No evidence of decline in malaria burden from 2006 to 2013 in a rural Province of Gabon: implications for public health policy.
The morbidity of malaria has steady declined in the urban regions of Gabon between 2000 and 2008, but caution should be exercised before generalizing this trend to the whole country because this finding has not been systematically confirmed in remote rural provinces. We conducted a retrospective survey using data on malaria cases recorded in North Eastern Gabon between 2006 and 2013 at health facilities in Makokou. Malaria data were analyzed, and associations with annual variations and patient age were assessed. A global increase in clinical and confirmed malaria cases was observed over the study period. The rate of infection was significantly higher in children aged between 0 to 4 years than in children of 5 years and above, and in adults. Contrary to prior observations in urban and semi-urban areas of Gabon, malaria burden remained mostly unchanged or even increased in Makokou in the Ogooué-Ivindo province during these last 8 years. The persistence of Plasmodium falciparum pockets of sustained malaria transmission in rural Gabon may be related to an inadequate coverage of key interventions, to poor treatment seeking behavior and/or to a decline efficacy of treatments. Our results highlight the need to better adapt malaria control strategies to local epidemiological contexts and to environmental constraints. Equitable delivery of health service to hard-to-reach populations constitutes a challenging issue for the health authorities of Gabon.


Surveillance and management of urologic complications after spinal cord injury.
Neurogenic bladder due to spinal cord injury has significant consequences for patients' health and quality of life. Regular surveillance is required to assess the status of the upper and lower urinary lower urinary tracts and prevent their deterioration. In this review, we examine surveillance techniques in neurogenic bladder, describe common complications of this disease, and address strategies for their management. This work represents the efforts of SIU-ICUD joint consultation on Urologic Management of the Spinal Cord injury. For this specific topic, a workgroup was formed and comprehensive literature search of English language manuscripts regarding neurogenic bladder management was performed using key words of neurogenic bladder. Articles were compiled, and recommendations in the chapter are based on group discussion and follow the Oxford Centre for Evidence-based Medicine system for Levels of Evidence (LOEs) and Grades of Recommendation (GORs). At a minimum, patients should undergo an annual history and physical examination, renal functional testing (e.g., serum creatinine), and upper tract imaging (e.g., renal ultrasonography). The existing evidence does not support the use of other modalities, such as cystoscopy or urodynamics, for routine surveillance. Urologic complications in neurogenic bladder patients are common and often more complex than in the general population. There is a shortage of high-quality evidence to support any particular neurogenic bladder surveillance protocol. However, there is consensus regarding certain aspects of regular genitourinary system evaluation in these patients. Proper surveillance allows the clinician to avoid or address common urological complications, and to guide, alter, or maintain appropriate therapeutic regimens for individual patients.


A multi-method exploration into the social networks of young teenagers and their physical activity behavior.
There is a need for novel interventions to target inadequate levels of adolescent physical activity behavior. Previous research indicates that better understanding of the processes by which social networks influence physical activity behavior in adolescents may be useful to enhance intervention design. This study used a multi-methods approach to aid our understanding about the role of social networks for adolescent physical activity behavior. The quantitative phase of data collection was analyzed using a three-step linear regression model using cross-sectional data from the WiSe study (n = 529 participants, 48.6% female, mean age 14.38 years (SD 0.32)). A demographically reflective sub-sample of schools were invited to take part in the qualitative phase, which involved focus group discussions. Thematic analysis was used to explore findings from the quantitative phase in greater depth, and identify other themes pertaining to the association between social networks and physical activity behavior. Males' physical activity behavior was predicted by their friend group (0.46, p = 0.007) whereas females' physical activity was predicted by their best friend (0.21, p = 0.03). The three main findings that were uncovered by the regression analysis were explored during the qualitative phase: 1) friends have similar physical activity behaviors; 2) friendship social networks may influence differently early adolescent male and female physical activity behavior; 3) popularity and sociability were not associated with physical activity behavior. Two additional themes emerged from the analysis of focus group data: 4) social norms and 5) external factors that may impact the relationship between adolescent physical activity behavior and social networks. The investigation of the interplay between the findings from each phase of the inquiry indicated that social networks influence in different ways and to different degrees the physical activity of adolescent males and females. In turn, these insights point to the need for a systematic tailoring process for the development and implementation of physical activity behavior interventions.


Mycobacterium tuberculosis H37Rv has a single nucleotide polymorphism in PhoR which affects cell wall hydrophobicity and gene expression.
Mycobacterium tuberculosis is a successful pathogen that can adapt to multiple environmental niches. As part of its repertoire of adaptive responses, two-component regulatory systems play a major role in co-ordinating gene expression at the global level. The PhoPR system controls major cellular functions, including respiration, lipid metabolism, the immediate and enduring hypoxic responses, stress responses and persistence. We identified a single nucleotide polymorphism (SNP) found in the sensor kinase (PhoR) of this system between two commonly used strains of M. tuberculosis, H37Rv (PhoR(P152)) and CDC1551 (PhoR(L152)). We constructed an isogenic strain of H37Rv carrying PhoR(L152), as well as strains containing two different copies of the PhoPR locus, to determine the functional consequences of the SNP on phenotypic traits. The previously identified Apr locus was not acid-inducible in H37Rv, although it was in the CDC1551 strain. Surprisingly, the acid-responsive expression was not completely dependent on the PhoR SNP, and the locus remained constitutively expressed even in the isogenic strain H37Rv:PhoR(L152). The pattern of expression in PhoPR merodiploid strains was more complex, with neither allele showing dominance. This suggests that Apr regulation is more complex than previously thought and that additional factors must be responsible for Apr upregulation in response to acid conditions. In contrast, differences we identified in cell hydrophobicity between the two strains were wholly dependent on PhoR, confirming its role as major regulator of cell wall composition. Thus the SNP in the sensor kinase has functional consequences which account for some of the differences between widely used laboratory strains.


Nurse Practitioner Management of a Blinatumomab Infusion Program: Impact on Patient Safety and Quality of Care.
The prognosis of children with acute lymphoblastic leukemia can be improved with the use of monoclonal antibodies such as blinatumomab. Many studies discuss the management and treatment of symptoms; however, none of them describe practical complications related to the continuous infusion of blinatumomab, especially during home-based therapy. The purpose of this study is to describe the experience gained over 4 years in the management of pediatric patients undergoing therapy with blinatumomab in an Italian tertiary hospital. The establishment of a nursing program dedicated to improving infusion pump management, patient support, quality of care, and patient safety will be discussed.


Sexual activity and ischemic heart disease.
Human sexuality is an important aspect of health and quality of life. Many patients with ischemic heart disease - and their partners - are concerned that sexual activity could exacerbate their cardiac condition, possibly causing myocardial infarction or cardiac death. Patients with ischemic heart disease who wish to initiate or resume sexual activity should be evaluated with a thorough medical history and physical examination. Sexual activity is reasonable for individuals with no or mild angina and those who can exercise ≥ 3-5 METS without angina, excessive dyspnea, or ischemic ST segment changes. For the patient who is considered not be at low cardiovascular (CV) risk or in whom the CV risk is unknown, an exercise stress test is reasonable in order to determine his or her exercise capacity and to ascertain if symptoms or ischemia may occur. Regular exercise and cardiac rehabilitation can be effective in reducing the risk of CV complications associated with sexual activity for the patient with ischemic heart disease.


Nicotinamide adenine dinucleotide treatment alleviates the symptoms of experimental autoimmune encephalomyelitis by activating autophagy and inhibiting the NLRP3 inflammasome.
Nicotinamide adenine dinucleotide (NAD + ) is an essential cofactor in numerous metabolic pathways, and so may support protective and reparative processes against central nervous system diseases such as multiple sclerosis (MS). Here, we investigated the therapeutic potential of NAD + administration in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS and the contributions of autophagic regulation and NLRP3 inflammasome activity. EAE was induced in female C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG) p35-55 and disease severity analyzed by neurological function score and histological scores of spinal cord sections stained with hematoxylin-eosin or luxol fast blue. Outcomes were compared among control mice and EAE groups receiving daily post-immunization vehicle injections, NAD + injections, injection of the autophagy inhibitor 3-methyladenine (3-MA), or co-injection of NAD + and 3-MA. Expression levels of autophagy-related proteins (Beclin1, LC3-II/I, and p62/SQSTM1) were assessed by Western blotting, the activated microglial cells were evaluated by immunohistochemistry, while mRNA expression levels of NOD-like receptor family pyrin domain containing 3 (NLRP3), interleukin (IL)-1β, IL-2, IL-17, IL-18, interferon-γ (IFN-γ) and IL-10 were detected by real-time PCR. The proportions of Th1 and Th17 cells in spleen were evaluated using flow cytometry. Treatment with NAD + alleviated demyelination, nerve injury, microglial activation and motor function abnormalities of EAE mice. In addition, NAD + increased the expressions of the autophagy-related proteins LC3-II/I and Beclin 1, and reduced the expression of p62. Treatment with NAD + also inhibited the expressions of NLRP3 and modulated the differentiation of Th1 and Th17 cells, reduced the expressions of the pro-inflammatory factors IL-1β, IL-2, IL-18, IFN-γ and IL-17, and increased the expression of anti-inflammatory IL-10. Conversely, 3-MA aggravated spinal cord inflammation and demyelination, and delayed spontaneous remission from EAE. Furthermore, the beneficial effects of NAD + were abolished by 3-MA cotreatment. Our results indicate that NAD + suppresses the NLRP3 inflammasome at least in part through the activation of autophagy to relieve the symptoms of EAE. Therefore, regulation of autophagy by NAD + treatment may be an effective therapeutic strategy for MS.


