Vision after trans-sylvian or temporobasal selective amygdalohippocampectomy: a prospective randomised trial.
Selective amygdalohippocampectomy (SAH) is an accepted surgical procedure for treatment of pharmacoresistant mesial temporal lobe epilepsy, but it may lead to postoperative visual field deficits (VFDs). Here we present a prospective randomised trial comparing the postoperative VFDs after either a trans-sylvian or temporobasal approach for SAH. Forty-eight patients were randomly assigned to trans-sylvian (n = 24) or temporobasal (n = 24) SAH. Postoperative VFD were quantitatively evaluated using automated static and kinetic perimetry. In 24 cases, diffusion tensor imaging-based deterministic fibre-tracking of the optic radiation was performed. The primary endpoint was absence of postoperative VFD. The secondary endpoint was seizure outcome and driving ability. Three patients (13 %) from the trans-sylvian group showed no VFD, compared to 11 patients (46 %) from the temporobasal group without VFD (p = 0.01, RR = 3.7; CI = 1.2-11.5). Fifteen patients from each group (63 %) became completely seizure-free (ILAE1). Among those seizure-free cases, five trans-sylvian (33 %) and ten temporobasal (66 %) patients could apply for a driving licence (NNT = 3) when VFDs were considered. Although the trans-sylvian group experienced more frequent VFDs, the mean functional visual impairment showed a tendency to be less pronounced compared with the temporobasal group. DTI-based tracking of the optic radiation revealed that a lower distance of optic radiation to the temporal base correlated with increased rate of VFD in the temporobasal group. Temporobasal SAH shows significantly fewer VFDs and equal seizure-free rate compared with the trans-sylvian SAH. However, in patients in whom the optic radiation is close to the temporal base, the trans-sylvian approach may be a preferred alternative.


Correlates of mobile screen media use among children aged 0-8: protocol for a systematic review.
Childhood is a crucial period for shaping healthy behaviours; however, it currently appears to be dominated by screen time. A large proportion of young children do not adhere to the screen time recommendations, with the use of mobile screen devices becoming more common than fixed screens. Existing systematic reviews on correlates of screen time have focused largely on the traditional fixed screen devices such as television. Reviews specially focused on mobile screen media are almost non-existent. This paper describes the protocol for conducting a systematic review of papers published between 2009 and 2015 to identify the correlates of mobile screen media use among children aged 0-8 years. A systematic literature search of electronic databases will be carried out using different combinations of keywords for papers published in English between January 2009 and December 2015. Additionally, a manual search of reference lists and citations will also be conducted. Papers that have examined correlates of screen time among children aged 0-8 will be included in the review. Studies must include at least one type of mobile screen media (mobile phones, electronic tablets or handheld computers) to be eligible for inclusion. This study will identify correlates of mobile screen-viewing among children in five categories: (i) child biological and demographic correlates, (ii) behavioural correlates, (iii) family biological and demographic correlates, (iv) family structure-related correlates and (v) socio-cultural and environmental correlates. PRISMA statement will be used for ensuring transparency and scientific reporting of the results. This study will identify the correlates associated with increased mobile screen media use among young children through the systematic review of published peer-reviewed papers. This will contribute to addressing the knowledge gap in this area. The results will provide an evidence base to better understand correlates of mobile screen media use and potentially inform the development of recommendations to reduce screen time among those aged 0-8 years. PROSPERO CRD42015028028 .


E6C15 (E = Si-Pb): polycyclic aromatic compounds with three planar tetracoordinate carbons.
A systematic exploration of the potential energy surface reveals two global minima with three planar tetra coordinate carbons (ptCs) and two global minima with three quasi-ptCs for E6C15 (E = Si-Pb) combinations. These consist of aromatic polycyclic templates suitable for further design of different materials without hindering the ptC texture.


1H NMR spectral studies on the polymerization mechanism of indole and its derivatives.
The existence of NH bond according to the hydrogen nuclear magnetic resonance ((1)H NMR) spectra of polyindole and its derivatives, such as poly(5-bromoindole), poly(5-cyanoindole), poly(5-nitroindole), poly(5-methylindole), proved polymerization of high-quality polyindoles, which were electrosynthesized from middle strong Lewis acid boron trifluoride diethyl etherate (BFEE) and its mixed electrolytes with additional diethyl ether, occurred at 2,3-position. The elongation of the conjugation length made the chemical shift of all the protons of polyindoles to lower field in comparison with those of monomers.


Acinic cell carcinoma of the parotid gland in childhood.
A 13-year-old girl underwent surgery at the Ear Nose and Throat Department of the Children's Hospital and Scientific Research Institute, Bambino Gesù, Rome, because of an acinic cell carcinoma of the parotid gland. Two years after total parotidectomy with preservation of the facial nerve, metastasis occurred in a lateral cervical lymph node. Acinic cell tumors are uncommon in childhood; in children under the age of 16 years only 35 cases have been reported. There are too few acinar cell carcinomas occurring in children to yield an idea of their natural course. The neoplasm is also referred to as 'acinar cell tumor', in contrast to acinar cell carcinoma, because the neoplasm may be benign or malignant. Unfortunately, there are no histological distinguishing features that permit the pathologist to determine which neoplasm will behave in an aggressive fashion.


FOLDABLE CAPSULAR VITREOUS BODY IMPLANTATION FOR COMPLICATED RETINAL DETACHMENT CAUSED BY SEVERE OCULAR TRAUMA.
To explore the effectiveness, safety and psychological impact of foldable capsular vitreous body (FCVB) implantation for complicated retinal detachment caused by severe ocular trauma. This was a prospective, single-arm, surgical interventional case series study. A standard 3-port 23-gauge pars plana vitrectomy was performed, and the FCVB was implanted into the vitreous cavity. Observed indicators, including the best-corrected visual acuity, intraocular pressure (IOP), retinal reattachment, complications, and patient satisfaction, were analyzed to evaluate the study. A total of 28 cases (eyes) were enrolled, with a mean follow-up of 16.93 ± 9.67 months and an average age of 51.11 ± 10.14 years, including 22 men (78.57%). The FCVB was successfully implanted, and the retina was reattached in all cases. The postoperative best-corrected visual acuity improved in 7 cases, and remained unchanged in 21 cases ( P > 0.05). The average IOP was 7.01 ± 2.43 mmHg before surgery and 8.54 ± 2.93 mmHg after surgery ( P < 0.05). Complications such as FCVB displacement, endophthalmitis, secondary glaucoma, silicone oil emulsification, and escape did not occur during the follow-up period. Patients with FCVB implantation are highly satisfied. Most patients feel hope, positive, and optimistic about life. Foldable capsular vitreous body implantation for complicated retinal detachment caused by severe ocular trauma is effective and safe, and it allows patients to face life positively and optimistically.


Understanding controversies in the α-ω and ω-β phase transformations of zirconium from nonhydrostatic thermodynamics.
Significant debate has been noted in the α-ω and ω-β phase transformations of zirconium. The initial pressure of the α-to-ω transformation at room temperature has been reported to vary from 0.25 to 7.0 GPa, while the hydrostatic transformation is believed to occur at approximately 2.2 GPa. Shear stress is commonly considered as a key factor leading to the discrepancy. However, the principal mechanisms previously proposed concluded that the phase transformation pressure would be decreased in the presence of shear stress. The experimental results of the α-ω transformation in zirconium are contrary to this conclusion. In the ω-β phase diagram of zirconium, the dT/dP along the phase boundary near the α-ω-β triple-point was reported to be either positive or negative, but no theoretical explanation, especially a quantitative one, has been proposed. This article aimed to quantitatively investigate and explain the controversies reported in the α-ω and ω-β phase transformations of zirconium by applying a new nonhydrostatic thermodynamic formalism for solid medium, which has recently been proposed and is capable of quantitatively estimating the impact of shear stress on phase transformations in solids.


The unique effects of supporting beginning teachers' psychological needs through learning communities and a teacher-mentor's support: A longitudinal study based on self-determination theory.
The induction period is considered one of the most difficult in a teacher's career. In Israel, support systems for beginning teachers (BTs) include a learning community (LC) and a mentoring process, over a 2-year period. The study was based on self-determination theory and examined how support for BTs' psychological needs and exploration from the LC facilitator and teacher-mentor contributed to their functioning. The study was conducted over 2 years during which BTs participated in LCs and were accompanied by a teacher-mentor. Questionnaires were administered to Bedouin-Arab and Jewish teachers, 308 interns in the first year, and 205 new teachers in the second. Results of SEM analysis indicated that supporting BTs' needs and exploration by LC facilitators in both years predicted their autonomous motivation, which in turn predicted positive feelings and satisfaction in the LC. The LC facilitators' support also predicted the BTs' autonomous motivation in teaching, which was also predicted by the teacher-mentors' support. This in turn positively predicted the BTs' sense of competence and self-actualization, and negatively predicted burnout. In both years, autonomous motivation mediated the association between the support the BTs received, and teacher outcomes in the LC and school. No significant differences were found between the two cultures. The effects found in the second year are above and beyond the effects of support from the LC facilitators and teacher-mentors in the first year. The study indicates the importance of combining multiple induction programs over time and highlights the importance of supporting BTs' needs during the induction period.


Plectin is a regulator of prostate cancer growth and metastasis.
Prostate cancer is responsible for over 30,000 US deaths annually, attributed largely to incurable metastatic disease. Here, we demonstrate that high levels of plectin are associated with localized and metastatic human prostate cancer when compared to benign prostate tissues. Knock-down of plectin inhibits prostate cancer cell growth and colony formation in vitro, and growth of prostate cancer xenografts in vivo. Plectin knock-down further impairs aggressive and invasive cellular behavior assessed by migration, invasion, and wound healing in vitro. Consistently, plectin knock-down cells have impaired metastatic colonization to distant sites including liver, lung, kidney, bone, and genitourinary system. Plectin knock-down inhibited number of metastases per organ, as well as decreased overall metastatic burden. To gain insights into the role of plectin in prostate cancer growth and metastasis, we performed proteomic analysis of prostate cancer plectin knock-down xenograft tissues. Gene set enrichment analysis shows an increase in levels of proteins involved with extracellular matrix and laminin interactions, and a decrease in levels of proteins regulating amino acid metabolism, cytoskeletal proteins, and cellular response to stress. Collectively these findings demonstrate that plectin is an important regulator of prostate cancer cell growth and metastasis.


