White Matter Microstructural Properties are Related to Inter-Individual Differences in Cognitive Instability after Sleep Deprivation.
Several diseases are characterized by cognitive instability, which is amplified in the conditions of sleep deprivation (SD). Cognitive instability in SD can be examined by the number of lapses on the psychomotor vigilance test (PVT), which is considered to be a gold standard in the field. However, the number of PVT lapses widely range according to inter-individual differences, from apparent cognitive resistance to severe cognitive impairment. In this study, tract-based spatial statistical analyses with multiple diffusion tensor imaging-derived characteristics (i.e., fractional anisotropy (FA), mean diffusivity, radial diffusivity, and axial diffusivity) were employed to investigate the relationships between the number of PVT lapses and the diffusion characteristics. A hierarchical linear regression model was then used to assess the contributions of tract-specific FA values in predicting PVT lapses. Finally, dichotomized analysis was used to investigate white matter (WM) differences between resilient and vulnerable groups. Our results showed significant negative correlations between numbers of PVT lapses and FA in multiple WM tracts, with the FA variations in the superior longitudinal fasciculus and splenium of the corpus callosum accounting for nearly 37.5% of individual variability in PVT lapses. In addition, dichotomized analyses indicated that the resilient participants exhibited significantly higher FA values compared with the vulnerable participants. Together, these findings suggest that cognitive instability after SD was closely associated with individual differences in WM integrity.


Abdominosacral coloanostomy made by invagination.
An abdominosacral 'closed' rectum resection is reported which, at the same time, enables the preparation of a provisional anal stoma for protection of the orifice.


Hematopoietic Stem Cell Transplantation in Acute Promyelocytic Leukemia in the Era of All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (ATO).
Acute promyelocytic leukemia (APL) currently represents one of the malignant hemopathies with the best therapeutic responses, following the introduction of all-trans retinoic acid (ATRA) and subsequently of arsenic trioxide (ATO) treatment. As a result, a large proportion of patients with APL achieve long-term responses after first-line therapy, so performing a hematopoietic stem cell transplant as consolidation of first complete remission (CR) is no longer necessary. Even in the case of relapses, most patients obtain a new remission as a result of therapy with ATO and ATRA, but an effective consolidation treatment is necessary to maintain it. The experience accumulated from studies published in the last two decades shows the effectiveness of hematopoietic stem cell transplantation (HSCT) in improving the outcome of patients who achieve a new CR. Thus, the expert groups recommend transplantation as consolidation therapy in patients with a second CR, with the indication for autologous HSCT in cases with molecular CR and for allogeneic HSCT in patients with the persistence of minimal residual disease (MRD) or with early relapse. However, there is a variety of controversial aspects related to the role of HSCT in APL, ranging from the fact that outcome data are obtained almost exclusively from retrospective studies and historical analyses to questions related to the type of transplantation, the impact of minimal residual disease, conditioning regimens, or the role of other therapeutic options. All these questions justify the need for controlled prospective studies in the following years.


Recent advances in airborne pathogen detection using optical and electrochemical biosensors.
The world is currently facing an adverse condition due to the pandemic of airborne pathogen SARS-CoV-2. Prevention is better than cure; thus, the rapid detection of airborne pathogens is necessary because it can reduce outbreaks and save many lives. Considering the immense role of diverse detection techniques for airborne pathogens, proper summarization of these techniques would be beneficial for humans. Hence, this review explores and summarizes emerging techniques, such as optical and electrochemical biosensors used for detecting airborne bacteria (Bacillus anthracis, Mycobacterium tuberculosis, Staphylococcus aureus, and Streptococcus pneumoniae) and viruses (Influenza A, Avian influenza, Norovirus, and SARS-CoV-2). Significantly, the first section briefly focuses on various diagnostic modalities applied toward airborne pathogen detection. Next, the fabricated optical biosensors using various transducer materials involved in colorimetric and fluorescence strategies for infectious pathogen detection are extensively discussed. The third section is well documented based on electrochemical biosensors for airborne pathogen detection by differential pulse voltammetry, cyclic voltammetry, square-wave voltammetry, amperometry, and impedance spectroscopy. The unique pros and cons of these modalities and their future perspectives are addressed in the fourth and fifth sections. Overall, this review inspected 171 research articles published in the last decade and persuaded the importance of optical and electrochemical biosensors for airborne pathogen detection.


Sequence-specific cleavage of BM2 gene transcript of influenza B virus by 10-23 catalytic motif containing DNA enzymes significantly inhibits viral RNA translation and replication.
One of the hallmarks of progression of influenza virus replication is the step involving the virus uncoating that occurs in the host cytoplasm. The BM2 ion channel protein of influenza B virus is highly conserved and is essentially required during the uncoating processes of virus, thus an attractive target for designing antiviral drugs. We screened several DNA enzymes (Dzs) containing the 10-23 catalytic motif against the influenza B virus BM2 RNA. Dzs directed against the predicted single-stranded bulge regions showed sequence-specific cleavage activities. The Dz209 not only showed significant intracellular reduction of BM2 gene expression in transient-expression system but also provided considerable protection against influenza B virus challenge in MDCK cells. Our findings suggest that the Dz molecule can be used as selective and effective inhibitor of viral RNA replication, and can be explored further for development of a potent therapeutic agent against influenza B virus infection.


Goat performance on pure Andropogon gayanus pastures or associated with legumes.
The objective of this study was to evaluate the grazing of goats in a grass monoculture system and in intercropping systems of grass + legumes. A randomized block design was adopted, with the treatments arranged in a split-plots scheme. The plots consisted of three cropping systems: monoculture-Andropogon gayanus cv. Planaltina; mixture I-A. gayanus cv. Planaltina + Stylosanthes cv. Campo Grande; and mixture II-A. gayanus cv. Planaltina + Calopogonium mucunoides. The subplots consisted of two grazing cycles. The highest (P = 0.04) total forage mass (TFM) was recorded in the mixture I (A. gayanus cv. Planaltina + Stylosanthes. cv. Campo Grande), which was 2.6 ± 0.1 tons DM/ha. The crude protein (CP) was lower in the monoculture which also showed the highest content of neutral detergent fiber (NDF). The grazing time in the monoculture was the longest (8.23 ± 1.14 h). The goats used a longer time for rumination (P < 0.01) in the mixture I. The lowest (P < 0.01) bite rate was found in mixture II in comparison to the other cropping systems. The bite rate was higher (P < 0.01) in grazing cycle II than in all the other cropping systems. In mixture I, the Stylosanthes cv. Campo Grande, and in mixture II, the C. mucunoides presented the lowest (P < 0.01) δ13C value in the forage. The highest forage intake occurred in the mixture systems (P < 0.01) in comparison to the monoculture. The mixture pastures presented better results for forage mass, nutritive value, and intake in comparison to the monoculture.


Regulatory-T-cell inhibition versus depletion: the right choice in cancer immunotherapy.
Tumour-induced expansion of regulatory T (T(Reg)) cells is an obstacle to successful cancer immunotherapy. The potential benefit of T(Reg)-cell depletion through the interleukin-2 receptor is lost by the concurrent elimination of activated effector lymphocytes and possibly by the de novo induction of T(Reg)-cell replenishment. In theory, the functional inactivation of T(Reg) cells will maintain them at high numbers in tumours and avoid their replenishment from the peripheral lymphocyte pool, which has the capacity to further suppress the effector lymphocyte anti-tumour response.


Multifactorial analysis of parameters influencing chemosensitivity of human cancer xenografts in nude mice.
The results of single-agent chemotherapy, with 11 anticancer agents, of 15 human gastro-intestinal and breast cancer lines xenografted into nude mice indicate inherent individuality of chemosensitivity spectrum of each tumor. The following 9 parameters have been measured as factors possibly relevant to chemosensitivity of tumor tissue or tumor-bearing mice: grade of histological differentiation, vascularity, percentage of necrosis, VDT, 3H-thymidine LI, human LDH activity in the cancer tissue, tissue/serum LDH ratio, TdR Pase activity, and serum CEA. These parameters exhibited presumably constant values for each tumor line. Chemosensitivity, i.e., inhibition of tumor growth by a given drug, was used as the dependent variable, and values of the 9 parameters in each cancer as the explanatory variables. Multiple regression analyses with stepwise deletion were performed for each of the 11 drugs. The equations for 8 drugs exhibited coefficients of determination of over 70%, and in particular those for M-83 (a derivative of mitomycin C), nimustine hydrochloride and doxorubicin exceeded 80% by equations with 3-4 parameters. Consequently, the estimated value for each line of effectiveness derived from the equations for these 8 drugs showed remarkable coincidences with the actual values for the inhibition rates of the corresponding drugs.


Tubulin binds specifically to the signal-transducing proteins, Gs alpha and Gi alpha 1.
Participation of cytoskeletal elements in regulation of hormonal response and responsiveness has been suggested by several laboratories. Addition of dimeric tubulin to rat cerebral cortex synaptic membranes causes stable inhibition of adenylyl cyclase, and the molecular basis for this effect appears to require a direct interaction between tubulin and G proteins. To test whether such tubulin-G protein interaction occurred, several purified G proteins were bound to nitrocellulose, and 125I-tubulin overlay studies were performed. 125I-Tubulin bound to the alpha subunits of Gs and Gil with high specificity and an apparent Kd of approximately 130 nM. Other G protein alpha subunits (alpha i2, alpha i3, alpha 0, and transducin) displayed a much lower affinity for tubulin, despite the much closer relationship of those proteins to alpha il than to alpha s. Association of beta gamma subunits with alpha il or alpha s did not alter the binding of tubulin to these G protein heterotrimers, and the binding of a hydrolysis-resistant GTP analog to the alpha subunits was similarly without effect. These results suggest that tubulin forms complexes with specific G proteins and these complexes might provide a locus for the interaction of cytoskeletal components and signal transduction cascades. These results also provide evidence of a functional distinction among the closely related alpha i subtypes.


