Biosynthesis in vitro of complement subcomponents C1q, C1s and C1 inhibitor by resting and stimulated human monocytes.
The capacity of cultured human monocytes to synthesize and to secrete the subcomponents of C1 and C1 inhibitor was examined. Non-stimulated monocytes secreted C1q and C1s from day 5 of culture. C1s reached a plateau immediately at its maximum level, whereas C1q secretion increased progressively until the end of the second week. Between day 12 and day 25, C1q secretion remained nearly constant (1-15 fmol/day per microgram of DNA, depending on the donor), whereas C1s secretion decreased and even in some cases stopped. C1r and C1 inhibitor were not secreted in detectable amounts by these resting cells. Stimulation of monocytes by yeasts, immunoglobulin G-opsonized sheep red blood cells or latex beads did not modify consistently C1q and C1s secretion. Activation by conditioned media from mitogen-, antigen- or allogeneic-stimulated lymphocyte cultures increased C1q production from 2 to 7 times and re-activated C1s secretion. Under the same conditions of activation, C1 inhibitor was secreted (up to 300 fmol/day per microgram of DNA) and C1r became detectable in culture supernatants. Isolated human monocytes are thus able to synthesize the whole C1 subcomponents; C1, if assembled, could be protected from non-immunological activation by locally produced C1 inhibitor. Activated monocytes appear to be a good tool for studying the assembly of C1 subcomponents and the role of C1 inhibitor in this process.


Angle stable locking reduces interfragmentary movements and promotes healing after unreamed nailing. Study of a displaced osteotomy model in sheep tibiae.
Large interfragmentary movements may delay bone-healing. The hypothesis of the present study was that a reduction of interfragmentary movements, especially of torsional rotation and bending angles, would support the healing process and lead to improved healing following unreamed tibial nailing. The objective of this study was to investigate healing of an unstable tibial osteotomy site following stabilization with unreamed nailing with a modified tibial device that had angle stable holes for the locking bolts. We compared those findings with healing after stabilization of such sites with standard unreamed tibial nailing. The duration of the study period was nine weeks. The site of a standardized displaced osteotomy (3-mm gap) in twelve ovine tibiae was stabilized with unreamed tibial nailing: six animals were treated with a modified nail that had angle stable holes for the locking bolts, and six were treated with standard unreamed tibial nailing. In vivo gait analysis with optical measurements of interfragmentary movements and simultaneous measurements of ground reaction parameters were performed three days after the operation and once weekly afterward. After the animals were killed at nine weeks, the treated and contralateral tibiae were explanted, the implants were removed, and radiographs were made and evaluated for bridged cortices. Each pair of tibiae was also mechanically tested until torsional failure, after which the whole callus region was subjected to histological and histomorphometric analysis. Throughout the examination period, the interfragmentary movements in all directions were significantly smaller in the group treated with the angle stable tibial nail than they were in the group treated with standard unreamed tibial nailing. The limbs treated with the angle stable tibial nails returned to almost full weight-bearing during the period of the investigation, whereas those treated with standard nailing did not. Histomorphometric analysis, radiographic data, and mechanical testing showed superior bone-healing following treatment with the angle stable tibial nail. Use of an angle stable tibial nail may help to reduce interfragmentary movements in vivo and thus lead to superior bone-healing compared with that following standard unreamed tibial nailing.


Prevalence of zoonotic (brugian) filariasis in Asia: A proportional meta-analysis.
Lymphatic filariasis is a public health problem and targeted for global elimination. WHO recommends mass drug administration to interrupt transmission of the parasites involved. There are concerns that transmission interruption may be difficult in areas of zoonotic filarial infections. This study aimed to estimate the pooled prevalence of zoonotic brugian filariasis, and to compare the pooled prevalence of brugian filariasis in human and animal populations in the same area based on available studies. A comprehensive literature search was conducted in health-related electronic databases (PubMed, Ovid MEDLINE, Index Medicus, google scholar). A random-effect meta-analysis of the pooled overall prevalence of filariasis in animal populations was conducted. Sixteen studies from four different Asian countries were identified. Studies were conducted most frequently in Thailand (n = 7), followed by Malaysia (n = 5), India (n = 3), and Sri Lanka (n = 1). Regardless of animal group, the pooled overall prevalence of animal Brugia infections was 13% (95%CI: 7-21%, I2:98%, 16 studies). On stratification, the pooled overall prevalence in the animal population was 19% (95%CI: 1-50%, I2: 99%, 3 studies) in India, 8% (95%CI: 2-7%, I2: 97%, 5 studies) in Malaysia, and 13% (95%CI: 7-20%, I2: 94%, 7 studies) in Thailand. The prevalence in the animal population was 17% (95%CI: 13-21%, 1 study) in Sri Lanka. The pooled overall prevalence of Brugia malayi was 13% (95%CI: 7-21%, I2:98%, 12 studies), while for Brugia pahangi this was 12% (95%CI: 7-19%, I2:86%, 7 studies). Regardless of animal group, geographic area, or diagnostic test, the prevalence of B. malayi was consistently high. On stratification by animal category, the pooled overall prevalence was 10% (95%CI: 6-14%, I2:92%, 13 studies) in cats, 12% (95%CI: 2-28%, I2: 99%, 6 studies) in dogs, and 55% (95%CI: 47-63%, 1 study) in leaf-eating monkeys. The findings show the extent of zoonotic Brugiainfections in domestic cats and dogs, suggesting that these animals are potential reservoirs for human brugian filariasis in the study countries. To substantiate this with more accuracy, future well designed whole genomic sequencing of individual mf collected from humans and B. malayi infected animals in the same area are needed.


Single-Arm, Open-Label, Multicenter Study to Evaluate the Safety and Performance of Dura Sealant Patch in Reducing Cerebrospinal Fluid Leakage Following Elective Cranial Surgery: The ENCASE Trial Study Protocol.
Cerebrospinal fluid (CSF) leakage is one of the most common neurosurgical complications, occurring in 4% to 32% of surgical cases, with a higher incidence in complicated skull base surgery, intradural spine surgery, and the surgery of the posterior fossa. Our group developed a Dural Sealant Patch (DSP) for watertight dural closure after cranial surgery. To clinically study for the first time the safety and performance of the DSP as a means of reducing CSF leakage in patients undergoing elective cranial intradural surgery with a dural closure procedure. We will conduct an open-label, single-arm, multicenter study with a 360 d (12 mo) follow-up. A total of 40 patients will be enrolled at 3 sites. The primary endpoint is a combination of occurrences of one of the following events: postoperative percutaneous CSF leakage, intraoperative leakage at 20 cm H2O, or postoperative wound infection. The secondary endpoints are pseudomeningocele and thickness of dura + DSP. Not more than 3 patients will meet the primary endpoint suggesting safety and efficacy. As a next step, a randomized controlled trial against the best current practice will follow to evaluate if DSP reduces CSF leakage while its safety is noninferior.


Retinopathy of prematurity in extremely low birthweight infants.
From 1977 to 1982, 108 infants weighing less than 1000 g at birth were examined in a nursery for premature babies for evidence of retinopathy of prematurity (ROP). Of these 108 infants, 88 were subjected to follow-up examinations for periods of 10 months to six years. ROP had been observed in 53% (47/88) of these children; it had been severe in 31% (27/88). Subsequently, 19% (17/88) of these children developed retrolental fibroplasia (RLF); all of these had had severe ROP, except one, in whom it is presumed to have been missed. The RLF was severe in only one eye of one child. Each of these infants had received only 25 mg of vitamin E by mouth. The writers consider that the case for the administration of large doses of vitamin E in the prevention of RLF is still not proven and conclude that, if vitamin E does have a protective effect, then a dose of 25 mg is sufficient.


Covariate effects on linkage and association using a general pair method.
The "general pair method" (GPM) is a nonparametric, identity-by-state (IBS) method of assessing linkage between a chromosomal marker and a binary phenotype. It is applicable to any pedigree structure, and uses marker information from affected as well as unaffected individuals. Results obtained here from nuclear families (Problem 2A) are contrasted with those from extended pedigrees (Problem 2B). Test statistics for chromosomal linkage between each marker and disease status are contrasted with tests for "direct association" which test the hypothesis that a particular allele is associated disease status across all pedigrees. A novel extension of the GPM is presented here for testing whether the strength of linkage (and/or association) depends on the levels of a covariate (i.e., dependency on gender, age, the levels of the "environmental factor," or the levels of the "quantitative phenotypes" supplied). The GPM is seen to have some power to detect major gene 1 on chromosome 5, and major gene 3 on chromosome 4. The gender interaction effects proved too small to detect. No direct associations are found.


Comparative effects of noradrenaline and serotonin in a central and a peripheral artery in vitro.
A comparative study was done on a central and a peripheral artery of the rabbit with noradrenaline, serotonin and K+ in vitro. The aorta was more sensitive to NA than to 5-HT whilst the cerebral artery responded better to 5-HT. In both vessels, K+ produced similar responses. The alpha-adrenoceptor antagonist, phentolamine, and the tryptaminergic receptor antagonists, methysergide and cyproheptadine reduced, competitively, the effects of the agonists. There was no significant difference in the degree of antagonism between the cerebral artery and the thoracic aorta. Potassium-induced contractions were also reversibly reduced by phentolamine but not by 5-HT antagonists. There was no cross-tolerance between 5-HT and noradrenaline and K+ in these arteries. These results indicate that there are differences in the sensitivities of these vessels to the vasoconstrictors. This is interesting in view of the fact that 5-HT has often been implicated in migraine, a central phenomenon.


