Intracellular retention of the MHC class I-related chain B ligand of NKG2D by the human cytomegalovirus UL16 glycoprotein.
Infection by human CMV induces expression of the cellular MHC class I-related chain A (MICA) and chain B (MICB) surface proteins, which function as ligands for the activating NKG2D receptor. Engagement of NKG2D triggers NK cells and costimulates Ag-specific effector CD8 alphabeta T cells. The potency of MHC class I-related chain-NKG2D in stimulating these anti-viral immune responses may be countered by a CMV-encoded transmembrane glycoprotein, UL16, which specifically binds MICB as well as two of the UL16-binding proteins that are ligands of NKG2D. However, the function and significance of these interactions are undefined. Using a stably transfected B cell line, we show that expression of UL16 results in loss of surface MICB. This effect is caused by the failure of newly synthesized MICB to mature and transit the secretory pathway due to physical association with UL16. The intracellular retention of these protein complexes is mediated by a tyrosine-based motif in the cytoplasmic tail sequence of UL16, which determines localization to or retrieval from the trans-Golgi network. Deletion of this motif restores surface expression of MICB, whereas UL16 may be redirected to endosomal compartments. Predictably, the retention of MICB abrogates the stimulatory function of NKG2D. These results suggest a potential mechanism of viral immune evasion. However, this activity remains to be confirmed with CMV-infected fibroblasts or endothelial cells, in particular because MICB is normally coexpressed with MICA, which is not retained by UL16.


Medicinal chemistry of selective neurokinin-1 antagonists.
The study of tachykinin NK1 (substance P) receptor antagonists has emerged as a field of great promise due to accumulating evidence that NK1 antagonists offer possible new treatment options in therapeutic areas ranging from pain, emesis, and pulmonary disorders to depression and anxiety. It is hoped that the unique mechanism of action of these agents, which involves modulation of effects mediated by the interaction of the neuropeptide substance P with it's G-protein coupled receptor, will provide improvements over existing therapies. For this reason many pharmaceutical companies are engaged in intense research programs with the goal of bringing safe and effective new drugs to the market. To date a wealth of diverse NK1 antagonists have been discovered, several of which have been evaluated in clinical trials. Despite rich structural diversity in this area of medicinal chemistry a number of structural features are commonly shared amongst otherwise unrelated antagonists. This theme and others are covered with the aim of conveying recent successful approaches to the discovery of potent and selective nonpeptide NK1 antagonists. This review focuses mainly on reports appearing in the year 2001 and the first half of 2002.


Maternal Intensive Care Unit Admission as an Indicator of Severe Acute Maternal Morbidity: A Population-Based Study.
Severe acute maternal morbidity (SAMM) accounts for any life-threatening complication during pregnancy or after delivery. Measuring and monitoring SAMM seem critical to assessing the quality of maternal health care. The objectives were to explore the validity of intensive care unit (ICU) admission as an indicator of SAMM by characterizing the profile of women admitted to an ICU and of their ICU stay, according to the association with other SAMM criterion. We performed a secondary analysis of the 2540 women with SAMM included in the epidemiology of severe acute maternal morbidity (EPIMOMS) multiregional prospective population-based study (2012-2013, n = 182,309 deliveries). The EPIMOMS definition of SAMM, based on national experts' consensus, is a combination of diagnosis, organ dysfunctions, and intervention criteria, including ICU admission. Among women with SAMM, we identified characteristics associated with maternal ICU admission with or with no other SAMM criterion compared with ICU admission, by using multivariable multinomial logistic regression models. Overall, 511 women were admitted to an ICU during or up to 42 days after pregnancy, for a population-based rate of 2.8 of 1000 deliveries (511/182,309; 95% confidence interval [CI], 2.6-3.1); 15.5% of them (79/511; 95% CI, 12.4-18.9) had no other SAMM criterion compared with ICU admission. Among women with SAMM, the odds of ICU admission with no other morbidity criterion were increased in women with preexisting medical conditions (adjusted odds ratio (aOR), 2.13; 95% CI, 1.17-3.86) and cesarean before labor (aOR, 3.12; 95% CI, 1.47-6.64). Women admitted to ICU with no other SAMM criterion had more often decompensation of a preexisting condition, no interventions for organ support, and a shorter length of stay than women admitted with other SAMM criteria. Among women with SAMM, 1 in 5 is admitted to an ICU; 15.5% of those admitted in ICU have no other SAMM criterion and a less acute condition. These results challenge the use of ICU admission as a criterion of SAMM.


Sputum microscopy for the diagnosis of HIV-associated pulmonary tuberculosis in Tanzania.
In many resource poor settings only sputum microscopy is employed for the diagnosis of HIV-associated pulmonary tuberculosis; sputum culture may not be available. We determined the diagnostic accuracy of sputum microscopy for active case finding of HIV-associated pulmonary tuberculosis using TB culture as the reference standard. 2216 potential subjects screened for a TB vaccine trial submitted 9454 expectorated sputum specimens: 212 (2.2%) were sputum culture positive for Mycobacterium tuberculosis (MTB), 31 (0.3%) for non-tuberculous mycobacteria, and 79 (0.8%) were contaminated. The overall sensitivity of sputum microscopy was 61.8% (131/212) and specificity 99.7% (9108/9132). Sputum microscopy sensitivity varied from 22.6% in specimens with < 20 colony forming units (CFU)/specimen to 94.2% in patients with > 100 CFU/specimen plus confluent growth. The incremental diagnostic value for sputum microscopy was 92.1%, 1.8% and 7.1% for the first, second and third specimens, respectively. The positive predictive value and negative predictive values for sputum microscopy were 84.5% and 99.1%, respectively. The likelihood ratio (LR) of a positive sputum microscopy was 235.1 (95% CI 155.8 - 354.8), while the LR of a negative test was 0.38 (95CI 0.32 - 0.45). The 212 positive sputum cultures for MTB represented 103 patients; sputum microscopy was positive for 57 (55.3%) of 103 patients. Sputum microscopy on 3 expectorated sputum specimens will only detect 55% of culture positive HIV-infected patients in active screening for pulmonary tuberculosis. Sensitivity is higher in patients with greater numbers of CFUs in the sputum. Culture is required for active case finding of HIV- associated pulmonary tuberculosis.


Self-Assembled Curved Macroporous Photonic Crystal-Based Surfactant Detectors.
Surfactants are extensively used as detergents, dispersants, and emulsifiers. Thus, wastewater containing high-concentration surfactants discharged to the environment pose a serious threat to the ecosystem. Unfortunately, conventional detection methods for surfactants suffer from the use of sophisticated instruments and cannot perform detections for various surfactants by a single analysis. The article reports the development of simple and sensitive surfactant detection using doctor-blade-coated three-dimensional curved macroporous photonic crystals on a cylindrical rod. The photonic crystals exhibit different hydrophobicities at various angular positions after surface modification. The penetration of aqueous surfactant solutions in the interconnected macropores causes red-shift as well as reduction in amplitude in the optical stop bands, resulting in surfactant detection with visible readout. The correlation between the surface tension, as well as the solution-infiltrated angular position, and the concentration of aqueous surfactant solutions has also been investigated in this study.


Mitochondrial translation and beyond: processes implicated in combined oxidative phosphorylation deficiencies.
Mitochondrial disorders are a heterogeneous group of often multisystemic and early fatal diseases, which are amongst the most common inherited human diseases. These disorders are caused by defects in the oxidative phosphorylation (OXPHOS) system, which comprises five multisubunit enzyme complexes encoded by both the nuclear and the mitochondrial genomes. Due to the multitude of proteins and intricacy of the processes required for a properly functioning OXPHOS system, identifying the genetic defect that underlies an OXPHOS deficiency is not an easy task, especially in the case of combined OXPHOS defects. In the present communication we give an extensive overview of the proteins and processes (in)directly involved in mitochondrial translation and the biogenesis of the OXPHOS system and their roles in combined OXPHOS deficiencies. This knowledge is important for further research into the genetic causes, with the ultimate goal to effectively prevent and cure these complex and often devastating disorders.


[Results of therapy for osteogenic sarcoma in children: perspectives of improvement].
A retrospective analysis of treatment of 67 children suffering localized osteogenic sarcoma received at the Institute's Clinic (1977-1995) has been carried out. The best 5-year survival results were obtained with the COSS-91 and PECOSS programs and those for pre- and post-operative COMBAP chemotherapy (77.8 and 70.0%, respectively). Another randomized comparative study of the effectiveness of different polychemotherapy and pre-operative radiation schedules are being planned.


Machine learning for predicting hepatitis B or C virus infection in diabetic patients.
Highly prevalent hepatitis B and hepatitis C virus (HBV and HCV) infections have been reported among individuals with diabetes. Given the frequently asymptomatic nature of hepatitis and the challenges associated with screening in some vulnerable populations such as diabetes patients, we conducted an investigation into the performance of various machine learning models for the identification of hepatitis in diabetic patients while also evaluating the significance of features. Analyzing NHANES data from 2013 to 2018, machine learning models were evaluated; random forest (RF), support vector machine (SVM), eXtreme Gradient Boosting (XGBoost), and least absolute shrinkage and selection operator (LASSO) along with stacked ensemble model. We performed hyperparameter tuning to improve the performance of the model, and selected important predictors using the best performance model. LASSO showed the highest predictive performance (AUC-ROC = 0.810) rather than other models. Illicit drug use, poverty, and race were highly ranked as predictive factors for developing hepatitis in diabetes patients. Our study demonstrated that a machine-learning-based model performed optimally in the detection of hepatitis among diabetes patients, achieving high performance. Furthermore, models and predictors evaluated from the current study, we expect, could be supportive information for developing screening or treatment methods for hepatitis care in diabetes patients.


