Immediate-type allergy related to okra (Hibiscus esculentus Linn) picking and packing.
Two workers (cases A and B) engaged in picking and packing okra who had complaints of work-related allergic symptoms showed distinct positive intradermal reactions to two brands of okra extracts only with thresholds of 1 x 10(-8) w/v for Case A and 1 x 10(-6) w/v for Case B. Both also showed positive reactions to okra extracts in the Prausnitz-Küstner test and in the provocative nasal test. The radioallergosorbent test scores to the okra extract were determined to be 2 (defined as clear positive) for Case A and 1 (border line) for Case B. These findings indicated that the allergic conditions of these cases were from an IgE-mediated immediate-type allergy induced by handling okra. To confirm the etiology of the two cases 14 farmers engaged in picking and packing okra were examined. Among them, 8 subjects (57%) showed positive intradermal reactions to okra extracts. A close association between intradermal reactions to okra extracts and complaints of work-related allergic symptoms was seen in these subjects. These results confirm that the okra may be capable of inducing IgE-mediated immediate-type allergy to workers handling okra.


Stimulation of oligonucleotide-directed gene correction by Redβ expression and MSH2 depletion in human HT1080 cells.
The correction of disease-causing mutations by single-strand oligonucleotide-templated DNA repair (ssOR) is an attractive approach to gene therapy, but major improvements in ssOR efficiency and consistency are needed. The mechanism of ssOR is poorly understood but may involve annealing of oligonucleotides to transiently exposed single-stranded regions in the target duplex. In bacteria and yeast it has been shown that ssOR is promoted by expression of Redβ, a single-strand DNA annealing protein from bacteriophage lambda. Here we show that Redβ expression is well tolerated in a human cell line where it consistently promotes ssOR. By use of short interfering RNA, we also show that ssOR is stimulated by the transient depletion of the endogenous DNA mismatch repair protein MSH2. Furthermore, we find that the effects of Redβ expression and MSH2 depletion on ssOR can be combined with a degree of cooperativity. These results suggest that oligonucleotide annealing and mismatch recognition are distinct but interdependent events in ssOR that can be usefully modulated in gene correction strategies.


Investigation of optimized end-bonding magnetoelectric heterostructure for sensitive magnetic field sensor.
This paper reports an optimized end-bonding magnetoelectric (ME) heterostructure FeCuNbSiB-PZT-FeCuNbSiB (FPF) for sensitive magnetic field sensor. The heterostructure is made by attaching magnetostrictive Fe73.5Cu1Nb3Si13.5B9 (FeCuNbSiB) foils at the free ends of piezoelectric Pb(Zr1-x,Tix)O3 (PZT) plates. Due to the structural advantages, the FPF has ∼3.12 times larger resonance voltage coefficient (αME,r) than traditional FeCuNbSiB/PZT laminate. And compared with the Metglas-PZT-Metglas heterostructure, the FPF heterostructure has stronger ME responses for the excellent magnetic characteristics of FeCuNbSiB. In experiments, the FPF heterostructure is optimal designed through adjusting the thickness of PZT plate (tp) and the length of FeCuNbSiB foil (L). The results demonstrate that the maximum αME,r of 662.1 (V/cm Oe) is observed at 13 Oe DC bias magnetic field when L = 15 mm and tp = 0.6 mm. Based on the giant ME coupling, the DC magnetic field sensitivity for the optimized FPF heterostructure is 3.89 nT at resonant frequency. These results are very promising for the cheap room-temperature magnetic field sensing technology.


A new liquid chromatography/mass spectrometry method for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine.
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a carcinogenic nitrosamine produced upon curing tobacco. It is present in tobacco smoke and undergoes metabolism to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in the lungs. NNAL undergoes further uridine diphosphate glucuronosyltransferase (UGT)-mediated metabolism to give N- and O-glucuronide metabolites, which together with free (non-conjugated) NNAL are then excreted in the urine. The ability to conduct validated analyses of free and conjugated NNAL in human urine is important in order to assess inter-individual differences in lung cancer risk from exposure to cigarette smoke. The use of stable isotope dilution (SID) methodology in combination with liquid chromatography/multiple reaction monitoring/mass spectrometry (LC/MRM-MS) provides the highest bioanalytical specificity possible for such analyses. We describe a novel derivatization procedure, which results in the formation of a pre-ionized N-propyl-NNAL derivative. The increased LC/MS sensitivity arising from this derivative then makes it possible to analyze free NNAL in only 0.25 mL urine. This substantial reduction in urine volume when compared with other methods that have been developed will help preserve the limited amounts of stored urine samples that are available from on-going longitudinal biomarker studies. The new high sensitivity SID LC/MRM-MS assay was employed to determine free and conjugated NNAL concentrations in urine samples from 60 individual disease-free smokers. Effects of inter-individual differences in urinary creatinine clearance on NNAL concentrations were then assessed and three metabolizer phenotypes were identified in the 60 subjects from the ratio of urinary NNAL glucuronides/free NNAL. Poor metabolizers (PMs, 14 subjects) with a ratio of NNAL glucuronides/free NNAL <2 (mean = 1.3), intermediate metabolizers (IMs, 36 subjects) with a ratio between 2 and 5 (mean = 3.4), and extensive metabolizers (EMs, 10 subjects) with a ratio >5 (mean = 11.1).


Stability of hemostatic proteins in canine fresh frozen plasma units.
The stability of hemostatic proteins, including coagulation factors II, VII, VIII, IX, and X and von Willebrand factor (vWf), in canine fresh frozen plasma (FFP) units stored for up to 1 year was studied. Plasma units from 7 donor dogs were subjected to 4 treatments following collection, including storage at -30 degrees C for 3 months, 6 months, and 1 year and storage at -20 degrees C for 6 months. Coagulant factor activity and vWf concentrations were measured at these times. Significant differences between prestorage and poststorage values were noted for factors VIII, IX, and X, and vWf. Differences seemed to be least pronounced for plasma stored for 3 months; however, a significant interaction between prestorage and poststorage differences and the 4 treatment groups could not be demonstrated. On the basis of factor content in the present study, 15-20 mL/kg of FFP stored for up to 1 year was capable of providing approximately 10-15 U/kg of vWf and factors VIII, IX, X, and II, whereas 10 mL/kg FFP provided at least 10 U/kg of factor VII.


mRNA Vaccine: How to Meet the Challenge of SARS-CoV-2.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high infectivity, pathogenicity, and variability, is a global pandemic that severely affected public health and the world economy. The development of safe and effective vaccines is crucial to the prevention and control of an epidemic. As an emerging technology, mRNA vaccine is widely used for infectious disease prevention and control and has significant safety, efficacy, and high production. It has received support and funding from many pharmaceutical enterprises and becomes one of the main technologies for preventing COVID-19. This review introduces the current status of SARS-CoV-2 vaccines, specifically mRNA vaccines, focusing on the challenges of developing mRNA vaccines against SARS-CoV-2, and discusses the relevant strategies.


Insulin-like growth factor-I and growth hormone have different effects on serum lipoproteins and secretion of lipoproteins from cultured rat hepatocytes.
GH has previously been shown to regulate serum lipoprotein levels and hepatic secretion of apolipoprotein-B (apo-B) and apo-E in the rat. The aim of this investigation was to study a possible role of insulin-like growth factor-I (IGF-I) in this regulation. Adult female rats were hypophysectomized and treated with recombinant human IGF-I (1.25 mg/kg.day) as a sc continuous infusion for 7 days. The effects of IGF-I were compared with those of bovine GH, given either as a continuous sc infusion or as two daily sc injections. All hypophysectomized rats were given replacement therapy with L-T4 and cortisol. Serum IGF-I concentrations increased to similar levels as a result of treatment with bovine GH and IGF-I. There was no effect of IGF-I on serum concentrations of glucose or insulin, whereas GH, independent of its mode of administration, increased serum insulin concentrations. Food intake was not affected by treatment with IGF-I. IGF-I had no effect on serum concentrations of cholesterol or apo-E, whereas GH given twice daily decreased serum cholesterol concentrations, and a continuous infusion of GH increased serum apo-E concentrations. Serum triglyceride and apo-B concentrations increased markedly as a result of IGF-I treatment, whereas GH had no effect on serum triglycerides, but decreased serum apo-B concentrations. Hepatocytes were isolated from hypophysectomized rats treated with L-T4 and cortisol alone or in combination with IGF-I and kept in short term cultures. In this system, IGF-I had no effect on the incorporation of [3H]glycerol in triglycerides or the mass of triglycerides in the cells and medium. There was no effect of IGF-I treatment on the secretion of apo-E or apo-B. Moreover, there was no effect of IGF-I treatment on the relationship between newly synthesized and secreted apo-B 48 and apo-B 100, as determined by [35S]methionine labeling of the proteins. In conclusion, the previously observed effects of GH on serum lipoproteins and hepatic apolipoprotein secretion does not seem to be mediated via IGF-I, but IGF-I has its own unique effects on serum triglyceride and apo-B levels. The increases in serum apo-B and serum triglyceride concentrations after IGF-I treatment were not dependent on increased hepatic secretion of apo-B or triglycerides.


Aprepitant in Anti-histamine-refractory Chronic Nodular Prurigo: A Multicentre, Randomized, Double-blind, Placebo-controlled, Cross-over, Phase-II trial (APREPRU).
The aim of this multicentre, randomized, double-blind, placebo-controlled, cross-over, phase-II study was to determine the antipruritic effect of aprepitant vs. placebo in 58 patients with anti-histamine-refractory chronic pruritus in chronic nodular prurigo. Patients were randomized to receive either first oral aprepitant 80 mg/day or placebo for 4 weeks. Following a 2-week wash-out phase, the patients were crossed-over to receive the other treatment for 4 weeks. Primary efficacy criterion was the intra-individual difference between mean itch intensity (visual analogue scale) at baseline compared with the end of treatment period. Prurigo lesions, pruritus course, quality of life, patient benefits, and safety were secondary parameters. No significant differences were found between aprepitant treatment and placebo for any of the parameters investigated. Under the experimental conditions of the study, aprepitant, 80 mg daily for 4 weeks, did not have an antipruritic effect in patients with chronic prurigo. (DRKS00005594; EudraCT Number: 2013-001601-85).