24-H pharyngeal pH monitoring in healthy volunteers: a normative study.
Gastropharyngeal reflux has been associated with disorders of the upper and lower airways. It may be shown by pharyngeal pH-metry, but reports on normality in healthy volunteers are scarce. No definite consensus has been reached considering the upper limit of normality (ULN). The aim of the present study was therefore to quantify the occurrence of pharyngeal acid exposure (pH < 4) in healthy volunteers and, further, to examine its relation to acid exposure of the oesophagus and oesophageal motility and its occurrence in relation to age, sex, and body position. Forty healthy volunteers underwent ambulatory 24-h pH-metry, using antimony electrodes positioned 2 cm above the upper oesophageal sphincter and 5 cm above the lower oesophageal sphincter on the basis of manometry. Technical artefacts were excluded before calculation of all results. Gastropharyngeal reflux occurred in most healthy volunteers without any significant relation to age, sex, or body weight. Pharyngeal acid reflux occurred mainly in the upright position. The ULN for pharyngeal acid exposure time was assessed to 0.9% (0.2% after exclusion of mealtimes). The ULN for the number of acid events in the pharynx was 18 (6.1). The corresponding ULNs for the oesophagus were 7% and 84. Gastropharyngeal reflux may be effectively monitored by ambulatory pH-metry. The present study provides reference limits, a prerequisite for evaluating the pathophysiologic importance of the phenomenon.


Identification of Novel Biomarkers for Predicting Kidney Injury Due to Drugs Using "Omic" Strategies.
Drug-induced kidney injury accounts for 20% of community- and hospital-acquired cases of acute kidney injury (AKI). The incidence is higher among older individuals, who often have co-existing morbidities and are exposed to more diagnostic procedures and therapies. While demographic and clinical components have been identified as risk factors, the proposed cellular mechanisms of drug-induced kidney injury are numerous and complicated. There are also limitations recognized in the use of traditional biomarkers, such as serum creatinine and blood urea nitrogen, to provide high sensitivity, specificity, and timeliness to identification of drug-induced kidney injury. Therefore, novel biomarkers are currently being investigated, identified, developed, and validated for their performance over the traditional biomarkers. This review will provide an overview of drug-induced kidney injury and will discuss what is known regarding "omic" (proteomic, genomic, transcriptomic, and metabolomic) biomarker strategies for drugs known to induce nephrotoxicity.


TREATMENT SWITCHING IN CANCER TRIALS: ISSUES AND PROPOSALS.
Treatment switching occurs when patients in a randomized clinical trial switch from the treatment initially assigned to them to another treatment, typically from the control to experimental treatment. This study discusses the issues this raises and possible approaches to addressing them in trials of cancer drugs. Stakeholders from around the world were invited to a 1.5-day Workshop in Adelaide, Australia. This study attempts to capture the key points from the discussion and the perspectives of the various stakeholder groups, but is not a formal consensus statement. Treatment switching raises challenging ethical issues with arguments for and against allowing it. It is increasingly common in cancer drug trials and presents challenges for the interpretation of results by regulators, clinicians, patients, and payers. Proposals are offered for good practice in the design, management, and analysis of trials and wider development programs for cancer drugs in which treatment switching has occurred or is likely to. Recommendations are also offered for further action to improve understanding of the importance and challenges of treatment switching and to promote agreement between key stakeholders on guidelines and other steps to address these challenges. The handling of treatment switching in trials is of concern to all stakeholders. On the basis of the discussions at the Adelaide International Workshop, there would appear to be common ground on approaches to addressing treatment switching in cancer trials and scope for the development of formal guidelines to inform the work of regulators, payers, industry, trial designers and other stakeholders.


Spontaneous Regression of Epithelioid Angiosarcoma in a Young Woman.
A 20-year-old Japanese woman with a history of pulmonary atresia was referred to our hospital after the detection of an abnormal mass in the right lung and mediastinal lymphadenopathy. A cytological specimen obtained by transbronchial brushing indicated that the pathological diagnosis was non-small cell lung cancer. During the follow-up period, the tumor spontaneously regressed. At four months after the diagnosis, she experienced sudden bleeding from the small intestine. The histological characteristics of the small intestine tumor were compatible with the cytological characteristics of the lung tumor. Detailed immunohistochemical analyses led to a final diagnosis of epithelial angiosarcoma of the small intestine, which might have formed metastatic lesions in the lung.


'Fasting and prayer don't concern the doctors ... they don't even know what it is': communication, decision-making and perceived social relations of Pakistani Muslim patients with long-term illnesses.
Pakistani Muslims have the poorest overall health profile in Britain, for reasons which at present remain poorly understood. We sought to explore the impact of religious identity and beliefs on self-management of long-term conditions, on patient-professional communication and decision-making and health inequalities within Pakistani Muslim communities. Ethnographic study involving in-depth interviews and participant observation. Religious identity plays a central role in many individuals' attempts to make sense of their personal illness narrative. Practitioners and patients are typically unwilling to engage in discussion about religious influences on patient decision-making, reflecting patients' lack of confidence in the appropriateness of raising such issues, and professionals' lack of awareness of their importance. Patients consequently receive little or no support from professionals about decisions involving such influences on self-care. The policy vacuum and lack of patient-professional engagement in this area allows the use of stereotypes of Pakistani Muslims by practitioners to remain unchallenged in most healthcare settings. Social dynamics within these settings reflect those in wider UK society, in which many Pakistani respondents believe they are unwelcome. These factors affect the psychosocial well-being of Pakistani Muslims and on their ability to manage long-term conditions. Shared understanding about the context in which patients manage long-term conditions is a precursor to effective lay-professional partnerships. Religious identity influences the health beliefs and practices of many British Pakistani Muslim patients. Failure to acknowledge and discuss this influence on long-term illness management leads to a vacuum in professional knowledge, inadequate support for patients' decision-making and poor responses to their requests for assistance. Findings indicate a need for practitioners to initiate more open discussion and raise questions about the pathways leading to higher rates of complications and the relationship between social status and health inequalities in this population.


Age-dependent availability and functionality of bone marrow stem cells in an experimental model of acute and chronic myocardial infarction.
The aim of this study was to investigate the effect of aging and timing of left ventricular ischemic injury on the availability and functionality of stem cells. We studied young and aged male inbred Lewis rats that were used as donors of bone marrow mononuclear cells (BM-MNCs), divided in four experimental groups: controls, sham operated, 48 h post-myocardial infarction (MI), and 28 days post-MI. In vitro studies included flow cytometry analysis, hematopoietic colony-forming capacity, and invasion assays of migration capacity. BM-MNCs from these groups were transplanted in female rats after MI induction. Late engraftment was evaluated by real-time PCR of the SRY chromosome. Percentage of CD34+/CD45+(low) cells was similar among different experimental groups in young rats, but was significantly higher in aged animals (p < 0.001), particularly 28 days post-MI. KDR+/CD34+ cells were increased 48 h after MI and decreased 28 days post-MI in young animals, while they were profoundly reduced in the aged group (p < 0.001). Triple staining for CD44+/CD29+/CD71+ cells was similar in different groups of aged rats, but we observed an intense increase 48 h post-MI in young animals. Colony-forming units and cytokine-induced migration were significantly attenuated 28 days after the MI. Late engraftment in infarcted transplanted female hearts was present, but considerably heterogeneous. Finally, recovery of left ventricular systolic function in transplanted female recipients was significantly influenced by donors' BM-MNCs groups (p < 0.01). We have demonstrated that aging and timing of myocardial injury are factors that may act synergistically in determining stem cell availability and function. Such interaction should be considered when planning new cell therapy strategies for acute and chronic ischemic heart disease in the clinical arena.


Facial preferences in early adolescent girls: pubertal maturity predicts preferences maturity.
Despite numerous studies on perception of facial attractiveness in adults, preferences in adolescents remain poorly recognized. The aim of present study was to explore facial preferences in girls at early adolescence (11-14 years old) and compare them with preferences of women. All females evaluated the same 30 male faces, which were also assessed by independent judges for several perceived features. Regardless of age, girls assessed attractiveness much the same as women, and the strengths of their preferences for specific facial features were similar to those of women. Except for the youngest girls, pubertal maturity (measured as the time elapsed since the menarche and breast development) correlated positively with the similarity of the girls' attractiveness evaluations to those of adult women and with strength of preference for cues to good biological quality (skin healthiness and sexy appearance). This remained true even after controlling for age and psychosexual development, suggesting thus that sex hormones are involved in development of facial preferences in pubescent girls.


Triglyceride-rich HDL3 from patients with familial hypercholesterolemia are less able to inhibit cytokine release or to promote cholesterol efflux.
Familial hypercholesterolemia (FH) is associated with heterogeneity of the onset and severity of coronary heart disease (CHD). In this study, we investigated different low-grade proinflammatory markers and the atheroprotective function of the HDL3 subfraction in FH-patients (n = 13) with identical LDL-receptor mutations and in age- and sex-matched healthy controls (n = 11). Compared with healthy controls, FH-patients had greater gene expressions of the proatherogenic mediators TNF-alpha and IL-8 in circulating peripheral blood mononuclear cells. In addition, they had a higher serum concentration of intercellular adhesion molecule-1 (ICAM-1) and a lower net antioxidant capacity. FH-derived HDL3 with a high level of triglycerides had a reduced capacity to inhibit the release of IL-8 from TNF-alpha-stimulated human umbilical vein endothelial cells (HUVEC) [1.864 mg/L (1.461-2.208 mg/L) vs. 1.466 mg/L (1.225-1.643 mg/L); P < 0.05; median (range)], and a reduced capacity to promote cholesterol efflux from lipid-loaded macrophages [12% (12-14%) vs. 15% (14-18%); P < 0.05; median (range)] compared with HDL3 with a lower triglyceride content. Notably, the degree of inhibition of IL-8 release from HUVEC by HDL3 was correlated with the ability of HDL3 to promote cholesterol efflux (r = -0.80, P = 0.03). In conclusion, compared with healthy controls, FH-patients are characterized by higher levels of low-grade proinflammatory markers, and FH-derived HDL3 with high triglyceride content may be more proatherogenic. These triglyceride rich-HDL3 might be partly responsible for the phenotypic variation among FH-patients with identical LDL-receptor mutations.