Regulation of juvenile hormone biosynthesis by 20-hydroxyecdysone during the fourth larval instar of the tobacco hornworm, Manduca sexta.
A previous study of the role of 20-hydroxyecdysone in the regulation of juvenile hormone (JH) biosynthesis during pupal commitment in the last (fifth, V) larval instar of Manduca sexta revealed that the increase in the hemolymph edysteroid titer that elicits commitment also stimulates the corpora allata (CA) to synthesize JHs I and III and/or their acids. This stimulation is exerted indirectly via the brain-corpora cardiaca and results in the postcommitment increase in the JH titer that is important for the molt to a pupa. The possibility that a similar form of interendocrine regulation of JH biosynthesis by 20-hydroxyecdysone is involved in the control of larval molting in Manduca was investigated for the molt from the fourth (IV) to the V larval instar. During the IV instar, the increase in the hemolymph ecdysteroid titer and the capacity of the CA to synthesize JHs I and III in vitro correlated temporally in a manner suggestive of CA regulation by 20-hydroxyecdysone. With an in vitro approach, physiological concentrations of 20-hydroxyecdysone (greater than or equal to 1 microgram ml-1 hemolymph) were shown to have a dose-dependent trophic effect on CA activity, specifically stimulating JH I synthesis. Since neither basally active nor stimulated CA contained significant amounts of JH I, it appears that 20-hydroxyecdysone acts at the level of biosynthesis rather than at the level of release. The specificity of 20-hydroxyecdysone stimulation of JH I synthesis was demonstrated by the inability of the biologically inactive ecdysteroids 22-isoecdysone and 5 alpha-ecdysone to activate the glands.(ABSTRACT TRUNCATED AT 250 WORDS)


Creating an ideal objective structured clinical exam for an obstetrics and gynecology medical student clerkship.
The objective of the study was to describe our experience with the Objective Structured Clinical Exam during the third-year obstetrics/gynecology clerkship. Our 8-station Objective Structured Clinical Exam is described in detail. We analyzed grades from the Objective Structured Clinical Exam for overall distribution, comparing among and between groups by year and among exam sites and correlating with the National Board of Medical Examiners subject exam and the final clerkship grades. The Objective Structured Clinical Exam is provided at 3 sites, 1 at a technically advanced simulation center. Most students (54.6%) received a grade of A; however, the mean grade from the Objective Structured Clinical Exam at the simulation center (3.41 on a 4-point grade-point average scale) was lower than that at the clinic sites (3.60, P = .005; 3.73, P < .001). Effect of rotation order was identified only in the first year. Grades from the Objective Structured Clinical Exam were positively but weakly correlated with National Board of Medical Examiners subject exam and final clerkship grades. An Objective Structured Clinical Exam in the obstetrics/gynecology clerkship can be administered with limited resources and provides a valuable assessment method.


Comparison of toxicity and mutagenicity of butyl methanesulfonate among human lymphoblast lines.
The toxic and mutagenic effects of butyl methanesulfonate (BMS) were compared among four diploid human lymphoblast lines, MIT-2, WI-L2, MGL8B-2 and GM 130. The toxic and mutagenic effects of 24-h exposure to BMS were similar for the MIT-2, WI-L2 and MGL8B-2 lines, while the GM 130 line was strikingly resistant to the toxic and mutagenic effects of BMS.


Optical probing of acetylcholine receptors on neurons in the medial habenula with a novel caged nicotine drug analogue.
A new caged nicotinic acetylcholine receptor (nAChR) agonist was developed, ABT594, which is photolysed by one- and two-photon excitation. The caged compound is photolysed with a quantum yield of 0.20. One-photon uncaging of ABT594 elicited large currents and Ca2+ transients at the soma and dendrites of medial habenula (MHb) neurons of mouse brain slices. Unexpectedly, uncaging of ABT594 also revealed highly Ca2+ -permeable nAChRs on axons of MHb neurons. Photochemical release of neurotransmitters has been instrumental in the study of their underlying receptors, with acetylcholine being the exception due to its inaccessibility to photochemical protection. We caged a nicotinic acetylcholine receptor (nAChR) agonist, ABT594, via its secondary amine functionality. Effective photolysis could be carried out using either one- or two-photon excitation. Brief flashes (0.5-3.0 ms) of 410 nm light evoked large currents and Ca2+ transients on cell bodies and dendrites of medial habenula (MHb) neurons. Unexpectedly, photorelease of ABT594 also revealed nAChR-mediated Ca2+ signals along the axons of MHb neurons.


A vitamin E long-chain metabolite and the inspired drug candidate α-amplexichromanol relieve asthma features in an experimental model of allergen sensitization.
Benefits for vitamin E intake in diseases with inflammatory components have been described and related in part, to endogenously formed metabolites (long-chain metabolites, LCM). Here, we have evaluated the role of LCM in relieving asthma features. To this aim, the endogenous vitamin E metabolite α-13'-carboxychromanol (α-T-13'-COOH) that acts as potent 5-lipoxygenase inhibitor has been administered either intraperitoneally or by oral gavage to BALB/c mice sensitized by subcutaneous injection of ovalbumin (OVA). We also have taken advantage of the metabolically stable α-T-13'-COOH derivative α-amplexichromanol (α-AC). Intraperitoneal treatment with α-T-13'-COOH reduced OVA-induced airway hyperreactivity (AHR) as well as peri-bronchial inflammatory cell infiltration. α-AC was more efficacious than α-T-13'-COOH, as demonstrated by better control of AHR and in reducing subepithelial. Both compounds exerted their protective function by reducing pulmonary leukotriene C4 levels. Beneficial effects of α-AC were coupled to inhibition of the sensitization process, as indicated by a reduction of IgE plasma levels, lung mast cell infiltration and Th2 immune response. Metabololipidomics analysis revealed that α-AC raises the pulmonary levels of prostanoids, their degradation products, and 12/15-lipoxygenase metabolites. Following oral administration, the pharmacodynamically different profile in α-T-13'-COOH and α-AC was abrogated as demonstrated by a similar and improved efficacy in controlling asthma features as well as by metabololipidomics analysis. In conclusion, this study highlights a role for LCM and of vitamin E derivatives as pharmacologically active compounds that ameliorate asthmatic features and defines an important role for endogenous vitamin E metabolites in regulating immune response underlying the sensitization process.


Effect of body mass index on recurrence following urethroplasty.
Limited investigation exists to understand whether obesity affects outcomes of urethral reconstruction. We sought to assess whether body mass index (BMI) is an independent predictor for stricture recurrence following urethroplasty. We performed a retrospective review of patients undergoing urethroplasty between 2007-2014, identifying 137 patients for study inclusion. Data collected included BMI and patient demographic and surgical characteristics, including age, stricture length and location, etiology, and urethroplasty technique. Stricture-free survival analysis was performed using Kaplan-Meier method. Logistic regression was performed to assess predictors for stricture recurrence using both univariate and multivariate models. Mean patient age and follow-up was 46.7 (±16.4) years and 91.8 (±30.5) months, respectively. A recurrence rate of 17% was identified, with a mean time to recurrence of 29 months. There was no difference when comparing the mean BMI in patients with and without recurrence (28.9 vs. 30.4 kg/m2, respectively) (P=0.4). A higher rate of stricture recurrence was seen when comparing the cohort with a BMI <25 kg/m2 versus remaining cohorts (BMI: 25-30 kg/m2; BMI >30 kg/m2). However, in univariate and multivariate analysis, BMI failed to demonstrate statistical significance as a predictor for urethroplasty outcome. On multivariate analysis, fasciocutaneous repair type was predictive of stricture recurrence. No additional potential predictors assessed were found to be significant. In the present study, BMI did not independently predict for stricture recurrence following urethroplasty.


Enhancing meat quality of weaned piglets with the dietary incorporation of Ulva lactuca and carbohydrases supplementation.
The impact of the dietary incorporation of 7% Ulva lactuca, a green seaweed, on the quality and nutritional value of piglet's meat was assessed. U. lactuca is rich in nutrients and bioactive compounds but its cell wall is composed of complex polysaccharides that reduce their bioavailability. Therefore, the effect of supplementing piglet diets with exogenous carbohydrases was also assessed here. A total of 40 male weaned piglets were divided into four dietary groups, each with 10 piglets: control (wheat, maize and soybean meal-based diet), UL (7% U. lactuca replacing the control diet), UL + R (UL and 0.005% Rovabio®), and UL + E (UL and 0.01% ulvan lyase). The piglets were fed the diets for 2 weeks. The results showed that incorporating U. lactuca in piglet diets did not influence most of the meat quality traits (P > 0.05). However, the incorporation of U. lactuca with the commercial carbohydrase (UL + R) increased the amount of the docosahexaenoic acid (DHA; 22:6n-3) in their meat (P = 0.011) compared with the control, by 54%. In addition, meat from piglets fed seaweed diets showed a nearly two-fold increase in iodine contents (P < 0.001). Meat tenderness, juiciness and overall acceptability of piglets fed the control diet and the UL diet were lower than those fed the diets containing seaweed and carbohydrases (P < 0.001). Overall, the findings indicate that 7% U. lactuca in the diets of weaned piglets had no major detrimental effects on meat quality and their carbohydrase supplementation has the potential to improve meat sensory traits.


Housing conditions during self-administration determine motivation for cocaine in mice following chronic social defeat stress.
Stress exposure has a lasting impact on motivated behavior and can exacerbate existing vulnerabilities for developing a substance use disorder. Several models have been developed to examine how stressful experiences shape drug reward. These range from locomotor sensitization and conditioned place preference to the propensity for drug self-administration or responding to drug-predictive cues. While self-administration studies are considered to have more translational relevance, most of the studies to date have been conducted in rats. Further, many self-administration studies are conducted in single-housed animals, adding the additional stressor of social isolation. We sought to establish how chronic social defeat stress (CSDS) and social housing conditions impact cocaine self-administration and cocaine-seeking behaviors in C57BL/6 mice. We assessed self-administration behavior (cocaine or saline, 0.5 mg/kg/infusion) in C57BL/6 mice subjected to 10-day CSDS or in unstressed controls. Mice were housed either in pairs or in isolation during self-administration. We compared the effect of housing on acquisition of self-administration, seeking, extinction, drug-induced reinstatement, and after re-exposure to the social stressor. Pair-housing during self-administration revealed increased social avoidance after CSDS is associated with decreased cocaine intake. In contrast, single-housing revealed stress-sensitive cocaine intake, with increased social avoidance after CSDS associated with increased early cocaine intake. Pair-, but not single-housed mice are susceptible to drug-induced reinstatement independent of CSDS history. Stress re-exposure sensitized cocaine-seeking in stressed single-housed mice. The social context surrounding cocaine intake can bidirectionally influence cocaine-related behaviors after psychosocial stress and should be considered when studying stress and drug cross-sensitization.


