Immunogenicity and safety of a quadrivalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT) administered to adults aged 56 Years and older: results of an open-label, randomized, controlled trial.
The burden of invasive meningococcal disease is substantial in older adults in whom the case fatality rate is high. Travelers to regions with high rates of meningococcal disease, such as Hajj pilgrims, are at increased risk of meningococcal infection, and disease transmission from travelers to their close contacts has been documented. In younger individuals, meningococcal conjugate vaccines offer advantages over polysaccharide vaccines in terms of duration of protection and boostability, and induction of herd immune effects through reductions in nasopharyngeal carriage of meningococci. To date, few data are available evaluating meningococcal conjugate vaccine use in adults >55 years of age. To evaluate the immunogenicity and safety of quadrivalent meningococcal serogroups A, C, W-135 and Y vaccine with all serogroups conjugated to tetanus toxoid (MenACWY-TT, Nimenrix™, GlaxoSmithKline, Belgium) and a licensed quadrivalent polysaccharide vaccine (MenPS, Mencevax™ GlaxoSmithKline, Belgium) in adults >55 years of age. This was a phase IIIb, open-label, randomized (3:1), controlled study conducted at one study center in Lebanon. A total of 400 healthy adults between 56 and 103 years of age without previous MenPS or tetanus toxoid vaccination within the previous 5 years or meningococcal conjugate vaccination at any time previously were included. They received a single-dose vaccination with MenACWY-TT or MenPS with blood sampling before and 1 month after vaccination. The main outcome measures were serum bactericidal activity (rabbit complement source: rSBA) vaccine response (VR) rate [rSBA titer of ≥1:32 in initially seronegative subjects (rSBA titer <1:8); ≥4-fold increase in subjects with pre-vaccination rSBA titers between 1:8 and 1:128, and ≥2-fold increase in subjects with pre-vaccination rSBA titers ≥1:128]. The percentages of subjects with rSBA titers ≥1:8 and ≥1:128 and rSBA geometric mean titers (GMTs) were assessed. Solicited adverse events were recorded for 4 days following vaccination, and all other adverse events, including the incidence of new onset chronic diseases, were recorded for 31 days after vaccination. One month after a single dose of MenACWY-TT, the rSBA VR rate in the MenACWY-TT group was 76.6 % for serogroup A, 80.3 % for serogroup C, 77.5 % for serogroup W-135 and 81.9 % for serogroup Y. VR rates in the MenPS group were 91.7, 84.8, 87.1 and 89.1 %, respectively. One month after vaccination, ≥93.2 % of subjects in the MenACWY-TT group and ≥93.9 % in the MenPS group had rSBA titers ≥1:128. In each group, GMTs increased by ≥13-fold for each serogroup. rSBA VR and GMTs tended to be lower in subjects who were over 65 years compared to 56-65 years of age. Only 6.3 % of MenACWY-TT recipients had anti-TT ≥0.1 IU/ml prior to vaccination, increasing to 28.1 % post-vaccination. The rSBA GMTs were 1.9- to 4-fold higher in anti-TT responders. Each local and general solicited symptom was reported by no more than 3.0 % of subjects in either group. No serious adverse events were considered vaccine related. In adults 56 years of age and older, MenACWY-TT was immunogenic, with a vaccine response rate ≥76 % and with ≥93 % of subjects achieving rSBA titers ≥1:128 against all four serogroups after a single dose. MenACWY-TT induced low anti-TT concentrations in this population, which deserves further study.


[Clinical and prognostic analysis of single-center multidisciplinary treatment for rhabdomyosarcoma in children].
Objective: To summarize the clinical characteristics, treatment response and prognostic factors of rhabdomyosarcoma (RMS) in children. Methods: The clinical characteristics such as age at diagnosis, primary tumor site, tumor size, pathological type, clinical stage, and risk grouping of 213 RMS patients (140 males and 73 females) treated in Hematology Oncology Center of Beijing Children's Hospital, Capital Medical University, from May 2006 to June 2018 were analyzed retrospectively. The clinical characteristics, overall survival (OS), event free survival (EFS) and prognostic factors of children treated with the Beijing Children's Hospital-Rhabdomyosarcoma (BCH-RMS) regimen were analyzed. Survival data were analyzed by Kaplan-Meier survival analysis, and single factor analysis was performed by Log-Rank test. Results: The diagnostic age of 213 cases was 48.0 months (ranged 3.0-187.5 months), of which 136 cases (63.8%) were younger than 10 years old. The head and neck region was the most common primary site of tumor (30%, 64 cases), followed by the genitourinary tract (26.8%, 57 cases). Among pathological subtypes, embryonal RMS accounted for 71.4% (152 cases), while alveolar RMS and anaplastic RMS accounted for only 26.8% (57 cases) and 1.9% (4 cases), respectively. According to the Intergroup Rhabdomyosarcoma Study Group (IRS), IRS-Ⅲ and Ⅳ accounted for 85.0% (181 cases) of all RMS patients. In all patients, 9.4% (20 cases) patients were divided in to low-risk group, 52.1% (111 cases) patients in to intermediate -risk group, 25.8% (55 cases) patients in to high-risk group, and 12.7% (27 cases) patients in to the central nervous system invasion group, respectively. All patients with RMS received chemotherapy. The cycles of chemotherapy were 13.5 (ranged 5.0-18.0) for patients without event occurrence, while 14.2 (ranged 3.0-30.0) for patients with event occurrence. Among the 213 patients, 200 patients had surgical operation, of whom 103 patients underwent surgery before chemotherapy and 97 patients at the end of chemotherapy, 21 patients had secondary surgical resection. Radiotherapy was performed in 114 patients. The follow-up time was 23.0 months (ranged 0.5-151.0 months) . There were 98 patients with relapsed or progressed disease and 67 patients with death. The median time to progression was 10 months, of which 67 (68.4%) relapse occurred within 1 year and no recurrence occurred after follow-up for more than 5 years. The 3-year EFS and 5-year EFS were (52±4) % and (48±4) %, while the 3-year OS and 5-year OS were (65±4) % and (64±4) % by survival analysis. The 5-year OS of the low-risk, intermediate-risk, the high-risk were 100%, (74±5) %, (48±8) %, and the 2-year OS of the central nervous system invasion group was (36±11) % (χ(2)=33.52, P<0.01). The 5-year EFS of the low-risk, intermediate-risk, the high-risk were (93±6) %, (51±5) %, (36±7) % and the 2-year EFS of the central nervous system invasion group was (31±10) % (χ(2)=24.73, P<0.01) . Survival factor analysis suggested that the OS of children was correlated with age(χ(2)=4.16, P=0.038), tumor TNM stage (χ(2)=22.02, P=0.001), IRS group (χ(2)=4.49, P<0.01) and the risk group (χ(2)=33.52, P<0.01). Conclusions: This study showed that the median age of newly diagnosed RMS patients was 4 years. The head and neck and the genitourinary tract were the most common primary origin of RMS. The OS was low in single-center RMS children. The median time to recurrence was 10 months, and recurrence was rare 3 years later.


Detection of mitomycin C-DNA adducts in human breast cancer cells grown in culture, as xenografted tumors in nude mice, and in biopsies of human breast cancer patient tumors as determined by (32)P-postlabeling.
Mitomycin C (MMC) is a DNA cross-linking agent that has been used in cancer chemotherapy for >20 years. However, little is known either qualitatively or quantitatively about the relationship between formation and repair of specific MMC-DNA adducts and specific biological outcomes. The goal of this study was to examine formation and removal of specific MMC-DNA adducts in breast cancer cells using a (32)P-postlabeling assay in relation to cytotoxicity and other biological end points. MMC-DNA adducts were measured in cultured human metastatic MDA-MB-435 cells, in the same cells xenografted as a mammary tumor in nude mice, and in metastatic tumor biopsies obtained from human breast cancer patients undergoing MMC-based therapy. MMC adducts corresponding to the CpG interstrand cross-link, the MMC-G bifunctional monoadduct, and two isomers of the MMC-G monofunctional monoadduct were detected in most samples. Despite similarities in the overall patterns of adduct formation, there were substantial differences between the cultured cells and the in vivo tumors in their adduct distribution profile, kinetics of adduct formation and removal, and relationship of specific adduct levels to cytotoxicity, suggesting that the in vivo microenvironment (e.g., degree of oxygenation, pH, activity of oxidoreductases, and other factors) of breast cancer cells may significantly modulate these parameters.


Vandetanib has antineoplastic activity in anaplastic thyroid cancer, in vitro and in vivo.
The antitumor activity of vandetanib [a multiple signal transduction inhibitor including the RET tyrosine kinase, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor (VEGFR), ERK and with antiangiogenic activity], in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C [undifferentiated thyroid cancer (TC)] and in an ATC‑cell line (AF), was investigated in the present study. Vandetanib (1 and 100 nM; 1, 10, 25 and 50 µM) was tested by WST‑1, apoptosis, migration and invasion assays: in primary ATC cells, in the 8305C continuous cell line, and in AF cells; and in 8305C cells in CD nu/nu mice. Vandetanib significantly reduced ATC cell proliferation (P<0.01, ANOVA), induced apoptosis dose‑dependently (P<0.001, ANOVA), and inhibited migration (P<0.01) and invasion (P<0.001). Furthermore, vandetanib inhibited EGFR, AKT and ERK1/2 phosphorylation and downregulated cyclin D1 in ATC cells. In 8305C and AF cells, vandetanib significantly inhibited the proliferation, inducing also apoptosis. 8305C cells were injected subcutaneously in CD nu/nu mice and tumor masses became detectable after 30 days. Vandetanib (25 mg/kg/day) significantly inhibited tumor growth and VEGF‑A expression and microvessel density in 8305C tumor tissues. In conclusion, the antitumor and antiangiogenic activity of vandetanib is very auspicious in ATC, opening the way to a future clinical evaluation.


Constitutive patterns of gene expression regulated by RNA-binding proteins.
RNA-binding proteins regulate a number of cellular processes, including synthesis, folding, translocation, assembly and clearance of RNAs. Recent studies have reported that an unexpectedly large number of proteins are able to interact with RNA, but the partners of many RNA-binding proteins are still uncharacterized. We combined prediction of ribonucleoprotein interactions, based on catRAPID calculations, with analysis of protein and RNA expression profiles from human tissues. We found strong interaction propensities for both positively and negatively correlated expression patterns. Our integration of in silico and ex vivo data unraveled two major types of protein-RNA interactions, with positively correlated patterns related to cell cycle control and negatively correlated patterns related to survival, growth and differentiation. To facilitate the investigation of protein-RNA interactions and expression networks, we developed the catRAPID express web server. Our analysis sheds light on the role of RNA-binding proteins in regulating proliferation and differentiation processes, and we provide a data exploration tool to aid future experimental studies.