Peptide partitioning properties from direct insertion studies.
Partitioning properties of polypeptides are at the heart of biological membrane phenomena and their precise quantification is vital for ab-initio structure prediction and the accurate simulation of membrane protein folding and function. Recently the cellular translocon machinery has been employed to determine membrane insertion propensities and transfer energetics for a series of polyleucine segments embedded in a carrier sequence. We show here that the insertion propensity, pathway, and transfer energetics into synthetic POPC bilayers can be fully described by direct atomistic peptide partitioning simulations. The insertion probability as a function of peptide length follows two-state Boltzmann statistics, in agreement with the experiments. The simulations expose a systematic offset between translocon-mediated and direct insertion free energies. Compared to the experiment the insertion threshold is shifted toward shorter peptides by approximately 2 leucine residues. The simulations reveal many hitherto unknown atomic-resolution details about the partitioning process and promise to provide a powerful tool for urgently needed calibration of lipid parameters to match experimentally observed peptide transfer energies.


Sharing moral values: anticipated ingroup respect as a determinant of adherence to morality-based (but not competence-based) group norms.
This research examines how moral values regulate the behavior of individual group members. It argues that group members behave in line with moral group norms because they anticipate receiving ingroup respect when enacting moral values that are shared by ingroup members. Data from two experimental studies offer evidence in support. In Study 1 (N = 82), morality-based (but not competence-based) ingroup norms determined whether members of a low-status group opted for individual versus collective strategies for status improvement. This effect was mediated by anticipated ingroup respect and emerged regardless of whether group norms prescribed collectivistic or individualistic behavior. These effects were replicated in Study 2 (N = 69), where no comparable effect was found as a result of moral norms communicated by a higher status outgroup. This indicates that social identity implications rather than interdependence or more generic concerns about social approval or importance of cooperation drive these effects.


Neuro-inspired spike-based motion: from dynamic vision sensor to robot motor open-loop control through spike-VITE.
In this paper we present a complete spike-based architecture: from a Dynamic Vision Sensor (retina) to a stereo head robotic platform. The aim of this research is to reproduce intended movements performed by humans taking into account as many features as possible from the biological point of view. This paper fills the gap between current spike silicon sensors and robotic actuators by applying a spike processing strategy to the data flows in real time. The architecture is divided into layers: the retina, visual information processing, the trajectory generator layer which uses a neuroinspired algorithm (SVITE) that can be replicated into as many times as DoF the robot has; and finally the actuation layer to supply the spikes to the robot (using PFM). All the layers do their tasks in a spike-processing mode, and they communicate each other through the neuro-inspired AER protocol. The open-loop controller is implemented on FPGA using AER interfaces developed by RTC Lab. Experimental results reveal the viability of this spike-based controller. Two main advantages are: low hardware resources (2% of a Xilinx Spartan 6) and power requirements (3.4 W) to control a robot with a high number of DoF (up to 100 for a Xilinx Spartan 6). It also evidences the suitable use of AER as a communication protocol between processing and actuation.


Recombination affects accumulation of damaging and disease-associated mutations in human populations.
Many decades of theory have demonstrated that, in non-recombining systems, slightly deleterious mutations accumulate non-reversibly, potentially driving the extinction of many asexual species. Non-recombining chromosomes in sexual organisms are thought to have degenerated in a similar fashion; however, it is not clear the extent to which damaging mutations accumulate along chromosomes with highly variable rates of crossing over. Using high-coverage sequencing data from over 1,400 individuals in the 1000 Genomes and CARTaGENE projects, we show that recombination rate modulates the distribution of putatively deleterious variants across the entire human genome. Exons in regions of low recombination are significantly enriched for deleterious and disease-associated variants, a signature varying in strength across worldwide human populations with different demographic histories. Regions with low recombination rates are enriched for highly conserved genes with essential cellular functions and show an excess of mutations with demonstrated effects on health, a phenomenon likely affecting disease susceptibility in humans.


DNA methylation at birth and lateral ventricular volume in childhood: a neuroimaging epigenetics study.
Lateral ventricular volume (LVV) enlargement has been repeatedly linked to schizophrenia; yet, what biological factors shape LVV during early development remain unclear. DNA methylation (DNAm), an essential process for neurodevelopment that is altered in schizophrenia, is a key molecular system of interest. In this study, we conducted the first epigenome-wide association study of neonatal DNAm in cord blood with LVV in childhood (measured using T1-weighted brain scans at 10 years), based on data from a large population-based birth cohort, the Generation R Study (N = 840). Employing both probe-level and methylation profile score (MPS) approaches, we further examined whether epigenetic modifications identified at birth in cord blood are: (a) also observed cross-sectionally in childhood using peripheral blood DNAm at age of 10 years (Generation R, N = 370) and (b) prospectively associated with LVV measured in young adulthood in an all-male sample from the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 114). At birth, DNAm levels at four CpGs (annotated to potassium channel tetramerization domain containing 3, KCTD3; SHH signaling and ciliogenesis regulator, SDCCAG8; glutaredoxin, GLRX) prospectively associated with childhood LVV after genome-wide correction; these genes have been implicated in brain development and psychiatric traits including schizophrenia. An MPS capturing a broader epigenetic profile of LVV - but not individual top hits - showed significant cross-sectional associations with LVV in childhood in Generation R and prospectively associated with LVV in early adulthood within ALSPAC. This study finds suggestive evidence that DNAm at birth prospectively associates with LVV at different life stages, albeit with small effect sizes. The prediction of MPS on LVV in a childhood sample and an independent male adult sample further underscores the stability and reproducibility of DNAm as a potential marker for LVV. Future studies with larger samples and comparable time points across development are needed to further elucidate how DNAm associates with this clinically relevant brain structure and risk for neuropsychiatric disorders, and what factors explain the identified DNAm profile of LVV at birth.


Chemists cluster in chicago to confer on cagey compounds.
Shrink a clump of matter to a few hundred atoms, and it enters a curious netherworld. Neither ordinary solids nor conventional small molecules, such atomic clusters have unique chemical, optical, and electronic properties. Since the mid-1970s, when advances in synthesizing and analyzing clusters first enabled researchers to explore this netherworld in earnest, clusters have nucleated a sizable field. Many of its participants gathered in Chicago on 15 to 22 September for the Sixth International Symposium on Small Particles and Inorganic Clusters, the first of the series to be held in the United States. At the top of the agenda for the 300 attendees were the field's old stalwarts, various kinds of metal clusters; its current darlings, the carbon clusters known as fullerenes; and a possible future superstar, silicon clusters.


Effects of Combined Exposure to Carbon Ions and Protons on the Pool of MCF-7 Breast Cancer Stem Cells In Vitro.
We studied the effects of single and combined action of protons and carbon ions 12C6+ on the pool of MCF-7 human breast cancer stem cells. Single irradiation with a beam of protons or carbon ions had no significant effects on the relative number of cancer stem cells (CSC). The effects of combined irradiation in a total equieffective dose of 4 Gy depended on the sequence of exposure to ionizing radiations: the relative number of CSC did not change after irradiation with carbon ions and then with protons, but increased in the case of the reverse sequence. The most favorable result, i.e. a decrease in the CSC pool, was observed in the case of sequential irradiation with carbon ions and protons and their equal contribution to total equieffective dose. In this case, the absolute number of CSC decreased by on average 2.1 times in comparison with the control (p<0.05). The revealed regularities are of interest for the further development of new methods of radiation therapy.


Rare inheritance of Leri-Weill Syndrome due to crossover of short stature Homeobox Gene (SHOX) Deletions between X and Y Chromosomes: a case report.
Leri-Weill syndrome (LWS) is a genetic disorder caused by deletions or mutations in the SHOX gene or by deletions downstream of the gene and is classically characterized by short stature, mesomelic shortening of forearms and legs, and Madelung deformity. Correct identification of short stature homeobox-containing gene (SHOX) deficiency in children with growth problems is vital for appropriate initiation of growth hormone therapy. We report a phenotypically normal 23 day old male infant born to a father diagnosed with Leri-Weill syndrome at age 12 years with a documented SHOX deletion on his X chromosome. The patient's fetal long bones had been found to be about three weeks delayed in growth on prenatal ultrasound during the second trimester. The infant underwent genetic evaluation at 23 days of life and was found to have a SHOX deletion on Yp11.32 identified using single nucleotide polymorphism microarray (SNP) analysis and confirmed by FISH using a SHOX gene probe. We report the case of a male infant diagnosed with Leri-Weill syndrome with an unusual documented inheritance between father and son due to crossover between X and Y chromosomes during paternal meiosis. Our case is the youngest patient in literature documented by FISH analysis to have an X to Y chromosome transfer and the first of these patients diagnosed prior to onset of short stature or Madelung deformity. Our patient was identified prior to growth failure and can now be monitored for growth abnormalities with the ability to implement growth augmentation therapy without delay. Our case highlights the importance of advising affected SHOX patients of risks to future offspring and supports screening off-spring of parents carrying SHOX abnormalities regardless of sex.


Prognostic value of bronchoalveolar lavage in patients with non-HIV pneumocystis pneumonia.
Non-HIV patients with pneumocystis pneumonia (PCP) have a poor prognosis. We aimed to evaluate the prognostic factors for in-hospital mortality in terms of the clinical findings, including the results of bronchoalveolar lavage fluid (BALF)-analyses, in non-HIV PCP patients. We retrospectively reviewed non-HIV PCP patients diagnosed using bronchoalveolar lavage between April 2006 and July 2012. For patients with a poor respiratory status, noninvasive positive pressure ventilation (NPPV) was used during the bronchoalveolar lavage (BAL) procedure. Data regarding demographics, laboratory findings and the prognosis were evaluated. A total of 29 non-HIV PCP patients were analyzed. NPPV was carried out safely and successfully in 12 patients during the BAL procedure. Twelve patients (41%) died. The multivariate logistic regression analysis identified only BALF neutrophilia to be a significant prognostic factor determining in-hospital mortality. The log-rank test showed that the patients with BALF neutrophilia (≥ 31%) had a significantly lower survival rate than the other patients (p=0.001). Only BALF neutrophilia was found to be a significant predictor of survival in patients with non-HIV PCP. Our data also emphasize the significance of performing BAL in such patients, as it provides both diagnostic and prognostic information.