Evaluation of the living kidney donor.
Living donor renal transplantation is the preferred treatment for end-stage renal failure as the risk-benefit ratio for the recipient usually very much favours this approach. However, the benefit for the donor is much harder to define and probably very small if pure medical criteria are considered. Nonetheless 'non-medical' issues (mostly socio-psychological) may outweigh the small medical risk. The medical pre-transplant evaluation of the potential donor must identify absolute contraindications and abnormalities, which would increase the peri-operative risk. Difficulties may arise, if during the process, minor abnormalities are detected that marginally increase the acute or especially the long-term risk or whose implications are not well defined. In this situation two options are available. If the transplant team assumes that donation per se is of no benefit for the donor, transplantation should not be performed. If, however, the supposed 'non-medical' benefit is large enough, this approach will be against the principle of 'doing no harm' because the individual is denied the possibility to help somebody and might suffer from the consequences. In these complicated cases the final decision should be with the potential donor after an intense discussion with everybody involved in the transplantation process. Such an approach, however, necessitates a post-donation follow-up programme to be offered.


Knowledge and Attitude of the General Population in Saudi Arabia Toward Weight Management Medications (WMMs): A Cross-Sectional Study.
Over the past decades, the global prevalence of obesity has tripled, with the Kingdom of Saudi Arabia experiencing a notably higher rate of increase. While lifestyle modifications remain the first line of treatment, pharmacological interventions are often employed when dietary and exercise interventions prove insufficient. However, safety concerns, misuse, and limited knowledge about weight management medications (WMMs) pose serious challenges. The objectives of this study were to determine the level of knowledge and examine attitudes towards WMMs among the general population, and to explore the factors associated with these knowledge levels and attitude patterns. A cross-sectional study was conducted among adults from the general population in Saudi Arabia from January 2023 to May 2023. Participants completed a validated, self-administered electronic questionnaire in Arabic language. The questionnaire captured sociodemographic, lifestyle and health data, knowledge about WMMs, and attitudes toward them. The outcome measures included knowledge and attitudes scores. Factors associated with knowledge and attitudes were analyzed using chi-square tests. Statistical significance was determined at a p-value of <0.05. Around 716 respondents were included in the final analysis. Most of the participants acknowledged diet 565 (78.9%) and exercise 621 (86.7%) as effective strategies to lose weight. Only 222 (31.0%) participants recognized pharmaceutical medications as a weight management strategy. Knowledge about specific weight loss medications varied, with the highest recognition for semaglutide (Ozempic®, Novo Nordisk, Bagsværd, Denmark) 236 (33.0%) and liraglutide (Saxenda®, Novo Nordisk, Bagsværd, Denmark) 228 (31.8%), while the other WMMs were not commonly known between participants. Regarding attitudes, the majority disagreed with statements that WMMs are more effective than diet/exercise 413 (57.7%), are safe 405 (56.6%), and are more convenient to use 408 (57.0%). Notably, about three-quarters [534 (74.6%)] of participants agreed that these medications require specialist's counseling. No correlation was observed between knowledge score and attitude score (Pearson's correlation coefficient r=0.03; p=0.330). Respondents' knowledge about WMMs was significantly influenced by age, monthly income, educational level, psychiatric history, and previous use of WMMs (p<0.05). Adequate knowledge was more prevalent among participants aged 26-35, earning more than 20K SAR monthly, postgraduates, those with a psychiatric history, and past users of WMMs. Attitudes toward WMMs, however, showed no significant association with sociodemographic or health-related factors (p>0.05). However, prior use of WMMs significantly correlated with attitudes (p=0.007), with past users demonstrating more favorable attitudes. This study reveals a limited knowledge and cautious attitude regarding WMMs in the Saudi population, despite the high prevalence of obesity. With prior use of WMMs correlating with better knowledge and more favorable attitudes, these findings emphasize the need for targeted interventions to enhance public awareness and safe usage of these medications.


Position statement and guidelines on support personnel in audiology. American Speech-Language Hearing Association.
This policy document of the American Speech-Language-Hearing Association (ASHA) reflects the Association's position that the Certificate of Clinical Competence-Audiology (CCC-A) is a nationally recognized quality indicator and education standard for the profession. The following statement includes the CCC-A as the appropriate credential for audiologists supervising support personnel. The consensus panel document's exclusion of the CCC-A conflicts with ASHA's policy. Member organizations that composed the consensus panel on support personnel in audiology included: Academy of Dispensing Audiologists (ADA), American Academy of Audiology (AAA), ASHA, Educational Audiology Association (EAA), Military Audiology Association (MAA), and the National Hearing Conservation Association (NHCA). Representatives to the panel included Donald Bender (AAA) and Evelyn Cherow (ASHA), co-chairs; James McDonald and Meredy Hase (ADA); Albert deChiccis and Cheryl deConde Johnson (AAA); Chris Halpin and Deborah Price (ASHA); Peggy Benson (EAA); James Jerome (MAA); and Lloyd Bowling and Richard Danielson (NHCA). ASHA's Legislative Council and Executive Board elected not to adopt the consensus panel document because it excluded the CCC-A. In all others aspects, the documents remain similar. This position statement and guidelines supersede the audiology sections of the Guidelines for the Employment and Utilization of Supportive Personnel (LC 32-80).


[Community-acquired and nosocomial pneumonia].
Mortality of pneumonia is low in the outside setting (1%) but rises up to 20% in hospital admitted patients. Early diagnosis and standardized therapy improve patient's prognosis. For community acquired pneumonia age, comorbidity and the setting of therapy (outside department, normal ward or intensive care unit) are the most important variables to choose an adequate antibiotic treatment. For nosocomial pneumonia risk stratification is according to severity of illness, length of hospital stay and antibiotic pretreatment. In the outpatient setting a 7-day monotherapy is mostly successful. In severe illness the combination of a betalactam antibiotic with a new fluorchinolon seems to be superior to an aminoglycosid therapy. Antibiotic resistance due to mistakes in antibiotic therapy is an increasing problem in the intensive care unit. Therefore, pneumonia preventive measures like influenza and pneumococcal vaccination become more important. Standardized hygienical procedures help to reduce nosocomial, mainly ventilator associated pneumonia.


Successful treatment of severe Shulman's syndrome by allogeneic bone marrow transplantation.
We describe a patient with severe Shulman's syndrome (ShS) (eosinophilic fasciitis). This auto-immune disease involved not only the skin and muscles, but the bone marrow as well - thereby fulfilling the criteria of severe aplastic anemia. As the disease was steroid-resistant, the patient underwent allogeneic bone marrow transplantation (BMT). Remission of ShS was achieved. Eight months later chronic GVHD developed and relapse of ShS (probably induced by GVHD) occurred. He was successfully treated with corticosteroids and the disappearance of GVHD was followed by cessation of the symptoms of ShS. At present (34 months following BMT) he is doing well and displays no signs of ShS or GVHD. This case suggests that an aggressive immunoablative preparative regimen with subsequent allogeneic BMT can result in long-lasting clinical remission of a severe auto-immune disease.


A Y-like social chromosome causes alternative colony organization in fire ants.
Intraspecific variability in social organization is common, yet the underlying causes are rarely known. In the fire ant Solenopsis invicta, the existence of two divergent forms of social organization is under the control of a single Mendelian genomic element marked by two variants of an odorant-binding protein gene. Here we characterize the genomic region responsible for this important social polymorphism, and show that it is part of a pair of heteromorphic chromosomes that have many of the key properties of sex chromosomes. The two variants, hereafter referred to as the social B and social b (SB and Sb) chromosomes, are characterized by a large region of approximately 13 megabases (55% of the chromosome) in which recombination is completely suppressed between SB and Sb. Recombination seems to occur normally between the SB chromosomes but not between Sb chromosomes because Sb/Sb individuals are non-viable. Genomic comparisons revealed limited differentiation between SB and Sb, and the vast majority of the 616 genes identified in the non-recombining region are present in the two variants. The lack of recombination over more than half of the two heteromorphic social chromosomes can be explained by at least one large inversion of around 9 megabases, and this absence of recombination has led to the accumulation of deleterious mutations, including repetitive elements in the non-recombining region of Sb compared with the homologous region of SB. Importantly, most of the genes with demonstrated expression differences between individuals of the two social forms reside in the non-recombining region. These findings highlight how genomic rearrangements can maintain divergent adaptive social phenotypes involving many genes acting together by locally limiting recombination.


Hypoxia positron emission tomography imaging with 18f-fluoromisonidazole.
The importance of hypoxia in disease pathogenesis and prognosis is gathering increasing clinical significance and having a greater impact on patient management and outcome. Previous efforts to evaluate hypoxia have included the invasive assessment of hypoxia with immunohistologic and histographic oxygen probes. The emergence of new radiotracers has allowed noninvasive assessment of hypoxia, with the most extensively investigated and validated positron emission tomography radiotracer of hypoxia to date being (18)F-fluoromisonodazole ((18)F-FMISO). This review discusses the relevance and biology of hypoxia in cells and organ systems, and reviews the laboratory and clinical applications of (18)F-FMISO in oncology and noncancer disease states.


Acidocella aromatica sp. nov.: an acidophilic heterotrophic alphaproteobacterium with unusual phenotypic traits.
Three obligately heterotrophic bacterial isolates were identified as strains of a proposed novel species of extremely acidophilic, mesophilic Alphaproteobacteria, Acidocella aromatica. They utilized a restricted range of organic substrates, which included fructose (but none of the other monosaccharides tested), acetate and several aromatic compounds (benzoate, benzyl alcohol and phenol). No growth was obtained on complex organic substrates, such as yeast extract and tryptone. Tolerance of the proposed type strain of the species (PFBC) to acetic acid was much greater than that typically reported for acidophiles. The bacteria grew aerobically, and catalyzed the dissimilatory reductive dissolution of the ferric iron mineral schwertmannite under both micro-aerobic and anaerobic conditions. Strain PFBC did not grow anaerobically via ferric iron respiration, though it has been reported to grow in co-culture with acid-tolerant sulfidogenic bacteria under strictly anoxic conditions. Tolerance of strains of Acidocella aromatica to nickel were about two orders of magnitude greater than those of other Acidocella spp., though similar levels of tolerance to other metals tested was observed. The use of this novel acidophile in solid media designed to promote the isolation and growth of other (aerobic and anaerobic) acidophilic heterotrophs is discussed.


