Knowledge, perceptions, and expectations of Artificial intelligence in radiography practice: A global radiography workforce survey.
Artificial Intelligence (AI) technologies have already started impacting clinical practice across various settings worldwide, including the radiography profession. This study is aimed at exploring a world-wide view on AI technologies in relation to knowledge, perceptions, and expectations of radiography professionals. An online survey (hosted on Qualtrics) on key AI concepts was open to radiography professionals worldwide (August 1st to December 31st 2020). The survey sought both quantitative and qualitative data on topical issues relating to knowledge, perceptions, and expectations in relation to AI implementation in radiography practice. Data obtained was analysed using the Statistical Package for Social Sciences (SPSS) (v.26) and the six-phase thematic analysis approach. A total of 314 valid responses were obtained with a fair geographical distribution. Of the respondents, 54.1% (157/290) were from North America and were predominantly clinical practicing radiographers (60.5%, 190/314). Our findings broadly relate to different perceived benefits and misgivings/shortcomings of AI implementation in radiography practice. The benefits relate to enhanced workflows and optimised workstreams while the misgivings/shortcomings revolve around de-skilling and impact on patient-centred care due to over-reliance on advanced technology following AI implementation. Artificial intelligence is a tool but to operate optimally it requires human input and validation. Radiographers working at the interface between technology and the patient are key stakeholders in AI implementation. Lack of training and of transparency of AI tools create a mixed response of radiographers when they discuss their perceived benefits and challenges. It is also possible that their responses are nuanced by different regional and geographical contexts when it comes to AI deployment. Irrespective of geography, there is still a lot to be done about formalised AI training for radiographers worldwide. This is a vital step to ensure safe and effective AI implementation, adoption, and faster integration into clinical practice by healthcare workers including radiographers. Advancement of AI technologies and implementation should be accompanied by proportional training of end-users in radiography and beyond. There are many benefits of AI-enabled radiography workflows and improvement on efficiencies but equally there will be widespread disruption of traditional roles and patient-centred care, which can be managed by a well-educated and well-informed workforce.


Predictors of participant dropout at various stages of a pediatric lifestyle program.
To evaluate baseline predictors of drop out at various stages in a lifestyle intervention for overweight and obese children. Children and their families (N = 248) (aged 8-14 years) attended a lifestyle intervention. At baseline, we assessed anthropometric and demographic data, measured competence and behavioral problems, and family functioning. Dropout rates were analyzed at various stages in treatment with logistic regression analyses. Children who had mothers of non-white descent, who had higher BMI SDS, who participated in fewer activities, who did not have breakfast regularly, and who did not live in families with a static adaptability structure were more likely to drop out between 0 and 12 months. Different characteristics predicted dropout at various stages of treatment: (1) having an ethnic minority status and being older predicted dropping out between 0 and 3 months; (2) having a nonwhite mother, participating in fewer activities, having higher delinquency scores, and not presenting the family as extremely positive predicted dropping out between 3 and 9 months; and (3) having a higher BMI SDS, having fewer social problems, and not living in families with a static adaptability structure predicted dropping out between 9 and 12 months of treatment. The results indicate different characteristics predict dropping out from a pediatric lifestyle program at various stages in treatment. These findings highlight the need for tailored interventions that target different characteristics at various stages of treatment to reduce drop out rates.


Amyotrophic lateral sclerosis patients show increased peripheral and intrathecal T-cell activation.
Several studies suggest a role for the peripheral immune system in the pathophysiology of amyotrophic lateral sclerosis. However, comprehensive studies investigating the intrathecal immune system in amyotrophic lateral sclerosis are rare. To elucidate whether compartment-specific inflammation contributes to amyotrophic lateral sclerosis pathophysiology, we here investigated intrathecal and peripheral immune profiles in amyotrophic lateral sclerosis patients and compared them with controls free of neurological disorders (controls) and patients with dementia or primary progressive multiple sclerosis. Routine CSF parameters were examined in 308 patients, including 132 amyotrophic lateral sclerosis patients. In a subgroup of 41 amyotrophic lateral sclerosis patients, extensive flow-cytometric immune cell profiling in peripheral blood and CSF was performed and compared with data from 26 controls, 25 dementia and 21 multiple sclerosis patients. Amyotrophic lateral sclerosis patients presented with significantly altered proportions of monocyte subsets in peripheral blood and increased frequencies of CD4+ and CD8+ T cells expressing the activation marker HLA-DR in peripheral blood (CD8+) and CSF (CD4+ and CD8+) compared with controls. While dementia and multiple sclerosis patients exhibited a comparable increase in intrathecal CD8+ T-cell activation, CD8+ T-cell activation in the peripheral blood in amyotrophic lateral sclerosis was higher than in multiple sclerosis patients. Furthermore, intrathecal CD4+ T-cell activation in amyotrophic lateral sclerosis surpassed levels in dementia patients. Intrathecal T-cell activation resulted from in situ activation rather than transmigration of activated T cells from the blood. While T-cell activation did not correlate with amyotrophic lateral sclerosis progression, patients with rapid disease progression showed reduced intrathecal levels of immune-regulatory CD56bright natural killer cells. The integration of these parameters into a composite score facilitated the differentiation of amyotrophic lateral sclerosis patients from patients of all other cohorts. To conclude, alterations in peripheral monocyte subsets, as well as increased peripheral and intrathecal activation of CD4+ and CD8+ T cells concomitant with diminished immune regulation by CD56bright natural killer cells, suggest an involvement of these immune cells in amyotrophic lateral sclerosis pathophysiology.


The G Protein Biased Small Molecule Apelin Agonist CMF-019 is Disease Modifying in Endothelial Cell Apoptosis In Vitro and Induces Vasodilatation Without Desensitisation In Vivo.
Signaling through the apelin receptor is beneficial for a number of diseases including pulmonary arterial hypertension. The endogenous small peptides, apelin and elabela/toddler, are downregulated in pulmonary arterial hypertension but are not suitable for exogenous administration owing to a lack of bioavailability, proteolytic instability and susceptibility to renal clearance. CMF-019, a small molecule apelin agonist that displays strong bias towards G protein signaling over β-arrestin (∼400 fold), may be more suitable. This study demonstrates that in addition to being a positive inotrope, CMF-019 caused dose-dependent vasodilatation in vivo (50 nmol 4.16 ± 1.18 mmHg, **p < 0.01; 500 nmol 6.62 ± 1.85 mmHg, **p < 0.01), without receptor desensitization. Furthermore, CMF-019 rescues human pulmonary artery endothelial cells from apoptosis induced by tumor necrosis factor α and cycloheximide (5.66 ± 0.97%, **p < 0.01) by approximately 50% of that observable with rhVEGF (11.59 ± 1.85%, **p < 0.01), suggesting it has disease-modifying potential in vitro. CMF-019 displays remarkable bias at the apelin receptor for a small molecule and importantly recapitulates all aspects of the cardiovascular responses to the endogenous ligand, [Pyr1]apelin-13, in vivo. Additionally, it is able to protect human pulmonary artery endothelial cells from apoptosis, suggesting that the beneficial effects observed with apelin agonists extend beyond hemodynamic alleviation and address disease etiology itself. These findings support CMF-019 as a G protein biased small molecule apelin agonist in vitro and in vivo that could form the basis for the design of novel therapeutic agents in chronic diseases, such as, pulmonary arterial hypertension.


Identification and Management of TP53 Gene Carriers Detected Through Multigene Panel Testing.
The increasing use of multigene panel tests may reveal an unexpected pathogenic variant in the tumor protein p53 (TP53) gene among individuals who do not meet clinical criteria for Li-Fraumeni syndrome (LFS). Among a registry-based sample of individuals with a pathogenic (P) or likely pathogenic (LP) variant in TP53, we sought to characterize the original clinical context in which genetic testing was performed, the personal and family history and whether they met clinical LFS criteria, and the follow-up care following diagnosis among those in whom this information was available. Among individuals with multigene panel testing (inclusive of the TP53 gene) who were part of either the Inherited Cancer Registry or the Vanderbilt Hereditary Cancer Registry protocols and were confirmed to have a P/LP variant in TP53, pedigree was reviewed to characterize personal and family history, including original clinical context for genetic testing and whether they met clinical diagnostic criteria for TP53. Subsequent cancer risk management options were documented through information collected in the study questionnaire and medical records. Among the 10 participants enrolled in one of the two registries with a germline TP53 P/LP variant detected through a multigene panel test, the most frequent clinical contexts for testing were genetic risk recognized in the survivorship care setting (50%) and a newly diagnosed breast cancer (40%). No participants met classic LFS diagnostic criteria and 6 of 10 met Chompret criteria (60%) at the time of testing. Among the seven participants in whom results of total body magnetic resonance imaging were available, only three had completely negative findings. The remaining four had findings, three of which were likely benign/incidental requiring additional follow-up, and one was consistent with metastatic disease in the vertebrae. Our findings suggest that individuals identified with a germline P/LP variant in TP53 through multigene panel tests have substantial variations in clinical phenotypes not previously recognized when only those with striking family histories suggestive of LFS were tested through targeted TP53 testing. The expansion of the clinical phenotype among carriers of a P/LP in TP53 in the era of multigene testing should be considered when making cancer risk management recommendations, which were developed based on patients with classic LFS.


Coexistence of superconductivity and ferromagnetism in two dimensions.
Ferromagnetism is usually considered to be incompatible with conventional superconductivity, as it destroys the singlet correlations responsible for the pairing interaction. Superconductivity and ferromagnetism are known to coexist in only a few bulk rare-earth materials. Here we report evidence for their coexistence in a two-dimensional system: the interface between two bulk insulators, LaAlO(3) (LAO) and SrTiO(3) (STO), a system that has been studied intensively recently. Magnetoresistance, Hall, and electric-field dependence measurements suggest that there are two distinct bands of charge carriers that contribute to the interface conductivity. The sensitivity of properties of the interface to an electric field makes this a fascinating system for the study of the interplay between superconductivity and magnetism.


