Acceptability of laparoscopy-assisted gastrectomy for patients with previous intra-abdominal surgery.
This study assessed the acceptability of laparoscopy-assisted gastrectomy (LAG) for patients with previous intra-abdominal surgery (PIS). Sixteen patients with PIS had undergone LAG; 9 of laparoscopy-assisted distal gastrectomy, 2 of laparoscopy-assisted total gastrectomy and 5 of laparoscopy-assisted remnant gastrectomy (LARG). Difficulty, safety, and accuracy of LAG were compared between patients with PIS and with no previous intra-abdominal surgery. An independent group of 11 cases with open remnant gastrectomy (ORG) was used for comparing with LARG. No significant difference was observed in conversion rate, intraoperative complication, operation time, blood loss, dissected lymph nodes, postoperative complications and hospital stay between PIS, and no PIS. There was no significant difference in operative time, dissected lymph nodes, and postoperative complications between LARG and ORG. Blood loss was lesser and postoperative hospital stay was shorter in LARG than in ORG. LAG for patients with PIS is acceptable.


Dynamics of Candida isolations from humans from 1992-1995 in Greifswald, Germany.
In the period 1992-95 there was a significant shift in the spectrum of Candida species in the University Hospital in Greifswald. During this time, the annual number of specimens taken for mycological investigations of adults increased threefold (total n = 11,568). The isolation rate of Candida species was 50.5%. The percentage of C. albicans isolates decreased from 76% to 54.4% with the lowest level in 1994. The opposite trend in the occurrence of non-C. albicans species was seen, for example the occurrence of C. glabrata, from 11.7% to 28.4%. We found only 98 strains of C. parapsilosis (1.4%) during the 4 years. The occurrence of Candida species in a variety of habitats was different. During the 4 years, the same annual percentages of C. albicans (mean 87.9%) were isolated from endoscopic oesophageal smears, whereas the distribution of Candida yeasts from the oral cavity, the respiratory tract, faeces and urine had changed. Over the years, at these locations, C. albicans was less frequently isolated and non-C. albicans species clearly increased. The highest occurrence of C. glabrata was found in urine, in which the isolation percentage almost doubled from 23.1% to 40.9% in 1994. In contrast to adults, in all specimens originating from a paediatric clinic that included neonatology the occurrence of C. albicans was high (83.5% in 1995), but the isolation rate of Candida species was low (12.3%). These results are important because of the differences in yeast susceptibility, of non-C. albicans species in particular, against antifungal drugs.


Excitons in a photosynthetic light-harvesting system: a combined molecular dynamics, quantum chemistry, and polaron model study.
The dynamics of pigment-pigment and pigment-protein interactions in light-harvesting complexes is studied with an approach that combines molecular dynamics simulations with quantum chemistry calculations and a polaron model analysis. The molecular dynamics simulation of light-harvesting (LH) complexes was performed on an 87 055 atom system comprised of a LH-II complex of Rhodospirillum molischianum embedded in a lipid bilayer and surrounded with appropriate water layers. For each of the 16 B850 bacteriochlorophylls (BChls), we performed 400 ab initio quantum chemistry calculations on geometries that emerged from the molecular dynamical simulations, determining the fluctuations of pigment excitation energies as a function of time. From the results of these calculations we construct a time-dependent Hamiltonian of the B850 exciton system from which we determine within linear response theory the absorption spectrum. Finally, a polaron model is introduced to describe both the excitonic and coupled phonon degrees of freedom by quantum mechanics. The exciton-phonon coupling that enters into the polaron model, and the corresponding phonon spectral function, are derived from the molecular dynamics and quantum chemistry simulations. The model predicts that excitons in the B850 BChl ring are delocalized over five pigments at room temperature. Also, the polaron model permits the calculation of the absorption and circular dichroism spectra of the B850 excitons from the sole knowledge of the autocorrelation function of the excitation energies of individual BChls, which is readily available from the combined molecular dynamics and quantum chemistry simulations. The obtained results are found to be in good agreement with the experimentally measured absorption and circular dichroism spectra.


Stromal edema in klf4 conditional null mouse cornea is associated with altered collagen fibril organization and reduced proteoglycans.
Klf4, one of the highly expressed transcription factors in the mouse cornea, plays an important role in maturation and maintenance of the ocular surface. In this study, the structure and proteoglycan composition of the Klf4 conditional null (Klf4CN) corneal stroma was investigated, to further characterize the previously reported Klf4CN stromal edema. Collagen fibril spacing and diameter were calculated from scattering intensity profiles from small angle synchrotron x-ray scattering patterns obtained across the cornea along a vertical meridian at 0.5-mm intervals. Collagen fibril organization and proteoglycans were visualized by electron microscopy (EM), with or without the cationic dye cuprolinic blue. Proteoglycans and glycosaminoglycans were further analyzed by fluorophore-assisted carbohydrate electrophoresis (FACE) and immunoblot analysis. Q-RT-PCR was used to measure the transcript levels. In the central cornea, the average collagen interfibrillar Bragg spacing increased from 44.5 nm (SD +/-1.8) in wild-type to 66.5 nm (SD +/-2.3) in Klf4CN, as measured by x-ray scattering and confirmed by EM. Mean collagen fibril diameter increased from 32 nm (SD +/-0.4) in wild-type to 42.3 nm (SD +/-4.8) in Klf4CN corneal stroma. Downregulation of proteoglycans detected by EM in the Klf4CN stroma was confirmed by FACE and immunoblot analysis. Q-RT-PCR showed that, whereas the Klf4CN corneal proteoglycan transcript levels remained unchanged, matrix metalloproteinase (MMP) transcript levels were significantly upregulated. The Klf4CN corneal stromal edema is characterized by increased collagen interfibrillar spacing and increased diameter of individual fibrils. The stroma also exhibits reduced interfibrillar proteoglycans throughout, which is possibly caused by increased expression of MMPs.


Resistance of AIDS-associated Kaposi's sarcoma cells to Fas-mediated apoptosis.
Escape of tumor cells from apoptotic-mediated stimuli results in tumor cell survival and resistance to cytotoxic mechanisms. Kaposi's sarcoma (KS) is the most common malignancy associated with AIDS, although its pathogenesis is not known. It is clinically important to determine whether AIDS-KS cells are resistant to apoptosis via the Fas system. Three isolates of AIDS-KS cells were studied. Although all KS cells express Fas on the cell surface, these cells were resistant to cytotoxic anti-Fas antibody (IgM, CH-11). Treatment of AIDS-KS cells with actinomycin D sensitized the tumor cells to anti-Fas cytotoxicity and apoptosis. Apoptosis was assessed by morphological changes and DNA fragmentation analysis. Three possible mechanisms related to AIDS-KS cells, resistance to anti-Fas cytotoxicity were examined. First, synthesis and secretion of soluble Fas by the tumor cells can neutralize antibody-induced cytotoxicity. However, none of the three types of KS cells expressed soluble Fas mRNA as determined by reverse transcription (RT)-PCR. Second, the expression of the proto-oncogene bcl-2 can protect cells from apoptotic signals. Analysis of bcl-2 mRNA by RT-PCR revealed that all three AIDS-KS cells express very low levels of bcl-2 mRNA. Third, the Fas-associated phosphatase-1 (FAP-1) is an antiapoptotic molecule reported to interact with Fas and can block transduction of the apoptotic signal. RT-PCR analysis revealed that all three types of AIDS-KS cells express high levels of FAP-1 mRNA, and treatment of KS cells with actinomycin D reduced the levels of FAP-1 mRNA significantly. These findings demonstrate that AIDS-KS cells are resistant to Fas-mediated apoptosis and suggest that FAP-1 may be involved in the acquisition of resistance of AIDS-KS to anti-Fas antibody-mediated apoptosis.


[Transplantation cardiaque pédiatrique : quel futur ?]
The future of pediatric heart transplantation. Pediatric heart transplantation developed in the 1980s, following the introduction of cyclosporine. The International Registry includes more than 14 000 patients (10 % of the whole). The results improved progressively. However, two drawbacks persist : a shortage of donors, particularly in infants and a high morbi-mortality on the long term. The rapid achievement of a pediatric artificial heart is unlikely. The future offers two directions. Firsly xenotransplantation : the production of genetically-modified pigs and new immuno-suppressive modalities allow long-term survival in heterologous pig/primate transplantation. Human clinical trials may begin soon, particularly in neonates. Secondly tissue engineering : constant advances (scaffolds, cells lines, growth factors) may make possible the production of a functional heart from the receivor's own stem-cells.


The associations of p53 overexpression with p53 codon 72 genetic polymorphism in esophageal cancer.
Variations in p53 codon 72 have been identified as significant predisposing factors for various cancers, but molecular mechanisms remain unclear. We investigated associations of p53 overexpression with codon 72 variants and other factors with esophageal cancer. Status of p53 overexpression was determined by immunohistochemical staining. Codon 72 polymorphisms and mutation of p53 was identified by PCR-RFLP and direct sequencing from exons 4 to 9, respectively. We evaluated 126 patients who underwent esophagectomy in the National Taiwan University Hospital, and found that the status of p53 overexpression was significantly influenced by presence of codon 72 polymorphisms. After adjustment for other possible confounders, the incidence of p53 overexpression was significantly decreased in patients with Pro/Pro genotype with an odds ratio (OR) of 0.21 (95% CI: 0.067-0.64) (p = 0.0065) compared with incidence in patients with Arg/Arg genotype. The incidence of p53 overexpression was additively increased with environmental exposure to cigarette smoke, alcohol, and areca quid. When compared with individuals exposed to only one of these environmental risk factors, patients who had exposure to two or three risk factors had ORs of 6.11 (95% CI: 1.80-20.75) and 6.22 (95% CI: 1.81-21.34) for p53 overexpression, respectively. Elderly patients (age >70 years) were also more likely to have p53 overexpression, with an OR of 5.63 (95% CI: 1.53-20.64) compared with overexpression among patients aged less than 55 years. Forty-one patients received further evaluation of p53 mutation. There was also a higher incidence of, but without reaching a statistical significance, p53 mutation in patients with p53 overexpression (OR[95% CI]: 2.18 [0.52-9.6]) and codon 72 Arg/Arg genotype (OR [95% CI] of 0.8 [0.13-4.2], comparing genotypes of Pro/Pro and Arg/Pro with Arg/Arg). Our data provide the first observations that the presence of p53 codon 72 variants can be a significant factor influencing p53 overexpression in esophageal cancer, with overexpression also influenced by combined or prolonged environmental exposures.