Feasibility and preliminary efficacy of guided internet-delivered cognitive behavioral therapy for insomnia after the loss of a child to cancer: Randomized controlled trial.
Bereaved individuals often experience sleep problems. The aim of this study was to evaluate feasibility and preliminary effects of internet-delivered cognitive behavioral therapy for insomnia (iCBT-i) in bereaved parents. Parents were randomized to iCBT-i (n = 10) or an active control group (n = 11). Primary outcome (insomnia) and secondary outcomes (prolonged grief, depression, posttraumatic stress, and grief rumination) were assessed pre- and post-treatment, with 9- and 18-month follow-ups. Feasibility was assessed post-treatment and one month later. Most parents reported positive effects of the treatment. The intervention group improved significantly from pre- to post-treatment and had a significantly larger reduction of insomnia when analyzed over all four time-points (Wald χ2 = 30.0, p < 0.001), although the effect at post-treatment was very small (d = 0.1) for insomnia. Thus, iCBT-i was feasible and was related to reduced insomnia and psychological distress in bereaved parents, both short- and long-term, but the results regarding the treatment effect are preliminary due to the small sample size.


The complexities associated with new psychoactive substances in influent wastewater: The case of 4-ethylmethcathinone.
Consumption of new psychoactive substances (NPS) is an international problem for health, policing, forensic, and analytical laboratories. The transience of these substances in the community, combined with continual slight structural changes to evade legislation makes the elucidation of NPS an analytical challenge. This is amplified in a matrix as complex as wastewater. For that reason, suspect and non-target methodologies, employing high resolution mass spectrometry are the most appropriate current tool to facilitate the identification of new and existing compounds. In the current work, a qualitative screening method of influent wastewater using liquid chromatography-high resolution mass spectrometry showed a strong signal at m/z 192.1382 - identical to that of two NPS standards that were in our method (pentedrone and 4-methylethcathinone), and with identical fragment ions, but the retention times did not match. This work shows the methodology followed to identify this compound, highlighting the challenges of the identifying "new" compounds in influent wastewater.


Benefit of insecticide-treated nets, curtains and screening on vector borne diseases, excluding malaria: a systematic review and meta-analysis.
Insecticide-treated nets (ITNs) are one of the main interventions used for malaria control. However, these nets may also be effective against other vector borne diseases (VBDs). We conducted a systematic review and meta-analysis to estimate the efficacy of ITNs, insecticide-treated curtains (ITCs) and insecticide-treated house screening (ITS) against Chagas disease, cutaneous and visceral leishmaniasis, dengue, human African trypanosomiasis, Japanese encephalitis, lymphatic filariasis and onchocerciasis. MEDLINE, EMBASE, LILACS and Tropical Disease Bulletin databases were searched using intervention, vector- and disease-specific search terms. Cluster or individually randomised controlled trials, non-randomised trials with pre- and post-intervention data and rotational design studies were included. Analysis assessed the efficacy of ITNs, ITCs or ITS versus no intervention. Meta-analysis of clinical data was performed and percentage reduction in vector density calculated. Twenty-one studies were identified which met the inclusion criteria. Meta-analysis of clinical data could only be performed for four cutaneous leishmaniasis studies which together showed a protective efficacy of ITNs of 77% (95%CI: 39%-91%). Studies of ITC and ITS against cutaneous leishmaniasis also reported significant reductions in disease incidence. Single studies reported a high protective efficacy of ITS against dengue and ITNs against Japanese encephalitis. No studies of Chagas disease, human African trypanosomiasis or onchocerciasis were identified. There are likely to be considerable collateral benefits of ITN roll out on cutaneous leishmaniasis where this disease is co-endemic with malaria. Due to the low number of studies identified, issues with reporting of entomological outcomes, and few studies reporting clinical outcomes, it is difficult to make strong conclusions on the effect of ITNs, ITCs or ITS on other VBDs and therefore further studies be conducted. Nonetheless, it is clear that insecticide-treated materials such as ITNs have the potential to reduce pathogen transmission and morbidity from VBDs where vectors enter houses.


Oblate deltahedra in dimetallaboranes: geometry and chemical bonding.
A new series of nonspherical and very oblate deltahedra, conveniently called the oblatocloso deltahedra, is found in dimetallaboranes among which the dirhenaboranes Cp2Re2B(n-2)H(n-2) (8 <or= n <or= 12) are the prototypes. The D(6h) hexagonal bipyramid is the first member of this series (n = 8). However, the higher members of the series are not bipyramids but are derivable from them by a number of diamond-square-diamond processes. A viable model for the skeletal bonding in the oblatocloso dimetallaboranes can be developed if the two metal vertices, typically degree 6 or 7 vertices, are assumed each to contribute five internal orbitals rather than the three internal orbitals assumed by the Wade-Mingos rules. This leads to 2n + 4 actual skeletal electrons for an n vertex oblatocloso dimetallaborane rather than the Wadean 2n - 4 skeletal electrons. The surface bonding of an n vertex oblatocloso dimetallaborane then consists of n three-center two-electron bonds similar to that in corresponding isocloso metallaboranes thereby leaving four orbitals and four electrons for a metal-metal double bond inside the deltahedron. Removal of one or two boron vertices from oblatocloso deltahedra leads to oblatonido and oblatoarachno dimetallaboranes, respectively, having the same number of skeletal electrons as the oblatocloso deltahedra from which they are derived.


Diagnostic tool for the diagnosis of physiological and pathological conditions of the uterus in cows postpartum.
An important task of veterinarians in cattle husbandry is the early diagnosis of postpartum complications that can lead to infertility. The aim of the study was the evaluation of a new device to distinguish between physiological and pathological conditions of the uterus based on the determination of the time of uterine involution and the physicochemical properties of the vaginal discharge (lochia) during the first weeks after parturition. A total of 173 black-and-white Holstein-Friesian dairy cows were examined for any pathological alteration of the uterine involution on days 1-2, 6-8, 11-14 postpartum and, in case of pathological findings, additionally on days 18-22, 23-27 and 28-30 after parturition. In addition to the standard examination a newly developed hand-held instrument ("Metrastatum") was used to differentiate between physiological and pathological uterine involution. It allows determination of the distance between the cervix and vulva (DCV) and simultaneous collection of lochial secretions. The best time to use the new instrument was 10-16 days postpartum. In healthy cows without disturbed puerperium, the average DCV was 25.7 cm (± 0.8 cm) in this phase. This distance decreased by 12.5 ± 0.3 cm compared to the first days. In contrast, in cows with postpartum problems, the DCV was significantly greater at (31 ± 0.7 cm) (p < 0.001). In these animals, the AGV was reduced only by an average of 8.4 ± 0.6 cm when compared to the first days. The mucus obtained with the dome-shaped rubber funnel of the instrument also differed in the cows of the 2 groups. In healthy cows without puerperal problems, the lochia were thick, colorless, transparent and sometimes cloudy. In case of puerperal disorders, the discharge was thin, light red to reddish brown, contained flakes and had a nasty odor depending on the form of the inflammation. The dual function of device helps to early diagnose puerperal disorders in cows and to select healthy animals for reproduction and sick cows for treatment depending on the form of uterine inflammation.


Study on the mutagenicity and antimutagenicity of beta-ionone in the Salmonella/microsome assay.
beta-Ionone (BIO) is a degraded (C(13)) sesquiterpenoid compound found in a variety of edible and aromatic plants. BIO and other ionone derivatives have been used in fragrance products and as flavoring food additives. In this study we investigated the mutagenic and antimutagenic activities of BIO using the Salmonella/microsome assay. Mutagenicity was evaluated by two tests with Salmonella typhimurium strains TA100, TA98, TA97a and TA1535, without and with addition of S9 mixture. A first assay was performed by the plate incorporation procedure and a confirmation test by the pre-incubation method. In either test, no increase in the number of his(+) revertant colonies over the negative (solvent) control values was noted with any of the four tester strains thereby indicating that BIO was not genotoxic in the Salmonella assay. Antimutagenic activity was investigated by testing (by the plate incorporation method) different non-toxic doses of BIO against one or more non-toxic doses of direct-acting (sodium azide: SA, 4-nitroquinoline-N-oxide: 4-NQNO, 2-nitrofluorene: 2-NF and nitro-o-phenylenediamine: NPD) as well as indirect-acting (cyclophosphamide: CP, benzo[a]pyrene: B[a]P, aflatoxin B1: AFB1, 2-aminoanthracene: 2-AA, and 2-aminofluorene: 2-AF) mutagens. BIO did not alter the effects of any direct-acting mutagen or B[a]P and 2-AF. Mutagenic effects of AFB1 and CP, however, were markedly and dose-dependently antagonized by BIO. It has been reported that, in the rat liver, activation of B[a]P and 2-AF depend on CYP1A1 activity, and that CYP2B subfamily is involved in the metabolic activation of CP and AFB1. It has also been described that BIO is a potent inhibitor of CYP2B1/2 and a weaker inhibitor of CYP1A1. Therefore, antagonism of CP-and AFB1-induced mutagenic effects by BIO could have been mediated-at least in part-by the inhibition of CYP2B enzymes.


Membrane-dependent actin polymerization mediated by the Legionella pneumophila effector protein MavH.
L. pneumophila propagates in eukaryotic cells within a specialized niche, the Legionella-containing vacuole (LCV). The infection process is controlled by over 330 effector proteins delivered through the type IV secretion system. In this study, we report that the Legionella MavH effector localizes to endosomes and remodels host actin cytoskeleton in a phosphatidylinositol 3-phosphate (PI(3)P) dependent manner when ectopically expressed. We show that MavH recruits host actin capping protein (CP) and actin to the endosome via its CP-interacting (CPI) motif and WH2-like actin-binding domain, respectively. In vitro assays revealed that MavH stimulates actin assembly on PI(3)P-containing liposomes causing their tubulation. In addition, the recruitment of CP by MavH negatively regulates F-actin density at the membrane. We further show that, in L. pneumophila-infected cells, MavH appears around the LCV at the very early stage of infection and facilitates bacterium entry into the host. Together, our results reveal a novel mechanism of membrane tubulation induced by membrane-dependent actin polymerization catalyzed by MavH that contributes to the early stage of L. pneumophila infection by regulating host actin dynamics.


[Classification of duties in surgical wards].
Night duties in surgical wards can be demanding physically and mentally. Staffing the emergency room, performing emergency operations and taking care of the admitted patients are only few of surgeons' tasks during these busy duties. Night duties can have different effects on the following day/days tasks, limiting some of the leisure activities and maybe life quality. Literature search, however, shows few studies about the subject. The aim of this study was twofold: to study the effects of night duties on the general health of surgeons and to classify duties according to these effects. Retrospective study based on modified Short Form Survey (SF)-12. Questionnaire forms were sent to all surgeons in the surgical department at Hvidovre Hospital. The questionnaire forms were sent to 64 surgeons and 38 answered (59.4%). The highest response rate was in the residents group (71.9%: 23/32), senior residents group (70%: 7/10) and the lowest rate in consultants group (36.4%: 8/22). Night duties have no significant effect on surgeons' general health. There is a trend, however, that these duties have an effect on hard physical and/or mental activities in the following day especially for female surgeons. not relevant. not relevant.


