Historical perspective: the problem of the origin of life in the context of developments in biology.
The structure of the history of scientific ideas on the origin of life, after Darwin's theory of evolution brought the problem into focus, is discussed. 19th-century theories in the mainstream of historical development already included some notion of chemical evolution. These theories were limited, however, by their reliance on a protoplasmic view of life, according to which the protoplasmic substance combines all vital properties. It was only when this holistic concept of protoplasm was abandoned that a clear distinction between different vital functions such as metabolism and replication was made. This led to two schools of thought in the origin of life field, one inspired by biochemistry and one by genetics. Oparin's theory, which was rooted in the metabolic traditions of biochemistry, provided a model which has had a lasting impact in methodological terms and which helped to transform the field from a largely theoretical one to an area of active research. Genetically based theories, on the other hand, had a delayed impact in this respect, because of long-lasting uncertainty regarding the structural basis of gene function.


Keyboard Contamination in Intensive Care Unit: Is Cleaning Enough? Prospective Research of In Situ Effectiveness of a Tea Tree Oil (KTEO) Film.
After the SARS-CoV-2 pandemic, disinfection practices and microbial load reduction have become even more important and rigorous. To determine the contamination of keyboard surface and the relative risk to transfer healthcare-associated pathogens to susceptible patients, as it frequently happens in Intensive Care Unit (ICU), a standard keyboard (SK), a cleanable keyless keyboard (KK) with smooth surface and a standard keyboard coated with a 3 M Tegaderm® film added with active essential oil (tea tree oil) (KTEO) were tested. S. aureus, including MRSA strains, were detected in ICU, with values ranging from 15% to 57%. Gram negative strains belonging to the Enterobacteriaceae family were also found with values ranging from 14% to 71%. Similar Gram positive and Gram negative strains were found on all surfaces, but with low percentage, and only environmental bacteria were detected using the settling plates method. The Microbial Challenge Test performed on KTEO showed high rates of decrease for all the pathogens with statistical significance both at 24 and 48 h (p = 0.003* and p = 0.040*, respectively). Our results suggest that the use of KTEO may be a feasible strategy for reducing the transmission of pathogens in health care setting and may be complementary to surface cleaning protocols.


Care necessities: the view of the patient and nursing team.
To compare care necessities as perceived by the patient and nursing team and to investigate the sociodemographic factors associated with these perceptions. A comparative study was conducted in units and hospitalized patients of a hospital institution in the state of São Paulo. The participants comprised 100 health professionals (50 nurses and 50 nursing technicians and auxiliaries) and 50 patients. A questionnaire was constructed and validated regarding care needs and was completed by the participants. Considering cut-off value kappa ≥ 0.61, or that is, good and very good intervals, the greatest agreement between the perception of the patients and the nursing team was in the areas of: Care and Communication, both with 92.6% agreement; followed by Basic Care with 74.1%. The lowest value was found in the field of Care Planning and Organization, 64.3%. In a general manner, there was an agreement between the care needs from the view of the patients themselves and the nursing team. Comparar como as necessidades de cuidados são percebidas pelo paciente e equipe de enfermagem e investigar os fatores sociodemográficos associados a estas percepções. Estudo comparativo realizado em unidades e internação de uma instituição hospitalar do interior do Estado de São Paulo. Os participantes foram 100 profissionais (50 enfermeiros e 50 técnicos e auxiliares de enfermagem) e 50 pacientes. Construiu-se e validou-se um questionário sobre necessidades de cuidados preenchido pelos participantes. Considerando-se valor de corte kappa ≥ 0,61, ou seja, intervalos bom e muito bom, houve maior alinhamento entre a percepção dos pacientes e equipe de enfermagem nos domínios O Ambiente do Cuidado e Comunicação, ambos com 92,6% de concordância; seguido de Cuidados Básicos, com 74,1%. O menor valor foi encontrado no domínio Planejamento e Organização do Cuidado, 64,3%. De maneira geral, observou-se alinhamento no atendimento das necessidades de cuidados no olhar do próprio paciente e da equipe de enfermagem.


Portable fiber-optic SPR platform for the detection of NS1-antigen for dengue diagnosis.
Here, we present a portable, selective and cost-effective fiber-optic surface plasmon resonance (SPR) based platform for early detection of Dengue virus. NS1 protein was targeted as the biomarker of dengue. Antibody-antigen specific binding was exploited for NS1 antigen detection. The binding of antibody was assisted by a self-assembled monolayer of alkanethiols on the surface of silver-coated unclad fiber. A wavelength interrogation mode of SPR was utilized to detect NS1 antigen in the dynamic range of 0.2-2.0 μg/ml. The 40 nm thick silver coated optical fiber exhibited resonance wavelength around 500 nm and change in resonance wavelength was monitored for each attachment step on the fiber. The sensitivity at the lowest concentration of NS1 antigen was found to be 54.7 nm/(μg/ml). The limit of detection of the sensor was found to be 0.06 μg/ml, which lies in the physiological range of NS1 protein present in the infected blood, hence the present technique may provide a very early detection advantage. Real blood serum samples were also successfully tested on the set-up, confirming compatibility with the conventional methods. The presented field-deployable platform has wide applications in mass monitoring of dengue, such as during outbreaks and epidemics.


Changes in triglyceride levels in ultra-high risk for psychosis individuals treated with omega-3 fatty acids.
The aim of this analysis was to assess changes in lipid parameters, specifically in triglyceride (TG) levels, in a population at ultra-high risk (UHR) for psychosis treated with ω-3 polyunsaturated fatty acids (PUFAs) versus placebo. Data were derived from a randomized, double-blind, placebo-controlled trial conducted at an early psychosis unit. Eighty-one individuals, aged 13-25 years, at UHR for psychosis participated in a 12-week intervention trial of 1.2 g/day of ω-3 PUFAs (n = 41) versus placebo (n = 40). Lipid and C-reactive protein levels were collected at baseline and after 12 weeks. Between-group comparisons showed no significant difference in TG levels after the intervention. However, in individuals with baseline TG levels above 150 mg dL-1 there was a significant mean TG reduction of 67.29 (SD 42.54; P = 0.006) in the ω-3 group (n = 7). In this sample of UHR individuals, a 12-week intervention with ω-3 PUFAs was effective in reducing previously elevated TG levels. This might introduce the possibility of altering the lipid profile and thus the risk of cardiovascular morbidity of UHR individuals.


The integration of T cell migration, differentiation and function.
T cells function locally. Accordingly, T cells' recognition of antigen, their subsequent activation and differentiation, and their role in the processes of infection control, tumour eradication, autoimmunity, allergy and alloreactivity are intrinsically coupled with migration. Recent discoveries revise our understanding of the regulation and patterns of T cell trafficking and reveal limitations in current paradigms. Here, we review classic and emerging concepts, highlight the challenge of integrating new observations with existing T cell classification schemes and summarize the heuristic framework provided by viewing T cell differentiation and function first through the prism of migration.


Role of carbohydrate in binding of IgG to the Fc receptor of neonatal rat enterocytes.
Monoclonal IgG1, IgG2a, IgG2b and IgG2c were prepared from rat hybridoma cells treated with tunicamycin in order to inhibit N-linked glycosylation. The IgG produced by these cells was about 70% lower in carbohydrate content compared to IgG from equivalent untreated cells, but was similar to the corresponding normal IgG in terms of antigen binding. However, the ability of carbohydrate deficient (CHO-) IgG to bind in vitro to Fc receptor extracted from jejunum of neonatal rats was impaired in most cases and, in all but one case, the amount of CHO- IgG transported from gut lumen to blood in vivo was markedly reduced. No reduction in binding of normal IgG to extracted receptor was observed in the presence of various sugars. It is postulated that N-linked carbohydrate acts to stabilize the structure within the IgG molecule which is responsible for binding to this Fc receptor, possibly in the CH2 domain.