Evidence for a calpeptin-sensitive protein-tyrosine phosphatase upstream of the small GTPase Rho. A novel role for the calpain inhibitor calpeptin in the inhibition of protein-tyrosine phosphatases.
Activation of the thiol protease calpain results in proteolysis of focal adhesion-associated proteins and severing of cytoskeletal-integrin links. We employed a commonly used inhibitor of calpain, calpeptin, to examine a role for this protease in the reorganization of the cytoskeleton under a variety of conditions. Calpeptin induced stress fiber formation in both forskolin-treated REF-52 fibroblasts and serum-starved Swiss 3T3 fibroblasts. Surprisingly, calpeptin was the only calpain inhibitor of several tested with the ability to induce these effects, suggesting that calpeptin may act on targets besides calpain. Here we show that calpeptin inhibits tyrosine phosphatases, enhancing tyrosine phosphorylation particularly of paxillin. Calpeptin preferentially inhibits membrane-associated phosphatase activity. Consistent with this observation, in vitro phosphatase assays using purified glutathione S-transferase fusion proteins demonstrated a preference for the transmembrane protein-tyrosine phosphatase-alpha over the cytosolic protein-tyrosine phosphatase-1B. Furthermore, unlike wide spectrum inhibitors of tyrosine phosphatases such as pervanadate, calpeptin appeared to inhibit a subset of phosphatases. Calpeptin-induced assembly of stress fibers was inhibited by botulinum toxin C3, indicating that calpeptin is acting on a phosphatase upstream of the small GTPase Rho, a protein that controls stress fiber and focal adhesion assembly. Not only does this work reveal that calpeptin is an inhibitor of protein-tyrosine phosphatases, but it suggests that calpeptin will be a valuable tool to identify the phosphatase activity upstream of Rho.


Osmotic stress-induced polyamine accumulation in cereal leaves : I. Physiological parameters of the response.
Putrescine and spermidine accumulate in cereal cells and protoplasts exposed to various osmotica (sorbitol, mannitol, proline, betaine, or sucrose). The response is fast (1-2 hour lag), massive (50- to 60-fold increase in putrescine), and is not due to release of putrescine from a bound form or to conversion from spermidine. It rather involves the activation of the biosynthetic pathway mediated by arginine decarboxylase (ADC; EC 126.96.36.199) (Flores and Galston 1982 Science 217: 1259). Polyamine accumulation and the rise in ADC activity in osmotically stressed tissue are prevented by ADC inhibitors (alpha-difluoromethylarginine, d-arginine, and l-canavanine) but are not affected by alpha-difluoromethylornithine and methylornithine, inhibitors of the alternative putrescine biosynthetic enzyme ornithine decarboxylase (EC 220.127.116.11). Putrescine accumulation by oat and corn leaves is maximal in solutions only slightly hyperosmotic (0.4 molar). The stress response, which declines with leaf age, is completely prevented by cycloheximide (10 to 50 micrograms per milliliter) when added during the first hour of exposure to osmoticum, and partially by transcription inhibitors (cordycepin, Actinomycin D, 5 to 20 micrograms per milliliter). Oat seedlings allowed to wilt by withholding water also show a rise in polyamine titer and ADC activity. This response is not readily reversible upon rewatering.


Endoscopic sinus surgery for sinonasal haemangiopericytomas.
Haemangiopericytomas are rare peri-vascular tumours with variable malignant potential. The nasal cavity and the paranasal sinuses are most often involved in the head and neck. Five cases of haemangiopericytomas treated by a strict endonasal endoscopic approach are presented. Bleeding and nasal obstruction are the most frequent symptoms. Computed tomography (CT) scan and magnetic resonance imaging (MRI) allowed pre-operative assessment. Angiography with embolization was needed in two of the five cases. None of our patients presented with malignant histology. Our five cases were operated on, and a total tumour excision was performed through the endoscopic endonasal approach. We had one recurrence with a mean follow-up of 4.5 years. We suggest that when the tumour is purely intranasal or strictly located in the ethmoid or sphenoid sinus, it can be removed via an endonasal approach under endoscopic guidance in experienced hands.


High b-value diffusion tensor imaging of the neonatal brain at 3T.
Diffusion-weighted MR imaging studies of the adult brain have shown that contrast between lesions and normal tissue is increased at high b-values. We designed a prospective study to test the hypothesis that diffusion tensor imaging (DTI) obtained at high b-values increases image contrast and lesion conspicuity in the neonatal brain. We studied 17 neonates, median (range) age of 10 (2-96) days, who were undergoing MR imaging for clinical indications. DTI was performed on a Philips 3T Intera system with b-values of 350, 700, 1500, and 3000 s/mm(2). Image contrast and lesion conspicuity at each b-value were visually assessed. In addition, regions of interest were positioned in the central white matter at the level of the centrum semiovale, frontal and occipital white matter, splenium of the corpus callosum, posterior limb of the internal capsule, and the thalamus. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values for these regions were calculated. Isotropic diffusion image contrast and lesion-to-normal-tissue contrast increased with increasing b-value. ADC values decreased with increasing b-value in all regions studied; however, there was no change in FA with increasing b-value. Diffusion image contrast increased at high b-values may be useful in identifying lesions in the neonatal brain.


Reversal of 3-(3,4-dichlorophenyl)-1,1-dimethylurea inhibition of carbon dioxide fixation in spinach chloroplasts and protoplasts by dicarboxylic acids.
3-(3,4-Dichlorophenyl)-1,1-dimethylurea (DCMU) inhibition of (14)CO(2) fixation in isolated intact spinach (Spinacia oleracea L.) chloroplasts was reversed (by about 34%) by l-malate but not by oxaloacetate (OAA). However, OAA reversed the DCMU inhibition in spinach protoplasts indicating an extrachloroplastic enzyme requirement. Extrachloroplastic OAA reduction was coupled with external dihydroxyacetone phosphate (DHAP) oxidation, and the malate formed from such coupling might then enter the chloroplasts. Evidence was presented using ruptured protoplasts that the export of recently formed 3-phosphoglyceric acid (PGA) out of chloroplasts in exchange for external DHAP was reversed by excess OAA. The PGA/DHAP shuttle across the chloroplast envelope was found to be regulated by the external concentrations of DHAP and OAA.


Moderating role of coping in the association between minority stress and suicidal ideation and suicide attempts among sexual and gender minority young adults.
This study examined associations of minority stressors (i.e., victimization, internalized homonegativity, and stigma consciousness), and coping styles (i.e., active, avoidant, and passive) with suicidal ideation and suicide attempts (suicidality) among sexual and gender minority (SGM) young adults, and whether coping style moderated these associations. Logistic regression analyses examined these associations among 1432 SGM young adults (ages 18-29). Minority stressors and passive coping were associated with a higher likelihood of suicidality. Avoidant coping was associated with a lower likelihood of lifetime suicidal ideation and attempts among sexual minority participants, and active coping with a lower likelihood of past-year suicidal ideation among sexual minority participants. Moderation analyses among sexual minority participants showed that when avoidant coping was high, associations between low victimization (compared with no victimization) and lifetime suicide attempts, and stigma consciousness and lifetime suicide attempts became non-significant, and the association between internalized homonegativity and lifetime suicide attempts became significant. Among gender minority participants, when passive coping was high the association between low victimization and lifetime suicidal ideation became significant. This study underlines the importance of minority stress and coping for suicidality among SGM young adults and the need for more research regarding the role of coping.


Neuroimaging in patients with abnormal blood glucose levels.
Smooth neuronal functioning requires an uninterrupted supply of energy that is provided by glucose under normal physiologic conditions. Significant variations in plasma glucose levels, be it hypoglycemia or hyperglycemia, can present with myriad clinical manifestations and may mimic stroke. At times, the diagnosis is either not apparent or not clinically suspected. Imaging can suggest the diagnosis in unsuspected cases and can help in the assessment of the extent of neuronal damage in known cases, making it vital for the neuroradiologist to be aware of both common and atypical neuroimaging findings in hypoglycemia and hyperglycemia.


Differences in Perceived Occupational Stress by Demographic Characteristics, of European Emergency Medical Services Personnel during the COVID-19 Virus Pandemic-An International Study.
The outbreak of the COVID-19 pandemic has brought commercial, social, and economic consequences in every country that has experienced substantial SARS-CoV-2 infection rates. The complete change in the environment that took place due to the outbreak of the pandemic can lead to stressful situations, especially among healthcare personnel. The research were conducted during the COVID-19 pandemic between the 27 March 2020 and the 20 April 2020. The research included 1984 employees of emergency medical systems in seven European countries. An internet-based questionnaire format was adopted for the study (ΩMc-Donald > 0.7). The highest level of stress was experienced by personnel in the United Kingdom M = 4.03, and the lowest by Norwegian employees M = 2.89. High levels of stress were also experienced by nurses from Spain and Poland. Women actively working in the healthcare system during the pandemic experienced higher stress levels than men. Women working in European emergency medical systems are more vulnerable to work-related stress, while carrying out emergency medical procedures during the pandemic. Differences in the level of stress experienced while carrying out duties in pre-hospital conditions were only found among Spanish emergency medical system personnel.


Detection of melanoma seeding during surgical procedures--an RT-PCR based model.
It has long been suggested that malignant cells may be shed into the blood stream during any given surgical procedure for cancer. A number of studies have now reported the detection of occult melanoma cells in peripheral blood using a reverse transcriptase polymerase chain reaction (RT-PCR) based assay. The principal aim of these studies has been to determine a prognostic value for the test and not to evaluate the influence of intervention upon results. In this pilot study we aimed to determine whether the assay could be used as a model to detect cells that are seeded during surgery. Peripheral blood samples were obtained pre- and post-operatively on twenty patients undergoing surgery for malignant melanoma - ten with primary disease and ten undergoing regional lymphadenectomy. A further ten patients undergoing surgery for non-melanoma conditions provided controls. Using RT-PCR, it was possible to identify tyrosinase transcripts in the peripheral blood of one of ten patients undergoing excision of local disease and four of ten undergoing surgery for regional metastatic disease. It was concluded that this technique does enable detection of a greater percentage of RT-PCR findings post-operatively. This in turn may provide a means for optimizing or comparing surgical techniques and provides a potential guide in the use of adjuvant therapies.


New ligands bearing chiral bioactive fragments.
[see reaction]. Reliable and practical synthetic routes for the construction of hybrid molecules bearing both a chelating center and a useful biofunction are presented. They comprise the sequential cross-coupling reaction between ethynylated synthons with iodo-substituted L-tyrosine derivatives and provide access to various rationally designed chiral ligands.