Monoclonal endothelial cell proliferation is present in primary but not secondary pulmonary hypertension.
The etiology and pathogenesis of the vascular lesions characterizing primary pulmonary hypertension (PPH), an often fatal pulmonary vascular disease, are largely unknown. Plexiform lesions composed of proliferating endothelial cells occur in between 20 and 80% of the cases of this irreversible pulmonary vascular disease. Recently, technology to assess monoclonality has allowed the distinction between cellular proliferation present in neoplasms from that in reactive nonneoplastic tissue. To determine whether the endothelial cell proliferation in plexiform lesions in PPH is monoclonal or polyclonal, we assessed the methylation pattern of the human androgen receptor gene by PCR (HUMARA) in proliferated endothelial cells in plexiform lesions from female PPH patients (n = 4) compared with secondary pulmonary hypertension (PH) patients (n = 4). In PPH, 17 of 22 lesions (77%) were monoclonal. However, in secondary PH, all 19 lesions examined were polyclonal. Smooth muscle cell hyperplasia in pulmonary vessels (n = 11) in PPH and secondary PH was polyclonal in all but one of the examined vessels. The monoclonal expansion of endothelial cells provides the first marker that allows the distinction between primary and secondary PH. Our data of a frequent monoclonal endothelial cell proliferation in PPH suggests that a somatic genetic alteration similar to that present in neoplastic processes may be responsible for the pathogenesis of PPH.


An ERP investigation of vertical reading fluency in Scrabble® experts.
Previous studies have found that competitive Scrabble expertise is associated with enhanced performance on visual lexical decision tasks (LDT), particularly for vertically presented stimuli. In the current study, we investigated the underlying mechanisms responsible for this vertical fluency. We examined behaviour and neural activity during LDT in 19 competitive Scrabble players and 18 matched controls. Using event related potentials (ERP), we investigated whether Scrabble expertise modulates the N170, P300, and late positive component (LPC), associated with visual-orthographic processing, working memory, and stimulus classification, respectively. Behavioural results replicated those from previous studies: Scrabble experts were significantly faster than controls to respond to vertical stimuli in LDT. ERP results showed Scrabble experts had larger P300 amplitudes in right parietal electrodes compared to controls, as well as greater differentiation in LPC amplitudes between vertical words and nonwords. These findings suggest that the mechanism underlying vertical fluency in Scrabble experts involves enhanced domain-specific working memory and stimulus classification processes. The results have implications for understanding the flexibility of the adult visual word recognition system, as well as the behavioural and neural consequences of training within this system.


Uropygial gland size and composition varies according to experimentally modified microbiome in Great tits.
Parasites exert important selective pressures on host life history traits. In birds, feathers are inhabited by numerous microorganisms, some of them being able to degrade feathers or lead to infections. Preening feathers with secretions of the uropygial gland has been found to act as an antimicrobial defence mechanism, expected to regulate feather microbial communities and thus limit feather abrasion and infections. Here, we used an experimental approach to test whether Great tits (Parus major) modify their investment in the uropygial gland in response to differences in environmental microorganisms. We found that males, but not females, modified the size of their gland when exposed to higher bacterial densities on feathers. We also identified 16 wax esters in the uropygial gland secretions. The relative abundance of some of these esters changed in males and females, while the relative abundance of others changed only in females when exposed to greater bacterial loads on feathers. Birds live in a bacterial world composed of commensal and pathogenic microorganisms. This study provides the first experimental evidence for modifications of investment in the defensive trait that is the uropygial gland in response to environmental microorganisms in a wild bird.


Personalized Predictions of Glioblastoma Infiltration: Mathematical Models, Physics-Informed Neural Networks and Multimodal Scans.
Predicting the infiltration of Glioblastoma (GBM) from medical MRI scans is crucial for understanding tumor growth dynamics and designing personalized radiotherapy treatment plans.Mathematical models of GBM growth can complement the data in the prediction of spatial distributions of tumor cells. However, this requires estimating patient-specific parameters of the model from clinical data, which is a challenging inverse problem due to limited temporal data and the limited time between imaging and diagnosis. This work proposes a method that uses Physics-Informed Neural Networks (PINNs) to estimate patient-specific parameters of a reaction-diffusion PDE model of GBM growth from a single 3D structural MRI snapshot. PINNs embed both the data and the PDE into a loss function, thus integrating theory and data. Key innovations include the identification and estimation of characteristic non-dimensional parameters, a pre-training step that utilizes the non-dimensional parameters and a fine-tuning step to determine the patient specific parameters. Additionally, the diffuse domain method is employed to handle the complex brain geometry within the PINN framework. Our method is validated both on synthetic and patient datasets, and shows promise for real-time parametric inference in the clinical setting for personalized GBM treatment.


Effective, selective coupling of propylene oxide and carbon dioxide to poly(propylene carbonate) using (salen)CrN3 catalysts.
The copolymerization of propylene oxide and CO2 has been investigated employing Cr(salen)N3 complexes as catalysts. Unfortunately the reaction could not be studied in real time via in situ IR spectroscopy, thereby obtaining detailed kinetic data, because of the copolymer limited solubility in most solvents. Investigations employing batch reactor runs concentrating on varying the cocatalyst, the equivalents of cocatalyst, and the steric and electronic structure of the catalyst through modification of the salen ligand were undertaken. It was discovered that the optimal catalyst for copolymer selectivity vs the monomeric propylene carbonate was one that contained a salen ligand with an electron-withdrawing phenylene backbone and electron-donating tert-butyl groups in the phenolate rings. This catalyst was used to investigate the effect of altering the nature of the cocatalyst and its concentration, the three cocatalysts being tricyclohexylphosphine (PCy3), PPN+ N3(-), and PPN+ Cl-, where PPN+ is the large very weakly interacting bis(triphenylphosphoramylidene)ammonium cation. By utilization of more or less than 1 equiv of PCy3 as cocatalyst, the yield of polymer was reduced. On the other hand, the PPN+ salts showed the best activity when 0.5 equiv was employed, and produced only cyclic when using over 1 equiv.


[Knowledge, opinions, and practices regarding Aedes aegypti].
The active participation of the community is indispensable for reducing Aedes aegypti mosquito populations so causes leading to their growth, actions taken, effects on the health and the people in charge of controlling such mosquitoes are all dealt with in this paper. 210 persons were interviewed from June 25 to 27, 1997. The causes of the growth of the mosquito population were: excessive garbage (59%), dirty waters (58%), open water reservoirs (50%) and lack of fumigation (21%). 40% of interviewed people did not know that these vectors can breed even in clean waters. They mentioned some effects on the health due to the mosquito bites. 51% said that mosquitoes should be jointly controlled by the State and the community but 35% believed that the State should be the sole responsible for this task. These opinions may determine that steps are not properly taken to avoid proliferation of vector and that the activities of the anti-vector program are not really understood since they do not meet the expectations.


The European sea bass Dicentrarchus labrax genome puzzle: comparative BAC-mapping and low coverage shotgun sequencing.
Food supply from the ocean is constrained by the shortage of domesticated and selected fish. Development of genomic models of economically important fishes should assist with the removal of this bottleneck. European sea bass Dicentrarchus labrax L. (Moronidae, Perciformes, Teleostei) is one of the most important fishes in European marine aquaculture; growing genomic resources put it on its way to serve as an economic model. End sequencing of a sea bass genomic BAC-library enabled the comparative mapping of the sea bass genome using the three-spined stickleback Gasterosteus aculeatus genome as a reference. BAC-end sequences (102,690) were aligned to the stickleback genome. The number of mappable BACs was improved using a two-fold coverage WGS dataset of sea bass resulting in a comparative BAC-map covering 87% of stickleback chromosomes with 588 BAC-contigs. The minimum size of 83 contigs covering 50% of the reference was 1.2 Mbp; the largest BAC-contig comprised 8.86 Mbp. More than 22,000 BAC-clones aligned with both ends to the reference genome. Intra-chromosomal rearrangements between sea bass and stickleback were identified. Size distributions of mapped BACs were used to calculate that the genome of sea bass may be only 1.3 fold larger than the 460 Mbp stickleback genome. The BAC map is used for sequencing single BACs or BAC-pools covering defined genomic entities by second generation sequencing technologies. Together with the WGS dataset it initiates a sea bass genome sequencing project. This will allow the quantification of polymorphisms through resequencing, which is important for selecting highly performing domesticated fish.


Home parenteral nutrition versus artificial hydration in malnourished patients with cancer in palliative care: a prospective, cohort survival study.
The evidence base for home parenteral nutrition (HPN) in patients with advanced cancer is lacking. To compare the survival of malnourished patients with cancer undergoing palliative care who received HPN with a homogeneous group of patients, equally eligible for HPN, who did not receive HPN. Prospective, cohort study; tertiary university hospital, home care, hospice. Patients were assessed for HPN eligibility according to the guidelines. In the eligible population, who received both HPN and chemotherapy was excluded, while who received only HPN was included in the HPN+ group and who received neither HPN nor chemotherapy but artificial hydration (AH) was included in the HPN- group. 301 patients were assessed for HPN eligibility and 86 patients (28.6%) were excluded for having severe organ dysfunction or Karnofsky performance status <50. In outcome analysis, 90 patients (29.9%) were excluded for receiving both HPN and chemotherapy, while 125 (41.5%) were included, 89 in HPN+ group (29.5%) and 36 in HPN- group (12%). The survival of the two groups showed a significant difference favouring patients receiving HPN (median overall survival: 4.3 vs 1.5 months, p<0.001). The multivariate analysis of the risk factors for mortality showed that not receiving HPN accounted for the strongest one (HR 25.72, 95% CI 13·65 to 48.44). Comparative survival associated with the use of HPN versus AH showed significantly longer survival in malnourished patients with advanced cancer receiving HPN. These data support the guideline recommendation that HPN should be considered when malnutrition represents the overriding threat for the survival of these patients.