The Elderly are Less Likely to Receive Recommended Radical Radiotherapy for Non-small Cell Lung Cancer.
The National Institute for Healthcare Excellence recommends continuous hyperfractionated, accelerated radiotherapy (CHART), concurrent chemoradiation (cCRT) and stereotactic ablative radiotherapy (SABR) for appropriate patients with non-small cell lung cancer (NSCLC), but these are not universally available in all UK radiotherapy centres. Reduced access to these treatments may be contributing to reduced survival, with the concern that elderly patients are less likely to receive guideline-recommended therapy (GRT). We report a prospective, UK national study of patients treated with curative-intent radiotherapy for NSCLC over a 2 month period. Clinical oncologists in all UK radiotherapy centres were contacted and asked to complete a proforma on all patients treated with curative-intent radiotherapy. Three hundred and seventeen records were returned from 82% of centres. Only 49% (95% confidence interval 43-55%) of patients received the GRT for their tumour type. Patients aged 70 years or over were less likely to access GRT than those under 70 years (40% compared with 60%, P = 0.001), both as a result of clinicians offering therapy less frequently (52% compared with 65%, P = 0.03) and a higher refusal of therapy (22% versus 8%, P = 0.02). A reluctance to travel to a different centre was a key component of these decisions. SABR was delivered to only 52% of suitable patients, mainly because it was not available in the local centre. In this study of UK curative-intent radiotherapy practice, a lack of local access seems to limit uptake of advanced radiotherapy techniques such as SABR, especially for patients aged over 70 years.


Dysregulation of VEGF-induced proangiogenic Ca2+ oscillations in primary myelofibrosis-derived endothelial colony-forming cells.
Endothelial progenitor cells could be implicated in the aberrant neoangiogenesis that occurs in bone marrow and spleen in patients with primary myelofibrosis (PMF). However, antivascular endothelial growth factor (VEGF) monotherapy had only a modest and transient effect in these individuals. Recently it was found that VEGF-induced proangiogenic intracellular Ca(2+) oscillations could be impaired in endothelial progenitor cells of subjects with malignancies. Therefore, we employed Ca(2+) imaging, wavelet analysis, and functional assays to assess whether and how VEGF-induced Ca(2+) oscillations are altered in PMF-derived endothelial progenitor cells. We focused on endothelial colony-forming cells (ECFCs), which are the only endothelial progenitor cell subtype capable of forming neovessels both in vivo and in vitro. VEGF triggers repetitive Ca(2+) spikes in both normal ECFCs (N-ECFCs) and ECFCs obtained from PMF patients (PMF-ECFCs). However, the spiking response to VEGF is significantly weaker in PMF-ECFCs. VEGF-elicited Ca(2+) oscillations are patterned by the interaction between inositol-1,4,5-trisphosphate-dependent Ca(2+) mobilization and store-operated Ca(2+) entry. However, in most PMF-ECFCs, Ca(2+) oscillations are triggered by a store-independent Ca(2+) entry pathway. We found that diacylglycerol gates transient receptor potential canonical 1 channel to trigger VEGF-dependent Ca(2+) spikes by recruiting the phospholipase C/inositol-1,4,5-trisphosphate signaling pathway, reflected as a decrease in endoplasmic reticulum Ca(2+) content. Finally, we found that, apart from being less robust and dysregulated as compared with N-ECFCs, VEGF-induced Ca(2+) oscillations modestly stimulate PMF-ECFC growth and in vitro angiogenesis. These results may explain the modest effect of anti-VEGF therapies in PMF.


[An extreme case of undoing and posing in a case of murder-suicide. A forensic pathological approach to crime scene investigation].
A 7-year-old boy was killed by his father by manual strangulation during a murder-suicide. After the killing of the son, the father showed typical "undoing" behaviour: He changed the boy's clothes and laid him down on the bed. Then he placed candles around his head, put pictures of the parents' wedding around him and a crucifix and a picture of the family into his hands. He broke off a rose in a vase next to the bed, lit the candles and took photographs of his dead son. Later he called his wife, threatened to kill the son and finally called the police to confess the murder and to announce his forthcoming suicide.


Coping styles and illicit drug use in older adults with HIV/AIDS.
The prevalence of HIV infection in older adults is increasing; by 2015, over half of adults living with HIV/AIDS in the United States will be over 50. This study describes the prevalence of drug use and examines psychosocial predictors of drug use in a sample of HIV-infected adults aged 50 and older. Participants were 301 HIV-positive older adults enrolled in a clinical trial of a coping intervention aimed to reduce their depressive symptoms. One-quarter used illicit drugs in the past 60 days (48% any cocaine, 48% weekly marijuana, 44% any other drugs) with an average of 36 days for marijuana and 15 days for cocaine. After controlling for demographics, self-destructive avoidance was positively associated and spiritual coping was negatively associated with drug use. These findings suggest that assessment of drug abuse should be a routine part of care for older patients in HIV clinics. Furthermore, interventions designed to increase spiritual coping and decrease self-destructive avoidance may be particularly efficacious for HIV-infected older adults.


Transport reversal in a thermal ratchet.
Transport of a Brownian particle moving in a periodic potential is investigated in the presence of a symmetric unbiased external force. The viscous medium is alternately in contact with two heat reservoirs. We present the analytical expression of the net current at the quasi-steady-state limit. It is found that the competition of the asymmetric parameter of the potential with the temperature difference leads to phenomena like current reversal. The competition between the two driving factors is a necessary but not a sufficient condition for current reversals.


Managing Crop Diseases Under Water Scarcity.
The significance of water scarcity to crop production and food security has been globally recognized as a pivotal sustainability challenge in the UN Sustainable Development Goals (86). The critical link between water scarcity and sustainability is adaptation. Various changes in water use practices have been employed to alleviate production constraints. However, the potential for these changes to influence crop diseases has received relatively little attention, despite the circumglobal importance of diseases to agricultural sustainability. This article reviews what is known about the realized effects of scarcity-driven alterations in water use practices on diseases in the field in order to raise awareness of the potential for both increased disease risk and possible beneficial effects on crop disease management. This is followed by consideration of the primary mechanistic drivers underlying disease outcomes under various water use adaptation scenarios, concluding with a vision for disease-water co-management options and future research needs.


Double-stranded RNA antibodies in systemic lupus erythematosus.
Antibodies to viral double-stranded RNA (ds RNA) have been found in 40% of patients with systemic lupus erythematosus (SLE) and 14-5% of patients with rheumatoid arthritis. These antibodies were diagnostically more specific SLE than those directed against artificial polynucleotides, poly I:C and poly A:U. Although not disease specific, high titres of antibody to ds viral RNA were found almost exclusively in SLE. Serial studies failed to show that RNA antibody levels correlated with disease activity. Although of considerable interest in experimental studies on the pathogenesis of SLE, ds viral RNA antibodies are of little clinical significance in the management of SLE.


Early-onset Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency.
Autoimmune cytopenia is a frequent manifestation of primary immunodeficiencies. Two siblings presented with Evans syndrome, viral infections, and progressive leukopenia. DNA available from one patient showed a homozygous frameshift mutation in tripeptidyl peptidase II (TPP2) abolishing protein expression. TPP2 is a serine exopeptidase involved in extralysosomal peptide degradation. Its deficiency in mice activates cell death programs and premature senescence. Similar to cells from naïve, uninfected TPP2-deficient mice, patient cells showed increased major histocompatibility complex I expression and most CD8(+) T-cells had a senescent CCR7-CD127(-)CD28(-)CD57(+) phenotype with poor proliferative responses and enhanced staurosporine-induced apoptosis. T-cells showed increased expression of the effector molecules perforin and interferon-γ with high expression of the transcription factor T-bet. Age-associated B-cells with a CD21(-) CD11c(+) phenotype expressing T-bet were increased in humans and mice, combined with antinuclear antibodies. Moreover, markers of senescence were also present in human and murine TPP2-deficient fibroblasts. Telomere lengths were normal in patient fibroblasts and granulocytes, and low normal in lymphocytes, which were compatible with activation of stress-induced rather than replicative senescence programs. TPP2 deficiency is the first primary immunodeficiency linking premature immunosenescence to severe autoimmunity. Determination of senescent lymphocytes should be part of the diagnostic evaluation of children with refractory multilineage cytopenias.


Scalable low-cost fabrication of disposable paper sensors for DNA detection.
Controlled integration of features that enhance the analytical performance of a sensor chip is a challenging task in the development of paper sensors. A critical issue in the fabrication of low-cost biosensor chips is the activation of the device surface in a reliable and controllable manner compatible with large-scale production. Here, we report stable, well-adherent, and repeatable site-selective deposition of bioreactive amine functionalities and biorepellant polyethylene glycol-like (PEG) functionalities on paper sensors by aerosol-assisted, atmospheric-pressure, plasma-enhanced chemical vapor deposition. This approach requires only 20 s of deposition time, compared to previous reports on cellulose functionalization, which takes hours. A detailed analysis of the near-edge X-ray absorption fine structure (NEXAFS) and its sensitivity to the local electronic structure of the carbon and nitrogen functionalities. σ*, π*, and Rydberg transitions in C and N K-edges are presented. Application of the plasma-processed paper sensors in DNA detection is also demonstrated.


Recovery of bacteria from broiler carcasses after spray washing with acidified electrolyzed water or sodium hypochlorite solutions.
A study was conducted to investigate the effects of spray washing broiler carcasses with acidified electrolyzed oxidizing water (EO) or sodium hypochlorite (HOCl) solutions for 5, 10, or 15 s. Commercial broiler carcasses were contaminated with 0.1 g of broiler cecal contents inoculated with 10(5) cells of Campylobacter and 10(5) cells of nalidixic acid-resistant Salmonella. Numbers of bacteria recovered from unwashed control carcasses were 6.7, 5.9, 6.3, and 3.9 log(10) cfu/mL for total aerobic bacteria, Escherichia coli, Campylobacter, and Salmonella, respectively. Washing in either EO (50 mg/L of sodium hypochlorite, pH 2.4, oxidation reduction potential of 1,180 mV) or HOCl (50 mg/L of sodium hypochlorite, pH 8.0) significantly reduced the levels of bacteria recovered from carcasses (P < 0.05). Carcasses washed with EO had slightly lower levels of total aerobic bacteria (0.3 log(10) cfu/mL) and E. coli (0.2 log(10) cfu/mL) than HOCl-treated carcasses; however, populations of Campylobacter and Salmonella were comparable after washing in either solution. Increasing the carcass washing time from 5 to 10 s lowered the levels of total aerobic bacteria (6.1 vs. 5.8 log(10) cfu/mL), E. coli (4.6 vs. 4.1 log(10) cfu/mL), Campylobacter (5.2 vs. 4.2 log(10) cfu/mL), and Salmonella (2.0 vs. 1.2 log(10) cfu/mL), but no further microbiological reductions occurred when washing time was extended from 10 to 15 s. Data from the present study show that washing poultry carcasses with EO is slightly better (total aerobic bacteria and E. coli) or equivalent to (Campylobacter and Salmonella) washing with HOCl. Washing broiler carcasses for a period equivalent to 2 inside-outside bird washers (10 s) provided greater reductions in carcass bacterial populations than periods simulating 1 (5 s) or 3 inside-outside bird washers (15 s).