Lack of Contribution of p66shc and Its Mitochondrial Translocation to Ischemia-Reperfusion Injury and Cardioprotection by Ischemic Preconditioning.
Whereas high amounts of reactive oxygen species (ROS) contribute to cardiac damage following ischemia and reperfusion (IR), low amounts function as trigger molecules in the cardioprotection by ischemic preconditioning (IPC). The mitochondrial translocation and contribution of the hydrogen peroxide-generating protein p66shc in the cardioprotection by IPC is unclear yet. In the present study, we investigated the mitochondrial translocation of p66shc, addressed the impact of p66shc on ROS formation after IR, and characterized the role of p66shc in IR injury per se and in the cardioprotection by IPC. The amount of p66shc in subsarcolemmal (SSM) and interfibrillar mitochondria (IFM) isolated from wildtype mouse left ventricles (LV) was determined after 40 min normoxic perfusion and after 30 min ischemia and 10 min reperfusion without and with IPC. The p66shc content in SSM (in % of normoxic controls, n = 5) was 174 ± 16% (n = 6, p < 0.05) after IR, and was reduced to 128 ± 13% after IPC (n = 6, p = ns). In IFM, the amount of p66shc remained unchanged (IR: 81 ± 7%, n = 6; IPC: 110 ± 5%, n = 6, p = ns). IR induced an increase in ROS formation in SSM and IFM isolated from mouse wildtype LV, which was more pronounced in SSM than in IFM (1.18 ± 0.18 vs. 0.81 ± 0.16, n = 6, p < 0.05). In mitochondria from p66shc-knockout mice (p66shc-KO), the increase in ROS formation by IR was not different between SSM and IFM (0.90 ± 0.11 vs. 0.73 ± 0.08, n = 6, p = ns). Infarct size (in % of the left ventricle) was 51.7 ± 2.9% in wildtype and 59.7 ± 3.8% in p66shc-KO hearts in vitro and was significantly reduced to 35.8 ± 4.4% (wildtype) and 34.7 ± 5.6% (p66shc-KO) by IPC, respectively. In vivo, infarct size was 57.8 ± 2.9% following IR (n = 9) and was reduced to 40.3 ± 3.5% by IPC (n = 11, p < 0.05) in wildtype mice. In p66shc-knockout mice, infarct sizes were similar to those measured in wildtype animals (IR: 56.2 ± 4.3%, n = 11; IPC: 42.1 ± 3.9%, n = 13, p < 0.05). Taken together, the mitochondrial translocation of p66shc following IR and IPC differs between mitochondrial populations. However, similar infarct sizes after IR and preserved infarct size reductions by IPC in p66shc-KO mice suggest that p66shc-derived ROS are not involved in the cardioprotection by IPC nor do they contribute to IR injury per se.


Estimates of the global and continental burden of animal tuberculosis in key livestock species worldwide: A meta-analysis study.
Zoonotic animal tuberculosis (TB) is a One Health paradigm infectious disease, caused by Mycobacterium tuberculosis complex bacteria, that affects different host species with varying levels of management. In most developed countries, official surveillance and control strategies support the longitudinal reporting of herd and/or animal prevalence. However, for under resourced countries without surveillance plans, this information may be obtained from cross-sectional studies only. The objective of this meta-analysis was to perform a worldwide estimate of the overall prevalence of animal TB in different livestock species whose importance in production systems varies according to the region of the world. The ISI's Web of Science and Google Scholar were searched combining keywords and related database-specific subject terms to identify relevant cohort or cross-sectional work published in this topic. A total of 443 articles were retrieved, screened, and a final set of 182 references included. Potential sources of variation were investigated using subgroup analyses and meta-regression. Prevalence estimates in five mammalian host groups were stratified according to host species, host characteristics, anatomical localization of lesions, sample size, geographical location, and diagnostic tests. The multivariable meta-regression analysis accounted for a range between 0% (farmed wild boar) and 68.71% (camelids) of the overall observed heterogeneity, indicating that the pondered predictors partially explain the observed variability. Differences in the overall prevalence of TB across hosts were small, with most groups showing values around 10%, except farmed wild boar (41%). The sample size emerged as an important moderator, with small size studies leading to the overestimation of prevalence. TB prevalence rates were very heterogeneous across continents and depended on the host, with lower values (below 10%) in Africa and Asia, while North America (33.6%, cattle), Europe (51%, goats), and South America (85.7%, pigs) exhibited higher rates, possibly related to greater densities of specific host groups managed on more intensive production systems. Stratification by diagnostic tests evidenced heterogeneous prevalence rates depending on the host group, possibly reflecting differences in test performance across different hosts. Results from this study highlight different TB burden scenarios, pinpointing host groups and diagnostics that should be prioritized in surveillance systems in different regions, thus providing policy-relevant information to catalyse TB control in settings with lower installed capacity and better resource allocation at the human-animal-environment interface.


The effects of an energy stimulator on blood electrolyte and lactate levels in athletes under training.
The effects of a mineral-vitamin-sugar preparation has been tested on a group of volley ball players under training. Plasma electrolytes (Na, K, Cl), erythrocyte electrolyte content, plasma lactate concentration and erythrocyte water content have been determined before and after a training session in three different experimental situations: a) controls; b) acute treatment with the energy stimulator; c) chronic treatment (8 days) with a similar preparation of the energy stimulator. The results are indicative of a significantly lower lactate production and a more stable electrolyte concentration after treatment with respect to the control data.


CTRP3 attenuates high-fat diet-induced male reproductive dysfunction in mice.
Recent studies have suggested a role for abdominal obesity in male infertility. Previous studies have found that cell apoptosis exerts an important role in obesity-related male infertility. C1q/TNF-related protein 3 (CTRP3), a paralog of adiponectin, has been proposed to exert anti-apoptotic effects and to attenuate diabetes-related cardiac injuries. However, the role of CTRP3 in high-fat diet (HFD)-induced spermatogenic impairment remains unclear. In the present study, we fed male mice an HFD for 24 weeks to induce obesity. The expression of CTRP3 was decreased by HFD feeding. Supplementation with the recombinant human globular domain of CTRP3 (0.25 μg/g/day) for 4 weeks beginning at 20 weeks of the HFD improved spermatogenic function in the HFD-fed mice, which were characterized by improved testis morphology, increased testis weight/body weight ratio, and increased sperm count, sperm viability, and sperm motility. We also found that CTRP3 infusion resulted in the attenuation of endoplasmic reticulum (ER) stress and the activation of silence information regulator 1 (SIRT1) in the testes of obese mice. Our in vitro study also suggested that CTRP3 attenuated the palmitic acid (PA)-induced reductions in sperm viability and motility via the inhibition of ER stress. Moreover, germ cell-specific Sirtuin1 knockout abolished the protective effects of CTRP3 in vivo and in vitro. In vitro studies of human sperm showed that the protective effects of CTRP3 on sperm viability and motility were abrogated by a specific inhibitor of SIRT1. Thus, our results demonstrated that CTRP3 expression protected against HFD-induced spermatogenic deficiency through the SIRT1/ER stress pathway.


Positive selection has driven the evolution of the Drosophila insulin-like receptor (InR) at different timescales.
The highly conserved insulin-signaling pathway influences very diverse processes including intermediary metabolism, reproduction, aging, and growth. The first pathway component is the insulin receptor that upon insulin binding triggers the signal-transduction cascade. Its variation, like that of other pathway components, might therefore affect many organismal traits. Variation at the "Insulin-like" receptor (InR) gene was surveyed both within Drosophila melanogaster and between species across the Drosophila phylogeny. In D. melanogaster, the level and pattern of variation at the approximately 8-kb region surveyed did not provide any indication of a recent selective event in this region. Maximum likelihood (ML) analyses revealed the past action of purifying selection acting differentially both across the phylogeny and along the studied gene. Moreover, the ML analyses and the McDonald and Kreitman test revealed the footprint of positive selection driving amino acid changes to fixation in the branch separating the Sophophora and the Drosophila subgenera, and in the D. melanogaster lineage, respectively. The oldest selective events could have affected either the insulin binding or the signal-transduction capacities of the receptor, whereas mutations affecting signal transduction would seem to underlie the more recent events.


Association of immature mosquitoes and predatory insects in urban rain pools.
Distribution among pools of six mosquito species and 23 predatory insect taxa were studied in temporary rain pools during the summer and fall season in Buenos Aires city. Both mosquito immatures and predators were disproportionally more abundant in pools with high flooded surface, depth, and duration. Mosquito immatures differed in their habitat use with respect to predators. Among mosquitoes, Ochlerotatus albifasciatus showed a different pattern when compared to the remaining culicids. More culicid and predatory insect taxa colonized the pools in those flooding events of longer duration. Ochlerotatus albifasciatus was the only mosquito species recorded during short duration events and the first one in colonizing the pools in long duration events. This species shared the pools mainly with early arriving adult predators. Three Culex species were recorded later and showed higher coexistence with most of the predatory taxa, mainly immatures of the genera Tropisternus, Rhantus, Liodessus, and Belostoma. A high heterogeneity between pools and seasons was observed. Multiple regression analyses showed a negative relationship of per capita change of Culex species with large-sized predators only in those cases where predators were collected in high abundances during the summer. No negative relationship of predators was detected in relation to per capita change and abundance of Ochlerotatus albifasciatus. Differences in duration of about two to three weeks seemed to significantly affect the abundance of both culicid and predatory taxa, suggesting that the urban pools analyzed in this study are on the extreme of suitable conditions for these aquatic insects.


Intestinal lesions in specific-pathogen-free lambs associated with a cryptosporidium from calves with diarrhea.
Small and large intestines of seven specific pathogen-free lambs infected with cryptosporidia from calves with diarrhea were examined by scanning and transmission electron microscopy and by light microscopy. The small intestine was infected in all the lambs, and the cecum and colon in three. Small intestinal alterations were severe villous atrophy and dilatation of the crypts of Lieberkühn. Epithelial cross-bridging between contiguous villi caused much villous fusion. Epithelial cells constituting the bridges were connected by desmosomal junctions, and were continuous with the epithelial coverings of the associated villi. The lamina propria was heavily infiltrated with neutrophil leukocytes. Infected crypts in cecum and colon were dilated and devoid of mucus-secreting cells, while the ridges between crypts were hypertrophied, and the lamina propria was infiltrated by neutrophils. Cell vegetations with adherent bacteria were present in the surface intestinal epithelium of two lambs infected for 11 and 14 days, respectively. No adherent bacteria were seen in any site in lambs killed up to six days post-inoculation.