Transurethral Enucleation With Bipolar Energy (TUEB):AINU Technique and Short-term Outcomes.
To present our transurethral enucleation with bipolar energy (TUEB) technique, wherein the enucleated adenoma is resected while keeping it attached near the verumontanum avoiding the need of a morcellator, and to evaluate the safety and short-term outcomes of our technique of TUEB for the treatment of symptomatic benign prostatic hypertrophy (BPH). This was a retrospective evaluation of prospectively maintained database of patients with symptomatic BPH who underwent TUEB from January 2016 to September 2017. Patients with a minimum follow-up period of 6 months were included in the study. All patients were assessed using the international prostate symptom score (IPSS), uroflometry (Q-max), and transrectal ultrasonography (TRUS) of the prostate. TUEB was indicated for patients with total prostate volumes >60 g on TRUS. Postoperative outcome measures, including urinary incontinence, Q-max, and IPSS, were recorded at each follow-up visit. A total of 103 patients underwent TUEB. The mean patient age was 64 ± 7 years, and the median operative time was 54 minutes (interquartile range [IQR]: 44-66). The median resected prostate weight was 39 g (IQR: 28-54 g), corresponding to approximately 87% of the assessed transitional zone volume. The mean postoperative hemoglobin drop of 1.08 ± 0.28 g/dL was clinically insignificant. There was significant improvement in the IPSS and Q-max postoperatively, when compared to baseline parameters (P < .05). Our TUEB technique is safe and effective in treating symptomatic BPH with acceptable complications and favorable short-term outcomes. TUEB allows near-complete enucleation of a prostate adenoma, followed by resection, thus avoiding the need for a morcellator.


Four-year experience with a recombinant hepatitis B vaccine.
Three hundred and forty-three healthy adults were vaccinated with five different lots of recombinant hepatitis B vaccine. Three hundred and forty (99.1%) individuals produced antibodies against hepatitis B surface antigen (anti-HBs). Peak anti-HBs concentrations were significantly higher in females and younger individuals. All anti-HBs positive individuals developed antibodies to the common determinant "a" of HBsAg. The vaccine was well tolerated, without severe side reactions. Persistence of anti-HBs was followed in 130 individuals for 3, and in 15 for 4 years after the first vaccination of these two groups. 21.7% and 32.3%, respectively, no longer had protective levels of anti-HBs after this time. The persistence of anti-HBs was dependent on peak anti-HBs levels, with consistent kinetics of anti-HBs decline. Revaccination of individuals whose specific antibody levels had fallen below 10 IU/l led to a prompt anti-HBs response. Comparison with individuals vaccinated with plasma-derived hepatitis B vaccine revealed no substantial differences between the two vaccines.


Epidemiology of Pregnancy-Associated Breast Cancer.
Breast cancer diagnosed during pregnancy or lactation up to 1 year post-partum is often referred to as pregnancy-associated breast cancer (PABC) , although the definition varies with length of post-partum period. The incidence rate has been reported to range from 17.5 to 39.9 per 100,000 births, but the rate is substantially lower during pregnancy (ranging from 3.0 to 7.7) than during the post-partum period (ranging from 13.8 to 32.2). The PABC incidence rate is increasing in many populations, and higher maternal age at birth is a likely explanation. Linkable population-based data on pregnancies and cancer are required to obtain reliable estimates of PABC incidence. In studies comparing outcomes in women with PABC to other young breast cancer patients, it is crucial to adjust for age, since the age distribution of PABC depends both on age at pregnancy and age at breast cancer. Large studies have shown similar prognosis for women with PABC compared to other young women with breast cancer, when accounting for differences in age, stage and other tumour characteristics.


A prominent anchoring effect on the kinetic control of drug release from mesoporous silica nanoparticles (MSNs).
This work demonstrated kinetically controlled release of model drugs (ibuprofen, FITC) from well-tailored mesoporous silica nanoparticles (MSNs) depending on the surface charges and molecular sizes of the drugs. The molecular interactions between entrapped drugs and the pore walls of MSNs controlled the release of the drugs through the pore channels of MSNs. Also, polydopamine (PDA) layer-coated MSNs (MSNs@PDA) was quite effective to retard the release of large FITC, in contrast to a slight retardation effect on relatively small Ibuprofen. Of all things, FITC (Fluorescein isothiocyanate)-labeled APTMS (3-aminopropyltrimethoxysilane) (APTMS-FITC conjugates) grafted onto the MSNs generate a pinch-effect on the pore channel (so-called a prominent anchoring effect), which was highly effective in trapping (or blocking) drug molecules at the pore mouth of the MSNs. The anchored APTMS-FITC conjugates provided not only tortuous pathways to the diffusing molecules, but also sustained release of the ibuprofen over a long period of time (∼7days). The fast release kinetics was predicted by an exponential equation based on Fick's law, while the slow release kinetics was predicted by Higuchi model.


Development of the opioid self-management scale for advanced Cancer patients with pain and examination of its validity and reliability.
Approximately 60% of outpatients with advanced cancer experience pain; therefore, self-management of opioid use is important for appropriate pain relief. To date, no studies have clearly described the concept of opioid self-management or assessed the factors involved, including the improvement of self-management abilities. This study developed, and evaluated the validity and reliability of an opioid self-management scale for advanced cancer patients with pain (OSSA). Opioid self-management in advanced cancer patients with pain was defined as the management of opioid medication performed by patients with advanced cancer to relieve cancer pain on their own. Three phases were required for validation and reliability of the OSSA: 1) testing content validity, 2) testing face validity, and 3) testing construct validity, concurrent validity and reliability. After a three-phase process, the OSSA consisted of 33 items on six subscales. The structural equation modeling was such that the χ2 value was 709.8 (p < 0.001, df = 467), goodness-of-fit index was 0.78, adjusted goodness-of-fit index was 0.73, root mean squares of approximation was 0.063, and comparative fit index was 0.92. The Pearson correlation coefficients between the total OSSA score and the 24-hour average pain or pain relief over 24 hours were - 0.21 (p < 0.05) and 0.26 (p < 0.01), respectively. Cronbach's α was 0.93. The intraclass correlation coefficient range was 0.59-0.90. The findings of this study show that the OSSA has acceptable validity and reliability, and that better self-management leads to greater pain relief. The OSSA can be considered effective for use in research, but shortened version should be prepared for realistic and practical clinical use.


The effect of micronised nitroscanate on Echinococcus granulosus and Taenia hydatigena infections in dogs.
Trials with micronised nitroscanate carried out on 170 dogs infected with either Echinococcus granulosus or Taenia hydatigena indicated that a single treatment at 62-5 mg/kg and 16 mg/kg respectively significantly reduced the proportion of dogs infected with tapeworms. Some evidence is presented that micronisation may give a fourfold increase in the efficiency of nitroscanate in worm removal without increasing the toxic effects to the dog.


Kinetics of functionally distinct T-lymphocyte subsets in heart transplant recipients after induction therapy with anti-CD25 monoclonal antibodies.
T cells are involved in the maintenance of immunocompetence and in the development of alloimmune responses in solid organ transplant recipients. The kinetics of functionally distinct T-cell subsets in peripheral blood has received little attention in the field of heart transplantation. We performed a simultaneous analysis of the maturation, activation, and regulatory profiles of T cells using 4-color flow cytometry in a study of 77 heart recipients. Induction therapy included 2 doses of anti-CD25 monoclonal antibodies (daclizumab). Lymphocyte subsets were prospectively evaluated at different times before and up to 1 year after transplantation in 46 heart recipients. A separate cross-sectional study was performed in 33 heart recipients who had received a transplant more than 1 year previously to evaluate abnormalities persisting in the long term. As compared with baseline values, a decrease in regulatory CD4+ T-cell percentages (CD4+CD127lowCD25highFoxP3+) was observed from day 7 to 12 months after transplantation. Interestingly, T cells expressing the beta chain of IL-2 (CD122+) remained stable during the first 3 months. A significant decrease in the activation status of CD4 T cells was documented from day 7 to 1 year after transplantation, while the activation status of CD8+ T cells remained stable during follow-up. Compared with values for healthy controls (n=36), higher CD8+ terminally differentiated effector memory percentages (CD8+CD45RA+CCR7-) were observed from baseline up to more than 1 year after transplantation. Rejection was associated with higher levels of these cells during the first 6 months after transplant. We characterized the abnormalities in distinct functional T-cell subsets at different times before and after heart transplantation. Some of these abnormalities should be further investigated as biomarkers of clinical complications.


Correlation of histopathological, cytological and flow cytometric findings in neoplastic and nonneoplastic lesions of the bladder.
Biopsy diagnosis, urine cytology and flow cytometry features of urine and bladder washings were compared in 81 cases of benign and malignant bladder disease. Some patients were followed by urine cytology and flow cytometry during treatment of tumors. There was a good correlation of the 3 parameters in relatively high grade tumors (II and III) but an inconsistent appearance of cells in the urine diagnosable by either urine cytology or flow cytometry for low grade lesions. High grade flat neoplasms may be detectable by urine cytology and flow cytometry before they are visible on endoscopy. Flow cytometry may indicate urothelial proliferation before it is apparent on urine cytology. Exfoliative benign lesions are diagnosed readily by the combination of urine cytology and flow cytometry. In benign and malignant lesions shedding of viable cells and, therefore, accessibility to urine cytology and flow cytometry are inconsistent. The need for repeated examinations in the case of low grade lesions suggests that the method is not reliable for single test screening programs but it is a valuable means of followup in cases of suspected or diagnosed disease.


The East and Southern Africa Ministerial Commitment: a review of progress toward fulfilling young people's sexual and reproductive health and rights (2013-2018).
Whilst significant progress has been made in recent years with respect to advancing health and education, the ESA region's young people still experience challenges in relation to their SRHR. This study brings together learning from the available data and reports, as well as the experiences of those closely connected with the process of affirmation/endorsement and implementation of the ESA Commitment between 2013 and 2018. Whilst challenges remain - particularly in relation to monitoring and accountability - the ESA Commitment has instigated notable progress, made possible in part by the emphasis on multisectoral collaboration between health and education sectors nationally and regionally. Sustained political, technical, and financial investment in young people's health and rights will ensure that the countries of the region are able to build upon these successes and deliver on their commitments to young people during this decade of action towards the realisation of the SDGs and harnessing the demographic dividend for Africa for years to come.


