King-Devick Test Reliability in National Collegiate Athletic Association Athletes: A National Collegiate Athletic Association-Department of Defense Concussion Assessment, Research and Education Report.
The King-Devick (KD) test has received considerable attention in the literature as an emerging concussion assessment. However, important test psychometric properties remain to be addressed in large-scale independent studies. To assess (1) test-retest reliability between trials, (2) test-retest reliability between years 1 and 2, and (3) reliability of the 2 administration modes. Cross-sectional study. Collegiate athletic training facilities. A total of 3248 intercollegiate student-athletes participated in year 1 (male = 55.3%, age = 20.2 ± 2.3 years, height = 1.78 ± 0.11 m, weight = 80.7 ± 21.0 kg) and 833 participated in both years. Time, in seconds, to complete the KD error free. The KD test reliability was assessed between trials and between annual tests over 2 years and stratified by test modality (spiral-bound cards [n = 566] and tablet [n = 264]). The KD test was reliable between trials (trial 1 = 43.2 ± 8.3 seconds, trial 2 = 40.8 ± 7.8 seconds; intraclass correlation coefficient [ICC] (2,1) = 0.888, P < .001), between years (year 1 = 40.8 ± 7.4 seconds, year 2 = 38.7 ± 7.7 seconds; ICC [2,1] = 0.827, P < .001), and for both spiral-bound cards (ICC [2,1] = 0.834, P < .001) and tablets (ICC [2,1] = 0.827, P < .001). The mean change between trials for a single test was -2.4 ± 3.8 seconds. Although most athletes improved from year 1 to year 2, 27.1% (226 of 883) of participants demonstrated worse (slower) KD times (3.2 ± 3.9 seconds) in year 2. The KD test was reliable between trials and years and when stratified by modality. A small improvement of 2 seconds was identified with annual retesting, likely due to a practice effect; however, 27% of athletes displayed slowed performance from year 1 to year 2. These results suggest that the KD assessment was a reliable test with modest learning effects over time and that the assessment modality did not adversely affect baseline reliability.


Toward osteomimetic formation of calcium phosphate coatings with carbonated hydroxyapatite.
Biomimetic production of coatings on various types of scaffolds is based mainly on simulated body fluid precipitation (SBF) of apatites, or, if the HCO3- is present, carbonated apatites. Recently, we proposed formation of calcium phosphates (CaP) precipitates by alkaline phosphatase (ALP) hydrolysing glycerophosphate in presence of calcium ions as an alternative to SBF. Since apatites synthesized in bone by the ALP activity contain carbonate anions, it was tempting to investigate whether the phosphatase method could be advanced into osteomimetic one. Therefore, taking example from the SBF studies, phosphatase incubation medium was enriched with carbonate ions at 4.2 and 27 mM concentration. X-ray diffraction of the precipitates disclosed peaks typical for hydroxyapatite (HAP). FTIR analysis showed that at both concentration of carbonate ions, apatites underwent both B and A substitution, more extensive at higher concentration. Thus, osteomimetic approach produced carbonated hydroxyapatites of the type encountered in bone tissue even at HCO3- concentration as low as 4.2 mM. Composite plates made of poly(ε-caprolactone) and mixture of β-tricalcium phosphate and hydroxyapatite at mass ratio of 1:0.5:0.5, respectively, were covered by CaP coatings, i.e., CaP-0, CaP-4.2, CaP-27, by incubation in phosphatase medium containing 0, 4.2 or 27 mM of NaHCO3, respectively. Pristine or coated PCL50 plates were used to study release of calcium and adsorption/desorption of proteins, or seeded with human bone marrow mesenchymal stem cells (hMSC) for study of cell adhesion, spreading and osteogenic differentiation. Introduction of carbonate into the CaP coatings significantly increased release of Ca2+ in a carbonate concentration-dependent manner; the release was up to 4 times higher, when compared to CaP-0 coating, and reached 0.41 ± 0.01 mM for CaP-27 after first 24 h. Coating CaP-4.2 yielded significantly higher adsorption of bovine serum albumin and cytochrome C than CaP-0. All of the CaP coatings improved significantly hMSC adhesion, however, only CaP-4.2 provided 2 times higher cell number than PCL50 after 2 weeks of culture. Interestingly, ALP activity calculated per cell number was the highest on pristine plates, presumably because hMSC differentiate preferentially into osteoblasts at lower seeding densities. It appears, therefore, that the osteomimetic approach may be useful for production of carbonated hydroxyapatite coatings, but requires further studies and replacing intestinal phosphatase used in this work with one originating from bone.


Tertiary lymphoid structures show infiltration of effective tumor-resident T cells in gastric cancer.
Several studies have reported that tissue-resident memory T cells (TRM cells) or tertiary lymphoid structures (TLSs) are associated with a good prognosis. The aim of this study was to clarify the association of TRM cells and TLSs in the tumor immune microenvironment in gastric cancer (GC). We performed immunohistochemical and immunofluorescence staining to detect the presence of CD103+ T cells and to assess the association between CD103+ T cells and TLSs. CD103+ T cells were observed in the tumor epithelium accompanied by CD8+ T cells and were associated with a better prognosis in GC. Furthermore, CD103+ T cells were located around TLSs, and patients with CD103high had more rich TLSs. Patients who had both CD103high cells and who were TLS-rich had a better prognosis than patients with CD103low cells and who were TLS-poor. Moreover, for patients who received PD-1 blockade therapy, CD103high and TLS-rich predicted a good response. Flow cytometry was performed to confirm the characteristics of CD103+ CD8+ T cells and showed that CD103+ CD8+ T cells in GC expressed higher levels of PD-1, granzyme B, and interferon-γ than CD103- CD8+ T cells. Our results suggested that CD103+ CD8+ cells in GC are correlated with TLSs, resulting in enhanced antitumor immunity in GC.


Carbon dioxide stimulates the production of amylovorin L by Lactobacillus amylovorus DCE 471, while enhanced aeration causes biphasic kinetics of growth and bacteriocin production.
The effects of both oxygen and carbon dioxide on growth of and product formation by Lactobacillus amylovorus DCE 471, a promising new sourdough starter culture, were assessed through controlled, in vitro fermentation experiments, using a temperature of 37 degrees C and a constant pH of 5.4. It was seen that aeration affected both cell growth and amylovorin L production. At aeration rates of 1 l min(-1) and more, the bacterial population was subjected to oxidative stress as reflected by biphasic growth patterns. During the first growth phase, the maximum specific growth rate increased with increasing aeration rates stabilizing at the highest oxygen concentrations. The maximum obtainable cell yields decreased. During the second growth phase, the amylovorin L production was stimulated at the highest aeration. However, amylovorin titers were never higher in the presence of oxygen compared with the anaerobic fermentations. Carbon dioxide did not influence cell growth of L. amylovorus DCE 471. The maximum specific growth rate and the biomass concentrations were merely affected. On the other hand, the maximum soluble bacteriocin titers coincided with the highest carbon dioxide flow rates. These results indicate that mild aeration of type II sourdoughs might enhance both cell yield and amylovorin L production by L. amylovorus DCE 471, thereby contributing to the competitiveness of the strain. Growth in an ecosystem together with yeasts producing carbon dioxide might exert a positive effect on the production of amylovorin L as well.


Rehabilitation of older adults with hip fracture: cognitive function and walking abilities.
To investigate the association between baseline cognitive function and the achievement of walking independence and its maintenance at 1 year in a population of older adults who underwent post-hip fracture (HF) surgery rehabilitation. Prospective cohort study. Department of rehabilitation and aged care. Three hundred six older adults admitted for post-HF surgery rehabilitation. All participants aged 65 and older who were completely unable to walk on admission but able to walk before fracture were stratified according to Mini-Mental State Examination score (0-15=moderately severe or severe cognitive impairment (CI), 16-23=mild to moderate CI, ≥24=no CI). Walking ability was defined according to the corresponding Barthel Index subitem, with walking independence at discharge being defined as a score of 12 or more out of 15. Walking ability 1 year after discharge was ascertained by telephone interviews with participants or proxies. At discharge, 29.6% of participants with moderately severe or severe CI (n=24), 51.9% with mild to moderate CI (n=56) and 78.6% of participants without CI (n=92) were able to walk independently. Among those who achieved walking independence and were alive at 1 year, 12 participants with moderately severe or severe CI (57.1%), 31 with mild to moderate CI (57.7%) and 73 without CI (78.9%) were still capable of walking independently. Although less frequently than in individuals with better cognitive function, walking independence is achievable after HF surgery rehabilitation, and can be maintained at 1 year also in those with moderately severe or severe CI.


Recurrence of an odontogenic keratocyst in a bone graft. Report of a case.
The recurrence of an odontogenic keratocyst in a bone graft after partial mandibulectomy and reconstruction is presented. The possible reasons for recurrence are discussed, and methods of treatment reviewed.


Leaching behaviour of bottom ash from RDF high-temperature gasification plants.
This study investigated the physical properties, the chemical composition and the leaching behaviour of two bottom ash (BA) samples from two different refuse derived fuel high-temperature gasification plants, as a function of particle size. The X-ray diffraction patterns showed that the materials contained large amounts of glass. This aspect was also confirmed by the results of availability and ANC leaching tests. Chemical composition indicated that Fe, Mn, Cu and Cr were the most abundant metals, with a slight enrichment in the finest fractions. Suitability of samples for inert waste landfilling and reuse was evaluated through the leaching test EN 12457-2. In one sample the concentration of all metals was below the limit set by law, while limits were exceeded for Cu, Cr and Ni in the other sample, where the finest fraction showed to give the main contribution to leaching of Cu and Ni. Preliminary results of physical and geotechnical characterisation indicated the suitability of vitrified BA for reuse in the field of civil engineering. The possible application of a size separation pre-treatment in order to improve the chemical characteristics of the materials was also discussed.


