Glaucoma-TrEl: A web-based interactive database to build evidence-based hypotheses on the role of trace elements in glaucoma.
Glaucoma is a chronic neurological disease that is associated with high intraocular pressure (IOP), causes gradual damage to retinal ganglion cells, and often culminates in vision loss. Recent research suggests that glaucoma is a complex multifactorial disease in which multiple interlinked genes and pathways play a role during onset and development. Also, differential availability of trace elements seems to play a role in glaucoma pathophysiology, although their mechanism of action is unknown. The aim of this work is to disseminate a web-based repository on interactions between trace elements and protein-coding genes linked to glaucoma pathophysiology. In this study, we present Glaucoma-TrEl, a web database containing information about interactions between trace elements and protein-coding genes that are linked to glaucoma. In the database, we include interactions between 437 unique genes and eight trace elements. Our analysis found a large number of interactions between trace elements and protein-coding genes mutated or linked to the pathophysiology of glaucoma. We associated genes interacting with multiple trace elements to pathways known to play a role in glaucoma. The web-based platform provides an easy-to-use and interactive tool, which serves as an information hub facilitating future research work on trace elements in glaucoma.


Selected decrease of haemocytes of the freshwater snail Planorbarius corneus (L.) (Gastropoda, Pulmonata) after bacteria injection.
The decrease of haemolymph phagocytic cells (SH) in Planorbarius corneus after bacterial injection seems to be mediated by humoral factor(s) released into the haemolymph. SH show different adhesiveness in vitro in the presence of bacterial metabolic products.


Systematic evaluation of avidin-biotin interaction by fluorescence spectrophotometry.
The avidin-biotin interaction was evaluated systematically by fluorescence spectroscopy under different conditions of temperature, pressure, pH, metal ions, incubation time and initial avidin concentration. The binding constant was calculated according to the modified Stern-Volmer equation, which deduced the existence of static quenching mechanism. The data obtained revealed that avidin-biotin interaction exhibited temperature, pH, metal ions, incubation time and initial avidin concentration sensitivity. The binding constants decreased with increase in temperature, while the binding sites were independent of temperature. The values of thermodynamic parameter ΔH (-149.85 kJ mol(-1)) and ΔS (-284.26 J mol(-1) K(-1)) suggested hydrogen bonds and van der Waals played a major role in the reaction. The binding constants between avidin and biotin increased firstly and then decreased gradually with the increase of pH values. Metal ions can also affected the binding constants between avidin and biotin. The association kinetics firstly acquired by the combination of the change in fluorescence per unit time and the modified Stern-Volmer equation indicated that the reaction time required to reach equilibrium was 2200 s, and the average reaction rate for the binding process was very high in the first 180 s. Reaction of the avidin in the first 180 s was more than 40% of the total avidin involved in the whole process.


Tendosynovial sarcoma. Clinicopathologic features, treatment, and prognosis.
Clinicopathologic features, treatment, and results are reported for 95 tendosynovial sarcomas identified from a prospective sarcoma data base established at Memorial Sloan-Kettering Cancer Center (MSKCC) in 1982. Eighty-five patients had definitive treatment of the primary tumor at MSKCC: Epithelial sarcomas were excluded. The local recurrence rate was 18%. Survival rates were not influenced by either the method of local treatment or the use of chemotherapy. The overall actuarial survival rate was 59% at 5 years (median, 92 months). For 25 patients who had resection of pulmonary metastases, the 5-year actuarial survival rate was 43% (median, 22 months) from the time of first thoracotomy. Sex, age, tumor site, and histologic subtype (monophasic versus biphasic) were not significant predictors of survival rates. Regional lymph node metastasis occurred in 3%. The incidence of distant metastasis was 49%, with an associated 5-year survival rate of 31% (median, 33 months). Tumor size was a highly significant prognostic feature, with 5-year survival rates of 86% for patients with tumors smaller than 5 cm and 22% for those with tumors larger than 10 cm (P less than 0.00001). Improvement of treatment results for tendosynovial sarcoma will require effective new systemic adjuvant therapeutic strategies.


A global meta-analysis of soil organic carbon in the Anthropocene.
Anthropogenic activities profoundly impact soil organic carbon (SOC), affecting its contribution to ecosystem services such as climate regulation. Here, we conducted a thorough review of the impacts of land-use change, land management, and climate change on SOC. Using second-order meta-analysis, we synthesized findings from 230 first-order meta-analyses comprising over 25,000 primary studies. We show that (i) land conversion for crop production leads to high SOC loss, that can be partially restored through land management practices, particularly by introducing trees and incorporating exogenous carbon in the form of biochar or organic amendments, (ii) land management practices that are implemented in forests generally result in depletion of SOC, and (iii) indirect effects of climate change, such as through wildfires, have a greater impact on SOC than direct climate change effects (e.g., from rising temperatures). The findings of our study provide strong evidence to assist decision-makers in safeguarding SOC stocks and promoting land management practices for SOC restoration. Furthermore, they serve as a crucial research roadmap, identifying areas that require attention to fill the knowledge gaps concerning the factors driving changes in SOC.


Chemical control over Asialo-GM1: A dual ligand for pili and Lectin A that activates swarming motility and facilitates adherence of Pseudomonas aeruginosa.
Glycolipid, ganglio-N-tetraosylceramide (asialo-GM1), on the mammalian cells are known to be recognized by type IV pili of Pseudomonas aeruginosa. In this work, we show that asialo-GM1 can also be recognized by Lectin A (LecA), another adhesin protein of the P. aeruginosa, by a fluorescent polarization assay, a label-free bacterial motility enabled binding assay, and bacterial mutant studies. On hydrated semi-solid gel surfaces, asialo-GM1 enables swarming and twitching motilities, while on solid surfaces facilitates the bacterial adherence of P. aeruginosa. These results indicate that asialo-GM1 can modulate bioactivities, adherence, and motilities, that are controlled by opposite signaling pathways. We demonstrate that when a solution of pilin monomers or LecA proteins are spread on hydrated gel surfaces, the asialo-GM1 mediated swarming motility is inhibited. Treatment of artificial liposomes containing asialo-GM1 as a component of lipid bilayer with pilin monomers or LecA proteins caused transient leakage of encapsulated dye from liposomes. These results suggest that pili and LecA proteins not only bind to asialo-GM1 but can also cause asialo-GM1 mediated leakage. We also show that both pili and LecA mutants of P. aeruginosa adhere to asialo-GM1 coated solid surfaces, and that a class of synthetic ligands for pili and LecA inhibits both pili and LecA-mediated adherence of P. aeruginosa on asialo-GM1-coated surfaces.


Singlet oxygen stimulates mitochondrial bioenergetics in brain cells.
Oxygen, in form of reactive oxygen species (ROS), has been shown to participate in oxidative stress, one of the major triggers for pathology, but also is a main contributor to physiological processes. Recently, it was found that 1267 nm irradiation can produce singlet oxygen without photosensitizers. We used this phenomenon to study the effect of laser-generated singlet oxygen on one of the major oxygen-dependent processes, mitochondrial energy metabolism. We have found that laser-induced generation of 1O2 in neurons and astrocytes led to the increase of mitochondrial membrane potential, activation of NADH- and FADH-dependent respiration, and importantly, increased the rate of maximal respiration in isolated mitochondria. The activation of mitochondrial respiration stimulated production of ATP in these cells. Thus, we found that the singlet oxygen generated by 1267 nm laser pulse works as an activator of mitochondrial respiration and ATP production in the brain.


Absence of satellite DNA synthesis during meiotic prophase in mouse and human spermatocytes.
Mouse spermatocytes were labelled in situ with 3H-thymidine at successive stages of meiosis. Isolated mouse as well as human spermatocytes were similarly labelled under in vitro conditions. DNA synthesis was followed either by tracking radioactivities in Cs2SO4 gradients or by measuring reassociation kinetics. Mouse satellite DNA and the 3 satellites of human DNA are labelled during S-phase but not during pachytene. In the mouse genome, there is a preferential labelling of regions containing foldbacks (human spermatocytes were not analyzed in this respect). The absence of detectable pachytene synthesis in satellite DNA is consistent with genetic evidence on the absence of crossing-over in constitutive heterochromatin.


Genetic susceptibility of vitamin D receptor gene polymorphisms on autosomal recessive primary microcephaly patients in Pakistani population: a case-control and in-silico study.
Autosomal recessive primary microcephaly (MCPH) is a rare genetic disorder that leads to reduced cerebral cortex caused by a mutation in corticogenesis. The expression of the Vitamin D receptor (VDR) gene is involved in the proliferation and differentiation of neural stem cells, and VDR polymorphisms have been associated with various neurological disorders. However, their relationship with MCPH has not been explored. This study aimed to investigate the association of VDR polymorphisms with MCPH due to its role in Wnt signaling pathway and its In-silico analysis. Blood samples of 64 MCPH patients and 52 controls were collected to genotype VDR SNPs (TaqI (rs731236), FokI (rs2228570) and BsmI (rs1544410). In-silico tools were also used to assess the effects of exonic SNPs on mRNA and protein structure and pathogenicity of exonic and intronic SNPs. The study found that serum 25-OH vitamin D3 levels were significantly different in MCPH patients and healthy controls (P = 0.000). The genetic analysis showed that VDR polymorphisms of FokI and BsmI were seven times more frequent in MCPH patients than in controls (P < 0.05) and the recessive model for TaqI and dominant model for BsmI polymorphisms were also associated with the pathogenesis of MCPH. In-silico analysis showed that the pathogenicity effects of rs2228570 and rs1544410 are neutral while rs731236 causes a silent mutation which has no effect on VDR protein. VDR polymorphisms of FokI and BsmI are associated with the risk of MCPH. These findings suggest that VDR polymorphisms play a role in MCPH, which could provide important insights for understanding the molecular mechanisms of the disease.


[Analog model of the interaction of the human body-temperature sensor-environment system].
A simple analog model of interaction in the system of human body and temperature sensor is described. It can be employed as an imitator in the development and adjustment of thermometric devices. Analytical expressions which describe this model operation and results of determining the real parameters of the system are reported.