Inborn Errors of Metabolism: Advances in Diagnosis and Therapy.
Inborn errors of metabolism (IEMs) are a large class of genetic disorders characterized by disruption of cellular biochemical functions. Although individual IEMs are rare, collectively they represent a large and diverse class of genetic conditions, with new disorders and disease mechanisms being described regularly. Advances in the understanding of the molecular and biochemical etiologies of many IEMs via modalities such as whole-exome sequencing and metabolomics have led to significant progress in detection and treatment in recent years. In this review, we examine the current state of newborn screening for IEMs, recent advances in therapy for IEMs (including glutaric aciduria type I, urea cycle disorders, mitochondrial disorders, and lysosomal storage disorders), and opportunities for further exploration and discovery.


Dimethylaniline functionalised pyrene fluorophores; dual colour pH switching in solution and self-assembled monolayers.
A pyrene charge transfer fluorophore with three ionizable N,N-dimethylaniline moieities was explored as an interfacial pH switch. The parent carboxylate compound and the thiolated derivative were shown by spectroscopy combined with DFT calculation to be successively and reversibly protonated. Protonation leads to progressive decrease of intensity of the 550 nm centered N,N-dimethylaniline to pyrene charge transfer emission which on protonation of the third site, leads to extinction of this transition and evolution of an intense blue (450 nm) pyrene-centered emission. Concomitant loss of the charge transfer absorbance was observed and the changes are reversed on neutralization of pH. A self-assembled monolayer of the thiolated derivative was prepared on gold and found from voltammetry of ferricyanide/ferrocyanide probe to form close packed monolayers. The probe voltammetry, label-free electrochemical impedance spectroscopy of the film was monitored as a function of pH and progressive, but reversible protonation steps were reflected in decreasing film resistance. The Stokes shift of the probe prevents self-quenching so a broad, charge transfer fluorescence centered around 540 nm was recorded for the self-assembled monolayer where as per solution, progressive and reversible reduction in intensity was observed. The facile assembly, impedance and optical switching make these materials potentially interesting as on-off or two colour on-off-on fluorescence switches with potential applications in logic gates or in responsive surface applications.


MMP9 gene polymorphism is not associated with polypoidal choroidal vasculopathy and neovascular age-related macular degeneration in a Chinese Han population.
Recently, one of our studies has revealed that the serum matrix metalloproteinase 9 (MMP9) level is elevated in polypoidal choroidal vasculopathy (PCV) but not in age-related macular degeneration (AMD). Previous studies have demonstrated that abnormal extracellular matrix (ECM) metabolism plays an important role in the pathogenesis of AMD and PCV. MMP9 is an important regulating enzyme in ECM metabolism, and the MMP9 gene may be a candidate gene for the susceptibility of PCV and AMD. In this study, we aimed to investigate whether the MMP9 gene polymorphism is associated with PCV and neovascular AMD (nAMD) in a Chinese Han population. We performed a case-control study in a Chinese Han population. Three tag single nucleotide polymorphisms (SNPs) (rs17576, rs3787268 and rs2274755) of the MMP9 gene were genotyped in 251 patients with PCV, 157 patients with nAMD, and 204 control individuals using the Multiplex SNaPshot system and the direct DNA sequencing technique. The three SNPs genotypes and allele frequencies in the PCV, nAMD and control groups were evaluated using PLINK software and binary logistic regression analysis. In the PCV, nAMD, and control groups, the minor allele frequencies were 0.2099, 0.2070 and 0.2108 for the rs17576 variant; 0.4442, 0.4522 and 0.4461 for the rs3787268 variant; and 0.1036, 0.1338 and 0.1225 for the rs2274755 variant, respectively. The three tag SNPs were not significantly associated with susceptibility to PCV (p = 0.9524, 0.9553, and 0.3672, respectively) or nAMD (p = 0.9015, 0.8692, and 0.6543, respectively). None of the p values for the additive, dominant, or recessive models were statistically significant in the PCV or nAMD group. No evidence was found to support an association between the MMP9 gene variants and susceptibility to either nAMD or PCV in a Chinese Han population.


Ethylene and jasmonate signaling converge on gibberellin catabolism during thigmomorphogenesis in Arabidopsis.
Touch induces marked morphological changes in plants, including reduced rosette diameters and delayed flowering, a process called thigmomorphogenesis. Previous studies have revealed that thigmomorphogenesis in Arabidopsis (Arabidopsis thaliana) results from touch-induced accumulation of jasmonic acid (JA) and GIBBERELLIN 2-OXIDASE7 (GA2ox7) transcripts, which encode a gibberellin (GA) catabolism enzyme, leading to reduced levels of active GAs. However, the mechanisms underlying thigmomorphogenesis remain uncharacterized. Here we showed that touch induces ethylene (ET) production in Arabidopsis. After touch treatment, ET biosynthesis and signaling mutants exhibited even greater thigmomorphogenic changes and more decreased GA4 contents than did wild-type plants. Biochemical analysis indicated that the transcription factor ETHYLENE INSENSITIVE3 (EIN3) of the ET pathway binds to the promoter of GA2ox8 (encoding another GA 2-oxidase performing the same GA modification as GA2ox7) and represses GA2ox8 transcription. Moreover, MYC2, the master regulator of JA signaling, directly promoted GA2ox7 expression by binding the MYC2 promoter. Further genetic analysis suggested that the ET and JA pathways independently control the expression of GA2ox8 and GA2ox7, respectively. This study reveals that the ET pathway is a novel repressor of touch-induced thigmomorphogenesis and highlights that the ET and JA pathway converge on GA catabolism but play opposite roles to fine-tune GA4 content during thigmomorphogenesis.


[Exposure to static magnetic field and health hazards during the operation of magnetic resonance scanners].
Magnetic resonance imaging (MRI) scanners belong to the most modern imaging diagnostic devices, which involve workers' exposure to static magnetic fields (SMF) during the preparation and performance of MRI examinations. This paper presents the data on workers' exposure to SMF in the vicinity of MRI scanners and the analysis of SMF-related biological effects and health hazards to find out whether softening the legislative requirements concerning protection against SMF exposure of workers involved in MRI diagnostics is justified. Measurements in the vicinity of 1.5 T MRI magnets showed that exposure to SMF by various scanners depends on both SMF of magnets and scanners design, as well as on work organization. In a routine examination of one patient the radiographer is exposed to SMF exceeding 0.5 mT for app. 1.5-7 min, and up to 1.3 min to SMF exceeding 70 mT. In examinations of patients who need more attention, the duration of exposure may be significantly longer. The mean values (B mean) of exposure to SMF are 5.6-85 mT (mean 30 +/- 19 mT, N = 16). These data demonstrate that only well designed procedures, proper organization of workplace and awareness of workers how to attend the patients without being exposed to strong SMF allow for meeting the requirements of labor law concerning workers' exposure to SMF. The analysis of the available literature on biological effects of SMF has disclosed the lack of data on health effects of many years exposure of workers and the abundance of data demonstrating the biological activity of SMF. Therefore, a radical softening of legislative requirements concerning the exposure of workers' head or trunk is premature, and what is more, it is not indispensable for the development of MRI diagnostic. Such an action should be preceded by extensive international investigations on the health status of workers exposed to electromagnetic fields by MRI scanners.


Development of neutralizing antibody responses against SARS-CoV-2 in COVID-19 patients.
The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) are new global problems. The understanding of the host immune response in COVID-19 and its implications in the development of therapeutic agents are new challenges. Here, we evaluated the development of immunoglobulin G (IgG) and neutralizing (Nt) antibodies in symptomatic hospitalized COVID-19 patients. We followed up 117 COVID-19 confirmed patients from a reference health center for COVID-19 during the epidemic in Santiago de Chile. One and two sequential blood samples from 117 to 68 cases were, respectively, obtained to evaluate the immune response. Immunofluorescence and neutralization assays in Vero E6 cells with a Chilean SARS-CoV-2 strain were performed. Out of the 68 patients, 44% were women and 56% men, and the most frequent comorbidities were hypertension (47.7%) and diabetes (27.4%). The most frequent symptoms or signs related to COVID-19 were dyspnea, cough, fever, myalgia, and headache. In all the study population, 76.1% and 60.7% of patients were positive for IgG and Nt antibodies in the first blood sample. All patients except one were positive for IgG and Nt antibodies in the second sample. IgG and Nt antibodies positivity increased significantly according to the disease evolution periods. Higher Nt antibody titers were observed in the first sample in patients under 60 years of age. Obese and diabetic patients had no increase in Nt antibodies, unlike normal weight and diabetes-free patients. Both hypertensive and normotensive patients showed a significant increase in Nt antibodies. These results show an early and robust immune response against SARS-CoV-2 infection during severe COVID-19.


Picture interpretation and Jungian typology.
This study examined a Jungian picture interpretation schema, which utilizes a specific quadrant method. This proposed schema, which is used in training at the C. G. Jung Institute in Zürich, attaches significance to specific areas of a drawing. The upper left of a drawing is associated with the father; the lower left with the unconscious; the lower right with the mother; and the upper right with the future. Three questions served as the foci of this study: Is the schema valid? Do certain types within Jung's personality theory respond better than others to the schema? Does the schema work best when it elicits a strong affective response from the person who created the picture? Subjects took one of two tests: a space domain test, or a colour associative test. The results revealed only two significant effects: a positive association (in the space domain test) between unconscious material with the unconscious quadrant and a negative association (in the colour associative test) of mother material with the mother quadrant. These results suggest that the Jungian quadrant schema used to interpret drawings is invalid and of minimal practical utility. Other methods of picture interpretation are discussed as well as suggestions for future research that would be helpful to this field.


Bayesian Multi-Plate High-Throughput Screening of Compounds.
High-throughput screening of compounds (chemicals) is an essential part of drug discovery, involving thousands to millions of compounds, with the purpose of identifying candidate hits. Most statistical tools, including the industry standard B-score method, work on individual compound plates and do not exploit cross-plate correlation or statistical strength among plates. We present a new statistical framework for high-throughput screening of compounds based on Bayesian nonparametric modeling. The proposed approach is able to identify candidate hits from multiple plates simultaneously, sharing statistical strength among plates and providing more robust estimates of compound activity. It can flexibly accommodate arbitrary distributions of compound activities and is applicable to any plate geometry. The algorithm provides a principled statistical approach for hit identification and false discovery rate control. Experiments demonstrate significant improvements in hit identification sensitivity and specificity over the B-score and R-score methods, which are highly sensitive to threshold choice. These improvements are maintained at low hit rates. The framework is implemented as an efficient R extension package BHTSpack and is suitable for large scale data sets.


