Impact of Oncological Therapy and Viscum album L Treatment on Cancer-Related Fatigue and Internal Coherence in Nonmetastasized Breast Cancer Patients.
Introduction:Viscum album L extracts (VA) are frequently used in integrative oncology. Aim of this study was to evaluate the impact of add-on VA applications on various patient-reported outcome measures. Methods: A longitudinal real-world study was conducted, using data from the Network Oncology clinical registry. Primary, nonmetastasized breast cancer patients treated with oncological standard therapy partly combined with VA applications were included. Internal Coherence Cancer-related Fatigue, and EORTC QLQ-C30 questionnaires were assessed at baseline and 6, 12, and 24 months later. Results: A total of 319 patients received standard oncological therapy and 40% of them additionally VA applications. After 6 and 12 months for patients treated with chemotherapy (Ctx) only a significant decline of the thermo-coherence, and worsening of fatigue was observed. For patients receiving VA applications but no Ctx, significant beneficial effects on thermo-coherence, fatigue, and seven EORTC QLQ-C30 scales were observed 24 months later. Adjusted multivariable long-term subgroup (n = 106) regression analysis revealed that Ctx, immuno-, and endocrine therapies had a worsening of 17, 17, and 6 point changes, respectively, for EORTC QLQ-C30 fatigue (P = .0004), while VA applications showed an improvement of 12 point change. A similar impact of improvement (add-on VA) and worsening (standard oncological treatment regimens) on EORTC QLQ-C30 insomnia (P = .009) and physical functioning (P = .005) were observed. Conclusions: In the present real-world study, add-on VA applications had a supportive effect on cancer-related fatigue, insomnia, physical functioning, and thermo-coherence. Thus, VA applications might be suited to alleviate symptom burden during anticancer therapy in breast cancer patients.


[Value of prostate-specific antigen density and transitional-zone prostate-specific antigen density in the diagnosis of prostate cancer].
With serum prostate specific antigen (PSA) levels of 4.1 to 10 ng/ml a significant number of patients are unnecessary subjected to biopsy. We try to determine if the calculation of prostate specific antigen density (PSAD) and prostate specific antigen density of the transition zone (PSADTZ) improve the capacity to discriminate between non-malignant disease and prostate cancer. A prospective study including 314 males with PSA levels between 4.1 and 10 ng/ml is reported. Transrectal ultrasonography and prostatic biopsy were performed in all of them and total prostate and transition-zone volumes were calculated. PSA density and PSA density of the transition zone were calculated for each patient. Receiver operating characteristics (ROC) curves for PSA, PSAD and PSADTZ were constructed for all the patients and for those patients with digital rectal examination unsuspicous of malignancy, determining the sensitivity and specificity for several cutoff values. The area under the curve for both, PSAD and PSADTZ, were greater than for PSA (p < 0.05), without any significant differences between PSADTZ and PSAD. The cutoff value of greatest diagnostic efficiency for PSAD was 0.17 ng/ml/cc (71.4% sensitivity and 55.7% specificity), while it was 0.41 ng/ml/cc for DPSATZ (70% sensitivity and 61.5% specificity). For those cases of normal digital rectal examination, no differences were observed between PSA and PSAD but they were between PSA and PSADTZ. In any event, the area under ROC curves was always less than 0.7, and, in order to avoid a large number of biopsies (high specificity), a large number of cancers are left without diagnosis (low sensitivity). We conclude that PSAD and PSADTZ are not excessively useful for adequately discriminating between patients with prostate cancer and those with non-malignant disease, particularly when digital rectal examination is normal.


Socioeconomic and ethnic differences in disease burden and disparities in physical function in older adults.
We investigated whether a greater burden of disease among poorer individuals and ethnic minorities accounted for socioeconomic and racial disparities in self-reported physical functioning among older adults. We used data from adults aged 60 years or older (n = 5556) in the Third National Health and Nutrition Examination Survey, 1988-1994 to test associations between education level, poverty index, and race/ethnicity and limitations in 11 functions. We adjusted for demographic features and measures of disease burden (comorbid conditions, smoking, hemoglobin level, serum albumin level, knee pain, body mass index, and skeletal muscle index). Associations between education and functional limitations were attenuated after adjustment, but those with 0-8 years of education were more likely than those with 13 or more years of education to have limitations in 3 functions. Poverty was associated with a higher likelihood of limitations despite adjustment. The likelihood of limitations among non-Hispanic Blacks and Mexican Americans was similar to that of non-Hispanic Whites after adjustment. Socioeconomic disparities in functional limitations among older Americans exist independent of disease burden, whereas socioeconomic differences and disease burden account for racial disparities.


The role of H2O2 outer diffusion on the performance of implantable glucose sensors.
The performance of an implantable glucose sensor is strongly dependent on the ability of their outer membrane to govern the diffusion of the various participating species. In this contribution, using a series of layer-by-layer (LBL) assembled outer membranes, the role of outwards of H(2)O(2) diffusion through the outer membrane of glucose sensors has been correlated to sensor sensitivity. Glucose sensors with highly permeable humic acids/ferric cations (HAs/Fe(3+)) outer membranes displayed a combination of lower sensitivities and better linearities when compared with sensors coated with lesser permeable outer membranes (namely HAs/poly(diallyldimethylammonium chloride) (PDDA) and poly(styrene sulfonate) (PSS)/PDDA). On the basis of a comprehensive evaluation of the oxygen dependence of these sensors in conjunction with the permeability of H(2)O(2) through these membranes, it was concluded that the outer diffusion of H(2)O(2) is crucial to attain optimized sensor performance. This finding has important implications to the design of various bio-sensing elements employing perm-selective membranes.


Protein interaction network analysis of mTOR signaling reveals modular organization.
The mammalian target of rapamycin (mTOR) is a serine-threonine kinase that acts as a central mediator of translation and plays important roles in cell growth, synaptic plasticity, cancer, and a wide range of developmental disorders. The signaling cascade linking lipid kinases (phosphoinositide 3-kinases), protein kinases (AKT), and translation initiation complexes (EIFs) to mTOR has been extensively modeled, but does not fully describe mTOR system behavior. Here, we use quantitative multiplex coimmunoprecipitation to monitor a protein interaction network (PIN) composed of 300+ binary interactions among mTOR-related proteins. Using a simple model system of serum-deprived or fresh-media-fed mouse 3T3 fibroblasts, we observed extensive PIN remodeling involving 27+ individual protein interactions after 1 h, despite phosphorylation changes observed after only 5 min. Using small molecule inhibitors of phosphoinositide 3-kinase, AKT, mTOR, MEK and ERK, we define subsets of the PIN, termed "modules", that respond differently to each inhibitor. Using primary fibroblasts from individuals with overgrowth disorders caused by pathogenic PIK3CA or MTOR variants, we find that hyperactivation of mTOR pathway components is reflected in a hyperactive PIN. Our data define a "modular" organization of the mTOR PIN in which coordinated groups of interactions respond to the activation or inhibition of distinct nodes, and demonstrate that kinase inhibitors affect the modular network architecture in a complex manner, inconsistent with simple linear models of signal transduction.


[Cavernostomy for Extensive Intrapulmonary Cavitary Abscesses That Turned into Destroyed Lungs].
Surgical resection of the infected lung with curative intent is the treatment of choice for lung abscesses that are difficult to control with medical treatment alone. However, lung resection is considered difficult in some cases. Herein, we report two cases of destroyed lungs with severe symptoms, for which palliative cavernostomy was performed instead of infected lung resection. Case 1 was a 45-year-old man who had granulomatosis with polyangiitis in both lungs. Steroid pulse and immunosuppression therapies were repeated, resulting in a huge, destroyed lung on the right side with chronic necrotizing bilateral aspergillosis, causing severe symptoms. Considering the bilateral spread and extension of the cavity lesions, cavernostomy was performed for the destroyed right lung. Case 2 was a 73-year-old woman who had undergone a left lower lobectomy for a metastatic lung tumor and developed a destroyed lung with severe symptoms in the residual left upper lobe caused by a non-tuberculous mycobacterial infection. Since a completion pneumonectomy with curative intent was considered too invasive for her poor general condition, cavernostomy was performed for the destroyed lung. Palliative operations significantly relieved the severe symptoms and improved the general conditions of these patients, enabling outpatient follow up.


Enhancing Pelvic Health: Optimizing the Services Provided by Primary Health Care Teams in Ontario by Integrating Physiotherapists.
Purpose: The purpose of this review was threefold: (1) to outline the current landscape of service provision for two common pelvic floor disorders, urinary incontinence (UI) and pelvic organ prolapse (POP); (2) to describe common pelvic floor dysfunctions (UI and POP) and the associated evidence-based, conservative care; and (3) to present the potential to integrate physiotherapists into inter-professional primary health care teams to optimize the provision of care for these disorders. Method: A literature review was undertaken and a case study was developed to describe evidence-informed conservative care for pelvic floor dysfunctions. Results: A variety of models exist to treat pelvic floor disorders. Physiotherapists and nurses are key care providers, and their scope and care provision overlaps. In Ontario specifically, both nurses and physiotherapists with additional postgraduate training in pelvic floor disorders are integrated into primary health care, but only to a very limited degree, and they are arguably well positioned to leverage their skills in their respective scopes of practice to optimize the provision of pelvic health care. Conclusions: Physiotherapists and nurses are shown to be key providers of effective, conservative care to promote pelvic health. There is an opportunity to integrate these types of provider into primary care organizations in Ontario; this collaborative care could translate into improved outcomes for patients and the health care system at large.