The relation between tunnel widening and bone mineral density after anterior cruciate ligament reconstruction: an experimental study in sheep.
The aim of this study was to analyze the relation between bone mineral density (BMD) and femoral tunnel enlargement (TE) in a previously validated sheep model of soft-tissue anterior cruciate ligament (ACL) reconstruction. Thirty sheep underwent ACL reconstruction by use of a soft-tissue graft at the age of 4 months. Graft fixation was achieved with the EndoButton (Smith & Nephew Endoscopy, Andover, MA) and Suture Washer (Smith & Nephew Endoscopy). Six animals were killed at 0, 3, 6, 12, and 24 weeks postoperatively. Each ACL-reconstructed knee was examined both by computed tomography to analyze the bone tunnel cross-sectional area and by dual-energy x-ray absorptiometry to analyze BMD. There was a significant increase in tunnel cross-sectional area. BMD decreased significantly within the first 3 weeks after surgery and increased thereafter. A positive correlation between TE and BMD was found. However, a subgroup analysis showed that there is no influence of BMD on the development of a tunnel widening. The hypothesis that a TE would be associated with a loss in BMD was not confirmed. Tunnel widening during the first 6 months after ACL reconstruction is not affected by the transient changes in BMD. There is no correlation between TE and BMD in an experimental sheep model of ACL reconstruction. Translational investigations will determine whether this is also true in humans.


Credentialing of surgical skills centers.
Major imperatives regarding quality of patient care and patient safety are impacting surgical care and surgical education. Also, significant emphasis continues to be placed on education and training to achieve proficiency, expertise, and mastery in surgery. Simulation-based surgical education and training can be of immense help in acquiring and maintaining surgical skills in safe environments without exposing patients to risk. Opportunities for repetition of tasks can be provided to achieve pre-established standards, and knowledge and skills can be verified using valid and reliable assessment methods. Also, expertise and mastery can be attained through repeated practice, specific feedback, and establishment of progressively higher learning goals. Simulation-based education and training can help surgeons maintain their skills in infrequently performed procedures and regain proficiency in procedures they have not performed for a period of time. In addition, warm-ups and surgical rehearsals in simulated environments should enhance performance in real settings. Major efforts are being pursued to advance the field of simulation-based surgical education. New education and training models involving validation of knowledge and skills are being designed for practicing surgeons. A competency-based national surgery resident curriculum was recently launched and is undergoing further enhancements to address evolving education and training needs. Innovative simulation-based surgical education and training should be offered at state-of-the-art simulation centers, and credentialing and accreditation of these centers are key to achieving their full potential.


Candidate genes influencing sensitivity and resistance of human glioblastoma to Semustine.
The prognosis of glioblastoma (GBM) is poor. The therapeutic outcome of conventional surgical and adjuvant treatments remains unsatisfactory, and therefore individualized adjuvant chemotherapy has aroused more attention. Microarrays have been applied to study mechanism of GBM development and progression but it has difficulty in determining responsible genes from the plethora of genes on microarrays unrelated to outcome. The present study was attempted to use bioinformatics method to investigate candidate genes that may influence chemosensitivity of GBM to Semustine (Me-CCNU). Clinical data of 4 GBM patients in Affymetrix microarray were perfected through long-term follow-up study. Differential expression genes between the long- and short-survival groups were picked out, GO-analysis and pathway-analysis of the differential expression genes were performed. Me-CCNU-related signal transduction networks were constructed. The methods combined three steps before were used to screen core genes that influenced Me-CCNU chemosensitivity in GBM. In Affymetrix microarray there were altogether 2018 differential expression genes that influenced survival duration of GBM. Of them, 934 genes were up-regulated and 1084 down-regulated. They mainly participated in 94 pathways. Me-CCNU-related signal transduction networks were constructed. The total number of genes in the networks was 466, of which 66 were also found in survival duration-related differential expression genes. Studied key genes through GO-analysis, pathway-analysis and in the Me-CCNU-related signal transduction networks, 25 core genes that influenced chemosensitivity of GBM to Me-CCNU were obtained, including TP53, MAP2K2, EP300, PRKCA, TNF, CCND1, AKT2, RBL1, CDC2, ID2, RAF1, CDKN2C, FGFR1, SP1, CDK6, IGFBP3, MDM4, PDGFD, SOCS2, CCNG2, CDK2, SDC2, STMN1, TCF7L1, TUBB. Bioinformatics may help excavate and analyze large amounts of data in microarrays by means of rigorous experimental planning, scientific statistical analysis and collection of complete data about survival of GBM patients. In the present study, a novel differential gene expression pattern was constructed and advanced study will provide new targets for chemosensitivity of GBM.


Protocol for the derivation, culturing, and differentiation of human iPS-cell-derived neuroepithelial stem cells to study neural differentiation in vitro.
Here, we present a revised protocol to derive neuroepithelial stem (NES) cells from human induced pluripotent stem cells. NES cells can be further differentiated into a culture of neurons (90%) and glia (10%). We describe how to derive and maintain NES cells in culture and how to differentiate them. In addition, we show the potential use of NES cells to study the role of reactive oxygen species in neuronal differentiation and a guideline for NES cell transfection. For complete details on the use and execution of this protocol, please refer to Calvo-Garrido et al. (2019); Falk et al. (2012).


[A 24-hour solid state Holter recording and analyzing system].
The design and functions of a new type of multi-channel solid-state Holter system were introduced in this paper. The flash memory card based recorder can record 24 hours or more of data from up to all 12 leads. The full function scanner software can analysis automatically and archive with complete editing capabilities.


Knockdown of astrocytic Grin2a exacerbated sleep deprivation-induced cognitive impairments and elevation of amyloid-beta.
Sleep disorders are associated with cognitive impairments, greater amyloid-β (Aβ) burden and increased risk of developing Alzheimer's disease, while the underlying mechanism is unclear. N-methyl-d-aspartate receptors (NMDARs), as vital modulators of cognition, are sensitive to sleep disturbance. Sleep deprivation (SD) could induce the alterations of neuronal NMDAR subunits expression, however the alterations of astrocytic NMDARs in SD have not been reported. Our previous study has demonstrated knockdown of astrocytic Grin2a (gene encoding NMDAR subunit GluN2A) could aggravate Aβ-induced cognitive impairments, but what role astrocytic GluN2A may play in SD is unknown. Here we focused on the changes and roles of hippocampal astrocytic GluN2A in SD. Our results showed SD increased the expression of astrocytic GluN2A. Specific knockdown of hippocampal astrocytic Grin2a aggravated SD-induced cognitive decline, elevated Aβ, and attenuated the SD-induced increase in autophagy flux. Our finding, for the first time, revealed a novel neuroprotective role for astrocytic GluN2A in SD, which may be helpful for developing new preventive and therapeutic targets to sleep disorders.


Evaluation of genotoxicity of combined soil pollution by cadmium and imidacloprid.
Cadmium (Cd) is one of the important pollutants of soil and the genotoxicity of Cd-contaminated soil was studied in combination with imidacloprid. The single cell gel electrophoresis or comet assay was used to quantify DNA strand breaks as a measure of DNA damage induced by Cd and imidacloprid contamination in soil. The soil was artificially contaminated by Cd (0.0, 0.2, 0.5, 1.0, 2.0 mg x kg(-1) dry soil) or Cd (0.0, 0.2, 0.5, 1.0, 2.0 mg x kg(-1) dry soil) and imidacloprid (0.5 mg x kg(-1) dry soil). Roots of Vicia faba were exposed to the contaminated soil for 2 h at 25 degrees C and were used in the comet assay. DNA damage was measured as the values of percentage of nuclei with tails, tail length, tail DNA, tail moment (TM), and Olive tail moment (OTM). DNA damages of root tips of Vicia faba increased after Cd treatment and there were dose-related increases in DNA damage measured as these parameters. However, the addition of imidacloprid further increased the DNA damage. These data confirmed the genotoxic effect of Cd to plants, and that the combined pollution with imidacloprid can enhance the genotoxicity of Cd.


Assessment of acute and chronic pain symptoms in children with cystic fibrosis.
Pain is important to assess and treat in children with cystic fibrosis (CF), because pain symptoms may limit children's ability to participate in their CF-related care and may reduce their overall well-being and quality of life. The aims of this study were to: 1) assess acute and chronic pain symptoms as reported by children with CF, and 2) examine the relationship between pain symptoms and disease severity as measured by percentage of forced expired volume in 1 sec (FEV1%). Forty-six children completed a self-report questionnaire assessing characteristics of chronic disease-related pain (frequency, intensity, duration, associated emotional upset, and location of pain). Children also rated their pain intensity associated with common CF-related procedures. The primary locations of pain reported were the abdominal/pelvic region, chest, and head/neck. Forty-six percent of the sample described pain occurring at least once per week. Most children reported their pain intensity as mild and of short duration. However, a small subgroup of children reported longer-lasting and moderately intense pain. Children with chest pain were found to be particularly at risk for experiencing more functional limitations and a significantly lower FEV1% compared to children without chest pain. The majority of children reported that nonpharmacological therapies (e.g., medication, rest, or distracting activities) provided some pain relief. Disease-related pain is common for children and adolescents with CF, suggesting that pain assessment should be a routine part of their clinical care. Further research is clearly needed to better understand the sources of pain and how best to provide relief.


Dynamic functional connectivity of the default mode network tracks daydreaming.
Humans spend much of their time engaged in stimulus-independent thoughts, colloquially known as "daydreaming" or "mind-wandering." A fundamental question concerns how awake, spontaneous brain activity represents the ongoing cognition of daydreaming versus unconscious processes characterized as "intrinsic." Since daydreaming involves brief cognitive events that spontaneously fluctuate, we tested the hypothesis that the dynamics of brain network functional connectivity (FC) are linked with daydreaming. We determined the general tendency to daydream in healthy adults based on a daydreaming frequency scale (DDF). Subjects then underwent both resting state functional magnetic resonance imaging (rs-fMRI) and fMRI during sensory stimulation with intermittent thought probes to determine the occurrences of mind-wandering events. Brain regions within the default mode network (DMN), purported to be involved in daydreaming, were assessed for 1) static FC across the entire fMRI scans, and 2) dynamic FC based on FC variability (FCV) across 30s progressively sliding windows of 2s increments within each scan. We found that during both resting and sensory stimulation states, individual differences in DDF were negatively correlated with static FC between the posterior cingulate cortex and a ventral DMN subsystem involved in future-oriented thought. Dynamic FC analysis revealed that DDF was positively correlated with FCV within the same DMN subsystem in the resting state but not during stimulation. However, dynamic but not static FC, in this subsystem, was positively correlated with an individual's degree of self-reported mind-wandering during sensory stimulation. These findings identify temporal aspects of spontaneous DMN activity that reflect conscious and unconscious processes.


mmView: a web-based viewer of the mmCIF format.
Structural biomolecular data are commonly stored in the PDB format. The PDB format is widely supported by software vendors because of its simplicity and readability. However, the PDB format cannot fully address many informatics challenges related to the growing amount of structural data. To overcome the limitations of the PDB format, a new textual format mmCIF was released in June 1997 in its version 1.0. mmCIF provides extra information which has the advantage of being in a computer readable form. However, this advantage becomes a disadvantage if a human must read and understand the stored data. While software tools exist to help to prepare mmCIF files, the number of available systems simplifying the comprehension and interpretation of the mmCIF files is limited. In this paper we present mmView - a cross-platform web-based application that allows to explore comfortably the structural data of biomacromolecules stored in the mmCIF format. The mmCIF categories can be easily browsed in a tree-like structure, and the corresponding data are presented in a well arranged tabular form. The application also allows to display and investigate biomolecular structures via an integrated Java application Jmol. The mmView software system is primarily intended for educational purposes, but it can also serve as a useful research tool. The mmView application is offered in two flavors: as an open-source stand-alone application (available from http://sourceforge.net/projects/mmview) that can be installed on the user's computer, and as a publicly available web server.


