Isolation and properties of Escherichia coli ATPase mutants with altered divalent metal specificity for ATP hydrolysis.
A method was devised for isolation of large numbers of energy-transducing ATPase (coupling factor) mutants based on a modification of the procedure of Hong and Ames (Hong, J. and Ames, B. N. (1971) Proc. Natl. Acad. Sci. U.S. 68, 3158-3162) for localized mutagenesis of any small region of the bacterial chromosome using transducing phages. The principle of this procedure is to mutate P1-transducing phage particles carrying the ATPase genes (Unc (uncoupled) DNA) using the strong chemical mutagen hydroxylamine. By transducing ilv- auxotrophs, a marker closely linked to Unc, to prototrophs, mutated Unc DNA can be introduced into the chromosome. We have used this method in conjunction with suitable selection procedures to isolate about 90 Unc- strains which have been classified by physiological, genetic, and biochemical criteria into three different phenotypes (Unc A, B, D). Mutants of the Unc D phenotype which were studied in detail were found to have the following properties: (1) aerobic growth yields on glucose are considerably lower than the wild type; growth occurs on glucose under anaerobic conditions; (2) Unc D lesions map near the ilv operon; (3) O2 uptake is comparable to the rate of wild type; (4) vesicles catalyze respiratory-dependent transhydrogenation, but show very low levels of Ca2+ ATP-dependent transhydrogenation; Mg2+ is ineffective; (5) oxidative phosphorylation is almost completely blocked irrespective of which metal ion is used; (6) the specific activity of ATPase is only about 20% of the wild type: (7) purified ATPase was found to have a marked specificity for Ca2+ as a divalent metal for ATP hydrolysis. A summary of properties of the new Unc mutants is discussed.


Pure flat epithelial atypia identified on core needle biopsy does not require excision.
Routine excision of flat epithelial atypia (FEA) of the breast found on core needle biopsy (CNB) is being questioned and a policy of selective excision of FEA was adopted in our area. The purpose of this study was to evaluate the upstage rate to malignancy across multiple diagnostic centers in our area following the policy of selective excision and to identify factors predictive of malignancy. Patients having excision of CNB FEA at our regional Hospital between 2013 and 2017 were identified. The primary endpoint was upstage to malignancy after excision. We also assessed for clinical, radiological, and pathological features associated with malignancy. We identified 187 patients. Eighty-nine had pure FEA, 71 had concurrent ADH, and 18 had other pathological lesions. Following surgical excision, 9 patients were upstaged to malignancy (4. 8%) with 8 having concurrent ADH (2 invasive ductal carcinoma, 6 DCIS) and 1 with concurrent Complex Sclerosing Lesion (DCIS). None of the pure FEA cases upstaged. The presence of ADH or CSL in the CNB were the only factors found to be predictive of upstaging (p = 0.001, p = 0.0001 respectively). The upstage rate to malignancy after excision of pure FEA at out center is 0%. Therefore, we recommend that pure FEA with radiology and pathology concordance does not require surgical excision and can instead be followed with serial imaging. However, patients with FEA in association with other high-risk lesions should be managed as per indicated for the other high-risk lesion and FEA with ADH should be excised.


Post-gastrulation synthetic embryos generated ex utero from mouse naive ESCs.
In vitro cultured stem cells with distinct developmental capacities can contribute to embryonic or extraembryonic tissues after microinjection into pre-implantation mammalian embryos. However, whether cultured stem cells can independently give rise to entire gastrulating embryo-like structures with embryonic and extraembryonic compartments remains unknown. Here, we adapt a recently established platform for prolonged ex utero growth of natural embryos to generate mouse post-gastrulation synthetic whole embryo models (sEmbryos), with both embryonic and extraembryonic compartments, starting solely from naive ESCs. This was achieved by co-aggregating non-transduced ESCs, with naive ESCs transiently expressing Cdx2 or Gata4 to promote their priming toward trophectoderm and primitive endoderm lineages, respectively. sEmbryos adequately accomplish gastrulation, advance through key developmental milestones, and develop organ progenitors within complex extraembryonic compartments similar to E8.5 stage mouse embryos. Our findings highlight the plastic potential of naive pluripotent cells to self-organize and functionally reconstitute and model the entire mammalian embryo beyond gastrulation.


A qualitative exploration of using financial incentives to improve vaccination uptake via consent form return in female adolescents in London.
Incentivising vaccine consent form return may improve vaccine uptake and be seen as less coercive than incentivising vaccination itself. We assessed the acceptability of financial incentives in this context among adolescent females and explored potential mechanisms by which incentives might change behaviour. Focus groups and analysis of free-text questionnaire responses. Study 1: 36 female secondary students in London (age 13-14) participated in six focus groups exploring the use of incentives in the context of vaccination. Data were analysed thematically. Study 2: was conducted to triangulate the findings of Study 1, by analysing free-text questionnaire responses from 181 female secondary students in London (age 12-13) reporting their opinion of incentivising consent form return. Data from Study 1 was also used to explore perceived potential mechanisms of action by which incentives might encourage consent form return. Focus group participants had positive attitudes towards incentives, with 61% of free-text responses also expressing this. Most focus group participants thought that incentives would encourage consent form return (18% of free-text respondents spontaneously also mentioned this). While incentivising consent form return was seen as ethical, focus group participants who incorrectly thought that vaccine receipt was being incentivised raised concerns about bribery, although only 4% of free text respondents reported these concerns. Frequently raised mechanisms of action included incentives increasing engagement with, and the perceived value of consent form return. Adolescents had positive views of financially incentivising consent form return to promote vaccine uptake, although care must be taken to reduce misconceptions regarding what is being incentivised. Incentivising vaccination was seen as coercive, but incentivising actions that increase the likelihood of vaccination (i.e. consent form return) were not. Incentives may encourage adolescents to return consent forms by helping them engage with this behaviour or increasing its' perceived value.


Fine structure of the arg-7 ciston in chlamydomonas reinhardi. Complementation between arg-7 mutants defective in argininosuccinate lyase.
In Chlamydomonas reinhardi, the arg-7 cistron is the structural gene for the enzyme argininosuccinate lyase which catalyzes the last reaction in the biosynthesis of arginine. Fourteen mutants (nine previously analyzed and five new mutants) defective in the lyase have been investigated so far: they all map within a cistron (length: 1.0--1.6 recombination units) of the linkage group I and fall within six groups of complementation. The enzyme activity found in the diploids formed by intragenic complementation was always lower than in wild-type haploid or diploid strains. The study of the denaturation curves obtained by heat treatment of the lyase indicates that in some diploids, several enzyme varieties can be present. These results and those previously obtained with diploids formed by intragenic and intergenic complementation (Matagne and Loppes, 1972; Matagne, 1976) are discussed in relation to the recent data showing that the argininosuccinate lyase is a multimeric enzyme probably composed of five identical polypeptide chains (Matagne and Schlösser, 1977).


ChrII-Encoded DNA Helicase: A Preliminary Study.
DNA helicases are unwinding enzymes that are essential for many cellular processes. Research has suggested that both the model microorganisms of a single chromosome and the model microorganisms of multiple chromosomes adopt DNA helicases encoded by chromosome I. Therefore, studying DNA helicases encoded by chromosome II may lay some foundation for understanding nucleic acid metabolism processes. To prove the existence of DNA helicase encoded by chromosome II and to reveal its difference compared to DNA helicase encoded by chromosome I. The DNA helicases of Pseudoalteromonas spongiae JCM 12884T and Pseudoalteromonas tunicata DSM 14096T were analyzed by sequence alignment and phylogenetic relationships with other known DNA helicases. Then, proteins of P. spongiae JCM 12884T and P. tunicata DSM 14096T were obtained by heterologous expression. N-terminal sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis were performed to confirm the form of proteins. A fluorescence resonance energy transfer (FRET) assay was used to measure the activity of helicases. DnaB-pspo and DnaB-ptun belong to the same family, the PRK08840 superfamily, and form a branch with helicases encoded by chromosome I. YwqA-pspo and YwqA-ptun have similar domains and form another branch with helicases encoded by chromosome II. All four helicases have DNA unwinding activity. YwqA is more efficient than DnaB for DNA unwinding, especially YwqA-pspo, which is encoded by bidirectional replication chromosome II. This is the first study to show that the existence of a DNA helicase encoded by chromosome II, and DNA helicase encoded by chromosome II is more efficient than chromosome I for DNA unwinding.


Characterization and application of a gall midge resistance gene (Gm6) from Oryza sativa 'Kangwenqingzhan'.
The resistance gene Gm6 was mapped and characterized using near-isogenic and pyramided lines, followed by marker-assisted selection to develop lines with resistance to both gall midge and brown planthopper. The Asian rice gall midge (GM; Orseolia oryzae; Diptera: Cecidomyiidae) is a major destructive pest affecting rice cultivation regions. The characterization of GM-resistance genes and the breeding of resistant varieties are together considered the most efficient strategy for managing this insect. Here, the Gm6 resistance gene derived from the Kangwenqingzhan (KW) variety was found to be located on the long arm of chromosome 4 using the F2 population of 9311/KW. The region was narrowed to a 90-kb segment flanked by the markers YW91 and YW3-4 using backcrossing populations. Based on no-choice feeding and host choice tests, GM development and growth in near-isogenic lines (NILs) were severely restricted compared to that in the 9311 control. On day 8, the average GM body length was 0.69 mm and 0.56 mm on NILs and 9311, respectively, and the differences were more significant at later time points. However, GM insects exhibited no host preference between NILs and 9311, and there was normal egg hatching on the resistant plants. We developed pyramided lines carrying BPH27, BPH36, and Gm6 by crossing and backcrossing with marker-assisted selection. These lines were similar to the KW parent in terms of agronomic traits while also exhibiting high resistance to brown planthopper (BPH) and GM. The present mapping and characterization of Gm6 will facilitate map-based cloning of this important resistance gene and its application in the breeding of insect-resistant rice varieties.


Role of IL-5 during primary and secondary immune response to acetylcholine receptor.
To analyze the role of the Th2 cytokine interleukin-5 (IL-5) in experimental autoimmune myasthenia gravis (EAMG) pathogenesis, we induced clinical EAMG in C57BL/6 and IL-5 gene-knockout (KO) mice in the C57BL/6 background. IL-5 KO mice had a significantly reduced incidence and severity of EAMG. Despite their increased resistance to EAMG, IL-5 KO mice displayed intact secondary antibody and lymphoproliferative responses to acetylcholine receptor (AChR) after immunization with this molecule. However, the relative resistance of IL-5 KO mice was associated with a reduced primary lymphocyte response to AChR, and reduced C3 levels in muscle extracts compared to those in C57BL/6 mice.


Cloning and chromosomal mapping of human cytochrome b5 reductase (DIA1).
We have isolated a cDNA clone that codes for human cytochrome b5 reductase. The cDNA was used to analyse, by Southern-blot hybridization, DNA isolated from a panel of 11 independent human-rodent somatic cell hybrids. The results indicate that cytochrome b5 reductase is encoded by a single gene located on human chromosome 22.