Osseous changes and condyle position in TMJ tomograms: impact of RDC/TMD clinical diagnoses on agreement between expected and actual findings.
The objective of this study was to evaluate the impact of clinical TMJ diagnosis, gender, and age on the agreement between expected and actual radiographic findings. A total of 204 patients with TMJ symptoms were examined using the Research Diagnostic Criteria (RDC/TMD). Expected radiographic findings were recorded. TMJ tomograms in closed and open mouth position were assessed for osseous changes and condyle position. Expected and actual findings were compared. Logistic regression analyses were performed with agreement on radiographic findings as the dependent variable and with clinical RDC/TMD diagnoses, gender and age as the independent variables. The number of radiographic findings was mostly underestimated. A clinical diagnosis of osteoarthritis and age increased the chance of overestimating osseous changes. Disc displacement and age decreased the chance of agreement on certain condyle positions. Tomography often revealed unexpected findings. It was not possible to select particular patient groups who would benefit more or less from a radiographic examination.


Human immunodeficiency virus-1 protease. 2. Use of pH rate studies and solvent kinetic isotope effects to elucidate details of chemical mechanism.
The pH dependence of the peptidolytic reaction of recombinant human immunodeficiency virus type 1 protease has been examined over a pH range of 3-7 for four oligopeptide substrates and two competitive inhibitors. The pK values obtained from the pKis vs pH profiles for the unprotonated and protonated active-site aspartyl groups, Asp-25 and Asp-25', in the monoprotonated enzyme form were 3.1 and 5.2, respectively. Profiles of log V/K vs pH for all four substrates were "bell-shaped" in which the pK values for the unprotonated and protonated aspartyl residues were 3.4-3.7 and 5.5-6.5, respectively. Profiles of log V vs pH for these substrates were "wave-shaped" in which V was shifted to a constant lower value upon protonation of a residue of pK = 4.2-5.2. These results indicate that substrates bind only to a form of HIV-1 protease in which one of the two catalytic aspartyl residues is protonated. Solvent kinetic isotope effects were measured over a pH (D) range of 3-7 for two oligopeptide substrates, Ac-Arg-Ala-Ser-Gln-Asn-Tyr-Pro-Val-Val-NH2 and Ac-Ser-Gln-Asn-Tyr-Pro-Val-Val-NH2. The pH-independent value for DV/K was 1.0 for both substrates, and DV = 1.5-1.7 and 2.2-3.2 at low and high pH (D), respectively. The attentuation of both V and DV at low pH (D) is consistent with a change in rate-limiting step from a chemical one at high pH (D) to one in which a product release step or an enzyme isomerization step becomes partly rate-limiting at low pH (D). Proton inventory data is in accord with the concerted transfer of two protons in the transition state of a rate-limiting chemical step in which the enzyme-bound amide hydrate adduct collapses to form the carboxylic acid and amine products.


[Mineral balance during nutritional recuperation of infants with protein deficiency].
Mineral requirements of normal infants change according to growth velocity. They are directly associated to needs for obtaining an adequate composition of new tissue, assure an optimal bone mineralization and for maintaining normal plasma mineral levels. Nutritional rehabilitation of malnourished infants determines increased mineral requirements, which may be not satisfied with usual infant formulas. We studied mineral retention (Ca, P, Mg, Zn and Cu) during nutritional recovery of 9 malnourished male infants (age: 2-7 mo; weight/age < 70%), fed two formulas, both with 85 Kcal/dL (356 KJoule/dL): the first based on whole cow's milk (LP) and the second on a modified cow's milk containing mineral recommendations for normal infants (LPM); balances were compared to normal for age and for length. Infants received each formula for 6 days, with the last 3 days on a metabolic balance Ca, Mg, and P showed high intakes and very low urinary excretions, calcium retention (68.5 +/- 22.7 and 61.4 +/- 16.7 mg/kg/d, for LP and LPM, respectively) were 3 times over normal mean for age (130 mg/d) and 2.5 times over the normal for length (155 mg/d). Mg retention (7.4 +/- 2.0 and 3.4 +/- 1.2 mg/kg/d)), for LP and LPM) were higher than normal for age (2.7 mg/d) or length (3.3 mg/d) and also those of P (LP: 74.8 +/- 7.1; LPM: 52.2 +/- 9.3 mg/kg/d), compared to a mean of 66 mg/d for the same age, or 79 mg/d for length. Zn retentions were comparable with both formulas (LP: 0.14 +/- 0.07 vs LPM: 0.18 +/- 0.06 mg/kg/d) and over normal requirements for age (0.3 mg/d) or length (0.5 mg/d). Copper retentions were significantly lower with LP than LPM (13.8 +/- 14.0 vs 40.0 +/- 13.2 micrograms/kg/d; p < 0.01), due to low intake with LP. We conclude that a high mineral retention is observed in infants recovering from malnutrition, when they are fed formulas with mineral content over its normal recommendations.


Transitional flow at the venous anastomosis of an arteriovenous graft: potential activation of the ERK1/2 mechanotransduction pathway.
We present experimental and computational results that describe the level, distribution, and importance of velocity fluctuations within the venous anastomosis of an arteriovenous graft. The motivation of this work is to understand better the importance of biomechanical forces in the development of intimal hyperplasia within these grafts. Steady-flow in vitro studies (Re = 1060 and 1820) were conducted within a graft model that represents the venous anastomosis to measure velocity by means of laser Doppler anemometry. Numerical simulations with the same geometry and flow conditions were conducted by employing the spectral element technique. As flow enters the vein from the graft, the velocity field exhibits flow separation and coherent structures (weak turbulence) that originate from the separation shear layer. We also report results of a porcine animal study in which the distribution and magnitude of vein-wall vibration on the venous anastomosis were measured at the time of graft construction. Preliminary molecular biology studies indicate elevated activity levels of the extracellular regulatory kinase ERK1/2, a mitogen-activated protein kinase involved in mechanotransduction, at regions of increased vein-wall vibration. These findings suggest a potential relationship between the associated turbulence-induced vein-wall vibration and the development of intimal hyperplasia in arteriovenous grafts. Further research is necessary, however, in order to determine if a correlation exists and to differentiate the vibration effect from that of flow related effects.


Endovascular versus open repair of asymptomatic popliteal artery aneurysm.
Popliteal artery aneurysm (PAA) is a focal dilatation and weakening of the popliteal artery. If left untreated, the aneurysm may thrombose, rupture or the clot within the aneurysm may embolise causing severe morbidity. PAA may be treated surgically by performing a bypass from the arterial segment proximal to the aneurysm to the arterial segment below the aneurysm, which excludes the aneurysm from the circulation. It may also be treated by a stent graft that is inserted percutaneously or through a small cut in the groin. The success of the procedure is gauged by the ability of the graft to stay patent over an extended duration. While surgical treatment is usually preferred in an emergency, the evidence on first line treatment in a non-emergency setting is unclear. To assess the effectiveness of an endovascular stent graft versus conventional open surgery for the treatment of asymptomatic popliteal artery aneurysms (PAA) on primary and assisted patency rates, hospital stay, length of the procedure and local complications. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched their Specialised Register (last searched June 2014) and CENTRAL (2014, Issue 5). Clinical trials databases were searched for any ongoing or unpublished studies. All randomised controlled trials (RCTs) comparing endovascular stent grafting versus conventional open surgical repair in patients undergoing unilateral or bilateral prophylactic repair of asymptomatic PAAs were included. Data were collected on primary and secondary patency rates (primary endpoints) as well as operating time, the length of hospital stay, limb salvage and local wound complications (secondary endpoints). A single RCT was identified that conformed to the inclusion criteria. There was a low risk of selection bias and detection bias. However, the risks of performance bias, attrition bias and reporting bias were unclear from the study. Despite being an RCT, the level of evidence was downgraded to moderate due to the small sample size, resulting in wide confidence intervals (CIs); only 30 PAAs were randomised over a period of five years (15 PAAs each in the groups receiving endovascular stent graft and undergoing conventional open surgery). The primary patency rate at one year was 100% in the surgery group and 93.3% in the endovascular group (P = 0.49). However, the assisted patency rate at one year was similar in both groups (100% patency). There was no clear evidence of a difference between the two groups in the primary or secondary patency rates at four years (13 grafts were patent from 15 PAA treatments in each group). However, the effects were imprecise and compatible with the benefit of either endovascular stent graft or surgery or no difference. Mean hospital stay was shorter in the endovascular group (4.3 days for the endovascular group versus 7.7 days for the surgical group; mean difference (MD) -3.40 days, 95% CI -4.42 to -2.38; P < 0.001). Mean operating time was also reduced in the endovascular group (75.4 minutes in the endovascular group versus 195.3 minutes in the surgical group; MD -119.20 minutes, 95% CI -137.71 to -102.09; P < 0.001). Limb salvage was 100% in both groups. Data on local wound complications were not published in the trial report. Due to the limitations of the current evidence from one small underpowered study, we are unable to determine the effectiveness of endovascular stent graft versus conventional open surgery for the treatment of asymptomatic PAAs. A larger ongoing multicentre RCT should provide more information in the future. However, it seems reasonable to suggest that endovascular repair should be considered as a viable alternative to open repair of PAA on a case by case basis.