Responding positively to "children who like to eat": Parents' experiences of skills-based treatment for childhood obesity.
This study aims to understand the challenges parents of preschoolers with obesity face. We assessed parents' experiences of a group treatment program focused on parenting skills; the treatment program was evaluated in a randomized controlled trial in Stockholm County. After completing the program's 10 weekly sessions, parents were invited to participate in a semi-structured interview. The interviews were audio recorded, transcribed and analyzed using thematic analysis. In total, 36 parents (67% mothers, mean age 39 years, 33% foreign background, 50% with university degree) were interviewed. Two main themes were developed: Emotional burden and Skills and strength from others. Emotional burden encompassed the parents' experiences of raising a child with obesity. Parents spoke about the difficulties of managing their child's appetite and of seeking help and treatment, as well as their feelings about the social stigma attached to obesity. Skills and strength from others encompassed the parents' experiences of participating in group treatment. Parents reported that they appreciated the practical behavior change techniques taught, especially those regarding food and how to make everyday life more predictable, and said the focus on parenting skills gave them the confidence to apply the techniques in everyday life. Parents also highlighted the strength of the group setting, saying it enabled them to discuss perceived challenges and learn from other parents. Our findings show that childhood obesity carries social and emotional implications for parents, and that an intervention that provides parents with skill-building and a discussion space can help in negotiating these implications. This suggests that childhood obesity intervention programs benefit from including a parent-based approach which offers training in parenting skills and support in managing socially and emotionally challenging situations.


BRAZILIAN BOOTY RETINOPATHY: PURTSCHER-LIKE RETINOPATHY WITH PARACENTRAL ACUTE MIDDLE MACULOPATHY ASSOCIATED WITH PMMA INJECTION INTO BUTTOCKS.
To report a case of Purtscher-like retinopathy with paracentral acute middle maculopathy preceded by febrile illness after filler injection into the buttock muscles bilaterally for cosmesis to achieve a "Brazilian booty." Retrospective case report. A 35-year-old female presented with febrile illness and then decreased vision after repeat polymethyl methacrylate injections into her buttock muscles in Mexico. Examination was significant for retinal whitening, especially in the perifoveal areas, and intraretinal hemorrhages. Optical coherence tomography and fluorescein angiography imaging were consistent with small-vessel ischemic disease in the retina and choroid. Once systemic infection was ruled out, patient was treated with high-dose intravenous and then oral steroids. Vision recovery was good, with retinal atrophy on optical coherence tomography in the previous areas of retinal whitening. A Purtscher-like retinopathy with paracentral acute middle maculopathy and loss of vision may occur after filler injection below the neck, not just the face. This is the first report of vision loss caused by filler injected outside the face.


Transcription initiation and termination on Leishmania major chromosome 3.
Genome projects involving Leishmania and other trypanosomatids have revealed that most genes in these organisms are organized into large clusters of genes on the same DNA strand. We have previously shown that transcription of the entire Leishmania major Friedlin (LmjF) chromosome 1 (chr1) initiates bidirectionally between two divergent gene clusters. Here, we analyze transcription of LmjF chr3, which contains two convergent clusters of 67 and 30 genes, separated by a tRNA gene, with a single divergent protein-coding gene located close to the "left" telomere. Nuclear run-on analyses indicate that specific transcription of chr3 initiates bidirectionally between the single subtelomeric gene and the adjacent 67-gene cluster, close to the "right" telomere upstream of the 30-gene cluster, and upstream of the tRNA gene. Transcription on both strands terminates within the tRNA-gene region. Transient-transfection studies support the role of the tRNA-gene region as a transcription terminator for RNA polymerase II (Pol II) and Pol III, and also for Pol I.


Concordance by sex in sibling pairs with schizophrenia is paternally inherited. Evidence for a pseudoautosomal locus.
The hypothesis that the gene for schizophrenia is located in the pseudoautosomal region of the sex chromosomes predicts that same-sex concordance will occur in paternally rather than maternally derived pairs. In 120 families that included at least one sibling pair with schizophrenia, affected members were significantly more likely to be of the same sex when there was a history of illness on the paternal than on the maternal side, the difference remaining significant when parent of origin was assessed by three different methods. The finding is as predicted by the pseudoautosomal hypothesis: therefore a search for the gene should be focused on this small (three megabase) region of the genome. The ratio of same to mixed sex pairs in paternally-derived cases (approximately 3:1) suggests the gene is located in the centromeric one-third of the pseudoautosomal region.


Immunocytochemical study of G(i)2alpha and G(o)alpha on the epithelium surface of the rat vomeronasal organ.
To investigate in detail the distribution of G protein subtypes G(i)2alpha and G(o)alpha along the surface of the vomeronasal epithelium, we used double labeling immunocytochemical methods and electron microscopy. We examined the immunoreactivity of these surface structures with antibodies against G(i)2alpha and G(o)alpha. G(i)2alpha- and G(o)alpha-positive cells were observed at the epithelial surface and were evenly distributed. Electron microscopy revealed that strong immunoreactivities to both antibodies were observed on the microvilli and knob-like surface structures of receptor cells. No immunoreactivity was found on the microvilli or surface membranes of supporting cells. This expression pattern is similar to that reported for putative pheromone receptors. These data confirm that there are two distinct classes of vomeronasal receptor cells expressed at the surface of the epithelium. These two classes of receptors correspond to the same G(i)2alpha- and G(o)alpha-positive cells distributed in cell body layers of the epithelium and in the axon terminals in the accessory olfactory bulb.


Direct interaction of pericentrin with cytoplasmic dynein light intermediate chain contributes to mitotic spindle organization.
Pericentrin is a conserved protein of the centrosome involved in microtubule organization. To better understand pericentrin function, we overexpressed the protein in somatic cells and assayed for changes in the composition and function of mitotic spindles and spindle poles. Spindles in pericentrin-overexpressing cells were disorganized and mispositioned, and chromosomes were misaligned and missegregated during cell division, giving rise to aneuploid cells. We unexpectedly found that levels of the molecular motor cytoplasmic dynein were dramatically reduced at spindle poles. Cytoplasmic dynein was diminished at kinetochores also, and the dynein-mediated organization of the Golgi complex was disrupted. Dynein coimmunoprecipitated with overexpressed pericentrin, suggesting that the motor was sequestered in the cytoplasm and was prevented from associating with its cellular targets. Immunoprecipitation of endogenous pericentrin also pulled down cytoplasmic dynein in untransfected cells. To define the basis for this interaction, pericentrin was coexpressed with cytoplasmic dynein heavy (DHCs), intermediate (DICs), and light intermediate (LICs) chains, and the dynamitin and p150(Glued) subunits of dynactin. Only the LICs coimmunoprecipitated with pericentrin. These results provide the first physiological role for LIC, and they suggest that a pericentrin-dynein interaction in vivo contributes to the assembly, organization, and function of centrosomes and mitotic spindles.


Adhesion and proliferation of human mesenchymal stem cells from dental pulp on porous silicon scaffolds.
In regenerative medicine, stem-cell-based therapy often requires a scaffold to deliver cells and/or growth factors to the injured site. Porous silicon (pSi) is a promising biomaterial for tissue engineering as it is both nontoxic and bioresorbable. Moreover, surface modification can offer control over the degradation rate of pSi and can also promote cell adhesion. Dental pulp stem cells (DPSC) are pluripotent mesenchymal stem cells found within the teeth and constitute a readily source of stem cells. Thus, coupling the good proliferation and differentiation capacities of DPSC with the textural and chemical properties of the pSi substrates provides an interesting approach for therapeutic use. In this study, the behavior of human DPSC is analyzed on pSi substrates presenting pores of various sizes, 10 ± 2 nm, 36 ± 4 nm, and 1.0 ± 0.1 μm, and undergoing different chemical treatments, thermal oxidation, silanization with aminopropyltriethoxysilane (APTES), and hydrosilylation with undecenoic acid or semicarbazide. DPSC adhesion and proliferation were followed for up to 72 h by fluorescence microscopy, scanning electron microscopy (SEM), enzymatic activity assay, and BrdU assay for mitotic activity. Porous silicon with 36 nm pore size was found to offer the best adhesion and the fastest growth rate for DPSC compared to pSi comporting smaller pore size (10 nm) or larger pore size (1 μm), especially after silanization with APTES. Hydrosilylation with semicarbazide favored cell adhesion and proliferation, especially mitosis after cell adhesion, but such chemical modification has been found to led to a scaffold that is stable for only 24-48 h in culture medium. Thus, semicarbazide-treated pSi appeared to be an appropriate scaffold for stem cell adhesion and immediate in vivo transplantation, whereas APTES-treated pSi was found to be more suitable for long-term in vitro culture, for stem cell proliferation and differentiation.


[Specific local anesthesia: pharmacology, administration and clinical use (author's transl)].
In order to achieve an optimal combination of principal and side effects of the various drugs used in local anesthesia, a thorough knowledge of pharmacology, anatomy and physiology is essential. The properties of the most commonly used short-acting (Lidocain) medium (Mepivacain) and long-acting (Bupivacain) local anesthetics are described, as well as the effect of the vasoconstrictors Adrenalin and Ornipressin, and of hyaluronidase. The advantages and drawbacks of the different application modalities are discussed. In clinical practice, the surgeon has to be aware of his particular local anesthetic needs at any given time and any stage of the operation, and should attempt to create ideal conditions by careful selection, combination and application of the different drugs. The choice is relatively easy in operations on the globe, the eye muscles and the lacrimal drainage system. In major lid operations, however, greater differentiation in the selection of drugs and methods of application is advisable.


Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction.
Idiosyncratic drug-induced liver injury (iDILI) encompasses the unexpected harms that prescription and non-prescription drugs, herbal and dietary supplements can cause to the liver. iDILI remains a major public health problem and a major cause of drug attrition. Given the lack of biomarkers for iDILI prediction, diagnosis and prognosis, searching new models to predict and study mechanisms of iDILI is necessary. One of the major limitations of iDILI preclinical assessment has been the lack of correlation between the markers of hepatotoxicity in animal toxicological studies and clinically significant iDILI. Thus, major advances in the understanding of iDILI susceptibility and pathogenesis have come from the study of well-phenotyped iDILI patients. However, there are many gaps for explaining all the complexity of iDILI susceptibility and mechanisms. Therefore, there is a need to optimize preclinical human in vitro models to reduce the risk of iDILI during drug development. Here, the current experimental models and the future directions in iDILI modelling are thoroughly discussed, focusing on the human cellular models available to study the pathophysiological mechanisms of the disease and the most used in vivo animal iDILI models. We also comment about in silico approaches and the increasing relevance of patient-derived cellular models.


Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project).
To evaluate the diagnostic sensitivity of antibodies to cyclic citrullinated peptide (CCP) in recent onset rheumatoid arthritis (RA) at diagnosis and 3 years later, and to evaluate anti-CCP antibody as a predictor of the disease course during 3 years. 242 patients with recent onset (< or =1 year) RA were followed up regularly during 3 years after inclusion in the Swedish multicentre study "TIRA" 1996-98. Anti-CCP antibodies were analysed by an enzyme immunoassay (EIA). Rheumatoid factors (RFs) were analysed by latex agglutination and two isotype-specific (IgM and IgA) EIAs. Disease activity was assessed by plasma CRP, ESR, 28 joint disease activity score, and the physician's global assessment of disease activity. Functional ability was evaluated by the Health Assessment Questionnaire. Overall, the diagnostic sensitivity of anti-CCP antibodies was 64% and the proportion of positive tests increased with the number of fulfilled classification criteria according to the American College of Rheumatology. The anti-CCP antibody results correlated with RF, but were better than RF as predictor of a more aggressive disease course. After 3 years 5/97 patients had changed anti-CCP status: 2 from negative to positive and 3 from positive to negative. The mean level of anti-CCP antibodies declined by 131 U/ml during the 3 year follow up (95% CI 34 to 228 U/ml). The anti-CCP antibody assay has a similar diagnostic sensitivity to that of RF in early RA, but is better as a predictor of the disease course over 3 years. Although the mean serum level declines, anti-CCP antibody positivity remains essentially unaltered 3 years after diagnosis and start of antirheumatic treatment.


[Effects of two trypanosomicide drugs, gention violet and WR6026, on platelet concentrates preservation].
In order to verify the viability of platelet concentrate during its preservation period when added with two trypanosomicidal chemical substances, gentian violet and quinoline WR6026, we tested these concentrates and verified the following parameters: number of platelets, pH and platelet aggregation test with a pair of agonists. Significant alterations were observed in the platelet concentrate treated with gentian violet suggesting important damage to the platelet viability. With WR6026 similar values to the controls were observed, opening new perspectives for the utilization of this salt for the chemoprophylaxis of transfusional Chagas' disease in highly endemic regions.


Unification of neural and wavelet networks and fuzzy systems.
This paper analyzes several commonly used soft computing paradigms (neural and wavelet networks and fuzzy systems, Bayesian classifiers, fuzzy partitions, etc.) and tries to outline similarities and differences among each other. These are exploited to produce the weighted radial basis functions paradigm which may act as a neuro-fuzzy unification paradigm. Training rules (both supervised and unsupervised) are also unified by the proposed algorithm. Analyzing differences and similarities among existing paradigms helps to understand that many soft computing paradigms are very similar to each other and can be grouped in just two major classes. The many reasons to unify soft computing paradigms are also shown in the paper. A conversion method is presented to convert perceptrons, radial basis functions, wavelet networks, and fuzzy systems from each other.


Malignancy risk in patients with giant cell arteritis: a population-based cohort study.
To determine the incidence of cancer in a population-based cohort of patients with giant cell arteritis (GCA) compared with age- and sex-matched referent subjects. Using the resources of the Rochester Epidemiology Project, all incident cases of GCA diagnosed between January 1, 1950 and December 31, 2004 were identified. For each GCA patient, 2 subjects without GCA of the same sex and similar age and length of medical history were selected. Diagnosis of malignancy was made by histopathology. Patients were followed until death, last contact, or December 31, 2006. Our study included 204 GCA patients and 407 non-GCA subjects. The GCA cohort had 163 (79%) women and 41 (21%) men, a mean +/- SD age of 76.0 +/- 8.2 years, and a median followup of 7.7 years. The non-GCA cohort consisted of 325 (80%) women and 82 (20%) men, a mean +/- SD age of 75.6 +/- 8.4 years, and a median followup of 8.1 years. During followup, 46 GCA patients and 76 non-GCA subjects developed cancer (hazard ratio [HR] 1.26, 95% confidence interval [95% CI] 0.87-1.83). Adjustment for smoking did not alter the results. The 1-, 10-, and 20-year cumulative incidences of any malignancy were 5.9%, 33.6%, and 50.0% among GCA patients and 2.6%, 27.0%, and 47.0% among non-GCA patients, respectively. There were no differences in hematologic or solid malignancies between both groups. Colon cancer appeared more commonly in the GCA group (P = 0.07). Mortality following cancer was similar in both cohorts (HR 0.80, 95% CI 0.52-1.24). GCA patients are not at an increased risk of first cancer after diagnosis.


FiCRoN, a deep learning-based algorithm for the automatic determination of intracellular parasite burden from fluorescence microscopy images.
Protozoan parasites are responsible for dramatic, neglected diseases. The automatic determination of intracellular parasite burden from fluorescence microscopy images is a challenging problem. Recent advances in deep learning are transforming this process, however, high-performance algorithms have not been developed. The limitations in image acquisition, especially for intracellular parasites, make this process complex. For this reason, traditional image-processing methods are not easily transferred between different datasets and segmentation-based strategies do not have a high performance. Here, we propose a novel method FiCRoN, based on fully convolutional regression networks (FCRNs), as a promising new tool for estimating intracellular parasite burden. This estimation requires three values, intracellular parasites, infected cells and uninfected cells. FiCRoN solves this problem as multi-task learning: counting by regression at two scales, a smaller one for intracellular parasites and a larger one for host cells. It does not use segmentation or detection, resulting in a higher generalization of counting tasks and, therefore, a decrease in error propagation. Linear regression reveals an excellent correlation coefficient between manual and automatic methods. FiCRoN is an innovative freedom-respecting image analysis software based on deep learning, designed to provide a fast and accurate quantification of parasite burden, also potentially useful as a single-cell counter.


Alternatives for sustained disaster risk reduction: A re-assessment.
Alternatives for sustained disaster risk reduction' was published in 2010 by Francophone and Anglophone researchers as a critique on the way disasters were studied and disaster risk reduction handled in the Francophone sphere. The authors criticized the dominant Francophone approach for being heavily hazard-centred and called for more emphasis on vulnerability to understand disasters and foster disaster risk reduction - a shift that had already taken place in the Anglophone disaster literature. Twelve years later, this paper draws upon a bibliographic analysis to examine if the arguments developed in the 2010 publication have stem attention in the Francophone disaster literature. The article finds that the shift towards the vulnerability paradigm has, to some extent, happened but took much longer in the French context than in the Spanish language and the Asian disaster literature. The article emphasises the need for a re-assessment of our practices and study of disasters, including reflections on what disasters are studied, how, by whom, and for whom. Eventually, alternatives for sustained disaster risk reduction now and in the future might include drawing upon more diverse ontologies and epistemologies that are pertinent locally, considering local people as co-researchers though participatory methods, and empowering local Francophone researchers to play a greater role in researching disasters and leading disaster risk reduction in their own localities.


[Evaluation of malaria cases in Diyarbakir between 1999 and 2004].
In this study; we investigated the prevalence and distribution of malaria in the city of Diyarbakir, retrospectively. The investigation was carried out according to age, gender and areas of settlement between 1999 and 2004. The records were obtained from the Health Directorship of the Ministry of Health in Diyarbakir. A total of 22,062 malaria cases (11,643 male, 10,419 female) had been reported during a period of five years. Compared to previous years, the prevalence of malaria had significantly decreased. However; since the geographic conditions in Diyarbakir are suitable for the reproduction of Anopheles spp. and malaria is still endemic in Diyarbakir, the fight against malaria should be continued.


Risk of fractures associated with treatment for benign prostate hyperplasia in men.
Treatment of benign prostate hyperplasia with α-blockers may affect blood pressure while treatment with 5-α-reductase inhibitors may affect conversion of testosterone potentially leading to osteoporosis. In our study, neither 5-α-reductase inhibitors nor α-blockers were associated with negative effects on fractures, α-blockers perhaps being associated with a limited decrease in fractures. The objective is to study fracture risk associated with drugs for benign prostate hyperplasia. The hypotheses were that (1) α-blockers may elevate fracture risk by causing presyncope/falls and (2) 5-α-reductase inhibitors may elevate fracture risk by lowering dihydrotestosterone. This is a nationwide case-control study using all 9,719 male fracture patients aged ≥60 years in the year 2000 as cases and drawing 29,156 age- and gender-matched controls. The main exposure was the use of the drugs mentioned above for benign prostate hyperplasia. Confounder control included social variables, contacts to hospitals and general practitioners, alcoholism and other variables. For the 5-α-reductase inhibitors, no change in overall risk of fractures was seen. No change in risk of hip, spine and forearm fractures was present. For the α-blockers, a decrease in overall risk of fractures was seen, as well as a decrease in the risk of hip and spine fractures, but only at average doses >0.5 defined daily doses per day. No decrease was seen for forearm fractures. A decreasing risk of any fracture, hip fractures and spine fractures were seen with increasing dose of α-blockers, while no such association was seen for the forearm fractures. Neither the 5-α-reductase inhibitors nor α-blockers were associated with negative effects on fracture risk. A small trend towards a decrease in fracture risk may be present for the α-blockers. However, more research is needed to confirm if this trend is real.


Prognostic impact of node involvement pattern in pulmonary pN1 squamous cell carcinoma patients.
Lymph node involvement is one of the most important prognostic factors in cancer patients. It is categorized based on the anatomic extent, but differences in node involvement patterns are not incorporated in the tumor, node, metastasis classification. Squamous cell carcinoma more frequently arises in the central airway and invades adjacent lymph nodes directly than the other histologic types. The purpose of this study was to evaluate the prognostic impact of lymph node involvement patterns in pulmonary pN1 SCC patients. We reviewed 120 consecutive patients with completely resected pN1 squamous cell carcinoma and classified them into two groups based on node involvement pattern: direct (all metastatic N1 nodes involved directly by the main tumor) and separate (one or more metastatic N1 nodes not directly involved by the main tumor) N1 groups. To compare the survival probability, 302 pN0 patients and 59 pN2 patients were also investigated. Univariate and multivariate analyses showed that the N1 node involvement pattern significantly associated with patient prognosis. The direct N1 group resulted in a much better 5-year overall survival rate of 67.7% compared with 32.4% for the separate N1 group (p < 0.01). The direct N1 group survival curve almost overlapped with the pN0 curve (p = 0.68), whereas the separate N1 group curve overlapped with the pN2 curve (p = 0.91). Direct N1 metastatic cases are highly curable, similar to pN0 patients. In contrast, separate N1 metastatic cases are destined to poor prognosis similar to pN2 patients.


