Passion is key: High emotionality in diversity statements promotes organizational attractiveness.
To attract and retain a more diverse workforce, organizations embrace diversity initiatives, expressed in diversity statements on their websites. While the explicit content of diversity statements influences attitudes towards organizations, much less is known about the effect of subtle cues such as emotions. In three pre-registered studies, we tested the effect of positive emotionality in diversity statements on attitudes towards organizations. Study 1 focused on the degree to which 600 European organizations employed emotionality in their diversity statements, finding that although their statements differed in the level of emotionality, on average, organizations avoided highly emotional words. Study 2 (N = 220 UK participants) tested the effect of original diversity statements on readers' attitudes towards an organization, demonstrating that the level of emotionality in the existing statements did not influence positive attitudes towards the organization. In Study 3 (N = 815 UK participants), we thus modified the diversity statements so that they contained high levels of positive emotionality that triggered more positive emotions and resulted in more positive attitudes towards an organization. Taken together, highly emotional words (e.g. passionate; happy; wholeheartedly) are key in diversity statements if organizations wish to increase their attractiveness among potential employees.


An outcomes analysis of outpatient parenteral antibiotic therapy (OPAT) in a large Asian cohort.
Outpatient parenteral antibiotic therapy (OPAT) facilitates early discharge, easing demands on inpatient resources and allowing patients the opportunity to restore home life. In Singapore, two large hospitals established a common prospective database in 2006. This study presents an analysis of all enrolled cases over 6 years to consider factors potentially causing adverse outcomes. In this prospective observational study, patients' first OPAT episodes, from initiation to completion, re-admission or early cessation, were recorded and analysed using Cox regression to identify factors associated with clinical deterioration leading to unplanned hospital re-admission. Of 2229 first episodes, 1874 (84.1%) completed treatment in OPAT as planned; 201 episodes (9.0%) were complicated by clinical deterioration and re-admitted. Other patients who failed to complete treatment were either re-admitted for elective procedures, experienced adverse drug reactions or peripherally inserted central catheter-related complications, or had other reasons for not completing treatment. Increased risk of clinical deterioration was associated with homecare OPAT (aHR=2.5, 95% CI 1.7-3.8; P<0.001), age >70 years (aHR=1.6, 95% CI 1.1-2.2; P=0.008) and non-private care (aHR=1.8, 95% CI 1.0-3.0; P=0.033). Diagnosis and type of antibiotic treatment were not significant risk factors for re-admission. OPAT provides intravenous antibiotics to those who would otherwise remain as hospital inpatients. In this large Asian cohort, clinical factors did not relate to the ability of patients to complete their treatment in OPAT. Criteria identified as significant warrant ongoing consideration as patients are assessed for acceptance into OPAT programmes.


Assessment of proliferating cell nuclear antigen expression in dysplastic intestinal type Barrett's esophagus. Gruppo Operativo per lo Studio delle Precancerosi Esofagee.
In the management of patients with Barrett's Esophagus (BE) the definition of a sub-group of patients at high risk for malignant transformation of the metaplastic epithelium is important. Undoubtedly, the histological evaluation of dysplasia is the most important and objective parameter to identify a malignant transformation of BE. In order to obtain additional data a group of cell proliferation markers was applied in dysplastic lesions. We studied PCNA in a selected group of patients with BE. One hundred six biopsies were examined, referring to fifty five patients with BE, who were followed up for a period of at least one year (1-5 years). All patients showed one or more biopsies positive for dysplasia. PCNA was detected immunohistochemically on formalin fixed and paraffin embedded biopsies, and positive cells were evaluated in a crude percent count. Our results showed a remarkable number of PCNA positive cells in high grade dysplasia and a variable amount of PCNA positive cells in the others groups. In addition, there was an overlap in the number of positive cases between low grade dysplasia (30%), indefinite (33%) and negative (34%). Therefore, the assessment of S-phase cells correlated with the degree of dysplasia seems to be of limited practical use. Cell proliferation is probably affected by many factors and mainly inflammation.


Using Monte Carlo simulation to determine combination vaccine price distributions for childhood diseases.
The Recommended Childhood Immunization Schedule provides guidelines that allow pediatricians to administer childhood vaccines in an efficient and effective manner. Research by vaccine manufacturers has resulted in the development of new vaccines that protect against a growing number of diseases. This has created a dilemma for how to insert such new vaccines into an already crowded immunization schedule, and prompted vaccine manufacturers to develop vaccine products that combine several individual vaccines into a single injection. Such combination vaccines permit new vaccines to be inserted into the immunization schedule without requiring children to be exposed to an unacceptable number of injections during a single clinic visit. Given this advantage, combination vaccines merit an economic premium. The purpose of this paper is to describe how Monte Carlo simulation can be used to assess and quantify this premium by studying four combination vaccines that may become available for distribution within the United States. Each combination vaccine is added to twelve licensed vaccine products for six childhood diseases (diphtheria, tetanus, pertussis, haemophilus influenzae type B, hepatitis B, and polio). Monte Carlo simulation with an integer programming model is used to determine the (maximal) inclusion price distribution of four combination vaccines, by randomizing the cost of an injection. The results of this study suggest that combination vaccines warrant price premiums based on the cost assigned to administering an injection, and that further developments and innovations in this area by vaccine manufacturers may provide significant economic and societal benefits.


Functional Tradeoffs Carry Phenotypes Across the Valley of the Shadow of Death.
Functional tradeoffs are often viewed as constraints on phenotypic evolution, but they can also facilitate evolution across the suboptimal valleys separating performance peaks. I explore this process by reviewing a previously published model of how disruptive selection from competing functional demands defines an intermediate performance optimum for morphological systems that cannot simultaneously be optimized for all of the functional roles they must play. Because of the inherent tradeoffs in such a system, its optimal morphology in any particular environmental context will usually be intermediate between the performance peaks of the competing functions. The proportional contribution of each functional demand can be estimated by maximum likelihood from empirically observed morphologies, including complex ones measured with multivariate geometric morphometrics, using this model. The resulting tradeoff weight can be mapped onto a phylogenetic tree to study how the performance optimum has shifted across a functional landscape circumscribed by the function-specific performance peaks. This model of tradeoff evolution is sharply different from one in which a multipeak Ornstein-Uhlenbeck (OU) model is applied to a set of morphologies and a phylogenetic tree to estimate how many separate performance optima exist. The multi-peak OU approach assumes that each branch is pushed toward one of two or more performance peaks that exist simultaneously and are separated by valleys of poor performance, whereas the model discussed here assumes that each branch tracks a single optimal performance peak that wanders through morphospace as the balance of functional demands shifts. That the movements of this net performance peak emerge from changing frequencies of selection events from opposing functional demands are illustrated using a series of computational simulations. These simulations show how functional tradeoffs can carry evolution across putative performance valleys: even though intermediate morphologies may not perform optimally for any one function, they may represent the optimal solution in any environment in which an organism experiences competing functional demands.


Measurement of pH, exudate composition and temperature in wound healing: a systematic review.
To assess the potential of measurements of pH, exudate composition and temperature in wounds to predict healing outcomes and to identify the methods that are employed to measure them. A systematic review based on the outcomes of a search strategy of quantitative primary research published in the English language was conducted. Inclusion criteria limited studies to those involving in vivo and human participants with an existing or intentionally provoked wound, defined as 'a break in the epithelial integrity of the skin', and excluded in vitro and animal studies. Data synthesis and analysis was performed using structured narrative summaries of each included study arranged by concept, pH, exudate composition and temperature. The Evidence Based Literature (EBL) Critical Appraisal Checklist was implemented to appraise the quality of the included studies. A total of 23 studies, three for pH (mean quality score 54.48%), 12 for exudate composition (mean quality score 46.54%) and eight for temperature (mean quality score 36.66%), were assessed as eligible for inclusion in this review. Findings suggest that reduced pH levels in wounds, from alkaline towards acidic, are associated with improvements in wound condition. Metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase (TIMP), neutrophil elastase (NE) and albumin, in descending order, were the most frequently measured analytes in wounds. MMP-9 emerged as the analyte which offers the most potential as a biomarker of wound healing, with elevated levels observed in acute or non-healing wounds and decreasing levels in wounds progressing in healing. Combined measures of different exudate components, such as MMP/TIMP ratios, also appeared to offer substantial potential to indicate wound healing. Finally, temperature measurements are highest in non-healing, worsening or acute wounds and decrease as wounds progress towards healing. Methods used to measure pH, exudate composition and temperature varied greatly and, despite noting some similarities, the studies often yielded significantly contrasting results. Furthermore, a limitation to the generalisability of the findings was the overall quality scores of the research studies, which appeared suboptimal. Despite some promising findings, there was insufficient evidence to confidently recommend the use of any of these measures as predictors of wound healing. pH measurement appeared as the most practical method for use in clinical practice to indicate wound healing outcomes. Further research is required to increase the strength of evidence and develop a greater understanding of wound healing dynamics.


An interactive voice response (IVR) system for adolescents with alcohol use disorders: a pilot study.
In order to understand predictors of relapse among adolescents treated for alcohol use disorders (AUD), it is important to accurately assess the daily circumstances associated with use. This pilot study investigates the feasibility and acceptability of an interactive voice response (IVR) system in adolescents with AOSUD. Twenty-six adolescents 14 to 19 years old, with a mean age of 16.8, who were enrolled into an adolescent treatment program for AUD consented to make phone calls for 14 successive evenings to an IVR system and answer 14 questions pertaining to daily use of alcohol and other drugs. The subjects were compensated for their participation. A satisfaction questionnaire was administered at the end of the study. Participants completed 72% of scheduled recordings, with an average of 10.1 calls per subject. Most participants reported that they answered the questions honestly and accurately and were very much satisfied with the IVR system. The preliminary data presented here suggests that the use of IVR for the purpose of generating daily reports in youth is feasible and acceptable. The utilization of IVR systems should be explored to improve efficacy and attainment of generalizability to heterogeneous adolescent populations and lifestyles including for other psychiatric disorders.