Beta-adrenoceptor control of cardiac adenylyl cyclase during development: agonist pretreatment in the neonate uniquely causes heterologous sensitization, not desensitization.
In the adult, increased stimulation of postsynaptic receptor sites produces compensatory desensitization that reduces tissue responsiveness. During development, however, responses in most systems increase with age and with the maturation of neuronal inputs. In the current study, we examined whether agonist-induced desensitization of cardiac beta-adrenergic receptor signaling mediated through adenylyl cyclase could be elicited in 6-, 15- and 25-day-old rats, and in adults. In each case, animals were pretreated with isoproterenol daily for four days preceding the experiment, and on the fifth day, cardiac membrane preparations were examined. Fifteen and 25-day-old animals and adults all exhibited desensitization, as demonstrated by a diminished cyclase response to isoproterenol in vitro. However, in 6-day-old animals, the enzymatic response to isoproterenol was enhanced by chronic pretreatment. Measurements of the G-protein-sensitive component of cyclase (decrement in activity obtained with deletion of GTP from the reaction mixture, stimulatory response to fluoride) indicated heterologous desensitization in the older animals, evidenced by diminished dependence on GTP and reduced response to fluoride; the 6-day-old animals showed enhanced GTP dependence and augmentation of the fluoride response. Uniquely in 6-day-old animals, the total catalytic activity of adenylyl cyclase, measured with forskolin-Mn2+, was markedly elevated by chronic isoproterenol pretreatment, whereas it was unaffected in older animals. These data suggest that regulation of receptor signaling is completely different early in neonatal life. Instead of producing desensitization of responses, agonist exposure promotes receptor signaling by enhancing expression and/or catalytic efficiency of adenylyl cyclase. In older animals, the predominant effect is heterologous desensitization mediated at the level of G-proteins. These developmental differences are likely to be important in the maintenance of tissue responsiveness during the period in which innervation develops, as well as in the ability of neurotrophic input to 'program' the responsiveness of target tissues.


Myocardial aging: functional alterations and related cellular mechanisms.
Studies that have examined the effect of age on the myocardium do not support the notion that a generalized decline in myocardial function occurs with adult aging but, rather, that certain specific changes in cardiac biochemistry and function occur. Although in many instances the molecular bases for these changes have not been precisely defined, sufficient clues regarding their nature are at hand to provide at least the first step toward an understanding of the dramatic effects of aging or time on the myocardium. A fundamental understanding of the effects of aging will provide an additional dimension to studies of myocardial biochemistry and function and may be useful in elucidating mechanisms of excitation-contraction coupling in the heart.


Free DNA in serum and plasma from normal adults.
Circulating DNA has been associated with several human disorders, including the nephritis of systemic lupus erythematosus (SLE), in which it is thought to play an etiological role. However, it remains unclear whether its appearance in the circulation is truly pathological. Several reports, each generally based on a single assay method, have disagreed as to whether DNA may circulate in normals. Some, but not all, of this disagreement may be explained by the recently described appearance of DNA in serum, but not plasma, apparently as the result of release from leukocytes in vitro. In the present report an attempt is made to clarify this problem. Normal plasma and serum samples were examined by four assays for DNA that were newly modified to enhance their specificity and/or sensitivity. Plasma DNA was undetectable by all four methods, the most sensitive of which could detect 0.05 mug/ml of native DNA (nDNA) or 0.1 mug/ml of single-stranded DNA (ssDNA). Serum DNA was present in 14 of 16 samples tested in variable concentrations with an estimated mean of 1.9 mug/ml. It is concluded that the appearance of DNA in adult human plasma is a pathological event. Presumably, previous reports describing detection of DNA in normal plasma were based on the measurement of non-DNAase-sensitive interfering substance. Furthermore, it is emphasized that the use of serum in studies dependent on sensitive assays for DNA (or anti-DNA antibody) introduces an ambiguity that may be avoided by substitution of carefully collected plasma for serum.


Intervention for Supravalvar Pulmonary Stenosis After the Arterial Switch Operation.
The arterial switch operation is standard of care for infants born with dextrotransposition of the great arteries. Supravalvar pulmonary stenosis is a common complication that may require reintervention-balloon angioplasty, stenting, or surgical augmentation. A subset of patients requires more than one reintervention. We performed a retrospective review of patients who underwent the arterial switch operation for dextrotransposition of the great arteries at a single institution between August 1990 and January 2014. Anatomic, perioperative and follow-up data were collected. Reinterventions were stratified in a site-specific manner. Statistical analysis was performed using IBM SPSS version 21 (IBM Corp, Armonk, NY). Of the 103 patients who met inclusion criteria, 28% (29) required reintervention for supravalvar pulmonary stenosis; 41% of those receiving primary reintervention required an additional 21 reinterventions. Balloon angioplasty of the main pulmonary artery and left pulmonary artery was associated with the need for multiple reinterventions (odds ratio 4.9, p = 0.051, and odds ratio 5.1, p = 0.029, respectively). Freedom from future reintervention at the main pulmonary artery and left pulmonary artery was significantly shorter after balloon angioplasty relative to alternative reintervention options (hazard ratio 10, p = 0.005, and hazard ratio 3.2, p = 0.02, respectively). Balloon angioplasty of the right pulmonary artery was not associated with an increased risk of reintervention (p = 0.42). Supravalvar pulmonary stenosis after the arterial switch operation for dextrotransposition of the great arteries is common and more than one reintervention are required in a subset of patients. The benefit of balloon angioplasty of the main pulmonary artery and left pulmonary artery was shown to be temporary. Attempting balloon angioplasties at these locations remain reasonable, although families should be counseled about the increased incidence of, and decreased time to, subsequent reintervention that is associated with this treatment option.


Sensory and Compositional Properties Affecting the Likeability of Commercially Available Australian Honeys.
Honey's composition and appearance is largely influenced by floral and geographic origins. Australian honeys are frequently sourced from supermarkets; however, properties associated with consumer preference and likeability remain relatively unknown. The aim of this study was to complete sensory and compositional analyses on a selection of commercially available Australian honeys. Samples (n = 32) were analysed for visual, olfactory and taste characteristics, with overall likeability assessed by the trained sensory panel (n = 24; M = 12). Compositional analysis included colour intensity (mAU); phenolic content; antioxidant characteristics (DPPH, CUPRAC); and physicochemical properties (pH, viscosity, total soluble solids). There were 23 honey samples that were significantly less liked when compared to the most liked honey (p < 0.05). The likeability of honey was positively associated with perceived sweetness (p < 0.01), and it was negatively associated with crystallisation; odour intensity; waxy, chemical, and fermented smell; mouthfeel; aftertaste; sourness; bitterness and pH (All p's < 0.05). The price (AUD/100 g) was not associated with likeability (p = 0.143), suggesting price value potentially does not influence consumer preferences. Conclusively, differences in likeability between the honey samples demonstrate that consumer perception of sampled honeys is diverse. Honey preference is primarily driven by the organoleptic properties, particularly perceived negative tastes, rather than their antioxidant capacity or phenolic content.


Increased renal secretion of norepinephrine and prostaglandin E2 during sodium depletion in the dog.
To determine whether vasoactive renal hormones modulate renal blood flow during alterations of sodium balance, simultaneous measurements of arterial and renal venous concentrations of norepinephrine and prostaglandin E2 (PGE2) and of plasma renin activity, as well as renal blood flow and systemic hemodynamics were carried out in 24 sodium-depleted and 28 sodium-replete anesthetized dogs. The mean arterial blood pressure of the sodium depleted dogs was not significantly different from that of the animals fed a normal sodium diet, but cardiac output was significantly lower (3.07 +/- 0.18 vs. 3.77 +/- 0.17 liters/min, mean +/- SEM; P < 0.01). Despite the higher total peripheral vascular resistance in the sodium-depleted dogs (46.1 +/- 2.9 vs. 37.0 +/- 2.1 arbitrary resistance U; P < 0.02), the renal blood flow and renal vascular resistance were not significantly different in the two groups. The arterial plasma renin activity and concentration of norepinephrine were higher in the sodium-depleted animals than in the controls; the arterial concentration of PGE2 was equal in both groups. The renal venous plasma renin activity was higher in the sodium-depleted dogs. Similarly, the renal venous norepinephrine concentration was higher in the sodium-depleted dogs than in the controls (457 +/- 44 vs. 196 +/- 25 pg/ml; P < 0.01); renal venous PGE2 concentration was also higher in the sodium depleted dogs (92 +/- 22 vs. 48 +/- 11 pg/ml; P < 0.01). Administration of indomethacin to five sodium-replete dogs had no effect on renal blood flow. In five sodium-depleted dogs indomethacin lowered renal blood flow from 243 +/- 19 to 189 +/- 30 ml/min (P < 0.05) and PGE2 in renal venous blood from 71 +/- 14 to 15 +/- 2 pg/ml (P < 0.02). The results indicate that moderate chronic sodium depletion, in addition to enhancing the activity of the renin-angiotensin system, also increases the activity of the renal adrenergic nervous system and increases renal PGE2 synthesis. In sodium-depleted dogs, inhibition of prostaglandin synthesis was associated with a significant decrease in renal blood flow. The results suggest that the renal blood flow is maintained during moderate sodium depletion by an effect of the prostaglandins to oppose the vasoconstrictor effects of angiotensin II and the renal sympathetic nervous system.


A novel and simple approach to regularise attention frameworks and its efficacy in segmentation.
Deep neural networks with attention mechanism have shown promising results in many computer vision and medical image processing applications. Attention mechanisms help to capture long range interactions. Recently, more sophisticated attention mechanisms like criss-cross attention have been proposed for efficient computation of attention blocks. In this paper, we introduce a simple and low-overhead approach of adding noise to the attention block which we discover to be very effective when using an attention mechanism. Our proposed methodology of introducing regularisation in the attention block by adding noise makes the network more robust and resilient, especially in scenarios where there is limited training data. We incorporate this regularisation mechanism in the criss-cross attention block. This criss-cross attention block enhanced with regularisation is integrated in the bottleneck layer of a U-Net for the task of medical image segmentation. We evaluate our proposed framework on a challenging subset of the NIH dataset for segmenting lung lobes. Our proposed methodology results in improving dice-scores by 2.5 % in this context of medical image segmentation.


Flower bud abortion influences clonal growth and sexual dimorphism in the understorey dioecious shrub Aucuba japonica (Cornaceae).
Sexual differences were investigated to determine the significance of flower bud abortion in the dioecious shrub Aucuba japonica Thunb. The mean number of flowers per inflorescence and the mean number of flowering inflorescences (as opposed to aborted inflorescences) per individual were greater in males than in females in 1997 and 1998. Reproductive investment by males was 0.4-times (1997) and 1.4-times (1998) that by females. In addition, females aborted 30.9% (1997) and 42.7% (1998) of their total flower buds without blooming, whereas no male flower buds aborted. One of the architectural traits of this shrub is that in the year that a flower bud is produced at the shoot apex, the shoot will branch into two or more shoots. Thus, there was less sexual difference in the number of current shoots per individual than there was in the number of flowering inflorescences. The relationship between annual growth and reproduction, and the probability of reproduction in the following year, suggested that the higher investment in female reproduction was manifested as a cost for reproductive frequency rather than as a cost for annual growth. The spatial distribution of both males and females was clumped, which may be the result of clonal growth. In addition, overall sex ratios were not skewed and the number of sprouts did not differ significantly between sexes. These results suggested that flower bud abortion by females might reduce sexual dimorphism in terms of clonal growth.