Anal cytology: is there a role for reflex HPV DNA testing?
There is an increased incidence of anal squamous carcinoma and its precursor lesions (anal intraepithelial neoplasia [AIN]) among persons who engage in anal-receptive sex. Analogous to cervical cancer screening, anal Papanicplaou (Pap) smears currently are used to screen these high-risk populations. Human papilloma virus (HPV) has been implicated in anal carcinoma pathogenesis and this study was performed to assess the potential role of HPV DNA testing as an adjunct to anal cytology. We correlated cytological diagnoses and HPV DNA (Digene Hybrid Capture [HC II] assay) in anal specimens collected in SurePath liquid medium from 118 patients; 54.8% of cases diagnosed as atypical squamous cells of undetermined significance (ASC-US) and 87.8% diagnosed as low-grade squamous intraepithelial lesion (LSIL) or above tested positive for high- risk HPV DNA (B+). High-grade SIL (HSIL) was present in 31 of the 51 patients with follow-up. Although a cytological diagnosis of ASC-US or above was a reliable indicator for AIN, cytology frequently did not accurately predict the grade of SIL in subsequent biopsy. Our findings suggest that reflex HPV DNA testing would be helpful in triaging patients diagnosed with ASC-US. However, patients diagnosed with LSIL or above should go directly to ansocopic biopsy.


Activated p53 induces NF-kappaB DNA binding but suppresses its transcriptional activation.
NF-kappaB plays an important role in oncogenesis. Recently, we have demonstrated that loss of p53 function enhances DNA binding and transcriptional activities of NF-kappaB via IKKalpha and IKKbeta, and that glycolysis, activated by NF-kappaB, has an integral role in oncogene-induced cell transformation. Here, we show that ectopically expressed p53 induces acetylation and phosphorylation at Ser 536 of p65, an NF-kappaB component, and enhances DNA-binding activity of NF-kappaB. However, activated p53 suppresses transcriptional activity of NF-kappaB. Under non-stimulating conditions, p65 formed a complex with IKKalpha and IKKbeta. Activated p53 bound to p65 on DNA and disrupted binding of p65 to IKKbeta. Moreover, histone H3 kinase activity, which requires transcriptional activation of NF-kappaB, was diminished by p53. Thus, activated p53 may suppress transcriptional activity of NF-kappaB through inhibition of IKK and histone H3 kinase on DNA, suggesting a novel p53-mediated suppression system for tumorigenesis.


Characterization of two cerebellar binding sites of [3H]Ro 15-4513.
Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H- imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate), a partial inverse agonist of central benzodiazepine receptors, binds to two distinct sites in the cerebellum. The binding to diazepam-sensitive (DZ-S) sites is displaced by different benzodiazepine receptor ligands, whereas the other site is insensitive to benzodiazepine agonists [diazepam-insensitive (DZ-IS)]. The binding of [3H]Ro 15-4513 was studied in pig cerebellar membranes and in receptors solubilized and purified from these. Micromolar concentrations of gamma-aminobutyric acid (GABA) decreased DZ-S binding at both 0 and 37 degrees C, whereas it had no effect on DZ-IS binding at 0 degrees C and was stimulatory at 37 degrees C. The pH profiles of [3H]Ro 15-4513 binding were quite similar in both binding sites in the pH range of 5.5-10.5 but differed at acidic pH values from those reported for flunitrazepam and Ro 15-1788 (flumazenil; ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H- imidazol[1,5-a][1,4]benzodiazepine-3-carboxylate) binding in DZ-S sites, suggesting that [3H]Ro 15-4513 does not interact with a histidine residue apparently present in the binding site. Zn2+, Cu2+, Co2+, and Ni2+ enhanced the binding to DZ-S sites, and the first three mentioned also enhanced the binding to DZ-IS sites. [3H]Ro 15-4513 binding activity was solubilized by various detergents. All detergents tested were more efficient in solubilizing DZ-S binding activity. High ionic strength improved especially the solubility of DZ-IS binding activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Demonstration of a platelet bypass mechanism in the clotting system using an acquired anticoagulant.
A lupus-type anticoagulant which causes strong inhibition of the partial thromboplastin time with kaolin (PTTK), the stypven time, and the thrombin generation tests has been investigated. All tests for platelet function were normal, as were all specific coagulation factor assays with the exception of a slightly reduced factor XI in this patient. A diethylaminoethyl-cellulose-immunoglobulin (DEAE-cellulose-IgG) fractionation of the patient's plasma produced two peaks containing inhibitory activity in the PTTK test. The first of these peaks had a cloudy appearance, suggesting the presence of immunoglobulin aggregates. Studies with IgG aggregates prepared from normal IgG and from the patient's IgG demonstrated that such aggregates were not the cause of inhibition. It was possible to neutralize the inhibitory activity of the purified IgG but not platelet-poor plasma (PPP) with a rabbit anti-IgG. The inhibition of the patient's PPP in the thrombin generation, the contact product, and the stypven time tests were corrected by the inclusion in the test system of platelets activated either by aggregation due to adenosine diphosphate (ADP) or formalin fixation and washing. These studies lend support to earlier findings that platelets interact at several sites in the coagulation cascade.


Sterilization in the United States.
Had no U.S. married couples obtained contraceptive sterilizations, there would have been about 800,000 unwanted births during 1971-1973 in addition to the 8.7 million births that actually occurred. More than half of U.S. couples elect sterilization within 10 years after their last wanted birth, and more than six in 10 are sterilized within 15 years.


Elimination of mycoplasma from leukemia-lymphoma cell lines using antibiotics.
Mycoplasmal contamination of cell culture systems continues to present major problems for basic research and for manufacturing of bioproducts. Previous work suggested that certain antibiotics have strong anti-mycoplasma properties and raised the prospect that the technically rather simple antibiotic treatment may be an appropriate means for mycoplasma eradication. We have developed and validated an effective strategy to eliminate mycoplasma from chronically infected cell cultures using antibiotics which have shown strong activity against these contaminants. Here, we describe our experience with the treatment of 123 consecutive mycoplasma-positive leukemia-lymphoma cell lines, comparing five different antibiotic regimens (in total 433 treatments). We optimized the antibiotic dose schedules and the duration of treatments. The various antibiotic treatments which were employed in parallel had a high efficacy, as 71% to 86% of the infected cultures were cleansed. Treatment failure may result from the resistance of the mycoplasmas to antibiotic therapy and the inability of the eukaryotic cells to survive the cytotoxic effects of the antibiotics. Resistance to mycoplasma eradication was observed in 3% to 20% of the cultures. Loss of the cell culture caused by cytotoxicity was seen in 3% to 11% of the treatments. With regard to the overall outcome, 96% of the cell lines were rendered mycoplasma-free with at least one of the antibiotic treatments and were permanently cured. In conclusion, antibiotic treatment represents the most practical and efficient option to cleanse mycoplasma-positive cell lines.


Modeling and Forecasting Vibrio Parahaemolyticus Concentrations in Oysters.
Vibrio parahaemolyticus (V.p) is an epidemiologically significant pathogen that thrives in coastal waters where oysters are harvested, posing high risks to human health and shellfish industry and requiring effective forecasting models for emergency preparedness and interventions. This study sought to develop forecasting models with differing lead times, which are able to predict the level of V.p in oysters in advance to mitigate the health risk to the general public and the economic loss to the shellfish industry. The Random Forest method along with 227 sampling datasets from two different geographic locations were utilized to: (1) Identify the most critical environmental predictors controlling the level of V.p in oysters, (2) Select the most important time lags for the environmental predictors as model input variables, and (3) Develop four forecasting models (RF-1Day, RF-2Day, RF-3Day, and RF-4Day) with the lead time of one to four days. The uncertainty involved in model predictions was quantified using the bootstrapping method. Results showed that V.p abundance in oysters is controlled by antecedent environmental conditions 1-11 days before. The antecedent environmental conditions can be described using time-lagged Sea Surface Temperature (SST) and salinity. The V.p abundance can well be forecasted 1 - 4 days in advance using the four models. The performance of the models decreases with increasing lead time. The RF-3Day and RF-4Day models can be employed primarily for emergency preparedness due to their relatively long lead time while the RF-1Day and RF-2Day models can be used primarily for management interventions due to their relatively high predictive performance.


A population-based study of hairy cell leukemia over a period of 20 years.
There are limited population-based studies of hairy cell leukemia (HCL), a rare chronic lymphoproliferative disorder of B-cells. We conducted a population-based study that included all patients diagnosed with HCL between 1996 and 2016 in Western Normandy. Recorded data focused on medical history, clinical presentation, biological results, treatment modalities in the first line and in relapsed/refractory patients and the occurrence of secondary malignancies. One hundred and twenty-three HCL patients were registered in the database. HCL represented 0.7% of all malignant hematological disorders and 3.0% of all leukemia. The overall age-standardized incidence ratio (SIR) was 0.39/100,000 inhabitants in men and 0.09/100,000 in women, and it remained stable over the 20-year period analyzed. One hundred and seven patients (88%) received first-line treatment, 33 patients (27%) received at least 2 lines of treatment and 14 patients (11%) received more than 2 lines. Cladribine used as first-line treatment induced a high hematological complete response (HCR) rate of 92%. The median overall survival (OS) was over 15 years, with 5-year and 10-year survival rates of 84% and 70.5%. No significant differences in OS were observed between men and women, between the calendar periods studied or between patients who received a single line treatment with IFN-α or PNA. The risk of relapse was higher with IFN-α treatment, requiring subsequent treatments in that patients. The time to next treatment (TTN) tends to be longer for PNAs compared to IFN-α even if difference is not significant. Secondary cancers were observed in 9/123 patients (7.3%) with solid tumors in 8 patients and hematological malignancy in one patient. Our data confirm in real life that single courses of cladribine administered to patients with HCL induce high response rates, the majority of which are HCR. Relapses seem less frequent than with IFN-α and the administration schedule is less restrictive for the patients. The emergence of chemo-immunotherapy and the development of effective new drugs such as recombinant immunotoxins and BRAF targeting will offer new possibilities in the management of HCL patients.


