Twelve Tips for Medical Education Leadership to Help Faculty in the Transition to Online Teaching.
This article was migrated. The article was marked as recommended. The COVID-19 pandemic has had innumerable profound impacts, many of which have resulted in irrevocable changes to both the practice of medicine and the teaching of medicine. Medical educators have adapted to the need for social distancing by providing virtual educational opportunities for their learners, often without training or experience in online teaching. Because these educators require both professional development and technical support for their online teaching to be sustainable and effective, departments need to provide immediate help and support. These twelve tips are designed for those in leadership roles who have recognized the need for investment in online education and are interested in strategies to ensure the success of their educational programs.


Working from home and productivity under the COVID-19 pandemic: Using survey data of four manufacturing firms.
The coronavirus disease 2019 (COVID-19) pandemic has impacted the world economy in various ways. In particular, the drastic shift to telework has dramatically changed how people work. Whether the new style of working from home (WFH) will remain in our society highly depends on its effects on workers' productivity. However, to the best of our knowledge, the effects of WFH on productivity are still unclear. By leveraging unique surveys conducted at four manufacturing firms in Japan, we assess within-company productivity differences between those who work from home and those who do not, along with identifying possible factors of productivity changes due to WFH. Our main findings are as follows. First, after ruling out the time-invariant component of individual productivity and separate trends specific to employee attributes, we find that workers who worked from home experienced productivity declines more than those who did not. Second, our analysis shows that poor WFH setups and communication difficulties are the major reasons for productivity losses. Third, we find that the mental health of workers who work from home is better than that of workers who are unable to work from home. Our result suggests that if appropriate investments in upgrading WFH setups and facilitating communication can be made, WFH may improve productivity by improving employees' health and well-being.


[Puberty induction using pulsatile LHRH administration].
Puberty is a maturational process of the hypothalamo-pituitary-gonadal axis resulting in growth and development of the genital organs and concomitantly physical changes. All these changes are the result of an increasing activity of the pituitary and consequently of the gonads caused by increased stimulation by the luteinizing hormone-releasing hormone (LHRH). Delayed puberty is a common problem in contrast to true hypogonadotropic hypogonadism. Since a few years pulsatile LHRH administration is applied to induce pubertal development in hypogonadotropic boys. Except for virilisation, development of the testes including spermatogenesis can be achieved. In contrast to boys, substitution with sex steroids brings about a satisfactory physiologic development of the sex characteristics in girls. The physiology and disorders of pubertal development as well as this new LHRH treatment to induce puberty will be discussed in this paper.


Isolated bulbar paralysis in a patient with medullar tau pathology: a case report.
Increased morbidity and mortality rates as well as some other manifestations in Alzheimer's disease can be explained by subcortical degeneration. Pathological evidence is scarce but confirmative. We report a 77-year-old patient who presented with a 6-year history of dyspnoea, stridor and dysphagia. Unexpectedly, histopathological examination disclosed extensive degeneration of the medulla by tau pathology. The majority of symptoms and signs could be explained by the medullary tau pathology. Whether the medullary tau pathology in this case was a rare aberrant progression of Alzheimer's disease or a new presentation of tauopathy concomitant with subclinical Alzheimer's disease should be elucidated by additional studies.


Sleep Quality in Older People: The Impact of Age, Professional Activity, Financial Situation, and Chronic Diseases During the SARS-CoV-2 Pandemic.
BACKGROUND The SARS-CoV-2 pandemic negatively affected health and social life, notably deteriorating sleep quality in older adults. Studies report inconsistent findings on sleep disturbances during this period, influenced by various physiological, emotional, and sociodemographic factors. This study aimed to identify these determining factors. MATERIAL AND METHODS The study was conducted among 342 people 60 years of age or older participating in online classes of randomly selected Senior Clubs and the University of the Third Age in the southern regions of Poland. RESULTS Sleep problems (PSQI >5 points) were diagnosed in 250 subjects (83.6%). Logistic regression analysis showed that the quality of sleep significantly depends on: age, as people aged 66-70 were more likely to have better sleep quality than people aged 60-65 (OR=3.07), and those over 70 scored better than people aged 60-65 (OR=2.87); current job - employed people have a better chance of better sleep quality (OR=3.08) than unemployed people; financial situation, people assessing their financial situation as very good/good had a better chance of better sleep quality (OR=2.00) compared to people assessing their financial situation as very bad, bad/average; chronic diseases, people without chronic diseases had a chance of better sleep quality (OR=2.45) than people with chronic diseases. CONCLUSIONS Age, financial situation, current job, and chronic disease were the most important factors determining sleep quality in older people. The identification of factors affecting sleep quality can be used as important data to develop interventions and programs to improve sleep quality.


[Study of serum albumin and BMI as nutritional markers in hemodialysis patients].
Protein calorie malnutrition as well as systemic inflammation and metabolic disorders are common among patients with chronic renal failure undergoing renal replacement therapy (haemodialysis), which contributes to its morbidity and mortality. The aims of this work was to evaluate the nutritional status of patients in a hemodialysis treatment through the assessment of biochemical parameters nutritional as albumin, and anthropometric parameters of body mass index during ten years of follow up. In this work has been followed 90 patients of both sexes with chronic kidney disease who were treated with hemodialysis regularly on our unit for ten years. All patients were conducted quarterly measurements of plasma albumin (Alb), and other biochemical determinations, and anthropometric measurements of height, weight and body mass index calculated by the formula weight/height², grouped n BMI < 23 kg/m² and albumin levels <3.8 g/dl according to the consensus of the panel of experts of the International Society for renal Nutrition and metabolism. During the 10 years all patients showed a significant decline in the biochemical parameters and the albumin, change in BMI does not presented significant changes in relation to malnutrition. Malnutrition in patients on dialysis is a fact patent, BMI does not correspond with the biochemical parameters were observed, for what nutritional impairment in these patients is mainly expressed by serum albumin.


Calcium and vitamin D: what is known about the effects on growing bone.
The objective of these investigations was to determine if the receptor-dependent effects of 1,25-dihydroxyvitamin D were essential for normal skeletal growth. Mice with targeted ablation of the vitamin D receptor were engineered, and the skeletal consequences of vitamin D receptor ablation were studied in the presence of normal and abnormal mineral ion homeostasis. Prevention of abnormal mineral ion homeostasis resulted in the development of a normal skeleton in the absence of a functional vitamin D receptor. The metabolic cause of rickets was found to be hypophosphatemia. The major receptor-dependent actions of 1,25-dihydroxyvitamin D on skeletal development are indirect and are a reflection of the role of this hormone on intestinal calcium absorption.


Human bone marrow lymphocytes: B and T cell precursors and subpopulations.
Characterization of the different lymphocyte populations in normal human bone marrow (BM) was attempted and compared to that in the peripheral blood (PB). B cells comprised 34% +/- 11% of lymphocytes in BM and 23% +/- 9% in PB. The majority of B cells carried IgM in BM and IgG in the PB. In the BM, cells carrying complement or Fc receptors were fewer than cells carrying Ig, but in the PB they were equal. T cells comprised 6% +/- 4% of lymphocytes in the BM and 62% +/- 7% in the PB. The majority of BM lymphocytes did not have B or T cell markers; these probably included B and T cell precursors. BM lymphocytes carrying surface Ig increased in a 7-day culture, whereas those of the PB decreased. Pokeweed mitogen induced Ig synthesis in B cells of PB but not those of BM. BM-T cells were more efficient than PB-T cells in inhibiting Ig synthesis of PB-B cells. These results indicate that the BM compartment contains immature B cells that are capable of partial differentiation and maturation in vitro. BM-B lymphocytes are probably not involved in the effector phase of the immune response since they are unable to synthesize Ig and because they carry few receptors for complement of Fc, BM-T lymphocytes are very few and have suppressor capability and therefore may play an essential role in regulation of Ig synthesis by B cells.


The short-term effects of cisplatin chemotherapy on bone turnover.
Cisplatin is an effective agent in the treatment of osteosarcoma of bone but little is known of its effects on normal bone turnover. Twenty-four dogs divided into three study groups were used to study the effect of cisplatin on normal bone turnover at the distant site of surgery. Group 1 served as the control group, group 2 received four cycles of cisplatin every 3 weeks before the surgery, and group 3 received four cycles postoperatively. The bone turnover rate was evaluated by measuring levels of systemic bone markers, osteocalcin, alkaline phospohatase, urine pyridinoline cross-links, and by determination histomorphometric indices. Histomorphological analysis showed poor correlation on bone formation with systemic bone markers at distant sites of surgery. Histomorphometrically normal bone turnover was affected by administration of cisplatin, but the effect was temporary, late, and less significant than what occurred at the surgical site. Our data showed that significant effects of cisplatin are observed at the site of active cellular induction and proliferation, such as implant-host interface, and less effects are seen at the sites of normal bone turnover.


Birdshot retinochoroidopathy.
Birdshot retinochoroidopathy (BSRC) is an uncommon, but well-characterized chronic, bilateral posterior uveitis, which is uniquely associated with the human leukocyte antigen-A29 phenotype. The disease presents predominantly in middle-aged Caucasian females who complain of blurred vision, floaters, photopsias, paracentral scotomas and nyctalopia. While autoimmune mechanisms are thought to play an important role in the pathogenesis of BSRC, its etiology remains unknown. Important questions remain in our understanding of BSRC with respect to its pathogenesis, epidemiology, optimal treatment, and prognosis, including the determinants of remission and relapse, as well as the best strategy for monitoring disease activity, progression and response to therapy with electroretinographic and psychophysical testing, established and emerging imaging modalities, and peripheral cytokines profiles.