Soliton trapping in fiber lasers.
We report on the soliton trapping in a fiber ring laser modelocked with a SESAM. It was observed that solitons along the two orthogonal polarization directions of the cavity with fairly large difference in central frequency and energy could be coupled together to form a group velocity locked vector soliton. In particular, due to that each of the coupled solitons forms its own soliton sidebands, two sets of soliton sidebands could be observed on the vector soliton spectrum. Numerical simulations have well confirmed the experimental observations.


Cardiac sympathetic afferent reflex control of cardiac function in normal and chronic heart failure states.
Cardiac sympathetic afferents are considered to be essential pathways for transmission of cardiac nociception to the central nervous system during myocardial ischaemia. However, a potential contribution of the CSAR control of cardiac dysfunction in both normal and chronic heart failure (CHF) states remains unknown. We found that activation of the CSAR evokes little increase in cardiac contractility with an exaggerated peripheral vasoconstriction in the CHF state. CSAR inhibition by epicardial lidocaine decreased cardiac contractility to a greater extent in CHF rats than sham rats. Furthermore, we also found that epicardial lidocaine paradoxically decreased left ventricular end-diastolic pressure (LVEDP) and left ventricular end-diastolic volume (preload) in CHF rats, which was not observed in sham rats. Chronic ablation of the CSAR by epicardial application of the afferent neurotoxin, RTX, selectively lowered diastolic blood pressure CHF rats. The observation suggests that CSAR has a differential effect on cardiac function in normal and CHF states. CSAR activation in normal state causes significant increase in cardiac contractility and cardiac output. The enhanced 'cardiac sympathetic afferent reflex' (CSAR) critically contributes to the exaggerated global sympathetic tone in chronic heart failure (CHF). However, a potential contribution of the cardio-cardiac reflex control of cardiac function in both normal and CHF states remains unknown. In this study, we evaluated the effects of direct activation or inhibition of the CSAR on cardiac function by pressure-volume (P-V) loop analysis in ∼12-week sham-operated and myocardial infarcted (MI) rats. In sham rats, acute CSAR activation by epicardial application of bradykinin (BK) increased heart rate (HR), left ventricular systolic pressure (LVSP), the maximum first derivative of left ventricular pressure (dp/dtmax ), and the slope of the end-systolic P-V relationship (ESPVR), suggesting that acute CSAR activation in the normal state enhances myocardial contractility. CSAR activation also decreased left ventricular (LV) systolic and diastolic volumes with little effect on LV end-diastolic pressure (LVEDP) or the end-diastolic P-V relationship (EDPVR) in sham rats. Compared to sham, CHF rats exhibit a reduced increase in the slope of the ESPVR and dp/dtmax in response to BK, indicating a poor contractile response to CSAR activation. Interestingly, BK application in CHF rats increased cardiac systolic and diastolic volumes and further increased the elevated LVEDP, neither of which was seen in sham rats. Following CSAR inhibition by epicardial lidocaine, blood pressure, HR, LVSP, dp/dt, LVEDP and ESPVR decreased in CHF rats whereas lidocaine had little effect in sham rats, indicating that the CSAR is tonically active in CHF and contributes to cardiac dysfunction. Furthermore, we found that epicardial lidocaine paradoxically decreased LV end-diastolic volume (preload) in CHF rats, which was not observed in sham rats. The decreased preload by lidocaine in CHF rats may be due to a reduction in peripheral vascular resistance since epicardial lidocaine significantly lowered peripheral (renal) sympathetic nerve activity in CHF rats but not in sham rats. Furthermore, chronic ablation of CSAR by epicardial application of a selective afferent neurotoxin, resiniferatoxin, selectively lowered diastolic blood pressure both at daytime and night-time with less effect on systolic blood pressure in CHF rats. Our data suggest that there is an imbalance between cardiac and peripheral responses to CSAR in CHF animals compared to sham-operated controls.


Magnetization transfer histogram parameters reflect all dimensions of MS pathology, including atrophy.
Magnetization transfer ratio (MTR) histogram analysis can be used as a method for quantifying overall disease burden in MS. We studied correlations between MTR histogram and clinical parameters in MS subgroups. Contrary to earlier studies we placed special emphasis on the lower MTR range, to explore the effect of partial volume averaging effects with CSF. Seventy-nine patients with MS [26 primary progressive (PP), and 53 'relapse-onset', including 26 secondary progressive (SP)], and 23 healthy individuals were studied. MR imaging included 3 mm 2D gradient-echo images with and without an off-resonance MT pulse. According to the visually determined cut-off, histogram parameters were classified as parenchymal or CSF-related variables. Clinical measurements included the Expanded Disability Status Scale (EDSS) as a measure of global impairment/disability and the Paced Auditory Serial Addition Test (PASAT) as a measure of cognition. SP MS patients differed from the other subgroups on many MTR variables, originating from both the lower and the higher MTR range. CSF-related low MTRs were clearly over-represented in SP patients, and showed a significant distinction between the SP and PP MS group. In the total group, as well as in the relapse-onset patients, significant correlations were found between MTR parameters and clinical parameters. No associations were found in the PP group. This explorative study suggests that MTR histogram analysis can distinguish between MS patients and controls, and best identifies the SP phenotype, partly as a result of increased CSF volume (atrophy). In addition, we show that MTR histogram analysis gives information about the level of impairment and disability in patients with a 'relapse-onset' course of MS, and therefore provides a useful tool to monitor the evolution of the disease in these patients.


Diet and food partitioning between juveniles of mutton Lutjanus analis, dog Lutjanus jocu and lane Lutjanus synagris snappers (Perciformes: Lutjanidae) in a mangrove-fringed estuarine environment.
Diet of juvenile mutton Lutjanus analis, dog Lutjanus jocu and lane Lutjanus synagris snappers were studied in the tropical Brazilian estuarine system of the Piraquê-açú and Piraquê-mirim Rivers to determine how these species share the resources in this restricted space. The three species prey principally upon Peracarida (L. synagris: relative importance index I(RIc) = 29%), Natantia (L. analis and L. synagris: I(RIc) = 39 and 38%, respectively), Reptantia (L. analis and L. jocu: I(RIc) = 28 and 43%, respectively) and Teleostei (L. jocu: I(RIc) = 24%). The three species use estuaries as nursery habitats but food overlap was not biologically significant due to a combination of interspecific differences in size, spatial distribution, microhabitat preferences and seasonal patterns of abundance and prey choice. Large marine protected areas incorporating essential habitats for all life stages are suggested to be the best tool for the management of these economically important species.


Influence of birth-related maternal and neonatal factors on the levels of energy metabolism mediators in infants born at 32 or fewer weeks of gestation.
Energy metabolism mediators, which include the adipokines (leptin, adiponectin, ghrelin) and insulin-like growth factor 1 [IGF-1], are hormone-like proteins, produced and expressed in the placenta and fetal membranes, with properties featuring metabolic adaptation and inflammatory processes. Due to the complexity of the metabolic adaptation of preterm neonates during the transition to extrauterine life, it becomes essential to recognize the factors that influence the alteration of the adipokines and IGF-1 levels in the early postpartum stage.This study assessed the significance of maternal-fetal-neonatal factors in predicting the levels of leptin, adiponectin, ghrelin, and IGF-1 in preterm infants born at 32 or fewer weeks of gestation, during the early stage of postnatal adaptation. Energy metabolism mediator levels were measured in urine samples obtained from extremely (less than 28 weeks) and very (28-32 weeks) preterm infants, within 48 h after their birth, and before the initiation of enteral nutrition. The urine samples were analyzed using enzyme-linked immunosorbent assay (ELISA) kits. The collected data included all birth-related maternal and neonatal factors such as maternal age, race/ethnicity, hypertensive disorders of pregnancy, diabetes, gravidity, parity, type of pregnancy, mode of delivery, and antenatal use of corticosteroids, antibiotics, magnesium sulfate, Apgar scores at 1 and 5 min, gestational age, and birth weight. We investigated the correlation between the levels of the tested mediators, the significance of the differences in their average levels based on the dichotomized maternal and neonatal factors, and the effect of the selected factors, in multiple regression models. Data from the regression models constructed for leptin, adiponectin, ghrelin, and IGF-1 are presented as regression coefficient β with Standard Error (SE) of β, coefficient of determination (R2), and adjusted R2. Before including the factor in regression models, we tested for the multicollinearity effect. Two-sided P values <0.05 were considered statistically significant. Among the 70 studied infants, 47.1% were male, 40.6% were white, 28.6% were extremely preterm, and 18.6% were born with a weight <750 grams. Except for a mild interplay between the adiponectin and IGF-1 levels, there was no correlation between the levels of the other studied mediators. Up to 20% variation in the tested energy metabolism mediator levels was dependent on some of the birth-related maternal and neonatal characteristics. For instance, leptin levels were reduced in association with male gender (-0.493 [0.190], p < 0.02) and increased in infants born to primigravids (0.562 [0.215], p < 0.02). Adiponectin levels were increased in infants born to nulliparous as compared to multiparous women (0.400 [0.171], p < 0.03). Ghrelin levels were reduced in males (-0.057 [0.026], p < 0.04). IGF-1 levels were increased in the urine of extremely preterm neonates (0.357 [0.111], p < 0.01) and preterm infants born with an Apgar less than three at 1 min (0. 340 [p < 0.153], p < 0.04). Nearly one-fifth of the variation in the urinary levels of the adipokines (leptin, adiponectin, ghrelin) and IGF-1 during the early postnatal stage in infants born at 32 or fewer weeks of gestation was predicated on one or more of the maternal and neonatal factors such as the infant's sex, extreme preterm gestation, a low Apgar score at 1 min, or birth to nulliparous women or primigravida mothers. Further studies will be required to explain the role of energy metabolism mediators in the postnatal adaptation of preterm-born infants.


Variability of skin temperature in the waking monkey.
Temperatures of the brain, skin, and nasal mucosa were recorded along with the cortical electroencephalogram (EEG) in chaired, conscious pigtail monkeys at 25 degrees C air temperature. In undisturbed animals, skin temperatures ranged from 34 to 37 degrees C. When the animal was alerted by visual or auditory stimuli, temperatures on the extremities, tail, nose, ears, and nasal mucosa dropped rapidly to 22-29 degrees C. Temperatures on the proximal limbs and trunk and most of the head remained steady at all times. Average hypothalamic temperature was 0.91 degrees C higher when the extremities, tail, nose, ears, and nasal mucosa were cool than when they were warm, the brain temperature change beginning 80-120 s after the change in peripheral temperatures. A slight decrease in EEG frequency, but no change in amplitude, occurred during skin warming. Anesthetic doses of barbiturate led to a rapid rise in temperature of the extremities, tail, nose, ears, and nasal mucosa and a drop in brain temperature. These large changes in skin temperature in conscious monkeys reflect changes in cutaneous blood flow, the resulting alteration in heat loss leading to a rapid change in deep body temperature. The experiments demonstrate the importance of the state of arousal on autonomic nervous control of peripheral vasomotor tone in the monkey.