Membrane effects of ethanol: bulk lipid versus lipid domains.
It has been well-established that ethanol fluidizes the bulk lipid of membranes and that this effect may alter cell function and be involved in ethanol sensitivity and tolerance. This hypothesis has been supported in several studies, however, there is also a considerable amount of data that do not support such an explanation, e.g., direct effect of ethanol on proteins, other membrane acting drugs, temperature effects, effects of ethanol on aged membranes and inconsistent effects of chronic ethanol consumption on lipid content. This review examined the bulk membrane fluidization hypothesis in light of those data and proposed a modification of the bulk membrane hypothesis that is based on recent data that show that ethanol and other alcohols have a specific effect on the structural properties of different membrane domains. This specific effect of ethanol is discussed within the context of how changes in fluidity of domains may alter membrane function.


Challenges of endovascular tube graft repair of thoracic aortic aneurysm: midterm follow-up and lessons learned.
Endovascular stent-graft repair has great potential in treatment of thoracic aortic aneurysms. This study analyzed a single center's experience with first-generation commercially produced thoracic stent grafts used to treat descending thoracic aortic aneurysms. Over 58 months 84 patients underwent endovascular stent-graft repair of descending thoracic aortic aneurysms; 22 patients received the Gore TAG stent graft, and 62 patients received the Talent thoracic endovascular stent-graft system. Each patient was enrolled in one of three distinct US Food and Drug Administration trials at Mount Sinai Medical Center in accordance with strict inclusion and exclusion criteria, including suitability for open surgery, aneurysm anatomy, and presence of comorbid medical illness. Mean age of this cohort was 71 +/- 12 years. There were 54 men and 30 women, and 74 (88%) had three or more comorbid illnesses. Primary technical success was achieved in 76 patients (90%). Mean follow-up was 15 months (range, 0-52 months). Successful aneurysm exclusion was achieved in 69 patients (82%). Major procedure-related or device-related complications occurred in 32 patients (38%). There were six proximal attachment failures (8%), four distal attachment failures (6%), one intergraft failure (1%), two mechanical device failures (3%), five periprocedural deaths (6%), and five late aneurysm ruptures (6%). At 40 months, overall survival was 67% (+/-10%), and freedom from rupture or from type I or type III endoleak was 74% (+/-10%). While promising, this midterm experience with commercially available devices highlights the shortcomings of current stent-graft technology. Three significant advancements are required to fulfill the potential of this important treatment method: a stent graft with a durable proximal and distal fixation device, enhanced engineering to accommodate high thoracic aortic fatigue forces, and a mechanism to adapt to aortic arch and visceral segment branches to enable treatment of lesions that extend to or include these vessels.


Reengineering CCA-adding enzymes to function as (U,G)- or dCdCdA-adding enzymes or poly(C,A) and poly(U,G) polymerases.
CCA-adding enzymes build and repair the 3'-terminal CCA sequence of tRNA. These unusual RNA polymerases use either a ribonucleoprotein template (class I) or pure protein template (class II) to form mock base pairs with the Watson-Crick edges of incoming CTP and ATP. Guided by the class II Bacillus stearothermophilus CCA-adding enzyme structure, we introduced mutations designed to reverse the polarity of hydrogen bonds between the nucleobases and protein template. We were able to transform the CCA-adding enzyme into a (U,G)-adding enzyme that incorporates UTP and GTP instead of CTP and ATP; we transformed the related Aquifex aeolicus CC- and A-adding enzymes into UU- and G-adding enzymes and Escherichia coli poly(A) polymerase into a poly(G) polymerase; and we transformed the B. stearothermophilus CCA-adding enzyme into a poly(C,A) polymerase by mutations in helix J that appear, based on the apoenzyme structure, to sterically limit addition to CCA. We also transformed the B. stearothermophilus CCA-adding enzyme into a dCdCdA-adding enzyme by mutating an arginine that interacts with the incoming ribose 2' hydroxyl. Most importantly, we found that mutations in helix J can affect the specificity of the nucleotide binding site some 20 A away, suggesting that the specificity of both class I and II enzymes may be dictated by an intricate network of hydrogen bonds involving the protein, incoming nucleotide, and 3' end of the tRNA. Collaboration between RNA and protein in the form of a ribonucleoprotein template may help to explain the evolutionary diversity of the nucleotidyltransferase family.


Immunohistochemical distinction of metastases of renal cell carcinoma with molecular analysis of overexpression of the chemokines CXCR2 and CXCR3 as independent positive prognostic factors for the tumorigenesis.
Renal cell carcinoma (RCC) represents, on average, over 90% of all malignancies of the kidney that occur in adults in both sexes. Chemokine receptors expression has been found in many kinds of cancer and at tumor metastasis site. We determined CXCR2 and CXCR3 expression in RCC by immunohistochemistry method and analyzed the prognostic value of these markers. Our finding demonstrated that CXCR3 were highly overexpressed in renal cancer tissues compared with those adjacent normal kidney tissues (P < 0.001). The results showed that high expression of CXCR3 was markedly correlated with metastasis (P = 0.021) and tumor stage (P = 0.031). CXCR2 were overexpressed in renal cancer tissues compared with those adjacent normal kidney tissues (P < 0.001). Our result showed that CXCR2 expression was correlated with high grade (P = 0.024), advanced stage (P = 0.029) and metastasis (P = 0.018). The log-rank test revealed that high CXCR2 and CXCR3 expressions are related to poorer overall survival (P < 0.001; P < 0.001). In conclusion, this study indicates the correlation of CXCR3 and CXCR3 with progression of RCC. In addition, high CXCR3 andCXCR2 expressions were correlated with shorter overall survival. © 2016 IUBMB Life, 68(8):629-633, 2016.


Polygenic risk, rapid childhood growth, and the development of obesity: evidence from a 4-decade longitudinal study.
To test how genomic loci identified in genome-wide association studies influence the development of obesity. A 38-year prospective longitudinal study of a representative birth cohort. The Dunedin Multidisciplinary Health and Development Study, Dunedin, New Zealand. One thousand thirty-seven male and female study members. We assessed genetic risk with a multilocus genetic risk score. The genetic risk score was composed of single-nucleotide polymorphisms identified in genome-wide association studies of obesity-related phenotypes. We assessed family history from parent body mass index data collected when study members were 11 years of age. Body mass index growth curves, developmental phenotypes of obesity, and adult obesity outcomes were defined from anthropometric assessments at birth and at 12 subsequent in-person interviews through 38 years of age. Individuals with higher genetic risk scores were more likely to be chronically obese in adulthood. Genetic risk first manifested as rapid growth during early childhood. Genetic risk was unrelated to birth weight. After birth, children at higher genetic risk gained weight more rapidly and reached adiposity rebound earlier and at a higher body mass index. In turn, these developmental phenotypes predicted adult obesity, mediating about half the genetic effect on adult obesity risk. Genetic associations with growth and obesity risk were independent of family history, indicating that the genetic risk score could provide novel information to clinicians. Genetic variation linked with obesity risk operates, in part, through accelerating growth in the early childhood years after birth. Etiological research and prevention strategies should target early childhood to address the obesity epidemic.


The management of parotid neoplasms.
In recent years, the management of parotid gland neoplasms has changed considerably, to include a more aggressive surgical approach and multimodality therapy. An organized approach to surgical management and the rationale for postoperative irradiation for selected tumors are presented. A review of several studies supporting the efficacy of postoperative irradiation is included. The principles of palliative management of adenoidcystic carcinoma are unlike those for most other malignancies, and include repeated use of limited procedures to control local and regional disease over extended periods of time, and delayed treatment of distant disease until the patient becomes symptomatic.


Correction of thin lips: "lip lift".
Thin, atrophied lips are a stigma of old age. This paper discusses the so-called lip lift, an operation that consists of lifting, everting, and increasing the bulk of the upper and lower lips by means of a simple but meticulous procedure along the vermilion border. An introductory study on lip aesthetics is presented. Preoperative planning is greatly emphasized. This technique has been used by the author in 32 cases as an adjunct to facial lifts or as a separate procedure. The patients were followed for up to 3 years. The results were quite satisfactory.


Clostridium perfringens's necrotizing acute pancreatitis: a case of success.
The authors report a case of a 62-year-old man with upper abdominal pain with few hours of onset and vomits. The initial serum amylase was 2306 U/L. The first CT showed signs of a non-complicated acute pancreatitis. He suffered clinical deterioration and for this reason he was admitted on the intensive care unit where he progressed to multiple organ failure in <24 h. A new CT scan was performed that showed pneumoperitoneum and pneumoretroperitoneum. He underwent an exploratory laparotomy and pancreatic necrosectomy and vacuum pack laparostomy were performed. Intraoperative peritoneal fluid culture was positive for Clostridium perfringens confirming the diagnosis. He was discharged from hospital after 61 days. According to our research this is the second case reported in literature of a spontaneous acute necrotizing pancreatitis caused by C. perfringens, with pneumoretroperitoneum and pneumoperitoneum on evaluation by CT scan, that survived after surgical treatment and vigorous resuscitation.


Texture variations suppress suprathreshold brightness and colour variations.
Discriminating material changes from illumination changes is a key function of early vision. Luminance cues are ambiguous in this regard, but can be disambiguated by co-incident changes in colour and texture. Thus, colour and texture are likely to be given greater prominence than luminance for object segmentation, and better segmentation should in turn produce stronger grouping. We sought to measure the relative strengths of combined luminance, colour and texture contrast using a suprathreshhold, psychophysical grouping task. Stimuli comprised diagonal grids of circular patches bordered by a thin black line and contained combinations of luminance decrements with either violet, red, or texture increments. There were two tasks. In the Separate task the different cues were presented separately in a two-interval design, and participants indicated which interval contained the stronger orientation structure. In the Combined task the cues were combined to produce competing orientation structure in a single image. Participants had to indicate which orientation, and therefore which cue was dominant. Thus we established the relative grouping strength of each cue pair presented separately, and compared this to their relative grouping strength when combined. In this way we observed suprathreshold interactions between cues and were able to assess cue dominance at ecologically relevant signal levels. Participants required significantly more luminance and colour compared to texture contrast in the Combined compared to Separate conditions (contrast ratios differed by about 0.1 log units), showing that suprathreshold texture dominates colour and luminance when the different cues are presented in combination.


