IMPACT OF COMORBIDITIES IN MEXICAN SARS-COV-2-POSITIVE PATIENTS: A RETROSPECTIVE ANALYSIS IN A NATIONAL COHORT.
The coronavirus disease 2019 outbreak is a significant challenge for health-care systems around the world. The objective of the study was to assess the impact of comorbidities on the case fatality rate (CFR) and the development of adverse events in patients positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the Mexican population. We analyzed the data from 13,842 laboratory-confirmed SARS-CoV-2 patients in Mexico between January 1, 2020, and April 25, 2020. We investigated the risk of death and the development of adverse events (hospitalization, pneumonia, orotracheal intubation, and intensive care unit [ICU] admission), comparing the number of comorbidities of each patient. The patient mean age was 46.6 ± 15.6 years, 42.3% (n = 5853) of the cases were women, 38.8% of patients were hospitalized, 4.4% were intubated, 29.6% developed pneumonia, and 4.4% had critical illness. The CFR was 9.4%. The risk of hospitalization (odds ratio [OR] = 3.1, 95% confidence interval [CI]: 2.7-3.7), pneumonia (OR = 3.02, 95% CI: 2.6-3.5), ICU admission (OR = 2, 95% CI: 1.5-2.7), and CFR (hazard ratio = 3.5, 95% CI: 2.9-4.2) was higher in patients with three or more comorbidities than in patients with 1, 2, or with no comorbidities. The number of comorbidities may be a determining factor in the clinical course and its outcomes in SARS-CoV-2-positive patients.


Two decade trends in birth weight and early childhood growth in Papua New Guinea.
At present, little is known about patterns of early growth and development in foraging and small-scale horticultural populations. Moreover, still less is known about secular changes in growth in these populations. Data collected in 1967, 1976, and 1989 are presented for birth weight and subsequent growth to 5 years among Au forager-horticulturalists of Papua New Guinea. Despite the launching of health campaigns over the last two decades aimed at bettering the nutritional status of the Au, the data show that average birth weight has remained stable and low at just over 2600 g. Weight- and length-for-age also show no significant changes among traditional Au over the last 20 years, and remain on average, at just below the U.S. 5th percentile. Evidence for the start of a positive secular trend in birth weight and subsequent growth is seen, however, among a small group of Au children residing in households that have a source of wage income. These individuals show an increase of 150 g in birth weight, and over the subsequent 5 years of growth average 93 g heavier and 2.6 cm taller than Au children in traditional households. In addition to providing baseline data on child growth in a forager-horticulturalist society, the findings provide evidence for a secular trend newly underway, and suggest that health promotion campaigns alone without socioeconomic development may be insufficient in effecting change in growth status in rural communities. Am. J. Hum. Biol. 10:483-493, 1998. © 1998 Wiley-Liss, Inc.


Insights into correlated motions and long-range interactions in CheY derived from molecular dynamics simulations.
CheY is a response regulator protein involved in bacterial chemotaxis. Much is known about its active and inactive conformations, but little is known about the mechanisms underlying long-range interactions or correlated motions. To investigate these events, molecular dynamics simulations were performed on the unphosphorylated, inactive structure from Salmonella typhimurium and the CheY-BeF(3)(-) active mimic structure (with BeF(3)(-) removed) from Escherichia coli. Simulations utilized both sequences in each conformation to discriminate sequence- and structure-specific behavior. The previously identified conformational differences between the inactive and active conformations of the strand-4-helix-4 loop, which are present in these simulations, arise from the structural, and not the sequence, differences. The simulations identify previously unreported structure-specific flexibility features in this loop and sequence-specific flexibility features in other regions of the protein. Both structure- and sequence-specific long-range interactions are observed in the active and inactive ensembles. In the inactive ensemble, two distinct mechanisms based on Thr-87 or Ile-95 rotameric forms, are observed for the previously identified g+ and g- rotamer sampling by Tyr-106. These molecular dynamics simulations have thus identified both sequence- and structure-specific differences in flexibility, long-range interactions, and rotameric form of key residues. Potential biological consequences of differential flexibility and long-range correlated motion are discussed.


[Clinical study on the effect of natural alpha-interferon (HLBI) in the treatment of adult T-cell leukemia].
The phase II trial of natural interferon-alpha (HLBI) in treatment of adult T-cell leukemia was carried out as a cooperative study. Of the 24 cases which could be evaluated, 3 cases in crisis type and 5 cases in chronic type with lymphadenopathy and/or skin infiltration achieved PR, giving a response rate of 33.3%. The anti-tumor effect of HLBI for skin lesion could be assessed in 16 cases with skin infiltration, giving a response rate of 50.0% (5 CR and 3 PR) and demonstrating a high efficacy. Of the 31 eligible patients, side effects were recognised in 27 (87.1%). Major subjective and objective symptoms were fever (38.7%), fatigue (25.8%), anorexia (12.9%) and nausea (12.9%), and leukopenia (22.6%), granulocytopenia (38.7%), thrombocytopenia (38.7), elevation of GPT (12.9%) and GOT (12.9%) were observed.


CeFePO: f-d hybridization and quenching of superconductivity.
As a homologue to the new, Fe-based type of high-temperature superconductors, the electronic structure of the heavy-fermion compound CeFePO was studied by means of angle-resolved resonant photoemission. It was experimentally found-and later on confirmed by local-density approximation (LDA) as well as dynamical mean-field theory (DMFT) calculations-that the Ce 4f states hybridize to the Fe 3d states of d{3z{2}-r{2}} symmetry near the Fermi level that discloses their participation in the occurring electron-correlation phenomena and provides insight into mechanism of superconductivity in oxopnictides.


Latexin exhibits tumor suppressor potential in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and latexin is downregulated in several types of human cancer. However, latexin expression in HCC remains unknown. mRNA expression of latexin in HCC samples and HCC-derived cell lines was detected by semi‑quantitative PCR and real-time PCR, while protein expression was assessed by immunohistochemistry. The role of latexin in the regulation of the proliferation of HCC-derived cells was investigated both in vitro and in vivo. Flow cytometry was used to differentiate cell cycle distribution in SK-hep-1 and YY-8103. In a total of 60 paired HCC specimens, compared with adjacent non-cancer tissues, latexin mRNA was downregulated in 42 specimens. Immunohistochemical analysis showed a significant reduction in latexin expression in HCC compared to control tissues. Overexpression of latexin inhibited SK-hep-1 and HepG2 cellular colony formation and tumor growth. Conversely, YY‑8103 and Focus cells transfected with shRNA enhanced colony formation and tumor growth. Latexin overexpression promoted cell cycle arrest in the G0/G1 phase in SK-hep-1 and silencing of latexin promoted the cell cycle transition from G0/G1 phase to S phase in YY-8103. The cyclin-dependent kinase inhibitors (CDKIs) (p21Cip1, p27Kip1, p15INK4B), cyclin D1 and cyclin E were shown to be differentially expressed in latexin-overexpressed cells and latexin-silenced cells. These results indicated that latexin may be an effective target for gene therapy.


Anaphylactoid reaction to recombinant tissue plasminogen activator.
Anaphylactoid reaction to recombinant tissue plasminogen activator for the thrombolytic treatment of acute ischemic stroke is an uncommon complication. An increased risk of anaphylaxis may be found in patients concomitantly being treated with angiotensin-converting enzyme inhibitors, as illustrated by this case report describing a patient who experienced an urticaric rash, hypotension, tachycardia, orolingual angioedema, and airway obstruction following intravenous administration of alteplase. Possible pharmacologic interactions resulting in excessive serum bradykinin and subsequent systemic hypersensitivity responses are discussed.


Synthesis and SAR of novel, potent and orally bioavailable benzimidazole inhibitors of poly(ADP-ribose) polymerase (PARP) with a quaternary methylene-amino substituent.
Poly(ADP-ribose) polymerases (PARPs) play significant roles in various cellular functions including DNA repair and control of RNA transcription. PARP inhibitors have been demonstrated to potentiate the effect of cytotoxic agents or radiation in a number of animal tumor models. Utilizing a benzimidazole carboxamide scaffold in which the amide forms a key intramolecular hydrogen bond for optimal interaction with the enzyme, we have identified a novel series of PARP inhibitors containing a quaternary methylene-amino substituent at the C-2 position of the benzimidazole. Geminal dimethyl analogs at the methylene-amino substituent were typically more potent than mono-methyl derivatives in both intrinsic and cellular assays. Smaller cycloalkanes such as cyclopropyl or cyclobutyl were tolerated at the quaternary carbon while larger rings were detrimental to potency. In vivo efficacy data in a B16F10 murine flank melanoma model in combination with temozolomide (TMZ) are described for two optimized analogs.


Child traffic accident injuries in Japan.
This study analyzes the characteristics of traffic accidents involving children. It discusses why children with certain attributes and in specific situations are exposed to a higher traffic accident risk, in light of their ability to deal with traffic and their body characteristics. Finally, based on these results, it offers some conclusions and recommendations on ways of improving child safety in road traffic.


A Density Functional Theory Study on Comparing the Reactivity of [Mn(13-TMC)(OOH)]2+ and [Mn(13-TMC)(O2)]+ for the Sulfoxidation of Thioanisole: Elucidation of Substrate and Non-Redox Metal Ion Effects.
The reactivities of [Mn(13-TMC)(OOH)]2+ (1) and [Mn(13-TMC)(O2)]+ (2) in the sulfoxidation of thioanisole have been compared using density functional theory methods. The orientation of the 13-TMC ligand and substrate and non-redox metal ion effects have been considered to improve the oxidation efficiency of 1 and 2. In 1, the syn- and anti-orientation of the 13-TMC ligand do not change the coordination of the Mn ion. In contrast, the orientation of the 13-TMC ligand regulates the geometry of 2, wherein the syn-13-TMC ligand exhibits the MnIII-peroxo (2hs and 2ls) species, while the anti-13-TMC shows the MnII-superoxo (2'hs and 2'ls) species. However, the MnII-superoxo species are found to be less stable than the MnIII-peroxo complexes by around +26.6 kcal/mol. The ground state geometries of 1 and 2 with the syn-13-TMC ligand are found to be more stable in the high- (S = 2) spin states (1hs and 2hs) than the low- (S = 1) spin complexes (1ls and 2ls), by +15.6 and +25.5 kcal/mol, respectively. The computed mechanistic pathways clearly indicate that the sulfoxidation of thioanisole by 1hs is kinetically (by +16.6 to +46.1 kcal/mol) and thermodynamically (+14.4 to +56.1 kcal/mol) more preferred than 1ls, 2hs, and 2ls species. This is mainly due to the feasible heterolytic O1-O2 bond cleavage followed by the proton transfer step. In addition, the molecular electrostatic potential analysis indicates that the higher oxidation efficacy of 1hs than 2hs is due to the -OOH moiety. The reactivity of 1hs is further enhanced by incorporating electron donating substituents in thioanisole, wherein the p-NH2 thioanisole decreases the ΔG‡ of 1hs by 28%. Interestingly, the incorporation of non-redox metal ions (Mn+ = Sc3+, Y3+, Mg2+, and Zn2+) improves the reactivity of 2hs, wherein the non-redox metal ions tend to bind with the oxygen atoms of 2hs and subsequently shift the one-electron reduction potential (E0(red) vs SCE) toward the positive side. The positive shift in the E0(red) is more evident in 2hs-Y3+ that significantly decreases the ΔG‡ of 2hs by 58.7%, which is in fact lower than the ΔG‡ of 1hs by +2.0 kcal/mol. Hence, in the presence of Y3+, the reactivity of 2hs is comparable with 1hs in the sulfoxidation of thioanisole.