[A case of anti-aquaporin 4 antibody-positive Sjögren syndrome associated with a relapsed myelitis in pregnancy].
It is known that pregnancy influences the relapsing rate of multiple sclerosis (MS); however, interaction between pregnancy and relapse of neuromyelitis optica (NMO), a distinct disease from MS, remains unclear. A 34-year-old woman who 1 year previously had clinical history of Sjögren syndrome complicated by myelitis with the presence of anti-AQP4 antibody in her serum, although there was no optic neuritis involvement, was neurologically normal at time of becoming pregnant. In the 22nd week of her pregnancy, however, she developed abdominal belt-shaped numbness and sensory impairment followed by weakness of bilateral lower limb leading to difficulty of her gait. MR imaging revealed hyperintense lesions within the spinal cord extending from C2 to T2 vertebral level with marked spinal cord swelling, indicating relapse of myelitis associated with anti-AQP4 antibody. She was treated with intravenous corticosteroid with marked benefits for her neurological status; she was able to walk without assistance after the treatment. However, in the 30th week she relapsed with myelitis at T2 to T9 vertebral level on MR imaging. Intravenous steroid administration again elicited improvement. She delivered a baby via Caesarean section at 34 weeks of pregnancy. After delivery, she started taking oral corticosteroid as preventive therapy for further relapse of myelitis; thus far she has had no relapse at 7 months of follow-up. There are few reports regarding the influence of pregnancy on anti-AQP4 antibody-positive myelitis. Although further investigation should be done to clarify the difference of immunological changes during pregnancy between NMO and conventional MS, our case together with previous reports indicate increased risk of relapse during pregnancy in NMO. It is necessary to remain vigilant against possible risk of relapse during pregnancy in patients with NMO and/or positive anti-AQP4 antibody. Intravenous steroid administration seems safe and effective against relapse of NMO during pregnancy.


[Preparation and characterization of human phage display antibody against peroxiredoxin I of lung adenocarcinoma].
To construct a human phage antibody library and screen the single chain variable fragment (ScFv) antibudies to peroxiredoxin I (Prx I) of lung adenocarcinoma. The total RNA was isolated from the lymph nodes of lung cancer patients to amplify V(H) and V(L) genes by RT-PCR. V(H) and V(L) were linked with a DNA linker by SOE-PCR to construct the single chain variable fragment gene. The ScFvs were coloned into the phage vector pCANTAB5E. The insert ratio of the ScFv antibody library was identified by PCR, and the products were digested by SfiI/NotI and analyzed with 1% agarose gel electrophoresis. Three rounds of panning against lung adenocarcinoma cell line A549 and Prx I were performed, and the positive clones were identified for soluble expression. The soluble antibodies were identified by SDS-PAGE and Western blotting, and ELISA and immunocytochemistry were used to characterize the activity of the antibodies. A recombination phage antibody library was constructed. The insert ratio of ScFv gene was 77% (23/30), and enzyme digestion identified the target product. The sixth phage harvest resulted in a yield 180 folds of that of the first one. Positive reactions to A549 cells were detected in 6 of 10 random clones, with a positivity rate of 60%. The soluble human ScFvs against Prx I of lung adenocarcinoma were expressed in E. coli HB2151 and confirmed by SDS-PAGE and Western blotting. ELISA and immunocytochemistry demonstrated a relative specific affinity of the soluble antibodies to A549 cells. ScFv antibodies against lung adenocarcinoma have been acquired by phage display antibody library technique, and the soluble antibodies have a relative avidity specific to human lung adenocarcinoma A549 cells overexpressing PrxI.


Chloroplast Biogenesis: XXIV. Intrachloroplastic Localization of the Biosynthesis and Accumulation of Protoporphyrin IX, Magnesium-Protoporphyrin Monoester, and Longer Wavelength Metalloporphyrins during Greening.
The intraplastidic localization of the endogenous metabolic pools from protoporphyrin to protochlorophyll was determined in Cucumis sativus. The endogenous protoporphyrin, Mg-protoporphyrin monoester + longer wavelength metalloporphyrins, protochlorophyllide and protochlorophyllide ester were membrane-bound. Protoporphyrin was synthesized in the stroma and subsequently became associated with the membranes. The membrane-associated protoporphyrin was then converted into Mg-protoporphyrin monoester + longer wavelength metalloporphyrins by membrane-bound enzymes. Although lysed plastids were capable of converting exogenous delta-aminolevulinic acid to protochlorophyllide, the net synthesis of protochlorophyllide from exogenous delta-aminolevulinic acid was lost upon segregating the lysed plastids into stromal and membrane fractions and then recombining the stromal and membrane fraction prior to incubation. The segregated membrane fraction was still capable of converting protoporphyrin into Mg-protoporphyrin monoester + longer wavelength metalloporphyrins in the presence or absence of the stromal fraction. These results indicated that although the reactions from protoporphyrin to Mg-protoporphyrin monoester and longer wavelength metalloporphyrins could survive a considerable degree of plastid disruption, the reactions from Mg-protoporphyrin monoester and longer wavelength metalloporphyrins to protochlorophyllide were more sensitive to structural disorganization.


Mesopore Formation and Silicon Surface Nanostructuration by Metal-Assisted Chemical Etching With Silver Nanoparticles.
This article presents a study on Metal-Assisted Chemical Etching (MACE) of silicon in HF-H2O2 using silver nanoparticles as catalysts. Our aim is a better understanding of the process to elaborate new 3D submicrometric surface structures useful for light management. We investigated MACE over the whole range of silicon doping, i.e., p++, p+, p, p-, n, n+, and n++. We discovered that, instead of the well-defined and straight mesopores obtained in p and n-type silicon, in p++ and n++ silicon MACE leads to the formation of cone-shaped macropores filled with porous silicon. We account for the transition between these two pore-formation regimes (straight and cone-shaped pores) by modeling (at equilibrium and under polarization) the Ag/Si/electrolyte (HF) system. The model simulates the system as two nanodiodes in series. We show that delocalized MACE is explained by a large tunnel current contribution for the p-Si/Ag and n-Si/HF diodes under reverse polarization, which increases with the doping level and when the size of the nanocontacts (Ag, HF) decreases. By analogy with the results obtained on heavily doped silicon, we finally present a method to form size-controlled cone-shaped macropores in p silicon with silver nanoparticles. This shape, instead of the usual straight mesopores, is obtained by applying an external anodic polarization during MACE. Two methods are shown to be effective for the control of the macropore cone angle: one by adjusting the potential applied during MACE, the other by changing the H2O2 concentration. Under appropriate etching conditions, the obtained macropores exhibit optical properties (reflectivity ~3 %) similar to that of black silicon.


[Influence of organizational commitment and professional nurses in conflict resolution strategies].
INTRODUCE: The changes in the health area and the set of structural changes in the nursing profession and career interfere in the dynamics and stability of the future of the nurses. To study the influence of organizational and professional commitment of the nurses in the strategies of conflict resolution. This is a quantitative, transversal and non-experimental research, following a descriptive-correlational way. Non-probabilistic sample of 102 nurses to perform duties in Health Units, mostly female (82.4%) with a mean age of 39.33 years and standard deviation 9.226. The measuring instrument consists of three scales calibrated and validated for the portuguese population: Organizational Commitment Questionnaire, Professional Commitment Scale and Inventory Strategies for Conflict Resolution, which assesses how individuals deal with conflict situations before higher (Form A), subordinate (Form B) and colleagues (Form C). Nurses demonstrate a moderate organizational commitment and higher affective commitment and normative commitment to the instrumental. Nurses demonstrate a moderate professional commitment and the results show that nurses have higher values on the dimensions of that interest and challenge the relevance dimension of nursing as a profession. The organizational commitment influences the adoption of strategies of conflict resolution as a conflict situation arises with the boss, subordinates or colleagues. The higher the level of organizational commitment higher the level of professional commitment. Nurses more engaged professionally demonstrate strategies that use more integrative and compromise in conflict resolution whether against the boss, subordinates or colleagues. The results ensure the need to promote and stimulate the affective commitment by the positive consequences it entails the organization and the profession. The organizational performance benefits from the stimulation of the conflict under certain conditions and that the constructive management of conflict is essential to organizational effectiveness.


Inorganic Boron-Based Nanostructures: Synthesis, Optoelectronic Properties, and Prospective Applications.
Inorganic boron-based nanostructures have great potential for field emission (FE), flexible displays, superconductors, and energy storage because of their high melting point, low density, extreme hardness, and good chemical stability. Until now, most researchers have been focused on one-dimensional (1D) boron-based nanostructures (rare-earth boride (REB₆) nanowires, boron nanowires, and nanotubes). Currently, two-dimensional (2D) borophene attracts most of the attention, due to its unique physical and chemical properties, which make it quite different from its corresponding bulk counterpart. Here, we offer a comprehensive review on the synthesis methods and optoelectronics properties of inorganic boron-based nanostructures, which are mainly concentrated on 1D rare-earth boride nanowires, boron monoelement nanowires, and nanotubes, as well as 2D borophene and borophane. This review paper is organized as follows. In Section I, the synthesis methods of inorganic boron-based nanostructures are systematically introduced. In Section II, we classify their optical and electrical transport properties (field emission, optical absorption, and photoconductive properties). In the last section, we evaluate the optoelectronic behaviors of the known inorganic boron-based nanostructures and propose their future applications.


Radiosensitization of breast cancer cells by TRAIL-endostatin-targeting gene therapy.
One of the key issues in cancer radiotherapy research is to sensitize tumor cells to the cell killing effects of ionizing radiation while leaving normal tissues intact. One potential approach to achieve this is gene-radiotherapy, i.e. a combination of radiation therapy and gene therapy. It is to choose certain exogenous radiation-inducible regulatory genes, for example, early growth response-1 (Egr-1), and transcript its downstream tumor-therapeutic genes under ionizing radiation so as to kill the tumor cells synergistically by the expressed gene products together after transfection and irradiation exposure. In this study, we engineered a plasmid encoding both TRAIL and endostatin under the control of the radiation-inducible Egr-1 promoter, and evaluated its anti-tumor efficacy in combination with radiotherapy. Our plasmid showed significant efficacy in up-regulating the levels of TRAIL and endostatin proteins after transfected into breast cancer cells and exposed to X-ray irradiation. The detected cellular effects in vitro manifested that TRAIL-endostatin-based gene therapy could enhance radiosensitizing effects in breast cancer cells in terms of tumor cell growth inhibition, promoting apoptosis and the induction of cell cycle arrest. In summary, our results suggest that TRAIL-endostain-targeting approach might be a promising method to sensitize solid tumors to radiation therapy.


Branch and bound computation of exact p-values.
P-value computation is often used in bioinformatics to quantify the surprise, or significance, associated with a given observation. An implementation is provided that computes the exact p-value associated with any observed sample, against a null multinomial distribution, using the likelihood-ratio statistic. The efficient branch and bound code, far exceeding the full enumeration implemented by commercial packages, is especially useful with small sample, sparse data and rare events, common scenarios in bioinformatics, where approximations are often inaccurate and inappropriate. This code base can also be adapted to compute exact p-values of other statistics in diverse sampling scenarios. Freely available at http://www.soe.ucsc.edu/~jill/src/.