Social Service Directors' Roles and Self-Efficacy in Suicide Risk Management in US Nursing Homes.
Nursing home (NH) residents have many risk factors for suicide in later life and transitions into and out of NHs are periods of increased suicide risk. The purpose of this study was to describe NH social service directors (SSDs) roles in managing suicide risk and to identify factors that influence self-efficacy in this area. This study used data from the 2019 National Nursing Home Social Services Directors survey (n = 924). One-fifth (19.7%) of SSDs reported a lack of self-efficacy in suicide risk management, as indicated by either needing significant preparation time or being unable to train others on intervening with residents at risk for suicide. Ordinal logistic regression identified SSDs who were master's prepared, reported insufficient social service staffing as a minor barrier (versus a major barrier) to psychosocial care, and those most involved in safety planning for suicide risk were more likely to report self-efficacy for training others. Implications include the need for targeted training of NH social service staff on suicide prevention, such as safety planning as an evidence-based practice. Likewise, sufficient staffing of qualified NH social service providers is critically important given the acute and chronic mental health needs of NH residents.


[Education for health and social justice based on the focus on capabilities: An opportunity for public health development].
Theoretical research on health education is presented, which is proposed from an emancipatory perspective and constitutes an opportunity to promote health in communities because it makes it possible to explain a concept of social justice. The vision of social justice that is put forward in this article is focused on the capabilities that are understood as a set of real opportunities for people to achieve the life they aspire to. This approach is relevant for public health work because it is centered around human development, allows the subject to be incorporated into a dialectical relationship with society and focuses on real opportunities. The differences between public health approaches are considered to understand social justice and the relevance of a health concept that makes it possible to transcend the biomedical approach focused on disease. The importance of advancing towards a pedagogical development of health education that exceeds the perspective of education focused on behavioral changes is acknowledged, in order to understand it as a social and political process with an emancipatory humanist base as an opportunity for the construction of public health.


Impaired left ventricular filling dynamics in patients with angina and angiographically normal coronary arteries: effect of beta adrenergic blockade.
To assess exercise performance and resting left ventricular filling dynamics in patients with syndrome X (SX) in basal conditions and after 10 days treatment with oral atenolol. Exercise performance was studied and left ventricular filling assessed by Doppler-derived transmitral flow pattern analysis in 22 patients (16 female, mean (SD) age 53 (4) years) with angina, a positive exercise test, and angiographically smooth coronary arteries. Patients were studied after two 10 day treatment periods with either atenolol or placebo in a single-blind, randomised, crossover trial. The same protocol was followed in 10 patients with documented coronary artery disease (CAD) and in 13 controls (C). Unlike the controls, patients with SX and those with CAD consistently showed exercise-induced ST segment abnormalities and impaired resting left ventricular filling while on placebo. Atenolol significantly reduced episodes of angina, completely prevented exercise-induced ST segment changes in 18 SX patients, and delayed their onset in all patients with CAD: in both groups the agent significantly improved Doppler-derived indices (mean (SD)) of ventricular filling (E/A 0.97 (0.27) v 1.22 (0.32) and 0.84 (0.21) v 1.19 (0.37), respectively). The objective documentation of left ventricular filling abnormalities may be useful in confirming the clinical diagnosis of SX and in providing objective evidence of therapeutic benefit. The similarity of the symptoms and electrocardiographic and ventricular filling abnormalities found in patients with SX and in those with CAD suggests that ischaemia is involved in both groups.


Response of muscle protein turnover to insulin after acute exercise and training.
To determine whether the enhanced insulin-sensitivity of glucose metabolism in muscle after acute exercise also extends to protein metabolism, untrained and exercise-trained rats were subjected to an acute bout of exercise, and the responses of protein synthesis and degradation to insulin were measured in epitrochlearis muscles in vitro. Acute exercise of both untrained and trained rats decreased protein synthesis in muscle in the absence or presence of insulin, but protein degradation was not altered. Exercise training alone had no effect on protein synthesis or degradation in muscle in the absence or presence of insulin. Acute exercise or training alone enhanced the sensitivities of both protein synthesis and degradation to insulin, but the enhanced insulin-sensitivities from training alone were not additive to those after acute exercise. These results indicate that: a decrease in protein synthesis is the primary change in muscle protein turnover after acute exercise and is not altered by prior exercise training, and the enhanced insulin-sensitivities of metabolism of both glucose and protein after either acute exercise or training suggest post-binding receptor events.


Lateral lakes of Trolard: anatomy, quantitation, and surgical landmarks. Laboratory investigation.
There is scant and conflicting information in the literature regarding the lateral lacunae, or lateral lakes of Trolard. As these venous structures can be encountered surgically, this study aimed at further elucidating their anatomy, identifying surgical landmarks, and associated quantitation. Thirty-five adult cadavers were dissected of lateral lacunae. Following quantitation of the lacunae, these structures were measured, as were the distances from them to the coronal and sagittal sutures. A mean of 1.9 lacunae were identified on the right sides and 1.4 lacunae on the left sides. Although there tended to be slightly more lacunae on the right sides, this difference did not reach statistical significance (p > 0.05). The average lengths of the lacunae were 3.2 and 2.0 cm for the right and left sides, respectively. The mean widths of these venous lakes were 1.5 cm for the right sides and 0.8 cm for the left sides. Lacunae were variably positioned but tended to cluster near the vertex of the skull. None were identified posterior to the lambdoid sutures, and only 5 were found to lie anterior to the coronal suture, with 4 of these located on right sides (p < 0.05). When lacunae were identified anterior to the coronal suture, they were generally 5-6 cm from this structure. The majority of lacunae could be identified between the coronal and lambdoid sutures and within 3 cm of the midline. Although the situation varies, lateral lacunae are concentrated posterior to the coronal suture and anterior to the lambdoid sutures. They are most often found within 3 cm of the sagittal suture. These previously unreported data could be useful to the neurosurgeon in planning surgical procedures that traverse the calvaria.


Electrospun and co-electrospun biopolymer nanofibers for skin wounds on diabetic patients: an overview.
Wound healing treatment in diabetic patients worldwide represents around 2.1 trillion dollars to global health sectors. This is because of the complications presented in the wound healing process of skin ulcers, such as a lack of macrophage and fibroblast growth factors (TGF-β1 and PDGF, respectively) that are both needed for extracellular matrix (ECM) synthesis. Therefore, there is a need for research on new and cost-effective materials to enable ECM synthesis. Such materials include co-electrospun nanofibers used as wound dressings, since they have a similar morphology to the ECM, and therefore, possess the advantage of using different materials to accelerate the wound healing process. Co-electrospun nanofibers have a unique structural configuration, formed by a core and a shell. This configuration allows the protection and gradual liberation of healing agent compounds, which could be included in the core. Some of the materials used in nanofibers are polymers, including natural compounds, such as chitosan (which has been proven to possess antimicrobial and therapeutic activity) and gelatin (for its cell growth, adhesion, and organisational capacity in the wound healing process). Synthetics such as polyvinyl-alcohol (PVA) (mainly as a co-spinning agent to chitosan) can also be used. Another bioactive compound that can be used to enhance the wound healing process is eugenol, a terpenoid present in different medicinal plant tissues that have scarring properties. Therefore, the present review analyses the potential use of co-electrospun nanofibers, with chitosan-PVA-eugenol in the core and gelatin in the shell as a wound dressing for diabetic skin ulcers.


The results of cervical nucleoplasty in patients with cervical disc disorder: a retrospective clinical study of 22 patients.
Nucleoplasty is a minimally invasive spinal surgery using a Coblation® technique that creates small voids within the disc. The purpose of this study was to evaluate the efficacy of cervical nucleoplasty in patients with cervical disc disorder. Between March 2008 and December 2009, 22 patients with cervical disc disorders were treated with cervical nucleoplasty after failed conservative treatment. All procedures were performed under local anesthesia, and fluoroscopic guidance and voids were created in the disc with the Perc™ DC Spine Wand™. Clinical outcomes were evaluated by the Modified Macnab criteria and VAS score at preprocedure, postprocedure 1 month, and 6 months. Six patients had one, eight patients had two and eight patients had three discs treated; a total of 46 procedures was performed. Mean VAS reduced from 9.3 at preprocedure to 3.7 at postprocedure 1 month and to 3.4 at postprocedure 6 months. There was no significant complication related to the procedure within the first month. Outcomes were good or excellent in 17/22 (77.3%) cases. Postprocedure magnetic resonance imaging was acquired in two patients after two months showing morphologic evidence of volume reduction of protruded disc material in one patient but not in the other. Percutaneous decompression with a nucleoplasty using a Coblation® technique in the treatment of cervical disc disorder is a safe, minimally-invasive and less uncomfortable procedure, with an excellent short-term clinical outcome.


[Diagnosis of triiodothyronine thyrotoxicosis].
The effectiveness and safety of different methods of radioimmunoassay to determine the thyroid function were studied in 298 patients: 172 with nodose toxic goiter and 116 with nodose euthyroid goiter. A "warm", "hot", "cold" and "autonomic" nodes, respectively, prevailed in nodose goiter, on skanning. Free triiodothyronine index and elevated serum triiodothyronine index (EST3I) were calculated to determine the effect of thyroxin-binding ability of globulin on the total triiodothyronine level. Three types of thyrotoxicosis (T3/4-, T3- and T4-thyrotoxicosis) were found as a result of using complex methods to record the tests, showing a functional state of the hypophyseal-thyroid system. A high informativeness of the main thyroid tests was detected, i.e. determination of the total thyroxin, serum triiodothyronine and thyroxin efficiency coefficient. EST3I has the most diagnostic significance, being especially valuable in T3-thyrotoxicosis detection.