Neural correlates of heart rate variability during emotion.
The vagal (high frequency [HF]) component of heart rate variability (HRV) predicts survival in post-myocardial infarction patients and is considered to reflect vagal antagonism of sympathetic influences. Previous studies of the neural correlates of vagal tone involved mental stress tasks that included cognitive and emotional elements. To differentiate the neural substrates of vagal tone due to emotion, we correlated HF-HRV with measures of regional cerebral blood flow (rCBF) derived from positron emission tomography (PET) and (15)O-water in 12 healthy women during different emotional states. Happiness, sadness, disgust and three neutral conditions were each induced by film clips and recall of personal experiences (12 conditions). Inter-beat intervals derived from electrocardiographic recordings during the 60-second scans were spectrally-analyzed, generating 12 separate measures of HF-HRV in each subject. The six emotion and six neutral conditions were grouped together and contrasted. We observed substantial overlap between emotion-specific rCBF and the correlation between emotion-specific rCBF and HF-HRV, particularly in the medial prefrontal cortex. Emotion-specific rCBF also correlated with HF-HRV in the caudate nucleus, periacqueductal gray and left mid-insula. We also observed that the elements of cognitive control inherent in this experiment (that involved focusing on the target mental state) had definable neural substrates that correlated with HF-HRV and to a large extent differed from the emotion-specific correlates of HF-HRV. No statistically significant asymmetries were observed. Our findings are consistent with the view that the medial visceromotor network is a final common pathway by which emotional and cognitive functions recruit autonomic support.


Contrast-induced nephropathy: the wheel has turned 360 degrees.
Contrast-induced nephropathy (CIN) has been a hot topic during the last 5 years due its association with increased morbidity and mortality. CIN is an important complication, particularly in patients with advanced chronic kidney disease (CKD) associated with diabetes mellitus. Methods to diminish the incidence of CIN have been highly contentious. They include choice of contrast, pharmacologic manipulation, and volume expansion. The pathophysiology of this complication remains uncertain, but reduction in renal blood flow and direct toxicity of tubular cells has been implicated. More than 900 publications under the heading CIN have been published during the last 5 years. Fewer than 5% of these publications are randomized prospective controlled studies. In spite of the large number of reports on CIN, very little has been changed. The use of the smallest possible dose of low- or iso-osmolar contrast media, volume expansion, stopping nephrotoxic drugs, and avoiding repeat contrast injections within 48 hours remain the most effective approach to reduce the risk of CIN.


A giant gamma-ray flare from the magnetar SGR 1806-20.
Two classes of rotating neutron stars-soft gamma-ray repeaters (SGRs) and anomalous X-ray pulsars-are magnetars, whose X-ray emission is powered by a very strong magnetic field (B approximately 10(15) G). SGRs occasionally become 'active', producing many short X-ray bursts. Extremely rarely, an SGR emits a giant flare with a total energy about a thousand times higher than in a typical burst. Here we report that SGR 1806-20 emitted a giant flare on 27 December 2004. The total (isotropic) flare energy is 2 x 10(46) erg, which is about a hundred times higher than the other two previously observed giant flares. The energy release probably occurred during a catastrophic reconfiguration of the neutron star's magnetic field. If the event had occurred at a larger distance, but within 40 megaparsecs, it would have resembled a short, hard gamma-ray burst, suggesting that flares from extragalactic SGRs may form a subclass of such bursts.


Effects of epidural analgesia on plasma catecholamines and cortisol in parturition.
To assess the effect of epidural block on plasma catecholamines and cortisol during labour and delivery, plasma epinephrine, norepinephrine and cortisol levels were determined in 26 healthy parturients, all of whom delivered vaginally (18 received an epidural block, eight had meperidine 50 mg intramuscularly). We found a significant drop of plasma epinephrine and cortisol and no significant reduction of plasma norepinephrine 1 h after administration of epidural block compared to preblock values. Observing the data during the whole course of labour in correlation with cervical dilatation, in the control group, where the parturients received meperidine, all hormones rose progressively up to the moment of delivery. One hour after delivery the catecholamines returned to normal levels; cortisol returned more slowly. In the epidural group the increase of plasma epinephrine and cortisol was significantly inhibited but not that of norepinephrine.


Influence of rootstocks on growth, yield, fruit quality and leaf mineral element contents of pear cv. 'Santa Maria' in semi-arid conditions.
Rootstocks play an essential role to determining orchard performance of fruit trees. Pyrus communis and Cydonia oblonga are widely used rootstocks for European pear cultivars. The lack of rootstocks adapted to different soil conditions and different grafted cultivars is widely acknowledged in pear culture. Cydonia rootstocks (clonal) and Pyrus rootstocks (seedling or clonal) have their advantages and disadvantages. In each case, site-specific environmental characteristics, specific cultivar response and production objectives must be considered before choosing the best rootstock. In this study, the influence of three Quince (BA 29, Quince A = MA, Quince C = MC) and a local European pear seedling rootstocks on the scion yield, some fruit quality characteristics and leaf macro (N, P, K, Ca and Mg) and micro element (Fe, Zn, Cu, Mn and B) content of 'Santa Maria' pear (Pyrus communis L.) were investigated. Trees on seedling rootstock had the highest annual yield, highest cumulative yield (kg tree(-1)), largest trunk cross-sectional area (TCSA), lowest yield efficiency and lowest cumulative yield (ton ha(-1)) in the 10(th) year after planting. The rootstocks had no significant effect on average fruit weight and fruit volume. Significantly higher fruit firmness was obtained on BA 29 and Quince A. The effect of rootstocks on the mineral element accumulation (N, K, Ca, Mg, Fe, Zn, Cu, Mn and B) was significant. Leaf analysis showed that rootstocks used had different mineral uptake efficiencies throughout the early season. The results showed that the rootstocks strongly affected fruit yield, fruit quality and leaf mineral element uptake of 'Santa Maria' pear cultivar. Pear seedling and BA 29 rootstock found to be more prominent in terms of several characteristics for 'Santa Maria' pear cultivar that is grown in highly calcareous soil in semi-arid climate conditions. We determined the highest N, P (although insignificant), K, Ca, Mg, Fe and Cu mineral element concentrations on the pear seedling and BA 29 rootstocks. According to the results, we recommend the seedling rootstock for normal density plantings (400 trees ha(-1)) and BA 29 rootstock for high-density plantings (800 trees ha(-1)) for 'Santa Maria' pear cultivar in semi-arid conditions.


Complementary and alternative medicine (CAM) use and delays in presentation and diagnosis of breast cancer patients in public hospitals in Malaysia.
Complementary and alternative medicine (CAM) is widely used among the breast cancer patients in Malaysia. Delays in presentation, diagnosis and treatment have been shown to impact the disease prognosis. There is considerable use of CAM amongst breast cancer patients. CAM use has been cited as a cause of delay in diagnosis and treatments in qualitative studies, however there had not been any confirmatory study that confirms its impact on delays. The purpose of this study was to evaluate whether the use of CAM among newly diagnosed breast cancer patients was associated with delays in presentation, diagnosis or treatment of breast cancer. This multi-centre cross-sectional study evaluating the time points of the individual breast cancer patients' journey from first visit, resolution of diagnosis and treatments was conducted in six public hospitals in Malaysia. All newly diagnosed breast cancer patients from 1st January to 31st December 2012 were recruited. Data were collected through medical records review and patient interview by using a structured questionnaire. Complementary and alternative medicine (CAM) was defined as the use of any methods and products not included in conventional allopathic medicine before commencement of treatments. Presentation delay was defined as time taken from symptom discovery to first presentation of more than 3 months. The time points were categorised to diagnosis delay was defined as time taken from first presentation to diagnosis of more than 1 month and treatment delay was defined as time taken from diagnosis to initial treatment of more than 1 month. Multiple logistic regression was used for analysis. A total number of 340 patients participated in this study. The prevalence of CAM use was 46.5% (n = 158). Malay ethnicity (OR 3.32; 95% CI: 1.85, 5.97) and not interpreting symptom as cancerous (OR 1.79; 95% CI: 1.10, 2.92) were significantly associated with CAM use. The use of CAM was associated with delays in presentation (OR 1.65; 95% CI: 1.05, 2.59), diagnosis (OR 2.42; 95% CI: 1.56, 3.77) and treatment of breast cancer (OR 1.74; 95% CI: 1.11, 2.72) on univariate analyses. However, after adjusting with other covariates, CAM use was associated with delays in presentation (OR 1.71; 95% CI: 1.05, 2.78) and diagnosis (OR 2.58; 95% CI: 1.59, 4.17) but not for treatment of breast cancer (OR 1.58; 95% CI: 0.98, 2.55). The prevalence of CAM use among the breast cancer patients was high. Women of Malay ethnicity and not interpreting symptom as cancerous were significantly associated with CAM use. The use of CAM is significantly associated with delay in presentation and resolution of diagnosis. This study suggests further evaluation of access to breast cancer care is needed as poor access may cause the use of CAM. However, since public hospitals in Malaysia are heavily subsidized and readily available to the population, CAM use may impact delays in presentation and diagnosis.


Harnessing benefits of helping others: a randomized controlled trial testing expressive helping to address survivorship problems after hematopoietic stem cell transplant.
Prior research supports the hypothesis that cancer survivors who help others face treatment experience a range of psychosocial and health-related benefits as a result of peer helping. This study investigates an expressive helping (EH) intervention designed to harness those benefits by targeting survivorship problems among cancer survivors treated with hematopoietic stem cell transplant. EH includes two components: (a) emotionally expressive writing (EW; writing one's deepest thoughts and feelings about the transplant experience in a series of brief, structured writing sessions) followed by (b) peer helping (PH; helping other people prepare for transplant by sharing one's own transplant experiences along with advice and encouragement through a written narrative). EH was compared with neutral writing (NW), EW (without PH), and PH (without EW) in a 4-arm randomized controlled trial in which survivors completed baseline measures, 4 structured writing exercises (with instructions depending on randomization), and postintervention measures including validated measures of general psychological distress, physical symptoms, and health-related quality of life (HRQOL). Among survivors with moderate-severe survivorship problems, EH reduced distress (compared with NW and PH; ps < .05) and improved physical symptoms (compared with NW, PH, and EW; ps < .002) and HRQOL (compared with NW; p = .02). Peer helping through writing benefits transplant survivors with moderate-severe survivorship problems, but only if they have first completed expressive writing.