Carcinosarcoma of the colon: a rare cause of colovesical fistula.
Carcinosarcomas are relatively rare tumors composed of both carcinomatous and sarcomatous components. The most common sites involved by this tumor are the head and neck, respiratory tract, uterus, ovaries, and fallopian tubes. Within the gastrointestinal tract this tumor most often occurs in the esophagus, followed by the stomach. Carcinosarcomas are very aggressive tumors associated with a poor prognosis. The first case of carcinosarcoma of the colon was reported in 1986. The case reported here is the only one involving an associated colovesical fistula.


Deep-Ultraviolet (DUV)-Induced Doping in Single Channel Graphene for Pn-Junction.
The electronic properties of single-layer, CVD-grown graphene were modulated by deep ultraviolet (DUV) light irradiation in different radiation environments. The graphene field-effect transistors (GFETs), exposed to DUV in air and pure O2, exhibited p-type doping behavior, whereas those exposed in vacuum and pure N2 gas showed n-type doping. The degree of doping increased with DUV exposure time. However, n-type doping by DUV in vacuum reached saturation after 60 min of DUV irradiation. The p-type doping by DUV in air was observed to be quite stable over a long period in a laboratory environment and at higher temperatures, with little change in charge carrier mobility. The p-doping in pure O2 showed ~15% de-doping over 4 months. The n-type doping in pure N2 exhibited a high doping effect but was highly unstable over time in a laboratory environment, with very marked de-doping towards a pristine condition. A lateral pn-junction of graphene was successfully implemented by controlling the radiation environment of the DUV. First, graphene was doped to n-type by DUV in vacuum. Then the n-type graphene was converted to p-type by exposure again to DUV in air. The n-type region of the pn-junction was protected from DUV by a thick double-coated PMMA layer. The photocurrent response as a function of Vg was investigated to study possible applications in optoelectronics.


Single-atom nanozymes for biological applications.
Nanozymes have been widely used as highly active and stable arterial enzymes due to their controllable electronic transfer and unique catalytic reaction route. However, the development of nanozymes is hindered by their ambiguous structure, insufficient activity and inadequate substrate selectivity. In comparison, single-atom nanozymes (SAzymes) hold superior catalytic activity 10-100 times higher than conventional nanozymes by maximizing the utilization of metal atom dispersion, and exhibit versatile catalytic selectivity through precisely adjusting the atom spatial configuration. In this review, we highlight several well-defined SAzymes, and discuss their accurate atom configuration, catalytic mechanisms, enzyme-like activity, and applications in cancer treatment, brain disease, and wound healing. It is of great significance to understand the advantages and properties of SAzymes for further medical development.


Auditory perception stability evaluation comparing binaural and loudspeaker Ambisonic presentations of dynamic virtual concert auralizations.
Auralizations can be computed in a variety of ways as well as be rendered over different sound reproduction systems. They are used as a design tool in architectural projects and for fundamental studies on spatial perception and cognition, hence requiring reliability and confidence in the obtained results. This study assessed this reliability through auditory perception stability by comparing the perceived differences between two rendering systems for a given set of second-order Ambisonic auralizations: virtual loudspeaker binaural rendering over head-tracked headphones versus 32-loudspeaker rendering. Anechoic extracts of jazz pieces have been recorded and presented in various acoustic conditions over these two systems, evaluated on the following criteria: Readability, distance, listener envelopment (LEV), apparent source width (ASW), reverberance, and loudness. Results show that consistent significant differences between scene conditions are comparably perceived across the two systems. However, significant effects of the sound reproduction system were observed for ASW, LEV, and reverberance in some configurations.


Functional CD95 ligand and CD95 death-inducing signaling complex in activation-induced cell death and doxorubicin-induced apoptosis in leukemic T cells.
Activation-induced cell death (AICD) in T cells is mediated by CD95 ligand (CD95L)/receptor interaction, which has also been implicated in apoptosis induction by some anticancer agents. In this article we show that both anti-CD3-triggering (AICD) and doxorubicin treatment led to the production of a functionally active CD95L in the CD3+/T-cell receptor-positive (TCR+) T leukemia cell line H9. CD95L-expressing H9 cells killed CD95-sensitive J16 or CEM target cells, but not CD95-resistant CEM or J16 cells overexpressing dominant negative FADD (J16/FADD-DN). By immunoprecipitation, CD95L was physically bound to CD95, suggesting that AICD and doxorubicin-induced apoptosis involve CD95L-mediated CD95 aggregation, thereby triggering the CD95 death pathway. CD95 aggregation was associated with the recruitment of FADD and caspase-8 to the CD95 receptor to form the CD95 death-inducing signaling complex (DISC), resulting in caspase-8 activation and cleavage of the effector caspase-3 and PARP. Blocking of the CD95L/receptor interaction by antagonistic antibodies to CD95 or to CD95L also blocked AICD and inhibited the early phase of doxorubicin-induced apoptosis, though cell death induced by doxorubicin eventually proceeded in a CD95-independent manner. These findings may explain some conflicting data on the role of death receptor systems in drug-induced apoptosis. Thus, in cells with an inducible CD95 receptor/ligand system, drug-induced apoptosis may be mediated by CD95L-initiated DISC formation and activation of downstream effector programs similar to AICD in T cells. (Blood. 2000;95:301-308)


Microalgae-based livestock wastewater treatment (MbWT) as a circular bioeconomy approach: Enhancement of biomass productivity, pollutant removal and high-value compound production.
The intensive livestock activities that are carried out worldwide to feed the growing human population have led to significant environmental problems, such as soil degradation, surface and groundwater pollution. Livestock wastewater (LW) contains high loads of organic matter, nitrogen (N) and phosphorus (P). These compounds can promote cultural eutrophication of water bodies and pose environmental and human hazards. Therefore, humanity faces an enormous challenge to adequately treat LW and avoid the overexploitation of natural resources. This can be accomplished through circular bioeconomy approaches, which aim to achieve sustainable production using biological resources, such as LW, as feedstock. Circular bioeconomy uses innovative processes to produce biomaterials and bioenergy, while lowering the consumption of virgin resources. Microalgae-based wastewater treatment (MbWT) has recently received special attention due to its low energy demand, the robust capacity of microalgae to grow under different environmental conditions and the possibility to recover and transform wastewater nutrients into highly valuable bioactive compounds. Some of the high-value products that may be obtained through MbWT are biomass and pigments for human food and animal feed, nutraceuticals, biofuels, polyunsaturated fatty acids, carotenoids, phycobiliproteins and fertilizers. This article reviews recent advances in MbWT of LW (including swine, cattle and poultry wastewater). Additionally, the most significant factors affecting nutrient removal and biomass productivity in MbWT are addressed, including: (1) microbiological aspects, such as the microalgae strain used for MbWT and the interactions between microbial populations; (2) physical parameters, such as temperature, light intensity and photoperiods; and (3) chemical parameters, such as the C/N ratio, pH and the presence of inhibitory compounds. Finally, different strategies to enhance nutrient removal and biomass productivity, such as acclimation, UV mutagenesis and multiple microalgae culture stages (including monocultures and multicultures) are discussed.


Financial and economic analyses of the impact of cattle mastitis on the profitability of Egyptian dairy farms.
This study aimed to evaluate and quantify the different factors affecting the costs of mastitis in cattle, to quantify the annual and monthly financial losses attributed to mastitis, and to estimate production losses using average linear scores found on The Dairy Herd Improvement Association somatic cell count (SCC) sheets and bulk tank SCC per lactation number. All data (bovine mastitis-associated costs and expenditures in Egyptian dairy herds) were analyzed using SPSS/PCT, 2001. A partial budget technique using spreadsheet software and the general linear model procedure was used to analyze the productive and financial measures. Mastitis was present in 57.1% of cows (240/420), while clinical mastitis (CM) was present in 19% of them (80/420). The geometric mean of SCC/ml in bulk tank milk samples of 150 cattle dairy farms was 556.3×103. The annual subclinical mastitis (SCM)-related economic loss was 21,933,258.6 LE, and the two most important cost components were the subsequent decrease in milk production and quality premium losses (93% and 7% of SCM costs, respectively). The quality premium loss was 1,369,602.1 LE. On the other hand, the annual economic loss due to decreased milk production as a result of SCM was 20,563,656.5 LE. The total cost of 80 CM cases, including the failure and preventive costs, was 1,196,871.4 LE, including 1,169,150.4 LE failure costs (106,336.0 LE in direct costs and 1,062,814.4 LE in indirect costs) and 27,721.0 LE preventive costs. The average cost per CM case was 28,760.9 LE, including veterinary time and consultation fees of 250.0 LE (1%), labor 562.5 LE (2%), premature culling 736,000.0 LE (77%), decreased milk production 4085.18 LE (13.7%), discarded milk 185.3 LE (1%), and drugs and treatments 328.9 LE (1%). The total costs of CM (expenditures) extra control and preventive measures, including the diagnosis of CM for 80 cows annually in 20 Egyptian dairy farms were 27,721.0 LE, representing 346.5 LE or 1% of the total cost of CM cases. The cost of monitoring and diagnostic measures was 8635.2 LE, representing 107.9 LE or 1% of the total cost of a case of CM. The method used for cost estimation, in this study, is highly adaptable to individual cattle farms and had a major role in assessing specific control and management measures. The concepts described in this paper help to improve our understanding of the full economic impact of clinical and subclinical mastitis in cattle in Egypt. Assessing the economic losses from mastitis to determine the economic costs and losses occurring in Egyptian dairy farms is critical for encouraging farmers to acknowledge the scale of the problem and implement effective management practices aimed at improving mastitis control and reducing the associated costs.


Missing repeated measures data in clinical trials.
Clinical trials typically collect longitudinal data, data that are collected repeated over time, such as laboratories, scans, or patient-reported outcomes. Due to a variety of reasons, this data can be missing, whether a patient stops attending clinical visits (ie, dropout) or misses assessments intermittently. Understanding the reasons for missing data as well as predictors of missing data can aid in determination of the missing data mechanism. The analysis methods used are dependent on the missing data mechanism and may make certain assumptions about the missing data itself. Methods for nonignorable missing data, which assumes that the missing data depend on the missing data itself, make stronger assumptions and include pattern-mixture models and shared parameter models. Missing data that are ignorable after adjusting for other covariates can be analyzed using methods that adjust for covariates, such as mixed-effects models or multiple imputation. Missing data that are ignorable can be analyzed using standard approaches that require complete case data, such as change from baseline or proportion of patients who declined at a specified time point. In clinical trials, truly ignorable data are rare, resulting in additional analysis methods required for proper interpretation of the results. Conducting several analyses under different assumptions, called sensitivity analyses, can determine the extent of the impact of the missing data.