Estradiol Enhances the Depolarizing Response to GABA and AMPA Synaptic Conductances in Arcuate Kisspeptin Neurons by Diminishing Voltage-Gated Potassium Currents.
Synaptic and intrinsic properties interact to sculpt neuronal output. Kisspeptin neurons in the hypothalamic arcuate nucleus help convey homeostatic estradiol feedback to central systems controlling fertility. Estradiol increases membrane depolarization induced by GABAA receptor activation in these neurons. We hypothesized that the mechanisms underlying estradiol-induced alterations in postsynaptic response to GABA, and also AMPA, receptor activation include regulation of voltage-gated potassium currents. Whole-cell recordings of arcuate kisspeptin neurons in brain slices from ovariectomized (OVX) and OVX+estradiol (OVX+E) female mice during estradiol negative feedback revealed that estradiol reduced capacitance, reduced transient and sustained potassium currents, and altered voltage dependence and kinetics of transient currents. Consistent with these observations, estradiol reduced rheobase and action potential latency. To study more directly interactions between synaptic and active intrinsic estradiol feedback targets, dynamic clamp was used to simulate GABA and AMPA conductances. Both GABA and AMPA dynamic clamp-induced postsynaptic potentials (PSPs) were smaller in neurons from OVX than OVX+E mice; blocking transient potassium currents eliminated this difference. To interrogate the role of the estradiol-induced changes in passive intrinsic properties, different Markov model structures based on the properties of the transient potassium current in cells from OVX or OVX+E mice were combined in silico with passive properties reflecting these two endocrine conditions. Some of tested models reproduced the effect on PSPs in silico, revealing that AMPA PSPs were more sensitive to changes in capacitance. These observations support the hypothesis that PSPs in arcuate kisspeptin neurons are regulated by estradiol-sensitive mechanisms including potassium conductances and membrane properties.SIGNIFICANCE STATEMENT Kisspeptin neurons relay estradiol feedback to gonadotropin-releasing hormone neurons, which regulate the reproductive system. The fast synaptic neurotransmitters GABA and glutamate rapidly depolarize arcuate kisspeptin neurons and estradiol increases this depolarization. Estradiol reduced both potassium current in the membrane potential range typically achieved during response to fast synaptic inputs and membrane capacitance. Using simulated GABA and glutamate synaptic inputs, we showed changes in both the passive and active intrinsic properties induced by in vivo estradiol treatment affect the response to synaptic inputs, with capacitance having a greater effect on response to glutamate. The suppression of both passive and active intrinsic properties by estradiol feedback thus renders arcuate kisspeptin neurons more sensitive to fast synaptic inputs.


Description and power analysis of two tests for detecting recent population bottlenecks from allele frequency data.
When a population experiences a reduction of its effective size, it generally develops a heterozygosity excess at selectively neutral loci, i.e., the heterozygosity computed from a sample of genes is larger than the heterozygosity expected from the number of alleles found in the sample if the population were at mutation drift equilibrium. The heterozygosity excess persists only a certain number of generations until a new equilibrium is established. Two statistical tests for detecting a heterozygosity excess are described. They require measurements of the number of alleles and heterozygosity at each of several loci from a population sample. The first test determines if the proportion of loci with heterozygosity excess is significantly larger than expected at equilibrium. The second test establishes if the average of standardized differences between observed and expected heterozygosities is significantly different from zero. Type I and II errors have been evaluated by computer simulations, varying sample size, number of loci, bottleneck size, time elapsed since the beginning of the bottleneck and level of variability of loci. These analyses show that the most useful markers for bottleneck detection are those evolving under the infinite allele model (IAM) and they provide guidelines for selecting sample sizes of individuals and loci. The usefulness of these tests for conservation biology is discussed.


Induction of type I interferons by bacteria.
Type I interferons (IFNs) are secreted cytokines that orchestrate diverse immune responses to infection. Although typically considered to be most important in the response to viruses, type I IFNs are also induced by most, if not all, bacterial pathogens. Although diverse mechanisms have been described, bacterial induction of type I IFNs occurs upon stimulation of two main pathways: (i) Toll-like receptor (TLR) recognition of bacterial molecules such as lipopolysaccharide (LPS); (ii) TLR-independent recognition of molecules delivered to the host cell cytosol. Cytosolic responses can be activated by two general mechanisms. First, viable bacteria can secrete stimulatory ligands into the cytosol via specialized bacterial secretion systems. Second, ligands can be released from bacteria that lyse or are degraded. The bacterial ligands that induce the cytosolic pathways remain uncertain in many cases, but appear to include various nucleic acids. In this review, we discuss recent advances in our understanding of how bacteria induce type I interferons and the roles type I IFNs play in host immunity.


[Some aspects of lifestyle and health status in students].
To study the lifestyle of students, the spread of bad habits and the self-appraisal of their health status, a sociological survey was made among the indigenous dwellers of a large industrial town and nonresident students. A slight deterioration of health indices was revealed in the students residing in a chemically polluted area of the town and in those who had come from other environmentally unfavorable areas of the republic. These changes may be associated not only with the known reorganization of the pattern of academic activities and lifestyle, but also with the adverse physicochemical influence of a new environment. Changing the environment may promote the strain of mechanisms responsible for adaptation and health destabilization.


Highly elevated ultraviolet-induced mutation frequency in isolated Chinese hamster cell lines defective in nucleotide excision repair and mismatch repair proteins.
We have isolated N-methyl-N'-nitro-N-nitrosoguanidine-resistant cell lines from 43-3B Chinese hamster ovary cells, which are deficient in the ERCC1 gene involved in nucleotide excision repair. By Western blotting analysis, we found cell lines that are deficient or decreased in the amount of MSH6, or PMS2, or MSH2 proteins. Cell extracts of these cell lines show reduced efficiency of G:T mismatch repair activity. Compared with 43-3B, these cell lines exhibit highly elevated UV-induced mutation rates, indicating that mammalian mismatch repair can suppress UV-induced mutagenesis and may play a role in the fidelity of DNA replication at the sites of UV damage.


Homogeneity of Aerosol Deposition and Mucociliary Clearance are Improved Following Ivacaftor Treatment in Cystic Fibrosis.
Using planar gamma scintigraphy of inhaled radioaerosols, we have developed new analytical methods for assessing homogeneity of aerosol deposition and time-dependent particle clearance on a pixel-by-pixel basis, and applied them to a therapeutic cystic fibrosis (CF) study. At baseline and 1 month after beginning treatment with ivacaftor, a cystic fibrosis transmembrane regulator modulator for CF patients with at least one copy of the G551D mutation (n = 13), initial deposition and subsequent mucociliary clearance (MCC) of radiolabeled particles (99mTechnetium-sulfur colloid, 5 μm mass median aerodynamic diameter) inhaled under controlled breathing conditions were measured. Improved homogeneity of deposition, that is, decreased areas of higher and lower particle deposition in the lungs, was observed following ivacaftor treatment. The mean number ratio (NR) of pixels with higher deposition, relative to lung size, decreased from 0.14 to 0.09 (p = 0.003) and mean NR of colder pixels decreased from 0.23 to 0.19 (p = 0.004). Particle clearance was also improved following treatment, with mean MCC through 60 minutes equal to 12% versus 24%, without and with treatment, respectively (p = 0.010). Pixel-level analysis of MCC showed that (1) the fraction of pixels clearing >30% at 60 minutes was increased from 0.13 to 0.32 (p = 0.007); and (2) the fraction of pixels clearing <5% at 60 minutes was decreased from 0.54 to 0.37 (p = 0.014), indicating an overall recruitment of more fast-clearing lung regions with ivacaftor treatment. These detailed pixel analyses of deposition and clearance homogeneity may supplement traditional methods that use large regions of interest for assessing efficacy and mechanisms of therapeutic intervention in patients with airways disease.


Surface normal reconstruction using circularly polarized light.
The polarization properties of reflected light capture important information about the object's inherent properties: material composition, i.e. index of refraction and scattering properties, and shape of the object, i.e. surface normal. Polarization information therefore has been used for surface reconstruction using a single-view camera with unpolarized incident light. However, this surface normal reconstruction technique suffers from a zenith angle ambiguity. In this paper, we have utilized circularly polarized light to solve for the zenith ambiguity by developing a detailed model using Mueller matrix formulism and division of focal plane polarization imaging technology. Experiment results validate our model for accurate surface reconstruction.


Gaseous signalling molecule SO2 via Hippo‑MST pathway to improve myocardial fibrosis of diabetic rats.
Recent studies have indicated the existence of an endogenous sulfur dioxide (SO2)‑generating system in the cardiovascular system. The present study aimed to discuss the function and regulatory mechanism of gaseous signal molecule SO2 in inhibiting apoptosis and endoplasmic reticulum stress (ERS) via the Hippo‑MST signaling pathway to improve myocardial fibrosis of diabetic rats. A total of 40 male Sprague‑Dawley rats were randomly divided into four groups (10 rats per group): Normal control group (control group), diabetic rats group [streptozotocin (STZ) group], SO2 intervention group (STZ+SO2 group) and diabetes mellitus rats treated with L‑Aspartic acid β‑hydroxamate (HDX) group (HDX group). Diabetic rats models were established by intra‑peritoneal injection of STZ (40 mg/kg) Following model establishment, intra‑peritoneal injection of Na2SO3/NaHSO3 solution (0.54 mmol/kg) was administered in the STZ+SO2 group, and HDX solution (25 mg/kg/week) was administered in the HDX group. A total of 4 weeks later, echocardiography was performed to evaluate rats' cardiac function; Masson staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and transmission electron microscopy examinations were performed to observe myocardial morphological changes. ELISA was employed to determine the SO2 content. Western blot analysis was performed to detect the expression of proteins associated with apoptosis, ERS and the Hippo‑MST signalling pathway. Compared with the control group, the STZ group and HDX group had a disordered arrangement of myocardial cells with apparent myocardial fibrosis, and echocardiography indicated that the cardiac function was lowered, there was an obvious increase of apoptosis in myocardial tissue, the expression levels of apoptosis‑associated protein B‑cell lymphoma associated protein X, caspase‑3 and caspase‑9 were upregulated, and Bcl‑2 expression was downregulated. The expression of ERS and Hippo‑MST pathway‑associated proteins, including CHOP, GRP94, MST1 and MST2, were significantly upregulated. By contrast, these above‑mentioned changes were reversed by SO2 treatment. Compared with STZ group, the HDX group had a further increase of myocardial fibrosis and apoptosis, while there were no statistically significant differences in the expression of Bax/Bcl‑2, caspase‑3, caspase‑9 and ERS and Hippo‑MST pathway‑associated proteins. The results of the present study demonstrated that the gaseous signal molecule SO2 can effectively improve the myocardial fibrosis of diabetic rats, and its mechanism may be associated with reduced apoptosis and ERS by downregulated Hippo‑MST pathway.


High AAV vector purity results in serotype- and tissue-independent enhancement of transduction efficiency.
The purity of adeno-associated virus (AAV) vector preparations has important implications for both safety and efficacy of clinical gene transfer. Early-stage screening of candidates for AAV-based therapeutics ideally requires a purification method that is flexible and also provides vectors comparable in purity and potency to the prospective investigational product manufactured for clinical studies. The use of cesium chloride (CsCl) gradient-based protocols provides the flexibility for purification of different serotypes; however, a commonly used first-generation CsCl-based protocol was found to result in AAV vectors containing large amounts of protein and DNA impurities and low transduction efficiency in vitro and in vivo. Here, we describe and characterize an optimized, second-generation CsCl protocol that incorporates differential precipitation of AAV particles by polyethylene glycol, resulting in higher yield and markedly higher vector purity that correlated with better transduction efficiency observed with several AAV serotypes in multiple tissues and species. Vectors purified by the optimized CsCl protocol were found to be comparable in purity and functional activity to those prepared by more scalable, but less flexible serotype-specific purification processes developed for manufacture of clinical vectors, and are therefore ideally suited for pre-clinical studies supporting translational research.