The Asian American family and mental health: implications for child health professionals.
The Asian American community has grown significantly in the United States during recent decades. The culture of their countries of origin as well as the society in which they currently live plays a pivotal role in their reaction to mental health and illness. Mental health issues are increasingly evident in Asian American communities. The need for the delivery of culturally competent health care and mental health services is paramount. A culturally competent framework that includes the use of a cultural competence model for practice can guide the health care provider in the recognition of problems, particularly in the children of Asian American families.


The safety of a field termination-of-resuscitation protocol.
A 1999 National Association of EMS Physicians position paper recommends that termination of resuscitation (TOR) be considered if the adult nontraumatic out-of-hospital cardiac arrest (OOHCA) patient receives cardiopulmonary resuscitation, definitive airway management, intravenous access, and at least 20 minutes of resuscitative efforts, yet remains in asystole or pulseless electrical activity with no return of spontaneous circulation (ROSC) in the field. To test the safety of this protocol, with survival to discharge as the primary endpoint. The study hypothesis was that the protocol is 100% specific: no patient who would be eligible for TOR survived to discharge. Utstein template data were collected prospectively for all OOHCA patients received at two academic emergency departments between August 1999 and January 2003, and retrospective OOHCA data were collected at one of the hospitals covering the interval October 1993 to June 2002. Each case was examined to determine whether the patient would have been eligible for TOR, and whether he or she survived. Three hundred sixty-six prospective and 135 retrospective cases were included. Twelve patients survived to discharge, but none were eligible for TOR, as all had ROSC in the field (specificity 100%, sensitivity 58%). Of the 63 patients who survived to admission, four were eligible for TOR (specificity 94%, sensitivity 64%). None of these four survived to discharge, and not regained consciousness prior to death. The proposed protocol appears to be safe, with 100% specificity for lack of survival to discharge in this sample. A small number of patients eligible for TOR did survive to admission, but none survived to discharge.


Cost and Treatment Characteristics of Sport-Related Knee Injuries Managed by Athletic Trainers: A Report From the Athletic Training Practice-Based Research Network.
Knee injuries are common during sport participation. However, little is known about the overall management and estimated direct costs of care associated with these injuries when under the care of athletic trainers. To describe the treatment characteristics and direct costs of care for athletic training services provided for patients with knee injuries. Descriptive study. Ninety-five athletic training facilities across 24 states. A total of 117 athletic trainers (females = 56.4%, age = 29.4 ± 8.7 years, years certified = 4.7 ± 6.0, years employed at site = 1.6 ± 4.1). Complete patient cases were identified using International Classification of Disease-10 diagnostic codes between 2009 and 2020. Summary statistics were calculated for patient demographics, treatment characteristics, and direct costs of care. Treatment characteristics included the type of athletic training service, duration, amount (eg, number of visits), and direct costs of care. A total of 441 patient cases were included. The most common injuries reported were cruciate ligament sprain (18.1%, n = 80), medial collateral ligament sprain (15.4%, n = 68), and knee pain (14.1%, n = 62). Injuries occurred most frequently during football (35.4%, n = 156), basketball (14.7%, n = 65), and soccer (12.7%, n = 56). A total of 8484 athletic training services were recorded over 4254 visits, with therapeutic exercise (29.8%, n = 2530), hot or cold pack (25.8%, n = 2189), and therapeutic activities (11.2%, n = 954) being the most frequently reported services. The median duration of care was 23 days and number of visits was 8. The median total cost of care was $564 per injury and $73 per visit. Patients with knee injuries demonstrated greater time loss than those with other lower extremity injuries. Thus, it is unsurprising that knee injuries were associated with a longer duration and higher cost of care than other lower extremity injuries such as ankle sprains. Future researchers should examine the effectiveness of common treatment strategies and aim to identify treatments that can reduce costs and improve patient outcomes.


Comparison of the diuretic renogram and the pressure perfusion study in children.
We evaluated 42 hydronephrotic kidneys with diuretic renography and pressure perfusion studies to diagnose or exclude the presence of obstruction. Both studies were highly accurate but a small number of false positive and false negative studies were observed with each testing modality. The advantages, disadvantages and potential sources of inaccuracy of each study are discussed, and a protocol for the evaluation of hydronephrosis incorporating both studies is proposed.


Ultrastructural studies of intraoral verruca vulgaris.
The literature offers conflicting views regarding the existence of verruca vulgaris in the oral cavity. In an attempt to clarify this issue, a series of ten oral lesions which had been diagnosed as verruca vulgaris and ten oral lesions diagnosed as squamous-cell papilloma were examined ultrastructurally. Six of the lesions diagnosed as verruca vulgaris contained the characteristic intranuclear viral particles which are normally found in that lesion. None of the lesions diagnosed as squamous-cell papilloma exhibited this type of intranuclear viral inclusions.


Effects of different compounding of formulae on content of gardenoside in Yin Chen Hao decoction.
In order to observe the effects of the ground and intact Zhi Zi (Fructus Gardeniae) and different combinations of the ingredients and refined single Chinese drug granules in Yin Chen Hao Decoction compound prescription on the contents of gardenoside (an effective component of the prescription), the contents of gardenoside were determined with reversed phase high performance liquid chromatography (HPLC), with acetonitrile-water (15:85) as mobile phase, at wave length 238 nm. The results indicated that the gardenoside-decocted-out rates in the decoctions prepared by different combinations of the ingredients with the ground Zhi Zi (Fructus Gardeniae) all were higher significantly than those in the decoction with intact Zhi Zi (Fructus Gardeniae), and generally, different combinations of the ingredients in the decoction had only little effect on the gardenoside-decocted-out rate.


24-hour central aortic systolic pressure and 24-hour central pulse pressure are related to diabetic complications in type 1 diabetes - a cross-sectional study.
Non-invasive measurements of 24 hour ambulatory central aortic systolic pressure (24 h-CASP) and central pulse pressure (24 h-CPP) are now feasible. We evaluate the relationship between 24 h central blood pressure and diabetes-related complications in patients with type 1 diabetes. The study was cross-sectional, including 715 subjects: 86 controls (C), 69 patients with short diabetes duration (< 10 years), normoalbuminuria (< 30 mg/24 h) without receiving antihypertensive treatment (SN), 211 with longstanding diabetes (≥ 10 years) and normoalbuminuria (LN), 163 with microalbuminuria (30-299 mg/24 h) (Mi) and 186 with macroalbuminuria (> 300 mg/24 h) (Ma).24 h-CASP and 24 h-CPP was measured using a tonometric wrist-watch-like device (BPro, HealthStats, Singapore) and derived using N-point moving average. In C, SN, LN, Mi and Ma mean ± SD 24 h-CASP was: 114 ± 17, 115 ± 13, 121 ± 13, 119 ± 16 and 121 ± 13 mmHg (p < 0.001); and 24 h-CPP: 38 ± 8, 38 ± 7, 44 ± 10, 46 ± 11 and 46 ± 11 mmHg, (p < 0.001).Following rigorous adjustment (24 h mean arterial pressure and conventional risk factors), 24 h-CASP and 24 h-CPP increased with diabetes, albuminuria degree, previous cardiovascular disease (CVD), retinopathy and autonomic dysfunction (p ≤ 0.031).Odds ratios per 1 standard deviation increase in 24 h-CASP, 24 h-CPP and 24 h systolic blood pressure (24 h-SBP) were for CVD: 3.19 (1.68-6.05), 1.43 (1.01-2.02) and 2.39 (1.32-4.33), retinopathy: 4.41 (2.03-9.57), 1.77 (1.17-2.68) and 3.72 (1.85-7.47) and autonomic dysfunction: 3.25 (1.65-6.41), 1.64 (1.12-2.39) and 2.89 (1.54-5.42). 24 h-CASP and 24 h-CPP was higher in patients vs. controls and increased with diabetic complications independently of covariates. Furthermore, 24 h-CASP was stronger associated to complications than 24 h-SBP.The prognostic significance of 24 h-CASP and 24 h-CPP needs to be determined in follow-up studies. ClinicalTrials.gov ID NCT01171248.


Evaluation of sulfonated aluminum phthalocyanines for use in photochemotherapy. A study on the relative efficiencies of photoinactivation.
The cellular photosensitivity caused by aluminum phthalocyanines sulfonated to different degrees (AlPcSn) has been investigated. The phototoxic effect increased with decreasing number of sulfonate groups on the macrocycle, with the exception of AlPcS1 which was less phototoxic than AlPcS2 but more phototoxic than AlPcS3 and AlPcS4. The tendency of the AlPcSns to aggregate in our cellular system increased with increasing lipophilicity of the sensitizers. The aggregates had little or no photosensitizing activity. The low efficiency of cell inactivation caused by AlPcS1 can be explained by the highly aggregated state of this sensitizer in the cells. AlPcS2 and AlPcS3 induced a lower degree of cell inactivation per fluorescing quantum and per quantum absorbed by monomeric species than did AlPcS2 and AlPcS1. AlPcS4 and AlPcS3 are therefore suggested to be in different intracellular locations than AlPcS2 and AlPcS1.


COVID-19 complicated by parainfluenza co-infection in a patient with chronic lymphocytic leukemia.
The number of people suffering from the new coronavirus SARS-CoV-2 continues to rise. In SARS-CoV-2, superinfection with bacteria or fungi seems to be associated with increased mortality. The role of co-infections with respiratory viral pathogens has not yet been clarified. Here, we report the course of COVID-19 in a CLL patient with secondary immunodeficiency and viral co-infection with parainfluenza.


A new type of ventriculo-atrial gap phenomenon in man.
A new type of ventriculo-atrial (V-A) gap phenomenon was observed in a patient who underwent a cardiac electrophysiology study and had complete antegrade infranodal A-V block but intact V-A conduction. During ventricular extrastimulus testing, a split retrograde His potential emerged from the ventricular electrogram. As the prematurity of the extrastimulus was increased, the later of the two retrograde His deflections disappeared suddenly at a critical coupling interval and V-A conduction was interrupted. More premature extrastimuli resulted in progressive delay in the His-Purkinje system and delayed appearance of the earlier retrograde His deflection. As a result of this delay, conduction through the His bundle eventually resumed, the second (split) retrograde His reappeared and conduction to the atria resumed. Thus, the initial site of block during the V-A gap phenomenon in this patient was located in the His bundle, with proximal delay occurring in the distal His-Purkinje system. The results indicate that the classic mechanism of gap phenomenon is operative. To our knowledge, this type of V-A gap phenomenon has not been previously described in man.