The emerging role of risk management.
This article discusses the emerging role of risk management for the PACU nurse. The risk management process is described in detail and compared with the nursing process in terms of assessment, planning, implementation, and evaluation. Tools that aid in assessment include incident reports, generic screening, patient complaints, and other factors. Specific examples relating to the PACU are used throughout the article. The article further describes skills needed in the field of risk management. Finally, implications for nursing are discussed including involvement in risk management, documentation, continuing education, and the position of risk manager.


Evaluation of O6-methylguanine DNA methyltransferase activity in patients with gastric cancer.
O6-Methylguanine DNA methyltransferase (O6-MGMT) reverses DNA alkylation damage produced alkylating agents. O6-MGMT is also a major determinant of cellular resistance to adjuvant chemotherapy with alkylating drugs. O6-MGMT activity was measured in samples from patients with gastric cancer, including tumor, adjacent normal appearing mucosa, and peripheral blood leukocytes (PBL). O6-MGMT activity of PBL from healthy individuals was evaluated as control. There was no significant difference between controls and patients for O6-MGMT activity in PBL. O6-MGMT activity was significantly increased in tumor tissue. Tumor O6-MGMT activity was found to be independent from tumor subgroups and tumor grade. A positive correlation was determined between O6-MGMT activity in tumor and in circulating PBL. The results indicate that O6-MGMT, a defense protein against alkylating agent-mediated carcinogenesis, increased in gastric tumors. This may explain the low response rate to drug combinations, including chloroethylnitrosoureas, exhibited by patients with gastric cancer.


Negative prognostic significance of two or more cytogenetic abnormalities in multiple myeloma patients treated with autologous stem cell transplantation.
Malignant plasma cells in multiple myeloma (MM) are frequently characterized by complex karyotypes and chromosome instability. These cytogenetic changes are considered important prognostic indicators in MM patients. We have studied samples from 68 patients with newly diagnosed MM who were treated with high-dose chemotherapy and autologous stem cell transplantation. G-banding revealed abnormal karyotypes in 14 of 55 patients (25%) who had informative conventional cytogenetics. The combination of cytoplasmic immunoglobulin light chain labeling and interphase fluorescent in situ hybridization (cIg-FISH) revealed the presence of genetic aberrations in 53 of 68 patients (78%). Chromosome 13 abnormalities were found in 33 patients (50%) and IgH rearrangements in 36 patients (56.25%). In IgH positive patients we performed subsequent examinations of IgH affecting translocations t(4;14) and t(11;14) and we found translocation t(11;14) in 8 patients (12.5%) and t(4;14) in 10 patients (15.5%). The occurrences of others chromosomal abnormalities with known prognostic impact in MM were as follows: del(17)(p13) was present in 5 patients (9.8%) and gain 1q21 in 14 patients (36%). Analysis of survival of patients with different cytogenetic abnormalities revealed shorter overall survival (OS) in patients with IgH rearrangements (p=0.020) and trend to shorter OS in patients with gain 1q21 (p=0.064), respectively. Remarkably, patients with two or more aberrations had significantly shorter overall survival (p=0.001), time to progression (p=0.036) and progression free survival (p=0.008). Our results show a high incidence of chromosomal abnormalities in MM patients and confirm the prognostic impact of selected chromosomal aberrations as well as cumulative effect of multiple cytogenetic changes occurring simultaneously.


On the Convergence of Learning-Based Iterative Methods for Nonconvex Inverse Problems.
Numerous tasks at the core of statistics, learning and vision areas are specific cases of ill-posed inverse problems. Recently, learning-based (e.g., deep) iterative methods have been empirically shown to be useful for these problems. Nevertheless, integrating learnable structures into iterations is still a laborious process, which can only be guided by intuitions or empirical insights. Moreover, there is a lack of rigorous analysis about the convergence behaviors of these reimplemented iterations, and thus the significance of such methods is a little bit vague. This paper moves beyond these limits and proposes Flexible Iterative Modularization Algorithm (FIMA), a generic and provable paradigm for nonconvex inverse problems. Our theoretical analysis reveals that FIMA allows us to generate globally convergent trajectories for learning-based iterative methods. Meanwhile, the devised scheduling policies on flexible modules should also be beneficial for classical numerical methods in the nonconvex scenario. Extensive experiments on real applications verify the superiority of FIMA.


11beta-Hydroxysteroid dehydrogenase type 1 inhibitors with oleanan and ursan scaffolds.
The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone to the active glucocorticoid cortisol, thereby acting as a cellular switch to mediate glucocorticoid action in many tissues. Several studies have indicated that 11beta-HSD1 plays a crucial role in the onset of type 2 diabetes and central obesity. As a consequence, selective inhibition of 11beta-HSD1 in humans might become a new and promising approach for lowering blood glucose concentrations and for counteracting the accumulation of visceral fat and its related metabolic abnormalities in type 2 diabetes. In this study, we present the synthesis and the biological evaluation of ursan or oleanan type triterpenoids which may act as selective 11beta-HSD1 inhibitors in liver as well as in peripheral tissues, like adipocytes and muscle cells. In order to rationalise the outcomes of the inhibition data, docking simulations of the ligands were performed on the experimentally determined structure of 11beta-HSD1. Furthermore, we discuss the structural determinants that confer enzymatic specificity. From our investigation, valuable information has been obtained to design selective 11beta-HSD1 blockers based on the oleanan and ursan scaffold.


Early Rapid Neurological Assessment for Acute Spinal Cord Injury Trials.
Clinical trials evaluating early therapies after spinal cord injury (SCI) are challenging because of the absence of a rapid assessment. The aim of this study was to determine whether the severity and level of SCI could be established from a brief neurological assessment capable of being used in an emergency setting. A brief assessment called the SPinal Emergency Evaluation of Deficits (SPEED) was developed and retrospectively evaluated in a cohort of 118 patients with SCI. Foot motor and sensory function was used to indicate injury severity. C3 dermatome sensation, handgrip strength and location of spinal pain were used to indicate the level of injury. With regard to injury severity, a high proportion of patients (94%) with no foot movement at the time of injury were initially diagnosed as motor complete (American Spinal Injury Association Impairment Scale [AIS] grade A-B), whereas all patients with foot movement were identified as motor incomplete (AIS grade C-D). This was reflected by a good correlation (rs = 0.79) and agreement (κ = 0.85) between the SPEED motor score and the acute hospital assessment. With respect to injury level, the majority of cases with cervical SCI (92%) had no or weak handgrip at the time of paramedic assessment, whereas all cases with thoracolumbar SCI had a strong handgrip. The location of spinal pain was also in accordance with the level of spinal injury. The SPEED assessment appears capable of accurately determining the severity and level of cervical SCI in the first hours post-injury. A neurological assessment that can be performed rapidly after injury is important for clinical trials of early therapy and to identify patients most likely to benefit from intervention.


PseudoCyc, a pathway-genome database for Pseudomonas aeruginosa.
A pathway-genome database (PGDB) describes the entire genome of an organism, as well as its biochemical pathways, reactions, and enzymes. Our PathoLogic software can generate a PGDB from an annotated genome of an organism, predicting the metabolic reactions and pathways corresponding to the enzymes present in the annotation. We have used PathoLogic to generate a PGDB for PSEUDOMONAS AERUGINOSA, strain PAO1, called 'PseudoCyc', which includes 139 predicted pathways and 800 predicted reactions involving 623 chemical species and 718 enzymes. Analysis of the PathoLogic predictions of arginine metabolism and the beta-ketoadipate pathway, which are landmark pathways in P. AERUGINOSA, showed that they were for the most part correctly predicted. These studies also provided possible locations for two genes involved in the beta-ketoadipate pathway, PCAI and PCAJ, which are missing from the PAO1 annotation. PseudoCyc adds an extended dimension to the genome of P. AERUGINOSA, providing researchers with a helpful tool for the analysis of the genomic, proteomic, and metabolic information of the organism. The finding of the probable location of the PCAI and PCAJ genes is but one example of the discoveries facilitated by such a PGDB. PseudoCyc, along with PGDBs for 12 other organisms, is available at http://BioCyc.org/.


Guided flapless surgery with immediate loading for the high narrow ridge without grafting.
Computer guided implant treatment allows implants and associated restorations to be precisely placed during the same procedure directly through the gingiva with reduced postoperative complications and surgical time. When bone height is adequate but very narrow, the virtual guided sleeve is often placed too deeply into the ridge crest interfering with the seating of the surgical template. This case report of a patient exhibiting very narrow residual ridges due to severe resorption describes a new computer guided procedure using a single surgical template maintaining bone height and immediate restoration without a mucoperiosteal flap. The success of this technique is the result of innovative modifications in the software as well as instrumentation. Modifications include planning a different implant length virtually to raise the position of guide sleeves, alteration of drilling sequences, modifications of the start drill, incorporation of osteotomes, and use of an alternative implant seating mount. The combination of these methods allows for deeper site preparation and implant seating beyond the default settings, without any crestal bone reduction. These modifications not only make the guided concept possible for the entire preparation and seating procedures, but also allow for the slight removal of bone that would interfere with the implant seating through the surgical template without a mucoperiosteal flap. This new approach to computer guided surgery maintains prosthetic precision in the fabrication of a provisional restoration prior to implantation with minimal delivery adjustments using prefabricated conical abutments when placing implants at differing levels into the high narrow ridge.


Two cases of adynamia episodica hereditaria: in vitro investigation of muscle cell membrane and contraction parameters.
Membrane potentials, current-voltage relationships, and contractile parameters were studied in intact muscle cell bundles obtained from two patients with adynamia episodica hereditaria. In a normal extracellular medium, the cell membranes had resting potentials of about -80 mV and their current-voltage relationships were not significantly different from control curves. In contrast to normal muscles the afflicted cells were paralyzed in a medium having 6-10 mmol/liter potassium. The mechanisms of paralysis in the two specimens were different from each other. Many fibers from one patient were spontaneously active even in normal solution. In high potassium solution spontaneous activity was increased and the cells gradually depolarized to values at which excitatory sodium current is normally inactivated. This depolarization was connected with an increased sodium conductance and was reversed by the application of tetrodotoxin (TTX). The fibers from the other patient were not spontaneously active. In high potassium solution they were paralyzed at membrane potential values at which normal fibers would still contract. The reason for this paralysis was a reduced excitability.