Mental health emergency admissions in the paediatric emergency department.
To evaluate the demographic characteristics, diagnoses and length of stay of mental health emergency attendance to the paediatric emergency department (ED), to determine the burdens these patients brought to the paediatric ED and to the national economy by examining hospital costs. This retrospective observational study was conducted in a tertiary hospital's paediatric ED in Turkey. Data were obtained from the electronic medical record system from January 2018 to January 2020. A total of 142 admissions were included of whom 60% were female. The mean age was 15.2 ± 1.8 years, 50% of cases were suicide attempts and 19% were alcohol intoxications. The majority (85.9%) of patients were discharged from the emergency observation unit. Among the diagnostic groups, the mean age was higher in patients with a history of substance abuse. There was a female predominance among patients who were admitted due to suicide attempts. Among the diagnostic groups, the duration of hospital stay and cost of hospitalization were higher in patients who were followed up with a diagnosis of suicide attempt. Mental health problems are frequent in the paediatric ED. We determined that the most common cause of attendance in paediatric emergencies was suicide attempts, and the length of hospital stay and hospital cost were higher in this diagnostic group. Although further research is necessary to determine national trends in paediatric mental health problems in the paediatric ED, screening strategies and early detection and interventions in primary healthcare may allow more effective care for childhood mental health problems.


Proliferative, lymphocytic, infundibular mural folliculitis and dermatitis with prominent follicular apoptosis and parakeratotic casts in four Labrador retrievers: preliminary description and response to therapy.
To describe the clinical, histopathological and immunohistochemical lesions and the response to therapy of a novel skin disease in four dogs, and to compare the lesions with those of other similar conditions. Clinical lesions, the histopathological findings in skin biopsy samples, immunohistochemistry for CD3 and cleaved caspase-3 and the response to therapy were evaluated. Clinical lesions included multifocal, coalescing, verrucous, crusted papules and plaques with erythematous borders and comedones or follicular casts. Lesions were in haired skin; they occurred at the edges of paw pads and claw beds in one dog. Histopathological lesions included ortho- and more prominent parakeratotic hyperkeratosis involving follicular infundibular epithelium, with cast formation and a papillary epidermal surface. Lymphocytic exocytosis affected all strata of follicular infundibular epithelium and epidermis. Variable numbers of acidophilic shrunken keratinocytes, often bordered by lymphocytes (satellitosis), occupied the more superficial strata of the follicular infundibular epithelium and epidermis. Immunohistochemistry revealed numerous CD3+ T lymphocytes and fewer cleaved caspase-3-positive apoptotic keratinocytes in the infundibular hair follicle epithelium and epidermis, with numerous CD3+ T lymphocytes and cleaved caspase-3-positive cells in the dermis. Two dogs responded completely to therapy with ciclosporin and remained lesion free off therapy; one dog responded to therapy with prednisone, azathioprine and ciclosporin, but relapsed; and one dog was not treated. The cause of the lesions is unknown; the presence of intraepithelial CD3+ lymphocytes and cleaved caspase-3-positive apoptotic keratinocytes and the positive response to immunosuppressive therapy suggest an immune response directed towards unidentified antigens expressed on the surface of keratinocytes.


A simplified laparoscopic ventral hernia repair: the scroll technique.
Laparoscopic ventral hernia repair has steadily gained recognition as an alternative to the open approach. However, the procedure can be technically challenging. The authors present their simple scroll technique for laparoscopic ventral hernia repair. A total of 174 patients underwent laparoscopic ventral hernia repair using the scroll technique. The technique entails fixation of the rolled mesh to the anterior abdominal wall before it is unfolded. Patient characteristics, operative time, and complications were analyzed and compared with pooled data from the available literature on laparoscopic ventral hernia repair. The mean operative time was comparable with that reported by others (mean, 102 vs. 100 min). The hospital stay was shorter (mean, 1.8 vs. 2.4 h). During a mean follow-up period of 28 months, the recurrence rate was lower than that reported by others (1.7% vs. 4.3%). There were no mortalities and no cases of inadvertent bowel injury. The authors' scroll technique for laparoscopic repair is simple, feasible, and reproducible, with a short learning curve and a low recurrence rate.


Use of computational biology to compare the theoretical tertiary structures of the most common forms of RhCE and RhD.
Computational biology analyses the theoretical tertiary structure of proteins and identifies the 'topological' differences between RhD and RhCE. Our aim was to identify the theoretical structural differences between the four isoforms of RhCE and RhD using computational biological tools. Physicochemical profile was determined by hydrophobicity and electrostatic potential analysis. Secondary and tertiary structures were generated using computational biology tools. The structures were evaluated and validated using Ramachandran algorithm, which calculates the single score, p-value and root mean square deviation (RMSD). Structures were overlaid on local refinement of 'RhAG-RhCE-ANK' (PBDID 7uzq) and RhAG to compare their spatial distribution within the membrane. All proteins differed in surface area and electrostatic distance due to variations in hydrophobicity and electrostatic potential. The RMSD between RhD and RhCE was 0.46 ± 0.04 Å, and the comparison within RhCE was 0.57 ± 0.08 Å. The percentage of amino acids in the hydrophobic thickness was 50.24% for RhD while for RhCE it ranged between 73.08% and 76.68%. The RHAG hydrophobic thickness was 34.2 Å, and RhCE's hydrophobic thickness was 33.83 Å. We suggest that the C/c antigens differ exofacially at loops L1 and L2. For the E/e antigens, the difference lies in L6. By contrast, L4 is the same for all proteins except Rhce. The physicochemical properties of Rh proteins made them different, although their genes are homologous. Using computational biology, we model structures with sufficient precision, similar to those obtained experimentally. An amino acid variation alters the folding of the tertiary structure and the interactions with other proteins, modifying the electrostatic environment, the spatial conformations and therefore the antigenic recognition.


Mitochondrial regulation of cancer associated nuclear DNA methylation.
The onset and progression of cancer is associated with the methylation-dependent silencing of specific genes, however, the mechanism and its regulation have not been established. We previously demonstrated that reduction of mitochondrial DNA content induces cancer progression. Here we found that mitochondrial DNA-deficient LNrho0-8 activates the hypermethylation of the nuclear DNA promoters including the promoter CpG islands of the endothelin B receptor, O6-methylguanine-DNA methyltransferase, and E-cadherin. These are unmethylated and the corresponding gene products are expressed in the parental LNCaP containing mitochondrial DNA. The absence of mitochondrial DNA induced DNA methyltransferase 1 expression which was responsible for the methylation patterns observed. Inhibition of DNA methyltransferase eliminated hypermethylation and expressed gene products in LNrho0-8. These studies demonstrate loss or reduction of mitochondrial DNA resulted in the induction of DNA methyltransferase 1, hypermethylation of the promoters of endothelin B receptor, O6-methylguanine-DNA methyltransferase, and E-cadherin, and reduction of the corresponding gene products.


Effect of distinct ECM microenvironments on the genome-wide chromatin accessibility and gene expression responses of hepatic stellate cells.
Hepatic stellate cells (HSCs) are one of the primary drivers of liver fibrosis in non-alcoholic fatty liver disease. Although HSC activation in liver disease is associated with changes in extracellular matrix (ECM) deposition and remodeling, it remains unclear how ECM regulates the phenotypic state transitions of HSCs. Using high-throughput cellular microarrays, coupled with genome-wide ATAC and RNA sequencing within engineered ECM microenvironments, we investigated the effect of ECM and substrate stiffness on chromatin accessibility and resulting gene expression in activated primary human HSCs. Cell microarrays demonstrated the cooperative effects of stiffness and ECM composition on H3K4 and H3K9 methylation/acetylation. ATAC sequencing revealed higher chromatin accessibility in HSCs on 1kPa compared to 25kPa substrates for all ECM conditions. Gene set enrichment analysis using RNA sequencing data of HSCs in defined ECM microenvironments demonstrated higher enrichment of NAFLD and fibrosis-related genes in pre-activated HSCs on 1kPa relative to 25kPa. Overall, these findings are indicative of a microenvironmental adaptation response in HSCs, and the acquisition of a persistent activation state. Combined ATAC/RNA sequencing analyses enabled identification of candidate regulatory factors, including HSD11B1 and CEBPb. siRNA-mediated knockdown of HSD11b1 and CEBPb demonstrated microenvironmental controlled reduction in fibrogenic markers in HSCs. STATEMENT OF SIGNIFICANCE: Hepatic stellate cells (HSCs) are one of the primary drivers of liver fibrosis in non-alcoholic fatty liver disease. Although HSC activation in liver disease is associated with changes in extracellular matrix (ECM) deposition and remodeling, it remains unclear how ECM regulates the phenotypic state transitions of HSCs. Using high-throughput cellular microarrays, coupled with genome-wide ATAC and RNA sequencing within engineered ECM microenvironments, we investigated the effect of ECM and substrate stiffness on chromatin accessibility and resulting gene expression in activated primary human HSCs. Overall, these findings were indicative of a microenvironmental adaptation response in HSCs, and the acquisition of a persistent activation state. Combined ATAC/RNA sequencing analyses enabled identification of candidate regulatory factors, including HSD11B1 and CEBPb. siRNA-mediated knockdown of HSD11b1 and CEBPb demonstrated microenvironmental controlled reduction in fibrogenic markers in HSCs.


