OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion.
Mitochondria amplify activation of caspases during apoptosis by releasing cytochrome c and other cofactors. This is accompanied by fragmentation of the organelle and remodeling of the cristae. Here we provide evidence that Optic Atrophy 1 (OPA1), a profusion dynamin-related protein of the inner mitochondrial membrane mutated in dominant optic atrophy, protects from apoptosis by preventing cytochrome c release independently from mitochondrial fusion. OPA1 does not interfere with activation of the mitochondrial "gatekeepers" BAX and BAK, but it controls the shape of mitochondrial cristae, keeping their junctions tight during apoptosis. Tightness of cristae junctions correlates with oligomerization of two forms of OPA1, a soluble, intermembrane space and an integral inner membrane one. The proapoptotic BCL-2 family member BID, which widens cristae junctions, also disrupts OPA1 oligomers. Thus, OPA1 has genetically and molecularly distinct functions in mitochondrial fusion and in cristae remodeling during apoptosis.


The functions of IRE1α in neurodegenerative diseases: Beyond ER stress.
Inositol-requiring enzyme 1 α (IRE1α) is a type I transmembrane protein that resides in the endoplasmic reticulum (ER). IRE1α, which is the primary sensor of ER stress, has been proven to maintain intracellular protein homeostasis by activating X-box binding protein 1 (XBP1). Further studies have revealed novel physiological functions of the IRE1α, such as its roles in mRNA and protein degradation, inflammation, immunity, cell proliferation and cell death. Therefore, the function of IRE1α is not limited to its role in ER stress; IRE1α is also important for regulating other processes related to cellular physiology. Furthermore, IRE1α plays a key role in neurodegenerative diseases that are caused by the phosphorylation of Tau protein, the accumulation of α-synuclein (α-syn) and the toxic effects of mutant Huntingtin (mHtt). Therefore, targeting IRE1α is a valuable approach for treating neurodegenerative diseases and regulating cell functions. This review discusses the role of IRE1α in different cellular processes, and emphasizes the importance of IRE1α in neurodegenerative diseases.


Designing of immunodiagnostic assay using polyclonal antibodies for detection of Shiga toxin producing pathogenic E. coli (STEC) strains.
Shiga toxin-producing Escherichia coli (STEC) are the leading causes of diarrhea and death of humans worldwide. Many diagnostic assays have been developed to aid for the diagnosis of STEC strain; however, they have limitations. Thus, this study was aimed at designing rapid, effective, sensitive and specific immunodiagnostic assay for STEC strain detection. Thus, a STEC isolate from Ethiopia was processed for LPS extraction and the LPS was used to immunize mice.. The produced antibody showed positive agglutination both on the purified LPS as well as the STEC isolate carrying LPS on their surface; however, agglutination of STEC was more pronounced. Mice immunized with LPS produced highest agglutination on tertiary immunization showing the progressive buildup of the antibody response against the antigen. Cultures from tryptone soya agar and when they refresh showed better agglutination than cultures on EMB as well as tryptone soya broth. Immunodiagnostic assay developed in this study could detect STEC strains including STEC in human feces rapidly (1-2 min), with high sensitivity (90.2%), specificity (89.5%) and accuracy (90.6%). However, further studies are still required to improve the sensitivity, specificity and reproducibility. Overall this diagnostic assay provided promising results that may curb current problem with detection methods in clinical health care and research laboratories.


Is There an Overlap in Immune Response Between Allergic Bronchopulmonary and Chronic Pulmonary Aspergillosis?
Chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA) are presumed to represent 2 distinct manifestations of Aspergillus species in the lung. To investigate any possible overlap of the immunological tests used for diagnosing ABPA in proven cases of CPA. In consecutive subjects with CPA, we calculated the proportion of subjects who tested positive for all the immunological investigations used to diagnose ABPA (Aspergillus fumigatus specific IgE >0.35 kUA/L, total IgE ≥500 IU/mL, and eosinophil count ≥500 cells/μL) or obligatory criteria (A. fumigatus specific IgE >0.35 kUA/L and total IgE ≥500 IU/mL). A total of 269 subjects (53.5% males) of CPA with the mean (standard deviation [SD]) age of 44.3 (14.7) years were enrolled. The most common underlying disease was previously treated pulmonary tuberculosis (n = 230, 85.5%). Ninety-three (34.6%) subjects had total IgE ≥500 IU/mL, whereas A. fumigatus specific IgE >0.35 kUA/L was seen in 112 (41.6%) subjects. Thirteen (4.8%) subjects met all the immunological criteria for ABPA, whereas 59 (21.9%) subjects met the obligatory criteria. Subjects meeting the obligatory criteria had significantly higher eosinophil count (P ≤ .0001), greater immediate cutaneous reactivity to Aspergillus antigen (CPA-others vs obligatory criteria, 9.8 ± 13.9 vs 13.9 ± 14.9 mm, P value = .048), higher A. fumigatus specific IgG (99.3 ± 61.9 vs 122 ± 66.6 mgA/L, P = .015), and greater number of fungal balls (0.9 ± 0.7 [range, 0-3] vs 1.1 ± 0.9 [range, 0-4], P = .026) compared with those without. Approximately 5% of subjects with CPA fulfilled all the immunological criteria used for diagnosing ABPA, whereas 22% met the obligatory criteria for ABPA. Whether these patients would require a different management protocol requires further investigation.


Corrigendum to "Fever of unknown origin and liver mass in a Saudi child" [Int J Pediatr Adolesc Med 2 (2) (2015) 79-83].
[This corrects the article DOI: 10.1016/j.ijpam.2015.06.002.].


Vildagliptin as add-on therapy to insulin improves glycemic control without increasing risk of hypoglycemia in Asian, predominantly Chinese, patients with type 2 diabetes mellitus.
The aim of the present study was to investigate the efficacy and safety of vildagliptin added onto insulin with or without metformin in an Asian, predominantly Chinese, population with type 2 diabetes mellitus (T2DM). In this 24-week, multicenter, double-blind, placebo-controlled trial, patients with T2DM inadequately controlled (HbA1c 7.5%-11.0%) on stable therapy with long-acting, intermediate-acting, or premixed insulin, with or without concomitant metformin, were randomized to receive vildagliptin 50 mg b.i.d. or placebo. Of 293 patients randomized, 146 received vildagliptin and 147 received placebo treatment. At baseline, the overall mean age of patients was 58.1 years, mean T2DM duration was 11.3 years, and mean HbA1c was 8.7%. The adjusted mean (±SE) change in HbA1c at Week 24 in the vildagliptin and placebo groups was -1.08 ± 0.12% and -0.38 ± 0.12%, respectively (between-treatment difference -0.70 ± 0.16%; P < 0.001). The between-group difference in fasting plasma glucose was -0.43 ± 0.38 mmol/L (P = 0.259). Significantly, more patients achieved HbA1c <7.0% with vildagliptin than with placebo (23.6% vs. 11.2%; P = 0.006). The incidence of adverse events in the vildagliptin and placebo groups was 43.8% and 46.3%, whereas that of serious adverse events was 3.4% and 6.8%, respectively. The frequency of hypoglycemia was lower in the vildagliptin than placebo group (2.7% vs. 5.4%). The addition of vildagliptin 50 mg b.i.d. significantly improved glycemic control without an increased risk of hypoglycemia in Asian, predominantly Chinese, patients with T2DM inadequately controlled on insulin, with or without metformin.


Pharmacokinetics and biotransformation of the prostacyclin analogue, ZK 36 374. III. Development of a radioimmunoassay and its application to the pharmacokinetics of ZK 36 374 in the rat.
The development of a radioimmunoassay for ZK 36 374, a chemically stable prostacyclin analogue, and its application to the pharmacokinetics of the drug in the rat is described. Antiserum against ZK 36 374 was raised in rabbits by immunization with ZK 36 374 coupled to bovine serum albumin via the carboxylic group. ZK 36 374 is extracted from plasma samples and purified from matrix constituents by means of octadecyl silyl cartridges. At a plasma concentration of 2.5 ng/ml intra- and interassay variations are 6 and 7%, respectively. The limit of detection is 0.5 ng/ml. After intravenous administration of 200 micrograms/kg to female Wistar rats a biphasic decline of the drug concentration in the plasma was observed with half-lives of 5 min and 3 h. Oral doses of 200 and 2000 micrograms/kg were very rapidly absorbed reaching maximum plasma levels of 3 and 32 ng/ml as early as 10-15 min p.admin.. Bioavailability at the two dose levels was calculated to be 8 and 13% of dose. Disposition was biphasic, as well, with a somewhat prolonged beta-phase after the highest dose.


Biochemical large-scale identification of MHC class I ligands.
The large-scale identification of MHC class I presented peptides is indispensable for gaining insight into the fundamental rules of immune recognition as well as it is an invaluable tool in identifying potential targets for the immunotherapy of disease. In this chapter we briefly review the existing strategies for the analysis of MHC ligandomes and provide an in-depth protocol for the immunoaffinity purification of MHC class I presented peptides from primary tissues or cells.


Incidence of xerostomia in locally advanced head-and-neck cancers in elderly patients treated with intensity-modulated radiotherapy.
Dysphagia and xerostomia are the main sequelae of radiotherapy for head and neck cancer (HNC) and the main factors in reducing the longterm patient quality of life. Intensitymodulated radiotherapy (IMRT) uses advanced technology to focus the high radiation doses on the targets and avoid irradiation of noninvolved tissues. During 2016-2017, 44 patients of locally advanced HNCs were treated with a curative intent with IMRT. They were in the age range of 65-75 years. The median age was 69 years. Thirtyfive patients were male and nine patients were female. Histopathologically, all had squamous cell carcinoma. Stage wise all were T3N2 or more. No concurrent chemotherapy was given. The Eastern Clinical Oncology Group criteria were used for grading the toxicities. Patients were assessed after 4 weeks of completion of treatment. The incidence of mucositis was of Grade 1-2 in 37 patients. Moreover, patients experienced severe mucositis. Six patients had treatment interruptions due to mucositis. Xerostomia was Grade 1-2 in 42 patients and Grade 3 in 2 patients. Dysphagia was Grade 1-2 only. No hematological toxicity was seen. Patients having dysphagia during the treatment were given nasogastric feed. Response wise 14 patients achieved complete response, 28 patients had partial response, and 2 had stable disease. There was no treatmentrelated mortality.