[Effect of microiontophoretic application of serotonin on the background impulse activity of visual cortex neurons in unanesthetized cats].
Sustained spike activity of neurones in the visual area (field 17) of the cerebral cortex and its changes induced by microionophoresis of serotonin was studied in experiments on unanaesthetized cats immobilized with diplacine. Neurones of field 17 with sustained activity are characterized by non-rhythmic, low-frequency discharges of a mixed type. 55 per cent of the studied neurones were sensitive to serotonin. They exhibited excitatory, inhibitory and phasic responses. The points discussed are: the importance of intracortical interactions between neurones in mechanisms of generation of their sustained spike activity, and the possible ;nvolvement of serotonin in ;he neurochemical processes of synaptic transmission in the visual area of the cerebral cortex.


HLA class II upregulation during viral infection leads to HLA-DP-directed graft-versus-host disease after CD4+ donor lymphocyte infusion.
CD8+ T cell-depleted (TCD) donor lymphocyte infusion (DLI) after TCD allogeneic hematopoietic stem cell transplantation (alloSCT) has been associated with a reduced risk of graft-versus-host disease (GVHD) while preserving conversion to donor hematopoiesis and antitumor immunity, providing a rationale for exploring CD4+ T cell-based immunotherapy for hematologic malignancies. Here, we analyzed the clinical course and specificity of T cell immune responses in 2 patients with acute myeloid leukemia (AML) who converted to full-donor chimerism but developed severe acute GVHD after prophylactic CD4+ DLI after 10/10-HLA-matched, but HLA-DPB1-mismatched TCD-alloSCT. Clonal analysis of activated T cells isolated during GVHD demonstrated allo-reactivity exerted by CD4+ T cells directed against patient-mismatched HLA-DPB1 molecules on hematopoietic cells and skin-derived fibroblasts only when cultured under inflammatory conditions. At the time of CD4+ DLI, both patients contained residual patient-derived T cells, including cytomegalovirus (CMV)-specific T cells as a result of CMV reactivations. Once activated by CMV antigens, these CMV-specific T cells could stimulate HLA-DPB1-specific CD4+ T cells, which in turn could target nonhematopoietic tissues in GVHD. In conclusion, our data demonstrate that GVHD after HLA-DPB1-mismatched CD4+ DLI can be mediated by allo-reactive HLA-DPB1-directed CD4+ T cells and that ongoing viral infections inducing HLA class II expression on nonhematopoietic cells may increase the likelihood of GVHD development. This trial is registered at http://www.controlled-trials.com/ISRCTN51398568/LUMC as #51398568.


Endovascular treatment of multiple severe atherosclerotic stenoses with cerebral hypoperfusion. Case report.
A 60-year-old man presented with syncope and transient left-sided motor weakness. Cerebral angiography revealed multiple severe atherosclerotic stenoses of bilateral internal carotid arteries, bilateral intracranial vertebral artery (VA), and left VA origin. A SPECT study showed poor cerebral perfusion and vascular reserve in the right cerebral hemisphere and the posterior circulation.We performed angioplasty and stentings for the VA stenoses first by using balloon-expandable stents. The patient had shown no syncope attack ever since, which might be due to an increased vascular reserve in the posterior circulation. The following bilateral carotid angioplasty and stentings could be performed safely. Angioplasty and stenting is feasible, and can improve cerebral perfusion even in a patient with multiple severe atherosclerotic stenoses by pre-operative appropriate haemodynamic assessment.


Cigarette smoking as a risk factor for schizophrenia or all non-affective psychoses.
Smoking tobacco is regarded as an epiphenomenon in patients with schizophrenia when it may be causal. We aimed to examine whether smoking status is related to the onset of schizophrenia or the broader diagnosis of non-affective psychosis, including schizophrenia. We used data from The Health Improvement Network primary care database to identify people aged 15-24 between 1 January 2004 and 31 December 2009. We followed them until the earliest of: first diagnosis of schizophrenia (or psychosis), patient left the practice, practice left THIN, patient died or 31 December 2014. In men, incidence rates for schizophrenia per 100 000 person years at risk were higher in smoking initiators (non-smoker who became a smoker during the study) than in non-smokers (adjusted IRR 1.94; 95% CI 1.29-2.91) and higher still in smokers (adjusted IRR 3.32; 95% CI 2.67-4.14). Among women, the incidence rate of schizophrenia was higher in smokers than in non-smokers (adjusted IRR 1.50; 95% CI 1.06-2.12), but no higher in smoking initiators than non-smokers. For non-affective psychosis, the pattern was similar for men but more evident in women where psychosis incidence rates were higher in smoking initiators (adjusted IRR 1.90; 95% CI 1.40-2.56) and in smokers (adjusted IRR 2.13; 95% CI 1.76-2.57) than in non-smokers. We found an important and strong association between smoking and incidence of schizophrenia. Smoking may increase risk through as yet unknown pathways or smoking may share genetic risk with schizophrenia and non-affective psychoses.


Machine and deep learning methods for clinical outcome prediction based on physiological data of COVID-19 patients: a scoping review.
Since the beginning of the COVID-19 pandemic, numerous machine and deep learning (MDL) methods have been proposed in the literature to analyze patient physiological data. The objective of this review is to summarize various aspects of these methods and assess their practical utility for predicting various clinical outcomes. We searched PubMed, Scopus, and Cochrane Library, screened and selected the studies matching the inclusion criteria. The clinical analysis focused on the characteristics of the patient cohorts in the studies included in this review, the specific tasks in the context of the COVID-19 pandemic that machine and deep learning methods were used for, and their practical limitations. The technical analysis focused on the details of specific MDL methods and their performance. Analysis of the 48 selected studies revealed that the majority (∼54 %) of them examined the application of MDL methods for the prediction of survival/mortality-related patient outcomes, while a smaller fraction (∼13 %) of studies also examined applications to the prediction of patients' physiological outcomes and hospital resource utilization. 21 % of the studies examined the application of MDL methods to multiple clinical tasks. Machine and deep learning methods have been shown to be effective at predicting several outcomes of COVID-19 patients, such as disease severity, complications, intensive care unit (ICU) transfer, and mortality. MDL methods also achieved high accuracy in predicting the required number of ICU beds and ventilators. Machine and deep learning methods have been shown to be valuable tools for predicting disease severity, organ dysfunction and failure, patient outcomes, and hospital resource utilization during the COVID-19 pandemic. The discovered knowledge and our conclusions and recommendations can also be useful to healthcare professionals and artificial intelligence researchers in managing future pandemics.


Urban air quality management using emission inventory estimates for three Indian cities: Faridabad, Lucknow and Pune.
Urban air quality is an issue of major concern across many cities and towns in India. In particular, high levels of particulate matter (both suspended particulate matter (SPM) and respirable suspended particulate matter (RSPM)) are responsible for non-compliance against air quality standards. This paper analyses the status of air quality in the 16 most polluted Indian cities identified for priority action by the Hon'ble Supreme Court of India. Each city has its own unique problems depending on the nature of activities being undertaken. Thus, three cities, Pune, Lucknow, and Faridabad, which represent a top-ten urban agglomerate (based on population), a predominantly residential city and an industrial town are chosen for detailed analyses of the air quality problem. The causal factors for poor air quality are determined and sectoral emission loads are estimated for each city adopting a uniform approach that facilitates comparative evaluation. These provide an estimate of the major contributors to air pollution with specific reference to particulate matter, which is a major pollutant of concern. For each of these cities, an air quality management plan is suggested that specifically accounts for the contributing factors in each city. Further, quantitative estimates of the likely improvements due to implementation of some of the specific measures are also provided. An overall comparative assessment of the air quality issues across different cities can provide useful insights in the development of the management plan for the remaining cities as well.


A novel test for selection on cis-regulatory elements reveals positive and negative selection acting on mammalian transcriptional enhancers.
Measuring natural selection on genomic elements involved in the cis-regulation of gene expression--such as transcriptional enhancers and promoters--is critical for understanding the evolution of genomes, yet it remains a major challenge. Many studies have attempted to detect positive or negative selection in these noncoding elements by searching for those with the fastest or slowest rates of evolution, but this can be problematic. Here, we introduce a new approach to this issue, and demonstrate its utility on three mammalian transcriptional enhancers. Using results from saturation mutagenesis studies of these enhancers, we classified all possible point mutations as upregulating, downregulating, or silent, and determined which of these mutations have occurred on each branch of a phylogeny. Applying a framework analogous to Ka/Ks in protein-coding genes, we measured the strength of selection on upregulating and downregulating mutations, in specific branches as well as entire phylogenies. We discovered distinct modes of selection acting on different enhancers: although all three have experienced negative selection against downregulating mutations, the selection pressures on upregulating mutations vary. In one case, we detected positive selection for upregulation, whereas the other two had no detectable selection on upregulating mutations. Our methodology is applicable to the growing number of saturation mutagenesis data sets, and provides a detailed picture of the mode and strength of natural selection acting on cis-regulatory elements.


Distinct Phenotypes Caused by Mutation of MSH2 in Trypanosome Insect and Mammalian Life Cycle Forms Are Associated with Parasite Adaptation to Oxidative Stress.
DNA repair mechanisms are crucial for maintenance of the genome in all organisms, including parasites where successful infection is dependent both on genomic stability and sequence variation. MSH2 is an early acting, central component of the Mismatch Repair (MMR) pathway, which is responsible for the recognition and correction of base mismatches that occur during DNA replication and recombination. In addition, recent evidence suggests that MSH2 might also play an important, but poorly understood, role in responding to oxidative damage in both African and American trypanosomes. To investigate the involvement of MMR in the oxidative stress response, null mutants of MSH2 were generated in Trypanosoma brucei procyclic forms and in Trypanosoma cruzi epimastigote forms. Unexpectedly, the MSH2 null mutants showed increased resistance to H2O2 exposure when compared with wild type cells, a phenotype distinct from the previously observed increased sensitivity of T. brucei bloodstream forms MSH2 mutants. Complementation studies indicated that the increased oxidative resistance of procyclic T. brucei was due to adaptation to MSH2 loss. In both parasites, loss of MSH2 was shown to result in increased tolerance to alkylation by MNNG and increased accumulation of 8-oxo-guanine in the nuclear and mitochondrial genomes, indicating impaired MMR. In T. cruzi, loss of MSH2 also increases the parasite capacity to survive within host macrophages. Taken together, these results indicate MSH2 displays conserved, dual roles in MMR and in the response to oxidative stress. Loss of the latter function results in life cycle dependent differences in phenotypic outcomes in T. brucei MSH2 mutants, most likely because of the greater burden of oxidative stress in the insect stage of the parasite.