An anti-neuroinflammatory that targets dysregulated glia enhances the efficacy of CNS-directed gene therapy in murine infantile neuronal ceroid lipofuscinosis.
Infantile neuronal ceroid lipofuscinosis (INCL) is an inherited neurodegenerative lysosomal storage disease (LSD) caused by a deficiency in palmitoyl protein thioesterase-1 (PPT1). Studies in Ppt1(-/-) mice demonstrate that glial activation is central to the pathogenesis of INCL. Astrocyte activation precedes neuronal loss, while cytokine upregulation associated with microglial reactivity occurs before and concurrent with neurodegeneration. Therefore, we hypothesized that cytokine cascades associated with neuroinflammation are important therapeutic targets for the treatment of INCL. MW01-2-151SRM (MW151) is a blood-brain barrier penetrant, small-molecule anti-neuroinflammatory that attenuates glial cytokine upregulation in models of neuroinflammation such as traumatic brain injury, Alzheimer's disease, and kainic acid toxicity. Thus, we used MW151, alone and in combination with CNS-directed, AAV-mediated gene therapy, as a possible treatment for INCL. MW151 alone decreased seizure susceptibility. When combined with AAV-mediated gene therapy, treated INCL mice had increased life spans, improved motor performance, and eradication of seizures. Combination-treated INCL mice also had decreased brain atrophy, astrocytosis, and microglial activation, as well as intermediary effects on cytokine upregulation. These data suggest that MW151 can attenuate seizure susceptibility but is most effective when used in conjunction with a therapy that targets the primary genetic defect.


Variants regulating ZBTB4 are associated with age-at-onset of Alzheimer's disease.
The identification of novel genetic modifiers of age-at-onset (AAO) of Alzheimer's disease (AD) could advance our understanding of AD and provide novel therapeutic targets. A previous genome scan for modifiers of AAO among families affected by early-onset AD caused by the PSEN2 N141I variant identified 2 loci with significant evidence for linkage: 1q23.3 and 17p13.2. Here, we describe the fine-mapping of these 2 linkage regions, and test for replication in 6 independent datasets. By fine-mapping these linkage signals in a single large family, we reduced the linkage regions to 11% their original size and nominated 54 candidate variants. Among the 11 variants associated with AAO of AD in a larger sample of Germans from Russia, the strongest evidence implicated promoter variants influencing NCSTN on 1q23.3 and ZBTB4 on 17p13.2. The association between ZBTB4 and AAO of AD was replicated by multiple variants in independent, trans-ethnic datasets. Our results show association between AAO of AD and both ZBTB4 and NCSTN. ZBTB4 is a transcriptional repressor that regulates the cell cycle, including the apoptotic response to amyloid beta, while NCSTN is part of the gamma secretase complex, known to influence amyloid beta production. These genes therefore suggest important roles for amyloid beta and cell cycle pathways in AAO of AD.


[Dedifferentiating intracerebral neuroblastoma resistant to x-ray and drug therapy -- a case report (author's transl)].
A new case of primary intracerebral neuroblastoma is reported. The patient, a 2 year old boy, was subjected to temporary successful craniotomy, postoperative irradiation and cytostatic therapy without any influence on the recurrence of the tumor. In contrast to the possible well-known maturation of neuroblastomas a dedifferentiating process occurred. The boy died 8 1/2 months after diagnosis.


Memory: obstacle avoidance without visual cues.
Avoiding obstacles is essential when we move about the world, yet little is known about how we do this when visual cues are not present to guide us. Recent evidence from behavioural studies in cats suggests that working memory may be crucial.


LIGHT-SABRE enables efficient in-magnet catalytic hyperpolarization.
Nuclear spin hyperpolarization overcomes the sensitivity limitations of traditional NMR and MRI, but the most general method demonstrated to date (dynamic nuclear polarization) has significant limitations in scalability, cost, and complex apparatus design. As an alternative, signal amplification by reversible exchange (SABRE) of parahydrogen on transition metal catalysts can hyperpolarize a variety of substrates, but to date this scheme has required transfer of the sample to low magnetic field or very strong RF irradiation. Here we demonstrate "Low-Irradiation Generation of High Tesla-SABRE" (LIGHT-SABRE) which works with simple pulse sequences and low power deposition; it should be usable at any magnetic field and for hyperpolarization of many different nuclei. This approach could drastically reduce the cost and complexity of producing hyperpolarized molecules.


Polynucleobacter aenigmaticus sp. nov. isolated from the permanently anoxic monimolimnion of a temperate meromictic lake.
The bacterial strain MWH-K35W1T was isolated from a permanently anoxic water layer of a meromictic lake located in the Austrian Salzkammergut area. The basically chemo-organoheterotrophic strain was isolated and maintained under aerobic conditions. Phylogenetic analyses of the 16S rRNA gene and the glutamine synthetase gene (glnA) of the strain suggested an affiliation to the genus Polynucleobacter and the cryptic species complex PnecC. Strain MWH-K35W1T shares with the type strains of the six free-living species of the genus Polynucleobacter affiliated with this species complex 16S rRNA gene sequence similarities of 99.6-99.9 %, while the type material of the obligate endosymbiont Polynucleobacternecessarius, which is also affiliated with this species complex, shares a gene sequence similarity of 99.1 %. Genome sequencing resulted in a genome size of 2.14 Mbp and a DNA G+C content of 45.98 mol%. Major fatty acids were C16 : 1ω7c, C18 : 1ω7c and C16 : 0. This strain is the first strain of the genus Polynucleobacter found to encode a proteorhodopsin-like protein but, in contrast to some other strains affiliated to this genus, it does not encode a putative anoxygenic photosynthesis system. Multilocus sequence analysis based on partial sequences of eight housekeeping genes, as well as average nucleotide identity (ANI) analyses, did not suggest that strain MWH-K35W1T belongs to a previously described species. We propose the name Polynucleobacter aenigmaticus for a novel species with strain MWH-K35W1T (=DSM 24006T=LMG 29706T) as the type strain.


Fluoroscopic Swallowing Abnormalities in Dysphagic Patients Following Anterior Cervical Spine Surgery.
To evaluate the precise objective fluoroscopic abnormalities in persons with dysphagia following anterior cervical spine surgery (ACSS). 129 patients with dysphagia after ACSS were age and sex matched to 129 healthy controls. All individuals underwent videofluoroscopic swallow study (VFSS). VFSS parameters abstracted included upper esophageal sphincter (UES) opening, penetration aspiration scale (PAS), and pharyngeal constriction ratio (PCR). Other data collected included patient-reported outcome measures of voice and swallowing, number of levels fused, type of plate, vocal fold immobility, time from surgery to VFSS, and revision surgery status. The mean age of the entire cohort was 63 (SD ± 11) years. The mean number of levels fused was 2.2 (±0.9). 11.6% (15/129) were revision surgeries. The mean time from ACSS to VFSS was 58.3 months (±63.2). The majority of patients (72.9%) had anterior cervical discectomy and fusion (ACDF). For persons with dysphagia after ACSS, 7.8% (10/129) had endoscopic evidence of vocal fold immobility. The mean UES opening was 0.84 (±0.23) cm for patients after ACSS and 0.86 (±0.22) cm for controls (P > .0125). Mean PCR was 0.12 (±0.12) for persons after ACSS and 0.08 (±0.08) for controls, indicating significant post-surgical pharyngeal weakness (P < .0125). The median PAS was 1 (IQR 1) for persons after ACSS as well as for controls. For ACSS patients, PCR had a weak correlation with EAT-10 (P < .0125). Chronic swallowing dysfunction after ACSS appears to be secondary to pharyngeal weakness and not diminished UES opening, the presence of aspiration, vocal fold immobility, or ACSS instrumentation factors.Level of Evidence: 3b.


Improved system identification with Renormalization Group.
This paper proposes an improved system identification method with Renormalization Group. Renormalization Group is applied to a fine data set to obtain a coarse data set. The least squares algorithm is performed on the coarse data set. The theoretical analysis under certain conditions shows that the parameter estimation error could be reduced. The proposed method is illustrated with examples.


beta-Adrenergic receptors in pediatric tumors: uncoupled beta 1-adrenergic receptor in Ewing's sarcoma.
beta-Adrenergic receptors were demonstrated in membrane preparations from 6 human Ewing's sarcomas and compared to those from 46 other pediatric cancers with the use of the beta-adrenergic antagonist (-)-(3H)dihydroalprenolol [(-)[3H]DHA]. In contrast to the high numbers of receptor sites found in Ewing's sarcomas (55-640 fmol x mg-1 protein; dissociation constant Kd, 1-2 nM), other childhood cancers (neuroblastoma, rhabdomyosarcoma, brain tumors, lymphoma, osteosarcoma, hepatoblastoma, yolk sac, and Wilms' tumor) contained in general fewer beta-adrenergic receptor sites. Characteristics of (-)-[3H]DHA binding were therefore more fully characterized in the Ewing's tumors. Competition of (-)-[3H]DHA binding by classical catecholamine agonists, as well as by subtype selective agents metoprolol and zinterol, demonstrated the presence of a homogeneous population of beta 1-adrenergic sites in several Ewing's tumors. Adenylate cyclase activity in all Ewing's sarcomas was enhanced by GTP and NaF. However, in spite of high numbers of beta-adrenergic receptors, (-)-isoproterenol was not very effective in the activation of adenylate cyclase activity in several of the Ewing's tumors tested. Neither guanyl-5'-yl-imidophosphate nor GTP altered agonist potency for the receptor site in these catecholamine-insensitive tumors. Hill coefficients obtained from the competition experiments with (-)-isoproterenol (in the presence or absence of guanine nucleotide) were approximately 1.0. These uncoupled receptors were resistant to N-ethylmaleimide denaturation and were densensitized only 50% during culture in the presence of (-)-isoproterenol. Thus Ewing's sarcomas are relatively rich in beta-adrenergic sites, and several tumors appear to have a coupling lesion involving guanine nucleotide-dependent regulatory protein interaction with beta-adrenergic receptors and adenylate cyclase, similar in phenotype to that described in the (unc) variant of S49 mouse lymphoma.


Rumination Syndrome and Dental Erosions in Children.
Rumination syndrome is the effortless regurgitation of recently ingested food with subsequent reswallowing or spitting out. Dental erosion (DE) affects 2% to 5% of the population. DE is defined as loss of tooth structure by a chemical process that does not involve bacteria. Our objective was to compare the frequency of DE among children with rumination syndrome with healthy controls. We enrolled 30 patients 4 to 21 years of age diagnosed with rumination syndrome, and 30 age- and sex-matched healthy control subjects. Patients were evaluated by pediatric dentists for presence of DE with Taji et al a validated grading system. Patients with rumination were more likely to have DE (P < 0.001). Of patients with rumination syndrome, 23 (77%) had DE, compared with 4 (13%) control subjects. DEs are more frequent in patients with rumination syndrome.