Effect of L-citrulline supplementation on blood pressure: a systematic review and meta-analysis of randomized controlled trials.
The objective of this study was to systematically investigate the efficacy of oral L-citrulline supplementation on systolic and diastolic blood pressure. Studies were identified by a search of electronic databases from inception to April 2018, and combined and stratified analyses were used. Fifteen trials were identified, and data from 424 participants were included. Pooled analysis showed significant reductions in systolic blood pressure by -7.54 mmHg (95% confidence interval (CI): -9.44, -5.63; P < 0.001, I2 = 14%) and diastolic blood pressure by -3.77 mmHg (95% CI: -5.67, -1.86, P < 0.001, I2 = 42%) following oral supplementation of L-citrulline or a watermelon extract. No changes were detected in controls. Significant heterogeneity (I2 = 42%, P = 0.04) was found for diastolic blood pressure, and subgroup analysis showed significant improvements in systolic and diastolic blood pressure, particularly for study durations: ≥6 weeks, lower doses: ≤4 g/day, and in participants with higher baseline values: ≥130/85 mmHg. In conclusion, L-citrulline improves systolic and diastolic blood pressure and may be more efficacious in pre-hypertensive and hypertensive populations.


Alteration of biochemical profiles after high-dose intravenous immunoglobulin administration in Kawasaki disease.
Intravenous immunoglobulin (IVIG) has been used as an immunomodulatory treatment for several immune-mediated diseases. Early effects of high-dose IVIG treatment on biochemical profiles including lipids and proteins were evaluated in patients with Kawasaki disease (KD). Twelve children with KD (9 boys) were treated with IVIG at 2 g/kg over a period of 12 h. Serial sera samples were collected from the patients four times: before IVIG treatment and 2 h, 24 h and 7 d after IVIG treatment. The samples were frozen at -20 degrees C before biochemical analysis. A significant decrease in albumin concentration was found 2 h and 24 h after IVIG treatment, but this recovered to the pretreatment level after 7 d. Total cholesterol and triglyceride increased slightly after 7 d. A significant decrease in HDL-cholesterol and C-reactive protein was seen 2 h and 24 h after IVIG treatment. High-dose IVIG affects immediate changes in protein profiles and HDL-cholesterol in KD. Changes in HDL-cholesterol induced by IVIG may be the result of changes in systemic protein metabolism.


Caenorhabditis elegans DAF-16/FOXO transcription factor and its mammalian homologs associate with age-related disease.
The insulin/IGF-1 signaling pathway is evolutionarily conserved and its function is mediated largely by FOXO transcription factors. Reduced insulin/IGF-1 signaling leads to translocation of FOXO proteins from the cytoplasm to the nucleus where they activate a set of genes that mediate oxidative stress, heat shock, and xenobiotic responses, innate immunity, metabolism, and autophagy. Disruptions in the insulin/IGF-1 signaling pathway affect lifespan in many species. Over the past two decades, the function of these FOXO proteins in age-related diseases has been extensively studied, in the model organism Caenorhabditis elegans as well as in humans. In this review we investigate the mechanisms by which FOXO proteins influence the development of age-related disease pathways in both species.


The molecular basis for the cytoadherence of Plasmodium falciparum-infected erythrocytes to endothelium.
Human erythrocytes infected with the human malaria parasite Plasmodium falciparum, bind to post-capillary venular endothelium and to uninfected red blood cells via specific receptor-ligand interactions. The interactions between malaria-parasitized erythrocytes and host cells is a highly cooperative and finely regulated process which contributes both to the evasion of host immune mechanisms and to the pathogenesis of the disease, in particular the development of cerebral malaria. The cellular and molecular interactions responsible for the adhesion of parasitized red cells to host cells are the subject of this review.


Chiral stationary phases based on chitosan bis(methylphenylcarbamate)-(isobutyrylamide) for high-performance liquid chromatography.
A series of chitosan bis(methylphenylcarbamate)-(isobutyrylamide) derivatives were synthesized by carbamylating chitosan isobutyrylamide with different methylphenyl isocyanates. Then the prepared chitosan derivatives were coated onto 3-aminopropyl silica particles, resulting in a series of new chiral stationary phases (CSPs) for high-performance liquid chromatography. It was observed that the chiral recognition abilities of these coated-type CSPs depended very much on the substituents on the phenyl moieties of the chitosan derivatives, the eluent composition, as well as the structure of racemates. As a typical example, the eluent tolerance of the prepared CSP with the best enantioseparation ability was investigated in detail, and the results revealed that the CSP exhibited extraordinary solvent tolerance and could still work without significant loss in enantioseparation capability after being flushed with chloroform (100%), ethyl acetate (100%) and even THF/n-hexane (70/30, v/v), while the traditional coated-type CSPs based on the cellulose and amylose derivatives, such as cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC) and amylose tris(3,5-dimethylphenylcarbamate) (ADMPC), might be dissolved or highly swollen in these eluents. Therefore, the application of the resultant CSPs could address the problem of the dissolution and high swelling of traditional coated-type CSPs in some unusual eluents, broadening the possibility of eluent choice. In addition, a comparison of the prepared CSPs with the well known CDMPC- and ADMPC- based CSPs concerning the chiral recognition ability was also made. Separation performances achieved on the as-prepared CSPs in different eluents were found to be even superior to CDMPC- and ADMPC-based CSPs for the tested chiral compounds. In summary, we could safely draw the conclusion that the CSPs derived from chitosan isobutyrylamide derivatives were capable of excellent chiral recognition ability, and meanwhile possessed satisfactory eluent tolerance in a wider range of solvents.


Do all patients with high-grade prostatic intraepithelial neoplasia on initial prostatic biopsy eventually progress to clinical prostate cancer?
To assess the clinical outcome of patients with a diagnosis of high-grade prostatic intraepithelial neoplasia (PIN) on initial prostatic biopsy, with a minimum of 5 years of follow-up, as such patients are at greater risk of having prostate cancer on subsequent biopsy. Between November 1992 and October 1998, 21 patients were identified as having PIN on their initial transrectal ultrasonography-guided prostate biopsy. None of these patients had a focus of cancer on the initial biopsy. Their medical data were reviewed retrospectively to determine the natural history of PIN in these patients. Patients who were not identified as having cancer were followed every 6-12 months with prostate-specific antigen (PSA) testing and digital rectal examinations (DRE). A mean (range) of 7 (2-8) cores were taken at initial biopsy; the mean age of the patients was 63 (53-77) years and mean PSA level 9.1 (4.9-17.6) ng/mL. Six patients had an abnormal DRE at presentation. A mean of 8 (7-10) cores were obtained on the second biopsy; six patients were diagnosed with cancer, with a mean Gleason score of 6 (5-7), while three were diagnosed with persistent PIN. These three patients had a third prostate biopsy which showed cancer of Gleason score 6 in one and benign prostatic hyperplasia in two. After a mean follow-up of 72.2 (60-84) months, none of the remaining 12 patients was diagnosed with clinically significant cancer. Five of these patients went on to a third prostate biopsy, with no evidence of cancer. One patient died from unrelated causes during this period. This study affirms our current practice of following patients with PIN conservatively if a second or third subsequent prostate biopsy is negative. Whether PIN is a premalignant lesion or merely a lesion associated with cancer needs to be addressed in multicentre studies with a follow-up of > 10 years.


Microarray Analysis Confirms ImmunoCAP-Fluorescence Enzyme Immunoassay Results on Specific IgE in Patients with Atopic Dermatitis and Suspected Birch Pollen-Related Food Allergy.
Previous studies demonstrated that birch pollen-related foods can cause late eczematous responses in birch pollen-sensitized patients with atopic dermatitis (AD). However, suitable markers to predict birch pollen-related food allergy in patients with AD are still lacking. We evaluated the correlation of the results from ImmunoCAP® fluorescence enzyme immunoassay (FEIA) singleplex and ImmunoCAP® immuno solid-phase allergen chip (ISAC) multiplex system in AD patients and investigated the diagnostic validity of allergen microarray analysis, measuring specific IgE (sIgE) with ImmunoCAP® ISAC to predict birch pollen-related food allergy in patients with AD. A total of 19 children and adults with AD, existing IgE-mediated birch pollen sensitization, and suspected birch pollen-related food allergy underwent a double-blind placebo-controlled food challenge (DBPCFC) in the clinical routine. Total and sIgE levels to birch pollen, Bet v 1, Bet v 2, and birch pollen-related foods (apple, carrot, celery, and hazelnut) were determined prior to the DBPCFC by ImmunoCAP®-FEIA. Additionally, allergen microarray ImmunoCAP® ISAC analysis was performed. Data were analyzed retrospectively. Twelve out of 19 patients (63% responders) experienced an allergic reaction upon DBPCFC. Overall, 7 patients (37%) developed a significant deterioration of AD with a median increase of 12.4 points in the scoring of atopic dermatitis (SCORAD) index (range 10.0-15.7). Oral allergy syndrome was the predominant immediate-type symptom (n = 11/12 responders). There were no differences in sensitization frequencies regarding allergens of the pathogenesis-related protein family 10 between responders and non-responders. In all patients, correlation of IgE levels determined with ImmunoCAP® ISAC and ImmunoCAP®-FEIA, respectively, was significant with high correlation coefficients regarding birch pollen allergen extract, rBet v 1, and rBet v 2 (rs > 0.8, p < 0.001) and lower but also significant correlation coefficients regarding food allergens (rs < 0.8, p < 0.05-<0.001). ImmunoCAP® ISAC microarray allows displaying a differentiated sensitization profile in birch pollen-sensitized patients with AD. However, IgE-mediated sensitization against birch pollen-related allergens revealed by the allergen multiplex system does not predict late eczematous reactions upon DBPCFC with birch pollen-related foods.


Possible relationship between Seismic Electric Signals (SES) lead time and earthquake stress drop.
Stress drop values for fourteen large earthquakes with M(W)> or =5.4 which occurred in Greece during the period 1983-2007 are available. All these earthquakes were preceded by Seismic Electric Signals (SES). An attempt has been made to investigate possible correlation between their stress drop values and the corresponding SES lead times. For the stress drop, we considered the Brune stress drop, Deltasigma(B), estimated from far field body wave displacement source spectra and Deltasigma(SB) derived from the strong motion acceleration response spectra. The results show a relation may exist between Brune stress drop, Deltasigma(B), and lead time which implies that earthquakes with higher stress drop values are preceded by SES with shorter lead time.


Should chromosomal microarray be offered to fetuses with ultrasonographic soft markers in second trimester: A prospective cohort study and meta-analysis.
To evaluate whether chromosomal microarray (CMA) should be offered to fetuses with ultrasonographic soft markers (USMs) in the second trimester. A prospective cohort study and meta-analysis were conducted. In the prospective cohort study, 564 fetuses with USMs were enrolled. In the meta-analysis, eligible articles describing copy number variations in fetuses with USMs were included. In the prospective cohort study, the diagnostic yields of CMA over non-invasive prenatal testing (NIPT) and karyotyping were significantly higher in fetuses with mild ventriculomegaly (MVM) than those in local control cohorts with normal ultrasound. However, the yields of CMA over NIPT and karyotyping in fetuses with other USMs were similar to controls. About ten studies, involving 405 fetuses with MVM and 1412 fetuses with other USMs, were included in the meta-analysis. The pooled diagnostic yields of CMA over NIPT and karyotyping in fetuses with MVM were 4.9% and 3.2%, respectively. In fetuses with other USMs, the yields of CMA over NIPT and karyotyping were 1.2% and 0.4%, respectively. It is reasonable to offer CMA as a first-tier test to fetuses with MVM. However, for fetuses with other USMs, the considerations to perform CMA should not differ from pregnancies with normal ultrasound.