A chemical approach to systematically designate the pyranopterin centers of molybdenum and tungsten enzymes and synthetic models.
The recent growth in the chemistry of the oxo-molybdenum enzymes has demonstrated the need for developing systematic methods for naming and abbreviating the novel pterin cofactors that bind to the metal ion via the sulfur atoms of an ene-1,2-dithiolate moiety. Historically, the term "molybdopterin" was coined to designate a special pterin that binds molybdenum and the molybdenum-bound form was termed the "molybdenum cofactor". However, recent studies have demonstrated that this novel pterin also binds tungsten. Furthermore, considerable variation has been found in the pterin entity itself. Taken together, these facts show that molybdenum- and tungsten-containing enzymes possess a family of cofactors rather than a single "molybdenum cofactor". This article proposes a unified methodology for describing these cofactors and their metal-free pterin units in light of recent results from protein crystallography. The various numbering schemes that have been used for this heterocycle are considered, as well as the IUPAC rules which are currently being used for related tricyclic compounds. A unified methodology for uniquely designating and abbreviating each cofactor is proposed. The available chemical and spectroscopic information on the pyranopterin entities that are present in the molybdenum and tungsten enzymes, the precursors to these centers, and synthetic pyranopterins are in part the basis of the systematic names and simplifying abbreviations.


Phytotoxicity of farm livestock manures in facultative heap composting using the seed germination index as indicator.
Static facultative heap composting of animal manure is widely used in China, but there is almost no systematic research on the phytotoxicity of the produced compost. Here, we evaluated the phytotoxic variation in compost produced by facultative heap composting of four types of animal manure (chicken manure, pig manure, sheep manure, and cattle manure) using different plant seeds (cucumber, radish, Chinese cabbage, and oilseed rape) to determine germination index (GI). The key factors that affected GI values were identified, including the dynamics of the phytotoxicity and microbial community during heap composting. Sensitivity to toxicity differed depending on the type of plant seed used. Phytotoxicity during facultative heap composting, evaluated by the GI, was in the order: chicken manure (0-6.6 %) < pig manure (14.4-90.5 %) < sheep manure (46.0-93.0 %) < cattle manure (50.2-105.8 %). Network analysis showed that the volatile fatty acid (VFA) concentration was positively correlated with Firmicutes abundance, and NH4+-N was correlated with Actinobacteria, Proteobacteria, and Bacteroidetes. More bacteria were stimulated to participate in conversions of dissolved organic carbon, dissolved nitrogen, VFA, and ammonia-nitrogen (NH4+-N) in sheep manure heap composting than that in other manure. The GI was most affected by VFA in chicken manure and cattle manure heap composting, while NH4+-N was the main factor affecting the GI in pig manure and sheep manure compost. The dissolved carbon and nitrogen content and composition, as well as the core and proprietary microbial communities, were the primary factors that affected the succession of phytotoxic substances in facultative heap composting, which in turn affected GI values. In this study, the key pathways of livestock manure composting that affected GI and phytotoxicity were found and evaluated, which provided new insights and theoretical support for the safe use of organic fertilizer.


Omalizumab and allergen immunotherapy for respiratory allergies: A mini-review from the Allergen-Immunotherapy Committee of the Italian Society of Pediatric Allergy and Immunology (SIAIP).
Although currently approved to treat severe asthma and chronic spontaneous urticaria, omalizumab has also been an effective and safe add-on treatment for other allergic diseases. Namely, omalizumab has been proposed to be used as add-on therapy in patients with allergic rhinitis and asthma and undergoing specific allergen immunotherapy (AIT). AIT is the only treatment that modifies the natural history of IgE-mediated diseases. This brief review summarizes the available evidence and controversies on the efficacy and safety of omalizumab combined with specific AIT.


Mouse models of DNA double-strand break repair and neurological disease.
The repair of DNA damage is essential for the prevention of disease. The DNA double-strand break (DSB) is a particularly hazardous lesion. DNA DSBs activate a coordinated cellular response involving cell cycle checkpoint activation and repair of the DNA break, or alternatively apoptosis. In the nervous system the inability to respond to DNA DSBs may lead to neurodegenerative disease or brain tumors. Therefore, understanding the DNA DSB response mechanism in the nervous system is of high importance for developing new treatments for neurodegeneration and cancer. In this regard, the use of mouse models represents an important approach for advancing our understanding of the biology of the DNA damage response in the nervous system.


Long-term myocardial recovery after mitral valve replacement in noncompaction cardiomyopathy.
Isolated noncompaction of the left ventricle is a congenital cardiomyopathy, which has been described recently, with literature limited to case reports and case series. Even though various complications have been reported with noncompaction cardiomyopathy, among them severe mitral regurgitation has been reported recently in a few cases. There is no great evidence in the literature about its management, apart from some cases of mitral valve repair and replacement in young patients. We are reporting a case of an elderly lady with isolated left ventricular noncompaction cardiomyopathy associated with severe mitral regurgitation treated with mitral valve replacement with one and half year of follow up demonstrating significant myocardial recovery.


Zellweger syndrome and associated brain malformations: report of a novel Peroxin1 (PEX1) mutation in a Native American infant.
Zellweger syndrome (cerebrohepatorenal syndrome) is very rare and is the most severe form of peroxisomal biogenesis disorders. These can be caused by mutations in any of the currently known Peroxin genes and typically present in the neonatal period with multiorgan involvement. Patients usually do not survive beyond 1 year of age. This article reports a case of Zellweger syndrome in a male Native American infant confirmed by clinical findings, imaging studies, and biochemical analysis. Genetic studies show a novel mutation (c.3030G>T, p. Glutamine1010Histidine) altering the last nucleotide of exon 19 in the Peroxin1 (PEX1) gene.


Nanocarrier based active targeting strategies against erythrocytic stage of malaria.
The Global Technical Strategy for Malaria 2016-2030 aims to achieve a 90% reduction in malaria cases, and strategic planning and execution are crucial for accomplishing this target. This review aims to understand the complex interaction between erythrocytic receptors and parasites and to use this knowledge to actively target the erythrocytic stage of malaria. The review provides insight into the malaria life cycle, which involves various receptors such as glycophorin A, B, C, and D (GPA/B/C/D), complement receptor 1, basigin, semaphorin 7a, Band 3/ GPA, Kx, and heparan sulfate proteoglycan for parasite cellular binding and ingress in the erythrocytic and exo-erythrocytic stages. Synthetic peptides mimicking P. falciparum receptor binding ligands, human serum albumin, chondroitin sulfate, synthetic polymers, and lipids have been utilized as ligands and decorated onto nanocarriers for specific targeting to parasite-infected erythrocytes. The need of the hour for treatment and prophylaxis against malaria is a broadened horizon that includes multiple targeting strategies against the entry, proliferation, and transmission stages of the parasite. Platform technologies with established pre-clinical safety and efficacy should be translated into clinical evaluation and formulation scale-up. Future development should be directed towards nanovaccines as proactive tools against malaria infection.


Instrument Tracking for Prone Lateral Surgery.
The prone lateral transpsoas approach for lumbar interbody fusion and posterior instrumentation enables a large surface area implant without disruption of the posterior spine musculature from a single position.1,2 The addition of virtual live fluoroscopy instrument tracking navigation to surgery provides multiple benefits, including a reduction in patient and surgeon radiation exposure, highly accurate and dynamic spatial tool localization, and flexible equipment and patient positioning.3,4 Here, we highlight the use of virtual live fluoroscopy in prone lateral spine surgery. A 75-year-old man presented with prior L3-L5 fusion and progressive lower extremity pain and weakness. Using the described techniques, the patient underwent a lateral retroperitoneal interbody fusion and posterior instrumentation at L2-L3. The operation proceeded without complication, and the patient reported improved ambulation at 6-week follow-up. The prone lateral transpsoas approach and minimally invasive posterior instrumentation for lumbar interbody fusion permits effective fusion without significant posterior muscle disruption from a single position. The integration of virtual live fluoroscopy enables real-time instrument tracking throughout the minimally invasive case, with reductions in patient and surgeon radiation exposure. Video 1 depicts the use and benefits of this technology in lateral spine surgery. Compared with computed tomography-guided navigation, virtual live fluoroscopy technology enables rapid remapping to iatrogenic anatomic changes for more fluid progression through the operation.5 Virtual live fluoroscopy instrument tracking is a valuable tool that increases the safety and efficiency of single-position lateral spine surgery.


Prevalence, Severity and Impact of Visuospatial Neglect in Geriatric Stroke Rehabilitation, a Cross-Sectional Study.
Visuospatial neglect (VSN) is a common cognitive deficit of lateralized attention after stroke and can have a negative influence on patients' daily activities, community participation, and caregiver burden. VSN prevalence has been investigated in several mixed-age populations, but rarely in only an older population. As the population in geriatric rehabilitation (GR) is understudied and VSN may influence rehabilitation goals in GR (return home), we examined the prevalence of VSN as well as associations between VSN (severity) and population characteristics and the impact of VSN on functioning, length of stay, and discharge destination after GR. Multicenter cross-sectional study. Stroke patients admitted to GR. Three VSN tests (Star cancelation task, Line bisection task, and Catherine Bergego Scale) were administered in the first 2 weeks of GR admission. To examine VSN severity, a composite score was calculated based on scores of the 3 tests. A total of 114 stroke patients were included [55.3% female; mean age 80.2 (SD 8.0) years]. VSN prevalence was 47.4%, in which allocentric and egocentric neglect were more prevalent than VSN during activities of daily living. Participants with VSN spent more days in GR compared to participants without VSN (median 68.5 vs 35.5 days) and had fewer home returns. In addition, VSN participants showed less mobility, lower cognitive functioning, and less independence during self-care compared to participants without VSN. Mobility, self-care, cognition, duration of rehabilitation, and home return were negatively associated with VSN severity. VSN is very prevalent in the GR stroke population. VSN severely hampers older people during daily activities and their rehabilitation process and, therefore, has a major personal and societal impact. Accordingly, systematic assessment of VSN in the early phase of geriatric rehabilitation with multiple VSN screening tests is recommended.