Physiological Responses and Prognostic Value of Common Exercise Testing Modalities in Idiopathic Pulmonary Fibrosis.
This pilot study aimed to compare physiological responses between cycle cardiopulmonary exercise tests (CPETs) and 6-min walk tests (6MWTs) and to assess their prognostic value among patients with idiopathic pulmonary fibrosis (IPF). Thirty-four patients with IPF (68 ± 8 yr) underwent CPETs and 6MWTs and were followed up for 40 mo. Differences, levels of agreement, and relative risks for mortality were analyzed between measured and estimated peak responses for the 2 tests. Compared with the CPET, oxygen uptake ((Equation is included in full-text article.)O2), heart rate (HR), and the nadir of SpO2 were lower during the 6MWT, whereas work rate (WR) was higher. Mean differences were as follows: (Equation is included in full-text article.)O2 =-1.9 mL/kg/min, 95% CI, -1.1 to -2.7, P < .001; HR =-9 beats/min, 95% CI, -4 to -14, P = .002; SpO2 =-6%, 95% CI, -4 to -7, P < .001; and WR = 9 W/min, 95% CI, 3 to 16, P = .008. Interclass correlations ranged from 0.84 to 0.90 and both tests demonstrated prognostic value for mortality. Significant differences and variation in peak physiological responses were observed between cycle CPETs and 6MWTs in patients with IPF. However, good agreement was evident, suggesting that both tests provide value for clinical and research settings. Future studies should compare the physiological responses between treadmill CPETs and 6MWTs for prognostic utility in IPF.


Predicting nurses' turnover and internal transfer behavior.
This research examined the predictability of internal job transfer and turnover behavior from nurses' career plans, work values, and job satisfaction. Values and career plans rather than job satisfaction were found to discriminate between persons who remained in their jobs, accepted internal transfers, or turned over within a one-year research period. Results raise doubts about nurses' use of internal transfer as a substitute for turnover and support the importance of employees' expectations about future satisfaction as a major determinant of job movement.


Role of nociceptin/orphanin FQ and NOP receptors in the response to acute and repeated restraint stress in rats.
Central nociceptin/orphanin FQ (N/OFQ)-expressing neurones are abundantly expressed in the hypothalamus and limbic system and are implicated in the regulation of activity of the hypothalamic-pituitary-adrenal axis (HPA) and stress responses. We investigated the role of the endogenous N/OFQ receptor (NOP) system using the nonpeptidic NOP antagonist, JTC-801 [N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxy-methyl)benzamide monohydrochloride], during the HPA axis response to acute physical/psychological stress (60 min of restraint). Although i.v. JTC-801 (0.05 mg/kg in 100 μl) had no significant effect on restraint-induced plasma corticosterone release at 30 or 60 min post-injection, i.v. JTC-801 (0.05 mg/kg in 100 μl) in quiescent rats significantly increased basal plasma corticosterone at the 30-min time-point compared to i.v. vehicle (1% dimethysulphoxide in sterile saline). Central injection of JTC-801 i.c.v. was associated with increased Fos expression in the parvocellular paraventricular nucleus 90 min after infusion compared to vehicle control. These findings contrast to the effects of i.c.v. UFP-101, a NOP antagonist that we have previously shown to have no effect on HPA activity in quiescent rats. To determine whether restraint stress was associated with compensatory changes in N/OFQ precursor (ppN/OFQ) or NOP receptor mRNAs, in a separate study, we undertook reverse transcriptase-polymerase chain reaction and in situ hybridisation analysis of ppN/OFQ and NOP transcripts in the brains of male Sprague-Dawley rats. In support of an endogenous role for central N/OFQ in psychological stress, we found that acute restraint significantly decreased preproN/OFQ transcript expression in the hippocampus 2 h after stress compared to unstressed controls. PpN/OFQ mRNA was also reduced in the mediodorsal forebrain 4 h after stress. NOP mRNA was reduced in the hypothalamus 2 h after restraint and at 4 h in mediodorsal forebrain and hippocampus. In situ hybridisation analysis showed that acute restraint significantly decreased ppNN/OFQ in the central amygdala, with significantly increased expression in bed nucleus and reticular thalamus associated with repeated restraint. There was a strong trend for reduced NOP mRNA in the bed nucleus of acute and repeated restraint groups, although there were no other significant changes seen. Although the exact mechanisms require elucidation, the findings obtained in the present study provide evidence indicating that the endogenous N/OFQ system is involved in both acute and chronic restraint stress responses. In summary, our findings confirm the significant role of endogenous NOP receptors and tonic N/OFQ function in the response to the psychological stress of restraint.


Evaluation of the New International Union Against Cancer TNM staging for gastric carcinoma.
The lymph node (N) classification in the International Union Against Cancer (UICC) TNM staging system for gastric adenocarcinoma has been revised. The new classification is based on the number of positive regional lymph nodes instead of the anatomic location of the regional lymph node metastasis. Both classification systems were compared for prognostic significance. A total of 4362 gastric carcinoma patients who underwent resection between 1969 and 1990 were analyzed. Thirteen percent of patients could not be staged according to the new system. Based on the previous classification, 647 patients were classified as pN1 and 711 patients as pN2. When reclassified, 587 patients remained pN1, 54 patients became pN2, and 6 patients became pN3. Of the 711 pN2 patients, 333 became pN1, 267 remained pN2, and 111 patients became pN3. Both lymph node classification methods defined groups with widely differing prognoses. The prognoses of patients classified as new pN2 were more homogeneous than those of the group classified as old pN2. Survival of new pT4/pN1 patients was significantly better than that of other subgroups in Stage IV. Nine potential prognostic factors, including lymph node metastasis, were studied in multivariate analysis. The hazard ratios were 1.38 (1.16-1.64) for pN1 and 2.55 (2.16-3.01) for pN2, based on the old classification. They were 1.51 (1.29-78) for pN1, 3.11 (2.56-3.78) for pN2, and 3.88 (2.98-5.05) for pN3, based on the new classification. The new N classification is superior as a prognostic factor to the old N classification, although there is inadequacy in stage grouping. [See editorial on pages 1763-5, this issue.]


A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations.
Molecular alterations involving the PI3K/AKT/mTOR pathway (including mutation, copy number, protein, or RNA) were examined across 11,219 human cancers representing 32 major types. Within specific mutated genes, frequency, mutation hotspot residues, in silico predictions, and functional assays were all informative in distinguishing the subset of genetic variants more likely to have functional relevance. Multiple oncogenic pathways including PI3K/AKT/mTOR converged on similar sets of downstream transcriptional targets. In addition to mutation, structural variations and partial copy losses involving PTEN and STK11 showed evidence for having functional relevance. A substantial fraction of cancers showed high mTOR pathway activity without an associated canonical genetic or genomic alteration, including cancers harboring IDH1 or VHL mutations, suggesting multiple mechanisms for pathway activation.


Involvement of norepinephrine in the control of activity and attentive processes in animal models of attention deficit hyperactivity disorder.
Functional and morphological studies in children affected by Attention Deficit Hyperactivity Disorder (ADHD) suggest a prefrontal cortex (PFc) dysfunction. This cortical region is regulated by subcortical systems including noradrenergic (NEergic), dopaminergic (DAergic), cholinergic, serotonergic, and histaminergic pathways. A wealth of data in humans and in animal models demonstrates altered dopamine (DA) regulation. Drugs that modulate norepinephrine (NE) transmission are also effective in ADHD patients, thus leading to the hypothesis of a NEergic disorder. This review covers the regulation of PFc functions by NE and the interaction between the NE and DA systems, as suggested by pharmacological, electrophysiological, morphological, and gene knock out (KO) studies. A negative feedback between NE and DA neurons emerges from KO studies because KO mice showing increased (NE transporter (NET) KO) or decreased (DBH and VMAT2 KO) NE levels are respectively associated with lower and higher DA levels. Locomotor activity can be generally predicted by the DA level, whereas sensitivity to amphetamines is by NE/DA balance. Some animal models of ADHD, such as spontaneously hypertensive rats (SHR), show alterations in the PFc and in the DA system. Evidence about a correlation between the NE system and hyper-locomotion activity in such animals has not yet been clarified. Therefore, this review also includes recent evidence on the behavioral effects of two NET blockers, reboxetine and atomoxetine, in two animal models of ADHD: SHR and Naples High Excitability rats. As these drugs modulate the DA level in the PFc, certain effects are likely to be due to a rebalanced DA system. We discuss the significance of the results for theories of ADHD and make suggestions for future experimentation.


Palladium-catalyzed transformations of salvinorin A, a neoclerodane diterpene from Salvia divinorum.
Transformations that selectively modify the furan ring present in a variety of naturals products would be useful in the synthesis of biological probes but remain largely underexplored. The neoclerodane diterpene salvinorin A, isolated from Salvia divinorum, is an example of a furan-containing natural product. Following selective bromination of salvinorin A, Suzuki-Miyaura and Sonogashira couplings were accomplished in moderate to good yields without hydrolyzing the labile C-2 acetate or altering the stereochemistry of the epimerizable centers.


Directed Evolution of Replication-Competent Double-Stranded DNA Bacteriophage toward New Host Specificity.
In the fight against antimicrobial resistance, bacteriophages are a promising alternative to antibiotics. However, due to their narrow spectra, phage therapy requires the careful matching between the host and bacteriophage to be effective. Despite our best efforts, nature remains as the only source of novel phage specificity. Directed evolution can potentially open an avenue for engineering phage specificity and improving qualities of phages that are not strongly selected for in their natural environments but are important for therapeutic applications. In this work, we present a strategy that generates large libraries of replication-competent phage variants directly from synthetic DNA fragments, with no restriction on their host specificity. Using the T7 bacteriophage as a proof-of-concept, we created a large library of tail fiber mutants with at least 107 unique variants. From this library, we identified mutants that have broadened specificity as evidenced by their novel lytic activity against Yersinia enterocolitica, a strain that the wild-type T7 was unable to lyse. Using the same concept, mutants with improved lytic efficiency and characteristics, such as lytic condition tolerance and resistance suppression, were also identified. However, the observed limitations in altering host specificity by tail fiber mutagenesis suggest that other bottlenecks could be of equal or even greater importance.