Mechanical ventilation of the neonate during magnetic resonance imaging.
Minimum deadspace manifolds have shown promise as a means for assuring effective ventilation of the ventilator-dependent patient undergoing magnetic resonance (MR) imaging. The use of these manifolds in the neonatal patient requires some modification. Six neonatal patients were studied utilizing a modified neonatal ventilator tubing. The results of this study demonstrate no significant difference in pre-study and post-study parameters for heart rate, respiratory rate, transcutaneous oxygen and carbon dioxide levels, oxygen saturation and end-tidal carbon dioxide levels, when utilizing the minimum deadspace manifold and single limb ventilator tubing.


Autosomal recessive agammaglobulinemia: the third case of Igβ deficiency due to a novel non-sense mutation.
This study describes the third case worldwide of autosomal recessive agammaglobulinemia due to a novel non-sense mutation in Igβ presenting with neutropenia, ecthyma and mild respiratory infections.


Isolation of a putative Candida albicans transcriptional regulator involved in pleiotropic drug resistance by functional complementation of a pdr1 pdr3 mutation in Saccharomyces cerevisiae.
Three Candida albicans genes, designated FCR (for fluconazole resistance), have been isolated by their ability to complement the fluconazole (FCZ) hypersensitivity of a Saccharomyces cerevisiae mutant lacking the transcription factors Pdr1p and Pdr3p. Overexpression of any of the three FCR genes in the pdr1 pdr3 mutant resulted in increased resistance of the cells to FCZ and cycloheximide and in increased expression of PDR5, a gene coding for a drug efflux transporter of the ATP-binding cassette superfamily and whose transcription is under the control of Pdr1p and Pdr3p. Deletion of PDR5 in the pdr1 pdr3 strain completely abrogated the ability of the three FCR genes to confer FCZ resistance, demonstrating that PDR5 is required for FCR-mediated FCZ resistance in S. cerevisiae. The FCR1 gene encodes a putative 517-amino-acid protein with an N-terminal Zn2C6-type zinc finger motif homologous to that found in fungal zinc cluster proteins, including S. cerevisiae Pdr1p and Pdr3p. We have constructed a C. albicans CAI4-derived mutant strain carrying a homozygous deletion of the FCR1 gene and analyzed its ability to grow in the presence of FCZ. We found that the fcr1Delta/fcr1Delta mutant displays hyperresistance to FCZ and other antifungal drugs compared to the parental CAI4 strain. This hyperresistance could be reversed to wild-type levels by reintroduction of a plasmid-borne copy of FCR1 into the fcr1Delta/fcr1Delta mutant. Taken together, our results indicate that the FCR1 gene behaves as a negative regulator of drug resistance in C. albicans and constitute the first evidence that FCZ resistance can result from the inactivation of a regulatory factor such as Fcr1p.


Using site-directed mutagenesis to probe the role of the D2 carotenoid in the secondary electron-transfer pathway of photosystem II.
Secondary electron transfer in photosystem II (PSII), which occurs when water oxidation is inhibited, involves redox-active carotenoids (Car), as well as chlorophylls (Chl), and cytochrome b 559 (Cyt b 559), and is believed to play a role in photoprotection. CarD2 may be the initial point of secondary electron transfer because it is the closest cofactor to both P680, the initial oxidant, and to Cyt b 559, the terminal secondary electron donor within PSII. In order to characterize the role of CarD2 and to determine the effects of perturbing CarD2 on both the electron-transfer events and on the identity of the redox-active cofactors, it is necessary to vary the properties of CarD2 selectively without affecting the ten other Car per PSII. To this end, site-directed mutations around the binding pocket of CarD2 (D2-G47W, D2-G47F, and D2-T50F) have been generated in Synechocystis sp. PCC 6803. Characterization by near-IR and EPR spectroscopy provides the first experimental evidence that CarD2 is one of the redox-active carotenoids in PSII. There is a specific perturbation of the Car(∙+) near-IR spectrum in all three mutated PSII samples, allowing the assignment of the spectral signature of Car D2 (∙+) ; Car D2 (∙+) exhibits a near-IR peak at 980 nm and is the predominant secondary donor oxidized in a charge separation at low temperature in ferricyanide-treated wild-type PSII. The yield of secondary donor radicals is substantially decreased in PSII complexes isolated from each mutant. In addition, the kinetics of radical formation are altered in the mutated PSII samples. These results are consistent with oxidation of CarD2 being the initial step in secondary electron transfer. Furthermore, normal light levels during mutant cell growth perturb the shape of the Chl(∙+) near-IR absorption peak and generate a dark-stable radical observable in the EPR spectra, indicating a higher susceptibility to photodamage further linking the secondary electron-transfer pathway to photoprotection.


SARS-CoV-2 transmission risk to healthcare workers performing tracheostomies: a systematic review.
Tracheostomy is a commonly performed procedure in patients with coronavirus disease 2019 (COVID-19) receiving mechanical ventilation (MV). This review aims to investigate the occurrence of SARS-CoV-2 transmission from patients to healthcare workers (HCWs) when tracheostomies are performed. This systematic review used the preferred reporting items for systematic reviews and meta-analysis framework. Studies reporting SARS-CoV-2 infection in HCWs involved in tracheostomy procedures were included. Sixty-nine studies (between 01/11/2019 and 16/01/2022) reporting 3117 tracheostomy events were included, 45.9% (1430/3117) were performed surgically. The mean time from MV initiation to tracheostomy was 16.7 ± 7.9 days. Location of tracheostomy, personal protective equipment used, and anaesthesia technique varied between studies. The mean procedure duration was 14.1 ± 7.5 minutes; was statistically longer for percutaneous tracheostomies compared with surgical tracheostomies (mean duration 17.5 ± 7.0 versus 15.5 ± 5.6 minutes, p = 0.02). Across 5 out of 69 studies that reported 311 tracheostomies, 34 HCWs tested positive for SARS-CoV-2 and 23/34 (67.6%) were associated with percutaneous tracheostomies. In this systematic review we found that SARS-CoV-2 transmission to HCWs performing or assisting with a tracheostomy procedure appeared to be low, with all reported transmissions occurring in 2020, prior to vaccinations and more recent strains of SARS-CoV-2. Transmissions may be higher with percutaneous tracheostomies. However, an accurate estimation of infection risk was not possible in the absence of the actual number of HCWs exposed to the risk during the procedure and the inability to control for multiple confounders related to variable timing, technique, and infection control practices.


Postpartum prevention of pertussis in a French maternity hospital: impact on general practitioners.
A protocol which combined giving parents' information and issuing them with a pertussis vaccine prescription was introduced in 2008 in the maternity ward of the Angers University Hospital, France. As a result, a vaccine coverage rate of 69% among mothers and 63% among fathers was achieved. The aim of this study was to assess the impact of this protocol on general practitioners in the county for which Angers is the main specialist maternity unit, in terms of their opinions on it and any changes they made to their practices. An anonymous, descriptive survey was carried out in 2009, via a questionnaire sent out to the 655 general practitioners (GPs). The response rate among the GPs was 77% (508/655). Of the respondents, 97.8% (497/508) were familiar with the vaccination recommendations and of these, 30.4% (150/495; missing data n=2) knew of them through the information letter given out by the maternity unit and 97.6% (482/494; missing data n=3) stated that they had informed their patients of them. Of the GPs who replied, 97.5% (476/488; missing data n=9) approved of the strategy, while 60.4% of them (285/472; missing data n=4) said they had changed their information practices since 2008 and 67.2% (307/457; missing data n=19) said they had changed their vaccination practices over the same period. Most of the GPs (53% (241/454); missing data n=43) approved of the maternity unit giving parents the vaccine. The pertussis prevention protocol introduced by the maternity unit was clearly understood by the general practitioners and led them to significantly change their information and vaccination practices.