G-CSF (filgrastim)-stimulated whole blood kept unprocessed at 4 degrees C does support a BEAM-like regimen in bad-risk lymphoma.
The purpose of this study was to demonstrate the reconstitutive potential of granulocyte colony-stimulating factor (G-CSF) (filgrastim; Neupogen-primed unprocessed whole blood after myelotoxic therapy in bad-risk lymphoma. Nine patients with resistant lymphoma were treated with BAM: a BEAM regimen modified to a 72 h course consisting of BCNU 300 mg/m2 i.v. (day 1), Ara-C 3000 mg/m2 i.v. q 12 h (day 2) and melphalan 140 mg/m2 i.v. (day 3). After 5 days stimulation with G-CSF (10 micrograms/kg) 1l of blood was drawn, kept unprocessed for 3 days and reinfused 24 h after completion of chemotherapy. Back-up peripheral stem cells were available for all patients. The neutrophil count reached 0.5 x 10(9)/l at a median of 16 days (range 11-25) and a platelet count of 10 x 10(9)/l was reached at a median of 20 days (range 11-NR (not reached)). The median length of hospital stay was short in these patients with a median of 19 days (range 17-33). In three patients platelet transfusion independence did not occur before day 28. Those patients received their back-up stem cells. Antibiotics had to be used in two patients. The median number of reinfused CD34+ cells was 0.28 x 10(6)/kg (range 0.01-0.59). When more than 0.2 x 10(6)/kg CD34+ cells were reinfused the time to recovery was comparable to that observed after 'classical PBSCT'. In conclusion, the use of G-CSF-stimulated unprocessed whole blood is easy to perform and a cheap technique to mobilize and collect stem cells that can serve as a stem cell source after severe myelotoxic therapy in bad-risk malignant lymphoma.


The near-death experience as status passage.
Near-death experiences are identity transitions with many of the major social features of status passage as these were originally formulated by Glaser and Strauss (Status Passage, Routledge & Kegan Paul, London 1971). These features are described and then compared with the similar experience of being a castaway after shipwreck. In this way, the clinical near-death experience can be analysed as one of a number of social near-death experiences. Viewed as status passage many of the psychological reactions can be usefully seen as context dependent processes rather than simply defence mechanisms or products of neurophysiology.


Beyond knockout rats: new insights into finer genome manipulation in rats.
The ability to "knockout" specific genes in mice via embryonic stem (ES) cell-based gene-targeting technology has significantly enriched our understanding of gene function in normal and disease phenotypes. Improvements on this original strategy have been developed to enable the manipulation of genomes in a more sophisticated fashion with unprecedented precision. The rat is the model of choice in many areas of scientific investigation despite the lack of rat genetic toolboxes. Most Recent advances of zinc finger nucleases (ZFNs) and rat ES cells are diminishing the gap between rat and mouse with respect to reverse genetic approaches. Importantly, the establishment of rat ES cell-based gene targeting technology, in combination with the unique advantages of using rats, provides new, exciting opportunities to create animal models that mimic human diseases more faithfully. We hereby report our recent results concerning finer genetic modifications in the rat, and propose their potential applications in addressing biological questions.


Reprint of "fish immunity to scuticociliate parasites".
Some species of scuticociliates (Ciliophora) behave as facultative parasites and produce severe mortalities in cultured fish. Pathogenic scuticociliates can cause surface lesions and can also penetrate inside the body, where they feed on tissue and proliferate in the blood and most internal organs, killing the host in a few days. In this review, we describe the current knowledge on the protective role of fish cellular and humoral immune responses against these parasites. Immune humoral factors, especially complement, are of particular importance in defending fish against these ciliates. However, knowledge about how the fish immune system responds to scuticociliates is scant, and the cellular and molecular events that occur during the response are not known. We also describe the possible mechanisms used by scuticociliates to avoid or resist the defensive reaction of the host. For example, the release of proteases can help parasites enter fish tissues and impair the fish cellular and humoral responses. Several vaccine formulations containing scuticociliates have induced a good antibody response and protection in fish immunized and challenged with homologous strains of particular species. However, protection was not achieved in fish immunized and challenged with heterologous strains, and the antigens involved in protection and the antigenic differences between heterologous strains have not yet been determined.


Helicobacter pylori infection in children: relation with current household living conditions.
Studies demonstrating that deprived household living conditions during childhood are risk factors for acquisition of Helicobacter pylori infection have been performed mainly in adults, who probably acquired the infection several decades ago. This study investigates whether deprived household living conditions remain important risk factors for infection in subjects (children) with recently acquired infection. To examine the relation between current household living conditions and acquisition of H pylori infection in childhood. Opportunistically recruited group of 367 children, aged 3 to 15 years, undergoing routine non-gastrointestinal day surgery. Anti-H pylori IgG antibodies measured by a commercial enzyme linked immunosorbent assay validated for use in children. Postal questionnaire collecting sociodemographic data and data on household living conditions. Infection was associated with social class and overcrowding in the household. After adjustment for age, social class, and household density, a positive association remained between infection with H pylori and bed-sharing between children and parents on one or two nights per week, odds ratio for infection (95% CI), 2.29 (1.21, 4.32) or more frequently, odds ratio for infection (95% CI), 2.95 (1.35, 6.45). The continuing importance of household living conditions in the acquisition of H pylori infection is confirmed and household crowding and sharing a bed with a parent are identified as risk factors for infection.


Growth potential in suture bone inlay grafts: a comparison of vascularized and free calvarial bone grafts.
The present study investigates transsutural growth in vascularized and free calvarial bone grafts and notes the effects of such growth on craniofacial development. The temporalis myoosseous flap served as a model of vascularized graft. In ten 8-week-old dogs, a standardized skeletal defect, including a segment of the zygomatico-maxillary suture, was created. The defect was reconstructed with a vascularized graft in half the animals and a corresponding free graft in the remaining animals. Growth was assessed by means of serial cephalometric radiography and direct osteometry. Vascularized bone grafts demonstrated persistent transsutural growth following transplantation. Growth at the recipient site was preserved, resulting in less restriction of vertical maxillary development.


Systemic sclerosis immunoglobulin induces growth and a pro-fibrotic state in vascular smooth muscle cells through the epidermal growth factor receptor.
It has been suggested that autoantibodies in systemic sclerosis (SSc) may induce the differentiation of cultured fibroblasts into myofibroblasts through platelet-derived growth factor receptor (PDGFR) activation. The present study aims to characterize the effects of SSc IgG on vascular smooth muscle cells (VSMCs) and to determine if stimulatory autoantibodies directed to the PDGFR can be detected, and whether they induce a profibrotic response in primary cultured VSMCs. Cultured VSMCs were exposed to IgG fractions purified from SSc-patient or control sera. VSMC responses were then analyzed for ERK1/2 and Akt phosphorylation, PDGFR immunoprecipitation, cellular proliferation, protein synthesis, and pro-fibrotic changes in mRNA expression. Stimulatory activity in IgG fractions was more prevalent and intense in the SSc samples. SSc IgG immunoprecipitated the PDGFR with greater avidity than control IgG. Interestingly, activation of downstream signaling events (e.g. Akt, ERK1/2) was independent of PDGFR activity, but required functional EGFR. We also detected increased protein synthesis in response to SSc IgG (p<0.001) and pro-fibrotic changes in gene expression (Tgfb1 +200%; Tgfb2 -23%; p<0.001)) in VSMCs treated with SSc IgG. When compared to control IgG, SSc IgG have a higher stimulation index in VSMCs. Although SSc IgG interact with the PDGFR, the observed remodeling signaling events occur through the EGFR in VSMC. Our data thus favour a model of transactivation of the EGFR by SSc-derived PDGFR autoantibodies and suggest the use of EGFR inhibitors in future target identification studies in the field of SSc.


Diagnostic accuracy of endoscopic ultrasonography (EUS) for the preoperative locoregional staging of primary gastric cancer.
Endoscopic ultrasound (EUS) is proposed as an accurate diagnostic device for the locoregional staging of gastric cancer, which is crucial to developing a correct therapeutic strategy and ultimately to providing patients with the best chance of cure. However, despite a number of studies addressing this issue, there is no consensus on the role of EUS in routine clinical practice. To provide both a comprehensive overview and a quantitative analysis of the published data regarding the ability of EUS to preoperatively define the locoregional disease spread (i.e., primary tumor depth (T-stage) and regional lymph node status (N-stage)) in people with primary gastric carcinoma. We performed a systematic search to identify articles that examined the diagnostic accuracy of EUS (the index test) in the evaluation of primary gastric cancer depth of invasion (T-stage, according to the AJCC/UICC TNM staging system categories T1, T2, T3 and T4) and regional lymph node status (N-stage, disease-free (N0) versus metastatic (N+)) using histopathology as the reference standard. To this end, we searched the following databases: the Cochrane Library (the Cochrane Central Register of Controlled Trials (CENTRAL)), MEDLINE, EMBASE, NIHR Prospero Register, MEDION, Aggressive Research Intelligence Facility (ARIF), ClinicalTrials.gov, Current Controlled Trials MetaRegister, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), from 1988 to January 2015. We included studies that met the following main inclusion criteria: 1) a minimum sample size of 10 patients with histologically-proven primary carcinoma of the stomach (target condition); 2) comparison of EUS (index test) with pathology evaluation (reference standard) in terms of primary tumor (T-stage) and regional lymph nodes (N-stage). We excluded reports with possible overlap with the selected studies. For each study, two review authors extracted a standard set of data, using a dedicated data extraction form. We assessed data quality using a standard procedure according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. We performed diagnostic accuracy meta-analysis using the hierarchical bivariate method. We identified 66 articles (published between 1988 and 2012) that were eligible according to the inclusion criteria. We collected the data on 7747 patients with gastric cancer who were staged with EUS. Overall the quality of the included studies was good: in particular, only five studies presented a high risk of index test interpretation bias and two studies presented a high risk of selection bias.For primary tumor (T) stage, results were stratified according to the depth of invasion of the gastric wall. The meta-analysis of 50 studies (n = 4397) showed that the summary sensitivity and specificity of EUS in discriminating T1 to T2 (superficial) versus T3 to T4 (advanced) gastric carcinomas were 0.86 (95% confidence interval (CI) 0.81 to 0.90) and 0.90 (95% CI 0.87 to 0.93) respectively. For the diagnostic capacity of EUS to distinguish T1 (early gastric cancer, EGC) versus T2 (muscle-infiltrating) tumors, the meta-analysis of 46 studies (n = 2742) showed that the summary sensitivity and specificity were 0.85 (95% CI 0.78 to 0.91) and 0.90 (95% CI 0.85 to 0.93) respectively. When we addressed the capacity of EUS to distinguish between T1a (mucosal) versus T1b (submucosal) cancers the meta-analysis of 20 studies (n = 3321) showed that the summary sensitivity and specificity were 0.87 (95% CI 0.81 to 0.92) and 0.75 (95% CI 0.62 to 0.84) respectively. Finally, for the metastatic involvement of lymph nodes (N-stage), the meta-analysis of 44 studies (n = 3573) showed that the summary sensitivity and specificity were 0.83 (95% CI 0.79 to 0.87) and 0.67 (95% CI 0.61 to 0.72), respectively.Overall, as demonstrated also by the Bayesian nomograms, which enable readers to calculate post-test probabilities for any target condition prevalence, the EUS accuracy can be considered clinically useful to guide physicians in the locoregional staging of people with gastric cancer. However, it should be noted that between-study heterogeneity was not negligible: unfortunately, we could not identify any consistent source of the observed heterogeneity. Therefore, all accuracy measures reported in the present work and summarizing the available evidence should be interpreted cautiously. Moreover, we must emphasize that the analysis of positive and negative likelihood values revealed that EUS diagnostic performance cannot be considered optimal either for disease confirmation or for exclusion, especially for the ability of EUS to distinguish T1a (mucosal) versus T1b (submucosal) cancers and positive versus negative lymph node status. By analyzing the data from the largest series ever considered, we found that the diagnostic accuracy of EUS might be considered clinically useful to guide physicians in the locoregional staging of people with gastric carcinoma. However, the heterogeneity of the results warrants special caution, as well as further investigation for the identification of factors influencing the outcome of this diagnostic tool. Moreover, physicians should be warned that EUS performance is lower in diagnosing superficial tumors (T1a versus T1b) and lymph node status (positive versus negative). Overall, we observed large heterogeneity and its source needs to be understood before any definitive conclusion can be drawn about the use of EUS can be proposed in routine clinical settings.