Transport and metabolism of folates by bacteria.
Transport of labeled folic acid (PteGlu), pteroylpolyglutamates (PteGlu3-5), 5-methyl-tetrahydrofolate (5-methyl-H4PteGlu), and methotrexate in late-log phase cells of Lactobacillus casei was active, and subject to inhibition by unlabeled pteroylmonoglutamates, pteroylpolyglutamates, and iodoacetate, but not glutamate or glutamate dipeptides. Pteroylpolyglutamates were transported without prior hydrolysis and shared a common uptake system with pteroylmonoglutamates. The affinity and maximum velocity of PteGlun uptake decreased with increasing glutamate chin length (Km:PteGlu1, 0.03 mum; PteGlu3, 0.32 mum; PteGlu4, 1.9 mum; PteGlu5, 3.7 mum) and comparisons with growth response curves suggested that polyglutamates were more effectively utilized by L. casei, once transported, than monoglutamate. No concentration of 5-methyl-H4PteGlu3-8 inside the cells was observed. The major folate metabolites found in L. casei preloaded with high levels of [3H]PteGlu (0.5 mum) were 10-formyl-H4PteGlu2 and 10-formyl-PteGlu. Both compounds were released, the monoglutamate more rapidly. Pteroyltriglutamate formation appeared to be a rate-limiting step in intracellular metabolism. No 10-formyl-Pte-Glu was found in iodoacetate-treated cells and efflux was inhibited. Cells preloaded with low levels of [3H]PteGlu (7 nm) metabolized the vitamin to polyglutamate forms, the major derivatives being H4PteGlun. First order exit rates of labeled folate from preloaded L. casei indicated an inhibition of PteGlu uptake with time. Exit rates dropped from 0.05 min-1 to greater than 0.002 min-1 as intracellular folate was metabolized from monoglutamate to polyglutamate derivatives (n larger than or equal to 3). In the latter case, materials lost by efflux were breakdown products and no folate of glutamate chain length greater than two was released. Pediococcus cerevisiae actively transported 5-methyl-H4PteGlu but did not take up to 5-methyl-H4PTeGlu3-8. No active accumulation of 5-methyl-H4PteGlu was observed in Streptococcus faecalis.


Abdominal stab wounds: self-inflicted wounds versus assault wounds.
Intentional penetrating wounds, self inflicted or inflicted by others, are increasingly common. As a result, it can be difficult for the forensic examiner to determine whether the cause is self-inflicted or not. This type of trauma has been studied from a psychological perspective and from a surgical perspective but the literature concerning the forensic perspective is poorer. The objective of this study was to compare the epidemiology of abdominal stab wounds so as to distinguish specific features of each type. This could help the forensic scientist to determine the manner of infliction of the wound. We proposed a retrospective monocentric study that included all patients with an abdominal wound who were managed by the visceral surgery department at Angers University Hospital. Demographic criteria, patient history, circumstances and location of the wound were noted and compared. A comparison was drawn between group 1 (self inflicted wound) and group 2 (assault). This study showed that the only significant differences are represented by the patient's prior history and the circumstances surrounding the wound, i.e. the scene and time of day. In our study, neither the site, nor the injuries sustained reveal significant clues as to the origin of the wound. According to our findings, in order to determine the cause, the forensic examiner should thus carefully study the circumstances and any associated injuries.


The impact of pancreatic duct drainage following pancreaticojejunostomy on clinical outcome.
The aim of this meta-analysis is to evaluate the effect of stenting the pancreatic duct during pancreaticojejunostomy formation on perioperative outcomes. Primary outcome measures were operative mortality and pancreatic fistula. Secondary outcomes were length of hospital stay, reoperation, delayed gastric emptying, estimated blood loss, and length of operation. Internal and external pancreatic stents were grouped together for the purposes of analysis. Six trials were included in this analysis comprising 732 patients. Pancreatic stent placement had no significant effect on operative mortality; however, there was a non-significant trend towards reduced pancreatic fistula. Estimated blood loss, length of operation, and length of hospital stay were significantly increased in association with pancreatic stent placement. There were no significant effects on reoperation or delayed gastric emptying. This analysis demonstrates a trend towards reduced pancreatic fistula with the use of pancreatic stents in pancreaticojejunostomy. However, there were insufficient data to confidently reject the null hypothesis that stenting has no beneficial effect. Further research is required to identify whether in certain subgroups, such as those with soft pancreatic texture and a non-dilated duct, stents may have a more important role in reducing fistula formation.


Collaborative environment for clinical reasoning and distance learning sessions.
The medical curriculum has changed with the adoption of the student-centered learning paradigm. Clinical reasoning learning (CRL) is used in order to develop and improve students' clinical reasoning and problem-solving skills. We have observed that, in complement to traditional CRL sessions, students commonly consult resources available on the internet. Based on this observation, our objective is to create computer tools to coordinate CRL sessions at distance, integrating these electronic resources at every step of the reasoning process. In order to create the system, we elaborated an object-oriented model of a computer-supported collaborative learning environment. The proposed system includes a local web-server to store electronic resources and a relational database to store their electronic addresses (urls). JAVA was used as the programming language. We developed a set of cooperative platform-independent tools. This environment includes a communication tool. Multimedia data exchange is possible. Information is shared thanks to an electronic notepad and whiteboard tools. This learning environment will be integrated in the French Virtual Medical University project, and is intended to be used for undergraduate, internships, residency or continuing medical education.


The novel compound Z060228 inhibits assembly of the HBV capsid.
The effective anti-HBV drugs on the market are mainly immunomodulators or nucleoside analogs. The uses of INF-α and lamivudine (3TC) are considerably limited by their low response rate, side effects, drug resistance and HBV recurrence. Thus, new mechanism-based drugs remain in urgent need. This study aimed to investigate the anti-HBV effects of the novel compound Z060228 and to confirm its anti-HBV mechanisms. HepG2.2.15 cells and HBV-transgenic mice were used to evaluate the anti-HBV activity of Z060228. Conformational changes of the capsid structure induced by Z060228 were detected with high-resolution electron microscopy (EM), size-exclusion chromatography (SEC), and atomic force microscopy (AFM). The HBV DNA replication in the supernatants of the HepG2.2.15 cells was effectively inhibited by Z060228 and Bay41-4109. In the liver of HBV-transgenic mice, the HBcAg content was significantly decreased and HBV DNA replication was also inhibited after high-dose (30 mg/kg) Z060228 treatment. Z060228 and Bay41-4109 exhibited similar effects on the self-assembly of Cp149. SEC data revealed that Z060228 altered the equilibrium (a state of stability) of Cp149 assembly. EM data further demonstrated that Z060228 could prevent Cp149 from self-assembling to the correct core particles. Additionally, AFM results showed that a low concentration of Z060228 caused Cp149 syncretizing, whereas a high concentration caused Cp149 to polymerize. Z060228 was demonstrated to be a potential capsid targeting anti-HBV drug candidate. The methods employed here could be used as a general strategy to study mechanisms of self-assembling protein-targeted drugs.


Misreporting of contraceptive hormone use in clinical research participants.
Researchers traditionally rely on participant self-report for contraceptive use. We hypothesized that self-reported contraceptive use by clinical research participants may disagree with objectively measured hormonal status. We enrolled women in Harare, Zimbabwe, aged 18-34, who by self-report had not used hormonal or intrauterine contraception for >30 days, or depot medroxyprogesterone acetate for >10 months, into a study designed to assess biologic changes with contraceptive initiation and use. Blood samples obtained at enrollment and each follow-up visit (N=1630 from 447 participants) were evaluated by mass spectrometry for exogenous hormones. We individually interviewed a subset of participants (n=20) with discrepant self-reported and measured serum hormones to better understand nondisclosure of contraceptive use. Discrepant with self-reported nonuse of hormonal contraception, synthetic progestogens were detectable in 120/447 (27%, 95% confidence interval 23%-31%) enrolled women. Measured exogenous hormones consistent with use of contraceptive pills (n=102), injectables (n=20) and implants (n=3) were detected at enrollment, with 7 women likely using >1 contraceptive. In-depth interviews revealed that participants understood the requirement to be hormone free at enrollment (100%). Most (85%) cited partner noncooperation with condoms/withdrawal and/or pregnancy concerns as major reasons for nondisclosed contraceptive use. All interviewed women (100%) cited access to health care as a primary motivation for study participation. Of participants who accurately reported nonuse of hormonal contraception at enrollment, 41/327 (12.5%) had objective evidence of nonstudy progestin use at follow-up that disagreed with self-reported nonuse. Women joining contraceptive research studies may misrepresent their use of nonstudy contraceptive hormones at baseline and follow-up. Objective measures of hormone use are needed to ensure that study population exposures are accurately categorized. Among Zimbabwean women participating in a contraceptive research study, 27% had objective evidence of use of nonstudy contraceptives at enrollment that disagreed with self-report. Studies that rely on self-report to identify contraceptive hormone exposure could suffer from significant misclassification.


Ticks and tick-borne microbes identified through passive and active surveillance in Alaska.
Rapid environmental change in Alaska and other regions of the Arctic and sub-Arctic has raised concerns about increasing human exposure to ticks and the pathogens they carry. We tested a sample of ticks collected through a combination of passive and active surveillance from humans, domestic animals, and wildlife hosts in Alaska for a panel of the most common tick-borne pathogens in the contiguous United States to characterize the diversity of microbes present in this region. We tested 189 pooled tick samples collected in 2019-2020 for Borrelia spp., Anaplasma spp., Ehrlichia spp., and Babesia spp. using a multiplex PCR amplicon sequencing assay. We found established populations of Ixodes angustus Neumann (Acari: Ixodidae), Ixodes uriae White (Acari: Ixodidae), and Haemaphysalis leporispalustris Packard (Acari: Ixodidae) in Alaska, with I. angustus found on a variety of hosts including domestic companion animals (dogs and cats), small wild mammals, and humans. Ixodes angustus were active from April through October with peaks in adult and nymphal activity observed in summer months (mainly July). Although no known human pathogens were detected, Babesia microti-like parasites and candidatus Ehrlichia khabarensis were identified in ticks and small mammals. The only human pathogen detected (B. burgdorferi s.s.) was found in a tick associated with a dog that had recently traveled to New York, where Lyme disease is endemic. This study highlights the value of a combined passive and active tick surveillance system to detect introduced tick species and pathogens and to assess which tick species and microbes are locally established.


Air pollutants and daily number of admissions to psychiatric emergency services: evidence for detrimental mental health effects of ozone.
Aim of the current study is to investigate the associations between daily levels of air pollutants (particulate matter, ozone, carbon monoxide, nitrogen dioxide) and daily admissions for mental disorders to the emergency department of two general hospitals in Umbria region (Italy). We collected data about daily admissions to psychiatric emergency services of two general hospitals, air pollutants' levels and meteorological data for the time period 1 January 2015 until 31 December 2016. We assessed the impact of an increase in air pollutants on the number of daily admissions using a time-series econometric framework. A total of 1860 emergency department admissions for mental disorders were identified. We observed a statistically significant impact of ozone levels on daily admissions. The estimated coefficient of O3 is statistically significant at the 1% level. All other pollutants were not significantly associated with the number of daily admissions. Short-term exposure to ozone may be associated with increased psychiatric emergency services admissions. Findings add to previous literature on existing evidence for air pollution to have an impact on mental health. Ozone may be considered a potential environmental risk factor for impaired mental health.