Potentially functional genetic variants in microRNA processing genes and risk of HBV-related hepatocellular carcinoma.
Genetic variations in miRNA processing genes may affect the biogenesis of miRNA, hence risk of HBV infection and hepatocellular carcinoma (HCC) development. In the present study, we hypothesized that potentially functional polymorphisms in 3'-untranslated region (UTR) of miRNA processing genes might contribute to susceptibility of HBV infection and HCC development. To test the hypothesis, we genotyped three selected SNPs (rs1057035 in DICER1, rs3803012 in RAN, and rs10773771 in PIWIL1) in a case-control study of 1300 HBV-positive HCC cancer cases, 1344 HBV persistent carriers, and 1344 HBV natural clearance subjects in Chinese. We observed that DICER1 rs1057035 CT/CC variant genotypes were associated with a significant decreased risk of HCC (adjusted OR = 0.79, 95% CI = 0.64-0.96) compared with wild-type TT and RAN rs3803012 AG/GG variant genotypes increased the risk of HBV persistent infection compared with AA genotype (adjusted OR = 1.35, 95% CI = 1.03-1.77). However, PIWIL1 rs10773771 CT/CC variant genotypes were associated with an approaching decreased risk of HCC (adjusted OR = 0.86, 95% CI = 0.73-1.01) and similar with RAN rs3803012 AG/GG (adjusted OR = 0.80, 95% CI = 0.61-1.06). Furthermore, reporter gene assays indicated that the three SNPs (rs1057035, rs3803012, and rs10773771) might change the binding ability of miRNAs to the 3'UTR of the three genes (DICER1, RAN, and PIWIL1), respectively. These findings indicated that DICER1 rs1057035, RAN rs3803012, and PIWIL1 rs10773771 might contribute to the risk of HBV-related HCC.


Isolated fetal ascites caused by bowel perforation due to colonic atresia.
An isolated fetal ascites is a rare ultrasonographic finding. It is commonly diagnosed in association with fetal genitourinary or gastrointestinal conditions, mainly bowel obstruction. We present the sonographic features and neonatal outcome of a fetus with a large bowel obstruction, perforation and subsequent development of meconium peritonitis, prenatally diagnosed as isolated fetal ascites. A colonic atresia should be also included in the differential diagnosis of isolated fetal ascites.


Association between non-alcoholic fatty liver disease and risk of atrial fibrillation in adult individuals: An updated meta-analysis.
Recent studies examined the association between non-alcoholic fatty liver disease (NAFLD) and risk of atrial fibrillation (AF) in adults, but the findings have been inconsistent. We provided a quantitative estimate of the magnitude of the association between NAFLD and risk of AF. We searched publication databases using predefined keywords to identify observational studies (published up to December 14, 2018), in which NAFLD was diagnosed by biopsy, imaging or biochemistry and AF was diagnosed by medical history and electrocardiograms. Data from selected studies were extracted and meta-analysis was performed using random-effects modelling. Nine cross-sectional and longitudinal studies were included in the final analysis (n = 364 919 individuals). Meta-analysis of data from 5 cross-sectional studies showed that NAFLD was associated with an increased risk of prevalent AF (random-effects odds ratio 2.07, 95% CI 1.38-3.10; I2 = 54.7%), independent of age, sex, body mass index, hypertension and other common AF risk factors. This risk was particularly high among patients with established diabetes (n = 1 study; random-effects odds ratio 5.17, 95% CI 2.05-13.02). Meta-analysis of data from 4 longitudinal studies showed that NAFLD was independently associated with a 10-year increased risk of incident AF only in type 2 diabetic patients (n = 1 study; random-effects hazard ratio 4.96, 95% CI 1.42-17.28). Sensitivity analyses did not modify these findings. Funnel plots did not reveal significant publication bias. NAFLD is associated with an increased risk of AF in middle-aged and elderly individuals (especially in those with type 2 diabetes). However, the observational design of the eligible studies does not allow for proving causality.


Secondary prevention of fragility fractures: are we following the guidelines? Closing the audit loop.
The aim of this study was to determine whether orthopaedic surgeons follow the British Orthopaedic Association (BOA) guidelines for secondary prevention of fragility fractures. A retrospective audit was conducted on patients with neck of femur fractures treated in our hospital between October and November 2003. A re-audit was conducted during the period August to October 2004. There were 27 patients in the initial study period. Twenty-six patients (96%)had full blood count measured with LFT and bone-profile measured in 18 patients (66%). Only nine patients (30%)had treatment for osteoporosis (calcium and vitamin D). Only one patient was referred for DEXA scan. Steps were taken in the form of creating better awareness among the junior doctors and nurse practitioners of the BOA guidelines. In patients above 80 years of age, it was decided to use abbreviated mental score above 7 as a clinical criteria for DEXA referral. A hospital protocol based on BOA guidelines was made. A re-audit was conducted during the period August to October 2004. There were 37 patients. All had their full blood count and renal profile checked (100%). The bone-profile was measured in 28 (75.7%) and LFT in 34 (91.9%) patients. Twenty-four patients (65%) received treatment in the form of calcium + vitamin D (20) and bisphosphonate (4). DEXA-scan referral was not indicated in 14 patients as 4 were already on bisphosphonates and for 10 patients their abbreviated mental score was less than 7. Among the remaining 23 patients, 9 patients (40%) were referred for DEXA scan. This improvement is statistically significant (P = 0.03, chi square test). The re-audit shows that, although there is an improvement in the situation, we are still below the standards of secondary prevention of fragility fractures with 60% of femoral fragility fracture patients not being referred for DEXA scan. A pathway lead by a fracture liaison nurse dedicated to osteoporotic fracture patients should improve the situation.


Effect of jejunal resection on the gastric acid secretory response to pentagastrin, histamine and feeding in dogs.
In dogs with gastric fistulas and denervated pouches from the oxyntic area, the acid secretory responses to a meal and to graded doses of histamine and pentagastrin were measured before and after resection of the upper half of the small bowel. Intestinal resection caused a small but significant increase in submaximal and maximal response from the pouch to histamine and pentagastrin without modification of the ED50. This effect was not observed in the innervated stomach. The response from the pouch to feeding was markedly increased and prolonged. These data indicate that both an increase in stimulation and an increase of the response to this stimulation are responsible for the increased acid secretion observed in the pouch when resected dogs were fed. These effects could be explained by the withdrawal of inhibitors of intestinal origin.


Isolation in patients with inflammatory rheumatic diseases during COVID-19 pandemic compared to healthy individuals: a questionnaire survey.
As a result of the pandemic, many patients with an inflammatory rheumatic disease (IRD) have isolated themselves. The lack of disease management together with fear of infection could lead to changes in physical- and mental health. The aim of this study was to evaluate the social- and health behaviour in patients with an IRD compared with the behaviour of healthy individuals during the COVID-19 pandemic. The study was a questionnaire survey answered by patients with an IRD and healthy individuals (HI). The questionnaire contained seven sections with questions regarding COVID-19 and quality of life including SF-36, EQ-5D-5L, and visual analogue scale (VAS) pain, fatigue and global health. Of 1663 invited participants, 661 patients with IRD and 266 HI were included in the analyses. Patients with an IRD felt more isolated during the COVID-19 pandemic compared with HI (IRD: 9.5% (61/644), HI: 3.1% (8/259), p-value = 0.001). More HI (5.4%) had been infected with COVID-19 than patients with an IRD (1.7%). Among patients with an IRD those with worse self-reported disease activity outcomes (VAS pain, fatigue and global health, all p-value < 0.001), worse social functioning and emotional well-being were more isolated than individuals with low disease activity. Patients with an IRD feel more isolated during the COVID-19 pandemic compared to HI. Isolation seems to be most pronounced in patients with worse disease related patient-reported outcomes and lower quality of life.


Aortic regurgitation in scleroderma.
Two cases of scleroderma with isolated aortic regurgitation are described. Other known causes of aortic regurgitation were not apparent. None of the patients gave a history of rheumatic fever. It appears likely that aortic regurgitation is related to scleroderma in these two patients. Aortic regurgitation in scleroderma is, however, rare.


Character and meaning of quasi-morphine withdrawal phenomena elicited by methylxanthines.
A quasi-morphine withdrawal syndrome (QMWS) is a pattern of behavior closely resembling the true withdrawal syndrome in the opiate-dependent animal, which can be elicited acutely by a nonopiate drug in an opiate-naive animal. The main criteria proposed for the QMWS, in addition to its resembling the true withdrawal syndrome, are that the effects of opiates and of opiate antagonists on the QMWS should parallel those on true opiate withdrawal. Drugs that wholly or largely fulfill these criteria are 3-isobutyl-1-methylxanthine (IBMX), theophylline, caffeine, ICI 63197, and RO 201724. From the evidence given, it is concluded that these drugs act by inhibiting brain cyclic AMP phosphodiesterase, thus raising the level of cyclic AMP in appropriate neurons. These findings are consistent with the view that the molecular mechanisms of opiate dependence is the hypertrophy of a neuronal cyclic AMP system in compensation for the inhibition by opiate of an adenylate cyclase. Our studies and those of others suggest that: a) very rapid tests for opiate activity and for addictive liability can be devised by use of IBMX; b) opiates may be used clinically to counter poisoning by caffeine or theophylline; and c) a relationship may exist between caffeine consumption and opiate addiction.


Tumor protein D52 expression is post-transcriptionally regulated by T-cell intercellular antigen (TIA) 1 and TIA-related protein via mRNA stability.
Although tumor protein D52 (TPD52) family proteins were first identified nearly 20 years ago, their molecular regulatory mechanisms remain unclear. Therefore, we investigated the post-transcriptional regulation of TPD52 family genes. An RNA immunoprecipitation (RIP) assay showed the potential binding ability of TPD52 family mRNAs to several RNA-binding proteins, and an RNA degradation assay revealed that TPD52 is subject to more prominent post-transcriptional regulation than are TPD53 and TPD54. We subsequently focused on the 3'-untranslated region (3'-UTR) of TPD52 as a cis-acting element in post-transcriptional gene regulation. Several deletion mutants of the 3'-UTR of TPD52 mRNA were constructed and ligated to the 3'-end of a reporter green fluorescence protein gene. An RNA degradation assay revealed that a minimal cis-acting region, located in the 78-280 region of the 5'-proximal region of the 3'-UTR, stabilized the reporter mRNA. Biotin pull-down and RIP assays revealed specific binding of the region to T-cell intracellular antigen 1 (TIA-1) and TIA-1-related protein (TIAR). Knockdown of TIA-1/TIAR decreased not only the expression, but also the stability of TPD52 mRNA; it also decreased the expression and stability of the reporter gene ligated to the 3'-end of the 78-280 fragment. Stimulation of transforming growth factor-β and epidermal growth factor decreased the binding ability of these factors, resulting in decreased mRNA stability. These results indicate that the 78-280 fragment and TIA-1/TIAR concordantly contribute to mRNA stability as a cis-acting element and trans-acting factor(s), respectively. Thus, we here report the specific interactions between these elements in the post-transcriptional regulation of the TPD52 gene.