Transient receptor potential channels as targets for phytochemicals.
To date, 28 mammalian transient receptor potential (TRP) channels have been cloned and characterized. They are grouped into six subfamilies on the basis of their amino acid sequence homology: TRP Ankyrin (TRPA), TRP Canonical (TRPC), TRP Melastatin (TRPM), TRP Mucolipin (TRPML), TRP Polycystin (TRPP), and TRP Vanilloid (TRPV). Most of the TRP channels are nonselective cation channels expressed on the cell membrane and exhibit variable permeability ratios for Ca(2+) versus Na(+). They mediate sensory functions (such as vision, nociception, taste transduction, temperature sensation, and pheromone signaling) and homeostatic functions (such as divalent cation flux, hormone release, and osmoregulation). Significant progress has been made in our understanding of the specific roles of these TRP channels and their activation mechanisms. In this Review, the emphasis will be on the activation of TRP channels by phytochemicals that are claimed to exert health benefits. Recent findings complement the anecdotal evidence that some of these phytochemicals have specific receptors and the activation of which is responsible for the physiological effects. Now, the targets for these phytochemicals are being unveiled; a specific hypothesis can be proposed and tested experimentally to infer a scientific validity of the claims of the health benefits. The broader and pressing issues that have to be addressed are related to the quantities of the active ingredients in a given preparation, their bioavailability, metabolism, adverse effects, excretion, and systemic versus local effects.


Specialized pathology review in patients with ovarian cancer: results from a prospective study.
A significant number of ovarian borderline tumors (BOTs) and metastatic nonovarian primaries are erroneously diagnosed as ovarian carcinomas. If BOTs are misdiagnosed as cancer, patients may not only experience nonbeneficial morbidity but may have to cope with an incorrect diagnosis of cancer for the rest of their lives. In cases of metastatic disease mistaken for an ovarian primary, more adequate therapeutic modalities may be withheld from some patients. Finally, clinical trials may be biased through unintended disregard of histological inclusion criteria. Patients were recruited for central pathology review according to a translational subprotocol of a prospectively randomized phase 3 study led by the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group. All original slides were requested, and a specialized central pathology review was performed by experienced gynecopathologists. In cases of clinically relevant diagnostic discrepancies, the pathologist responsible for the original diagnosis was contacted. If a given discrepancy could not be resolved, a panel of experts was involved for clarification. Four hundred fifty-four patients with an original diagnosis of ovarian, tubal, or peritoneal epithelial carcinoma were recruited. In 6.8% (31 patients), a major diagnostic discrepancy of clinical relevance was found. Most frequently (15 patients), serous BOT had been misdiagnosed as invasive cancer. Ovarian metastases constituted the second most frequent misdiagnosis (13 patients). Minor discrepancies not affecting patient treatment were found in 28.2% (128 patients). Specialized central pathology review could help to avoid overtreatment of patients with BOT and inappropriate treatment of patients with ovarian metastases. The implementation of a specialized case review process may translate into enhanced patient safety in clinical trials of ovarian carcinomas. Furthermore, central pathology review may increase the rigor and ultimately the transferability of clinical research into practice and should therefore become a standard procedure in study protocols evaluating new therapies.


Effects of Mobile Learning in Medical Education: A Counterfactual Evaluation.
The aim of this research is to contribute to the general system education providing new insights and resources. This study performs a quasi-experimental study at University of Salamanca with 30 students to compare results between using an anatomic app for learning and the formal traditional method conducted by a teacher. The findings of the investigation suggest that the performance of learners using mobile apps is statistical better than the students using the traditional method. However, mobile devices should be considered as an additional tool to complement the teachers' explanation and it is necessary to overcome different barriers and challenges to adopt these pedagogical methods at University.


The construction and assessment of a statistical model for the prediction of protein assay data.
The focus of this work is the development of a statistical model for a bioinformatics database whose distinctive structure makes model assessment an interesting and challenging problem. The key components of the statistical methodology, including a fast approximation to the singular value decomposition and the use of adaptive spline modeling and tree-based methods, are described, and preliminary results are presented. These results are shown to compare favorably to selected results achieved using comparitive methods. An attempt to determine the predictive ability of the model through the use of cross-validation experiments is discussed. In conclusion a synopsis of the results of these experiments and their implications for the analysis of bioinformatic databases in general is presented.


Toxicological evaluation for the hazard assessment of tire crumb for use in public playgrounds.
Disposal of used tires has been a major problem in solid waste management. New uses will have to be found to consume recycled tire products. One such proposed use is as ground cover in playgrounds. However, concern has been expressed regarding exposure of children to hazardous chemicals and the environmental impact of such chemicals. We designed a comprehensive hazard assessment to evaluate and address potential human health and environmental concerns associated with the use of tire crumb in playgrounds. Human health concerns were addressed using conventional hazard analyses, mutagenicity assays, and aquatic toxicity tests of extracted tire crumb. Hazard to children appears to be minimal. Toxicity to all aquatic organisms (bacteria, invertebrates, fish, and green algae) was observed; however, this activity disappeared with aging of the tire crumb for three months in place in the playground. We conclude that the use of tire crumb in playgrounds results in minimal hazard to children and the receiving environment.


Development and optimization of a sensitive pseudovirus-based assay for HIV-1 neutralizing antibodies detection using A3R5 cells.
Sensitive assays for HIV-1 neutralizing antibody detection are urgently needed for vaccine immunogen optimization and identification of protective immune response levels. In this study, we developed an easy-to-use HIV-1 pseudovirus neutralization assay based on a human CD4+ lymphoblastoid cell line A3R5 by employing a high efficient pseudovirus production system. Optimal conditions for cell counts, infection time, virus dose and concentration of DEAE-dextran were tested and identified. For T-cell line-adapted tier 1 virus strains, significantly higher inhibitory efficiency was observed for both monoclonal neutralizing antibody (4 fold) and plasma (2 fold) samples in A3R5 than those in TZM-bl assay. For circulating tier 2 strains, the A3R5 pseudovirus assay showed even much higher sensitivity for both neutralizing antibody (10 fold) and plasma (9 fold) samples. When sequential neutralizing antibody seroconverting samples were tested in both A3R5 and TZM-bl assays, the seroconverting points could be detected earlier for tier 1 (15.7 weeks) and tier 2 (68.3 weeks) strains in A3R5 assay respectively. The high sensitive pseudovirus assay using more physiological target cells could serve as an alternative to the TZM-bl assay for evaluation of vaccine-induced neutralizing antibodies and identification of the correlates of protection.


Monitoring food safety violation reports from internet forums.
Food-borne illness is a growing public health concern in the world. Government bodies, which regulate and monitor the state of food safety, solicit citizen feedback about food hygiene practices followed by food establishments. They use traditional channels like call center, e-mail for such feedback collection. With the growing popularity of Web 2.0 and social media, citizens often post such feedback on internet forums, message boards etc. The system proposed in this paper applies text mining techniques to identify and mine such food safety complaints posted by citizens on web data sources thereby enabling the government agencies to gather more information about the state of food safety. In this paper, we discuss the architecture of our system and the text mining methods used. We also present results which demonstrate the effectiveness of this system in a real-world deployment.


Needs for end-of-life care by home care nurses among non-cancer patients in Korea and Japan.
The purpose of this study was to undertake a comprehensive assessment of each stage of the end-of-life process and the home care nursing needs of non-cancer patients. The total number of eligible patients was 117 in Korea and 121 in Japan, aged ≥ 40, receiving continuous home care nursing throughout the beginning, stable, and at final death stages and ultimately dying at home. The need for the 'management of physical symptoms' increased as patients progressed through the end-of-life stages to death. In both countries, the needs for 'loss and grief care' and 'coordination among care team members' were significantly higher in the stable stage than in the beginning or final death stages. Further research is needed to develop tailored nursing care programmes that meet the specific needs of patients in each stage of the end-of-life care at home.


Human DNA quantitation using Alu element-based polymerase chain reaction.
Human forensic casework requires sensitive quantitation of human nuclear DNA from complex sources. Widely used commercially available systems detect both nonhuman and human primate DNA, often require special equipment, and have a detection limit of approximately 0.1ng. Multicopy Alu elements include recently integrated subfamilies that are present in the human genome but are largely absent from nonhuman primates. Here, we present two Alu element-based alternative methods for the rapid identification and quantitation of human DNA, inter-Alu PCR and intra-Alu PCR. Using SYBR green-based detection, the effective minimum threshold level for human DNA quantitation was 0.01ng using inter-Alu- and 0.001ng using intra-Alu-based PCR. Background cross-amplification with nonhuman DNA templates was detected at low levels using inter-Alu-based PCR, but was negligible using intra-Alu-based PCR. These Alu-based methods have several advantages over currently available systems. First, the assays are PCR based and no additional unique equipment is required. Second, the high copy number of subfamily-specific Alu repeats in the human genome makes these assays human specific within a very sensitive linear range. The introduction of these assays to forensic laboratories will undoubtedly increase the sensitivity and specificity of human DNA detection and quantitation from complex sources.


Exercise prior to influenza vaccination for limiting influenza incidence and its related complications in adults.
Influenza is an infectious virus affecting both humans and animals. In humans, symptoms present as fever, cough, sore throat, runny nose, headache, muscle and joint pain, and malaise. The epidemiological profile of influenza is influenced by multiple factors, including transmissibility of the virus and the susceptibility of the population. Annually, influenza is estimated to infect 5% to 10% of adults, with higher rates in winter seasons in countries with seasonal variation. Exercise could be an intervention to enhance immune response and limit influenza incidence and its related complications. To assess the efficacy and safety of short and long-term exercise prior to influenza vaccination in enhancing influenza prevention in adults. We searched CENTRAL (2015, Issue 11), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 3 November 2015), Embase (1974 to 3 November 2015), CINAHL (1981 to 3 November 2015), LILACS (Latin American and Caribbean Health Sciences, 1982 to 3 November 2015), PEDro (1980 to 3 November 2015), SPORTDiscus (1985 to 3 November 2015), the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov (November 2015). Randomised controlled trials (RCTs) of short- and long-term exercise prior to influenza vaccination for the general adult population were eligible for inclusion. Two review authors independently extracted and checked data from the included trials using a standard form. We used the random-effects model due to differences in the type, duration, intensity and frequency of exercise in the analysis. We included six trials published between 2007 and 2014 that randomised 599 adult participants. Study size ranged from 46 to 158 participants. Participants were aged between 18 years and 80 years; we could not derive gender proportions, as participants' sex was not reported in all studies. One study was available in abstract form only.We did not find a significant difference in outcomes between people who exercised and those who did not exercise before receiving influenza vaccination.Pre-vaccination exercises included endurance activities such as walking or using a treadmill, and resistance activities included biceps curls and lateral raises. Five of the studies provided one session of exercise between 25 and 50 minutes. In five studies, exercise was undertaken on the same day as the vaccination. One study provided exercise over a period of eight weeks before vaccination, with one 2½ hour supervised session, plus daily home exercise practice of 45 minutes. Exercise intensity ranged from 55% to 85% of maximal heart rate. Control group participants undertook a range of activities, including quiet rest, sitting, reading, meditation or unspecified activity.One study reported numbers of people who contracted influenza; no significant difference was reported between exercise and no-exercise participants. None of the included studies reported complications related to influenza illness. Only one study, which we assessed as providing low-quality evidence, reported numbers of people who experienced adverse events. This study reported no significant difference in outcomes between people who exercised and those who did not. No studies reported numbers of working days or days lost related to influenza illness. Only two studies reported participant-centred outcomes.Overall, study quality was unclear; we assessed five of the six included studies to have at least four unclear 'Risk of bias' domains (allocation concealment, blinding of outcome assessment, selective reporting and other bias). Insufficient reporting in four studies about selective reporting did not provide enough information to enable judgement; only two studies were included in trials registers. From the available evidence, we found that exercising before influenza vaccination is neither beneficial nor harmful. However, study data were limited and of low quality. Small sample sizes, study design limitations, exercise types, and focus on biochemical rather than participant-centred outcomes strongly influenced our findings.