Air-gap eccentricity fault detection, isolation, and estimation for synchronous generators based on eigenvalues analysis.
Air-gap eccentricity fault causes rotor-stator rub and consequently damage to Synchronous Generators (SGs). In this paper, a fault diagnosis approach to diagnose the eccentricity fault for SGs is presented. In this approach, the state matrix eigenvalues based on the subspace identification are estimated, and those are used for fault diagnosis. Two dq models of SGs in faulty and healthy conditions are employed to present the theoretical foundation of the method. As the main advantage, the introduced fault diagnosis method is working properly for either linear or nonlinear loads of SGs. The stator and field currents and voltages, and rotor rotational speed are required signals in the introduced approach. The method is validated using experimental data of SGs in Iran-Safir (ER24) diesel-electric locomotives.


Indomethacin and salicylate decrease epinephrine-induced glycogenolysis.
Epinephrine (E) produces an immediate (0-30 minutes) rise in hepatic glucose production (Ra), largely due to activation of glycogenolysis; thereafter, E-stimulated gluconeogenesis becomes the major factor maintaining glucose production. To investigate the possible role of arachidonic acid metabolites on Ra during E stimulation, we infused E in trained conscious dogs before and during administration of two inhibitors of arachidonic acid metabolism, indomethacin (INDO) and salicylate (S). On separate days, experimental animals were treated with both oral and IV INDO and oral acetylsalicylic acid and IV sodium salicylate. Ra and glucose utilization (Rd), both in mg x kg-1 min-1, were calculated by isotope dilution using 3-3H-glucose. After achieving steady state specific activity, control (C) and experimental animals (n = 6 per group) received E (0.1 ug x kg-1 min-1) for 150 minutes, raising plasma levels to approximately 1500 pg/mL in each group. In C, plasma glucose (G; mg/dL) rose by 17 +/- 5 at 10 minutes and 19 +/- 3 at 20 minutes due to an initial spike in Ra (2.7 +/- 0.2 to 4.9 +/- 0.5; P less than 0.01) at 10 minutes. INDO and S treatment attenuated this initial (10-20 minutes) rise in G (P less than 0.05) due to a lower stimulated Ra at 10 minutes (3.3 +/- 0.1 with INDO; 3.0 +/- 0.5 with S; P less than 0.05). After 20 minutes Ra was not different in the 3 groups; no overall differences in Rd, glucose clearance, or plasma insulin levels occurred with INDO or S treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


The association between glaucoma and all-cause mortality in middle-aged and elderly Chinese people: results from the China Health and Retirement Longitudinal Study.
This population-based, prospective cohort study investigated the association between glaucoma and mortality in older adults. Participants aged 45 years or older at baseline (47.9% male) were enrolled in 2011 for the China Health and Retirement Longitudinal Study (CHARLS). All-cause mortality was observed during 7 years of follow-up. The baseline data were collected in the 2011 CHARLS, and participants were followed up for 7 years (until 2018). The risk of all-cause mortality was investigated using Cox proportional-hazards regression with age as the time scale, adjusting for significant risk factors and comorbid conditions. Among the 14,803 participants included, the risk of all-cause death was significantly higher among people with glaucoma than among those without glaucoma, after adjustment for other confounders (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.04 to 2.03). In a subgroup analysis based on the mean age of death, among those who were 75 years and older (n=1,231), the risk of all-cause death was significantly higher in patients with glaucoma than in those without glaucoma (HR, 1.89; 95% CI, 1.24 to 1.89). Participants with glaucoma had a higher risk of all-cause mortality, especially those aged 75 years and above. Our findings revealed potential mechanisms underlying an association between glaucoma and all-cause mortality. They also highlighted the importance of glaucoma management to prevent premature death in middle-aged and older adults.


Granuloma faciale: exclusively extrafacial.
We report a case of granuloma faciale over distal extremities in a 60-year-old man without facial lesions who did not show any response to dapsone.


[A correlation of EEG characteristics of pregnant women with the level of their anxiety].
It has been shown that the EEG of pregnant women with high anxiety level is characterized by a lower occipital alpha and theta rhythm spectral power if compared to the EEG of women with low anxiety level. The frequency of the alpha rhythm of their EEG was reliably higher. Pregnant women with high anxiety level with a pregnancy interruption threat diagnosis have an essentially lower occipital alpha rhythm spectral power than women of this group without such a diagnosis. And vice versa, the occipital alpha rhythm spectral power in the EEG of pregnant women with low anxiety level with a pregnancy interruption threat diagnosis is essentially higher and its frequency essentially lower than the EEG of women without that diagnosis. The data received are interpreted as a change in hormone regulation during the pregnancy period, as well as psychogenic influence on the pregnancy.


A novel curricular framework to develop grant writing skills among MD-PhD students.
Physician-scientists have long been in high demand owing to their role as key drivers of biomedical innovation, but their dwindling prevalence in research and medical communities threatens ongoing progress. As the principal avenue for physician-scientist development, combined MD-PhD training programs and NIH-funded Medical Scientist Training Programs (MSTPs) must address all aspects of career development, including grant writing skills. The NIH F-series grants - the F30 grant in particular - model the NIH format of federal funding, and are thus ideal opportunities to acquire biomedical research grant preparation experience. Therefore, in this report, we describe a curricular model through which predoctoral MSTP students obtain exposure to - and training for - F-series grant conceptualization, writing, and evaluation. Since the development of these longitudinal courses, we observed trending improvements in student funding success rates, particularly among original submissions, and perceived benefits among participating students.


alpha-Amylase biosynthesis: evidence for temporal sequence of NH2-terminal peptide cleavage and protein glycosylation.
During the biosynthesis of secretory proteins, an NH2-terminal peptide, referred to as a signal peptide, is cotranslationally cleaved off after the protein enters the cisternal space of the endoplasmic reticulum. It also has been reported that the core glycosylation reaction of some secretory and viral membrane glycoproteins occurs as a cotranslational event. However, despite a huge amount of work, no decisive answer has been given as to the temporal sequence of proteolytic cleavage of the signal peptide and glycosylation on the polysomes for any secretory or membrane glycoprotein. We show here that proteolytically processed and already glycosylated chains of rice seed alpha-amylase exist on the polysomes; furthermore, our results provide direct evidence that glycosylation is preceded by proteolytic processing during the biosynthesis of the alpha-amylase molecule.


Vancomycin dosing chart for use in patients with renal impairment.
A new vancomycin dosing chart for use in patients with impaired renal function is described. The chart has been adapted from a previously published nomogram, based on a linear relationship between vancomycin clearance and creatinine clearance. Doses are designed to achieve an average steady-state serum concentration of approximately 15 mg/L. Use of the chart necessitates first measuring or estimating the patient's body weight and creatinine clearance. The chart provides the advantages of generating an exact dose and dosing interval, as well as being somewhat easier to use than the original nomogram. Predicted average steady-state serum concentrations resulting from the dosing chart range from 12.1 to 18.2 mg/L, with a mean of 15.0 mg/L.


Cartilaginous lesions of bone.
Cartilaginous lesions of the skeleton are very unusual. It is extremely important to correlate the roentgenographic features, the clinical features, and the histological features to arrive at a definite diagnosis. Most cartilaginous lesions are benign or of low-grade malignancy. However, there are some subtypes of chondrosarcoma that behave in a highly aggressive fashion.


Induction of labor in grand multiparous women and previous cesarean section: is it safe?
To compare the outcome of induced and spontaneous labor in grand multiparous women with one previous lower segment cesarean section, so that the safety of labor induction could be assessed. In 56 women labor was induced and their outcomes were compared with those of 177 women with spontaneous labor. All women were multiparous and had had one previous cesarean section. There were no significant differences in the incidences of 1- and 5-min Apgar scores, congenital malformation, cesarean section rates and uterine scar dehiscence or uterine rupture. There were 4 cases of intrauterine fetal death in the induction group, but no case of intrapartum or early neonatal death in the 2 groups. In the study group, 80.4% of the women delivered vaginally compared with 84.3% in the control group. In this moderate-sized study, we may conclude that when there is no absolute indication for repeating cesarean section, induction of labor may be a safe option in these high-risk women.


Effects of tetrandrine on rabbit platelet aggregation and platelet activating factor generation.
To study the effects of tetrandrine (Tet) on platelet aggregation and platelet activating factor (PAF) generation in rabbit platelet-rich plasma (PRP). The aggregation rate of platelets induced by calcimycin (Cal) and PAF and the inhibition rate of Tet on platelet aggregation were measured. The amount of PAF in PRP stimulated with Cal and treated with Tet was also measured. Cal 1-8 mumol.L(-1) and PAF 9.5-190.5 pmol.L(-1) induced platelet aggregation. At the final concentrations of 4-64 mumol.L(-1), Tet inhibited the aggregation induced by Cal 4 mumol.L(-1) and PAF 142.9 pmol.L-1. The IC50 (95% confidence limits) were 8.6 (6.0-12.2) mumol.L-1 for Cal and 14.0 (6.4-30.4) mumol.L(-1) for PAF. In the PRP aggregation by Cal, there was a marked increase in PAF content. Tet dependented the release of PAF from platelets by Cal in a concentration-dependent manner, with IC50 of 21 (8-54) mumol.L(-1). The inhibition effect of Tet on platelet aggregation might be concerned with the reduction of endogenous PAF generation.


Death by hanging while watching violent pornographic videos on the Internet - suicide or accidental autoerotic death?
In deaths by hanging, it may sometimes be difficult to differentiate between autoerotic accident and suicide. Our report deals with a 30-year-old man who was found hanged in the living room of his flat. The deceased was wearing headphones connected to a PC. Within the deceased's view was a computer screen showing the last picture of a video file downloaded from the Internet with the head of an unclothed, allegedly hanged female. The deceased's left hand was inside his trousers in the genital region. The autopsy did not only show findings typical for hanging, but also advanced sarcoidosis, which was known to the victim. Although this basic illness could have been a possible motive for suicide, the circumstances in the presented case pointed more in the direction of an accidental autoerotic death. As far as we know, this is the first description of a death during autoerotic activity in which sexual stimulation was achieved by watching a video file downloaded from the Internet.