Enhancing medication therapy in Parkinson's disease by establishing an interprofessional network including pharmacists.
Background Optimizing therapy regimens through collaboration and combination of available resources is a promising approach to improve quality of life for patients with Parkinson's disease (PD). Aim The aim of this project was to enhance patient-oriented therapy and interprofessional collaboration by establishing a regional PD network. Setting The network is located in a rural area in Germany. It covers primary, secondary and tertiary care facilities across professional boundaries. Development Recruitment of PD specialists and patient support groups was done by the local newspaper to spread the word. The network was initially open to all healthcare professionals, who stated a focus or special interest in PD. A working group for medication was founded within the network by asking for interested participants. Problems in the medication process were discussed within the group. As a consequence, therapy recommendations (quickcards) and a specific medication plan were developed and a certified education curriculum for pharmacists was developed. Implementation The network grew to > 150 participants across all disciplines and sectors. Quickcards were adjusted, approved and implemented by the network during interquartile meetings. Certified education was implemented and became a requirement for participating pharmacists. Evaluation The quickcards on medication plan and drug-drug-interactions were approved to be useful and feasible by the network by unanimous assent. Overall satisfaction with certified education was high (mean of 1.4 on a scale between 1 = high and 6 = low). Conclusion A regional interprofessional PD network with pharmacists was established and new standards were established. Future research needs to measure the effects on patient outcomes.


The Shape of the Nasal Cavity and Adaptations to Sniffing in the Dog (Canis familiaris) Compared to Other Domesticated Mammals: A Review Article.
Dogs are a good starting point for the description and anatomical analysis of turbinates of the nose. This work aimed at summing up the state of knowledge on the shape of the nasal cavity and airflow in these domestic animals and dealt with the brachycephalic syndrome (BOAS) and anatomical changes in the initial airway area in dogs with a short and widened skull. As a result of artificial selection and breeding concepts, the dog population grew very quickly. Modern dog breeds are characterized by a great variety of their anatomical shape. Craniological changes also had a significant impact on the structure and physiology of the respiratory system in mammals. The shape of the nasal cavity is particularly distinctive in dogs. Numerous studies have established that dogs and their olfactory ability are of great importance in searching for lost people, detecting explosives or drugs as well as signaling disease in the human body. The manuscript describes the structure of the initial part of the respiratory system, including the nasal turbinates, and compares representatives of various animal species. It provides information on the anatomy of brachycephalic dogs and BOAS. The studies suggest that further characterization and studies of nasal turbinates and their hypertrophy are important.


Significant differences among physician specialties in management recommendations of BRCA1 mutation carriers.
The National Comprehensive Cancer Network (NCCN) has published guidelines for hereditary breast and ovarian cancer syndrome (HBOCS) management. Little data exist on compliance with these guidelines among different physician specialties. We performed an on-line case-based survey by randomly sampling physicians from five specialties, Family Medicine (FM), Obstetrics and Gynecology (OG), General Surgery (GS), Internal Medicine (IM), and Hematology and Oncology (HO). The physicians (n = 225) were asked to provide HBOCS management of healthy women ages 40-42 in the presence of a familial BRCA1 mutation. For women negative for the BRCA1 mutation, 59% of the physicians recommended appropriate surveillance although with significant differences among specialties; P = 0.01. Using an aggregate screening intensity score, physicians clearly recommended more intense screening for mutation positive than negative women (P < 0.0001), but only 16% of physicians followed NCCN guidelines for BRCA1-positive women. Seventy-six percent of all physicians recommended breast MRI with significant variation among specialties ranging from 62% of FM to 89% of OG (P = 0.0020). Similarly, 63% of physicians recommended prophylactic oophorectomy, with 76 and 78% of GS and OG compared to 38% of IM (P < 0.0001) and 57% recommended prophylactic mastectomy ranging from 84% of HO to 32% of FM (P < 0.0001). Independent of specialty, respondents with BRCA testing experience recommended more intense management than those without; P = 0.021. Management recommendations of BRCA1 mutation carriers are not consistent with NCCN guidelines and vary by medical specialty and genetic testing experience. Targeted education of physicians by specialty is needed, so that optimal management is offered to these high-risk women.


The primary body-wall musculature in the arrow-worm Sagitta setosa (Chaetognatha): an ultrastructural study.
The primary musculature of Sagitta is mainly made up of two kinds of alternating fibers, A and B. These fibers differ markedly in their localization in the muscular tissue, by the development of their SR and their mitochondria, and the shape of their myofibrils. Their contractile apparatus is similar and possesses myofibrils of regular thickness with very short I bands, flanked by invaginations which are large compartments communicating with the extracellular space. This fiber diversity appears and is maintained in the presence of an apparent common innervation. Nerve ending-like structures are scattered in the epidermis against the basement membrane and there are no nerve beneath this. The presence of at least two kinds of fibers in the primary musculature and the presence of the secondary musculature would suggest that the displacements of sagitta may be more complex than is generally admitted. The specializations of the trunk musculature underline the degree of specialization in the Chaetognatha phylum.


A comparison of the direct outcomes of percutaneous needle fasciotomy and limited fasciectomy for Dupuytren's disease: a 6-week follow-up study.
The demand for percutaneous needle fasciotomy (PNF) as treatment for Dupuytren's disease is increasing because of its limited invasiveness, good outcome, limited number of complications, quick recovery, and overall patient satisfaction. This randomized controlled trial was designed to test whether these short-term expectations are sound by comparing this treatment with limited fasciectomy (LF) with regard to these aspects. We treated 166 rays: 88 by PNF and 78 by LF. Total passive extension deficit (TPED) improvement at 1 week and at 6 weeks were the primary outcome parameters; patient satisfaction, hand-function recovery, and complication rate were secondary outcome parameters. We used the Disabilities of the Arm, Shoulder, and Hand questionnaire to measure disabilities of the upper extremity before and after treatment and all adverse effects and complications were recorded. Overall TPED improvement was best at 6 weeks. In the PNF group TPED improved by 63% versus 79% in the LF group; this difference was statistically significant. Results at the proximal interphalangeal joint were worse than those at the metacarpophalangeal and distal interphalangeal joints for both the PNF and LF groups. The rays classified before surgery as Tubiana stages I and II showed no difference between these treatments, but for rays higher than stage II LF clearly was superior to PNF as a treatment modality. The rate of major complications in the LF group was 5% versus 0% in the PNF group. Patient satisfaction was almost equal but direct hand function after treatment was considered better in the PNF group, as was the degree of discomfort that patients experienced. This was underscored by the Disabilities of the Arm, Shoulder, and Hand scores in the PNF group, which were significantly lower than those in the LF group at all time points measured. In the short term and in cases with a TPED of 90 degrees or less PNF is a good treatment alternative to LF for treatment of Dupuytren's disease. Therapeutic, Level I.


Mutation screening analysis of the retinoblastoma related gene RB2/p130 in sporadic ovarian cancer and head and neck squamous cell cancer.
To investigate the involvement of the RB2/p130 gene in the pathogenesis of sporadic ovarian cancer in addition to head and neck squamous cell carcinoma (HNSCC). Paired tumour and patient matched normal DNA samples from 43 sporadic ovarian tumours and 39 normal/tumour HNSCC DNA samples were screened. The mutation screen used polymerase chain reaction (PCR) amplification followed by single strand conformation polymorphism analysis and direct sequencing of the PCR products. Exons 19 and 20 (B domain) and exons 21 and 22 (C-terminus) were analysed for mutations. These exons were chosen because most of the point mutations in RB2/p130 are located in the C-terminal region and mutations in these exons have been identified previously in nasopharyngeal carcinomas and primary lung tumours. No abnormal band shifts were seen in the samples analysed, and no bands directly sequenced revealed the presence of mutations. Genetic alterations in the RB2/p130 gene (exons 19-22) are unlikely to be involved directly in the pathogenesis of sporadic ovarian cancer or HNSCC.


Toxicological and microbiological characterization of cow stable dust.
Exposure to farm environment has been shown to both protect from allergic diseases and increase the risk of respiratory syndromes. Mechanisms have been previously investigated by using farm dust extracts or specific components of dust. The use of authentic farm dust would better reflect the natural exposure. The aim of our study was to highlight the importance of proper assessment of the cow stable dust characteristics before conducting further investigations. For this purpose, we characterized microbiome and size distribution of unprocessed cow stable dust and its toxicological properties, as they have been often overlooked in search of protective factors. Stable dust samples from four Finnish dairy farms were collected by utilizing two different collection methods. Toxicological potential was analysed by stimulating co-cultures of lung epithelial and macrophage-like cells with dust. Size and mass distributions of airborne particles in the stables and bacterial and fungal microbiota of the dust were analysed. Stimulation with dust did not affect viability, but heightened oxidative stress responses and cytokine secretion, and slightly reduced the metabolic activity. There were a few differences in responses between farms, however, the differences were mainly in the intensity and not in the direction of the response. Cellular responses induced by dusts collected by different sampling methods did not differ substantially. Unprocessed stable dust samples showed relatively low direct toxicity but were able to trigger immune responses in studied cell model. This suggest that these dust collection methods could be utilized when investigating e.g. asthma-protective mechanisms.