[A case of unusual total anomalous pulmonary venous drainage (supra cardiac type)].
Here we report a case of total anomalous pulmonary venous drainage (TAPVD) appearing in an unusual way with Ib type of Darling's classification. The patient was a five-month old male baby. We found that the left pulmonary vein traveled down and then horizontally behind the heart and flowed into SVC together with right middle, lower pulmonary and right superior anterior pulmonary veins. On the other hand the right superior posterior pulmonary vein flowed into SVC directly. We performed a radical operation on this patient by making an internal conduit using a Gore-Tex patch, but he died of LOS on the 2nd postoperative day. We have reviewed and discussed the preoperative diagnosis, the type of surgical procedures and the prognosis of TAPVD in this paper in the light of our case.


Diabetes in acromegaly--a study of 34 cases.
The incidence and severity of diabetes mellitus (DM) in 34 patients with acromegaly were studied. The incidence was higher (55.9%) than any other series reported. Nineteen had DM, of which 10 were symptomatic. Only one had diabetic retinopathy. Glucose tolerance was improved after successful treatment of acromegaly.


New technique using intraductal ultrasonography for the diagnosis of bile duct cancer.
We investigated the extent to which BDca can be visualized and diagnosed via a percutaneous fistula using IDUS. IDUS was performed in 42 cases, including 15 of normal bile ducts; 12 of choledocholithiasis, and 15 of BDca. The depth of invasion of the BDca was diagnosed with a 93% accuracy rate by visualizing the EP or MA or both. The infiltration of BDca into the surrounding organs was clearly visualized and diagnosed with an accuracy of 100% in the RHA, 93% in the PV, and 93% in the pancreas. These accuracy rates were higher than those obtained by computed tomography or angiography. We believe, therefore, that IDUS should be further studied as a diagnostic modality for staging malignancy in the biliary field.


Pathological studies on central nervous tissues of rats infected with Rattus serotype hantavirus (SR-11 strain).
Newborn rats inoculated intraperitoneally with a hantavirus strain (SR-11) developed neurological signs such as ataxia and limb paralysis. The main histological lesions were scattered and multiple neuronal degeneration and necrosis with eosinophilic cytoplasmic inclusion bodies (CIB) in the brain, spinal cord and ganglia. Immunohistochemically, the viral antigen was detected in neurons, capillary endothelial and glial cells throughout the nervous tissue and CIB were identified as consisting of hantaviral antigen (nucleocapsid protein). Ultrastructurally, CIB in the neurons consisted of an accumulation of granular or filamentous materials, or both. They were seen near a well-developed Golgi apparatus and associated with well-developed rough endoplasmic reticulum and increased numbers of ribosomes. The present results suggested that this virus strain was highly infective in neurons of the newborn rats and that excess production of viral antigen which accumulated as CIB resulted in the neuronal changes.


Radiological features of brain hemorrhage through automated segmentation from computed tomography in stroke and traumatic brain injury.
Radiological assessment is necessary to diagnose spontaneous intracerebral hemorrhage (ICH) and traumatic brain injury intracranial hemorrhage (TBI-bleed). Artificial intelligence (AI) deep learning tools provide a means for decision support. This study evaluates the hemorrhage segmentations produced from three-dimensional deep learning AI model that was developed using non-contrast computed tomography (CT) imaging data external to the current study. Non-contrast CT imaging data from 1263 patients were accessed across seven data sources (referred to as sites) in Norway and Sweden. Patients were included based on ICH, TBI-bleed, or mild TBI diagnosis. Initial non-contrast CT images were available for all participants. Hemorrhage location frequency maps were generated. The number of estimated haematoma clusters was correlated with the total haematoma volume. Ground truth expert annotations were available for one ICH site; hence, a comparison was made with the estimated haematoma volumes. Segmentation volume estimates were used in a receiver operator characteristics (ROC) analysis for all samples (i.e., bleed detected) and then specifically for one site with few TBI-bleed cases. The hemorrhage frequency maps showed spatial patterns of estimated lesions consistent with ICH or TBI-bleed presentations. There was a positive correlation between the estimated number of clusters and total haematoma volume for each site (correlation range: 0.45-0.74; each p-value < 0.01) and evidence of ICH between-site differences. Relative to hand-drawn annotations for one ICH site, the VIOLA-AI segmentation mask achieved a median Dice Similarity Coefficient of 0.82 (interquartile range: 0.78 and 0.83), resulting in a small overestimate in the haematoma volume by a median of 0.47 mL (interquartile range: 0.04 and 1.75 mL). The bleed detection ROC analysis for the whole sample gave a high area-under-the-curve (AUC) of 0.92 (with sensitivity and specificity of 83.28% and 95.41%); however, when considering only the mild head injury site, the TBI-bleed detection gave an AUC of 0.70. An open-source segmentation tool was used to visualize hemorrhage locations across multiple data sources and revealed quantitative hemorrhage site differences. The automated total hemorrhage volume estimate correlated with a per-participant hemorrhage cluster count. ROC results were moderate-to-high. The VIOLA-AI tool had promising results and might be useful for various types of intracranial hemorrhage.


Natriuretic response to saline load in one-kidney/one-clip hypertensive rats.
Parameters of renal function were studied in conscious and anesthetized one-kidney (1K) and one-kidney/one-clip (1K-1C) rats. Effective renal blood flow (ERBF) was significantly lower in anesthetized 1K-1C rats than in conscious ones (12.1 +/- 1.6 vs. 16.4 +/- 1.2 ml/min). Renal function was evaluated in two-kidney (2K), 1K and 1K-1C unanesthetized rats. ERBF was lower in 1K and 1K-1C animals than in 2K rats. Glomerular filtration rate (GFR) and urinary sodium excretion (UNa.V) were not affected by uninephrectomy with or without clipping the renal artery. In 1K-1C rats, mean arterial pressure (MAP) increased from 100 +/- 2 to 140 +/- 1 mm Hg. Subsequently, the renal ability of unanesthetized rats to handle Na was studied by a sustained extracellular fluid volume expansion (EFVE) in all groups. During EFVE, MAP remained unchanged in the 2K and 1K groups and decreased significantly in the 1K-1C group, ERBF did not change and GFR increased to the same extent in all groups. The increase in UNa.V was 40% higher in 2K than in 1K or 1K-1C rats. These findings indicate that the relatively smaller natriuretic response to a saline load of 1K rats with or without a clip in the renal artery, as compared with 2K rats, could be ascribed to renal mass reduction. Finally, the study shows the advantage of performing studies of renal function in hypertension in conscious rather than anesthetized rats.


Inflammatory response in enterocolitis in the piebald lethal mouse model of Hirschsprung's disease.
Mucosal immune defense responses in two clinical forms of enterocolitis complicating congenital megacolon in the piebald lethal mouse model of Hirschsprung's disease were investigated. Significant histological and immunocytochemical differences were seen in the ganglionic segment of colon between piebald mice with early clinical onset of acute illness and piebald mice with late onset enterocolitis. The number of IgA-containing plasma cells infiltrating the lamina propria of the gut in the former group were significantly increased (p less than 0.001) compared to the latter group of mice and healthy controls. This study suggests that the two forms of enterocolitis complicating congenital megacolon in piebald mice have different etiologies.


Health properties of Yerba Mate.
Yerba Mate, also called Paraguay tea, is obtained from the dried leaves (approximately 95%) and stems (about 5%) of the evergreen shrub-tree Ilex paraguariensis. Each year, the consumption of yerba mate becomes increasingly popular in North America and Europe. The fashion for Paraguay tea has also reached Poland. During the period 2012 - 2018, as much as an 8-fold increase has been observed in the import of this raw material to our country. The aim of the study is analysis of the present state of knowledge concerning the health effects of Yerba Mate, based on selected scientific literature. The consumption of yerba mate may exert a beneficial effect on human health and its consumption is recommended in the treatment of obesity and while practicing sports. Nevertheless, it should be remembered that a very high consumption of the tea, especially when very hot, may increase the risk of occurrence of cancer, which has not been unequivocally confirmed by scientific studies to-date. It has been confirmed that this beverage shows a number of beneficial health effects, including: a protective effect on liver cells, stimulation of the central nervous system, anti-inflammatory effect, as well as a positive effect on the cardiovascular system.


Exogenous high-mobility group box 1 protein injection improves cardiac function after myocardial infarction: involvement of Wnt signaling activation.
Exogenous high-mobility group box 1 protein (HMGB1) injection could prevent left ventricular remodeling and enhance left ventricular function during myocardial infarction (MI). However, the mechanism remains unclear. This paper was to investigate in the mechanism of cardioprotection of HMGB1 during MI in rats. Anesthetized male rats were treated once with HMGB1 (200 ng) 4 h after MI and then executed after 7 and 28 days, respectively. Cardiac function, collagen deposition, and dishevelled-1 and β-catenin protein expression were measured. After MI 7 days or 28 days, the left ventricular ejection fraction (LVEF) was significantly decreased compared to that of sham-operated control group (P < 0.05). However, the LVEF HMGB1-treated groups were significantly higher compared to those of the MI group in both 7 days and 28 days (P < 0.05). The collagen volume fraction was significantly reduced in the HMGB1-treated group in infarcted border zone. HMGB1 could activate the expression of dishevelled-1 and β-catenin proteins (P < 0.05). Our study suggested that exogenous high-mobility group box 1 protein injection improves cardiac function after MI, which may be involved in Wnt/β-catenin signaling activation.