Plasma Soluble Urokinase-Type Plasminogen Activator Receptor Is Not Associated with Neurological Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage.
Aneurysmal subarachnoid hemorrhage (aSAH) is a common cause of death or long-term disability. Despite advances in neurocritical care, there is still only a very limited ability to monitor the development of secondary brain injury or to predict neurological outcome after aSAH. Soluble urokinase-type plasminogen activator receptor (suPAR) has shown potential as a prognostic and as an inflammatory biomarker in a wide range of critical illnesses since it displays an association with overall immune system activation. This is the first time that suPAR has been evaluated as a prognostic biomarker in aSAH. In this prospective population-based study, plasma suPAR levels were measured in aSAH patients (n = 47) for up to 5 days. suPAR was measured at 0, 12, and 24 h after patient admission to the intensive care unit (ICU) and daily thereafter until he/she was transferred from the ICU. The patients' neurological outcome was evaluated with the modified Rankin Scale (mRS) at 6 months after aSAH. suPAR levels (n = 47) during the first 24 h after aSAH were comparable in groups with a favorable (mRS 0-2) or an unfavorable (mRS 3-6) outcome. suPAR levels during the first 24 h were not associated with the findings in the primary brain CT, with acute hydrocephalus, or with antimicrobial medication use during 5-days' follow-up. suPAR levels were associated with generally accepted inflammatory biomarkers (C-reactive protein, leukocyte count). Plasma suPAR level was not associated with either neurological outcome or selected clinical conditions. While suPAR is a promising biomarker for prognostication in several conditions requiring intensive care, it did not reveal any value as a prognostic biomarker after aSAH.


[The relation of aerogenic to anaerogenic aeromonads of the "Hydrophila-Punctata-group" in river water depending on the load of waste (author's transl)].
The analysis of the relation of the aerogenic and anaerogenic Aeromonas-Species of the "Hydrophila-Punctata-Group" in moving waters of a varying load of waste demonstrates that in the sewage water the anaerogenic subspecies A.hydrophila subsp. anaerogenes and A.punctata subsp. caviae predominate over the aerogenic species A.hydrophila and A.punctata with an average of 78%. Polysaprobic rivers and brooks show a similar relation. To the contrary, the aerogenic Aeromonads-mainly A.hydrophila-dominate over the anaerogenic Aeromonads in oligosaprobic brooks with a low range of variation of the individual value with 90% on the average. The alpha- and beta-mesosaprobic rivers show-with a great variation of the values indicated at each test place-a relation of aerogenic to anaerogenic Aeromonads of 39:61 for the alpha-mesosaprobics and 43:57 for the beta-mesosaprobics on an average; consequently, they are close to each other in average analysis. The great differences in the individual value of both groups seem, however, to make it possible that the determination of the relation of the aerogenic Aeromonads to the anerogenic could show a more sensitive system of waste contamination or of waste load than the saprobic system used in comparison. Since the anaerogenic subspecies A.hydrophila subsp. anerogenes and A.punctata subsp. caviae are very similar to each other from the ecological point of view and A.hydrophila of the aerogenic species is the widely predominating microorganism it seems to be sufficient for practical purpose to determine the relation of aerogenic to anaerogenic Aeromonads of the "Hydrophila-Punctata-Group"; a further differentiation does not assist in obtaining more information at the present time.


1,3-Bis(ethylamino)-2-nitrobenzene, 1,3-bis(n-octylamino)-2-nitrobenzene and 4-ethylamino-2-methyl-1H-benzimidazole.
1,3-Bis(ethylamino)-2-nitrobenzene, C(10)H(15)N(3)O(2), (I), and 1,3-bis(n-octylamino)-2-nitrobenzene, C(22)H(39)N(3)O(2), (II), are the first structurally characterized 1,3-bis(n-alkylamino)-2-nitrobenzenes. Both molecules are bisected though the nitro N atom and the 2-C and 5-C atoms of the ring by twofold rotation axes. Both display intramolecular N-H...O hydrogen bonds between the amine and nitro groups, but no intermolecular hydrogen bonding. The nearly planar molecules pack into flat layers ca 3.4 A apart that interact by hydrophobic interactions involving the n-alkyl groups rather than by pi-pi interactions between the rings. The intra- and intermolecular interactions in these molecules are of interest in understanding the physical properties of polymers made from them. Upon heating in the presence of anhydrous potassium carbonate in dimethylacetamide, (I) and (II) cyclize with formal loss of hydrogen peroxide to form substituted benzimidazoles. Thus, 4-ethylamino-2-methyl-1H-benzimidazole, C(10)H(13)N(3), (III), was obtained from (I) under these reaction conditions. Compound (III) contains two independent molecules with no imposed internal symmetry. The molecules are linked into chains via N-H...N hydrogen bonds involving the imidazole rings, while the ethylamino groups do not participate in any hydrogen bonding. This is the first reported structure of a benzimidazole derivative with 4-amino and 2-alkyl substituents.


An evaluation of audiology service improvement documentation in England using the chronic care model and content analysis.
Implementation of the chronic care model (CCM) is associated with improved outcomes for patients. It follows that any proposed policy or implementation plan that maps highly onto the CCM is more likely to lead to improved outcomes. The aim of this study was to compare long-term condition (LTC) policy documents and audiology quality standard documents with the CCM and to highlight the need for further research in service implementation and clinical outcome. We carried out a keyword-in-context content analysis of relevant documents. Documents relating to health department policy on LTCs, audiology service improvement initiatives in England and the CCM. This analysis shows that current audiology implementation documents in England map poorly onto the CCM compared to health policy documents relating to the management of LTCs. The biggest discrepancies occur in self-management support, delivery system design, and decision support. These elements are supported by the best evidence of potential improvements in clinical outcome. Our content analysis of audiology service quality improvement documents in England suggests they compare poorly to some elements of the CCM. We discuss the implications this might have for future research.


[Focal nature of tularemia along the course of the Irtysh-Karaganda Canal].
The results of the epizootological survey of the track of the Irtysh-Karaganda canal for tularemia for the period of 1971-1982 are presented. Out of 928 fecal samples from mouse-hunting birds, 16 contained the specific antigen. From Arctic shrews a strain of Francisella tularensis was isolated.


Diarylnitroxide diradicals: low-temperature oxidation of diarylamines to nitroxides.
A low temperature method, in which the progress of the oxidation of secondary diarylamines with DMDO at low temperatures is monitored by magnetic resonance spectroscopy (EPR and NMR) and magnetic studies by a Superconducting Quantum Interference Device (SQUID), is developed for preparation of the first m-phenylene based diarylnitroxide diradical. EPR spectroscopy and magnetic studies (SQUID) indicate that the diradical in the dichloromethane matrix predominantly adopts anticonformation ( 2A-anti) and possesses triplet ground state. Similar oxidation experiments for conformationally constrained aza[1 4]metacyclophane provide evidence for the formation of small amounts of the corresponding diarylnitroxide diradical. Both diarylnitroxide diradicals could only be detected at low temperatures (-80 degrees C and below).


Community Pharmacies Mood Intervention Study (CHEMIST): feasibility and external pilot randomised controlled trial protocol.
Objectives:Refine a bespoke enhanced support intervention (ESI) (including self-help materials, intervention manual and training) for implementation by community pharmacy (CP) staff to people with sub-threshold depression and long-term conditions (LTCs) based upon evidence-supported interventions in primary careDevelop and refine study procedures (recruitment strategies and set up, screening, participant recruitment, assessment, suitability of outcome measures and data collection procedures) for testing in the pilot study phaseDesign: A case series/qualitative studySetting: UK community pharmacyPopulation: Adults with long-term health conditions who screen-positive for depression but who do not reach the threshold for DSM IV Moderate Depressive disorderIntervention: Enhanced support intervention (ESI) delivered by an appropriately trained community pharmacy team member involving four to six sessions over four months. ESI is a modified form of an intervention within the collaborative care framework for sub-threshold depression validated in previous studies in UK primary care which appears suitable for implementation in community settings.Sample size: 20-30 participantsOutcomes: Study implementation (recruitment and attrition rates), quality of data collection at baseline and 4 months and ESI adherence (number of contacts, DNA and drop out) as per objectives 1a/bQualitative evaluation: Semi-structured interviews with up to 10 participants and ESI facilitators and focus group(s) (range of pharmacy staff n = 8-10) will be conducted to explore the acceptability of the intervention and feasibility of the study, training and study procedures. Objectives:Quantify the flow of participants (eligibility, recruitment and follow-up rate)Evaluate proposed recruitment, assessment and outcome measure collection methodsExamine the delivery of the enhanced support intervention in a community pharmacy setting (intervention uptake, retention and dose) to inform process evaluationProcess evaluation, using semi-structured interviews with participants across a range of socio-economic settings, and pharmacy staff to explore the acceptability of the ESI within community pharmacy, elements of the intervention that were considered useful (or not) and appropriateness of study proceduresDesign: Pilot randomised controlled trial, including a prospective economic and qualitative evaluationSetting: As abovePopulation: As aboveIntervention: As above with adaptations post feasibility studyComparator: Usual careSample size: 100 participantsOutcomes: Data will be used to estimate recruitment, intervention delivery and study completion rates as per objectives 2a-d. Definitive estimates of the effectiveness of ESI will not be made.Primary outcome: Depression severity (Patient Health Questionnaire 9) at four months.Secondary outcomes: Patient acceptance, uptake and attrition. ICD10 depression status, anxiety (GAD 7), health-related quality of life (SF-12v2) and health-state utility (EQ5D 3L) will be measured at four months.Economic evaluation: The incremental cost per QALY will be calculated from both the NHS and societal perspective.Process evaluation: Using mixed methods, potential mediators/moderators of the intervention, the acceptability (to participants and pharmacy staff), barriers and facilitators to the use of ESI in community pharmacy, and impact on usual practice will be examined. Semi-structured interviews with approximately 30 study participants, 20 pharmacy staff and eight GPs near participating pharmacies will be conducted. ISRCTN: ISRCTN11290592Protocol version number: Version 4.1 (dated 16th January 2018)Study Sponsor Tees Esk and Wear Valleys NHS Foundation Trust.


Role of laterodorsal tegmentum projections to nucleus accumbens in reward-related behaviors.
The laterodorsal tegmentum (LDT) is associated with reward considering that it modulates VTA neuronal activity, but recent anatomical evidence shows that the LDT also directly projects to nucleus accumbens (NAc). We show that the majority of LDT-NAc inputs are cholinergic, but there is also GABAergic and glutamatergic innervation; activation of LDT induces a predominantly excitatory response in the NAc. Non-selective optogenetic activation of LDT-NAc projections in rats enhances motivational drive and shifts preference to an otherwise equal reward; whereas inhibition of these projections induces the opposite. Activation of these projections also induces robust place preference. In mice, specific activation of LDT-NAc cholinergic inputs (but not glutamatergic or GABAergic) is sufficient to shift preference, increase motivation, and drive positive reinforcement in different behavioral paradigms. These results provide evidence that LDT-NAc projections play an important role in motivated behaviors and positive reinforcement, and that distinct neuronal populations differentially contribute for these behaviors.