Certifying the quantumness of a generalized coherent control scenario.
We consider the role of quantum mechanics in a specific coherent control scenario, designing a "coherent control interferometer" as the essential tool that links coherent control to quantum fundamentals. Building upon this allows us to rigorously display the genuinely quantum nature of a generalized weak-field coherent control scenario (utilizing 1 vs. 2 photon excitation) via a Bell-CHSH test. Specifically, we propose an implementation of "quantum delayed-choice" in a bichromatic alkali atom photoionization experiment. The experimenter can choose between two complementary situations, which are characterized by a random photoelectron spin polarization with particle-like behavior on the one hand, and by spin controllability and wave-like nature on the other. Because these two choices are conditioned coherently on states of the driving fields, it becomes physically unknowable, prior to measurement, whether there is control over the spin or not.


Uptake and intracellular distribution of lanthanum.
The present investigation of the cellular distribution of lanthanum was undertaken in order to control the validity of the "Lanthanum method" used for the study of the cell calcium compartments. The presence of lanthanum was evaluated in the isolated guinea-pig heart and its subcellular fractions perfused with a lanthanum-containing Tyrode solution. Lanthanum was determined by instrumental neutron activation analysis. Under the adopted experimental conditions (30-min incubation in the presence of 12.5 microM lanthanum), lanthanum is carried across the cell membrane and is taken up by subcellular organelles. These results confirm the limited validity of investigations based on of the "Lanthanum method".


[Finite element simulation of bone grafting process for avascular necrosis of femoral head].
Based on the unilateral CT images of a clinical patient in stage III for avascular necrosis of femoral head, three-dimensional finite element models of proximal femur are established, including normal model, necrosis model and prothetic model. Based on the same set of CT images, the material properties are assigned to the three finite element models respectively. Finally, the process of bone grafting for avascular necrosis of femoral head is simulated with finite element analysis. The results indicate that when the necrosis parts of femoral head are removed, the stress and displacement of proximal femur increase accordingly, and after the surgical operation of bone grafting, the stress and displacement of proximal femur can decrease effectively and become closer to the normal state. All the results indicate that the bone grafting operation is effective and reliable.


Study on oxidative stress and antioxidant level in patients of acute myocardial infarction before and after regular treatment.
In acute myocardial infarction (AMI), lack of oxygen delivery to myocardium leads to generation of reactive oxygen species (ROS) which play an important role in the pathogenesis of AMI. Endogenous anti-oxidants protect the myocardial tissues from the deleterious effect of free radical mediate injury. The study evaluates the extent of oxidative stress and antioxidant status against ROS in AMI patients and amelioration of oxidative stress after regular treatment and also assesses the association between oxidative stress and risk factors for atherosclerosis like dyslipidemia and diabetes mellitus (DM). The study was conducted on 72 AMI patients and age and sex matched 18 healthy controls. Patients were assigned to four groups, AMI without dyslipidemia or DM, with dyslipidemia, with DM and with both dyslipidemia and DM. Plasma malondialdehyde (MDA) and GSH content and vitamin E levels were determined on admission into hospital and on the 5th day of treatment. Plasma MDA level increased significantly (p < 0.001) and erythrocyte GSH and plasma vitamin E levels were decreased (p < 0.001) in all the groups of patients as compared to control. On the 50th day of regular treatment MDA level reduced (p < 0.001) and GSH and vitamin E levels increased (p < 0.001) in patients. The plasma MDA level was significantly higher (p < 0.001) in patients with both dyslipidemia and DM or with only DM in comparison to patients without dyslipidemia and DM. The difference in the GSH level between patients with risk factors and without risk factors was not significant. It may be conclude that an imbalance exists between oxidant and antioxidant molecules in AMI patients which shift towards oxidative side and regular treatment restores this balance. There may be some association between oxidative stress in AMI and risk factors like dyslipidemia and diabetes mellitus.


Accessible bioprinting: adaptation of a low-cost 3D-printer for precise cell placement and stem cell differentiation.
The precision and repeatability offered by computer-aided design and computer-numerically controlled techniques in biofabrication processes is quickly becoming an industry standard. However, many hurdles still exist before these techniques can be used in research laboratories for cellular and molecular biology applications. Extrusion-based bioprinting systems have been characterized by high development costs, injector clogging, difficulty achieving small cell number deposits, decreased cell viability, and altered cell function post-printing. To circumvent the high-price barrier to entry of conventional bioprinters, we designed and 3D printed components for the adaptation of an inexpensive 'off-the-shelf' commercially available 3D printer. We also demonstrate via goal based computer simulations that the needle geometries of conventional commercially standardized, 'luer-lock' syringe-needle systems cause many of the issues plaguing conventional bioprinters. To address these performance limitations we optimized flow within several microneedle geometries, which revealed a short tapered injector design with minimal cylindrical needle length was ideal to minimize cell strain and accretion. We then experimentally quantified these geometries using pulled glass microcapillary pipettes and our modified, low-cost 3D printer. This systems performance validated our models exhibiting: reduced clogging, single cell print resolution, and maintenance of cell viability without the use of a sacrificial vehicle. Using this system we show the successful printing of human induced pluripotent stem cells (hiPSCs) into Geltrex and note their retention of a pluripotent state 7 d post printing. We also show embryoid body differentiation of hiPSC by injection into differentiation conducive environments, wherein we observed continuous growth, emergence of various evaginations, and post-printing gene expression indicative of the presence of all three germ layers. These data demonstrate an accessible open-source 3D bioprinter capable of serving the needs of any laboratory interested in 3D cellular interactions and tissue engineering.


Mapping Vaccine Names in Clinical Trials to Vaccine Ontology using Cascaded Fine-Tuned Domain-Specific Language Models.
Vaccines have revolutionized public health by providing protection against infectious diseases. They stimulate the immune system and generate memory cells to defend against targeted diseases. Clinical trials evaluate vaccine performance, including dosage, administration routes, and potential side effects. ClinicalTrials.gov is a valuable repository of clinical trial information, but the vaccine data in them lacks standardization, leading to challenges in automatic concept mapping, vaccine-related knowledge development, evidence-based decision-making, and vaccine surveillance. In this study, we developed a cascaded framework that capitalized on multiple domain knowledge sources, including clinical trials, Unified Medical Language System (UMLS), and the Vaccine Ontology (VO), to enhance the performance of domain-specific language models for automated mapping of VO from clinical trials. The Vaccine Ontology (VO) is a community-based ontology that was developed to promote vaccine data standardization, integration, and computer-assisted reasoning. Our methodology involved extracting and annotating data from various sources. We then performed pre-training on the PubMedBERT model, leading to the development of CTPubMedBERT. Subsequently, we enhanced CTPubMedBERT by incorporating SAPBERT, which was pretrained using the UMLS, resulting in CTPubMedBERT + SAPBERT. Further refinement was accomplished through fine-tuning using the Vaccine Ontology corpus and vaccine data from clinical trials, yielding the CTPubMedBERT + SAPBERT + VO model. Finally, we utilized a collection of pre-trained models, along with the weighted rule-based ensemble approach, to normalize the vaccine corpus and improve the accuracy of the process. The ranking process in concept normalization involves prioritizing and ordering potential concepts to identify the most suitable match for a given context. We conducted a ranking of the Top 10 concepts, and our experimental results demonstrate that our proposed cascaded framework consistently outperformed existing effective baselines on vaccine mapping, achieving 71.8% on top 1 candidate's accuracy and 90.0% on top 10 candidate's accuracy. This study provides a detailed insight into a cascaded framework of fine-tuned domain-specific language models improving mapping of VO from clinical trials. By effectively leveraging domain-specific information and applying weighted rule-based ensembles of different pre-trained BERT models, our framework can significantly enhance the mapping of VO from clinical trials.


Recent progress in understanding the evolution of carnivorous lentibulariaceae (lamiales).
Carnivorous plants have emerged as model systems for addressing many ecological and evolutionary questions, and since Lentibulariaceae comprise more than half of all known carnivorous species (325 spp.), they are of particular interest. Studies using various molecular markers have established that Lentibulariaceae and their three genera are monophyletic with Pinguicula being sister to a Genlisea-Utricularia-clade, while the closest relatives of the family remain uncertain. Character states of the carnivorous syndrome in related proto-carnivorous lamialean families apparently emerged independently. In Utricularia, the terrestrial habit has been reconstructed as plesiomorphic, and an extension of subgenus Polypompholyx is warranted. In the protozoan-attracting Genlisea, subgenus Tayloria is revealed as basal lineage. In Pinguicula, the six major lineages found reflect radiations in clearly defined geographic regions, whereas most previously recognized subgeneric taxa are non-monophyletic. Genlisea and Utricularia exhibit substitutional rates that rank among the highest in angiosperms for the molecular markers analyzed. One possible explanation for this lies in selective constraints on a wide range of genomic regions that may have been lowered due to the use of an alternative mode of acquiring nutrients.


Smart pH-responsive upconversion nanoparticles for enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.
A smart pH-responsive photodynamic therapy system based on upconversion nanoparticle loaded PEG coated polymeric lipid vesicles (RB-UPPLVs) was designed and prepared. These RB-UPPLVs which are promising agents for deep cancer photodynamic therapy applications can achieve enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.