ATR-FTIR spectroscopy studies of iron-sulfur protein and cytochrome c1 in the Rhodobacter capsulatus cytochrome bc1 complex.
Redox transitions in the Rhodobacter capsulatus cytochrome bc(1) complex were investigated by perfusion-induced attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy combined with synchronous visible spectroscopy, in both the wild type and a cytochrome c(1) point mutant, M183K, in which the midpoint potential of heme was lowered from the wild-type value of 320 mV to 60 mV. Overall redox difference spectra of the wild type and M183K mutant were essentially identical, indicating that the mutation did not cause any major structural perturbation. Spectra were compared with data on the bovine bc(1) complex, and tentative assignments of several bands could be made by comparison with available data on model compounds and crystallographic structures. The bacterial spectra showed contributions from ubiquinone that were much larger than in the bovine enzyme, arising from additional bound and adventitious ubiquinone. The M183K mutant enabled selective reduction of the iron-sulfur protein which in turn allowed the IR redox difference spectra of ISP and cytochrome c(1) to be deconvoluted at high signal/noise ratios, and features of these spectra are interpreted in light of structural and mechanistic information.


A comparison between patients with gastrointestinal stromal tumours diagnosed with isolated liver metastases and liver metastases plus sarcomatosis.
This study was conducted to compare overall survival (OS) in patients presenting with isolated hepatic metastases with that of patients with synchronous metastatic disease to the liver and sarcomatosis on a background of gastrointestinal stromal tumours (GISTs). Patients presenting with metastatic GISTs during 1999-2009 were identified. Survival outcomes were compared between groups. Of the 193 patients with GISTs, 43 patients presented with isolated hepatic metastases and 16 presented with synchronous metastases to the liver and sarcomatosis. Thirteen patients with metastases to the liver and sarcomatosis underwent surgery, and 34 patients with metastatic disease solely to the liver underwent hepatic resection. The proportion of patients treated with preoperative tyrosine kinase inhibitor (TKI) therapy was similar in both groups. Similar OS was observed in both groups (isolated liver metastases group: 40.5 months; liver metastases and sarcomatosis group: 28.7 months; P = 0.620). Overall survival in patients with GIST and metastatic disease to the liver and sarcomatosis is similar to that in patients with isolated metastatic liver disease. Although patients with a greater disease burden might be expected to show worse survival, these data do not reflect this assumption.


Semi-occluded vocal tract exercises in healthy young adults: Articulatory, acoustic, and aerodynamic measurements during phonation at threshold.
Semi-occluded vocal tract exercises (SOVTEs) are increasingly popular as therapeutic exercises for patients with voice disorders. This popularity is reflected in the growing research literature, investigating the scientific principles underlying SOVTEs and their practical efficacy. This study examines several acoustic, articulatory, and aerodynamic variables before, during, and after short-duration (15 s) SOVTEs with a narrow tube in air. Participants were 20 healthy young adults, and all variables were measured at threshold phonation levels. Acoustic variables were measured with a microphone and a neck accelerometer, and include fundamental frequency, glottal open quotient, and vocal efficiency. Articulatory variables were measured with ultrasound, and include measures of the tongue tip, tongue dorsum, and posterior tongue height, and horizontal tongue length. Aerodynamic variables were measured with an intraoral pressure transducer and include subglottal, intraoral, and transglottal pressures. Lowering of the posterior tongue height and tongue dorsum height were observed with gender-specific small changes in the fundamental frequency, but there were no significant effects on the transglottal pressure or vocal efficiency. These findings suggest that the voices of healthy young adults already approach optimal performance, and the continued search for scientific evidence supporting SOVTEs should focus on populations with voice disorders.


GRETA, a new multifermenter system for structural genomics and process optimization.
As part of the Structural Proteomics In Europe (SPINE) project, the automated multifermenter system GRETA has been developed with structural genomics as a major application. GRETA comprises 6-24 parallel fermentation chambers, each with individual control of fermentation parameters such as temperature, stirring, pH, dissolved oxygen concentration and feed profiles. Six human proteins were used to optimize the GRETA fermentation processes and to compare these processes with typical baffled-flask protocols used in structural genomics projects. The optimized GRETA processes allows several times more protein to be produced per litre of culture with limited manual intervention and constitutes a potentially useful alternative both for scale-up production in structural proteomic projects and for fermentation-process optimization.


Exceptional catalytic activity of oxygen evolution reaction via two-dimensional graphene multilayer confined metal-organic frameworks.
Oxygen evolution reaction (OER) plays a key role in many renewable energy technologies such as water splitting and metal-air batteries. Metal-organic frameworks (MOFs) are appealing to design efficient OER electrocatalysts, however, their intrinsic poor conductivity strongly hinders the activity. Here, we show a strategy to boost the OER activity of poor-conductive MOFs by confining them between graphene multilayers. The resultant NiFe-MOF//G gives a record-low overpotential of 106 mV to reach 10 mA cm-2 and retains the activity over 150 h, which is in significant contrast to 399 mV of the pristine NiFe-MOF. We use X-ray absorption spectroscopy (XAS) and computations to demonstrate that the nanoconfinement from graphene multilayers not only forms highly reactive NiO6-FeO5 distorted octahedral species in MOF structure but also lowers limiting potential for water oxidation reaction. We also demonstrate that the strategy is applicable to other MOFs of different structures to largely enhance their electrocatalytic activities.


Secondary Traumatization and Differentiation Among the Wives of Former POWs: A Reciprocal Association.
Repercussions of war captivity may transmit to spouses of former prisoners of war (POW) via posttraumatic stress symptoms (PTSS). Overidentification with their partners underlies the PTSS experienced by former wives of POWs, thus implying impaired self-differentiation. Although wives' indirect exposure to their husbands' captivity and subsequent PTSS has been associated with the wives' PTSS and differentiation, the combined effects remain unclear. Furthermore, previous cross-sectional studies could not illuminate directionality. This prospective study investigates (a) the moderating role of indirect exposure to captivity in the association between husbands' PTSS and wives' PTSS and differentiation; and (b) the directionality of the association between wives' differentiation and PTSS over time. The wives of both former POWs (n = 143) and combatants (n = 102) were assessed 30 (T1) and 38 (T2) years after the 1973 Yom Kippur War. The wives of former POWs endorsed higher PTSS and fusion differentiation, η2p = .06 to .14. Indirect exposure to captivity moderated the associations between husbands' PTSS and wives' PTSS, Cohen's f2 = .01 to .03. The association between the wives' differentiation and PTSS over time was bidirectional, β = -0.18 to 0.68; R2 = .54 to .73. Results suggest a vicious cycle between PTSS and differentiation, and the need for clinical interventions that further differentiation for spouses of prolonged trauma victims.


The enigma of ribonuclease P evolution.
The 5'-end maturation of tRNAs is catalyzed by the ribonucleoprotein enzyme ribonuclease P (RNase P) in all organisms. Here we provide, for the first time, a comprehensive overview on the representation of individual RNase P protein homologs within the Eukarya and Archaea. Most eukaryotes have homologs for all four protein subunits (Pop4, Rpp1, Pop5 and Rpr2) present in the majority of Archaea. Pop4 is the only RNase P protein subunit identifiable in all Eukarya and Archaea with available genome sequences. Remarkably, there is no structural homology between bacterial and archaeal-eukaryotic RNase P proteins. The simplest interpretation is that RNase P has an 'RNA-alone' origin and progenitors of Bacteria and Archaea diverged very early in evolution and then pursued completely different strategies in the recruitment of protein subunits during the transition from the 'RNA-alone' to the 'RNA-protein' state of the enzyme.


Monitoring dendritic cell activation and maturation.
Since the 1997 discovery that the first identified human homologue of Drosophila Toll could activate the innate immune system, the innate arm of immunity has rapidly taken on a new light as an important player in the recognition of pathogens and damaged self. The recognition of danger by dendritic cells (DC) is a crucial step in activating the adaptive immune system. Different DC express varied subsets of pattern recognition receptors (PRR), enabling both overlap and exclusivity in the recognition of danger signals by DC. PRR-mediated DC maturation and activation can be measured by changes in the surface expression of costimulatory molecules and changes in size and shape of the DC and by their production of different cytokines.


Inhaled powder formulation of naked siRNA using spray drying technology with l-leucine as dispersion enhancer.
Pulmonary delivery of short interfering RNA (siRNA) has been widely studied in both animal and clinical studies to treat various respiratory diseases by gene silencing through RNA interference. Some of these studies showed that the administration of naked siRNA (without the use of any delivery vectors) could achieve satisfactory gene silencing effect, a unique feature to pulmonary delivery. Liquid aerosols were mostly used with very limited studies on the use of powder aerosols for siRNA. In this study, siRNA was co-spray dried with mannitol and l-leucine, the latter being a dispersion enhancer. To the best of our knowledge, this is the first time that siRNA in its naked form was formulated into an inhalable dry powder using spray drying technology. The aerosol performance of the powder was evaluated by Next Generation Impactor (NGI). The presence of l-leucine in the formulation could improve the aerosolization of siRNA-containing powders. Results from the X-ray photoelectron spectroscopy (XPS) suggested that l-leucine was enriched on the particle surface and promote powder dispersion. Among the different siRNA formulations being examined, the one that contained 50% w/w of l-leucine exhibited the best aerodynamic performance, with a high emitted fraction (EF) of around 80% and a modest fine particle fraction (FPF) of 45%. Importantly, the integrity of siRNA was successfully retained as evaluated by gel retardation assay and high performance liquid chromatography (HPLC).


Clomiphene citrate elicits estrogen agonistic/antagonistic effects differentially via estrogen receptors alpha and beta.
Clomiphene citrate (CC) is known to possess dual actions as an estrogen agonist and an estrogen antagonist. To see how the dual actions of CC are exerted through estrogen receptor alpha (ER alpha) and/or ER beta we developed a cell-based transcription assay system in which 293T cells were transfected with the luciferase reporter plasmid with estrogen responsive element and either human ER alpha or ER beta expression plasmid. CC at lower doses (10(-10) M and 10(-12) M), but not higher doses (10(-6) M and 10(-8) M) elicited estrogenic activity via ER alpha. However, CC at concentrations between 10(-6) M and 10(-12) M did not elicit any estrogenic activity via ER beta. In the presence of 17beta-estradiol (E2), CC behaved either as an agonist or as an antagonist via ER alpha depending on the concentrations of E2, i.e., antagonistic when combined with the higher E2 concentrations, agonistic with the lower E2 concentrations. On the other hand, via ER beta, CC acted as an estrogen antagonist regardless of the concentration of E2 added together. In conclusion, CC acts as an estrogen agonist/antagonist via ER alpha in a coexisting estrogen concentration-dependent way whereas it acts as an estrogen antagonist via ER beta whether or not estrogen is present.