Epstein-Barr Virus-induced Gene 3 as a Novel Biomarker in Metastatic Melanoma With Infiltrating CD8+ T Cells: A Study Based on The Cancer Genome Atlas (TCGA).
Epstein-Barr virus-induced gene 3 (EBI3) is an immunomodulatory protein-coding gene. So far, the prognostic role of EBI3 in human metastatic melanoma has been unclear. This study aimed to evaluate the EBI3 expression as a potential biomarker using the public database with tumor-infiltrating lymphocytes (TILs) data. Survival analyses were performed in the database of The Cancer Genome Atlas (TCGA) and GSE65904, GSE19234, GSE22153, and GSE22154. The mRNA levels, the distribution pattern of TILs, and the estimated fractions of TILs from the TCGA database were integrated. Higher EBI3 expression in tumors was significantly associated with longer overall survival in TCGA and the other independent cohorts. Interestingly, the patients with high EBI3 expression had a brisk pattern of TILs and increased CD8+ T cells over regulatory T cells with less pigmentation-related gene expressions. EBI3 could serve as a novel biomarker in metastatic melanoma with a favorable TILs profile.


Use of Ambroxol as Therapy for Gaucher Disease.
Ambroxol was identified as an enhancer of stability and residual activity of several misfolded glucocerebrosidase variants in 2009. To assess hematologic and visceral outcomes, biomarker changes, and safety of ambroxol therapy for patients with Gaucher disease (GD) without disease-specific treatment. Patients with GD who could not afford enzyme replacement therapy were enrolled and received oral ambroxol from May 6, 2015, to November 9, 2022, at Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China. Thirty-two patients with GD (29 with GD type 1, 2 with GD type 3, and 1 with GD intermediate types 2-3) were enrolled. Of those, 28 patients were followed up for longer than 6 months; 4 were excluded due to loss of follow-up. Data analyses were performed from May 2015 to November 2022. An escalating dose of oral ambroxol (mean [SD] dose, 12.7 [3.9] mg/kg/d). Patients with GD receiving ambroxol were followed up in a genetic metabolism center. Biomarkers of chitotriosidase activity and glucosylsphingosine level, liver and spleen volumes, and hematologic parameters were measured at baseline and various time points throughout the ambroxol treatment. A total of 28 patients (mean [SD] age, 16.9 [15.3] years; 15 male patients [53.6%]) received ambroxol for a mean (SD) duration of 2.6 (1.7) years. Two patients with severe symptoms at baseline experienced deterioration of hematologic parameters and biomarkers and were deemed nonresponders; clinical response was observed in the other 26 patients. After 2.6 years of ambroxol treatment, the mean (SD) hemoglobin concentration improved from 10.4 (1.7) to 11.9 (1.7) g/dL (mean [SD], 1.6 [1.7] g/dL; 95% CI, 0.8-2.3 g/dL; P < .001), and the mean (SD) platelet count improved from 69 (25) to 78 (30) × 103/µL (mean [SD], 9 [22] × 103/µL; 95% CI, -2 to 19 × 103/µL; P = .09). The mean (SD) spleen volume decreased from 17.47 (7.18) to 12.31 (4.71) multiples of normal (MN) (mean [SD], -5.16 [5.44] MN; 95% CI, -10.19 to -0.13; P = .04), and the mean (SD) liver volume decreased from 1.90 (0.44) to 1.50 (0.53) MN (mean [SD], -0.39 [0.42] MN; 95% CI, -0.75 to -0.04; P = .03). Biomarker median percentage changes from baseline were -43.1% for chitotriosidase activity (from 14 598 [range, 3849-29 628] to 8312 [range, 1831-16 842] nmol/mL/h; z = -3.413; P = .001) and -34.1% for glucosylsphingosine level (from 251.3 [range, 73.6-944.2] to 165.7 [range, 21.3-764.8] ng/mL; z = -2.756; P = .006). Patients were divided into subgroups according to age when initiating treatment; those who received treatment at a younger age (mean [SD] age, 6.3 [2.7] years) experienced more rapid improvements: hemoglobin concentration increased by 16.5% (from 10.3 [1.5] to 12.0 [1.5] g/dL; mean [SD] change, 1.6 [1.6] g/dL; 95% CI, 0.7-2.5 g/dL; P = .002), and platelet count increased by 12.0% (from 75 [24] to 84 [33] × 103/µL; mean [SD] change, 9 [26] × 103/µL; 95% CI, -5 to 24 × 103/µL; P = .17); whereas chitotriosidase activity decreased by 64.0% (from 15 710 [range, 4092-28 422] to 5658 [range, 1146-16 843] nmol/mL/h; z = -2.803; P = .005), and glucosylsphingosine level decreased by 47.3% (from 248.5 [range, 122.8-674.9] to 131.0 [range, 41.1-448.5] ng/mL; z = -2.385; P = .02). Three of the 28 patients experienced mild and transient adverse events. In this case series of ambroxol repurposing among patients with GD, long-term treatment with ambroxol was safe and associated with patient improvement. Improvements in hematologic parameters, visceral volumes, and plasma biomarkers were larger among patients with relatively mild symptoms of GD and patients who received initial treatment at younger ages.


A genetic instrument for Mendelian randomization of fibrinogen.
Mendelian randomization studies on fibrinogen commonly use a single genetic variant as an instrument, but this may explain only a small proportion of the total phenotypic variance. We examined the contribution of multiple common single nucleotide polymorphisms (SNPs) and haplotypes in the entire fibrinogen gene cluster to plasma fibrinogen levels in two prospective cohorts, for use as instruments in future Mendelian randomization studies. Genotypes for 20 SNPs were determined in 2,778 middle-age (49-64 years) men from the Second-Northwick-Park-Heart Study (NPHS-II). These were replicated in 3,705 men from the Whitehall-II study (WH-II). Plasma fibrinogen levels were determined six times in NPHS-II and three times in WH-II. The minor alleles of four SNPs from the FGB gene, two from the FGA gene, and one from the FGG gene were associated with higher plasma fibrinogen levels. SNP rs1800790 (-455G>A) commonly used in Mendelian randomization studies was associated with R2=1.22% of the covariate adjusted residual variance in fibrinogen level. A variable selection procedure identified one additional SNP: rs2070011 (FGA) altogether explaining R2=1.45% of the residual variance in fibrinogen level. Using these SNPs no evidence for causality between the fibrinogen levels and coronary heart diseases was found in instrumental variables analysis. In the replication cohort, WH-II, the effects of the two SNPs on fibrinogen levels were consistent with the NPHS-II results. There is statistical evidence for several functional sites in the fibrinogen gene cluster that determine an individual's plasma fibrinogen levels. Thus, a combination of several SNPs will provide a stronger instrument for fibrinogen Mendelian randomization studies.


Comparison of effects of pitavastatin and atorvastatin on plasma coenzyme Q10 in heterozygous familial hypercholesterolemia: results from a crossover study.
An open, randomized, four-phased crossover study using 4 mg of pitavastatin or 20 mg of atorvastatin was performed to compare their efficacy and safety, especially regarding plasma levels of coenzyme Q10 (CoQ10) in 19 Japanese patients with heterozygous familial hypercholesterolemia. Pitavastatin and atorvastatin caused significant and almost comparable reductions in serum levels of total cholesterol (-35.4 vs. -33.8%), low-density lipoprotein cholesterol (-42.8 vs. -40.7%), and triglyceride (-26.1 vs. -29.4%), and significantly increased serum levels of high-density lipoprotein cholesterol (12.1 vs. 11.4%). Under these conditions, plasma levels of CoQ10 were reduced by atorvastatin (-26.1%, P=0.0007) but not by pitavastatin (-7.7%, P=0.39), although no adverse events or abnormalities of liver and muscle enzyme were observed after either statin treatment. It remains to be seen whether the observed changes in CoQ10 levels are related to the long-term safety of this drug.


Petromylidenes A⁻C: 2-Alkylidene Bile Salt Derivatives Isolated from Sea Lamprey (Petromyzon marinus).
Three novel bile acid derivatives, petromylidenes A⁻C (1⁻3), featuring uncommon alkylidene adductive scaffolds, were isolated from water conditioned with sexually mature male sea lampreys (Petromyzon marinus). Their structures were elucidated by mass spectrometry and NMR spectroscopy, and by comparison to spectral data of related structures. The identification of compounds 1⁻3, further illustrates the structural diversity of the 5α bile salt family. Compounds 1⁻3 exhibited notable biological properties as well, including high olfactory potencies in adult sea lampreys and strong behavioral attraction of ovulated female sea lampreys. Electro-olfactogram recordings indicated that the limit of detection for 1 was 10-9 M, 2 was 10-11 M, and 3 was less than 10-13 M. These results suggested 1⁻3 were likely male pheromones, which guide reproductive behaviors in the sea lamprey.


Cytotoxic activity of new racemic and optically active N-phosphonoalkyl bicyclic β-amino acids against human malignant cell lines.
The cytotoxic effects of novel racemic and optically active constrained N-phosphonoalkyl bicyclic β-amino acids were tested against a panel of human tumor cell lines. All of the compounds investigated exhibited different concentration-dependent antiproliferative effects against the HT-29, MDA-MB-231, HepG2 and HeLa cell lines after 24 h treatment. The most sensitive cells were the HeLa cells at various concentrations of the four compounds tested. The aminophosphonate 3 exerted the most pronounced antiproliferative effect against the HeLa cells (inhibition of the cell vitality up to 70% at 0.5 mg/ml) and was not toxic to the normal Lep3 cells at lower concentration. Furthermore, the N-phosphonophenyl derivatives 1 and 2 displayed antiproliferative effect against mainly the MDA-MB-231 tumour cells at higher concentration.


Pathological involvement of primary sensory neurons in Werdnig-Hoffmann disease.
Seven patients with the typical clinical picture and muscle biopsy findings of classical Werdnig-Hoffmann disease showed Wallerian degeneration in their biopsied sural nerves. In dorsal root ganglia of one patient there were residual nodules and several chromatolytic neurons. By electron microscopy the changes of chromatolysis were confirmed and found to be consistent with an axonal reaction. Involvement of the primary sensory neuron is probably a regular pathologic feature of Werdnig-Hoffmann disease. The type of abnormality suggests in initial failure of the axon distal to the nerve roots.