Effect of moxifloxacin on bacterial pathogenicity factors in comparison with amoxicillin, clarithromycin and ceftriaxone.
Moxifloxacin is a recent fluoroquinolone with an antibacterial spectrum encompassing both aerobic Gram-negative and Gram-positive strains, as well as anaerobic bacteria. In this study the activity of moxifloxacin against Streptococcus pneumoniae, Staphylococcus aureus, Moraxella catarrhalis, Haemophilus influenzae, Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa, and effects of subinhibitory concentrations on bacterial morphology and adhesion properties were compared with those of amoxicillin, clarithromycin and ceftriaxone. The in vitro activity of moxifloxacin against Gram-positive and Gram-negative pathogens was equal to or better than that of comparators. Subinhibitory concentrations of moxifloxacin significantly affected bacterial morphology of S. pneumoniae, M. catarrhalis, H. influenzae and P. aeruginosa, leading to formation of spherical forms and filaments. Moreover, bacterial adhesion to buccal cells and fibroblasts was reduced after treatment with 1/4 and 1/8 X MIC of moxifloxacin. In conclusion, subinhibitory concentrations of moxifloxacin remarkably interfere with some bacterial pathogenic factors, thereby contributing to its antimicrobial activity.


Quantification of the effect of kvp on edge-enhancement index in phase-contrast radiography.
This study was performed to measure the dependence of edge-enhancement in polychromatic phase-contrast radiography on x-ray tube operating voltage. Measurements of edge enhancement were made at tube voltages from 40 to 86 kVp using a tungsten anode x-ray tube with a nominal focal spot size of 100 micrometers. A relatively weak attenuating, sharp edge consisting of a thin lucite sheet (3 mm) in air was imaged utilizing phase-contrast radiography (PC-R). PC-R images were acquired at different radiographic techniques in which x-ray tube voltage was varied from 40 to 86 kVp. The image receptor was a single emulsion x-ray mammography cassette. Optical density profiles across the edge of the object were obtained using a film digitizer and edge-enhancement indices were calculated. Increasing kVp resulted in a gradual decrease of the edge-enhancement index. Even at the highest kVp (86), however, important edge-enhancement effects were evident. While there is some degradation in the edge-enhancement effect of phase-contrast radiography at higher kVps, the decrease from 40 to 86 kVp is relatively small (11%). Our results suggest that further investigation into the role of phase-contrast imaging at higher kVp values for the purpose of patient dose reduction while still realizing the advantage of phase-contrast effects for improved soft-tissue detectability is warranted.


Stimulation of toll-like receptor 2 by Coxiella burnetii is required for macrophage production of pro-inflammatory cytokines and resistance to infection.
Innate and adaptive immune responses are initiated upon recognition of microbial molecules by Toll-like receptors (TLRs). We have investigated the importance of these receptors in the induction of pro-inflammatory cytokines and macrophage resistance to infection with Coxiella burnetii, an obligate intracellular bacterium and the etiological agent of Q fever. By using a Chinese hamster ovary/CD14 cell line expressing either functional TLR2 or TLR4, we determined that C. burnetii phase II activates TLR2 but not TLR4. Macrophages deficient for TLR2, but not TLR4, produced less tumor necrosis factor-alpha and interleukin-12 upon C. burnetii infection. Furthermore, it was found that TLR2 activation interfered with C. burnetii intracellular replication, as macrophages from TLR2-deficient mice were highly permissive for C. burnetii growth compared with macrophages from wild type mice or TLR4-deficient mice. Although LPS modifications distinguish virulent C. burnetii phase I bacteria from avirulent phase II organisms, electrospray ionization-mass spectrometry analysis showed that the lipid A moieties isolated from these two phase variants are identical. Purified lipid A derived from either phase I or phase II LPS failed to activate TLR2 and TLR4. Indeed, the lipid A molecules were able to interfere with TLR4 signaling in response to purified Escherichia coli LPS. These studies indicate that TLR2 is an important host determinant that mediates recognition of C. burnetii and a response that limits growth of this intracellular pathogen.


Mechanism of pectoral fin outgrowth in zebrafish development.
Fins and limbs, which are considered to be homologous paired vertebrate appendages, have obvious morphological differences that arise during development. One major difference in their development is that the AER (apical ectodermal ridge), which organizes fin/limb development, transitions into a different, elongated organizing structure in the fin bud, the AF (apical fold). Although the role of AER in limb development has been clarified in many studies, little is known about the role of AF in fin development. Here, we investigated AF-driven morphogenesis in the pectoral fin of zebrafish. After the AER-AF transition at ∼36 hours post-fertilization, the AF was identifiable distal to the circumferential blood vessel of the fin bud. Moreover, the AF was divisible into two regions: the proximal AF (pAF) and the distal AF (dAF). Removing the AF caused the AER and a new AF to re-form. Interestingly, repeatedly removing the AF led to excessive elongation of the fin mesenchyme, suggesting that prolonged exposure to AER signals results in elongation of mesenchyme region for endoskeleton. Removal of the dAF affected outgrowth of the pAF region, suggesting that dAF signals act on the pAF. We also found that the elongation of the AF was caused by morphological changes in ectodermal cells. Our results suggest that the timing of the AER-AF transition mediates the differences between fins and limbs, and that the acquisition of a mechanism to maintain the AER was a crucial evolutionary step in the development of tetrapod limbs.


Bacterial colonization of tunneled right atrial catheters in pediatric oncology: a comparison of sterile saline and bacteriostatic saline flush solutions.
In a double-blind, randomized controlled trial, children with malignant diseases had their tunneled right atrial catheters flushed with either sterile saline or bacteriostatic saline, once per week for 26 weeks. There was no significant difference in the rates of catheter colonization between the two groups, which did differ, however, in terms of the time from entry into the study to the first infective event (64 +/- 34 days vs. 146 +/- 27 days; p less than 0.001). This was strongly suggestive of a seasonal effect, as all of the colonizations in the bacteriostatic saline group were delayed until the summer months. We conclude that the use of a bacteriostatic saline flush solution for tunneled right atrial catheters is beneficial in efforts to prevent catheter colonization.


Dissimilar expression of multidrug resistance mdr1 and bcrp by the replication of hepatitis C virus: role of the nonstructural 5A protein.
Multidrug resistance associated with the overexpression of ATP-dependent binding cassette (ABC) proteins is widely accepted as an important cause of treatment failure in patients with neoplastic or infectious diseases. Some of them play also a pivotal role in detoxification processes. Herein, we investigated the effect of hepatitis C virus (HCV) replication and nonstructural 5A (NS5A) protein on the expression and functional activity of two ABC transport proteins: MDR1 and BCRP. RT-quantitative real-time polymerase chain reaction (qPCR) was carried out for mdr1 and bcrp mRNAs in both Huh7 cells expressing NS5A and Huh7.5 cells containing either full-length- or subgenomic-HCV replicon systems. The functional activity of these pumps was studied by performing a dye efflux assay with DiOC2 and Rhodamine 123. A dose-dependent down-regulation of mdr1 expression was documented in Huh7 cells expressing the NS5A protein, as well as in both replicon systems. In contrast, a significant increase of bcrp expression in both systems was recorded, which were in full agreement with the dye efflux assay results. These results warrant further in vivo studies in HCV patients with cholestasis and/or patients that are refractive to the pharmacotherapy due to the activity of these pumps.


A novel animal model to study hot flashes: no effect of gonadotropin-releasing hormone.
Menopausal hot flashes compromise the quality of life for most women. The physiological mechanisms underlying hot flashes remain poorly understood, and the absence of an animal model to investigate hot flashes hinders investigations in this field. We first developed the sheep as a model to study peripheral skin temperature changes using fever-inducing lipopolysaccharide (LPS; 200 microg/kg) administered to ovary-intact ewes. Because a strong correlation between luteinizing hormone pulses and hot flashes has previously been reported, we then determined whether intravenous gonadotropin-releasing hormone (GnRH; 1 mg), a dose sufficient to elevate cerebrospinal fluid-GnRH concentrations, could modulate ear skin temperature in both ovariectomized and low-estrogen-replaced ovariectomized ewes. Some ewes responded to LPS in heart rate and abdominal temperature, but there was no significant effect on either parameter or cheek temperature for the group. In contrast, LPS injection caused a significant (P < 0.001) change in skin temperature at the ear. Ear temperature showed no significant change in response to GnRH relative to control injections in both ovariectomized and low estrogen ewes. We developed a model animal system in the ewe that can accurately detect small changes in peripheral skin temperature. This system has the potential to be extremely useful in future studies investigating the pathology of hot flashes and holds several advantages over previous model systems developed for this research. GnRH per se does not seem to be involved in thermoregulatory events.


Should Donors Consent to Export Their Corneas? Examination of Eye Tissue and Eye Care Sector Opinion.
Corneal tissue international activity is only possible because of the willingness of export populations to donate their corneas on their death. Current predonation public education campaigns and at-the-point-of-donation consent practice generally includes consent for transplantation, research, and/or training. It is unclear whether a consent-for-export step is universally included in the consent process or, indeed, whether it should. We interviewed eye tissue and eye care professionals from around the world, who exported, imported, or did neither to understand current consent-for-export awareness and determine opinion on future practice. During wider qualitative grounded-theory semistructured interviews with sector experts, to determine whether Australia should export, we captured sector opinion on consent-for-export. We used saturation and sentiment methods to determine opinion and χ2 correlation coefficients to examine association, using an α of P = 0.05. We interviewed 92 individuals, 83 of whom discussed consent-for-export. Of those, 51% (42/83) demonstrated some awareness of the practice; however, there were contradictions between interviewees from the same location. Regardless of current awareness, 57% (41/72) believed donors should be informed or consented for export. Their approval did not extend to donor-directed decisions, which would allow donors to decide which nation their donation should be sent, with 62.5% (45/72) opposing that notion. Our research indicates that the consent-for-export practice is not universally applied by exporting nations and that eye tissue and eye care professionals have limited awareness of the practice. Universally implementing a consent-for-export step within general consent practice would improve awareness, reduce confusion, and support donor wishes.