Development of Orientation to the Future during Early Adolescence: A Four-Year Longitudinal Study and Two Cross-Sectional Comparisons.
In 1982, fifty-seven 11-year-old and forty-eight 15-year-old adolescents were interviewed about their hopes and fears for the future. Similarly, in 1987, fifty-seven 11-year-old and fifty-six 15-year-old adolescents were interviewed. The content and extension of each hope and fear as well as the levels of planning, realization, internality, probability estimation and overall emotional evaluation were estimated from the answers. As expected, adolescents' hopes concerned major developmental tasks, i.e. occupation, education, family and property related topics. Both 11- and 15-year-olds extended their thinking to the same stage of their future life, about the age of twenty. A comparison of extension according to hope content showed that adolescents' orientation to the future reflected the 'cultural prototype' of expected life-span development. Levels of planning, realization and knowledge concerning hopes increased with age as did internality and optimism concerning the future, especially among boys.


Effects of olfactory tract lesions on sexual and feeding behavior in the goldfish.
The paired olfactory tracts (OTs) of goldfish each have a lateral (LOT) and medial (MOT) olfactory tract, the latter with medial (mMOT) and lateral (lMOT) subdivisions. Bilateral OT section (OTX) reduced, while unilateral OT section (UNI) did not impair, male sexual behavior and feeding responses to a complex food odor; in contrast, female sexual behavior, induced in both sexes by prostaglandin treatment, was little affected by OTX. Experiments in which control fish were given UNI and treatment groups received UNI plus selective section of the remaining OT assessed the role of the OT subdivisions in the two olfactory-influenced behaviors (male sexual behavior and feeding). LOT section did not affect courtship, while MOT section reduced courtship to the low levels seen in OTX males; within the MOT, the mMOT may be more important than the lMOT for courtship expression. In contrast to male sexual behavior, feeding responses were less affected by MOT than LOT section. With respect to male sexual behavior, these findings demonstrate differential functions for the anatomically distinct subdivisions of the goldfish olfactory tracts, possibly related to their distinct terminal fields within the telencephalon.


Computationally efficient mechanism discovery for cell invasion with uncertainty quantification.
Parameter estimation for mathematical models of biological processes is often difficult and depends significantly on the quality and quantity of available data. We introduce an efficient framework using Gaussian processes to discover mechanisms underlying delay, migration, and proliferation in a cell invasion experiment. Gaussian processes are leveraged with bootstrapping to provide uncertainty quantification for the mechanisms that drive the invasion process. Our framework is efficient, parallelisable, and can be applied to other biological problems. We illustrate our methods using a canonical scratch assay experiment, demonstrating how simply we can explore different functional forms and develop and test hypotheses about underlying mechanisms, such as whether delay is present. All code and data to reproduce this work are available at https://github.com/DanielVandH/EquationLearning.jl.


PAH Profiles in Suspended Particulate Matter from an Urbanized River Within the Brazilian Amazon.
The distribution, seasonal variation and sources of 16 polycyclic aromatic hydrocarbons (PAH) from suspended particulate matter (SPM) of the Aurá River, a small amazon typical river located in Northern Brazil, were determined. Gas chromatography-mass spectrometry analysis of SPM revealed a mixture of PAH from different origins and a seasonal variation of PAH primary source for the studied area. Pyrene was the dominant PAH in both studied periods. Total PAH content (ΣPAH) ranged from lower than quantification limit (< LOQ) to 2498.2 ng g-1 dw during the dry season and < LOQ to 2865.8 ng g-1 dw during the wet season. Low molecular weight PAH (LMW) represented 51% of ΣPAH during the dry season and 29% during the wet season. It was noted, by comparing previous data, that the main source of these compounds was altered after the deactivation of an irregular landfill next to the river.


Biosynthesis of cholic acid in rat liver. 24-Hydroxylation of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestanoic acid.
Conversion of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-[7beta-3H]cholestanoic acid into 3alpha, 7alpha, 12alpha, 24-tetrahydroxy-5beta-cholestanoic acid in rat liver was catalyzed either by the mitochondrial fraction fortified with the 100,000 times g supernatant fluid or the microsomal fraction fortified with 100,000 times g supernatant fluid and ATP. The microsomal system was more active than the mitochondrial system. With the microsomal system the rate of reaction was considerably faster with free 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestanoic acid as substrate than with the corresponding coenzyme A ester. Addition of coenzyme A inhibited the activity. Addition of cofactors other than ATP and coenzyme A did not markedly influence the reaction. The 100,000 times g supernatant fluid could be substituted with a protein fraction obtained by ammonium sulfate precipitation and Sephadex chromatography of the 100,000 times g supernatant fluid. The reaction was not catalyzed by a mixed function oxidase since there was no incorporation of 18O into the product when the reaction was performed in an atmosphere containing 18O2. On the other hand, oxygen may be obligatory since there was almost complete inhibition when the reaction was performed in an atmosphere consisting of nitrogen. Carbon monoxide did not inhibit the reaction. One atom of deuterium was incorporated into the product when the reaction was performed in a medium containing deuterated water. It was concluded that microsomal 24-hydroxylation of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestanoic acid involves the combined action of a desaturase and a hydratase. The reaction catalyzed by the hydratase appears to be stereospecific since the 24alpha epimer of 3alpha, 7alpha,12alpha-trihydroxy-5beta-cholestanoic acid was the predominant product. In contrast to the microsomal system, the mitochondrial system was not stimulated by the addition of ATP and was not inhibited by coenzyme A. The coenzyme A ester of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestanoic acid was 24-hydroxylated more efficiently than the free acid.


Identification of dissimilatory nitrate reduction to ammonium (DNRA) and denitrification in the dynamic cake layer of a full-scale anoixc dynamic membrane bioreactor for treating hotel laundry wastewater.
Identification of dissimilatory nitrate reduction to ammonium (DNRA) and denitrification in the dynamic cake layer of a full-scale anoixc dynamic membrane bioreactor (AnDMBR) for treating hotel laundry wastewater was studied. A series of experiments were conducted to understand the contributions of DNRA and canonical denitrification activities in the dynamic cake layer of the AnDMBR. The dynamic cake layer developed included two phases - a steady transmembrane pressure (TMP) increase at 0.24 kPa/day followed by a sharp TMP jump at 1.26 kPa/day four to five days after the AnDMBR start-up. The nitrogen mass balance results showed that canonical denitrification was predominant during the development of the dynamic cake layer. However, DNRA activity and accumulation of bacteria equipped with a complete DNRA pathway showed a positive correlation to the development of the dynamic cake layer. Our metagenomic analysis identified an approximately 18% of the dynamic cake layer bacterial community has a complete DNRA pathway. Pannonibacter (1%), Thauera (0.8%) and Pseudomonas (3%) contained all genes encoding for funcional enzymes of both DNRA (nitrate reductase and DNRA nitrite reductase) and denitrification (nitrate reductase, nitrous oxide reductase and nitric oxide reductase). No other metagenome-assembled genomes (MAGs) possessed a complete cononical denitrification pathway, indicating food-chain-like interactions of denitrifiers in the dynamic cake layer. We found that COD loading rate could be used to control DNRA and canonical denitrification activities during the dynamic cake layer formation.