The first stereoselective Ficini-Claisen rearrangement using chiral ynamides.
The first asymmetric Ficini-Claisen rearrangement using chiral ynamides is described. At relatively low temperatures, the Ficini-Claisen rearrangement can be efficiently promoted by p-nitrobenzenesulfonic acid leading to high diastereoselectivity for a range of different allylic alcohols and chiral ynamides. [reaction: see text]


High ultrasensitive serum C-reactive protein may be related to freezing of gait in Parkinson's disease patients.
C-reactive protein (CRP) is a biomarker of systemic inflammation that has been linked to accelerated decline in walking speed in older adults. The aim of the present study was to compare the CRP levels of PD patients with vs patients without freezing of gait (FOG). Patients and controls participating in the COPPADIS-2015 study that performed blood extraction for determining molecular serum biomarkers were included. Patients with FOG were identified as those with a score of 1 or greater on item-3 of the Freezing of Gait Questionnaire (FOG-Q). Immunoassay was used for determining ultrasensitive CRP (US-CRP) level (mg/dL). In the PD group (n = 225; 61.8 ± 9.5 years old, 61.8% males), 32% of the patients presented FOG but none in the control group (n = 65; 60.3 ± 6.1 years old, 56.9% males) (p < 0.0001). Differences in US-CRP level were significant in patients with FOG vs patients without FOG and vs controls (0.31 ± 0.52 vs 0.16 ± 0.21 vs 0.21 ± 0.22; p = 0.04). Significant differences were also observed between patients with vs without FOG (p = 0.001) but not between patients and controls (p = 0.163). US-CRP level was related to FOG (OR = 4.369; 95% CI 1.105-17.275; p = 0.036) along with H&Y (OR = 2.974; 95% CI 1.113-7.943; p = 0.030) and non-motor symptoms burden (NMSS total score; OR = 1.017; 95% CI 1.005-1.029; p = 0.006) after adjusting for age, gender, disease duration, equivalent daily levodopa dose, number of non-antiparkinsonian drugs per day, motor fluctuations, cognition, motor phenotype, and chronic use of anti-inflammatory drugs. The present study suggests that serum US-CRP level is related to FOG in PD patients. Inflammation could be linked to FOG development.


Big Data and Health Research-The Governance Challenges in a Mixed Data Economy.
Denmark is a society that has already moved towards Big Data and a Learning Health Care System. Data from routine healthcare has been registered centrally for years, there is a nationwide tissue bank, and there are numerous other available registries about education, employment, housing, pollution, etcetera. This has allowed Danish researchers to study the link between exposures, genetics and diseases in a large population. This use of public registries for scientific research has been relatively uncontroversial and has been supported by facilitative regulation that allows data to be used without the consent of data subjects. However, in the future much of the data will not be held by public authorities but by private companies. What are the implications of this shift for the governance of the research use of the data? This paper will argue that increased involvement of Research Ethics Committees and better training of researchers are necessary; and that some form of consent will have to be re-introduced. Four different consent models will be discussed: Opt-Out, Broad/Blanket consent, Dynamic consent, and Meta consent. It will be argued that a governance model including a possibility for citizens to make meta-choices strikes the best balance between individual and public interests.


Expression of brain-derived neurotrophic factor in mature spermatozoa from fertile and infertile men.
Neurotrophins, a family of growth factor, are not only required for the survival and differentiation of the nervous system but also important for the development of reproductive tissues. We identified the expression of brain-derived neurotrophic factor (BDNF) transcript and protein in human spermatozoa. The presence of BDNF in human spermatozoa was investigated using RT-PCR, immunofluorescence and Western blotting. Real-time PCR and ELISA were employed to determine expression levels of BDNF. BDNF mRNA and protein were detected in human spermatozoa. Immunofluorescence staining showed that BDNF protein was localized in the head, neck, and tail of human spermatozoa. The amount of BDNF mRNA expressed in spermatozoa of oligoasthenozoospermic group was lower than that of fertile group (P < 0.05). The concentration of BDNF in seminal plasma from oligoasthenozoospermic group (2.8 ± 0.7 ng/ml) was both lower than that from fertile group (3.6 ± 0.4 ng/ml) and asthenozoospermic group (3.4 ± 0.5 ng/ml) (P < 0.05). The data showed that the decrease in BDNF transcript and protein in oligoasthenozoospermic group may be associated with pathogenesis in some types of male infertility.


The effect of activated charcoal on N-acetylcysteine absorption in normal subjects.
The discovery of the effectiveness of oral antidotes such as N-acetylcysteine (NAC) for acetaminophen poisonings has raised questions about the appropriateness of concomitant administration with activated charcoal. A number of studies have attempted to clarify this question without complete success. This study was designed to evaluate the difference in serum levels of NAC when given with activated charcoal. Nineteen patients completed a two-phase cross-over study in which they served as their own controls. Each subject in phase 1 received 140 mg/kg of diluted, chilled NAC orally, and venous blood samples were drawn for analysis. Phase 2 consisted of a 100-g dose of activated charcoal followed by NAC. Samples were transported immediately and assayed using spectrophotometry. A reduction in peak NAC level of 29% (P less than .02) and a reduction of total area under the curve (AUC) of 39% (P less than .001) was noted. Although it may be preferable to avoid completely the use of activated charcoal when using NAC to treat overdoses of acetaminophen, we recommend that if these agents are used together, doses of NAC be increased by 40% to compensate for the decreased oral absorption of NAC.


An overview of sexual behaviour research in later life-Quantitative and qualitative findings.
This article provides an overview of current sexual behaviour research in later life by describing associated factors, including the physical and psychological benefits. Recent systematic reviews were interrogated for findings on sexual behaviour research in adults aged 60+. Regardless of research methods employed, all studies showed that there were a range of physical and psychological benefits to remaining sexually active in later life. While quantitative studies placed an emphasis on measuring penile-vaginal intercourse, they provided no definitive conclusion about the benefits due to 'inconsistent results' across studies. Qualitative studies described the myriad ways in which older adults redefine what constitutes sexual activity despite the onset of dysfunction and disability. While the different research methods show that engaging in sexual behaviour has physical and psychological benefits at all adult ages, there is limited conclusive evidence about what the overall benefits might be in later life.


Interaction of FCE 22176, a stable prostacyclin analogue, with different prostaglandins in guinea-pig trachea and atria.
FCE 22176, a stable derivative of a PGI2 analogue, was studied in guinea-pig isolated atria and trachea. The compound was without inotropic or chronotropic effects in spontaneously beating atria and did not alter tracheal tone. By contrast, FCE 22176 competitively antagonized the inotropic effect of PGI2 on atria, and inhibited the PGI2-induced contraction of tracheal chains. Furthermore, in tracheal chains, FCE 22176 was able to antagonize the contractile effect of PGF2 alpha, and to enhance PGE2-induced relaxation. These data support our previous findings that FCE 22176 is a PGI2 antagonist, and provide evidence also for a more complex effect on prostaglandin receptors.


Life Expectancy after Stroke Based On Age, Sex, and Rankin Grade of Disability: A Synthesis.
Stroke is a leading cause of death and disability in the developed world. The major factor affecting long term survival (other than age) is known to be the severity of disability. Yet to our knowledge there are no studies reporting life expectancies stratified by both age and severity. Remaining life expectancy is a key measure of health. We identified 11 long-term follow-up studies of stroke patients that reported the multivariate effects of age, sex, the modified Rankin Scale (mRS) grade of disability, and other factors. From these we computed the composite effects of these factors on survival, then used these to calculate age-, sex-, and mRS-specific mortality rates. Finally we used the rates to construct life tables, and hence obtain life expectancies. Life expectancy varies by age, sex, and mRS. The life expectancies of males age 70, for example, were 13, 13, 11, 8, 6, and 5 years for Rankin Grades 0-5, respectively, representing reductions of 1, 1, 3, 6, 8, and 9 years from the corresponding general population figure. These figures demonstrate the importance of rehabilitation following stroke, and can be used in discussion of public policy and benchmarking of future results.


Metagenomic analysis of methanogen populations in three full-scale mesophilic anaerobic manure digesters operated on dairy farms in Vermont, USA.
The microbial communities that produce biogas as a result of anaerobic digestion of manure remain poorly understood. Using next-generation sequencing, methanogen populations were investigated in three full scale mesophilic anaerobic digesters operated on dairy farms. A combined 50 246 non-chimeric sequence reads covering the V1-V3 hypervariable regions of the methanogen 16S rRNA gene were assigned to 307 species-level operational taxonomic units (OTUs). The Blue Spruce Farms (BSF) and Green Mountain Dairy (GMD) anaerobic digesters were found to have nearly identical methanogen profiles, with the overwhelming predominance of OTU 1 (98.5% and 99.7%, respectively), which showed 99.2% sequence identity to Methanosarcina thermophila. In contrast, methanogens from the Chaput Family Farms (CFF) anaerobic digester were more diverse, with five major OTUs belonging to four distinct phylogenetic groups (Methanomicrobiales, Methanosarcinales, Methanoplasmatales, and Methanobacteriales). Differences in management practices and years of operation were hypothesized as potential factors responsible for differences in the methanogen profiles.


A serine proteinase in the penetration glands of the cercariae of Plagiorchis elegans (Trematoda, Plagiorchiidae).
Cercariae of Plagiorchis elegans secrete a serine proteinase from their penetration glands. The enzyme hydrolyzes both azocoll and gelatin at the optimal pH of 8.4 but is incapable of hydrolyzing elastin at the pH range of 7.2-10.0 Ca2+ and Mg2+ activate it, whereas metal chelators (1 mM EGTA, 1 mM EDTA) and serine proteinase inhibitors (1 mM PMSF and 0.1 mM DFP) act as strong inhibitors. The proteinase activity is insensitive to thiol-blocking compounds and to 5 mM 1,10-phenanthroline, a relatively specific chelator of zinc. It appears, therefore, that the active proteinase represents a metalenzyme complex rather than a metalloenzyme. Being capable of hydrolyzing N-blocked L-alanine-1-naphthylester, N-blocked L-methionine-1-naphthylester, and naphthyl AS-D chloroacetate at pH 6.8, the proteinase is insensitive to 1 mM p-nitrophenyl phosphate, an inhibitor of some mammalian esterproteinases. The enzyme does not split N-blocked DL-phenylalanine-2-naphthylester, nonspecific esterase substrates (1-naphthyl acetate, 1-naphthyl butyrate, 5-bromoindoxyl acetate), or several N-blocked L-aminoacyl- and N-blocked L-peptidyl-naphthylamides bearing L-arginine, L-alanine, L-phenylalanine, L-leucine, or L-proline at the P1 subsite. At operative pH values of 4.8 and 3.8 generated during electrophoresis in a stacking and a resolving gel, respectively, the cercarial proteinase migrates toward the cathode. The separated enzyme produces three bands of proteolysis in a gelatin-containing polyacrylamide gel at the optimal pH of 8.4. The presence of the proteinase in the penetration glands, in the secretory canals, and in the secretion from the glands suggests that the enzyme facilitates penetration, thus enabling the larvae to force their way through tissues of their hosts.


Reporter gene vectors and assays.
Gene reporter systems play a key role in gene expression and regulation studies. This review describes the ideal reporter systems, including reporter expression vector design. It summarizes the many uses of genetic reporters and outlines the currently available and commonly used reporter systems. Each system is described in terms of the reporter gene, the protein it encodes, and the assays available for detecting presence of the reporter. In addition, each reporter system is analyzed in terms of its recommended uses, advantages, and limitations.