[Chyme homeostasis in the gastroduodenal portion of the digestive tract under different nutritional diets].
The concentration of chyme ingredients and volumetric velocity of the chyme transfer from the duodenum to the jejunum were investigated in experiments on normal preoperated dogs with fistulas implanted into the stomach, duodenum and jejunum after feeding different diets throughout the entire process of active digestion. It has been established that as a result of exchange between the medium filling the gastroduodenal part of the alimentary tract and blood, an enteral medium is formed in the duodenum, with the composition of this medium being relatively constant as regards the concentration and constituent ingredients. It has been also shown that the direction of the balanced flows of the nutrients depends on their concentration in the diet and that both immediate exchange of substances between the enteral and internal media, which is effected according to the concentration gradient, and regulatory alterations in the secretion are involved in homeostasis of the enteral medium.


Alkali-metal ion catalysis and inhibition in nucleophilic displacement reactions at carbon, phosphorus and sulfur centres. IX. p-Nitrophenyl diphenyl phosphate.
We report on the catalytic effects by alkali-metal ions in the ethanolysis of p-nitrophenyl diphenyl phosphate, in continuation of our studies on alkali-metal ion catalysis and inhibition in nucleophilic displacement reactions at carbon, phosphorus and sulfur centres. The following selectivity order of catalytic reactivity was observed for nucleophilic displacement at the phosphorus center with p-nitrophenoxide as leaving group: Li+ > Na+ > K+ > Cs+. A minor reaction pathway with phenoxide leaving was also found. The kobs data have been dissected into reaction pathways by free ions (kEtO) and by ion pairs (kMOEt), with the latter being dominant, in a 4-membered transition-state. Further analysis is given in terms of initial-state and transition-state stabilization by the alkali-metal ions in terms of the Eisenman model (electrostatic interaction vs. desolvation). Results of ab-initio MO calculations are presented based on interaction between M+ and a model bipyramidal phosphorane intermediate and compared with the sulfurane analogue.


The Ku70 autoantigen interacts with p40phox in B lymphocytes.
Ku70, a regulatory component of the DNA-dependent protein kinase, was identified by a yeast two-hybrid screen of a B lymphocyte cDNA library as a partner of p40phox, a regulatory component of the O2--producing NADPH oxidase. Truncated constructs of p40phox and Ku70 were used to map the interacting sites. The 186 C-terminal amino acids (aa) of Ku70 were found to interact with two distinct regions of p40phox, the central core region (aa 50-260) and the C-terminal extremity (aa 260-339). In complementary experiments, it was observed that Ku70 binds to immobilized recombinant p40phox fusion protein and that p40phox and Ku70 from a B lymphocyte cell extract comigrate in successive chromatographies on Q Separose, Superose 12 and hydroxylapatite columns. Moreover, we report that Ku70 and p40phox colocalize in B lymphocytes and in transfected Cos-7 cells. We also show that the two NADPH oxidase activating factors, p47phox and p67phox are substrates for DNA-PK in vitro and that they are present together with p40phox in the nucleus of B cells. These results may help solve the paradox that the phox protein triad, p40phox, p47phox and p67phox, is expressed equally in B lymphocytes and neutrophils, whereas the redox component of the NADPH oxidase, a flavocytochrome b, which is well expressed in neutrophils, is barely detectable in B lymphocytes.


Optimization of acrylic-styrene latex-based biofilms as a platform for biological indoor air treatment.
Biotechnologies have emerged as a promising solution for indoor air purification with the potential to overcome the inherent limitations of indoor air treatment. These limitations include the low concentrations and variability of pollutants and mass-transfer problems caused by pollutant hydrophobicity. A new latex-based biocoating was herein optimized for the abatement of the volatile organic compounds (VOCs) toluene, trichloroethylene, n-hexane, and α-pinene using acclimated activated sludge dominated by members of the phylum Patescibacteria. The influence of the water content, the presence of water absorbing compounds, the latex pretreatment, the biomass concentration, and the pollutant load was tested on VOC removal efficiency (RE) by varying the formulation of the mixtures. Overall, hexane and trichloroethylene removal was low (<30%), while high REs (>90%) were consistently recorded for toluene and pinene. The assays demonstrated the benefits of operating at high water content in the biocoating, either by including mineral medium or water absorbing compounds in the latex-biomass mixtures. The performance of the latex-based biocoating was likely limited by VOC mass-transfer rather than by biomass concentration in the biocoating. The latex-based biocoating supported a superior toluene and pinene removal than biomass in suspension when VOC loading rate was increased by a factor of 4.


Connectivity reflects coding: a model of voltage-based STDP with homeostasis.
Electrophysiological connectivity patterns in cortex often have a few strong connections, which are sometimes bidirectional, among a lot of weak connections. To explain these connectivity patterns, we created a model of spike timing-dependent plasticity (STDP) in which synaptic changes depend on presynaptic spike arrival and the postsynaptic membrane potential, filtered with two different time constants. Our model describes several nonlinear effects that are observed in STDP experiments, as well as the voltage dependence of plasticity. We found that, in a simulated recurrent network of spiking neurons, our plasticity rule led not only to development of localized receptive fields but also to connectivity patterns that reflect the neural code. For temporal coding procedures with spatio-temporal input correlations, strong connections were predominantly unidirectional, whereas they were bidirectional under rate-coded input with spatial correlations only. Thus, variable connectivity patterns in the brain could reflect different coding principles across brain areas; moreover, our simulations suggested that plasticity is fast.


Partitioning lung and plasma proteins: circulating surfactant proteins as biomarkers of alveolocapillary permeability.
1. The alveolocapillary membrane faces an extraordinary task in partitioning the plasma and lung hypophase proteins, with a surface area approximately 50-fold that of the body and only 0.1-0.2 micron thick. 2. Lung permeability is compromised under a variety of circumstances and the delineation between physiological and pathological changes in permeability is not always clear. Although the tight junctions of the epithelium, rather than the endothelium, are regarded as the major barrier to fluid and protein flux, it is becoming apparent that the permeability of both are dynamically regulated. 3. Whereas increased permeability and the flux of plasma proteins into the alveolar compartment has dire consequences, fortuitously the flux of surfactant proteins from the airspaces into the circulation may provide a sensitive means of non-invasively monitoring the lung, with important implications for treatment modalities. 4. Surfactant proteins are unique in that they are present in the alveolar hypophase in high concentrations. They diffuse down their vast concentration gradients (approximately 1:1500-7000) into the circulation in a manner that reflects lung function and injury score. Surfactant proteins vary markedly in size (approximately 20-650 kDa) and changes in the relative amounts appear particularly diagnostic with regard to disease severity. Alveolar levels of surfactant proteins remain remarkably constant despite respiratory disease and, unlike the flux of plasma proteins into the alveolus, which may reach equilibrium in acute lung injury, the flux of surfactant proteins is unidirectional because of the concentration gradient and because they are rapidly cleared from the circulation. 5. Ultimately, the diagnostic usefulness of surfactant proteins as markers of alveolocapillary permeability will demand a sound understanding of their kinetics through the vascular compartment.


The T----C substitution at -198 of the A gamma-globin gene associated with the British form of HPFH generates overlapping recognition sites for two DNA-binding proteins.
Defects in the developmental changes of human hemoglobin production characterized by the continued expression of fetal globin during adult life are classified as hereditary persistence of fetal hemoglobin (HPFH). Among the various molecular lesions associated with this phenotype, the non-deletion forms with point mutations in the promoter region are thought to provide mechanistic clues for gamma-globin gene regulation. The natural occurrence of four different base substitutions mapping within six nucleotides of a homopurine.homopyrimidine motif in the upstream promoter region demarcate a potential control element. To assess its importance for transcriptional activity, we compared the -202 (C----G), -198 (T----C) and -196 (C----T) HPFH mutations with the normal sequence in binding studies with nuclear proteins from erythroid and non-erythroid cells. Wildtype DNA and HPFH mutations at -202 or -196 showed only a weak protein interaction of unclear functional significance. In contrast, -198 (T----C) generated overlapping, high-affinity binding sites for two ubiquitous nuclear proteins. One cognate protein was identified as the transcription factor Sp1. The second one was termed NF-G.C as it interacted strongly with the homopolymer poly(dG).poly(dC). The generation of additional recognition sites for trans-acting factors by the -198 HPFH mutation correlated with a modest increase in promoter activity in vitro specifically with nuclear extracts from erythroid cells. The activation appears to be mediated by binding of Sp1, but it requires interaction with an erythroid-specific factor, most likely GF-1. Templates containing the -196 HPFH mutation showed a transcriptional activity identical to wildtype. This suggests that despite the topological proximity of the mutations, the HPFH phenotype may be established by different mechanisms.


Evaluation of direct immunofluorescence, enzyme immunoassay, centrifugation culture, and conventional culture for the detection of respiratory syncytial virus.
Four methods of detecting respiratory syncytial virus (RSV) from clinical specimens were evaluated. A total of 410 specimens consisting of nasopharyngeal washes, aspirates, and swabs were simultaneously tested for the presence of RSV by direct immunofluorescence assay (DFA), enzyme immunoassay (EIA) (Kallestad Pathfinder), shell vial centrifugation culture (SVC), and conventional culture. DFA identified 146 (83%) of the 175 positive cases, EIA detected 153 (87%), SVC detected 127 (73%), and conventional culture detected 70 (40%). Conventional culture isolated an additional 19 respiratory viruses other than RSV. DFA and EIA were able to detect nonviable virus not isolated by a culture method, and SVC isolated low-titer virus not detected by conventional culture. DFA and EIA gave similar results; however, the EIA system was less dependent on technical expertise. The use of SVC enhanced the conventional culture system with 63 RSV isolates not recovered from the tube culture. We recommend complementary use of both culture and nonculture methods in the detection of RSV.