Prospective Longitudinal Assessment of Quality of Life and Activities of Daily Living as Patient-Reported Outcome Measures in Recurrent/Progressive Glioma Treated with High-dose Salvage Re-irradiation.
To evaluate quality of life (QOL) and activities of daily living (ADL) longitudinally in patients treated with salvage re-irradiation for recurrent/progressive glioma. Secondary end points included post-re-irradiation survival. Patients with diffuse glioma, aged 18-70 years with preserved performance status and unequivocal evidence of recurrence/progression with a minimum 2-year time interval from index radiation therapy were eligible. QOL was assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) and brain cancer module (BN20). ADL was assessed using a modified Barthel's index. Assessments were carried out longitudinally, first before re-irradiation, at completion of re-irradiation and subsequently periodically on follow-up. Summary scores were calculated from raw scores as per the EORTC scoring manual; higher functional scores and lower symptom scores indicating better QOL. Summary mean scores for the modified Barthel's index were also calculated, with lower scores indicating higher disability. Differences between the summary scores at different time points were tested using the Friedman test. In total, 225 assessments were carried out in 60 patients accrued on the study. A significant improvement in scores was noted for physical function (P < 0.001), emotional function (P = 0.002), cognitive function (P = 0.009) and social functioning (P = 0.047) over time. Role function scores (P = 0.182) and global health status scores (P = 0.074) remained stable. Among symptom scores, fatigue showed a statistically significant improvement over time (P = 0.01), whereas other symptom scores remained largely stable. There was a significant increase in the modified Barthel's index score over time (P = 0.001), suggesting greater functional independence. At a median follow-up of 12.9 months, the 1-year Kaplan-Meier estimates with 95% confidence intervals of post-re-irradiation progression-free survival and overall survival were 45.1% (31.5-58.7%) and 62.2% (49.2-75.2%), respectively. High-dose salvage re-irradiation in carefully selected patients with recurrent/progressive glioma is associated with stable QOL (preserved functional domains and reduced symptom burden) and improvement in ADL (greater functional independence) over time with encouraging survival outcomes.


Activities of Daily Living Performance in Persons With Dementia: Comparing Care Partners' and Clinicians' Appraisal and Associated Factors.
Persons living with dementia require assistance in making day-to-day and health care decisions. Health care professionals select treatments based on the care partner (CP) report of the person's function; however, the accuracy of CPs' appraisal has received limited exploration. Retrospective analyses of observational, programmatic data were performed across 161 dyads (CPs and persons with dementia) participating in an evidence-based, community-level dementia intervention program. We examined the differences in the appraisal of activities of daily living performance by CPs versus occupational therapists specialized in dementia treatment and investigated factors related to this discrepancy. The discrepancy in the assessment of function is common between CPs and clinicians. CPs tend to overestimate the abilities of persons with dementia. Appraisal discrepancy was most strongly associated with (1) sex of the person with dementia, (2) timing of assessment performance, (3) number of behavioral symptoms of the person with dementia, and (4) cognitive abilities of the person with dementia. Many factors influence the ability of CPs to appraise the function of persons with dementia. The inaccurate appraisal could result in insufficient daily assistance for, or even unnecessary health care utilization, of the person with dementia. Timeliness of intervention is crucial as their health status may change quickly.


SMAD2 and SMAD3 differentially regulate adiposity and the growth of subcutaneous white adipose tissue.
Adipose tissue is the primary site of energy storage, playing important roles in health. While adipose research largely focuses on obesity, fat also has other critical functions, producing adipocytokines and contributing to normal nutrient metabolism, which in turn play important roles in satiety and total energy homeostasis. SMAD2/3 proteins are downstream mediators of activin signaling, which regulate critical preadipocyte and mature adipocyte functions. Smad2 global knockout mice exhibit embryonic lethality, whereas global loss of Smad3 protects mice against diet-induced obesity. The direct contributions of Smad2 and Smad3 in adipose tissues, however, are unknown. Here, we sought to determine the primary effects of adipocyte-selective reduction of Smad2 or Smad3 on diet-induced adiposity using Smad2 or Smad3 "floxed" mice intercrossed with Adiponectin-Cre mice. Additionally, we examined visceral and subcutaneous preadipocyte differentiation efficiency in vitro. Almost all wild type subcutaneous preadipocytes differentiated into mature adipocytes. In contrast, visceral preadipocytes differentiated poorly. Exogenous activin A suppressed differentiation of preadipocytes from both depots. Smad2 conditional knockout (Smad2cKO) mice did not exhibit significant effects on weight gain, irrespective of diet, whereas Smad3 conditional knockout (Smad3cKO) male mice displayed a trend of reduced body weight on high-fat diet. On both diets, Smad3cKO mice displayed an adipose depot-selective phenotype, with a significant reduction in subcutaneous fat mass but not visceral fat mass. Our data suggest that Smad3 is an important contributor to the maintenance of subcutaneous white adipose tissue in a sex-selective fashion. These findings have implications for understanding SMAD-mediated, depot selective regulation of adipocyte growth and differentiation.


Evidence for variable rates of recombination in the MHV genome.
Mouse hepatitis virus has been shown to undergo RNA recombination at high frequency during mixed infection. Temperature-sensitive mutants were isolated using 5-fluorouracil and 5-azacytidine as mutagen. Six RNA+ mutants that reside within a single complementation group mapping within the S glycoprotein gene of MHV-A59 were isolated which did not cause syncytium at the restrictive temperature. Using standard genetic techniques, a recombination map was established that indicated that these mutants mapped into two distinct domains designated F1 and F2. These genetic domains may correspond to mutations mapping within the S1 and S2 glycoproteins, respectively, and suggest that both the S1 and S2 domains are important in eliciting the fusogenic activity of the S glycoprotein gene. In addition, assuming that most distal ts alleles map roughly 4.0 kb apart, a recombination frequency of 1% per 575-676 bp was predicted through the S glycoprotein gene. Interestingly, this represents a threefold increase in the recombination frequency as compared to rates predicted through the polymerase region. The increase in the recombination rate was probably not due to recombination events resulting in large deletions or insertions (greater than 50 bp), but rather was probably due to a combination of homologous and nonhomologous recombination. A variety of explanations could account for the increased rates of recombination in the S gene.


Influences of barley and oat silages for beef cows on occurrence of myopathy in their calves.
Sixteen pregnant Shorthorn cows were winter-fed either oat or barley silage, both of which were low in selenium (less than .1 ppm). Two months before calving, as well as at calving and a month later, four cows on each diet were given intramuscularly a preparation containing 1360 IU of vitamin E and 30 mg selenium as sodium selenite. Barley silage lipids contained higher linoleic (33.2 versus 22.3%) and palmitic acids (32.3 versus 23.1%), and lower oleic (6.3 versus 22.1%) and linolenic acids (20.9 versus 30.9%) than oat silage. Three calves born from the untreated dams on barley silage died from nutritional muscular dystrophy by 50 days of age whereas none of the calves either from the untreated cows on oat silage or from any of the selenium/vitamin E treated cows. Milk from untreated cows fed barley silage contained a higher proportion of linoleic acid than that from treated cows or from those on oat silage. The incidence of nutritional muscular dystrophy was associated closely with ingestion by the calves of an increased amount of dietary dienoic acid. It appears an advantage to include oat silage in winter feeding programs for beef cows to reduce the risk of development of nutritional muscular dystrophy in the offspring.


Did Cognitive Attentional Syndrome Symptoms Predict Stress- and Trauma-Related Symptoms in the Initial Phase of the COVID-19 Pandemic? Results from a Two-Wave Study on a Sample of Polish Internet Users.
According to metacognitive theory, Cognitive Attentional Syndrome (CAS) is a transdiagnostic factor and a main mechanism of psychopathology maintenance. The main goal of this study is to examine whether CAS predicted stress- and trauma-related symptomatology in the first months of the COVID-19 pandemic and three months later. Initially, 1792 participants were recruited online via social media; the data were collected at two time points. The measures included the Cognitive Attentional Syndrome Questionnaire, the Adjustment Disorder-New Module 20, the International Trauma Questionnaire, and additional measures. Structural equation modeling was conducted in order to determine the relations between the reported stressors, CAS, and symptomatology. At both time points, CAS was a significant mediator between the stressors and symptoms of adjustment disorder. Despite the decrease in the intensity of adjustment disorder symptoms between waves, it was a significant predictor of other psychopathologies at both time points, except for traumatic stress. The findings confirm the assumption that CAS is a transdiagnostic factor of psychopathology and has a mediating role in the relationship between stressors and adjustment disorder and co-occurring symptomatology. The effect was particularly significant in the initial phase of the pandemic, which was highly stressful for many people.


Successful treatment of twin-twin transfusion syndrome by occlusion of placental vessel anastomoses using enbucrilate.
Twin-twin transfusion syndrome is a serious obstetric complication unique to monochorionic twin gestations. Occlusion of vessel anastomoses is recommended to improve the perinatal outcome. A 36-year-old, gravida 1, woman had a monochorionic twin pregnancy which was found to be affected by twin-twin transfusion syndrome at 26 weeks' gestation. The condition was successfully treated by occlusion of placental vessel anastomoses using enbucrilate under color Doppler ultrasonographic guidance. At 35 weeks of gestation, two male infants were delivered by cesarean section. The birth weights of the babies were 2,470 and 1,750 g, and both were thriving. Targeted therapeutic ablation of vessel anastomoses involved in twin-twin transfusion syndrome using color Doppler ultrasonographic guidance is minimally invasive and may effectively obliterate interfetal transfusion, contributing to the survival of both twins.