Lurasidone in adolescents and adults with schizophrenia: from clinical trials to real-world clinical practice.
Lurasidone is an atypical antipsychotic agent approved in the European Union for the treatment of schizophrenia in adults and adolescents (13-17 years). Clinical trials have shown a generally favorable balance between efficacy and tolerability. This paper provides a review and commentary regarding the use of lurasidone in adults and adolescents with schizophrenia. The available information about efficacy, tolerability, dosing, and switching is analyzed, highlighting the strategies that may be most useful in real-world clinical practice. Virtual case studies, designed based on the authors' clinical experience with real-world patients, are provided. Lurasidone is efficacious in adolescents and adults in a wide range of symptoms of schizophrenia. Choosing the right dose for each patient and combining lurasidone with other medications is key to treatment success. Lurasidone has proven effective both in adolescents and adults in treating the acute phase of schizophrenia and reducing the risk of relapse. It has shown a relatively favorable tolerability profile, with minimal effects on metabolic parameters and prolactin levels.


Alternative mRNA splicing of G protein-coupled receptors.
Alternative mRNA splicing as an important mechanism for generating protein diversity has been implicated to affect 60-70% of human genes (Wang et al., 2008). The G protein-coupled receptors (GPCRs), the largest group of membrane receptors, have a broad distribution and function. Posttranslational modifications or/and association with regulatory proteins can govern cell- and tissue-specific pharmacological, signaling, and regulatory characteristics of GPCRs. However, increasing body of evidence suggests that alternative splicing of GPCRs is a mechanism that can modulate GPCRs' function (Einstein et al., 2008). Many GPCRs have a potential to undergo alternative pre-mRNA splicing (~50%). Due to a general lack of isoform-specific antibodies, GPCRs' alternative splicing is mainly studied on mRNA level employing various PCR techniques. Functional characteristics (including signaling and structure) of alternatively spliced GPCRs are studied in overexpression system employing standard biochemical techniques. In this chapter, we will describe the methods for detection and quantification of alternatively spliced GPCR mRNA. As the experimental paradigm, we use type 1 corticotropin-releasing hormone receptor (CRH-R1).


Scanning electron microscopy of acellular glomeruli in nephrotic syndrome.
All cellular elements were extracted from portions of 13 renal biopsies performed for nephrotic syndrome and the acellular glomerular basement membrane (GBM) examined by scanning electron microscopy (SEM). Five biopsy specimens did not contain subepithelial deposits by light microscopy (LM), immunofluorescence (IF), and transmission electron microscopy (TEM). SEM of the acellular GBM showed a uniform slightly granular surface identical to that previously reported for normal human GBM. Eight biopsy specimens contained subepithelial deposits by LM, IF, and TEM. SEM showed complete extraction of deposits and a spectrum of clearly visualized diffuse GBM alterations in response to subepithelial deposits. Shallow pits or indentations of the GBM were noted in two cases stage I MGN which correlated with numerous "pinholes" visualized by LM in tangential sections of the GBM on silver stain. A complex reticular pattern of GBM elaboration was observed in cases of stage II MGN corresponding to "spikes" visualized by LM on silver stain. SEM of glomeruli following cell extraction permits the first direct three-dimensional visualization of the GBM alterations occurring in various stages of subepithelial immune complex formation.


Group 3 Innate Lymphoid Cells Program a Distinct Subset of IL-22BP-Producing Dendritic Cells Demarcating Solitary Intestinal Lymphoid Tissues.
Solitary intestinal lymphoid tissues such as cryptopatches (CPs) and isolated lymphoid follicles (ILFs) constitute steady-state activation hubs containing group 3 innate lymphoid cells (ILC3) that continuously produce interleukin (IL)-22. The outer surface of CPs and ILFs is demarcated by a poorly characterized population of CD11c+ cells. Using genome-wide single-cell transcriptional profiling of intestinal mononuclear phagocytes and multidimensional flow cytometry, we found that CP- and ILF-associated CD11c+ cells were a transcriptionally distinct subset of intestinal cDCs, which we term CIA-DCs. CIA-DCs required programming by CP- and ILF-resident CCR6+ ILC3 via lymphotoxin-β receptor signaling in cDCs. CIA-DCs differentially expressed genes associated with immunoregulation and were the major cellular source of IL-22 binding protein (IL-22BP) at steady state. Mice lacking CIA-DC-derived IL-22BP exhibited diminished expression of epithelial lipid transporters, reduced lipid resorption, and changes in body fat homeostasis. Our findings provide insight into the design principles of an immunoregulatory checkpoint controlling nutrient absorption.


Perhexiline maleate induced cirrhosis.
Perhexiline maleate is a potent anti-anginal drug which may cause alcoholic-type hepatitis and cirrhosis. We report a case of a patient who developed cirrhosis on a relatively low dose within 16 mth.


Jaw and Dental Abnormalities.
Deviations from anthropometric norms related to facial skeletal development are a relatively normal occurrence in the dental management of the vast majority of patients. A consideration for correction is usually warranted only when there is associated morbidity, functional impairment, or psychosocial detriment. The vast majority of jaw and dental abnormalities are developmental and present themselves within a continuum of clinically conspicuous to overtly obvious. This article highlights a variety of developmental abnormalities that present with structural disharmony of the maxillomandibular complex and secondarily associated dental structures.


Components of Salvia miltiorrhiza and Panax notoginseng Protect Pericytes Against OGD/R-Induced Injury via Regulating the PI3K/AKT/mTOR and JNK/ERK/P38 Signaling Pathways.
Salvia miltiorrhiza (SAL) and Panax notoginseng (PNS) are widely used in treating of ischemic stroke. However, it is unknown which components of SAL and PNS protect brain microvascular pericytes after an ischemic stroke. We evaluated the protective effects and mechanisms of SAL and PNS components in pericytes subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Pericytes were subjected to OGD/R. Cell Counting Kit-8 (CCK-8) was used to evaluate cell viability. ROS and SOD kits were used to detect oxidative stress. Flow cytometry was performed to analyze cell apoptosis. To evaluate cell migration, a scratch assay was performed. Expression of cleaved caspase-3, Bcl-2, Bax, VEGF, Ang-1, PDGFR-β, PI3K/AKT/mTOR, and JNK/ERK/P38 signaling pathways were identified using western blot. The results revealed that salvianolic acid B (Sal B), salvianolic acid D (Sal D), notoginsenoside R1 (R1), ginsenoside Rb1 (Rb1), and ginsenoside Rg1 (Rg1) increased the cell viability of pericytes subjected to OGD/R, reduced the level of ROS, and increased the expression of SOD. The components reduced cell apoptosis, increased the protein level of Bcl-2/Bax, reduced the level of cleaved caspase-3/caspase-3, increased cell migration, and enhanced the levels of Ang-1, PDGFR-β, and VEGF. The components could activate PI3K/AKT/mTOR pathway while inhibiting the JNK/ERK/P38 pathway. Studies found that Sal B, Sal D, R1, Rb1, and Rg1 inhibited oxidative stress and apoptosis while increasing the release of pro-angiogenic regulators of pericytes related to the PI3K/AKT/mTOR and JNK/ERK/P38 signaling pathways. This provides a potential foundation for developing monomeric drugs for treating ischemic stroke.


Protection from secondhand smoke in countries belonging to the WHO European Region: an assessment of legislation.
Comprehensive smokefree laws, as recommended by the WHO Framework Convention of Tobacco Control (WHO FCTC), are the most effective tool to protect the population from secondhand smoke (SHS) and to ensure healthy environments. Studies evaluating how laws govern SHS protection are scarce. This study assessed the level of protection from SHS of laws from countries belonging to the WHO European Region. A new methodology system was developed to evaluate the smokefree legislation according to the principles provided by the WHO guidelines for the correct implementation of Article 8 of the FCTC. For each law, six main sectors and 28 facilities were evaluated. Overall 68 laws from 48 countries from the WHO European Region were reviewed. 'Education' and 'Public transport' were the most protected sectors from SHS. Many WHO European laws do not provide protection from SHS across all public sectors. For example, 48.5% of general health facilities and 71.2% of restaurants are unprotected from SHS. The level of protection provided in the 28 facilities studied was low; many WHO European laws still allow smoking under certain conditions, permitting smoking in designated and/or ventilated areas. Nine years after the adoption of the WHO FCTC there are still legal formulas in which smoking is allowed in several facilities, through the inclusion of separated areas, ventilated areas and other conditions. Tobacco control efforts still face the challenge of eradicating the legal clauses that prevent 100% smokefree environments.


BDNF deregulation in Rett syndrome.
BDNF is the best-characterized neurotrophin in terms of its gene structure and modulation, secretion processing, and signaling cascades following its release. In addition to diverse features at the genetic and molecular levels, the abundant expression in several regions of the central nervous system has implicated BDNF as a potent modulator in many aspects of neuronal development, as well as synaptic transmission and plasticity. Impairments in any of these critical functions likely contribute to a wide array of neurodevelopmental, neurodegenerative, and neuropsychiatric diseases. In this review, we focus on a prevalent neurodevelopmental disorder, Rett syndrome (RTT), which afflicts 1:15,000 women world-wide. We describe the consequences of loss-of-function mutations in the gene encoding the transcription factor methyl-CpG binding protein 2 (MeCP2) in RTT, and then elaborate on the current understanding of how MeCP2 controls BDNF expression. Finally, we discuss the literature regarding alterations in BDNF levels in RTT individuals and MeCP2-based mouse models, as well as recent progress in searching for rational therapeutic interventions. This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'.


Collapsing cristobalitelike structures in silica analogues at high pressure.
The cristobalitelike forms of the ternary silica analogues BPO4 and BAsO4 were investigated at high pressure by x-ray diffraction and theoretical methods. The behavior of these compounds represents an extreme case in which the tilt angle of the constituent tetrahedra increases in a spectacular way at high pressure resulting in a major change in topology from a cristobalitelike framework towards a "collapsed cristobalite" structure. These compounds provide the first examples of the collapse of a framework structure to a close-packed form in a continuous manner without an intervening phase transition.


Successful endoluminal repair of a popliteal artery aneurysm using the Wallgraft endoprosthesis.
To describe the first application of the Wallgraft endovascular prosthesis to aneurysm exclusion in the popliteal artery. A 61-year-old man was admitted to our institution with a popliteal artery aneurysm complicated by associated popliteal vein compression, deep venous thrombosis, and pulmonary embolism. The endovascular procedure was performed percutaneously with local anesthesia using a low-profile, covered stent (Wallgraft Endoprosthesis). The aneurysm was successfully excluded from the arterial circulation, and there were no postprocedural complications. Follow-up evaluation with appropriate imaging at 10 months revealed no endoleaks. This initial result indicates that percutaneous deployment of the Wallgraft endoprosthesis, with its smaller diameter and flexible design, may offer significant advantages over currently available devices for repair of popliteal artery aneurysms. This method obviates the need for general anesthesia or surgical exposure, which is particularly beneficial in patients with comorbid illnesses.