Changes in histamine metabolism in the brains of mice with streptozotocin-induced diabetes.
Histamine (HA) metabolism in the brain of mice with streptozotocin (STZ)-induced diabetes was examined. The levels of tele-methylhistamine (t-MH), a major metabolite of brain HA, significantly increased 3 and 4 weeks after STZ injection. However, the HA turnover rates in the diabetic mice, determined from the accumulation of t-MH after the administration of pargyline, were not different from the control values when the animals were allowed free access to food. When the mice were starved for 15 h 4 weeks after STZ treatment, the brain levels of L-histidine decreased significantly, whereas HA turnover increased significantly. Such changes were not observed in starved control mice. Histidine decarboxylase or HA N-methyltransferase activity did not change after starvation in either diabetic or control mice. These results show that the histaminergic (HAergic) activity in the brains of diabetic mice remains within normal range as long as the animals are allowed free access to food. However, they also indicate that a marked enhancement of HAergic activity accompanied by a decrease in the brain L-histidine level occurs in starved diabetic mice.


PDK1 promotes the inflammatory progress of fibroblast-like synoviocytes by phosphorylating RSK2.
This study investigated the role of PDK1 in inflammatory response which is initiated by TNF-α and analyzed the association between PDK1 and RSK2. TNF-α were added into MH7A cells to induce inflammation condition. Through overexpressing or suppressing PDK1 in MH7A cells, the role of PDK1 in cell invasiveness and inflammatory factors was determined. Levels of MMPs protein and inflammatory cytokines were assessed with PDK1 siRNA and TNF-α treatment. Inhibition of RSK2 was used to investigate the function of RSK2 on PDK1-induced inflammation. The phosphorylation of RSK2 was detected when PDK1 was inhibited. Luciferase reporter assay was performed to detect the transcriptional activity of NF-κB. We found highly expressed PDK1 could promote cell invasion and secretion of IL-1β and IL-6 in MH7A cells. Inhibition of RSK2 reduced the PDK1-induced cell invasion and cytokines secretion in MH7A cells. In response to TNF-α, PDK1 could phosphorylate RSK2 and activated RSK2, then promoting the activation of NF-κB. This may be a possible therapeutic option of rheumatoid arthritis.


Retrosternal subclavian-femoral artery bypass.
In three cases we have used a retrosternal and extraperitoneal approach to revascularize the lower extremities with a subclavian-femoral artery bypass. This technique is as easy technically as the conventional subcutaneous axillofemoral bypass and has the advantage of avoiding extrinsic compression, thus improving long-term patency.


Total synthesis of the mycolactones.
[structure: see text] The first total synthesis of the mycolactones is reported. This work unambiguously confirms our earlier relative and absolute stereochemical assignment of the mycolactones.


External Beam Radiation Therapy for Liver Metastases.
Stereotactic ablative radiotherapy (SABR) commonly is used for small liver metastases. Modern conformal radiotherapy techniques, including 3-dimensional conformal radiotherapy and intensity-modulated radiation therapy, enable the safe delivery of SABR to small liver volumes. For larger tumors, the safe delivery of SABR can be challenging due to a more limited volume of healthy normal liver parenchyma and the proximity of the tumor to radiosensitive organs, such as the stomach, duodenum, and large intestine. Controlling respiratory motion, the use of image guidance, and increasing the number of radiation fractions sometimes are necessary for the safe delivery of SABR in these situations.


Chewable tablet with herbal extracts and propolis arrests Wuhan and Omicron variants of SARS-CoV-2 virus.
Prevention of COVID-19 is of paramount importance for public health. Some natural extracts might have the potential to suppress COVID-19 infection. Therefore, this study aimed to design a standardised, efficient, and safe chewable tablet formulation (with propolis and three herbal extracts) for possible prevention against two variants (Wuhan B.1.36 and Omicron BA.1.1) of SARS-CoV-2 virus and other viral infections. Green tea, bilberry, dried pomegranate peel, and propolis extracts were selected for this purpose. Cytotoxicity and antiviral activity of each component, as well as the developed chewable tablet, were examined against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus using Vero E6 cells with the xCELLigence real-time cell analyser-multiple plates system. Anti-inflammatory and analgesic activities, as well as mutagenicity and anti-mutagenicity of the chewable tablet were also analysed. Compared to the control, it was observed that the chewable tablet at concentrations of 110 and 55 µg/mL had antiviral activity rates of 101% and 81%, respectively, for the Wuhan variant and 112% and 35%, respectively, for the Omicron variant. The combination of herbal extracts with propolis extract were synergically more effective (∼7-fold higher) than that of individual extract. The present work suggests that a combination of herbal extracts with propolis at suitable concentrations can effectively be used as a food supplement for the prevention of both variants of the SARS-CoV-2 virus in the oral cavity (the first entry point of the SARS-CoV-2 virus).


AWC thermosensory neuron interferes with information processing in a compact circuit regulating temperature-evoked posture dynamics in the nematode Caenorhabditis elegans.
Elucidating how individual neurons encode and integrate sensory information to generate a behavior is crucial for understanding neural logic underlying sensory-dependent behavior. In the nematode Caenorhabditis elegans, information flow from sensory input to behavioral output is traceable at single-cell level due to its entirely solved neural connectivity. C. elegans processes the temperature information for regulating behavior consisting of undulatory posture dynamics in a circuit including two thermosensory neurons AFD and AWC, and their postsynaptic interneuron AIY. However, how the information processing in AFD-AWC-AIY circuit generates the posture dynamics remains elusive. To quantitatively evaluate the posture dynamics, we introduce locomotion entropy, which measures bandwidth of the frequency spectrum of the undulatory posture dynamics, and assess how the motor pattern fluctuates. We here found that AWC disorders the information processing in AFD-AWC-AIY circuit for regulating temperature-evoked posture dynamics. Under slow temperature ramp-up, AWC adjusts AFD response, whereby broadening the temperature range in which animals exhibit fluctuating posture undulation. Under rapid temperature ramp-up, AWC increases inter-individual variability in AIY activity and the fluctuating posture undulation. We propose that a compact nervous system recruits a sensory neuron as a fluctuation inducer for regulating sensory-dependent behavior.


Risk of amputation under diuretics in patients with or at risk of lower extremity arterial disease: A systematic review and meta-analysis.
Recently, increased risk of amputation under sodium glucose cotransporter-2 inhibitors has been debated. Similar concerns have been raised with other "traditional" diuretics, more particularly in patients with or at risk of lower extremity arterial disease (LEAD). To collect all available data on any potential risk of amputation associated with diuretics in patients with or at risk of LEAD. Additionally, we looked for other limb-related events in these patients. We searched in PubMed, Embase and Scopus databases up to February 2021 for references, using peripheral or lower extremity arterial disease, diuretics and amputation keywords, excluding case reports, experimental animal studies and non-English reports. Among the 1376 hits identified in the databases, six studies were finally included in this review, including one cross-sectional and five longitudinal studies (total of 47,612 participants). One study was limited to thiazide diuretics, one focused on loop diuretics and the remainder mixed all diuretics. All studies reported a significant association between diuretic use and amputation risk in patients with or at high risk of LEAD. Despite some limitations in several studies, the meta-analysis showed an increased risk of amputation associated with diuretics (odds ratio: 1.75, 95% confidence interval: 1.53-1.99; P<0.001). Beyond amputation, patients with or at risk of LEAD under diuretics appeared to be at increased risk of other lower limb events, mostly in the presence of other comorbidities, including diabetes. Although the amount of data in the literature is scarce, this first systematic review and meta-analysis favours an increased risk of amputation in patients with or at risk of LEAD under diuretics. Further prospective studies must be conducted to provide a better understanding of the mechanisms. Meanwhile, the use of diuretics in these patients should be parsimonious, considering alternatives whenever possible.


Triterpenoidal lupin saponins from the Chilean legume Lupinus oreophilus Phil.
Two lupin saponins, 3beta,21alpha,22beta,24-tetrahydroxyolean-12-en-3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl-21-O-alpha-L-arabinopyranoside and 3beta,21alpha,22beta,24-tetrahydroxyolean-12-en-3-O-beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl-21-O-alpha-L-rhamnopyranoside, along with eight other saponins and one triterpene previously reported from other legumes, were isolated from the aerial parts of Lupinus oreophilus collected in northern Chile. The structures of the isolated compounds were established with the help of extensive spectroscopic techniques.


Relaxant effect of oxime derivatives in isolated rat aorta: role of nitric oxide (NO) formation in smooth muscle.
Various oxime derivatives were evaluated as nitric oxide (NO) donors in arteries. Relaxation of rat aortic rings was used for bioassay of NO production, and electron paramagnetic resonance spectroscopy for demonstration of NO elevation. In rings with or without endothelium or adventitia, hydroxyguanidine and hydroxyurea were almost inactive, whereas formamidoxime, acetaldoxime, acetone oxime, acetohydroxamic acid and formaldoxime elicited relaxation. Active compounds increased NO levels in endothelium-denuded rings. Formaldoxime was the most potent agent for both relaxation and NO elevation in aortic rings, and it also increased NO in human aortic smooth muscle cells. In endothelium-denuded rings, relaxation was inhibited by a NO scavenger (2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide) and by inhibitors of soluble guanylyl-cyclase (1H[1,2,4,]oxadiazolo[4,3-a]quinoxalin-1-one) or cyclic GMP-dependent protein kinases (Rp-8-bromo cyclic GMP monophosphorothioate). Neither N(omega)-nitro-l-arginine methylester (a NO synthases inhibitor) nor proadifen (a cytochrome P450 inhibitor) decreased the effect of oxime derivatives. However, 7-ethoxyresorufin (7-ER, an inhibitor of P4501A(1) which can also inhibit various NADPH-dependent reductases) abolished the relaxant effect of these compounds, without affecting the one of glyceryl trinitrate (GTN) or 2-(N,N-diethylamino)-diazenolate-2-oxide. 7-ER also abolished formaldoxime-induced NO increase in aortic rings. In rings tolerant to GTN, formaldoxime-induced relaxation and NO elevation were not different from those obtained in control rings. In conclusion, some oxime derivatives release NO by 7-ER-sensitive pathways in aortic smooth muscle, thus eliciting vasorelaxation. Pathways of NO formation are likely distinct from NO synthases and from those responsible for GTN biotransformation. Oxime derivatives could be useful for NO delivery in arteries in which endothelial NO synthase activity is impaired.