Dual role of B7-H6 as a novel prognostic marker in hepatocellular carcinoma.
B7 homolog 6 (B7-H6), a new member of the B7 family, is identified as an activating ligand for cytotoxicity triggering receptor 3 (NKp30) expressing on natural killer cells. The purpose of this study was to investigate the clinical significance of B7-H6 in hepatocellular carcinoma (HCC). We evaluated B7-H6 expression by immunohistochemistry in a cohort of 90 HCC tumors with clinical follow-up, the potential relationship between the B7-H6 expression and the clinicopathological characteristics of HCC patients was also analyzed. Stable B7-H6 knockdown in hepatoma cell line was established to explore the function and mechanism of B7-H6 in HCC. This study showed that high expression of B7-H6 was significantly associated with smaller tumor size, single tumor number in HCC, but no significant association was found between B7-H6 overexpression and other clinicopathological parameters. Moreover, Kaplan-Meier survival analysis showed that high expression of B7-H6 was significantly correlated with better survival of HCC patients. Knockdown of B7-H6 inhibited tumor cell proliferation and induced cell apoptosis. However, it also impaired the sensitivity of tumor cells to NK-mediated lysis together with significantly decreased degranulation and IFN-γ release of NK cells. These results indicated that B7-H6 has a dual role in HCC. It could be an independent indicator for better survival of HCC and maybe a potential target for future cancer treatment.


Effect of redox state of Ag on indoor formaldehyde degradation over Ag/TiO2 catalyst at room temperature.
Ag/TiO2 catalysts were prepared via in-situ synthesis and impregnation methods. The effect of redox state of Ag species on catalytic activity of Ag/TiO2 catalysts was studied. The Ag-i-300 catalyst with partially oxidized state of Ag species shows superior catalytic activity, keeping HCHO removal efficiency at an extraordinary level of 100% during the 200 min's reaction. The Ag/TiO2 catalysts were characterized by XPS, UV-Vis, BET, XRD, TEM, and in-situ DRIFTS technologies. XPS and TEM results exhibit that the partially oxidized state of Agδ+ (0 < δ < 1) and high dispersion of Ag species are beneficial for the oxidation of HCHO over Ag/TiO2 catalysts. According to the above results, a reaction pathway for HCHO oxidation over Ag-i-300 catalyst was also proposed.


N-acetylserotonin Derivative Exerts a Neuroprotective Effect by Inhibiting the NLRP3 Inflammasome and Activating the PI3K/Akt/Nrf2 Pathway in the Model of Hypoxic-Ischemic Brain Damage.
Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the main causes of neonatal disability and death. As a derivative of N-acetylserotonin, N-[2-(5-hydroxy-1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide (HIOC) can easily cross the blood-brain barrier and have a long half-life in the brain. In this study, the hypothesis was verified that HIOC plays a neuroprotective role in the HIE model and its potential mechanism was evaluated. Firstly, an HIE rat model was established to deliver HIOC, revealing that it can reduce cerebral infarction volume, cerebral edema, and neuronal apoptosis. The results of immunofluorescence staining, Western blots and RT-PCR further showed that HIOC could inhibit the activation of the NLRP3 inflammasome and the expression of related proteins. Finally, the activation of the phosphatidylinositol-3-kinase (PI3K)/Akt/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by HIOC was verified in vitro and in vivo. It was discovered that HIOC could increase the nuclear translocation of Nrf2, and that this induction can be reversed by the PI3K/Akt pathway inhibitor LY294002. In general terms, the neuroprotective effect of HIOC was confirmed in the HIE model, which is related to the activation of the Pi3k/Akt/Nrf2 signal pathway and the inhibition of the NLRP3 inflammasome.


Development of potentiometric urea biosensor based on urease immobilized in PVA-PAA composite matrix for estimation of blood urea nitrogen (BUN).
A urea biosensor was developed using the urease entrapped in polyvinyl alcohol (PVA) and polyacrylamide (PAA) composite polymer membrane. The membrane was prepared on the cheesecloth support by gamma-irradiation induced free radical polymerization. The performance of the biosensor was monitored using a flow-through cell, where the membrane was kept in conjugation with the ammonia selective electrode and urea was added as substrate in phosphate buffer medium. The ammonia produced as a result of enzymatic reaction was monitored potentiometrically. The potential of the system was amplified using an electronic circuit incorporating operational amplifiers. Automated data acquisition was carried by connecting the output to a 12-bit analog to digital converter card. The sensor working range was 1-1000 mM urea with a response time of 120 s. The enzyme membranes could be reused 8 times with more than 90% accuracy. The biosensor was tested for blood urea nitrogen (BUN) estimation in clinical serum samples. The biosensor showed good correlation with commercial Infinitytrade mark BUN reagent method using a clinical chemistry autoanalyzer. The membranes could be preserved in phosphate buffer containing dithiothreitol, beta-mercaptoethanol and glycerol for a period of two months without significant loss of enzyme activity.


[Spontaneous resolution of branch retinal vein occlusion in cases with non-ischemic macular edema. Significance of a waiting period before considering treatment with vitrectomy].
It is well established that some patients with branch retinal vein occlusion undergo a spontaneous resolution after a suitable waiting period. We present a series of 22 patients with initial acuity under 0.2 for whom we allowed three months of observation before considering vitrectomy. 13% of the patients developed enough spontaneous improvement to be excluded from subsequent treatment. We thus believe a waiting period should be considered before instituting treatment in patients with this particular problem.


Exploring the burden of the primary family caregivers of schizophrenia patients in Taiwan.
The purpose of the present study was to investigate the burden of the primary family caregivers of schizophrenia patients and the factors that affect caregiver burden. A total of 126 pairs of patients and their primary family caregivers were recruited from the day care and acute wards of two teaching general hospitals. Demographic information was collected. All patients went through an interview with a senior psychiatrist using the Brief Psychiatric Rating Scale (BPRS). The Caregiver Burden Inventory-Brief Version and the Chinese Health Questionnaire (CHQ) were used to assess the caregiver burden and the caregivers' health condition. One-way analysis of variance and Pearson correlation were used to analyze the relationship between demographic factors and caregiver burden. Multiple regression was used to analyze predictors of burden of caregivers. Statistical significance in this study was defined as P <or= 0.05. The caregiver burden scores (25.9 +/- 10.7; range, 3-61) indicated a moderate burden level. Among the five dimensions of burden, caregiver anxiety (2.13 +/- 0.86) was the highest, followed by dependency of the patient (1.85 +/- 1.02), feeling shame and guilt (1.56 +/- 1.02), and family interference (1.43 +/- 0.83). The burden level of stigmata (1.32 +/- 1.24) was the lowest. The first three rankings of burden were 'I worry about his/her safety when he/she is alone' (2.26 +/- 1.15), 'I worry that she/he will become sick at any time' (2.23 +/- 1.10), and 'I feel he/she depends on me very much' (2.02 +/- 1.29). Patient satisfaction with medical staff support (P = 0.00), CHQ scores of the caregivers (P = 0.00), and the BPRS scores of the patients (P = 0.01) were significantly associated with the caregiver burden scores. The physical and mental health condition of the primary family caregiver of schizophrenia patients was the most important factor determining the caregiver burden level. Comprehensive multidisciplinary care of chronic schizophrenia patients is needed, care that supports the needs and improves the psychiatric symptoms of the patients, helps to decrease the caregiver burden level, and facilitates family participation in treatment.


Studies on RES function in rats and mice after different doses of fluosol.
Changes in the activity of the RES were examined by: 1. the clearance of colloidal carbon in rats (expressed by the elimination constant K); 2. determination of the tolerance of endotoxin in mice and that of gram negative enterobacteria in rats (expressed in both methods by the lethality); 3. evaluation of the temporal course of weight and the amount of PFCs taken up by two chief organs of the RES--liver and spleen. The results revealed a distinct temporal action of PFCs on the function of the RES which was terminated before cellular responses ended.


Comorbidity Index as a Selection Tool for Living Donor Liver Transplantation in Elderly Patients.
Previously published data have shown that age alone is not a contraindication for living donor liver transplantation (LDLT). However, careful evaluation is needed to identify the patients who are unlikely to benefit from LDLT. We hypothesized that the Charlson Comorbidity Index (CCI) could be used as one of the criteria for risk stratification in elderly patients undergoing LDLT. There were 951 patients who underwent LDLT between October 2004 and February 2018. All recipients who were older than 60 years of age at the time of transplantation were identified. The comorbidity score was retrospectively assessed for each elderly patient according to the Charlson Comorbidity Index. Univariate and multivariate Cox regression analyses were performed to identify independent predictive factors for survival in elderly patients after LDLT. There were 96 patients (10.1%) in the age of > 60 years. All patients received the right lobe of their donor. Out of these patients, 18 (18.7%) died in the median time of 4 months. The remaining 78 patients (81.2%) are alive, with a median survival of 33 months. The CCI of these patients was significantly lower compared to the other 18 patients (2 versus 4). None of the patients with a CCI above 4 survived longer than 12 months. The results of the multivariate Cox regression analyses have shown that pulmonary disease, renal disease, and CCI are independent negative predictive factors for survival. The results of our study show clearly that the CCI has a significant influence on survival after LDLT in elderly patients and can be used as one of the selection criteria for LDLT in elderly patients.


Evidence for redox cycling of lawsone (2-hydroxy-1,4-naphthoquinone) in the presence of the hypoxanthine/xanthine oxidase system.
This study reports that lawsone (2-hydroxy-1,4-naphthoquinone) undergoes redox cycling in the presence of the hypoxanthine/xanthine oxidase system. The rate of cytochrome c reduction obtained in the presence of 80 microM lawsone was almost three times the rate of cytochrome c reduction measured in its absence. This increase in the rate of cytochrome c reduction was partially inhibited by superoxide dismutase, suggesting the involvement of O(2)(.-) in this process. It is remarkable to note that, even though lawsone is considered to be a non-redox-cycling quinone in vitro, this quinone was shown to be more toxic in vivo in rats than menadione, causing haemolytic anemia of an oxidative nature and renal damage. The view that this quinone is a non-redox-cycling quinone was based on the inability of one-electron-transferring flavoenzymes such as NADPH-cytochrome c reductase to reduce this naphthoquinone. Our finding that lawsone, like menadione, undergoes redox cycling in the presence of the hypoxanthine/xanthine oxidase system could explain the observed oxidative damage of tissues inflicted by this quinone in rats in vivo. Such an observation therefore reconciles the in vivo toxicity results of this naphthoquinone with those of in vitro experiments.


