A comparison of the accuracy of two minimally invasive breast biopsy methods: a systematic literature review and meta-analysis.
The primary objective was to quantify and compare the accuracy and failure rates of directional vacuum assisted biopsy (DVAB) and core needle biopsy (CNB) when used under stereotactic (ST) guidance to biopsy suspicious breast lesions identified with screening mammography. We performed a systematic review of the literature published from January 1996 to July 2004, reporting all-comers populations in Western-style health care systems (i.e., North America, Europe, Australia or New Zealand), referred after screening mammography for breast biopsy using DVAB or CNB under ST guidance. Meta-analyses were conducted for DVAB and CNB, using open surgical biopsy and/or long-term clinical and/or mammogram follow-up as the diagnostic reference standard. The main outcomes of interest were those of greatest clinical relevance, i.e., miss rates and underestimation rates for malignancy. Also, technical failure rate and non-diagnostic rate were assessed for each biopsy method. Thirty-five studies qualified for the review. There were 12 studies with a DVAB group (n=5,119 patients), and 25 studies with a CNB group (n=6,236). There were no studies including both a DVAB and a CNB group, thus precluding any direct, within-study comparisons of accuracy. Overall agreement rate between DVAB and the reference standard was 97.3%, and between CNB and the reference standard, 93.5%. The frequency of technical failures with CNB was slightly higher than DVAB (5.7 vs. 1.5%), as was the frequency of non-diagnostic samples (2.1 vs. 0%). Of the non-diagnostic CNB samples, 23% were subsequently found to be malignant on reference standard. In multivariate analyses using four covariates (procedure type, geographic location, reference standard, and patient position), there were no significant predictors of agreement rates, but some variables were significant predictors of miss rates. For benign to malignant upgrades, study location was a significant predictor, with more upgrades in non-NA locations. For atypia to malignant upgrades, the type of procedure was a significant predictor, with more underestimations in CNB studies. The best available evidence suggests that, in screening populations referred for minimally invasive breast biopsy biopsy requiring ST guidance, DVAB may provide lower miss and underestimation rates for clinically relevant diagnoses than does CNB.


Transcriptional regulation of transferrin receptor expression by cultured lymphoblastoid T cells treated with phorbol diesters.
Expression of transferrin receptors (TFR) is required for lymphocyte proliferation. Treatment of lymphoblastic leukemia cell lines with phorbol diester tumor promoters decreases proliferation and induces differentiation. Among changes induced by phorbol diesters is decreased cell surface expression of TFR. To elucidate effects of phorbols on lymphocyte growth and differentiation, we examined TFR expression by measuring 125I-transferrin binding, levels of TFR mRNA by Northern analysis and dot-blot hybridization, and rates of TFR gene transcription by nuclear run-on experiments in CCRF-CEM lymphoblastoid T cells treated with PMA or phorbol dibutyrate. Cell surface expression of TFR was decreased 60 to 85% within 2 min of exposing cells to phorbols and remained decreased for 96 h. Steady state levels of TFR mRNA decreased to less than 30% of control after 48 h. After treating cells with actinomycin D, estimated TFR mRNA t 1/2 was 2.7 h and was unaltered in phorbol-treated cells. Levels of TFR mRNA were not affected by treatment of cells with cycloheximide in either control or phorbol-treated cells. Therefore, post transcriptional mRNA processing by protein factors did not account for decreased TFR mRNA in phorbol-treated cells. Compared to baseline levels, rates of TFR gene transcription in PMA-treated cells increased up to two-fold during the initial 6 h of culture, then decreased over the ensuing 12 h to less than 10% of baseline values. This pattern was not seen in control cultures. Therefore, regulation of TFR gene transcription is a consequence of treating CEM cells with phorbol diesters. Cell surface expression of TFR in phorbol-treated lymphoblastoid T cells may be mediated in part at the level of gene transcription.


[The isolation of Vibrio fluvialis on the territory of the USSR].
For the first time V. fluvialis strains were detected on the territory of the USSR. The taxonomic position of these vibrios was determined by their nucleotide DNA composition (the content of guanine + cytosine was 49.3-51.0 mole%) and the characteristic features of their phenotype. The individual features of the strains consisted in their capacity for agglutination with cholera antisera, groups 01 and Inaba, in diagnostic dilutions in the presence of differences in genomes and phenotypes with cholera vibrios. Molecular hybridization DNA-DNA also gave no confirmation of their relationship to cholera vibrios (23-26% homology). The comparative study of V. fluvialis strains from the USSR and other countries by a broader set of their phenotypical signs confirmed their identity.


Dichotic listening in children: the reflection of verbal and attentional changes with age.
A sample of 290 kindergarten children (147 girls), all native Hebrew speakers, were tested by two dichotic listening tests: (a) a digits test (low verbal workload) and (b) a words test (high verbal workload). The same subjects were tested one year later (at the end of their first year at school) by the same tests. In both tests and both testing sessions the free recall procedure was used. It was found that the performance difference between ears significantly decreased and overall performance significantly increased in the digits test in the second testing session. Differences between sessions in ear difference in the words test were not significant, although overall performance in the second session increased. These data lend support to the hypothesis that the change with age in the between-ears difference is mainly related to an improvement in verbal processing efficiency, which in turn allows the allocation of more verbal resources to the inferior input channel, without a decrease in resources allocated to the preferred one. As expected, increase in available verbal resources was clearly manifested under low verbal workload conditions but not under high workload conditions, where task demands did not allow significant increase in verbal resources to be allocated to the inferior channel. This hypothesis also predicted highly consistent ear preference owing to its being solely determined by the verbal processors of the dominant-to-speech hemisphere. The inconsistent ear preference between tests found in more than a third of the subjects of this sample could not therefore be accounted for by the stated hypothesis. The analysis of performance in subjects who showed left-ear preference in only one test and right-ear advantage on the other occasions indicated that whenever the left ear was preferred it was accompanied by significantly smaller ear difference and lower overall performance compared with those manifested by the same subjects in the same test in the other testing session. These data are better accounted for by the hypothesis that two different pools of resources are involved in splitting attention between ears in the free recall of dichotically presented verbal stimuli: one which is controlled by verbal processors of the dominant-to-speech hemisphere and the other by a spatial attentional mechanism. However, it seems that changes in dichotic test performance within the first year at school can mainly be attributed to increase in verbal resources rather than to improvement in allocation of spatially controlled resources.


Comparison of Two Questionnaires for Dry Eye Symptom Assessment: The Ocular Surface Disease Index and the Symptom Assessment in Dry Eye.
The aim of this study was to compare patient-reported symptoms of dry eye disease (DED) as assessed by the Ocular Surface Disease Index (OSDI), a 12-item symptom frequency-based questionnaire, and the Symptom Assessment iN Dry Eye (SANDE), a 2-item frequency- and severity-based visual analog scale. Clinic-based evaluation of a diagnostic test. A total of 114 patients with DED. Patients were administered the OSDI and SANDE questionnaires at baseline and follow-up visits to evaluate DED-related symptoms. The correlations between both questionnaires' scores were evaluated using the Spearman coefficient, and their clinical differences were assessed using Bland-Altman analysis. Baseline and follow-up visit OSDI and SANDE dry eye symptom scores. At the baseline visit, the OSDI and SANDE questionnaire scores were significantly correlated (R = 0.64; P < 0.001). Moreover, a significant correlation was found between changes in the OSDI and SANDE scores from baseline to follow-up visits (R = 0.47; P < 0.001). A Bland-Altman analysis, after score normalization, revealed a difference (bias) of less than 2 centesimal units between the scores of the 2 questionnaires. Data collected from the SANDE questionnaire showed a significant correlation and negligible score differences with those from the OSDI, suggesting that the SANDE visual analog scale-based questionnaire has the potential to provide clinicians with a short, quick, and reliable measure for DED symptoms.


Sporobolomyces agrorum sp. nov. and Sporobolomyces sucorum sp. nov., two novel basidiomycetous yeast species isolated from grape and apple must in Italy.
During a survey of yeast populations associated with grape and apple musts used for wine and cider fermentation, respectively, six pink-coloured ballistoconidia-forming yeasts belonging to the order Sporidiobolales (Basidiomycota) were isolated. Phylogenetic analysis inferred using sequences of the internal transcribed spacer (ITS), the D1/D2 domain of the large subunit rRNA gene, the small subunit (SSU) rRNA gene and DNA-directed RNA polymerase II subunit (RPB2) indicated that the six isolates were separated in two novel species. One of the new species, Sporobolomyces agrorum sp. nov., isolated from grape must, had Sporobolomyces roseus and Sporobolomyces metaroseus as its closest relatives, but showed four/two and 16 nucleotide substitutions in the D1/D2 and ITS regions, respectively, to these two species. The other novel species, Sporobolomyces sucorum sp. nov., was found in apple must and was closely related to Sporobolomyces pararoseus and Sporobolomyces patagonicus, but showed two/three and five substitutions in those two regions for its closest relatives. We detected additional representatives of this species, most of them isolated from grapes whose sequences were already available on public databases. A sexual stage could not be observed for the novel species.


From reptilian phylogenomics to reptilian genomes: analyses of c-Jun and DJ-1 proto-oncogenes.
Genome projects have revolutionized our understanding of both molecular biology and evolution, but there has been a limited collection of genomic data from reptiles. This is surprising given the pivotal position of reptiles in vertebrate phylogeny and the potential utility of information from reptiles for understanding a number of biological phenomena, such as sex determination. Although there are many potential uses for genomic data, one important and useful approach is phylogenomics. Here we report cDNA sequences for the c-Jun(JUN) and DJ-1(PARK7) proto-oncogenes from 3 reptiles (the American alligator, Nile crocodile, and Florida red-belly turtle), show that both genes are expressed in the alligator, and integrate them into analyses of their homologs from other organisms. With these taxa it was possible to conduct analyses that include all major vertebrate lineages. Analyses of c-Jun revealed an unexpected but well-supported frog-turtle clade while analyses of DJ-1 revealed a topology largely congruent with expectation based upon other data. The conflict between the c-Jun topology and expectation appears to reflect the overlap between c-Jun and a CpG island in most taxa, including crocodilians. This CpG island is absent in the frog and turtle, and convergence in base composition appears to be at least partially responsible for the signal uniting these taxa. Noise reduction approaches can eliminate the unexpected frog-turtle clade, demonstrating that multiple signals are present in the c-Jun alignment. We used phylogenetic methods to visualize these signals; we suggest that examining both historical and non-historical signals will prove important for phylogenomic analyses.