A tribute to Lance Secretan.
Lance Secretan's philosophy in short can be summarized as "reawakening spirit and values in the workplace." "Oneness," "divinity," "spirit," "love," and "kindness"--they are words you would expect from a religious leader like Buddha or the quintessential guru, Mahatma Gandhi. They are not the words customarily used in the board room. However, Secretan believes that they are essential vocabulary for modern industry CEOs.


Secondary acute myeloid leukemia early after therapy for Hodgkin's disease--a case report.
A case of acute myeloid leukemia (AML) after successful therapy for Hodgkin's disease (HD) is reported. The patient was diagnosed with stage IIB HD at the age of 25. She was treated with chemotherapy and radiotherapy (RT), and complete remission (CR) was achieved. Seven months after the CR was obtained the patient developed AML. Knowing that the prognosis of patients with secondary AML (sAML) after primary HD is poor we decided to perform autologous peripheral stem cells' transplantation.


The heimlich device in thoracic surgery.
Pneumothoraces and malignant pleural effusions are commonly encountered clinical problems in a general thoracic surgical practice. Pneumothoraces may be either iatrogenic or non-iatrogenic. Iatrogenic pneumothoraces can occur following transbronchial or percutaneous transthoracic lung biopsy, percutaneous central venous catheter insertion, or thoracentesis. Non-iatrogenic pneumothoraces are encountered frequently in the patient with chronic obstructive pulmonary disease and spontaneous rupture of pulmonary bullae, as well as blunt or penetrating thoracic trauma. Alternatively, pneumothoraces may be idiopathic or "simple pneumothoraces."


Potent, selective pyrone-based inhibitors of stromelysin-1.
In an effort to develop alternatives to hydroxamate-based matrix metalloproteinase inhibitors (MPIs), we have utilized the drug discovery program LUDI enhanced with the structural coordinates of a bioinorganic model complex. This method has yielded the first pyrone-based MPIs. The inhibitors demonstrate nanomolar potency against MMP-3 and are selective for MMP-3 over MMP-2 and MMP-1. We postulate that the potency and unusual selectivity profile of these MPI is attributable to the pyrone chelating group.


Nutritional status in patients with advanced lung cancer undergoing chemotherapy: a prospective observational study.
Purpose: The consequences of malnutrition include increased risk of many complications. The assessment and management of nutritional problems are essential in supportive care of patients undergoing therapy. The primary objective of the present study was to assess changes in the nutritional status in lung cancer patients who had undergone chemotherapy.Patients and methods: Preliminary and post-chemotherapy assessments of patients' nutritional status and medical characteristics were conducted using the Patient-Generated Subjective Global Assessment (PG-SGA) from July 2014 to May 2016 at Harbin Medical University Cancer Hospital. Four hundred sixty-five advanced lung cancer patients (51.8% men and 48.2% women with a mean (SD) age of 60.2 ± 9.8 years) participated in the present study. PG-SGA was assessed prior to the initiation of chemotherapy and after four cycles of chemotherapy.Results: We found that 11.4% of the patients were severely malnourished and 65.6% of the patients were moderately malnourished prior to chemotherapy. After chemotherapy, 52.9% of the patients were considered moderately malnourished, whereas 33.8% were severely malnourished. The nutritional status had deteriorated in the majority of patients. After chemotherapy, there was a rise in the prevalence of nutrition impact symptoms.Conclusions: A deteriorated nutritional status was the result of the side effects caused by chemotherapy in the patients of the present study. These findings highlight that more attention should be paid to improve the nutritional status in patients with advanced lung cancer undergoing chemotherapy, and proper nutrition education and nutritional support should be provided to these patients.


Proteomic analysis of Atg8-dependent recruitment of phagosomal proteins in the enteric protozoan parasite Entamoeba histolytica.
Autophagy is one of the bulk degradation systems and is conserved throughout eukaryotes. In the enteric protozoan parasite Entamoeba histolytica, the causative agent of human amebiasis, Atg8 is not exclusively involved in autophagy per se but also in other membrane traffic-related pathways such as phagosome biogenesis. We previously reported that repression of atg8 gene expression by antisense small RNA-mediated transcriptional gene silencing (gs) resulted in growth retardation, delayed endocytosis, and reduced acidification of endosomes and phagosomes. In this study, to better understand the role of Atg8 in phagocytosis and trogocytosis, we conducted a comparative proteomic analysis of phagosomes isolated from wild type and atg8-gs strains. We found that 127 and 107 proteins were detected >1.5-fold less or more abundantly, respectively, in phagosomes isolated from the atg8-gs strain, compared to the control strain. Among 127 proteins whose abundance was reduced in phagosomes from atg8-gs, a panel of proteins related to fatty acid metabolism, phagocytosis, and endoplasmic reticulum (ER) homeostasis was identified. Various lysosomal hydrolases and their receptors also tend to be excluded from phagosomes by atg8-gs, reinforcing the notion that Atg8 is involved in phagosomal acidification and digestion. On the contrary, among 107 proteins whose abundance increased in phagosomes from atg8-gs strain, ribosome-related proteins and metabolite interconversion enzymes are enriched. We further investigated the localization of several representative proteins, including adenylyl cyclase-associated protein and plasma membrane calcium pump, both of which were demonstrated to be recruited to phagosomes and trogosomes via an Atg8-dependent mechanism. Taken together, our study has provided the basis of the phagosome proteome to further elucidate molecular events in the Atg8-dependent regulatory network of phagosome/trogosome biogenesis in E. histolytica.


Evidence for school transmission of Neisseria meningitidis during a Vermont outbreak.
A meningitis outbreak due to Neisseria meningitidis, serogroup C, serotype 2b, occurred in central Vermont in February, 1984. The highest incidence was in Northfield, where 7 cases occurred (129 per 100,000 population). Of these 7 cases 2 were students at Northfield High School and 5 were younger children; all had had close contact with Northfield High School students or staff in the week before illness. A case-control study demonstrated that these cases had significantly more exposure to Northfield High School students or staff in the 2 weeks before illness (112 hours) than did controls (8 hours) (P = 0.006). This finding was confirmed by a second case-control study designed to determine risk factors for the entire outbreak. School children in Northfield and their household contacts were given meningococcal A-C vaccine and sulfisoxazole prophylaxis. No further cases of meningococcal disease occurred in Northfield after the week that these control methods were initiated. Transmission of the outbreak strain of N. meningitidis appears to have occurred in a school setting with subsequent illness in household and close contacts of carriers of the outbreak strain.


Comparison of an antigen-capture enzyme-linked immunosorbent assay with bacterial culture for detection of Salmonella in poultry-hatchery environmental samples.
An antigen-capture, monoclonal-antibody-based enzyme-linked immunoassay (ELISA) that detects a broad range of Salmonella serovars in various serogroups was developed and compared with standard culture procedures for detection of Salmonella in 1055 field samples collected from poultry-hatchery environments. The diagnostic sensitivity of the ELISA relative to culture was 99.9% and the diagnostic specificity 99.6%. The extensive culture procedure included nonselective enrichment (NSE) as well as primary selective enrichment (PSE) and delayed secondary enrichment (DSE) with Hajna tetrathionate (TT) and Rappaport-Vassiliadis (RV) selective-enrichment broths. Significantly more Salmonella-positive samples were detected by ELISA and culture at the DSE stage than at the NSE and PSE stages (P < 0.05). Significantly more RV than TT broths were positive for Salmonella by culture and ELISA by the DSE stage (P < 0.05). This ELISA procedure could be a reliable screening test for the detection of Salmonella in hatchery samples.


Cellular Assays for Dynamic Quantification of Deubiquitinase Activity and Inhibition.
Deubiquitinases (DUBs) are proteolytic enzymes that catalyze the removal of ubiquitin from protein substrates. The critical role of DUBs in regulating protein ubiquitination makes them attractive drug targets in oncology, neurodegenerative disease, and antiviral development. Biochemical assays for quantifying DUB activity have enabled characterization of substrate preferences and discovery of small molecule inhibitors. However, assessing the efficacy of these inhibitors in cellular contexts to support clinical drug development has been limited by a lack of tractable cell-based assays. To address this gap, we developed a two-color flow cytometry-based assay that allows for sensitive quantification of DUB activity and inhibition in living cells. The utility of this system was demonstrated by quantifying the potency of GRL0617 against the viral DUB SARS-CoV-2 PLpro, identifying potential GRL0617 resistance mutations, and performing structure-function analysis of the vOTU domain from the recently emerged Yezo virus. In addition, the system was optimized for cellular DUBs by modifying a GFP-targeting nanobody to recruit USP7 and USP28 to benchmark a panel of reported inhibitors and assess inhibition kinetics. Together, these results demonstrate the utility of these assays for studying DUB biology in a cellular context with potential to aid in inhibitor discovery and development.


Factors affecting condom use among fishers in Elmina fishing community in Ghana.
Although it is well known that low condom usage among fishers contributes to high HIV prevalence in fishing communities, little is known about the attitudes, beliefs, and behaviors of fishers when it comes to the use of condoms. This article is a follow-up to a cross-sectional study that used a mix-method design for data collection and analysis to examine the connection between mobility and the risk of contracting HIV among 385 fishers in the Elmina fishing community of Ghana. The Health Belief Model is utilized in the discussions to analyze attitudes and actions toward condom use among the fishers in Elmina. Over 40% of respondents who said they had intercourse in the previous year did not use condoms. The results show that male fishers are more likely than female fishers to use condoms during sexual activity, and younger fishers are more likely to use condoms than older fishers. More condoms were used by educated fishers than by less educated or uneducated fishers. According to the study, female fishers use less condoms than male fishers since they are unable to convince their partners to use them when they refuse to. Additionally, the findings show that slightly more than one in 10 respondents did not use condoms because they believed their sexual partner to be attractive and unlikely to carry any sexual infection. There is a general low perception of HIV susceptibility and severity resulting in the low condom usage among the fisherfolks according to the results. The article urges civil society organizations in the study area to investigate ways to incorporate the provision of free condoms to fishers and at the numerous fishing destination sites along the coast of Elmina. The regular use of condoms in Elmina and the nearby fishing areas should also be emphasised through this outreach or mobile HIV service outlets.