The null allele in the horse esterase (Es) system detected by enzyme assay and rocket immunoelectrophoresis in heterozygous animals.
The detection of the recessive null allele of horse serum esterase (Es) is possible in heterozygotes Es+/EsO which by starch gel electrophoresis appear like homozygotes Es+/Es+. Two methods are proposed, the titration of enzymatic activity of esterase and the immunochemical titration of esterase as antigen. These methods can be applied to solve the cases of suspect parentage or in population studies.


Strain-dependent variability in nitrous oxide withdrawal seizure frequency.
Exposure to nitrous oxide produces handling induced convulsions following withdrawal in mice. Since strain differences in responsiveness to the antinociceptive potency of N2O have been found, we examined whether there were differences in susceptibility to N2O withdrawal seizures. Significant differences were found between mouse strains, varying between 100% and 0% of mice exhibiting withdrawal seizures. There was a lack of correlation between the sensitivity of the mouse strains to N2O-induced analgesia and N2O withdrawal seizures, suggesting different mechanisms of action.


The relation between saliva estriol levels in pregnancy and infant birth weight.
Specimens of saliva were obtained from 106 women with normal pregnancies and from 42 women, whose children turned out to small for dates (birthweight below the 10th centile). Saliva estriol was highly significantly (P less than 0.0001) decreased in the group with a newborn with a birthweight below the 10th centile (500 +/- 340 ng/ml, mean +/- SD) when compared with the group with infants whose birthweight was over the 10th centile (813 +/- 449 ng/ml). Estriol determination in saliva seems to be a simple, non invasive method of aiding the detection of fetal growth retardation.


Image-Guided Transcranial Doppler Ultrasound for Monitoring Posthemorrhagic Vasospasms of Infratentorial Arteries: A Feasibility Study.
A considerable number of patients with subarachnoid hemorrhage (SAH) develop vasospasms of the infratentorial arteries. Transcranial Doppler sonography (TCD) is used to screen for vasospasm. In this study, we used a technical modification that combines TCD with an image guidance device that the operator can use to navigate to the ultrasonic window and to predefined intracranial vascular targets. Our aim was to analyze the feasibility, spatial precision, and spatial reproducibility of serial image-guided TCD of infratentorial and-for comparison-supratentorial arteries in the clinical setting of monitoring for vasospasm after SAH. The study included 10 SAH patients, who each received 5 serial image-guided TCD examinations. Using computed tomography angiography data, trajectories to the infratentorial and supratentorial cerebral arteries were planned and loaded into an image guidance device tracking the Doppler probe. As a measure of spatial precision and spatial reproducibility, we analyzed the distances between the positions of preplanned vascular targets and optimal Doppler signals. The mean distance between preplanned and optimal target points was 4.8 ± 2.1 mm (first exam), indicating high spatial precision. The spatial precision decreased with increasing depth of the vascular target. In all patients, image-guided TCD detected all predefined supratentorial and infratentorial vascular segments. There were no significant changes in spatial precision in serial exams, indicating high reproducibility. Image-guided TCD is feasible for supratentorial and infratentorial arteries. It shows high spatial precision and reproducibility. This study provides a basis for future clinical studies on image-guided TCD for post-SAH vasospasm screening.


An effect of androgens on the length of the poly(A)-tail and alternative splicing cause size heterogeneity of the messenger ribonucleic acids encoding cystatin-related protein.
The 22-kilodalton glycoprotein, expressed in the rat ventral prostate under the influence of androgens, is structurally a cystatin-related protein (CRP), as has been shown by copy DNA sequencing. In fact, two slightly different forms (CRP-1 and CRP-2) are expressed in the prostate; one of them (CRP-1) is also expressed in the exorbital lacrymal gland. In both glands, the CRP-1 messenger RNA (mRNA)s are androgen regulated. Moreover, androgens also influence the size of these mRNAs, which show marked heterogeneity (from 760-950 nucleotides). Indeed, the smaller forms are predominant in castrated animals, whereas the large forms are observed immediately after androgen induction. Hybridization with oligo(dT) followed by ribonuclease H treatment revealed that differences in length of the poly(A)-tail are responsible for this effect of androgens. Indeed, two well defined forms of CRP mRNA subsisted after removal of the poly(A)-tail by this treatment. In the less abundant shorter form (CRP-1 delta), 123 nucleotides are deleted by alternative splicing at the junction between the third and the fourth exon. The variant mRNA encodes a truncated protein, wherein the last 27 amino acids are replaced by a hydrophobic stretch of 8 amino acids. No alternative splicing was observed for the CRP-2 mRNA.


Development of the default-mode network during childhood and adolescence: A longitudinal resting-state fMRI study.
The default-mode network (DMN) is a set of functionally connected regions that play crucial roles in internal cognitive processing. Previous resting-state fMRI studies have demonstrated that the intrinsic functional organization of the DMN undergoes remarkable reconfigurations during childhood and adolescence. However, these studies have mainly focused on cross-sectional designs with small sample sizes, limiting the consistency and interpretations of the findings. Here, we used a large sample of longitudinal resting-state fMRI data comprising 305 typically developing children (6-12 years of age at baseline, 491 scans in total) and graph theoretical approaches to delineate the developmental trajectories of the functional architecture of the DMN. For each child, the DMN was constructed according to a prior parcellation with 32 brain nodes. We showed that the overall connectivity increased in strength from childhood to adolescence and became spatially similar to that in the young adult group (N = 61, 18-28 years of age). These increases were primarily located in the midline structures. Global and local network efficiency in the DMN also increased with age, indicating an enhanced capability in parallel information communication within the brain system. Based on the divergent developmental rates of nodal centrality, we identified three subclusters within the DMN, with the fastest rates in the cluster mainly comprising the anterior medial prefrontal cortex and posterior cingulate cortex. Together, our findings highlight the developmental patterns of the functional architecture in the DMN from childhood to adolescence, which has implications for the understanding of network mechanisms underlying the cognitive development of individuals.


Barriers and facilitators for implementation of the SWORD evidence-based psychological intervention for fear of cancer recurrence in three different healthcare settings.
Fear of cancer recurrence (FCR) interventions are effective, but few are implemented. This study aimed to identify barriers and facilitators for implementing the evidence-based blended SWORD intervention in routine psycho-oncological care. Semi-structured interviews with 19 cancer survivors and 18 professionals from three healthcare settings assessed barriers and facilitators in six domains as described by the determinant frameworks of Grol and Flottorp: (1) innovation, (2) professionals, (3) patients, (4) social context, (5) organization, and (6) economic and political context. In the innovation domain, there were few barriers. Facilitators included high reliability, accessibility, and relevance of SWORD. In the professional domain, physicians and nurses barriers were lack of self-efficacy, knowledge, and skills to address FCR whereas psychologists had sufficient knowledge and skills, but some were critical towards protocolized treatments, cognitive behavioral therapy, or eHealth. Patient domain barriers included lack of FCR awareness, negative expectations of psychotherapy, and unwillingness/inability to actively engage in treatment. A social context domain barrier was poor communication between different healthcare professionals. Organization domain barriers included inadequate referral structures to psychological services, limited capacity, and complex legal procedures. Economic and political context domain barriers included lack of a national implementation structure for evidence-based psycho-oncological interventions and eHealth platform costs. Implementation strategies should be targeted at patient, professional, organizational and economic and political domains. Identified barriers and facilitators are relevant to other researchers in psycho-oncology that aim to bridge the research-practice gap. This study contributes to the implementation of evidence-based psychological interventions for cancer survivors, who can benefit from these services.


Physical stability of a recombinant alpha 1-antitrypsin injection.
Physical stability of a recombinant alpha 1-antitrypsin (rAAT) injection solution, namely, loss of rAAT to particulate formation was studied. The rAAT injection solution (1.0 mg/ml, pH 7.5, triple buffer of phosphate, Tris, and glycine, 0.075 M each) was filtered through a 0.2-micron filter and packaged in individual vials with rubber stoppers and aluminum seals. The vials were stored at 90, 80, 60, 45, 35, and 25 degrees C, and samples taken at predetermined time intervals for each storage condition. Each sample was then filtered through a 0.2-micron filter to remove particulates. The filtrate was then assayed for total protein by the biuret-phenol method. A typical first-order loss of rAAT was observed. Data were fitted to a first-order kinetics, and the shelf life (defined as t90, the time for the product to reach 90% remaining) was calculated from the resultant rate constant. The shelf lives were plotted against reciprocals of storage temperatures (a modified Arrhenius plot). A linear regression line (r = 0.9831) was drawn through the data points and extrapolated to 4 degrees C. At 4 degrees C, the predicted shelf life of the rAAT solution is 5.1 months. In real life, a batch of the rAAT solution showed that 61% of the rAAT remained in the filtrate after 18 months of storage at 4 degrees C. The observed stability compares fairly well with the predicted value of 69% for the same duration of storage at 4 degrees C. From the slope of the linear regression line, the activation energy for the particulate formation of the rAAT was calculated to be 19 kcal. This value is comparable to the activation energy of 20 kcal for ovalbumin denaturation reaction reported by Simpson and Kauzmann.


The functional somatic symptom.
The functional somatic symptom is a disorder that is prevalent in diverse patient populations. It is a heterogeneous disorder composed of a number of separate but often overlapping psychiatric disorders. The consultation-liaison psychiatrist is often consulted by his or her physician colleagues for help in the diagnosis and treatment of this difficult group of patients. This requires an understanding of the different dynamic formulations available to explain these disorders and a treatment strategy that emphasizes a collaborative approach to the long-term management of these patients.


Old lessons learned anew: family-based methods for detecting genes responsible for quantitative and qualitative traits in the Genetic Analysis Workshop 17 mini-exome sequence data.
Family-based study designs are again becoming popular as new next-generation sequencing technologies make whole-exome and whole-genome sequencing projects economically and temporally feasible. Here we evaluate the statistical properties of linkage analyses and family-based tests of association for the Genetic Analysis Workshop 17 mini-exome sequence data. Based on our results, the linkage methods using relative pairs or nuclear families had low power, with the best results coming from variance components linkage analysis in nuclear families and Elston-Stewart model-based linkage analysis in extended pedigrees. For family-based tests of association, both ASSOC and ROMP performed well for genes with large effects, but ROMP had the advantage of not requiring parental genotypes in the analysis. For the linkage analyses we conclude that genome-wide significance levels appear to control type I error well but that "suggestive" significance levels do not. Methods that make use of the extended pedigrees are well powered to detect major loci segregating in the families even when there is substantial genetic heterogeneity and the trait is mainly polygenic. However, large numbers of such pedigrees will be necessary to detect all major loci. The family-based tests of association found the same major loci as the linkage analyses and detected low-frequency loci with moderate effect sizes, but control of type I error was not as stringent.