The eco-evolutionary dynamics of Batesian mimicry.
Batesian mimicry is a strategy in which palatable prey species (mimic-species) resemble unpalatable prey species with aposematism (model-species). Theoretical studies on Batesian mimicry have been conducted in terms of their evolutionary significance and ecological consequences. However, despite the importance of eco-evolutionary feedback, the evolution and population dynamics of mimicry complex have long been explored separately. Previous studies on the dynamics of mimicry complex have proposed the possibility of the extinction of unpalatable species due to high predation by predators confusing palatable and unpalatable species. If the abundance of palatable species was large in comparison with unpalatable species, predation pressure on both unpalatable and palatable species became severe, resulting in the extinction of the unpalatable species. We hypothesized that palatable species evolved not to be similar to unpalatable species when unpalatable species became rare, because this situation is no longer advantageous for palatable species to mimic unpalatable species. Here, we constructed the eco-evolutionary dynamics of unpalatable and palatable species, and demonstrated that the evolutionary process of palatable species, which has been overlooked in previous theoretical studies, could rescue the unpalatable species from extinction. We modeled predators' foraging decisions based on signal detection theory. We assumed that palatable species evolve in a trait space, in which there are separate adaptive peaks on either side of an adaptive valley for mimicry and cryptic phenotypes. Then, we derived the stability conditions of the equilibria. As a result, the evolution of a cryptic phenotype in palatable species was driven when unpalatable species was rare, which mitigated predation pressure on unpalatable species through the reduction in the probability to be attacked. This could work to rescue unpalatable species from extinction.


Differential expression of AQP1 in microdomain-enriched membranes of renal cell carcinoma.
Human aquaporin-1 (AQP1) is the most studied member of the aquaporin family, acting as molecular water channel. It is also considered a differentiation marker for proximal renal tubular cells, from which clear cells renal cell carcinoma (RCC) originates, playing an important role in urine formation. We therefore studied AQP1 expression at the proteomic level in RCC and normal tissues, mainly focusing on microdomain-enriched membranes in which AQP1 is highly concentrated. Subcellular fractions were prepared through differential centrifugation, and microdomain-enriched fractions were purified from a plasma membrane-enriched fraction by 1% Triton X-100 treatment followed by ultracentrifugation in sucrose gradient. After SDS-PAGE and Western blot analyses with antibodies against AQP1, lower expression levels of AQP1 isoforms were observed in each subcellular fraction of RCC compared to fractions from normal kidney tissues. The presence of AQP1 in the immunoreactive bands was verified by MALDI-TOF-MS and LC-ESI-MS/MS analysis. Glycosylation of AQP1 was also investigated using N-glycosidase F, confirming the presence of a N-glycosylated isoform of AQP1 in the 35-45-kDa region. These results highlight an under-expression of AQP1 protein and its glycosylated isoforms in homogenate and subcellular fraction obtained from RCC tissue compared to adjacent normal cortex.


A review on alum sludge reuse with special reference to agricultural applications and future challenges.
Alum salts are commonly used in the water industry to promote coagulation in the production of clean drinking water, which results in the generation and accumulation of 'waste' by-product 'alum sludge' in large volumes. Effective and efficient management of alum sludge in an economically and environmentally sustainable manner remains a significant social and environmental concern with ever increasing demand for potable water as a result of rapidly escalating world population and urban expansion. Various intensive practices have been employed to reuse the alum sludge in an attempt to figure out how to fill the gap between successful drinking water treatment process and environmentally friendly alum sludge management for over the years. This paper primarily aimed at comprehensive review of the existing literature on alum sludge characteristics, its environmental concerns and their potential utilization, especially in agricultural and horticultural sectors leading to update our recent state of knowledge and formulate a compendium of present and past developments. Different types of alum sludge utilizations in various fields were recognized and examined. The strengths, weaknesses, opportunities and potential risks of alum sludge reuse options with particular reference to agriculture were highlighted and knowledge gaps were identified. Research priorities and future challenges that will support in the development of effective alumsludgemanagement practices in agriculture with multi-prong strategies were discussed.


Sperm cryopreservation and assisted reproductive technology outcome in patients with spinal cord injury.
This study aimed to describe spinal cord injured patients' semen characteristics before and after cryopreservation, and assisted reproductive technology cycles outcome compared to the infertile population. Data about sperm analysis and assisted reproductive technology (ART) cycles outcomes for 78 men with spinal cord injury referred for sperm cryopreservation between 1998 and 2013 were retrospectively analysed and compared with a reference group consisting of every Intra Cytoplasmic Sperm Injection (ICSI) cycle performed in our in vitro fertilization unit over the 2009-2014 period. Semen was collected by penile vibratory stimulation (PVS), electroejaculation or via testis biopsies. Fresh and frozen semen parameters and ART outcomes with frozen-thawed sperm were measured. Patients were divided into three groups according to the sperm retrieval methods: 37 electroejaculations, 37 PVSs and four surgical sperm retrievals. Low ejaculate volume was observed in 33% of the patients, and oligozoospermia in 37% of the patients. Specimens from 77 of the patients contained motile sperm and were therefore frozen for future use. There was no statistical difference for any of the fresh semen parameters between all groups. Twenty of them underwent ICSI leading to five live births, while four underwent intrauterine insemination. ART with frozen-thawed spermatozoa can provide men with SCI with comparable results as in the infertile population.


Clinical competency: the right assessment tools?
Effective assessment of competency of student nurses in clinical practice is vital. Use of simulation rather than real life settings can be used to assess competency. Development of information technology and its use in teaching clinical skills offers opportunities for assessment. Clinical governance increases the need to scrutinize the assessment of practice. Ongoing assessment of clinical competency for qualified nurses is also important.


A joint method for marker-free alignment of tilt series in electron tomography.
Electron tomography (ET) is a widely used technology for 3D macro-molecular structure reconstruction. To obtain a satisfiable tomogram reconstruction, several key processes are involved, one of which is the calibration of projection parameters of the tilt series. Although fiducial marker-based alignment for tilt series has been well studied, marker-free alignment remains a challenge, which requires identifying and tracking the identical objects (landmarks) through different projections. However, the tracking of these landmarks is usually affected by the pixel density (intensity) change caused by the geometry difference in different views. The tracked landmarks will be used to determine the projection parameters. Meanwhile, different projection parameters will also affect the localization of landmarks. Currently, there is no alignment method that takes interrelationship between the projection parameters and the landmarks. Here, we propose a novel, joint method for marker-free alignment of tilt series in ET, by utilizing the information underlying the interrelationship between the projection model and the landmarks. The proposed method is the first joint solution that combines the extrinsic (track-based) alignment and the intrinsic (intensity-based) alignment, in which the localization of landmarks and projection parameters keep refining each other until convergence. This iterative approach makes our solution robust to different initial parameters and extreme geometric changes, which ensures a better reconstruction for marker-free ET. Comprehensive experimental results on three real datasets show that our new method achieved a significant improvement in alignment accuracy and reconstruction quality, compared to the state-of-the-art methods. The main program is available at https://github.com/icthrm/joint-marker-free-alignment. Supplementary data are available at Bioinformatics online.


Unbiased Scene Graph Generation via Two-Stage Causal Modeling.
Despite the impressive performance of recent unbiased Scene Graph Generation (SGG) methods, the current debiasing literature mainly focuses on the long-tailed distribution problem, whereas it overlooks another source of bias, i.e., semantic confusion, which makes the SGG model prone to yield false predictions for similar relationships. In this paper, we explore a debiasing procedure for the SGG task leveraging causal inference. Our central insight is that the Sparse Mechanism Shift (SMS) in causality allows independent intervention on multiple biases, thereby potentially preserving head category performance while pursuing the prediction of high-informative tail relationships. However, the noisy datasets lead to unobserved confounders for the SGG task, and thus the constructed causal models are always causal-insufficient to benefit from SMS. To remedy this, we propose Two-stage Causal Modeling (TsCM) for the SGG task, which takes the long-tailed distribution and semantic confusion as confounders to the Structural Causal Model (SCM) and then decouples the causal intervention into two stages. The first stage is causal representation learning, where we use a novel Population Loss (P-Loss) to intervene in the semantic confusion confounder. The second stage introduces the Adaptive Logit Adjustment (AL-Adjustment) to eliminate the long-tailed distribution confounder to complete causal calibration learning. These two stages are model agnostic and thus can be used in any SGG model that seeks unbiased predictions. Comprehensive experiments conducted on the popular SGG backbones and benchmarks show that our TsCM can achieve state-of-the-art performance in terms of mean recall rate. Furthermore, TsCM can maintain a higher recall rate than other debiasing methods, which indicates that our method can achieve a better tradeoff between head and tail relationships.