Matrix metalloproteinase-2 expression and promoter/enhancer activity in skeletal muscle atrophy.
Matrix metalloproteinase-2 (MMP-2) appears to be the dominant MMP activated during skeletal muscle atrophy. However, little is known about cell-specific regulatory mechanisms of MMP-2 transcription in vivo. In this study, we used a mouse model of muscle atrophy induced by complete Achilles tendon transection. Time-dependent muscle weight loss, nuclei density reduction, and extracellular matrix degeneration were observed consistently after Achilles tendon transection. Increased MMP-2 expression was confirmed at the mRNA and protein level. Experiments using transgenic mice with a MMP-2 promoter/enhancer reporter construct demonstrated markedly increased MMP-2 promoter/enhancer activity in atrophic skeletal muscle. Tissue-specific upregulation of MMP-2 promoter activity was observed not only in myocytes, but also in blood vessels, nerve, and fascia. The transcription factors c-Jun and FosB were expressed at high levels in atrophic muscle, suggesting a role in MMP-2 upregulation. These findings show that increased MMP-2 activity in disused atrophic muscle and supporting tissues is regulated, at least in part, by increased MMP-2 promoter/enhancer activity.


Inhibition of protein synthesis in reticulocyte lysates by a double-stranded RNA component in HeLa mRNA.
Double-stranded RNA (dsRNA) inhibits protein synthesis initiation in rabbit reticulocyte lysates by the activation of a latent dsRNA-dependent cAMP-independent protein kinase which phosphorylates the alpha-subunit of the eukaryotic initiation factor eIF-2. In this study, we describe a dsRNA-like component which is present in preparations of HeLa mRNA (poly A+) isolated from total cytoplasmic RNA. The inhibitory species in the HeLa cytoplasmic mRNA was detected by (a) its ability to inhibit protein synthesis with biphasic kinetics in reticulocyte lysates translating endogenous globin mRNA, and (b) by the inefficient translation of HeLa cytoplasmic mRNA in a nuclease-treated mRNA-dependent reticulocyte lysate. The inhibitory component was characterized as dsRNA by several criteria including (i) the ability to activate the lysate dsRNA-dependent eIF-2 alpha kinase (dsI); (ii) the prevention of both dsI activation and inhibition of protein synthesis by high levels of dsRNA or cAMP; (iii) the reversal of inhibition by eIF-2; and (iv) the inability to inhibit protein synthesis in wheat germ extracts which lack latent dsI. By the same criteria, the putative dsRNA component(s) appears to be absent from preparations of HeLa mRNA isolated exclusively from polyribosomes.


Faecal proteomics in the identification of biomarkers to differentiate canine chronic enteropathies.
Canine chronic enteropathy (CCE) is a collective term used to describe a group of idiopathic enteropathies of dogs that result in a variety of clinical manifestations of intestinal dysfunction. Clinical stratification into food-responsive enteropathy (FRE) or non-food responsive chronic inflammatory enteropathy (CIE), is made retrospectively based on response to treatments. Faecal extracts from those with a FRE (n = 5) and those with non-food responsive chronic inflammatory enteropathies (CIE) (n = 6) were compared to a healthy control group (n = 14) by applying TMT-based quantitative proteomic approach. Many of the proteins with significant differential abundance between groups were pancreatic or intestinal enzymes with pancreatitis-associated protein (identified as REG3α) and pancreatic M14 metallocarboxypeptidase proteins carboxypeptidase A1 and B identified as being of significantly increased abundance in the CCE group. The reactome analysis revealed the recycling of bile acids and salts and their metabolism to be present in the FRE group, suggesting a possible dysbiotic aetiology. Several acute phase proteins were significantly more abundant in the CCE group with the significant increase in haptoglobin in the CIE group especially notable. Further research of these proteins is needed to fully assess their clinical utility as faecal biomarkers for differentiating CCE cases. SIGNIFICANCE: The identification and characterisation of biomarkers that differentiate FRE from other forms of CIE would prove invaluable in streamlining clinical decision-making and would avoid costly and invasive investigations and delays in implementing effective treatment. Many of the proteins described here, as canine faecal proteins for the first time, have been highlighted in previous human and murine inflammatory bowl disease (IBD) studies initiating a new chapter in canine faecal biomarker research, where early and non-invasive biomarkers for early clinical stratification of CCE cases are needed. Pancreatitis-associated protein, pancreatic M14 metallocarboxypeptidase along with carboxypeptidase A1 and B are identified as being of significantly increased abundance in the CCE groups. Several acute phase proteins, were significantly more abundant in the CCE group notably haptoglobin in dogs with inflammatory enteropathy. The recognition of altered bile acid metabolism in the reactome analysis in the FRE group is significant in CCE which is a complex condition incorporating of immunological, dysbiotic and faecal bile acid dysmetabolism. Both proteomics and immunoassays will enable the characterisation of faecal APPs as well as other inflammatory and immune mediators, and the utilisation of assays, validated for use in analysis of faeces of veterinary species will enable clinical utilisation of faecal matrix to be fully realised.


What causes the abnormal phenotype in a 49,XXXXY male?
The chromosome replication pattern of a man with 49,XXXXY was analyzed using 3H-thymidine and autoradiography as well as BrdU and acridine orange. The former technique showed a highly irregular replication pattern; the latter revealed one early replicating X chromosome, and the other three more or less asynchronously replicating. Two hypotheses seem to explain best the abnormal phenotype of males with an XXXXY sex chromosome constitution: The number of the always active regions (tip of Xp) and of the possibly always active regions (the Q-dark regions on both sides of the centromere) is increased from one to four. The replication pattern of the late-replicating X chromosomes is highly asynchronous, which might affect the phenotype. The possibility that more than one X chromosome might remain active in some cells, an even more abnormal and obviously deleterious situation, is still open.


A case of Hodgkin's disease arising from an intraglandular lymph node in the parotid gland.
Malignant lymphoma of the parotid gland region, especially Hodgkin's disease of the gland, is an extremely rare disorder. We have recently experienced a case initially suspected of being pleomorphic adenoma and later, on postoperative histopathological examination, diagnosed as Hodgkin's disease. The present report describes this case of Hodgkin's disease arising from an intraglandular lymph node in the parotid gland.


Immobilization of cells by electrostatic droplet generation: a model system for potential application in medicine.
The process of electrostatic extrusion as a method for cell immobilization was investigated that could be used for potential applications in medicine. An attempt was made to assess the effects of cell addition and polymer concentration on the overall entrapment procedure, ie, on each stage of immobilization: polymer-cell suspension rheological characteristics, electrostatic extrusion process, and the process ofgelation. The findings should contribute to a better understanding of polymer-cell interactions, which could be crucial in possible medical treatments. Alginate-yeast was used as a model system for carrier-cells. The electrostatic extrusion was considered as a complex two-phase flow system and the effects of cell and alginate concentrations on the resulting microbead size and uniformity were assessed. Under investigated conditions, microbeads 50-600 microm in diameter were produced and the increase in both alginate and cell concentrations resulted in larger microbeads with higher standard deviations in size. We attempted to rationalize the findings by rheological characterization of the cell-alginate suspensions. Rheological characterization revealed non-Newtonian, pseudoplastic behavior of cell-alginate suspensions with higher viscosities at higher alginate concentrations. However, the presence of cells even at high concentrations (5x10(8) and 1x10(9) cells/mL) did not significantly affect the rheological properties of Na-alginate solution. Lastly, we investigated the kinetics of alginate gelation with respect to the quantity of Ca2+ ions and cell presence. The gelation kinetics were examined under conditions of limited supply with Ca2+ ions, which can be essential for immobilization of highly sensitive mammalian cells that require minimal exposure to CaCl2 solution. The molar ratio of G units to Ca2+ ions of 3.8:1 provided complete crosslinking, while the increase in alginate concentration resulted in prolonged gelation times but higher strength of the resulting gel. The cell presence decreased the rate of network formation as well as the strength of the obtained Ca-alginate hydrogel.


Spectrum of disorders associated with enlarged sylvian fissures in infancy.
Disproportionate enlargement of the sylvian fissures (ESF) on MRI of an infant's CNS suggests underdevelopment of the cortical operculum. We reviewed charts of infants with isolated ESF. Conditions associated with ESF included feeding difficulties and facial dysmorphism (syndromic or nonsyndromic). There may be an embryologic link between growth of the opercular cortex and development of the face.


The use of reverse-phase high-performance liquid chromatography and precolumn derivatization with dansyl chloride for quantitation of specific amino acids in collagen and elastin.
A rapid and accurate reverse-phase high-performance liquid chromatography procedure for amino acid analysis of connective tissue proteins has been optimized. The method is based on quantitative dansyl chloride precolumn derivatization of protein hydrolyzates and chromatographic separation of the dansyl derivatives on Ultrasphere ODS C18 column. High molar uv absorption of Pro and Hyp derivatives, quantitation of low Des and Ide amounts (60 pmol), and good separation of all the amino acid derivatives (CV mostly less than 0.1%) including Hyl overcome the difficulties of other methods in producing reliable single run amino acid analysis of collagen and elastin. The use of fluorescence detector and the possibility of concentrating derivatized samples would give even higher sensitivity to the system. The procedure appeared to be suitable for single run analysis of other proteins, particularly those having an unbalanced amino acid composition.


Comparison of Intaglio Surface Adjustment in the Oral Cavity for Lithium Disilicate Crowns Fabricated Using Different Scanners.
A clinical study to evaluate the intraoral adjustment of crowns fabricated using different scanners. A total of 15 patients requiring single ceramic crowns were recruited. Impressions were made according to four protocols: a conventional approach and using three intraoral scanners (IOSs) (CS3600 (Carestream Dental, Atlanta, GA), i500 (Medit, Seoul, Republic of Korea), and EZIS PO (DDS, Seoul, Republic of Korea)). Four crowns per patient were fabricated using lithium disilicate ceramic. An experienced dentist performed the internal adjustment in the oral cavity. Three-dimensional analysis was conducted using an inspection software program (Geomagic Control X; 3D Systems, Rock Hill, SC). Statistical analysis was conducted using one-way analysis of variance and Tukey's honest significance difference tests (α = 0.05). A significant difference was observed in the intraoral adjustment among the conventional approach and the three IOSs (F = 213.7, p < 0.001). Crowns fabricated by conventional impressions (20.1 ± 1.4 µm) displayed better three-dimensional conformity before and after intraoral adjustment than IOS groups (29.6 ± 4.3 µm) (p < 0.001). Crowns fabricated using conventional impressions required fewer intraoral adjustments of the intaglio surface than those fabricated using IOSs.