First record of Ochlerotatus (Finlaya) japonicus japonicus (Theobald, 1901) in metropolitan France.
Ochlerotatus (Finlaya) japonicus japonicus is a potential vector of arboviruses such as Japanese encephalitis virus and West Nile virus. The latter already is present in France. We report the species for the 1st time in metropolitan France and in Europe. Two larvae were collected in July and October 2000 in used tires in a village in northwestern France. Collections were made in a stack of recycled tires from a company that imports from the USA and Japan. The lack of other mutes of introduction for the species confirms tires as a means of worldwide spread. Larval stages found in the area indicate that the species is reproducing locally.


State of the Journal, 2023.
The American Journal of Occupational Therapy (AJOT) has maintained its top-ranking status in the field of occupational therapy, as evidenced by an increase in its 2-yr impact factor. As the Editor-in-Chief enters her second 3-yr term, the journal faces both challenges and opportunities stemming from trends in academic publishing. The editorial team seeks to navigate these shifts while fostering meaningful research dissemination and translation. Key outcomes for 2023 showcase the journal's dedication to addressing diverse occupational therapy needs. A special issue on autism and mental health in 2023 and upcoming themes on recovery after neurological injury and play in occupational therapy in 2024 exemplify AJOT's commitment to relevant topics. The AJOT Authors & Issues interview series and an active presence on social media platforms further bolster research engagement and translation. Despite challenges, AJOT's impact factor and rankings in the rehabilitation category have demonstrated its global influence and leadership. The journal's commitment to diversity, equity, and inclusion (DEI) is evident through initiatives such as AJOT's DEI Committee and DEI article collection, as well as AJOT's comprehensive approach to combating bias. As AJOT looks ahead to 2024, its goals include reviving State of the Science articles, updating our Author Guidelines to incorporate artificial intelligence and bias-free language policies, and fostering engagement through the AJOT Instagram account and monthly AJOT Authors & Issues discussions. With its dedication to rigorous research and meaningful translation, AJOT remains a crucial resource for occupational therapy professionals striving to make evidence-based decisions.


Resumption of Sport at the United States Olympic and Paralympic Training Facilities During the COVID-19 Pandemic.
In this brief report, we describe the safety of reopening US Olympic and Paralympic Training facilities (USOPTFs) during the coronavirus disease 2019 (COVID-19) pandemic from July 2020 through October 2020. We evaluated the prevalence of COVID-19 infection at the time of reentry and cardiopulmonary sequelae of COVID-19 in elite athletes. All athletes returning to a USOPTF were required to go through a reentry protocol consisting of an electronic health history, a 6-day quarantine including twice-daily symptom surveys, COVID-19 polymerase chain reaction and antibody testing, physical examination, 12-lead electrocardiogram, high-sensitivity cardiac troponin I, and pulmonary function testing. Athletes with current or prior COVID-19 infection also underwent an echocardiogram, cardiology consultation, and additional testing as indicated. All athletes followed rigorous infection prevention measures and minimized contact with the outside community following reentry. At the time of this report, 301 athletes completed the reentry protocol among which 14 (4.7%) tested positive for active (positive polymerase chain reaction test, n = 3) or prior (positive antibody test, n = 11) COVID-19 infection. During the study period, this cohort accrued 14,916 days living and training at USOPTFs. Only one (0.3%) athlete was subsequently diagnosed with a new COVID-19 infection. No cardiopulmonary pathology attributable to COVID-19 was detected. Our findings suggest that residential elite athlete training facilities can successfully resume activity during the COVID-19 pandemic when strict reentry and infection prevention measures are followed. Dissemination of our reentry quarantine and screening protocols with COVID-19 mitigation measures may assist the global sports and medical community develop best practices for reopening of similar training centers.


[Effect of phenylcarboxylic acids on phagocytic activity of neutrophils].
Neutrophylic phagocytosis is affected by a lot of factors, including phenylcarboxylic acids secreted by bacteria into blood to protect from phagocytosis. The paper describes the most likely mechanism of inhibiting action of these acids, which is associated with the formation of strong pi-complexes between the pi-bonds of the molecular benzene ring of the acids and pi-bonds of unsaturated fatty acid molecules of the neutrophilic membrane. This fact was used to calculate the minimum inhibitory concentration of an acid and to show that there may be saturation in inhibition from the concentration. The experiment wherein the acids were added to blood at varying concentrations has confirmed the inhibitory effect of the acids, as well as saturation. Data processing indicates the unifactor inhibition of phagocytosis and confirms the postulated exponential inhibition at acid concentrations of to about 10(-7) mole/l. There is saturation with further acid concentration increases and there is a further reduced phagocytosis due to the influence of pH at a concentration of more than 10(-5) mole/l.


Cancer patient and staff perceptions of caring and clinical care in free versus forced choice response formats.
Two questions were investigated: whether cancer patients (n = 32) and staff (n = 30) have different cognitive representations of the concepts 'caring' (Swedish: 'omvårdnad') and 'clinical care' (Swedish: 'vård'), and whether results differ between forced vs. free choice response formats. Two Swedish versions of the CARE-Q instrument were used: (i) a CARE-Q sorting (forced format) and (ii) a CARE-Questionnaire (free format). Four groups of patients and 4 groups of staff completed (i) the forced format/caring, (ii) the forced format/clinical care, (iii) the free format/caring and (iv) the free format/clinical care versions, respectively. Participants were asked to rank the importance of 50 CARE-Q behaviours for the specific method/concept combination. Results demonstrated that neither patients nor staff, to any great extent, valued CARE-Q subscales differently when regarded as examples of 'caring' vs. 'clinical care'. Further, the free vs. forced choice format did not influence patient and staff perceptions of the importance of CARE-Q subscales, except that both groups gave higher values to all subscales in the free choice response format. The assumptions that different cognitive representations of the concepts or the response formats had affected previous CARE-Q results were not substantiated.


The role of nitric oxide and protein kinase C in lipopolysaccharidemediated vascular hyporeactivity.
Overactivation of nitric oxide and protein kinase C (PKC) pathway has been reported to play a role in the pathogenesis of vascular hyporesponsiveness of endotoxic shock. In this study we investigated the role of nitric oxide and PKC in lipopolysaccharide (LPS) mediated vascular hyporeactivity. Contraction to phenylephrine and endothelium-dependent and independent vasodilation in the presence and absence of a nonspecific NO inhibitor (L-NAME) and potent PKC inhibitor (chelerythrine) were examined. In LPS treated rats, contractile response of aortic rings to phenylephrine and relaxation in response to acetylcholine were reduced, but relaxation induced by sodium nitroprusside remained unchanged. The attenuation of contractile response to phenylephrine in the presence of L-NAME and chelerythrine was more pronounced in aortic ring isolated from LPS treated rats than control. L-NAME decreased acetylcholine -dependent vasodilation in both group but it was more pronounced in LPS treated rats. Chelerythrine pretreatment improved maximal relaxation to acetylcholine in aortic ring isolated from LPS treated rats. These data indicate that the vascular hyporesponsiveness to phenylephrine and acetylcholine after treatment with LPS may be related to an enhanced NO production in the smooth muscle cells and PKC plays a role as an intracellular mediator of LPS-induce NOS activity and vascular suppression.


Coupled IL-2-dependent extracellular feedbacks govern two distinct consecutive phases of CD4 T cell activation.
T cells integrate cell-specific Ag receptor signaling with shared signals mediated by secreted cytokines, which often involve regulatory feedback loops. IL-2 signaling, for example, reduces the synthesis of IL-2 and increases the synthesis of IL-2Rα-chain, whereas both genes require TCR signaling for their activation. The ways by which T cells dynamically integrate these private and public signals during activation are not well understood. We combined robotics, multiparameter flow cytometry, and real-time quantitative PCR to analyze T cell activation at high temporal resolution over several days. Two distinct temporal phases of T cell activation were evident. First, Ag-dependent signals activated low IL-2Rα and high IL-2 production, independent of IL-2 signaling. Subsequently, secreted IL-2 acted as a shared resource driving high IL-2Rα expression, reduced IL-2 synthesis, and cell proliferation. This transition was independent of continued TCR signaling. Our data allowed the determination of the parameters of the IL-2-mediated extracellular positive and negative feedback circuits and demonstrated that the two loops are coupled and become activated at a similar level of IL-2 signaling. We propose that temporal separation of private and shared signals allows T cells to first integrate Ag-specific responses and subsequently share information leading to collective decision making.


Contrast gain control and retinogeniculate communication.
Visual information processed in the retina is transmitted to primary visual cortex via relay cells in the lateral geniculate nucleus (LGN) of the dorsal thalamus. Although retinal ganglion cells are the primary source of driving input to LGN neurons, not all retinal spikes are transmitted to the cortex. Here, we investigate the relationship between stimulus contrast and retinogeniculate communication and test the hypothesis that both the time course and strength of retinogeniculate interactions are dynamic and dependent on stimulus contrast. By simultaneously recording the spiking activity of synaptically connected retinal ganglion cells and LGN neurons in the cat, we show that the temporal window for retinogeniculate integration and the effectiveness of individual retinal spikes are inversely proportional to stimulus contrast. This finding provides a mechanistic understanding for the phenomenon of augmented contrast gain control in the LGN-a nonlinear receptive field property of LGN neurons whereby response gain during low-contrast stimulation is enhanced relative to response gain during high-contrast stimulation. In addition, these results support the view that network interactions beyond the retina play an essential role in transforming visual signals en route from retina to cortex.


[Fiber in enteral nutrition: systematic review of the literature].
It has been suggested that adding fibre to enteral nutrition (EN) formulas may achieve a normalization of the gastrointestinal tract's functions by reducing the incidence of diarrhoea and constipation. However, this supposition is based on the demonstrated effect of fibre in natural feeding. There have so far been no firm recommendations on the use, amount or type of fibre that is most advisable in EN. To establish the scientific evidence existing on the benefits gained by adding fibre to EN formulas compared with the use of fibre-free formulas. Bibliographical search on PubMed, on the register of Randomized Prospective Trials (RPT) of the Cochrane Library and manual search. RPT comparing fibre-free formulas with isocaloric ad isonitrogen formulas containing fibre in total EN. Four independent reviewers revised the references selected. The data were analyzed using the RevMan 4.1 programme from the Cochrane Library. Of 286 references, 25 fulfilled the inclusion criteria. The data were grouped by population and outcome variable. The addition of fermentable fibre to the EN formulas tends to reduce the incidence of diarrhoea in critically-ill and post-surgery patients (OR = 0.66; 95% CI 0.46-0.95; p = 0.19). The use of formulas with insoluble fibre seems to increase the frequency of depositions and reduce the need for laxatives in immobilized patients receiving long-term EN but the data are insufficient. In people with normal gastrointestinal functions, the frequency of depositions is similar when using formulas with and without fibre (DPM = -0.97; 95% CI -0.12-[-0.02]; p < 0.0001). There is currently insufficient evidence to recommend the systematic use of formulas containing fibre in total EN. However, in critically-ill and post-surgery patients, the use of formulas with fermentable fibre tends to reduce the incidence of diarrhoea. Although information is still lacking. The formulas with insoluble fibre seem to diminish constipation in chronic EN, whereas in other situations where the digestive system is working appropriately, no benefit has been shown. It is necessary to increase the number and quality of these trials in order to be able to establish firm recommendations on the use of EN formulas containing fibre.