Quality of Evidence Supporting the Role of Acupuncture for the Treatment of Irritable Bowel Syndrome.
To systematically collate, appraise, and synthesize the current evidence on acupuncture for irritable bowel syndrome (IBS). Systematic reviews (SRs)/meta-analyses (MAs) of acupuncture for IBS were searched in eight databases. For quality evaluation of the enrolled studies, Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) was used for methodological quality, Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) for reporting quality, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for evidence quality. Ten studies were included in our review. According to AMSTAR-2, only one study met all the criteria and was rated as high methodological quality, and the rest were rated as low or very low methodological quality. According to the PRISMA checklist, most of the items were fully reported, with the exception of Q5 (protocol and registration), Q8 (search), and Q27 (funding). With the GRADE system, no outcome measure was rated as high quality. Acupuncture may be a promising therapy for IBS. However, this conclusion must be treated with caution since the quality of SRs/MAs providing evidence is generally low.


The molecular basis of myocardial hypertrophy and heart failure.
Heart failure (HF) is the inability of the heart to cope with the metabolic demands of the periphery. It is the common end-stage of many frequent cardiac diseases and is characterized by relentless progression. Mechanisms of progression include renal sodium and water retention, neurohumoral activation and alterations of the protein composition (gene programme) of the heart itself. In this review, we explain the often confusing terminology in the subject, briefly touch upon the peripheral mechanisms of HF, and then focus on the changes in the gene programme of the failing heart and the molecular mechanisms leading to them. Understanding the basic processes underlying HF will help uninitiated readers to gain insight into recent novel approaches to its treatment.


The triose phosphate-3-phosphoglycerate-phosphate translocator from spinach chloroplasts: nucleotide sequence of a full-length cDNA clone and import of the in vitro synthesized precursor protein into chloroplasts.
The nucleotide sequence of several cDNA clones coding for the phosphate translocator from spinach chloroplasts has been determined. The cDNA clones were selected from a lambda gt10 library prepared from poly(A)+ mRNA of spinach leaves using oligonucleotide probes modeled from amino acid sequences of tryptic peptides prepared from the isolated translocator protein. A 1439 bp insert of one of the clones codes for the entire 404 amino acid residues of the precursor protein corresponding to a mol. wt of 44,234. The full-length clone includes 21 bp at the transcribed non-coding 5' region with the ribosome initiation sequence ACAATGG, a 1212 bp coding region and 199 bp at the non-coding 3' region excluding the poly(A) tail which starts 17 bp downstream from a putative polyadenylation signal, AATAAT. According to secondary structure predictions the mature part of the chloroplast phosphate translocator exhibits high hydrophobicity and consists of at least seven membrane-spanning segments. Using plasmid-programmed wheat germ lysate the precursor protein was synthesized in vitro and could be imported into spinach chloroplasts where it is inserted into the inner envelope membrane.


Still spending dollars, still searching for sense: advanced practice nursing in an era of regulatory and economic turmoil.
Regulatory and market forces are dramatically affecting the practice prospects for advanced practice nurses (APNs). Examples include the designation of APNs as primary care providers by for-profit capitated systems, the elimination of "geographic" practice boundaries by the advent of telepractice, and the revision of governmental reimbursement provisions for entire categories of APNs. Educational, political, and economic challenges necessitate an increased APN leadership role in national and state policy reform efforts.


Metabolomics as a tool for in situ study of chronic metal exposure in estuarine invertebrates.
Estuaries are subject to intense human use globally, with impacts from multiple stressors, such as metal contaminants. A key challenge is extending beyond traditional monitoring approaches to understand effects to biota and system function. To explore the metabolic effects of complex metal contaminants to sediment dwelling (benthic) fauna, we apply a multiple-lines-of-evidence approach, coupling environmental monitoring, benthic sampling, total metals analysis and targeted metabolomics. We characterise metabolic signatures of metal exposure in three benthic invertebrate taxa, which differed in distribution across sites and severity of metal exposure: sipunculid (very high), amphipod (high), maldanid polychaete (moderate). We observed sediment and tissue metal loads far exceeding sediment guidelines where toxicity-related adverse effects may be expected, for metals including, As, Cd, Pb, Zn and Hg. Change in site- and taxa-specific metabolite profiles was highly correlated with natural environmental drivers (sediment total organic carbon and water temperature). At the most metal influenced sites, metabolite variation was also correlated with sediment metal loads. Using supervised multivariate regression, taxa-specific metabolic signatures of increased exposure and possibility of toxic effects were characterised against multiple reference sites. Metabolic signatures varied according to each taxon and degree of metal exposure, but primarily indicated altered cysteine and methionine metabolism, metal-binding and elimination (lysosomal) activity, coupled to change in complex biosynthesis pathways, responses to oxidative stress, and cellular damage. This novel multiple-lines-of-evidence approach combining metabolomics with traditional environmental monitoring, enabled detection and characterisation of chronic metal exposure effects in situ in multiple invertebrate taxa. With capacity for application to rapid and effective monitoring of non-model species in complex environments, these approaches are critical for improved assessment and management of systems that are increasingly subject to anthropogenic drivers of change.


[Effects of menthol as an additive in tobacco products and the need for regulation].
Menthol is the most widely used and the most prominent tobacco additive in tobacco products advertised and marketed by the tobacco industry. Besides its characteristic flavor, it possesses a variety of pharmacological properties facilitating tobacco smoke inhalation and potentiating dependence. These properties of menthol not only favor tobacco initiation and consumption but can also prevent smoking cessation. This article summarizes the effect of menthol as an additive in tobacco products and its effect on tobacco consumption that causes a number of chronic diseases and premature death and, therefore, counteracts tobacco control measures. Currently, there is no legislative regulation in Germany that considers the health hazard, addiction-enhancing and attractiveness-increasing properties of additives permitted in tobacco products. Effective regulation or even a ban could contribute to a reduction of tobacco consumption and, hence, save many people from a long-lasting tobacco dependence.


Folic Acid does not limit endothelial dysfunction induced by ischemia and reperfusion: a human study.
Nitric oxide synthase (NOS) uncoupling is a condition of increased production of superoxide anion associated with a decreased production of nitric oxide (NO) by this enzyme. Folic acid can prevent and/or reverse NOS uncoupling in the setting of diabetes, smoking, hypercholesterolemia, and nitrate tolerance. Whereas animal studies showed a protective effect of folic acid in ischemia and reperfusion (IR) injury, no study tested whether folic acid administration limits IR-induced endothelial dysfunction in humans. In a double-blind, parallel study, 20 healthy young male volunteers were randomized to receive folic acid, 10 mg/d for 7 days, or matching placebo. At the end of the treatment period, endothelium-dependent, flow-mediated dilation (FMD) of the radial artery was measured before and after IR injury (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). There was no difference at baseline between groups in any variable. In the placebo group, IR significantly blunted FMD (before IR, 6.7+/-1.0%; after IR, 1.5+/-1.3%, P<0.01). A similar effect was observed in the folic acid group (before IR, 6.3+/-1.1%; after IR, 2.1+/-1.0%, P=ns compared with placebo). As opposed to animal studies, high-dose folic acid does not protect the vascular endothelium from IR injury in humans.


Radial mass transfer of cross-bridges in a tetanized ferret heart muscle.
An X-ray diffraction experiment on ferret heart muscle was made to examine the relationship between tension and mass transfer from the thick to the thin filament associated with the interaction of cross-bridges with actin. A ferret papillary muscle was electrically stimulated for 8 s in the presence of 5 microM ryanodine to give a tetanus. At different extracellular Ca2+ concentrations (2-20 mM), a linear relationship was found between the tension and the mass transfer. It was concluded that a change in tension caused by altering the extracellular Ca2+ concentration is due to a change in the number of myosin heads bound to actin. This is in contrast to the results obtained on skinned preparations, which showed a markedly nonlinear relationship between the number of heads in the vicinity of the thin filaments and force. It was found that the tension per myosin head is similar in twitch and tetanus of cardiac muscle. Also, a similar fraction of myosin heads is recruited in tetanus of cardiac and skeletal muscles.


A comparative proteomics resource: proteins of Arabidopsis thaliana.
Using an integrative genome annotation pipeline (iGAP) for proteome-wide protein structure and functional domain assignment, we analyzed all the proteins of Arabidopsis thaliana. Three-dimensional structures at the level of the domain are assigned by fold recognition and threading based on a novel fold library that extends common domain classifications. iGAP is being applied to proteins from all available proteomes as part of a comparative proteomics resource. The database is accessible from the web.


The inhibition of rat liver chromatin protease by congeners of the phenylboronic acids.
A group of arylalkylboronic acids were synthesized in order to investigate the inhibitory potential of these compounds for rat liver chromatin protease (EC 3.4--). The effect of side chain length, side chain substitution and aromatic substitution on proteolytic activity in chromatin dissociated in salt and urea was assayed. It was determined that a side chain length two carbons long provided the greatest inhibitory effect with complete inhibition attainable at 20 mM concentration of phenylethylboronic acid. Aryl substitution in the ortho position proved to be the most potent structural change with complete inhibition attained by 1 mM concentration of 0-methylphenylethylboronic acid. The binding of these two inhibitors proved to be reversible.


Chemosystematic investigations of irregular diterpenes in Anisotome and related New Zealand Apiaceae.
A chemosystematic HPLC-UV and HPLC-MS investigation of New Zealand members of the Apiaceae was performed. Diterpenes were identified and quantified in methanolic extracts from subaerial parts of 28 taxa and 54 samples of Aciphylla, Anisotome, Apium, Gingidia, Lignocarpa, Oreomyrrhis, and Scandia. Six diterpenes (1-2, 4-7) and four polyacetylenes (8-11) were identified. The known compounds were the diterpenes anisotomenoic acid 1, anisotomene-1-ol 2, 16-acetoxyanisotomenoic acid 4 and anisotomene-1,12-diol 5; and the polyacetylenes falcarinol 8, falcarindiol 9, (+)-9(Z),17-octadecadiene-12,14-diyne-1,11,16-triol 10, and (+)-9(Z),17-octadecadiene-12,14-diyne-1,11,16-triol 1-acetate 11. New irregular diterpenes 13,14-dihydroanisotom-12E-ene-1,14-diol 6 and 14-methoxy-13,14-dihydroanisotom-12E-ene-1-ol 7 were isolated from A. haastii. Isomers of the new semi-synthetic diterpene 16-hydroxyanisotomenoic acid 3 were detected in extracts of Anisitone flexuosa. Structure elucidation was performed by HR mass spectrometry and 1D and 2D NMR spectroscopy. In crude extracts, compounds were identified by their HPLC retention times and their on-line HPLC-UV and MS spectra. Anisotomene diterpenes occurred in eight out of 16 species of the genus Anisotome, but were not detected in any of the other genera. In contrast, polyacetylenes were present in all the genera investigated.