Health state descriptions, valuations and individuals' capacity to walk: a comparative evaluation of preference-based instruments in the context of spinal cord injury.
This study explores variation in health state descriptions and valuations derived from preference-based health-related quality of life instruments in the context of spinal cord injury (SCI). Individuals living with SCI were invited to complete a web-based, cross-sectional survey. The survey comprised questions regarding demographics, SCI classifications and characteristics, secondary health complications and conditions, quality of life and SCI-specific functioning in activities of daily living. Four preference-based health status classification systems were included; Assessment of Quality of Life 8-dimension questionnaire (AQoL-8D), EQ-5D-5L, Health Utilities Index (HUI) and SF-6D (derived from the SF-36v2). In addition to descriptive comparisons of index scores and item/dimension responses, analyses explored dimension-level correlation and absolute agreement (intraclass correlation coefficient (ICC)). Subgroup analyses examined the influence of individuals' self-reported ability to walk. Of 609 invitations, 364 (60 %) individuals completed the survey. Across instruments, convergent validity was seen between pain and mental health dimensions, while sizeable variation pertaining to issues of mobility was observed. Mean index scores were 0.248 (HUI-3), 0.492 (EQ-5D-5L), 0.573 (AQoL-8D) and 0.605 (SF-6D). Agreement ranged from 'slight' (HUI-3 and SF-6D; ICC = 0.124) to 'moderate' (AQoL-8D and SF-6D; ICC = 0.634). Walking status had a markedly different impact on health state valuations across instruments. Variation in the way that individuals are able to describe their health state across instruments is not unique to SCI. Further research is necessary to understand the significant differences in index scores and, in particular, the implications of framing mobility-related questions in the context of respondents' ability to walk.


"Of sheep and men": earliest direct evidence of caprine domestication in southern Africa at Leopard Cave (Erongo, Namibia).
The origins of herding practices in southern Africa remain controversial. The first appearance of domesticated caprines in the subcontinent is thought to be c. 2000 years BP; however, the origin of this cultural development is still widely debated. Recent genetic analyses support the long-standing hypothesis of herder migration from the north, while other researchers have argued for a cultural diffusion hypothesis where the spread of herding practices took place without necessarily implicating simultaneous and large population movements. Here we document the Later Stone Age (LSA) site of Leopard Cave (Erongo, Namibia), which contains confirmed caprine remains, from which we infer that domesticates were present in the southern African region as early as the end of the first millennium BC. These remains predate the first evidence of domesticates previously recorded for the subcontinent. This discovery sheds new light on the emergence of herding practices in southern Africa, and also on the possible southward routes used by caprines along the western Atlantic coast.


Discovery of a Novel Anti-Cancer Agent Targeting Both Topoisomerase I & II as Well as Telomerase Activities in Human Lung Adenocarcinoma A549 Cells In Vitro and In Vivo: Cinnamomum verum Component Cuminaldehyde.
Cinnamomum verum is used to make the spice cinnamon and has been used for more than 5000 years by both of the two most ancient forms of medicine in the words: Ayurveda and traditional Chinese herbal medicines for various applications such as adenopathy, rheumatism, dermatosis, dyspepsia, stroke, tumors, elephantiasis, trichomonas, yeast, and virus infections. We evaluated the anticancer effect of cuminaldehyde (CuA), a constituent of the bark of the plant, and its underlying molecular biomarkers associated with carcinogenesis in human lung adenocarcinoma A549 cells. The results show that cuminaldehyde suppressed proliferation and induced apoptosis as indicated by mitochondrial membrane potential loss, activation of caspase 3 and 9, increase in annexin V+PI+ cells, and morphological characteristics of apoptosis, including blebbing of plasma membrane, nuclear condensation, fragmentation, apoptotic body formation, and comet with elevated tail intensity and moment. In addition, cuminaldehyde also induced lysosomal vacuolation with increased volume of acidic compartments (VAC), suppressions of both topoisomerase I & II as well as telomerase activities in a dose-dependent manner. Further study reveals the growth-inhibitory effect of cuminaldehyde was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of cuminaldehyde against A549 cells is accompanied by downregulations of proliferative control involving apoptosis, both topoisomerase I & II as well as telomerase activities, together with an upregulation of lysosomal vacuolation and VAC. Similar effects (including all of the above-mentioned effects) were found in other cell lines, including human lung squamous cell carcinoma NCI-H520 and colorectal adenocarcinoma COLO 205 (results not shown). Our data suggest that cuminaldehyde could be a potential agent for anticancer therapy.


Wildlife resistance and protection in a changing New England landscape.
Rapid changes in climate and land use threaten the persistence of wildlife species. Understanding where species are likely to occur now and in the future can help identify areas that are resistant to change over time and guide conservation planning. We estimated changes in species distribution patterns and spatial resistance in five future scenarios for the New England region of the northeastern United States. We present scenario-specific distribution change maps for nine harvested wildlife species, identifying regions of increasing, decreasing, or stable habitat suitability within each scenario. Next, we isolated areas where species occurrence probability is high (p > 0.7) and resistant to change across all future scenarios. Resistance was also evaluated relative to current land protection to identify patterns in and out of Protected Areas (PAs). Generally, species distributions declined in area over the 50-year assessment period (2010-2060), with the greatest average declines occurring for moose (-40.9%) and wild turkey (-22.1%). Species resistance varied considerably across the region, with coyote demonstrating the highest average regional resistance (91.81% of the region) and moose demonstrating the lowest (0.76% of the region). At the state level, average focal species resistance was highest in Maine (the largest state) and lowest in Massachusetts. Many of the focal species showed high overlap in resistance and land protection. Coyote, white-tailed deer, and black bear had the highest probability of resistance, given protection, while moose and wild turkey had the highest probability of protection, given resistance. Overall, relatively small portions of New England-ranging between 0.25% and 21.12%-were both protected and resistant for the focal species. Our results provide estimates of resistance that can inform conservation planning for commonly harvested species that are important ecologically, economically, and culturally to the region. Expanding protected area coverage to include resistant areas may provide longer term benefits to these species.


Two brothers with a 7.0 kb gene deletion associated with isolated growth hormone deficiency type 1A.
Familial growth hormone deficiency type 1A is an autosomal recessive disease, caused by various homogenous deletions of both alleles of growth hormone gene 1 (hGH1). The hGH1 gene deletion is an event occurring between the 5' and the 3' flanking regions by unequal recombination, which causes a deletion in the hGH1 gene, mostly of 6.7 kb and rarely 7.6 or 7.0 kb in size. Two brothers diagnosed with GH deficiency syndrome were sent to our hospital for further evaluation. DNA samples of the probands and controls were amplified by PCR; restriction endonuclease analysis was done with Sma I enzyme and the patterns were evaluated. Gel electrophoresis results showed that the two brothers had a 7.0 kb deletion. These are the third and fourth cases reported with a 7.0 kb deletion. Both patients responded well to replacement therapy and did not develop antibodies against rGH. No other relatives presented with macro deletions in the hGH1 gene.


Constitutive overexpression of BAFF in autoimmune-resistant mice drives only some aspects of systemic lupus erythematosus-like autoimmunity.
To determine whether overexpression of BAFF can promote systemic lupus erythematosus (SLE)-like autoimmunity in mice that are otherwise autoimmune-resistant. We used class II major histocompatibility complex (MHC)-deficient C57BL/6 (B6) mice as a model of resistance to SLE and Sles1-bearing B6 mice as a model of resistance to the autoantibody-promoting capacity of the Sle1 region. We generated BAFF-transgenic (Tg) counterparts to these respective mice and evaluated lymphocyte phenotype, serologic autoimmunity, renal immunopathology, and clinical disease in the BAFF-Tg and non-Tg mouse sets. Although constitutive BAFF overexpression did not lead to B cell expansion in class II MHC-deficient B6 mice, it did lead to increased serum IgG autoantibody levels. Nevertheless, renal immunopathology was limited, and clinical disease did not develop. In B6 and B6.Sle1 mice, constitutive BAFF overexpression led to increased numbers of B cells and CD4+ memory cells, as well as increased serum IgG and IgA autoantibody levels. Renal immunopathology was modestly greater in BAFF-Tg mice than in their non-Tg counterparts, but again, clinical disease did not develop. Introduction of the Sles1 region into B6.Sle1.Baff mice abrogated the BAFF-driven increase in CD4+ memory cells and the Sle1-driven, but not the BAFF-driven, increase in serum IgG antichromatin levels. Renal immunopathology was substantially ameliorated. Although constitutive BAFF overexpression in otherwise autoimmune-resistant mice led to humoral autoimmunity, meaningful renal immunopathology and clinical disease did not develop. This raises the possibility that BAFF overexpression, even when present, may not necessarily drive disease in some SLE patients. This may help explain the heterogeneity of the clinical response to BAFF antagonists in human SLE.


Regulatory changes raise troubling questions for genomic testing.
By 6 October 2014, many laboratories in the United States must begin honoring new individual data access rights created by recent changes to federal privacy and laboratory regulations. These access rights are more expansive than has been widely understood and pose complex challenges for genomic testing laboratories. This article analyzes regulatory texts and guidances to explore which laboratories are affected. It offers the first published analysis of which parts of the vast trove of data generated during next-generation sequencing will be accessible to patients and research subjects. Persons tested at affected laboratories seemingly will have access, upon request, to uninterpreted gene variant information contained in their stored variant call format, binary alignment/map, and FASTQ files. A defect in the regulations will subject some non-CLIA-regulated research laboratories to these new access requirements unless the Department of Health and Human Services takes swift action to avert this apparently unintended consequence. More broadly, all affected laboratories face a long list of daunting operational, business, compliance, and bioethical issues as they adapt to this change and to the Food and Drug Administration's recently announced plan to publish draft guidance outlining a new oversight framework for lab-developed tests.