Effect of dietary Aroclor 1254 exposure on lung and kidney cytochromes P450 in female rats: evidence for P4501A2 expression in kidney.
In this report, we have investigated the effect of dietary exposure to Aroclor 1254 (1-100 ppm) given chronically or discontinuously over an 84-day time interval to the female F344 rat. Cytochrome P4501A was quantified in lung and kidney by measuring the dealkylation of ethoxyresorufin substrate and by Western immunoblotting. P4501A displayed a dose- and time-dependent increase in both extrahepatic organs. The kidney appeared to be more responsive to induction than lung at all doses (maximum of 500-fold induction following 84 days exposure to 100 ppm). Further, there was evidence by enzymatic activity, immunoblotting and Northern analysis of total RNA for the presence of 1A2 in the most highly induced kidneys. The decline in 1A induction observed following discontinuous exposure was more prominent in the kidney than in the lung. These data demonstrate the sensitivity of kidney to P4501A induction capacity as compared to lung, although the persistence of the induction response was evident in lung and not kidney.


Analytical behavior data for chemicals determined using AOAC multiresidue methodology for pesticide residues in foods.
Analytical methods capable of detecting more than one pesticide residue simultaneously (multiresidue methods) become more effective with an increase in the number of chemicals whose behavior through the various steps of the method has been documented. Since 1970, the method behavior data related to the AOAC official method for residues of 25 chlorinated and phosphated pesticides and polychlorinated biphenyls have been extended to include information on twice as many chemicals as was previously available. The value of having a large bank of method behavior data is outlined and the experimental protocol by which the data were collected is described. A complete listing is included of the available data on the analytical behavior of over 300 pesticidal and/or industrial chemicals.


WITHDRAWN: Common NLRP3 inflammasome inhibitors and Covid-19: Divide and Conquer.
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The cyclooxygenase-2 inhibitor rofecoxib (Vioxx) in the treatment of cervical dysplasia grade II-III A phase II trial.
To determine whether the cyclooxygenase (COX)-2 inhibitor rofecoxib increases the regression rates of cervical intraepithelial neoplasia (CIN) grade II and III. A prospective, randomized, placebo-controlled, double-blind study with rofecoxib 25 mg daily for 6 [corrected] months as active treatment for patients with CIN II and III was started in May 2004 [corrected] and was halted after rofecoxib withdrawal in October 2004 [corrected] A total of 16 patients with CIN II (n=9) and CIN III (n=7) were included in our study. Eight and eight patients received rofecoxib and placebo, respectively. Regression rates in the rofecoxib and placebo arm were statistically not significant (25% versus 12.5%) after a mean of 87 (46.3) days of treatment. No severe side effects were noted during the therapy; no dropouts were recorded. A conservative treatment of CIN II and III is feasible. Inhibitors of COX, especially COX-2, were seen as candidates for cancer chemoprevention. Our study was halted after rofecoxib was withdrawn. The results obtained should be added to those already published for planning future studies on medical therapies for high grade CIN.


How do early socioeconomic circumstances impact inflammatory trajectories? Findings from Generation XXI.
The association between socioeconomic position and markers of inflammation in adults, including C-reactive protein (CRP), is well-established. We hypothesized that children from families of less-advantaged socioeconomic circumstances may be at higher inflammatory risk during childhood and, consequently, throughout their life course. Thus, we aimed to investigate whether early socioeconomic circumstances impact CRP trajectories using repeated measures of data from a population-based birth cohort. Data from 2510 participants of Generation XXI, a prospective Portuguese population-based birth cohort, were included in this study. Early socioeconomic circumstances comprised maternal education and occupation, paternal education and occupation, and household income at the child's birth. Venous blood samples were collected from the children at ages four, seven, and ten years, and high-sensitivity CRP (Hs-CRP) was quantified. Hs-CRP trajectories were computed using a linear mixed-model approach. Participants from less-advantaged socioeconomic circumstances presented higher levels of Hs-CRP by age of ten years. The higher the mother´s education and disposable household income, the lower the minimum value of the log Hs-CRP observed throughout childhood. Further, the age at which that minimum log Hs-CRP value was reached occurs later, meaning that children born in more-advantaged socioeconomic circumstances had lower levels of log Hs-CRP compared with children from less-advantaged families. Poor socioeconomic circumstances early in life are associated with increased inflammation levels throughout the first decade of life. This study demonstrates that social inequalities may impact population health beginning at very early ages.


The impact of the total motile sperm count on the success of intrauterine insemination with husband's spermatozoa.
The purpose of this study was to evaluate the relationship between the total motile sperm count and the success of IUI treatment cycles with postwashed husband spermatozoa in couples with infertility in a large patient population. When 939 couples underwent 1375 cycles of IUI with varying etiologies of infertility which included male factor, endometriosis, tubal factor, ovulatory dysfunction, uterine factor, cervical factor, and unexplained infertility, the results were 207 pregnancies. The overall pregnancy rate per cycle was 15.1% (207/1375). The total motile sperm count were significantly increased in the pregnant group than the nonpregnant group (38.7 x 10(6) versus 28.6 x 10(6); P < 0.001). There was a trend toward an increased success rate with increased total motile sperm count. Significance was reached when the total motile sperm count exceeded 5 x 10(6). Life table analysis was performed and the curve representing a cumulative chance of pregnancy calculated from our data reached 72%. Our findings suggest that a final postwashed total motile sperm count used for IUI may be considered predictive of the success for pregnancy and allow couples to be informed of the chances of success.


Paint solvent to food additive: an environmental route of dehalogenation for 4-chlorobenzotrifluoride.
In an effort to reduce volatile organic compounds (VOCs) in paint solvents, replacements containing non-VOC compounds have been proposed. One such compound is 4-chlorobenzotrifluoride (CBTF), for which environmental fate studies have not been conducted. The objective of the present study was to determine the products of the atmospheric oxidation of CBTF and the aqueous fate of these products. Smog chamber experiments were performed to measure the kinetics and mechanism of atmospheric oxidation. A rate constant of 2.22 (+/-0.30) x 10(-13) cm3 molecule(-1) s(-1) was determined for the reaction of hydroxyl radicals with CBTF in 700 Torr of air at 296 K. Using offline sampling and gas chromatography coupled to mass spectroscopic analysis, it was determined that 2-chloro-5-trifluoromethylphenol (o-CTFP) was the primary product of CBTF atmospheric oxidation. Aqueous photolysis of o-CTFP in deionized water proceeded at a rate of 1.3 (+/-0.1) x 10(-4) s(-1), corresponding to a half-life of 1.5 +/- 0.1 h and a quantum yield of 6.6 (+/-0.4) x 10(-4). The mechanism of photolysis was investigated using liquid chromatography coupled to tandem mass spectrometry, which suggested that degradation of o-CTFP occurred via photonucleophilic displacement of chlorine, followed by photoinduced hydrolysis of the trifluoromethyl group to yield 3,4-dihydroxybenzoic acid (an approved food additive considered to be nontoxic).


Prey-mediated effects of mCry51Aa2-producing cotton on the predatory nontarget bug Orius majusculus (Reuter).
Genetically engineered (GE) cotton, MON 88702, is protected against certain sucking pests, such as plant bugs and thrips, by producing mCry51Aa2, a modified protein from Bacillus thuringiensis (Bt). Predatory pirate bugs (Orius spp.), natural enemies contributing to biological pest control, are also sensitive to the insecticidal protein when exposed continuously to high concentrations. We evaluated effects of MON 88702 on Orius majusculus when fed prey types with different mCry51Aa2 concentrations. When neonates were provided exclusively Tetranychus urticae spider mites reared on MON 88702 (high mCry51Aa2 content), adverse effects on predator survival and development were confirmed, compared with specimens fed prey from near-isogenic non-Bt cotton. When fed a mixture of T. urticae and Ephestia kuehniella eggs (mCry51Aa2-free), predator life table parameters were similar to the treatment where eggs were fed exclusively. When mCry51Aa2-containing spider mites were provided for a limited time at the beginning or the end of juvenile development, effects were less pronounced. While pirate bug nymphs showed similar consumption rates for prey from Bt and non-Bt cotton, choice experiments revealed a preference for E. kuehniella eggs over spider mites. Lepidopteran larvae (Spodoptera littoralis, high mCry51Aa2 content) or cotton aphids (Aphis gossypii, mCry51Aa2-free) reared on MON 88702 as alternative prey did not result in adverse effects on O. majusculus. Our study suggests limited risk of mCry51Aa2-producing cotton for O. majusculus, because its sensitivity for the Bt protein is relatively low and its natural food consists of diverse prey species with varying concentrations of Bt protein.


Metabolic shifts during fruit development in pungent and non-pungent peppers.
Fruit pungency is caused by the accumulation of capsaicinoids, secondary metabolites whose relation to primary metabolism remains unclear. We have selected ten geographically diverse accessions of Capsicum chinense Jacq with different pungency levels. A detailed metabolic profile was conducted in the fruit placenta and pericarp at 20, 45, and 60 days after anthesis aiming at increasing our understanding of the metabolic changes in these tissues across fruit development and their potential connection to capsaicin metabolism. Overall, despite the variation in fruit pungency among the ten accessions, the composition and metabolite levels in both placenta and pericarp were uniformly stable across accessions. Most of the metabolite variability occurred between the fruit developmental stages rather than among the accessions. Interestingly, different metabolite adjustments in the placenta were observed among pungent and non-pungent accessions, which seem to be related to differences in the genetic background. Furthermore, we observed high coordination between metabolites and capsaicin production in C. chinense fruits, suggesting that pungency in placenta is adjusted with primary metabolism.


The future of DNA-DNA hybridization studies.
This article draws on many vertebrate examples to assess the future of DNA-DNA hybridization studies. I first discuss whether applications of the method have reached the point of diminishing returns, or rather the start of a great leap forward, in our evolutionary understanding. Vertebrate groups whose relationships are especially likely to be illuminated include parrots, pigeons, bats, pinnipeds, mammalian carnivores, frogs, and rodents. There are at least two reasons why classifications based on DNA-DNA hybridization may prove to differ from classifications based on particular character, whether these be noncoding DNA sequences or protein sequences or anatomical characters. Because evolutionary relationships can now be deduced independently of anatomical characters, this should permit a renaissance in comparative anatomical studies of adaptation. The origin of major functional shifts from changes in a small fraction of the genome is illustrated by polar bears, sea otters, warblers, vultures, and especially by humans.