Effects of the visual environment on object localization in posterior cortical atrophy and typical Alzheimer's disease.
Visual processing deficits in Alzheimer's disease are associated with diminished functional independence. While environmental adaptations have been proposed to promote independence, recent guidance gives limited consideration to such deficits and offers conflicting recommendations for people with dementia. We evaluated the effects of clutter and color contrasts on performances of everyday actions in posterior cortical atrophy and memory-led typical Alzheimer's disease. 15 patients with posterior cortical atrophy, 11 with typical Alzheimer's disease and 16 healthy controls were asked to pick up a visible target object as part of two pilot repeated-measures investigations from a standing or seated position. Participants picked up the target within a controlled real-world setting under varying environmental conditions: with/without clutter, with/without color contrast cue and far/near target position. Task completion time was recorded using a target-mounted inertial measurement unit. Across both experiments, difficulties locating a target object were apparent through patient groups taking an estimated 50-90% longer to pick up targets relative to controls. There was no evidence of effects of color contrast when locating objects from standing/seated positions and of any other environmental conditions from a standing position on completion time in any participant group. Locating objects, surrounded by five distractors rather than none, from a seated position was associated with a disproportionately greater effect on completion times in the posterior cortical atrophy group relative to the control or typical Alzheimer's disease groups. Smaller, not statistically significant but directionally consistent, ratios of relative effects were seen for two distractors compared with none. Findings are consistent with inefficient object localization in posterior cortical atrophy relative to typical Alzheimer's disease and control groups, particularly with targets presented within reaching distance among visual clutter. Findings may carry implications for considering the adverse effects of visual clutter in developing and implementing environmental modifications to promote functional independence in Alzheimer's disease.


Sulfoximine Assisted C-H Activation and Annulation via Vinylene Transfer: Access to Unsubstituted Benzothiazines.
In this study, we report the synthesis of unsubstituted 1,2-benzothiazines through a redox-neutral Rh(III)-catalyzed C-H activation and [4+2]-annulation of S-aryl sulfoximines with vinylene carbonate. Notably, the introduction of an N-protected amino acid ligand significantly enhances the reaction rate. The key aspect of this redox-neutral process is the utilization of vinylene carbonate as an oxidizing acetylene surrogate and an efficient vinylene transfer agent. This vinylene carbonate enables the cyclization with the sulfoximine motifs, successfully forming a diverse array of 1,2-benzothiazine derivatives in moderate to good yields. Importantly, this study highlights the potential of Rh(III)-catalyzed C-H activation and [4+2]-annulation reactions for the synthesis of optically pure 1,2-benzothiazines with high enantiomeric purity.


Synovial incorporation of polyacrylamide hydrogel after injection into normal and osteoarthritic animal joints.
Polyacrylamide hydrogel (PAAG) is a non-toxic, non-degradable synthetic product, used for years in the augmentation of soft tissues. Preliminary results in animals and humans have suggested long-lasting beneficial effects on symptoms of osteoarthritis (OA). The aim of this histopathological study was to investigate whether intra-articular injection of PAAG is integrated into synovial tissue in normal and OA animal joints, and if this integration is sustained. (A) A prospective, controlled, longitudinal study of normal knee joints injected with PAAG was performed in 10 rabbits, following the animals up to 1 year, and (B) a post mortem examination was carried out up to 2 years post-injection on 18 horse joints which had previously been treated with 1-2 injections of 2 ml PAAG for clinically and radiologically diagnosed OA. Integration of the injected gel was evident at day 10 in the rabbit and by day 14 in the horse, with proliferation and invasion of synovial cells into the gel. By day 90 in rabbit joints and day 30 in horse joints, the gel had formed a sub-synovial layer, which was traversed by thin strands of connective tissue with vessels and covered by a synovial lining facing the joint cavity. This histological appearance persisted up to 2 years post-injection in horse joints. Intra-articular injection of PAAG results in a stable, long-lasting sub-synovial layer of gel traversed with thin strands of connective tissue. Further studies to explore potential effects on synovial inflammation and pain are warranted.


[Gene diagnosis of adult polycystic kidney disease--linkage analysis between APKD gene and alpha-globin gene 3'HVR].
Genomic DNA PvuII fragments containing the 3'HVR from 52 unrelated Chinese of Han nationality varied between 1.7 kb and 10.0 kb and showed high polymorphism. The genomic DNA PvuII fragments from five families with adult polycystic kidney disease (APKD) were analyzed using the alpha-globin gene 3' HVR (hypervariable region) as probe. The results showed a close linkage between 3'HVR and the APKD gene and segregation according to Mendelian laws. The maximum Lod score for linkage between 3' HVR and APKD was 3.372 at a recombination fraction theta = 0.01. The alpha-globin gene 3'HVR probe can therefore be used for presymptomatic gene diagnosis and prenatal diagnosis in the Han ethnic group.


Design and characterization of novel activated protein C variants for the proteolysis of cytotoxic extracellular histone H3.
Extracellular histone H3 is implicated in several pathologies including inflammation, cell death, and organ failure. Neutralization of histone H3 is a strategy that was shown beneficial in various diseases, such as rheumatoid arthritis, myocardial infarction, and sepsis. It was shown that activated protein C (APC) can cleave histone H3, which reduces histone cytotoxicity. However, due to the anticoagulant properties of APC, the use of APC is not optimal for the treatment of histone-mediated cytotoxicity, in view of its associated bleeding side effects. This study aimed to investigate the detailed molecular interactions between human APC and human histone H3, and subsequently use molecular docking and molecular dynamics simulation methods to identify key interacting residues that mediate the interaction between APC and histone H3 and to generate novel optimized APC variants. After molecular simulations, the designed APC variants 3D2D-APC (Lys37-39Asp and Lys62-63Asp) and 3D2D2A-APC (Lys37-39Asp, Lys62-63Asp, and Arg74-75Ala) were recombinantly expressed and their abilities to function as anticoagulant, to bind histones, and to cleave histones were tested and correlated with their cytoprotective properties. Compared with wild type-APC, both the 3D2D-APC and 3D2D2A-APC variants showed a significantly decreased anticoagulant activity, increased binding to histone H3, and similar ability to proteolyze histone H3. Our data show that it is possible to rationally design APC variants that may be further developed into therapeutic biologicals to treat histone-mediated disease, by proteolytic reduction of histone-associated cytotoxic properties that do not induce an increased bleeding risk.


Chronic inflammatory diseases increase the risk of post-thrombotic syndrome: A prospective cohort study.
Clinical management of patients with deep vein thrombosis (DVT) is centered around their risk of recurrent venous thromboembolism (VTE) and post-thrombotic syndrome (PTS). While chronic inflammatory disease (CID) has been established as a risk factor of (recurrent) VTE, research about its potential impact on PTS is lacking. We aimed to assess the risk of PTS in patients with CID, stratifying for the use of anti-inflammatory treatment. Consecutive patients with proximal DVT and no active cancer between 2003 and 2018 received a two-year prospective follow-up. CID included inflammatory bowel disease, rheumatic diseases, and gout. Residual venous obstruction (RVO) was assessed by compressive ultrasound after 3-6 months. PTS was diagnosed using the Villalta score after 6-24 months. Hazard ratios (HR) and odds ratios (OR) were adjusted for patient characteristics. The medical ethics committee approved this study. In total 82 of 801 patients had CID (10.2 %). PTS more often developed in patients with CID (35.4% vs. 18.9 %, p < 0.001) than in those without CID (HR 1.72 [1.15-2.58]). The prevalence of RVO was similar in patients with and without CID (36.8% vs. 41.4 %), and RVO was strongly associated with PTS in patients with CID (OR 3.21 [1.14-9.03]). Moreover, patients with untreated CID (44 %, n = 36) more often had RVO than those with treated CID (51.6% vs. 26.7 %, p = 0.027), and accordingly had a higher risk of PTS (HR 2.18 [1.04-4.58]). Patients with CID had an increased risk of developing PTS, especially those without anti-inflammatory treatment, possibly due to an unfavorable impact on RVO-related venous pathology.


Rab7 regulates transport from early to late endocytic compartments in Xenopus oocytes.
Rab7 has been shown to localize to late endosomes and to mediate transport from early to late endosome/lysosome in mammalian cells and in yeast. We developed a novel assay to quantify transport from early to late endosomes using the Xenopus oocyte. Oocytes were pulsed with avidin after which the oocytes were incubated to allow avidin transport to a late compartment. The oocytes were then allowed to internalize biotin-horseradish peroxidase (HRP). The oocytes were then injected with test proteins and incubated further to allow transport of biotin-HRP from early endosomes to late endosomal/lysosomal compartments. Transport was quantified by assessing the formation of HRP-biotin-avidin complexes. Injection of Rab7:wild-type (WT) and Rab7:Q67L, a GTPase defective mutant, stimulated transport. Rab5:WT had no effect. Rab7:WT-stimulated transport was inhibited by nocodazole, suggesting a role for intact microtubules. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, blocked Rab7:WT-stimulated transport, but Rab7:Q67L-stimulated transport was unaffected by the drug. Rab7:Q67L is constitutively activated and may not require phosphatidylinositol 3-kinase activity for activation. Rab7-stimulated transport requires N-ethylmaleimide-sensitive factor (NSF) activity as transport was blocked by N-ethylmaleimide and ATPase defective NSF mutants. Our results indicate that sequentially acting endocytic Rab GTPases utilize similar factors although their modes of action may be different.


Synthesis, structure, and optical properties of Pt(II) and Pd(II) complexes with oxazolyl- and pyridyl-functionalized DPPM-type ligands: a combined experimental and theoretical study.
New square-planar complexes [Pt(1(-H))2] (2a) [1(-H) = (oxazolin-2-yl)bis(diphenylphosphino)methanide] and [Pd(1(-H))2] (2b), of general formula [M{(Ph2P)2C---C---NCH2CH2O}2] (M = Pt, 2a; M = Pd, 2b), result from deprotonation of 2-{bis(diphenylphosphino)methyl}oxazoline (1) at the PCHP site. The new, functionalized dppm-type ligand 4-{bis(diphenylphosphino)methyl}pyridine, (Ph2P)2CH(4-C5H4N) (4), was prepared by double lithiation and phosphorylation of 4-picoline. In the presence of NEt3, the reactions of 2 equiv of 4 with [PtCl2(NCPh)2] and [Pd(acac)2] (acac = acetylacetonate) afforded [Pt(4(-H))2] (5a) [4(-H) = bis(diphenylphosphino)(pyridin-4-yl)methanide] and [Pd(4(-H))2] (5b), of general formula [M{(Ph2P)2C(4-C5H4N)}2] (M = Pt, 5a; M = Pd, 5b), respectively. In the absence of base, the reactions of 2 equiv of 4 with [PtCl2(NCPh)2] and [PdCl2(NCPh)2] afforded (5a·2HCl) (6a) and (5b·2HCl) (6b), respectively, in which the PCHP proton of 4 has migrated from carbon to nitrogen to give a pyridinium derivative of general formula [M{(Ph2P)2C(4-C5H4NH)}2]Cl2 (M = Pt, 6a; M = Pd, 6b). The complexes 3a, 5a·2MeOH, and 6b·4CH2Cl2 have been structurally characterized by X-ray diffraction. The absorption/emission properties of the Pt(II) complexes 2a and 5a and the Pd(II) complexes 2b and 5b have been investigated by UV-vis spectroscopy and theoretical analysis based on density functional theory. The UV-vis absorption spectra of the neutral complexes recorded in dilute N,N'-dimethylformamide solutions are dominated by intense spin-allowed intraligand transitions in the region below 350 nm. The complexes exhibit charge-transfer bands between 350 and 500 nm. The experimental and theoretical absorption spectra agree qualitatively and point to two low-lying ligand-to-metal charge transfer states that contribute to the bands observed between 350 and 500 nm. The complexes are emissive in frozen solutions at 77 K, in the pure solid state, and when doped into films of poly(methyl methacrylate) but are nonemissive in solution. A red shift is observed when Pt(II) is replaced by Pd(II).