[Hypoglycemia in the newborn infant subsequent to hyperplasia of beta cells of the pancreas].
A case of hypoglycemia of difficult control and resistant to treatment due to hypersinsulinism as a result of hypertrophy of beta celis of the pancreas in the newborn perior is analyzed. Based on this case, hypoglycemia of the newborn is discussed, analyzed etiology, pathogenesis, symptomatology, diagnosis and treatment. Emphasis is place on the lack of clear symptoms and signs at this age, on the differential diagnosis, on the entities with which it can be associated or confused, and on the need to make an early diagnosis in order to prevent brain damage.


Effects of procedure, upright equilibrium time, sex and BMI on the precision of body fluid measurements using bioelectrical impedance analysis.
Extensive work has addressed the validity of bioimpedance (BIA) measurements and the effect of posture on fluid homeostasis. However, limited research has investigated effects of subject preparation. This study aimed to determine the precision of total body water (TBW) and extracellular water (ECW) measurements using a stand-on multifrequency BIA (MFBIA seca mBCA 514/515), in three pre-test procedures: supine, sitting, and following walking, with specific reference to the influence of sex and body mass index (BMI). Fifty three healthy, ambulatory men (n=26, age:32.5±9.4 years) and women (n=27, age:35.2±10.3 years) received repeat MFBIA measurements (six measurements from 0 to 15 min). Agreement and precision were evaluated for each condition and paired time points. Significant TBW sex differences from supine posture were observed for walking (females) and sitting (males) postures. For BMI (⩽24.9 kg m-2) significant TBW differences from supine were observed for both sitting and walking and significant ECW differences from sitting were also observed with both supine and walking. There was no significant effect of sex or BMI (⩾25.0 kg m-2) on ECW measures. Irrespective of sex or BMI, there was close agreement in TBW and ECW precision over the three protocols. Practitioners can have confidence in the precision of TBW and ECW measurements within a 15 min time period and pre-testing conditions (supine, sitting or walking) in healthy subjects, though must be cautious in assessments when pre-test postures change. Further research to examine the impact of pre-testing procedures on stand-on MFBIA BIA measurements, including subjects with fluid disturbance, is warranted.


The complications of scar formation associated with intrathecal pump placement.
A 40-year-old man had an intrathecal morphine-baclofen pump inserted for the treatment of severe dystonia affecting all limbs and severe low back pain. The etiology of his dystonic symptoms, despite thorough investigations, was uncertain. At age 45, the patient fell resulting in a cervical spinal cord injury. He underwent C2 through C5 instrumentation and fusion for cervical spine stabilization. Subsequently, an intrathecal morphine-baclofen pump was implanted to control pain and decrease spasticity. The patient ultimately died at age 48 from complications of pneumonia, and an autopsy was performed. Gross pathologic examination revealed that the intrathecal catheter entered the posterior aspect of the lumbar thecal sac, but coursed superiorly in the anterior intradural space. The catheter tip exited the thecal sac in the upper thoracic spine and became embedded in a fibrotic scar. Displacement of the catheter tip of the intrathecal morphine-baclofen pump and subsequent formation of scar tissue resulted in decreased drug delivery, contributing to diminished pain control and functional status. Catheter displacement and epidural scar formation must be considered as a potential cause of ineffective pain control and decreased functional status in patients with intrathecal morphine-baclofen pumps.


Characterization of a monoclonal antibody, RTE-21, that binds to keratohyalin granule-associated proteins in epithelial cells of human skin and thymus.
The role of skin and thymic epithelium in the promotion of T-cell activation and maturation is currently an area of great interest. In thymus, epithelium is located in the cortex, medulla, and in medullary epithelial swirls called Hassall's bodies. During studies of antigens shared by skin and thymic epithelial cells, we produced a murine monoclonal antibody (RTE-21) raised against the rat thymic epithelial cell line, IT26R21, that identified an antigen present in terminally differentiated epithelium of normal human skin and thymus. In indirect immunofluorescence studies, antibody RTE-21 identified cytoplasmic granules located in the stratum granulosum of normal human skin, Hassall's bodies of human thymus, and in a subset of cells of the IT26R21 rat thymic epithelial cell line. Moreover, the granular reactivity pattern of antibody RTE-21 in the stratum granulosum could be extracted by 1 M potassium phosphate (1 M KPO4). A 1 M KPO4 extract of epidermis containing keratohyalin granule proteins was dialyzed against distilled water, solubilized in reduced sample buffer and subjected to polyacrylamide gel electrophoresis and Western immunoblot analysis. In this assay, antibody RTE-21 recognized proteins of 70, 36, 34, and 30 kDa. Using antibody RTE-21 and indirect immunofluorescence, we demonstrated that keratohyalin granules in human thymus were localized exclusively to Hassall's bodies. These data support the notion that human thymic Hassall's bodies result from terminal differentiation of medullary thymic epithelium. Thus, antibody RTE-21 should be an important probe for the study of skin and thymic epithelial cell maturation in vitro and in vivo.


The gas-phase dipeptide analogue acetyl-phenylalanyl-amide: a model for the study of side chain/backbone interactions in proteins.
The issue of the influence of the side chain/backbone interaction on the local conformational preferences of a phenylalanine residue in a peptide chain is addressed. A synergetic approach is used, which combines gas-phase UV spectroscopy as well as gas-phase IR/UV double-resonance experiments with DFT and post Hartree-Fock calculations. N-Acetyl-Phe-amide was chosen as a model system for which three different conformers were observed. The most stable conformer has been identified as an extended beta(L) conformation of the peptide backbone. It is stabilized by a weak but significant NH-pi interaction bridging the aromatic ring on the residue (i) with the NH group on residue (i+1), with the aromatic side chain being in an anti conformation. This stable conformation corresponds to the common NH(i+1)-aromatic(i) interaction encountered in proteins for the three aromatic residues (phenylalanine, tyrosine, and tryptophan), which illustrates the relevance of gas-phase investigations to structural biology issues. The two other less abundant conformers have been assigned to two gamma-folded backbone conformations that differ by the orientation of the side chain. In all cases, the IR data provided spectroscopic fingerprints of these interactions. Finally, the strong conformational dependence of the fluorescence yield found for N-acetyl-Phe-amide illustrates the role of the environment on the excited-state dynamics of these species, which is often exploited by biochemists to monitor protein structural changes from tryptophan lifetime measurements.


Preference for children and subsequent fertility in Matlab: does wife-husband agreement matter?
This study examines wife-husband preference for children and subsequent fertility for a period of 5 years in the treatment and comparison areas of Matlab, Bangladesh. The two data sets used were: the In-depth Survey (1984) and the Demographic Surveillance System (1984-89). In the case of wives' preferences for children, subsequent childbearing was 13.8% higher than desired in the treatment area and 44.7% higher than desired in the comparison area. After controlling for all variables in the model, the likelihood of giving birth was 1.78 times higher for wives who wanted no more children, but whose husbands did want more, compared with couples where neither husband nor wife wanted more children. For couples where the wife wanted more, but the husband did not want more children, the likelihood of giving birth was 0.63 times that of couples where both the husband and wife wanted more children. This finding suggests that to enhance the decline in fertility in these two areas of Matlab, it will be necessary to motivate both wives and husbands to cease childbearing.


Preclinical Pharmacokinetics and Pharmacodynamic Target of SCY-078, a First-in-Class Orally Active Antifungal Glucan Synthesis Inhibitor, in Murine Models of Disseminated Candidiasis.
SCY-078 (MK-3118) is a novel, semisynthetic derivative of enfumafungin and represents the first compound of the triterpene class of antifungals. SCY-078 exhibits potent inhibition of β-(1,3)-d-glucan synthesis, an essential cell wall component of many pathogenic fungi, including Candida spp. and Aspergillus spp. SCY-078 is currently in phase 2 clinical development for the treatment of invasive fungal diseases. In vitro disposition studies to assess solubility, intestinal permeability, and metabolic stability were predictive of good oral bioavailability. Preclinical pharmacokinetic studies were consistent with once-daily administration to humans. After intravenous delivery, plasma clearance in rodents and dogs was low, representing <15% and <25% of hepatic blood flow, respectively. The terminal elimination-phase half-life was 5.5 to 8.7 h in rodents, and it was ∼9.3 h in dogs. The volume of distribution at steady-state was high (4.7 to 5.3 liters/kg), a finding suggestive of extensive tissue distribution. Exposure of SCY-078 in kidney tissue, a target organ for invasive fungal disease such as candidiasis, exceeded plasma by 20- to 25-fold for the area under the concentration-time curve from 0 h to infinity (AUC0-∞) and Cmax SCY-078 achieved efficacy endpoints following oral delivery across multiple murine models of disseminated candidiasis. The pharmacokinetic/pharmacodynamic indices Cmax/MIC and AUC/MIC correlated with outcome. Target therapeutic exposure, expressed as the plasma AUC0-24, was comparable across models, with an upper value of 11.2 μg·h/ml (15.4 μM·h); the corresponding mean value for free drug AUC/MIC was ∼0.75. Overall, these results demonstrate that SCY-078 has the oral and intravenous (i.v.) pharmacokinetic properties and potency in murine infection models of disseminated candidiasis to support further investigation as a novel i.v. and oral treatment for invasive fungal diseases.


[Clinical study of the effectiveness of a preservative-free tear substitute].
57 patients with dry eye syndrome of various etiology were treated with a preservative-free hydrogel in an open clinical trial. All patients enrolled in the 12 weeks study had a history of pretreatment with usual commercial tear substitutes which was either insufficient for relief of complaints or caused hypersensitivity. Detailed analysis of patients self assessment of their condition (by means of a linear scale), tear film break-up time, Schirmer Test, and physician's assessment of therapeutical results revealed that in about 90% of cases existing patient complaints and findings related to dry eye syndrome were significantly improved by symptomatic therapy with this preservative-free gel.