Cyclic AMP-dependent phosphorylation of the rat brain ryanodine receptor.
Phosphorylation of the rat brain ryanodine receptor was studied using a monoclonal antibody, Ry-1, against the cardiac ryanodine receptor. A large polypeptide with the same SDS-PAGE mobility as that of the canine cardiac receptor was detected in rat brain membranes by immunoblotting. The brain ryanodine receptor was solubilized from the microsomal membranes with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS), and more than 85% of the solubilized receptor was immunoprecipitated by Ry-1. Immunoprecipitated receptors were phosphorylated by cAMP-dependent protein kinase. The ryanodine receptor was also expressed in cultured fetal rat brain neurons and was phosphorylated by treating the cells with dibutyryl cAMP. The number of cells showing a caffeine-induced Ca2+ transient was increased significantly in the phosphorylating condition. These results suggest that the Ca channel activity of the brain ryanodine receptor is regulated by cAMP-dependent phosphorylation.


The microrandomized trial for developing digital interventions: Experimental design and data analysis considerations.
Just-in-time adaptive interventions (JITAIs) are time-varying adaptive interventions that use frequent opportunities for the intervention to be adapted-weekly, daily, or even many times a day. The microrandomized trial (MRT) has emerged for use in informing the construction of JITAIs. MRTs can be used to address research questions about whether and under what circumstances JITAI components are effective, with the ultimate objective of developing effective and efficient JITAI. The purpose of this article is to clarify why, when, and how to use MRTs; to highlight elements that must be considered when designing and implementing an MRT; and to review primary and secondary analyses methods for MRTs. We briefly review key elements of JITAIs and discuss a variety of considerations that go into planning and designing an MRT. We provide a definition of causal excursion effects suitable for use in primary and secondary analyses of MRT data to inform JITAI development. We review the weighted and centered least-squares (WCLS) estimator which provides consistent causal excursion effect estimators from MRT data. We describe how the WCLS estimator along with associated test statistics can be obtained using standard statistical software such as R (R Core Team, 2019). Throughout we illustrate the MRT design and analyses using the HeartSteps MRT, for developing a JITAI to increase physical activity among sedentary individuals. We supplement the HeartSteps MRT with two other MRTs, SARA and BariFit, each of which highlights different research questions that can be addressed using the MRT and experimental design considerations that might arise. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Initial and intermediate-term treatment of the phantom thrombus (primary non-occlusive mural thrombus on normal arteries).
An embolic event originating from thrombus on an otherwise un-diseased or minimally diseased proximal artery (Phantom Thrombus) is a rare but significant clinical challenge. All patients from a single center with an imaging defined luminal thrombus with a focal mural attachment site on an artery were evaluated retrospectively. We excluded all patients with underlying anatomic abnormalities of the vessel at the attachment site. Six patients with a mean age of 62.5 years were identified over a 2.5-year period. All patients had completed treatment for or had a current diagnosis of malignancy and none were on antiplatelets or other anticoagulants. Four thrombi originated in the aorta proximal to the renal arteries and one originated distal. One thrombus was found in the common carotid artery and one was in an arterialized vein graft. Mean follow-up was 22 months. None of the patients underwent removal or exclusion of the embolic source. With systemic anticoagulation, four of the phantom thrombi were resolved on imaging within 8 weeks, one resolved after 72 weeks. One phantom thrombus reoccurred after 6 months on reduced anticoagulant dosing. There was one acute and one death in follow-up (26 months). One patient required a partial foot amputation secondary to tissue necrosis from the initial thromboembolic event. Arterial thrombi forming on otherwise normal vessels are a distinct clinical entity. In patients with a phantom thrombus, a strategy of therapeutic anticoagulation for management of the embolic source seems to be safe and effective over both the short and intermediate-term.


Effect of Quercetin Monoglycosides on Oxidative Stress and Gut Microbiota Diversity in Mice with Dextran Sodium Sulphate-Induced Colitis.
The pathogenesis of inflammatory bowel disease (IBD) is linked to an intricate association of environmental, microbial, and host-related factors. This study examined the potential effects of dietary addition of two preparations from onion, one comprising quercetin aglycone alone (Q: 0.15% polyphenols, quercetin aglycone:quercetin monoglycosides, 98:2) and another comprising quercetin aglycone with monoglycosides (Q+MQ: 0.15% total polyphenols, quercetin aglycone:quercetin monoglycosides, 69:31), on dextran sodium sulphate- (DSS-) induced colitis in mice. The results revealed a significant decrease in the body weight gain of the mice with DSS-induced colitis, which was counteracted by the dietary Q or Q+MQ supplementation. Meanwhile, the oxidative stress indicated by myeloperoxidase (MPO), reduced glutathione (GSH), malondialdehyde (MDA), and serum nitrate (NO) concentrations was higher in mice with DSS-induced colitis than in the control group mice, but dietary Q or Q+MQ supplementation counteracted this trend. The colitis mice demonstrated reduced Chao1, angiotensin-converting enzyme (ACE), and Shannon indices and an increased Simpson index, but the colitis mice receiving dietary Q or Q+MQ exhibited higher Chao1, ACE, and Shannon indices and a reduced Simpson index. In conclusion, this research showed that even at a low dose, dietary Q or Q+MQ supplementation counteracts DSS-induced colitis in mice, indicating that Q or Q+MQ may be used as an adjuvant therapy for IBD patients.


Influence of nar (nitrate reductase) genes on nitrate inhibition of formate-hydrogen lyase and fumarate reductase gene expression in Escherichia coli K-12.
In Escherichia coli, aerobiosis inhibits the synthesis of enzymes for anaerobic respiration (e.g., nitrate reductase and fumarate reductase) and for fermentation (e.g., formate-hydrogen lyase). Anaerobically, nitrate induces nitrate reductase synthesis and inhibits the formation of both fumarate reductase and formate-hydrogen lyase. Previous work has shown that narL+ is required for the effects of nitrate on synthesis of both nitrate reductase and fumarate reductase. Another gene, narK (whose function is unknown), has no observable effect on formation of these enzymes. We report here our studies on the role of nar genes in fumarate reductase and formate-hydrogen lyase gene expression. We observed that insertions in narX (also of unknown function) significantly relieved nitrate inhibition of fumarate reductase gene expression. This phenotype was distinct from that of narL insertions, which abolished this nitrate effect under certain growth conditions. In contrast, insertion mutations in narK and narGHJI (the structural genes for the nitrate reductase enzyme complex) significantly relieved nitrate inhibition of formate-hydrogen lyase gene expression. Insertions in narL had a lesser effect, and insertions in narX had no effect. We conclude that nitrate affects formate-hydrogen lyase synthesis by a pathway distinct from that for nitrate reductase and fumarate reductase.


Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis.
Ursodeoxycholic acid (UDCA) has shown effectiveness as a colon cancer chemopreventive agent in preclinical studies. In addition, a recent report suggests that it also may decrease the risk for developing colorectal dysplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We sought to evaluate the effect of UDCA on colorectal neoplasia in a group of patients with UC and PSC enrolled in a randomized, placebo-controlled trial. From a prior, randomized, placebo-controlled trial of UDCA therapy in PSC at our center, we followed-up patients with concomitant UC to assess the effect of UDCA on the development of colorectal dysplasia and cancer as compared with placebo. Fifty-two subjects were followed-up for a total of 355 person-years. Those originally assigned to receive UDCA had a relative risk of 0.26 for developing colorectal dysplasia or cancer (95% confidence interval, 0.06-0.92; P = 0.034). Many of the patients originally assigned to the placebo group eventually received open-label UDCA. Assigning these patients to the UDCA group from the time they began active therapy did not change the magnitude of the protective effect (relative risk, 0.26; 95% confidence interval, 0.07-0.99; P = 0.049). UDCA significantly decreases the risk for developing colorectal dysplasia or cancer in patients with UC and PSC.


Evaluation of bacterial resistance to essential oils and antibiotics after exposure to oregano and cinnamon essential oils.
Essential oils (EOs) are excellent antimicrobial agents sometimes used in active food packaging. This work studies the susceptibility of 48 clinical isolates and 12 reference strains of Gram-negative bacilli to oregano essential oil, cinnamon essential oil, and combinations of both. Furthermore, the tendency of the clinical isolates to develop resistance to these EOs and to different antibiotics after sequential oregano or cinnamon exposure was studied. For this purpose, antibiotic susceptibility (through disk diffusion assays and minimum inhibitory concentration [MIC] determination) and oregano and cinnamon susceptibility (through MIC and minimum bactericidal concentration [MBC] determination) were compared after 50 passages in the presence or absence of subinhibitory concentrations of oregano and cinnamon essential oils. The results showed that all strains were susceptible to both EOs and their combination independently of the antibiotic resistance profile. In addition, neither synergistic nor antagonistic effects were observed between oregano and cinnamon essential oils at the concentrations tested. After the sequential exposure to both EOs, only Serratia marcescens, Morganella morganii, and Proteus mirabilis treated with oregano changed their antibiotic resistance profile and/or increased their resistance to this EO. However, the changes in antibiotic and oregano resistance were not related.


Bioavailability of gold nanomaterials to plants: importance of particle size and surface coating.
We used the model organisms Nicotiana tabacum L. cv Xanthi (tobacco) and Triticum aestivum (wheat) to investigate plant uptake of 10-, 30-, and 50-nm diameter Au manufactured nanomaterials (MNMs) coated with either tannate (T-MNMs) or citrate (C-MNMs). Primary particle size, hydrodynamic size, and zeta potential were characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), and electrophoretic mobility measurements, respectively. Plants were exposed to NPs hydroponically for 3 or 7 days for wheat and tobacco, respectively. Volume averaged Au concentrations were determined using inductively coupled plasma mass spectrometry (ICP-MS). Spatial distribution of Au in tissue samples was determined using laser ablation ICP-MS (LA-ICP-MS) and scanning X-ray fluorescence microscopy (μXRF). Both C-MNMs and T-MNMs of each size treatment bioaccumulated in tobacco, but no bioaccumulation of MNMs was observed for any treatment in wheat. These results indicate that MNMs of a wide range of size and with different surface chemistries are bioavailable to plants, provide mechanistic information regarding the role of cell wall pores in plant uptake of MNMs, and raise questions about the importance of plant species to MNM bioaccumulation.