Spatiotemporal signaling underlies progressive vascular rarefaction in myocardial infarction.
Therapeutic angiogenesis represents a promising avenue to revascularize the ischemic heart. Its limited success is partly due to our poor understanding of the cardiac stroma, specifically mural cells, and their response to ischemic injury. Here, we combine single-cell and positional transcriptomics to assess the behavior of mural cells within the healing heart. In response to myocardial infarction, mural cells adopt an altered state closely associated with the infarct and retain a distinct lineage from fibroblasts. This response is concurrent with vascular rarefaction and reduced vascular coverage by mural cells. Positional transcriptomics reveals that the infarcted heart is governed by regional-dependent and temporally regulated programs. While the remote zone acts as an important source of pro-angiogenic signals, the infarct zone is accentuated by chronic activation of anti-angiogenic, pro-fibrotic, and inflammatory cues. Together, our work unveils the spatiotemporal programs underlying cardiac repair and establishes an association between vascular deterioration and mural cell dysfunction.


[Prevalence of antinuclear antibodies in primary biliary cirrhosis, with negative antimitochondrial antibodies].
Recently it has been described in the literature a subpopulation of PBC patients with negative AMA that might represent patients with ANA positive autoimmune cholangitis. We review 25 cases of PBC (23 females) with AMA negative. Our aim was to determine the frequency of ANA(+) in this group. We studied serum transaminases, total bilirubin, AMA and ANA by indirect immunofluorescence considering positive dilutions of 1:40. All patients had elevated alkaline phosphatase (641 +/- 389 U/l). Total bilirubin was below 2.5 in 59%. Thirteen patients had esophageal varices. The histologic stage was I-II in eleven and III-IV in 14 cases. Fourteen patients (56%) has ANA(+) (dilution 1:40), 44% had lower dilutions. We confirm the presence of a subpopulation of PBC AMA negative, ANA positive patients and the observations of different and diverse immune alterations in PBC patients.


The autophagic response to Staphylococcus aureus provides an intracellular niche in neutrophils.
Staphylococcus aureus is a major human pathogen causing multiple pathologies, from cutaneous lesions to life-threatening sepsis. Although neutrophils contribute to immunity against S. aureus, multiple lines of evidence suggest that these phagocytes can provide an intracellular niche for staphylococcal dissemination. However, the mechanism of neutrophil subversion by intracellular S. aureus remains unknown. Targeting of intracellular pathogens by macroautophagy/autophagy is recognized as an important component of host innate immunity, but whether autophagy is beneficial or detrimental to S. aureus-infected hosts remains controversial. Here, using larval zebrafish, we showed that the autophagy marker Lc3 rapidly decorates S. aureus following engulfment by macrophages and neutrophils. Upon phagocytosis by neutrophils, Lc3-positive, non-acidified spacious phagosomes are formed. This response is dependent on phagocyte NADPH oxidase as both cyba/p22phox knockdown and diphenyleneiodonium (DPI) treatment inhibited Lc3 decoration of phagosomes. Importantly, NADPH oxidase inhibition diverted neutrophil S. aureus processing into tight acidified vesicles, which resulted in increased host resistance to the infection. Some intracellular bacteria within neutrophils were also tagged by Sqstm1/p62-GFP fusion protein and loss of Sqstm1 impaired host defense. Together, we have shown that intracellular handling of S. aureus by neutrophils is best explained by Lc3-associated phagocytosis (LAP), which appears to provide an intracellular niche for bacterial pathogenesis, while the selective autophagy receptor Sqstm1 is host-protective. The antagonistic roles of LAP and Sqstm1-mediated pathways in S. aureus-infected neutrophils may explain the conflicting reports relating to anti-staphylococcal autophagy and provide new insights for therapeutic strategies against antimicrobial-resistant Staphylococci.Abbreviations: ATG: autophagy related; CFU: colony-forming units; CMV: cytomegalovirus; Cyba/P22phox: cytochrome b-245, alpha polypeptide; DMSO: dimethyl sulfoxide; DPI: diphenyleneiodonium; EGFP: enhanced green fluorescent protein; GFP: green fluorescent protein; hpf: hours post-fertilization; hpi: hours post-infection; Irf8: interferon regulatory factor 8; LAP: LC3-associated phagocytosis; lyz: lysozyme; LWT: london wild type; Map1lc3/Lc3: microtubule-associated protein 1 light chain 3; NADPH oxidase: nicotinamide adenine dinucleotide phosphate oxidase; RFP: red fluorescent protein; ROS: reactive oxygen species; RT-PCR: reverse transcriptase polymerase chain reaction; Sqstm1/p62: sequestosome 1; Tg: transgenic; TSA: tyramide signal amplification.


Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma Foundation.
These consensus guidelines have been compiled with input from the Scientific Advisors of the International Myeloma Foundation. Their production involved several steps including: A 3-day Scientific Advisors meeting, during which each specific area was presented and discussed (May 2002). Review of key literature, especially randomized study results, but also Medline, Internet, Cochrane database searches, and prior guidelines (Br J Haematol 115: 522-540, 2001). Feedback from patients participating in the International Myeloma Foundation, patient programs. These guidelines encompass both the published literature and expert opinions. Recommendations based upon expert opinions are identified as such. The intent is for the guidelines to be international in scope, plus provide recommendations for both clinical practice and research approaches. 'Consensus' reflects general, although not necessarily unanimous, agreement. Details are discussed as appropriate. For convenience, the recommendations are divided into: 1. Diagnostic criteria. 2. Staging and prognostic factors. 3. Frontline therapy. 4. High-dose therapy and transplant. 5. Maintenance therapy. 6. Supportive care and management of specific complications. 7. Novel therapies and new technologies.


Nanoparticles augment the therapeutic window of RT and immunotherapy for treating cancers: pivotal role of autophagy.
Immunotherapies are now emerging as an efficient anticancer therapeutic strategy. Cancer immunotherapy utilizes the host's immune system to fight against cancer cells and has gained increasing interest due to its durable efficacy and low toxicity compared to traditional antitumor treatments, such as chemotherapy and radiotherapy (RT). Although the combination of RT and immunotherapy has drawn extensive attention in the clinical setting, the overall response rates are still low. Therefore, strategies for further improvement are urgently needed. Nanotechnology has been used in cancer immunotherapy and RT to target not only cancer cells but also the tumor microenvironment (TME), thereby helping to generate a long-term immune response. Nanomaterials can be an effective delivery system and a strong autophagy inducer, with the ability to elevate autophagy to very high levels. Interestingly, autophagy could play a critical role in optimal immune function, mediating cell-extrinsic homeostatic effects through the regulation of danger signaling in neoplastic cells under immunogenic chemotherapy and/or RT. In this review, we summarize the preclinical and clinical development of the combination of immunotherapy and RT in cancer therapy and highlight the latest progress in nanotechnology for augmenting the anticancer effects of immunotherapy and RT. The underlying mechanisms of nanomaterial-triggered autophagy in tumor cells and the TME are discussed in depth. Finally, we suggest the implications of these three strategies combined together to achieve the goal of maximizing the therapeutic advantages of cancer therapy and show recent advances in biomarkers for tumor response in the evaluation of those therapies.


Sindbis virus mutants selected for rapid growth in cell culture display attenuated virulence in animals.
Mutants of Sindbis virus were selected for rapid growth in baby hamster kidney (BHK) cell cultures and screened for attenuation of virulence in suckling mice. Comparisons among independently isolated virulent and attenuated strains, as well as a classical reversion analysis, showed that accelerated penetration of BHK cells was correlated with attenuation in vivo. Both phenotypic changes resulted from a reorganization of virion structure as detected by monoclonal antibodies. These results suggest that mutants selected for rapid growth in cell culture may be useful as attenuated vaccines and for studies of the molecular basis of virus pathogenesis.


Identification and characterization of PhbF: a DNA binding protein with regulatory role in the PHB metabolism of Herbaspirillum seropedicae SmR1.
Herbaspirillum seropedicae SmR1 is a nitrogen fixing endophyte associated with important agricultural crops. It produces polyhydroxybutyrate (PHB) which is stored intracellularly as granules. However, PHB metabolism and regulatory control is not yet well studied in this organism. In this work we describe the characterization of the PhbF protein from H. seropedicae SmR1 which was purified and characterized after expression in E. coli. The purified PhbF protein was able to bind to eleven putative promoters of genes involved in PHB metabolism in H. seropedicae SmR1. In silico analyses indicated a probable DNA-binding sequence which was shown to be protected in DNA footprinting assays using purified PhbF. Analyses using lacZ fusions showed that PhbF can act as a repressor protein controlling the expression of PHB metabolism-related genes. Our results indicate that H. seropedicae SmR1 PhbF regulates expression of phb-related genes by acting as a transcriptional repressor. The knowledge of the PHB metabolism of this plant-associated bacterium may contribute to the understanding of the plant-colonizing process and the organism's resistance and survival in planta.


Psychophysics of reading. XVII. Low-vision performance with four types of electronically magnified text.
Most people with low vision need magnification to read. Page navigation is the process of moving a magnifier during reading. Modern electronic technology can provide many alternatives for navigating through text. This study compared reading speeds for four methods of displaying text. The four methods varied in their page-navigation demands. The closed-circuit television (CCTV) and MOUSE methods involved manual navigation. The DRIFT method (horizontally drifting text) involved no manual navigation, but did involve both smooth-pursuit and saccadic eye movements. The rapid serial visual presentation (RSVP) method involved no manual navigation, and relatively few eye movements. There were 7 normal subjects and 12 low-vision subjects (7 with central-field loss, CFL group, and 5 with central fields intact, CFI group). The subjects read 70-word passages at speeds that yielded good comprehension. Taking the CCTV reading speed as a benchmark, neither the normal nor low-vision subjects had significantly different speeds with the MOUSE method. As expected from the reduced navigational demands, normal subjects read faster with the DRIFT method (85% faster) and the RSVP method (169%). The CFI group read significantly faster with DRIFT (43%) and RSVP (38%). The CFL group showed no significant differences in reading speed for the four methods.