[Structural chromosome aberrations in the peripheral blood lymphocytes in patients with precancer and endometrial cancer].
The level of chromosomal aberrations in cultured blood lymphocytes from patients with hyperplasia, atypical hyperplasia of endometrium and endometrial cancer was studied. Chromosomal aberration frequency significantly increased up to 5.000 +/- 00.47% in patients with atypical and endometrial hyperplasia and to 5.21 +/- 00.53% in patients with endometrial cancer in comparison to 0.67 +/- 0.21% in the control. All indices were more pronounced in endometrial cancer patients with pathology in pedigree.


Clinical studies on the use of antibiotic- and antiseptic-bonded catheters to prevent catheter-related infection.
Central venous catheter-related infections are common despite adherence to hygienic guidelines for insertion and maintenance of these devices. It has been suggested that coating of intravascular catheters with antimicrobial agents, either antibiotics or antiseptics, could reduce the incidence of catheter-related infections. Recent studies have demonstrated the efficacy of antibiotic-coated and antiseptic-impregnated catheters in reducing bacterial colonisation and infection. Preliminary results of pilot studies indicate that silver impregnation of intravascular catheters may be effective. At present, these antimicrobial-bonded catheters seem to be an important addition to the choice of preventive strategies, but their definitive role and possible disadvantages such as induction of resistance still have to be clearly delineated.


Human and murine skeletal muscle reserve cells.
Study of stem cell phenotype and functions requires their proper isolation. Stem cells isolated from skeletal muscle are a useful tool to explore molecular pathways involved in the regulation of myogenesis. Among progenitor cells, a subset of cells, called reserve cells, has been identified, in vitro, in myogenic cell cultures. This subset of cells remains undifferentiated while the main population of progenitor cells commits to terminal myogenic differentiation. When replated, these reserve cells grow as new colonies of progenitors. At the time of differentiation, they reform both differentiated myotubes and undifferentiated reserve cells. Here, we present a protocol to obtain and further isolate reserve cells from both human and murine myogenic cell cultures, together with techniques to analyze their cell cycle status.


Adding value to remote monitoring: Co-design of a health literacy intervention for older people with chronic disease delivered by telehealth - The telehealth literacy project.
To co-design, test and evaluate a health literacy, chronic disease self-management and social support intervention for older people delivered by group videoconferencing into the home. The Telehealth Literacy Project (THLP) was a mixed methods, quasi-experimental, non-randomised trial nested within a telehealth remote monitoring study. An intervention group (n = 52) participated in five, weekly videoconference group meetings lasting for 1.5 h and a control group (n = 60) received remote monitoring only. Outcomes were measured using the nine-scale Health Literacy Questionnaire (HLQ) and two scales of the Health Education Impact Questionnaire (heiQ). Semi-structured interviews and focus group data were thematically analysed. At 3 month follow-up, univariate analysis identified small effects in the intervention group only, with improved health literacy behaviours (five HLQ scales) and self-management skills (two heiQ scales). ANOVA of HLQ scales indicated no significant differences between the two groups over time indicating a contributing effect of the remote monitoring project. Intervention participants reported improved perception of companionship, emotional and informational support. The THLP delivered with telemonitoring indicates potential to improve social support and some health literacy factors in older people. Patient education can be delivered by group videoconferencing.


A method for testing denture adhesives.
An in vitro test is described that simulates the in vivo fate of a denture adhesive, namely destruction, dilution, and dissolution of the adhesive, by repeated measurement of tensile bond strength for the adhesive in isotonic saline over time. The bond strengths were measured under two different settings of the testing machine. The main compositions of three denture adhesive pastes, Fittydent, Fixodent, and Super Poli-Grip and one powder adhesive, Super Wernet's, were determined by infrared spectroscopy. The tensile bond strengths of these adhesives and those of pure tragacanth gum were subjected to a three-way analysis of variance. The Fittydent and Super Poli-Grip adhesives exhibited the best results over time. The most appropriate of the described methods for testing denture adhesives seem useful; however, when seen in relation to the results of a published clinical study where the patients were asked to evaluate the retention and the duration of some of these adhesives, there are indications that the clinical validity of the method might be improved if paste adhesives are tested at temperatures above 35 degrees C.


Two-dimensional gel electrophoresis: recent advances in sample preparation, detection and quantitation.
A strength of two-dimensional polyacrylamide gel electrophoresis (2D PAGE) is its ability to resolve and investigate the abundance of several thousand proteins in a single sample. This enables identification of the major proteins in a tissue or subcellular fraction by mass spectrometric methods. In addition, 2D PAGE can be used to compare quantities of proteins in related samples, such as those from altered environments or from mutant and wild type, thus allowing the response of classes of proteins to be determined. Those proteins showing a correlated difference in expression may participate in related processes, and this subsequently helps to define protein function. Although there are many limitations of the 2D gel technology that mean it will never be comprehensive in protein coverage, its use for the identification of relatively abundant proteins is now widespread. However, there are still surprisingly few examples of quantitative analysis of changes in protein abundance. In this review we highlight recent advances towards true quantitative analysis of 2D gels that will lead to better prediction of protein function. Despite the development of promising alternatives, 2D PAGE is likely to remain in extensive use for the foreseeable future, because the technology is now simple and readily available to many laboratories.


Anti-asthmatic activity of standardized hydro-ethanolic and aqueous extracts of Stachytarpheta cayennensis (Rich.) Vahl in a murine model.
Stachytarpheta cayennensis (Verbenaceae) has been used in Brazilian traditional medicine to treat asthma and other respiratory diseases. To investigate the effects of different doses of standardized hydro-ethanolic (SCH) and aqueous (SCA) extracts of aerial parts of S. cayennensis using a murine ovalbumin (OVA)-induced asthma model. The major constituents of the plant extracts were identified and standardized by ultra-performance liquid chromatography coupled with mass spectrometry. Balb/c mice were challenged with OVA solution and treated concomitantly by intraperitoneal injection of standardized SCH or SCA extracts at 50, 100, and 200 mg/kg concentrations. OVA-challenged control animals were treated with either dexamethasone (OVA-DEX) or saline solution (OVA-SAL). After challenge, we assessed in vivo bronchial hyperresponsiveness, airway inflammation (number of cells), peribronchial inflammation (histological analysis) and production of OVA-specific IgE and interleukin (IL)-4, IL-5, and IL-13 (ELISA). Acteoside, isoacteoside, and ipolamiide were the major constituents of SCH and SCA. The respective concentrations of acteoside in SCH and SCA were 78 and 98 μg/mL, while those of ipolamiide were 30 and 19 μg/mL. Treatment with 200 mg/kg of SCH or SCA decreased IL-4, IL-5, and IL-13 in lung homogenates. These reductions were accompanied by a lower influx of inflammatory cells (eosinophils, lymphocytes, and macrophages) to the airways and lungs. In addition to the anti-inflammatory effects, administration of SCA, but not SCH, ameliorated the parameters of bronchial hyperresponsiveness and decreased levels of circulating OVA-specific IgE. The results presented herein demonstrate for the first time the anti-asthmatic activity of S. cayennensis extracts in a murine model, thereby supporting the ethnopharmacological uses of the plant.


A survey of emergency physicians regarding due process, financial pressures, and the ability to advocate for patients.
A 1998 survey of emergency physicians indicated that many were threatened with adverse actions when advocating regarding the quality of care or raising concerns about financial issues. To assess the current state of these issues. An anonymous electronic survey of emergency physicians was conducted using the American Medical Association's database. Of the 1035 emergency physicians who received the survey, 389 (37.6%) answered the questions. Over half had been in practice for 16 or more years and 86% were board certified. Of those who knew the answer to the question, 62% (197 of 317) reported that their employer could terminate them without full due process and 76% (216 of 284) reported that the hospital administration could order their removal from the clinical schedule. Nearly 20% reported a possible or real threat to their employment if they raised quality-of-care concerns. Financial pressures related to admission, discharge, and transfer of patients were also noted by a number of respondents. Physicians who worked for contract management companies reported a higher incidence of impaired practice rights. Practicing emergency physicians continue to report substantial concerns regarding their ability to speak up about the quality of care and pressure regarding financial matters related to patient care.


Snail mediates GDF-8-stimulated human extravillous trophoblast cell invasion by upregulating MMP2 expression.
Extravillous trophoblast (EVT) cell invasion is a tightly regulated process that requires for a normal pregnancy. The epithelial-mesenchymal transition (EMT) has been implicated in EVT cell invasion. Growth differentiation factor-8 (GDF-8), a member of the transforming growth factor-beta (TGF-β) superfamily, is expressed in the human placenta and promotes EVT cell invasion by upregulating the expression of matrix metalloproteinase 2 (MMP2). However, the underlying molecular mechanism of GDF-8-induced MMP2 expression remains undetermined. Therefore, the present study aims to examine the role of Snail and Slug, the EMT-related transcriptional regulators, in GDF-8-stimulated MMP2 expression and cell invasion in HTR-8/SVneo human EVT cell line and primary cultures of human EVT cells. HTR-8/SVneo and primary cultures of human EVT cells were used to examine the effect of GDF-8 on MMP2 expression and explore the underlying mechanism. For gene silencing and overexpression, the HTR-8/SVneo cell line was used to make the experiments more technically feasible. The cell invasiveness was measured by Matrigel-coated transwell invasion assay. GDF-8 stimulated MMP2 expression in both HTR-8/SVneo and primary EVT cells. The stimulatory effect of GDF-8 on MMP2 expression was blocked by the inhibitor of TGF-β type-I receptors, SB431542. Treatment with GDF-8 upregulated Snail and Slug expression in both HTR-8/SVneo and primary EVT cells. The stimulatory effects of GDF-8 on Snail and Slug expression were blocked by pretreatment of SB431542 and siRNA-mediated knockdown of SMAD4. Interestingly, using the siRNA knockdown approach, our results showed that Snail but not Slug was required for the GDF-8-induced MMP2 expression and cell invasion in HTR-8/SVneo cells. The reduction of MMP2 expression in the placentas with preeclampsia (PE) was also observed. These findings discover the physiological function of GDF-8 in the human placenta and provide important insights into the regulation of MMP2 expression in human EVT cells. Video Abstract.


COVID-19: From pathogenesis models to the first drug trials.
The number of people infected with SARS-CoV-2, and sadly dying from COVID-19, has exploded, and so the amount of literature on the novel coronavirus and the disease it causes has increased proportionately. The case numbers in some countries are beyond the epidemic peak, but the uncertainty about a second wave keeps politicians and societies under pressure. Appropriate decision-making and winning support from the population depends on precise scientific information rather than leaving the field to scaremongers of all proveniences. This mini-review is an update of earlier reports (Brüssow, Microb Biotechnol 2020a;13:607; Brüssow, Microb Biotechnol 2020b; https://doi.org/10.1111/1751-7915.13592).