Immunocytochemical localization of microtubule-associated protein 1 in rat cerebellum using monoclonal antibodies.
Immunohistochemical staining with monoclonal antibodies showed that microtubule-associated protein 1 (MAP1) has a restricted cellular distribution in the rat cerebellum. Anti-MAP1 staining was found only in neurons, where it was much stronger in dendrites than in axons. There were striking variations in the apparent concentration of MAP1 in different classes of neurons. Purkinje cells were the most strongly labeled, while granule cell neurons gave a faint, threshold-level reaction with the antibody. The reaction of Golgi neurons was intermediate between these two extremes. Equivalent results were obtained using two different methods of tissue preparation. Thus MAP1 appears to be a neuron-specific protein that is highly concentrated in dendrites and occurs at markedly different levels in different types of neurons. These observations provide further indications of heterogeneity among brain microtubules.


Road Less Traveled: Drug Hypersensitivity to Fluoroquinolones, Vancomycin, Tetracyclines, and Macrolides.
While fluoroquinolones, vancomycin, macrolides, and tetracyclines are generally safe antibiotics, they can induce both immediate and delayed hypersensitivity reactions (HSRs). Historically, less has been published on allergies to these antibiotics compared to beta lactams, but the prevalence of non-beta lactam HSRs is increasing. To fluoroquinolones, immediate HSRs are more common than delayed reactions. Both IgE and non-IgE mechanisms, such as the mast cell receptor Mas-related G protein-coupled receptor X2 (MRGPRX2), have been implicated in fluoroquinolone-induced anaphylaxis. Skin testing for fluoroquinolones is controversial, and the gold standard for diagnosis is a graded dose challenge. To vancomycin, the most common reaction is vancomycin infusion reaction (previously called "red man syndrome"), which is caused by infusion rate-dependent direct mast cell degranulation. Severity can range from flushing and pruritis to angioedema, bronchospasm, and hypotension that mimic type I HSRs. MRGPRX2 has been implicated in vancomycin infusion reactions. IgE-mediated HSRs to vancomycin are rare. Vancomycin skin testing yields high false positive rates. Thus, direct provocation challenge with slower infusion rate and/or antihistamine pre-treatment is preferred if symptoms are mild to moderate, and desensitization can be considered if symptoms are severe. To tetracyclines, non-IgE-mediated and delayed HSRs predominate with cutaneous reactions being the most common. There is no standardized skin testing for tetracyclines, and avoidance is generally recommended after a severe reaction because of the paucity of data for testing. Graded dose challenges and desensitizations can be considered for alternative or index tetracyclines if there are no alternatives. With macrolides, urticaria/angioedema is the most common immediate HSR, and rash is the most common delayed HSR. The predictive value for skin testing to macrolides is similarly poorly defined. In general, HSRs to fluroquinolones, vancomycin, macrolides, and tetracyclines are challenging to diagnose given the lack of validated skin testing and in vitro testing. Direct provocation challenge remains the gold standard for diagnosis, but the benefits of confirming an allergy may not outweigh the risk of a severe reaction. Skin testing, direct provocation challenge, and/or desensitization to the index non-beta lactam antibiotic or alternatives in its class may be reasonable approaches depending on the clinical context and patient preferences.


Poloxamer 188 decreases susceptibility of artificial lipid membranes to electroporation.
The effect of a nontoxic, nonionic block co-polymeric surface active agent, poloxamer 188, on electroporation of artificial lipid membranes made of azolectin, was investigated. Two different experimental protocols were used in our study: charge pulse and voltage clamp. For the charge pulse protocol, membranes were pulsed with a 10-micronsecond rectangular voltage waveform, after which membrane voltage decay was observed through an external 1-M omega resistance. For the voltage clamp protocol the membranes were pulsed with a waveform that consisted of an initial 10-microsecond rectangular phase, followed by a negative sloped ramp that decayed to zero in the subsequent 500 microseconds. Several parameters characterizing the electroporation process were measured and compared for the control membranes and membranes treated with 1.0 mM poloxamer 188. For both the charge pulse and voltage clamp experiments, the threshold voltage (amplitude of initial rectangular phase) and latency time (time elapsed between the end of rectangular phase and the onset of membrane electroporation) were measured. Membrane conductance (measured 200 microseconds after the initial rectangular phase) and rise time (tr; the time required for the porated membrane to reach a certain conductance value) were also determined for the voltage clamp experiments, and postelectroporation time constant (PE tau; the time constant for transmembrane voltage decay after onset of electroporation) for the charge pulse experiments. The charge pulse experiments were performed on 23 membranes with 10 control and 13 poloxamer-treated membranes, and voltage pulse experiments on 49 membranes with 26 control and 23 poloxamer-treated membranes. For both charge pulse and voltage clamp experiments, poloxamer 188-treated membranes exhibited a statistically higher threshold voltage (p = 0.1 and p = 0.06, respectively), and longer latency time (p = 0.04 and p = 0.05, respectively). Also, poloxamer 188-treated membranes were found to have a relatively lower conductance (p = 0.001), longer time required for the porated membrane to reach a certain conductance value (p = 0.05), and longer postelectroporation time constant (p = 0.005). Furthermore, addition of poloxamer 188 was found to reduce the membrane capacitance by approximately 4-8% in 5 min. These findings suggest that poloxamer 188 adsorbs into the lipid bilayers, thereby decreasing their susceptibility to electroporation.


A DNA-protein complex involved in bacteriophage phi chi 174 particle formation.
A varphiX-specific DNA-protein complex has been isolated from varphiX-infected cells. This complex contains infective circular single-stranded DNA, the proteins of the genes F, G, H, and J in the same proportions as in the phage particle, and, in addition, the gene D-protein. The D-protein makes up 12-22% of the protein part of the complex. The sedimentation value of the complex is about 140 S. In vitro, the complex can be converted to the normal 114S phage particle (with a concomitant loss of its D-protein) or to an uninfective 70S particle and a small amount of free single-stranded DNA. The fast sedimenting particle is not associated with membranes.


Nuclear localization signals for four distinct karyopherin-β nuclear import systems.
The Karyopherin-β family of proteins mediates nuclear transport of macromolecules. Nuclear versus cytoplasmic localization of proteins is often suggested by the presence of NLSs (nuclear localization signals) or NESs (nuclear export signals). Import-Karyopherin-βs or Importins bind to NLSs in their protein cargos to transport them through nuclear pore complexes into the nucleus. Until recently, only two classes of NLS had been biochemically and structurally characterized: the classical NLS, which is recognized by the Importin-α/β heterodimer and the PY-NLS (proline-tyrosine NLS), which is recognized by Karyopherin-β2 or Transportin-1. Structures of two other Karyopherin-βs, Kap121 and Transportin-SR2, in complex with their respective cargos were reported for the first time recently, revealing two new distinct classes of NLSs. The present paper briefly describes the classical NLS, reviews recent literature on the PY-NLS and provides in-depth reviews of the two newly discovered classes of NLSs that bind Kap121p and Transportin-SR respectively.


Trophic disruption: a meta-analysis of how habitat fragmentation affects resource consumption in terrestrial arthropod systems.
Habitat fragmentation is a complex process that affects ecological systems in diverse ways, altering everything from population persistence to ecosystem function. Despite widespread recognition that habitat fragmentation can influence food web interactions, consensus on the factors underlying variation in the impacts of fragmentation across systems remains elusive. In this study, we conduct a systematic review and meta-analysis to quantify the effects of habitat fragmentation and spatial habitat structure on resource consumption in terrestrial arthropod food webs. Across 419 studies, we found a negative overall effect of fragmentation on resource consumption. Variation in effect size was extensive but predictable. Specifically, resource consumption was reduced on small, isolated habitat fragments, higher at patch edges, and neutral with respect to landscape-scale spatial variables. In general, resource consumption increased in fragmented settings for habitat generalist consumers but decreased for specialist consumers. Our study demonstrates widespread disruption of trophic interactions in fragmented habitats and describes variation among studies that is largely predictable based on the ecological traits of the interacting species. We highlight future prospects for understanding how changes in spatial habitat structure may influence trophic modules and food webs.


Depression in Gulf War veterans: a systematic review and meta-analysis.
Although post-traumatic stress disorder (PTSD) has been a focus of attention in 1990/1991 Gulf War veterans, the excess risk of depression has not been clearly identified. We investigated this through a systematic review and meta-analysis of studies comparing depression in Gulf War veterans to depression in a comparison group of non-deployed military personnel. Multiple electronic databases and grey literature were searched from 1990 to 2012. Studies were assessed for eligibility and risk of bias according to established criteria. Of 14 098 titles and abstracts assessed, 14 studies met the inclusion criteria. Gulf War veterans had over twice the odds of experiencing depression [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.88-2.76] and dysthymia or chronic dysphoria (OR 2.39, 95% CI 2.0-2.86) compared to non-deployed military personnel. This finding was robust in sensitivity analyses, and to differences in overall risk of bias and psychological measures used. Despite divergent methodologies between studies, depression and dysthymia were twice as common in Gulf War veterans and are important medical conditions for clinicians and policymakers to be aware of in managing Gulf War veterans' health.