High resolution photon time-tagging lidar for atmospheric point cloud generation.
The application of time-correlated single photon counting hardware and techniques to atmospheric lidar is presented. The results establish the viability of adapting photon time-tagging techniques to atmospheric lidar systems, facilitating high-range resolution (millimeter-level precision) and dynamic system observing capabilities that address the variety of atmospheric scatterers often present in atmospheric lidar profiles. The technique is demonstrated through measurements made by a high repetition rate, low pulse energy, elastic scattering, photon counting lidar. Detection probabilities with a non-zero system dead-time are derived and tested using acquired data. Atmospheric point cloud generation and the statistical implications on data retrievals utilizing this approach are presented. The results show an ability to preserve backscattered intensities while generating photon detections at picosecond resolution from a variety atmospheric scatterers.


Feasibility of intraoperative corneal topography monitoring during photorefractive keratectomy.
We propose a feasibility study of new corneal topography technology with the aim of monitoring intraoperative corneal topography during excimer laser photorefractive keratectomy. The PAR system measures corneal topography with single grid projection and triangulation but requires fluorescent fluid to be deposited on the corneal surface for shape extraction. We propose and demonstrate a novel corneal topography system based on structured incoherent visible light projection and triangulation that does not require addition of fluorescent fluid. We used a binary liquid crystal spatial light modulator to display multiple fringe patterns onto the cornea. The depth accuracy of the corneal topography system was measured using a white reflected test sphere mounted on a micrometer translation stage. The performance of the corneal topography system was tested on 5 de-epithelialized swine eyes in vitro ablated with a VISX excimer laser. Depth accuracy on the test sphere was 0.5+/-0.75 microm over an area of 17.6 mm2. On de-epithelialized swine corneas, ablation at the apex of the cornea treated with an excimer laser was measured without addition of fluorescein. This new corneal topography system achieved an adequate level of accuracy on a test sphere.


Calibrated Link Budget of a Silicon Photonics WDM Transceiver with SOA and Semiconductor Mode-Locked Laser.
Based on the single channel characterization of a Silicon Photonics (SiP) transceiver with Semiconductor Optical Amplifier (SOA) and semiconductor Mode-Locked Laser (MLL), we evaluate the optical power budget of a corresponding Wavelength Division Multiplexed (WDM) link in which penalties associated to multi-channel operation and the management of polarization diversity are introduced. In particular, channel cross-talk as well as Cross Gain Modulation (XGM) and Four Wave Mixing (FWM) inside the SOA are taken into account. Based on these link budget models, the technology is expected to support up to 12 multiplexed channels without channel pre-emphasis or equalization. Forward Error Correction (FEC) does not appear to be required at 14 Gbps if the SOA is maintained at 25 °C and MLL-to-SiP as well as SiP-to-SOA interface losses can be maintained below 3 dB. In semi-cooled operation with an SOA temperature below 55 °C, multi-channel operation is expected to be compatible with standard 802.3bj Reed-Solomon FEC at 14 Gbps provided interface losses are maintained below 4.5 dB. With these interface losses and some improvements to the Transmitter (Tx) and Receiver (Rx) electronics, 25 Gbps multi-channel operation is expected to be compatible with 7% overhead hard decision FEC.


Diabetes and impaired fasting glycemia in a rural population of Bangladesh.
To determine the prevalence of type 2 diabetes and impaired fasting glycemia (IFG) in a rural population of Bangladesh. A cluster sampling of 4,923 subjects >/=20 years old in a rural community were investigated. Fasting plasma glucose, blood pressure, height, weight, and girth of waist and hip were measured. BMI and waist-to-hip ratio (WHR) were calculated. Total cholesterol, triglycerides, and HDL cholesterol were also estimated. We used the 1997 American Diabetes Association diagnostic criteria. The crude prevalence of type 2 diabetes was 4.3% and IFG was 12.4%. The age-standardized prevalence of type 2 diabetes (95% CI) was 3.8% (3.12-4.49) and IFG was 13.0% (11.76-14.16). The subjects with higher family income had significantly higher prevalence of type 2 diabetes (5.9 vs. 3.5%, P < 0.001) and IFG (15.6 vs. 10.8%, P < 0.001) than those with lower income. Employing logistic regression in different models, we found that wealthy class, family history of diabetes, reduced physical exercise, and increased age, BMI, and WHR were the important predictors of diabetes. Total cholesterol, triglycerides, and HDL cholesterol showed no association with diabetes and IFG. The prevalence of diabetes and IFG in the rural population was found to be on the increase compared with the previous reports of Bangladesh and other Asian studies. Older age, higher obesity, higher income, family history of diabetes, and reduced physical activity were proved significant risk factors for diabetes and IFG, whereas plasma lipids showed no association with diabetes and IFG. Further study may address whether diabetes is causally associated with insulin deficiency or insulin resistance.


Does daily nurse staffing match ward workload variability? Three hospitals' experiences.
Nurse shortage and rising healthcare resource burdens mean that appropriate workforce use is imperative. This paper aims to evaluate whether daily nursing staffing meets ward workload needs. Nurse attendance and daily nurses' workload capacity in three hospitals were evaluated. Statistical process control was used to evaluate intra-ward nurse workload capacity and day-to-day variations. Statistical process control is a statistics-based method for process monitoring that uses charts with predefined target measure and control limits. Standardization was performed for inter-ward analysis by converting ward-specific crude measures to ward-specific relative measures by dividing observed/expected. Two charts: acceptable and tolerable daily nurse workload intensity, were defined. Appropriate staffing indicators were defined as those exceeding predefined rates within acceptable and tolerable limits (50 percent and 80 percent respectively). A total of 42 percent of the overall days fell within acceptable control limits and 71 percent within tolerable control limits. Appropriate staffing indicators were met in only 33 percent of wards regarding acceptable nurse workload intensity and in only 45 percent of wards regarding tolerable workloads. The study work did not differentiate crude nurse attendance and it did not take into account patient severity since crude bed occupancy was used. Double statistical process control charts and certain staffing indicators were used, which is open to debate. Wards that met appropriate staffing indicators prove the method's feasibility. Wards that did not meet appropriate staffing indicators prove the importance and the need for process evaluations and monitoring. Methods presented for monitoring daily staffing appropriateness are simple to implement either for intra-ward day-to-day variation by using nurse workload capacity statistical process control charts or for inter-ward evaluation using standardized measure of nurse workload intensity. The real challenge will be to develop planning systems and implement corrective interventions such as dynamic and flexible daily staffing, which will face difficulties and barriers. The paper fulfils the need for workforce utilization evaluation. A simple method using available data for daily staffing appropriateness evaluation, which is easy to implement and operate, is presented. The statistical process control method enables intra-ward evaluation, while standardization by converting crude into relative measures enables inter-ward analysis. The staffing indicator definitions enable performance evaluation. This original study uses statistical process control to develop simple standardization methods and applies straightforward statistical tools. This method is not limited to crude measures, rather it uses weighted workload measures such as nursing acuity or weighted nurse level (i.e. grade/band).


Trichothiodystrophy causative TFIIEβ mutation affects transcription in highly differentiated tissue.
The rare recessive developmental disorder Trichothiodystrophy (TTD) is characterized by brittle hair and nails. Patients also present a variable set of poorly explained additional clinical features, including ichthyosis, impaired intelligence, developmental delay and anemia. About half of TTD patients are photosensitive due to inherited defects in the DNA repair and transcription factor II H (TFIIH). The pathophysiological contributions of unrepaired DNA lesions and impaired transcription have not been dissected yet. Here, we functionally characterize the consequence of a homozygous missense mutation in the general transcription factor II E, subunit 2 (GTF2E2/TFIIEβ) of two unrelated non-photosensitive TTD (NPS-TTD) families. We demonstrate that mutant TFIIEβ strongly reduces the total amount of the entire TFIIE complex, with a remarkable temperature-sensitive transcription defect, which strikingly correlates with the phenotypic aggravation of key clinical symptoms after episodes of high fever. We performed induced pluripotent stem (iPS) cell reprogramming of patient fibroblasts followed by in vitro erythroid differentiation to translate the intriguing molecular defect to phenotypic expression in relevant tissue, to disclose the molecular basis for some specific TTD features. We observed a clear hematopoietic defect during late-stage differentiation associated with hemoglobin subunit imbalance. These new findings of a DNA repair-independent transcription defect and tissue-specific malfunctioning provide novel mechanistic insight into the etiology of TTD.


Influence of low linoleic and linolenic acids in milk replacer on calf performance and lipids in blood plasma, heart, and liver.
In a 6-wk study with 3-d-old calves (n = 32), we compared effects of low or adequate essential fatty acids in milk replacers on calf performance, feed utilization, and fatty acids in blood plasma, heart, and liver lipids. Four dietary treatments were hydrogenated coconut oil, as low-essential fatty acid basal; basal plus linoleic acid; basal plus linoleic plus linolenic acids; tallow control. None of the calves fed low essential fatty acid diet developed any external deficiency signs seen in monogastric animals. Supplementation of basal diet with essential fatty acids had no influence on weight gains, feed efficiency, or digestibility of lipids, nitrogen, and dry matter. Effects of low essential fatty acid intake were decreased resistance of erythrocytes to lysis, and in tissue lipids, marked reduction of linoleic acid and elevation of trienoic acid, palmitoleic acid, and ratio of trienoic acid to arachidonic acid, all indicative of low essential fatty acid status. Essential fatty acid intake in milk replacer may be more important than indicated here for longer term vealer calves, and where stresses, such as infectious diseases and high environmental temperature, are present.