Prediction of Indoor Air Exposure from Outdoor Air Quality Using an Artificial Neural Network Model for Inner City Commercial Buildings.
NO₂ and particulate matter are the air pollutants of most concern in Ireland, with possible links to the higher respiratory and cardiovascular mortality and morbidity rates found in the country compared to the rest of Europe. Currently, air quality limits in Europe only cover outdoor environments yet the quality of indoor air is an essential determinant of a person's well-being, especially since the average person spends more than 90% of their time indoors. The modelling conducted in this research aims to provide a framework for epidemiological studies by the use of publically available data from fixed outdoor monitoring stations to predict indoor air quality more accurately. Predictions are made using two modelling techniques, the Personal-exposure Activity Location Model (PALM), to predict outdoor air quality at a particular building, and Artificial Neural Networks, to model the indoor/outdoor relationship of the building. This joint approach has been used to predict indoor air concentrations for three inner city commercial buildings in Dublin, where parallel indoor and outdoor diurnal monitoring had been carried out on site. This modelling methodology has been shown to provide reasonable predictions of average NO₂ indoor air quality compared to the monitored data, but did not perform well in the prediction of indoor PM2.5 concentrations. Hence, this approach could be used to determine NO₂ exposures more rigorously of those who work and/or live in the city centre, which can then be linked to potential health impacts.


Coping, problem solving, depression, and health-related quality of life in patients receiving outpatient stroke rehabilitation.
To investigate whether patients with high and low depression scores after stroke use different coping strategies and problem-solving skills and whether these variables are related to psychosocial health-related quality of life (HRQOL) independent of depression. Cross-sectional study. Two rehabilitation centers. Patients participating in outpatient stroke rehabilitation (N=166; mean age, 53.06±10.19y; 53% men; median time poststroke, 7.29mo). Not applicable. Coping strategy was measured using the Coping Inventory for Stressful Situations; problem-solving skills were measured using the Social Problem Solving Inventory-Revised: Short Form; depression was assessed using the Center for Epidemiologic Studies Depression Scale; and HRQOL was measured using the five-level EuroQol five-dimensional questionnaire and the Stroke-Specific Quality of Life Scale. Independent samples t tests and multivariable regression analyses, adjusted for patient characteristics, were performed. Compared with patients with low depression scores, patients with high depression scores used less positive problem orientation (P=.002) and emotion-oriented coping (P<.001) and more negative problem orientation (P<.001) and avoidance style (P<.001). Depression score was related to all domains of both general HRQOL (visual analog scale: β=-.679; P<.001; utility: β=-.009; P<.001) and stroke-specific HRQOL (physical HRQOL: β=-.020; P=.001; psychosocial HRQOL: β=-.054, P<.001; total HRQOL: β=-.037; P<.001). Positive problem orientation was independently related to psychosocial HRQOL (β=.086; P=.018) and total HRQOL (β=.058; P=.031). Patients with high depression scores use different coping strategies and problem-solving skills than do patients with low depression scores. Independent of depression, positive problem-solving skills appear to be most significantly related to better HRQOL.


Identification and synthesis of acyl-phosphatidylglycerol in Acinetobacter sp. HO1-N.
A minor phospholipid from Acinetobacter sp. HO1-N was identified as acyl-phosphatidylglycerol. Acyl-phosphatidylglycerol synthesis by outer-membrane preparations appeared to be a result of phospholipase A activity.


Molecularly Functionalized SnO2 Films by Carboxylic Acids for High-Performance Perovskite Solar Cells.
Metal oxides are commonly employed as electron transport layers (ETLs) for n-i-p perovskite solar cells (PSCs), but the presence of surface traps and their mismatched energy alignment with perovskites limits the corresponding device performance. Therefore, the interfacial modification of ETLs by functional molecules becomes an important strategy for tailoring the interfacial properties and facilitating an efficient charge extraction and transport in PSCs. However, an in-depth understanding of the influences of their molecular structures on the surface chemistry and electronic properties of ETLs is rarely discussed. Herein, three carboxylic acid-based molecules with different chemical structures were employed to modify the SnO2 ETL and their effects on the performance of PSCs were systematically investigated. We found that the alkyl-chain length and carboxyl number in molecular structures can dramatically alter their binding strength to SnO2, providing a good strategy to fine-tune their film quality, electron mobility, and energy offset at the cathode interface. Benefiting from the optimal coordination ability of citric acid (CA) to SnO2, the corresponding PSCs show better charge transport properties and suppressed nonradiative recombination, leading to a champion efficiency of 23.1% with much improved environmental stability, highlighting the potential of rational design of molecular modifiers for high-performance ETLs applied in PSCs.


Mach's square-or-diamond phenomenon in microgravity during parabolic flight.
In a classic demonstration, Ernst Mach showed that the same figure could be perceived as a square or as a diamond depending on the orientation of the subject relative to gravity. Such phenomenon is based on the use of a geocentric reference frame for object perception. If the central nervous system perceives an object with respect to the gravitationally defined vertical, what will happen if this reference frame is removed? We investigated the Mach phenomenon in subjects placed in short-term microgravity during parabolic flight. Subjects were presented with a square with a corner pointing upwards, and asked whether they perceived it as a diamond or square with the head upright or tilted 45 degrees in roll both in normal gravity and when free-floating in microgravity during parabolic flight. The addition of a rectangular frame around the figure was also investigated. In contrast to the normal gravity condition, with the head tilted the subjects still perceived a diamond figure in microgravity, indicating that they had switched from a geocentric to an egocentric reference frame. Also in contrast to the normal gravity condition, adding a rectangular frame around the figure did not significantly change the perception of the object in microgravity, suggesting that an intrinsic reference determined by the axis of elongation or symmetry of the object does not easily override an egocentric reference frame like it does for a geocentric reference frame.


Emergency peripartum hysterectomy: 2-year experiences in non-tertiary center.
The aim of this study was to evaluate risk factors, indications and materno-fetal outcomes for emergency peripartum hysterectomy. Retrospective evaluation was made of 23 cases. Maternal and neonatal outcomes, need for referral to the tertiary center and related complications were compared to those at the initial diagnosis for surgery, location of delivery, type of surgery and the admission diagnosis. The risk factors associated with emergency peripartum hysterectomy were also investigated. Significance was evaluated at p values of <0.01 and <0.05. There was a correlation between peripartum hysterectomy and uterine atony or uterine rupture (p < 0.01). The referral rates of patients with home delivery were significantly higher than those of patients who delivered in hospital (p = 0.02) but no significant difference was observed in the neonatal outcomes (p = 0.38). There was no significant difference in the rates of maternal complications between home and hospital delivery (p = 0.068). According to the indication for surgery, no significant difference was observed between the rates of referral to the tertiary center, maternal outcomes, complications, or need for maternal intensive care (p > 0.05). However, a highly significant difference was observed between the neonatal outcomes (p = 0.001). The results of this study showed the most important risk factors associated with peripartum hysterectomy to be uterine atony, grand multiparity, and uterine rupture. Maternal intensive care, maternal death, neonatal death, or neonatal intensive care were associated with home delivery or delayed presentation at hospital.


Ramsey hunt syndrome after antimonial treatment for American Cutaneous Leishmaniasis.
Ramsay Hunt Syndrome (RHS), also known as herpes zoster oticus, is caused by the reactivation of varicella zoster virus (VZV) in the geniculate ganglion of the facial nerve. Herein, we report a case of Ramsey Hunt Syndrome in a patient after antimonial treatment for Cutaneous Leishmaniasis. The patient presented with microvesicles grouped on an erythematous base, starting in the neck and ascending towards the scalp margin on the right side of the head. The patient also developed grade V peripheral facial palsy the day after initiating the herpes zoster treatment, this outcome corroborated the assumption of Ramsey Hunt Syndrome.


High-fat and combined high-fat-high-fructose diets impair episodic-like memory and decrease glutamate and glutamine in the hippocampus of adult mice.
Diet-induced obesity is associated with premature cognitive decline. Elevated consumption of fats and sugars in humans and rodents has been associated with deficits in recognition memory, which is modulated by the hippocampus. Alterations in excitatory and inhibitory neurotransmitters in this area have been observed after hypercaloric diets, but the effects on episodic-like memory are not conclusive. To investigate the effects of hypercaloric diets on memory and their relationship with γ-aminobutyric acid (GABA), glutamate and glutamine and their genetic expression in the hippocampus. A control diet (CD), a high-fat diet (HFD) and a combined high-fat-high-fructose diet (HFFrD) were administered to 30 C57BL/6 adult mice for 10 weeks. The discrimination indexes and exploration time of the novel object recognition (NOR) and novel object location (NOL) tasks were evaluated and GABA, glutamate and glutamine concentrations and their genetic expression were obtained from the hippocampus. The HFFrD induced lower discrimination indexes, decreased exploration time in the recognition memory tasks, and lowered the concentrations of glutamate and glutamine, and HFD increased their expression in the hippocampus. These findings suggest that a possible adaptative long-term mechanism in the hippocampal neurotransmitters, and this possibility may underlie the episodic-like memory deficits in mice fed HFD and HFFrD.


The sustainability of Lean in pediatric healthcare: a realist review.
Lean is a quality improvement management system from the Toyota manufacturing industry. Since the early 2000's, Lean has been used as an intervention for healthcare improvement. Lean is intended to reduce costs and improve customer value through continuous improvement. Despite its extensive use, the contextual factors and mechanisms that influence the sustainability of Lean in healthcare have not been well studied. Realist synthesis is one approach to "unpack" the causal explanations of how and why Lean is sustained or not in healthcare. We conducted a realist synthesis using the context (C) + mechanim (M) = outcome (O) heuristic, to further develop and refine an initial program theory with seven CMO hypotheses, on the sustainability of Lean efforts across pediatric healthcare. Our search strategy was multi-pronged, iterative, and purposeful in nature, consisting of database, gray literature, and contact with three healthcare organizations known for Lean implementation. We included primary research studies, published and unpublished case studies or reports, if they included Lean implementation with a pediatric focus and sustainability outcome. We used the Normalization Process Theory and the National Health Services Sustainability Model, an operational definition for Lean and a comprehensive definition for sustainability as guidance for data extraction and analysis. Our initial program theory with was refined using a blend of abductive and retroductive analytical processes. We identified six published primary research studies, two published quality improvement case studies, and three unpublished quality improvement case reports. Five CMO hypotheses from our initial program theory were substantially supported after synthesis, "sense-making and value congruency," "staff engagement and empowerment," and the "ripple effect" or causal pathway between Lean implementation outcomes that served as facilitating or hindering contexts for sustainability. Overall, there was variation with the conceptualization and measurement of sustainability. This study is the first to examine Lean sustainability in pediatric healthcare using realist methods. Future research should examine whether the predictors of implementation are the same or different to sustainability and evaluate the underlying mechanisms that influence the sustainability of Lean. There is also a need for research to develop and test conceptual models and frameworks on sustainability. PROSPERO-CRD42015032252 .