Kidney abnormalities in low density lipoprotein receptor associated protein knockout mice.
Mice lacking the LDL receptor associated protein (RAP) have a severe defect of thyroglobulin secretion into the colloid, associated with moderately increased serum TSH levels and histological features of early goiter. RAP is expressed also in renal proximal tubule cells, where it functions as a molecular chaperone for the endocytic receptor megalin, which is responsible for reabsorption of low molecular weight proteins from the glomerular filtrate. Here we investigated whether the thyroid phenotype in RAP knockout (KO) mice is associated with kidney alterations. By immunohistochemistry, we found that in RAP KO mice megalin expression on the apical membrane of renal proximal tubule cells was markedly reduced, with intracellular retention of the receptor. The reduced expression of megalin was associated with its impaired function. Thus, urinary protein concentrations and urinary protein excretion in 24 h were higher in RAP KO than in wild-type mice. Coomassie staining of urine samples revealed an increased intensity of low molecular mass bands in the urine of RAP KO mice, indicating that they had low molecular weight proteinuria. Therefore, we concluded that disruption of the RAP gene determines not only thyroid abnormalities, but also a severe defect of megalin expression and function in the kidney.


Fibrous Dysplasia With Atypical Bilateral Upper Extremity Pattern.
Fibrous dysplasia (FD) typically presents unilaterally in the lower limbs, or in the skull, mandible, or pelvis. Bilateral presentation is rarely reported. Most cases are diagnosed in the teens with 75% of patients diagnosed before the age of 30 years. In this case, a 63-year-old woman with suspected diagnosis of malignancy was referred to 99mTc-MDP scan and found to have polyostotic FD in bilateral upper extremities. Nuclear medicine can play an important role in diagnosing FD cases with atypical presentation and help risk stratification for more aggressive transformation.


Human T cells express a functional ionotropic glutamate receptor GluR3, and glutamate by itself triggers integrin-mediated adhesion to laminin and fibronectin and chemotactic migration.
T cells may encounter glutamate, the major excitatory neurotransmitter in the nervous system, when patrolling the brain and in glutamate-rich peripheral organs. Moreover, glutamate levels increase in the CNS in many pathological conditions in which T cells exert either beneficial or detrimental effects. We discovered that normal human T cells, human T leukemia cells, and mouse anti-myelin basic protein T cells express high levels of glutamate ion channel receptor (ionotropic) of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype 3 (GluR3). The evidence for GluR3 on T cells includes GluR3-specific RT-PCR, Western blot, immunocytochemical staining and flow cytometry. Sequencing showed that the T cell-expressed GluR3 is identical with the brain GluR3. Glutamate (10 nM), in the absence of any additional molecule, triggered T cell function: integrin-mediated T cell adhesion to laminin and fibronectin, a function normally performed by activated T cells only. The effect of glutamate was mimicked by AMPA receptor-agonists and blocked specifically by the selective receptor-antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6-nitro-7-sulfamoylbenzo[f]quinoxalin-2,3-dione (NBQX), and by relevant anti-integrin mAbs. Glutamate also increased the CXCR4-mediated T cell chemotactic migration toward the key chemokine CXCL12/stromal cell-derived factor-1. GluR3 expression on normal, cancer and autoimmune-associated T cells and the ability of glutamate to directly activate T cell function could be of substantial scientific and clinical importance to normal neuroimmune dialogues and to CNS diseases and injury, and especially to: 1) T cell transmigration to the CNS and patrolling in the brain, 2) T cell-mediated multiple sclerosis, and 3) autoimmune epilepsy, as neurotoxic anti-GluR3 Abs are found and suspected to cause/potentiate seizures and neuropathology in several types of human epilepsies. Thus far, GluR3 was found only on neurons and glia cells; our results reveal a novel peripheral source of this antigenic receptor.


CT perfusion stroke lesion threshold calibration between deconvolution algorithms.
CTP is an important diagnostic tool in managing patients with acute ischemic stroke, but challenges persist in the agreement of stroke lesion volumes and ischemic core-penumbra mismatch profiles determined with different CTP post-processing software. We investigated a systematic method of calibrating CTP stroke lesion thresholds between deconvolution algorithms using a digital perfusion phantom to improve inter-software agreement of mismatch profiles. Deconvolution-estimated cerebral blood flow (CBF) and Tmax was compared to the phantom ground truth via linear regression for one model-independent and two model-based deconvolution algorithms. Using the clinical standard of model-independent CBF < 30% and Tmax > 6 s as reference thresholds for ischemic core and penumbra, respectively, we determined that model-based CBF < 15% and Tmax > 6 s were the corresponding calibrated thresholds after accounting for quantitative differences revealed at linear regression. Calibrated thresholds were then validated in 63 patients with large vessel stroke by evaluating agreement (concordance and Cohen's kappa, κ) between the two model-based and model-independent deconvolution methods in determining mismatch profiles used for clinical decision-making. Both model-based deconvolution methods achieved 95% concordance with model-independent assessment and Cohen's kappa was excellent (κ = 0.87; 95% confidence interval [CI] 0.72-1.00 and κ = 0.86; 95% CI 0.70-1.00). Our systematic method of calibrating CTP stroke lesion thresholds may help harmonize mismatch profiles determined by different software.


RabGAPs in skeletal muscle function and exercise.
The two closely related RabGAPs TBC1D1 and TBC1D4 are key signaling factors of skeletal muscle substrate utilization. In mice, deficiency in both RabGAPs leads to reduced skeletal muscle glucose transport in response to insulin and lower GLUT4 abundance. Conversely, Tbc1d1 and Tbc1d4 deficiency results in enhanced lipid use as fuel in skeletal muscle, through yet unknown mechanisms. In humans, variants in TBC1D1 and TBC1D4 are linked to obesity, insulin resistance and type 2 diabetes. While the specific function in metabolism of each of the two RabGAPs remains to be determined, TBC1D1 emerges to be controlling exercise endurance and physical capacity, whereas TBC1D4 may rather be responsible for maintaining muscle insulin sensitivity, muscle contraction, and exercise. There is growing evidence that TBC1D1 also plays an important role in skeletal muscle development, since it has been found to be associated to meat production traits in several livestock species. In addition, TBC1D1 protein abundance in skeletal muscle is regulated by both, insulin receptor and insulin-like growth factor-1 (IGF-1) receptor signaling. This review focuses on the specific roles of the two key signaling factors TBC1D1 and TBC1D4 in skeletal muscle metabolism, development and exercise physiology.


Metal stents: a new treatment of malignant ureteral obstruction.
We report our experience with the use of metallic self-expandable and balloon expandable stents for the treatment of malignant ureteral obstruction. We treated 12 consecutive patients with malignant ureteral obstruction, for a total of 14 ureters with stents placed. We placed metallic balloon expandable stents in 6 patients and self-expandable metallic stents in the remaining 6. Mean patient age was 65 years and mean followup was 9 months (range 8 to 16). Of the ureters 11 were patent without any additional manipulations during followup of 8 to 16 months. Secondary interventions were needed in 3 cases because of obstructive urothelial hyperplastic reaction, tumor ingrowth and local recurrence of the primary cancer invading the upper end of the stent. Two patients died 2 and 10 months after placement of the stent. Both types of metal stents have advantages and disadvantages that must be balanced against each other when choosing the ideal device for the treatment of obstruction. Implantation of a metal self-expanding or balloon expanding stent is safe and effective for the palliative treatment of malignant ureteral obstruction in late stage cancer patients.


[A mathematical model for re-analysis of the relationship between essence of syndromes in traditional Chinese medicine and clinical biochemical indicators based on the residual-split method and its application].
Studying the essence of syndromes (Zheng) in traditional Chinese medicine (TCM) is a fundamental challenge in basic theoretical research of TCM. The relationship between any given syndrome and biochemical indicators is one of the important aspects of the study. As the indexes selected in each study are specific to a particular Western medical disease diagnosis, and the disease factor is inevitably introduced into the study, the effect of disease factor on the index changes cannot be assessed effectively by traditional data processing methods. This is known as "the same syndrome with different reasons", which has resulted in confusion in TCM research. This study aimed at providing a mathematical tool to address this issue. Based on information theory and the residual-split method, the syndrome information, which was covered in the index variation, was quantitatively calculated in this paper as an independent part of the disease factor. A mathematical model capable of objectively assessing and statistically testing the effect of the syndrome factor on the index changes was established. Applying this model to literature data of studies on the relationship between cyclic nucleotides and yang-deficiency syndrome showed following results. First, the values of yang-deficiency syndrome information were negative for cyclic adenosine monophosphate (cAMP) while positive for cyclic guanosine monophosphate (cGMP) in all included literature. This indicated that the group of yang-deficiency syndrome was correlated with an obvious trend of reduced cAMP levels and increased cGMP levels. Second, the statistical test results of yang-deficiency syndrome information of the two indexes were different among the literature included. The quality of original data was considered as a possible reason. Third, the significant differences between the yang-deficiency group of a specific disease and the normal group may, in some cases, be caused by a disease factor rather than a syndrome factor. The mathematical model provided a reasonable mathematical tool for the analysis of disease factor and syndrome factor in clinical research of TCM, suggesting that the mathematical model may give rise to innovative ideas and methods in the study of syndromes.