New Roles for Occupational Therapy to Promote Independence Among Youth Aging Out of Foster Care.
Occupational therapy practitioners are qualified to address the needs of young adults transitioning out of the foster care system; yet, to date, the degree to which practitioners have addressed these needs has been limited. The literature on foster care clearly documents the myriad of long-term challenges that this population faces as a result of their lack of preparedness in independent living, academic, and vocational skills. Moreover, it is clear that existing programs are inadequate for meeting the needs of this population because they rarely include individualized, occupation-based, client-centered approaches for skill development. In this article, we argue that by design, the foster care system marginalizes its "members." Occupational therapy's emphasis on occupational justice provides practitioners with an ideal opportunity to remediate the injustice that this population often experiences. To support our position, we describe exploratory work that has been conducted with stakeholders and transitioning youth in Miami, Florida.


WITHDRAWN: Specialist epilepsy nurses for treating epilepsy.
Epilepsy is a common serious neurological condition with a 0.5% prevalence. As a result of the perceived deficiencies and suggestions to improve the quality of care offered to people with epilepsy, two models of service provision have been suggested by researchers: specialist epilepsy out-patient clinics (as opposed to the management of patients in general neurology clinics or general medical clinics) and nurse-based liaison services between primary (GP) and secondary/tertiary (hospital-based) care. To overview the evidence from controlled trials investigating the effectiveness of specialist epilepsy nurses compared to routine care. We searched the Cochrane Central Register of Controlled Trials (TheCochraneLibrary Issue 4, 2004), MEDLINE (October 2004), GEARS, EMBASE, ECRI, Effectiveness Healthcare Bulletin, Effectiveness Matters, Bandolier, Evidence Based Purchasing, National Research Register and PsycINFO databases. Randomized controlled and quasi-randomized trials which considered specialist epilepsy nurse interventions with standard or alternative care were included in this review. Two reviewers independently selected trials for inclusion and extracted data. Outcomes investigated included: seizure frequency; appropriateness of medication prescribed; social or psychological functioning scores; knowledge about epilepsy scores; costs of care and adverse effects. Three trials were included, two based in general practice and one in a neurology centre. The population of patients differed between trials, for example one study excluded patients with learning disabilities, and one only recruited patients with a new diagnosis. In view of this heterogeneity we decided not to pool results in a meta-analysis. As yet, there is no convincing evidence that specialist epilepsy nurses improve outcomes for people with epilepsy overall. Important outcomes (eg seizure frequency, psychosocial functioning, knowledge of epilepsy, general health status, work days lost, depression and anxiety scores) show no significant improvement. There is some evidence that people who have not had an epileptic seizure in the last six months are less at risk for depression. There is also evidence that newly diagnosed patients whose knowledge about epilepsy is poor may improve their epilepsy knowledge scores after nurse intervention. It is clearly plausible that specialist epilepsy nurses could improve quality in epilepsy care. However, there is as yet little evidence to support this assumption as the present research base is small. Further research is needed to investigate the effectiveness of specialist epilepsy nurses before such recommendations can be made.


Use of Gabapentin for Alcohol Withdrawal Syndrome in the Hospital Setting: A Randomized Open-Label Controlled Trial.
Background/objectives: Patients hospitalized with alcohol withdrawal syndrome (AWS) are typically treated with CIWA-directed benzodiazepines to prevent complications, such as seizures and delirium tremens. Gabapentin is an evidence-based alternative to benzodiazepines in the outpatient setting, but there is limited data for hospitalized patients with AWS. This study compared fixed-dose gabapentin to CIWA-directed benzodiazepines for AWS in the hospital setting. Methods: This open-label, randomized controlled trial enrolled 88 adults from February 1, 2017 to August 16, 2020 with a risk of complicated alcohol withdrawal as defined by the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) ≥4. Patients were randomized within 16 h of admission to either fixed-dose gabapentin taper or continued CIWA-directed benzodiazepine administration. The primary outcome was the length of stay (LOS). Secondary outcomes included seizure, delirium tremens, ICU transfer, and patient-reported symptoms (alcohol cravings, anxiety, sleepiness). Results: LOS was shorter, but not statistically different in the gabapentin group compared to the benzodiazepine group. Because benzodiazepines were received in both gabapentin and benzodiazepine groups before randomization, the mean amount of benzodiazepines received in each group was also not statistically different, although the amount received by the gabapentin group was less than half of that received by the benzodiazepine group (4.3 vs. 10.6 mg, p = 0.146 by per protocol analysis). There were no statistical differences in secondary measures. Conclusions: Fixed-dose gabapentin taper showed similar outcomes compared to CIWA-directed benzodiazepines for the treatment of hospitalized patients with mild/moderate AWS, but the interpretation of the results is limited due to under-enrollment and the use of benzodiazepines in both groups pre-enrollment.Clinical trial registration: NCT03012815.


Cognitive Rehabilitation and Exposure/Sorting Therapy (CREST) for Hoarding Disorder in Older Adults: A Randomized Clinical Trial.
To compare the efficacy of Cognitive Rehabilitation and Exposure/Sorting Therapy (CREST) with geriatric case management (CM) in a sample of older adults meeting DSM-5 diagnostic criteria for hoarding disorder (HD). Fifty-eight older adults with HD were enrolled in a randomized controlled trial between December 2011 and March 2014. Thirty-one participants received CREST, and 27 participants received CM. Both interventions consisted of 26 individual sessions over a period of 6 months and included several home visits by the study therapists (CREST) or nurses (CM). The Saving Inventory-Revised (SI-R) and the UCLA Hoarding Severity Scale (UHSS) were the main outcome measures. Participants in the CREST condition had significantly greater improvement on the SI-R than participants in the CM group (group × time interaction: β = 3.95, SE = 1.81, P = .029), with participants who completed the CREST condition averaging a 38% decrease in symptoms and participants who completed the CM condition averaging a 25% decrease in symptoms. In contrast, there was not a significant group × time interaction effect on the UHSS (β = 1.23, SE = 0.84, P = .144), although participants did report greater improvement in symptoms in the CREST condition (35%) than in the CM condition (24%). Treatment gains were maintained at 6-month follow-up. CREST appears to be an efficacious treatment compared to CM for older adults, but CM also showed meaningful benefits. ClinicalTrials.gov identifier: NCT01227057.


Mannosylated lipoarabinomannans from Mycobacterium avium subsp. paratuberculosis alters the inflammatory response by bovine macrophages and suppresses killing of Mycobacterium avium subsp. avium organisms.
Analysis of the mechanisms through which pathogenic mycobacteria interfere with macrophage activation and phagosome maturation have shown that engagement of specific membrane receptors with bacterial ligands is the initiating event. Mannosylated lipoarabinomannan (Man-LAM) has been identified as one of the ligands that modulates macrophage function. We evaluated the effects of Man-LAM derived from Mycobacterium avium subsp. paratuberculosis (MAP) on bovine macrophages. Man-LAM induced a rapid and prolonged expression of IL-10 message as well as transient expression of TNF-α. Preincubation with Man-LAM for up to 16 h did not suppress expression of IL-12 in response to interferon-γ. Evaluation of the effect of Man-LAM on phagosome acidification, phagosome maturation, and killing of Mycobacterium avium subsp. avium (MAA) showed that preincubation of macrophages with Man-LAM before addition of MAA inhibited phagosome acidification, phagolysosome fusion, and reduced killing. Analysis of signaling pathways provided indirect evidence that inhibition of killing was associated with activation of the MAPK-p38 signaling pathway but not the pathway involved in regulation of expression of IL-10. These results support the hypothesis that MAP Man-LAM is one of the virulence factors facilitating survival of MAP in macrophages.


Re-recognition of the role of roughness in keloid assessment.
Under visual observation, keloids are more rough than normal skin. This roughness may be used to assess the activity and severity of keloids but lacks the support of objective and accurate evidence. The purpose of this study was to verify the role of roughness in the development of keloids and to clarify the advantage of roughness in the comprehensive assessment of keloids. Patients with keloids who attended Peking Union Medical College Hospital were recruited. Keloids were classified into progressive, stable, and atrophic stages based on the change in size over the past year and blood perfusion. The keloids were evaluated using the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS). The roughnesses of the keloid and normal skin were measured using the Phaseshift Rapid In vivo Measurement Of the Skin (PRIMOS), and blood perfusion was measured using laser speckle contrast imaging (LSCI). Thirty-three patients with a total of 81 keloids were included. The surface roughness values Sa, Sq, and Sz of the keloid region were 243.70 (143.85-328.05), 316.20 (179.85-475.20), and 1708.20 (1098.30-4087.20), respectively, which were 4.87, 4.80, and 3.08 times higher than those of normal skin. There were significant differences in roughness among the different keloid stages. A significantly strong correlation between roughness and other assessed indices was found. Roughness as a morphological characteristic is of great value in the evaluation of keloids. It is recommended as an important examination for keloids.


Using a synthesis of the research literature related to the aetiology of adolescent idiopathic scoliosis to provide ideas on future directions for success.
This review is atypical by design. It has used a synthesis of the available literature relating to the aetiology of AIS to draw attention to the lack of progress in this area despite intensive research for more than 100 years. The review has argued that if progress is to be made in this area then significant changes in approach to the problem must be made. Such changes have been outlined and major areas of potential focus identified with the intention of creating debate and discussion. There is no doubt that people are working hard in this area of research but this review has deliberately attempted to question its achievements and future directions."It is not enough to be busy, so are the ants. The question is what are you so busy about.'Walden - Henry David Thoreau.