Upwelling as a stressor event during embryonic development: Consequences for encapsulated and early juvenile stages of the marine gastropod Acanthina monodon.
Upwelling phenomena alter the physical and chemical parameters of the sea's subsurface waters, producing low levels of temperature, pH and dissolved oxygen, which can seriously impact the early developmental stages of marine organisms. To understand how upwelling can affect the encapsulated development of the gastropod Acanthina monodon, capsules containing embryos at different stages of development (initial, intermediate and advanced) were exposed to upwelling conditions (pH = 7.6; O2 = 3 mg L-1; T° = 9 °C) for a period of 7 days. Effects of treatment were determined by estimating parameters such as time to hatching, number of hatchlings per capsule, percentage of individuals with incomplete development, and shell parameters such as shell shape and size, shell strength, and the percentage of the organic/inorganic content. We found no significant impacts on hatching time, number of hatchlings per capsule, or percentage of incomplete development in either the presence or absence of upwelling, regardless of developmental stage. On the other hand, latent effects on encapsulated stages of A. monodon were detected in embryos that had been exposed to upwelling stress in the initial embryonic stage. The juveniles from this treatment hatched at smaller sizes and with higher organic content in their shells, resulting in a higher resistance to cracking 30 days after hatching, due to greater elasticity. Geometric morphometric analysis showed that exposure to upwelling condition induced a change in the morphology of shell growth in all post-hatching juveniles (0-30 days), regardless of embryonic developmental stage at the time of exposure. Thus, more elongated shells (siphonal canal and posterior region) and more globular shells were observed in newly hatched juveniles that had been exposed to the upwelling condition. The neutral or even positive upwelling exposure results suggests that exposure to upwelling events during the encapsulated embryonic phase of A. monodon development might not have major impacts on the future juvenile stages. However, this should be taken with caution in consideration of the increased frequency and intensity of upwelling events predicted for the coming decades.


Trends in the epidemiology and prescribing of medication for allergic rhinitis in England.
To investigate recent trends in the recorded incidence, lifetime prevalence and prescribing of symptom relief medication for allergic rhinitis in England. Analysis of primary healthcare datasets. The UK prevalence of allergic rhinitis has increased very significantly over recent decades. Analysis of primary healthcare datasets offers the possibility to advance understanding about the changing epidemiology and management of allergic rhinitis. QRESEARCH is one of the world's largest national aggregated health databases containing the records of over nine million patients. We extracted data on all patients with a recorded diagnosis of allergic rhinitis and calculated annual age-sex standardized incidence and lifetime period prevalence rates for each year from 2001-2005. We also analysed prescribing trends for antihistamines and drugs used in nasal allergy in those with a recorded diagnosis of allergic rhinitis. Age-sex standardized incidence, lifetime prevalence rates and prescribing trends for symptom relief medication for allergic rhinitis in England. The age-sex standardized incidence of allergic rhinitis was 5.57 per 1000 person-years in 2001 and increased by 33.0% to 7.41 per 1000 person-years in 2005 (P<0.001). Lifetime age-sex standardized prevalence of a recorded diagnosis of allergic rhinitis increased by 43.2% from 46.35 per 1000 in 2001 to 66.37 per 1000 in 2005 (P<0.001). Over this period a 41.7% overall increase in prescriptions for antihistamines and drugs used in nasal allergy was observed (antihistamines 45.5%, drugs used in nasal allergies 35.5%). Recorded incidence and lifetime prevalence of allergic rhinitis have increased substantially in recent years. A similar increase in prescriptions for antihistamines and drugs used in nasal allergy in patients with allergic rhinitis is also observed.


Treatment costs of diarrheal disease and all-cause pneumonia among children under-5 years of age in Colombia.
We estimate treatment costs associated with diarrheal disease and all-cause pneumonia among children under-5 years of age in Colombia and assess similarities or differences with previous cost estimations in developing countries of the Americas. Macro-costing methods were used to carry out an analysis of diarrhea and all-cause pneumonia costs in Colombia in 2010. The perspective of the health care system was taken. Data were extracted from a health insurer database that includes information on health service utilization among 130,800 children from low-income households. Lengths of stay for hospital admissions and frequencies of cases at all levels of care registered in the database were estimated. There were 1456 diarrheal disease cases among the 130,800 children (aged ≥ 60 months) included in the study. The median cost per case was $27.10 (interquartile range [IQR]: $15.60-77.40). A total of 1545 all-cause pneumonia cases were reported to the insurer in 2010, resulting in a frequency of 1181 cases per 100,000 children (95% confidence interval [CI]=1122, 1240). The overall cost of all-cause pneumonia cases was $858,791, and the median cost per case treated was $263 (IQR: $27-546). Comparisons by level of care showed that costs were significantly different for the two diseases (p<.05). Costs for the diseases did not differ by age group (p>.05). Diarrhea and all-cause pneumonia constitute a significant economic and health burden in Colombia. The relatively large size of our sample allowed us to provide reliable national estimates of the costs associated with these diseases. Our results for Colombia are similar to previous estimates from developing countries in the Americas. These data provide valid estimates that may be used decision makers in other countries to make appropriate recommendations on the introduction of rotavirus and pneumococcal vaccines.


A computerized human reference brain for rCBF/SPET technetium-99m exametazime (HMPAO) investigation of elderly.
Using the bull's eye approach, a reference brain from the single photon emission tomography (SPET) images of 10 subjects aged 62-81 years with excellent mental and physical health was constructed. SPET images were acquired twice, 1 week apart, using a single detector rotating gamma camera collecting 64 planar images over a 360 degrees orbit. The centre of each transaxial slice was first defined with an automatic edge detecting algorithm applied to an anterior-posterior and a side profile of the brain. Each slice was divided into 40 sectors. Maximum counts/pixel in each sector was picked. The 40 maximum count values from one transaxial slice were allowed to form a horizontal row in a new parametric image on the x-axis and slice number from the vertex to the basal parts of the brain on the y-axis. This new image was scaled to a 64 x 16 pixel matrix by interpolation, which meant a normalization of all studies to the same size. The parametric image in each subject was scaled with regard to intensity by a factor calculated by a normalization procedure using the least squares analysis. Mean and SD for each pixel were calculated, thereby constructing a "mean parametric image", and a "SD parametric image". These two images are meant to be used as the reference brain for evaluation of patient studies. This method can be used for objective measurements of diffuse brain changes and for pattern recognition in larger groups of patients. Statistical multifactorial analysis of parameters used for acquisition and data processing is possible.


Predicted Influences of Artificial Intelligence on the Domains of Nursing: Scoping Review.
Artificial intelligence (AI) is set to transform the health system, yet little research to date has explored its influence on nurses-the largest group of health professionals. Furthermore, there has been little discussion on how AI will influence the experience of person-centered compassionate care for patients, families, and caregivers. This review aims to summarize the extant literature on the emerging trends in health technologies powered by AI and their implications on the following domains of nursing: administration, clinical practice, policy, and research. This review summarizes the findings from 3 research questions, examining how these emerging trends might influence the roles and functions of nurses and compassionate nursing care over the next 10 years and beyond. Using an established scoping review methodology, MEDLINE, CINAHL, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews, Cochrane Central, Education Resources Information Center, Scopus, Web of Science, and ProQuest databases were searched. In addition to the electronic database searches, a targeted website search was performed to access relevant gray literature. Abstracts and full-text studies were independently screened by 2 reviewers using prespecified inclusion and exclusion criteria. Included articles focused on nursing and digital health technologies that incorporate AI. Data were charted using structured forms and narratively summarized. A total of 131 articles were retrieved from the scoping review for the 3 research questions that were the focus of this manuscript (118 from database sources and 13 from targeted websites). Emerging AI technologies discussed in the review included predictive analytics, smart homes, virtual health care assistants, and robots. The results indicated that AI has already begun to influence nursing roles, workflows, and the nurse-patient relationship. In general, robots are not viewed as replacements for nurses. There is a consensus that health technologies powered by AI may have the potential to enhance nursing practice. Consequently, nurses must proactively define how person-centered compassionate care will be preserved in the age of AI. Nurses have a shared responsibility to influence decisions related to the integration of AI into the health system and to ensure that this change is introduced in a way that is ethical and aligns with core nursing values such as compassionate care. Furthermore, nurses must advocate for patient and nursing involvement in all aspects of the design, implementation, and evaluation of these technologies. RR2-10.2196/17490.


Simian immunodeficiency virus (SIV) gag DNA-vaccinated rhesus monkeys develop secondary cytotoxic T-lymphocyte responses and control viral replication after pathogenic SIV infection.
The potential contribution of a plasmid DNA construct to vaccine-elicited protective immunity was explored in the simian immunodeficiency virus (SIV)/macaque model of AIDS. Making use of soluble major histocompatibility class I/peptide tetramers and peptide-specific killing assays to monitor CD8(+) T-lymphocyte responses to a dominant SIV Gag epitope in genetically selected rhesus monkeys, a codon-optimized SIV gag DNA vaccine construct was shown to elicit a high-frequency SIV-specific cytotoxic T-lymphocyte (CTL) response. This CTL response was demonstrable in both peripheral blood and lymph node lymphocytes. Following an intravenous challenge with the highly pathogenic viral isolate SIVsm E660, these vaccinated monkeys developed a secondary CTL response that arose with more rapid kinetics and reached a higher frequency than did the postchallenge CTL response in control plasmid-vaccinated monkeys. While peak plasma SIV RNA levels were comparable in the experimentally and control-vaccinated monkeys during the period of primary infection, the gag plasmid DNA-vaccinated monkeys demonstrated better containment of viral replication by 50 days following SIV challenge. These findings indicate that a plasmid DNA vaccine can elicit SIV-specific CTL responses in rhesus monkeys, and this vaccine-elicited immunity can facilitate the generation of secondary CTL responses and control of viral replication following a pathogenic SIV challenge. These observations suggest that plasmid DNA may prove a useful component of a human immunodeficiency virus type 1 vaccine.