Effects of a Rehabilitation Program Using a Patient-Personalized Exergame on Fear of Falling and Risk of Falls in Vulnerable Older Adults: Protocol for a Randomized Controlled Group Study.
Older adults often experience physical, sensory, and cognitive decline. Therefore, they have a high risk of falls, which leads to severe health and psychological consequences and can induce fear of falling. Rehabilitation programs using exergames to prevent falls are being increasingly studied. Medimoov is a movement-based patient-personalized exergame for rehabilitation in older adults. A preliminary study showed that its use may influence functional ability and motivation. Most existing studies that evaluate the use of exergames do not involve an appropriate control group and do not focus on patient-personalized exergames. This study aims to evaluate the effects of Medimoov on risk of falls and fear of falling in older adults compared with standard psychomotor rehabilitation. This is a serial, comparative, randomized controlled group study. Both groups (n=25 in each) will receive psychomotor rehabilitation care. However, the methods of delivery will be different; one group will be exposed to the Medimoov exergame platform, and the other only to traditional means of psychomotor rehabilitation. The selection criteria will be (1) age of 65 years or older, (2) ability to answer a questionnaire, (3) ability to stand in a bipedal position for at least 1 minute, (4) score of 13 or greater on the Short Fall Efficacy Scale, and (5) stable medical condition. An evaluation will be made prior to starting the intervention, after 4 weeks of intervention, and at the end of the intervention (after 8 weeks), and it will focus on (1) risk of falls, (2) fear of falling, and (3) cognitive evaluations. Physical activity outside the session will also be assessed by actimetry. The outcome assessment will be performed according to intention-to-treat analysis. The protocol (2019-11-22) has been approved by the Comité de Protection des Personnes Nord-Ouest I-Université de Rouen (2019-A00395-52), which is part of the French national ethical committee. The study received funding in February 2020. As of October 2020 (submission date), and due to the context of the COVID-19 pandemic, a total of 10 participants out of 50 had been enrolled in the study. The projected date for the end of the data collection is December 2021. Data analyses have not been started yet, and publication of the results is expected for Spring 2022. The effects of psychomotor rehabilitation using the Medimoov exergame platform on the risk and fear of falls will be evaluated. This pilot study will be the basis for larger trials. ClinicalTrials.gov NCT04134988; https://clinicaltrials.gov/ct2/show/NCT04134988. DERR1-10.2196/24665.


[Ultrasound scanning of thickening of the gallbladder wall and its diagnostic significance in critical care patients].
In a prospective study including 398 intensive-care patients, we analysed the ultrasonographic relevance of a gallbladder wall thickening. In 24 of 398 (6%) cases a wall thickening was found that could be differentiated into two types of walls. In 20.8% (5/24) the gallbladder wall thickening was an expression of an acute cholecystitis. In further differential diagnosis of a gallbladder wall thickening pathological states with hypoalbuminaemia occupy the prime position. The pathological mechanism has not yet been completely clarified. Hypoalbuminaemia without inflammatory alterations of the organ was found in 37.5% of the cases with gallbladder wall thickening. In 41.6% of the patients the wall thickening had to be taken as a non-specific ultrasonographic sign. On the whole, therefore, gallbladder wall thickening has thus to be valued primarily as non-specific sign. In a few cases only, it implies an autonomous affection of the gallbladder.


Near-field effects on coherent anti-Stokes Raman scattering microscopy imaging.
We introduce a numerical method, the finite-difference time-domain (FDTD) method, to study the near-field effects on coherent anti-Stokes Raman Scattering (CARS) microscopy on nanoparticles. Changes of the induced nonlinear polarization, scattering patterns, and polarization properties against different diameters of spherical nanoparticles are calculated and discussed in details. The results show that due to near-field effects, the induced nonlinear polarization is significantly enhanced at the water-particle interface, with 1.5-fold increase in intensity compared to that inside the particles, and the near-field enhancement increases with decreasing diameters of nanoparticles. The enhanced scattering dominates over the scattering contribution from the particles when the nanoparticle size decreases down to the scale of less than a half wavelength of excitation light. Further studies show that near-field effects make the induced perpendicular polarization of CARS signals being strictly confined within the nanoparticles and the particle-water interface, and this perpendicular polarization component could contribute approximately 20% to the backward scattering. The ratio values of the perpendicular polarization component to the total CARS signals from nanoparticles sizing from 75 nm to 300 nm in backward scattering are approximately 3 to 5 times higher than those in forward scattering. Therefore, near-field effects can play an important role in CARS imaging. Employing the perpendicular polarization component of CARS signals can significantly improve the contrast of CARS images, and be particularly useful for revealing the fine structures of bio-materials with nano-scale resolutions.


Climate-dependent costs of reproduction: survival and fecundity costs decline with length of the growing season and summer temperature.
Costs of reproduction are expected to vary with environmental conditions thus influencing selection on life-history traits. Yet, the effects of habitat conditions and climate on trade-offs among fitness components remain poorly understood. For 2-5 years, we quantified costs of experimentally increased reproduction in two populations (coastal long-season vs. inland short-season) of two long-lived orchids that differ in natural reproductive effort (RE; 30 vs. 75% fruit set). In both species, survival costs were found only at the short-season site, whereas growth and fecundity costs were evident at both sites, and both survival and fecundity costs declined with increasing growing season length and/or summer temperature. The results suggest that the expression of costs of reproduction depend on the local climate, and that climate warming could result in selection favouring increased RE in both study species.


Developmental expression of HERV-R (ERV3) and HERV-K in human tissue.
The human endogenous retroviruses (HERVs), ERV3 (HERV-R) and HERV-K, are both known to be transcriptionally active in human placenta. In the case of ERV3 there is also indirect evidence for its participation in cellular differentiation. In this study we examined the expression of ERV3 (HERV-R) and HERV-K in human normal fetal tissues by in situ hybridization. The highest level of ERV3 env expression was detected in primitive adrenal cortex. Elevated levels of expression were also found in the following developing tissues: kidneys (tubules), tongue, heart, liver, and central nervous system. Tissue-specific expression was found for HERV-K rec (former cORF) but not for pol/int transcripts. The highest rec expression was found in placenta and levels slightly higher than sense control were found in the rest of the tissues examined. Pol/Int was not possible to quantitate. It appears that ERV3 is expressed in an organ-specific way during embryogenesis and might suggest a possible role in the development and differentiation of human tissues.


Catholic Ownership, Physician Leadership and Operational Strategies: Evidence from German Hospitals.
Previous research has revealed that Catholic hospitals are more likely follow a strategy of horizontal diversification and maximization of the number of patients treated, whereas Protestant hospitals follow a strategy of horizontal specialization and focus on vertical differentiation. However, there is no empirical evidence pertaining to this mechanism. We conduct an empirical study in a German setting and argue that physician leadership mediates the relationship between ownership and operational strategies. The study includes the construction of a model combining data from a survey and publicly available information derived from the annual quality reports of German hospitals. Our results show that Catholic hospitals opt for leadership structures that ensure operational strategies in line with their general values, i.e., operational strategies of maximizing volume throughout the overall hospital. They prefer part-time positions for chief medical officers, as chief medical officers are identified to foster strategies of maximizing the overall number of patients treated. Hospital owners should be aware that the implementation of part-time and full-time leadership roles can help to support their strategies. Thus, our results provide insights into the relationship between leadership structures at the top of an organization, on the one hand, and strategic choices, on the other.


The Effect of High Parity on the Occurrence of Anaemia in Pregnant Women.
To compare high-para and low-para women with respect to haematological findings, determinants, and consequences secondary to anaemia. Descriptive cohort study. Place and Duration of the Study: Maternity and Child Hospital, Hail, Saudi Arabia and Specialist Care Hospital (private), Islamabad, Pakistan, from April 2022 to April 2023. The study population comprised of pregnant women in the last trimester, with the exception of those women who had more than one fetus and history of haematological disease. Purposive non-probability sampling technique was adopted. Hospital data were retrieved retrospectively for the past obstetrical, contraception usage, and supplement history. Blood parameters, type of delivery, and maternofetal complications were noted down. For qualitative-variable and quantitative-variable comparisons, Chi-square test and t-test were applied, respectively. Significance level was kept at p ≤0.05. The frequency of severe anaemia in high-para was 52%. High parity and anaemia had a significant dose-response relationship (p <0.05). There was a significant difference (p <0.05) in blood parameters between high-para and low-para groups. Main determinants identified for anaemia were lack of intake of iron-rich food (36%) followed by inadequate intake of oral iron (25%). Preterm birth (68%) and post-partum haemorrhage (96%) were significantly associated (p <0.05) with high parity. There was a significantly high proportion (83%) of high-para women with more than 3 cesarean deliveries and admissions in ICU. High parity and anaemia had a significant dose-response relationship. High parity was the main determinant of maternal and fetal admissions in ICU. Parity, Comparison, Maternal anaemia, Haematological findings, Diet, Contraception, Cost-effective.


Restoring Cellular Energetics Promotes Axonal Regeneration and Functional Recovery after Spinal Cord Injury.
Axonal regeneration in the central nervous system (CNS) is a highly energy-demanding process. Extrinsic insults and intrinsic restrictions lead to an energy crisis in injured axons, raising the question of whether recovering energy deficits facilitates regeneration. Here, we reveal that enhancing axonal mitochondrial transport by deleting syntaphilin (Snph) recovers injury-induced mitochondrial depolarization. Using three CNS injury mouse models, we demonstrate that Snph-/- mice display enhanced corticospinal tract (CST) regeneration passing through a spinal cord lesion, accelerated regrowth of monoaminergic axons across a transection gap, and increased compensatory sprouting of uninjured CST. Notably, regenerated CST axons form functional synapses and promote motor functional recovery. Administration of the bioenergetic compound creatine boosts CST regenerative capacity in Snph-/- mice. Our study provides mechanistic insights into intrinsic regeneration failure in CNS and suggests that enhancing mitochondrial transport and cellular energetics are promising strategies to promote regeneration and functional restoration after CNS injuries.


[Effects of different concentrations of nitrogen and phosphorus on growth and active components of Salvia miltiorrhiza].
With annual Salvia miltiorrhiza seedlings as experimental material, using "3414" optimal regression design recommended by the Ministry of Agriculture and regularly watered with nutrient solution, through the dynamic sampling of S. miltiorrhiza in different growing stages, and the growth index, dry weight of plant root and content of active components were measured. The potted experiments were applied to study the effects of different nitrogen and phosphorus ratios on the growth, dry matter accumulation and accumulation of active components of S. miltiorrhiza, in order to explore a compatible fertilization method of nitrogen and phosphorus ratio that are suitable for production and quality of S. miltiorrhiza. The results reported as follows:①High concentrations of nitrogen fertilizer was beneficial to dry matter accumulation of S. miltiorrhiza aerial parts, and low concentration of nitrogen fertilizer transferred the dry matter accumulation to underground, and N1P1 could make the transfer ahead of time;②Regression analysis showed that in the early growth stage (before early July), we could use the nitrogen and phosphorus as basic fertilizer at a concentration of 1.521,0.355 g•L⁻¹ respectively to promote the growth of S. miltiorrhiza and at a concentration of 2.281,0.710 g•L⁻¹ respectively to promote the dry matter accumulation of root (after mid-August);③Five kinds of active components of S. miltiorrhiza decreased with the increase of nitrogen concentration, and increased with the increase of the concentration of phosphate fertilizer. Nitrogenous fertilizer, phosphate fertilizer in N-P=2∶3 ratio was more suitable for the accumulation of salvianolic acids, in N-P=1∶2 ratio was more suitable for the accumulation of tanshinone.