Prevalence and Outcome of Acute Respiratory Distress Syndrome in Traumatic Brain Injury: A Systematic Review and Meta-Analysis.
Acute respiratory distress syndrome (ARDS) in patients with traumatic brain injury (TBI) is associated with increased mortality. Information on the prevalence of ARDS and its neurological outcome after TBI is sparse. We aimed to systematically review the prevalence, risk factors, and outcome of ARDS in TBI population. PubMed and four other databases (Embase, Cochrane Library, Web of Science Core Collection, and Scopus) from inception to July 6, 2020. Randomized controlled trials (RCTs) and observational studies in patients older than 18 years old. Two independent reviewers extracted the data. Study quality was assessed by the Cochrane Risk of Bias tool for RCTs, the Newcastle-Ottawa Scale for cohort and case-control studies. Good neurological outcome was defined as Glasgow Outcome Scale ≥ 4. Random-effects meta-analyses were conducted to estimate pooled outcome prevalence and their 95% confidence intervals (CI). We included 20 studies (n = 2830) with median age of 44 years (interquartile range [IQR] = 35-47, 64% male) and 79% (n = 2237) suffered severe TBI. In meta-analysis, 19% patients (95% CI = 0.13-0.27, I2 = 93%) had ARDS after TBI. The median time from TBI to ARDS was 3 days (IQR = 2-5). Overall survival at discharge for the TBI cohort was 70% (95% CI = 0.64-0.75; I2 = 85%) and good neurological outcome at any time was achieved in 31% of TBI patients (95% CI = 0.23-0.40; I2 = 88%). TBI cohort without ARDS had higher survival (67% vs. 57%, p = 0.01) and good neurological outcomes (34% vs. 23%, p = 0.02) compared to those with ARDS. We did not find any specific risk factors for developing ARDS. In this meta-analysis, approximately one in five patients had ARDS shortly after TBI with the median time of 3 days. The presence of ARDS was associated with worse neurological outcome and mortality in TBI. Further research on prevention and intervention strategy of TBI-associated ARDS is warranted.


Catechol-Isolated Atomically Dispersed Nanocatalysts for Self-Motivated Cocatalytic Tumor Therapy.
Nanocatalytic tumor therapy based on Fenton nanocatalysts has attracted considerable attention because of its therapeutic specificity, enhanced outcomes, and high biocompatibility. Nevertheless, the rate-determining step in Fenton chemistry, which involves the transition of a high-valence metallic center (FeIII) to a Fenton-active low-valence metallic center (FeII), has hindered advances in nanocatalyst-based therapeutics. In this study, we constructed mesoporous single iron atomic nanocatalysts (mSAFe NCs) by employing catechols from dopamine to coordinate and isolate single iron atoms. The catechols also serve as reductive ligands, generating a field-effect-based cocatalytic system that instantly reduces FeIII species to FeII species within the mSAFe NCs. This self-motivated cocatalytic strategy enabled by mSAFe NCs accelerates the kinetics of the Fenton catalytic reaction, resulting in remarkable performance for nanocatalytic tumor therapy both in vitro and in vivo.


Modified Laryngeal Forceps for Arytenoid Cartilage Dislocation Caused by Endotracheal Intubation: A Retrospective Case-Control Pilot Study.
Background: Arytenoid cartilage dislocation is considered as a rare laryngeal injury and closed reduction is commonly used as the first choice for the arytenoid dislocation. However, the tools of closed reduction vary, and there is no dedicated tool for closed reduction, and the treatment outcome varies from person to person. This study compared the treatment outcome of the modified laryngeal forceps and traditional laryngeal forceps. Material and Methods: This study conformed to the strengthening the reporting of observational studies in epidemiology guidelines regarding retrospective studies. From May 2021 to February 2023, the records of 28 patients with arytenoid cartilage dislocation caused by endotracheal intubation were reviewed. They were divided into the traditional group (n = 14) and the modified group (n = 14) by gender. Indirect or direct laryngoscopy, video stroboscopy, high-resolution computed tomography, and cricoarytenoid joint 3-dimensional reconstruction were used to evaluate arytenoid position and motion. Clinical characteristics, voice function, procedural skill, and treatment outcome for each case were recorded. Results: Each patient was diagnosed with arytenoid dislocation caused by endotracheal intubation. There was no significant difference in the treatment outcome between the traditional group and the modified group (P > .05). However, the median time interval between closed reduction and the return of normal voice in the traditional group was 31.08 ± 10.56 days, which was significantly longer than the median time of 17.92 ± 3.83 days in the modified group (P < .05). Conclusion: Closed reduction with the modified laryngeal forceps under local anesthesia is an effective and safe procedure. Compared with traditional laryngeal forceps, the modified laryngeal forceps can shorten the treatment duration.


EZH2 and STAT6 expression profiles are correlated with colorectal cancer stage and prognosis.
To investigate the role of enhancer of zeste homologue 2 (EZH2) and STAT6 immunohistochemistry in the evaluation of clinical stages and prognosis of colorectal cancer (CRC). The expression patterns were examined by immunohistochemistry in both tumor and adjacent non-neoplastic tissues of 119 CRC patients who underwent operation during the time period from 2002 to 2004. The positive rates of EZH2 and STAT6 in CRC cases were 69.7% (83 of 119) and 60.5% (72 of 119), respectively, and there was significant difference when compared with tumor adjacent non-neoplastic tissues (P < 0.05). In all CRC cases, patients with EZH2-positive, or STAT6-positive expression had lower survival rates than those with EZH2-negative or STAT6-negative expression (P = 0.002 and P = 0.005, respectively). Co-expression of EZH2 and STAT6 showed significantly higher levels in CRC cases of high clinical TNM stages (P = 0.001), and the expression of STAT6 was also correlated with lymph node metastasis and distant metastasis (P = 0.001 and P = 0.016, respectively). Multivariate analysis revealed that EZH2 expression was an independent prognostic indicator of CRC (P = 0.039). EZH2 and STAT6 expressions have significant values in distinguishing clinical stages of CRC and predicting the prognosis of the patients.


The Good Investment.
The authors reflect on the article in this issue entitled "Borrow or Serve? An Economic Analysis of Options for Financing a Medical School Education" by Marcu and colleagues, which makes a compelling case that a medical school education is a good investment, no matter what financing option students use, from federal service programs to federal loans. The lead author of this Commentary shares lessons learned from his own medical school education, which was funded by an Armed Forces Health Professions Scholarship, and from his current position interacting with medical students across the United States.Regardless of the financing path they choose, all students should understand basic financial concepts and the details of the various pathways that are available to pay for their medical school education, as well as how each could potentially impact their own future and that of their families. One underappreciated aspect of financing a medical school education is that federal repayment scenarios can link loan payments to income, rather than debt levels, which means that all physicians are able to afford their loan payments no matter what specialty they practice, what they are paid, or where they live.Medical education, while expensive, remains the good investment. An MD degree can lead to a lifetime of personal fulfillment and societal contributions. Everyone, with rare exceptions, accepted to a U.S. medical school will be able to finance their medical education via a path that aligns with their personal values and priorities.


Baicalein promotes the microglia M2 polarization and suppresses apoptosis by targeting HMOX1/PDE4D to alleviate Alzheimer's disease.
Alzheimer's disease (AD) is a neurodegenerative disorder that has quickly becoming one of the most expensive, lethal, and burdening diseases of this century. In the past twenty years, hundreds of drugs have been tested while only several have been authorized by FDA for AD treatment, hence, searching for candidate agent with therapeutic potential for AD is imminent. Controlling polarization direction of microglia is crucial in AD therapy. Recent research suggests that baicalein has potential to reduce neuroinflammation and prevent neurodegenerative diseases by affecting microglia, while the specific molecular mechanism of baicalein in regulating microglia in the treatment of AD is still unclear. In this study, we investigated how baicalein affected microglial polarization in AD and potential biological mechanisms. In cell experiments, it was verified that baicalein significantly shifted the BV-2 microglia phenotype from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype, inhibited the microglial apoptosis and pro-inflammatory factors, promoted the microglial Aβ uptake and anti-inflammatory factors after LPS stimulated. In APP/PS1 mice, it was found that baicalein decreased the Aβ plaque deposition in brain, attenuated NLRP3 inflammasome activation and neuronal apoptosis in APP/PS1 mice. Furthermore, bioinformatics analysis and experiment validated that HMOX1 is a target of baicalein, and we elucidated that baicalein modulated the microglial polarization to inhibit neuroinflammation and neural injury through targeting on the HMOX1/PDE4D axis in AD. In conclusion, our findings indicate the therapeutic effect of baicalein for AD, and baicalein might serve a potential agent for AD treatment.


Structural performance of a hybrid FRP-aluminum modular triangular Truss system subjected to various loading conditions.
A novel hybrid FRP-aluminum truss system has been employed in a two-rut modular bridge superstructure composed of twin inverted triangular trusses. The actual flexural behavior of a one-rut truss has been previously investigated under the on-axis loading test; however, the structural performance of the one-rut truss subjected to an off-axis load is still not fully understood. In this paper, a geometrical linear finite element model is introduced and validated by the on-axis loading test; the structural performance of the one-rut truss subjected to off-axis load was numerically obtained; the dissimilarities of the structural performance between the two different loading cases are investigated in detail. The results indicated that (1) the structural behavior of the off-axis load differs from that of the on-axis load, and the off-axis load is the critical loading condition controlling the structural performance of the triangular truss; (2) under the off-axis load, the FRP trussed members and connectors bear certain out-of-plane bending moments and are subjected to a complicated stress state; and (3) the stress state of these members does not match that of the initial design, and optimization for the redesign of these members is needed, especially for the pretightened teeth connectors.


Artemisia carvifolia Buch silver nanoparticles downregulate the Rap2A gene in liver cancer.
Liver cancer is the second main reason of death globally. In the current study, Rap2A protein a member of Ras Gtpase was selected as a drug target for liver cancer which has been identified as an oncogene in different types of tumors. The present study aimed to evaluate Artemisia carvifolia Buch extract and its silver nanoparticles against liver cancer targeting the Rap2A gene. The synthesized silver nanoparticles showed an absorbance peak at 450 nm by a UV-Vis spectrophotometer. SEM revealed that polyhedral silver nanoparticles had a size ranging from 80 ± 6 nm. Furthermore, amines, aldehydes, ketones and alcohols of Artemisia carvifolia were found involved in the reduction and stabilization of nanoparticles by FTIR. Moreover, XRD and EDX confirmed the cubic crystalline nature and particle elemental composition, respectively. Furthermore, the cytotoxicity against HePG2 cancer cell lines was also found significant with an IC50 value of 2.57 µM for silver nanoparticles and 11.57 µM for plant extract. The gene expression and protein level of Rap2A were also decreased in plant extract and nanoparticle-treated cells compared to control groups. The apoptotic potential of extract and nanoparticles was also determined by evaluating the apoptotic pathway genes and protein including BAX, caspase 3, 8 and 9. Significantly elevated levels of expression of these genes by real-time qPCR along with increased protein levels by ELISA were found. This is the first-ever report describing the synthesis and efficacy of silver nanoparticles of Artemisia carvifolia Buch against liver cancer.