[Psychosomatic analysis of laryngectomized patients].
The psychosocial influences of laryngectomy were evaluated in patients with head and neck cancer. Five patients who had indications for surgery, refused laryngectomy. They preferred their occupational activities and pleasure in their social lives to losing their voices. 'Mourning work' is a psychological technical term and represents a psychological process that is set in train by the loss of a loved object, and the mourning work stage in terms of speech loss was one of denial in these subjects. Forty-three laryngectomized patients were analyzed as to postoperative daily life and mental state. The relationship between the QOL (quality of life) of laryngectomized patients and the degree of depression were also investigated on a Self-rating Depression Scale. Only 21.6% of patients could continue the same work postoperatively, while 44.8% answered that their postoperative mental state tended to be more passive than the preoperative state. The patients who regretted having a laryngectomy showed significant depression in comparison with the patients who accepted laryngectomy. It seemed that patients who regretted having a laryngectomy suffered from 'pathological' mourning. Thus, we must assist those undergoing laryngectomy in transferring from 'pathological' mourning to 'healthy' mourning.


[Multifocal motor neuropathy--unusual cause of hypoglossal palsy].
Multifocal motor neuropathy with conduction block (MMN-CB) very rarely presents with cranial nerve symptoms. We describe a 72-year old man who was referred for a neurological evaluation because of a one-year long history of right-sided hypoglossal palsy with fasciculations. Since the examination also revealed slight atrophy in the hands, a motor neuron disease (MND) was suspected. The neurophysiological examination revealed bilateral ulnar conduction blocks indicative of MMN-CB. The patient was treated with lvlg and improved considerably. A short review of MMN-CB and of hypoglossal palsies is presented. This is, to the best of our knowledge, the first case described in which MMN-CB presents with hypoglossal palsy.


Bone Microarchitecture Assessed by HR-pQCT as Predictor of Fracture Risk in Postmenopausal Women: The OFELY Study.
Several cross-sectional studies have shown that impairment of bone microarchitecture contributes to skeletal fragility. The aim of this study was to prospectively investigate the prediction of fracture (Fx) by bone microarchitecture assessed by high-resolution peripheral computed tomography (HR- pQCT) in postmenopausal women. We measured microarchitecture at the distal radius and tibia with HR-pQCT in the OFELY study, in addition to areal BMD with dual-energy X-ray absorptiometry (DXA) in 589 women, mean ± SD age 68 ± 9 years. During a median [IQ] 9.4 [1.0] years of follow-up, 135 women sustained an incident fragility Fx, including 81 women with a major osteoporotic Fx (MOP Fx). After adjustment for age, women who sustained Fx had significantly lower total and trabecular volumetric densities (vBMD) at both sites, cortical parameters (area and thickness at the radius, vBMD at the tibia), trabecular number (Tb.N), connectivity density (Conn.D), stiffness, and estimated failure load at both sites, compared with control women. After adjustment for age, current smoking, falls, prior Fx, use of osteoporosis-related drugs, and total hip BMD, each quartile decrease of several baseline values of bone microarchitecture at the radius was associated with significant change of the risk of Fx (HR of 1.39 for Tb.BMD [p = 0.001], 1.32 for Tb.N [p = 0.01], 0.76 for Tb.Sp.SD [p = 0.01], 1.49 [p = 0.01] for Conn.D, and 1.27 for stiffness [p = 0.02]). At the tibia, the association remained significant for stiffness and failure load in the multivariate model for all fragility Fx and for Tt.BMD, stiffness, and failure load for MOP Fx. We conclude that impairment of bone microarchitecture-essentially in the trabecular compartment of the radius-predict the occurrence of incident fracture in postmenopausal women. This assessment may play an important role in identifying women at high risk of fracture who could not be adequately detected by BMD measurement alone, to benefit from a therapeutic intervention. © 2017 American Society for Bone and Mineral Research.


[Ratio of amylase clearance and creatinine clearance in the diagnosis of acute pancreatitis].
In 21 healthy volunteers the ratio of amylase clearance and creatinine clearance (Cam/Ccr) was determined in urine collected at admission, after a 1-hour collection period and after a 2-hour collection period. The normal values were 1.8 +/- 1.6%, 1.9 +/- 2% and 2.0 +/- 1.7% respectively. They were comparable with those published by others. The reproducibility of the method was acceptable (r = 0.62). When compared with serum amylase determinations, Cam/Ccr showed neither better sensitivity in 19 patients suffering an acute episode of proven pancreatitis, nor better specificity in 19 patients with acute abdomen but no evidence of pancreatitis.


Bone and maxillofacial abnormalities in thalassemia: a review of the literature.
Thalassemia is an inherited blood disorder due to an imbalanced globin chain synthesis leading to anaemia that requires regular blood transfusions and iron-chelating therapy. Of all organ failures secondary to iron deposit, and all the complications, heart failure still represents the first cause of death. Osteopenia and osteoporosis can be considered important causes of morbidity in a population whose lifespan is getting longer, with a strong impact on their quality of life. Authors have reported mainly bone, oral and maxillofacial abnormalities and relative complications, especially in terms of traumatic risk, in patients affected by thalassemia. As examples, this study reports bone modifications in three clinical cases; one of these was also complicated with a femoral fracture, surgically treated with the same criteria of metastatic femoral bone disease. More research on this topic is necessary for the prevention of several complications caused by this disease, and to carefully plan dental or traumatologic operations.


The epidemiology of falls and syncope.
Falls, syncope, and the associated complications are among the most serious problems that face the elderly population. The most common underlying causes and risk factors for falls include muscle weakness, gait and balance problems, visual impairment, cognitive impairment, depression, functional decline, and particular medications (especially in the presence of environmental hazards). Studies have identified the relative risks for these factors that enable a fairly accurate prediction of who is at high risk for falls and what areas to target for falls-prevention activity. Causes and risk factors for syncope have not been studied as well in the older population. The most serious types of syncope have underlying cardiac etiologies but they cause less than 25% of the reported cases. The largest category of syncope (approximately 40%) is syncope of unknown etiology, which defies careful diagnostic evaluation but seems to be fairly benign. The epidemiology of these syndromes can provide extremely helpful insights for developing falls-prevention strategies.


Autogenic Feedback Training Exercise and pilot performance: enhanced functioning under search-and-rescue flying conditions.
Studies have shown that autonomous mode behavior is one cause of aircraft fatalities due to pilot error. In such cases, the pilot is in a high state of psychological and physiological arousal and tends to focus on one problem, while ignoring more critical information. This study examined the effect of training in physiological self-recognition and regulation, as a means of improving crew cockpit performance. Seventeen pilots were assigned to the treatment and control groups matched for accumulated flight hours. The treatment group contained 4 pilots from HC-130 Hercules aircraft and 4 HH-65 Dolphin helicopter pilots; the control group contained 3 pilots of HC-130s and 6 helicopter pilots. During an initial flight, physiological data were recorded on each crewmember and an instructor pilot rated individual crew performance. Eight crewmembers were then taught to regulate their own physiological response levels using Autogenic-Feedback Training Exercise (AFTE). The remaining participants received no training. During a second flight, treatment participants showed significant improvement in performance (rated by the same instructor pilot as in pretests) while controls did not improve. The results indicate that AFTE management of high states of physiological arousal may improve pilot performance during emergency flying conditions.


Sepsis-induced regulation of lipoprotein lipase expression in rat adipose tissue and soleus muscle.
Hypertriglyceridemia of sepsis is associated with suppressed tissue lipoprotein lipase (LPL) activities. We investigated the effect of sepsis on lipoprotein lipase gene expression in epididymal fat and soleus muscle from control and septic rats in the fasted and fed state. After 24 h of sepsis, LPL activity decreased significantly in epididymal fat from fasted rats by 45% along with a 57% reduction in LPL mRNA levels and LPL mass. Transcription rate, measured by nuclear run-on assay, decreased by 70% in epididymal fat from fasted septic rats compared to fasted control rats. The synthesis rate of LPL in epididymal fat decreased by 31% while the LPL relative synthesis declined by 50% during sepsis. The turnover rate was not altered. Sepsis in fed rats did not lead to a significant decrease in LPL mRNA in epididymal fat but did lower LPL activity and LPL mass by 45%. The sepsis-induced suppression in soleus LPL activity, LPL mRNA levels, and LPL mass in the fasted state also was observed when septic rats were fed. The results indicate that during fasting sepsis, LPL expression in epididymal fat and possibly soleus muscle involves transcriptional regulation. During sepsis in the fed state, the regulation of LPL in adipose tissue may involve posttranslational mechanisms.


Inflammation-induced expression of sialyl LewisX is not restricted to alpha1-acid glycoprotein but also occurs to a lesser extent on alpha1-antichymotrypsin and haptoglobin.
Acute and chronic inflammation-induced expression of sialyl LewisX has already been shown to occur on alpha1-acid glycoprotein. We now demonstrate that this phenomenon is not restricted to alpha1-acid glycoprotein but also occurs on two other acute-phase proteins. ie on alpha1-antichymotrypsin and on haptoglobin. The level of expression of sialyl LewisX on these proteins was lower than on alpha1-acid glycoprotein, in all likelihood because alpha1-acid glycoprotein is the only acute-phase protein containing tetraantennary glycans. No expression of sialyl LewisX was detectable on alpha1-protease inhibitor, a protein with a high diantennary glycan content. Non-sialylated LewisX was not detectable on these major acute-phase proteins in any of the conditions studied. This indicates that the majority of the a3-linked fucose residues are present as sialyl LewisX on alpha1-acid glycoprotein, alpha1-antichymotrypsin and haptoglobin. The absolute contribution to the total phenotype in plasma of protein containing this determinant in a multivalent form was highest for alpha1-acid glycoprotein. This leads us to propose that alpha1-acid glycoprotein is, among the acute-phase proteins studied, the one with the highest potential for interference with the extravasation of leukocytes by binding to the selectins.