Towards a repository of synthetic electrograms for atrial activation detection in atrial fibrillation.
Recently, the analysis of the spatio-temporal behavior of atrial fibrillation activation patterns has been widely investigated with the aim to better understand the arrhythmia implications on the heart electrical activity. Most of the proposed techniques are based on atrial activation timing detections. Unfortunately atrial activation timings are not easily recognizable on the electrograms (EGMs) and an approach to support the validation of such techniques is highly desirable. The aim of this study is to provide an effective workflow for the generation of synthetic unipolar atrial electrograms (SEGMs) in atrial fibrillation (AF) condition and with different levels of noise. Real EGMs signals were obtained from a dataset of 6 subjects that underwent ablation. Each SEGM was obtained by modeling the three principal components of an EGM starting from real signals: atrial far-field (Afar), atrial near-field (Anear) and the ventricular far-field (Vfar). Afar was generated using an autoregressive model applied on segments from real EGMs not characterized by ventricular or atrial activations; Anear and Vfar were extracted directly from the real signals. A Gamma distribution and an atrio-ventricular node model were used to locate both Anear and Vfar on Afar, respectively. Three electrophysiologists with different levels of expertise evaluated the realism of the SEGMs on a set of 100 randomly selected signals including 50 EGMs and 50 SEGMs. Analysis was repeated by the three experts on a subset of 21 signals. The time required to generate the synthetic EGMs was less than 1 min once annotated EGMs are available. The cardiologists succeeded in distinguishing real from synthetic EGMs in 45%, 43% and 35% of the signals, respectively. By repeating the evaluation, 28%, 0% and 48% of signals were classified differently, including 67%, 52% and 36% of correct classifications. The proposed approach proved to be effective in producing SEGMs which are difficult to distinguish from real EGMs. This study provides a tool for realistic SEGM generation from real EGMs in AF condition with different levels of noise and at different AF rates. The tool may be easily adopted to obtain SEGMs in different arrhythmic conditions. SEGMs generated in this study are shared with the scientific community as a first step towards a repository of synthetic and real atrial signals supporting the benchmarking of new approaches to investigate AF.


2-Bromo-5-hydroxyphenylporphyrins for photodynamic therapy: photosensitization efficiency, subcellular localization and in vivo studies.
Photodynamic therapy (PDT) is a therapeutic modality capable of inducing cell death by oxidative stress through activation of a sensitizer by light. Aryl-porphyrin with hydroxyl groups are good photosensitizers and presence of bromine atoms can enhance the photodynamic activity through heavy atom effect. These facts and our previous work made pertinent to compare the photodynamic capacity of tetraaryl brominated porphyrin (TBr4) with the corresponding diaryl (BBr2) derivative. Cell cultures were incubated with the sensitizers, ranging from 50nM to 10μM and irradiated until 10J. Cell proliferation was analysed by MTT assay. Flow cytometry studies evaluated cell death pathways, mitochondrial membrane potential and ROS. For in vivo studies Balb/c nu/nu mice were injected with 4×10(6)cells. After PDT, monitoring was carried out for 12 days to establish Kaplan-Meier survival curves. Tumours were excised and histological analysis was performed. Both sensitizers seem to accumulate in the mitochondria. The molecules have no intrinsic cytotoxicity or in non-tumour cells at therapeutic concentrations. Both sensitizers induced a significant decrease of cell proliferation and growth of xenografts of melanoma and colorectal adenocarcinoma. Diaryl BBr2 is more efficient than tetraaryl TBr4, concerning intracellular ROS production, mitochondrial disruption and induction of cell death. The main cell death pathway is necrosis. TBr2 and BBr4 are promising sensitizers with good photodynamic properties and have the ability to induce cell death in human melanoma and colorectal adenocarcinoma in vitro and in vivo. We consider that BBr2 is a molecule that should be the subject of extensive studies towards clinical use.


Safety and efficacy evaluation of gelatin-based nanoparticles associated with UV filters.
The safety and efficacy assessment of nanomaterials is a major concern of industry and academia. These materials, due to their nanoscale size, can have chemical, physical, and biological properties that differ from those of their larger counterparts. The encapsulation of natural ingredients can provide marked improvements in sun protection efficacy. This strategy promotes solubility enhancement of flavonoids and yields an improved active ingredient with innovative physical, physicochemical and functional characteristics. Rutin, a flavonoid, has chemical and functional stability in topical vehicles exerting a synergistic effect in association with ultraviolet (UV) filters. However, the solubility of rutin is a limiting factor. Additionally, this bioactive compound does not have tendency to permeate across the stratum corneum. As an alternative to common synthetic based sunscreens, rutin-entrapped gelatin nanoparticles were designed. The present study investigated the pre-clinical safety of gelatin nanoparticles (GNPs) using an in vitro method and also assessed the clinical safety and efficacy of the association of GNPs with three commonly used chemical UV filters (ethylhexyl dimethyl PABA, ethylhexyl methoxycinnamate and methoxydibenzoylmethane). The non-irritant and adequate safety profile under sun-exposed skin conditions of the nanomaterials and the emulsions qualified the products for clinical efficacy assays. The in vivo results indicated that the GNPs increased the antioxidant protection of the emulsions developed. However, the presence of rutin in the nanosized material did not enhance performance on the SPF test. In conclusion, these findings characterized the nanomaterials as an innovative platform for multifunctional bioactive sunscreens.


Prevalence and risk factors for postpartum depression in Sri Lanka: A population-based study.
Previous studies in Sri Lanka have shown a high prevalence of postpartum depression (PPD). Postpartum depression screening using the Edinburgh Postnatal Depression Scale (EPDS) has been validated and included in routine postnatal care in 2012. This study aimed to estimate the prevalence of PPD at 10 days and 4 weeks postpartum in 2017 in two medical officer of health (MOH) areas in Sri Lanka, and to assess the association between risk factors and postpartum depression. An EPDS total score higher than 9 was used to estimate the prevalence of postpartum depression. PPD outcomes were assessed by mothers' responses to the EPDS. Potential risk factors were extracted from routine paper-based medical records. The associations were examined using simple and multivariable linear regression and multivariate logistic regression models. A total of 1349 mothers in the two areas, 523 from Dankotuwa and 826 from Bope Poddala, were included. The prevalence of PPD was 15.5% and 7.8% among mothers assessed 10 days postpartum (in Dankotuwa) and 4 weeks postpartum (in Bope Poddala), respectively. EPDS total scores were positively related to delivery age of mothers. Presence of postpartum depression was significantly associated with delivery age over 35, having more than 4 living children and mothers' diseases. Mothers who attended prenatal sessions and whose partners were employed were less likely to report postpartum depression. The prevalence of PPD in Sri Lanka was 15.5% at 10 days and 7.8% at 4 weeks postpartum. Future studies on the effect of time since delivery on postpartum depression screening outcomes are warranted.


Association of familial colorectal cancer with variants in the E-cadherin (CDH1) and cyclin D1 (CCND1) genes.
About 20% of colorectal cancer (CRC) patients show some kind of familiarity, which might be caused by yet unknown combinations of low penetrance susceptibility genes. We aimed to identify genetic factors for familial CRC (fCRC) in a unique study design that includes phenotypic extremes as represented by fCRC cases and 'hyper-normal' controls without CRC history and no adenomatous polyps on colonoscopy. Candidate gene variants were determined by allele-specific amplification (SLC10A2 c.169C>T and c.171G>T) and restriction fragment length polymorphism assays (CCND1 c.870A>G; CDH1 -160C>A; TP53 R72P; VDR T2M). In total, 98 patients with fCRC, 96 patients with sporadic CRC, and 220 hyper-normal controls were included. The minor allele of the CDH1 -160C>A polymorphism occurred significantly more often in controls compared to fCRC cases (OR = 0.664; p = 0.042). Homozygosity of the minor allele was significantly associated with affiliation to the control group (OR = 0.577; p = 0.029), indicating that both heterozygous and homozygous carriers of the common allele are at-risk for CRC. With respect to the CCND1 c.870A>G mutation, comparison of fCRC and sporadic CRC cases showed that A/A homozygosity was more common than G/G homozygosity among fCRC patients compared to controls (OR = 2.119; p = 0.045). However, no differences in allele or genotype frequencies were detected between sporadic CRC cases and controls, and no associations were observed for SLC10A2, TP53, and VDR polymorphisms. We report a potential association of variants in the CCND1 and CDH1 genes with fCRC using a unique study design with phenotypic extremes.


The superiority of combination chemotherapy over single agent chemotherapy in small cell lung carcinoma.
From June 1974 to October 1976, 288 patients with small cell undifferentiated lung carcinoma were entered into a randomized, controlled study comparing the two noncycle-active induction regimens of cyclophosphamide vs. the combination of cyclophosphamide, doxorubicin and imidazole carboximide (DTIC). Patients were stratified by extent of disease, previous radiotherapy and performance status. Responding patients and those who did not progress were then randomized to receive their initial regimen alone, or their initial regimen with added cycle-active therapy (vincristine, hydroxyurea and methotrexate). While only 4/34 (12%) evaluable patients treated with cyclophosphamide achieved a response (greater than 50% regression), a final total of 119/217 (57%) evaluable patients on the three drugs have responded (p = 0.005). The survival curve for all the combination-treated patients was significantly better than for those treated with cyclophosphamide alone (p = 0.012). There was no demonstrable statistical superiority in length of remission or survival for patients on the combination who received in addition cycle-active consolidation therapy. In the combination chemotherapy group, survival duration was longer for patients with limited disease than extensive disease (p = 0.035). There was a strong correlation between quality of remission produced by the combination and survival.


Nasal ciliary motility: a new tool in estimating the time of death.
Determination of time since death is one of the most difficult and crucial issue in forensic medicine. Apart from body cooling, which is commonly used in the early postmortem interval (PMI), supravital reactions are the most interesting postmortem changes for time of death estimation. Nasal ciliary motility has been occasionally observed in postmortem period although no studies have focused on this phenomenon for forensic purposes. We aimed to evaluate the diagnostic usefulness of ciliary motility as a potential tool in estimating the time of death. Specimens of ciliated epithelium from 100 consecutive cadavers were obtained by scraping the nasal mucosa at three different postmortem intervals. The samples were then smeared on a slide, and an in vitro evaluation of ciliary movement was analyzed by phase-contrast microscopy. A postmortem nasal ciliary motility was observed, and a statistically significant relationship between decreasing ciliary movements and increasing postmortem interval was detected even in presence of putrefactive changes of nasal ultrastructure integrity. Some peculiar causes of death seem to influence ciliary motility in the early PMI, while no significant correlations with sex or age were observed. According to the results of this study, postmortem evaluation of nasal ciliary motility may be a bona fide and a feasible option for estimating the time of death.