[Haemorrhagic proctocolitis as primary manifestation of lymphogranuloma venereum in an HIV-positive male].
This is a case report of lymphogranuloma venereum (LGV) manifesting as haemorrhagic proctocolitis in a homosexual HIV-positive male. The primary symptom was a rectal abscess, which was initially surgically treated and subsequently insufficiently treated with single-dose tablet azithromycin. The patient's symptoms were successfully treated after a 21-day doxycycline regime. LGV is a sexually transmitted infection with a rising incidence among persons with risk behaviour. This case report underlines the importance, that all positive rectal screenings for Chlamydia trachomatis should be routinely serotyped.


Structured team approach to the agitated patient in the emergency department.
Behavioural disturbance and aggression in the ED is an increasing problem. The present study describes the characteristics of patients with acute behavioural disturbance and their emergent treatment in an ED with a structured team approach. This was a retrospective review of acute behavioural emergencies that required response from the Code Black (CB) Team (duress response team) in the ED during 2006. The hospital security log and hospital incident-reporting system identified all documented CB, and the patients' medical records were reviewed. Information extracted included patient demographics and presenting complaint, details of the CB, the use of pharmacological sedation, physical restraint and patient disposition. Injuries to hospital staff were also extracted. There were 122 patients, median age 32 years (interquartile range: 24-43 years, range: 14-81 with 71 male patients (58%) who accounted for 143 CB activations. The primary problems were deliberate self-poisoning or self-harm (38%), alcohol and illicit drug intoxication (33%) and psychiatric, organic illness and drug withdrawal (29%). One hundred and eight (89%) patients had a past history of alcohol/illicit drug abuse or psychiatric illness. Indications for CB activation were threatening harm to others or behaving violently in 67% of cases. Combined pharmacological sedation and physical restraint were required on 66 (46%) occasions, pharmacological sedation alone on 20 (14%), physical restraint alone on 14 (10%) and neither on 43 (30%) occasions. Benzodiazepines were most commonly used for initial sedation, including i.m. (29%), i.v. midazolam (20%), diazepam (42%) and antipsychotics (9%), most commonly droperidol. More diazepam and droperidol were used for subsequent pharmacological sedation. A staff member was injured on only one occasion (0.7%). Acute behavioural disturbance was common in the present study, and underlying causes were predominantly organic in nature. A team approach appears to be valuable in managing these incidents.


Opioids for the Treatment of Chronic Pain: Mistakes Made, Lessons Learned, and Future Directions.
An overreliance on opioids has impacted all types of pain management, making it undoubtedly a root cause of the "epidemic" of prescription opioid abuse in the United States. Yet, an examination of the statistics that led the US Centers for Disease Control and Prevention to declare that prescription opioid abuse had reached epidemic levels shows that the abuse occurrences and deaths are arising outside the hospital or hospice setting, which strongly implicates the outpatient use of opioids to treat chronic pain. Such abuse and related deaths are occurring in chronic pain patients themselves and also through diversion. Overprescribing to outpatients has afforded distressed and vulnerable individuals access to these highly addictive drugs. The focus of this article is on what we have learned since opioid treatment of chronic pain was first popularized at the end of the 20th century and how this new information can guide chronic pain management in the future.


[Treatment of functional ileus: adrenergic blockade and stimulation (author's transl)].
Intestinal stimulation is among the basic therapeutic procedures in functional ileus. But the majority of cases of functional ileus is due not to paralysis but to adrenergic inhibition. Thus the primary treatment should not be to stimulate but to act against the inhibition. In over 100 patients a combined treatment schedule consisted of primary adrenergic blockade (trifluperidol, dihydroergotamine or chlorpromazine) followed by low doses of stimulants (ceruletide, neostigmine). 52 patients who had not responded to high doses of peristalsis-stimulating drugs acted as their own controls: in 48 of them intestinal function was restored by sympathicolysis. If indications and application are properly observed the method has a low risk and provides effective treatment of functional ileus, especially in cases resistant to other forms of treatment.


[Outcomes of surgical management of patients with thromboses of the superficial and deep venous system].
Presented herein are the outcomes of examination, surgical management and conservative treatment of 211patients presenting with phlebothromboses of the superficial and deep venous system of the lower limbs. Of these, 119 were treated conservatively and 92 underwent various types of surgical intervention, however those treated conservatively were not included into the final analysis. The diagnosis was verified using ultrasonographic duplex scanning (USDS) of the venous system of the inferior vena cava basin, allowing of assessing the condition of the superficial and deep venous system of the both lower extremities, followed by determining the length of the thrombotic lesion. Based on the findings of USDS, 68 (74%) patients were found to have thrombosis of the superficial veins and 24 (26%) subjects were diagnosed with deep-vein thrombosis. All the patients in order to prevent thromboembolic complications were subjected to active surgical policy. Also studied were methods of surgical management in patients with various-localization thromboses. Based on the obtained findings, it was determined that surgical treatment of patients with thromboses of the superficial and deep venous system of the lower limbs is a justified method to prevent the development of pulmonary thromboembolism.


Structural, biochemical, and physiological characterization of photosynthesis in leaf-derived cup-shaped galls on Litsea acuminata.
The source and sink relationships between insect-induced galls and host plant leaves are interesting. In this research, we collected cup-like galls induced by Bruggmanniella sp. (Diptera: Cecidomyiidae) on host leaves of Litsea acuminata and assessed them to investigate source-sink relationships between galls and host leaves. We characterized several of their photosynthetic characteristics including chlorophyll fluorescence (Fv/Fm), stomatal conductance, and photosynthetic capacity, biochemical components such as total soluble sugar, starches, free amino acids, and soluble proteins. The structural analyses were performed under confocal, light, and scanning electron microscopies. Compared with host leaves, galls exhibited slightly lower chlorophyll fluorescence; however, stomatal conductance and photosynthetic capacity were not detected at all. Galls accumulated higher total soluble sugars and free amino acids but less soluble proteins than host leaves. No stomata was observed on exterior or interior gall surfaces under light or scanning electron microscopy, but their inner surfaces were covered with fungal hyphae. Confocal imagery showed a gradient of chloroplasts distribution between gall outer and inner surfaces. Our results strongly suggest that leaf-derived cecidomyiid galls are a type of chlorophyll-deficient non-leaf green tissue and consists on a novel sink in L. acuminate.


[The comparative assessment of follow-up for hypertensive patients].
The quality of outpatient follow-up was compared in hypertensive patients of the primary care system in 1995 vs 1997. Case records have been retrospectively analyzed for 1301 patients and 1335 ones treated in 6 Kemerovo outpatient clinics in 1995 and 1997, respectively. A special sheet was used for recording the data. More investigations of the target organs were made in 1997. An increase was found in the number of tests for total cholesterol, creatinine, blood glucose, blood count, urinalysis, ultrasound scanning of the kidneys and adrenals, ECG. More patients were taking drugs. Adelphan administration decreased by 32%, clophelin by 30%. More frequently were prescribed ACE inhibitors, calcium antagonists, beta-adrenoblockers. Quality of care for hypertensive patients is still low. This is explained by deficient social care, poor medical education of the patients, rejection of active treatment by many patients.


Performance of global assessments of hip, knee, and back symptom change.
The objective of this study is to compare patients' global assessments of change in knee, hip, and back symptoms with actual changes over time in pain, function, and radiographic severity. The participants (n = 894, 80% female, mean age = 66 years) completed two assessments (mean of 4 years apart) as part of a study on the genetics of generalized osteoarthritis. At both assessments, participants completed the Western Ontario and McMaster Universities OA Index (WOMAC), and radiographic severity was assessed for knees, hips, and low back. At the second assessment, participants described changes in knee, hip, and low back symptoms as worse, better, same, or never had symptoms. Analysis of covariance models examined mean changes in WOMAC scores and radiographic severity according to categories of the global assessment measures. Statistical significance was examined for linear trend. Mean WOMAC total, pain, and function scores decreased (indicating improvement) among participants who indicated joint symptoms were better, showed little change among those who reported symptoms were the same/never had symptoms, and increased among those who reported symptoms were worse. For all analyses except the comparison of WOMAC pain change according to global assessment of low back symptom change, there was a statistically significant linear trend (p < 0.05). Patterns were similar for changes in radiographic severity, but the tests of linear trend were not statistically significant. Results support the concordance of these global assessments of joint symptom change with actual changes in self-reported symptoms. These global assessments may be useful for assessing change over time when baseline data are unavailable.


Increased Iron Deficiency and Iron Deficiency Anemia in Children with Zinc Deficiency.
The aim of the present study is to determine the presence of iron (Fe) deficiency and Fe deficiency anemia in children with zinc (Zn) deficiency. This retrospective study comprised 560 patients aged 6 months to 16 years in whom Zn levels in hair samples were measured concurrently with serum levels of ferritin, Fe, Fe-binding capacity, and blood count analysis. For all patients, we retrospectively assessed serum ferritin, serum Fe, Fe-binding capacity, transferrin saturation index, red blood cell count, hemoglobin levels, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution width (RDW). Patients were divided into two groups according to the level of the hair Zn level as Zn deficiency (hair Zn level <100 µg/g) and without Zn deficiency (hair Zn level >100 µg/g). Data were analyzed to determine whether there was a significant difference between any of these parameters and the presence of Fe deficiency and Fe deficiency anemia between patients with and without Zn deficiency. A total of 238 patients had Zn levels <100 µg/g, and 322 patients had Zn levels >100 µg/g. The median ferritin level was 16.2 (9.8-24.9) ng/mL in the Zn-deficient group and 18.7 (12-29.3) ng/mL in those without Zn deficiency group. The presence of Fe deficiency was higher in the Zn deficiency group (60.1%) than in the without Zn deficiency group (50%; p<0.05). The presence of Fe deficiency anemia was significantly higher in the Zn deficiency group (20.2%) than in the without Zn deficiency group (12.7%; p<0.05). There were very weak negative significant correlation between hair Zn and RDW level (r=-0.24; p<0.001) and weak positive correlation between hair Zn and MCV (r=0.31; p<0.001). Fe deficiency and Fe deficiency anemia increased in patients with zinc deficiency.