Studies on the mechanisms of somatostatin release after insulin induced hypoglycaemia in man.
Insulin-induced hypoglycaemia, which stimulates gastric acid secretion, is associated with an increase in circulating somatostatin levels in man. In order to assess the mechanisms involved in this rise, six normal volunteers connected to a Biostator for continuous glucose monitoring were studied, on three separate occasions. On each occasion after basal blood sampling, 0.15 i.u./kg body weight of insulin was administered i.v. and further samples were obtained intermittently over 150 min. On one occasion, dextrose was infused by the Biostator to prevent hypoglycaemia, while on the other two, a constant infusion of either normal saline or the specific H2 antagonist cimetidine was administered. Insulin plus dextrose caused no significant changes in circulating somatostatin levels, whereas insulin plus saline was associated with a marked, sustained and significant rise in all subjects; insulin plus cimetidine also produced a rise but it was delayed; the area under the curve was significantly (P less than 0.05) greater with insulin plus saline than with insulin plus cimetidine. These results show that in man insulin itself does not stimulate somatostatin secretion directly, but indirectly via hypoglycaemia. Further, the inhibition of gastric acid secretion with cimetidine reduces somatostatin release during insulin-induced hypoglycaemia. This suggests that gastric acid may mediate somatostatin secretion associated with insulin-induced hypoglycaemia.


Cognitive effects of cranial irradiation in leukaemia: a survey and meta-analysis.
Central nervous system (CNS) prophylaxis involving cranial irradiation has frequently been found to result in cognitive deficits in survivors of childhood acute lymphoblastic leukaemia. The existence of this effect is still controversial, however, as is the question of factors that might affect its severity. The literature is surveyed and a meta-analysis undertaken on 30 IQ comparisons, which shows a substantial average decrement in irradiated subjects. The effect is larger when radiation is administered at a younger age and appears to be progressive. The effect may comprise two elements, one common to young cancer patients and one specific to CNS prophylaxis.


PAR-1 is a novel mechano-sensor transducing laminar flow-mediated endothelial signaling.
Recent studies have indicated that protease-activated receptor-1 (PAR-1) is involved in cytoprotective and anti-inflammatory responses in endothelial cells (ECs). However, the role of PAR-1 in laminar flow-mediated atheroprotective responses remains unknown. Herein, we investigated whether PAR-1 regulates laminar flow-mediated mechanotransduction in ECs. Confocal analysis showed that PAR-1 was internalized into early endosomes in response to laminar flow. In addition, flow cytometry analysis showed that cell surface expression of PAR-1 was reduced by laminar flow, suggesting that PAR-1 was activated in response to laminar flow. Depletion of PAR-1 using human PAR-1 siRNA inhibited unidirectional laminar flow-mediated actin stress fiber formation and cellular alignment as well as atheroprotective gene expressions in HUVECs. Moreover, PAR-1 knockdown inhibited laminar flow-stimulated eNOS phosphorylation, and inhibited the phosphorylations of Src, AMPK, ERK5 and HDAC5. Furthermore, PAR-1 depletion inhibited laminar flow-mediated anti-inflammatory responses as demonstrated by reduced TNFα-induced VCAM-1 expression and by monocyte adhesion to HUVECs, and prevented laminar flow-mediated anti-apoptotic response. An investigation of the role of PAR-1 in vasomotor modulation using mouse aortic rings revealed that acetylcholine-induced vasorelaxation was diminished in PAR-1 deficient mice compared to littermate controls. Taken together, these findings suggest that PAR-1 be viewed as a novel pharmacologic target for the treatment of vascular diseases, including atherosclerosis.


Sialolipoma of salivary glands: Two case reports and review of the literature.
Sialolipoma is a rare neoplasm of salivary glands, described as a distinct entity by Nagao et al. in 2001. Thirty-six cases of sialolipoma in minor and major salivary glands have been reported thus far in addition to the two new cases of sialolipoma arising in the major salivary glands in this study. Thirty-six cases of sialolipoma published in English language reports were analyzed considering gender, age, location, size, duration of symptoms, treatment mode, follow-up, and histologic findings. Congenital sialolipomas were considered in this study. The first case occurred in a 45-year-old female and presented as a localized swelling in right parotid area. The second case occurred in an 18-year-old female as a swelling in the left parotid region. On histopathological examination, these lesions were diagnosed as sialolipoma.


lncRNA NEF inhibits glioma by downregulating TGF-β1.
NEF is a tumor suppressing long non-coding (lnc)RNA in hepatocellular carcinoma. Based on current literature, the involvement of NEF in other human diseases is still unknown. The current study aimed to investigate the potential involvement of NEF in glioma, which is a type of rare, but aggressive malignancy. It was determined that NEF expression was downregulated in tumor tissues compared with adjacent heathy tissues. A low blood NEF level in patients with glioma effectively distinguished patients from healthy controls who had high blood NEF levels. Blood NEF levels were significantly correlation with distant tumor metastasis, but not tumor growth. Blood NEF levels were negatively correlated with blood transforming growth factor (TGF)-β1 levels in patients with distant tumor metastasis, but not in patients with non-metastatic glioma and healthy controls. NEF overexpression inhibited cancer cell migration and invasion. In addition, NEF overexpression downregulated TGF-β1 expression. The authors of the current study concluded that lncRNA NEF may inhibit glioma cell migration and invasion by downregulating TGF-β1.


Carbon ion radiotherapy for recurrent ameloblastoma: A case report.
Ameloblastoma is a kind of benign, odontogenic tumor of epithelial origin, and surgery is mainstay treatment method; however, recurrence is common, and usually the treatment for recurrence is still surgery. We report on a patient of recurrent ameloblastoma treated with carbon ion radiation therapy and achieved a good efficacy. A 25-year-old female with relapse of an ameloblastoma was referred to the Wuwei Heavy Ion Center for carbon ion therapy. She had been initially diagnosed with ameloblastoma 8 years ago and underwent operation of right mandible ameloblastoma. After she transferred to our center, she accepted a dose of 60 GyE carbon ion radiation therapy, and the efficacy is good. Carbon ion radiation therapy can be an effective treatment option for ameloblastoma.


Current Trends in MOF (Metal-Organic Framework) and Metal X-ides.
Metal-organic frameworks (MOFs) are a class of porous two- or three-dimensional infinite structure materials consisting of metal ions or clusters and organic linkers, which are connected via coordination bonds [...].


Validation of the Australian version of the Chronic Kidney Disease Self-Management instrument.
The aim of this study is to evaluate the validity and reliability of the modified Chronic Kidney Disease Self-Management instrument in an English-speaking population. There is growing evidence that self-management behaviours can improve outcomes for people with chronic kidney disease. However, there are few suitable instruments available. The study was cross sectional, with a test-retest protocol. Adults with chronic kidney disease attending a primary health care between June and December 2015 completed the Chronic Kidney Disease Self-Management instrument. Construct validity was determined using exploratory factor analysis, internal consistency and test-retest reliability using Cronbach's α and intraclass correlation. For convergent validity, the relationships between knowledge, self-efficacy and self-management were investigated. The Australian version of the Chronic Kidney Disease Self-Management instrument has 17 items grouped into four factors: self-integration, seeking social support, adherence to lifestyle modification and problem solving. The instrument demonstrated good reliability. Self-efficacy was positively correlated with self-management scores, although there was no correlation between chronic kidney disease knowledge and self-management. The Australian version of the Chronic Kidney Disease Self-Management instrument was found to be a valid and reliable patient-reported outcome measure. It can be used in clinical practice to support self-management, as well as future research.


A harmonization effort for acceptable daily exposure application to pharmaceutical manufacturing - Operational considerations.
A European Union (EU) regulatory guideline came into effect for all new pharmaceutical products on June 1st, 2015, and for all existing pharmaceutical products on December 1st, 2015. This guideline centers around the use of the Acceptable Daily Exposure (ADE) [synonymous with the Permitted Daily Exposure (PDE)] and operational considerations associated with implementation are outlined here. The EU guidance states that all active pharmaceutical ingredients (API) require an ADE; however, other substances such as starting materials, process intermediates, and cleaning agents may benefit from an ADE. Problems in setting ADEs for these additional substances typically relate to toxicological data limitations precluding the ability to establish a formal ADE. Established methodologies such as occupational exposure limits or bands (OELs or OEBs) and the threshold of toxicological concern (TTC) can be used or adjusted for use as interim ADEs when only limited data are available and until a more formal ADE can be established. Once formal ADEs are derived, it is important that the documents are routinely updated and that these updates are communicated to appropriate stakeholders. Another key operational consideration related to data-poor substances includes the use of maximum daily dose (MDD) in setting cross-contamination limits. The MDD is an important part of the maximum allowable/safe concentration (MAC/MSC) calculation and there are important considerations for its use and definition. Finally, other considerations discussed include operational aspects of setting ADEs for pediatrics, considerations for large molecules, and risk management in shared facilities.


The Hsp70 peptide-binding domain determines the interaction of the ATPase domain with Tim44 in mitochondria.
Ssc1, a molecular chaperone of the Hsp70 family, drives preprotein import into the mitochondrial matrix by a specific interaction with the translocase component Tim44. Two other mitochondrial Hsp70s, Ssc3 (Ecm10) and Ssq1, show high sequence homology to Ssc1 but fail to replace Ssc1 in vivo, possibly due to their inability to interact with Tim44. We analyzed the structural basis of the Tim44 interaction by the construction of chimeric Hsp70 proteins. The ATPase domains of all three mitochondrial Hsp70s were shown to bind to Tim44, supporting the active motor model for the Hsp70 mechanism during preprotein translocation. The peptide-binding domain of Ssc1 sustained binding of Tim44, while the peptide-binding domains of Ssc3 and Ssq1 exerted a negative effect on the interaction of the ATPase domains with Tim44. A mutation in the peptide-binding domain of Ssc1 resulted in a similar negative effect not only on the ATPase domain of Ssc1, but also of Ssq1 and Ssc3. Hence, the determination of a crucial Hsp70 function via the peptide-binding domain suggests a new regulatory principle for Hsp70 domain cooperation.