A preliminary conceptual framework for the design, development, and use of client-oriented information systems in health.
Client-oriented information systems (COIS) in the health care arena are defined and discussed. The antecedents of these systems, as well as current examples of the systems, are described. Prior studies in this area suggest content for COIS but demonstrate lack of a conceptual framework to guide the design, development, adoption, and use of these systems. The purpose of the paper is to suggest a preliminary conceptual framework for future study of COIS that draws upon concepts from the field of management information systems.


MOG antibody seropositivity in a patient with encephalitis: beyond the classical syndrome.
The presence of circulating anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) has been described in sera of patients with different inflammatory conditions of the central nervous system. In adults the core clinical feature is usually characterised by acute myelitis and/or optic neuritis. We here report an atypical case with serum and cerebrospinal fluid MOG-Abs and a clinical picture suggestive for acute encephalitis. A 31-year-old Indian man presented with altered mental status, slight fever, and ataxia. Brain magnetic resonance imaging noted a widespread involvement of the white matter associated with slight cortical and subcortical damage in absence of contrast enhancement. An extensive infectious screening resulted negative while autoimmune analysis revealed the presence of MOG-Abs, detected with live cell-based assay. After treatment with intravenous immunoglobulins a marked and prompt clinical and radiological improvement was observed. To date, several areas of uncertainty still remain regarding clinical features and prognosis of subjects with MOG-Abs. The description of atypical cases is crucial, since recognition of this condition leads to prompt treatment and better prognosis, as in the case here reported.


Development of a treatment train for the remediation of a hazardous industrial waste landfill leachate: A big challenge.
This study focuses on the development of a treatment train for a leachate from a hazardous industrial waste landfill (HIWL) previously treated by: (i) catalytic oxidation with hydrogen peroxide (H2O2) for sulphide and sulphite conversion into oxidized sulphur species, including sulphate, and (ii) chemical precipitation of sulphate as barite. The complete treatment line counted on four more stages: (iii) 1st biological oxidation for removal of biodegradable organic compounds and nitrogen species, (iv) coagulation with ferric chloride (coagulant dose of 100 mg Fe L-1, pH 2.8) for removal of a fraction of recalcitrant organics and suspended solids, (v) photo-Fenton oxidation using ultraviolet A (UVA) radiation (PF-UVA) (pH 2.8, initial total dissolved iron content of 140 mg L-1, treatment time of ~4 h) for recalcitrant organics degradation and biodegradability improvement, and (vi) 2nd biological oxidation for removal of the biodegradable organic matter resulting from the PF-UVA process. The use of anodic oxidation or photoelectro-Fenton processes in stage (v) demonstrated to be unfeasible. A chemical oxygen demand (COD) below 1000 mg O2 L-1, a common limit imposed by municipal wastewater treatment plants (MWWTPs) to effluents discharged into the municipal sewer, was achieved after a feasible treatment time (~4 h) using the multistep approach. The remediation of the HIWL leachate proved to be a big challenge.


Postsynaptic potentials recorded from medullary neurones following stimulation of carotid sinus nerve.
Projections of the carotid sinus nerve (CSN) onto medullary neurones were studied with intracellular recording. Three types of postsynaptic potentials (EPSP, EP-IPSP and IPSP) were recorded by stimulation of the ipsilateral CSN. Of the total of 121 neurones, positions of 54 were identified by intracellular dye. The other 67 were positioned by extrapolation. They were distributed over 5 medullary nuclei: (1) nucleus of the solitary tract (NTS); (2) paramedian reticular nucleus (NPR); (3) perihypoglossal nucleus (PXII); (4) lateral tegmental field (FTL); and (5) nucleus ambiguus. Since penetration of microelectrodes and injection of dye into the NTS neurones was difficult, neurones of the other 4 nuclei were examined. The IPSPs were dominant in small NPR neurones, while the EPSPs were dominant in large neurones of the other 3 nuclei. Both the NA and PXII neurones showed forms of a motor type neurone, while the FTL neurones showed various forms. The EPSPs with onset latency as short as 2-4 msec were frequently recorded in different nuclei. This strongly suggests that the CSN projects monosynaptically onto different nuclei in the medulla.


Effective chemotherapy for advanced carcinoma of the cervix with bleomycin, cisplatin, vincristine, and methotrexate.
This study was designed as a Phase II clinical trial in advanced recurrent or metastatic squamous cell carcinoma of the cervix with a combination of bleomycin (B: 10 u/m2/d) and cisplatin (P: 20 mg/m2/d) administered for five consecutive days in intravenous infusion for 7 hours and vincristine (V: 1 mg/m2) and methotrexate (M: 40 mg/m2) administered only on day one of each cycle which was repeated every 28 days up to a maximum of 6 times. Over a period of 2 years, 15 evaluable patients with measurable disease received at least 3 courses of therapy. Six had recurrent disease and nine had distant metastases. All had previous radiation therapy. There were two dropouts after the first course due to nausea and vomiting which was practically universal. Other side effects included: mild paresthesias of the extremities (89%), stomatitis (41%), diarrhea (17%), moderate pancytopenia and hypomagnesemia which was reduced from 65% to 17% when magnesium sulfate 10% was administered with cisplatin. Sixty-six percent of the evaluable patients achieved remission (7 partial and 3 complete) usually before the fourth course of therapy. The disease-free interval was of 29.7 +/- 15 weeks in all responders (40.6 +/- 15.5 weeks in complete responders). The mean survival from the start of BPVM therapy was of 55.8 +/- 33.3 weeks in responders and of only 14 +/- 2.9 weeks in nonresponders (P less than 0.01). It is concluded that BPVM is an effective combination chemotherapy in advanced squamous cell carcinoma of the cervix. These results should be confirmed in a Phase III trial.


[Clinical records: our experience during the 1st year].
To describe the evolution of attendance indicators over a period of a year on introducing a new model of health care. Observational and descriptive. A local primary health care consulting-room. Population in the census, population requesting care, population with medical records, the number of visits and reasons for attendance. The introduction of clinical records, medical and nursing consultations by appointment, long-treatment booklets and a basic recording system. 54% of the population was recorded. Morbidity indicators, the first and subsequent visits and the number of prescriptions per patient were all stable. The percentage of bureaucratic reasons for attendance went down and the proportion of scheduled attendances increased. Requests for complementary tests and referrals to specialists also increased. The greatest effort in opening clinical records took place during the first four months. The most telling indicators of the evolution of attendances are the percentages of bureaucratic visits and scheduled ones, the requests for complementary tests and referrals to specialists. Other common attendance indicators have contributed no additional information, yet have supposed a greater effort of data-gathering.


Porphyrin-based mixed-valent Ag(i)/Ag(ii) and Cu(i)/Cu(ii) networks as efficient heterogeneous catalysts for the azide-alkyne "click" reaction and promising oxidation of ethylbenzene.
By using a new porphyrin-based linker, two unusual mixed-valent Ag(i,ii)- and Cu(i,ii)-organic networks were synthesized. Most strikingly, 1 and 2 exhibit highly efficient catalytic activities for the azide-alkyne "click" reaction and oxidation of ethylbenzene.


Effect of captopril on the vascular permeability changes induced by C5a, histamine and compound 48/80.
The modulating effect of captopril, an inhibitor of angiotensin-converting enzyme, on the vascular permeability changes induced by intradermal injections of C5a, histamine and compound 48/80, was evaluated in guinea-pigs. Cutaneous vascular permeability changes were measured by the extravasation of intravenously injected 125I-bovine serum albumin. Intraperitoneal injection of 12.5, 25, or 50 mg/kg of captopril 30 min prior to the injection of C5a (10(-11) mol) significantly enhanced the increase in vascular permeability induced by this agent (P less than 0.02). This may be explained by the known property of captopril as an inhibitor of carboxypeptidase. No effect was observed when captopril was injected either 2 or 4 h before the injection of C5a. In contrast, the same doses of captopril, when injected intraperitoneally 2 h before the injection of histamine (10(-8) mol) or compound 48/80 (10 micrograms), significantly suppressed the increase in vascular permeability induced by these agents (P less than 0.02). This suppressive effect occurred in a captopril dose-dependent manner. The ability of captopril to modulate the vascular permeability response induced by vasoactive agents indicates that it is a potentially useful tool to dissect the relative roles of mediators involved in inflammatory processes.


Extending the description of the clinical research nursing workforce.
The role of Clinical Research Nurses across the globe has not been evaluated to identify similarities or differences among specific activities. This study's aims were to determine differences in Clinical Research Nurses most frequently performed activities, if these activities are reflective of those previously described in the literature, and job titles Clinical Research Nurses use to self-identify. An online cross-sectional survey distributed via snowball sampling through email, social media, and research nurses' networks included questions on frequency of activities performed and information related to job titles. Pearson's chi-square test is analyzed for associations between the groups. Respondents returned 252 questionnaires, 233 were eligible for analysis. Research nurse activities performed internationally showed both similarities and differences. Any between country comparisons will be limited to the United States and the United Kingdom. The three most common tasks reported were recruitment 120 (51.5%), monitoring the research participant for potential adverse events 187 (80.2%) and providing nursing leadership within the interdisciplinary team 169 (72.5%). Considering the context and range of activities of the original Clinical Research Nursing Domain of Practice, broadening the framework to include the leadership domain will better serve as a foundation for the specialty practice.


[Ultrastructure of the ovaries of guinea pigs immunized with preparations of purified and unpurified antigens of the zona pellucida of xenogenic ova].
The state of the guinea pig ovaries has been studied electron microscopically in 8-15 and 30 days after an active immunization course with purified and non-purified antigens of the ovum zona pellucida has been completed. Both antigens produce early total morphofunctional rearrangements in the ovaries: increasing process of follicular atresia and disturbance of folliculogenesis, accompanied with hyperplasia of the interstitial tissue. The non-purified antigen produces more pronounced changes in the cavitary follicles: disturbances of cellular communications, barrier function of the follicular epithelium becomes weak, its respiratory, plastic and secretory function changes with subsequent distension of the follicle and with an enhanced development of connective tissue in its membranes. Injection of the purified antigen results in progressive atresia of the cavitary follicles and in hyperplasia of the interstitial tissue. Reduction of the corpus luteum is not observed.