High-performing physicians are more likely to participate in a research study: findings from a quality improvement study.
Participants in voluntary research present a different demographic profile than those who choose not to participate, affecting the generalizability of many studies. Efforts to evaluate these differences have faced challenges, as little information is available from non-participants. Leveraging data from a recent randomized controlled trial that used health administrative databases in a jurisdiction with universal medical coverage, we sought to compare the quality of care provided by participating and non-participating physicians prior to the program's implementation in order to assess whether participating physicians provided a higher baseline quality of care. We conducted clustered regression analyses of baseline data from provincial health administrative databases. Participants included all family physicians who were eligible to participate in the Improved Delivery of Cardiovascular Care (IDOCC) project, a quality improvement project rolled out in a geographically defined region in Ontario (Canada) between 2008 and 2011. We assessed 14 performance indicators representing measures of access, continuity, and recommended care for cancer screening and chronic disease management. In unadjusted and patient-adjusted models, patients of IDOCC-participating physicians had higher continuity scores at the provider (Odds Ratio (OR) [95% confidence interval]: 1.06 [1.03-1.09]) and practice (1.06 [1.04-1.08]) level, lower risk of emergency room visits (Rate Ratio (RR): 0.93 [0.88-0.97]) and hospitalizations (RR:0.87 [0.77-0.99]), and were more likely to have received recommended diabetes tests (OR: 1.25 [1.06-1.49]) and cancer screening for cervical cancer (OR: 1.32 [1.08-1.61] and breast cancer (OR: 1.32 [1.19-1.46]) than patients of non-participating physicians. Some indicators remained statistically significant in the model after adjusting for provider factors. Our study demonstrated a participation bias for several quality indicators. Physician characteristics can explain some of these differences. Other underlying physician or practice attributes also influence interest in participating in quality improvement initiatives and existing quality levels. The standard for addressing participation bias by controlling for basic physician and practice level variables is inadequate for ensuring that results are generalizable to primary care providers and practices.


Differential and integral cross sections in OH(X) + Xe collisions.
Differential cross sections (DCSs) for inelastic collisions of OH(X) with Xe have been measured at a collision energy of 483 cm(-1). The hydroxyl (OH) radicals were initially prepared in the X(2)Π3/2 (v = 0, j = 1.5, f) level using the hexapole electric field selection method. Products were detected state-selectively by [2 + 1] resonance-enhanced multiphoton ionization of OH, combined with velocity-map imaging. Integral cross sections in OH(X) + Xe at a collision energy of 490 cm(-1) were also measured by laser-induced fluorescence. The results are compared with exact close-coupling quantum mechanical scattering calculations on the only available ab initio potential energy surface (PES). The agreement between experimental and theoretical results is generally very satisfactory. This highlights the ability of such measurements to test the available PES for such a benchmark open-shell system. The agreement between experiment and theory for DCSs is less satisfactory at low scattering angles, and possible reasons for this disagreement are discussed. Finally, theoretical calculations of OH(X) + He DCSs have been obtained at various collision energies and are compared with those of OH(X) + Xe. The role of the reduced mass in the DCSs and partial cross sections is also examined.


Systematic analysis of Arabidopsis organelles and a protein localization database for facilitating fluorescent tagging of full-length Arabidopsis proteins.
Cells are organized into a complex network of subcellular compartments that are specialized for various biological functions. Subcellular location is an important attribute of protein function. To facilitate systematic elucidation of protein subcellular location, we analyzed experimentally verified protein localization data of 1,300 Arabidopsis (Arabidopsis thaliana) proteins. The 1,300 experimentally verified proteins are distributed among 40 different compartments, with most of the proteins localized to four compartments: mitochondria (36%), nucleus (28%), plastid (17%), and cytosol (13.3%). About 19% of the proteins are found in multiple compartments, in which a high proportion (36.4%) is localized to both cytosol and nucleus. Characterization of the overrepresented Gene Ontology molecular functions and biological processes suggests that the Golgi apparatus and peroxisome may play more diverse functions but are involved in more specialized processes than other compartments. To support systematic empirical determination of protein subcellular localization using a technology called fluorescent tagging of full-length proteins, we developed a database and Web application to provide preselected green fluorescent protein insertion position and primer sequences for all Arabidopsis proteins to study their subcellular localization and to store experimentally verified protein localization images, videos, and their annotations of proteins generated using the fluorescent tagging of full-length proteins technology. The database can be searched, browsed, and downloaded using a Web browser at http://aztec.stanford.edu/gfp/. The software can also be downloaded from the same Web site for local installation.


Detection of Helicobacter pylori in stool specimens by PCR and antigen enzyme immunoassay.
A highly sensitive seminested PCR assay to detect Helicobacter pylori DNA in feces was developed. PCR with stool specimens and a novel antigen enzyme immunoassay (EIA) for H. pylori detection in feces were evaluated as diagnostic tools and in follow-up with samples from 63 infected and 37 noninfected persons. Infected individuals received eradication therapy followed by endoscopic follow-up 35 days after the start of treatment. At that time, a second stool specimen was obtained from 55 of these patients. Before eradication, the sensitivity of PCR was 93.7% and that of EIA 88.9%. Specificities were 100 and 94.6%, respectively. Of the 55 follow-up specimens, 41 originated from patients from whom H. pylori had been eradicated. Of these, 21 were still positive by PCR and 13 were positive by EIA, indicating that 1 month may be too short a period for follow-up evaluation of stool specimens by these tests.


Exposure to an agricultural contaminant, 17β-trenbolone, impairs female mate choice in a freshwater fish.
Despite the pivotal role sexual selection plays in population dynamics and broader evolutionary processes, the impact of chemical pollution on female mate choice is poorly understood. One group of chemical contaminants with the potential to disrupt the mechanisms of female mate choice is endocrine disrupting chemicals (EDCs); a broad class of environmental pollutants that can interfere with the endocrinology of organisms at extremely low concentrations. Recent research has revealed that estrogenic EDCs can affect female mate choice in fish, but the impact of androgenic EDC exposure is yet to be studied. To address this, we investigated the effects of an environmentally relevant concentration of trenbolone - an androgenic steroid used as a growth promoter in the cattle industry - on female mate choice in wild-caught guppies (Poecilia reticulata). We exposed male and female guppies to 17β-trenbolone for 21 days (measured concentration 4ng/L) via a flow-through system, and found that trenbolone-exposed female guppies spent less time associating with males, and were less choosy, compared to unexposed females. In contrast, trenbolone had no impact on male reproductive behavior or morphology. This is the first study to show that androgenic EDC exposure can disrupt female mate choice, highlighting the need for studies to investigate the behavioral impacts of environmental contaminants on both sexes.


Social cognitive predictors of intention to test for variant Creutzfeldt-Jakob disease in those affected by haemophilia and other clotting disorders.
Individuals with bleeding disorders are at increased risk of variant Creutzfeldt-Jakob disease. This study explored social cognitive predictors of screening intentions. Ninety men and women with bleeding disorders, recruited through the Haemophilia Society, completed an extended Theory of Planned Behaviour questionnaire to predict intention to screen for variant Creutzfeldt-Jakob disease. Extended Theory of Planned Behaviour variables accounted for 57 per cent of the variance in intention. Self-efficacy and anticipated affect predicted intention directly, while attitudes were mediated by anticipated affect. Simple interventions that already exist address relevant predictive components of intention to screen for variant Creutzfeldt-Jakob disease and could be used to aid decision-making.


eRNA profiling uncovers the enhancer landscape of oesophageal adenocarcinoma and reveals new deregulated pathways.
Cancer is driven by both genetic and epigenetic changes that impact on gene expression profiles and the resulting tumourigenic phenotype. Enhancers are transcriptional regulatory elements that are key to our understanding of how this rewiring of gene expression is achieved in cancer cells. Here, we have harnessed the power of RNA-seq data from hundreds of patients with oesophageal adenocarcinoma (OAC) or its precursor state Barrett's oesophagus coupled with open chromatin maps to identify potential enhancer RNAs and their associated enhancer regions in this cancer. We identify ~1000 OAC-specific enhancers and use these data to uncover new cellular pathways that are operational in OAC. Among these are enhancers for JUP, MYBL2, and CCNE1, and we show that their activity is required for cancer cell viability. We also demonstrate the clinical utility of our dataset for identifying disease stage and patient prognosis. Our data therefore identify an important set of regulatory elements that enhance our molecular understanding of OAC and point to potential new therapeutic directions.


Involvement of lay visitors in general practice assessment visits.
Six practice assessment visits which jointly involved lay and medical visitors were arranged by the patient liaison group of the Royal College of General Practitioners. These visits were inspired by the 'What sort of doctor' report published by the RCGP in 1985. A subgroup of the patient liaison group adapted the assessment grid from the report to take account of involving lay visitors with doctors on practice visits. The visits were educationally valuable to the lay visitors, and also prompted some practical changes in the practices. This experiment might have further application in the development of fellowship by assessment or even in the process of reaccreditation of general practitioners.