Incidence and clinical spectrum of rhabdomyolysis in general neurology: a retrospective cohort study.
The objective of this retrospective cohort study was to evaluate demographic, clinical and laboratory characteristics of patients with rhabdomyolysis as defined by a serum creatine kinase (sCK) activity > 950 U/L. A total of 248 patients were recruited from the Department of Neurology, Medical University of Vienna, between 01/2000 and 12/2017, with a median sCK activity of 2,160 U/l (IQR 1,342-4,786). Seizures (31.9%), illicit drugs/alcohol (9.7%) and exercise (8.5%) were the most common trigger factors. Rhabdomyolysis incidence rates in specific neurological diseases as estimated by the ratio between rhabdomyolysis cases and the total number of cases with the corresponding disease were highest in myopathies (49.8/1,000 person-years, 95% CI 32.3-67.4), followed by epilepsy (16.4/1,000 person-years, 95% CI 12.8-20.0) and stroke (11.9/1,000 person-years, 95% CI 8.4-15.4). The half-life of sCK activity was 1.5 days in the total cohort. In myopathies, sCK activity was significantly higher as compared to other disease entities 7 days after the peak measurement (p = 0.0023). Acute kidney injury (AKI) developed in 18 patients (7.3%) with no AKI-related deaths during the study period. In conclusion, rhabdomyolysis occurred in a broad range of neurological entities but was associated with a favorable prognosis in most cases rarely resulting in AKI and death.


An enhanced Runge Kutta boosted machine learning framework for medical diagnosis.
With the development and maturity of machine learning methods, medical diagnosis aided with machine learning methods has become a popular method to assist doctors in diagnosing and treating patients. However, machine learning methods are greatly affected by their hyperparameters, for instance, the kernel parameter in kernel extreme learning machine (KELM) and the learning rate in residual neural networks (ResNet). If the hyperparameters are appropriately set, the performance of the classifier can be significantly improved. To boost the performance of the machine learning methods, this paper proposes to improve the Runge Kutta optimizer (RUN) to adaptively adjust the hyperparameters of the machine learning methods for medical diagnosis purposes. Although RUN has a solid mathematical theoretical foundation, there are still some performance defects when dealing with complex optimization problems. To remedy these defects, this paper proposes a new enhanced RUN method with a grey wolf mechanism and an orthogonal learning mechanism called GORUN. The superior performance of the GORUN was validated against other well-established optimizers on IEEE CEC 2017 benchmark functions. Then, the proposed GORUN is employed to optimize the machine learning models, including the KELM and ResNet, to construct robust models for medical diagnosis. The performance of the proposed machine learning framework was validated on several medical data sets, and the experimental results have demonstrated its superiority.


P53 mediates ceramide-induced apoptosis in SKN-SH cells.
Ceramide induces apoptotic cell death in a dose- and time-dependent manner in neuroblastoma SKN-SH cells. Pretreatment with caspase inhibitors blocks cell death, suggesting that a set of caspase activities including caspase 1, as well as caspase 3, are involved in ceramide-induced apoptosis in SKN-SH cells. Treatment with a caspase inhibitor 3 h after ceramide addition did not inhibit cell death, although caspase activity was substantially reduced. Ceramide-induced apoptosis is accompanied by accumulation of p53 followed by an increase of Bax and decrease of Bcl-2 levels. Inhibition of p53 expression with p53 antisense oligonucleotides inhibits apoptosis and prevents the increase in Bax and decrease in Bcl-2. Furthermore, pretreatment with p53 antisense oligonucleotides markedly inhibits the induction of caspase activity. These results suggest that p53 regulates the ratio Bcl-2/Bax and the expression/activation of caspases during ceramide-induced apoptosis in SKN-SH cells. Caspase inhibition did not alter the expression of p53, Bcl-2 and Bax. Thus ceramide-induced reduction in the Bcl-2/Bax ratio, increase in caspase activity, and apoptosis is dependent upon increases in cellular p53 levels which play a critical role in the regulation of apoptotic cell death.


Priority Analysis of Educational Needs of Forest Healing Instructors Related to Programs for Cancer Survivors: Using Borich Needs Assessment and the Locus for Focus Model.
This study aimed to identify the priority of educational needs to strengthen the competency of forest healing instructors who operate forest healing programs for cancer survivors. A survey was conducted with 91 forest healing instructors using a questionnaire. The average perceived importance of the forest healing program for cancer survivors of forest healing instructors was higher compared to the average knowledge of the forest healing instructors. The Borich needs assessment model showed the highest educational need in the domains of "Cancer survivors' overview" and "Health status screening method". In addition, deriving the priority of educational needs using the Borich needs assessment model and the focus trajectory model revealed that the highest priority was for "Health status screening method" and "Effective communication with cancer survivors". These results can be used as basic data for developing a forest healing instructors training program for cancer survivors that reflects the instructors' needs and the characteristics of cancer survivors.


Di- and trisubstituted pyrazolo[1,5-a]pyridine derivatives: synthesis, dopamine receptor binding and ligand efficacy.
Based on the lead molecule FAUC 113, a series of di- and trisubstituted pyrazolo[1,5-a]pyridine derivatives was synthesized and investigated for their dopamine receptor binding profile. The carbonitrile 11a (FAUC 327) showed excellent pharmacological properties combining high D4 affinity (K(i)=1.5 nM) and selectivity with significant intrinsic activity (31%) in low nanomolar concentrations (EC50=1.5 nM).


Sodium houttuyfonate inhibits inflammation by blocking the MAPKs/NF-κB signaling pathways in bovine endometrial epithelial cells.
Sodium houttuyfonate (SH) has traditionally been used for the therapy of inflammatory diseases. In this research, we tried to assess the anti-inflammatory effects of SH on LPS-induced bovine endometrial epithelial cell (bEEC) inflammation. SH cell toxicity was measured using the MTT and LDH assays, and inflammatory cytokine expression was assessed by ELISA, qRT-PCR and Western blotting. We demonstrated that SH was not cytotoxic to bEECs, and that it significantly decreased the LPS-induced mRNA and protein expression of tumor necrosis factor (TNF) α, interleukin (IL)-1β, IL-6 and IL-8. Furthermore, in LPS-induced bEECs, SH inhibited IκBα degradation and NF-κB p65 phosphorylation, and suppressed the phosphorylation of the mitogen-activated protein kinases (MAPKs), p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). In conclusion, we found that SH could effectively block the NF-κB-mediated signaling pathway and reduce the inflammatory process, thereby exerting a protective effect on bEECs.


Interactions of Cathinone NPS with Human Transporters and Receptors in Transfected Cells.
Pharmacological assays carried out in transfected cells have been very useful for describing the mechanism of action of cathinone new psychoactive substances (NPS). These in vitro characterizations provide fast and reliable information on psychoactive substances soon after they emerge for recreational use. Well-investigated comparator compounds, such as methamphetamine, 3,4-methylenedioxymethamphetamine, cocaine, and lysergic acid diethylamide, should always be included in the characterization to enhance the translation of the in vitro data into clinically useful information. We classified cathinone NPS according to their pharmacology at monoamine transporters and receptors. Cathinone NPS are monoamine uptake inhibitors and most induce transporter-mediated monoamine efflux with weak to no activity at pre- or postsynaptic receptors. Cathinones with a nitrogen-containing pyrrolidine ring emerged as NPS that are extremely potent transporter inhibitors but not monoamine releasers. Cathinones exhibit clinically relevant differences in relative potencies at serotonin vs. dopamine transporters. Additionally, cathinone NPS have more dopaminergic vs. serotonergic properties compared with their non-β-keto amphetamine analogs, suggesting more stimulant and reinforcing properties. In conclusion, in vitro pharmacological assays in heterologous expression systems help to predict the psychoactive and toxicological effects of NPS.


Local and systemic hemostatics as an adjunct to control bleeding in trauma.
Although surgical and angiointervention techniques remain the cornerstone for the management of severe bleeding after trauma, adjunct therapeutic strategies such as local or systemic hemostatic agents can play an important role. This article reviews the role and efficacy of the available hemostatic agents.


Protracted course of coronavirus disease with severe acute respiratory distress syndrome: a case report.
Coronavirus disease (COVID-19) is a growing concern worldwide. Approximately 5% of COVID-19 cases require intensive care. However, the optimal treatment for respiratory failure in COVID-19 patients is yet to be determined. A 79-year-old man with severe acute respiratory distress syndrome due to COVID-19 was admitted to our intensive care unit. Prone ventilation was effective in treating the patient's hypoxemia. Furthermore, the patient received lung protective ventilation with a tidal volume of 6-8 mg/kg (predicted body weight). However, the patient's respiratory failure did not improve and he died 16 days after admission because of multiple organ failure. Serial chest computed tomography revealed a change from ground-glass opacity to consolidation pattern in both lungs. We report a protracted case of COVID-19 in a critically ill patient in Japan. Although prone ventilation could contribute to treating hypoxemia, its efficacy in preventing mortality from COVID-19 is unknown.


In regard to Cuccia et al.: impact of hydrogel peri-rectal spacer insertion on prostate gland intra-fraction motion during 1.5 T MR-guided stereotactic body radiotherapy.
We read the article entitled "Impact of hydrogel peri-rectal spacer insertion on prostate gland intra-fraction motion during 1.5 T MR-guided stereotactic body radiotherapy" with great interest. In that study, the author reported that there is a statistically significant difference in the rotational antero-posterior shifts between the spacer and the non-spacer groups. Also, there was no statistically significant difference between the groups in terms of translational shifts. However, there are some points about the study. In this letter, we aimed to clarify these points.