Bilateral Medial Medullary Infarction Accompanied by Cerebral Watershed Infarction: A case report.
Bilateral medial medullary infarction is a rare stroke subtype, and its diagnosis has become possible by brain magnetic resonance imaging. In this report, we describe a case in which acute bilateral medial medullary infarction accompanied by cerebral watershed infarction was clearly identified by diffusion-weighted imaging, and we discuss the mechanisms of bilateral medial medullary infarction accompanied by cerebral watershed infarction.


Evaluation of aortic regurgitation by cardiac cine magnetic resonance imaging: planar analysis and comparison to Doppler echocardiography.
Cine magnetic resonance imaging (MRI) displays cardiac flow in cine loop fashion on multiple tomographic sections. Since laminar flow is easily distinguished from turbulent flow, cine MRI may be uniquely suited to the study of valvular regurgitation: the entire cardiac volume can be sampled and the regurgitant jet at the valve plane can be depicted. We therefore assessed aortic regurgitation (AR) by cine MRI in 35 patients and 11 normal volunteers and compared results to pulsed (n = 32) or color flow Doppler (n = 14). The extent of the flow disturbance was estimated for both cine MRI and Doppler by indexing the size of the maximal, single plane regurgitant jet area (JA) to the left ventricular (LV) area. Cine MRI JA/LV ratio compared well with pulsed (r = 0.81) and color flow (r = 0.88) Doppler; classification as mild (less than 20%), moderate (20-40%), and severe (greater than 40%) AR by both methods was identical in 43 of 46 cases with no differences of more than one grade. Overall sensitivity and specificity of cine MRI, compared to Doppler, were 94 and 95%, respectively. Cine MRI also depicted the regurgitant jet at the valve plane in 11 patients. Thus planar analysis of cine MRI images in patients with AR provides a semiquantitative assessment of the AR flow disturbance which is similar to Doppler but, in addition, can image the entire cardiac volume and the regurgitant jet at the valve plane.


Evaluation of rapid techniques for the detection of mycobacteria in sputum with scanty bacilli or clinically evident, smear negative cases of pulmonary and extra-pulmonary tuberculosis.
The objective of the current study was to compare two rapid methods, the BBL Mycobacteria Growth Indicator Tube (MGIT TM) and Biotec FASTPlaque TB TM (FPTB) assays, with the conventional Löwenstein-Jensen (LJ) media assay to diagnose mycobacterial infections from paucibacillary clinical specimens. For evaluation of the clinical utility of the BBL MGIT TM and FPTB assays, respiratory tract specimens (n = 208), with scanty bacilli or clinically evident, smear negative cases and non-respiratory tract specimens (n = 119) were analyzed and the performance of each assay was compared with LJ media. MGIT and FPTB demonstrated a greater sensitivity (95.92% and 87.68%), specificity (94.59% and 98.78%), positive predictive value (94.91% and 99.16%) and negative predictive value (96.56% and 90.92%), respectively, compared to LJ culture for both respiratory tract and non-respiratory tract specimens. However, the FPTB assay was unable to detect nontuberculous mycobacteria and few Mycobacterium tuberculosis complex cases from paucibacillary clinical specimens. It is likely that the analytical sensitivity of FPTB is moderately low and may not be useful for the direct detection of tuberculosis in paucibacillary specimens. The current study concluded that MGIT was a dependable, highly efficient system for recovery of M. tuberculosis complexes and nontuberculous mycobacteria from both respiratory and non-respiratory tract specimens in combination with LJ media.


Pollution of modern metalworking fluids containing biocides by pathogenic bacteria in France. Reexamination of chemical treatments accuracy.
Pollution by pathogenic bacteria was examined in 150 French metalworking fluid samples. Gram-negative micro-organisms such as Salmonella spp., Shigella spp., and Vibrio spp. as well as Gram-positive cocci were never isolated. Nevertheless opportunistic pathogens such as Pseudomonas aeruginosa and Klebsiella pneumoniae still contaminated these fluids with an isolation frequency of 17% of samples for each. These two micro-organisms failed to grow or even survive in vitro in sterile cutting fluids protected by biocides. Preliminary growth of other micro-organisms such as Pseudomonas putida or Pseudomonas fluorescens, which are the major part of the indigenous microflora, seemed to be a prerequisite for their growth. These former two Pseudomonas could resist three different classes of biocides and, at least in the case of formaldehyde-releasers, adaptation was followed by biocide deterioration. Resistance magnification was observed in the presence of the three different types of biocides and, in the case of formaldehyde releasers the resistance and deterioration levels were close to those recommended by the manufacturers. This is probably the reason why the preliminary growth of Pseudomonas putida allowed in vitro differed growth of Klebsiella pneumoniae and Pseudomonas aeruginosa. Due to relatively high isolation frequencies of opportunistic pathogens (17% of samples) periodical microbiological examination of cutting fluids should be carried out in order to evaluate risks for human health. Wearing masks and gloves is still recommended, at least in France.


[Immunophenotype analysis of leukemic mantle cell lymphoma].
Mantle cell lymphoma (MCL) is a kind of mature B-cell neoplasms with significantly poor prognosis and is usually misdiagnosed. With the development of flow cytometry and cytogenetic technique, most patients were at leukemic phase when diagnosed. This study was purposed to investigate the immunophenotypes of MCL, the immunophenotype information of 22 leukemic MCL patients was analyzed retrospectively. All the patients were conformed t(11;14) translocation by fluorescence in situ hybridization. Immunophenotypes were detected by a four-color flow cytometry including CD3, CD4, CD5, CD8, CD10, CD19, CD20, CD22, CD23, CD25, CD38, CD103, CD148, CD200, FMC7, ZAP-70, κ, λ. The results showed that CD19, CD5, CD20 and monoclonal sIg expressed in all 22 patients with CD20 high expression; CD22 expressed weakly in 17 patients; CD23 expressed in 6 patients including 2 cases highly expressed; FMC7 expressed in 12 patients. 5 patients were 4-point score and 17 patients had a score less than 4 according to CLL scoring system. CD148 and CD200 were detected in 18 patients, in which CD200 expressed negatively in 11 patients, CD200 expressed weakly in 7 patients with median fluorescence intensity (MFI) 25.8 (6.6 - 254.26); CD148 expressed positively in all 18 patients with median MFI: 337 (73.4 - 1341.9). It is concluded that the atypical immunophenotype is common in leukemia MCL, thereby the diagnosis of MCL needs comprehensively analyze with morphocytology, immunophenotype and cytogenetic, CD200 and CD148 as new bio-markers can differentiate MCL from chronic B cell lymphoproliferative disease.


Inhibition of neuron-specific CREB dephosphorylation is involved in propofol and ketamine-induced neuroprotection against cerebral ischemic injuries of mice.
Propofol and ketamine may provide certain degree of neuroprotection, but the underlying mechanism remains unclear to date. The cAMP response element-binding protein (CREB) was proposed that its phosphorylation at Ser133 (P-CREB) constituted a convergence point involved in neuroprotection. The purpose of this study was to determine whether different dosages of propofol and ketamine could provide neuroprotection against permanent middle cerebral artery occlusion (MCAO)-induced ischemic injuries and the involvement of P-CREB. Eighty adult male BALB/c mice that underwent 6 h MCAO were randomly divided into eight groups: Sham-operation; MCAO + saline; MCAO + 25, 50, 100 mg/kg propofol; and MCAO + 25, 50, 100 mg/kg ketamine (intraperitoneal injection 30 min following MCAO). We found that 50, 100 (not 25) mg/kg propofol, and 25 (not 50 and 100) mg/kg ketamine could significantly reduce the infarct volume, edema ratio and neurological deficit (n = 10 per group) as well as inhibit the decrease of P-CREB level in peri-infarct region when compared with that of MCAO + saline group (n = 6 per group). In addition, the results of double-labeled immunofluorescent staining showed that P-CREB co-localized with neuron-specific marker, NeuN, in the peri-infarct region of 50 mg/kg propofol and 25 mg/kg ketamine treated 6 h MCAO mice (n = 4 per group). These results suggested that inhibition of neuron-specific P-CREB dephosphorylation in the peri-infarct region is involved in high dose propofol and low dose ketamine-induced neuroprotection of 6 h MCAO mice.


Toronto tele-retinal screening program for detection of diabetic retinopathy and macular edema.
There are currently low rates of screening for diabetic retinopathy (DR) and sight-threatening diabetic macular edema (DME) in Ontario. To present results of the Toronto Tele-Retinal screening program for patients with diabetes mellitus and to evaluate thebenefit of optical coherence tomography (OCT) in combination with monoscopic colour fundus photographs for detection of DME. All electronic medical records for adults with type I and II diabetes mellitus screened through the Toronto Tele-Retinal screening program between September 2013 to August 2017 across 7 sc~reening sites in urban and rural settings were reviewed. Monoscopic colour fundus photographs were graded for presence or absence of DR and DME alone and in combination with OCT scans. A total of 775 patient screens, consisting of 566 first-time screens and 209 re-screens were completed over the 48-month study period. Approximately 37% of all patients with a mean disease duration of 7years had never had an eye examination. Across the sample, 27% of patients had DR, with majority graded to have mild DR, whereas DME was detected in 5% of patients in at least 1 eye. Of all DME detected in the Toronto Tele-Retinal screening program, 38% required the use of adjunct OCT. Other pathologies, including age-related macular degeneration (19%) and glaucomatous or optic nerve findings (8%), were also identified. Tele-retinal screening programs may circumvent low rates of DR screening for patients with diabetes mellitus and increase the rate of detection of DME with monoscopic colour fundus photographs and adjunct OCT.


Paraneoplastic polyneuropathy preceding the diagnosis of Hodgkin's disease and non-small cell lung cancer in a patient with concomitant Borrelia burgdorferi infection.
A patient with painful peripheral neuropathy is presented, whose symptoms were thought to result from an infection with Borrelia burgdorferi sensu lato. Investigations of the cerebrospinal fluid for signs of inflammation and borrelial antibodies were negative, and the patient did not benefit from repeated antibiotic treatment. Electrophysiologic studies and sural nerve biopsy showed axonal neuropathy consistent with a paraneoplastic syndrome. Further workup revealed mediastinal Hodgkin's disease (HD; nodular sclerosing subtype) Ann Arbor stage II and non-small cell cancer of the lung (stage T1N0M0). Surgical resection of the lung cancer and combined chemo- and radiotherapy for HD resulted in complete remission of both malignancies. While the preexisting neurologic symptoms persisted during treatment, neurography showed some improvement of the distal nerves. During radiation therapy the patient developed transient left-sided brachial plexopathy. This case illustrates that the diagnosis of borreliosis in patients with isolated painful peripheral neuritis cannot be based solely upon positive IgG titers and supports the requirement for a thorough workup for an underlying--potentially curable--disease. In addition, singular pulmonary lesions in the setting of HD should be suspected to have a separate cause.


