greater increases in BMD did not necessarily predict greater decreases in fracture risk.


Effect of the Zataria multiflora on systemic inflammation of experimental animals model of COPD.
The effects of Zataria multiflora (Z. multiflora) on systemic inflammation in guinea pigs model of COPD were examined. Control animals, COPD (induced by exposing animals to cigarette smoke), COPD+drinking water containing three concentrations of the extract of Z. multiflora, and COPD+dexamethasone were studied (n=6 for each group). Serum levels of IL-8 and malondialdehyde (MDA), total blood WBC (P<0.01 for all cases), and eosinophil counts (P<0.05) were higher and weight changes (P<0.05) were lower in the COPD group compared to controls. IL-8 level (P<0.001) and weight changes (P<0.01 to P<0.001) in all treated groups with Z. multiflora and total WBC number and MDA level in treated groups with two higher concentrations of the extract and lymphocytes percentage (P<0.05) in the highest concentration of Z. multiflora and dexamethasone (P<0.05 to P<0.001) were significantly improved compared to the COPD group. Results showed a preventive effect of hydroethanolic extract from Z. multiflora on all measured parameters in animals model of COPD which was comparable or even higher (in the highest concentration) compared to the effect of dexamethasone at the concentration used.


Do familiar landmarks reset the global path integration system of desert ants?
It is often suggested that animals may link landmark memories to a global coordinate system provided by path integration, thereby obtaining a map-like representation of familiar terrain. In an attempt to discover if desert ants form such associations we have performed experiments that test whether desert ants recall a long-term memory of a global path integration vector on arriving at a familiar food site. Ants from three nests were trained along L-shaped routes to a feeder. Each route was entirely within open-topped channels that obscured all natural landmarks. Conspicuous artificial landmarks were attached to the channelling that formed the latter part of the route. The homeward vectors of ants accustomed to the route were tested with the foodward route, either as in training, or with the first leg of the L shortened or extended. These ants were taken from the feeder to a test area and released, whereupon they performed a home vector. If travelling the latter part of a familiar route and arriving at a familiar food site triggers the recall of an accustomed home vector, then the home vector should be the same under both test conditions. We find instead that the home vector tended to reflect the immediately preceding outward journey. In conjunction with earlier work, these experiments led us to conclude in the case of desert ants that landmark memories do not prime the recall of long-term global path integration memories. On the other hand, landmark memories are known to be linked to local path integration vectors that guide ants along a segment of a route. Landmarks thus seem to provide procedural information telling ants what action to perform next but not the positional information that gives an ant its location relative to its nest.


DNA Conformational Changes Play a Force-Generating Role during Bacteriophage Genome Packaging.
Motors that move DNA, or that move along DNA, play essential roles in DNA replication, transcription, recombination, and chromosome segregation. The mechanisms by which these DNA translocases operate remain largely unknown. Some double-stranded DNA (dsDNA) viruses use an ATP-dependent motor to drive DNA into preformed capsids. These include several human pathogens as well as dsDNA bacteriophages-viruses that infect bacteria. We previously proposed that DNA is not a passive substrate of bacteriophage packaging motors but is instead an active component of the machinery. We carried out computational studies on dsDNA in the channels of viral portal proteins, and they reveal DNA conformational changes consistent with that hypothesis. dsDNA becomes longer ("stretched") in regions of high negative electrostatic potential and shorter ("scrunched") in regions of high positive potential. These results suggest a mechanism that electrostatically couples the energy released by ATP hydrolysis to DNA translocation: The chemical cycle of ATP binding, hydrolysis, and product release drives a cycle of protein conformational changes. This produces changes in the electrostatic potential in the channel through the portal, and these drive cyclic changes in the length of dsDNA as the phosphate groups respond to the protein's electrostatic potential. The DNA motions are captured by a coordinated protein-DNA grip-and-release cycle to produce DNA translocation. In short, the ATPase, portal, and dsDNA work synergistically to promote genome packaging.


Efficacy of Rituximab in Refractory Inflammatory Myopathy Associated With Coexistence of Behçet's Disease and Antiphospholipid Syndrome.
A 43-year-old Caucasian male initiated myalgias and loss of muscle strength in the upper and lower limbs, but especially at the shoulder and pelvic girdle. Creatinine phosphokinase was elevated seven-fold above the normal reference value and aldolase was slightly elevated. He had a previous diagnosis of Behçet's disease, antiphospholipid syndrome and hypertriglyceridaemia. At this time, he was on azathioprine 150 mg daily, colchicine 1 mg daily, warfarin and fenofibrate 200 mg daily. Fenofibrate was stopped and creatinine phosphokinase re-evaluated 2 months later, but it was higher, with persistent myalgias. By this time, prednisolone was restarted and the azathioprine dose reduced until it was discontinued. Nevertheless, 2 months after stopping azathioprine, the patient remained symptomatic and creatinine phosphokinase was persistently elevated. At this point, the authors requested myositis antibody testing to exclude overlap with a third autoimmune disorder, and Ro52 antibody was positive. Electromyography was normal. Magnetic resonance imaging of lower limb muscles was compatible with polymyositis. Muscular biopsy of the medial gastrocnemius revealed inflammatory myopathy. The authors proposed treatment with rituximab and after 3 months, the patient had clinically and analytically improved, with reduction of creatinine phosphokinase, without adverse reactions. As we can see in this case, rituximab could be a secure treatment for patients with idiopathic inflammatory myopathy without improvement on glucocorticoids plus another immunosuppressive agent. This patient has a rare overlap syndrome, since this is the first case of an association between inflammatory myopathy, Behçet's disease and antiphospholipid syndrome described in the literature. This is the first case report in the literature of an association between inflammatory myopathy, Behçet's disease and antiphospholipid syndrome.Rituximab could be a secure treatment for refractory idiopathic inflammatory myopathy.This case report highlights the importance of a methodical diagnostic work-up for an accurate diagnosis.