Comprehensive Review of Quality of Publications and Meta-analysis of Genetic Damage in Mammalian Cells Exposed to Non-Ionizing Radiofrequency Fields.
There have been numerous published studies reporting on the extent of genetic damage observed in animal and human cells exposed in vitro and in vivo to non-ionizing radiofrequency fields (RF, electromagnetic waves that carry energy as they propagate in air and dense media). Overall, the data are inconsistent; while some studies have suggested significantly increased damage in cells exposed to RF energy compared to unexposed and/or sham-exposed control cells, others have not. Several variables in exposure conditions used in the experiments might have contributed to the controversy. In this comprehensive review, four specific quality control measures were used to determine the quality of 225 published studies in animal and human cells exposed in vitro and in vivo to RF energy, and the results from 2,160 tests with different sample sizes were analyzed. The four specific quality control measures were as follows: 1. "Blind" collection/analysis of the data to eliminate individual/observer "bias"; 2. Adequate description of "dosimetry" for independent replication/confirmation; 3. Inclusion of "positive controls" to confirm the outcomes; and 4. Inclusion of "sham-exposed controls" which are more appropriate to compare the data with those in RF exposure conditions. In addition, meta-analysis of the genetic damage in cells exposed to RF energy and control cells, thus far available in the RF literature database, was performed to obtain the "d" values, i.e., standardized mean difference between these two types of cells or the effect size. The relationship between d values and the above-mentioned quality control measures was ascertained. In addition, the correlation between the quality control measures and the conclusions reported in the publications (no significant difference between the cells exposed to RF energy and control cells; increased damage in former cells compared to the latter; increased, no significant difference and decreased damage in cells exposed to RF energy in the same experiment; or decreased damage in cells exposed to RF energy) was examined. The overall conclusions were as follows: 1. When all four quality control measures were mentioned in the publication, the d values were smaller compared to those when one or more quality control measures were not mentioned in the investigation; 2. Based on the inclusion of quality control measures, the weighted outcome in cells exposed to RF energy (d values) indicated a very small effect, if any; 3. The number of published studies reporting no significant difference in genetic damage of cells exposed to RF energy, compared to that of control cells, increased with increased number of quality control measures employed in investigations; 4. The number of published studies reporting increased genetic damage in cells exposed to RF energy decreased with increased number of quality control measures; and 5. There was a "bias" towards the publications reporting increased genetic damage in cells exposed to RF energy even with very small sample size. Overall, the results from this study underscore the importance of including quality control measures in investigations so that the resulting data are useful, nationally and internationally, in evaluating "potential" health risks from exposure to RF energy.


The effectiveness of gluten-free dietary interventions: A systematic review.
Celiac disease is a chronic autoimmune gastroenterological disorder in which the digestion of gluten leads to damage and constant inflammation in the small intestine. Moreover, there are associated physical and mental health problems related to celiac disease, i.e., a lower health-related quality of life and increased depression and anxiety symptoms. The only effective treatment for celiac disease is lifelong adherence to a gluten-free diet. However, researchers suggest that strict adherence to a gluten-free diet ranges from 42 to 80%, depending on the definition and method of assessment that was utilized. This review examines interventions designed for those who need to adhere to life-long dietary measures and their success in terms of increasing gluten-free dietary adherence and improving their health-related quality of life. In April 2022, the Scopus, Web of Science, PubMed and ProQuest databases were searched using the following terms: "coeliac disease" OR "celiac disease" AND "gluten free diet" AND "intervention" AND "health related quality of life" AND "diabetes." Eight studies were suitable for this review. The studies were used to analyze different intervention techniques and their impact on gluten-free dietary adherence, quality of life, and the reasons for dietary nonadherence. The studies revealed statistically significant improvements in the knowledge base regarding celiac disease and the gluten-free diet, dietary adherence and quality-of-life satisfaction immediately after the intervention and at a three-month follow-up. Some studies were also focused on behavioral and cognitive aspects of nonadherence to dietary measures.


Novel DNA repair alkyltransferase from Caenorhabditis elegans.
O6-alkylguanine DNA-alkyltransferase (AGT) is a widely distributed DNA repair protein that protects living organisms from endogenous and exogenous alkylation damage to DNA at the O6-position of guanine. The search of the C. elegans genome database for an AGT protein revealed the presence of a protein (cAGT-2) with some similarity to known AGTs in addition to the easily recognized cAGT-1 protein. The predicted protein sequence of cAGT-2 contains the amino acid sequence -ProCysHisPro- at the presumed active site of the protein, whereas all other known AGTs have -ProCysHisArg-. A truncated version of the cAGT-2 protein was expressed in E. coli. This purified recombinant protein was able to repair O6-methylguanine and O4-methylthymine adducts in DNA in vitro and also reacted with the bulky benzyl adduct in O6-benzylguanine. This fragment of cAGT-2 (104 amino acids) is the smallest protein possessing AGT activity yet described. The full-length cAGT-2 protein (274 amino acids) totally lacks the N-terminal domain present in all other known AGTs but has a long C-terminal extension that has significant homology to histone 1C. Expression of cAGT-2 in an E. coli strain lacking endogenous AGT activity provided modest but statistically significant resistance to the toxicity of N-methyl-N'-nitro-N-nitrosoguanidine, confirming that cAGT-2 is an alkyltransferase.


A young lady with post-partum jaundice and right upper quadrant lump abdomen: an unusual etiology.
Intraductal papillary mucinious neoplasm-biliary type is the biliary counterpart of intraductal papillary mucinious neoplasm-pancreatic type. We report a rare case of intraductal papillary mucinous tumor arising from extrahepatic biliary system. The diagnosis was established on histopathological analysis following endoscopic retrograde cholangiopancreatography-guided biopsy. Isolated papillary adenoma of the bile duct is extremely rare, and in this unusual case the patient was a 22-year-old young lady who had delivered a healthy infant 6 weeks previously.


Effectiveness and prescription pattern of lipid-lowering therapy and its associated factors among patients with type 2 diabetes mellitus in Malaysian primary care settings.
Cardiovascular diseases (CVDs) are the main complication leading to morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). There is a large amount of evidence to support the use of lipid-lowering therapy (LLT) for the prevention of CVD. This study aimed to assess the effectiveness and prescription quality of LLT among T2DM patients and to identify its associated factors. A multicenter cross-sectional study included 816 T2DM patients from four different primary care centers in Pahang, Malaysia. We involved LLT-eligible T2DM patients as per the national clinical practice guidelines (CPG). The assessment of therapy effectiveness focused on the attainment of target lipid measures stated in the CPG. Evaluation of the prescription quality was classified into appropriate, potentially inappropriate, and inappropriate, based on the compliance with guidelines and existence of potential safety concerns. Binomial logistic regression was employed to identify the predictors of LLT effectiveness and prescription quality. The overall percentage of T2DM patients receiving statin therapy was 87.6% (715/816). Statin therapy was appropriately prescribed in 71.5% of the cases. About 17.5% of the LLT prescriptions have at least one significant drug interaction with co-prescribed medications. The achievement of the primary target of low-density lipoprotein cholesterol (LDL-C) levels was observed in only 37% of T2DM patients. The LLT indication and appropriateness of prescription were significantly associated with the attainment of LDL-C treatment goals. Primary prevention, Malay race, and hypertension were identified as predictors for appropriate prescribing of LLT among T2DM subjects. There is a need to enhance the quality of LLT prescribing in the primary care setting to cover all eligible high-risk patients and ensure patient safety. Strategies to improve the achievement of LDL-C goals among patients with T2DM, such as investigating the potential role of the combination therapy and high-intensity statin therapy, are required.


Virulence characteristics of clinical and environmental isolates of Vibrio vulnificus.
Twenty-four randomly selected clinical and environmental Vibrio vulnificus isolates were tested for virulence in iron-overloaded mice (250 mg of iron dextran per kg of body weight). The log10 50% lethal doses of 17 isolates were lower by greater than or equal to 3.5 log10 units in iron-overloaded mice than in control mice. These isolates were classified as virulent. The 50% lethal doses of these virulent isolates were also lower in mice that were immunosuppressed by treatment with cyclophosphamide (150 mg/kg). Four of the seven isolates initially classified as avirulent were virulent in mice that were simultaneously iron overloaded and immunosuppressed. These isolates were classified as moderately virulent. The remaining three isolates were avirulent under all conditions. The incidence of virulent strains among clinical and environmental isolates did not differ. The virulent isolates produced high titers of hemolysin, were resistant to inactivation by serum complement, produced phenolate siderophore, and utilized transferrin-bound iron. The moderately virulent isolates differed from the virulent isolates only in their increased sensitivity to inactivation by serum complement. The avirulent isolates differed from those of the other two classes in their inability to either produce significant amounts of phenolate siderophore or utilize transferrin-bound iron. A modified agar plate diffusion method for transferrin-bound iron utilization was developed to differentiate the two classes of virulent isolates from the avirulent isolates in vitro.


A statistical analysis of the Medicare hospital routine nursing salary cost differential.
From July 1971 (but effective retroactively to July 1, 1969) to October 1981, Medicare hospital reimbursement methods assumed that patients in the qualifying categories of the aged, pediatric, maternal, and kidney transplant cases consumed 8.5 percent more routine nursing resources than patients outside these categories. Consequently, the Medicare program paid this nursing differential to hospitals for all its hospitalized beneficiaries in these categories. The purpose of this study is to investigate whether hospitals with more qualifying Medicare patients do, in fact, have higher per diem routine nursing salary costs. This study tests this hypothesis while attempting to hold constant the influences of other factors such as local area wages, hospital size, occupancy rate, type of control, and geographic region. Using 1979 data from over 4,500 hospitals, and 1977, 1978, and 1979 data from a sample of 1200 hospitals, this study looks at the relationship between per diem hospital routine nursing salary costs and the proportion of qualifying Medicare routine patient days in two models. Model I incorporates the framework of the Section 223 routine cost limits and Model II incorporates a comprehensive set of variables representing the hospitals' production and output characteristics. The evidence from this study provides little empirical basis to support the existence of a strong or sizeable relationship and, hence, does not support payment of the Medicare routine nursing salary cost differential.


Monolayer and interfacial permeation.
Transport across physical-chemical interfaces is considered in connection with three particular problems of biological interfaces: the structure and properties of cell membranes, the properties of the lung surfactant, and the effects of ionic currents across excitable membranes. With regard to cell membranes, studies of monolayer permeation suggest that permselectivity on the basis of size is a property of bilayer structure and probably gives rise to the observed dependence of the permeability on partition coefficients. The permeabilities of lipid and protein monolayers are consistent with the bimolecular leaflet (BML) model of the membrane and not with mosaic models. Experiments with the lung surfactant indicate that, in addition to its surface tension-lowering properties, it is unusual in its ability to form a strong two-dimensional network, which probably contributes to alveolar stability. Finally, the results of studies of interfacial ionic transference suggest a new way of accounting for the ionic fluxes in excitable membranes during an action potential without assuming ion-selective pores or carriers. In the suggested mechanism, it is possible to account for the change in ionic selectivity and the proper phasing of the fluxes, as well as other aspects of excitation in natural membranes.