Clinical and histological characteristics of canine ocular gliovascular syndrome.
To characterize the clinical, diagnostic, and histopathologic findings in dogs with canine ocular gliovascular syndrome (COGS). The archives at the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) were used to identify eyes with COGS. Histopathological inclusion criteria included: a neovascular membrane extending from the optic nerve head or retina, clusters of spindle cells lacking vascularization within the vitreous, and histological signs of glaucoma. Special and immunohistochemical (IHC) staining techniques were performed. Clinical data, treatments, and outcomes were obtained from case records and information provided by submitting veterinarians. Thirty-seven eyes of 36 dogs were identified with COGS. The average age at diagnosis was 8.8 years (±2.2). The relative risk for a Labrador retriever affected by COGS was significantly greater (9.3 times) (P < 0.0001) when compared to all other dog breeds within the COPLOW database. Most dogs presented with hyphema and secondary glaucoma; average intraocular pressure was 39 mmHg (±19). Average time to enucleation or evisceration was 27 days. Vitreal cells stained positive with IHC for glial fibrillary acidic protein in 14 of 17 globes, and vascular endothelial growth factor was expressed in the vitreal cells in five of five globes. We have defined a syndrome associated with vitreal glial cell aggregates and neovascular proliferation from the optic nerve or retina, which leads to neovascular glaucoma. The inflammation and secondary glaucoma resulting from this syndrome appear poorly responsive to conventional medical therapies. The exact etiology of COGS remains undetermined, but a systemic etiology is unlikely.


Absence of the gamma subunit of the skeletal muscle dihydropyridine receptor increases L-type Ca2+ currents and alters channel inactivation properties.
In skeletal muscle the oligomeric alpha(1S), alpha(2)/delta-1 or alpha(2)/delta-2, beta1, and gamma1 L-type Ca(2+) channel or dihydropyridine receptor functions as a voltage sensor for excitation contraction coupling and is responsible for the L-type Ca(2+) current. The gamma1 subunit, which is tightly associated with this Ca(2+) channel, is a membrane-spanning protein exclusively expressed in skeletal muscle. Previously, heterologous expression studies revealed that gamma1 might modulate Ca(2+) currents expressed by the pore subunit found in heart, alpha(1C), shifting steady state inactivation, and increasing current amplitude. To determine the role of gamma1 assembled with the skeletal subunit composition in vivo, we used gene targeting to establish a mouse model, in which gamma1 expression is eliminated. Comparing litter-matched mice with control mice, we found that, in contrast to heterologous expression studies, the loss of gamma1 significantly increased the amplitude of peak dihydropyridine-sensitive I(Ca) in isolated myotubes. Whereas the activation kinetics of the current remained unchanged, inactivation of the current was slowed in gamma1-deficient myotubes and, correspondingly, steady state inactivation of I(Ca) was shifted to more positive membrane potentials. These results indicate that gamma1 decreases the amount of Ca(2+) entry during stimulation of skeletal muscle.


Quantitative analysis of the secretome of TGF-beta signaling-deficient mammary fibroblasts.
Transforming growth factor beta (TGF-beta) is a master regulator of autocrine and paracrine signaling pathways between a tumor and its microenvironment. Decreased expression of TGF-beta type II receptor (TbetaRII) in stromal cells is associated with increased tumor metastasis and shorter patient survival. In this study, SILAC quantitative proteomics was used to identify differentially externalized proteins in the conditioned media from the mammary fibroblasts with or without intact TbetaRII. Over 1000 proteins were identified and their relative differential levels were quantified. Immunoassays were used to further validate identification and quantification of the proteomic results. Differential expression was detected for various extracellular proteins, including proteases and their inhibitors, growth factors, cytokines, and extracellular matrix proteins. CXCL10, a cytokine found to be up-regulated in the TbetaRII knockout mammary fibroblasts, is shown to directly stimulate breast tumor cell proliferation and migration. Overall, this study revealed hundreds of specific extracellular protein changes modulated by deletion of TbetaRII in mammary fibroblasts, which may play important roles in the tumor microenvironment. These results warrant further investigation into the effects of inhibiting the TGF-beta signaling pathway in fibroblasts because systemic inhibition of TGF-beta signaling pathways is being considered as a potential cancer therapy.


[In vitro analysis of the influence of different tooth positions and retention depths of the pulp cavity on the accuracy of digital impression of the endocrown].
To evaluate the influence of tooth position and retention depth of the dental pulp cavity on the accuracy of intraoral digital impression of endocrown preparation. Dental pulp cavities with retention depths of 2, 3, 4 and 5 mm were prepared on 8 auatomic resin tooth models, including 4 right maxillary first molar (16) and 4 right mandibular first molar (46).Each cavity were scanned for 10 times using 3shape trios3, with micro-CT scans as the reference.All the scan data were exported, and the reference models were obtained by 3D reconstruction with Mimics 2021 software.Gomagic Wrap 2017 was used to analyze the 3D models.The average absolute deviation values were calculated to evaluate the accuracy of the digital models. There was no significant difference in the authenticity and precision between models 16 and 46.The mean maximum positive and negative deviations of the model 16 were less than those of the model 46(P<0.05), and for both the models 16 and 46, the mean maximum positive deviation was significantly greater than the mean maximum negative deviation (P<0.05).The authenticity of the 5 mm group was lower than that of the 2 mm, 3 mm and 4 mm groups (P<0.05).The precision was higher in 2 mm group than in 4 mm and 5 mm groups (P<0.05), and higher in 3 mm group than in 5 mm group (P<0.05).The mean maximum positive and negative deviations in 2 mm group were lower than those in 5 mm group (P<0.05). The position of teeth has little influence on intraoral digital impression of the endocrown.The retention depth of the dental pulp cavity affects the accuracy of intraoral digital impression of the endocrown, and a greater depth results in a greater deviation.


A novel IMU-based clinical assessment protocol for Axial Spondyloarthritis: a protocol validation study.
Clinical assessment of spinal impairment in Axial Spondyloarthritis is currently performed using the Bath Ankylosing Spondylitis Metrological Index (BASMI). Despite being appreciated for its simplicity, the BASMI index lacks sensitivity and specificity of spinal changes, demonstrating poor association with radiographical range of motion (ROM). Inertial measurement units (IMUs) have shown promising results as a cost-effective method to quantitatively examine movement of the human body, however errors due to sensor angular drift have limited their application to a clinical space. Therefore, this article presents a wearable sensor protocol that facilitates unrestrained orientation measurements in space while limiting sensor angular drift through a novel constraint-based approach. Eleven healthy male participants performed five BASMI-inspired functional movements where spinal ROM and continuous kinematics were calculated for five spine segments and four spinal joint levels (lumbar, lower thoracic, upper thoracic and cervical). A Bland-Altman analysis was used to assess the level of agreement on range of motion measurements, whilst intraclass correlation coefficient (ICC), standardised error measurement, and minimum detectable change (MDC) to assess relative and absolute reliability. Continuous kinematics error was investigated through root mean square error (RMSE), maximum absolute error (MAE) and Spearman correlation coefficient (ρ). The overall error in the measurement of continuous kinematic measures was low in both the sagittal (RMSE = 2.1°), and frontal plane (RMSE = 2.3°). ROM limits of agreement (LoA) and minimum detectable change were excellent for the sagittal plane (maximum value LoA 1.9° and MDC 2.4°) and fair for lateral flexion (overall value LoA 4.8° and MDC 5.7°). The reliability analysis showed excellent level of agreement (ICC > 0.9) for both segment and joint ROM across all movements. The results from this study demonstrated better or equivalent accuracy than previous studies and were considered acceptable for application in a clinical setting. The protocol has shown to be a valuable tool for the assessment of spinal ROM and kinematics, but a clinical validation study on Axial Spondyloarthritis patients is required for the development and testing of a novel mobility index.


Effects of electrochemical reduction reactions on the biodegradation of recalcitrant organic compounds (ROCs) and bacterial community diversity.
Five bacterial species, capable of degrading the recalcitrant organic compounds (ROCs) diethyleneglycol monomethylether (DGMME), 1-amino-2-propanol (APOL), 1-methyl-2- pyrrolidinone (NMP), diethyleneglycol monoethylether (DGMEE), tetraethyleneglycol (TEG), and tetrahydrothiophene 1,1-dioxide (sulfolane), were isolated from an enrichment culture. Cupriavidus sp. catabolized 93.5+/-1.7 mg/l of TEG, 99.3+/-1.2 mg/l of DGMME, 96.1+/-1.6mg/l of APOL, and 99.5+/-0.5mg/l of NMP in 3 days. Acineobacter sp. catabolized 100 mg/l of DGMME, 99.9+/-0.1 mg/l of NMP, and 100 mg/l of DGMEE in 3 days. Pseudomonas sp.3 catabolized 95.7+/-1.2 mg/l of APOL and 99.8+/-0.3 mg/l of NMP. Paracoccus sp. catabolized 98.3+/-0.6 mg/l of DGMME and 98.3+/-1.0 mg/l of DGMEE in 3 days. A maximum 43+/-2.0 mg/l of sulfolane was catabolized by Paracoccus sp. in 3 days. When a mixed culture composed of the five bacterial species was applied to real wastewater containing DGMME, APOL, NMP, DGMEE, or TEG, 92~99% of each individual ROC was catabolized within 3 days. However, at least 9 days were required for the complete mineralization of sulfolane. Bacterial community diversity, analyzed on the basis of the TGGE pattern of 16S rDNA extracted from viable cells, was found to be significantly reduced in a conventional bioreactor after 6 days of incubation. However, biodiversity was maintained after 12 days of incubation in an electrochemical bioreactor. In conclusion, the electrochemical reduction reaction enhanced the diversity of the bacterial community and actively catabolized sulfolane.


Electrochemical Deposition of Copper on Bioactive Porous Titanium Dioxide Layer: Antibacterial and Pro-Osteogenic Activities.
Ti surfaces must exhibit antibacterial activity without cytotoxicity to promote bone reconstruction and prevent infection simultaneously. In this study, we employed a two-step electrochemical treatment process, namely, microarc oxidation (MAO) and cathodic electrochemical deposition (CED), to modify Ti surfaces. During the MAO step, a porous TiO2 (pTiO2) layer with a surface roughness of approximately 2.0 μm was generated on the Ti surface, and in the CED step, Cu was deposited onto the pTiO2 layer on the Ti surface, forming Cu@pTiO2. Cu@pTiO2 exhibited a similar structure, adhesion strength, and crystal phase to pTiO2. Moreover, X-ray photoelectron spectroscopy (XPS) confirmed the presence of Cu in Cu@pTiO2 at an approximate concentration of 1.0 atom %. Cu@pTiO2 demonstrated a sustained release of Cu ions for a minimum of 28 days in a simulated in vivo environment. In vitro experiments revealed that Cu@pTiO2 effectively eradicated approximately 99% of Staphylococcus aureus and Escherichia coli and inhibited biofilm formation, in contrast to the Ti and pTiO2 surfaces. Moreover, Cu@pTiO2 supported the proliferation of osteoblast-like cells at a rate comparable to that observed on the Ti and pTiO2 surfaces. Similar to pTiO2, Cu@pTiO2 promoted the calcification of osteoblast-like cells compared with Ti. In summary, we successfully conferred antibacterial and pro-osteogenic activities to Ti surfaces without inducing cytotoxic effects or structural and mechanical alterations in pTiO2 through the application of MAO and CED processes. Moreover, we found that the pTiO2 layer promoted bacterial growth and biofilm formation more effectively than the Ti surface, highlighting the potential drawbacks of rough and porous surfaces. Our findings provide fundamental insights into the surface design of Ti-based medical devices for bone reconstruction and infection prevention.