12-month outcomes of community engagement versus technical assistance to implement depression collaborative care: a partnered, cluster, randomized, comparative effectiveness trial.
Depression collaborative care implementation using community engagement and planning (CEP) across programs improves 6-month client outcomes in minority communities, compared with technical assistance to individual programs (resources for services [RS]). However, 12-month outcomes are unknown. To compare effects of CEP and RS on mental health-related quality of life (MHRQL) and use of services among depressed clients at 12 months. Matched health and community programs (n = 93) in 2 communities randomly assigned to receive CEP or RS. (ClinicalTrials.gov: NCT01699789). Self-reported MHRQL and services use at baseline, 6 months, and 12 months. Los Angeles, California. 1018 adults with depressive symptoms (8-item Patient Health Questionnaire score ≥10), 88% of whom were an ethnic minority. CEP and RS to implement depression collaborative care. The primary outcome was poor MHRQL (12-item mental health composite score ≤40) at baseline, 6 months, and 12 months; the secondary outcome was use of services at 12 months. At 6 months, the finding that CEP outperformed RS to reduce poor MHRQL was significant but sensitive to underlying statistical assumptions. At 12 months, some analyses suggested that CEP was advantageous to MHRQL, whereas others did not confirm a significant difference favoring CEP. The finding that CEP reduced behavioral health hospitalizations at 6 months was less evident at 12 months and was sensitive to underlying statistical assumptions. Other services use did not significantly differ between interventions at 12 months. Data are self-reported, and findings are sensitive to modeling assumptions. In contrast to 6-month results, no consistent effects of CEP on reducing the likelihood of poor MHRQL and behavioral health hospitalizations were found at 12 months. Still, given the needs of underresourced communities, the favorable profile of CEP, and the lack of evidence-based alternatives, CEP remains a viable strategy for policymakers and communities to consider. National Institute of Mental Health, Robert Wood Johnson Foundation, California Community Foundation, National Library of Medicine, and National Institutes of Health/National Center for Advancing Translational Science for the UCLA Clinical and Translational Science Institute.


Case report: Left gaze and facial nerve palsies after ventral intermediate thalamic nucleus deep brain stimulation implantation.
Deep brain stimulation (DBS) to the ventral intermediate nucleus (VIM) of the thalamus has become a common procedure for some refractory, medication-resistant movement disorders like essential tremors. The most common adverse effects from this surgery include dysarthria and gait disturbances. This case report details a left gaze and ipsilateral facial nerve palsy following overshot cannula insertion into the pons during a VIM DBS procedure. Initial patient presentation after surgery revealed significant impairment of horizontal gaze to the left. This improved during follow-up visits and after the recession of the bilateral medial recti. When considering complications of the VIM DBS procedure, surgeons should be aware of the risks of cannula overshot given the anatomic proximity between the thalamus and brainstem. Furthermore, patients should be aware of this risk when making their surgical decision. All patients who undergo VIM DBS should be assessed for cranial nerve deficits after placement.


Frequent mutation in Chinese patients with infantile type of GSD II in Taiwan: evidence for a founder effect.
Glycogen storage disease type II (GSD II, Pompe's disease), an autosomal recessive inherited disease, is caused by the deficiency of acid alpha-D-glucosidase, which results in the impaired glycogen degradation in lysosome and causes excess glycogen accumulation in lysosome. In Taiwan, the infantile form of GSD II is the most common type of glycogen storage diseases. The frequency of C1935A mutant allele is 0.8 in these Chinese patients. In this study, we analyzed four single point polymorphic markers (324, 1203, 2065, 2338) by ACRS-based RFLP We observed that the alleles possessing the C1935A mutation in 19 of 25 Chinese patients who were heterozygous or homozygous have conserved polymorphic markers, and all of C1935A mutant alleles in these patients are linked to a specific haplotype. The allele frequency of this specific haplotype in 19 Chinese patients and in 42 normal individuals is 0.95 and 0.17, respectively (P<0.005, chi2 = 66.018). This result suggests that the C1935A mutation in Chinese patients with infantile form of GSD II is due to the founder effect.


Correlates of intentions to obtain genetic counseling and colorectal cancer gene testing among at-risk relatives from three ethnic groups.
An understanding of factors associated with interest in genetic counseling and intentions to obtain colorectal cancer susceptibility testing is an important foundation for developing education, counseling, and genetic services and policies. A survey was mailed to first-degree relatives of patients diagnosed with colorectal cancer. The respondents (n = 426, 77% response rate) are siblings and adult children of Caucasian, Japanese, and Hawaiian ethnicity. Data collection was guided by a conceptual framework and included questions on demographics, family cancer history, predisposing factors (cancer worry, perceived risk, well-being), and enabling factors (decision preferences, social support, and health care factors). Logistic regression analysis on two binary dependent variables (interest in counseling and intentions to get genetic testing) was performed using Generalized Estimating Equations to account for family clusters. Forty-five % of respondents were interested in genetic counseling, and 26% "definitely" intended to get genetic testing for colon cancer when available. For counseling interest, the most important predictors were education, Hawaiian ethnicity, cancer worry, and family support. Cancer worry, perceived risk, and age (older) were directly, and Japanese ethnicity was inversely, associated with testing intentions. High rates of interest in cancer genetic testing are similar to those found in other studies. Ethnic differences reveal a paradox between objective population risk (higher for Japanese) and greater concerns (among Hawaiians). The substantial lack of awareness of family history warrants further research. Culturally sensitive education and counseling are needed for managing the likely high demand for personalized information about hereditary cancer risk.


Specificity of antibody tests for human immunodeficiency virus in alcohol and parenteral drug abusers with chronic liver disease.
Parenteral drug abusers are at risk for acquired immunodeficiency syndrome (AIDS), which is caused by human immunodeficiency virus (HIV). We tested stored sera for antibody to HIV (anti-HIV) using two enzyme-linked immunosorbent assay (ELISA) methods and Western blot. The patients were parenteral drug abusers who had undergone percutaneous liver biopsy for chronic liver disease. Current or former alcohol abuse was noted in 88 (80%) of the 110 patients. The sensitivities of the two ELISA tests in comparison with Western blot, the more specific test for HIV, were 100 and 94%, respectively; the specificities were 94 and 99%. Western blot was positive in 36 (33%) of 110 patients. False-positive ELISA reactions for anti-HIV were seen in five (7%) of 70 patients with negative Western blot analyses. Compared to true-negatives, false-positives had significantly more years of alcohol abuse, younger ages of onset of alcohol abuse, greater frequencies of jaundice and edema, higher levels of alkaline phosphatase, total billirubin, total protein, and globulins, and lower levels of serum albumin. In a stepwise logistic regression, only hyperglobulinemia was significantly associated with a false-positive anti-HIV. We conclude that: (a) ELISA tests for anti-HIV are useful for screening abusers of alcohol and parenteral drugs with chronic liver disease for HIV infection, but positive results must be confirmed with more specific tests such as Western blot; (b) false-positive ELISA reactions in this population are associated with hyperglobulinemia; and (c) studies of HIV testing are needed in other populations of patients with alcoholism or liver disease.


Quick and selective extraction of Z-ligustilide from Angelica sinensis using magnetic multiwalled carbon nanotubes.
A facile and highly efficient magnetic solid-phase extraction method has been developed for Z-ligustilide, the major therapeutic agent in Angelica sinensis. The solid-phase adsorbent material used was prepared by conjugating carbon nanotubes with magnetic Fe3 O4 nanoparticles via a hydrothermal reaction. The magnetic material showed a high affinity toward Z-ligustilide due to the π-π stacking interaction between the carbon nanotubes and Z-ligustilide, allowing a quick and selective exaction of Z-ligustilide from complex sample matrices. Factors influencing the magnetic solid-phase extraction such as the amount of the added adsorbent, adsorption and desorption time, and desorption solvent, were investigated. Due to its high extraction efficiency, this method was proved highly useful for sample cleanup/enrichment in quantitative high-performance liquid chromatography analysis. The proposed method had a linear calibration curve (R(2) = 0.9983) over the concentration between 4 ng/mL and 200 μg/mL Z-ligustilide. The accuracy of the method was determined by the recovery, which was from 92.07 to 104.02%, with the relative standard deviations >4.51%.


Arene C(sp(2))-H Metalation at Ni(II) Modeled with a Reactive PONCPh Ligand.
Coordination of the reactive phosphinitopyridylphenyl PONCPh ligand L(H) to NiBr2 initially yields paramagnetic brown NiBr2(L(H)) (1), but addition of triethylamine results in fast and facile cyclometalation at Ni(II), giving NiBr(κ(3)-P,N,C-L) (2) as well-defined species. This is a rare example of direct cyclometalation at Ni(II) from a C-H bond in a ligand structure other than encumbering ligands (e.g., ECE pincers). Diamagnetic yellow complex 2 reacts instantaneously with HBF4 to give purple [NiBr(κ(3)-P,N-L(H))]BF4 (3). A very unusual (an)agostic Ni(CPh-H) interaction in the solid-state structure of 3 was unequivocally demonstrated using single-crystal X-ray crystallography and was interpreted by density functional theory calculations (quantum theory of atoms in molecules and electron localization function analysis). These compounds may be viewed as models for key intermediates in the Ni-catalyzed C-H functionalization of arenes.


A novel framework based on a data-driven approach for modelling the behaviour of organisms in chemical plume tracing.
We propose a data-driven approach for modelling an organism's behaviour instead of conventional model-based strategies in chemical plume tracing (CPT). CPT models based on this approach show promise in faithfully reproducing organisms' CPT behaviour. To construct the data-driven CPT model, a training dataset of the odour stimuli input toward the organism is needed, along with an output of the organism's CPT behaviour. To this end, we constructed a measurement system comprising an array of alcohol sensors for the measurement of the input and a camera for tracking the output in a real scenario. Then, we determined a transfer function describing the input-output relationship as a stochastic process by applying Gaussian process regression, and established the data-driven CPT model based on measurements of the organism's CPT behaviour. Through CPT experiments in simulations and a real environment, we evaluated the performance of the data-driven CPT model and compared its success rate with those obtained from conventional model-based strategies. As a result, the proposed data-driven CPT model demonstrated a better success rate than those obtained from conventional model-based strategies. Moreover, we considered that the data-driven CPT model could reflect the aspect of an organism's adaptability that modulated its behaviour with respect to the surrounding environment. However, these useful results came from the CPT experiments conducted in simple settings of simulations and a real environment. If making the condition of the CPT experiments more complex, we confirmed that the data-driven CPT model would be less effective for locating an odour source. In this way, this paper not only poses major contributions toward the development of a novel framework based on a data-driven approach for modelling an organism's CPT behaviour, but also displays a research limitation of a data-driven approach at this stage.


[Alpha- and beta-oscillations of dynamics of the area and weight of receptive fields of cat striate neurons under conditions of classical and combined mapping].
In 22 acute experiments in anesthetized and immobilized adult cats the dynamics of 83 receptive fields (RF) of 47 striate neurons was studied by temporal slices method. Classical mapping revealed wave-like changes in the area and weight of neuronal RFs. Special mathematical analysis showed that such changes represented a sum of a slow non-oscillatory and comparatively fast components. The slow component was a biphasic up and down RF dynamics. In most cases, the oscillation frequencies were within the alpha- and beta- EEG frequency ranges. When the RF center was activated additionally during combined mapping, the oscillations frequencies remained unchanged, but the duration and amplitude of non-oscillatory component substantially decreased. Mechanisms underlying the RF dynamics and its functional significance are discussed.