A multigenerational effect of parental age on offspring size but not fitness in common duckweed (Lemna minor).
Classic theories on the evolution of senescence make the simplifying assumption that all offspring are of equal quality, so that demographic senescence only manifests through declining rates of survival or fecundity. However, there is now evidence that, in addition to declining rates of survival and fecundity, many organisms are subject to age-related declines in the quality of offspring produced (i.e. parental age effects). Recent modelling approaches allow for the incorporation of parental age effects into classic demographic analyses, assuming that such effects are limited to a single generation. Does this 'single-generation' assumption hold? To find out, we conducted a laboratory study with the aquatic plant Lemna minor, a species for which parental age effects have been demonstrated previously. We compared the size and fitness of 423 laboratory-cultured plants (asexually derived ramets) representing various birth orders, and ancestral 'birth-order genealogies'. We found that offspring size and fitness both declined with increasing 'immediate' birth order (i.e. birth order with respect to the immediate parent), but only offspring size was affected by ancestral birth order. Thus, the assumption that parental age effects on offspring fitness are limited to a single generation does in fact hold for L. minor. This result will guide theorists aiming to refine and generalize modelling approaches that incorporate parental age effects into evolutionary theory on senescence.


Physical and transcript map of the autosomal dominant colobomatous microphthalmia locus on chromosome 15q12-q15 and refinement to a 4.4 Mb region.
Congenital microphthalmia is a developmental disorder characterized by shortened axial length of the eye. We have previously mapped the gene responsible for autosomal dominant colobomatous microphthalmia in a 5-generation family to chromosome 15q12-q15. Here, we set up a physical and transcript map of the 13.8 cM critical region, flanked by loci D15S1002 and D15S1040. Physical mapping and genetic linkage analysis using 20 novel polymorphic markers allowed the refinement of the disease locus to two intervals in close vicinity, namely a centromeric interval, bounded by microsatellite DNA markers m3-m17, and a telomeric interval, m76-m24, encompassing respectively 1.9 and 2.5 Mb. Moreover, we excluded three candidate genes, CKTSF1B1, KLF13 and CX36. Finally, although a phenomenon of anticipation was suggested by phenotypic and pedigree data, no abnormal expansion of three trinucleotide repeats mapping to the refine interval was found in affected individuals.


Molecular detection of fungal communities in the Hawaiian marine sponges Suberites zeteki and Mycale armata.
Symbiotic microbes play a variety of fundamental roles in the health and habitat ranges of their hosts. While prokaryotes in marine sponges have been broadly characterized, the diversity of sponge-inhabiting fungi has barely been explored using molecular approaches. Fungi are an important component of many marine and terrestrial ecosystems, and they may be an ecologically significant group in sponge-microbe interactions. This study tested the feasibility of using existing fungal primers for molecular analysis of sponge-associated fungal communities. None of the eight selected primer pairs yielded satisfactory results in fungal rRNA gene or internal transcribed spacer (ITS) clone library constructions. However, 3 of 10 denaturing gradient gel electrophoresis (DGGE) primer sets, which were designed to preferentially amplify fungal rRNA gene or ITS regions from terrestrial environmental samples, were successfully amplified from fungal targets in marine sponges. DGGE analysis indicated that fungal communities differ among different sponge species (Suberites zeteki and Mycale armata) and also vary between sponges and seawater. Sequence analysis of DGGE bands identified 23 and 21 fungal species from each of the two sponge species S. zeteki and M. armata, respectively. These species were representatives of 11 taxonomic orders and belonged to the phyla of Ascomycota (seven orders) and Basidiomycota (four orders). Five of these taxonomic orders (Malasseziales, Corticiales, Polyporales, Agaricales, and Dothideomycetes et Chaetothyriomcetes incertae sedis) have now been identified for the first time in marine sponges. Seven and six fungal species from S. zeteki and M. armata, respectively, are potentially new species because of their low sequence identity (< or =98%) with their references in GenBank. Phylogenetic analysis indicated sponge-derived sequences were clustered into "marine fungus clades" with those from other marine habitats. This is the first report of molecular analysis of fungal communities in marine sponges, adding depth and dimension to our understanding of sponge-associated microbial communities.


The impact of a planned health education approach on the control of hypertension in a high risk population.
This paper reports on the effectiveness of a planned health education programme on enhancing the control of hypertension in a community demonstrating the highest rates of high blood pressure, cerebrovascular disease, and diseases of the heart in the State of Maryland. Within the community intervention programme, a specific focus was directed at younger black males (ages 18-49) who demonstrated the lowest rates of awareness, treatment, and control for their hypertension, as compared to all other age/race/sex groups. The programme consisted of targeted screenings, outreach, and follow-up; influencing specific health beliefs regarding diagnosis and treatment; and family and community support strategies. Formally trained community health workers provided educational counselling, monitoring, outreach and follow-up services in coordination with a community-wide health provider task force. Results to date indicate that this planned health education approach has been successful in significantly improving the control of hypertension in a high-risk population.


Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: a novel role for the cAMP pathway.
The interleukin-12 (IL-12) cytokine family plays important roles in the orchestration of innate and adaptive immunity by dendritic cells (DCs). The regulation of IL-12 expression has been thoroughly studied, but little is known about factors governing the expression of IL-23 and IL-27, 2 novel IL-12 family members acting on memory and naive T cells, respectively. We report that the expression of these cytokines by DCs was critically dependent on the mode of activation. DC activation by CD40L predominantly induced IL-12. Ligands of the Toll-like receptor (TLR) 3 and TLR4 induced IL-12 and IL-27, whereas exposure to intact Escherichia coli resulted in high expression of IL-12, IL-27, and IL-23. The nucleotide adenosine triphosphate (ATP) has been shown to inhibit IL-12 production by P2 receptors. We found that ATP also inhibited IL-27 expression but enhanced IL-23 expression. Interestingly, the reciprocal regulation of IL-12/IL-27 and IL-23 by ATP was mediated by 2 distinct P2 receptors and was also induced by prostaglandin E(2) by cyclic adenosine monophosphate (cAMP)-elevating EP2/EP4 receptors. As a consequence, DCs were selectively impaired in their ability to induce interferon-gamma (IFN-gamma) in naive T cells but continued to promote IFN-gamma and IL-17 production in memory T cells. These studies identify P2 receptors as promising targets for the design of novel strategies to manipulate specific stages of T-cell responses and to treat IL-12- and IL-23-mediated disorders.


[The health condition of workers of enterprises with different level of ecological pollution].
The article considers the functional conditions of organism of workers depending on the location of enterprise. The dependencies of values of indicators of functional conditions and health on different enterprises from ecological pollution of their locations are established The subjective opinion of workers concerning their health conditions and capacity for work was found out. The relationship between workers' morbidity and percentage of persons systematically engaged in physical training is determined. The prospective decrease of morbidity of workers of enterprises was calculated for case of 100% coverage of all working persons with physical training


Dermoscopy in China: current status and future prospective.
Dermoscopy is a useful technique for improving the diagnostic accuracy of various types of skin disorders. In China, dermoscopy has been widely accepted, and domestic researchers have made tremendous progress in the field of dermoscopy. The main purpose of this review is to summarize the current status of dermoscopy in China and identify its future directions. Articles included in this review were obtained by searching the following databases: Wanfang, China National Knowledge Infrastructure, PubMed, and the Web of Science. We focused on research published before 2019 with keywords including dermoscopy, dermoscopic, dermoscope and trichoscopy. A total of 50 studies were selected. Of these studies, 20 studies were in Chinese and 30 in English, research samples of all the studies were collected from Chinese populations. Since 2000, more than 380 articles about dermoscopy have been published in domestic or foreign journals. Dermoscopy can improve the diagnostic accuracy of neoplastic diseases, evaluating the therapeutic effect of treatment, and determining the treatment endpoint, and it can also assist in the differential diagnosis of inflammatory diseases and in the assessment of the severity of the disease. In addition, researches about the applications of dermoscopy during surgical treatment have been published. Training courses aiming to improve the diagnostic ability of dermatologists, either face-to-face or online, have been offered. The Chinese Skin Image Database, launched in 2017 as a work platform for dermatologists, has promoted the development of dermoscopy in China. Computer-aided diagnostic systems based on the Chinese population are ready for use. In the future, cooperation, resource sharing, talent development, image management, and computer-aided diagnosis will be important directions for the development of dermoscopy in China. Dermoscopy has been widely used and developed in China, however, it still needs to address more challenges in the future.


Children's exposure to intimate partner violence: Impacts and interventions.
Exposure to intimate partner violence is increasingly being recognized as a form of child maltreatment; it is prevalent, and is associated with significant mental health impairment and other important consequences. The present article provides an evidence-based overview regarding children's exposure to intimate partner violence, including epidemiology, risks, consequences, assessment and interventions to identify and prevent both initial exposure and impairment after exposure. It concludes with specific guidance for the clinician.


Body size and the risk of biliary tract cancer: a population-based study in China.
Though obesity is an established risk factor for gall bladder cancer, its role in cancers of the extrahepatic bile ducts and ampulla of Vater is less clear, as also is the role of abdominal obesity. In a population-based case-control study of biliary tract cancer in Shanghai, China, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for biliary tract cancer in relation to anthropometric measures, including body mass index (BMI) at various ages and waist-to-hip ratio (WHR), adjusting for age, sex, and education. The study included 627 patients with biliary tract cancer (368 gall bladder, 191 bile duct, 68 ampulla of Vater) and 959 healthy subjects randomly selected from the population. A higher BMI at all ages, including early adulthood (ages 20-29 years), and a greater WHR were associated with an increased risk of gall bladder cancer. A high usual adult BMI (>or=25) was associated with a 1.6-fold risk of gall bladder cancer (95% CI 1.2-2.1, P for trend <0.001). Among subjects without gallstones, BMI was also positively associated with gall bladder cancer risk. Regardless of BMI levels, increasing WHR was associated with an excess risk of gall bladder cancer risk, with those having a high BMI (>or=25) and a high WHR (>0.90) having the highest risk of gall bladder cancer (OR=12.6, 95% CI 4.8-33.2), relative to those with a low BMI and WHR. We found no clear risk patterns for cancers of the bile duct and ampulla of Vater. These results suggest that both overall and abdominal obesity, including obesity in early adulthood, are associated with an increased risk of gall bladder cancer. The increasing prevalence of obesity and cholesterol stones in Shanghai seems at least partly responsible for the rising incidence of gall bladder cancer in Shanghai.