Interchangeability of 2 diphtheria-tetanus-acellular pertussis vaccines in infancy.
Currently, 4 diphtheria-tetanus-acellular pertussis (DTaP) vaccines are licensed for pediatric use in the United States, and 2 are commercially available. Although a single manufacturer's DTaP vaccine should be used for all 3 doses of the primary immunization series, some circumstances result in infants receiving DTaP vaccines from more than 1 manufacturer. The purpose of this study was to evaluate the safety and immunogenicity of a mixed sequence of 2 different DTaP vaccines. In this multicenter, observer-blinded, controlled study, 449 infants were randomized into 1 of 3 groups (1:1:1 ratio) to receive Tripedia at 2, 4, and 6 months of age (control group); Tripedia at 2 and 4 months of age and Infanrix at 6 months of age; or Tripedia at 2 months and Infanrix at 4 and 6 months of age. Other vaccines were administered concurrently as separate injections according to the recommended childhood immunization schedule. Safety was monitored closely, and standard enzyme immunoassays were used to measure antibody concentrations to each antigen of the DTaP vaccines. The rates of injection-site and systemic adverse events were similar in each study group, and there were no clinically significant differences among groups after any dose. Infants in all 3 groups responded well to each antigen contained in both vaccines, with 97% to 100% seroprotection or vaccine response rates after the 3-dose primary series. Postvaccination geometric mean antibody concentrations and seroprotection or vaccine response rates to nearly all vaccine antigens were as high or higher in the mixed-sequence groups as in the control group. Initiating the primary immunization series with 1 or 2 doses of Tripedia and completing the 3-dose series with Infanrix is as safe and at least as immunogenic as administering Tripedia for all 3 doses.


Serial representation of items during working memory maintenance at letter-selective cortical sites.
A key component of working memory is the ability to remember multiple items simultaneously. To understand how the human brain maintains multiple items in memory, we examined direct brain recordings of neural oscillations from neurosurgical patients as they performed a working memory task. We analyzed the data to identify the neural representations of individual memory items by identifying recording sites with broadband gamma activity that varied according to the identity of the letter a subject viewed. Next, we tested a previously proposed model of working memory, which had hypothesized that the neural representations of individual memory items sequentially occurred at different phases of the theta/alpha cycle. Consistent with this model, the phase of the theta/alpha oscillation when stimulus-related gamma activity occurred during maintenance reflected the order of list presentation. These results suggest that working memory is organized by a cortical phase code coordinated by coupled theta/alpha and gamma oscillations and, more broadly, provide support for the serial representation of items in working memory.


The Importance of Skincare for Neonates and Infants: An Algorithm.
The skin of neonates and infants undergoes a maturation process from birth and is susceptible to barrier disruption. The current algorithm follows a US-based consensus paper on skincare approaches using gentle cleansers and moisturizers in neonatal and healthy infant skin. This summary provides clinical information for pediatric dermatologists, dermatologists, and pediatric healthcare providers treating neonates and infants. The project used a modified Delphi process comprising virtual discussions followed by an online follow-up replacing the use of a questionnaire. During the virtual meeting, the systematic literature review results and a draft algorithm addressing over-the-counter skincare for neonates and infants with healthy skin were discussed and adopted using evidence coupled with the expert opinion and experience of the panel. The algorithm addresses three clinical signs: xerosis, erythema, and erosion/bulla. A growing body of evidence recognizes the benefits of ongoing daily use of non-alkaline cleansers and ceramides containing moisturizers to reduce inflammation and maintain a healthy skin barrier function. Diaper rash is common in infants presenting as erythema or, in more severe cases, skin erosion. Skin protection with a barrier cream and frequent diaper changes using disposable diapers resolves most cases; however, if the rash continuous despite appropriate care, rule out a candida infection. The current algorithm focuses on neonatal and infant healthy skin that can benefit from skincare. When applied from birth onwards, gentle cleansers and moisturizers containing barrier lipids help maintain the protective skin barrier. J Drugs Dermatol. 2021;20(11):1195-1205. doi:10.36849/JDD.6219.


Predicting factors for the experience of HIV testing among women who have given birth in Cambodia.
HIV testing and counselling is an entry point for the prevention of mother-to-child transmission of HIV (PMTCT) services, and it is important to determine predictors for HIV testing to improve the acceptance of HIV testing. The aim of this study was to assess predictive determinants for HIV testing asking mothers who had already given birth. Mothers who came to a childhood immunization in Phnom Penh, Cambodia with a child (children) aged 6-24 months were randomly selected in January and February 2006. A cross-sectional survey with a semi-structured questionnaire including a question about the experience of HIV testing was conducted to the mothers at the clinic by trained interviewers. Of the 315 respondents, 193 mothers (61.3%) had ever been tested for HIV and 265 mothers (84.1%) showed the necessary of permission by partners before HIV testing. In a multivariate logistic regression analysis, basic knowledge about HIV transmission [adjusted odd's ratio (aOR): 2.875, 95% CI: 1.668-4.956] as the best predictor, the number of children (aOR: 2.186, 95% CI: 1.241-3.852) and partner's education level (aOR: 1.950, 95% CI: 1.044-3.641) remained statistically significant, however the necessity of permission by partners did not (aOR: 1.691, 95% CI: = 0.859-3.328). Since some mothers ever tested might have obtained the permission with the perception of their partners before tested, it should be still highlighted that involvement of partners is an important strategy. Education on HIV transmission to young women and men through communication and health education strategies involving partners seems to lead PMTCT services to be more acceptable.


Simulation of transmission and persistence of African swine fever in wild boar in Denmark.
African swine fever (ASF) is caused by ASF virus (ASFV) and is currently circulating in the eastern part of Europe posing a serious risk regarding transmission to western European countries. Wild boar is a main driver of the transmission and persistence of ASFV in the endemic infected countries in Europe. Some European countries free from ASF, such as Denmark and the Netherlands, have limited population sizes of wild boar, but have large swine productions. In these countries, the patterns of transmission and persistence of ASFV in the existing wild boar population, in case of introduction of ASFV, are unknown. It is important to get a better understanding of ASFV in these wild boar populations, in order to better manage the existing wild boar population and thereby minimize the risk of virus introduction and transmission to domestic pigs, in case of an ASFV incursion. We created an agent-based spatio-temporal model and simulated the transmission of ASFV within Danish wild boar populations, using actual landscape data. The model was run with 50 and 100 wild boar groups used as initial population sizes, respectively, either distributed across the southern part of the mainland (Jutland) or across both the southern and middle parts of Jutland, where wild boar groups are believed to exist. At first, the model was run without ASFV for 25 years to assess wild boar population dynamics in both regions. Thereafter, ASFV was added to the model 1 year after initiation and run for up to another 4 years. The model predicted that wild boar populations may increase drastically over the next 25 years, if wild boar groups were distributed across both southern and middle Jutland and no mitigation actions were taken, while the population sizes will be restricted, if groups were distributed only across the southern part of Jutland. The density of the population is an important factor affecting the transmission and persistency of the disease. Model results indicated that ASF epidemics in the simulated populations would generally persist for few months. However, due to the high stochasticity of the process, in certain situations the epidemics may last for more than one year, posing a serious risk of ASFV introduction to domestic pigs.


Status of the "protein kinase CK2-HMG14" system in age-related amnesia in rats.
The experiments described here demonstrate that disruption of the phosphorylation of transcription factors of the HMG cAMP/Ca-independent protein kinase CK2 class may be the cause of decreased gene expression in age-related cognitive deficits. Amnesia for a conditioned passive avoidance reaction (CPAR) in aged rats (24 months old) was accompanied by decreases in the synthesis of synaptosomal proteins and transcription in nuclei isolated from cortical, hippocampal, and striatal neurons. There was a decrease in chromatin protein kinase CK2 activity and a significant decrease in the phosphorylation of HMG14 by protein kinase CK2. Selective activators of protein kinase CK2 (1-ethyl-4-carbamoyl-5-methylcarbamoylimidazole and 1-ethyl-4,5-dicarbamoylimidazole) increased HMG14 phosphorylation by protein kinase CK2, increased transcription, increased the synthesis of synaptosomal proteins, and decreased amnesia for the CPAR in aged rats. Thus, activation of the "protein kinase CK2-HMG14" system is accompanied by optimization of synaptic plasticity in aged animals. The results provide evidence for the high therapeutic potential of protein kinase CK2 activators.


Fluoroscopically guided infiltration of the cervical nerve root: an indirect approach through the ipsilateral facet joint.
Transforaminal infiltrations in the cervical spine are governed by a higher rate of vascular puncture than in the lumbar spine. The purpose of our study is to assess the safety and efficacy of percutaneous, fluoroscopically guided nerve root infiltrations in cases of cervical radiculopathy. An indirect postero-lateral approach was performed through the ipsilateral facet joint. During the last 2 years, 25 patients experiencing cervical radiculopathy underwent percutaneous, fluoroscopically guided nerve root infiltrations by means of an indirect postero-lateral approach through the ipsilateral facet joint. The intra-articular position of the needle (22-gauge spinal needle) was fluoroscopically verified after injection of a small amount of contrast medium which also verified dispersion of the contrast medium periradicularly and in the epidural space. Then a mixture of long-acting glucocorticosteroid diluted in normal saline (1.5/1 mL) was injected intra-articularly. A questionnaire with a Numeric Visual Scale (NVS) scale helped assess pain relief, life quality, and mobility improvement. A mean of 2.3 sessions was performed in the patients of our study. In the vast majority of our patients 19/25 (76%), the second infiltration was performed within 7-10 days of the first one. Comparing the pain scores prior (mean value 8.80 ± 1.080 NVS units) and after (mean value 1.84 ± 1.405 NVS units), there was a mean decrease of 6.96 ± 1.695 NVS units [median value 7 NVS units (P < 0.001) in terms of pain reduction, effect upon mobility, and life quality. There were no clinically significant complications noted in our study. Fluoroscopically guided transforaminal infiltrations through the ipsilateral facet joint seem to be a feasible, efficacious, and safe approach for the treatment of patients with cervical radiculopathy. This approach facilitates needle placement and minimizes risk of complications.