Comments on "A comparison of different physical stomach models and an analysis of shear stresses and strains in these system" by Zhong and Langrish (2020).
Understanding of the fate of foods or specific nutrient(s) during digestion within the different compartments of the gastrointestinal (GI) tract is important for making healthier food products and formulate appropriate dietary advice. In vitro GI models have been extensively employed for digestion-related studies in recent years because they can overcome many of the difficulties associated with human or animal studies as the latter are not always technically, financially and ethically feasible. The origins, mechanisms, advantages/disadvantages and applications of typical in vitro physical stomach models have been summarized and compared in many review papers. These will contribute to the design and construction of more advanced and physiologically-relevant in vitro GI models. The letter to the editor comments on a recently published review paper aiming to clarify some inaccurate descriptions of the rat and human stomach systems in terms of the mechanisms of gastric peristalsis and the materials of construction for the stomach models.


The effects of sample handling on proteomics assessed by reverse phase protein arrays (RPPA): Functional proteomic profiling in leukemia.
Reverse phase protein arrays (RPPA) can assess protein expression and activation states in large numbers of samples (n > 1000) and evidence suggests feasibility in the setting of multi-institution clinical trials. Despite evidence in solid tumors, little is known about protein stability in leukemia. Proteins collected from leukemia cells in blood and bone marrow biopsies must be sufficiently stable for analysis. Using 58 leukemia samples, we initially assessed protein/phospho-protein integrity for the following preanalytical variables: 1) shipping vs local processing, 2) temperature (4 °C vs ambient temperature), 3) collection tube type (heparin vs Cell Save (CS) preservation tubes), 4) treatment effect (pre- vs post-chemotherapy) and 5) transit time. Next, we assessed 1515 samples from the Children's Oncology Group Phase 3 AML clinical trial (AAML1031, NCT01371981) for the effects of transit time and tube type. Protein expression from shipped blood samples was stable if processed in ≤72 h. While protein expression in pre-chemotherapy samples was stable in both heparin and CS tubes, post-chemotherapy samples were stable in only CS tubes. RPPA protein extremes is a successful quality control measure to identify and exclude poor quality samples. These data demonstrate that a majority of shipped proteins can be accurately assessed using RPPA. SIGNIFICANCE: RPPA can assess protein abundance and activation states in large numbers of samples using small amounts of material, making this method ideal for use in multi-institution clinical trials. However, there is little known about the effect of preanalytical handling variables on protein stability and the integrity of protein concentrations after sample collection and shipping. In this study, we used RPPA to assess preanalytical variables that could potentially affect protein concentrations. We found that the preanalytical variables of shipping, transit time, and temperature had minimal effects on RPPA protein concentration distributions in peripheral blood and bone marrow, demonstrating that these preanalytical variables could be successfully managed in a multi-site clinical trial setting.


Older age and duration of exposure to type 2 diabetes in selective screening of asymptomatic carotid artery stenosis for primary stroke prevention-A single institution experience.
To evaluate the incidence and risk factors for carotid artery stenosis amongst asymptomatic type 2 diabetes from a single Malaysian tertiary institution. This is a prospective cross-sectional study of asymptomatic type 2 diabetics selected from the outpatient ophthalmology and endocrine clinics for carotid duplex ultrasound scanning performed by a single radiologist. The duplex ultrasound criteria were based on the North American Symptomatic Carotid Endarterectomy Trial (NASCET) classification of carotid artery stenosis. Univariate and multivariate analysis was performed to identify possible risk factors of carotid artery stenosis. Amongst the 200 patients, the majority were males (56%) and Malay predominance (58.5%). There were 12/200 patients (6%) with mean age of 69.2 years identified to have carotid artery stenosis. Univariate analysis of patients with asymptomatic carotid artery stenosis identified older age of 69.2 years (p=0.027) and duration of exposure to diabetes of 17.9 years (p=0.024) as significant risk factors. Patients with longer exposure of diabetes and older age were risk factors of carotid artery stenosis in asymptomatic type 2 diabetics. These patients should be considered for selective screening of carotid artery stenosis during primary care visit for early identification and closer surveillance for stroke prevention.


Automated methods for detection of bacteriuria.
Urine specimens represent a large portion of cultures received by the clinical microbiology laboratory. Much time and effort are spent screening these specimens and approximately 80 percent show no growth. The methods employed for detection of bacteriuria include microscopic, chemical, culture, and automated. The most widely used procedure has been an agar plate culture method. However, this method requires overnight incubation and therefore results are delayed. Within the last decade many automated methods have been introduced for detecting bacteriuria, and results are available more rapidly than with the agar plate culture method. In addition to decreased detection time, these systems are accurate and cost-effective. The purpose of this report is to review these automated bacteriuria screening systems, which include bioluminescence, colorimetry, electrochemical screening, electrical impedance, microcalorimetry, photometry, and radiometry. Accuracy, detection time, and cost are also discussed in this review.


Clinical features and treatment of intracranial chordoid meningioma: a report of 30 cases.
To discuss the clinical characteristics and prognosis of chordoid meningioma (CM). Tumour samples of CM from 30 patients were re-examined. The postoperative outcomes were analyzed on the basis of clinical observations. The survival probabilities were calculated using the Kaplan-Meier method. Thirty-two operations were performed in 30 cases, including 27 operations for total removal and five operations for subtotal removal. The median follow-up period was 34.0 months. Tumour recurred in five patients, with a median recurrence time of 32.0 months. No systemic manifestations of Castleman's syndrome were found. The majority (80%) of tumours were found in the supratentorial compartments. The MIB-1 labelling index (MIB-1 LI) varied from 1% to 10%. In univariate analyses, the presence of aggressive factors (P = 0.001) and the extent of resection (P = 0.037) were related to progression-free survival (PFS). The MIB-1 LI (P = 0.50) and postoperative radiotherapy (P = 0.62) were not related to PFS. Chordoid meningioma is a rare subtype of meningioma, and is often found supratentorially. There is an absence of association with Castleman's syndrome. Aggressive factors and the extent of resection are helpful in predicting recurrence. It might be more pertinent to downgrade CM to grade I, unless it shows aggressive factors.


[2 families with benign myopathy predominantly on the limb girdle with dominant autosomal heredity].
Very few authenticated cases of benign muscular dystrophy affecting mainly the girdles and of dominant autosomal inheritance have been documented. Two families were seen with this type of transmission, and certain common characteristics noted: proximal weakness and amyotrophy, frequency of muscle contractures, mainly distal, true calf hypertrophy, slow progression and benign nature and finally a fairly uniform semiology in the same family, an atypical finding in dominant autosomal hereditary disease.


Temperature response to antipyretic therapy in children: relationship to occult bacteremia.
The response of rectal temperature to antipyretic therapy was studied in an attempt to identify a clinical characteristic that would distinguish children with occult bacteremia from those with sterile cultures of blood. Children 3-24 months of age with initial temperature recordings of 38.9 degrees C or greater had a blood culture drawn and received a standard dose (10mg/kg) of either aspirin or acetaminophen. Temperature was again recorded 60-120 minutes later. During the period of investigation, 255 patients were studied; 16 had bacteremia, and 239 had sterile blood cultures. There was no difference in the response to antipyretic therapy between the two groups. The mean decrease in temperature for each was similar (1.3 versus 1.05 degrees C, P = 0.14). The authors conclude that response to antipyretic therapy does not distinguish children who are bacteremic from those who are not.


Repeated exposures to hyperbaric air suppress neurite outgrowth in PC12 cells.
Hyperbaric exposure induces lesions of the CNS in scuba divers. Repeated exposures to hyperbaric air at 0.5 MPa for 30 min with short intervals suppressed NGF-stimulated neurite outgrowth, concomitant with a decrease in the protein expression of ERK in PC12 cells. Hyperbaric exposure most likely causes direct lesions of neural cells.


A nomogram model for the risk prediction of type 2 diabetes in healthy eastern China residents: a 14-year retrospective cohort study from 15,166 participants.
Risk prediction models can help identify individuals at high risk for type 2 diabetes. However, no such model has been applied to clinical practice in eastern China. This study aims to develop a simple model based on physical examination data that can identify high-risk groups for type 2 diabetes in eastern China for predictive, preventive, and personalized medicine. A 14-year retrospective cohort study of 15,166 nondiabetic patients (12-94 years; 37% females) undergoing annual physical examinations was conducted. Multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) models were constructed for univariate analysis, factor selection, and predictive model building. Calibration curves and receiver operating characteristic (ROC) curves were used to assess the calibration and prediction accuracy of the nomogram, and decision curve analysis (DCA) was used to assess its clinical validity. The 14-year incidence of type 2 diabetes in this study was 4.1%. This study developed a nomogram that predicts the risk of type 2 diabetes. The calibration curve shows that the nomogram has good calibration ability, and in internal validation, the area under ROC curve (AUC) showed statistical accuracy (AUC = 0.865). Finally, DCA supports the clinical predictive value of this nomogram. This nomogram can serve as a simple, economical, and widely scalable tool to predict individualized risk of type 2 diabetes in eastern China. Successful identification and intervention of high-risk individuals at an early stage can help to provide more effective treatment strategies from the perspectives of predictive, preventive, and personalized medicine.


Characterization of the genomic organization of the region bordering the centromere of chromosome V of Podospora anserina by direct sequencing.
A Podospora anserina BAC library of 4800 clones has been constructed in the vector pBHYG allowing direct selection in fungi. Screening of the BAC collection for centromeric sequences of chromosome V allowed the recovery of clones localized on either sides of the centromere, but no BAC clone was found to contain the centromere. Seven BAC clones containing 322,195 and 156,244bp from either sides of the centromeric region were sequenced and annotated. One 5S rRNA gene, 5 tRNA genes, and 163 putative coding sequences (CDS) were identified. Among these, only six CDS seem specific to P. anserina. The gene density in the centromeric region is approximately one gene every 2.8kb. Extrapolation of this gene density to the whole genome of P. anserina suggests that the genome contains about 11,000 genes. Synteny analyses between P. anserina and Neurospora crassa show that co-linearity extends at the most to a few genes, suggesting rapid genome rearrangements between these two species.