Processing Guar Gum into polyester fabric based promising mixed matrix membrane for water treatment.
A reactive and mechano-chemically stable support was prepared from Ag-nanoparticles decorated polyester fabric which was subsequently coated by a casting solution containing polyvinylidene fluoride matrix, guar gum (GG) exo-polysaccharide hydrophilic agent, and UiO-66 filler. FE-SEM, XRD, FT-IR, water contact angle technique, and mechanical stability tests were applied to characterize the prepared membranes. The water contact angle measurements indicated the hydrophilicity of the prepared membrane which can be attributed to the nature of bio-GG and UiO-66. The prepared membrane was employed for purifying contaminated waters containing N-cetyl-N,N,N-trimethylammonium bromide (CTAB) and congo-red (CR) dye through a cross-module set-up. The central composite design was also exploited to study the effect of operational parameters such as CTAB and CR concentration, pH solution, and pressure on the removal efficiency. Particularly, the bio-based GG/UiO-66 dispersion showed excellent self-healing properties, which enabled an effective pollutant separation ability and facilitated the recyclability/sustainability of the as-prepared membrane.


Past, present and future EEG in the clinical workup of dementias.
Electroencephalography (EEG), as non-invasive, global measure of neuronal activity, is a prime candidate functional marker of synapse dysfunction and loss in dementias. Nevertheless, EEG currently has no established role in the clinical workup of individual patients. This opinion paper presents our critical view on why EEG has so far failed to keep its promise, and where we believe EEG will be clinically useful for patients threatened with cognitive decline in the future. Individual EEGs are an integral outcome of many causally intermixing upstream factors contributing to dementia. Therefore, EEG cannot become a clinically useful "simple" stand-alone biomarker of some pathognomic accumulations of specific brain proteins, but rather offer unique opportunities for more comprehensive and richly faceted insights into the functional status of brain systems. EEG may thus remain an essential window into the brain when it comes to the at-risk and presymptomatic phases of dementias, where it can be uniquely informative about concepts such as burdens of plasticity and repair, cognitive reserve, and sleep. Jointly with rapid gains in usability, portability, machine learning, closed loop systems, and understanding of the role of EEG-based sleep stages for memory and brain repair, EEG may come to keep its initial promise after all.


A case of fatal cryptococcus meningitis with intraventricular granuloma.
Differential diagnostic difficulties in a case of probably spontaneous cryptococcus meningitis in a young girl are the reason for an extensive presentation of this case. The problems of CSF examination are discussed. In the course of the disease an intraventricular mycetoma had arisen, and caused the picture of a space-occupying process. Histological examination revealed an atypical reaction of the perifocal brain tissue, the possible causes of which are evaluated.


Is physical illness a risk factor for eating disorders in children and adolescents? A preliminary investigation.
This study investigates the correlation between early-onset eating disorders and past history of physical illness. Subjects for this study were children and adolescents aged between 7 and 19 years, and were divided into two groups: those with anorexia nervosa (n=62) and those with "other eating disorders" (n=28). Data on medical history were obtained retrospectively from the patient's files and coded by a consultant psychiatrist. There was no significant difference between the two groups in relation to a history of prior physical illness. However, those with anorexia nervosa were significantly more likely to have suffered more than one serious physical illness prior to the onset of their eating disorder, and both groups were significantly more likely to have had a prior physical illness than an adult control group [Patton, G. C., Wood, K., & Johnson-Sabine. Br. J. Psychiatry 149 (1986) 756.]. Thus, it appears that a past history of physical illness is a significant risk factor for early-onset eating disorders in general, and for anorexia nervosa in particular when there has been more than one physical illness.


Continuous invasive blood pressure and cardiac output monitoring during cesarean delivery: a randomized, double-blind comparison of low-dose versus high-dose spinal anesthesia with intravenous phenylephrine or placebo infusion.
Prevention of hemodynamic instability during cesarean delivery during spinal anesthesia has been the aim of several studies. Noninvasive monitoring has been used in all previous studies. This is the first study in healthy pregnant women with continuous invasive recording of arterial blood pressure, cardiac output, and systemic vascular resistance. The aim of this randomized trial was to compare the effects of two different intrathecal doses of bupivacaine, with or without intravenous phenylephrine infusion, on cardiac output and systolic blood pressure. In this double-blinded study, 80 healthy women scheduled to undergo elective cesarean delivery were randomly assigned to one of four different groups receiving 7 mg spinal bupivacaine with or without a concomitant low-dose infusion of phenylephrine (0.25 microg . kg(-1) . min(-1)) or 10 mg spinal bupivacaine with or without phenylephrine infusion. All patients had 4 microg sufentanil added to the spinal solution and had cohydration with 750 ml saline, 0.9%. The low-dose spinal bupivacaine group with intravenous phenylephrine infusion was the most stable group regarding all hemodynamic variables. The authors found significant differences between this group and the group that was given the high dose of bupivacaine with intravenous placebo infusion regarding cardiac output (P = 0.005), systemic vascular resistance (P < 0.0001), and systolic blood pressure (P = 0.012). This study shows that low-dose bupivacaine (with sufentanil), combined with a low-dose infusion of phenylephrine and moderate cohydration, gives the best hemodynamic stability during spinal anesthesia for cesarean delivery.


IgE and IgG antibodies to Malassezia spp. yeast extract in patients with atopic dermatitis.
The presence of immunoglobulins to Malassezia spp. surface proteins in the sera from patients with atopic dermatitis and healthy subjects was studied. It was found that 28% of 25 examined patients with atopic dermatitis had IgE antibodies to Malassezia spp. surface protein preparation. All patients and 5 healthy subjects had IgG antibodies to this preparation. The presence and concentration of specific IgE antibodies in patients with atopic dermatitis correlated with reverse titers of IgG antibodies to this preparation (r=0.782). The medians of values reciprocal to IgG antibody titers in patients with atopic dermatitis with and without specific IgE antibodies to the preparation and in healthy subjects were 64, 1024, and 16, respectively. The preparation derived from Candida albicans (candidine) and previously derived preparation from Malassezia did not cross-react. According to immunoblotting data, the preparation contains allergens presented by proteins with molecular weights 15, 36, 52-56, and 78.4 kDa.


Influenza A and Sendai viruses preferentially bind to fucosylated gangliosides with linear poly-N-acetyllactosaminyl chains from human granulocytes.
Influenza A and Sendai viruses are known to bind to various extent to neolacto-series gangliosides IV3Neu5Ac-nLcOse4Cer, IV6Neu5Ac-nLcOse4Cer, and VI3Neu5Ac-nLcOse6Cer, which are the dominant gangliosides of human granulocytes. Recently, minor gangliosides of granulocytes were characterized and found to express sialyl Lewis(x) and VIM-2 epitopes. These long chain linear monosialogangliosides with nLcOse8, and nLcOse10, cores, carrying one to three fucoses, are shown in this study to bind with strong avidity to influenza A/PR/8/34 (H1N1), A/X-31 (H3N2), and Sendai virus (Z-strain) using the overlay technique. These and recent data from other groups imply that selectins and virus hemagglutinins are capable of competing with lipid bound sialyl Lewis(x) and VIM-2 epitopes on myeloid cells during inflammatory reactions.


Energy drinks: health risks and toxicity.
To describe the epidemiology and toxicity of caffeinated energy drink exposures in Australia. Retrospective observational study analysing data from calls regarding energy drink exposures recorded in the database of an Australian poisons information centre over 7 years to 2010. Type of exposure; co-ingestants; symptoms reported; and reported hospitalisations. Callers reported 297 exposures to energy drinks, which showed an increasing annual trend from 12 in 2004 to 65 in 2010. Median age for the 217 subjects with recreational exposure was 17 years (interquartile ratio [IQR], 15-21; range, 11-60) and 57% were male. One hundred recreational users co-ingested other substances, predominantly alcohol (50) or other caffeinated products (44). The number of energy drinks consumed in one session varied greatly (median, 5 units; IQR, 3-8; range, 1-80). Most subjects who reported recreational use reported experiencing symptoms (87%). The most common symptoms were palpitations, agitation, tremor and gastrointestinal upset. Twenty-one subjects had signs of serious cardiac or neurological toxicity, including hallucinations, seizures, arrhythmias or cardiac ischaemia. At least 128 subjects (57 with no co-ingestants) required hospitalisation. Reports of caffeine toxicity from energy drink consumption are increasing, particularly among adolescents, warranting review and regulation of the labelling and sale of these drinks. Educating adolescents and increasing the community's awareness of the hazards from energy drinks is of paramount importance.


Can serial qualitative polymerase chain reaction monitoring predict outcome of pulmonary tuberculosis treatment?
The aim of this study was to assess the use of qualitative one-tube nested polymerase chain reaction (PCR) for monitoring the treatment response in smear-positive pulmonary tuberculosis, and the factors determining the negative conversion of sputum smear, culture, and PCR during treatment. A total of 53 patients receiving a standard short course of chemotherapy with 24 months follow-up period after treatment cessation were included in the study. Sputum specimens were collected serially for smear, culture, and PCR until the treatment was complete. The conversion rate for sputum culture, smear, and PCR at 8 weeks after treatment were 84.9, 58.5, and 47.1%, and at 16 weeks of treatment were 100, 88.7, and 79.2%, respectively. At the end of the treatment period, there were four PCR persisters, one of whom had disease relapse. Only cavitary disease had an influence over the negative conversion of the smear and PCR at 8 weeks (RR 3.5, 95% CI 1.04-11.95, P=0.04 for smear; RR 5.06, 95% CI 1.196-21.42, P=0.03 for PCR). Qualitative PCR was not useful for monitoring therapy in smear-positive pulmonary tuberculosis. Mycobacterium DNA was cleared slowly in cavitary disease. The PCR may be performed at the time of treatment cessation to identify those with potential for disease relapse.


Biodiversity is overlooked in the diets of different social groups in Brazil.
Food biodiversity is essential for improving nutrition and reducing hunger in populations worldwide. However, in middle and low-income countries, the biodiversity of food production does not necessarily represent food consumption patterns by population. We used Brazil, one of the world's megabiodiverse countries, as a case study to investigate the following questions: what is the prevalence of consumption of biodiverse foods in Brazil, and what are the socioeconomic factors that influence their consumption throughout the country? We used data from a Brazilian representative national dietary survey to estimate the frequency of food consumption of unconventional food plants, edible mushrooms, and wild meat, in according to socioeconomic variables. Thus, we investigated the socioeconomic predictors of Unconventional Food Plants consumption using methods of Machine Learning (ML) and multiple zero-inflated Poisson (ZIP) regression. We showed that biodiverse food consumption in Brazil is low, just related by 1.3% of the population, varying in according to area, ethnicity, age, food insecurity, sex, and educational level. Our findings of low utilization of biodiversity suggest an important mismatch between the rich biodiversity of the country and its representation in the human diet.