Compound A uptake and metabolism to mercapturic acids and 3,3,3-trifluoro-2-fluoromethoxypropanoic acid during low-flow sevoflurane anesthesia: biomarkers for exposure, risk assessment, and interspecies comparison.
Sevoflurane is degraded during low-flow anesthesia to fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether ("compound A"), which causes renal necrosis in rats but is not known to cause nephrotoxicity in surgical patients. Compound A is metabolized to glutathione S-conjugates and then to cysteine S-conjugates, which are N-acetylated to mercapturic acids (detoxication pathway), or metabolized by renal beta-lyase to reactive intermediates (toxification pathway) and excreted as 3,3,3-trifluoro-2-fluoromethoxypropanoic acid. This investigation quantified compound A metabolites in urine after low-flow sevoflurane administration, to assess relative flux via these two pathways. Patients (n = 21) with normal renal function underwent low-flow (11 min) sevoflurane anesthesia designed to maximize compound A formation. Inspiratory, expiratory, and alveolar compound A concentrations were quantified. Urine mercapturic acids and 3,3,3-trifluoro-2-fluoromethoxypropanoic acid concentrations were measured by gas chromatography and mass spectrometry. Sevoflurane exposure was 3.7 +/- 2.0 MAC-h. Inspired compound A maximum was 29 +/- 14 ppm; area under the inspired concentration versus time curve (AUCinsp) was 78 +/- 58 ppm x h. Compound A dose, calculated from pulmonary uptake, was 0.39 +/- 0.35 mmol (4.8 +/- 4.0 micromol/kg) and correlated with AUCinsp (r2 = 0.84, P < 0.001). Mercapturic acids excretion was complete after 2 days, whereas 3,3,3-trifluoro-2-fluoromethoxypropanoic acid excretion continued for 3 days in some patients. Total (3-day) mercapturates and fluoromethoxypropanoic acid excretion was 95 +/- 49 and 294 +/- 416 micromol, respectively (1.2 +/- 0.6 and 3.6 +/- 5.0 micromol/kg). Compound A doses during 3.7 MAC-h, low-flow sevoflurane administration in humans are substantially less than the threshold for renal toxicity in rats (200 micromol/kg). Compound A metabolites quantification may provide a biomarker for compound A exposure and relative metabolism via toxification and detoxication pathways. Compared with previous investigations, relative metabolic flux (fluoromethoxypropanoic acid/mercapturates) through the toxification pathway was sixfold greater in rats than in humans. Species differences in dose and metabolism may influence compound A renal effects.


Phosphorylation-induced activation of the response regulator VraR from Staphylococcus aureus: insights from hydrogen exchange mass spectrometry.
A two-component system consisting of the histidine kinase vancomycin-resistance-associated sensor and the response regulator vancomycin-resistance-associated regulator (VraR) allows Staphylococcus aureus to sense antibiotic-related cell wall stress and to mount a suitable response. An experimental structure of full-length VraR is not available yet, but previous work points to similarities between VraR and the well-characterized NarL. This work employs hydrogen exchange mass spectrometry to gain insights into the phosphorylation-induced activation of VraR, a process that primes the protein for dimerization and DNA binding. Whereas VraR is highly dynamic, phosphorylated VraR shows less extensive deuteration. This rigidification is most dramatic within the receiver domain, which carries the phosphorylation site D55. Alterations in the DNA-binding domain are much less pronounced. Changes in deuteration within the receiver domain are consistent with a Y-T coupling mechanism. In analogy to NarL, the activation of VraR is thought to involve separation and subsequent reorientation of the two domains, thereby allowing the alpha8-turn-alpha9 element to engage in DNA binding. The current work suggests that this structural transition is triggered by a reduction in the effective length of the linker through enhanced hydrogen bonding. In addition, separation of the two domains may be favored by the establishment of noncovalent protein-protein interactions and intradomain contacts at the expense of previously existing interdomain bonds. alpha9 appears to be packed against the receiver domain in nonactivated VraR. Support is presented for alpha1 as a dimerization interface in phosphorylated VraR, whereas protein-protein interactions for nonphosphorylated VraR are impeded by extensive disorder in this region.


Ethics of Clinical Decision-Making for Older Drivers: Reporting Health-Related Driving Risk.
The number of older drivers will continue to increase as the population ages. Health care professionals have the responsibility of providing care and maintaining confidentiality for their patients while ensuring public safety. This article discusses the ethics of clinical decision-making pertaining to reporting health-related driving risk of older drivers to licensing authorities. Ethical considerations inherent in reporting driving risk, including autonomy, confidentiality, therapeutic relationships, and the uncertainty about determining individual driving safety and risk, are discussed. We also address the moral agency of reporting health-related driving risk and raise the question of whose responsibility it is to report. Issues of uncertainty surrounding clinical reasoning and concepts related to risk assessment are also discussed. Finally, we present two case studies to illustrate some of the issues and challenges faced by health care professionals as they seek to balance their responsibilities for their patients while ensuring road safety for all citizens.


Reduced-intensity allogeneic stem cell transplantation for patients whose prior autologous stem cell transplantation for hematologic malignancy failed.
Autologous hematopoietic stem cell transplantation (autoSCT) is an effective treatment for patients with various hematologic malignancies. Despite the significant improvement in the overall outcome, disease progression after transplantation remains the major cause of treatment failure. With longer follow-up, therapy-related myelodysplasia/acute myelogenous leukemia is becoming an important cause of treatment failure. The prognosis for these 2 groups of patients is very poor. Allogeneic hematopoietic stem cell transplantation (alloSCT) is a potential curative treatment for these patients. However, the outcome with conventional myeloablative alloSCT after failed autoSCT is typically poor because of high transplant-related mortality. In an attempt to reduce the treatment-related toxicity, we studied a reduced-intensity conditioning regimen followed by alloSCT for patients with progressive disease or therapy-related myelodysplasia/acute myelogenous leukemia after autoSCT. This report describes the outcomes of 28 patients with hematologic malignancies who received a reduced-intensity alloSCT after having treatment failure with a conventional autoSCT. Fourteen patients received a hematopoietic stem cell transplant from a related donor and 14 from an unrelated donor. The conditioning regimen consisted of low-dose (2 Gy) total body irradiation with or without fludarabine in 4 patients and the combination of melphalan (140 mg/m(2)) and fludarabine in 24. Cyclosporine and mycophenolate mofetil were used for posttransplantation immunosuppressive therapy, as well as graft-versus-host disease (GVHD) prophylaxis, in all patients. All patients engrafted and had >90% donor chimerism on day 100 after SCT. Currently, 13 patients (46%) are alive and disease free, 7 patients (25%) developed disease progression after alloSCT, and 8 (32%) died of nonrelapse causes. Day 100 mortality and nonrelapse mortality were 25% and 21%, respectively. With a median follow-up of 24 months for surviving patients, the 2-year probabilities of overall survival, event-free survival, and relapse rates were 56.5%, 41%, and 41.9%, respectively. Six patients (21%) developed grade III to IV acute GVHD. Among 21 evaluable patients, 15 (67%) developed chronic GVHD. We conclude that (1) reduced-intensity alloSCT is feasible and has an acceptable toxicity profile in patients who have previously received autoSCT and that (2) although follow-up was short, a durable remission may be achieved in some patients who would otherwise be expected to have a poor outcome.


Olfactory sensory axon growth and branching is influenced by sonic hedgehog.
Olfactory sensory neuron (OSN) axons extend from the olfactory epithelium to the olfactory bulb without branching until they reach their target region, the glomerulus. In this report, we present evidence to support the involvement of sonic hedgehog in promoting rat olfactory sensory axons to branch and to enter into the glomerulus. Sonic hedgehog (Shh) protein is detected in the glomeruli of the olfactory bulb, whereas its transcript is expressed in the mitral and tufted cells, suggesting that Shh in the glomeruli is produced by mitral and tufted cells. In primary OSN cultures, Shh-N peptide promotes olfactory axon branching. When Shh function is neutralized in vivo by its antibody, growth of newly generated OSN axons into the glomeruli is vastly reduced.


The relationship of brain-tissue loss volume and lesion location to cognitive deficit.
We examined the relationship of preinjury intelligence, a lesion-severity variable (brain-tissue loss volume), and lesion location to the persistence of cognitive deficits in Vietnam veterans with penetrating brain wounds. Using stepwise multiple linear regression procedures, we found that preinjury intelligence predicted a significant amount of the variance on postinjury cognitive testing, being a better predictor for tests requiring a number of complementary cognitive processes (e.g., intelligence tests) than for tests measuring a specific cognitive process (e.g., face recognition). Brain-tissue volume loss was found to play a larger role when a global cognitive measure was used, but a smaller role when a specific cognitive process was measured. Finally, lesion location was shown to be a significant predictor of performance only for specific cognitive processes. Nevertheless, preinjury intelligence/education appears to play an even larger role in postinjury performance than either brain-tissue loss volume or a particular structural loss.


[Artificially induced suppurative diseases].
128 cases of artificially caused purulent diseases have been analysed. All the cases were masked as chronic septicemia, recurrent abscesses, nonhealing wounds and fever of the unclear origin. The specific features of artificial diseases have been pointed out: social status, occupation, provoking factors, specific clinical signs--multiple hospitalizations, dominating location of postoperative scars and abscesses. Diagnostic principles, including psychological ang psychiatric testing are discussed. The neuro-psychiatric disorders were detected in most cases. Prevention of such diseases is analysed.


Overweight status and eating patterns among adolescents: where do youths stand in comparison with the healthy people 2010 objectives?
This study determined the prevalence of Minnesota urban youths reaching the Healthy People 2010 objectives for obesity and intake of fat, calcium, fruits, vegetables, and grains and compared prevalence rates across sociodemographic characteristics. The study sample included 4746 adolescents (aged 11-18 years) from the Minneapolis/St. Paul area who completed dietary surveys and participated in anthropometric measurements as part of a school-based population study. Considerable gaps were seen between the existing prevalence rates for obesity and nutrient and food patterns and the targeted Healthy People 2010 prevalence rates. For example, 12.5% of the girls and 16.6% of the boys had body mass index values at or greater than the 95th percentile (target = 5%). Only 29.5% of the girls and 42.5% of the boys were meeting the daily recommended intakes for calcium (target = 75%). Similarly, percentages of youths consuming the recommended amounts of fat, fruits, vegetables, and grains were lower than the targeted percentages. There were large sociodemographic disparities in obesity and eating patterns, particularly across race/ethnicity and socioeconomic status. Concerted public health efforts are needed to achieve the Healthy People 2010 objectives for obesity and nutrition and to reduce racial/ethnic and socioeconomic disparities.