An intracranial complication of nasogastric intubation. Case report.
A case is presented in which a patient who had suffered severe facial fractures erroneously had a nasogastric tube placed in the intracranial cavity. It is believed that no such complication of nasogastric intubation has been reported previously.


Anthropometric study of the knee and its correlation with the size of three implants available for arthroplasty.
To define the anthropometric profile of the knee in a Brazilian population with gonarthrosis using intraoperative measurements; and to evaluate the compatibility of three implants available for total knee arthroplasty. Morphometric data were collected prospectively from 117 subjects with gonarthrosis. Six dimensions in the distal femur and two in the proximal tibia were documented in 118 knees while performing total arthroplasty. These data were compared with the dimensions of three implants available for total knee arthroplasty. The statistical analysis showed that more than a quarter of the patients presented an unsatisfactory relationship between the knee and prosthesis. The implants evaluated need to be adjusted to better fit Brazilian patients.


[49-year-old patient with staphylococcal endocarditis and thyrotoxic crisis].
We report the case of a 49-year-old woman who presented with typical features of thyroid crisis. Besides the confirmation of severe thyreotoxicosis a native valve endocarditis due to Staphylococcus aureus was diagnosed. Diagnostic criteria and therapies of these life-threatening disorders are discussed and a possible association in the present case is evaluated.


Pharmacokinetics and Bioequivalence of Two Formulations of Rosuvastatin Following Single-dose Administration in Healthy Chinese Subjects Under Fasted and Fed Conditions.
The main objective of the study was to evaluate the bioequivalence of two rosuvastatin calcium tablets in healthy Chinese subjects under fasted and fed conditions. The study was carried out using a randomized, open-label, two-formulation, two-sequence, two-period, single-dose crossover design, with a washout period of 7 days. Both the fasted study and fed study enrolled 28 subjects. In each study period, the subjects were administrated a single oral dose of the test product or reference product of rosuvastatin 10 mg. Blood samples were collected from pre-dose to 72 hours after administration with 16 time points in total. Bioequivalence evaluation was performed using ln-transformed pharmacokinetic parameters of rosuvastatin, including Cmax , AUC0-t , and AUC0-∞ . In the present study, 95% confidence intervals (CIs) of test/reference geometric mean ratios (GMRs) of Cmax , AUC0-t , and AUC0-∞ under the fasted and fed conditions were all within the acceptance range of 80%-125%. Additionally, only one subject experienced one adverse event (AE). High-fat meals reduced the Cmax , AUC0-t , and AUC0-∞ , but had no significant effects on the λz, t1/2 , or Tmax of rosuvastatin. In the current study, the test product was bioequivalent to the reference product, and a single dose of rosuvastatin (10 mg) was well-tolerated. Food decreased the systemic exposure of rosuvastatin without the effects on the Tmax or elimination rate.


Quality control of lymph node dissection in the Dutch randomized trial of D1 and D2 lymph node dissection for gastric cancer.
BACKGROUND: Variability among surgeons and reduced protocol adherence threaten the conduct and outcome of surgical multicenter trials. We introduced, in the Dutch Gastric Cancer Trial of D1 and D2 (extended) lymph node dissection for gastric cancer, a novel way of managing instruction, quality control, and evaluation of protocol adherence.METHODS: Of 1078 patients entered in the Dutch trial, 711 patients with potentially curative resections were evaluated. Numbers and locations of lymph nodes detected at pathological investigation were compared according to the guidelines of the Japanese Research Society for the Study of Gastric Carcer. Non-compliance indicated inadequate removal of lymph node stations, whereas contamination indicated that lymph nodes were detected outside the intended level of dissection. Protocol adherence during the course of the trial, and the impact on complications, hospital mortality, and survival were evaluated.RESULTS: Major non-compliance was noted in 15.3% of D1 and 25.9% of D2 patients. Contamination was present in 22.9% of D1 and 23.5% of D2 patients, and was limited to one or two lymph node stations only. Intensification of quality control resulted in only a marginal improvement in protocol adherence and in the number of lymph nodes detected. There was no association between protocol adherence and the occurrence of complications or long term survival.CONCLUSIONS: Contamination proved an important parameter to substantiate protocol adherence by the surgeon, whereas non-compliance had a multifactorial cause. Non-adherence to the protocol did not lead to increased hospital morbidity and mortality, but also had no impact on long term survival.


Removal of feedback inhibition of delta 1-pyrroline-5-carboxylate synthetase, a bifunctional enzyme catalyzing the first two steps of proline biosynthesis in plants.
delta 1-Pyrroline-5-carboxylate synthetase (P5CS) catalyzes the first two steps in proline biosynthesis in plants. The Vigna aconitifolia P5CS cDNA was expressed in Escherichia coli, and the enzyme was purified to homogeneity. The Vigna P5CS exhibited two activities, gamma-glutamyl kinase (gamma-GK) and glutamic acid-5-semialdehyde (GSA) dehydrogenase. The gamma-GK activity of the P5CS was detected by the hydroxamate assay and by a [14C]glutamate assay. The native molecular mass of the P5CS was 450 kDa with six identical subunits. The Vigna P5CS showed a Km of 3.6 mM for glutamate, while the Km for ATP was 2.7 mM. The gamma-GK activity of the P5CS was competitively inhibited by proline, while its GSA dehydrogenase activity was insensitive to proline. In addition, a protein inhibitor of the P5CS was observed in the plant cell. Western blot showed that the level of the P5CS was enhanced in Vigna root under salt stress. A single substitution of an alanine for a phenylalanine at amino acid residue 129 of the P5CS resulted in a significant reduction of proline feedback inhibition. The 50% inhibition values of gamma-GK activity of the wild type and the mutant P5CS were observed at 5 mM and 960 mM proline, respectively. The other properties of the mutant P5CS remained unchanged. These results may allow genetic manipulation of proline biosynthesis and overproduction of proline in plants for conferring water stress tolerance.


The ground reaction force thresholds for detecting postural stability in participants with and without flat foot.
Foot mobility commonly contributes to injury via altered motion of the lower extremities. However, there is a lack of understanding of sensitive kinetic changes with flat foot. The purpose of this study was to investigate the threshold that best distinguishes between participants with and without flat foot. The kinetic stability index was developed based on the three-dimensional data from the ground reaction force (GRF) during one leg standing. In total, 34 control participants and 30 participants with flat foot were asked to maintain one leg standing for 25s with the contra lateral hip and knee flexed approximately 90°. The various thresholds (3, 7, 15, 30, 50, and 200N) were analyzed by the kinetic stability index. The standing time was not significantly different between groups (t=1.07, p=0.28); however, there were significant differences on threshold level (F=369.23, p=0.001) as well as group interactions with threshold (F=6.72, p=0.01). The post hoc test indicated that less than 15N was the best to detect the kinetic stability index between the groups. Clinicians need to understand sensitive threshold settings to differentiate the participants with and without flat foot. The threshold changes might be altered to detect postural deficits by the kinetic stability index.


Computation of the equivalent airway resistance: a comparison with routine evaluations of plethysmographic measurements.
Equivalent (effective) values of airway resistance were determined for total breaths, inspiration and expiration in spontaneously breathing patients by means of an off-line processing system. An improvement in the alveolar pressure determination was achieved by subtracting thermal pressure drifts of the pressure plethysmograph and by taking into account instantaneous values of the intrathoracic gas volume. Equivalent resistance values were compared with the results of several simulated routine evaluations. It was found that the equivalent resistance is best approximated by the graphical procedure using average pressure points at +/- 0.5 liter/sec flow levels.


Development of an ultra-high-performance supercritical fluid chromatography method for the analysis of phenols in the pyrolysis aqueous fraction.
The pyrolysis process consists of the thermal decomposition of biomass in an inert atmosphere, which produces a liquid (bio-oil) composed of a complex mixture of organic compounds, including an oil and water phase. The aqueous fraction can reach up to 45% w/w, and understanding its composition is of utmost importance in determining its intended destination, whether for the reuse of compounds in industrial applications or for treating the effluent for disposal. In this study, a fast, direct, and efficient method using ultra-high-performance supercritical fluid chromatography (UHPSFC) was developed and optimized for monitoring phenols in aqueous samples obtained from the pyrolysis processing of six different biomass sources. The following parameters were evaluated for method optimization: stationary phase type, mobile phase flow, organic modifier, sample diluent, temperature, pressure, and modifier gradient time. With a total analysis time of 26 min, out of the fourteen (14) investigated phenolic compounds, eleven (11) were successfully separated after method optimization, and among them, five (5) were quantified in all six aqueous fractions. The aqueous fractions of residue from cowpea pod (1.89 mg.mL-1), sugar apple (3.09 mg.mL-1), and acerola (4.79 mg.mL-1) presented lower concentrations compared to grape (8.16 mg.mL-1), pine nuts (6.68 mg.mL-1), and guava (6.05 mg.mL-1) fractions. However, even at lower concentrations, all biomasses showed promising results regarding the phenolic compound content, analytes that have high added value for the chemical industry.


Non-malignant FDG uptake in infradiaphragmatic adipose tissue: a new site of physiological tracer biodistribution characterised by PET/CT.
The purpose of this study was to characterise a benign pattern of infradiaphragmatic 18F-fluorodeoxyglucose (FDG) uptake in cancer patients using PET/CT. Infradiaphragmatic foci of FDG uptake, localised by PET/CT in regions of normal fat tissues, were demonstrated, in conjunction with fatty uptake in the neck and shoulders, in 9 of 1,241 (0.7%) patients. The imaging and clinical characteristics of this pattern and its possible clinical significance were assessed. PET/CT precisely localised infradiaphragmatic fat uptake (IDFU) within normal retroperitoneal fatty tissue of the perirenal space (nine patients) and in the paracolic or parahepatic space (four patients). Perirenal uptake was bilateral in five patients and focal in six. Paracolic and parahepatic uptake was bilateral in three patients and linear in all four patients. There was no evidence of malignancy at any of the sites during a follow-up period of 9-21 months. IDFU was significantly more prevalent in young patients assessed for monitoring response to therapy, and was always associated with the benign supradiaphragmatic uptake pattern, although its prevalence was significantly lower. There were no significant differences between the clinical characteristics of these two patterns of benign fatty FDG uptake. It is concluded that PET/CT allows for precise identification of increased FDG uptake in abdominal fatty tissue and further exclusion of disease at such sites. This benign uptake may represent increased glucose consumption in activated brown adipose tissue, similar to the mechanism suggested for supradiaphragmatic uptake. Recognition of this benign IDFU pattern is important for correct interpretation of abdominal PET findings in cancer patients.