Possible association between IgG4-associated systemic disease with or without autoimmune pancreatitis and non-Hodgkin lymphoma.
IgG4-associated systemic disease (ISD) is a multiorgan fibroinflammatory disorder whose pancreatic manifestation is called autoimmune pancreatitis (AIP). We describe 3 patients who developed non-Hodgkin lymphoma during the follow-up of ISD. At our institution's pancreas clinic, we have prospectively and retrospectively examined patients with ISD with (n = 101) or without (n = 10) AIP (mean age, 59 years; 90 males and 21 females). We reviewed the medical records of all 111 patients to identify patients who developed non-Hodgkin lymphoma during the follow-up since their first presentation of ISD. Standardized incidence rate was calculated. The 111 patients with ISD with or without AIP had 331 patient-years of observation during which 3 patients had a diagnosis of non-Hodgkin lymphoma 3 to 5 years after the diagnosis of ISD. In these patients who later developed lymphoma, ISD involved the pancreas (AIP) in 2 and salivary gland in 1. Non-Hodgkin lymphoma had extranodal involvement in all patients (liver [n = 2], adrenal glands [n=1], kidney [n= 1], and lung [n = 1]). Standardized incidence rate was 16.0 (95% confidence interval, 3.3-45.5). We report 3 cases of non-Hodgkin lymphoma that developed during the follow-up of ISD suggesting that patients with ISD may be at an increased risk of developing non-Hodgkin lymphoma.


Characterization of 5'-flanking region of heart myosin light chain 2A gene. Structural and functional evidence for promoter activity.
Two recombinant clones, lambda LC5 and lambda LC13, encompassing the entire regulatory myosin light chain 2 (MLC2A) gene of chicken heart muscle were isolated. Of these, lambda LC5 which contains a large 5'-flanking sequence of about 7.0 kb, was characterized by a partial nucleotide sequence analysis. A TATA-like sequence (TATTTTTA) and a CAAT-box (CAAAAGT) are located at positions -32 and -59, respectively, which most likely constitute the functional promoter region in the gene. Based on primer extension reaction with a synthetic 20-mer corresponding to the 5'-leader sequence and total poly(A+) RNA, the probable transcription initiation site in the gene was located. The gene promoter activity was demonstrated following transient expression of recombinant genomes containing the chicken upstream sequence fused to the bacterial chloramphenicol acetyltransferase (CAT) or to the rat preproinsulin II genes. The extracts from a Quail fibroblast cell line (QT35) transfected with the construct (pLCo5.2iCat) containing the putative chicken promoter, and the CAT gene promoted the formation of 3'-acetate chloramphenicol. Another construct (pBC12LC5.2f) contains the rat preproinsulin II gene placed under the control of chicken promoter and a simian virus 40 origin of replication. Transfection of COS cell line with pBC12LC5.2f DNA resulted in an efficient expression of rat preproinsulin mRNA initiating from the chicken promoter. The transfection assay also allowed detection of chicken MLC2A gene transcripts by S1-nuclease protection of end-labeled DNA probes. A comparison of the MLC2A upstream gene sequence with those available for skeletal myosin light chains revealed no common sequence elements, suggesting that cardiac MLC2A gene promoter region has diverged considerably from its counterparts in skeletal muscle.


"Connecting the dots" - The transfer of bioscience knowledge by new graduate nurses to the clinical setting: A qualitative study.
Little is known regarding the transfer of bioscience knowledge gained during undergraduate nursing studies into clinical practice. To explore the experiences of new registered nurses in applying bioscience concepts in their day-to-day nursing practice. Descriptive qualitative design. Fifteen recently graduated registered nurses (RNs) who were working in acute care settings participated in the study. Semi-structured, face-to-face individual interviews were conducted. Interview data were audio-recorded and thematically analysed. Four themes were identified from the qualitative interviews. The first and second themes demonstrated nurses' realisation of the relevance of theoretical bioscience knowledge learnt within the classroom to their practice and how this evidence-based knowledge translated into confidence in decisions made. The third and fourth themes revealed the impact bioscience knowledge had on RNs' relationships with patients and family members, which was viewed as providing compassionate care. The application of knowledge in biosciences gained during their undergraduate years, provided the basis for RNs to trust in their own clinical judgment and to speak with conviction. 'Connecting the dots' between bioscience knowledge and clinical practice provided the platform for RNs to gain and build trust with their patients. The practical utility of bioscience knowledge in everyday practice allowed RNs to contextualise their nursing care regimen and tailor holistic nursing care delivery to individual patient needs.


The in vitro construction of a tissue engineered bioprosthetic heart valve.
Heart valve replacement with either a nonliving xenograft or a mechanical prosthesis is an effective therapy for valvular heart disease. Both of these approaches have limitations, including their inability to grow, repair, and remodel. In addition, a mechanical prosthesis requires long-term anticoagulation therapy. This study demonstrates the in vitro creation of tissue engineered heart valve tissue using cardiovascular cells on degradable polymer matrices, 40 heart valve leaflets were created using this technique from two sources. Xenograft leaflets were created using human dermal fibroblasts and bovine aortic endothelial cells (n = 20) or allograft valve leaflets were created using sheep myofibroblasts and sheep endothelial cells (n = 20). A mixed sheep cell population was obtained consisting of endothelial cells and myofibroblasts. Endothelial cells were labelled with acethylated low density lipoprotein (Ac-Dil-LDL) and cells were separated into two groups using an activated cell sorter: LDL positive cells comprised of a pure endothelial cell population and LDL negative cells comprised of mixed cell population containing myofibroblasts and smooth muscle cells. The LDL negative cells were seeded on a synthetic polyglycolic acid (PGA) mesh and grown in vitro to form a tissue-like fibroblast-mesh core. Endothelial cells were then seeded onto the surface of the fibroblast-mesh core, forming a single monolayer. Histological evaluation of these constructs revealed an inner core of LDL negative cells and outer endothelial-like cells which were factor VIII positive. There was no evidence of capillary formation from endothelial cells invading the myofibroblasts and smooth muscle matrix and the endothelial lining appeared complete. It is feasible to construct allogenic heart valve tissue which could be used to make a valve.


Psychological depression and 17-year risk of death from cancer.
Psychological depression, measured in 1957-1958 by the Minnesota Multiphasic Personality Inventory at the baseline examination of 2,020 middle-aged employed men, was associated (p less than 0.001) with a twofold increase in odds of death from cancer during 17 years of follow-up. The association did not vary appreciably in magnitude among the early (1958-1962), middle (1963-1968), and later (1969-1974) years of follow-up, persisted after adjustment for age, cigarette smoking, use of alcohol, family history of cancer, and occupational status, and was apparently not specific to any particular site or type of cancer. This result, predicted in advance on the basis of findings by other investigators, is consistent with the hypothesis that psychological depression is related to impairment of mechanisms for preventing the establishment and spread of malignant cells.


Regulation of vimentin gene expression in the ocular lens.
Vimentin expression in the lens is striking due to the reported mesenchymal preference of vimentin and the epithelial origin of the lens. The amount of chicken vimentin mRNA levels determined by Northern blot analysis increased 3-fold from 7 to 14 days of embryonic lens development and then decreased 10-fold at 16 days of development, suggesting that post-transcriptional processes may contribute to the level of cytoplasmic vimentin mRNA during lens development. To analyze the mechanisms governing vimentin gene expression in the lens at the level of transcription, a series of chicken vimentin 5'-flanking region deletions were fused to the bacterial CAT gene and transfected into fibroblasts and lens cultures derived from three species. The -160 to +1 sequence conferred equal promoter activity in cultured chicken lens epithelial cells and fibroblasts. The -321 to -160 sequences increased promoter activity in all cultures, but more strongly in fibroblasts than in lens cells. Sequence elements in the region -608 to -321 repressed promoter activity in lens cells and fibroblasts. Promoter activity was partially restored in fibroblasts but not in lens cells by -767 to -608 sequences. Vimentin gene expression in the lens thus appears to be controlled by multiple positive- and negative-acting elements in its 5'-flanking sequence.


The human β-globin enhancer LCR HS2 plays a role in forming a TAD by activating chromatin structure at neighboring CTCF sites.
The human β-globin locus control region (LCR) hypersensitive site 2 (HS2) is one of enhancers for transcription of the β-like globin genes in erythroid cells. Our previous study showed that the LCR HS2 has active chromatin structure before transcriptional induction of the β-globin gene, while another enhancer LCR HS3 is activated by the induction. To compare functional difference between them, we deleted each HS (ΔHS2 and ΔHS3) from the human β-globin locus in hybrid MEL/ch11 cells. Deletion of either HS2 or HS3 dramatically diminished the β-globin transcription and disrupted locus-wide histone H3K27ac and chromatin interaction between LCR HSs and gene. Surprisingly, ΔHS2 weakened interactions between CTCF sites forming the β-globin topologically associating domain (TAD), while ΔHS3 did not. CTCF occupancy and chromatin accessibility were reduced at the CTCF sites in the ΔHS2 locus. To further characterize the HS2, we deleted the maf-recognition elements for erythroid activator NF-E2 at HS2. This deletion decreased the β-globin transcription and enhancer-promoter interaction, but did not affect interactions between CTCF sites for the TAD. In light of these results, we propose that the HS2 has a role in forming a β-globin TAD by activating neighboring CTCF sites and this role is beyond typical enhancer activity.


ROS-regulated phosphorylation of ITPKB by CAMK2G drives cisplatin resistance in ovarian cancer.
Platinum resistance accounts for much of the high mortality and morbidity associated with ovarian cancer. Identification of targets with significant clinical translational potential remains an unmet challenge. Through a high-throughput synthetical lethal screening for clinically relevant targets using 290 kinase inhibitors, we identify calcium/calmodulin-dependent protein kinase II gamma (CAMK2G) as a critical vulnerability in cisplatin-resistant ovarian cancer cells. Pharmacologic inhibition of CAMK2G significantly sensitizes ovarian cancer cells to cisplatin treatment in vitro and in vivo. Mechanistically, CAMK2G directly senses ROS, both basal and cisplatin-induced, to control the phosphorylation of ITPKB at serine 174, which directly regulates ITPKB activity to modulate cisplatin-induced ROS stress. Thereby, CAMK2G facilitates the adaptive redox homeostasis upon cisplatin treatment and drives cisplatin resistance. Clinically, upregulation of CAMK2G activity and ITPKB pS174 correlates with cisplatin resistance in human ovarian cancers. This study reveals a key kinase network consisting of CAMK2G and ITPKB for ROS sense and scavenging in ovarian cancer cells to maintain redox homeostasis, offering a potential strategy for cisplatin resistance treatment.