Whole-brain multivariate hemodynamic deconvolution for functional MRI with stability selection.
Conventionally, analysis of functional MRI (fMRI) data relies on available information about the experimental paradigm to establish hypothesized models of brain activity. However, this information can be inaccurate, incomplete or unavailable in multiple scenarios such as resting-state, naturalistic paradigms or clinical conditions. In these cases, blind estimates of neuronal-related activity can be obtained with paradigm-free analysis methods such as hemodynamic deconvolution. Yet, current formulations of the hemodynamic deconvolution problem have three important limitations: (1) their efficacy strongly depends on the appropriate selection of regularization parameters, (2) being univariate, they do not take advantage of the information present across the brain, and (3) they do not provide any measure of statistical certainty associated with each detected event. Here we propose a novel approach that addresses all these limitations. Specifically, we introduce multivariate sparse paradigm free mapping (Mv-SPFM), a novel hemodynamic deconvolution algorithm that operates at the whole brain level and adds spatial information via a mixed-norm regularization term over all voxels. Additionally, Mv-SPFM employs a stability selection procedure that removes the need to select regularization parameters and also lets us obtain an estimate of the true probability of having a neuronal-related BOLD event at each voxel and time-point based on the area under the curve (AUC) of the stability paths. Besides, we present a formulation tailored for multi-echo fMRI acquisitions (MvME-SPFM), which allows us to better isolate fluctuations of BOLD origin on the basis of their linear dependence with the echo time (TE) and to assign physiologically interpretable units (i.e., changes in the apparent transverse relaxation ΔR2∗) to the resulting deconvolved events. Remarkably, we demonstrate that Mv-SPFM achieves comparable performance even when using a single-echo formulation. We demonstrate that this algorithm outperforms existing state-of-the-art deconvolution approaches, and shows higher spatial and temporal agreement with the activation maps and BOLD signals obtained with a standard model-based linear regression approach, even at the level of individual neuronal events. Furthermore, we show that by employing stability selection, the performance of the algorithm depends less on the selection of temporal and spatial regularization parameters λ and ρ. Consequently, the proposed algorithm provides more reliable estimates of neuronal-related activity, here in terms of ΔR2∗, for the study of the dynamics of brain activity when no information about the timings of the BOLD events is available. This algorithm will be made publicly available as part of the splora Python package.


Affiliative Parent-Adolescent Bedtime and Waketime Interactions are Associated with Adolescent Sleep.
The current study examined whether evening and morning affiliation (i.e., warmth) and autonomy (i.e., more or less in charge) around sleep routines predicted adolescent sleep on weekdays. Participants were 28 parent (Mage = 43.19; 85.17% mothers) and adolescent (Mage = 12.34 years) dyads who completed the same electronic diaries morning and evening for 10 days, with a total number of 221 nights observed across dyads. Sleep duration and sleep quality were assessed via the Pittsburgh Sleep Diary; degree of affiliation and autonomy around bedtime and waketime routines were assessed with single items on a visual analog scale. Multilevel modeling was utilized to evaluate the effects of more or less affiliation or autonomy on sleep outcomes (i.e., duration and quality) between and within dyads. Across all participants, adolescents who reported more affiliative interactions with their parent around bedtime and waketime slept longer and had better sleep quality at night. Further, when adolescents experienced greater than average affiliative interactions with their parent than was typical for them, they had better sleep quality that night. Adolescent sleep quality and duration were not impacted by whether or not adolescents were in charge of their bedtime and waketime routines. Findings support parents' role in social and emotional security and highlight the importance of affiliative parent interactions around the sleep period for optimal sleep for young adolescents.


Therapeutic Effects of Doxycycline on the Quality of Repaired and Unrepaired Achilles Tendons.
Achilles tendon tears are devastating injuries, especially to athletes. Elevated matrix metalloproteinase (MMP) activity after a tendon injury has been associated with deterioration of the collagen network and can be inhibited with doxycycline (Doxy). Daily oral administration of Doxy will enhance the histological, molecular, and biomechanical quality of transected Achilles tendons. Additionally, suture repair will further enhance the quality of repaired tendons. Controlled laboratory study. Randomized unilateral Achilles tendon transection was performed in 288 adult male Sprague-Dawley rats. The injured tendons were either unrepaired (groups 1 and 2) or surgically repaired (groups 3 and 4). Animals from groups 2 and 4 received Doxy daily through oral gavage, and animals from groups 1 and 3 served as controls (no Doxy). Tendons were harvested at 1.5, 3, 6, and 9 weeks after the injury (n = 18 per group and time point). The quality of tendon repair was evaluated based on the histological grading score, collagen fiber orientation, gene expression, and biomechanical properties. In surgically repaired samples, Doxy enhanced the quality of tendon repair compared with no Doxy ( P = .0014). Doxy had a significant effect on collagen fiber dispersion, but not principal fiber angle. There was a significant effect of time on the gene expression of MMP-3, MMP-9 and TIMP1, and Doxy significantly decreased MMP-3 expression at 9 weeks. Doxy treatment with surgical repair increased the dynamic modulus at 6 weeks but not at 9 weeks after the injury ( P < .001). Doxy also increased the equilibrium modulus and decreased creep strain irrespective of the repair group. Doxy did not have a significant effect on the histology or biomechanics of unrepaired tendons. The findings indicate that daily oral administration of Doxy accelerated matrix remodeling and the dynamic and equilibrium biomechanics of surgically repaired Achilles tendons, although such enhancements were most evident at the 3- to 6-week time points. The inhibition of MMPs at the optimal stage of the repair process may accelerate Achilles tendon repair and improve biomechanical properties, especially when paired with surgical management.


Physical therapists' perceptions of sexual boundaries in clinical practice in the United States.
Physical therapists' perceptions of sexual boundaries in clinic settings in the United States have not been studied. Given the magnitude of potential consequences of sexual boundary violations, examination of this topic is imperative. The purpose of this study was to describe the perceptions of sexual boundaries among licensed physical therapists in the United States. Licensed physical therapists from Arkansas, Kansas, Maine, Ohio, and Oregon were contacted by email and asked to complete a sexual boundaries questionnaire via Survey Monkey™; 967 surveys (7.3%) were returned. While most physical therapists practice within the profession's Code of Ethics, there are practitioners who date current and former patients, and condone patients' sexual banter in the clinic. Almost half (42%) of the participants acknowledged feeling sexually attracted to a patient. While gender differences were seen throughout the analyses, generally, the demographic and professional variables did not account for meaningful variance. Results were similar to previous research on physiotherapists in other countries. Sexuality is part of the physical therapy practice environment and physical therapists' understanding of sexual boundaries is ambiguous. These data can inform professional conversation on sexual boundaries in physical therapy practice leading to greater understanding and decreased potential for violations.


Maternal genetic risk for depression and child human capital.
We here address the causal relationship between the maternal genetic risk for depression and child human capital using UK birth-cohort data. We find that an increase of one standard deviation (SD) in the maternal polygenic risk score for depression reduces their children's cognitive and non-cognitive skill scores by 5 to 7% of a SD throughout adolescence. Our results are robust to a battery of sensitivity tests addressing, among others, concerns about pleiotropy and dynastic effects. Our Gelbach decomposition analysis suggests that the strongest mediator is genetic nurture (through maternal depression itself), with genetic inheritance playing only a marginal role.


The hazardous effects of tobacco smoking on male fertility.
The substantial harmful effects of tobacco smoking on fertility and reproduction have become apparent but are not generally appreciated. Tobacco smoke contains more than 4000 kinds of constituents, including nicotine, tar, carbonic monoxide, polycyclic aromatic hydrocarbons, and heavy metals. Because of the complexity of tobacco smoke components, the toxicological mechanism is notably complicated. Most studies have reported reduced semen quality, reproductive hormone system dysfunction and impaired spermatogenesis, sperm maturation, and spermatozoa function in smokers compared with nonsmokers. Underlying these effects, elevated oxidative stress, DNA damage, and cell apoptosis may play important roles collaboratively in the overall effect of tobacco smoking on male fertility. In this review, we strive to focus on both the phenotype of and the molecular mechanism underlying these harmful effects, although current studies regarding the mechanism remain insufficient.


A high frequency of germline BRCA1/2 mutations in western Sweden detected with complementary screening techniques.
Dominant inheritance is presumed in 6-10% of breast and ovarian cancers. Mutations in BRCA1 and BRCA2 genes are the most commonly identified causative genes in such families. The frequency of mutation carriers with breast/ovarian cancer depends on the population studied, and display considerable variation that coincides with ethnic and geographical diversity. Mutation analyses were performed in 143 families registered at the Cancer Genetic Counseling Clinic of western Sweden. In a thorough mutation screening procedure, the entire BRCA1 and BRCA2 genes were analyzed using a combination of complementary mutation detection techniques. Mutations in either BRCA1 or BRCA2 were detected in 36% (52 out of 143) of all screened families. All families were clinically evaluated regarding age at diagnosis, type of cancer and number of cancer cases in the family. Among high-risk families, the mutation detection rate was 39% (46 out of 117). The detection rate observed among families with cases of ovarian cancer (42 out of 62, 68%), was substantially higher than in families with only breast cancer (10 out of 81, 12%). Age at ovarian cancer did not seem to have an effect on the detection rate. The analyses revealed 11 frameshift mutations, 4 nonsense mutations and 2 large deletions. Notably, the BRCA1 c.3171ins5 mutation accounted for 34 of 52 (65%) identified mutations. Seven mutations are novel: BRCA1c.409_410del; c.1912T>G; c.2228_2229del; c.3029delA; c.3433delA, a large deletion covering exons 1-3 of BRCA1and one BRCA2 mutation; BRCA2c.6287_6290del. We have shown that the founder mutation BRCA1 c.3171ins5 has a great influence on western Swedish breast/ovarian cancer families along with a high number of mutations unique for the region. In order to achieve a high mutation detection rate we suggest a combination of several detection techniques.


Histamine H2 antagonists and the nervous system.
In extensive clinical trials, both cimetidine and ranitidine appeared free of central nervous system side effects. The potential for neurologic complications became apparent only after these drugs had been subjected to the test of general use. The incidence of side effects is generally low, but in the elderly and in patients with renal or hepatic failure, both of these drugs can produce confusional states. Ranitidine may also cause severe headache.