A comprehensive review on functional beverages from cereal grains-characterization of nutraceutical potential, processing technologies and product types.
Due to growing consumer interest in fitness and wellbeing, foods and beverages with therapeutic and functional qualities are in higher demand. In addition to being significant staple crops and major providers of nutrition and energy, cereals are rich in bioactive phytochemicals with health benefits. Cereal grains offer a lot of promise for processing into functional beverages since these include a wide variety of bioactive phytochemicals such as phenolic compounds, carotenoids, dietary fibres, phytosterols, tocols, gamma-oryzanol, and phytic acid. Despite the fact that a wide variety of beverages made from cereal grains are produced globally, they have received very little technological and scientific attention. The beverages confer replacements for milk made from cereal grains, roasted cereal grain teas and fermented non-alcoholic cereal grain drinks. This review emphasizes on the three primary kinds of functional beverages made from cereal grains. Further, the potential applications and directions for the future related to these beverages are discussed with elaborated processing methods, health benefits and product attributes. Cereal grain-based beverages may represent a promising new class of healthy functional beverages in our daily lives as the food industry gets more diverse.


Effect of concentrated growth factors on frequency of alveolar Osteitis following partially-erupted mandibular third molar surgery: a randomized controlled clinical study.
The aim of this prospective study was to assess the effectiveness of concentrated growth factors (CGF) in preventing the development of alveolar osteitis (AO) after the extraction of partially-erupted mandibular third molars. Seventy patients (26 men and 44 women) 18 years or older (mean age 25.86; range 18-35) underwent 140 third molar extractions. All the patients presented with bilateral, partially-erupted mandibular third molars and underwent surgical extractions. In each case, one socket received CGF and the other served as a control. The predictor variable was the CGF application and the sides were categorized as 'CGF' and 'non-CGF'. The outcome variable was the development of AO during the first postoperative week. Other study variables included age and gender. Data were analyzed using Cochran's Q test with the significance level set at a P value less than 0.05. The overall frequency of AO was 11.4% for the control group. The frequency of AO in the CGF group was significantly lower than in the non-CGF group (p < 0.001). Based on the results of this study, application of CGF fibrin gel may decrease the risk of AO development after mandibular third molar surgery. This study was registered in ClinicalTrials.gov database on November 1, 2019 (ID: NCT04151147 , retrospectively registered).


Chronic myelogenous leukemia after lymphoid irradiation and heart transplantation.
We have previously reported a case of recurrent cardiac rejection in a heart transplant recipient successfully treated with total lymphoid irradiation. Five years after transplantation chronic myelogenous leukemia was diagnosed in this patient. The long-term effects of total lymphoid irradiation in the heart transplant population have not been reported. Based on the known relationships among irradiation, gene translocations, and leukemia, we postulate that this patient's chronic myelogenous leukemia may be a long-term sequela of previous total lymphoid irradiation.


Evaluating maintenance electroconvulsive therapy in Bipolar Disorders: 3-year mirror-image study.
Maintenance electroconvulsive therapy (mECT) is underused in the treatment of bipolar disorder (BD). We aimed to study the real-life effectiveness of mECT in BD. Naturalistic 3-year mirror-image study in individuals diagnosed with BD who underwent mECT at a tertiary hospital. Intra-subject comparisons of psychiatric hospitalization were performed using McNemar test. Days and number of psychiatric hospitalizations before and during mECT were compared through wilcoxon signed-rank test. Mean annual days and mean annual number of psychiatric hospitalizations per patient were compared by means of the rate ratio (RR) estimation through a generalized estimating equation (GEE) model. A total of 43 patients were included and 37 required psychiatric hospitalization during the study. The use of mECT showed an effectiveness of 62.2% for preventing psychiatric hospitalizations (p<0.01). We found significant reduction in days and number of psychiatric hospitalizations during mECT compared to before mECT (p<0.01). Comparison of the 3-year period before/during mECT showed a reduction in mean annual days (RR=0.14; 95%CI: 0.07-0.29) and mean annual number (RR=0.24; 95%CI: 0.13-0.43) of psychiatric hospitalizations, without substantial changes for adjusted models for gender and age of onset of the illness. The main limitations of this study consisted of the mirror-image retrospective naturalistic study design, the relatively small sample size, and possibly patient selection bias. mECT reduced the number of psychiatric hospitalizations and hospitalization days in BD. The use of mECT outlines a mood stabilizing effect in BD. This naturalistic study supports the effectiveness of mECT in BD across several mood states.


L-Tryptophan prevents Escherichia coli biofilm formation and triggers biofilm degradation.
The effect of deletion of trp operon and tna operon on the Escherichia coli biofilm formation was investigated in order to elucidate the role of L-tryptophan metabolism in biofilm formation. trp operon deletion mutants ΔtrpC, ΔtrpD and ΔtrpE deficient in L-tryptophan biosynthesis showed higher biofilm formation. In addition, ΔtnaC with increased L-tryptophan degradation activity showed higher biofilm formation. On the contrary, ΔtnaA deletion mutant which lost L-tryptophan degradation activity showed low biofilm formation. From these results, it was suggested that decrease of intracellular L-tryptophan level induced biofilm formation and increase of L-tryptophan repressed biofilm formation. So the effect of the addition of L-tryptophan to the medium on the E. coli biofilm formation was investigated. L-Tryptophan addition at starting culture decreased biofilm formation and furthermore L-tryptophan addition after 16 h culture induced the degradation of preformed biofilm. From the above results, it was suggested that maintenance of high intracellular L-tryptophan concentration prevents E. coli biofilm formation and elevation of intracellular L-tryptophan concentration triggers degradation of matured biofilm.


Electron microscopy of composite and intranuclear keratohyalin granules in geographic tongue of psoriasis.
Composite and intranuclear keratohyalin granules were observed in an electron-microscopic study of geographic tongue of psoriasis. The significance of intranuclear keratohyalin is not known, but it seems to be related to the disturbed proliferation and differentiation of keratinocytes in psoriasis.


Plastic changes following imitation-based speech and language therapy for aphasia: a high-density sleep EEG study.
BACKGROUND OBJECTIVE: measurement of plastic brain changes induced by a novel rehabilitative approach is a key requirement for validating its biological rationale linking the potential therapeutic gains to the changes in brain physiology. Based on an emerging notion linking cortical plastic changes to EEG sleep slow-wave activity (SWA) regulation, we aimed to assess the acute plastic changes induced by an imitation-based speech therapy in individuals with aphasia by comparing sleep SWA changes before and after therapy. A total of 13 left-hemispheric stroke patients underwent language assessment with the Western Aphasia Battery (WAB) before and after 2 consecutive high-density (hd) EEG sleep recordings interleaved by a daytime session of imitation-based speech therapy (Intensive Mouth Imitation and Talking for Aphasia Therapeutic Effects [IMITATE]). This protocol is thought to stimulate bilateral connections between the inferior parietal lobule and the ventral premotor areas. A single exposure to IMITATE resulted in increases in local EEG SWA during subsequent sleep over the same regions predicted by the therapeutic rationale, particularly over the right hemisphere (unaffected by the lesion). Furthermore, changes in SWA over the left-precentral areas predicted changes in WAB repetition scores in our group, supporting the role of perilesional areas in predicting positive functional responses. Our results suggest that SWA changes occurring in brain areas activated during imitation-based aphasia therapy may reflect the acute plastic changes induced by this intervention. Further testing will be needed to evaluate SWA as a non-invasive assessment of changes induced by the therapy and as a predictor of positive long-term clinical outcome.


A quality assurance study on the accuracy of measuring physical function under current conditions for use of clinical video telehealth.
To determine whether conditions for use of clinical video telehealth technology might affect the accuracy of measures of physical function. Repeated measures. Veterans Administration Medical Center. Three healthy adult volunteers for a sample size of n=30 independent trials for each of 3 physical function tasks. None. Three tasks capturing differing aspects of physical function: fine-motor coordination (number of finger taps in 30s), gross-motor coordination (number of gait deviations in 10ft [3.05m]), and clinical spatial relations (identifying the proper height for a cane randomly preset ±0-2in [5.1cm] from optimal), with performance simultaneously assessed in person and video recorded. Interrater reliability and criterion validity were determined for the measurement of these 3 tasks scored according to 5 methods: (1) in person (community standard), (2) slow motion review of the video recording (criterion standard), and (3-5) full speed review at 3 Internet bandwidths (64kps, 384kps, and 768kps). Fine-motor coordination-Interrater reliability was variable (r=.43-.81) and criterion validity was poor at 64kps and 384kps, but both were acceptable at 768kps (reliability r=.74, validity β=.81). Gross-motor coordination-Interreliability was variable (range r=.53-.75) and criterion validity was poor at all bandwidths (β=.28-.47). Motionless spatial relations-Excellent reliability (r=.92-.97) and good criterion validity (β=.84-.89) at all the tested bandwidths. Internet bandwidth had differing effects on measurement validity and reliability for the fine-motor task, the gross-motor task, and spatial relations, with results for some tasks at some transmission speeds well below acceptable quality standards and community standards.


Impairment of brain mitochondrial function by reactive nitrogen species: the role of glutathione in dictating susceptibility.
Mitochondrial enzymes involved in energy metabolism display varying degrees of sensitivity towards reactive nitrogen species such as peroxynitrite (ONOO-). With regards to the electron transport chain, cytochrome oxidase appears particularly sensitive. Inhibition of this component may lead to an increase in mitochondrial superoxide formation, exacerbation of cellular oxidative stress and further mitochondrial damage. Impairment of the electron transport chain may lead to a loss of membrane potential, ATP deficiency, opening of the permeability transition pore and the release of factors capable of initiating apoptosis. Reduced glutathione will react, via a number of diverse reactions, with reactive nitrogen species and hence is capable of limiting mitochondiral damage. Loss of brain glutathione may therefore be an important factor in those neurological conditions in which there is evidence of excessive nitric oxide formation and mitochondrial damage.


Categorical Perception of Control.
The self is a distinct entity from the rest of the world, and actions and sensory feedback are our channels of interaction with the external world. This study examined how the sense of control influences people's perception of sensorimotor input under the framework of categorical perception. Twenty human participants (18 males, two females) took part in both experiments. Experiment 1 showed that the sensitivity (d') of detecting a 20% change in control from no change was higher when the changes occurred at the control-category boundary than within each category. Experiment 2 showed that the control categories greatly affected early attention allocation, even when the judgment of control was unnecessary to the task. Taken together, these results showed that our perceptual and cognitive systems are highly sensitive to small changes in control that build up to a determinant change in the control category within a relatively narrow boundary zone between categories, compared with a continuous, gradual physical change in control.