Feeder-supported in vitro exercise model using human satellite cells from patients with sporadic inclusion body myositis.
Contractile activity is a fundamental property of skeletal muscles. We describe the establishment of a "feeder-supported in vitro exercise model" using human-origin primary satellite cells, allowing highly-developed contractile myotubes to readily be generated by applying electrical pulse stimulation (EPS). The use of murine fibroblasts as the feeder cells allows biological responses to EPS in contractile human myotubes to be selectively evaluated with species-specific analyses such as RT-PCR. We successfully applied this feeder-supported co-culture system to myotubes derived from primary satellite cells obtained from sporadic inclusion body myositis (sIBM) patients who are incapable of strenuous exercise testing. Our results demonstrated that sIBM myotubes possess essentially normal muscle functions, including contractility development, de novo sarcomere formation, and contraction-dependent myokine upregulation, upon EPS treatment. However, we found that some of sIBM myotubes, but not healthy control myotubes, often exhibit abnormal cytoplasmic TDP-43 accumulation upon EPS-evoked contraction, suggesting potential pathogenic involvement of the contraction-inducible TDP-43 distribution peculiar to sIBM. Thus, our "feeder-supported in vitro exercise model" enables us to obtain contractile human-origin myotubes, potentially utilizable for evaluating exercise-dependent intrinsic and pathogenic properties of patient muscle cells. Our approach, using feeder layers, further expands the usefulness of the "in vitro exercise model".


Total mercury and methyl-mercury contents and accumulation in polar microbial mats.
Although polar regions are considered isolated and pristine areas, the organisms that inhabit these zones are exposed to global pollution. Heavy metals, such as mercury, are global pollutants and can reach almost any location on Earth. Mercury may come from natural, volcanic or geological sources, or result from anthropogenic sources, in particular industrial or mining activities. In this study, we have investigated one of the most prominent biological non-marine communities in both polar regions, microbial mats, in terms of their Hg and methyl-mercury (MeHg) concentrations and accumulation capacities. The main hypotheses posed argued on the importance of different factors, and to test them, we have measured Hg concentrations in microbial mats that were collected from 6 locations in different ecological situations. For this purpose, the direct anthropogenic impacts, volcanic influences, proximity to the seashore, latitudinal gradients and C contents were investigated. Our results show that, other than the direct anthropogenic influence, none of the other hypotheses alone satisfactorily explains the Hg content in microbial mats. In contrast, the MeHg contents were noticeably different between the investigated locations, with a higher proportion of MeHg on the McMurdo Ice Shelf (Antarctica) and a lower proportion on Ward Hunt Island (High Arctic). Furthermore, our results from in situ experiments indicated that the microbial mats from South Shetland Islands could quickly accumulate (48 h) Hg when Hg dissolved salts were supplied. Over short-term periods, these mats do not transform Hg into MeHg under field conditions.


Spontaneous formation of dynamical patterns with fractal fronts in the cyclic lattice Lotka-Volterra model.
Dynamical patterns, in the form of consecutive moving stripes or rings, are shown to develop spontaneously in the cyclic lattice Lotka-Volterra model, when realized on square lattice, at the reaction limited regime. Each stripe consists of different particles (species) and the borderlines between consecutive stripes are fractal. The interface width w between the different species scales as w(L,t) approximately L(alpha)f(t/L(z)), where L is the linear size of the interface, t is the time, and alpha and z are the static and dynamical critical exponents, respectively. The critical exponents were computed as alpha=0.49+/-0.03 and z=1.53+/-0.13 and the propagating fronts show dynamical characteristics similar to those of the Eden growth models.


Automated determination of the antitrypsin activity of serum.
An automated determination of the serum antitrypsin activity is described in which all reaction parameters have been optimized. The determination is carried out by measuring the difference between the activity of a standard amount of trypsin with and without addition of serum. Trypsin activity is measured using N-alpha-benzoyl-L-arginine-p-nitroanilide as a substrate. The assay is performed by means of an automatic enzyme reaction rate analyser the Vitatron AKES. The antitrypsin activity is expressed in Inhibitor Units making standardization of the trypsin preparation superfluous. Normal values of the antitrypsin activity for some of the most frequently occurring genetic variants of alpha1-antitrypsin are given.


Effect of carbamazepine (Tegretol) on seizure and EEG patterns in monkeys with alumina-induced focal motor and hippocampal foci.
Qualitative and quantitative aspects of chronic carbamazepine (Tegretol) medication on focal seizures and associated interictal EEG abnormalities in Rhesus monkeys with alumina-induced foci in either the sensorimotor cortex or the hipocampus was investigated. In both groups of animals, carbamazepine produced qualitative control of visible seizures and reduced intracortical spike propagation, but did not cause complete normalization of the background EEG; quantitative indices, such as spike density and amount of paroxysmal discharge representative of abnormal EEG activity, were significantly reduced with respect to predrug values during medication and after cessation as well. Threshold to pentylenetetrazol was elevated by carbamazepine in both groups of epileptic monkeys. Aggressivity and other clinical manifestations in monekys with hippocampal foci were markedly reduced by carbamazepine.


Long-term efficacy of interventions for actinic keratosis: protocol for a systematic review and network meta-analysis.
Actinic keratoses (AK) are common precancerous lesions of the skin due to cumulative sun exposure. A variety of interventions are available for the treatment; however, the majority of randomised controlled trials (RCTs) and meta-analyses focus on short-term efficacy outcomes. This network meta-analysis aims to investigate the long-term (> 12 months) efficacy of interventions for AK. To identify relevant studies, we will perform a systematic literature research in MEDLINE, Embase, and CENTRAL and hand-search pertinent trial registers. Two authors will independently screen titles and abstracts for eligibility. We will include RCTs with an inter-individual (parallel arm) design. The study population includes patients with a clinical or histopathologic diagnosis of AK. Eligibility will be restricted to the following interventions: surgical approaches, cryosurgery, ablative laser treatment, topical drug treatment with 5-fluorouracil, imiquimod, ingenol mebutate, diclofenac, or photodynamic therapy. As outcomes, we will consider the following endpoints: (1) the participant complete clearance rate, (2) the participant partial clearance rate, (3) the lesion-specific clearance, (4) the mean lesion reduction per patient, and (5) the number of withdrawals due to adverse events after at least 12 months after the end of treatment. Monotherapy or placebo will serve as a comparison. Estimates of effects from individual studies will be pooled using a random-effects model. Heterogeneity will be evaluated based on I2 and chi-square test. The risk of bias will be estimated with the Cochrane Risk of Bias Tool by two review authors independently. The quality of evidence of the outcomes will be assessed with the GRADE approach. A network meta-analysis will be performed to combine direct and indirect evidence from the included RCTs. The potential of interventions to achieve a sustained clearance of AK has not been assessed to date. To investigate the long-term efficacy of interventions is important as the natural disease course is highly variable and relapses occur frequently even after initial lesion clearance. This review will help to set a framework for clinical decision making in patients with AK. CRD42018095903 (PROSPERO).


Evaluation of an occupational medicine patient consultation note assessment tool.
Medical education focuses on assessment, diagnosis and management of various clinical entities. The communication of this information, particularly in the written form, is rarely emphasized. Though there have been assessment tools developed to support medical learner improvement in this regard, none are oriented to occupational medicine (OM) practice. This study was aimed to develop and evaluate an assessment tool for consultation letters, by modifying a previously validated assessment tool to suit practice in OM. Using an iterative process, OM specialists added to the Consultation Letter Rating Scale (CLRS) of the Royal College of Physicians and Surgeons of Canada (henceforth abbreviated as RC) additional questions relevant to communication in the OM context. The tool was then used by two OM specialists to rate 40 anonymized OM clinical consultation letters. Inter-rater agreement was measured by percent agreement, kappa statistic and intraclass correlation. There was generally good percent agreement (>80% for the majority of the RC and OM questions). Intraclass correlation for the five OM questions total scores was slightly higher than the intraclass correlations for the five RC questions (0.59 versus 0.46, respectively), suggesting that our modifications performed at least as well as the original tool. This new tool designed specifically for evaluation of patient consultation notes in OM provides a good option for medical educators in a variety of practice areas in providing non-summative, low-stakes assessment and/or feedback to nurture increased competency in written communication skills for postgraduate trainees in OM.


Hemi-capitate Arthroplasty for Dorsal Fracture-Dislocations of the Proximal Interphalangeal Joint: Surgical Technique and Illustrative Case.
Osteochondral graft from the carpal bone allows anatomical joint reconstruction in unstable dorsal fracture-dislocations with > 50% of the articular surfaces. The most used graft is the dorsal hamate. Hemi-hamate arthroplasty is technically challenging and has anatomical incongruity, and many authors have evolved various modifications in the palmar buttress reconstruction of the middle phalanx base. Therefore, there are no universally accepted treatment modalities for these complex articular injuries. This article describes the dorsal capitate as the osteochondral graft for middle phalanx volar articular surface reconstruction. Hemi-capitate arthroplasty was done on a 40-year-old man with an unstable dorsal fracture dislocation of the PIP joint. The osteochondral capitate graft united well, and the joint congruency was good at the final follow-up. The surgical technique, illustrative images, and rehabilitation are discussed. With the evolving technical modifications and complications in Hemi-hamate arthroplasty, distal capitate may be considered a reliable and alternate osteochondral graft for unstable PIP joint fracture-dislocations. The online version contains supplementary material available at 10.1007/s43465-023-00853-2.


Interactions between androgen receptor signaling and other molecular pathways in prostate cancer progression: Current and future clinical implications.
In last years several improvements have been made in the management of prostate cancer (PCa). Androgen receptor (AR) is considered the main driver in PCa growth and progression and most drugs are directed against AR pathway. Once PCa spreads outside the prostate, androgen deprivation therapy (ADT) represents the cornerstone of treatment in hormone-sensitive prostate cancer (HSPC). Unfortunately, the response is only transient and most patients eventually develop castration-resistant prostate cancer (CRPC). Most resistance mechanisms depend on maintenance of AR signalling in castration environment. Recent discoveries of multiple growth-promoting and survival pathways in PCa suggest the importance of alternative mechanisms involved in disease progression, such as DNA damage response pathway, PTEN/PI3K/AKT/mTOR pathway, cell cycle pathway, WNT pathway, TMPRSS2/ETS fusion, neuroendocrine pattern and immune system response. In this review, we discuss the interplay between AR signaling and other molecular pathways involved in PCa pathogenesis and their therapeutic implication in advanced disease.