Prediction of attitudes toward disabled persons: a multivariate analysis.
University students N equals 326 were asked to complete the Attitude Toward Disabled Persons (ATDP) scale Form 0, and their summated scores were correlated with six demographic and experiential variables. A multiple correlation of .25 was obtained between the attitude variable and a composite of the predictors. Intensity of contact with disabled persons accounted for the most variance in attitude scores.


Stem cell mobilization in normal donors.
We studied peripheral blood and apheresis samples from 39 consecutive normal donors who were parents or siblings of patients who received matched or mismatched bone marrow transplants using a combination of rhG-CSF-mobilized peripheral blood stem cells (PBSCs) and bone marrow (BM). BM was harvested from donors 1-7 days before starting rhG-CSF treatment: 12 micrograms/kg/day rhG-CSF was administered by continuous s.c. infusion for 4-7 days. Peripheral blood progenitor cells were harvested by leukapheresis using an automated continuous-flow blood cell separator, beginning on day 4 of rhG/CSF, for 1-4 consecutive days. Peak peripheral blood CD34+ cell and CFU-GM levels were reached simultaneously on day 5 or 6 of rhG-CSF administration. Median peak levels were 1.65% for CD34+ cells (range 0.34%-4.7%) and 142 CFU-GM/10(5) plated cells (range 16-700). The greatest numbers of CD34+ cells and CFU-GM, expressed per liter of blood volume processed, were harvested during the second and third leukapheresis: CD34+ cells 37.77 +/- 25.48 x 10(6) and CFU-GM 3.32 +/- 2.51 x 10(6) during the second leukapheresis, and CD34+ cells 37.01 +/- 16.33 x 10(6) and CFU-GM 3.82 +/- 4.36 x 10(6) during the third. The number of CD34+ cells and CFU-GM did not correlate with the sex, age, or body weight of the donors. This study indicates that this protocol for administration of rhG-CSF mobilizes large numbers of hematopoietic progenitor cells into the peripheral blood and that bone marrow harvesting before G-CSF administration does not impair stem cell mobilization.


Assessment of Variation in State Regulation of Generic Drug and Interchangeable Biologic Substitutions.
Brand-name drugs, including biologics, have been the primary source of increasing prescription drug spending in the US. Each state has drug product selection laws that regulate whether and how pharmacists can substitute prescriptions for brand-name drugs with more affordable equivalents, either small-molecule generic drugs or interchangeable biologics, but the details of these laws can vary. To examine the variation in state drug product selection laws with regard to factors that may affect which version of a drug is dispensed. A cross-sectional analysis was performed, using a legal database, to obtain information on state laws of all states plus Washington, DC, as they existed on September 1, 2019. Whether substitution was mandatory or permissive, patient consent was needed prior to substitution, patient notification of substitution was required independent of the drug's packaging, and/or pharmacists were protected from special risk of liability for substitution. For small-molecule and biologic drugs, descriptive statistics were generated for the 4 exposure variables. In addition, for small-molecule drugs, a generic substitution score with a maximum of 1 point was assigned for each exposure variable (range, 0-4 points), with higher scores indicating regulatory requirements limiting substitution. This cross-sectional analysis of the generic drug substitution regulations in the 50 US states and Washington, DC, found that for small-molecule drugs, 19 states required pharmacists to perform generic substitution; 7 states and Washington, DC, required patient consent; 31 states and Washington, DC, mandated patient notification independent of the drug's packaging, and 24 states did not explicitly protect pharmacists from greater liability. Nine states and Washington, DC, had a generic substitution score for small-molecule drugs of 3 or higher, and 45 states had more stringent requirements for interchangeable biologic substitution, most commonly mandatory physician notification. The findings of this study suggest that there is a need for optimizing state drug product selection laws to promote generic and interchangeable biologic substitution, which may help improve medication adherence and reduce drug spending.


Correlation of Walking Activity and Cardiac Hospitalizations in Coronary Patients for 1 Year Post Cardiac Rehabilitation: The More Steps, the Better!
Reducing risk by improving fitness is one of the main objectives of cardiac rehabilitation (CR). To estimate how the number of steps/day post-CR affects coronary patients' prognosis, we analyzed its correlation with the occurrence of death, hospitalizations, and heart complaints, and if and how other variables (ejection fraction (EF), gender, age) relate to those. One hundred eleven patients (male = 91, female = 20; average age ± standard deviation (SD): 61 ± 11 years) who had been in CR due to recent coronary revascularization or chronic coronary syndrome could be enrolled. Patients were advised to document their steps (daily), blood pressure (daily), weight (weekly) and occurrences of a cardiac event in a diary for 1 year post-CR. A Cox proportional hazard model was used to examine the influence of steps/day, EF, gender, and age until the occurrence of an event. Kaplan-Meier curves were generated to compare patients' profiles. Average steps/day of patients post-CR were 7333 (SD 4426). Increased walking activity reduced risk for cardiac hospitalization (constant steps/day: 5000 vs 7500, hazard rate (HR) reduction of 0.43; 10 000 vs 12 500, HR reduction of 0.20) and risk was higher in patients with an EF < 55% versus EF ⩾ 55% (HR increase of 2.88). Median follow-up time post-CR was 218 days. No patient died, 25 were hospitalized. Monitoring the number of steps of coronary patients post CR could be valuable for estimating patients' prognosis.


Lack of suppressor cell activity in the spleens of mice with radiation-induced osteogenic sarcomas.
C57BL/6J mice were used both for induction of osteogenic sarcomas by injection of 90Sr and for induction of sarcomas and carcinomas by injection of 9,10-dimethyl-1,2-benzanthracene. The osteogenic sarcomas had a relatively long induction period; they possessed low immunogenicity and failed to activate splenic suppressor cells either in the original tumor-bearing host or in mice bearing transplanted osteogenic sarcomas. In contrast, and in agreement with previous work, 9,10-dimethyl-1,2-benzanthracene-induced tumors had a relatively short induction period; they possessed high immunogenicity and activated splenic suppressor cells in mice bearing transplanted tumors. These results suggest the possibility that the immunogenicity of tumors correlates with the ability of tumors to activate suppressor cells.


4,1',6'-Trichloro-4,1',6'-trideoxysucrose monohydrate.
At 160 K, the glucopyranosyl ring in 1,6-dichloro-1,6-dideoxy-beta-D-fructofuranosyl 4-chloro-4-deoxy-alpha-D-glucopyranoside monohydrate, C(12)H(19)Cl(3)O(8).H(2)O, has a near ideal (4)C(1) chair conformation, while the fructofuranosyl ring has a (4)T(3) conformation. The conformation of the sugar molecule is quite different to that of sucralose, particularly in the conformation about the glycosidic linkage, which affects the observed pattern of intramolecular hydrogen bonds. A complex series of intermolecular hydrogen bonds links the sugar and water molecules into an infinite three-dimensional framework.


Recent experiments towards a model for fluid secretion in Rhodnius Upper Malpighian Tubules (UMT).
Three different methods have been used to improve a model for fluid secretion in Upper Malpighian Tubules (UMT) of the blood sucking insect Rhodnius prolixus. (I) In the first, UMT double perfusions in 5th instar Rhodnius were used to measure their fluid secretion rate. They were stimulated to secrete with 5-HT. Double perfusions allowed access separately to the basolateral and the apical cell membranes with pharmacological agents known to block different ion transport functions, namely ATPases, cotransporters and/or countertransporters and ion and water channels: ouabain, bafilomycin A1, furosemide, bumetanide, SITS, acetazolamide, amiloride, DPC, BaCl(2), pCMBS and DTT. The basic assumption is that changes in water movement reflect changes in ion transport mechanisms. (II) Intracellular Na(+) concentrations were measured with a fluorometric method in dissected R. prolixus UMT, under several experimental conditions. (III) ATPase activities were measured in R. prolixus UMT. A tentative model for the function of the UMT cell is presented. We find that (a) at the basolateral cell membrane, fundamental is a Na(+)-K(+)-2Cl(-) cotransporter; of intermediate importance are the Na(+)-K(+)-ATPase and a ouabain-insensitive Na(+)-ATPase, ion channels and Rp-MIP water channels. (b) At the apical cell membrane, most important are a V-H(+)-ATPase; and a K(+) and/or Na(+)-H(+) exchanger.


Electromyography evaluation of masseter and temporalis, bite force, and quality of life in elderly patients during the adaptation of mandibular implant-supported overdentures.
The aim of this study was to investigate the outcomes of the installation of two implant-supported overdentures until such treatment is complete. Although this treatment is well established in the literature, there are no studies comparing what happens to muscles and the quality of life (QoL) of patients during the treatment. We selected 13 completely edentulous patients, according to inclusion and exclusion criteria, to rehabilitate with mandibular overdentures retained by two dental implants and a complete denture as antagonists. We evaluated the efficacy of the treatment and its evolution in five steps: (i) initially, with the old complete dentures, (ii) after the implants' placement with the mandibular prosthesis relined, (iii) after the placement of the healing abutments, (iv) after the installation and adaptation of new prostheses, and (v) after a 3-month follow-up period. At each stage, we evaluated patients via temporal and masseter electromyography (EMG), molar and incisive bite force, and QoL. The results for EMG found a decrease in muscle activity during rest, the mastication of raisins, and lateral movements when the overdentures were installed. For the bite force and QoL, there was a gradual improvement from the placement of the healing abutments period (P ˂ 0.05), which was sustained until the follow-up. Comfort and stability improved during the treatment, demonstrated by the QoL and bite force results. These results are positive for elderly patients who might refuse an implant-supported overdenture due to treatment length.


Well-rounded devices: the fabrication of electronics on curved surfaces - a review.
With the arrival of the internet of things and the rise of wearable computing, electronics are playing an increasingly important role in our everyday lives. Until recently, however, the rigid angular nature of traditional electronics has prevented them from being integrated into many of the organic, curved shapes that interface with our bodies (such as ergonomic equipment or medical devices) or the natural world (such as aerodynamic or optical components). In the past few years, many groups working in advanced manufacturing and soft robotics have endeavored to develop strategies for fabricating electronics on these curved surfaces. This is their story. In this work, we describe the motivations, challenges, methodologies, and applications of curved electronics, and provide a outlook for this promising field.