Whither British general practice after the 2004 GMS contract? Stories and realities of change in four UK general practices.
The purpose of this article is to provide answers to two questions: what has been the impact of nGMS on practice organisation and teamwork; and how do general practice staff perceive the impact? The article is based on comparative in-depth case studies of four UK practices. There was a discrepancy between changes observed and the way practice staff described the impact of the contract. Similar patterns of organisational change were apparent in all practices. Decision-making became concentrated in fewer hands. Formally or informally constituted "elite" multidisciplinary groups monitored and controlled colleagues' behaviour for maximum performance and remuneration. This convergence of organisational form was not reflected in the dominant "story" each practice constructed about its unique ethos and style. The "stories" also failed to detect negative consequences to the practice flowing from its adaptation to the contract. The paper highlights how collective "sensemaking" in practices may fail to detect and address key organisational consequences from the nGMS.


Microglia retard dengue virus-induced acute viral encephalitis.
Patients with dengue virus (DENV) infection may also present acute viral encephalitis through an unknown mechanism. Here, we report that encephalitic DENV-infected mice exhibited progressive hunchback posture, limbic seizures, limbic weakness, paralysis, and lethality 7 days post-infection. These symptoms were accompanied by CNS inflammation, neurotoxicity, and blood-brain barrier destruction. Microglial cells surrounding the blood vessels and injured hippocampus regions were activated by DENV infection. Pharmacologically depleting microglia unexpectedly increased viral replication, neuropathy, and mortality in DENV-infected mice. In microglia-depleted mice, the DENV infection-mediated expression of antiviral cytokines and the infiltration of CD8-positive cytotoxic T lymphocytes (CTLs) was abolished. DENV infection prompted the antigen-presenting cell-like differentiation of microglia, which in turn stimulated CTL proliferation and activation. These results suggest that microglial cells play a key role in facilitating antiviral immune responses against DENV infection and acute viral encephalitis.


Student midwives' views on maternity care just before their graduation.
To report a hermeneutic study of student midwives' views on maternity care just before their graduation. background: Woman-centred care, which is the hallmark of midwifery, is taught to midwifery students around the globe. Woman-centred care is advantageous for women at low obstetric risk. However, adopting this ideology might be a problem for student midwives whose clinical placements are mainly in a medicalized obstetric-led hospital setting. A hermeneutic phenomenological study was conducted. In 2010, three focus groups were held where 19 student midwives participated. Data were transcribed verbatim and analysed using van Manen's approach. The choice for midwifery was a 'positive' choice and not the result of an elimination process. Students' description of a midwife as a coach was in line with the international definition of a midwife. With regard to maternity care, midwifery students identified two types of care, factory-style care and tailored care, both of which were ascribed to caregivers and hospital culture. Furthermore, student midwives made the distinction between hierarchy and teamwork, referring to the professional relations in maternity care. Hierarchy was driven by tradition, it implied that decisions were made top-down, and it resulted in impersonal relations. Midwifery students felt it was unjust that midwives were not allowed to perform deliveries while having the legal autonomy to do so. In spite of the medicalized context, midwifery education succeeded in educating midwives who hold a woman-centred ideology. Midwifery students linked style of care to a person rather than to a profession.


Pharmacological inhibition of Bmi1 by PTC-209 impaired tumor growth in head neck squamous cell carcinoma.
Bmi1 (B lymphoma Mo-MLV insertion region 1 homolog) contributes to human tumorigenesis via epigenetic transcriptional silencing and represents a novel therapeutic target with great potentials. Here we sought to determine the therapeutic efficiency of PTC-209, a potent and selective Bmi1 inhibitor, in head neck squamous cell carcinoma (HNSCC) cells and a HNSCC xenograft model. The mutation pattern, mRNA level of Bmi1 in HNSCC and its associations with clinicopathological parameters were determined through comprehensive data mining and interrogation using publicly available databases GENT, cBioPortal, Oncomine and TCGA. The PTC-209, a selective and potent Bmi1 inhibitor, was exploited and its effect on Bmi1 expression was measured in two HNSCC cell lines Cal27 and FaDu. The phenotypical changes of HNSCC cells were observed upon PTC-209 treatment in vitro. Moreover, the therapeutic effects of PTC-209 for HNSCC were determined in a xenograft animal model. Through comprehensive data mining and interrogation, we found that Bmi1 mRNA was frequently overexpressed in a subset of HNSCC samples. Our data revealed that PTC-209 robustly reduced the expression of Bmi1 in Cal27 and FaDu cells presumably by post-transcriptional repression and ubiquitin-proteasomal degradation. PTC-209 treatment resulted in impaired cell proliferation, G1-phase cell cycle arrest, compromised migration and invasiveness, and increased cell apoptosis and chemosensitivity to 5-FU and cisplatin in vitro. Moreover, PTC-209 exposure reduced colony formation, tumorsphere formation and the percentage of ALDH1+ subpopulation in both Cal27 and FaDu cells. Importantly, in vivo PTC-209 administration significantly reduced tumor growth in a HNSCC xenograft model probably by Bmi1 inhibition and impaired cell proliferation. Our findings indicate that pharmacological inhibition of Bmi1 is a novel therapeutic strategy for HNSCC patients, especially with those with aberrant Bmi1 overexpression.


Deformation and flexural properties of denture base polymer reinforced with glass fiber sheet.
The purpose of this study was to investigate the deformation and flexural properties of acrylic and urethane polymers reinforced with glass fiber sheet. Four types of specimen--self-curing resin plate (R), light-curing oligomer plate containing a reinforcement (GO), and self-curing resin plate containing a reinforcement on one (GR) or both (GRG) sides--were prepared with three thicknesses: 1.5, 2.4, and 3.0 mm. Gaps between polymerized test specimen and a standard metal plate were measured at the corner (C), middle of the long sides (LS), and middle of the short sides (SS). The gaps for R were 0-2.0 microm. GO and GR markedly deformed at Points C, LS, and SS, and the degree of deformation increased as GO became thinner. Flexural strength was significantly increased by the reinforcement (p < 0.05). The flexural moduli of 3.0-mm thick R, GO, and GR were significantly smaller than that of 1.5-mm thick specimens.


The Impact Of Patient Suicide on Doctors and Nurses: A Critical Interpretive Meta-Synthesis.
To provide a conceptual overview of how medical doctors and nurses experience patient suicide. A systematic search identified ten qualitative papers for this interpretive meta-synthesis. Constructs were elicited and synthesized via reciprocal translational analysis. Findings comprised four inter-related themes: (1) Intrinsic but taboo: patient suicide perceived as inevitable yet difficult to discuss. (2) Significant emotional impact: clinicians deeply affected, with resilience important for mitigating impact. (3) Failure and accountability: intense self-scrutiny, guilt and shame, with blame attributed differently across professions. (4) Legacy of patient suicide: opportunities for growth but lack of postvention guidance. Patient suicide affects clinicians profoundly. Further research should evaluate postvention procedures to inform effective guidance and support, acknowledging professional differences.HighlightsPatient suicide profoundly affects doctors and nurses as "suicide survivors."Despite common themes, professions differed in blame attributions.Organizations must develop postvention responses to meet clinicians' pastoral needs.


Degradation of acetaldehyde and its precursors by Pelobacter carbinolicus and P. acetylenicus.
Pelobacter carbinolicus and P. acetylenicus oxidize ethanol in syntrophic cooperation with methanogens. Cocultures with Methanospirillum hungatei served as model systems for the elucidation of syntrophic ethanol oxidation previously done with the lost "Methanobacillus omelianskii" coculture. During growth on ethanol, both Pelobacter species exhibited NAD+-dependent alcohol dehydrogenase activity. Two different acetaldehyde-oxidizing activities were found: a benzyl viologen-reducing enzyme forming acetate, and a NAD+-reducing enzyme forming acetyl-CoA. Both species synthesized ATP from acetyl-CoA via acetyl phosphate. Comparative 2D-PAGE of ethanol-grown P. carbinolicus revealed enhanced expression of tungsten-dependent acetaldehyde: ferredoxin oxidoreductases and formate dehydrogenase. Tungsten limitation resulted in slower growth and the expression of a molybdenum-dependent isoenzyme. Putative comproportionating hydrogenases and formate dehydrogenase were expressed constitutively and are probably involved in interspecies electron transfer. In ethanol-grown cocultures, the maximum hydrogen partial pressure was about 1,000 Pa (1 mM) while 2 mM formate was produced. The redox potentials of hydrogen and formate released during ethanol oxidation were calculated to be EH2 = -358±12 mV and EHCOOH = -366±19 mV, respectively. Hydrogen and formate formation and degradation further proved that both carriers contributed to interspecies electron transfer. The maximum Gibbs free energy that the Pelobacter species could exploit during growth on ethanol was -35 to -28 kJ per mol ethanol. Both species could be cultivated axenically on acetaldehyde, yielding energy from its disproportionation to ethanol and acetate. Syntrophic cocultures grown on acetoin revealed a two-phase degradation: first acetoin degradation to acetate and ethanol without involvement of the methanogenic partner, and subsequent syntrophic ethanol oxidation. Protein expression and activity patterns of both Pelobacter spp. grown with the named substrates were highly similar suggesting that both share the same steps in ethanol and acetalydehyde metabolism. The early assumption that acetaldehyde is a central intermediate in Pelobacter metabolism was now proven biochemically.


Management of pediatric open tibia fractures with supracutaneous locked plates.
We evaluated the novel application of supracutaneous locked plates in pediatric open tibia fractures. Pediatric open tibia fractures stabilized with a locked supracutaneous plate from January 2011 to December 2014 were reviewed. Twenty-eight children, mean age 8.9 years, with 29 open tibia fractures were included. Nine of these children who had metaphyseal or metadiaphyseal fractures did not require joint spanning. The mean follow-up duration was 13.5 months. The mean time to uneventful union was 11.46 weeks, with no unacceptable malunion. Supracutaneous locked plates showed early union and no refractures. They could favorably replace tubular external fixators in stabilizing pediatric open tibia fractures.