Land cover, land use and malaria in the Amazon: a systematic literature review of studies using remotely sensed data.
The nine countries sharing the Amazon forest accounted for 89% of all malaria cases reported in the Americas in 2008. Remote sensing can help identify the environmental determinants of malaria transmission and their temporo-spatial evolution. Seventeen studies characterizing land cover or land use features, and relating them to malaria in the Amazon subregion, were identified. These were reviewed in order to improve the understanding of the land cover/use class roles in malaria transmission. The indicators affecting the transmission risk were summarized in terms of temporal components, landscape fragmentation and anthropic pressure. This review helps to define a framework for future studies aiming to characterize and monitor malaria.


The politics of urban informality in Philadelphia's recovery house movement.
There are some 60,000 vacant properties in the city of Philadelphia, 30,000 of which are abandoned row houses. In the neighbourhood of Kensington, street-level entrepreneurs have reconfigured hundreds of former working-class row homes to produce the Philadelphia recovery house movement: an extra-legal poverty survival strategy for addicts and alcoholics located in the city's poorest and most heavily blighted zones. The purpose of this paper is to explore, ethnographically, the ways in which informal poverty survival mechanisms articulate with the restructuring of the contemporary welfare state and the broader political economy of Philadelphia. It is argued that recovery house networks accommodate an interrelated set of political rationalities animated not only by retrenchment and the churning of welfare bodies, but also by the agency of informal operators and the politics of self-help. Working as an alternative and partially vestigial boundary institution or buffer zone to formal regimes of governance, the recovery house movement reflects the 'other story' of the new urban politics in Philadelphia.


A Multi-stage Segmentation Method for Tongue Ecchymosis.
Tongue diagnosis is an important component of traditional Chinese medicine (TCM), in which tongue ecchymosis is the main diagnostic basis for the blood stasis syndrome of TCM. Most of the existing methods are unsupervised and cannot accurately segment tongue ecchymosis. In this paper, we propose a multi-stage segmentation method for tongue ecchymosis. We first employ an object detection model for rough localization of tongue ecchymosis, and then use the unsupervised clustering and the watershed transform for rough segmentation and fine segmentation of tongue ecchymosis respectively. To the best of our knowledge, we are the first to combine machine learning and deep learning to segment tongue ecchymosis. Experimental results show that the tongue ecchymoses obtained by our method are more similar to the real tongue ecchymoses compared with the existing methods, and the Intersection-over-Union (IoU) is improved by 0.12 compared with the latest method.Clinical Relevance-Tongue ecchymosis obtained by this paper is the main diagnostic basis for the blood stasis syndrome of TCM.


Salidroside Protects Dopaminergic Neurons by Enhancing PINK1/Parkin-Mediated Mitophagy.
Parkinson's disease (PD) is a common neurodegenerative disease characterized by the degeneration of nigrostriatal dopaminergic (DA) neurons. Our previous studies have suggested that salidroside (Sal) might play neuroprotective effects against PD by preserving mitochondrial Complex I activity. However, the exact mechanism of the neuroprotective effect of Sal remains unclear. Growing evidence indicates that PINK1/Parkin-mediated mitophagy is involved in the development of PD. In this study, we investigated whether Sal exerts a neuroprotective effect by modulating PINK1/Parkin-mediated mitophagy. Results showed that Sal alleviated MPTP-induced motor deficits in pole test. Moreover, Sal diminished MPTP-induced degeneration of nigrostriatal DA neurons as evidenced by upregulated TH-positive neurons in the substantia nigra, increased DAT expression, and high dopamine and metabolite levels in the striatum. Furthermore, in comparison with the MPP+/MPTP group, Sal considerably increased the mitophagosome and mitophagy flux. Moreover, in comparison with the MPP+/MPTP group, Sal evidently enhanced the mitochondrial expression of PINK1 and Parkin, accompanied by an increase in the colocalization of mitochondria with Parkin. However, transfection of MN9D cells with PINK1 siRNA reversed Sal-induced activated mitophagy and cytoprotective effect. In conclusion, Sal may confer neuroprotective effects by enhancing PINK1/Parkin-mediated mitophagy in MPP+/MPTP-induced PD models.


Immunoadsorption assay for bone alkaline phosphatase compared with wheat germ agglutinin precipitation assay in serum from (pre)pubertal girls.
The performance characteristics of two bone alkaline phosphatase (ALP; EC 184.108.40.206) assays, a wheat germ agglutinin (WGA) precipitation assay and a new immunoadsorption assay (IAA), were compared. The within- and between-run imprecision of the IAA (3.6-4.2% and 3.6-7.7%) was comparable with that of the WGA assay. The mean cross-reactivity with liver ALP appeared to be 4% in the WGA assay and 11% in the IAA. The reference ranges in a group of 155 healthy Caucasian (pre)pubertal schoolgirls were: 149-401 U/L (total ALP, 30 degrees C), 105-349 U/L (bone ALP, 30 degrees C, WGA assay), and 58-205 U/L (bone ALP, 25 degrees C, IAA). Comparison of the WGA assay (x) with the IAA (y) demonstrated a correlation coefficient of 0.95 [Deming regression equation: y = (0.56 +/- 0.01)x + (2.0 +/- 1.5); Sy[symbol: see text]x = 5.3 U/L]. Correlation studies of the WGA assay and the IAA results with total ALP demonstrated r = 0.98 and 0.96, respectively.


Mapping the Energetic Costs of Free-Swimming Gilthead Sea Bream (Sparus aurata), a Key Species in European Marine Aquaculture.
Measurement of metabolic rates provides a valuable proxy for the energetic costs of different living activities. However, such measurements are not easy to perform in free-swimming fish. Therefore, mapping acceleration from accelerometer tags with oxygen consumption rates (MO2) is a promising method to counter these limitations and could represent a tool for remotely estimating MO2 in aquaculture environments. In this study, we monitored the swimming performance and MO2 of 79 gilthead sea bream (Sparus aurata; weight range, 219-971 g) during a critical swimming test. Among all the fish challenged, 27 were implanted with electromyography (EMG) electrodes, and 27 were implanted with accelerometer tags to monitor the activation pattern of the red/white muscles during swimming. Additionally, we correlated the acceleration recorded by the tag with the MO2. Overall, we found no significant differences in swimming performance, metabolic traits, and swimming efficiency between the tagged and untagged fish. The acceleration recorded by the tag was successfully correlated with MO2. Additionally, through EMG analyses, we determined the activities of the red and white muscles, which are indicative of the contributions of aerobic and anaerobic metabolisms until reaching critical swimming speed. By obtaining insights into both aerobic and anaerobic metabolisms, sensor mapping with physiological data may be useful for the purposes of aquaculture health/welfare remote monitoring of the gilthead sea bream, a key species in European marine aquaculture.


A role for myosin II clusters and membrane energy in cortex rupture for Dictyostelium discoideum.
Blebs, pressure driven protrusions of the cell membrane, facilitate the movement of eukaryotic cells such as the soil amoeba Dictyostelium discoideum, white blood cells and cancer cells. Blebs initiate when the cell membrane separates from the underlying cortex. A local rupture of the cortex, has been suggested as a mechanism by which blebs are initiated. However, much clarity is still needed about how cells inherently regulate rupture of the cortex in locations where blebs are expected to form. In this work, we examine the role of membrane energy and the motor protein myosin II (myosin) in facilitating the cell driven rupture of the cortex. We perform under-agarose chemotaxis experiments, using Dictyostelium discoideum cells, to visualize the dynamics of myosin and calculate changes in membrane energy in the blebbing region. To facilitate a rapid detection of blebs and analysis of the energy and myosin distribution at the cell front, we introduce an autonomous bleb detection algorithm that takes in discrete cell boundaries and returns the coordinate location of blebs with its shape characteristics. We are able to identify by microscopy naturally occurring gaps in the cortex prior to membrane detachment at sites of bleb nucleation. These gaps form at positions calculated to have high membrane energy, and are associated with areas of myosin enrichment. Myosin is also shown to accumulate in the cortex prior to bleb initiation and just before the complete disassembly of the cortex. Together our findings provide direct spatial and temporal evidence to support cortex rupture as an intrinsic bleb initiation mechanism and suggests that myosin clusters are associated with regions of high membrane energy where its contractile activity leads to a rupture of the cortex at points of maximal energy.


Convergence and divergence in the evolution of the APOBEC3G-Vif interaction reveal ancient origins of simian immunodeficiency viruses.
Naturally circulating lentiviruses are abundant in African primate species today, yet their origins and history of transmitting between hosts remain obscure. As a means to better understand the age of primate lentiviruses, we analyzed primate genomes for signatures of lentivirus-driven evolution. Specifically, we studied the adaptive evolution of host restriction factor APOBEC3G (A3G) in Old World Monkey (OWM) species. We find recurrent mutation of A3G in multiple primate lineages at sites that determine susceptibility to antagonism by the lentiviral accessory protein Vif. Using a broad panel of SIV Vif isolates, we demonstrate that natural variation in OWM A3G confers resistance to Vif-mediated degradation, suggesting that adaptive variants of the host factor were selected upon exposure to pathogenic lentiviruses at least 5-6 million years ago (MYA). Furthermore, in members of the divergent Colobinae subfamily of OWM, a multi-residue insertion event in A3G that arose at least 12 MYA blocks the activity of Vif, suggesting an even more ancient origin of SIV. Moreover, analysis of the lentiviruses associated with Colobinae monkeys reveal that the interface of the A3G-Vif interaction has shifted and given rise to a second genetic conflict. Our analysis of virus-driven evolution describes an ancient yet ongoing genetic conflict between simian primates and lentiviruses on a million-year time scale.