Changes in percentages of perceived met needs for care over time in a Canadian longitudinal cohort.
There is a paucity of research on determinants associated with changes in perceived met needs for care over time. This study used a longitudinal cohort to explore changes in percentages of perceived met needs over time and to identify its related determinants. Data analyzed was from a longitudinal community-based survey. A total of 150 participants received at least one type of help both at baseline and a 2-year follow-up. Multivariate analyses were used. Perceived met needs of the study sample slightly increased over time. People who had a higher percentage of met needs at baseline were less likely to have an increase in percentage of perceived met needs at the 2-year follow-up, whereas, those who had a higher value of wellbeing and an increase in the value of mental wellbeing over time, were associated with an increase in the percentage of met needs at the 2-year follow-up. Determinants associated with changes in percentages of perceived met needs could be the target for improving perceived need for mental health care. Findings of this study indicate the need for longitudinal studies in perceived need for mental health services.


Germ cell tumor in the hypothalamo-neurohypophysial region: clinical features and treatment.
Twenty-one patients with germ cell tumors (17 germinomas and 4 teratomas) involving the hypothalamic-neurohypophysial (HN) region were reviewed retrospectively. Eleven patients were males and 10 females, and their ages ranged from 7 to 45 years (average 18.5 years). Diabetes insipidus was the initial and the most prominent symptom in most germinomas; in teratomas the most prominent symptom was visual disturbance. Fifteen patients with germinomas were treated by radiotherapy, and 4 with teratomas were treated by surgical resection alone. Two recent germinoma patients with extensive CSF dissemination were treated with systemic chemotherapy consisting of anticancer platinum drugs and etoposide, which resulted in a complete disappearance of the tumors. Patients with germinoma treated after the introduction of CT scanning had a greatly improved mortality rate, and their actual survival rate was 87.5% over 10 years. On the basis of this review, the authors consider that diagnosis at an early stage of the disease and chemotherapy, which can be an effective therapeutic alternative to radiation therapy, may improve not only the mortality rate but also the quality of life of patients with HN germ cell tumors.


A Prognosis Tool Based on Fuzzy Anthropometric and Questionnaire Data for Obstructive Sleep Apnea Severity.
Obstructive sleep apnea (OSA) are linked to the augmented risk of morbidity and mortality. Although polysomnography is considered a well-established method for diagnosing OSA, it suffers the weakness of time consuming and labor intensive, and requires doctors and attending personnel to conduct an overnight evaluation in sleep laboratories with dedicated systems. This study aims at proposing an efficient diagnosis approach for OSA on the basis of anthropometric and questionnaire data. The proposed approach integrates fuzzy set theory and decision tree to predict OSA patterns. A total of 3343 subjects who were referred for clinical suspicion of OSA (eventually 2869 confirmed with OSA and 474 otherwise) were collected, and then classified by the degree of severity. According to an assessment of experiment results on g-means, our proposed method outperforms other methods such as linear regression, decision tree, back propagation neural network, support vector machine, and learning vector quantization. The proposed method is highly viable and capable of detecting the severity of OSA. It can assist doctors in pre-diagnosis of OSA before running the formal PSG test, thereby enabling the more effective use of medical resources.


Bundle branch reentrant ventricular tachycardia: cumulative experience in 48 patients.
The clinical, electrophysiologic features and follow-up of 48 patients with inducible bundle branch reentrant (BBR) tachycardia are presented. Forty-eight patients were identified in whom a diagnosis of BBR tachycardia was made during electrophysiologic evaluation. The clinical presentation was syncope or sudden death in 38 patients, and sustained palpitations during wide QRS complex tachycardia in 5 patients. Electrophysiologic studies were performed in 5 additional patients for various other reasons. Structural heart disease was present in 45 patients. Idiopathic dilated cardiomyopathy and coronary artery disease were the anatomical substrates in 19 (39%) and 24 (50%) patients, respectively, severe aortic regurgitation was present in 2 patients, and no organic heart disease was identified in 3. All 48 patients had evidence of His-Purkinje system disease. BBR tachycardia with left and right bundle branch block morphologies was induced in 46 and 5 patients, respectively, and interfascicular BBR tachycardia was initiated in 2 patients. Ventricular tachycardia of a myocardial origin was induced in 11 patients. Management of BBR tachycardia included transcatheter bundle branch ablation in 28 patients, and antiarrhythmic drug therapy in 16 patients. Four patients were treated with implantable defibrillators. After a mean follow-up of 15.8 months in 42 patients, there were 13 deaths due to congestive heart failure, 4 sudden cardiac deaths, 3 nonsudden cardiac deaths, and 3 noncardiac related deaths. Sustained BBR, a form of monomorphic ventricular tachycardia, is a highly malignant arrhythmia usually seen in patients with structural heart disease. Three different types of BBR tachycardia are described. If distinguished from ventricular tachycardia of a myocardial origin, catheter ablation of the right bundle branch can be easily performed and effectively eliminates BBR. During follow-up, congestive heart failure is the most common cause of death in this population.


Hypofibrinolysis associated with vasculopathy in non insulin dependent diabetes mellitus.
The pathogenesis of diabetic vasculopathy has been related to modifications in hemostasis and fibrinolysis. 50 non insulin dependent diabetes mellitus patients have been studied. Euglobulin clot lysis time, fibrin plate, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI) activity, Protein C and S, cholesterol, triglycerides and Hb A1c were determined in blood samples. Diabetic patients showed decreased fibrinolytic activity, as measured by ECLT, with clearly increased PAI levels. Fibrinolytic response to venous occlusion was lower than normal. Vascular complications were associated both with an even higher PAI activity and with a decreased fibrinolytic response to venous occlusion. Elevated PAI activity and decreased fibrinolytic response to stimulus may contribute to vascular disease in diabetes.


Low frequency of asymptomatic carriage of toxigenic Clostridium difficile in an acute care geriatric hospital: prospective cohort study in Switzerland.
The role of asymptomatic carriers of toxigenic Clostridium difficile (TCD) in nosocomial cross-transmission remains debatable. Moreover, its relevance in the elderly has been sparsely studied. To assess asymptomatic TCD carriage in an acute care geriatric population. We performed a prospective cohort study at the 296-bed geriatric hospital of the Geneva University Hospitals. We consecutively recruited all patients admitted to two 15-bed acute-care wards. Patients with C. difficile infection (CDI) or diarrhoea at admission were excluded. First bowel movement after admission and every two weeks thereafter were sampled. C. difficile toxin B gene was identified using real-time polymerase chain-reaction (BD MAX(TM)Cdiff). Asymptomatic TCD carriage was defined by the presence of the C. difficile toxin B gene without diarrhoea. A total of 102 patients were admitted between March and June 2015. Two patients were excluded. Among the 100 patients included in the study, 63 were hospitalized and 1 had CDI in the previous year, and 36 were exposed to systemic antibiotics within 90 days prior to admission. Overall, 199 stool samples were collected (median 2 per patient, IQR 1-3). Asymptomatic TCD carriage was identified in two patients (2 %). We found a low prevalence of asymptomatic TCD carriage in a geriatric population frequently exposed to antibiotics and healthcare. Our findings suggest that asymptomatic TCD carriage might contribute only marginally to nosocomial TCD cross-transmission in our and similar healthcare settings.


A new molecular risk pathway for postpartum mood disorders: clues from steroid sulfatase-deficient individuals.
Postpartum mood disorders develop shortly after childbirth in a significant proportion of women. These conditions are associated with a range of symptoms including abnormally high or low mood, irritability, cognitive disorganisation, disrupted sleep, hallucinations/delusions, and occasionally suicidal or infanticidal ideation; if not treated promptly, they can substantially impact upon the mother's health, mother-infant bonding, and family dynamics. The biological precipitants of such disorders remain unclear, although large changes in maternal immune and hormonal physiology following childbirth are likely to play a role. Pharmacological therapies for postpartum mood disorders can be effective, but may be associated with side effects, concerns relating to breastfeeding, and teratogenicity risks when used prophylactically. Furthermore, most of the drugs that are used to treat postpartum mood disorders are the same ones that are used to treat mood episodes during non-postpartum periods. A better understanding of the biological factors predisposing to postpartum mood disorders would allow for rational drug development, and the identification of predictive biomarkers to ensure that 'at risk' mothers receive earlier and more effective clinical management. We describe new findings relating to the role of the enzyme steroid sulfatase in maternal postpartum behavioural processes, and discuss how these point to a novel molecular risk pathway underlying postpartum mood disorders. Specifically, we suggest that aberrant steroid hormone-dependent regulation of neuronal calcium influx via extracellular matrix proteins and membrane receptors involved in responding to the cell's microenvironment might be important. Testing of this hypothesis might identify novel therapeutic targets and predictive biomarkers.


Towards a phenomenology of caregiving: growth in the caregiver is a vital component.
The classical notions of 'virtue' and 'leisure' offer excellent insights into the essentially moral nature of medical practice. This is especially evident in the understanding that professional caregiving has the potential to enhance the moral character as well as the moral awareness of the practitioner. Reflective awareness of the moral nature of the caregiving process can also contribute to coping with negative stress, which almost always has its origins in frustrations rooted in moral quandaries and evaluations. Understanding the process required arises from implementation of caregiving in combination with deliberate, conscious development of spiritual awareness and reflection on moral meaning.


Gene expression of LOX-1, VCAM-1, and ICAM-1 in pre-atherosclerotic mice.
To identify markers of the earliest stage of atherosclerosis, endothelial dysfunction, we evaluated the gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in very young pre-atherosclerotic mice. Furthermore, the plasma levels of the soluble VCAM-1 and ICAM-1 were compared to the gene expression profiles. Gene expressions of LOX-1 and VCAM-1 were up-regulated in young apoE(-/-) mice, and thus, it seems probable that these genes play a role in pre-atherosclerosis. Contrarily, the gene expression profile of ICAM-1 did not show any apparent differences between the groups, questioning the involvement of this molecule in the early development of atherosclerosis. Plasma levels of sVCAM-1 and sICAM-1 were similar in all mice and did not correlate with the vascular gene expression of the corresponding genes. It therefore seems likely that these circulating markers are not suited to detect early atherosclerosis.