DEPRESSIVE AND EATING DISORDERS IN PATIENTS POST-BARIATRIC SURGERY WITH WEIGHT REGAIN: A DESCRIPTIVE OBSERVATIONAL STUDY.
Although bariatric surgery is today's gold standard treatment for obesity, weight regain affects the success rate of the procedure. Recent studies have identified psychiatric and neurological factors as possible causes. The aim of this study was to evaluate the influence of psychiatric diseases on the outcome and long-term success of bariatric surgeries and find a weight regain threshold that has an acceptable sensibility to mental health-related issues to be used in research and clinical studies. This is a observational study of bariatric patients submitted to Roux-en-Y bypass or sleeve gastrectomy, with a postoperative time of 2-10 years to access weight regain, depression, and binge-eating disorder. Of 217 patients studied, 163 were women and 54 were men, with an average postoperative time of 5.2±2.6 years. Weight regain was experienced in 35% of the patients, binge-eating disorder in 24.9%, and depression in 24%. The greater weight before surgery, body mass index (BMI), percentage increase to maximum weight loss, and time postoperatively all have a significant positive correlation with weight regain (p=0.045, p=0.026, p<0.001, and p<0.001, respectively). A significant association between binge-eating disorder, depression, and anxiety with weight regain (p=0.004, p=0.008, and p=0.001, respectively) was found. The significant weight regain rates with significant impact on psychiatric disorders highlight the need for continuous postoperative monitoring focused on the psychiatric aspects of obesity to aid surgeries' long-term success.


Axial Spondyloarthritis: Dual-Energy Virtual Noncalcium CT in the Detection of Bone Marrow Edema in the Sacroiliac Joints.
Purpose To determine the diagnostic performance of dual-energy virtual noncalcium (VNCa) CT in the detection of bone marrow edema in study participants with sacroiliitis associated with axial spondyloarthritis. Materials and Methods In this prospective study, 47 consecutive participants (mean age, 27 years; age range, 14-41 years [28 male; mean age, 24 years; age range, 14-37 years] [19 female; mean age, 29 years; age range, 17-41 years]) underwent dual-energy CT and 3.0-T MRI between April 2016 and December 2017. Two independent readers visually evaluated all sacroiliac joints for the presence of abnormal marrow attenuation on dual-energy VNCa images using a four-point classification system (0, no edema; 1, mild edema; 2, moderate edema; 3, severe edema). CT numbers on VNCa images were determined with region-of-interest-based quantitative analysis. MRI was the reference standard for presence of bone marrow edema. Results Sensitivity, specificity, and accuracy of readers 1 and 2, respectively, in the identification of bone edema at CT were 87% and 93% (48 and 51 of 55), 94% and 91% (32 and 31 of 34), and 90% and 92% (80 and 82 of 89). Interobserver agreement was excellent (κ = 0.81). CT numbers from VNCa images increased from no edema to severe edema (P < .001). The area under the receiver operating characteristic curve was 0.93 for reader 1 and 0.91 for reader 2 in differentiation of the presence of bone marrow edema from no edema. A cutoff value of -33 HU derived from reader 1 yielded overall sensitivity, specificity, and accuracy of 90% (49 of 55), 83% (28 of 34), and 87% (77 of 89) in the detection of any extent of edema in the sacroiliac joints. Conclusion Dual-energy VNCa CT images had excellent diagnostic performance in evaluation of the extent of bone marrow edema in study participants with sacroiliitis associated with axial spondyloarthritis. © RSNA, 2018 See also the editorial by Guggenberger in this issue.


Effects of xylazine on cecal mechanical activity and cecal blood flow in healthy horses.
Mechanical activity of the cecal body, lateral cecal arterial blood flow, carotid arterial pressure, and heart rate were measured in 6 conscious healthy horses 30 minutes before and for 120 minutes after IV administration of xylazine at dosages of 1.1 mg/kg of body weight, 0.55 mg/kg, and 0.275 mg/kg. Xylazine at a dosage of 1.1 mg/kg reduced the mean motility index (the product of the mean amplitude of contractions and the total duration of contractile activity divided by the recording time) of the circular and longitudinal muscle layers for the first, second, third, and fourth 30-minute periods after administration of xylazine. Xylazine at a dosage of 0.55 mg/kg reduced the motility index of the circular and longitudinal muscle layers for the first and second 30-minute periods after administration of xylazine. Xylazine at a dosage of 0.275 mg/kg reduced the motility index of the circular and longitudinal muscle layers for the first 30-minute period after administration of xylazine. Mean lateral cecal arterial blood flow was significantly (P less than 0.05) lower than the base-line value at 2 and 4 minutes after administration of all 3 xylazine dosages and at 8 minutes after administration of xylazine dosages of 1.1 mg/kg and 0.55 mg/kg. All dosages of xylazine caused transient hypertension and bradycardia, followed by hypotension.


Physical activity influences in a disadvantaged African American community and the communities' proposed solutions.
The purpose of this assessment is to increase our understanding of how safety and environmental factors influence physical activity among African American residents living in a low-income, high-crime neighborhood and to get input from these residents about how to best design physical activity interventions for their neighborhood. Twenty-seven African American adult residents of a low-income, high-crime neighborhood in a suburban southeastern community participated in three focus groups. Participants were asked questions about perceptions of what would help them, their families, and their neighbors be more physically active. Two independent raters coded the responses into themes. Participants suggested three environmental approaches in an effort to increase physical activity: increasing law enforcement, community connectedness and social support, and structured programs. Findings suggest that safety issues are an important factor for residents living in disadvantaged conditions and that the residents know how they want to make their neighborhoods healthier.


Coronavirus disease 2019 in solid organ transplant recipients in the setting of proactive screening and contact tracing of Qatar.
Clinical data on Coronavirus Disease 2019 (COVID-19) in solid organ transplant (SOT) recipients are limited. We herein report the initial clinical experience with COVID-19 in SOT recipients in Qatar. All SOT recipients with laboratory-confirmed COVID-19 up to May 23, 2020 were included. Demographic and clinical data were extracted retrospectively from the hospital's electronic health records. Categorical data are presented as frequency and percentages, while continuous variables are summarized as medians and ranges. Twenty-four SOT recipients with COVID-19 were identified (kidney 16, liver 6, heart 1, and liver and kidney 1). Organ transplantation preceded COVID-19 by a median of 60 months (range 1.7-184). The median age was 57 years (range 24-72), and 9 (37.5%) transplant recipients were females. Five (21%) asymptomatic patients were diagnosed through proactive screening. For the rest, fever (15/19) and cough (13/19) were the most frequent presenting symptoms. Five (20.8%) patients required invasive mechanical ventilation in the intensive care unit (ICU). Eleven (46%) patients developed acute kidney injury, including three in association with drug-drug interactions involving investigational COVID-19 therapies. Maintenance immunosuppressive therapy was modified in 18 (75%) patients, but systemic corticosteroids were not discontinued in any. After a median follow-up of 226 days (26-272), 20 (83.3%) patients had been discharged home, 2 (8.3%) were still hospitalized, 1 (4.2%) was still in the ICU, and 1 (4.2%) had died. Our results suggest that asymptomatic COVID-19 is possible in SOT recipients and that overall outcomes are not uniformly worse than those in the general population. The results require confirmation in large, international cohorts.


Genetic approaches to the nosology of deafness.
Profound deafness of childhood is a heterogeneous entity. Perhaps 50% of cases owe their handicap to mendelian segregation of single genes. Various types of genetic methods, combined with clinical and statistical analyses, are described by means of which an initial approach can be made to the problem of the estimation of the number of different gene loci involved and of the prevalence of the various abnormal alleles, as well as of the definition of their modes of action.


Definition of a core module for the nuclear retrograde response to altered organellar gene expression identifies GLK overexpressors as gun mutants.
Retrograde signaling can be triggered by changes in organellar gene expression (OGE) induced by inhibitors such as lincomycin (LIN) or mutations that perturb OGE. Thus, an insufficiency of the organelle-targeted prolyl-tRNA synthetase PRORS1 in Arabidopsis thaliana activates retrograde signaling and reduces the expression of nuclear genes for photosynthetic proteins. Recently, we showed that mTERF6, a member of the so-called mitochondrial transcription termination factor (mTERF) family, is involved in the formation of chloroplast (cp) isoleucine-tRNA. To obtain further insights into its functions, co-expression analysis of MTERF6, PRORS1 and two other genes for organellar aminoacyl-tRNA synthetases was conducted. The results suggest a prominent role of mTERF6 in aminoacylation activity, light signaling and seed storage. Analysis of changes in whole-genome transcriptomes in the mterf6-1 mutant showed that levels of nuclear transcripts for cp OGE proteins were particularly affected. Comparison of the mterf6-1 transcriptome with that of prors1-2 showed that reduced aminoacylation of proline (prors1-2) and isoleucine (mterf6-1) tRNAs alters retrograde signaling in similar ways. Database analyses indicate that comparable gene expression changes are provoked by treatment with LIN, norflurazon or high light. A core OGE response module was defined by identifying genes that were differentially expressed under at least four of six conditions relevant to OGE signaling. Based on this module, overexpressors of the Golden2-like transcription factors GLK1 and GLK2 were identified as genomes uncoupled mutants.


The Ngaglik study: an inquiry into birth interval dynamics and maternal and child health in rural Java.
Preliminary analysis of the Ngaglik Study has been able to confirm much of what we knew about birth interval dynamics from past retrospective studies, while also adding new insights into birth spacing and maternal and child health in rural Java. In Ngaglik, a median duration of breast-feeding of over 2 years is associated with durations of lactational amenorrhoea of over a year on average, despite the very early introduction of other foods in the infant diet. Postpartum abstinence appears to play a role in birth spacing for many women, though as previous research has shown, it does not extend throughout the breast-feeding period and tends to be more abbreviated among younger, higher socioeconomic status individuals. The extent to which maternal nutrition affects the return of postpartum fecundity will be a central topic for more detailed investigation, though preliminary results do not lend support to nutrition as a major determinant. The anthropometry of women during pregnancy shows strong evidence of nutritional stress during the third trimester and, in general, provides valuable data for comparison with other Indonesian and international data. Maternal nutritional measurement during the postpartum period is perhaps even more valuable, since few studies anywhere have recorded detailed patterns of change during the months following childbirth. Among Ngaglik women, for example, upper arm measurements show very low values immediately after parturition, rising during the early months postpartum prior to a gradual decline. Nutritional indicators for lactators are somewhat higher than for non-lactators over the first year postpartum. Morbidity data for both mothers and children show frequent reported illness episodes and a wide variety of modern and traditional treatment patterns. The more than 8 000 observations of infant growth provide one of the few sources of such information for an Indonesian population, and data on primary tooth eruption will be used to relate dentition patterns to exact ages of child. A distinctive feature of the Ngaglik Study is the inclusion of attitudinal data and information on beliefs and customs, which will aid in interpreting behaviour patterns, will allow future detailed analysis to be set in a cultural context, and will help in the design of modern health and nutrition intervention programmes aimed at women and children during their most vulnerable stages of the life-cycle.