Serotype Distribution, Antimicrobial Susceptibility, Multilocus Sequencing Type and Virulence of Invasive Streptococcus pneumoniae in China: A Six-Year Multicenter Study.
Background: Streptococcus pneumoniae is an important human pathogen that can cause severe invasive pneumococcal diseases (IPDs). The aim of this multicenter study was to investigate the serotype and sequence type (ST) distribution, antimicrobial susceptibility, and virulence of S. pneumoniae strains causing IPD in China. Methods: A total of 300 invasive S. pneumoniae isolates were included in this study. The serotype, ST, and antimicrobial susceptibility of the strains, were determined by the Quellung reaction, multi-locus sequence typing (MLST) and broth microdilution method, respectively. The virulence level of the strains in the most prevalent serotypes was evaluated by a mouse sepsis model, and the expression level of well-known virulence genes was measured by RT-PCR. Results: The most common serotypes in this study were 23F, 19A, 19F, 3, and 14. The serotype coverages of PCV7, PCV10, PCV13, and PPV23 vaccines on the strain collection were 42.3, 45.3, 73.3 and 79.3%, respectively. The most common STs were ST320, ST81, ST271, ST876, and ST3173. All strains were susceptible to ertapenem, levofloxacin, moxifloxacin, linezolid, and vancomycin, but a very high proportion (>95%) was resistant to macrolides and clindamycin. Based on the oral, meningitis and non-meningitis breakpoints, penicillin non-susceptible Streptococcus pneumoniae (PNSP) accounted for 67.7, 67.7 and 4.3% of the isolates, respectively. Serotype 3 strains were characterized by high virulence levels and low antimicrobial-resistance rates, while strains of serotypes 23F, 19F, 19A, and 14, exhibited low virulence and high resistance rates to antibiotics. Capsular polysaccharide and non-capsular virulence factors were collectively responsible for the virulence diversity of S. pneumoniae strains. Conclusion: Our study provides a comprehensive insight into the epidemiology and virulence diversity of S. pneumoniae strains causing IPD in China.


Cloning and characterization of bfpTVW, genes required for the transcriptional activation of bfpA in enteropathogenic Escherichia coli.
Expression of the bundle-forming pilus (BFP) of enteropathogenic Escherichia coli (EPEC) is regulated at the transcriptional level by growth phase, temperature, calcium and ammonium. Genes required for the transcriptional activation of bfpA were localized to a 1.8 kb fragment of the enteroadherent factor (EAF) plasmid of EPEC that is separated from the bfp operon by 6 kb. Within this fragment three identically oriented and closely spaced open reading frames (ORFs) were identified and designated bfpT, bfpV and bfpW. bfpT is predicted to encode a 31.8 kDa protein that shares homology with the AraC family of transcriptional regulators, including the presence of a conserved C-terminal DNA-binding helix-turn-helix motif. Insertional inactivation of bfpT led to the loss of bfpA transcription, BfpA protein production and the localized adherence (LA) phenotype; this mutant phenotype could be complemented by introduction of bfpTVW and, on separate plasmids, bfpT + bfpW. However, introduction of bfpT + bfpV, bfpV alone, bfpW alone, or bfpV + bfpW did not enable recovery of the wild-type phenotype. Maximal efficiency of bfpA transcription required all three genes, but bfpV and bfpW each enhanced transcription providing bfpT was also present. A series of deletions of the bfpA upstream promoter region was prepared; with respect to the bfpA transcription start site, sequence between nucleotides -94 and -55 was found to bind bfpT. BfpT also bound a DNA fragment containing the eaeA promoter region on the EPEC chromosome. From these results we conclude that bfpTV W causes transcriptional activation of bfpA, and possibly eaeA, by a trans-acting mechanism that may co-ordinately regulate the expression of EPEC virulence determinants.


Free D-aspartate in mammals.
D-Aspartate (D-Asp) is an endogenous amino acid present in nervous and endocrine tissues in mammals. A high concentration of D-Asp is observed in embryos, which disappears in nervous tissues after delivery, but increases temporarily in endocrine glands, particularly in the pituitary, pineal and adrenal glands at the specific stages. In the pineal gland, D-Asp that is apparently derived from other tissues suppresses melatonin secretion from parenchymal cells. Additionally, D-Asp levels increase in the testis just before birth and during maturation. The amino acid is presumed to be synthesized by the pituitary gland and testis. In the testis, D-Asp produced inside the seminiferous tubules acts on Leydig cells following release to enhance testosterone synthesis by activating the expression of Steroidogenic Acute Regulatory protein. Mammalian cells appear to contain all the molecular components required to regulate D-Asp homeostasis, as they can synthesize, release, take up, and degrade the amino acid. These findings collectively indicate that D-Asp is a novel type of messenger in the mammalian body.


Leisure mobility changes during the COVID-19 pandemic - An analysis of survey and mobile phone data in Sweden.
The COVID-19 pandemic affected travelling in general, and the leisure mobility and the spatial distribution of travellers in particular. In most parts of the world, both domestic and international travel has been replaced by restrictive policies and recommendations on mobility. A modal shift from public transport towards private cars and micro-mobility was also observed. This study seeks to trace the implications of the COVID-19 pandemic for leisure mobility. We use a unique Swedish database containing daily mobility patterns of pseudonymised mobile phone users, combined with a survey on vacation transport behaviour. By contrasting mobility patterns for selected holiday days during the unaffected summer of 2019 with corresponding dates in 2020 and 2021, we are able to model and detect the pandemic effects on tourism and recreational mobility. Moreover, by identifying the general mobility patterns, we analyse whether and how the transport mode has changed. Using data on the spatial distribution of recreational amenities, we identify locations that were favoured during the pandemic. In Sweden, even though the pandemic decreased in spread and severity during the summers, most travel restrictions were still enforced, international vacations uncommon, and larger vacation spots, such as amusement parks and cultural institutions, were closed down. Swedish vacation homes in remote or rural areas were quickly booked. This change in recreational behaviour, where less populated areas, open air and nature recreation were favoured over indoor or crowded urban cultural activities, was more substantial in 2021 than in 2020. This result shows how policies can effectively be developed, so that Swedes respond properly to recommendations and adjust their vacation plans.


Long-Term Physical HRQOL Decreases After Single Lung as Compared With Double Lung Transplantation.
Single lung transplantation (SLT) and double lung transplantation (DLT) are associated with differences in morbidity and mortality, although the effects of transplant type on patient-reported outcomes are not widely reported and conclusions have differed. Previous studies compared mean health-related quality of life (HRQOL) scores but did not evaluate potentially different temporal trajectories in the context of longitudinal follow-up. To address this uncertainty, this study was designed to evaluate longitudinal HRQOL after SLT and DLT with the hypothesis that temporal trajectories differ between SLT and DLT. Patients transplanted at a single institution were eligible to be surveyed at 1 month, 3 months, 6 months, and then annually after transplant using the Short Form 36 Health Survey, with longitudinal physical component summary (PCS) and mental component summary (MCS) scores as the primary outcomes. Multivariable mixed-effects models were used to evaluate the effects of transplant type and time posttransplant on longitudinal PCS and MCS after adjusting age, diagnosis, rejection, Lung Allocation Score quartile, and intubation duration. Time by transplant type interaction effects were used to test whether the temporal trajectories of HRQOL differ between SLT and DLT recipients. HRQOL scores were referenced to general population norms (range, 40 to 60; mean, 50 ± 10) using accepted standards for a minimally important difference (½ SD, 5 points). Postoperative surveys (n = 345) were analyzed for 136 patients (52% male, 23% SLT, age 52 ± 13 years, LAS 42 ± 12, follow-up 37 ± 29 months [range, 0.6 to 133]) who underwent lung transplantation between 2005 and 2016. After adjusting for model covariates, overall posttransplant PCS scores have a significant downward trajectory (p = 0.015) whereas MCS scores remain stable (p = 0.593), with both averaging within general population norms. The time by transplant type interaction effect (p = 0.002), however, indicate that posttransplant PCS scores of SLT recipients decline at a rate of 2.4 points per year over the total observation period compared to DLT. At approximately 60 months, the PCS scores of SLT recipients, but not DLT recipients, fall below general population norms. The trajectory of physical HRQOL in patients receiving SLT declines over time compared with DLT, indicating that, in the longer term, SLT recipients are more likely to have physical HRQOL scores that fall substantively below general population norms. Physical HRQOL after 5 years may be a consideration for lung allocation and patient counseling regarding expectations when recommending SLT or DLT.


Quantitative assessment of chronic lung disease of infancy using computed tomography.
The aims of this study were to determine whether infants and toddlers with chronic lung disease of infancy (CLDI) have smaller airways and lower lung density compared with full-term healthy controls. Multi-slice computed tomography (CT) chest scans were obtained at elevated lung volumes during a brief respiratory pause in sedated infants and toddlers; 38 CLDI were compared with 39 full-term controls. For CLDI subjects, gestational age at birth ranged from 25 to 29 weeks. Airway size was measured for the trachea and the next three to four generations into the right lower lobe; lung volumes and tissue density were also measured. The relationship between airway size and airway generation differed between the CLDI and full-term groups; the sizes of the first and second airway generations were larger in the shorter CLDI than in the shorter full-term subjects. The increased size in the airways in the CLDI subjects was associated with increasing mechanical ventilation time in the neonatal period. CLDI subjects had a greater heterogeneity of lung density compared with full-term subjects. Our results indicate that quantitative analysis of multi-slice CT scans at elevated volumes provides important insights into the pulmonary pathology of infants and toddlers with CLDI.


Kiaman magnetic interval in the Western United States.
Late-Paleozoic red beds in the western United States indicate that Earth's magnetic field was reversed for a period of the order of 50 x 10(6) years. This finding agrees with similar results from igneous rocks in Australia, indicating, that the long period of reversal in the magnetic field was worldwide. The rocks on the two continents appear to be essentially equivalent in time, suggesting early magnetization of the red beds. The time spectrum of reversals is irregular in geologic time, but present evidence suggests reversals characterized by time scales of 10(4) or 10(5), 10(6), and 50 x 10(6) years. The 50 x 10(6) year period of steady reversed field is found in the late Paleozoic and is termed the Kiaman magnetic interval.