Telepharmacy for remote hospital inpatients in north-west Queensland.
Clinical pharmacy service delivery is currently a significant challenge in remote areas. Mount Isa Base Hospital provides clinical pharmacy support to ten remote sites across an area of over 300,000 square kilometres. These sites do not have on-site pharmacists available and, due to the vast distances and unpredictable travel conditions, the outreach pharmacist from Mount Isa Base Hospital only visits sporadically. Provision of direct patient care and advice on medication safety with this model was restricted and insufficient. Telepharmacy provides an opportunity for these services to be vastly expanded. In an attempt to increase pharmacist accessibility for remote hospital sites, the Mount Isa Base Hospital pharmacy department developed an inpatient telepharmacy service. Telehealth equipment is being used to communicate directly with patients and hospital staff, review inpatient medication charts, generate patient medication lists, identify and resolve clinical interventions and provide medication-related advice and counselling. As a result of this implementation, all patients and health professionals in remote north-west Queensland hospitals now have access to a pharmacist. The number of inpatient medication reviews, clinical interventions and patient-pharmacist/clinician-pharmacist interactions occurring at each remote hospital site has increased. Since service initiation, 106 medication-related reviews have been completed via telepharmacy, including 48 patient interactions, and 111 medication-related interventions have been made. This paper outlines the process for the development of an inpatient telepharmacy service for remote hospitals and discusses the benefits and limitations associated with implementation.


Vacuum decay constraints on a cosmological scalar field.
If the potential of a scalar field phi which currently provides the "dark energy" of the Universe has a minimum at phi = -M(0)(4)<0, then quantum-mechanical fluctuations could nucleate a bubble of phi at a negative value of the potential. This bubble would then expand at the speed of light. Given that no such bubble enveloped us in the past, we find that any minimum in V(phi) must be separated from the current phi value by more than min[1.5M(0),0.21M(Pl)], where M(Pl) is the Planck mass. We also show that vacuum decay renders a cyclic or ekpyrotic universe with M(0)(4) > or approximately 10(-10)M(4)(Pl) untenable.


C3:CH50 ratio as a proposed composite marker for eculizumab monitoring in atypical hemolytic uremic syndrome: Preliminary results.
Treatment of atypical hemolytic uremic syndrome (aHUS) by the complement C5 inhibitor eculizumab (Soliris®) is highly effective but unfortunately, associated with an economic pressure on the health care systems even in high incomes countries. Despite spacing infusions having been proposed as the unique solution to minimize this economic impact, no reliable laboratory assays are available to tailor such therapy optimization. We aimed to propose and evaluate a complement composite marker for eculizumab efficacy monitoring in aHUS. We have retrospectively analyzed complement profiles data of eight aHUS patients under eculizumab from the International Registry of HUS/Thrombotic Thrombocytopenia Purpura, and calculated a novel marker "C3:CH50 ratio" by dividing C3 value by CH50 one for each sample during induction and maintenance periods. The results significance was compared to the currently used biomarkers for eculizumab tailoring. In contrast to the current biomarkers used for eculizumab efficacy monitoring like CH50 and soluble or deposit membrane attack complexes, "C3:CH50 ratio" seems to be the most interesting one since its value at pre-eculizumab dosage equaled 0.92 ± 0.2 while the post-eculizumab one increased significantly to reach 24.54 ± 10.7; P < 0.001. Furthermore, this ratio correlated negatively with platelets count (r = -0.722, P = 0.018) while no correlation was found within the thrombotic microangiopathy (TMA) biomarkers and complement blockade for the other parameters that change in pre and post-eculizumab therapy. As far as we know, this is the first study that suggests a post-eculizumab parameter correlating simultaneously with drug's activity (complement inhibition) and disease activity (platelets counts). Nonetheless, the limited number of patients enrolled in this study should be considered in larger studies to guide eculizumab optimization by indicating the time when subsequent withdrawal or infusion spacing is allowed or recommended.


An Update on Choroidal Layer Segmentation Methods in Optical Coherence Tomography Images: a Review.
Choroid is one of the structural layers, playing a significant role in physiology of the eye and lying between the sclera and the retina. The segmentation of this layer could guide ophthalmologists in diagnosing most of the eye pathologies such as choroidal tumors and polypoidal choroidal vasculopathy. High signal-to-noise ratio and high speed imaging in Spectral-Domain Optical Coherence Tomography (SD-OCT) make choroidal imaging feasible. Several variables such as pre-operative axial length (AXL), time of day and age affect thickness of the choroidal vascularization and should be considered for segmentation of this layer. These days most of the eye specialists manually segment the choroidal layer which is time-consuming, tiresome and dependent on human errors. To overcome these difficulties, some studies have introduced different automatic choroidal segmentation methods. In this paper, we have conducted a comprehensive review on existing recently published methods for automatic choroidal segmentation algorithms.


The endoplasmic reticulum stress transducer OASIS is involved in the terminal differentiation of goblet cells in the large intestine.
OASIS is a basic leucine zipper transmembrane transcription factor localized in the endoplasmic reticulum (ER) that is cleaved in its transmembrane region in response to ER stress. This novel ER stress transducer has been demonstrated to express in osteoblasts and astrocytes and promote terminal maturation of these cells. Additionally, OASIS is highly expressed in goblet cells of the large intestine. In this study, we investigated the roles of OASIS in goblet cell differentiation in the large intestine. To analyze the functions of OASIS in goblet cells, we examined morphological changes and the expression of goblet cell differentiation markers in the large intestine of Oasis(-/-) mice. By disrupting the Oasis gene, the number of goblet cells and production of mucus were decreased in the large intestine. Oasis(-/-) goblet cells showed abnormal morphology of mucous vesicles and rough ER. The expression levels of mature goblet cell markers were lower, and conversely those of early goblet cell markers were higher in Oasis(-/-) mice, indicating that differentiation from early to mature goblet cells is impaired in Oasis(-/-) mice. To determine the association of OASIS with other factors involved in goblet cell differentiation, in vitro experiments using a cell culture model were performed. We found that OASIS was activated in response to mild ER stress that is induced in differentiating goblet cells. Knockdown of the Oasis transcript perturbed goblet cell terminal differentiation. Together, our data indicate that OASIS plays crucial roles in promoting the differentiation of early goblet cells to mature goblet cells in the large intestine.


Determination of free and total sulfites in wine using an automatic flow injection analysis system with voltammetric detection.
An automated flow injection analysis (FIA) system, based on an initial analyte separation by gas-diffusion and subsequent determination by square-wave voltammetry (SWV) in a flow cell, was developed for the determination of total and free sulfur dioxide (SO(2)) in wine. The proposed method was compared with two iodometric methodologies (the Ripper method and a simplified method commonly used by the wine industry). The developed method displayed good repeatability (RSD lower than 6%) and linearity (between 10 and 250 mg l(-1)) as well as a suitable LOD (3 mg l(-1)) and LOQ (9 mg l(-1)). A major advantage of this system is that SO(2) is directly detected by flow SWV.


An Inpatient Geriatrics Program with a Focus on Any Type of Cognitive Impairment Reduces Mortality.
No matter what type of cognitive impairment an older hospitalized patient has, the risk of mortality is increased. To describe a hospital-based geriatrics program with a focus on any type of cognitive impairment and to determine whether this program was associated with reduced mortality over time. Retrospective chart review of all patients age 70+ admitted during a 3-year period (2017-2019, N=20,401), to a 500-bed community-based hospital (Level 1 Trauma Center and Stroke Center). A multicomponent geriatrics program was developed and implemented throughout 2018 and included: geriatric consultation, data collection, review of the data with hospital leaders, a geriatrics task force, clinician education and a Delirium Unit. Monthly mortality rates for patients with and without cognitive impairment over the 3-year period. To control for other variables associated with mortality, pre-post implementation analyses were performed (2017 versus 2019). A linear regression analysis showed a significant downward trend in mortality over time for patients with cognitive impairment [R2=0.4, P<.0001, (correlation coefficient -0.6, 95% CI, -0.8 to -0.4)] but not among patients without cognitive impairment [R2=0.0, P=0.829, (correlation coefficient 0.0, 95% CI, -0.3 to 0.3)]. When controlling for other variables, there was still a decrease in mortality risk among patients with cognitive impairment. Although there are limitations to this study, a multicomponent geriatrics program with an emphasis on any type of cognitive impairment, may be associated with improved mortality.


Familial Aggregation of Systemic Lupus Erythematosus and Coaggregation of Autoimmune Diseases in Affected Families.
Relatives of patients with systemic lupus erythematosus (SLE) appear to be at higher risk of SLE and other autoimmune diseases, but estimates of individual familial risks are largely unavailable or unreliable. Furthermore, relative contributions of genetic, shared, and unshared environmental factors to SLE susceptibility remain unclear. To examine familial aggregation and heritability of SLE and the relative risks (RRs) of other autoimmune diseases in relatives of patients with SLE. A population-based family study using the Taiwan National Health Insurance Research Database was conducted. Participants included all individuals (N = 23,658,577) registered with that database in 2010; of these, 18,283 had SLE. We identified 21,009,551 parent-child relationships, 17,168,340 full sibling pairs, and 342,066 twin pairs. Diagnoses of SLE were ascertained from March 1, 1995, to December 31, 2010, and analysis was conducted between March 1 and August 15, 2014. The prevalence and RRs of SLE and other autoimmune diseases in relatives and spouses of patients with SLE as well as the relative contributions of heritability, shared, and nonshared environmental factors to SLE susceptibility. Among the more than 23 million participants, the RRs (95% CIs) for SLE were 315.94 (210.66-473.82) for twins of the patients, 23.68 (20.13-27.84) for siblings, 11.44 (9.74-13.43) for parents, 14.42 (12.45-16.70) for offspring, and 4.44 (2.38-8.30) for spouses without genetic similarity. The accountability for phenotypic variance of SLE was 43.9% for heritability, 25.8% for shared environmental factors, and 30.3% for nonshared environmental factors. The RRs (95% CIs) in individuals with a first-degree relative with SLE were 5.87 (4.89-7.05) for primary Sjögren syndrome, 5.40 (3.37-8.65) for systemic sclerosis, 2.95 (2.04-4.26) for myasthenia gravis, 2.77 (1.45-5.32) for idiopathic inflammatory myositis, 2.66 (2.28-3.11) for rheumatoid arthritis, 2.58 (1.16-5.72) for multiple sclerosis, 1.68 (1.22-2.32) for type 1 diabetes mellitus, 1.39 (0.66-2.91) for inflammatory bowel diseases, and 0.86 (0.43-1.71) for vasculitis. The individual risks of SLE and other autoimmune diseases were increased in families that included patients with SLE. The heritability of SLE was estimated to be 43.9%. These data should be considered when counseling families with affected members.