Clinical assessment of oral malodor using autofluorescence of tongue coating.
The aim of this study was to evaluate whether a new method using quantitative light-induced fluorescence-digital (QLF-D) was appropriate for the diagnosis of oral malodor by quantifying the fluorescence of tongue coating. This study examined 103 healthy subjects who have an oral malodor as a main complaint. The levels of oral malodor were measured by organoleptic scores (OLS) and volatile sulfur compound (VSC) levels. The fluorescent tongue coating images captured by QLF-D were quantified as the integrated fluorescence score (IF score) by multiplying the intensity and area of fluorescence. The correlations between the fluorescence parameters and OLS as well as VSC levels and the diagnostic accuracy of the IF score were evaluated. The IF score of tongue coating showed a significant positive correlation with the OLS (r=0.54, p<0.01) and the VSC levels (r=0.49, p<0.01). This score was significantly differed with the level of oral malodor (p<0.001), and its AUC was 0.72 in identifying the patient with definite oral malodor (≥OLS 2). A new method quantifying tongue coating fluorescence detected by QLF-D can be used to diagnose oral malodor and assess its severity in the clinical practice.


Ophthalmic manifestations of central nervous system tuberculosis--two case reports.
In this report, we present two unusual ocular manifestations due to CNS tuberculosis. One of the cases is a 7 years' old boy with brain stem tuberculoma who presented with horizontal gaze palsy. The other is a 14 years' old girl with temporal lobe tuberculoma who presented with unilateral sixth nerve paresis and papilledema. Both responded well to treatment with antitubercular drugs. It highlights the importance of gaze palsy as a rare manifestation of CNS tuberculosis.


Lupus erythematosus in neonates, children, and adolescents.
Neonatal LE should be suspected in any infant with an erythematous or scaling dermatitis, especially if it is distributed on the head and neck or if there is a history of photosensitivity. It should also be suspected in any infant with congenital heart block. A biopsy, though helpful, is not necessary since the diagnostic abnormality is the presence of anti-Ro(SSA) antibodies in infant's serum. When the disease is diagnosed, the infant can be effectively treated with a mild topical steroid and sun avoidance, with or without sun-screens, until the age of 12 months when the autoantibodies have presumably degraded. The child then should be observed periodically through adulthood for the onset of SLE. Mothers of infants with neonatal LE need to be checked for the presence of anti-Ro antibodies and SLE, Sjögren's syndrome, or thyroiditis. The recurrence of neonatal LE in some, but not all, future pregnancies must be anticipated. As more of these infants are followed into adulthood, we will learn how often neonatal LE is a marker for adult-onset SLE.


Olanzapine induces glucose intolerance through the activation of AMPK in the mouse hypothalamus.
Treatment with atypical antipsychotic drugs is known to increase the risk of glucose intolerance and diabetes. However, the mechanism of this effect is unclear. Since central adenosine 5'-monophosphate-activated protein kinase (AMPK) plays an important role in regulating nutrient homeostasis, the present study was performed to examine the involvement of central AMPK in the glucose intolerance induced by olanzapine, an atypical antipsychotic drug, in mice. Acute intraperitoneal treatment with olanzapine dose-dependently increased blood glucose levels in the glucose tolerance test. Intracerebroventricular administration of olanzapine also increased blood glucose levels in the glucose tolerance test. The glucose intolerance induced by both intraperitoneal and intracerebroventricular treatment with olanzapine was significantly attenuated by intracerebroventricular pretreatment with the AMPK inhibitor compound C. Intracerebroventricular treatment with the AMPK activator AICAR increased blood glucose levels in the glucose tolerance test, and this increase was inhibited by compound C. Moreover, the hypothalamic level of phosphorylated AMPK after glucose injection was significantly increased by intracerebroventricular pretreatment with olanzapine. Olanzapine did not affect plasma glucagon and insulin levels. Our results indicate that acute treatment with olanzapine causes glucose intolerance through the activation of hypothalamic AMPK. The present study suggests that the inhibition of central AMPK activity may have a therapeutic effect on the metabolic disturbance induced by atypical antipsychotic drugs.


Nonlinear Kalman Filtering for acoustic emission source localization in anisotropic panels.
Nonlinear Kalman Filtering is an established field in applied probability and control systems, which plays an important role in many practical applications from target tracking to weather and climate prediction. However, its application for acoustic emission (AE) source localization has been very limited. In this paper, two well-known nonlinear Kalman Filtering algorithms are presented to estimate the location of AE sources in anisotropic panels: the Extended Kalman Filter (EKF) and Unscented Kalman Filter (UKF). These algorithms are applied to two cases: velocity profile known (CASE I) and velocity profile unknown (CASE II). The algorithms are compared with a more traditional nonlinear least squares method. Experimental tests are carried out on a carbon-fiber reinforced polymer (CFRP) composite panel instrumented with a sparse array of piezoelectric transducers to validate the proposed approaches. AE sources are simulated using an instrumented miniature impulse hammer. In order to evaluate the performance of the algorithms, two metrics are used: (1) accuracy of the AE source localization and (2) computational cost. Furthermore, it is shown that both EKF and UKF can provide a confidence interval of the estimated AE source location and can account for uncertainty in time of flight measurements.


Retracted: Effect of Ghrelin Intervention on the Ras/ERK Pathway in the Regulation of Heart Failure by PTEN.
[This retracts the article DOI: 10.1155/2022/1045681.].


Biosynthesis ofFusarium mycotoxins and genomics ofFusarium verticillioides.
Analyses of mycotoxin biosynthetic genes inFusarium indicate that interspecies variation in trichothecene structure can result from differences in gene function and interspecies variation in fumonisin production/non-production can result from differences in the presence/absence of genes. Such variation is not always correlated with phylogenetic relationships of species as determined by sequencing primary metabolic genes; distantly related species can share the same mycotoxin biosynthetic genotype and resulting phenotype, while more closely related species can differ. These findings provide further evidence that the evolution of mycotoxin biosynthesis inFusarium has not always been congruent with the evolution of species.


Meperidine-halothane interaction in dogs.
We studied the interaction of meperidine and halothane in 24 unmedicated, spontaneously breathing dogs. Intramuscular (i.m.) injections of meperidine, 2.75 mg/kg, 5.5 mg/kg and 11.0 mg/kg reduced the minimal alveolar concentration (MAC) of halothane required for anaesthesia. The magnitude and duration of MAC depression were dose related. Plasma meperidine concentrations following an i.m. injection of 2.75 mg/kg were lower in the awake, unsedated dogs than in the dogs anaesthetized with halothane.


A novel point mutation in a 3' splice site of the NADH-cytochrome b5 reductase gene results in immunologically undetectable enzyme and impaired NADH-dependent ascorbate regeneration in cultured fibroblasts of a patient with type II hereditary methemoglobinemia.
Hereditary methemoglobinemia with generalized deficiency of NADH-cytochrome b5 reductase (b5R) (type II) is a rare disease characterized by severe developmental abnormalities, which often lead to premature death. Although the molecular relationship between the symptoms of this condition and the enzyme deficit are not understood, it is thought that an important cause is the loss of the lipid metabolizing activities of the endoplasmic reticulum-located reductase. However, the functions of the form located on outer mitochondrial membranes have not been considered previously. In this study, we have analyzed the gene of an Italian patient and identified a novel G-->T transversion at the splice-acceptor site of the 9th exon, which results in the complete absence of immunologically detectable b5R in blood cells and skin fibroblasts. In cultured fibroblasts of the patient, NADH-dependent cytochrome c reductase, ferricyanide reductase, and semidehydroascorbate reductase activities were severely reduced. The latter activity is known to be due to b5R located on outer mitochondrial membranes. Thus, our results demonstrate that the reductase in its two membrane locations, endoplasmic reticulum and outer mitochondrial membranes, is the product of the same gene and suggest that a defect in ascorbate regeneration may contribute to the phenotype of hereditary methemoglobinemia of the generalized type.


Transplantation with higher dose of natural killer cells associated with better outcomes in terms of non-relapse mortality and infectious events after allogeneic peripheral blood stem cell transplantation from HLA-matched sibling donors.
Little is known about the role of the CD56+ natural killer (NK) cell dose on the outcome of allogeneic peripheral blood stem cell transplantation (PBSCT). Recently, higher dose of NK cells has been associated with a lower incidence of severe graft-versus-host disease (GVHD). The current study attempted to evaluate the effect of the NK cell dose on transplant outcomes in allogeneic PBSCT setting. Sixty-one cytokine mobilized PBSC recipients were analyzed according to the infused dose of CD34+ cells and NK cells in relation to overall survival (OS), non-relapse mortality (NRM), GVHD, and infectious events. The group received a higher dose of NK cells (> or =5 x 10(7)/kg) showed a lower incidence of NRM (P = 0.0186) and infectious events (P = 0.0107). In a multivariate analysis, a higher dose of NK cells was correlated to better transplant outcomes for NRM (P = 0.042) with CD34+ cell dose (P = 0.018), and for infectious events (P = 0.013) with CD34+ cell dose (P = 0.016). Higher NK cell infusion group also showed a faster immune recovery in serial measurements at days +90, +180, and +365. High dose of NK cells may play an important role in improving transplant outcomes, in terms of reducing NRM and infectious events together with CD34+ cells.


25-Hydroxyvitamin D isomerizes to pre-25-hydroxyvitamin D in solution: considerations for calibration in clinical measurements.
Reference standards for the vitamin D metabolites 25-hydroxyvitamin D3, 25-hydroxyvitamin D2, and 3-epi-25-hydroxyvitamin D3 were evaluated using liquid chromatography (LC) with ultraviolet (UV) absorbance and mass spectrometric (MS) detection to assess purity. The chromatograms for solutions of all three 25(OH)D compounds, obtained using a pentafluorophenyl (PFP) stationary phase, revealed peaks that increased in area over time and had MS spectra that were nearly identical to the parent compound, indicating isomers had formed in solution that were unrelated to the reference standard purity. However, when the purity evaluations were completed with a cyanopropyl stationary phase, the isomeric products coeluted with the parent compounds and were not observable. The rates of formation of the isomeric products were found to increase when heated and were confirmed to be pre-25-hydroxyvitamin D compounds using spectral information from both MS detection and nuclear magnetic resonance (NMR) spectroscopy. The rates of conversion of 25(OH)D3 to pre-25(OH)D3 was studied in solutions of ethanol and bovine serum albumin (BSA) in phosphate-buffered saline (PBS). The solutions prepared with BSA/PBS were found to form twice as much pre-25(OH)D3 as the solutions in ethanol. The isomerization of 25(OH)D in solution has implications for calibration of 25(OH)D in clinical measurements, which are discussed.


A tool for processing decay scheme data that encompasses coincidence summing calculations.
A description is given of the tool implemented in GESPECOR to process coincidence summing corrections and derive decay scheme data. The method of analysis produces relevant decay scheme data and the joint emission probability for any group of photons (gamma emissions, X-rays, annihilation photons resulting from beta(+) decay) emitted in the decay of any nuclide with less than 100 levels.