Reverse chemical mutagenesis: identification of the mutagenic lesions resulting from reactive oxygen species-mediated damage to DNA.
An understanding of the contribution of reactive oxygen species to mutagenesis has been hampered by the vast number of different chemical modifications they cause in DNA. Even though many of these DNA alterations have been catalogued, the identification of specific lesions that cause mutations has depended on testing one modification at a time. In this study we present another approach to identify key mutagenic lesions from a pool of oxidatively modified nucleotides. dCTP was treated with an oxygen radical-generating system containing FeSO4, H2O2, and ascorbic acid. The modification products were separated by reverse-phase and anion-exchange HPLC and then incorporated by human immunodeficiency virus reverse transcriptase into a DNA that contains a target gene for scoring for mutations. One of the mutagenic species isolated was identified as 5-hydroxy-2'-deoxycytidine. It is incorporated efficiently into DNA and causes C-->T transitions in Escherichia coli at a frequency of 2.5%, which is more mutagenic than any previously identified oxidative DNA lesion.


Appetitive vs. defensive responses to emotional cues. Autonomic measures and brain oscillation modulation.
The present study explored the effect of the subjective evaluation and the individual differences related to BIS and BAS (Behavioural Inhibition and Activation System) on autonomic measures and brain oscillations, in response to appetitive and aversive emotional stimuli. Multiple measures were recorded, such as psychophysiological (skin conductance response, heart rate, and electromyography) and frequency bands (delta, theta, alpha, and gamma), during viewing IAPS figures, that varied in terms of pleasantness (appetitive vs. aversive) and arousing power (high vs. low intensity). Both BIS and BAS measures were significant in modulating behavioural, autonomic and brain oscillations responses. Withdrawal (BIS system) and appetitive (BAS system) behaviour showed opposite patterns of responses by the subjects. Also, frontal cortical site response was more significant than other sites. Nevertheless, no specific lateralization effect was found as a function of BIS/BAS dichotomy. Moreover, autonomic variables and frequency band modulations were found to be effected by valence and arousal rating per se, with an increased response for high arousing and negative or positive stimuli in comparison with low arousing and neutral stimuli. The effects of subjective evaluation and individual differences were discussed at light of coping activity model of emotion comprehension.


Pushing Retinal Imaging Forward: Innovations and Their Clinical Meaning - The 2022 Ophthalmologica Lecture.
Retinal imaging has greatly expanded our understanding of various pathological conditions. This article presents a summary of the key points covered during the 2022 Ophthalmologica Lecture held at the Euretina Congress in Hamburg. The first part of the article focuses on the use of optical coherence tomography angiography to examine and comprehend the choroid in age-related macular degeneration (AMD). Subsequently, we delve into the discussion of the "postreceptor neuronal loss" theory in AMD, which was studied using en face structural optical coherence tomography (OCT). Following that, we explore pertinent findings obtained through cross-sectional OCT in retinal and optic nerve diseases, such as AMD, diabetic macular edema, pathologic myopia, central serous chorioretinopathy, and Leber's hereditary optic neuropathy.


Talar morphology, phylogenetic affinities, and locomotor adaptation of a large-bodied amphipithecid primate from the late middle eocene of Myanmar.
A well-preserved fossil talus [National Museum of Myanmar Primates (NMMP) 82] of a large-bodied primate is described from the late middle Eocene Pondaung Formation of central Myanmar. The specimen was collected at Thandaung Kyitchaung, a well-known amphipithecid primate-bearing locality near the village of Mogaung. NMMP 82 adds to a meager but growing sample of postcranial remains documenting the large-bodied primates of the Pondaung Formation. This new talus exhibits a suite of features that resemble conditions found in living and fossil haplorhine primates, notably anthropoids. As such, the phylogenetic signal deriving from the morphology of NMMP 82 conflicts with that provided by NMMP 20, a partial skeleton (including a fragmentary calcaneus) of a second large-bodied Pondaung primate showing undoubted adapiform affinities. Analysis subtalar joint compatibility in a hypothetical NMMP 82/NMMP 20 combination (talus/calcaneus) reveals a substantial degree of functional mismatch between these two tarsal bones. The functional incongruence in subtalar joint morphology between NMMP 20 and NMMP 82 is consistent with the seemingly divergent phylogenetic affinities of these specimens, indicating that two higher level taxa of relatively large-bodied primates are documented in the Pondaung Formation. On the basis of its size and morphology, we refer the NMMP 82 talus to the large-bodied amphipithecid Pondaungia. The occurrence of anthropoid-like tali in the Pondaung Formation obviates the need to invoke homoplasy to explain the shared, derived dental characters that are common to amphipithecids and undoubted anthropoids. Functionally, the NMMP 82 talus appears to have pertained to a primate that is engaged in active quadrupedalism in an arboreal environment along broad and subhorizontal branches. The primate taxon represented by NMMP 82 was capable of climbing and leaping, although it was not particularly specialized for either of these activities.


Revisiting occult cancer screening in patients with unprovoked venous thromboembolism.
Unprovoked venous thromboembolism (VTE) can be the first manifestation of an unknown cancer. A recently published individual patient data meta-analysis (IPDMA) reported a prevalence of occult cancer detection of 5.2% (95% CI, 4.1% to 6.5%) over a one-year follow-up period, approximately 50% lower than the previously reported 12-month period prevalence. Although an extensive screening strategy was associated with a 2-fold higher probability of cancer detection at initial screening in the IPDMA, not enough evidence exists yet to support the routine use of these tests in patients with unprovoked VTE. It is likely that a subgroup of patients with unprovoked VTE is at higher risk of occult cancer detection and might benefit from closer clinical surveillance. A newly derived and validated clinical predictive rule seems to be able to stratify patients with unprovoked VTE accordingly to their underlying risk of occult cancer detection. The low incidence of occult cancer detection (<3%) in the low-risk group is reassuring for clinicians. Future studies are required to better define the risks and benefits of an extensive occult cancer screening strategy in high risk patients sub-group with unprovoked VTE. To date, the Scientific and Standardized Committee from the International Society of Thrombosis and Haemostasis suggests that patients with unprovoked VTE should only undergo a limited cancer screening including thorough medical history and physical examination, basic laboratory investigations, chest X-ray as well as age- and gender-specific cancer screening according to national guidelines.


Involvement of the CXCR7/CXCR4/CXCL12 axis in the malignant progression of human neuroblastoma.
Neuroblastoma (NB) is a typical childhood and heterogeneous neoplasm for which efficient targeted therapies for high-risk tumors are not yet identified. The chemokine CXCL12, and its receptors CXCR4 and CXCR7 have been involved in tumor progression and dissemination. While CXCR4 expression is associated to undifferentiated tumors and poor prognosis, the role of CXCR7, the recently identified second CXCL12 receptor, has not yet been elucidated in NB. In this report, CXCR7 and CXCL12 expressions were evaluated using a tissue micro-array including 156 primary and 56 metastatic NB tissues. CXCL12 was found to be highly associated to NB vascular and stromal structures. In contrast to CXCR4, CXCR7 expression was low in undifferentiated tumors, while its expression was stronger in matured tissues and specifically associated to differentiated neural tumor cells. As determined by RT-PCR, CXCR7 expression was mainly detected in N-and S-type NB cell lines, and was slightly induced upon NB cell differentiation in vitro. The relative roles of the two CXCL12 receptors were further assessed by overexpressing CXCR7 or CXCR4 receptor alone, or in combination, in the IGR-NB8 and the SH-SY5Y NB cell lines. In vitro functional analyses indicated that, in response to their common ligand, both receptors induced activation of ERK1/2 cascade, but not Akt pathway. CXCR7 strongly reduced in vitro growth, in contrast to CXCR4, and impaired CXCR4/CXCL12-mediated chemotaxis. Subcutaneous implantation of CXCR7-expressing NB cells showed that CXCR7 also significantly reduced in vivo growth. Moreover, CXCR7 affected CXCR4-mediated orthotopic growth in a CXCL12-producing environment. In such model, CXCR7, in association with CXCR4, did not induce NB cell metastatic dissemination. In conclusion, the CXCR7 and CXCR4 receptors revealed specific expression patterns and distinct functional roles in NB. Our data suggest that CXCR7 elicits anti-tumorigenic functions, and may act as a regulator of CXCR4/CXCL12-mediated signaling in NB.


Health and healthcare variables associated with Italy's excess mortality during the first wave of the COVID-19 pandemic: An ecological study.
Healthcare factors have strongly influenced the propagation of COVID-19. This study aims to examine whether excess mortality during the first phase of the COVID-19 outbreak in Italy was associated with health, healthcare, demographic, and socioeconomic, provincial-level indicators. This ecological study concerns the raw number of deaths reported from February 1 to April 30, 2020 and the mean number of deaths occurred during the same months from 2015 to 2019, per province. Information on socioeconomic factors and healthcare settings was extracted from updated databases on the Italian National Institute of Statistics (ISTAT) website. A multivariate model and four multilevel models were constructed to test the association between excess mortality and the analysed indicators across 107 Italian provinces. The hospitalization rate in long-term care wards and the cardiovascular disease mortality rate correlate positively with excess mortality (p <0.05), while higher densities of licensed physicians and of general practitioners are associated with lower excess mortality (p <0.05). After controlling for the COVID-19 cumulative incidence in each province, only the density of licensed physicians remains negatively associated with excess mortality (p <0.01). Some health and healthcare variables (in particular, the density of physicians) are strongly associated with excess mortality during the first wave of the COVID-19 pandemic in Italy and should be targeted to increase the resilience of health systems.