Cytosolic epoxide hydrolase.
Epoxide hydrolase activity is recovered in the high-speed supernatant fraction from the liver of all mammals so far examined, including man. For some as yet unexplained reason, the rat has a very low level of this activity, so that cytosolic epoxide hydrolase is generally studied in mice. This enzyme selectively hydrolyzes trans epoxides, thereby complementing the activity of microsomal epoxide hydrolase, for which cis epoxides are better substrates. Cytosolic epoxide hydrolase has been purified to homogeneity from the livers of mice, rabbits and humans. Certain of the physicochemical and enzymatic properties of the mouse enzyme have been thoroughly characterized. Neither the primary amino acid, cDNA nor gene sequences for this protein are yet known, but such characterization is presently in progress. Unlike microsomal epoxide hydrolase and most other enzymes involved in xenobiotic metabolism, cytosolic epoxide hydrolase is not induced by treatment of rodents with substances such as phenobarbital, 2-acetylaminofluorene, trans-stilbene oxide, or butylated hydroxyanisole. The only xenobiotics presently known to induce cytosolic epoxide hydrolase are substances which also cause peroxisome proliferation, e.g., clofibrate, nafenopin and phthalate esters. These and other observations indicate that this enzyme may actually be localized in peroxisomes in vivo and is recovered in the high-speed supernatant because of fragmentation of these fragile organelles during homogenization, i.e., recovery of this enzyme in the cytosolic fraction is an artefact. The functional significance of cytosolic epoxide hydrolase is still largely unknown. In addition to deactivating xenobiotic epoxides to which the organism is exposed directly or which are produced during xenobiotic metabolism, primarily by the cytochrome P-450 system, this enzyme may be involved in cellular defenses against oxidative stress.


Shook Ones: Understanding the Intersection of Nonfatal Violent Firearm Injury, Incarceration, and Traumatic Stress Among Young Black Men.
Violent injury is a leading cause of death and disability among young Black men, with the highest rates occurring in low-income urban populations. Hospital-based violence intervention programs (HVIPs) offer a promising opportunity to address the biopsychosocial factors that adversely affect this population. However, there are major gaps between the needs of young Black male survivors of violent injury and the forms of care provided by HVIPs. Patient-centered outcomes research provides a useful mode of inquiry to develop strategies to decrease these differences. Care for survivors, including treatment for traumatic stress disorders, must be reconceptualized to center the lived experiences of young Black men. This paper qualitatively explores how these survivors of gun violence express symptoms of traumatic stress and the ways in which their narratives can inform the implementation of the biopsychosocial model in HVIPs. A phenomenological variant ecological systems theory framework was used to analyze participant narratives to aid in understanding their symptoms of traumatic stress and post-injury affective changes as both psychologically and socially important experiences. Such insight may inform changes to HVIP practice to address persistent health disparities related to violence.


Suspected Gastroparesis With Concurrent Gastroesophageal Reflux Disease Induced by Low-Dose Liraglutide.
A 74-year-old woman with type 2 diabetes mellitus presented with nausea and abdomen distension. Four days prior, liraglutide 0.6 mg had been commenced. An abdominal computed tomography scan revealed gastric dilatation without mechanical obstruction which clinically suggested gastroparesis (GP). Her symptoms resolved after liraglutide discontinuation. A gastroscopy revealed reflux esophagitis. Taken together, GP may have developed along with reflux esophagitis due to liraglutide administration. Liraglutide's action inhibits gastric motility. Physicians should be cognizant of the side effects of GLP-1 agonists even in low dose in patients who have gastric emptying symptoms suggesting GP.


Studying the effect of oxygen availability and matrix structure on population density and inter-strain interactions of Listeria monocytogenes in different dairy model systems.
Due to the ubiquitous character of Listeria monocytogenes multiple strains of the pathogen may end up co-existing in/on the same final products and could potentially cause infection during consumption. Such multiple strain contamination may occur in different stages of the food supply chain. The present study evaluated the effect of oxygen availability and matrix structure on inter-strain interactions of L. monocytogenes that may occur at high population levels in/on different dairy model systems. L. monocytogenes strains C5 and ScottA (4b), 6179 (1/2a) and PL25 (1/2b) were selected as resistant to different antibiotics (enabling selective enumeration of each strain in co-culture) and inoculated (2.0-3.0 log CFU/mL, g or cm2) in Ricotta and Camembert broth (1 dairy product: 2 ¼ Ringer solution) and in/on dairy-based structured media (dairy broth supplemented with 0.6 and 1.4% agar), in single and two-strain cultures (1:1 strain ratio). Bacterial growth was assessed during storage at 7 °C, under aerobic, hypoxic and anoxic conditions. Every experimental treatment was tested with three biological replicates and two technical repeats (n = 3 × 2). The simultaneously presence of different strains of the pathogen in/on the same substrate did not affect neither the duration of the lag phase nor the growth rate of the co-cultured strains. The observed inter-strain interactions were related with the final population reached/decrease during storage and occurred after the "critical" population density of ca. 6.0 log CFU/mL, g or cm2. The phenomenon was more pronounced in/on Ricotta than in/on Camembert-based substrates, indicating that the composition and the available nutrients of the substrate may affect the interactions that expressed as difference in the final population level between singly and co-cultured strains. Under aerobic and hypoxic conditions, most of the observed interactions were more pronounced in dairy-based broths and were mitigated with the addition of agar. The elimination of oxygen resulted in a prolonged lag time, which lasted at least 5 days and no observed interactions by the end of storage, due to low microbial counts. Investigating inter-strain interactions during growth in/on different substrates, which may have undergone temperature abuse during their transport along the supply chain or during storage in household refrigerators, could assist in explaining the mismatch between clinical and food samples during outbreak investigations.


Digit loss due to Demodex spp. infestation in a dog: clinical and pathological features.
Here we describe a rare clinical manifestation of canine pododemodicosis. A dog was presented with pedal erythema, scaling, crusting, severe edema and digit loss. The following diseases were taken into account for the differential diagnosis: pododemodicosis, lethal acrodermatitis, zinc responsive dermatosis and pemphigus foliaceus. Results from skin biopsies revealed the presence of Demodex spp. of mites in the follicular infundibula and a severe inflammatory process (pododemodicosis). Upon the acaricidal treatment, the patient exhibited favorable signs of clinical improvement.


Bioleaching of heavy metals from pig manure with indigenous sulfur-oxidizing bacteria: effects of sulfur concentration.
The purpose of this work was to study the sulfur concentration on bioleaching of heavy metals from pig manure employing indigenous sulfur-oxidizing bacteria. Also, the variations in physicochemical properties of pig manure before and after bioleaching were investigated. The results showed that sulfur concentration significantly affected the rate of acidification, sulfate production and metal solubilization during pig manure bioleaching process. A Michaelis-Menten type equation was utilized to interpret the relationships between sulfur concentration, sulfate production and metal solubilization in the bioleaching process. The rates of metal solubilization during pig manure bioleaching were well described by a first order kinetic equation related to time. After 12 days of bioleaching, 93%-97% of Zn, 96%-98% of Mn and 48%-94% of Cu were leached out from pig manure, respectively. The metals remaining in the pig manure residual were mainly existed in stable forms. In addition, elemental analysis showed that bioleaching process could significantly modify the dewaterbility and organic composition of pig manure. However, fertility analysis found that 9.0%-19.1% of nitrogen, 68.5%-71.0% of phosphorus, 76.5%-78.8% of potassium and 47.5%-49.4% of the total organic carbon (TOC) were lost from pig manure in the bioleaching process. Therefore, bioleaching process used in this study could be applied to remove heavy metals effectively from the pig manure, but more detailed studies need to be done to decrease the nutrients loss from pig manure.


Demographic and clinical characteristics of patients with ANCA-positive vasculitis in a Colombian University Hospital over a 12-year period: 2005-2017.
Vasculitides associated with anti-neutrophil cytoplasmic antibodies are heterogeneous, systemic, low prevalence and high morbidity and mortality entities. They include granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. In Latin America, there are few descriptive registries of these patients. The objective of the study was to describe the demographic and clinical characteristics and in-hospital morbidity and mortality of patients with vasculitis associated with anti-neutrophil cytoplasmic antibodies in a university hospital in Colombia. This was a cross-sectional descriptive study. We performed computer searches with terms related to patients with anti-neutrophil cytoplasmic antibody-associated vasculitis, between 2005 and 2017 who met the American College of Rheumatology classification criteria for vasculitis associated with anti-neutrophil cytoplasmic antibodies, and their clinical and laboratory characteristics. One hundred and six patients with anti-neutrophil cytoplasmic antibody-associated vasculitis were included in the study. The average age was 55 years, and 57.5% were women. In 68.8% of the cases, the diagnosis was made during hospitalization, with an average hospital stay of 16.6 days (± 12.22). The distribution by type of vasculitis was: granulomatosis with polyangiitis 52%, microscopic polyangiitis 45.2% and eosinophilic granulomatosis with polyangiitis 1.8%. Alveolar hemorrhage occurred in 35% of patients; 20.7% had variable renal involvement, of which 53.8% progressed to advanced kidney disease. Treatment included glucocorticoids 91.5%, cyclophosphamide 62.2%, plasmapheresis 14.1%, and 41.5% required renal replacement therapy. In-hospital mortality was 16.5%, Sepsis was the most common cause of death. We present clinical information on a group of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis; renal involvement was the the most common type of affectation. Both the clinical and serological characteristics of our registry were similar to those described in other Latin American and European cohorts, and a lower in-hospital mortality rate was evidenced.


ERK differentially regulates Th17- and Treg-cell development and contributes to the pathogenesis of colitis.
Although the development of T-cell subsets is mainly regulated by a master transcriptional regulator and phosphorylation of the STAT protein in response to distinct cytokine stimulation, accumulating data indicate that other signaling pathways are also involved in regulating or fine-tuning T-cell lineage commitment. In this report, we investigated the role of ERK, mitogen-activated protein kinase (MAPK), in Th17 and Treg cell development. We demonstrate that blockade of ERK activation inhibited Th17-cell development while upregulating Treg cells under Th17 polarization conditions. Inhibition of ERK decreased IL-6 induction of RAR-related orphan receptor γt but enhanced TGF-β induction of Foxp3, and ERK inhibitor-treated T cells under Th17 conditions possessed suppressive function in vitro because they produced more IL-10 and TGF-β and inhibited naïve T-cell proliferation and IFN-γ production at levels comparable with that of Treg cells. Furthermore, ERK inhibitor-treated T cells under Th17 polarization conditions had a decreased potency to induce colitis in vivo. Collectively, our data demonstrated that the ERK pathway differentially regulates Th17- and Treg-cell differentiation, and thus interfering with the ERK pathway could represent a therapeutic treatment for inflammatory bowel diseases and other Th17-related autoimmune diseases.