The transporter PHO84/NtPT1 is a target of aluminum to affect phosphorus absorption in Saccharomyces cerevisiae and Nicotiana tabacum L.
The molecular mechanism of aluminum toxicity in biological systems is not completely understood. Saccharomyces cerevisiae is one of the most used model organisms in the study of environmental metal toxicity. Using an unbiased metallomic approach in yeast, we found that aluminum treatment caused phosphorus deprivation, and the lack of phosphorus increased as the pH of the environment decreased compared to the control strain. By screening the phosphate signaling and response pathway (PHO pathway) in yeast with the synthetic lethality of a new phosphorus-restricted aluminum-sensitive gene, we observed that pho84Δ mutation conferred severe growth defect to aluminum under low-phosphorus conditions, and the addition of phosphate alleviated this sensitivity. Subsequently, the data showed that PHO84 determined the intracellular aluminum-induced phosphorus deficiency, and the expression of PHO84 was positively correlated with aluminum stress, which was mediated by phosphorus through the coordinated regulation of PHO4/PHO2. Moreover, aluminum reduced phosphorus absorption and inhibited tobacco plant growth in acidic media. In addition, the high-affinity phosphate transporter NtPT1 in tobacco exhibited similar effects to PHO84, and overexpression of NtPT1 conferred aluminum resistance in yeast cells. Taken together, positive feedback regulation of the PHO pathway centered on the high-affinity phosphate transporters is a highly conservative mechanism in response to aluminum toxicity. The results may provide a basis for aluminum-resistant microorganisms or plant engineering and acidic soil treatment.


Bicondylar Hoffa fracture: open reduction internal fixation using the swashbuckler approach.
Coronal plane fractures of the femoral condyle are infrequent injuries and are often missed. Unilateral bicondylar coronal plane fractures are even rarer, with only eight reported cases in scientific literature, and are often associated with other injuries. We present here a case of unilateral bicondylar Hoffa fracture that presented in our emergency department and was managed with open reduction and internal fixation by lateral parapatellar arthrotomy using the swashbuckler approach with satisfactory results.


[Veterinary environmental epidemiology: the case of respiratory pathology in the dog].
The correlation between environmental pollution and human health is one of the most important topics in public health. Environmentally-induced diseases generally show multifactorial etiology and their occurrence is dose-related; they can be included among the emergent diseases also in veterinary medicine. The epidemiological study of naturally occurring environmental diseases in animals, regarded as sentinel health events, can provide valuable information on agents being studied in human environmental epidemiological research. The epidemiologic aspects of naturally occurring diseases of domestic animals have so far received inadequate attention. Surveys have usually consisted of descriptive pathologic reports or of simple listings of case. There has been little or no attempt to relate the number of cases to the underlying population, thus there is little information on the prevalence rates of various animal diseases compiled according to age, breed, sex or environment. This paper reviews epidemiological studies of pet animals with spontaneously occurring respiratory diseases and attempts to determine the value of the animal in general and the dog in particular as a comparative model for environmental health.


Coumarin necrosis, neonatal purpura fulminans, and protein C deficiency.
Protein C (PC), a 62,000-molecular weight vitamin K-dependent serine protease zymogen, is a natural anticoagulant that occurs in plasma at 4 mg/L. Activated PC inactivates clotting factors V and VIII and is also profibrinolytic. Activated PC is enhanced in its anticoagulant activity by protein S (PS), another vitamin K-dependent protein. Protein S is found in platelets and endothelial cells as well as in plasma. Inherited PC deficiency and PS deficiency have been associated with venous thrombosis. Both heterozygous PC and PS deficiency appear to be inherited in an autosomal dominant manner in some families. Homozygous PC deficiency presents as neonatal purpura fulminans and results in massive venous thrombosis of the skin and other organs within the first few days of life. Symptomatic heterozygous PC deficiency and PS deficiency have been treated with oral anticoagulants, successfully minimizing recurrence of thrombosis. Coumarin-induced skin necrosis, a rare complication of oral anticoagulant therapy usually seen within three to five days of initiation of therapy, has also been associated with heterozygous PC deficiency. The short half-life of PC (six to eight hours) compared with most of the vitamin K-dependent clotting factors (greater than 30 hours) is the probable reason for this paradoxical response to oral anticoagulants in some PC-deficient patients, since a transient imbalance of procoagulant and anticoagulant factors may exist during initiation of oral anticoagulant therapy. Acquired deficiency of the PC pathway occurs in disseminated intravascular coagulation and possibly other diseases such as those associated with a lupus anticoagulant.


Women's views on anxiety in pregnancy and the use of anxiety instruments: a qualitative study.
To explore women's experience of anxiety in pregnancy and views on the use of anxiety instruments in antenatal care. Anxiety in pregnancy is associated with adverse birth outcomes, developmental and behavioural problems in infants and postnatal depression. Despite recommendations for routine psychological assessment in pregnancy, the optimal methods to identify anxiety in pregnancy have not been confirmed. A qualitative study using two focus group discussions was undertaken. Focus group one included women in a community setting and focus group two included women in a hospital clinic setting who had received additional support for anxiety in pregnancy. Participants were women who had given birth within the past nine months and considered themselves to have been anxious during their pregnancy. Three main themes were identified using template analysis: sources of support, administration of anxiety instruments and the use of instruments to prompt discussion. Women stated that anxiety instruments could help them to identify their anxious feelings and prompt a discussion around those feelings. However, they expressed concerns surrounding the administration of anxiety instruments and questioned how useful they would be in helping women access help and support. The introduction of anxiety instruments in antenatal care may present an opportunity to discuss women's emotional health and anxieties. Providing women with sufficient time to discuss their anxious feelings, identified by such instruments, could facilitate access to additional support.


Recurrence of iris melanoma after proton beam therapy.
A retrospective service evaluation to report on recurrence of iris melanoma after proton beam therapy (PBT). The cohort comprised 150 consecutive eyes with iris melanoma treated with proton beam radiotherapy. Treatment consisted of 53.1 Gy of proton beam irradiation delivered in four fractions over four consecutive days. Main outcome measures were local tumour control and tumour-related mortality. A total of 150 patients were treated. The median follow-up time was 66 months (range, 12-108 months). The tumour ultrasound thickness ranged from 1.1 mm to 4.9 mm, with a median of 2.4 mm. The tumours in these patients had a median largest basal diameter of 6.7 mm (range, 2.9-8.4 mm), involving more than two clock hours of iris or angle in five patients. The ciliary body was involved in three patients. Eight patients (5.3%) presented with local recurrence, diagnosed after a median follow-up of 24 months (range, 12-84 months). The recurrence was focal in two patients and diffuse in six. Six eyes were enucleated whereas one eye underwent iridocyclectomy and one received a second course of PBT. PBT provides excellent local tumour control and ocular preservation with good retention of vision. Most recurrences occur because the extent of the tumour is clinically underestimated but some tumours are radioresistant. Recurrence can occur several years after treatment. These findings indicate the need for wide safety margins and even radiotherapy of the entire anterior segment in patients with diffuse disease. Surveillance after treatment needs to be lifelong.


Role of myocardial ischemia and left ventricular wall motion abnormalities as contributory factors in the genesis of exercise-induced ST-segment elevation in Q-wave myocardial infarction.
In patients with a previous myocardial infarction, controversy exists regarding the significance of postexercise ST-segment elevation in the infarct-related leads. Although usually admitted to be a sign of left ventricular dysfunction or myocardial aneurysm, other studies however have related this finding to transient myocardial ischemia and to the presence of jeopardized but viable myocardium in the infarct area. The aim of the present study was to assess the significance of postexercise ST-segment elevation in Q-wave leads as a marker of transmural ischemia or left ventricular dysfunction in 36 consecutive patients, 16 with exercise-induced ST-segment elevation in infarct-related leads. Patients were evaluated by treadmill exercise testing, coronary angiography and ventriculography, thallium-201 tomographic scintigraphy and radionuclide ventriculography within 3 months of the first myocardial infarction. Sixteen patients (group I) had exercise-induced ST segment elevation and 20 (group II) postexercise inversion, no change or pseudonormalization of the T wave in infarct-related leads. The study showed no difference in infarct-related artery, vessel disease or luminal diameter stenosis in groups I and II. The overall agreement between ST shifts and myocardial perfusion in the infarct area was 30.56% with a kappa coefficient of -0.33 (p = NS). The overall agreement between ST shifts and wall motion abnormalities was 69.44% with a kappa coefficient of 0.39 (p < 0.01), stress-induced ST-segment elevation being associated with severe wall contractile disorders in 85% of the patients. In conclusion stress-induced ST-segment elevation in Q wave leads, although not a marker of wall motion abnormalities, is associated with akinesia or dyskinesia of the left ventricular wall.


Sense of coherence and health in women: a 25-year follow-up study.
Health and Sense of Coherence (SOC) has been shown to be intertwined and argued to have a reciprocal relationship. The theory of SOC implies relatively stable scores during adulthood, however there are few longitudinal studies on the association between SOC and mental and somatic health. The main aim of the present study was to examine how SOC and self-rated health (SRH) are related during 25 years of follow-up. Using paper questionnaires distributed by postal services, 415 mothers were followed from childbirth and 25 years prospectively. SOC was measured at three, 12 and 25 years after inclusion. Self-reports on health status were obtained at the 25-year follow-up. The association between SOC and self-reported health as well as the effect of sociodemographic factors and experience of stressful life events was assessed through regression models. SOC scores increased between three and 12 years after inclusion, and slightly decreased at the 25-year follow-up. Women of good health had a higher SOC-score at all three measurements compared to women of poor health. Multiple logistic regression showed that the likelihood of reporting good health increased with the number of times the women had reported SOC-scores above the 75th percentile. Moreover, women who had not been through a divorce were close to 60% more likely to report good health compared to women who had been through a divorce, whereas women not reporting stressful life events during the past two years were more than twice as likely to report good health. Symptoms below cut-off for postpartum depression and not having been through a divorce were associated with SOC scores above the 75th percentile. This 25-year follow-up study of a cohort of women reports good stability of SOC assessments in the vast majority of women. There was a stronger and more stable SOC in women with better health. The findings are in line with other studies on the predictive value of SOC and self-perceived health.


Effect of cohesion and shear modulus on the stability of a stretched granular layer.
The main mechanism of the cellular pattern which forms at the surface of a thin layer of a cohesive granular material submitted to in-plane stretching has been identified as the "strain softening" arising from the features of grain-grain interactions. We perform measurements of the strain field associated with such structures by using a correlation image technique and additionally characterize the cohesion and shear modulus of the samples. We show that for high cohesion, the layer is fragile and the surface deformation is highly nonlinear, whereas at low cohesion, a smooth and linearly growing structure is observed as a function of external stretching. Analysis of the wavelength as a function of cohesion along with independent measurement of the shear modulus indicate that a simple model of strain softening is acceptable if a mechanism of cluster formation due to cohesion is taking place.