SHORT ROOT and INDETERMINATE DOMAIN family members govern PIN-FORMED expression to regulate minor vein differentiation in rice.
C3 and C4 grasses directly and indirectly provide the vast majority of calories to the human diet, yet our understanding of the molecular mechanisms driving photosynthetic productivity in grasses is largely unexplored. Ground meristem cells divide to form mesophyll or vascular initial cells early in leaf development in C3 and C4 grasses. Here we define a genetic circuit composed of SHORT ROOT (SHR), INDETERMINATE DOMAIN (IDD), and PIN-FORMED (PIN) family members that specifies vascular identify and ground cell proliferation in leaves of both C3 and C4 grasses. Ectopic expression and loss-of-function mutant studies of SHR paralogs in the C3 plant Oryza sativa (rice) and the C4 plant Setaria viridis (green millet) revealed the roles of these genes in both minor vein formation and ground cell differentiation. Genetic and in vitro studies further suggested that SHR regulates this process through its interactions with IDD12 and 13. We also revealed direct interactions of these IDD proteins with a putative regulatory element within the auxin transporter gene PIN5c. Collectively, these findings indicate that a SHR-IDD regulatory circuit mediates auxin transport by negatively regulating PIN expression to modulate minor vein patterning in the grasses.


A statistical description of the human tracheobronchial tree geometry.
Most physiological studies which made use of lung geometry have utilized average deterministic models of the tracheobronchial tree geometry, such as Weibel's Model A (1963). However, as shown by morphometric studies, it is well known that there are significant inter-subject and intra-subject variabilities in the structural components of the human lung. Hence, inherent inaccuracies exist when deterministic dimensions for lung geometry are used. In this paper, a statistical description of the lung geometry is presented. Using Weibel's Model A as the underlying average model, probability distributions for the lengths and the diameters of airways and for the number and volume of alveoli are proposed based on morphometric data. As a check for consistency, the probability distribution of the functional residual capacity is derived from those associated with airways and alveoli and it is compared with reported data. Results of this comparison are favorable, suggesting that the statistical description presented herein represents a self-consistent model for lung geometry which can be used for studies of problems related to pulmonary physiology.


Spin label detection of intermolecular interactions in carbonmonoxy sickle hemoglobin.
With recently developed spin label techniques for monitoring macromolecular rotational motion, heme-liganded sickle cell hemoglobin in the presence of inositol hexaphosphate is shown to exhibit restricted motional freedom as compared to liganded normal adult human hemoglobin. This motional restriction is dependent on both hemoglobin concentration and temperature.


Ten year results of a randomised trial comparing two conservative treatment strategies for small size breast cancer.
We report the 10-year results of a randomised clinical trial in which two different breast conservation treatment strategies were compared in women with small, non-metastatic primary breast cancer: quadrantectomy, axillary dissection and radiotherapy (QUART) versus tumorectomy and axillary dissection followed by external radiotherapy and a boost with 192Ir implantation (TART). No second surgery was given to women with affected surgical margins. Axillary node positive women received adjuvant medical therapy. From 1985-1987, this trial accrued 705 patients, 360 in the QUART and 345 in the TART arm. Crude cumulative incidence curves for intrabreast tumour recurrence (IBTR) and metastases as first events and mortality curves in each of the two treatment arms were computed. A crude cumulative incidence curve of IBTR as a second event (in women who had already had a local recurrence) was also computed. The two groups were compared in terms of hazard for IBTR, metastases or death occurrence by using Cox regression models, both with and without adjustment for patient age, tumour size, number of metastatic axillary nodes and histology. Possible interactions between the aforementioned prognostic factors and the type of surgery were also investigated. The two groups were well matched for baseline patient and tumour characteristics, the only exception being resection margins, which were more often positive in the TART group. At the Cox model, a significant difference between groups was detected for IBTR (P < 0.0001), but not for distant metastases and overall survival. In particular, 5- and 10-year estimates of crude cumulative incidence of IBTR were 4.7 and 7.4% in the QUART group and 11.6 and 18.6% in the TART group. The difference was not substantially affected by patient or disease characteristics. Likewise, the status of resection margins in women who underwent TART treatment did not significantly influence the risk of occurrence of IBTRs. Finally, the rate of second IBTR occurrence was relatively high, when compared with the rate of IBTR occurrence as first event. In summary, the results of this trial show that a better local control of the disease can be obtained with the more extensive surgical resection, i.e. QUART.


The distribution of power and heat produced by interstitial microwave antenna arrays: I. Comparative phantom and canine studies.
To adequately plan and administer localized hyperthermia with interstitial microwave antennas, the thermal distribution patterns generated by such antennas must be characterized. This study evaluated the performance of single node 915 MHz antennas operating either alone or as a 2 cm square array of four parallel antennas using both muscle-equivalent phantoms and canine thigh muscle. Two types of measurements were compared. Specific absorption rate (SAR), where temperature increases resulting from short duration microwave pulses were used to define power distribution, and temperature gradients during simulated hyperthermia treatments. SAR measurements in phantoms were comparable to those obtained in non-perfused canine muscle demonstrating the usefulness of the phantom for these measurements. For a single antenna there was a rapid decrease in power radially which resulted in a steep thermal gradient at distances within 0.5 cm. However, the power generated by a four-antenna array was highest along its central axis and declined to approximately 50% near the antennas at the array periphery. Along the central axis of the array power decreased most rapidly distal to the antenna nodes. The distribution of temperature measured during simulated hyperthermia treatments in phantoms paralleled the SAR distribution and was comparable to the temperature gradient observed in perfused canine muscle, suggesting that phantoms could be used to predict temperature distributions in resting muscle tissue.


Linker histones: paradigm lost but questions remain.
Linker histones (LH) represent a diverse family of proteins that bind to nucleosomes and bring them together to form a 30-nm chromatin fiber. Although the structure of the globular domain of linker histones H1 and H5 has been solved, the details of its interaction with the nucleosome are not understood in full. Recent data on the location of LH in nucleosome are discussed here.


Immunologically induced salpingitis in rats.
Eustachian salpingitis was induced with type II collagen in rats. The inflammatory reaction spread from the tubal submucous layer toward the surrounding tissue. Lymphocytes and plasmacytes were the major cells found in the inflammatory infiltrates. Bone resorption with many osteoclasts and mononuclear cells infiltrating into the muscle were also observed. These findings suggest that an immune response against type II collagen can induce eustachian salpingitis.


Stable chimerism induced in noninbred rabbits by neonatal injection of spleen cells from alltoype-suppressed adult donors. II. Distribution of donor and recipient allotypes on blood lymphocytes, in serum immunoglobulins, and in specific antibodies.
Long-lasting and stable lymphoid cell chimerism has been noted in three littermates of a group of five rabbits given injections at birth of spleen cells of an allotype-suppressed adult rabbit. The chimeric state manifested itself by the simultaneous display of light and heavy chain markers directed by donor and recipient genotypes in serum immunoglobulins (Ig), on blood lymphocytes, and on antibody molecules made in response to stimulation with three test antigens. Although the genotypes of two of the chimeras were found to be a1a1/b9b9 and the third to be a1a1/b6b9, phenotypically all three were a1a2/b5b6b9. By all of the criteria used to analyze to distribution of allotypes, Ig with the recipients' own allotypes predominated over that controlled by the donor's genotype. With only minor deviations the same proportions of recipient to donor types prevailed in total serum Ig and in the antibody fractions tested.


Effect of protein hydrolysis on the dialysability of amino acids and minerals in infant formulas.
The objectives of this study were to evaluate the dialysed quantities of amino acids and minerals (calcium, phosphorus, magnesium, iron and zinc) in two types of infant formulas, one with a basis of native cow milk proteins and the other highly hydrolysed, to evaluate the possible application of Miller's in vitro method in amino acid and mineral availability studies. The percentage of dialysis differed between proteins. The hydrolysis treatment applied to the proteins significantly increased the dialysis percentage of almost all the amino acids. The dialysability of all the minerals was statistically greater in the formula made with a basis of hydrolysed proteins. Miller's method was seen to be of use for showing the effect which the hydrolysis treatment has on the availability of amino acids. Despite its limitations of having to be carried out in vitro, the study suggests that the nutritional value in relation with amino acids, minerals and trace elements differs between the both types of formulas.


Outcomes of Early-Pregnancy Antithyroid Drug Withdrawal in Graves' Disease: A Preliminary Prospective Follow-Up Study.
Objective: The use of antithyroid drugs (ATDs) carries potential risk for teratogenic effects. For women with well-controlled hyperthyroidism on a low dose of ATDs, drug withdrawal upon pregnancy is recommended by international medical guidelines. Therefore, it is necessary to determine the characteristics of patients suitable for ATD withdrawal, subsequent changes in thyroid function after ATD discontinuation, and its impact on pregnancy and offspring outcomes. Methods: This prospective study recruited 63 pregnant women with well-controlled Graves' hyperthyroidism who had stopped ATDs during early pregnancy. Patients were followed up until the end of pregnancy and data on pregnancy outcomes were collected. Results: Overall, 20 patients (31.7%) had rebound of hyperthyroidism. Patients with either subnormal thyrotropin (TSH) levels (TSH <0.35 mIU/L, odds ratio [OR] = 5.12, confidence interval [CI = 1.29-20.34], p = 0.03) or positive thyrotropin receptor antibody (TRAb) (TRAb >1.75 IU/L, OR = 3.79, [CI = 1.17-12.30], p = 0.02) at the time of ATDs withdrawal presented a higher risk of rebound than those with either normal TSH levels or negative TRAb. Patients with both subnormal TSH and positive TRAb at the time of ATD withdrawal were more likely to experience rebound (83.3%, 5/6) than those with both normal TSH and negative TRAb (13%, 3/23, OR = 33.33, [CI = 2.83-392.60], p = 0.003). The prevalence of adverse pregnancy outcomes was significantly higher in patients who experienced rebound compared with those who did not (55.0% vs. 9.3%, OR = 11.92, [CI = 3.08-46.18], p = 0.0002). Conclusions: Subnormal TSH levels and TRAb positivity at the time of ATD withdrawal in early pregnancy may be associated with rebound of Graves' hyperthyroidism. Rebound of hyperthyroidism during pregnancy may increase the risk of adverse pregnancy outcomes. Larger prospective studies are needed to confirm these findings.


Virus-Derived Small RNAs and microRNAs in Health and Disease.
MicroRNAs (miRNAs) are short noncoding RNAs that can regulate all steps of gene expression (induction, transcription, and translation). Several virus families, primarily double-stranded DNA viruses, encode small RNAs (sRNAs), including miRNAs. These virus-derived miRNAs (v-miRNAs) help the virus evade the host's innate and adaptive immune system and maintain an environment of chronic latent infection. In this review, the functions of the sRNA-mediated virus-host interactions are highlighted, delineating their implication in chronic stress, inflammation, immunopathology, and disease. We provide insights into the latest viral RNA-based research-in silico approaches for functional characterization of v-miRNAs and other RNA types. The latest research can assist toward the identification of therapeutic targets to combat viral infections.