Effects of lactation on fetal survival and development in rabbit does mated shortly after parturition.
Primiparous rabbit does were mated within 12 h after parturition (d 0). They were immediately weaned (Group W; n = 31) or allowed to suckle 10 young rabbits (Group L; n = 32). Blood samples were collected at d 0, 7, 17, and 28. Feed intake and live weight were measured weekly and pregnant does (Group W, n = 24; Group L = 25) were slaughtered at d 28. Feed intake was 78% higher in L than in W females throughout gestation (P < .001). However, L females lost weight during the second half of gestation (-243 +/- 25 g) compared with W females, which gained weight (246 +/- 20 g). The weights of carcass, skin, and adipose tissues were severely reduced at d 28 in the L group (P < .01). Ovulation rate (11.0 +/- .3 corpora lutea) and early embryonic mortality (< d 15) were similar in both groups (12.3 +/- 2%), whereas late embryonic mortality (> or = d 15) was higher in L than in W does (13.9 +/- 3 vs 3.9 +/- 1%; P < .01). Fetal weight was reduced by nearly 20% in L compared with W females (P < .01). Plasma concentrations of progesterone were lower in L than in W females at d 7 and 17 (P < .001), whereas concentrations of estradiol were similar in both groups throughout gestation. These results indicate that fetal survival and development can be impaired in lactating females.


Genetic variation in receptor protein tyrosine phosphatase sigma is associated with type 2 diabetes in Swedish Caucasians.
Previously, it has been demonstrated that receptor protein tyrosine phosphatase sigma (RPTPsigma) is involved in glucose homeostasis and insulin signaling in several animal models. The aim of this study was to evaluate whether polymorphisms in this gene influence the development of type 2 diabetes (T2D) in humans. We investigated how genetic variations in the RPTPsigma gene influence susceptibility to impaired glucose tolerance (IGT) and T2D, in Swedish men and women. Genotyping of single nucleotide polymorphisms (SNPs) was performed by dynamic allele-specific hybridization in a total of 1057 Swedish Caucasians including 497 subjects with normal glucose tolerance (NGT), 262 subjects with IGT, and 298 patients with T2D. SNPs rs1143699, rs4807015, and rs1978237 were found to be associated with T2D. SNP rs1143699 was associated with male T2D patients when compared with NGT controls (odds ratio; OR = 1.57; P = 0.029). SNP rs4807015 showed association with T2D patients when compared with NGT controls (OR = 1.32; P = 0.025). Finally, SNP rs1978237 was associated with T2D patients when compared with NGT controls (OR = 1.59; P = 0.002). Logistic regression analysis demonstrated that for SNP rs1143699 in men, C/C homozygosity conveys an increased risk of T2D (OR = 2.19; P = 0.035), while SNP rs4807015 was associated with an increased risk of T2D in both men and women (OR = 1.74; P = 0.029). SNP rs1978237 also demonstrated a risk of T2D in men and women (OR = 1.59; P = 0.026). This study provides evidence for association of SNPs in the RPTPsigma gene with T2D in Swedish Caucasians. SNPs rs1143699, rs4807015, and rs1978237 confer an increased risk of developing T2D.


High Potential of Bacterial Adhesion on Block Bone Graft Materials.
Bone graft infections represent a challenge in daily clinics, resulting in increased patient discomfort and graft removal. The aim of this study was to investigate the initial adhesion of five representative pathogens on three different block bone graft materials (xenogeneic, alloplastic and allogeneic) and to assess if chlorhexidine (CHX) can effectively control the initial bacterial adhesion. Three different block bone grafting materials (Tutobone®, Endobon® and human spongiosa) were incubated with Escherichia coli, Staphylococcus aureus, Streptococcus mutans, Enterococcus faecalis and Pseudomonas aeruginosa in the presence or absence of 0.2% CHX solution. Bacterial adhesion was assessed by the direct counting of the colony-forming units (CFUs) and visualized by scanning electron microscopy (SEM). Overall, the selected bacterial species adhered successfully to all tested bone replacement scaffolds, which showed similar bacterial counts. The lg CFU values ranged from 5.29 ± 0.14 to 5.48 ± 0.72 for E. coli, from 4.37 ± 0.62 to 5.02 ± 0.48 for S. aureus, from 4.92 ± 0.34 to 4.95 ± 0.21 for S. mutans, from 4.97 ± 0.40 to 5.22 ± 0.13 for E. faecalis and from 4.23 ± 0.54 to 4.58 ± 0.26 for P. aeruginosa. CHX did not interfere with initial microbial adhesion, and yet it killed all adhered bacterial cells. Thus, CHX can be used to prevent subsequent biofilm infections.


Antigen-induced and non-antigen-induced histamine release from rat mast cells sensitized with mouse antiserum.
Marked IgE-mediated histamine release from rat mast cells sensitized in vitro with mouse antiserum occurs in the presence of added Ca++ and phosphatidylserine (PS), although a considerable degree of antigen-induced histamine release which may utilize intracellular or cell-bound calcium is also observed. The decay in the responsiveness to Ca++ of the sensitized cells stimulated by antigen in Ca++-free medium in the presence of PS is relatively slow, and maximum release is produced by Ca++ added 1 min after antigen. Histamine release also occurs when Ca++ is added after PS in the absence of antigen to the sensitized cells suspended in Ca++-free medium. Unlike the antigen-induced release, the intensity of this non-antigen-induced release varies depending on both mast-cell and antiserum pools. A heat-labile factor(s), which is different from antigen-specific IgE antibody and is also contained in normal mouse serum, is involved in this reaction. In the antigen-nondependent (PS + Ca++)-induced release, no decay in the responsiveness to Ca++ is observed after PS addition. Both the antigen-induced and non-antigen-induced release are completed fairly rapidly and are dependent of temperature, pH and energy.


The PI3k inhibitors: new hopes in the battle against advanced NSCLC.
In terms of both incidence and mortality, lung tumor is the most common cancer in the world today. Among lung tumors, 80% are classified as non-small-cell lung cancer (NSCLC) and are mostly diagnosed at an advanced stage (either locally advanced or metastatic disease). Platinum-based doublet chemotherapy, the standard treatment for advanced NSCLC, has reached a plateau of effectiveness and achieves mostly partial responses in only 30%-40% of patients and a modest survival increase. Thus, the search for new molecularly targeted therapies is mandatory. The phosphatidylinositol 3-kinase (PI3K) pathway is frequently over activated in human cancers playing a critical role both in the initiation and progression of NSCLC. Activating mutations of this pathway play a role in the development of resistance to chemotherapy and to the Epidermal Growth Factor Receptor Tyrosine Kinase inhibitors (EGFR-TKIs) erlotinib and gefitinib. These mutations are observed in 2-5 % of non-squamous NSCLC and 8-10 % of squamous NSCLC. In this paper, we describe the available data and the possible future role of PI3k inhibitors in the treatment of advanced NSCLC.


The burden and costs of prevention and management of genital disease caused by HPV in women: a population-based registry study in Finland.
The aim of this study was to evaluate the total burden and health care provider costs of prevention, management and treatment of HP-related genital disease outcomes including all organized and opportunistic screening tests. Information about HPV-related disease outcomes in the Finnish female population of 2.7 million was obtained from nationwide population-based registry data. We estimated the incidence, health care resource use, health provider costs and life years lost due to cervical, vaginal and vulvar cancer and intraepithelial neoplasia (CIN, VaIN, VIN), cervical adenocarcinoma in situ, and external genital warts. The average annual disease burden of HPV-related genital disease in the female population of Finland comprises altogether 241 cases of cervical, vaginal and vulvar cancer, 2,898 new cases of CIN, 34,432 cases of minor cytological abnormalities, and almost 4,000 cases of external genital warts. The total annual costs of screening, further diagnostics and treatment of HPV-related genital disease were € 44.7 million of which the annual costs due to cervical cancer screening were € 22.4 million and due to diagnostics, management and treatment of HPV-related genital disease outcomes were € 22.3 million. The latter included € 8.4 million due to minor cervical abnormalities detected by the current cervical screening practice. The extensive opportunistic Pap testing fails to keep the incidence of cervical cancer from increasing among women aged 30-34. In addition opportunistic screening among this and younger age group detects a significant number of cytological abnormalities, most of which are probably treated unnecessarily.


Doxycycline sclerotherapy for post-traumatic inguinal lymphocele in a child.
Lymphoceles are abnormal collections of lymphatic fluid caused by a disruption in the lymphatic channels and leakage of lymph. This most commonly occurs after surgical procedures, but occasionally lymphoceles may be the result of trauma, more commonly penetrating trauma. Lymphoceles resulting from blunt trauma are rare in both adults and children. In the adult population, there are few published case reports, and management principles vary. To date, there are no reports of traumatic lymphoceles in the paediatric population, and therefore there is no precedent for treatment. Here, we report the case of a young boy who developed an inguinal lymphocele from a bicycle handle bar injury which was successfully treated with doxycycline sclerotherapy.


A neural computational model for animal's time-to-collision estimation.
The time-to-collision (TTC) is the time elapsed before a looming object hits the subject. An accurate estimation of TTC plays a critical role in the survival of animals in nature and acts as an important factor in artificial intelligence systems that depend on judging and avoiding potential dangers. The theoretic formula for TTC is 1/τ≈θ'/sin θ, where θ and θ' are the visual angle and its variation, respectively, and the widely used approximation computational model is θ'/θ. However, both of these measures are too complex to be implemented by a biological neuronal model. We propose a new simple computational model: 1/τ≈Mθ-P/(θ+Q)+N, where M, P, Q, and N are constants that depend on a predefined visual angle. This model, weighted summation of visual angle model (WSVAM), can achieve perfect implementation through a widely accepted biological neuronal model. WSVAM has additional merits, including a natural minimum consumption and simplicity. Thus, it yields a precise and neuronal-implemented estimation for TTC, which provides a simple and convenient implementation for artificial vision, and represents a potential visual brain mechanism.