Fronto-parietal mirror neuron system modeling: Visuospatial transformations support imitation learning independently of imitator perspective.
Although the human mirror neuron system (MNS) is critical for action observation and imitation, most MNS investigations overlook the visuospatial transformation processes that allow individuals to interpret and imitate actions observed from differing perspectives. This problem is not trivial since accurately reaching for and grasping an object requires a visuospatial transformation mechanism capable of precisely remapping fine motor skills where the observer's and imitator's arms and hands may have quite different orientations and sizes. Accordingly, here we describe a novel neural model to investigate the dynamics between the fronto-parietal MNS and visuospatial processes during observation and imitation of a reaching and grasping action. Our model encompasses i) the inferior frontal gyrus (IFG) and inferior parietal lobule (IPL), regions that are postulated to produce neural drive and sensory predictions, respectively; ii) the middle temporal (MT) and middle superior temporal (MST) regions that are postulated to process visual motion of a particular action; and iii) the superior parietal lobule (SPL) and intra-parietal sulcus (IPS) that are hypothesized to encode the visuospatial transformations enabling action observation/imitation based on different visuospatial viewpoints. The results reveal that when a demonstrator executes an action, an imitator can reproduce it with similar kinematics, independently of differences in anthropometry, distance, and viewpoint. As with prior empirical findings, similar model synaptic activity was observed during both action observation and execution along with the existence of both view-independent and view-dependent neural populations in the frontal MNS. Importantly, this work generates testable behavioral and neurophysiological predictions. Namely, the model predicts that i) during observation/imitation the response time increases linearly as the rotation angle of the observed action increases but remain similar when performing both clockwise and counterclockwise rotation and ii) IPL embeds essentially view-independent neurons while SPL/IPS includes both view-independent and view-dependent neurons. Overall, this work suggests that MT/MST visuomotion processes combined with the SPL/IPS allow the MNS to observe and imitate actions independently of demonstrator-imitator spatial relationships.


Localisation of the human blue cone pigment gene to chromosome band 7q31.3-32.
Blue cone pigment (BCP) is one of three types of cone photoreceptors responsible for normal colour vision. In this study, the BCP gene has been localised to chromosome 7q31.3-32 by fluorescent in situ hybridisation of cosmid clones containing the gene. This is consistent with previous mapping of the BCP gene to chromosome 7q31-35.


Six new species of Triomicrus Sharp from southern China (Coleoptera: Staphylinidae: Pselaphinae).
Seven species of the genus Triomicrus Sharp are recognized in southern China, six of them are described as new: T. acutus and T. nanlingensis Shen & Yin, sp. n. (Guangdong), T. pinnatus Shen & Yin, sp. n. (Guangdong and Hunan), T. cochlis Shen & Yin, sp. n. (Guangdong, Hunan and Guangxi), and T. cavus Shen & Yin, sp. n. and T. longus Shen & Yin, sp. n. (Guangxi). A key for the identification of Triomicrus in southern China is presented.


A preclinical randomized controlled study of ischemia treated with Ginkgo biloba extracts: Are complex components beneficial for treating acute stroke?
The rigorous design of preclinical experimental studies of candidate neuroprotectants for the treatment of acute ischemic stroke is crucial for the success of subsequent randomized clinical trials. The efficacy of Ginkgo biloba extracts (GBEs) in complex mixtures for the treatment of acute ischemic stroke remains unclear. In this preclinical randomized controlled trail (pRCT), the effects of a novel (n)GBE containing pinitol versus traditional (t)GBE without pinitol were evaluated on the mouse models of acute transient and permanent stroke, separately. The sample size, an important aspect of study design, was calculated based on our experimental data. Mice with ischemia that were induced by transient middle cerebral artery occlusion (tMCAO) or permanent distal middle cerebral artery occlusion (pdMCAO), were treated with vehicle, nGBE, tGBE, or pinitol alone by tail-vein injection. Our results showed that nGBE significantly reduced infarct size in mice with tMCAO compared with vehicle-treated control mice. Both nGBE and tGBE significantly reduced infarct size in mice with pdMCAO compared with the vehicle-treated controls. None of the three treatments rescued weight loss or prevented the neurological deficits in either the tMCAO- or pdMCAO-model mice. These findings suggest that nGBE, which includes all of the components of tGBE and pinitol, is neuroprotective in two ischemic stroke models. Additional studies of complex GBE mixtures for stroke treatment compared to single component medications are undergoing evaluation.


Postacute Care Setting, Facility Characteristics, and Poststroke Outcomes: A Systematic Review.
To synthesize research comparing poststroke health outcomes between patients rehabilitated in skilled nursing facilities (SNFs) and those in inpatient rehabilitation facilities (IRFs) as well as to evaluate relations between facility characteristics and outcomes. PubMed and CINAHL searches spanned January 1, 1998, to October 6, 2016, and encompassed MeSH and free-text keywords for stroke, IRF/SNF, and study outcomes. Searches were restricted to peer-reviewed research in humans published in English. Observational and experimental studies examining outcomes of adult patients with stroke rehabilitated in an IRF or SNF were eligible. Studies had to provide site of care comparisons and/or analyses incorporating facility-level characteristics and had to report ≥1 primary outcome (discharge setting, functional status, readmission, quality of life, all-cause mortality). Unpublished, single-center, descriptive, and non-US studies were excluded. Articles were reviewed by 1 author, and when uncertain, discussion with study coauthors achieved consensus. Fourteen titles (0.3%) were included. The types of data, time period, size, design, and primary outcomes were extracted. We also extracted 2 secondary outcomes (length of IRF/SNF stay, cost) when reported by included studies. Effect measures, modeling approaches, methods for confounding adjustment, and potential confounders were extracted. Data were abstracted by 1 author, and the accuracy was verified by a second reviewer. Two studies evaluating community discharge, 1 study evaluating the predicted probability of readmission, and 3 studies evaluating all-cause mortality favored IRFs over SNFs. Functional status comparisons were inconsistent. No studies evaluated quality of life. Two studies confirmed increased costs in the IRF versus SNF setting. Although substantial facility variation was described, few studies characterized sources of variation. The few studies comparing poststroke outcomes indicated better outcomes (with higher costs) for patients in IRFs versus those in SNFs. Contemporary research on the role of the postacute care setting and its attributes in determining health outcomes should be prioritized to inform reimbursement system reform.


Thioredoxin binding protein (TBP)-2/Txnip and α-arrestin proteins in cancer and diabetes mellitus.
Thioredoxin binding protein -2/ thioredoxin interacting protein is an α-arrestin protein that has attracted much attention as a multifunctional regulator. Thioredoxin binding protein -2 expression is downregulated in tumor cells and the level of thioredoxin binding protein is correlated with clinical stage of cancer. Mice with mutations or knockout of the thioredoxin binding protein -2 gene are much more susceptible to carcinogenesis than wild-type mice, indicating a role for thioredoxin binding protein -2 in cancer suppression. Studies have also revealed roles for thioredoxin binding protein -2 in metabolic control. Enhancement of thioredoxin binding protein -2 expression causes impairment of insulin sensitivity and glucose-induced insulin secretion, and β-cell apoptosis. These changes are important characteristics of type 2 diabetes mellitus. Thioredoxin binding protein -2 regulates transcription of metabolic regulating genes. Thioredoxin binding protein -2-like inducible membrane protein/ arrestin domain containing 3 regulates endocytosis of receptors such as the β(2)-adrenergic receptor. The α-arrestin family possesses PPXY motifs and may function as an adaptor/scaffold for NEDD family ubiquitin ligases. Elucidation of the molecular mechanisms of α-arrestin proteins would provide a new pharmacological basis for developing approaches against cancer and type 2 diabetes mellitus.


High-dose VP-16 with intermediate-dose cytosine arabinoside in the treatment of relapsed acute nonlymphocytic leukemia.
In a study of 11 adult patients with acute nonlymphocytic leukemia (ANLL), infusion therapy with high-dose VP-16 and intermediate-dose cytosine arabinoside was administered. Response was assessed with reference to bone marrow aspirations performed on days 1; 12, 13, or 14; and 21 of treatment. All 7 of the patients with ANLL in relapse achieved marrow hypoplasia, and 3 of them achieved complete response. LFTs were elevated in most patients but no evidence of hepatocellular necrosis was observed. It is concluded that the value of VP-16 in ANLL may have been underestimated in the past because of inadequate dosing.


Biomarkers and factors in small cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis.
The aim of this meta-analysis was to summarize the available results of immunotherapy predictors for small cell lung cancer (SCLC) and to provide evidence-based information for their potential predictive value of efficacy. We searched PubMed, EMBASE, Web of Science, The Cochrane Library, and ClinicalTrials (from January 1, 1975 to November 1, 2021). The hazard ratios (HR) and its 95% confidence intervals (CIs) and tumor response rate of the included studies were extracted. Eleven studies were eventually included and the pooled results showed that programmed cell death ligand 1 (PD-L1) positive: objective response rate (ORR) (relative risk [RR] = 1.39, 95% CI [0.48, 4.03], p = 0.54), with high heterogeneity (p = 0.05, I2 = 56%); disease control rate [DCR] (RR = 1.31, 95% CI [0.04, 38.57], p = 0.88), with high heterogeneity (p = 0.04, I2 = 75%); overall survival (OS) (HR = 0.89, 95% CI [0.74, 1.07], p = 0.22); and progression-free survival (PFS) (HR = 0.83, 95% CI [0.59, 1.16], p = 0.27), with high heterogeneity (p = 0.005, I2 = 73.1%). TMB-High (TMB-H): OS (HR = 0.86, 95% CI [0.74, 1.00], p = 0.05); PFS (HR = 0.71, 95% CI [0.6, 0.85], p < 0.001). Lactate dehydrogenase (LDH) >upper limit of normal (ULN): OS (HR = 0.95, 95% CI [0.81, 1.11], p = 0.511). Asian patients: OS (HR = 0.87, 95% CI [0.72, 1.04], p = 0.135); White/Non-Asian patients: OS (HR = 0.83, 95% CI [0.76, 0.90], p < 0.001). Liver metastasis patients: OS (HR = 0.93, 95% CI [0.83, 1.05], p = 0.229); PFS (HR = 0.84, 95% CI [0.67, 1.06], p = 0.141). Central nervous system (CNS) metastasis patients: OS (HR = 0.91, 95% CI [0.71, 1.17], p = 0.474); PFS (HR = 1.03, 95% CI [0.66, 1.60], p = 0.903). The available research results do not support the recommendation of PD-L1 positive and TMB-H as predictors for the application of immune checkpoint inhibitors (ICIs) in SCLC patients. LDH, baseline liver metastasis and CNS metastasis may be used as markers/influencing factors for predicting the efficacy of ICIs in SCLC patients. Non-Asian SCLC patients had better efficacy with ICIs in our results.