The Effect of Delayed Chemotherapy on the Decrease of CA125 in Epithelial Ovarian Cancer During Coronavirus Disease Pandemic in 2020.
To investigate whether patients with epithelial ovarian cancer were affected by delayed chemotherapy during the coronavirus disease pandemic in 2020. A delay of more than 21 days in the planned chemotherapy was defined as "delayed chemotherapy." Forty-five patients with epithelial ovarian, fallopian tube, and peritoneal cancer were delayed between January 1 and March 30, 2020 in the First Affiliated Hospital of Chongqing Medical University. Thirty-two cases were enrolled in this study. Neoadjuvant chemotherapy was used in 8 cases; palliative chemotherapy was used in 5 cases; and maintenance chemotherapy was used in 19 cases. Data included age, pathological type, surgical pathological stage, chemotherapy time and CA125 levels were collected. The half-life of CA125 and the decrease in CA125 levels before and after delayed chemotherapy were calculated. No patient got coronavirus disease. Compared with patients of ovarian cancer, fallopian tube epithelial cancer and peritoneal epithelial cancer in the same periods in 2019, the half-life of CA125 in neoadjuvant chemotherapy group and recurrence chemotherapy group were more than 20 days, but there was no significant difference. Only when the delayed chemotherapy took place before CA125 turned negative, accompanied by an interval of more than 60 days, the CA125 half-life and the decreased range of CA125 were totally affected. There was no evidence to support that once chemotherapy was delayed it would influence the decrease of CA125, but whether it would affect the long-term effects such as recurrence and five-year survival rate remains to be further followed up.


Comparative assessment of time-related bioactive glass and calcium hydroxide effects on mechanical properties of human root dentin.
Suspensions of micro- or nanoparticulate SiO(2)-Na(2)O-CaO-P(2)O(5) bioactive glasses could potentially be used as dressings in traumatized front teeth with open apices as an alternative to Ca(OH)(2). These materials have a disinfecting capacity similar to Ca(OH)(2), but bear the advantage of bioactivity. However, because bioactive glasses initially act as alkaline biocides just as Ca(OH)(2) does, they may also negatively affect mechanical dentin properties over time. This was assessed in the current study using standardized human root dentin bars. Specimens were immersed in 1:20 (wt vol(-1)) suspensions of nanometric bioactive glass 45S5 or calcium hydroxide for 1, 10, or 30 days. Control specimens were immersed in pure saline for 30 days (n = 20 per group). Subsequently, modulus of elasticity (E) and flexural strength (FS) of the specimens were determined. Results were compared between groups using one-way anova and Scheffé's post-hoc test. Ca(OH)(2) caused a significant (P < 0.001) 35% drop in mean flexural strength values compared to the control treatment after 10 days. No further change was observed between 10 days and 30 days. Bioactive glass caused a 20% drop in mean flexural strength as compared to the control after 10 days. However, this difference did not reach statistical significance (P > 0.05). No effects of either material on dentin modulus of elasticity values were observed. It was concluded that the calcium hydroxide suspension affected the dentin more than the bioactive glass counterpart; however, the effect was self-limiting and probably restricted to superficial dentin layers, as suggested by the mere decrease in flexural strength but not in modulus of elasticity values.


[Gummi armeniacae collected from apricot trees in armenia - perspective source of arabinogalactan].
The subjects of this inquiry were apricot tree gums - Gummi armeniacae, collected from different regions of Republic Armenia. The samples of gums were analyzed by the method of gas-liquid chromatography. As a result arabinogalactans were revealed in apricot tree gums. Due to the presence of sufficient resources of Gummi armeniacae in Armenian flora their usage in the water soluble arabinogalactan's obtaining process is quite perspective.


An MCM2-related gene is expressed in proliferating cells of intact and regenerating planarians.
The minichromosome maintenance (MCM2-7) gene family encodes conserved proteins, which are essential for DNA replication licensing in eukaryotes. They are abundant in proliferating cells, and specific MCM transcripts undergo cell cycle-dependent oscillations. Here we report the characterization of a planarian MCM2 homologue, DjMCM2, which represents the first molecular marker for detecting proliferating cells in planarians. DjMCM2-expressing cells are broadly distributed in the mesenchymal space of the body, with the exception of the cephalic region, and are preferentially accumulated in the peripheral area of the dorso-lateral mesenchyme, along the anteroposterior axis. During regeneration, no DjMCM2 transcripts are observed within the blastema, according to the current view that this structure is not a proliferation site in planarians. Spatio-temporal changes in DjMCM2 RNA expression pattern in the stump parallel blastema growth, coordinately with the orientation of the cut. X-ray irradiation results in the disappearance of DjMCM2 expression, thus confirming that these transcripts are detected specifically in proliferating cells, visualized as neoblasts by in situ hybridization in dissociated cells. In addition to neoblasts, rare large DjMCM2-expressing cells are observed in macerates of tissues excised just below the wound, suggesting that cell types other than neoblasts may be sporadically recruited for proliferation in planarians.


Study of intestinal function in anorectal malformations: the role of Bowel management in quality of life.
We aimed at investigating bowel function in children and adolescents with anorectal malformations (ARMs) and assess their quality of life (QoL), in order to define a personal program of bowel management improving both clinical condition and self-confidence. A total of 55 patients treated for ARM by Posterior Sagittal Ano-Recto-Plasty (PSARP) from 2000 to 2014 were included into the study. The parents of 41 patients answered two telephone questionnaires about the parents' self-efficacy and about QoL (GIQLI). A modified Peña score system was used to evaluate intestinal function. Twenty patients underwent anorectal manometry. After clinical assessment, all patients underwent an individual bowel management program. A median follow-up of 91.3 months was performed. A significant inverse correlation was found between Peña score and GIQLI (r:-0.93, p<0.0001). Anorectal manometry paralleled the Peña score, showing an association between megarectum and constipation and soiling subdomains, especially in patients with higher ARM. Patients who carefully followed the bowel management program had significant improvements in both continence (0.93±1.1 vs 0.45±0.9, p=0.0005) and Peña score (4.6±3 vs 3.4±2.5, p<0.0001), which positively affected their self-confidence (100±26.6 vs 110±23, p<0.0001). The synergy of different scores and the evaluation of anorectal physiology proved useful to define the bowel management program, which seems to significantly impact both bowel function and QoL, with specific regard to soiling. Moreover, the Peña score might be also quantitatively used, as it parallels with both anorectal manometry and GIQLI, and the latter seems to be suitable for children. Further studies are required to confirm our findings.


[Mesenteric and splenic vein thrombosis in a female patient with essential thrombocytosis and activated protein C resistance].
Splenic venous thrombosis is a rare disease in which an underlying hypercoagulable state can often be found. A 27-years old female patient with recurrent mesenteric venous and splenic thrombosis as a severe complication of an association of resistance to activated protein C and essential thrombocythemia is presented in this report. Establishing the diagnosis of essential thrombocytosis was particularly difficult because this was the case of the so called "silent" myeloproliferative disorder. The number of thrombocytes was almost normal before the splenectomy performed because of the splenic venous thrombosis. Thus, spontaneous growth of erythroid and megakaryocyte colonies in vitro and the clinical course of the disease were the clues for establishing the diagnosis, because the number of thrombocytes reached the values over 1500 x 10(9)/l after only 1.5 years of the follow-up. The case of this patient was interesting particularly from the surgical point of view because of the management strategy.


Homogeneous Bose gas of dipolar molecules in the mean field approximation.
We present a mean field analysis of the effects of molecular rotation on the excitation spectrum and stability of ultracold dipolar gases. For an unpolarized homogeneous gas interacting with a pure dipole-dipole interaction, we find that for the rotational state L = 1 the dipole-dipole interaction causes a splitting of the translation-rotation energy levels into a single M = 0 and a doubly degenerate M = ±1 excitation. For all other rotational states, the dipole-dipole interaction does not lead to coupling of translations and rotations and therefore has no effect on the rotational degeneracy of the excitations. The addition of arbitrarily small electric fields is found to introduce instabilities similar to those known to arise in the fully polarized dipolar gas. As in the case of a fully polarized gas, addition of a large enough short range repulsive potential is seen to stabilize the system, with the critical value of the repulsive interaction required for stabilization being larger when rotations are included.


ICAM-1 and P-selectin expression in a model of NSAID-induced gastropathy.
A growing body of experimental evidence suggests that neutrophilic polymorphonuclear leukocyte (PMN)-endothelial cell interactions play a critical role in the pathophysiology of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. The objective of this study was to directly determine whether the expression of endothelial cell adhesion molecules is enhanced in a model of NSAID-induced gastropathy. Gastropathy was induced in male Sprague-Dawley rats via oral administration of indomethacin (Indo, 20 mg/kg). Lesion scores, blood-to-lumen clearance of 51Cr-EDTA (mucosal permeability), and histological analysis (epithelial necrosis) were used as indexes of gastric mucosal injury. Gastric mucosal vascular expression of intercellular adhesion molecule 1 (ICAM-1) or P-selectin were determined at 1 and 3 h after Indo administration using the dual radiolabeled monoclonal antibody (MAb) technique. For some experiments, a blocking MAb directed at either ICAM-1 (1A29) or P-selectin (RMP-1) or their isotype-matched controls was injected intravenously 10 min before Indo administration. We found that P-selectin expression was significantly increased at 1 h but not 3 h after Indo administration, whereas ICAM-1 expression was significantly increased at both 1 and 3 h after Indo treatment. The blocking ICAM-1 and P-selectin MAbs both inhibited Indo-induced increases in lesion score, mucosal permeability, and epithelial cell necrosis. However, the Indo-induced gastropathy was not associated with significant PMN infiltration into the gastric mucosal interstitium, nor did Indo reduce gastric mucosal blood flow. We propose that NSAID-induced gastric mucosal injury may be related to the expression of P-selectin and ICAM-1; however, this mucosal injury does not appear to be dependent on the extravasation of inflammatory cells or mucosal ischemia.