Reduced ING1b gene expression plays an important role in carcinogenesis of non-small cell lung cancer patients.
We performed a clinical study on ING1b gene expression and p53 gene status in relation to p53 target genes. Eighty-eight tumors from surgically treated non-small cell lung cancer (NSCLC) patients were studied. PCR-single-strand conformational polymorphism after sequencing was performed to investigate ING1 and p53 gene status. Quantitative reverse transcription-PCR was performed to evaluate the gene expression of ING1b, p21, and bax. The results of p21 and bax expression were confirmed with immunohistochemistry. Only two carcinomas (2.3%) had nonmissense mutations of ING1b. Thirty-seven carcinomas (42.0%) had reduced ING1b gene expression. Thirty-seven carcinomas (42.0%) had mutations of p53. In total, 63 carcinomas (71.6%) had either reduced ING1b expression or mutant p53. The p21 gene expression ratio was significantly lower in the ING1b-reduced tumors than in the ING1b-positive tumors (P = 0.0029). Similarly, the bax gene expression ratio was significantly lower in the ING1b-reduced tumors than in the ING1b-positive tumors (P < 0.0001), and it was also significantly lower in tumors that had either reduced ING1b expression or mutant p53 than in tumors that had both positive ING1b expression and wild-type p53 (P = 0.0331). Reduction of ING1b gene expression was associated with reduced p21 and bax gene expression in NSCLCs. The present study is the first clinical report to confirm the positive role of ING1b in regulating p21 and bax gene expression. ING1b might be one of the tumor suppressor genes that could play a role in carcinogenesis in NSCLC patients.


[Size of myocardial sarcomeres and their potential use in the histological diagnosis of acute myocardial infarct].
Measurements of sarcomeres in papillary muscles of the right and left ventricles of the heart revealed the lack or an insignificant per cent of relaxed sarcomeres in patients dying with some diseases including ischemic heart disease without acute myocardial infarction and in those dying with acute myocardial infarction outside the zone of ischemic damage. Relaxation of sarcomeres in large groups of muscle fibers detectable even without measurements allows the diagnosis of acute myocardial infarction at a very early stage. Conditions of fixation may affect the size of sarcomeres. This should be kept in mind in analysing their sizes.


Prioritizing comparative effectiveness research: are drug and implementation trials equally worth funding?
Comparative effectiveness research (CER) is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat and monitor a clinical condition, or to improve the delivery of care. The purpose of this article is to compare--within the scope of CER--the value of implementation and drug trials. Implementation trials have limitations similar to drug trials in terms of generalizability of results outside the trial setting and ability to identify best practice. However, in contrast to drug trials, implementation trials do not provide value in terms of ruling out harm, as implementation strategies are unlikely to cause harm in the first place. Still, implementation trials may provide good value when there is a high error probability in deciding whether implementation will be cost effective or if costs associated with making an erroneous decision are high. Yet the low risk of implementation programmes to cause harm may also allow for alternative approaches to identify best implementation practice, perhaps outside the scope of rigorous trials and testing. One such approach that requires further investigation is a competitive market for quality of care, where implementation programmes may be introduced without prior evaluation.


Visualization of lipid droplets in C. elegans by light and electron microscopy.
The powerful forward and reverse genetic tools, and emerging sets of biochemical assays for fat metabolites, make Caenorhabditis elegans an attractive model organism for elucidating conserved mechanisms in fat storage. The ability to observe lipid droplets in live animals at single cell resolution offers a unique advantage for studying cellular fat storage in vivo. In this chapter, we describe transgenic technologies for expressing fluorescent lipid droplet marker proteins at near-physiological levels. Methods to visualize these markers using sensitive confocal microscopy systems are detailed. Additional methods for visualizing lipid droplets by transmission electron microscopy and detection of lipid droplet associated proteins by immunoelectron microscopy are described.


Assisting international medical graduates applying for their first post in the UK: what should be done?
The number of international medical graduates (IMGs) passing the Professional and Linguistic Assessment Board (PLAB) examination was six times greater in 2004 than in 2000. This has resulted in unprecedented numbers of applicants for junior posts, with some attracting over 1,000 overseas graduates. The Royal College of Physicians working group on IMGs was established in 2004 to address the problems that face newly qualified IMGs. The group has ascertained and now publishes current levels of competition for junior posts in order to inform overseas graduates of the levels of competition they are likely to encounter. The group is seeking ways of selecting applicants when such large numbers apply for posts and is looking at ways of improving clinical attachments. The paper considers these and other difficulties that IMGs face when they first seek employment in the UK and discusses possible solutions.


Population assessment of the American crocodile, Crocodylus acutus (Crocodilia: Crocodylidae) on the Pacific coast of Costa Rica.
The American crocodile, Crocodylus acutus, is widely distributed in the American neotropics. It is endangered throughout most of its range and is listed as vulnerable by the International Union for the Conservation of Natural Fauna and Flora (IUCN) and on Appendix I of the Convention for the International Trade in Endangered Species of Wild Flora and Fauna (CITES). Despite this listing, there are few published reports on population status throughout most of its range. We investigated the status of the C. acutus, at several locations along the Pacific coast of Costa Rica. We carried out spotlight and nesting surveys from 2007-2009 along the Costa Rican Pacific coast in four distinct areas, coastal areas of Las Baulas (N=40) and Santa Rosa (N=9) National Parks and the Osa Conservation Area (N=13), and upriver in Palo Verde National Park (N=11). We recorded crocodile locations and standard environmental data at each observation. Encounter rates, population structure, distribution within each area and data on successful nesting (presence of hatchlings, nests, etc) were determined. We attempted to capture all crocodiles to record standard morphometrics. A total of 586 crocodiles were observed along 185.8km of survey route. The majority of animals encountered (54.9%) were either hatchlings (<0.5m) or juveniles (0.5-1.25m). The average non-hatchling encounter rate per survey for the Pacific coast was 3.1 crocodiles/km, with individual encounter rates ranging from 1.2 crocodiles/km to 4.3 crocodiles/ km in Las Baulas National Park and the Osa Conservation Area respectively. Distribution of size classes within the individual locations did not differ with the exception of Santa Rosa and Las Baulas National Parks, where hatchlings were found in water with lower salinities. These were the first systematic surveys in several of the areas studied and additional work is needed to further characterize the American crocodile population in Costa Rica.


[Monitoring of tienopyridines or glycoprotein IIb/IIIa-receptor antagonists: simple platelet function tests].
Platelet function analyses were known as mystified, complicated, and time consuming laboratory investigations with a high coefficient of variation. Only in rare cases they led to precise interpretations under routine clinical laboratory conditions. In the first line they were focussed on bleeding tendencies. Only few were suited to evaluate the state of hyperaggregability of platelets. This short presentation of the GTH-Symposium 2004 gives a survey on the most simple and practicable tests for checking platelet function which may be used for the monitoring of therapy with tienopyridines and glycoprotein IIb/IIIa-receptor antagonists.


Treatment of Periodontal Disease with an Octenidine-based Antiseptic in HIV-positive Patients.
To evaluate the effects of a periodontal therapy with subsequent application of an octenidine (OCT)-based antiseptic in HIV-positive patients receiving highly active antiretroviral therapy. HIV-positive patients with a clinically diagnosed periodontal disease were randomly divided into two groups (n = 30/group). Both groups initially received a periodontal therapy. Patients in the OCT group additionally used an OCT-based mouthwash. Subgingival plaque samples and periodontal indices were analysed prior to treatment onset as well as one and 3 months post-treatment. Periodontal therapy has resulted in a significant decrease in the values of all periodontal indices one and 3 months following the therapy completion (P = 0.000). The effects of the two applied therapeutic protocols differed significantly in terms of the variation in the PBI (F = 4.617; P = 0.017) and the PD (F = 3.203; P = 0.044) value. In the patients in the OCT group, a more pronounced decrease in the PBI and PD was noted at 1-month follow-up as well as a greater increase in the PD value 3 months upon treatment completion. In the OCT group, no more atypical microorganisms were detectable 1 month post-treatment, while in the control group they were found in 34.5% of patients. The periodontal therapy bears good results in HIV-positive patients. Additional administration of OCT contributes to the significant decline in the PBI and DS values and eliminates atypical microorganisms within 1 month post-treatment. However, more favourable results were not noted in the OCT group at the 3-month assessment.


Is minimally invasive surgery beneficial in the management of esophageal cancer? A meta-analysis.
Open esophagectomy for cancer is a major oncological procedure, associated with significant morbidity and mortality. Recently, thoracoscopic procedures have offered a potentially advantageous alternative because of less operative trauma compared with thoracotomy. The aim of this study was to utilize meta-analysis to compare outcomes of open esophagectomy with those of minimally invasive esophagectomy (MIE) and hybrid minimally invasive esophagectomy (HMIE). Literature search was performed using Medline, Embase, Cochrane Library, and Google Scholar databases for comparative studies assessing different techniques of esophagectomy. A random-effects model was used for meta-analysis, and heterogeneity was assessed. Primary outcomes of interest were 30-day mortality and anastomotic leak. Secondary outcomes included operative outcomes, other postoperative outcomes, and oncological outcomes in terms of lymph nodes retrieved. A total of 12 studies were included in the analysis. Studies included a total of 672 patients for MIE and HMIE, and 612 for open esophagectomy. There was no significant difference in 30-day mortality; however, MIE had lower blood loss, shorter hospital stay, and reduced total morbidity and respiratory complications. For all other outcomes, there was no significant difference between the two groups. Minimally invasive esophagectomy is a safe alternative to the open technique. Patients undergoing MIE may benefit from shorter hospital stay, and lower respiratory complications and total morbidity compared with open esophagectomy. Multicenter, prospective large randomized controlled trials are required to confirm these findings in order to base practice on sound clinical evidence.