Increasing prevalence of headache in 7-year-old schoolchildren.
Reports of increased prevalence of headache in adults and clinical impressions of similar trends in children prompted this epidemiological study on migraine and other headaches. The first stage was carried out in 1974 in children starting school, and the second stage in 1992 using the identical study design, the same age group, and a similar urban child population. The overall prevalence of present headache (having occurred in the previous 6 months) was found to be significantly increased over time, from 14.4% in 1974 to 51.5% in 1992. Similarly, the prevalence of migraine headache had increased from 1.9% to 5.7%. The causes of the increase are as yet unknown. The highest but not significant increases were found in schools which were situated in the districts of the city with the highest social instability, which was reflected in the high percentage of council houses and also in the higher frequency of family relocations. Increase over time in the prevalence of migraine and other headaches in children appears to be at least as clear as in adults. This should alarm the community to study the underlying stress factors and to try to relieve the children's distress.


[Skin damage after postoperative tangential irradiation in breast cancer].
Incidence of telangiectasia and ulcer among 118 postoperated breast cancer patients, who were tangentially irradiated at Department of Radiology, Kyushu University from 1961 to 1980, followed more than 5 years were evaluated. Telangiectasia occurred in 5% at 20-35 Gy, in 50% at 50-55 Gy. Ulcer occurred in 5% at 50-55 Gy, in 50% at 70-75 Gy. Skin tolerance dose in Rubin's Table (1972) is correct.


CgRel involved in antibacterial immunity by regulating the production of CgIL17s and CgBigDef1 in the Pacific oyster Crassostrea gigas.
The NF-κB/Rel transcription factors play essential roles in the induction and regulation of innate immune responses. In the present study, the full-length cDNA of CgRel from the Pacific oyster Crassostrea gigas was of 2,647 bp with an RHD and an IPT domain. The mRNA of CgRel was found to be constitutively expressed in all the tested tissues including gills, hepatopancreas, gonad, adductor muscle, labial palps, mantle, hemocytes, and ganglion. After lipopolysaccharide (LPS) stimulation, the expression level of CgRel mRNA in hemocytes was up-regulated to the first peak at 3 h (3.06-fold compared to the control group, p < 0.001) and second peak at 48 h (1.96-fold, p < 0.05). It increased significantly at 3 h (7.68-fold compared to the control group, p < 0.001), 24 h (3.63-fold, p < 0.05) and 48 h (1.99-fold, p < 0.05) post Vibrio splendidus stimulation, respectively. The protein of CgRel was translocated from cytoplasm into nucleus of oyster hemocytes after LPS stimulation. The mRNA expression levels of interleukin17s (CgIL17s) and big defensin (CgBigDef1) in hemocytes were examined after the expression of CgRel was silenced by RNAi. The transcripts of CgIL17-1 (0.25-fold of the control group, p < 0.01), CgIL17-2 (0.12-fold, p < 0.01), CgIL17-4 (0.33-fold, p < 0.01), CgIL17-6 (0.27-fold, p < 0.05) and CgBigDef1 (0.38-fold, p < 0.01) in CgRel-knockdown oysters decreased significantly at 12 h after LPS stimulation. The results indicated that CgRel played important roles in the immune defense against bacteria by regulating the expression of CgIL17 and CgBigDef1.


Clinical pharmacokinetics of lansoprazole.
Lansoprazole, a benzimidazole derivative with antisecretory and antiulcer activities, inhibits the acid pump activity at the final stage of the enzyme process and therefore reduces the acid secretion of parietal cells. Lansoprazole is converted to active metabolites in the acid environment of these cells. It is rapidly absorbed from a gastric acid-resistant formulation and is approximately 97% bound in human plasma. Single dose pharmacokinetics of lansoprazole appear to be linear over the range from 15 to 60mg. Food and time of dose influence absorption after single doses, but do not modify the antisecretory effect of multiple doses. Lansoprazole is extensively metabolised following oral administration into sulphone and 5-hydroxylated metabolites by the cytochrome P450 enzymes CYP3A4 and CYP2C18. Two other metabolites have been identified in plasma: sulphide and hydroxylated sulphone. Mean plasma elimination half-life (t1/2) is between 1.3 and 2.1 hours in healthy volunteers. 15 to 23% of the total dose is found in urine as free and conjugated hydroxylated metabolites, while unchanged lansoprazole is not detected. The pharmacokinetic profile of the drug is not modified by multiple administration. In healthy elderly volunteers, area under the plasma concentration-time curve (AUC) and t1/2 are significantly greater after single administration occurs to the same extent as in young volunteers. Renal failure has no influence on the pharmacokinetics of lansoprazole, but severe hepatic failure causes a significant decrease in clearance and an increase in the AUC and t1/2 of lansoprazole. This is accompanied by modifications in the AUC of metabolites, but severe hepatic failure has minimal effect on accumulation of the drug after multiple administration. The pharmacokinetics of lansoprazole in patients with acid-related disorders do not differ from those in healthy volunteers. Studies of interactions of lansoprazole with warfarin, prednisone, theophylline, phenazone (antipyrine), diazepam, phenytoin and oral contraceptives suggest minimal risk of any clinically significant interaction.


Pharmacological studies of 'sapo' from the frog Phyllomedusa bicolor skin: a drug used by the Peruvian Matses Indians in shamanic hunting practices.
The dried skin secretion from Phyllomedusa bicolor, 'sapo', is used by the Matses Indians of the Northern Peru, in shamanic rites mainly designed to improve luck in hunting. When rubbed into burned, exposed areas of the skin, the drug causes the prompt appearance of violent peripheral gastrointestinal and cardiovascular effects soon followed by remarkable central effects (increase in physical strength, heightening of senses, resistance to hunger and thirst, exalted capacity to face stress situations). All the peripheral and most of the central effects of 'sapo' can be ascribed to the exceptionally high content of the drug (up to 7% of its weight) in potently active peptides, easily absorbed through the burned, inflamed areas of the skin. The concentration in 'sapo' of the single peptides (phyllocaerulein, phyllomedusin, phyllokinin, demorphins and deltorphins) has been determined by bioassay, and peptide contents were correlated with the different symptoms of the 'sapo' intoxication.


Neurofeedback in children with ADHD: specific event-related potential findings of a randomized controlled trial.
In a randomized controlled trial, we could demonstrate clinical efficacy of neurofeedback (NF) training for children with ADHD (Gevensleben et al., 2009a). The present investigation aimed at learning more about the neuronal mechanisms of NF training. Children with ADHD either completed a NF training or a computerized attention skills training (ratio 3:2). NF training consisted of one block of theta/beta training and one block of slow cortical potential (SCP) training, each comprising 18 training units. At three times (pre-training, between the two training blocks and at post-training), event-related potentials (ERP) were recorded during the Attention Network Test. ERP analysis focused on the P3, reflecting inter alia attentional resources for stimulus evaluation, and the contingent negative variation (CNV), primarily related to cognitive preparation. After NF training, an increase of the CNV in cue trials could be observed, which was specific for the SCP training. A larger pre-training CNV was associated with a larger reduction of ADHD symptomatology for SCP training. CNV effects reflect neuronal circuits underlying resource allocation during cognitive preparation. These distinct ERP effects are closely related to a successful NF training in children with ADHD. In future studies, neurophysiological recordings could help to optimize and individualize NF training. The findings contribute to a better understanding of the mechanisms underlying NF training in children with ADHD.


Linear discriminant analysis on electrocardiogram achieved classification of cardiac involvement status in amyloid light-chain amyloidosis.
Cardiac amyloidosis (CA) is the most crucial determinant of amyloid light-chain (AL) amyloidosis patients' prognosis. We attempted cardiac involvement prediction by 12‑lead electrocardiograph (ECG) and echocardiography (UCG) in AL amyloidosis patients. Fifty patients with histologically confirmed AL amyloidosis underwent gadolinium-enhanced magnetic resonance imaging (Gd-MRI), and CA was assessed using late gadolinium enhancement. ECG and UCG parameters were measured on admission. Fisher's linear discriminant analysis was used to create a model for predicting CA using the ECG and UCG parameters. Prediction by five ECG parameters [QTc(B), QRS-T-angle, III-QRS, aVF-QRS, and V3-R] showed the best performance. Average sensitivity and specificity in the modeling sets, utilizing a linear discriminator based on these five variables, were 99.2 % and 96.8 % and in validation sets, 94.2 % and 90.3 %, respectively. In addition, we tested this model on an additional 26-patient cohort and survival analysis using the Kaplan-Meier method, and significant differences between CA positively predicted and negatively predicted patients were observed. Here, we suggest the application of a condensed classical multivariate statistical technique for the diagnosis of CA. It can be used as a guide to invasive endomyocardial biopsy for those in whom Gd-MRI is contraindicated and as a guide for repeat Gd-MRI in follow-up of AL amyloidosis.


Protein kinase Czeta-dependent LKB1 serine 428 phosphorylation increases LKB1 nucleus export and apoptosis in endothelial cells.
LKB1 is a serine-threonine protein kinase that, when inhibited, may result in unregulated cell growth and tumor formation. However, how LKB1 is regulated remains poorly understood. The aim of the present study was to define the upstream signaling events responsible for peroxynitrite (ONOO(-))-induced LKB1 activation. Exposure of cultured human umbilical vein endothelial cells to a low concentration of ONOO(-) (5 microM) significantly increased the phosphorylation of LKB1 at Ser(428) and protein kinase Czeta (PKCzeta) at Thr(410). These effects were accompanied by increased activity of the lipid phosphatase PTEN, decreased activity and phosphorylation (Ser(473)) of Akt, and induction of apoptosis. ONOO(-) enhanced Akt-Ser(473) phosphorylation in LKB1-deficient HeLa S3 cells or in HeLa S3 cells transfected with kinase-dead LKB1. Conversely, ONOO(-) inhibited Akt Ser(473) phosphorylation when wild type LKB1 were reintroduced in HeLa S3 cells. Further analysis revealed that PKCzeta directly phosphorylated LKB1 at Ser(428) in vitro and in intact cells, resulting in increased PTEN phosphorylation at Ser(380)/Thr(382/383). Finally, ONOO(-) enhanced PKCzeta nuclear import and LKB1 nuclear export. We conclude that PKCzeta mediates LKB1-dependent Akt inhibition in response to ONOO(-), resulting in endothelial apoptosis.