Effects on muscle tissue remodeling and lipid metabolism in muscle tissue from adult patients with polymyositis or dermatomyositis treated with immunosuppressive agents.
Polymyositis (PM) and dermatomyositis (DM) are autoimmune muscle diseases, conventionally treated with high doses of glucocorticoids in combination with immunosuppressive drugs. Treatment is often dissatisfying, with persisting muscle impairment. We aimed to investigate molecular mechanisms that might contribute to the persisting muscle impairment despite immunosuppressive treatment in adult patients with PM or DM using gene expression profiling of repeated muscle biopsies. Paired skeletal muscle biopsies from six newly diagnosed adult patients with DM or PM taken before and after conventional immunosuppressive treatment were examined by gene expression microarray analysis. Selected genes that displayed changes in expression were analyzed by Western blot. Muscle biopsy sections were evaluated for inflammation, T lymphocytes (CD3), macrophages (CD68), major histocompatibility complex (MHC) class I expression and fiber type composition. After treatment, genes related to immune response and inflammation, including inflammasome pathways and interferon, were downregulated. This was confirmed at the protein level for AIM-2 and caspase-1 in the inflammasome pathway. Changes in genes involved in muscle tissue remodeling suggested a negative effect on muscle regeneration and growth. Gene markers for fast type II fibers were upregulated and fiber composition was switched towards type II fibers in response to treatment. The expression of genes involved in lipid metabolism was altered, suggesting a potential lipotoxic effect on muscles of the immunosuppressive treatment. The anti-inflammatory effect of immunosuppressive treatment was combined with negative effects on genes involved in muscle tissue remodeling and lipid metabolism, suggesting a negative effect on recovery of muscle performance which may contribute to persisting muscle impairment in adult patients with DM and PM.


Antiemetic Corticosteroid Rotation from Dexamethasone to Methylprednisolone to Prevent Dexamethasone-Induced Hiccup in Cancer Patients Treated with Chemotherapy: A Randomized, Single-Blind, Crossover Phase III Trial.
To assess whether the rotation of dexamethasone to methylprednisolone decreases the intensity of dexamethasone-induced hiccup (DIH) in cancer patients treated with chemotherapy. Adult patients who experienced DIH within 3 days after the administration of dexamethasone as an antiemetic were screened. Eligible patients were randomly assigned to receive dexamethasone (n = 33) or methylprednisolone (n = 32) as an antiemetic (randomization phase). In the next cycle of chemotherapy, the dexamethasone group received methylprednisolone and vice versa in the methylprednisolone group (crossover phase). The primary endpoint was the difference in hiccup intensity as measured using the numeric rating scale (NRS) between two groups. No female patients were enrolled, although the study did not exclude them. At the randomization phase, hiccup frequency was 28/33 (84.8%) in the dexamethasone group versus 20/32 (62.5%) in the methylprednisolone group (p = .04). Intensity of hiccup was significantly higher in the dexamethasone group than that in the methylprednisolone group (mean NRS, 3.5 vs. 1.4, p < .001). At the crossover phase, hiccup intensity was further decreased after the rotation of dexamethasone to methylprednisolone in the dexamethasone group (mean NRS, 3.5 to 0.9, p < .001), while it was increased by rotating methylprednisolone to dexamethasone in the methylprednisolone group (mean NRS, 1.4 to 3.3, p = .025). There were no differences in emesis intensity between the two groups at either the randomization or crossover phases. Clinicaltrials.gov identifier: NCT01974024. Dexamethasone-induced hiccup is a male-predominant phenomenon that can be ameliorated by rotating dexamethasone to methylprednisolone without compromising the antiemetic efficacy. In this randomized, multicenter, phase III trial, hiccup intensity was significantly lower when the antiemetic corticosteroid was rotated from dexamethasone to methylprednisolone without a change in emesis intensity than that when dexamethasone was maintained. At the crossover phase, hiccup intensity was increased again if dexamethasone was readministered instead of methylprednisolone. The present study demonstrated that dexamethasone-induced hiccup can be improved by rotating from dexamethasone to methylprednisolone without compromising its antiemetic efficacy.


Distribution and heritability of peripheral eye length in Chinese children and adolescents: the Guangzhou Twin Eye Study.
Peripheral eye length (PEL) provides a measure of overall eye shape, which may play a role in the development of myopia. The current study explores the distribution and heritability of PEL, relative PEL (RPEL, defined as PEL minus axial eye length) and relative ratio PEL (RRPEL, defined as PEL divided by axial eye length) in Chinese children and adolescents. Subjects included both male and female youths participating in the Guangzhou Twin Eye Study. Eye length was measured by partial coherence laser interferometry axially, 40° temporally (PEL-T(40)) and 40° nasally (PEL-N(40)). Structural equation modeling (SEM) was used to estimate the relative contribution of genetic and environmental factors on PEL, RPEL, and RRPEL, adjusting for age and sex. We examined 104 monozygotic (MZ) and 54 dizygotic (DZ) twins aged 8 to 20 years old. The intraclass correlation coefficients were 0.89 for PEL-T(40), 0.92 for PEL-N(40), 0.80 for RPEL-T(40), 0.73 for RPEL-N(40), 0.77 for RRPEL-T(40), and 0.73 for RRPEL-N(40) in MZ pairs, and 0.52, 0.50, 0.39, 0.58, 0.37, and 0.58 in DZ pairs, respectively. The best fit adjusted models estimated that additive genetic effects accounted for approximately 86.2%, 89.8%, 79.9%, 75.5%, 77.1%, and 74.5% of the variance for the above mentioned traits, respectively, while dominant genetic effects and shared environmental factors were negligible. Additive genetic effects had a substantial influence on phenotypic variation in PEL and RPEL, suggesting genetic rather than environmental factors play a major role in determining eye shape.


Magic Numbers and Stabilities of Photoionized Water Clusters: Computational and Experimental Characterization of the Nanosolvated Hydronium Ion.
The stability and distributions of small water clusters generated in a supersonic beam expansion are interrogated by tunable vacuum ultraviolet (VUV) radiation generated at a synchrotron. Time-of-flight mass spectrometry reveals enhanced population of various protonated water clusters (H+(H2O)n) based upon ionization energy and photoionization distance from source, suggesting there are "magic" numbers below the traditional n = 21 that predominates in the literature. These intensity distributions suggest that VUV threshold photoionization (11.0-11.5 eV) of neutral water clusters close to the nozzle exit leads to a different nonequilibrium state compared to a skimmed molecular beam. This results in the appearance of a new magic number at 14. Metadynamics conformer searches coupled with modern density functional calculations are used to identify the global minimum energy structures of protonated water clusters between n = 2 and 21, as well as the manifold of low-lying metastable minima. New lowest energy structures are reported for the cases of n = 5, 6, 11, 12, 16, and 18, and special stability is identified by several measures. These theoretical results are in agreement with the experiments performed in this work in that n = 14 is shown to exhibit additional stability, based on the computed second-order stabilization energy relative to most cluster sizes, though not to the extent of the well-known n = 21 cluster. Other cluster sizes that show some additional energetic stability are n = 7, 9, 12, 17, and 19. To gain insight into the balance between ion-water and water-water interactions as a function of the cluster size, an analysis of the effective two-body interactions (which sum exactly to the total interaction energy) was performed. This analysis reveals a crossover as a function of cluster size between a water-hydronium-dominated regime for small clusters and a water-water-dominated regime for larger clusters around n = 17.


A Markov-model simulation of IVF programs for PCOS patients indicates that coupling myo-Inositol with rFSH is cost-effective for the Italian Health System.
Accumulating evidence suggests that oral supplementation with myo-Inositol (myo-Ins) is able to reduce the amount of gonadotropins and days of controlled ovarian hyperstimulation (COS) necessary to achieve adequate oocyte maturation in assisted reproduction technology (ART) protocols, particularly in women affected by polycystic ovary syndrome (PCOS). We used computational calculations based on simulation modellings. We simulated in vitro fertilization (IVF) procedures-with or without intracytoplasmic sperm injection (ICSI)-with 100,000 virtual patients, accounting for all the stages of the entire IVF procedure. A Monte Carlo technique was used to account for data uncertainty and to generate the outcome distribution at each stage. We considered virtual patients with PCOS undergoing IVF cycles to achieve pregnancy. Computational data were retrieved from clinical experience and published data. We investigated three parameters related to ART protocols: cost of single procedure; efficacy to achieve ongoing pregnancy at 12 gestational weeks; overall cost per single pregnancy. The administration of oral myo-Ins during COH protocols, compared to the standard COH with recombinant Follicle Stimulating Hormone (rFSH) only, may be considered a potential strategy to reduce costs of ART for the Italian Health System.


Glycosomes: parasites and the divergence of peroxisomal purpose.
Peroxisomes are membrane-bounded organelles that compartmentalize a variety of metabolic functions. Perhaps the most divergent peroxisomes known are the glycosomes of trypanosomes and their relatives. The glycolytic pathway of these organisms resides within the glycosome. The development of robust molecular genetic and proteomic approaches coupled with the completion of the genome sequence of the pathogens Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major provides an opportunity to determine the complement of proteins within the glycosome and the function of compartmentation. Studies now suggest that regulation of glycolysis is a strong driving force for maintenance of the glycosome.


Nesprins anchor kinesin-1 motors to the nucleus to drive nuclear distribution in muscle cells.
During skeletal muscle development, nuclei move dynamically through myotubes in a microtubule-dependent manner, driven by the microtubule motor protein kinesin-1. Loss of kinesin-1 leads to improperly positioned nuclei in culture and in vivo. Two models have been proposed to explain how kinesin-1 functions to move nuclei in myotubes. In the cargo model, kinesin-1 acts directly from the surface of the nucleus, whereas in an alternative model, kinesin-1 moves nuclei indirectly by sliding anti-parallel microtubules. Here, we test the hypothesis that an ensemble of Kif5B motors acts from the nuclear envelope to distribute nuclei throughout the length of syncytial myotubes. First, using an inducible dimerization system, we show that controlled recruitment of truncated, constitutively active kinesin-1 motors to the nuclear envelope is sufficient to prevent the nuclear aggregation resulting from depletion of endogenous kinesin-1. Second, we identify a conserved kinesin light chain (KLC)-binding motif in the nuclear envelope proteins nesprin-1 and nesprin-2, and show that recruitment of the motor complex to the nucleus via this LEWD motif is essential for nuclear distribution. Together, our findings demonstrate that the nucleus is a kinesin-1 cargo in myotubes and that nesprins function as nuclear cargo adaptors. The importance of achieving and maintaining proper nuclear position is not restricted to muscle fibers, suggesting that the nesprin-dependent recruitment of kinesin-1 to the nuclear envelope through the interaction of a conserved LEWD motif with kinesin light chain might be a general mechanism for cell-type-specific nuclear positioning during development.