Evaluation of gastrointestinal motility with MRI: Advances, challenges and opportunities.
Dynamic magnetic resonance imaging (MRI) of gastrointestinal motility has developed rapidly over the past few years. The non-invasive and non-ionizing character of MRI is an important advantage together with the fact that it is fast and can visualize the entire gastrointestinal tract. Advances in imaging and quantification techniques have facilitated assessment of gastric, small intestinal, and colonic motility in a clinical setting. Automated quantitative motility assessment using dynamic MRI meets the need for non-invasive techniques. Recently, studies have begun to examine this technique in patients, including those with IBD, pseudo-obstruction and functional bowel disorders. Remaining challenges for clinical implementation are processing the large amount of data, standardization and validation of the numerous MRI metrics and subsequently assessment of the potential role of dynamic MRI. This review examines the methods, advances, and remaining challenges of evaluation of gastrointestinal motility with MRI. It accompanies an article by Khalaf et al. in this journal that describes a new protocol for assessment of pan-intestinal motility in fasted and fed state in a single MRI session.


Inflammation index predicts radiation-induced lung injury and prognosis in lung tumors treated with stereotactic body radiation therapy.
To investigate the effect of inflammation-based indexes in predicting radiation pneumonitis (RP) and prognosis in lung tumor patients treated with stereotactic body radiation therapy (SBRT). The data of one hundred and seventy-two patients with 272 lung lesions from November 2015 to December 2020 were retrospectively analyzed. Pretreatment hematological indexes including platelet count, neutrophil count, and lymphocyte count were collected before treatment. Systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were calculated. The receiver operating characteristic (ROC) curve was established to predict the RP and overall survival of patients, and the Youden index was calculated to determine the cutoff values of SII, NLR, and PLR before radiotherapy. Pretreatment SII, NLR, and PLR could predict RP in lung tumor patients treated with SBRT, the optimal cutoff values of SII, NLR, and PLR were 355.38, 2.04, and 141.09, respectively. Pretreatment PLR could predict survival and the optimal cutoff value of PLR was 166.83, patients with a PLR > 166.83 predict worse overall survival (OS) (P < 0.001). The 1-year and 2-year OS for patients with a PLR ≤ 166.83 were 96.3% and 82.4%, while for those with a PLR > 166.83 were 82.0% and 58.5%, respectively. In lung tumor patients treated with SBRT, pretreatment SII, NLR, and PLR can effectively predict RP and a higher PLR predicts poor OS. These inflammation-based indexes could serve as reliable and convenient predictors to guide treatment for physicians in clinical practice.


Effect of antidepressants and neuroleptics on phosphoinositide metabolism in human platelets.
The effect of tricyclic antidepressants (imipramine, desipramine, amitriptyline) and several other antidepressants like iprindole, a monoamine oxidase inhibitor phenelzine, trazodone and mianserin as well as cocaine (a potent inhibitor of norepinephrine uptake), and neuroleptics (haloperidol, thioridazine, chlorpromazine) on [3H]inositol phosphate formation was investigated in human platelets. Basal and thrombin-induced [3H]inositol monophosphate ([3H]IP1), [3H]inositol bisphosphate ([3H]IP2) and [3H]inositol trisphosphate ([3H]IP3) production were measured in [3H]myoinositol-labeled platelets in the presence of lithium chloride and in the presence or absence of test drugs. Desipramine, imipramine, amitriptyline and iprindole inhibited thrombin-stimulated formation of [3H]IP2 and [3H]IP3 in human platelets but had no significant effect on [3H]IP1 formation. In contrast, trazodone, mianserin, cocaine and phenelzine had no effect on inositol phosphate formation in thrombin-stimulated human platelets. The neuroleptics thioridazine and chlorpromazine also decreased thrombin-stimulated [3H]IP2 and [3H]IP3 production but not [3H]IP1 in human platelets, whereas haloperidol had no significant effect. The effect of antidepressants and neuroleptics on the level of [3H]phosphatidylinositol ([3H]PI), [3H]phosphatidylinositol 4-phosphate ([3H]PIP) and [3H]phosphatidylinositol 4,5-bisphosphate ([3H]PIP2) was also determined. All of the drugs tested except phenelzine and thioridazine increased the accumulation of [3H]PI, [3H]PIP and [3H]PIP2. Thioridazine increased levels of [3H]PI but decreased the level of [3H]PIP and [3H]PIP2, whereas phenelzine had no effect on [3H]PI, [3H]PIP and [3H]PIP2 interconversion in human platelets.(ABSTRACT TRUNCATED AT 250 WORDS)


Biochemical mechanisms of tumor invasion and metastases.
Tumor invasion and metastases is the major cause of treatment failure for cancer patients. There is a great need to develop new clinical methods to predict the clinical aggressiveness of a patient's tumor and to identify and eradicate clinically silent micrometastases. Such new methods may be derived from basic research into the biochemical mechanisms of invasion and metastases. We have isolated proteins involved in tumor cell attachment, invasion, and locomotion. The 'laminin receptor' is a tumor cell surface protein which specifically binds laminin, a glycoprotein of basement membranes. The laminin receptor may play a role in tumor cell attachment. 'Type IV collagenase' is a metalloproteinase which cleaves type IV basement membrane collagen but not interstitial collagens. The 'autocrine motility factor' is a secreted protein which binds to the cell surface and profoundly stimulates cell locomotion. All of these proteins appear to be augmented in actively metastatic tumor cells, at least in the models studied. They may provide strategies for diagnosis and therapy of metastases.


Responses of specific-pathogen-free chicks to concomitant infections of reovirus (WVU-2937) and infectious bursal disease virus.
Specific-pathogen-free white leghorn chicks concomitantly infected with both infectious bursal disease virus (IBDV) and reovirus (WVU-2937) on day 1 had significantly lower (P less than 0.05) virus-neutralizing- and precipitating-antibody geometric mean titers (GMT) to reovirus than chicks infected with only reovirus on day 1 but had a similar incidence of inflammation of the metatarsal digital flexor tendons. Chicks infected with IBDV on day 7 and reovirus on day 14 had a greater incidence of inflammation of the tarsometatarsal digital flexor tendons and lower neutralizing- and precipitating-antibody GMT to reovirus than chicks infected with only reovirus on day 14. Chicks infected with both viruses on day 1 had a significantly lower (P less than 0.05) neutralizing-antibody GMT to IBDV than chicks infected with only IBDV.


Optimization of Transcranial Direct Current Stimulation of Dorsolateral Prefrontal Cortex for Tinnitus: A Non-Linear Dose-Response Effect.
Neuromodulation is defined as the process of augmenting neuroplasticity via invasive or non-invasive methods. Tinnitus is the perception of sound in the absence of its external source. The objective of this study was to optimize the parameters of transcranial direct current stimulation (tDCS) of dorsolateral prefrontal cortex (DLPFC) for tinnitus suppression. The following factors were optimized in the dose-response design (n = 111): current intensity (1.5 mA or 2 mA), stimulation duration (20 min or 30 min), and number of stimulation sessions (2, 4, 6, 8, or 10), with a 3-4 day washout period between each session. Participants underwent a minimum of 2 sessions in 1 week or maximum of 10 sessions in 5 weeks' time. Tinnitus loudness was measured in pre-post design using a 10-point numeric rating scale. There was a significant reduction in tinnitus loudness after tDCS of DLPFC. There was no significant difference between the intensity and duration of stimulation. As the number of sessions increased, there was a higher reduction in the tinnitus loudness; however, this effect plateaued after 6 sessions.


What Do We Find Attractive about the Face?: Survey Study with Application to Aesthetic Surgery.
The appearance of the face is one of the most important factors influencing our perception of beauty. However, few studies have attempted to quantitate what one perceives as beauty. Therefore, this study was conducted with the goal of providing physicians with anatomical data that demonstrate which facial traits most influence our perception of one's attractiveness. In the first phase of the study, faces of 60 participants (30 males and 30 females) were photographed. Next, the photographs were shown to another group of 120 study members (60 males and 60 females), who evaluated the facial features using a Visual Analogue Scale. The highest rated facial parts were then measured using the ImageJ program. In men, the most attractive parts of the face were Type 1:2 lips, a Type IV nose of medium width, blue eyes, brown hair, and a very narrow face. Among females, the most attractive parts of the face were Type 2:1 lips, Type III and V noses of medium width, dark brown eyes, blonde hair, and a narrow face. This is the first study in which the most aesthetically important facial parts have been comprehensively examined. The results obtained in our study show a higher degree of representativeness compared to other studies due to a different methodological approach and can be used as an aesthetic guide and can help in the planning of aesthetic surgery such as lip augmentation and rhinoplasty. Clin. Anat. 33:214-222, 2020. © 2019 Wiley Periodicals, Inc.


A mean field model for movement induced changes in the beta rhythm.
In electrophysiological recordings of the brain, the transition from high amplitude to low amplitude signals are most likely caused by a change in the synchrony of underlying neuronal population firing patterns. Classic examples of such modulations are the strong stimulus-related oscillatory phenomena known as the movement related beta decrease (MRBD) and post-movement beta rebound (PMBR). A sharp decrease in neural oscillatory power is observed during movement (MRBD) followed by an increase above baseline on movement cessation (PMBR). MRBD and PMBR represent important neuroscientific phenomena which have been shown to have clinical relevance. Here, we present a parsimonious model for the dynamics of synchrony within a synaptically coupled spiking network that is able to replicate a human MEG power spectrogram showing the evolution from MRBD to PMBR. Importantly, the high-dimensional spiking model has an exact mean field description in terms of four ordinary differential equations that allows considerable insight to be obtained into the cause of the experimentally observed time-lag from movement termination to the onset of PMBR (∼ 0.5 s), as well as the subsequent long duration of PMBR (∼ 1 - 10 s). Our model represents the first to predict these commonly observed and robust phenomena and represents a key step in their understanding, in health and disease.