Ureteral Involvement Within an Incarcerated Inguinal Hernia in a Patient With Crossed-fused Renal Ectopia.
Crossed-fused renal ectopy is an uncommon abnormality of the genitourinary tract that results from errors during embryological development. Ureteral herniation represents another rare anatomic event and can often occur from spontaneous, postoperative, and congenital causes (Allam, Johnson, Grewal & Johnson 2015; Pollack, Popky & Blumberg 1975). Here, we discuss the complex clinical course of a patient with crossed-fused renal ectopia who presents with symptoms due to ureteroinguinal herniation and provide a brief overview of the literature. We highlight the clinical considerations in the management of this patient and provide a potential anatomical and embryological explanation for his presentation.


Part-time versus full-time employment and mental health for people with and without disability.
This paper investigates the relationship between part-time and full-time employment and mental health for people with and without disability, as well as differences in the relationship by age and sex. Using data from 13,219 working-aged people (15-64 years) in the labour force who participated in five annual waves of a longitudinal cohort study in Australia, the analysis used fixed effect regression models to examine within-person changes in mental health associated with changes in employment status (full-time; part-time; unemployed). Differences in the relationship between employment status and mental health by disability, sex, and age were assessed. Among people with disability, there was evidence that working part-time and full-time were associated with a 4.2-point (95% CI 2.6, 5.7) and 6.0-point (95% CI 4.4, 7.6) increase in mental health scores compared with when they were unemployed. For people without disability, there were much smaller differences in mental health associated with working part-time (β = 1.0, 95% CI 0.2, 1.9) and full-time (β = 1.4, 95% CI 0.5, 2.2) compared with when they were unemployed. The positive effects of both part-time and full-time employment were of greater magnitude for people with disability aged younger than 45 years compared to those aged 45 years and older. The results of this study suggest that both part-time and full-time employment may have beneficial effects on the mental health of people with disability, particularly for younger people. The findings underscore the value of employment for people with disability, given we found much larger beneficial mental health effects in comparison to people without disability.


Sex Differences in the Association of Pretransfusion Hemoglobin Levels with Brain Structure and Function in the Preterm Infant.
To assess sex-specific differences in early brain structure and function of preterm infants after red blood cell (RBC) transfusions. A single-center subset of infants with a birth weight <1000 g and gestational age 22-29 weeks were enrolled from the National Institute of Child Health and Human Development's Neonatal Research Network Transfusion of Prematures Trial. Hemoglobin (Hb) concentration obtained directly before each transfusion (pretransfusion Hb [ptHb]) was obtained longitudinally throughout each infant's neonatal intensive care unit stay and used as a marker of degree of anemia (n = 97). Measures of regional brain volumes using magnetic resonance imaging were obtained at ∼40 weeks postmenstrual age or at hospital discharge, if earlier (n = 29). Measures of brain function were obtained at 12 months corrected age using the Bayley Scales of Infant & Toddler Development, 3rd Edition (n = 34). PtHb was positively correlated with neonatal cerebral white matter volume in males (B = +0.283; P = .006), but not females (B = -0.099; P = .713), resulting in a significant sex interaction (P = .010). Bayley-III gross motor scores and a pooled mean score were significantly lower in association with higher ptHb in females (gross motor score: B = -3.758; P = .013; pooled mean score: B = -1.225; P = .030), but not males (gross motor score: B = +1.758; P = .167; pooled mean score: B = +0.621; P = .359). Higher ptHb was associated with descriptively lower performance on multiple Bayley-III subscales in females, but not in males. This study demonstrates sex-specific associations between an early marker of anemia and RBC transfusion status (ie, ptHb) with both neonatal white matter volume and early cognitive function at age 12 months in preterm infants.


Immunohistochemical, Flow Cytometric, and ELISA-Based Analyses of Intracellular, Membrane-Expressed, and Extracellular Hsp70 as Cancer Biomarkers.
The major stress-inducible 70 kDa heat shock (stress) protein 70 (Hsp70) is frequently overexpressed in highly aggressive tumor cells and thus might serve as a tumor-specific biomarker of aggressive disease and/or therapeutic resistance. We have previously shown that, in contrast to normal cells, tumor cells present Hsp70 on their plasma membrane. In order to elucidate the role of intracellular, membrane-bound and extracellular Hsp70 as a potential tumor biomarker in cancer, herein we describe protocols for the staining of cytosolic Hsp70 in tumor formalin-fixed paraffin-embedded (FFPE) sections from patients with glioblastoma multiforme using immunohistochemistry, for detecting the expression of plasma membrane-bound Hsp70 by a range of cancer-derived cells using multi-parametric flow cytometry using the cmHsp70.1 monoclonal antibody (mAb) and for the measurement of free and vesicular-associated Hsp70 in the circulation of patients with cancer using a unique enzyme-linked immunosorbent assay (ELISA).


Impact of emerging pollutant florfenicol on enhanced biological phosphorus removal process: Focus on reactor performance and related mechanisms.
Florfenicol (FF), an emerging pollutant antibiotic that is difficult to biodegrade, inevitably enters sewage treatment facilities with high level. To date, however, the performance and related mechanism of FF on enhanced biological phosphorus removal (EBPR) have not been reported. In order to fill this gap, this work investigated the potential impacts of FF on EBPR and revealed the relevant mechanisms. The effect of FF on EBPR was dose-dependent, that was, low dose had no effect on EBPR, while high FF concentration inhibited EBPR. Mechanism investigation showed that FF had no effect on anaerobic phosphate release, but reduced oxic phosphorus uptake. Three-dimensional Excitation-emission Matrix fluorescence spectroscopy and X-ray photoelectron spectroscopy analysis showed that FF affected the structure and components of activated sludge extracellular polymers (EPS). High content of FF stimulated sludge to secrete more EPS. High level of FF reduced the relative abundance of microorganisms responsible for biological phosphorus removal. Microbiological community structure analysis indicated 2.0 mg FF/L increased the relative abundance of Candidatus_Competibacter and Terrimonas from 9.22 % and 12.49 % to 19.00 % and 16.28 %, respectively, but significantly reduced the relative abundance of Chinophagaceae from 11.32 % to 0.38 %, compared with the blank.


Concrete enclosure for shielding a neutron source.
In the aim to design a shielding for a 0.185 TBq (239)PuBe isotopic neutron source several Monte Carlo calculations were carried out using MCNP5 code. First, a point-like source was modeled in vacuum and the neutron spectrum and ambient dose equivalent were calculated at several distances ranging from 5 cm up to 150 cm, these calculations were repeated modeling a real source, including air, and a 1×1×1 m(3) enclosure with 5, 15, 20, 25, 30, 50 and 80 cm-thick Portland type concrete walls. At all the points located inside the enclosure neutron spectra from 10(-8) up to 0.5 MeV were the same regardless the distance from the source showing the room-return effect in the enclosure, for energies larger than 0.5 MeV neutron spectra are diminished as the distance increases. Outside the enclosure it was noticed that neutron spectra becomes "softer" as the concrete thickness increases due to reduction of mean neutron energy. With the ambient dose values the attenuation curve in terms of concrete thickness was calculated.