Scene Context Impairs Perception of Semantically Congruent Objects.
Visual scene context is well-known to facilitate the recognition of scene-congruent objects. Interestingly, however, according to predictive-processing accounts of brain function, scene congruency may lead to reduced (rather than enhanced) processing of congruent objects, compared with incongruent ones, because congruent objects elicit reduced prediction-error responses. We tested this counterintuitive hypothesis in two online behavioral experiments with human participants (N = 300). We found clear evidence for impaired perception of congruent objects, both in a change-detection task measuring response times and in a bias-free object-discrimination task measuring accuracy. Congruency costs were related to independent subjective congruency ratings. Finally, we show that the reported effects cannot be explained by low-level stimulus confounds, response biases, or top-down strategy. These results provide convincing evidence for perceptual congruency costs during scene viewing, in line with predictive-processing theory.


Mindfulness as a Potential Moderator Between Child Behavior Problems and Maternal Well-Being.
Mindfulness-based programs can help lower psychological distress among parents of children with developmental disabilities. However, less is known about the functions of mindfulness in relation to parental outcomes. In a cross-sectional survey, mothers of children with developmental disabilities (N = 313) reported on their child's behavior problems, trait mindfulness, mindful parenting, and a range of outcomes (anxiety and depression symptoms, parenting stress, family satisfaction, and positive gain). Neither trait mindfulness or mindful parenting acted as moderators between child behavior problems and outcome variables, although both had main effect (compensatory) associations with parent outcomes. Benefits of mindfulness-based programs may be general rather than specifically in the context of high child behavior problems, given the lack of evidence for the moderating function of mindfulness.


Mecamylamine inhibits nicotine but not capsaicin irritation on the tongue: psychophysical evidence that nicotine and capsaicin activate separate molecular receptors.
Using a two-alternative forced-choice (2-AFC) discrimination test coupled with category intensity ratings, we investigated the effect of mecamylamine, an antagonist of neuronal nicotinic acetylcholine receptors (nAchRs), on oral irritation elicited by nicotine or capsaicin. Mecamylamine (0.075%) was first delivered to one side of the tongue with distilled H2O delivered to the other side. After 10 min either capsaicin (1 ppm) or nicotine (0.12%) was applied bilaterally to the tongue, and subjects were asked to choose which side yielded a stronger sensation (2-AFC) as well as to provide a rating of the irritation intensity difference between the two sides of the tongue. When nicotine was given after mecamylamine, a significant proportion of subjects chose the mecamylamine-untreated side as yielding stronger irritation. When capsaicin was given after mecamylamine, both sides of the tongue were chosen in equal numbers. These data indicate that mecamylamine reduced irritation elicited by nicotine but not capsaicin, and provide further evidence that nicotine oral irritation is mediated via a neuronal nAchR while capsaicin activates trigeminal fibers via a separate molecular receptor.


Gaps in the civil registration and vital statistics systems of low- and middle-income countries and the health sector's role in improving the situation.
Civil Registration and Vital Statistics (CRVS) is an essential administrative system that provides legal identification to all individuals and accurate statistical data of vital events, such as birth and death rates within the population. Globally, CRVS has been considered a priority issue, especially for low- and middle-income countries where the coverage of this system is poor. This may be attributed to factors such as inefficiency of laws, poor inter-ministerial cooperation, and a lack of awareness among people. To address these issues and improve coverage of the CRVS, the health sector could play a key role by acting as an entry point, collecting accurate vital data, and utilizing information from CRVS. However, the function of the health sector in implementing CRVS has not been fully analyzed in most countries. Further investigation is necessary to develop effective measures to strengthen CRVS.


High burden of antimicrobial resistance in Asia.
Antimicrobial resistance is associated with high mortality rates and high medical costs. Marked variations in the resistance profiles of bacterial and fungal pathogens as well as the quality of public hygiene have had a considerable impact on the effectiveness of antimicrobial agents in Asian countries. In Asia, one of the epicentres of antimicrobial drug resistance, there is an alarming number of antibiotic-resistant species, including penicillin- and erythromycin-resistant Streptococcus pneumoniae, ampicillin-resistant Haemophilus influenzae, multidrug-resistant (MDR) Acinetobacter baumannii, extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (particularly mediated by CTX-M-9, CTX-M-14 and CTX-M-15), New Delhi metallo-β-lactamase 1 (NDM-1)-producing Enterobacteriaceae, MDR Salmonella enterica serotypes Choleraesuis and Typhi, carbapenem-resistant A. baumannii (OXA-58 and OXA-23 carbapenemases) and azole-resistant Candida glabrata. A few clones of MDR A. baumannii and hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA) have been widely disseminated in hospital settings in Asia, and K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains have been widely distributed in China. In addition, the emergence of extensively drug-resistant Mycobacterium tuberculosis (XDR-TB) has illustrated the need for regular monitoring of resistance profiles of clinical isolates as well as the deliberative use of fluoroquinolones. Continuous surveillance of resistance data from clinical isolates as well as implementation of strict infection control policies in healthcare settings are required to mitigate the progression of antimicrobial resistance.


The importance of auditory, olfactory, and visual cues for insect foraging in owl monkeys (Aotus nancymaae).
Nocturnal mammals have unique sensory adaptations to facilitate foraging at night. Owl monkeys (Aotus spp.) are pair-living nocturnal platyrrhines adept at capturing insect prey under low-light conditions. Owl monkeys use acoustic and chemical cues in intraspecific communication and use olfaction to detect fruit as they forage. We conducted an experiment to determine which cues (auditory, olfactory, and visual) Aotus nancymaae rely upon when foraging for insects. We scored the behavior of 23 captive owl monkeys during a series of trials in which monkeys were provided sensory boxes with insect cues either present (experimental box) or absent (control box). Each cue was tested alone and in combination with all other cues (multimodal cues). We used generalized linear mixed models to determine which cues elicited the greatest behavioral response. Owl monkeys approached and spent more time near experimental boxes than control boxes. Male owl monkeys were quicker than their female partners to approach the sensory boxes, suggesting that males may be less neophobic than females. The owl monkeys exhibited behaviors associated with olfaction and foraging (e.g., sneezing, trilling) during trials with multimodal cues and when only olfactory cues were present. When only visual or auditory cues were present, owl monkeys exhibited fewer foraging-related behaviors. After approaching a sensory box, however, they often touched boxes containing visual cues. A. nancymaae may rely on olfactory cues at night to detect a food source from several meters away and then rely more on visual cues once they are closer to the food source. Their use of sensory cues during insect foraging differs from nocturnal strepsirrhines, possibly reflecting physiological constraints associated with phylogeny, given that owl monkeys evolved nocturnality secondarily from a more recent diurnal ancestor.


Combining Oxygenated Cold Perfusion With Normothermic Ex Vivo Perfusion Improves the Outcome of Donation After Circulatory Death Porcine Kidney Transplantation.
Ex vivo machine perfusion is a novel preservation technique for storing and assessing marginal kidney grafts. All ex vivo perfusion techniques have advantages and shortcomings. The current study analyzed whether a combination of oxygenated hypothermic machine perfusion (oxHMP) followed by a short period of normothermic ex vivo kidney perfusion (NEVKP) could combine the advantages of both techniques. Porcine kidneys were exposed to 30 min of warm ischemia followed by perfusion. Kidneys underwent either 16-h NEVKP or 16-h oxHMP. The third group was exposed to 16-h oxHMP followed by 3-h NEVKP (oxHMP + NEVKP group). After contralateral nephrectomy, grafts were autotransplanted and animals were followed up for 8 d. All animals survived the follow-up period. Grafts preserved by continuous NEVKP showed improved function with lower peak serum creatinine and more rapid recovery compared with the other 2 groups. Urine neutrophil gelatinase-associated lipocalin, a marker of kidney injury, was found to be significantly lowered on postoperative day 3 in the oxHMP + NEVKP group compared with the other 2 groups. A short period of NEVKP after oxHMP provides comparable short-term outcomes to prolonged NEVKP and is superior to oxHMP alone. A combination of oxHMP with end-ischemic NEVKP could be an attractive, practical strategy to combine the advantages of both preservation techniques.


Neonatal truncus arteriosus repair: surgical techniques and clinical management.
Truncus arteriosus is now ideally repaired in the neonatal period with low morbidity and mortality. Published reports have documented mortality rates in the range of 4% to 5% with mean age at repair as low as 11 days. The physiologic basis for improved outcomes with earlier repair is the avoidance of damaging sequelae of pulmonary overcirculation and heart failure. Data show that baseline mean pulmonary artery pressure is lower in infants undergoing earlier repair. Improved operative outcomes also have been achieved with aggressive truncal valve repair versus replacement in the presence of truncal valve dysfunction, right ventricular outflow tract reconstructive techniques that are patient anatomy-specific, and use of regional perfusion techniques for repair of associated interrupted aortic arch. In addition, a heightened awareness of anomalies of coronary artery ostial location, number, angle of takeoff, and degree of patency can result in avoidance of inadvertent injury to the artery and associated myocardial insult.


Proposal for Updated Nomenclature and Classification of Potential Causative Mechanism in Patent Foramen Ovale-Associated Stroke.
Recent epidemiologic and therapeutic advances have transformed understanding of the role of and therapeutic approach to patent foramen ovale (PFO) in ischemic stroke. Patent foramen ovale is likely responsible for approximately 5% of all ischemic strokes and 10% of those occurring in young and middle-aged adults. Randomized clinical trials have demonstrated that, to prevent recurrent ischemic stroke in patients with PFO and an otherwise-cryptogenic index ischemic stroke, PFO closure is superior to antiplatelet medical therapy alone; these trials have provided some evidence that, among medical therapy options, anticoagulants may be more effective than antiplatelet agents. These new data indicate a need to update classification schemes of causative mechanisms in stroke, developed in an era in which an association between PFO and stroke was viewed as uncertain. We propose a revised general nomenclature and classification framework for PFO-associated stroke and detailed revisions for the 3 major stroke subtyping algorithms in wide use.