Large-pore ultrasmall mesoporous organosilica nanoparticles: micelle/precursor co-templating assembly and nuclear-targeted gene delivery.
A novel micelle/precursor co-templating assembly strategy is successfully developed to synthesize large-pore ultrasmall mesoporous organosilica nanoparticles (MONs). Furthermore, elaborately designed MONs with a cell-penetrating peptide (TAT) (MONs-PTAT) are constructed for highly efficient intranuclear gene delivery. They exhibit a high loading capacity, improved protection for the loaded gene, and enhanced transfection efficiencies of EGFP plasmid (pEGFP).


Value of in situ ovarian volume measured during cesarean delivery to assess the potential of diminished ovarian reserve.
We aimed to determine the value of mean ovarian volume (OV) determined by three-dimensional in situ measurement of ovaries during cesarean delivery (CD) to assess the potential of diminished ovarian reserve (DOR) evaluated by hormonal and ultrasonographic parameters 3 months after the cesarean delivery. Each ovary was measured underwent CD in three dimensions, and three months after CD, the mean OV, serum AMH, FSH, LH, and estradiol levels, and antral follicle count (AFC) values were recorded as well as other demographic and obstetric parameters. After categorizing the study subjects as having a potential of DOR by the criteria of serum AMH <1 pg/mL and AFC value ≤6, in patients with a potential of DOR, the mean intra-operative and post-operative OVs were significantly decreased (p < 0.05). Considering the correlation coefficients obtained by the correlations of post-operative AMH level and AFC value with the mean intra-operative and post-operative OV values, the mean intra-operative OV provided significantly higher correlation coefficients (p < 0.05). These findings, overall, support the diagnostic value of mean OV determined by the in situ measurement of three dimensions of left and right ovaries during cesarean delivery for the screening of potential for the DOR.


Validity of self-reported sexual behaviors in adolescent women using biomarker outcomes.
To determine the criterion-related validity of alternative approaches to the measurement of sexual intercourse using sexually transmitted diseases (STD) as a biomarker (the criterion). Analyses are based on an urban sample of 255 adolescent women, 15 to 19 years of age, treated for genitourinary infections with Neisseria gonorrhoeae, Chlamydia trachomatis or Trichomonas vaginalis who returned 3 months later for reexamination. Subjects completed self-administered questionnaires at enrollment and at 3 months. Genitourinary cultures were obtained at enrollment, 2 to 4 weeks later at a test-of-treatment visit (TOT), and at 3 months. Two hundred fourteen of the 255 adolescents also returned for a TOT culture; 186 of these 214 (73%) were free of infection 2 to 4 weeks after enrollment and 30% (56/186) acquired a subsequent STD by 3 months. The validity of questions about sexual behavior differed. No adolescent who denied interim intercourse by reporting "0" sexual partners or "0" coitions acquired an interval STD. Adolescents who denied regular intercourse (vaginal sex) or failed to indicate the number of interim coitions were at high risk for new STD-23% and 21%, respectively. A new measure of sexual intercourse using both the number of sexual partners and the number of coitions contained no missing data; adolescents classified as not having had interim sexual intercourse were free of infection at 3 months, whereas 32% of those who reported intercourse acquired an interim infection. These data suggest that high-risk urban adolescent women can accurately report whether they have engaged in vaginal intercourse. The validity of the report appears sensitive to the wording and content of the questions.


Amygdaloid metabotropic glutamate receptor subtype 7 is involved in the acquisition of conditioned fear.
The metabotropic glutamate receptor subtype 7 (mGluR7) is presynaptically located and modulates transmitter release. An earlier study from our group demonstrated that systemic administration of N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082), a selective allosteric mGluR7 agonist, attenuates the acquisition of conditioned fear measured by fear-potentiated startle. Aim of this study was to explore whether this effect is mediated by the basolateral amygdala, a crucial brain structure for acquisition of conditioned fear. Therefore, AMN082 was locally injected into the basolateral amygdala of rats and the effects of these injections on the acquisition of conditioned fear was measured. Our data clearly show that intra-amygdala injection of AMN082 impairs fear acquisition. This finding demonstrates that amygdaloid mGluR7 controls the learning of conditioned fear.


HLA-A10 in pemphigus among Japanese.
The frequency of the major histocompatibility antigen, HLA-A10, was significantly increased (corrected P less than .025) in 43 unrelated patients with pemphigus vulgaris (41.9%) and in 25 patients with pemphigus foliaceus (48.0%), when compared with 60 unrelated healthy controls (16.7%). No significant correlations with other HLA or differences between pemphigus vulgaris and pemphigus foliaceus were observed. Both forms of pemphigus were considered to link with the HLA-A10.


Screening for diabetes on a vascular ward: lessons from an audit.
Owing to the high prevalence of diabetes mellitus in patients with peripheral arterial disease, screening for this disorder is necessary on a vascular ward. Our current practice of random plasma glucose (RPG) testing on every admission was reviewed. This test, although crude, excludes diabetes if the cutoff level is set as low as 6.0 mmol/L. A total of 36% of our patients had an abnormal result, but this was not further acted upon. A further 19% had no test result recorded at all. This practice is inadequate and has resulted in the following implementations: (1) every patient with clinical evidence of arterial disease should have their RPG level measured; (2) patients with a level > 6.0 mmol/L should have a fasting plasma glucose level estimated; and (3) patients with an abnormal fasting plasma glucose level should be referred to the diabetic clinic.


A look into retinal organoids: methods, analytical techniques, and applications.
Inherited retinal diseases (IRDs) cause progressive loss of light-sensitive photoreceptors in the eye and can lead to blindness. Gene-based therapies for IRDs have shown remarkable progress in the past decade, but the vast majority of forms remain untreatable. In the era of personalised medicine, induced pluripotent stem cells (iPSCs) emerge as a valuable system for cell replacement and to model IRD because they retain the specific patient genome and can differentiate into any adult cell type. Three-dimensional (3D) iPSCs-derived retina-like tissue called retinal organoid contains all major retina-specific cell types: amacrine, bipolar, horizontal, retinal ganglion cells, Müller glia, as well as rod and cone photoreceptors. Here, we describe the main applications of retinal organoids and provide a comprehensive overview of the state-of-art analysis methods that apply to this model system. Finally, we will discuss the outlook for improvements that would bring the cellular model a step closer to become an established system in research and treatment development of IRDs.


Hypoxia provokes leukotriene-dependent neutrophil sequestration in perfused rabbit hearts.
Isolated rabbit hearts were perfused with salt solution containing autologous 111In-labeled neutrophils to determine whether 1) hypoxia provoked myocardial neutrophil sequestration, 2) neutrophil accumulation could be suppressed by inhibition of lipoxygenase and 3) hypoxic myocardium generated radioimmunoassayable leukotriene B4 (LTB4). Whereas accumulation of 111In-labeled neutrophils by normoxic hearts was minimal, induction of acute myocardial hypoxia by perfusion with hypoxic medium caused a rapid uptake of 111In-labeled neutrophils. Sequestered neutrophils were not released during a subsequent 20-min normoxic perfusion period. Hypoxia-induced neutrophil uptake was prevented by nordihydroguaiaretic acid (NDGA) or diethylcarbamazine (DEC), two structurally different inhibitors of lipoxygenase. Although no radioimmunoassayable LTB4 could be detected in neutrophil-free perfusate from normoxic or hypoxic preparations, hypoxia caused an approximate 2-fold increase in myocardial tissue levels of LTB4. Tissue levels of LTB4 reverted to control values after 20 min of normoxic perfusion. Infusion of exogenous LTB4 also provoked myocardial neutrophil uptake. Viewed collectively, these observations suggest that in isolated buffer-perfused rabbit hearts hypoxia induces LTB4 release from resident myocardial cells, which promotes avid neutrophil sequestration.


The long-term results of conservative management of severely displaced fractures of the calcaneus.
A subjective, objective and radiographic study of 21 patients with comminuted calcaneal fractures showing severe involvement of the subtalar joint is reported. The average follow-up was 14.6 years (range 8 to 29 years). Only patients with unilateral closed fractures and no associated injuries to either lower limb were admitted to the study. All were treated by early active mobilisation of the ankle, and the subtalar and the midtarsal joints. Seventy-six per cent of the patients achieved a good result with minor symptoms which did not interfere with their occupation or leisure requirements. Although two-thirds of the patients reached a point of maximal recovery at two to three years, 24% continued to improve for six years. None of the patients experienced any deterioration after this time. Neither the degree of clinical stiffness nor the degeneration of the subtalar joint, assessed radiographically, correlated with the severity of symptoms or functional disability. The role of the soft tissues in the aetiology of residual symptoms is discussed.


Health, Health Care, and Systems Science: Emerging Paradigm.
Health is a continuum of an optimized state of a biologic system, an outcome of positive relationships with the self and others. A healthy system follows the principles of systems science derived from observations of nature, highlighting the character of relationships as the key determinant. Relationships evolve from our decisions, which are consequential to the function of our own biologic system on all levels, including the genome, where epigenetics impact our morphology. In healthy systems, decisions emanate from the reciprocal collaboration of hippocampal memory and the executive prefrontal cortex. We can decide to change relationships through choices. What is selected, however, only represents the cognitive interpretation of our limited sensory perception; it strongly reflects inherent biases toward either optimizing state, making a biologic system healthy, or not. Health or its absence is then the outcome; there is no inconsequential choice. Public health effort should not focus on punitive steps (e.g. taxation of unhealthy products or behaviors) in order to achieve a higher level of public's health. It should teach people the process of making healthy decisions; otherwise, people will just migrate/shift from one unhealthy product/behavior to another, and well-intended punitive steps will not make much difference. Physical activity, accompanied by nutrition and stress management, have the greatest impact on fashioning health and simultaneously are the most cost-effective measures. Moderate-to-vigorous exercise not only improves aerobic fitness but also positively influences cognition, including memory and senses. Collective, rational societal decisions can then be anticipated. Health care is a business system principally governed by self-maximizing decisions of its components; uneven and contradictory outcomes are the consequences within such a non-optimized system. Health is not health care. We are biologic systems subject to the laws of biology in spite of our incongruous decisions that are detrimental to health. A biologic system/a human body originates from structural, deterministic genes as well as shared epigenetic memory of our ancestors affecting our bodily function and structure. The political governing systems' vertical hierarchy has control over money and laws, neither of which materially affect individual lifestyle/behavioral choices toward health. Improved health comes from focusing on enhancing the biologic age and not the chronologic one, which simply represents a linear time from a birth certificate to a death certificate and is applicable only in its extremes. "Age-related diseases" are simply reflections of a given culture. Biologic age, reflecting the actual state of health, could be used in all health-related assessments including health-life insurance premiums, licensing of job categories, etc., all with a broader and healthy societal impact.