Abnormally low prolactin levels in schizophrenia patients after switching to aripiprazole in a randomized trial: a biomarker for rebound in psychotic symptoms?
Switching to aripiprazole from other antipsychotics can avoid antipsychotic-induced hyperprolactinemia but may result in an abnormally low prolactin level. This study aimed to assess whether the aripiprazole-induced abnormally low prolactin level was a biomarker for subsequent rebound of positive symptoms in schizophrenia patients. Participants were 63 patients in an 8-week trial of switching to aripiprazole, in which preswitching antipsychotics were maintained for the first 2 weeks and aripiprazole was fixed at 15 mg orally throughout the trial. A prolactin level of < 3.7 ng/ml was defined as abnormally low, and an increase of two or more points in the positive subscore of the Positive and Negative Syndrome Scale at two adjacent ratings was defined as a psychotic rebound. Among 63 patients, 25 (39.7%) had an abnormally low prolactin level and 21 (33.3%) had a psychotic rebound after switching to aripiprazole. In patients with abnormally low prolactin levels, 48.0% of them had a rebound in psychotic symptoms, whereas in those without abnormally low prolactin levels 23.7% did so. Multivariable logistic regression analysis with adjustment for sex, early age at onset, and preswitching medications revealed that abnormally low prolactin levels were associated with psychotic rebound (adjusted odds ratio = 3.55, 95% confidence interval = 1.02, 12.5). Furthermore, there was concurrency between the trend of the cumulative proportion of patients having an abnormally low prolactin level and that of the cumulative proportion of patients having a rebound in psychotic symptoms. An abnormally low prolactin level after switching to aripiprazole in schizophrenia patients was a potential warning sign of a psychotic rebound. Hence, monitoring of prolactin levels after switching to aripiprazole may help avoid such rebound in schizophrenia. NCT00545467 ; Date of registration: 17/10/2007.


Changes in hemopoiesis of mice of the C3H strain following transplantation of Gardner lymphosarcoma and infection with LDH-virus. III. Blood proteins.
Inoculation of bone marrow and spleen cells of C3H/Sumice strain mice demonstrated that on the ninth day of growth of Gardner lymphosarcoma these tissues were invaded with tumor cells. The weights of mice with advanced tumors increased. Yet the deterioration of health status of mice is characterized by decreased food and water consumption, as well as by lower concentrations of proteins in mouse sera and plasma. The albumin fraction shows a remarkable drop. These changes could not be detected in tumor free mice following LDH-virus infection. The treatment with L-asparaginase influenced the manifestations of tumor growth, but not the effectivity of LDH-virus contaminating the tumor as demonstrated by the increased activity of lactate-dehydrogenase in the mouse sera.


Manikya Bhasma is a nanomedicine to affect cancer cell viability through induction of apoptosis.
Ayurveda is an ancient medicine system practiced in the Indian sub-continent. Ayurvedic Bhasma is incinerated herbo-metallic/mineral preparations that consist of the particles in the range of nano/micrometers with therapeutic effects against different diseases. Manikya Bhasma (MB) is composed of purified ruby, orpiment, and purified arsenic sulfide. This study was conducted to identify the potential of MB as a nanomedicine that can be used for the treatment of cancer. Biophysical characterization to determine the morphology and composition of bhasma particles was done using several techniques such as DLS, FTIR, FETEM, FESEM, EDX, and XRD. Cell viability assays were conducted to identify the cytotoxic effect of MB against different cancer cell lines and also to determine the mode of death caused by MB. The biophysical characterization of MB indicates that it is crystalline with a particle size of 70 nm. MB exhibits anticancer activity against MDAMB-231, HeLa, HCT-116, DLD-1, MG-63 cancer cells with an IC50 in the range of 105-155 μg/mL. MB induces oxidative stress in cancer cells, which in turn affects their cell-cycle with an accumulation of cells in the G1-phase. Also, apoptosis induced by MB involves loss of mitochondrial membrane potential, the release of Cyt c, activation of caspases, and DNA degradation. Our study highlights the dual potential of MB as a nano-carrier to deliver the drugs and exerting cytotoxic effects against cancer cells.


Inheritance of Histone (H3/H4): A Binary Choice?
Histones carry information in the form of post-translational modifications (PTMs). For this information to be propagated through cell cycles, parental histones and their PTMs need to be maintained at the same genomic locations. Yet, during DNA replication, every nucleosome in the genome is disrupted to allow passage of the replisome. Recent data have identified histone chaperone activities that are intrinsic components of the replisome and implicate them in maintaining parental histones during DNA replication. We propose that structural and kinetic coordination between DNA replication and replisome-associated histone chaperone activities ensures positional inheritance of histones and their PTMs. When this coordination is perturbed, histones may instead be recycled to random genomic locations by alternative histone chaperones.


Characterization of specific interactions of coenzymes, regulatory nucleotides and cibacron blue with nucleotide binding domains of enzymes by analytical affinity chromatography.
The dissociation constant for the complex of rhodanese and Cibacron Blue, determined by analytical affinity chromatography using rhodanese immobilized on controlled-pore glass (CPG) beads (200 nm pore diameter) and aminohexyl-Cibacron Blue, was 44 microM which agreed well with the kinetic inhibition constant, suggesting that the dye binds at or near the active site of this enzyme. Formation of a binary complex of the dye and lactate dehydrogenase (LDH) was also characterized by direct chromatography of LDH on CPG/immobilized Cibacron Blue (KD = 0.29 microM). The binary complex formed between LDH and NADH was characterized by analytical affinity chromatography using both CPG/immobilized LDH and immobilized Cibacron Blue. Since the dye competes with NADH in binding to the active site of LDH, competitive elution chromatography using the immobilized dye allows determination of the dissociation constant of the soluble LDH.NADH complex. Agreement between the dissociation constants determined by direct chromatography of NADH on immobilized LDH (KD = 1.4 microM) and that determined for the soluble complex (KD = 2.4 microM) indicates that immobilization of LDH did not affect the interaction. Formation of various binary, ternary and quaternary complexes of bovine liver glutamate dehydrogenase (GDH) with glutamate, NADPH, NADH, and ADP was also investigated using immobilized GDH. This approach allows characterization of the enzyme/ligand interactions without the complicating effect of enzyme self-association. The affinity for NADPH is considerably greater in the ternary complex (including glutamate) as compared to the binary complex (0.38 microM vs 22 microM); however, occupancy of the regulatory site by ADP greatly reduces the affinity in both complexes (6.4 microM and 43 microM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Drug information centers: meeting future needs for drug information.
Future trends in drug information services are discussed. Drug information centers (DICs) have developed from being the first clinical pharmacy service 20 years ago to providing a necessary support role for clinical pharmacy practitioners today. The necessary training for drug information pharmacists is described, and continued involvement of these pharmacists in clinical practice is recommended. The shift of health care from hospitals to outpatient clinics means that DICs will have to provide drug information services to community practitioners in the future. Alternative funding sources for DICs, including fee-for-service payment plans, must be developed. The merits of establishing regional DICs and marketing services directly to patients are outlined.


Familiar-face recognition and comparison: source analysis of scalp-recorded event-related potentials.
We studied the event-related potentials elicited by categorical matching of faces. The purpose was to find cortical sources responsible for face recognition and comparison. Nineteen healthy volunteers participated in the study. Each trial began with one of the two cues (S1) followed by consecutive pictures (S2 and S3). Each picture was a photograph of a familiar face with a superimposed abstract dot pattern. One cue directed attention to compare faces and another to compare patterns. 128-channel electroencephalogram was recorded. Spatio-temporal multiple dipole source models were generated using Brain Electromagnetic Source Analysis 2000, for the window of 80-600 ms from S3 onset. The obtained model for face recognition and comparison contained 8 dipoles explaining 97% of grand average and about 90% of individual data and showing temporal and spatial separation of sources: in the frontal region, in the occipital cortex, and in the bilateral medial temporal and inferotemporal regions. Different faces elicited larger components than same person's faces around 400 ms, mainly explained by frontal dipoles. The sources in our models estimate the activity common for both Face task conditions (the recognition of a familiar person) and also differential activity, related to the match/mismatch item processing.


Socioeconomic status differs between breast cancer patients treated with mastectomy and breast conservation, and affects patient-reported preoperative information.
Breast cancer treatment is reported to be influenced by socioeconomic status (SES). Few reports, however, stem from national, equality-based health care systems. The aim of this study was to analyse associations between SES, rates of breast-conserving surgery (BCS), patient-reported preoperative information and perceived involvement in Sweden. All women operated for primary breast cancer in Sweden in 2013 were included. Tumour and treatment data as well as socioeconomic data were retrieved from national registers. Postal questionnaires regarding preoperative information about breast-conserving options and perceived involvement in the decision-making process had previously been sent to all women receiving mastectomy. Of 7735 women, 4604 (59.5%) received BCS. In addition to regional differences, independent predictors of BCS were being in the middle or higher age groups, having small tumours without clinically involved nodes, being born in Europe outside Sweden, having a higher education than primary school and an intermediate or high income per household. Women with smaller, clinically node-negative tumours felt more often involved in the surgical decision and informed about breast-conserving options (both p < 0.001). In addition, women who perceived that BCS was discussed as an alternative to mastectomy were more often in a partnership (p < 0.001), not born in Sweden (p = 0.035) and had an employment (p = 0.031). Socioeconomic factors are associated with surgical treatment even in a national health care system that is expected to offer all women the same standard of care. This should be taken into account and adapted to in preoperative counselling on surgical options in breast cancer.