Evaluation of Taenia solium and Taenia crassiceps cysticercal antigens for the serodiagnosis of neurocysticercosis.
We evaluated the usefulness of seven cysticercal antigen extracts, four from Taenia solium cysticerci (whole parasite-TsoW, membrane-TsoMe, vesicular fluid-TsoVF and scolex-TsoSc) and three from T. crassiceps cysticerci (whole parasite-TcraW, membrane-TcraMe and vesicular fluid-TcraVF), for serodiagnosis of neurocysticercosis with an enzyme-linked immunosorbent assay (ELISA). Cysticercus-specific IgG were screened in serum samples from 23 patients with neurocysticercosis, 32 patients with other infections and 48 healthy persons. The best results were obtained with the TsoVF-ELISA (91.3% sensitivity; 96.2% specificity) and TcraVF-ELISA (91.3% sensitivity; 95% specificity). The ELISA done with whole parasite and membrane extracts from cysts of T. solium and T. crassiceps and the scolex extract from T. solium cysts showed a low performance in terms of sensitivity, ranging from 47.8% to 73.9%. None of the antigen preparations from T. solium and T. crassiceps cysticerci used in this study showed outstanding performance for the serodiagnosis of neurocysticercosis. However, considering the results obtained with the seven antigen preparations, vesicular fluid from T. solium and T. crassiceps cysticerci may be useful for detecting specific antibodies in sera from patients with neurocysticercosis.


Community pharmacies and the empowerment of self-care in the United States.
As part of self-care, patients prevent diseases or conditions, maintain, or enhance their current health status, and address current health challenges. As a key member of the healthcare team, the role of the pharmacist in relation to self-care is important, given the ease of access to pharmacists in a variety of care settings. To describe the structure and function of self-care within community pharmacies throughout the United States (U.S.). The literature within the U.S. was reviewed related to self-care definitions and practice, the role and training of the pharmacist, and challenges and opportunities for pharmacists. Within the U.S., self-care is broader than simply products found in the "over-the-counter" (OTC) section of pharmacies; it includes pharmacists involvement in disease prevention, evaluation and maintenance of current health status, and assistance in managing health challenges. There is growing recognition of the significance of pharmacists in aiding patients in self-care, due to publication of outcomes related to pharmacist-provided self-care support. Accreditation standards require student pharmacists to develop knowledge and competency related to the broadest definition of self-care; resources exist related to curricular content and student evaluation and assessment support. The evolving role of the pharmacist in relation to self-care has presented challenges in terms of recognition and renumeration for services and workload issues. Efforts are currently underway to address these challenges. Spiraling health care costs, poor health outcomes, and continued health disparities indicate a need to better support U.S. patients on their health care journey, which often begins with self-care. There is a plethora of opportunities for pharmacists to advocate for expanding roles related to self-care, including participation in national efforts to recognize the outcomes of pharmacists in self-care.


The role of serotonin in the genesis of hypertension in preeclampsia.
While it is generally accepted that preeclampsia is a disease of the microvasculature characterized by an imbalance between prostacyclin and thromboxane and that the evidence for enhanced responsiveness to some vasopressors is present weeks before clinical disease, the specific cause of the hypertension characterizing the syndrome is unknown. A number of endogenous vasopressor substances have been examined without conclusive findings. Pharmacologic and methodologic advances over the last decade have resulted in a body of information implicating serotonin as a mediator in the genesis of preeclamptic hypertension. This information is summarized and a possible mechanism of delivery and action is suggested.


How does drought affect native grasses' photosynthesis on the revegetation of iron ore tailings?
The revegetation of areas degraded by iron ore mining is a difficult challenge mainly due to water availability and impoverished metal-rich substrates. We sought to understand the photosynthetic responses to drought of native tropical grasses Paspalum densum (Poir.) and Setaria parviflora (Poir.) grown in iron ore tailing. The grass P. densum presented better photosynthetic adjustments when grown in the iron ore tailing and S. paviflora in response to water stress. Both species accumulated iron above the phytotoxic threshold when grown in an iron ore tailing. The net photosynthesis, stomatal conductance, transpiration, and water use efficiency decreased followed by a reduction in leaf relative water content in response to water stress for both species. The photochemical efficiency of photosystem II only decreased at the point of maximum drought. At this point, the water-stressed grass grown in the iron ore tailing presented higher H2O2 concentrations, particularly S. parviflora. After rehydration, full recovery of photosynthetic variables was achieved with decreased malondialdehyde concentrations, increased catalase activity, and, consequently, decreased H2O2 concentrations in leaves for both species. The fast recovery of the native grasses P. densum and S. parviflora to drought in the iron ore tailing substrate is indicative of their resistance and potential use in the revegetation of impoverished mined areas with high iron content and seasonal water deficit.


Diverse Rhizobium strains isolated from root nodules of Trifolium alexandrinum in Egypt and symbiovars.
Berseem clover (T. alexandrinum) is the main forage legume crop used as animal feed in Egypt. Here, eighty rhizobial isolates were isolated from root nodules of berseem clover grown in different regions in Egypt and were grouped by RFLP-16S rRNA ribotyping. Representative isolates were characterized using phylogenetic analyses of the 16S rRNA, rpoB, glnA, pgi, and nodC genes. We also investigated the performance of these isolates using phenotypic tests and nitrogen fixation efficiency assays. The majority of strains (<90%) were closely related to Rhizobium aegyptiacum and Rhizobium aethiopicum and of the remaining strains, six belonged to the Rhizobium leguminosarum genospecies complex and only one strain was assigned to Agrobacterium fabacearum. Despite their heterogeneous chromosomal background, most of the strains shared nodC gene alleles corresponding to symbiovar trifolii. Some of the strains closely affiliated to R. aegyptiacum and R. aethiopicum had superior nodulation and nitrogen fixation capabilities in berseem clover, compared to the commercial inoculant (Okadein®) and N-added treatments. R. leguminosarum strain NGB-CR 17 that harbored a nodC allele typical of symbiovar viciae, was also able to form an effective symbiosis with clover. Two strains with nodC alleles of symbiovar trifolii, R. aegyptiacum strains NGB-CR 129 and 136, were capable of forming effective nodules in Phaseolus vulgaris in axenic greenhouse conditions. This adds the symbiovar trifolii which is well-established in the Egyptian soils to the list of symbiovars that form nodules in P. vulgaris.


Productive and Qualitative Traits of Amaranthus Cruentus L.: An Unconventional Healthy Ingredient in Animal Feed.
Agronomic traits, oil content, fatty acid composition, antioxidant activity, and total phenolic content were studied on eight A. cruentus accessions cultivated in Southern Italy. A one-way ANOVA model was performed to compare accessions and the Principal Components Analysis was applied to identify patterns in our dataset and highlight similarities and differences. A. cruentus showed valuable seed yield (0.27 kg/m2, on average) comparable to the main tradition cereals used for animal feeding. Seed-oil composition showed significant differences among the accessions. Data showed a higher lipid content than most cereal grains (from 5.6 to 7.3%). Approximately 60% of fatty acids were unsaturated; linoleic fatty acid ranged from 19 to 34%, oleic acid from 29 to 36%, and alfa-linolenic fatty acid from 0.3 to 0.5%, respectively. The saturated/unsaturated fatty acid ratio ranged from 0.5 to 0.8, the hypocholesterolemic:hypercholesterolaemic ratio from 1.7 to 2.7, the Atherogenic Index from 0.38 to 0.66, the Thrombogenic Index from 0.85 to 1.48, the total phenolic content from 0.14 to 0.36 mg/g seeds, and the antioxidant activity (DPPH•) from 0.30 to 0.50. The studied seed-oil composition evidenced A. cruentus as a healthy ingredient for animal feed and consequently, as a possible substitute for traditional cereals. Accessions from Mexico and Arizona emerged for their high qualitative traits.


Stenting of the right ventricular outflow tract in the symptomatic infant with tetralogy of Fallot.
Repair of neonatal tetralogy of Fallot (TOF) has low mortality. Debate continues regarding the initial management of cyanotic or duct-dependent infants with TOF and adverse risk factors. While repair can and has been performed in these patients, it is associated with increased morbidity. We review the effectiveness of right ventricular outflow tract (RVOT) stenting in the symptomatic young infant with TOF. Clinical, echocardiographic, angiographic and haemodynamic data were reviewed for nine patients who underwent 11 RVOT stenting procedures from October 1994 to August 2007. The pulmonary valve was deemed unsalvageable in all patients (median valve diameter 3.7 mm (range 2.7-4.2), Z-score -6.7 (range -9.7 to -5.4). RVOT stenting improved arterial oxygen saturation from a median of 73% (60-85%) to 94% (90-98%) (p = 0.008). Median Z-score for the left pulmonary artery increased from -4.9 (-7.8 to -2.4) before stent implantation to -1.5 (-4.2 to -0.2) (p = 0.02) before surgical repair. Median Z-score for the right pulmonary artery increased from -3.7 (-6.8 to -1.9) to -0.8 (-2.5 to 0.1) (p = 0.008). Median Nakata index increased from 56 mm(2)/m(2) (21-77) to 150 mm(2)/m(2) (123-231) (p = 0.008). There were no procedural complications. Six patients have undergone successful repair. There were no deaths. In the symptomatic young infant with TOF, stenting of the RVOT provides a safe and effective management strategy, improving arterial oxygen saturation and encouraging pulmonary artery growth.


Pilot survey of the prevalence of neurologic disorders in the Parsi community of Bombay.
There is a paucity of trained neurologists in developing countries. We designed a questionnaire to rapidly screen a community of 851 people (Parsis living in a colony in Bombay, India) for possible neurologic diseases. This questionnaire was pretested and found to have a sensitivity of 100 percent for detecting epilepsy, febrile seizures (only in children), completed stroke, peripheral neuropathy, movement disorders, cerebral palsy, mental retardation, and severe dementia. The screening questionnaire was administered by trained lay health workers. One hundred and sixty-three people were identified by this questionnaire as possibly having neurologic disease. Neurologists later examined these 163 people and found that 80 of them actually suffered from at least one of the neurologic diseases of interest (positive predictive value = 48 percent). The most common neurologic disorders were peripheral neuropathy (32 cases), essential tremor (13 cases), stroke (12 cases), Parkinson's disease (six cases), and epilepsy (four cases).


[Conventional radiography and digital radiography of the thorax: evaluation of anatomo-radiological parameters].
We report the results of a comparative study of digital and conventional chest radiographs to detect normal anatomical structures of the thorax. A digital Toshiba unit (TCR 201) was used to examine 100 selected patients who were diagnosed with no chest pathologic conditions. The images in both modes were submitted for interpretation to five radiologists. The depiction of nine normal anatomical structures was more accurate on digital than on conventional radiographs. The mean confidence levels achieved in viewing digital images were higher than those obtained with conventional radiographs. This difference was statistically significant (p = 0.002).