Perfluorochemicals: potential sources of and migration from food packaging.
Perfluorochemicals are widely used in the manufacturing and processing of a vast array of consumer goods, including electrical wiring, clothing, household and automotive products. Furthermore, relatively small quantities of perfluorochemicals are also used in the manufacturing of food-contact substances that represent potential sources of oral exposure to these chemicals. The most recognizable products to consumers are the uses of perfluorochemicals in non-stick coatings (polytetrafluoroethylene (PTFE)) for cookware and also their use in paper coatings for oil and moisture resistance. Recent epidemiology studies have demonstrated the presence of two particular perfluorochemicals, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in human serum at very low part per billion levels. These perfluorochemicals are biopersistent and are the subject of numerous studies investigating the many possible sources of human exposure. Among the various uses of these two chemicals, PFOS is a residual impurity in some paper coatings used for food contact and PFOA is a processing aid in the manufacture of PTFE used for many purposes including non-stick cookware. Little information is available on the types of perfluorochemicals that have the potential to migrate from perfluoro coatings into food. One obstacle to studying migration is the difficulty in measuring perfluorochemicals by routine conventional analytical techniques such as GC/MS or LC-UV. Many perfluorochemicals used in food-contact substances are not detectable by these conventional methods. As liquid chromatography-mass spectrometry (LC/MS) develops into a routine analytical technique, potential migrants from perfluoro coatings can be more easily characterized. In this paper, data will be presented on the types of perfluoro chemicals that are used in food packaging and cookware. Additionally, research will be presented on the migration or potential for migration of these chemicals into foods or food simulating liquids. Results from migration tests show mg kg(-1) amounts of perfluoro paper additives/coatings transfer to food oil. Analysis of PTFE cookware shows residual amounts of PFOA in the low microg kg(-1) range. PFOA is present in microwave popcorn bag paper at amounts as high as 300 microg kg(-1).


Microneedles as an Alternative Strategy for Drug Delivery.
The transdermal route has been widely studied in the last decade due to its multiple advantages, where one of the most promising transdermal systems are microneedles, these allow the delivery of drugs in a painless way and with easy application, being very attractive for patients with chronic treatments. This review highlights the new research that develops this approach to transdermal therapies, including examples of materials and methods used for their manufacture and presenting an overview of the clinical trials currently available in Cochrane in a demonstrative way to understand the growing popularity of this strategy.


Topoisomerase II inhibition in mitosis produces numerical and structural chromosomal aberrations in human fibroblasts.
We investigated the effects of treatment of mitotic human fibroblasts with the topoisomerase II inhibitor etoposide (VP-16) on chromosome segregation at anaphase and the genetic consequence to daughter cells of topoisomerase inhibition during mitosis. The most striking effect of VP-16 treatment during mitosis was the production of anaphase cells with several entangled chromosomes (catenated anaphase cells). To analyze the effects of sister chromatid catenation at anaphase on the daughter cells, several interphase methodologies were applied to binucleated human fibroblasts that were blocked during cytokinesis. Post-treatment of mitotic cells with the cytokinesis inhibitor cytochalasin-B maintains the reciprocal products of a mitotic division in the same cytoplasm, allowing the distribution of whole chromosomes or chromosome fragments in daughter nuclei or micronuclei to be followed. The presence of micronuclei containing kinetochores, as detected by antikinetochore staining, suggested that VP-16 treatment during mitosis induces chromosome loss in binucleated fibroblasts. Induction of aneuploid cells for chromosomes 7 and 11 was observed by double in situ hybridization using chromosome-specific alphoid probes in binucleated fibroblasts. In addition, double in situ hybridization with adjacent alphoid and classical satellite DNA probes to chromosome 1 demonstrated that both numerical and structural aberrations contribute to the genetic effects of topoisomerase II inhibition in mitosis.


Bismuth ferrite as low-loss switchable material for plasmonic waveguide modulator.
We propose new designs of plasmonic modulators, which can be used for dynamic signal switching in photonic integrated circuits. We study performance of a plasmonic waveguide modulator with bismuth ferrite as a tunable material. The bismuth ferrite core is sandwiched between metal plates (metal-insulator-metal configuration), which also serve as electrodes. The core changes its refractive index by means of partial in-plane to out-of-plane reorientation of ferroelectric domains in bismuth ferrite under applied voltage. As a result, guided modes change their propagation constant and absorption coefficient, allowing light modulation in both phase and amplitude control schemes. Due to high field confinement between the metal layers, existence of mode cut-offs for certain values of the core thickness, and near-zero material losses in bismuth ferrite, efficient modulation performance is achieved. For the phase control scheme, the π phase shift is provided by a 0.8-μm long device with propagation losses 0.29 dB/μm. For the amplitude control scheme, up to 38 dB/μm extinction ratio with 1.2 dB/μm propagation loss is predicted.


Endoscopic ultrasonography (EUS)-guided laser ablation (LA) of adrenal metastasis from pancreatic adenocarcinoma.
Endoscopic ultrasonography (EUS)-guided laser ablation (LA) is potentially applicable to tumours in the left lobe of the liver and pancreas. This report seeks to introduce the novel use of EUS-guided LA for left adrenal metastases from pancreatic adenocarcinoma. A 70-year-old female was referred to our hospital for dull abdominal pain and tiredness for 1 month. Computed tomography (CT) discovered a 1.0 × 1.7 cm mass in the area of the left adrenal gland. The lesion was highly suspicious for metastasis due to her history of pancreatic adenocarcinoma 1 year ago, which was removed through radical surgery. Intraoperative frozen-section pathology revealed a tumour invading the left adrenal gland. The left adrenal mass was clearly visualised on EUS and exhibited irregular hyper-enhancement during contrast. The tumour was successfully treated by four sessions of EUS-guided LA. After the procedure, symptomatic relief was achieved and remained. At the 4-month follow-up, contrast-enhanced CT revealed that the volume of the target was significantly decreased. Here, we introduced a new method for left adrenal metastasis using thermal ablation through EUS. As a potential alternative access to the percutaneous approach, EUS-guided LA may provide a minimally invasive treatment to relieve the tumour burdens and symptoms when applied accurately.


The Impact of Transitioning From In-Person to Virtual Heart Transplantation Selection Committee Meetings: Observational Study.
Heart transplant selection committee meetings have transitioned from in-person to remote video meetings during the COVID-19 pandemic, but how this impacts committee members and patient outcomes is unknown. The aim of this study is to determine the perceived impact of remote video transplant selection meetings on usability and patient care and to measure patient selection outcomes during the transition period from in-person to virtual meetings. A 35-item anonymous survey was developed and distributed electronically to the heart transplant selection committee. We reviewed medical records to compare the outcomes of patients presented at in-person meetings (January-March 2020) to those presented during video meetings (March-June 2020). Among 83 committee members queried, 50 were regular attendees. Of the 50 regular attendees, 24 (48%) were physicians and 26 (52%) were nonphysicians, including nurses, social workers, and coordinators; 46 responses were received, 23 (50%) from physicians and 23 (50%) from nonphysicians, with 41 responses fully completed. Overall, respondents were satisfied with the videoconference format and felt that video meetings did not impact patient care and were an acceptable alternative to in-person meetings. However, 54% (22/41) preferred in-person meetings, with 71% (15/21) of nonphysicians preferring in-person meetings compared to only 35% (7/20) of physicians (P=.02). Of the 46 new patient evaluations presented, there was a statistically nonsignificant trend toward fewer patients initially declined at video meetings compared with in-person meetings (6/24, 25% compared to 10/22, 45%; P=.32). The transition from in-person to video heart transplant selection committee meetings was well-received and did not appear to affect committee members' perceived ability to deliver patient care. Patient selection outcomes were similar between meeting modalities.


Activation of Egr-1 in human lung epithelial cells exposed to silica through MAPKs signaling pathways.
The alveolar type II epithelial cell, regarded historically as a key target cell in initial injury by silica, now appears to be important in both defense from lung damage as well as elaboration of chemokines and cytokines. The molecular basis for silica-induced epithelial cell injury is poorly understood. In this study we explored the activation of nuclear factor Egr-1 and related signal pathway. Human II alveolar epithelial line A549 cells were exposed to silica for indicated time to assay the expression and activation of Egr-1 and upstream MAPKs. Immunofluorescence, western-blot techniques, RT-PCR, Electrophoretic mobility shift assay (EMSA), transient transfection assay, kinase inhibitor experiments were performed. It was found that the expression of Egr-1 at mRNA and protein level was significantly increased in A549 cells after administration with silica and the activity of Egr-1 peaked by silica treatment for 60 minutes. Furthermore, phosphorylated-ERK1/2, P38 MAPKs (the upstream kinase of Egr-1) ballooned during 15-30minutes, 30-60minutes respectively after silica exposure in A549 cells. By administration of ERK1/2, P38 inhibitor, the expression and transcription of Egr-1 were both markedly decreased. But PKC inhibitor did not prevent the increase of Egr-1. These results indicated Egr-1 played a critical role in silica-induced pulmonary fibrosis in an ERK1/2, P38 MAPKs-dependent manner, which suggests Egr-1 is an essential regulator in silicosis, and underlines a new molecular mechanism for fibrosis induced by silica.