Brain regional acetylcholinesterase activity and muscarinic acetylcholine receptors in rats after repeated administration of cholinesterase inhibitors and its withdrawal.
Activity of acetylcholinesterase (AChE) and specific binding of [(3)H]quinuclidinyl benzilate (QNB), [(3)H]pirenzepine (PZP) and [(3)H]AF-DX 384 to muscarinic acetylcholine receptor (mAChR) preparations in the striatum, hippocampus and cortex of rats were determined 1, 6 and 11 days after the last treatment with an organophosphate DDVP, a carbamate propoxur or a muscarinic agonist oxotremorine as a reference for 7 and 14 days. AChE activity was markedly decreased in the three regions 1 day after the treatment with DDVP for 7 and 14 days with a gradual recovery 6 to 11 days, and much less decreased 1, 6 and 11 days after the treatment with propoxur for 7 days but not for 14 days in the hippocampus and cortex. The binding of [(3)H]-QNB, PZP and AF-DX 384 in the three regions was generally decreased by the treatment with DDVP for 7 and 14 days. Such down-regulations were generally restored 6 or 11 days after the treatment for 7 but not for 14 days. The down-regulation or up-regulation as measured by [(3)H]-QNB, PZP and AF-DX 384 was observed 1, 6 or 11 days after treatment with propoxur for 7 days and/or 14 days. Repeated treatment with oxotremorine produced similar effects except AChE activity to DDVP. These results suggest that repeated inhibition of AChE activity may usually cause down-regulation of mAChRs with some exception in the hippocampus when a reversible antiChE propoxur is injected.


Ethical issues associated with the assessment of exaggeration, poor effort, and malingering.
The use of effort tests is standard practice in forensic neuropsychology. There is a tremendous amount of good information available in test manuals and the research literature regarding the proper and responsible use of these tests. However, it is clear that there are numerous ethical issues and considerations associated with the assessment of exaggeration, poor effort, and malingering. Many of these issues are discussed, and recommendations are provided.


Microbiological deterioration of frozen parfried potatoes upon holding after thawing.
Frozen parfried potatoes were thawed and stored at 55, 45, and 34 F (12.8, 7.2, 1.1 C). Significant changes in flavor and texture did not occur at these temperatures until the total bacterial count exceeded 100 million per gram. These sensory changes were produced after 4, 8, and 20 days of storage at 55, 45, and 34 F, respectively. Detectable color change appeared sooner and probably was not of microbial origin. It is unlikely that any health hazard exists under the range of conditions studied. Nevertheless, it seems undesirable to market food with such a high bacterial count. At half the storage periods given above, the count did not exceed 100,000 per gram.


The impact of ebinyo, a form of dental mutilation, on the malocclusion status in Uganda.
The practice of extraction of ebinyo or false teeth is based on the belief that the rubbing of herbs on the gum (in the region of the canine) or the removal of the primary and/or permanent canine tooth buds will lead to the relief of childhood fevers and diarrhoea. The reported prevalence of this practice in Uganda and neighbouring countries is varied. A survey carried out in Kampala to determine the occlusal traits of fourteen-year-old children offered an opportunity to assess the effects of ebinyo (a dental mutilation based on local customs and superstitions) on the occlusal status of the sample population. 402 children aged fourteen years were examined according to the criteria of the Federation Dentaire Internationale Commission on Classification and Statistics for Oral Conditions method for measuring occlusal traits (COCSTOC-MOT) proposed by Baume et al. (1973). The most common dental anomaly was teeth missing due to extraction or trauma. Canines (28%) and mandibular first molars (28%) exhibited the highest frequency. Missing canines were four times more common in girls than boys, and three times greater in the maxilla than the mandible. Canines also accounted for 12.8% of the malformed teeth observed in the study. The results of this study show that the practice of ebinyo, although carried out early in the life of the child, can impact on the occlusal status in the permanent dentition years later.


Changing parenteral nutrition administration sets every 24 h versus every 48 h in newborn infants.
To determine whether changing total parenteral nutrition fluid administration sets (TAS) every 48 h rather than every 24 h results in a greater infusate contamination rate. Prospectively, 166 infants were assigned at random to have TAS changed either every 24 h or every 48 h. Samples of the infusate were cultured to determine contamination rates of the infusate in the sets and were tested from 149 of these infants. TAS was replaced every 24 h in the control group, and 445 amino acid plus dextrose solutions (AADS) and 449 lipid emulsions samples were taken for bacterial culture. Fungal cultures were also performed on 449 samples. The study group had TAS replaced every 48 h, and 454 samples of AADS were cultured for bacteria. The numbers of lipid emulsion samples sent for bacterial culture and fungal culture were 449 and 440, respectively. Information on type of intravenous access device, administration of antibiotics and blood cultures was also collected. There was no difference in bacterial contamination rates for AADS or lipid emulsion from TAS changed every 24 or 48 h (c2, P>0.05). Lipid emulsion sampled from the 24 h group showed a statistically significant higher rate of fungal contamination than specimens from the 48 h group (P<0.01). Changing TAS every 48 h versus 24 h does not increase the contamination rate of infusate in newborns.


Surface topographic characterization for polyamide composite injection molds made of aluminum and copper alloys.
In order to ensure flexibility and rapid new product development, the mold industry made use of soft materials for cavity inserts in injection molds. However, materials of this kind are prone to wear. This article analyzes the topographic characterization of the surface and wear processes in injection molds cavities. Two materials have been used to produce the cavities: aluminum alloy EN AW‐6082 T4 and copper alloy Cu Zn39 Pb3. The surface topography was measured with the use of optical interferometry profiling technology; roughness and surface parameters were determined according to ISO 4287, ISO 25178, and EUR 15178N. In order to complete this research, an experimental part with different thicknesses and shapes was designed, and cavity inserts of aluminum and copper were made. Polyamide PA6, with 30% fiberglass reinforcement, was employed in the experimental procedure. Measurements of cavity mold surfaces were performed after 9,200 cycles on each mold and at different locations on the mold. The surface measurement was made with a white light vertical scanning interferometry, also known as coherence scanning interferometry (ISO DIS 25178‐604). The results are analyzed and differences between the two types of cavity inserts materials are discussed.


Rheolytic thrombectomy of chronic coronary occlusion.
Percutaneous intervention in patients with intracoronary thrombus continues to pose a significant clinical challenge. In this report, we describe the successful treatment of a 44-year-old patient with an extensive chronic thrombotic occlusion of the right coronary artery using a rheolytic thrombectomy catheter. Despite angiographic documentation of coronary thrombosis 104 days prior to treatment and a voluminous thrombus burden (60 mm in length x 3 mm in diameter), rapid recanalization was accomplished with this device without embolic complications. At 1 year clinical follow-up, the patient has remained symptom free. The design of this novel device and its mechanism of action are described.


Hydration needs throughout the lifespan.
In 2004, the Institute of Medicine (IOM) issued a report presenting reference intake information about water, sodium, potassium, and other electrolytes for Americans and Canadians. The report established, for the first time, adequate intakes (AI) for total water (from drinking water, beverages, and food) for healthy people. An AI is the recommended average daily intake level based on observed or experimentally-determined approximations or estimates of nutrient intake by a group or groups of apparently health people that are assumed to be adequate. The AI for water is based on US survey data. The recommendations about water intake are for healthy populations--they do not apply to at-risk groups.


A cytotoxic tantalum(v) half-sandwich complex: a new challenge for metal-based anticancer agents.
Despite the biological relevance of complexes of various transition metals, tantalum complexes have long been neglected by bioinorganic chemists. Herein, we demonstrate potential chemotherapeutic applicability of the [Ta(η5-Cp*)Cl2(salaph)] (1) complex, containing deprotonated Schiff base 2-{(E)-[(2-hydroxyphenyl)imino]methyl}phenol (H2salaph), which shows strong cytotoxicity in cancer cells, related to the induction of apoptosis and apoptosis-related processes, but shows low cytotoxicity in healthy cells.


Regional Birth Outcomes after the 2011 Great East Japan Earthquake and Tsunami in Miyagi Prefecture.
This study was aimed to analyze post-disaster birth outcomes in coastal and inland regions of Miyagi Prefecture, Japan. Primary data sets were compiled from birth records of obstetric facilities and 12,808 patients were analyzed for baseline birth outcomes by region. Regional risk analysis of the low-birth-weight rate and premature birth rate were conducted using multi-level logistic regression analysis. From overall baseline birth outcomes, a preterm birth rate was 4.6% and low-birth-weight rate was 8.8%. Regional analysis revealed that a preterm birth rate was 3.2% (coastal) and 5.0% (inland), respectively, and the rate of low birth weight was 6.5% in the coastal and 8.5% in the inland region. In the risk analysis of low-birth-weight rate and preterm birth rate, the risk in the coastal region could not be considered any higher than in the inland region (adjusted odds ratio 0.91 [0.73-1.14] and 0.85 [0.46-1.59], respectively). The incidence of preterm birth and low birth weight were not adversely affected by the disaster. Early transfer and intensive medical intervention may have led to those findings. Further survey will be necessary to determine the long-term effects in both mothers and children. Sugawara J , Iwama N , Hoshiai T , Tokunaga H , Nishigori H , Metoki H , Okamura K , Yaegashi N . Regional birth outcomes after the 2011 Great East Japan Earthquake and tsunami in Miyagi Prefecture. Prehosp Disaster Med. 2018;33(2):215-219.


Binge drinking among Latino youth: role of acculturation-related variables.
This research examined the relationship between acculturation-related variables and binge drinking behavior among nationally representative samples of Mexican American, Cuban American, and Puerto Rican youth. It explored the relationship between length of residence in the United States, type of language spoken in the home (Spanish vs. English) and binge drinking in each of these subgroups. Results suggest that Latino youths with no prior history of alcohol consumption remain largely unaffected by these acculturation-related variables. Youth with a previous history of alcohol consumption experience greater likelihood of binge drinking as a function of the acculturation-related variables, but the relationships are complex.


Genetic variants of ribosomal DNA and mitochondrial DNA between swamp and river buffaloes.
To clarify the genetic relationship between Swamp and River buffaloes, the restriction fragment length polymorphisms (RFLPs) of nuclear genomic ribosomal DNA (rDNA) and cytoplasmic mitochondrial DNA (mtDNA) were analysed. Blood or liver samples from 73 Swamp and three River buffaloes were collected in East and South-east Asian countries. DNA samples from cattle, goats and sheep were used for comparisons. The analysis of rDNA allowed water buffaloes, cattle, goats and sheep to be characterized by four distinct repeat-types. However, swamp and river buffaloes showed the same repeat-type. Divergence of water buffalo and cattle is considered to have occurred approximately four to six million years ago. The RFLPs for mtDNA divided water buffaloes into three haplotypes, swamp-1, swamp-2 and river types. Swamp-1 accounted for 91% of all swamp buffaloes while swamp-2 was observed only in water buffaloes from Thailand (9%). All river buffaloes were of the same haplotype. No differences were observed between swamp and river buffaloes at the rDNA level. In contrast, a few distinct differences between them were found at the mtDNA level. Therefore, mtDNA polymorphisms provide an adequate means for classifying water buffaloes into either swamp or river buffaloes.