Occupational exposure to blood and bodily fluids among healthcare workers in Serbian general hospitals.
The risk of occupational bloodborne infections (HBV, HCV, and HIV) among healthcare workers remains a serious issue in developing countries. The aim of this study was to estimate occupational exposure to bloodborne infections among general hospital workers in Serbia. This cross-sectional study was conducted in the spring of 2013 and included 5,247 healthcare workers from 17 general hospitals. The questionnaire was anonymous, self-completed, and included sociodemographic information with details of blood and bodily fluid exposure over the career and in the previous year (2012). Significant predictors of sharps injuries were determined with multiple logistic regressions. The distribution of accidents in 2012 was equal between the genders (39 %), but in entire career it was more prevalent in women (67 %). The most vulnerable group were nurses. Most medical doctors, nurses, and laboratory technicians reported stabs or skin contact with patients' blood/other bodily fluid/tissue as their last accident. Healthcare workers from the north/west part of the country reported a significantly lower number of accidents over the entire career than the rest of the country (p<0.001). The south of Serbia stood out as the most accident-prone in 2012 (p=0.042).


'A Knife into My Heart': Cries, Compassion and Ethical Life.
The subtitle to the conference upon which this journal issue is based invited us to 'follow Crowter'. This paper does so primarily by following the person and only thereby attends to the legal judgment. In particular, it will attend to her comment that When mum told me about the discrimination against babies like me in the womb, I felt like a knife had been put into my heart. It made me feel less valued than other people. The argument is that (I) there are strong reasons for such an approach from the field of theological ethics and that this is valuable for pastoral theology and for bioethics. With this case made, the argument proceeds (II) by following and building on three elements of Heidi Crowter's words concerning (a) the knife (b) the heart and (c) the person. The argument concludes (III) with theological reflection and deliberation regarding institutions, practices and actions which will make for 'ethical society', principally focussed on ecclesial life.


CircRNA_101951 promotes migration and invasion of colorectal cancer cells by regulating the KIF3A-mediated EMT pathway.
Colorectal cancer (CRC) is one of the most lethal tumor types worldwide. Circular RNAs (circRNAs), which are covalent closed loops of RNA, perform vital roles for the proliferation and metastasis of a variety of tumor types. In the present study, the expression, function and molecular mechanisms of action of a novel circRNA, circRNA_101951, were examined in CRC. The expression levels of circRNA_101951 in CRC tissue and cell lines were examined using reverse transcription-quantitative (RT-qPCR). Cell proliferation, the clone formation ability, cell apoptosis, the cell cycle and the cell migratory and invasive abilities were examined using MTT assays, colony formation assays, flow cytometric assays, and cell migration and invasion assays, respectively. The effects of circRNA_101951 on Kinesin II family member 3A (KIF3A) related gene expression were examined using RT-qPCR and western blot assays. The results indicated that circRNA_101951 was increased in CRC tissues and cell lines. The downregulation of circRNA_101951 inhibited cell proliferation and colony formation as well as cell migration and invasion of CRC cell lines. In addition, the downregulation of circRNA_101951 blocked the KIF3A-mediated epithelial-mesenchymal transition (EMT) pathway, which was detected by examining the expression levels of KIF3A and EMT related proteins. In conclusion, the current data revealed that circRNA_101951 may act as a potential biomarker for patients with CRC, and provided a novel insight demonstrating that the suppression of circRNA_101951 may be a potential therapeutic strategy for CRC.


Trends in serious ocular trauma in Scotland.
To report trends in serious, sight-threatening ocular trauma in Scotland. A prospective, population-based, observational study of patients with ocular trauma admitted to hospital in Scotland during a 12-month period (2008-2009), conducted through the British Ophthalmic Surveillance Unit. Data on circumstances of the injuries and visual outcomes were collected using protocols standardised to those from an earlier study (1991-1992) to allow direct comparisons over time. In all, 0.3% of all emergency admissions in Scotland were for ocular trauma. Significant differences were observed between the time periods in where an injury occurred (P=0.009): a reduction of those occurring in a sports/leisure facility (8.2%) and an increase in those occurring on the street (21.4%). Assaults remained the most common cause of injury (31%). Gender differences persisted with females more likely to have an injury from falls (OR=8.67; 95% CI: 2.41-31.49; P=0.002), or in the home (OR=5.40; 95% CI: 1.69-17.16; P=0.009 ), and less likely to have one in the workplace (P=0.06). Poor visual outcome was associated with injuries occurring in the home (OR=4.33, P=0.047), in a public place (OR=6.25, P=0.047), and those caused by a fall (OR 42.75, P<0.001); or assault (OR 7.29, P=0.019). Half of those with a poor outcome have no perception of light. Serious ocular trauma remains an infrequent, sight-threatening event, associated with significant monocular visual morbidity. The findings suggest a shift from corporate to personal responsibility for risk awareness, health, and safety.


Prevalence of hypothyroidism and Graves disease in sarcoidosis.
The association of sarcoidosis (S) and thyroid autoimmunity has been reported by several studies in a wide range of variability. The aim of our study was to evaluate the prevalence of clinical and subclinical thyroid disorders in patients with S vs gender-matched and age-matched control subjects. Thyroid hormones and antithyroid antibodies, thyroid ultrasonography and fine-needle aspiration were performed in 111 patients with S who had been consecutively referred to the Respiratory Pathophysiology Section of the University of Pisa, and the results were compared to 333 gender-matched and age-matched control subjects from the same geographic area. The odds ratio for subclinical hypothyroidism for female patients with S vs control subjects was 2.7 (95% confidence interval [CI], 1.3 to 5.9); for anti-thyroid peroxidase antibody titer (AbTPO) positivity, 2.2 (95% CI, 1.2 to 3.9); and for thyroid autoimmunity, 1.9 (95% CI, 1.1 to 3.2). The mean values of thyroid-stimulating hormone and AbTPO were higher in female S patients than in control subjects (p < 0.01). A significantly higher prevalence of clinical hypothyroidism (four patients) and Graves disease (three patients) was observed in female S patients than in control subjects (none; p = 0.005 and 0.0026, respectively). Two cases of papillary thyroid cancer were detected in S patients. No significant difference between S patients and control subjects was detected for free triiodothyronine and thyroxine, antithyroglobulin autoantibodies, thyroid volume and nodularity, and subclinical hyperthyroidism. Thyroid function, AbTPO antibodies, and ultrasonography should be tested as part of the clinical profile in female S patients. Subjects who are at high risk (female subjects, those with positive AbTPOs, and those with hypoechoic and small thyroid) should have thyroid function follow-up and appropriate treatment in due course.


Mitochondrial Dyshomeostasis as an Early Hallmark and a Therapeutic Target in Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis (ALS) is a fatal multisystem disease characterized by progressive death of motor neurons, loss of muscle mass, and impaired energy metabolism. More than 40 genes are now known to be associated with ALS, which together account for the majority of familial forms of ALS and only 10% of sporadic ALS cases. To date, there is no consensus on the pathogenesis of ALS, which makes it difficult to develop effective therapy. Accumulating evidence indicates that mitochondria, which play an important role in cellular homeostasis, are the earliest targets in ALS, and abnormalities in their structure and functions contribute to the development of bioenergetic stress and disease progression. Mitochondria are known to be highly dynamic organelles, and their stability is maintained through a number of key regulatory pathways. Mitochondrial homeostasis is dynamically regulated via mitochondrial biogenesis, clearance, fission/fusion, and trafficking; however, the processes providing "quality control" and distribution of the organelles are prone to dysregulation in ALS. Here, we systematically summarized changes in mitochondrial turnover, dynamics, calcium homeostasis, and alterations in mitochondrial transport and functions to provide in-depth insights into disease progression pathways, which may have a significant impact on current symptomatic therapies and personalized treatment programs for patients with ALS.


Characteristic values of the lumbar load of manual patient handling for the application in workers' compensation procedures.
The human spine is often exposed to mechanical load in vocational activities especially in combination with lifting, carrying and positioning of heavy objects. This also applies in particular to nursing activities with manual patient handling. In the present study a detailed investigation on the load of the lumbar spine during manual patient handling was performed. For a total of 13 presumably endangering activities with transferring a patient, the body movements performed by healthcare workers were recorded and the exerted action forces were determined with regard to magnitude, direction and lateral distribution in the time course with a "measuring bed", a "measuring chair" and a "measuring floor". By the application of biomechanical model calculations the load on the lowest intervertebral disc of the lumbar spine (L5-S1) was determined considering the posture and action force data for every manual patient handling. The results of the investigations reveal the occurrence of high lumbar load during manual patient handling activities, especially in those cases, where awkward postures of the healthcare worker are combined with high action forces caused by the patient's mass. These findings were compared to suitable issues of corresponding investigations provided in the literature. Furthermore measurement-based characteristic values of lumbar load were derived for the use in statement procedures concerning the disease no. 2108 of the German list of occupational diseases. To protect healthcare workers from mechanical overload and the risk of developing a disc-related disease, prevention measures should be compiled. Such measures could include the application of "back-fairer" nursing techniques and the use of "technical" and" small aids" to reduce the lumbar load during manual patient handling. Further studies, concerning these aspects, are necessary.


[C reactive protein and procalcitonin levels for the diagnosis of invasive bacterial infections in allogenic hematopoietic stem cell transplantation recipients].
The main causes of complications of allogenic hematopoietic stem cell transplantation are infections and graft versus host disease. To assess the predictive value of C reactive protein (CRP) and procalcitonin (PCT) in the diagnosis of invasive bacterial infections in children with febrile neutropenia after an allogenic hematopoietic stem cell transplantation. Prospective follow up of patients aged 18 years or less, with febrile neutropenia after an allogenic hematopoietic stem cell transplantation. In all patients, cultures from sterile sites, CRP and PCT determinations were done. CRP levels were also measured prior to transplantation and three times per week for 30 days after the procedure. An independent evaluator, blinded to the results of CRP and PCT, classified children as with or without invasive bacterial infection. Thirty three patients aged 9+/-5 years (21 males) were studied. Eight had an invasive bacterial infection. Sensitivity, specificity, positive and negative predictive values of a CRP > or = 90 mg/L for the diagnosis of invasive bacterial infection were 25, 80, 29 and 77%, respectively. The figures for a PCT > or = 0.7 ng/ml were 43, 78, 38 and 82%, respectively. No differences in repeated CRP values measured during evolution, were observed. A CRP > or = 90 mg/L or a PCT > or = 0.7 ng/ml had a high specificity and negative predictive value but low sensitivity for the diagnosis of invasive bacterial infections in recipients of allogenic hematopoietic stem cell transplantation.