Non-myogenic Contribution to Muscle Development and Homeostasis: The Role of Connective Tissues.
Skeletal muscles belong to the musculoskeletal system, which is composed of bone, tendon, ligament and irregular connective tissue, and closely associated with motor nerves and blood vessels. The intrinsic molecular signals regulating myogenesis have been extensively investigated. However, muscle development, homeostasis and regeneration require interactions with surrounding tissues and the cellular and molecular aspects of this dialogue have not been completely elucidated. During development and adult life, myogenic cells are closely associated with the different types of connective tissue. Connective tissues are defined as specialized (bone and cartilage), dense regular (tendon and ligament) and dense irregular connective tissue. The role of connective tissue in muscle morphogenesis has been investigated, thanks to the identification of transcription factors that characterize the different types of connective tissues. Here, we review the development of the various connective tissues in the context of the musculoskeletal system and highlight their important role in delivering information necessary for correct muscle morphogenesis, from the early step of myoblast differentiation to the late stage of muscle maturation. Interactions between muscle and connective tissue are also critical in the adult during muscle regeneration, as impairment of the regenerative potential after injury or in neuromuscular diseases results in the progressive replacement of the muscle mass by fibrotic tissue. We conclude that bi-directional communication between muscle and connective tissue is critical for a correct assembly of the musculoskeletal system during development as well as to maintain its homeostasis in the adult.


MDMA toxicity: no evidence for a major influence of metabolic genotype at CYP2D6.
3,4 Methylenedioxymethamphetamine (MDMA or ecstasy) has become a major drug of abuse over the last decade. It produces a mixture of systemic and neuropsychological effects. Animal studies show a range of short- and long-term toxic effects, both systemically and neurochemically. In humans, toxicity and death due to the drug have been attributed to a variety of causes, with 'idiosyncratic', or non-dose-related, reactions often cited. It has recently been established that MDMA is metabolized via the cytochrome P450 enzyme, debrisoquine hydroxylase. This enzyme is coded by the gene CYP2D6. This gene contains mutations which effect the function of the enzyme, and individuals homozygous for these mutations are known as poor metabolizers. Between 3 and 10% of the Caucasian population are thus affected, and therefore may be less able to metabolize MDMA. In this paper we examine the hypothesis that individuals selected on the basis of having had an adverse reaction to MDMA will be more likely than the general population to have homozygous mutations at CYP2D6. We obtained retrospectively seven cases of toxicity or death thought to be due to MDMA. DNA was extracted from these patients, and their genotype ascertained. None of this small sample was shown to be homozygous for the mutation at CYP2D6. Three possible explanations are offered for these results. (1) The non-dose-related nature of MDMA toxicity may be due, either alone or in combination, to contaminants in the drug, or ambient environmental/physiological factors. (2) Our genotyping methods may have missed one of the rare additional mutations which effect gene function at CYP2D6. (3) Our study sample may be too small to demonstrate a statistically significant result. A larger study is currently under way.


e-Mentorship: Navigation strategy for promoting oncology nurse engagement in research.
There is a high need for research mentorship among Canadian oncology nurses. E-mentorship is an effective vehicle for linking oncology nurses with experienced researchers across the country who can help them navigate the road and increase their engagement in research. E-mentorship also has the potential to build research capacity more broadly by strengthening national networks and connections among researchers, cancer care organizations and oncology nurses at the point of care. Innovative strategies are needed to more easily identify and recruit researchers who are committed to advancing oncology nursing practice through effective mentorship.


[About effectiveness and perspective of application of test of venereal disease research laboratory (VDRL) for diagnostic of neurosyphilis in the Russian Federation].
The comparative evaluation of effectiveness of different nontreponema tests in analysis of cerebrospinal fluid. The liquor from 100 patients with syphilis was analyzed using Bordet-Gengou test, VDRL test and micro-precipitation reaction with cardiolipin antigen. The Bordet-Gengou test and VDRL test made in Russia or abroad are equally effective in analysis of positive samples of liquor and twice surpass the same capacity of micro-precipitation reaction with cardiolipin antigen in case of neurosyphilis with symptoms and thrice surpass in case of asymptomatic neurosyphilis. VDRL test is a simple standardized nontreponema reaction which can substitute labor-consuming non-unified liquorologic complex in laboratory diagnostic of neurosyphilis. The testing of liquor on the basis of micro-precipitation reaction with cardiolipin antigen is non-effective and results in false negative results in Bordet-Gengou and VDRL positive tests determining high risk of erroneous clinical considerations.


Neurite outgrowth on cryostat sections of innervated and denervated skeletal muscle.
To localize factors that guide axons reinnervating skeletal muscle, we cultured ciliary ganglion neurons on cryostat sections of innervated and denervated adult muscle. Neurons extended neurites on sections of muscle (and several other tissues), generally in close apposition to sectioned cell surfaces. Average neurite length was greater on sections of denervated than on sections of innervated muscle, supporting the existence of functionally important differences between innervated and denervated muscle fiber surfaces. Furthermore, outgrowth was greater on sections of denervated muscle cut from endplate-rich regions than on sections from endplate-free regions, suggesting that a neurite outgrowth-promoting factor is concentrated near synapses. Finally, 80% of the neurites that contacted original synaptic sites (which are known to be preferentially reinnervated by regenerating axons in vivo) terminated precisely at those contacts, thereby demonstrating a specific response to components concentrated at endplates. Together, these results support the hypothesis that denervated muscles use cell surface (membrane and matrix) molecules to inform regenerating axons of their state of innervation and proximity to synaptic sites.


Female control of male reproductive function in a Mexican Snake.
Male Thamnophis melanogaster court immediately when exposed to estrogen-treated, attractive females and continue courting for 6 to 8 days. Males exposed to estrogen-treated females will court both intact and ovariectomized females. These males undergo a period of testicular recrudescence, whereas males exposed only to ovariectomized females do no. Sexual attractivity can be induced in female T. melanogaster without estrogen treatment by heavy feeding, which results in significant increases in liver size and activity.


An overview of meningitis and meningococcal septicaemia.
This article provides an overview of meningitis and meningococcal septicaemia, which can have devastating effects. Nurses working in acute and primary care must be able to recognise the causes and symptoms of these conditions, and have up-to-date knowledge of treatment, prevention and potential after effects.


Quality of Work Life Among Nurses: A case study from Ad Dakhiliyah Governorate, Oman.
Quality of work life (QWL) is an important indicator of job-related satisfaction among nurses; however, there is little information regarding the QWL of nurses in Oman. Therefore, this study aimed to explore factors affecting QWL among nurses working in governmental health institutions in Ad Dakhiliyah Governorate, Oman. This descriptive cross-sectional study was conducted between September and November 2018 at 29 governmental health institutions in Ad Dakhiliyah Governorate. A total of 374 nurses employed at these institutions were recruited via stratified random sampling. A demographic questionnaire incorporating Brooks' Quality of Nursing Work scale was used to collect data. A total of 345 nurses participated in the study (response rate: 92.2%). The mean age was 33.3 ± 5.1 years and the majority were female (90.7%), married (88.7%), of Omani nationality (70.1%) and had a diploma degree (70.7%). Overall, the nurses demonstrated moderate levels of QWL (mean total score: 179.99 ± 24.17). Both job designation and nationality were found to be significant predictors of QWL (P = 0.041 and <0.001, respectively). The findings of this study represent a baseline for further research on this important topic. As with all healthcare professionals, the QWL of nurses indirectly affects quality of patient care and associated health outcomes. As such, identifying areas of poor QWL among nurses can help in the development of initiatives to improve their professional satisfaction, thereby enhancing job performance and employee retention.


Description of Pandoraea gen. nov. with Pandoraea apista sp. nov., Pandoraea pulmonicola sp. nov., Pandoraea pnomenusa sp. nov., Pandoraea sputorum sp. nov. and Pandoraea norimbergensis comb. nov.
A polyphasic taxonomic study was performed on a group of isolates tentatively identified as Burkholderia cepacia, Ralstonia pickettii or Ralstonia paucula (formerly known as CDC group IVc-2). The isolates were mainly cultured from sputum of cystic fibrosis patients or from soil. SDS-PAGE of whole-cell proteins and AFLP fingerprinting distinguished at least five different species, and this was confirmed by DNA-DNA hybridizations. 16S rDNA sequence analysis of representative strains indicated that these organisms belong to the beta-subclass of the Proteobacteria, with the genera Burkholderia and Ralstonia as closest neighbours. Based on genotypic and phenotypic characteristics, the organisms were classified in a novel genus, Pandoraea. The DNA base composition of the members of the new genus is between 61.2 and 64.3 mol%. This novel genus includes four new species, Pandoraea apista (the type species) (type strain is LMG 16407T), Pandoraea pulmonicola (type strain is LMG 18106T), Pandoraea pnomenusa (type strain is LMG 18087T) and Pandoraea sputorum (type strain is LMG 18819T), and Pandoraea norimbergensis (Wittke et al. 1997) comb. nov. (type strain is LMG 18379T). The available clinical data indicate that at least some of these organisms may cause chronic infection in, and can be transmitted amongst, cystic fibrosis patients.


Macrophage activation downregulates the degradative capacity of the phagosome.
The phagosome is key to most macrophage functions. It is the site of degradation of particulate material, of bacterial killing and the generation of peptides for antigen presentation. Despite its role at the fulcrum of the innate and acquired immune systems, little is known about the physiology of this organelle in activated macrophages. In this study, we utilize fluorometric techniques to characterize functional alterations in the lumenal environment of the maturing phagosome following stimulation of macrophages with interferon-gamma and/or lipopolysaccharide. In addition to modulating the kinetics of phagosomal acidification, activation results in a phagosome with diminished hydrolytic activities that varies markedly with the activation status of the cell. Differential levels of proteolytic, lipolytic and beta-galactosidase activities were observed in the phagosome but not in the total lysosomal extract, indicating selective delivery of enzymes to the developing phagosome. Despite the suppression of hydrolytic activities observed in early phagosomes, late phagosomes exhibit an enhanced and protracted accumulation of lysosomal cargo. The data are consistent with limiting proteolysis in the early phagosome to maximize epitope generation and antigen presentation while sequestering the degradative capacity in the late phagolysosome.