Sport fish consumption and body burden levels of chlorinated hydrocarbons: a study of Wisconsin anglers.
Sport-caught fish consumption is the major source of polychlorinated biphenyls (PCBs) exposure for the general population. To assess this and 2,2'-bis-(p-chlorophenyl)-1,1-dichloroethylene (DDE) exposure, we surveyed 801 Wisconsin anglers for fishing and consumption habits and comprehension of and compliance with the Wisconsin fish consumption health advisory. The mean annual number of sport-caught fish meals was 18. Seventy-two percent of anglers were familiar with the health advisory and 57% had changed their fishing or fish consumption habits as a result of the advisory. The mean PCB serum congener sum level for 192 anglers was 2.2 micrograms/l (range = nondetectable to 27.1 micrograms/l); mean DDE was 6.3 micrograms/l (range = nondetectable to 40.0 micrograms/l). Statistically significant positive Spearman correlations were observed between sport-caught fish meals and PCB and DDE sera levels (R = .21 and .14, respectively) and between kilograms of fish caught and PCB sera levels (R = .25). These results demonstrate that anglers may provide a population for assessment of PCBs and DDE associated morbidity and mortality.


Cardiac amyloidosis: diagnostic challenges and recent advancement in the treatment of transthyretin amyloidosis (ATTR).
ATTR-CA is an under-reported cause of congestive heart failure (CHF) and cardiac arrhythmias. Heightened clinical suspicion along with a multimodal investigative approach is often required in diagnosing this potentially fatal condition. Tafamidis and inotersen have shown promising results in terms of progression-free survival by ameliorating CHF symptoms and peripheral neuropathies in clinical trials. In this case series of five patients, we present three wild-type cardiac amyloidosis (ATTRwt-CA), one familial cardiac amyloidosis (ATTRm-CA) and one primary cardiac (AL-CA). The diagnostic modality was different for each patient. ATTRwt-CA, ATTRm-CA and AL-CA patients received tafamidis, inotersen and chemotherapy with bone marrow stem-cell transplantation, respectively.


Effect of non-linearity in predicting Doppler waveforms through a novel model.
In pregnancy, the uteroplacental vascular system develops de novo locally in utero and a systemic haemodynamic & bio-rheological alteration accompany it. Any abnormality in the non-linear vascular system is believed to trigger the onset of serious morbid conditions like pre-eclampsia and/or intrauterine growth restriction (IUGR). Exact Aetiopathogenesis is unknown. Advancement in the field of non-invasive doppler image analysis and simulation incorporating non-linearities may unfold the complexities associated with the inaccessible uteroplacental vessels. Earlier modeling approaches approximate it as a linear system. We proposed a novel electrical model for the uteroplacental system that uses MOSFETs as non-linear elements in place of traditional linear transmission line (TL) model. The model to simulate doppler FVW's was designed by including the inputs from our non-linear mathematical model. While using the MOSFETs as voltage-controlled switches, a fair degree of controlled-non-linearity has been introduced in the model. Comparative analysis was done between the simulated data and the actual doppler FVW's waveforms. Normal pregnancy has been successfully modeled and the doppler output waveforms are simulated for different gestation time using the model. It is observed that the dicrotic notch disappears and the S/D ratio decreases as the pregnancy matures. Both these results are established clinical facts. Effects of blood density, viscosity and the arterial wall elasticity on the blood flow velocity profile were also studied. Spectral analysis on the output of the model (blood flow velocity) indicated that the Total Harmonic Distortion (THD) falls during the mid-gestation. Total harmonic distortion (THD) is found to be informative in determining the Feto-maternal health. Effects of the blood density, the viscosity and the elasticity changes on the blood FVW are simulated. Future works are expected to concentrate mainly on improving the load with respect to varying non-linear parameters in the model. Heart rate variability, which accounts for the vascular tone, should also be included. We also expect the model to initiate extensive clinical or experimental studies in the near future.


Flavin mononucleotide-binding domain of the flavoprotein component of the sulfite reductase from Escherichia coli.
The flavoprotein component (SiR-FP) of the sulfite reductase from Escherichia coli is an octamer containing one FAD and one FMN as cofactors per polypeptide chain. We have constructed an expression vector containing the DNA fragment encoding for the FMN-binding domain of SiR-FP. The overexpressed protein (SiR-FP23) was purified as a partially flavin-depleted polymer. It could incorporate FMN exclusively upon flavin reconstitution to reach a maximum flavin content of 1.2 per polypeptide chain. Moreover, the protein could stabilize a neutral air-stable semiquinone radical over a wide range of pHs. During photoreduction, the flavin radical accumulated first, followed by the fully reduced state. The redox potentials, determined at room temperature [E'1 (FMNH./FMN) = -130 +/- 10 mV and E'2 (FMNH2/FMNH.) = -335 +/- 10 mV], were very close to those previously reported for Salmonella typhimurium SiR-FP [Ostrowski, J., Barber, M. J., Rueger, D. C., Miller, B. E., Siegel, L. M., & Kredich, N. M. (1989) J. Biol. Chem. 264, 15796-15808]. Both the radical and fully reduced forms of SiR-FP23 were able to transfer their electrons to cytochrome c quantitatively. Altogether, the results presented herein demonstrate that the N-terminal end of E. coli SiR-FP forms the FMN-binding domain. It folds independently, thus retaining the chemical properties of the bound FMN, and provides a good model of the FAD-depleted form of native SiR-FP. Moreover, the FMN prosthetic group in SiR-FP23 and native SiR-FP is compared to that of cytochrome P450 reductase and bacterial cytochrome P450, which also contain one FAD and one FMN per polypeptide chain.


Eight new HLA-A alleles associated with antigens in the A2 CREG.
This report describes eight novel HLA-A alleles. Seven of these new alleles contain substitutions previously reported in other HLA-A alleles, suggesting an origin resulting from a gene conversion mechanism. Of these seven, A*2431 contains a substitution previously associated with a larger polymorphic motif. A*0247 contains a substitution at a previously polymorphic position, but encodes an amino acid change previously unreported in any HLA-A, -B or -C alleles.


Unlocking the mystery behind the activation phenomenon of T1 lipase: a molecular dynamics simulations approach.
The activation of lipases has been postulated to proceed by interfacial activation, temperature switch activation, or aqueous activation. Recently, based on molecular dynamics (MD) simulation experiments, the T1 lipase activation mechanism was proposed to involve aqueous activation in addition to a double-flap mechanism. Because the open conformation structure is still unavailable, it is difficult to validate the proposed theory unambiguously to understand the behavior of the enzyme. In this study, we try to validate the previous reports and uncover the mystery behind the activation process using structural analysis and MD simulations. To investigate the effects of temperature and environmental conditions on the activation process, MD simulations in different solvent environments (water and water-octane interface) and temperatures (20, 50, 70, 80, and 100°C) were performed. Based on the structural analysis of the lipases in the same family of T1 lipase (I.5 lipase family), we proposed that the lid domain comprises α6 and α7 helices connected by a loop, thus forming a helix-loop-helix motif involved in interfacial activation. Throughout the MD simulations experiments, lid displacements were only observed in the water-octane interface, not in the aqueous environment with respect to the temperature effect, suggesting that the activation process is governed by interfacial activation coupled with temperature switch activation. Examining the activation process in detail revealed that the large structural rearrangement of the lid domain was caused by the interaction between the hydrophobic residues of the lid with octane, a nonpolar solvent, and this conformation was found to be thermodynamically favorable.


Upper alveolar carcinoma--a 30 year survey.
Primary malignancy of the upper alveolus is an infrequent type of intra-oral carcinoma. This study reviews in detail 50 patients with a primary tumor of the upper alveolus who were treated at the Cancer Control Agency of British Columbia and Vancouver area hospitals, between 1940-1970 inclusive. Sixteen per cent had exposure to possible industrial carcinogens; 34 per cent had previous leukoplakia. The common presenting symptoms were pain (78 per cent) and swelling (64 per cent). Only 22 per cent had tumors confined to the upper alveolus. Fifty-two per cent had extensive lesions (i.e. T3 and T4). Twenty-six per cent had palpable cervical lymph nodes with potential metastatic disease. Treatment consisted of surgery, radiotherapy, or a combination of both. Complications are detailed. The five year survival rate is 44 per cent; and the 10 year survival rate 24 per cent. Treatment rationale is discussed.


Cost-effectiveness of mediastinal lymph node staging in non-small cell lung cancer.
To assess the cost-effectiveness of various modes of mediastinal staging in non-small cell lung cancer (NSCLC) in a single-payer health care system. We performed a decision analysis to compare the health outcomes and costs of 4 mediastinal staging strategies: no invasive staging, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), mediastinoscopy, and EBUS-TBNA followed by mediastinoscopy if EBUS-TBNA is negative. We determined incremental cost effectiveness ratios (ICER) for all strategies and performed comprehensive deterministic sensitivity analyses using a willingness to pay threshold of $80,000/quality adjusted life year (QALY). Under the base-case scenario, the no invasive mediastinal staging strategy was least effective (QALY, 5.80) and least expensive ($11,863), followed by mediastinoscopy, EBUS-TBNA, and EBUS-TBNA followed by mediastinoscopy with 5.86, 5.87, and 5.88 QALYs, respectively. The ICER was ∼$26,000/QALY for EBUS-TBNA staging and ∼$1,400,000/QALY for EBUS-TBNA followed by mediastinoscopy. The mediastinoscopy strategy was dominated. Once pN2 exceeds 2.5%, EBUS-TBNA staging is cost-effective (∼$80,000/QALY). Once the pN2 reaches 57%, EBUS-TBNA followed by mediastinoscopy is cost-effective (ICER ∼$79,000/QALY). Once EBUS-TBNA sensitivity exceeds 25%, EBUS-TBNA staging is cost-effective (ICER ∼$79,000/QALY). Once pN2 exceeds 25%, confirmatory mediastinoscopy should be added, in cases of EBUS-TBNA sensitivity ≤ 60%. Invasive mediastinal staging in NSCLC is unlikely to be cost-effective in clinical N0 patients if pN2 <2.5%. In patients with probability of mediastinal metastasis between 2.5% and 57% EBUS-TBNA is cost-effective as the only staging modality. Confirmatory mediastinoscopy should be considered in high-risk patients (pN2 > 57%) in case of negative EBUS-TBNA.


Beta-adrenergic stimulation of cyclic AMP is defective in cultured dermal fibroblasts of psoriatic subjects.
Epidermal cells from psoriatic lesions demonstrate a very low cAMP response to beta-adrenergic stimuli. We have shown that a similar abnormality occurs in dermal fibroblasts from affected areas of skin. The cells, after 5-12 passages in tissue culture, had a much reduced response to 10(-8) M and 10(-6) M isoproterenol when compared with fibroblasts from control subjects. The abnormality was not abolished by the addition of the phosphodiesterase inhibitor, 3-isobutyl-I-methylxanthine. Other putative agonists tested were vasoactive intestinal peptide and peptide histidine methionine. Neither of these had an effect on dermal fibroblasts from either normal controls or from lesions of psoriasis.