Pharmacokinetics of the new pyrimidine derivative NS-7, a novel Na+/Ca2+ channel blocker. 1st communication: plasma concentrations and excretions after a single intravenous 14C-NS-7 injection to rats, dogs and monkeys.
Plasma concentration profiles and excretion were investigated after a single intravenous injection of 14C-NS-7 (4-(fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride, CAS 178429-67-9), a novel Na+/Ca2+ channel blocker, to rats, dogs and monkeys. Plasma protein binding of this drug was determined in vitro and in vivo. AUC0-infinity values for radioactivity and NS-7 after the intravenous administration of 14C-NS-7 to male rats increased with the dose, namely from 0.04 to 5 mg/kg (radioactivity) and from 0.2 to 5 mg/kg (NS-7), indicating the linearity of the drug's pharmacokinetics. Plasma concentrations of the unchanged drug after the intravenous injection of 0.2 mg/kg 14C-NS-7 decreased biexponentially, respective t1/2 beta values being 15.9 h in the male and 22.4 h in the female rats. The t1/2 beta values difference in the males and females might be due to sex differences in NS-7 metabolism. Urinary and fecal excretions of radioactivity within 168 h of administration were 33.0 and 61.4% of the dose in the male and 35.0 and 53.2% in the female rats. No radioactivity was detected in air exhaled from the males and females collected for 168 h after NS-7 administration. Within 24 h of administration, respective biliary excretions for the male and female rats were 26.1 and 11.9% of the dose. Of this excreted radioactivity, 34.9% was reabsorbed in the males. NS-7 plasma concentrations decreased biexponentially after intravenous administration of 0.2 mg/kg 14C-NS-7 to dogs and monkeys. The elimination half-life was 18 h for the dogs and 9.52 h for the monkeys. Urinary and fecal excretions of radioactivity within 168 h of administration were 24.2 and 70.0% of the dose for the dogs, and 63.3 and 24.8% for the monkeys. These species differences in excretion may be due to differences in urinary metabolite compositions. In vitro protein binding of NS-7 showed no marked species differences and was independent of the NS-7 concentration. Binding of 14C-NS-7 in the sera of rats, dogs, monkeys and humans was 90.7%, 73.5% 79.0% and 87.1%, respectively. Binding to human serum albumin, alpha 1-acid glycoprotein and lipoprotein was 56.2%, 45.4% and 79.5%, in the range of 4-40 ng/ml. In vivo binding in rat serum 5 min, 6 h and 24 h after the intravenous injection of 14C-NS-7(0.2 mg/kg) ranged from 89.6 to 90.6%.


Using nylon strips to dispense mosquito attractants for sampling the malaria vector Anopheles gambiae s.s.
Synthetic versions of human derived kairomones can be used as baits when trapping host seeking mosquitoes. The effectiveness of these lures depends not only on their attractiveness to the mosquitoes but also on the medium from which they are dispensed. We report on the development and evaluation of nylon strips as a method of dispensing odorants attractive to the malaria vector, Anopheles gambiae s.s. (Giles). When a synthetic blend of attractants was dispensed using this method, significantly more mosquitoes were trapped than when two previous methods, open glass vials or low density polyethylene sachets were used. We conclude that the nylon strips are suitable for dispensing odorants in mosquito trapping operations and can be adopted for use in rural and remote areas. The nylon material required is cheap and widely available and the strips can be prepared without specialized equipment or electricity.


Progesterone receptors in normal, dysplastic and tumourous feline mammary glands. Comparison with oestrogen receptors status.
The aims of the study were to standardise an immunohistochemical (IHC) method for the detection of progesterone receptors (PR) on formalin-fixed, paraffin wax-embedded tissue sections of feline mammary gland tumours and dysplasias, comparing the results with those obtained using the radiolabelled ligand dextran coated charcoal (DCC) assay applied to frozen tissue samples from the same cases. Also, to define the immunohistochemical distribution of PR in the different cellular compartments of the lesions and to compare the oestrogen receptor (ER) and PR status of the feline mammary lesions. Proliferative mammary lesions collected from 34 cats were studied; 25 malignant tumours and 9 benign tumours and dysplasias. PR protein was present at a concentration of 5 fmol mg(-1) (positivity threshold) in 37.5 per cent of malignant tumours and 66.7 per cent of benign tumours and dysplasias while immunoreative products to PR antibody were found in the nuclei of tumour cells in 38.5 per cent and 66.7 per cent of the cases, respectively. Concordance between DCC-PR and IHC-PR was 88.5 per cent (P<0.001). The specificity (true negatives) and sensitivity (true positives) of the IHC method were 89.4 per cent and 87.5 per cent respectively. The presence of PR was linked to the absence of ovariectomy (P<0.02). Oestrogen receptors, detected by either method, were also detected in half the cases in which PR had been detected. In malignant tumours, the most prevalent groups were the ER + PR + and ER-PR + groups.


Enhanced isolation and culture of highly efficient psychrophilic oil-degrading bacteria from oil-contaminated soils in South Korea.
It is known that isolation of oil-degrading bacterial strains is difficult at low temperatures, and the biodegradation efficiency of oil-contaminated soil is significantly reduced in cold weather. In this study, 14 strains were isolated from oil-contaminated soil that grew well at 10°C by using a newly developed culture method. 11 of the 14 isolates were successfully cultured in mineral salts medium containing 1,500 ppm of oil components, 500 ppm each kerosene, gasoline, and diesel as carbon sources, at 10°C for 2 weeks. The oil degradation efficiencies of these 11 isolates ranged from 36% to 100%, as measured by total petroleum hydrocarbon (TPH) degradation analyses. Three strains (Pseudomonas simiae G1-10O, P. taiwanensis Y1-4, and P. koreensis Gwa2) displayed complete degradation (100%), and six others (R frederiksbergensis G2-2, P arsenicoxydans Y2-1, R umsongensis Gwa3, P. migulae Gwa5, RhodococcusjialingiaeY 1-l , and R. qingshengii Y2-2) showed relatively high degradation efficiencies (> 70%). This study suggests that these isolates can be effectively utilised in thetreatment of oil-contaminated soil in landfarming, especially during winter.


Cardiovascular risk and the omega-3 index.
A reliable risk factor for sudden cardiac death (SCD) for the general population remains to be defined. We propose the omega-3 index, defined as the combined percentage of eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) in red blood cell membranes. It reflects the EPA + DHA status of a given individual. It can be determined by a standardised and reproducible laboratory procedure. Several lines of evidence support the omega-3 index as a risk factor for SCD: in epidemiological studies, a steep dependence of risk for SCD and the omega-3 index has been observed between 6.5% (risk 0.1) and 3.3% (risk 1.0). EPA + DHA are antiarrhythmic on the supraventricular and ventricular levels. Dietary EPA + DHA reduce the incidence of SCD. Cardiac societies recommend EPA + DHA for prevention of SCD. The omega-3 index can assess risk for SCD and monitor therapy with EPA + DHA. Moreover, it compares very favourably with other risk factors for SCD.


Chronic cough in young adults in relation to smoking habits, childhood environment and chest illness.
A survey of the respiratory symptoms and smoking habits of a population of 20-year-olds- followed since birth- was repeated when they reached the age of 25. The association of cough prevalence with current smoking habits and with lower respiratory tract illness in childhood found in the survey at age 20 was confirmed and in each instance appears to have increased in strength over the 5 years. At age 25, however, the prevalence of cough was associated at a statistically significant level with fathers' occupation; and this association with social class of origin could not be explained by persisting differences in social status based on the educational levels attained by early adult life. The association with exposure to air pollution in childhood, although more obvious than before, could be due to chance. The prevalence of cough increased between the ages of 20 and 25 among those who smoked throughout or who started to smoke during this period. It declined for those who never smoked and for those who were smoking at 20 but had given up by 25. The implications of these changing patterns of respiratory disease behaviour at a crucial stage between adolescence and adult life are briefly discussed.


Effects of different water storage procedures on the dissolved Fe concentration and isotopic composition of chemically contrasted waters from the Amazon River Basin.
Although recent studies have investigated the Fe isotopic composition of dissolved, colloidal and particulate phases from continental and oceanic natural waters, few efforts have been made to evaluate whether water sample storage and the separation of different pore-size fractions through filtration can cause any change to the Fe isotopic compositions. The present study investigates the possible biases introduced by different water storage conditions on the dissolved Fe concentration and isotopic composition of chemically different waters. Water samples were collected from an organic-rich river and from mineral particulate-rich rivers. Filtered and unfiltered water samples were stored either at room temperature or frozen at -18°C in order to assess possible biases due to (i) different water storage temperature, and (ii) storage of bulk (unfiltered) vs filtered water. Iron isotope measurements were performed by Multicollector Inductively Coupled Plasma Mass Spectrometry with a Thermo Electron Neptune instrument, after Fe purification using anion-exchange resins. Our data reveal that bulk water storage at room temperature without filtration produces minor changes in the dissolved Fe isotopic composition of mineral particulate-rich waters, but significant isotopic composition changes in organic-rich waters. In both cases, however, the impact of the different procedures on the Fe concentrations was strong. On the other hand, the bulk water stored frozen without filtration produced more limited changes in the dissolved Fe concentrations, and also on isotopic compositions, relative to the samples filtered in the field. The largest effect was again observed for the organic-rich waters. These findings suggest that a time lag between water collection and filtration may cause isotopic exchanges between the dissolved and particulate Fe fractions. When it is not possible to filter the samples in the field immediately after collection, the less detrimental approach is to freeze the bulk water sample until filtration, to reduce isotopic artifacts.


Sleep and attachment in early childhood: a series of meta-analyses.
Empirical findings regarding the association between child attachment and sleep have been inconsistent. The objectives of this series of meta-analyses were to assess the size of the association between child sleep and attachment and to examine whether study methodology (attachment measure, sleep measure) and age moderate this association. Sixteen studies (2783 children aged from 6 to 38 months) were included. Significant associations were found between attachment security and sleep efficiency (r = .18) and attachment resistance and sleep problems (r = .18). There were significant moderator effects of sleep measure and age of the child, with the size of the association between sleep and attachment security increasing with age (R2 analog = .67). Inconsistent findings are likely due to inter-study variabilities in methodology and to a developmental effect on the sleep-attachment association.