Kinetics of thermal aggregation of glycogen phosphorylase b from rabbit skeletal muscle: mechanism of protective action of alpha-crystallin.
The kinetics of thermal aggregation of glycogen phosphorylase b (Phb) from rabbit skeletal muscle have been studied by dynamic light scattering (0.08M Hepes, pH 6.8, containing 0.1M NaCl; 48 degrees C). The hydrodynamic radius of the start aggregates determined from the initial linear parts of the dependences of the hydrodynamic radius (R(h)) on time was found to be 16.7 +/- 1.0 nm. At rather high values of time, the R(h) value for the protein aggregates becomes proportional to t(1/1.8) = t(0.56) suggesting that the aggregation process proceeds in the regime of diffusion-limited cluster-cluster aggregation. In the presence of alpha-crystallin, a protein possessing the chaperone-like activity, the process of protein aggregation switches to the regime of reaction-limited cluster-cluster aggregation as indicated by the exponential dependence of the R(h) value on time. It was shown that the addition of alpha-crystallin raises the rate of thermal inactivation of Phb. These data in combination with the results of the study of interaction of Phb with alpha-crystallin by analytical ultracentrifugation suggest that alpha-crystallin interacts with the intermediates of unfolding of the Phb molecule.


Embryological exposure to valproic acid disrupts morphology of the deep cerebellar nuclei in a sexually dimorphic way.
Autism spectrum disorders (ASD) is diagnosed in males at a much higher rate than females. For this reason, the majority of autism research has used male subjects exclusively. However; more recent studies using genetic sex as a factor find that the development of the male and female brain is differentially affected by ASD. That is, the natural sex-specific differences that exist between male and female brains lead to sexually dimorphic expressions of autism. Here we investigate the putative sexual dimorphism that exists in the deep cerebellar nuclei of male and female rats exposed to valproic acid (VPA) on embryological day 12.5. We find natural sex-specific differences in adult nucleus area, length, and estimated cell populations. Therefore VPA exposure during embryology creates some sex-specific deficits such as higher cell counts in the VPA males and lower cell counts in the VPA females. At the same time, some effects of VPA exposure occur regardless of sex. That is, smaller nucleus area and length lead to truncated nuclei in both VPA males and females. These deficits are more pronounced in the VPA males suggesting that genetic sex could play a role in teratogenic susceptibility to VPA. Taken together our results suggests that VPA exposure induces sexually dimorphic aberrations in morphological development along a mediolateral gradient at a discrete region of the hindbrain approximate to rhombomere (R) 1 and 2. Sex-specific disruption of the local and long-range projections emanating from this locus of susceptibility could offer a parsimonious explanation for the brain-wide neuroanatomical variance reported in males and females with ASD.


Different characteristics of microbial diversity and special functional microbes in rainwater and topsoil before and after 2019 new coronavirus epidemic in Inner Mongolia Grassland.
Grassland ecosystems are vital terrestrial ecosystems. As areas sensitive to climate change, they are critical for assessing the effects of global climate change. In China, grasslands account for over 40% of the land area. There is currently limited information on microbial diversity evolution in different grassland areas, particularly microorganisms with ice nucleation activity (INA) and their potential resources with potential influence to regulate regional precipitation and climate. We used Illumina MiSeq to sequence the 16S rRNA V3-V4 hypervariable region and performed a simple droplet freezing experiment to determine the variation in the grassland microbial community species composition and community structure. Rainwater and topsoil samples from the Hulunbuir Grassland in Inner Mongolia collected over three years were characterized. The dominant bacterial genus in the rainwater was Massilia, and the dominant fungus was Cladosporium. Additionally, the dominant bacteria in the soil were Sphingomonas, and the dominant fungus was Gibberella. There were differences in the microbial communities before and after the coronavirus disease epidemic. Pathogenic microorganisms exhibited inconsistent responses to environmental changes. The low relative abundance of known high-INA microorganisms and the higher freezing temperature indicated that unknown high-efficiency biological ice nucleating particles may be present. We found significant differences in species diversity and richness between the rainwater and soil populations in grassland areas by analyzing the sample community structures. Our research results revealed the species composition and structure of the microbiota in grassland ecosystems in China, indicating that environmental media and human activities may affect the microbiota in the grassland area and indicating underlying microorganisms with high INA.


Fluorimetric Detection of Zn2+, Mg2+, and Fe2+ with 3-Hydroxy-4-Pyridylisoquinoline as Fluorescent Probe.
The suitability of 3-hydroxy-4-pyridylisoquinoline to operate as fluorescent chemosensor for the detection of metal ions was investigated. For that purpose, the interactions of the title compound with selected metal ions were investigated by absorption and emission spectroscopy. The complexation of Zn2+, Fe2+, Mg2+ with 1:1 and 2:1 stoichiometry leads to characteristic optical responses that depend significantly on the employed solvents, thus allowing for the fluorimetric identification and detection of particular metal cations in a matrix-based pattern analysis or by fluorimetric titrations.


Nucleotide sequence of a Guinea-Bissau-derived human immunodeficiency virus type 2 proviral clone (HIV-2CAM2).
We report the complete nucleotide sequence of a human immunodeficiency virus type 2 (HIV-2) isolate from Guinea-Bissau (HIV-2CAM2). The genomic organization of HIV-2CAM2 is identical to that of other HIV-2 isolates but contains a stop codon in the pol gene. The deduced amino acid sequences of the viral proteins show variation of 20% in the gag, pol and vpx regions, and 25 to 45% in the tat, env and nef regions when compared to other isolates of HIV-2. This is greater than the variation observed between isolates of HIV-1.


Effect of acupoint therapies on chemotherapy-induced nausea and vomiting: A systematic review protocol.
Patients suffering from chemotherapy-induced nausea and vomiting (CINV) might have negative adherence of treatment. Acupoint therapies, including acupuncture, acupressure, acupoints injection, massage, and moxibustion, are safe medical procedures with minimal side effects for CINV, but studies about overall safety and effectiveness of acupoint therapies have not been scientifically and methodically evaluated in recent years. Evaluating the overall safety and effectiveness of acupoint therapies in patients with CINV is the purpose of this review. Relevant randomized controlled trials (RCTSs) are being searched in the following electronic databases: PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), Wanfang Data Knowledge Service Platform, and Chinese Biomedical Literature Database (CBM). We will also attempt to obtain the unpublished academic data by contacting the colleague, professor, or Institute of Traditional Chinese Medicine. The RCTs of the acupoint therapies for CINV patients will be searched in the databases from inception to July 2019. The primary outcomes are defined as severity, duration and frequency of nausea or vomiting, or both. The secondary outcomes are defined as any adverse events and quality of life. Performing the meta-analysis by using RevMan version 5 software. Mean difference (MD) or standardized mean difference (SMD) will express the continuous variables, while relative risk (RR) will express the categorical variables. The results of this review will provide a high-quality synthesis to evaluate the effectiveness and safety of acupoint therapies for CINV. This review will provide evidence to estimate whether acupoint therapies are effective interventions for CINV. Evidence whether acupoint therapies are effective interventions for CINV will be provided by this systematic review. This knowledge will recommend better acupoint therapies and selections of acupoints which might be helpful in treating CINV. The findings of this systematic review will be disseminated via various forms of presentation and publication of the data in a journal or electronic databases. CRD42019125538.


Validity of the 30-Second Sit-to-Stand test as a measure of lower extremity function in persons with multiple sclerosis: Preliminary evidence.
The 30-Second Sit-To-Stand (30SSTS) is a quick, inexpensive, safe, and widely used clinical measure of lower extremity function. To date, there is limited evidence regarding the use of 30SSTS in multiple sclerosis (MS). The purpose of this study was to examine the construct validity of the 30SSTS test in persons with MS compared with non-MS healthy controls. Twenty ambulatory persons with MS and twenty age- and sex-matched healthy controls completed the 30SSTS, Timed 25-Foot Walk (T25FW), Timed Up and Go (TUG), Six-Minute Walk (6MW), and Godin Leisure-Time Exercise Questionnaire (GLTEQ). Persons with MS also completed the Patient Determined Disease Steps (PDDS) and 12-item MS Walking Scale (MSWS-12). Persons with MS had significantly worse performance on the TUG (mean difference [95% confidence interval] = 1.4 [0.5, 2.3] sec) and 6MW (-259.2 [-450.8, -67.6] ft), but not on the 30SSTS (-1.6 [-1.5, 4.6] reps) and T25FW (-0.59 [-0.1, 1.2] ft/sec) compared with controls. There were significant moderate-to-strong correlations between the 30SSTS with T25FW, TUG, and 6MW scores in persons with MS (r = 0.48, -0.65 and 0.61, respectively), whereas the 30SSTS was only significantly associated with 6MW scores (r = 0.43) in controls. The 30SSTS was negatively associated with MS-related walking disability assessed by the PDDS and MSWS-12 (rs = -0.52 and -0.64, respectively), but was not significantly associated with the GLTEQ in MS and controls (r = 0.30 and 0.17, respectively). This study provides initial support for the construct validity of the 30SSTS as a measure of lower extremity function in persons with MS. Our findings warrant the inclusion of the 30SSTS as a feasible and valid measure of physical function in clinical research and practice involving persons with MS.


[Antibodies in systemic autoimmune diseases. Special mention to systemic lupus erythematosus].
Autoantibodies are the expression of humoral response to self-antigens and they may be diagnostic of autoimmune diseases. Studies in systemic lupus erythematosus (SLE) have shown that autoantibodies react with macromolecular structures such as the nucleosome or the spliceosome. These self-antigens are complexes of protein-DNA or protein-RNA like those recognized by anti-dsDNA or anti-RNPs (U1, Sm, Ro, La) antibodies respectively. Recent knowledge on innate immunity has shed more light on the pathological role of these autoantibodies. The antigen-antibody complexes formed as the result of an increase of sel-antigens in the blood as a consequence of an increase in apoptosis, attach to dendritic FcγII or B cell receptors. Through the attachment to the receptor, the macrocomplex is internalized within the cell and recognized in the endosomic membranes by receptors of the innate immune system named TLR (Toll-like receptor). There are at least 13 TLRs localized either in the cellular or the endosomic membranes. Of the latter group, TLR-7 is specific for ssRNA, and TLR-9 is specific for CpG DNA. The reaction of the immunocomplexes with the receptor triggers a kinase cascade that leads to IFNα production. The IFNα is a molecule of the innate and adaptative immune system responsible for the immune deregulation and pathological signs in the SLE. It plays an important role in antigen presentation to the autoreactive quiescent autoreactive T cells and in increasing the life span of dendritic and B cells. In addition, the increase in self-antigens released by greater apoptosis enhances the production of autoantibodies and their effect on the increase of IFNα production.