Diversification rates of the "Old Endemic" murine rodents of Luzon Island, Philippines are inconsistent with incumbency effects and ecological opportunity.
Diversity-dependent cladogenesis occurs when a colonizing lineage exhibits increasing interspecific competition as it ecologically diversifies. Repeated colonization of a region by closely related taxa may cause similar effects as species within each lineage compete with one another. This may be particularly relevant for secondary colonists, which could experience limited diversification due to competition with earlier, incumbent colonists over evolutionary time. We tested the hypothesis that an incumbent lineage may diminish the diversification of secondary colonists in two speciose clades of Philippine "Old Endemic" murine rodents-Phloeomyini and Chrotomyini-on the relatively old oceanic island of Luzon. Although phylogenetic analyses confirm the independent, noncontemporaneous colonization of Luzon by the ancestors of these two clades, we found no support for arrested diversification in either. Rather, it appears that diversification of both clades resulted from constant-rate processes that were either uniform or favored the secondary colonists (Chrotomyini), depending on the method used. Our results suggest that ecological incumbency has not played an important role in determining lineage diversification among Luzon murines, despite sympatric occurrence by constituent species within each lineage, and a substantial head start for the primary colonists.


Insights into redox sensing metalloproteins in Mycobacterium tuberculosis.
Mycobacterium tuberculosis, the pathogen that causes tuberculosis, has evolved sophisticated mechanisms for evading assault by the human host. This review focuses on M. tuberculosis regulatory metalloproteins that are sensitive to exogenous stresses attributed to changes in the levels of gaseous molecules (i.e., molecular oxygen, carbon monoxide and nitric oxide) to elicit an intracellular response. In particular, we highlight recent developments on the subfamily of Whi proteins, redox sensing WhiB-like proteins that contain iron-sulfur clusters, sigma factors and their cognate anti-sigma factors of which some are zinc-regulated, and the dormancy survival regulon DosS/DosT-DosR heme sensory system. Mounting experimental evidence suggests that these systems contribute to a highly complex and interrelated regulatory network that controls M. tuberculosis biology. This review concludes with a discussion of strategies that M. tuberculosis has developed to maintain redox homeostasis, including mechanisms to regulate endogenous nitric oxide and carbon monoxide levels.


Morphophenotypic characteristics of intralymphatic cancer and stromal cells susceptible to lymphogenic metastasis.
The intravessel microenvironment has significant effects on cancer metastasis. The aim of the present study was to determine how the morphologic and immunophenotypic features of cancer cells and infiltrating stromal cells within the permeated lymphatic vessels are associated with lymphogenic metastasis. A total of 137 primary lung adenocarcinoma patients with extratumoral lymphatic permeations were examined. Morphologically, the floating cancer nests within the permeated lymphatic vessels were divided into two types: Type A, consisting of a single large cancer nest; and Type B, consisting of multiple small cancer nests. We compared the clinicopathologic characteristics and the immunophenotypes of the cancer cells and infiltrating stromal cells between the Type A and Type B nests. Eleven of 54 Type A patients (20%) had intrapulmonary metastases, compared with 36 of 83 Type B patients (43%; P = 0.006). Immunohistochemically, Type B cancer cells expressed significantly higher levels of CD44 than Type A cancer cells (mean scoresAUTHOR: Scores - what is this score? Is it the number of cells expressing CD44 or the concentration of CD44 or some other type of scoring system? 43.0 vs 20.5, respectively) and E-cadherin (60.5 vs 31.5, respectively), but lower levels of Geminin (11.9% vs 20.3%, respectively) and cleaved caspase 3 (2.4% vs 7.8%AUTHOR: 11.9% vs 20.3%, respectively) and cleaved caspase 3 (2.4% vs 7.8%, - what do the percentages here refer to? The number of cells expressing geminin and caspase 3? The levels of these factors? Please clarify., respectively). Moreover, a significantly larger number of CD204-positive macrophages were present within the cancer-permeated lymphatic vessels in Type B patients than in Type A patients (mean number 9.5 vs 4.6, respectively). The present study reveals that intralymphatic cancer cell and stromal cell phenotypes are susceptible to lymphogenic metastasis, suggesting that lymphogenic metastasis may be affected by the intralymphatic microenvironment they create.


A community-engaged infection prevention and control approach to Ebola.
The real missing link in Ebola control efforts to date may lie in the failure to apply core principles of health promotion: the early, active and sustained engagement of affected communities, their trusted leaders, networks and lay knowledge, to help inform what local control teams do, and how they may better do it, in partnership with communities. The predominant focus on viral transmission has inadvertently stigmatized and created fear-driven responses among affected individuals, families and communities. While rigorous adherence to standard infection prevention and control (IPC) precautions and safety standards for Ebola is critical, we may be more successful if we validate and combine local community knowledge and experiences with that of IPC medical teams. In an environment of trust, community partners can help us learn of modest adjustments that would not compromise safety but could improve community understanding of, and responses to, disease control protocol, so that it better reflects their 'community protocol' (local customs, beliefs, knowledge and practices) and concerns. Drawing on the experience of local experts in several African nations and of community-engaged health promotion leaders in the USA, Canada and WHO, we present an eight step model, from entering communities with cultural humility, though reciprocal learning and trust, multi-method communication, development of the joint protocol, to assessing progress and outcomes and building for sustainability. Using examples of changes that are culturally relevant yet maintain safety, we illustrate how often minor adjustments can help prevent and treat the most serious emerging infectious disease since HIV/AIDS.


Validation and calibration of self-reported height and weight in the Danish Health Examination Survey.
Body mass index (BMI) derived from self-reported information is widely used and the validity is therefore crucial. We aim at testing the validity of self-reported height and weight, and to test if the accuracy of self-reported information can be improved by calibration by testing if calibration improved the ability to predict diabetes. Data from Danish Health Examination Survey (DANHES) was used. 15 692 participants who had both filled out questionnaire and participated in health examination, and 54 725 participants with questionnaire alone, were included. Data was analyzed using Pearson's R, Cohens Kappa, linear regression and Cox-regression. Self-reported values of height and weight were calibrated using coefficients obtained from linear regression analysis. To evaluate if the calibration improved the ability to predict diabetes, Akaike's information criterion was used. Self-reported height, weight and BMI were highly correlated with measured values (R ≥ 0.92). BMI was under-reported by 0.32 kg m-2 and 0.38 kg m-2 in women and men. The hazard ratio (HR) (95% confidence interval) for diabetes according to measured BMI was 2.09 (1.89-2.27) and for self-reported BMI was 1.60 (1.50-1.70) per 5 kg m-2. Calibrated values of self-reported BMI improved the predictive value of BMI for the risk of diabetes. Self-reported height and weight correlated highly with physical measurement of height and weight. Measured values of BMI were more strongly associated with diabetes risk as compared to self-reported values. Calibration of the self-reported values improved the accuracy of self-reported height and weight.


Parity, mode of birth, and long-term gynecological health: A follow-up study of parous and nonparous women in the Australian Longitudinal Study on Women's Health cohort.
Although gynecological health issues are common and cause considerable distress, little is known about their causes. We examined how birth history is associated with urinary incontinence (UI), severe period pain, heavy periods, and endometriosis. We studied 7700 women in the Australian Longitudinal Study on Women's Health with an average follow-up of 10.9 years after their last birth. Surveys every third year provided information about birth history and gynecological health. Logistic regression was used to estimate how parity, mode of birth, and vaginal tears were associated with gynecological health issues. Presented results are adjusted odds ratios (OR) with 95% confidence intervals. UI was reported by 16%, heavy periods by 31%, severe period pain by 28%, and endometriosis by 4%. Compared with women with two children, nonparous women had less UI (OR 0.35 [0.26-0.47]) but tended to have more endometriosis (OR 1.70 [0.97-2.96]). Also, women with only one child had less UI (OR 0.77 [0.61-0.98]), but more severe period pain (OR 1.24 [1.01-1.51]). Women with 4+ children had more heavy periods (OR 1.42 [1.07-1.88]). Compared with women with vaginal birth(s) only, women with only cesarean sections or vaginal birth after cesarean section had less UI (ORs 0.44 [0.34-0.58] and 0.55 [0.40-0.76]), but more endometriosis (ORs 1.91 [1.16-3.16] and 2.31 [1.25-4.28]) and heavy periods (ORs 1.21 [1.00-1.46] and 1.35 [1.06-1.72]). Vaginal tear(s) did not increase UI after accounting for parity and birth mode. While women with vaginal childbirth(s) reported more urinary incontinence, they had less menstrual complaints and endometriosis.


Taurine deficiency and dilated cardiomyopathy in golden retrievers fed commercial diets.
Golden retrievers are over-represented in cases of taurine-deficient dilated cardiomyopathy and recently a surge in cases has prompted further investigation. To describe the clinical, dietary, and echocardiographic features in golden retrievers diagnosed with taurine deficiency and dilated cardiomyopathy, and to determine specific dietary associations. A second aim was to determine the whole blood taurine concentrations in a representative sample of healthy golden retrievers. Twenty-four client-owned golden retrievers with documented taurine deficiency and dilated cardiomyopathy and 52 healthy client-owned golden retrievers. In this multicenter prospective observational study, baseline and follow-up echocardiographic data, complete diet and medical histories, and whole blood, plasma, or serum taurine concentrations were obtained. Baseline and follow-up echocardiographic data were compared. Associations were evaluated between specific diets and taurine deficiency or congestive heart failure. The prevalence of low whole blood taurine concentrations in the healthy golden retrievers was calculated. Twenty-three of 24 dogs diagnosed with taurine deficiency and dilated cardiomyopathy were fed diets that were either grain-free, legume-rich, or a combination of these factors. None of these diets were feeding trial tested using Association of American Feed Control Officials (AAFCO) procedures. Twenty-three of 24 dogs had significant improvement in their echocardiographic parameters and normalization of taurine concentrations following diet change and taurine supplementation. Nine of 11 dogs diagnosed with congestive heart failure (CHF) had resolution of their congestion at follow-up with five no longer requiring diuretic therapy and four tolerating diuretic dose reduction by >50%. Certain diets and diet characteristics were associated with the development of taurine deficiency. Taurine deficiency and dilated cardiomyopathy in golden retrievers is likely multifactorial, including a combination of dietary, metabolic, and genetic factors.