Upregulation and maintenance of gap junctional communication in lens cells.
The cells of the lens are joined by an extensive network of gap junction intercellular channels consisting of connexins 43, 46, and 50. We have proposed, and experimentally supported, the hypothesis that fibroblast growth factor (FGF) signaling is required for upregulation of gap junction-mediated intercellular coupling (GJIC) at the lens equator. The ability of FGF to increase GJIC in cultured lens cells requires sustained activation of extracellular signal-regulated kinase (ERK). In other cell types, activation of ERK has been shown to block GJIC mediated by connexin43 (Cx43). Why ERK signaling does not block lens cell coupling is not known. Another unresolved issue in lens gap junction regulation is how connexins, synthesized before the loss of biosynthetic organelles in mature lens fiber cells, avoid degradation during formation of the organelle-free zone. We have addressed these questions using serum-free cultures (termed DCDMLs) of primary embryonic chick lens epithelial cells. We show that FGF stimulates ERK in DCDMLs via the canonical Ras/Raf1 pathway, and that the reason that neither basal nor growth factor-stimulated GJIC is blocked by activation of ERK is because it is not mediated by Cx43. In fibroblastic cells, the normally rapid rate of degradation of Cx43 after its transport to the plasma membrane is reduced by treatments that either directly (ALLN; epoxomicin) or indirectly (generation of oxidatively un/mis-folded proteins by arsenic compounds) prevent the ubiquitin/proteasome system (UPS) from acting on its normal substrates. We show here that Cx45.6 and Cx56, the chick orthologs of mammalian Cx50 and Cx46, behave similarly in DCDMLs. When organelles lyse during the maturation of fiber cells, they release into the cytosol a large amount of new proteins that have the potential to saturate the capacity, and/or compromise the function, of the UPS. This would serve to spare gap junctions from degradation during formation of the organelle-free zone, thereby preserving GJIC between mature fiber cells despite the lack of de novo connexin synthesis.


The Holistic Health Status of Chinese Homosexual and Bisexual Adults: A Scoping Review.
Background: Same-sex marriage is currently not legalized in China, despite the considerably large number of homosexual and bisexual Chinese populations. At the same time, their holistic health status remains unclear. This is the first scoping review conducted to comprehensively examine all the available literature and map existing evidence on the holistic health of homosexual and bisexual Chinese. Methods: This scoping review used the framework of Arksey and O'Malley and followed the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for scoping reviews (PRISMA-ScR). A comprehensive search strategy was carried out across 20 English (EN) and Chinese (both traditional and simplified) electronic databases from January 1, 2001, to May 31, 2020. Two reviewers conducted the reference screening and study selection independently and consulted a third senior reviewer whenever a consensus must be achieved. Data extraction was conducted using a structured data form based on the Cochrane template, after which a narrative synthesis of the findings was performed. Results: A total of 2,879 references were included in the final analysis, with 2,478 research articles, 167 reviews, and 234 theses. Regarding the study populations, the vast majority of studies centered on men only (96.46%), especially men who have sex with men (MSM). Only 1.32% of the studies targeted female sexual minorities. The geographical distribution of all research sites was uneven, with most of them being conducted in mainland China (95.96%), followed by Hong Kong (2.05%), Taiwan (2.02%), and Macau (0.06%). Regarding the specific study focus in terms of the health domain, around half of the studies (45.93%) focused on sexual health only, and an additional quarter of the studies (24.15%) investigated both sexual health and social well-being. Meanwhile, the studies focusing on mental health only accounted for approximately 15% of the total. Conclusions: This scoping review revealed that previous research focused more on male than female sexual minorities, on disease-centered surveys than person-centered interventions, and investigations on negative health conditions than positive health promotion. Therefore, investigations centered on the female sexual minorities and corresponding person-centered interventions are highly needed. Review Registration: The protocol of this review has been registered within Open Science Framework (https://osf.io/82r7z) on April 27, 2020.


Treatment of recalcitrant non-union with a capacitively coupled electrical field. A preliminary report.
Twenty-two well established non-unions in twenty patients were treated with a capacitively coupled electrical signal (sine wave, sixty kilohertz, five volts peak to peak) that was applied non-invasively through stainless-steel capacitor plates placed on the skin surface overlying the approximate site of the non-union. The average age of the eleven female and nine male patients in this series was 38.4 years, and the average duration of the twenty-two non-unions was 3.3 years. Seventeen of the non-unions were labeled recalcitrant, meaning that they had failed to heal after either previous bone-grafting or another type of electrical stimulation, or both. Five of the non-unions had not been previously treated. Seventeen (77.3 per cent) of the non-unions achieved solid osseous union after an average of 22.5 weeks of treatment with capacitive coupling. The results in this small series were not affected by the non-union being recalcitrant, by the fact that one patient bore full weight on the extremity in a cast, by the presence of osteomyelitis, or by the presence of remaining metallic internal-fixation devices in the bone. Since capacitive coupling is non-invasive, involves portable equipment, allows full weight-bearing on the lower extremity in a cast, is easy to apply, and does not require precise localization of the capacitor plates, it has distinct advantages over other methods of treating non-union with electricity.


Pattern of medication utilization in hospitalized patients with COVID-19 in three District Headquarters Hospitals in the Punjab province of Pakistan.
In Pakistan, a wide range of repurposed drugs are recommended to manage hospitalized patients with COVID-19. Therefore, the current study was conducted to evaluate the pattern of utilization of repurposed drugs and other potential therapeutic options among hospitalized patients with COVID-19 in Pakistan. This retrospective, multicenter, descriptive study enrolled consecutive hospitalized patients with COVID-19 who were admitted between March 1, 2021, and April 30, 2021, from three District Headquarter Hospitals in the Punjab province of Pakistan. We described patient and clinical characteristics and medications, stratified by COVID-19 severity during hospitalization: mild, moderate, and severe. In addition, an analytical study of drug utilization was conducted. A total of 444 hospitalized patients with COVID-19 were included. Remdesvir, corticosteroids, antibiotics, and antithrombotics were administered to 45.0%, 93.9%, 84.9%, and 60.1% of patients, respectively. Specifically, dexamethasone was the most commonly used corticosteroid among the included patients (n = 405; 91.2%), irrespective of their clinical severity. Only 60.1% of patients hospitalized with COVID-19 in our cohort received antithrombotic therapy, and the prevalence of use was especially low (27.8%) in patients with mild illness. Of 444 patientsscreened, 399 (89.9%) patients had been discharged, and 45 patients (10.1%) died. We provided an important glimpse into the utilization patterns of several medications of interest for the treatment of COVID-19 in Pakistan, which had not been entirely evidence-based, especially concerning systemic corticosteroids and antibiotics.


Correlated photon emission from multiatom Rydberg dark States.
We consider three-level atoms driven by two resonant light fields in a ladder scheme where the upper level is a highly excited Rydberg state. We show that the dipole-dipole interactions between Rydberg excited atoms prevents the formation of single particle dark states and leads to strongly correlated photon pairs from atoms separated by distances large compared to the emission wavelength. For a pair of atoms, this enables realization of an efficient photon-pair source with on average one pair every 30 μs.


The Effect of Head Model Simplification on Beamformer Source Localization.
Beamformers are a widely-used tool in brain analysis with magnetoencephalography (MEG) and electroencephalography (EEG). For the construction of the beamformer filters realistic head volume conductor modeling is necessary for accurately computing the EEG and MEG leadfields, i.e., for solving the EEG and MEG forward problem. In this work, we investigate the influence of including realistic head tissue compartments into a finite element method (FEM) model on the beamformer's localization ability. Specifically, we investigate the effect of including cerebrospinal fluid, gray matter, and white matter distinction, as well as segmenting the skull bone into compacta and spongiosa, and modeling white matter anisotropy. We simulate an interictal epileptic measurement with white sensor noise. Beamformer filters are constructed with unit gain, unit array gain, and unit noise gain constraint. Beamformer source positions are determined by evaluating power and excess sample kurtosis (g2) of the source-waveforms at all source space nodes. For both modalities, we see a strong effect of modeling the cerebrospinal fluid and white and gray matter. Depending on the source position, both effects can each be in the magnitude of centimeters, rendering their modeling necessary for successful localization. Precise skull modeling mainly effected the EEG up to a few millimeters, while both modalities could profit from modeling white matter anisotropy to a smaller extent of 5-10 mm. The unit noise gain or neural activity index beamformer behaves similarly to the array gain beamformer when noise strength is sufficiently high. Variance localization seems more robust against modeling errors than kurtosis.


[Temporary amaurosis from retrobulbar lidocaine injection in late glaucoma patients].
Temporary amaurosis occurred after retrobulbar injection of lidocaine in 12 cases of antiglaucoma surgery in 4 years, and 10 of the patients were of late glaucoma. Lidocaine has a strong penetration potential which blocks the visual pathway, particularly for late glaucoma eyes in which the remnant optic nerve fibers may be especially sensitive to the drug. Therefore, the authors refrain from retrobulbar lidocaine in late glaucoma patients.


Long-term gait deviations in anterior cruciate ligament-reconstructed females.
Little is known of the potential long-term gait alterations that occur after an anterior cruciate ligament (ACL) reconstruction. In particular, variables, such as impact loading, which have been previously associated with joint deterioration, have not been studied in walking and running after an ACL reconstruction. The purpose of this study was to define the alterations in impact forces, loading rates, and the accompanying sagittal plane kinematic and kinetic mechanics at the time of impact between the ACL-reconstructed group and a healthy control group. Forty females (20 with ACL reconstruction and 20 controls) participated in the study. An instrumented gait analysis was performed on all subjects. Between-group and between-limb comparisons were made for the initial vertical impact force, loading rate, and sagittal plane knee and hip angles as well as moments. During walking and running, the ACL cohort had significantly greater initial vertical impact force (P = 0.002 and P = 0.001, respectively) and loading rates (P = 0.03 and P = 0.01, respectively), as well as a smaller knee extensor moment and hip angle during walking (P = 0.000 and P = 0.01, respectively). There was a trend toward a smaller knee moment and hip angle during running (P = 0.08 and P = 0.06, respectively) as well as a larger hip extensor moment during walking (P = 0.06) in the ACL group. No differences were found for hip extensor moment during running and for knee angles between groups during walking or running. Lastly, no between-limb differences were found for any variable. Gait deviations such as elevated impact loading and loading rates do not resolve long term after an individual has resumed previous activity levels and these may contribute to the greater risk of early joint degeneration in this population.