Responsiveness and convergent validity of QLU-C10D and EQ-5D-3L in assessing short-term quality of life following esophagectomy.
This study assessed the responsiveness and convergent validity of two preference-based measures; the newly developed cancer-specific EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D) relative to the generic three-level version of the EuroQol 5 dimensions (EQ-5D-3L) in evaluating short-term health related quality of life (HRQoL) outcomes after esophagectomy. Participants were enrolled in a multicentre randomised controlled trial to determine the impact of preoperative and postoperative immunonutrition versus standard nutrition in patients with esophageal cancer. HRQoL was assessed seven days before and 42 days after esophagectomy. Standardized Response Mean and Effect Size were calculated to assess responsiveness. Ceiling effects for each dimension were calculated as the proportion of the best level responses for that dimension at follow-up/post-operatively. Convergent validity was assessed using Spearman's correlation and the level of agreement was explored using Bland-Altman plots. Data from 164 respondents (mean age: 63 years, 81% male) were analysed. HRQoL significantly reduced on both measures with large effect sizes (> 0.80), and a greater mean difference (0.29 compared to 0.16) on QLU-C10D. Both measures had ceiling effects (> 15%) on all dimensions at baseline. Following esophagectomy, ceiling effects were observed with self-care (86%), mobility (67%), anxiety/depression (55%) and pain/discomfort (19%) dimensions on EQ-5D-3L. For QLU-C10D ceiling effects were observed with emotional function (53%), physical function (16%), nausea (35%), sleep (31%), bowel problems (21%) and pain (20%). A strong correlation (r = 0.71) was observed between EQ-5D-3L anxiety and QLU-C10D emotional function dimensions. Good agreement (3.7% observations outside the limits of agreement) was observed between the utility scores. The QLU-C10D is comparable to the more widely applied generic EQ-5D-3L, however, QLU-C10D was more sensitive to short-term utility changes following esophagectomy. Cognisant of requirements by policy makers to apply generic utility measures in cost effectiveness studies, the disease-specific QLU-C10D should be used alongside the generic measures like EQ-5D-3L. The trial was registered with the Australian New Zealand Clinical Trial Registry (ACTRN12611000178943) on the 15th of February 2011.


Cost-effectiveness of routine screening for proximal deep venous thrombosis in acquired brain injury patients admitted to rehabilitation.
Determine the prevalence of proximal deep venous thrombosis (DVT) among acquired brain injury patients on admission to rehabilitation and assess cost-effectiveness of routine ultrasound screening for proximal DVT in those patients. Prospective study, sequential case series. University tertiary care rehabilitation center. One hundred sixteen traumatic brain injury patients (TBI) and 48 nontraumatic brain injury patients were admitted to our brain injury (BI) unit over a 21-month period and screened for a DVT on admission to rehabilitation utilizing real time, Doppler, and color Doppler ultrasound. Patients with a previous clinically recognized and treated DVT were excluded. No patients had been treated with prophylactic anticoagulation or intermittent anticoagulation since their BI and all patients were within 4 months of the original injury. Fourteen patients in total (8.5%) were found to have a DVT in the thigh or popliteal area, 9 of the 116 patients in the TBI group (7.8%), and 5 of the 48 patients in the nontraumatic BI group (10.4%). Statistically, there was no significant difference in the total number of detected proximal lower extremity DVTs between the TBI and the nontraumatic BI groups (Fisher's exact test). In the TBI group 22 patients had associated lower extremity or pelvic fractures, but this factor appeared not to be significant, because only 1 of the 22 patients was discovered to have a DVT. The average admission Glascow Coma Score (GCS) of the TBI group was 8.6 but there was no correlation with the GCS and prevalence of DVT. The additional cost of screening for and treating the additional DVTs utilizing color Doppler ultrasound is conservatively estimated to be $674.84 per patient admitted to the BI rehabilitation unit. It can be estimated the cost of saving one life is $129,527.83. DVT screening in this patient population appears to be more cost-effective than mass screening programs for either breast cancer or colorectal cancer. The cost per year of life saved, estimated at only $2,977.65 ($129,527.83/43.5 years) for DVT screening for brain injury patients on admission to rehabilitation, is lower than those costs proposed for comparable programs with significant social support.


Reporting Clinical Significance in Hip Arthroscopy: Where Are We Now?
Although p values are standard for reporting statistical significance of patient-reported outcome measures (PROMs), the shift toward clinically important outcome values, including minimal clinically important difference (MCID) and substantial clinical benefit (SCB), necessitates re-evaluation of the current literature. We sought to answer two questions regarding studies on primary hip arthroscopy performed for the treatment of femoroacetabular impingement syndrome (FAIS). (1) Do such studies reporting statistical significance on common PROMs meet published MCID/SCB thresholds? (2) What proportion of such studies report both statistical and clinical significance? We identified four papers published in two journals defining MCID/SCB values on the modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living (HOS-ADL), Hip Outcome Score-Sport (HOS-Sport), international Hip Outcome Tool (iHOT-33), and its short version (iHOT-12) for different groups of FAIS patients undergoing hip arthroscopy. We reviewed these two journals from the dates of publication to the present to identify papers reporting changes in post-operative PROMs. The difference in pre- and post-operative scores on each PROM was calculated and compared to MCID/SCB thresholds. Twelve studies were included. Ten studies (83%) evaluated mHHS (90% met MCID, 50% met SCB), seven (58%) evaluated HOS-ADL (100% met MCID/SCB) and HOS-Sport (100% met MCID, 57% met SCB), and one (8%) evaluated iHOT-33 (met MCID/SCB) and iHOT-12 (met MCID). Most studies met MCID and SCB at both 1- and 2-year timepoints. Of the studies evaluated, 50% reported clinical relevance. Nearly all studies evaluated met MCID, while fewer met SCB. Only half discussed these clinical measures. It is proposed that all future studies report both statistical and clinical significance as standard best practice.


A novel nomogram for early prediction of death in severe neurological disease patients with electroencephalographic periodic discharges.
To investigate death-related factors in patients with electroencephalographic (EEG) periodic discharges (PDs) and to construct a model for death prediction. This case-control study enrolled a total of 80 severe neurological disease patients with EEG PDs within 72 h of admission to the neuroscience intensive care unit (NICU). According to modified Rankin scale (mRS) scores half a year after discharge, patients were divided into a survival group (<6 points) and a death group (6 points). Their relevant clinical and biochemical indicators as well as EEG characteristics were retrospectively analyzed. Logistic regression analysis was used to identify the risk factors associated with the death of patients with EEG PDs. A death risk prediction model and an individualized nomogram prediction model were constructed, and the prediction performance and concordance of the models were evaluated. Multivariate logistic regression analysis showed that the involvement of both gray and white matter in imaging, disappearance of EEG reactivity, occurrence of stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs), and an interval time of 0.5-4 s were independent risk factors for death. A regression model was established according to the multivariate logistic regression analysis, and the area under the curve of this model was 0.9135. The accuracy of the model was 87.01%, the sensitivity was 87.17%, and the specificity was 89.17%. A nomogram model was constructed, and a concordance index of 0.914 was obtained after internal validation. The regression model based on risk factors has high accuracy in predicting the risk of death of patients with EEG PDs. This model can help clinicians in the early assessment of the prognosis of severe neurological disease patients with EEG PDs.


COVID-19 morbidity in lower versus higher income populations underscores the need to restore lost biodiversity of eukaryotic symbionts.
The avoidance of infectious disease by widespread use of 'systems hygiene', defined by hygiene-enhancing technology such as sewage systems, water treatment facilities, and secure food storage containers, has led to a dramatic decrease in symbiotic helminths and protists in high-income human populations. Over a half-century of research has revealed that this 'biota alteration' leads to altered immune function and a propensity for chronic inflammatory diseases, including allergic, autoimmune and neuropsychiatric disorders. A recent Ethiopian study (EClinicalMedicine 39: 101054), validating predictions made by several laboratories, found that symbiotic helminths and protists were associated with a reduced risk of severe COVID-19 (adjusted odds ratio = 0.35; p<0.0001). Thus, it is now apparent that 'biome reconstitution', defined as the artificial re-introduction of benign, symbiotic helminths or protists into the ecosystem of the human body, is important not only for alleviation of chronic immune disease, but likely also for pandemic preparedness.


Influence of cimetidine on steady state concentration and metabolite formation from antipyrine infused with a rectal osmotic mini pump.
The utility of an osmotic rectal drug delivery system as a tool in steady-state pharmacokinetic interaction studies has been investigated using the cimetidine-antipyrine interaction. Antipyrine was administered to six healthy male volunteers at the rate of 15 mg/h until steady-state was reached. Cimetidine 400 mg was then given followed by 200 mg cimetidine after 2, 4 and 6 h. Antipyrine kinetics in plasma and saliva were assessed, and metabolite excretion was determined in urine. Antipyrine levels in plasma and saliva increased shortly after cimetidine administration, indicating inhibition of antipyrine metabolizing enzymes. From the metabolite data it was concluded that all major metabolic pathways of antipyrine were affected to the same extent. The effect lasted somewhat longer than anticipated on the basis of the plasma cimetidine concentrations, but it had disappeared within 48 hours after cessation of treatment. It is concluded that the osmotic rectal drug delivery system is a useful tool in pharmacokinetic interaction studies, because it provides very constant steady-state concentrations, thus permitting investigation of the time course of drug interactions.