Determination of the aminoglycoside antibiotics sisomicin and netilmicin in dried blood spots on filter discs, by high-performance liquid chromatography with pre-column derivatization and fluorimetric detection.
A simple method for the determination of the aminoglycoside antibiotic sisomicin or its 1-N-ethyl derivative, netilmicin in whole blood, using dried blood spots (DBSs) on filter-paper punched discs has been developed. Sisomicin or netilmicin in the DBSs were recovered most effectively in 0.5 M Na2HPO4 using ultrasonication. The eluates from the DBSs were treated by ultrafiltration for deproteinization and subjected to pre-column fluorescent derivatization using o-phthalaldehyde and beta-mercaptopropionic acid in 0.05 M KH2PO4-borate buffer (pH 9.0), followed by determination by reversed-phase high-performance liquid chromatography. The detection limits of sisomicin and netilmicin in the DBSs on punched discs (10.1 microliters of whole blood) were 0.053 and 0.50 micrograms per ml of whole blood, respectively (signal-to-noise ratio greater than or equal to 2). The method permits a simple collection of blood at the microlitre level and should prove particularly useful for monitoring sisomicin and netilmicin in blood at therapeutic levels in geriatric and paediatric patients.


Clinical features and etiology of patients with erythema ab igne: A retrospective multicenter study.
The aim of this study was to investigate the demographic and clinical features, etiology of patients with erythema ab igne (EAI) who presented to our clinics. The present study was conducted on 71 patients who were admitted to our dermatology clinics between April 2018 and June 2019 and were diagnosed with EAI by clinical or histopathological examination. Age, gender, localization of lesions, and etiologic causes of lesions were recorded. Of the 71 patients, 48 (67.6%) were women and 23 (32.4%) were men. The mean age of the patients was 28.6 ± 10.4 years. Most of the lesions were localized (60.6%, n = 43) on the anterior aspect of both legs. Among the etiological reasons, 53 (74.6%) patients had exposure to heater, 14 (19.7%) patients had exposure to stove, 2 (2.8%) patients had laptop use, 1 (1.4%) patient had tandoor contact, and 1 (1.4%) patient had exposure to hot water bag. One patient was diagnosed with bullous EAI. In conclusion, EAI was also more common in females and lower extremities, which is in accordance with the literature. However, the mean age of occurrence in our study is younger when compared with that in the literature. One case of EAI due to the use of tandoor in our study has not been reported previously. It should be kept in mind that bullous EAI may develop in patients with diabetes mellitus.


The second messenger pathway for germ cell-mediated stimulation of Sertoli cells.
Treatment of cultured rat Sertoli cells with FSH or dibutyryl cAMP for 30 min resulted in phosphorylation of the same Sertoli cell proteins. Different Sertoli cell proteins were phosphorylated after calcium ionophore A23187 and 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment. A23187 stimulated the phosphorylation of hsp27, while TPA alone had no effect. TPA plus A23187 resulted in phosphorylation of a 14 kDa protein, in addition to hsp27. The effect of TPA plus A23187 was identical to that of germ cells on Sertoli cell protein phosphorylation. FSH-stimulated cAMP production by Sertoli cells was reduced by prior exposure of Sertoli cells to germ cells. The results indicate that germ cells stimulate Sertoli cells by the inositol trisphosphate/diacylglycerol mediated second messenger pathway. The results also suggest that the germ cell-activated pathway interacts within Sertoli cells to modulate Sertoli cell response to FSH.


Receptor-specific delivery of protein antigen to dendritic cells by a nanoemulsion formed using top-down non-covalent click self-assembly.
A new class of targeted and immune-evading nanocarrier made using only biological components and facile processes is assembled in a bottom-up fashion. Simple top-down sequential addition of immune-evading or receptor-specific antibody elements conjugated to biosurfactant protein DAMP4 promotes self-assembly at an interface previously formed in the presence of peptide surfactant AM1, leading to a functional display at the interface through non-covalent molecular self-assembly.


Man with leg rash.
A 51-year-old male presented to the ED with a rash to his left thigh (figure 1) with erythema, swelling and pain. He endorsed paraesthesias, pruritus, fevers, vomiting and diarrhoea. Initial vitals were unremarkable. He was well appearing with an 8×8 cm violaceous patch on his left medial thigh with vesicles, surrounding erythema and induration with a second, smaller lesion on the right thigh. Both rashes were extremely tender.emermed;34/10/686/F1F1F1Figure 1Erythematosus and vesicular rash in bilateral legs.A bedside ultrasound image of the rash was obtained (figure 2).emermed;34/10/686/F2F2F2Figure 2Bedside ultrasound of rash. What is the most likely cause of the patient's rash?A. Herpes zosterB. CellulitisC. Necrotising fasciitisD. Bullous pemphigoid.


Changes of extracellular potassium activity induced by electric current through brain tissue in the rat.
Ion-selective micro-electrodes have been used to measure K+ and Ca2+ activity changes in extracellular space beneath the surface of the neocortex and cerebellar cortex during current flow across the tissue surface in anaesthetized rats. Inward currents produced decreases of [K+]o and outward currents produced increases, with insignificant changes in [Ca2+]o. Changes of [K+]o were largest just under the surface of the tissue, but were detectable down to depths of ca. 1 mm. With appropriate sitting of electrodes in the cerebellar cortex, currents of 22 microA mm-2 for 400 sec produced changes averaging -42% for inward current and +66% for outward current. The [K+]o changes near the surface were most rapid immediately after the onset of current and more gradual after some tens of seconds. Deeper within the tissue the rate of change was more uniform and after the end of stimulation the return to base line was slower. The amplitude, depth dependence and time course of the [K+]o changes were in reasonable agreement with the results calculated for a model in which K+ moves partly through extracellular space but primarily through membranes and cytoplasm within the tissue. The [K+]o changes were not attributable to variations in neuronal activity, although unit activity could be modified by current, since alternating currents failed to produce [K+]o changes and neither 0.1 mM-tetrodotoxin nor 5 mM-Mn2+ abolished the changes. The [K+]o changes were not abolished by topically applied ouabain (4 X 10(-4) M), 2,4-dinitrophenol (20 mM) or iodoacetate (10 mM), or by asphyxiation. Consequently the [K+]o changes are not dependent on metabolism. The data suggest that there is a selective mechanism for passive K+ transport in an electrochemical gradient within brain tissue that results in higher K+ fluxes than could be supported by ionic mobility in the extracellular fluid. This mechanism exists not only at the surface but within the brain parenchyma and may involve current flow through glial cells.


Correction to: 4-Repeat tau seeds and templating subtypes as brain and CSF biomarkers of frontotemporal lobar degeneration.
The original version of this article unfortunately contained a mistake. The Panel A in the published figure 5 is incorrect. The corrected Figure 5 is placed in the following page.


Adaptive tutorials versus web-based resources in radiology: a mixed methods analysis in junior doctors of efficacy and engagement.
Radiology education is limited in undergraduate Medicine programs. Junior doctors might not have the necessary background to effectively order and interpret diagnostic imaging investigations. Furthermore, junior doctors are often time-poor, balancing clinical commitments with ongoing learning, leadership and teaching responsibilities. Previous studies have demonstrated the efficacy of radiology-themed online adaptive tutorials for senior medical students. Such adaptive tutorials might therefore be an efficient and effective form of radiology education for junior doctors. A randomised controlled crossover trial was performed to evaluate the impact of adaptive tutorials on learning the indications for, and interpretation of, basic imaging studies, compared with peer-reviewed web-based resources. Ninety-one volunteer junior doctors, comprising 53 postgraduate year 1 (PGY 1) and 38 postgraduate year 2 (PGY 2), were randomly allocated into two groups. In the first phase of the trial, focusing on head CT, one group accessed adaptive tutorials while the other received web-based resources. In the second phase of the trial, focusing on chest CT, the groups crossed over. Following each phase of the trial, participants completed exam-style online assessments. At the conclusion of the study, participants also completed an online questionnaire regarding perceived engagement and efficacy of each type of educational resource. Junior doctors completed the adaptive tutorials significantly faster than the relevant web-based resources for both head CT and chest CT (p = 0.03 and < 0.01 respectively). Mean quiz scores were higher in the groups receiving adaptive tutorials on head CT and chest CT (86.4% vs 83.5 and 77.7% vs 75% respectively). However, in contrast to previous studies in senior medical students, these differences were not statistically significant. Participants reported higher engagement and perceived value of adaptive tutorials, compared with web-based resources. Adaptive tutorials are more time-efficient than existing web-based resources for learning radiology by junior doctors, while both types of resources were equally effective for learning in this cohort. Junior doctors found the adaptive tutorials more engaging and were more likely to recommend these resources to their colleagues.


Warfarin necrosis of the skin and subcutaneous tissue of the male external genitalia.
Gangrene of the male external genitalia is an uncommon urologic problem with a limited differential diagnosis. To the etiologic spectrum we add warfarin-induced penile gangrene. Pathophysiology, diagnosis and treatment are discussed.


Human hepatocellular carcinoma tumor xenografts. Their androgen-receptor status and growth responses to castration.
Castrated or sham-operated male athymic mice were inoculated with cells from the human hepatocellular carcinoma cell line PLC/PRF/5. There were no significant differences between the two groups with respect to the number of animals developing tumors, the time to tumor development, or the subsequent rate of increase in either tumor base area or mouse serum alpha-fetoprotein concentration. Androgen receptors were assayed in nuclei obtained from three separate liver cancer cell lines and from normal adult human liver. Similar concentrations, ranging from 235 to 550 fmol/mg DNA, of nuclear androgen receptors were detected in all tissues. Low percentages of androgen receptors were retained on DNA-cellulose. Although the presence of receptors implies the potential for metabolic effects of androgens in normal and malignant liver, our in vivo studies suggest that castration does not alter significantly the growth of liver cancer xenografts in athymic mice.