Local tissue reactions after nerve repair with ethyl-cyanoacrylate compared with epineural sutures.
Anastomosis of a nerve with cyanoacrylate following a lesion has previously been shown to indicate morphological and functional recovery to an extent comparable to that of conventional epineural sutures. In this study we examined the local tissue reactions after transection and repair of rat sciatic nerve, and compared sutures with a synthetic ethyl-cyanoacrylate adhesive. Many ED-1-immunoreactive macrophages were found accumulating on either side of the repair site whereas neurofilament labelling was less pronounced distal to the repair site seven days after reparation with cyanoacrylate compared with sutures. After six months, when reinnervation was completed, the difference in ED-1-immunoreactivity was still present but to a less extent. These results indicate that ethyl-cyanoacrylate seems to induce an increased inflammatory reaction, which may lead to accelerated Wallerian degeneration, and could therefore have benefits over conventional sutures for reconstruction of peripheral nerves.


Molecular characterization of Osh6p, an oxysterol binding protein homolog in the yeast Saccharomyces cerevisiae.
Oxysterol binding protein (OSBP) and its homologs have been shown to regulate lipid metabolism and vesicular transport. However, the exact molecular function of individual OSBP homologs remains uncharacterized. Here we demonstrate that the yeast OSBP homolog, Osh6p, bound phosphatidic acid and phosphoinositides via its N-terminal half containing the conserved OSBP-related domain (ORD). Using a green fluorescent protein fusion chimera, Osh6p was found to localize to the cytosol and patch-like or punctate structures in the vicinity of the plasma membrane. Further examination by domain mapping demonstrated that the N-terminal half was associated with FM4-64 positive membrane compartments; however, the C-terminal half containing a putative coiled-coil was localized to the nucleoplasm. Functional analysis showed that the deletion of OSH6 led to a significant increase in total cellular ergosterols, whereas OSH6 overexpression caused both a significant decrease in ergosterol levels and resistance to nystatin. Oleate incorporation into sterol esters was affected in OSH6 overexpressing cells. However, Lucifer yellow internalization, and FM4-64 uptake and transport were unaffected in both OSH6 deletion and overexpressing cells. Furthermore, osh6Delta exhibited no defect in carboxypeptidase Y transport and maturation. Lastly, we demonstrated that both the conserved ORD and the putative coiled-coil motif were indispensable for the in vivo function of Osh6p. These data suggest that Osh6p plays a role primarily in regulating cellular sterol metabolism, possibly stero transport.


Economic comparisons of the pharmacotherapy of depression: an overview.
As many countries find that their health care expenditure is taking up an increasing proportion of their financial resources, economic aspects of care processes have become more important in the choice of optimal strategies. This review of the economic studies of the comparative treatment of depression shows that nearly every aspect of treatment has important economic consequences. Cost-of-illness studies have documented the high burden on society of this disorder, and the associated loss of productivity and work. Comparative cost-effectiveness/utility studies, the majority of which are based on modelling techniques, have consistently shown a better cost-effectiveness ratio of the newer antidepressants over more traditional tricyclic antidepressants (TCAs), when all therapy-related costs are taken into account.


Generalized staphylococcal scalded skin syndrome in an anephric boy undergoing hemodialysis.
Generalized staphylococcal scalded skin syndrome (SSSS) is a toxin-related epidermolytic disease that predominantly affects previously healthy infants and children younger than 5 years. In contrast, the majority of the reported adult cases have been associated with underlying diseases, suggesting that immunosuppression and renal insufficiency are important predisposing conditions for this age group. We report herein a case of adult-type SSSS in an anephric 10-year-old boy. Patients undergoing hemodialysis who have chronic renal failure may be uniquely predisposed to the SSSS by virtue of their decreased glomerular filtration rate, associated uremic immunodeficiency, and a high incidence of Staphylococcus aureus bacteremia.


Diagnosing and treating comorbid (complicated) bipolar disorder.
Comorbidity is the rule, not the exception, in bipolar disorder. The most common mental disorders that co-occur with bipolar disorder in community studies include anxiety, substance use, and conduct disorders. Disorders of eating, sexual behavior, attention-deficit/hyperactivity, and impulse control, as well as autism spectrum disorders and Tourette's disorder, co-occur with bipolar disorder in clinical samples. The most common general medical comorbidities are migraine, thyroid illness, obesity, type II diabetes, and cardiovascular disease. Bipolarity is a marker for comorbidity, and comorbid disorders, especially multiple conditions occurring when a patient is young, may be a marker for bipolarity. Relatively few controlled clinical studies have examined the treatment of bipolar disorder in the context of comorbid conditions (i.e., complicated or comorbid bipolar disorder). However, the first step in treating any type of complicated bipolar disorder--stabilizing a patient's mood--may be associated with improving the comorbid disorder. Standard mood stabilizers, atypical antipsychotics, and non-antimanic antiepileptic agents are emerging as potentially useful treatments for several of the disorders that frequently co-occur with bipolar disorder, and therefore may be useful treatments for comorbid bipolar disorder.


A Rare Case of Aortic Valve Thrombosis in Patient with Idiopathic Hypereosinophilic Syndrome.
Idiopathic hypereosinophilic syndrome (HES) is characterized by persistent eosinophilia and eosinophil-mediated organ-system damage. Cardiac thrombosis and thromboembolic complications represent common causes of morbidity and mortality and usually involve cardiac ventricles or mitral and prosthetic valves, while the involvement of the aortic valve is extremely rare in HES. Here we report peculiar multimodality images of an atypical case of extended thrombosis of the aortic valve, complicated by myocardial ischemia and asymptomatic cerebral ischemia, likely due to thrombus embolization, occurring in a 48-year-old man with HES. Prompt anticoagulant and steroid therapy lead to rapid and complete resolution of the thrombotic lesions, allowing preserving the native valve and preventing further embolic events.


The prevalence of intestinal parasites in the province of Izmir, Turkey.
Stool samples of a total of 2,047 people in Izmir province were examined by wet mount, formalin ethyl acetate concentration, and trichrome staining methods with an aim to reveal the prevalence of intestinal parasites in Izmir together with related personal and environmental risk factors. Geographical mapping showing the density and variation of the species of intestinal parasites in Izmir was done after all maps were scaled, and the coordinates were determined with GeoMedia5.0. The prevalence of the intestinal parasites was found to be 25.6% in Izmir, with a variation between the districts. Blastocystis hominis was the leading parasite, and the prevalence of parasites was higher in children compared to adults; however, the difference was statistically insignificant. There was also no significant difference between the parasite prevalence and sex, marital status, education, income, frequent eating outside, and habitual raw meat eating. Significant differences were found between the parasite prevalence and crowded families, early immigrants, individuals with no social security, and people living in close contact with their livestock. The parasites were found to be less common among individuals who had been drinking bottled water and living in a house with a sewage system. The results demonstrated a correlation between the intestinal parasites and environmental conditions in our study group. We further plan to expand the study group to cover all regions of Turkey.


[Early diagnosis of alpha fetoprotein nonproducing primary liver cancer].
A comparative study on 150 cases of alpha fetoprotein (AFP) nonproducing primary liver cancer (PLC) in subclinical and moderate stages and 133 cases of intrahepatic solid space-occupying lesion (SOL) other than PLC was undertaken. All were operated and proven by pathology. The results indicated that in the intrahepatic SOL patients with negative serum AFP the diagnosis of PLC could be established if any one of the following items was confirmed: (1) Definite evidence of liver cirrhosis; (2) Hypoecho or inhomogeneous echo sonodensity on ultrasonography plus positive serum HBsAg; (3) Positive 99mTc-PMT liver scan (4) No overfilling of SOL on blood pool scintiscan plus positive HBsAg; (5) No enhancement after injection of contrast medium on computed tomography plus positive HBsAg. The positive rates of the above items in PLC and non-PLC groups were: (1) 73.2% vs. 0.9%, (2) 48.1% vs. 9.6%, (3) 64.3% vs. 14.3%, (4) 27.3% vs. 3.9% and (5) 34.6% vs. 0%, respectively. Statistically, these differences were significant. In conclusion, according to the above mentioned criteria, detection rate of over 90% with over 85% specificity can be obtained for AFP negative PLC.


Potential risk factors for Cryptosporidium infection in dairy calves.
Fecal samples from 7,369 calves on 1,103 farms were examined for cryptosporidia in a nationwide survey, using monoclonal antibody technique. Cryptosporidium oocysts were found in calves from 652 (59.1%) of the farms and in 1,648 (22.4%) of the tested calves. Almost half the calves between 7 and 21 days of age had cryptosporidia in their fecal samples. Prevalence was highest during the summer. Farms with multiple-cow maternity facilities and farms with > 100 milking cows were the most likely to have calves with cryptosporidia.


[STAT signaling pathway mediates high glucose induced cardiac fibroblasts proliferation and collagen deposition in vitro].
To observe the signal transducers and activator of transcriptions (STATs) protein expression changes and investigate the functional role of STATs pathway in case of high glucose-induced cardiac fibroblasts (CFs) proliferation and collagen deposition in vitro. Rat cardiac fibroblasts were isolated from 1- to 3-day-old SD rats, cells from the second to fourth passages were used for the experiment. CFs were cultured in Dulbecco's modified Eagle's medium, supplemented with 5.5 mmol/L glucose (NG), 5.5 mmol/L glucose plus 19.4 mmol/L mannose (OC) or 25 mmol/L glucose (HG) in the presence of absence of STAT1 inhibitor (fludarabine, FLU) and STAT3 inhibitor (S3I-201). After 24 h and 48 h culture in vitro, the proliferation of CFs was measured by 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. After 12 h and 24 h culture in vitro, the production of type I and III collagen was evaluated using real-time quantitative PCR and ELISA. After 0, 30, 60 and 120 min culture in vitro, the phosphorylated expression of STAT1 and STAT3 was analyzed by Western blot. CFs proliferation was significantly enhanced post 24 h and 48 h HG stimulation, and procollagen I and III mRNA expression was significantly upregulated post 12 h and 24 h HG stimulation. Deposition of collagen I and III was also significantly increased post 24 h and 72 h HG stimulation. STAT1 phosphorylation in CFs was increased after 120 min HG stimulation and STAT3 phosphorylation in CFs was increased post 60 min and 120 min HG stimulation. FLU and S3I-201 could inhibit HG-induced CFs proliferation and suppress of which was stimulated by FLU and S3I-201 could both suppress upregulated procollagen I and III mRNA expression and the deposition of collagen types I and III post HG stimulation. STAT1 phosphorylation inhibition resulted in less mRNA downregulation of procollagen type III than that of procollagen type I post 12 h HG stimulation. The STAT3 phosphorylation inhibition resulted in more significantly upregulated procollagen type III mRNA expression than procollagen type I mRNA expression at 12 h post HG stimulation. HG could enhance the protein expression of phosphorylated STAT1 and STAT3 in CFs, which are responsible for HG-induced increased CFs proliferation and collagen deposition in vitro.