Chronic unpredictable stress negatively regulates hippocampal neurogenesis and promote anxious depression-like behavior via upregulating apoptosis and inflammatory signals in adult rats.
Psychological and physical stress play a pivotal role in etiology of anxiety and depression. Chronic psychological and physical stress modify various physiological phenomena, as a consequence of which oxidative stress, decreased neurotransmitter level, elevated corticosterone level and altered NSC homeostasis is observed. However, the precise mechanism by which chronic stress induce anxious depression and modify internal milieu is still unknown. Herein, we show that exposure to CUS increase oxidative stress, microgliosis, astrogliosis while it reduces hippocampal NSC proliferation, neuronal differentiation and maturation in adult rats. CUS exposure in rats reduce dopamine and serotonin level in cortex and hippocampus, which result in increased anxiety and depression-like phenotypes. We also found elevated level of NF-κB and TNF-α while decreased anti-inflammatory cytokine IL-10 level, that led to increased expression of Bax and cleaved Caspase-3 whereas down regulation of antiapoptotic protein Bcl2. Additionally, CUS altered adult hippocampal neurogenesis, increased gliosis and neuronal apoptosis in cerebral cortex and hippocampus which might be associated with reduced AKT and increased ERK signaling, as seen in the rat brain tissue. Taken together, these results indicate that CUS induce oxidative stress and neuroinflammation which directly affects NSC dynamics, monoamines levels and behavioral functions in adult rats.


Endocrine and psychosocial moderators of mindfulness-based stress reduction for the prevention of perimenopausal depressive symptoms: A randomized controlled trial.
The menopause transition is associated with an increased risk of depressive symptoms. The current study aimed to test whether Mindfulness-Based Stress Reduction, an 8-week group intervention involving meditation and yoga, might reduce the risk of depressive symptoms among perimenopausal women. A secondary aim was to examine baseline characteristics, including sensitivity to estradiol fluctuation, as a moderator of treatment effects. 104 healthy women from the community in the menopause transition were enrolled and randomized to MBSR (n = 52) or a waitlist control condition (n = 52). Randomization was carried out using a random number generator and opaque sealed envelopes. Depressive symptoms, the main outcome, were assessed every two weeks for 6 months using the Center for Epidemiologic Studies Depression Scale (CES-D). The occurrence of an elevated CES-D score (≥16) and of a major depressive episode were pre-identified secondary outcomes. The following surveys were used to assess additional outcomes of interest every two months: the Perceived Stress Scale, Spielberger Trait Anxiety Inventory, Connor-Davidson Resilience Scale, and Pittsburgh Sleep Quality Index. Baseline characteristics examined as potential moderators of treatment benefit included: baseline CES-D score, past depressive episodes, recent stressful life events, a history of physical or sexual abuse, and emotional sensitivity to reproductive hormone fluctuation. Outcome assessors were blinded to the participants' assigned treatment arm. Outcome data were available for 44 women assigned to MBSR and 51 women in the waitlist condition. Women randomized to MBSR reported fewer depressive symptoms, less perceived stress, less anxiety, increased resilience, and improved sleep (ps < 0.001). Furthermore, several baseline characteristics predicted a greater mood benefit of MBSR, including: a history of major depression (p for the interaction <0.001), a greater number of recent stressful life events (p < .001), being in the early menopause transition (p = .002), and an increased emotional sensitivity to reproductive hormone fluctuation (p = .004). There were no group differences in the occurrence of major depressive episodes (p > .05). MBSR appears to be an effective intervention for the prevention of depressive symptoms in the menopause transition.


Measuring fruit and vegetable intake: is five-a-day enough?
Validation of a self-monitoring "portions' measurement of fruit and vegetable (F&V) consumption against a standard of weighed intakes. Component of a randomized controlled trial. Subjects attended research centres in Reading and Glasgow for instruction and monitoring but undertook free-living dietary changes at home. A study sample of 42 adult men and women fulfilling the main recruitment criterion of eating less than five F&V portions/day but contemplating increasing intakes and providing weighted baseline reported energy intakes exceeding (estimated basal metabolic rate x 1.1). Subjects attended an intensive group advice session which included the specific relationship of high F&V intake with reduced risk of disease; practicalities; portion definition and measurement recording. The target was to exceed five F&V portions/day for 8 weeks. Self-recorded simultaneous weighed inventories and F&V portion measures. Data from subjects who were not evident under-recorders showed correlations between portion and weighed intakes of r = 0.73, (P < 0.000), although the portions measure tended to under-estimate intakes. Using 80 g/portion the "5-a-day' concept tends to create false negatives (namely consumption could be greater than 400 g whilst recording fewer than five discrete portions) but rarely false positives (namely recorded consumption of less than 400 g did not give measures of more than five discrete portions). The data suggest that the five portions F&V/day health message, if used in conjunction with defined discrete portions, would encourage desirable consumption exceeding 400 g.


Atypical structural connectivity of language networks in autism spectrum disorder: A meta-analysis of diffusion tensor imaging studies.
Patients with autism spectrum disorder (ASD) often show pervasive and complex language impairments that are closely associated with aberrant structural connectivity of language networks. However, the characteristics of white matter connectivity in ASD have remained inconclusive in previous diffusion tensor imaging (DTI) studies. The current meta-analysis aimed to comprehensively elucidate the abnormality in language-related white matter connectivity in individuals with ASD. We searched PubMed, Web of Science, Scopus, and Medline databases to identify relevant studies. The standardized mean difference was calculated to measure the pooled difference in DTI metrics in each tract between the ASD and typically developing (TD) groups. The moderating effects of age, sex, language ability, and symptom severity were investigated using subgroup and meta-regression analysis. Thirty-three DTI studies involving 831 individuals with ASD and 836 TD controls were included in the meta-analysis. ASD subjects showed significantly lower fractional anisotropy or higher mean diffusivity across language-associated tracts than TD controls. These abnormalities tended to be more prominent in the left language networks than in the right. In addition, children with ASD exhibit more pronounced and pervasive disturbances in white matter connectivity than adults. These results support the under-connectivity hypothesis and demonstrate the widespread abnormal microstructure of language-related tracts in patients with ASD. Otherwise, white matter abnormalities in the autistic brain could vary depending on the developmental stage and hemisphere. LAY SUMMARY: This meta-analysis explored abnormalities in white matter connectivity in language networks of individuals with ASD. Significantly reduced white matter integrity was found in all language-associated tracts in subjects with ASD compared with TD controls. In addition, structural disturbances of language networks in the autistic brain exhibit a leftward tendency, and more prominent abnormalities are observed in younger people with ASD than in adults.


Comparison of pain management in paediatric surgical patients in two hospitals in France and Canada.
Pain management in children has improved substantially over the last few years but continues to vary widely across institutions. Our objective was to describe the evaluation and treatment of pain in paediatric patients in two hospitals (Robert Debré in Paris, France, and Sainte-Justine, Montréal, Canada) and to compare conformity with quality criteria. Retrospective medical chart of a total of 200 patients with uncomplicated appendectomy, spinal fusion, ureteroneocystostomy, or laparoscopic cholecystectomy were analysed, with special attention to nurses' entries, prescriptions, and medication administration sheets. Patient characteristics and variables pertaining to pain evaluation (tool and result) and treatment (date, prescription and administration details) were collected. Quality criteria for evaluating conformity with guidelines were taken from the literature. Any change in medication, dosage, or dosing interval was taken as a new prescription. About 929 prescriptions and 2,388 numerical pain scores were recorded for 200 patients. Pain was recorded at 70.8% of vital-sign evaluations at the Robert-Debré Hospital compared to 30.9% at the Sainte-Justine hospital (P < 0.0001). A validated age-appropriate pain evaluation tool was used in 97.4 and 94.1% of evaluations in these two hospitals, respectively (P < 0.0001). Analgesic dosage was appropriate in 92.5% of prescriptions at Robert-Debré and 86.0% of those at Sainte-Justine (P = 0.002). This study documents differences in post-operative pain management between two paediatric hospitals. We found differences between the two hospitals regarding the frequency of pain evaluation, the use of validated tools for evaluating pain, and analgesic dosages. Continued efforts to educate prescribing physicians and other healthcare providers are needed to improve pain management in children.


Comparison of prognostic value of MRI and FIGO stage among patients with cervical carcinoma treated with radiotherapy.
To compare the efficacy of MRI and FIGO stage, we performed retrospective multicenter analysis of patients with Stage II-III disease treated with radiation alone. From three institutions, 164 patients diagnosed with cervical carcinoma were entered into the study. The majority of this cohort received intracavitary brachytherapy combined with external beam radiotherapy (n = 161). Uni- and multivariate analyses were performed to identify the prognostic factors for overall survival (OAS), disease-free survival (DFS), pelvic control (PC), and distant metastasis-free survival (DMFS). The 5-year OAS, DFS, PC, and DMFS rates were 68.8%, 60.4%, 77.4%, and 71.7%, respectively. Using uni- and multivariate analyses, both large tumor size/volume and positive lymph node enlargement (LN) showed a significantly unfavorable influence on survival and local and/or distant failure (p < 0.05). Using these two prognostic factors, patients were divided into three subgroups; the 5-year DFS rates of patients with risk 0 (volume </=50 cc and negative LN), 1 (volume >50 cc or positive LN), and 2 (volume >50 cc and positive LN) were 72.9%, 53.3%, and 26.1%, respectively (p < 0.0001). Among patients with volume </=50 cc, disease stage proved to be a significantly prognostic factor of OAS, DFS, and PC (p < 0.05). However, these correlations were not observed in the large volume group (p > 0.05). MRI will provide more useful and practical information than will FIGO stage classification for patients with bulky disease, although this will remain a prognostic factor for patients with nonbulky disease (volume </=50 cc). With the aid of MRI, accurate and practical evaluation of clinical outcome could be achieved.


On the genetics of the Rett syndrome.
Ever since its recognition as a separate disease, the Rett syndrome has been reported to afflict girls only. For this reason, heredity has consistently remained at the forefront of discussions regarding putative causes. On account of the gravity of the disorder and the want for adequate therapy, the clarification of its genesis is of great practical importance in consideration of the possibility of descendants. J Wahlström reports a breakpoint at Xp22 in two sisters with the disease and in their healthy mother. This finding is questionable as being typical of the syndrome in light of recent chromosomal findings. In addition to Wahlström's two-step-mutation hypothesis, an earlier suggestion of an X-chromosomal dominant new mutation is under discussion again. Further genetic findings are expected from a yet-to-be-completed interpretation of all relevant data hitherto observed in approximately 160 probands and their families.