Monitoring the succession of the biota grown on a selective medium for pseudomonads during storage of minced beef with molecular-based methods.
In the present study, the succession of the biota grown on a selective medium for pseudomonads (pseudomonas agar based medium - PAB) during the storage of meat under different conditions was monitored. Thus, minced beef was stored aerobically and under modified atmosphere packaging in the presence (MAP+) and absence (MAP-) of oregano essential oil at 0, 5, 10 and 15 °C. A total of 267 pure cultures were recovered from PAB throughout the storage period and subjected to PCR-Denaturing gradient gel electrophoresis (PCR-DGGE) for their differentiation. In parallel, the direct analysis of the whole cultivable community (WCC) from the same medium was applied. These two approaches were used in order to indicate the lack of selectivity. Fifteen different DGGE fingerprints were obtained after PCR - DGGE analysis of the isolates, which were assigned to Pseudomonas putida (3 fingerprints), Pseudomonas fragi and Pseudomonas fluorescens, Pseudomonas spp., Serratia liquefaciens (2), Citrobacter freundii, Serratia grimesii, Hafnia alvei (3), Rahnella spp. and Morganella morganii. Twelve of them occurred during the direct analysis of the WCC. The biota succession found to be affected from the different storage conditions. However, the outcome of the two strategies was quite different, which is leading to the use of different appropriated molecular approaches in order to widen the knowledge of bacterial succession of meat.


The culture of human osteoblasts upon bone graft substitutes.
In order to assess the ability of six potential bone graft substitutes to support the growth of human osteoblasts, these cells were grown in culture and then plated onto fragments of the six materials and cultured for a further period of 15 days. Tests to confirm the osteoblastic phenotype of the cells included spectrophotometric alkaline phosphatase assay; Western blotting of secreted osteocalcin, osteonectin, bone sialoprotein, and collagen type I; and mineralization within the cultures provided with a supplemented medium. Cells were seeded onto the materials in 24-well plates (Nunc, Naperville, IL) at density levels 12,500 cells/cm2 and 25,000 cells/cm2. Specimens were examined after the 15-day culture period by scanning electron microscopy. At a seeding density of 12,500 cells/cm2 results showed that the human osteoblasts had greatest affinities for demineralized rat bone and demineralized Surgibone, whilst few osteoblasts were found attached to Pyrost, Surgibone, or coral. The collagen matrix of Callopat hydrated in the culture media exposing the hydroxyapatite crystals within it, and these became the foci for cell attachment and growth. At a seeding density of 25,000 cells/cm2 the osteoblasts had attached to and proliferated upon the surfaces of all the materials, forming multilayers, with the exception of Surgibone. These experiments demonstrated that all the materials, with the exception of nondemineralized Surgibone, were biocompatible for human osteoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)


Eczematous dermatitis due to subcutaneous teriparatide injection.
Teriparatide, or recombinant human parathyroid hormone, is approved for the treatment of osteoporosis. Possible cutaneous adverse events of teriparatide are urticaria, injection site pain, swelling, bruising, and pruritus. However, there have been no reports of widespread eczematous reactions caused by teriparatide. A 47-year-old male was recently diagnosed with osteogenesis imperfecta and prior to teeth extractions, he was subcutaneously injected with teriparatide. The patient developed multiple pruritic erythematous papules and plaques on his abdomen, around the site of the injection. A skin biopsy was done, which showed mild spongiosis and superficial perivenular lymphocytic infiltration with a few eosinophils. Drug-related eczematous changes were most likely suspected and in addition to the discontinuation of the injection, topical steroid was prescribed, in which dramatic improvements were observed. We report the eczematous hypersensitivity reaction caused by teriparatide, which is an adverse reaction that has not been reported before.


Soft-tissue dimensional change following guided bone regeneration on peri-implant defects using soft-type block or particulate bone substitutes: 1-year outcomes of a randomized controlled clinical trial.
To compare the peri-implant soft-tissue dimensional changes following guided bone regeneration between particulate (particle group) and collagenated soft-block-type (block group) biphasic calcium phosphate (BCP). This study investigated 35 subjects: 18 in the particle group and 17 in the block group. Cone-beam computed tomography obtained at 6 months post surgery and optical impressions taken periodically (before surgery, 6 months post surgery, and 1 year post surgery) were superimposed. The ridge contour changes over time and the peri-implant mucosal thicknesses were measured diagonally and horizontally, and analysed statistically. The increases in diagonal (1.12 ± 0.78 mm) and horizontal (2.79 ± 1.90 mm) ridge contour of the block group were significantly higher than those in the particle group during the first 6 months (p < .05); however, the contour hardly changed thereafter (diagonal: 0.07 ± 0.75 mm; horizontal: -0.34 ± 1.26 mm), resulting in the 1-year contour changes similar between the two groups. Regardless of the type of BCP, the ridge contour increased significantly over 1 year when the dehiscence defect had a contained configuration (p < .05). The increase in soft-tissue dimensions for 1 year was similar between the two groups. The mucosal contour increase was larger when the surgery was conducted in a more contained defect, and this was not influenced by the type of BCP.


The importance of hemodynamic considerations in essential hypertension.
Hypertension is a major risk factor for cardiovascular morbidity and mortality. Antihypertensive therapy consistently reduces complications from stroke and congestive heart failure, whereas benefits from the treatment of ischemic heart disease events are variable. Several plausible explanations, including hemodynamic hypotheses, have been put forth to account for the failure of treatment to more favorably influence mortality from ischemic heart disease. The effect of hypertension on coronary heart disease is probably much more complex than a simple elevation of arterial pressure. Some of these complexities include the potential separate risks of high total peripheral resistance, high cardiac output, increased myocardial power that reflects pressure times flow, and several structural and functional vascular changes. These factors may act in concert to unfavorably alter the balance between myocardial oxygen supply and demand. Several of these factors will be highlighted in an attempt to offer alternative or adjunctive pathophysiologic examinations for the high-risk subgroups of obesity and the failure of antihypertensive therapy to normalize the rate of coronary heart disease events.


Butriptyline: improved gas-liquid chromatographic method using a nitrogen-phosphorus detector for its determination in serum.
We report a sensitive and specific method for the determination of butriptyline concentrations in serum by gas-liquid chromatography with a nitrogen phosphorus detector. The detection limit is 2 ng/ml, based on 3 ml of serum or plasma. The method has been validated in human volunteers receiving a single oral dose of 75 mg butriptyline hydrochloride.


Latent ocular deviations in patients with advanced AIDS.
The purpose of this study is to determine horizontal latent ocular deviations in patients with advanced AIDS (CD4+ count <0.050 x 10(9)/l) and to compare with normal values by means of the von Graefe technique. Twenty patients aged between 17 and 44 years with AIDS and aged-matched control groups were submitted to study. The AC/A ratio was also measured in both groups using the Gradient test. The AIDS patients showed a horizontal latent deviation value of 0.28+/-1.07delta exo at near (40 cm.) and 2.12+/-1.37delta eso at distance (6 m). The AC/A ratio obtained was 2.03+/-0.65. Statistically significant differences were obtained in relation to aged-matched control group at near and at distance (p<0.01). The horizontal latent ocular deviation at near and at distance in advanced AIDS patients showed lower values than the expected. The AC/A relationship also was lower. The results obtained in this study indicate that AIDS patients suffer a divergence insufficiency, which could add to other visual complaints such as blurred vision, photophobia, nyctalopia and reading difficulty.


Contrast media-related complications during cardiac catheterization using Hexabrix or Renografin in high-risk patients.
Contrast media may lead to adverse reactions during cardiac catheterization. Hexabrix has less hemodynamic and electrophysiologic effects than Renografin-76. To assess relative complication rates using these agents, 82 patients with heart failure or "unstable" ischemic syndromes and undergoing catheterization were prospectively randomized to receive either Hexabrix or Renografin. Clinical diagnoses, hemodynamics before contrast media administration, left ventricular ejection fraction, case duration, contrast volume and cine film quality were similar in the 2 groups. The condition of 1 patient assigned to receive Renografin was deemed too unstable and Hexabrix was safely used. In the other patients, a total of 17 adverse reactions occurred (7 before administration of contrast and thus unrelated: 4 Hexabrix- and 3 Renografin-assigned patients, difference not significant). Three contrast-induced adverse reactions were considered minor (Hexabrix 2, Renografin 1, difference not significant). Severe adverse reactions requiring intervention, such as pulmonary edema and hypotension, were more frequent in patients who received Renografin (6 of 38, 16%) as compared with Hexabrix (1 of 43, 2%) (p less than 0.05). It is concluded that in high-risk patients undergoing cardiac catheterization, Hexabrix is tolerated better than Renografin and should be considered for routine use.


Oral HIV Self-Implemented Testing: Performance Fidelity Among African American MSM.
Oral-Self Implemented HIV Testing (Oral-SIT) offers a low-cost way to extend the reach of HIV testing systems. It is unclear, however, if high risk populations are able to perform the test with high fidelity. Using a simulation-based research design, we administered desensitized Oral-SIT kits to African American MSM (AAMSM; 17-24 years, N = 178). Participants were HIV negative or never tested, and had never self-administered an Oral-SIT kit. We assessed performance fidelity, and hypothesized antecedents. High levels of social stigma were associated with lower levels of training knowledge (Range = No Errors: 51.9%, 4 Errors: 0.6%) and performance fidelity (Range = No Errors: 39.9%, 3 Errors: 1.7%). Training knowledge and prior testing history were positively associated with performance fidelity. The present work extends research on HIV-related social stigma and suggests that social stigma inhibits knowledge acquisition and task performance. The Oral-SIT training materials were understood by individuals with a wide-range of educational backgrounds. Interventions are needed, however, to further improve Oral-SIT performance fidelity.


Histone deacetylase inhibitor AR42 regulates telomerase activity in human glioma cells via an Akt-dependent mechanism.
Epigenetic regulation via abnormal activation of histone deacetylases (HDACs) is a mechanism that leads to cancer initiation and promotion. Activation of HDACs results in transcriptional upregulation of human telomerase reverse transcriptase (hTERT) and increases telomerase activity during cellular immortalization and tumorigenesis. However, the effects of HDAC inhibitors on the transcription of hTERT vary in different cancer cells. Here, we studied the effects of a novel HDAC inhibitor, AR42, on telomerase activity in a PTEN-null U87MG glioma cell line. AR42 increased hTERT mRNA in U87MG glioma cells, but suppressed total telomerase activity in a dose-dependent manner. Further analyses suggested that AR42 decreases the phosphorylation of hTERT via an Akt-dependent mechanism. Suppression of Akt phosphorylation and telomerase activity was also observed with PI3K inhibitor LY294002 further supporting the hypothesis that Akt signaling is involved in suppression of AR42-induced inhibition of telomerase activity. Finally, ectopic expression of a constitutive active form of Akt restored telomerase activity in AR42-treated cells. Taken together, our results demonstrate that the novel HDAC inhibitor AR42 can suppress telomerase activity by inhibiting Akt-mediated hTERT phosphorylation, indicating that the PI3K/Akt pathway plays an important role in the regulation of telomerase activity in response to this HDAC inhibitor.