Guanine nucleotide dependent and independent reconstitution of G-proteins with adenylate cyclase: stimulation or attenuation of the enzyme by Gi alpha subunits.
The alpha subunits of five members of the Gi family of bovine brain proteins were reconstituted with adenylate cyclase in phospholipid vesicles. Our results support both the views that much of the inhibition of the enzyme by Gi is due to the action of its liberated beta gamma subunits, and that the alpha subunits themselves interact with the enzyme. Inhibition of basal or Gs-stimulated adenylate cyclase activity is small or undetectable by alpha subunits of Go, Go* and Gi-2B. On the other hand, adenylate cyclase activity is stimulated by the alpha subunits of Gi-1 and Gi-2A. The G proteins act in the absence of added GTP when reconstituted with phospholipids of low but not high fluidity.


[Psychological study of the intellectual-personality characteristics of neurotic patients (according to findings from use of the experimental Vygotskii-Sakhorov method)].
The author describes some special traits in accomplishing the modified techniques for a formation of conceptions according to Vigotsky-Sakharov's test in patients with different forms of neuroses (neurasthenia, hysteria, psychasthenia). A study of conceptual thinking in such patients revealed a dissociation between the possibility of a practical mastering of the task and its verbalization on a conceptual level which is characteristic of hysteria.


Characterization of cross-reactive and serotype-specific epitopes on the nucleocapsid proteins of hantaviruses.
The hantavirus nucleocapsid (N) protein fulfills several key roles in virus replication and assembly and is the major antigen in humoral immune responses in humans and mice. Here we report on epitopes involved in serotype-specific and cross-reactive recognition of the N proteins of hantaviruses using monoclonal antibodies (mAbs) against the N proteins of Andes virus (ANDV) and Sin Nombre virus (SNV). The mAbs define at least twelve different epitopic patterns which span eight sequences, including amino acids 17-59, 66-78, 79-91, 157-169, 222-234, 244-263, 274-286 and 326-338 on the SNV and ANDV N proteins. Studies on the cross-reactivity of these mAbs with different hantavirus N proteins indicated that epitopes located within amino acids 244-286 are related to serotype specificity. We analyzed further the location of epitopes with available three-dimensional structure information including the N-terminal coiled-coil and derived exposed and hidden residues of these epitopes. The generated recombinant N proteins and the characterized mAbs are functional tools being now available for hantavirus diagnostics and replication studies.


Effects of calcium and substrate on force-velocity relation and energy turnover in skinned smooth muscle of the guinea-pig.
Mechanical properties and rate of ATP breakdown (JATP) have been determined in the chemically skinned guinea-pig taenia coli at 22 degrees C. The influence of varied [Ca2+], [Mg ATP] and muscle length were investigated. The shortening response after a step decrease in force (isotonic quick release) was highly curvilinear in the first 100-200 ms. This effect was shown to be a time-dependent response to the force step and not primarily caused by the shift along the length-force relation associated with shortening. Maximal shortening velocity (Vmax) decreased gradually following the release. At pCa (= -log [Ca2+]) 4.5, Vmax at 20 and 1000 ms after release was 0.49 +/- 0.07 and 0.041 +/- 0.004 (mean +/- S.E. of mean, n = 5) lengths s-1 respectively. Unloaded shortening velocity obtained from length steps of different magnitude (slack test) also showed a gradual decrease after the release, consistent with the isotonic release results. Increasing [Ca2+] from the relaxed state at pCa 9 (1 microM-calmodulin present) gave increased isometric force to a maximum at pCa 4.5. Half-maximal response was obtained at pCa 6.1. JATP at maximal force at pCa 4.5 was about 3 times the basal rate at pCa 9. The relation between JATP and force was highly non-linear, with a marked increase in JATP with little alteration in force at the highest [Ca2+]. When force was reduced to zero at pCa 4.5 by shortening the muscle to 0.3 L0 (L0 being the length giving maximal active force), JATP decreased by about 30%. At two levels of [Ca2+] giving similar force (pCa 5.75 and 4.5) the energetic tension cost obtained by length variations was lower at the low [Ca2+]. At pCa 6.0, Vmax and force were decreased to the same extent relative to their values at pCa 4.5. At pCa 5.75, where there was no reduction in force but a 25% decrease in isometric JATP, Vmax was unchanged relative to pCa 4.5. Force, Vmax and JATP were all dependent on [Mg ATP]. Half-maximal response was obtained at 0.1 mM for force and Vmax, and at 0.5 mM for JATP. The results are discussed in relation to a possible influence of both Ca2+ and Mg ATP on kinetic properties of the cross-bridge cycle.


[Retrospective analysis of transpulmonary and pulmonary arterial measurement of cardiac output in ARDS patients].
To investigate the agreement (and its potential dependency on extra-vascular lung water) between transpulmonary (TPID) and standard pulmonary artery (PAID) thermodilution cardiac output measurements. One hundred and sixty simultaneous cardiac output measurements using transpulmonary and pulmonary artery thermodilution techniques were retrospectively compared in 18 patients with acute respiratory distress syndrome. In addition, extravascular lung water was determined using a double indicator technique (temperature and indocyanine green). Mean (+/- SD) difference ("bias") was 0.03 L/min (+/- 1.04 L/min), linear regression analysis resulted in TPID = 0.87 PAID + 1.16 (r = 0.91). Mean extra vascular lung water was 1625 mL (minimum-maximum: 403-3266 mL) and therefore markedly elevated as could have been expected in patients with ARDS. Bias (PAID-TPID) was not dependent on extravascular lung water. Transpulmonary and pulmonary artery thermodilution methods can be used interchangeably. The results demonstrate for the first time in humans that transpulmonary thermodilution provides valid cardiac output values in patients with markedly increased fluid content of the lungs.


Functional immunophenotyping of children with critical status asthmaticus identifies differential gene expression responses in neutrophils exposed to a poly(I:C) stimulus.
The host immune response to a viral immune stimulus has not been examined in children during a life-threatening asthma attack. We determined whether we could identify clusters of children with critical asthma by functional immunophenotyping using an intracellular viral analog stimulus. We performed a single-center, prospective, observational cohort study of 43 children ages 6-17 years admitted to a pediatric intensive care unit for an asthma attack between July 2019 to February 2021. Neutrophils were isolated from children, stimulated overnight with LyoVec poly(I:C), and mRNA was analyzed using a targeted Nanostring immunology array. Network analysis of the differentially expressed transcripts for the paired LyoVec poly(I:C) samples was performed. We identified two clusters by functional immunophenotyping that differed by the Asthma Control Test score. Cluster 1 (n = 23) had a higher proportion of children with uncontrolled asthma in the four weeks prior to PICU admission compared with cluster 2 (n = 20). Pathways up-regulated in cluster 1 versus cluster 2 included chemokine receptor/chemokines, interleukin-10 (IL-10), IL-4, and IL-13 signaling. Larger validation studies and clinical phenotyping of children with critical asthma are needed to determine the predictive utility of these clusters in a larger clinical setting.


Common Genetic Influences on Impulsivity Facets are Related to Goal Management, Psychopathology, and Personality.
In this study, we characterized the genetic/environmental commonality and heterogeneity of impulsivity facets and tested the hypothesis that goal-management is central to their common variance. 764 young-adult twins completed the UPPS-P Impulsive Behavior Scale and measures of goal management, personality, and psychopathology. We found common genetic influences across all impulsivity facets except sensation seeking. These impulsivity genetic influences explained 40.0% of variance in goal-management ability. Other results supported three hypotheses concerning heterogeneity: that sensation seeking is independent of other facets, that urgency is more related to psychopathology than lack of premeditation, and that lack of perseverance is more similar to urgency than lack of premeditation. Thus, impulsivity facets show considerable heterogeneity in addition to common variation related to goal-management abilities.


Developing a Microbubble-Based Contrast Agent for Synchrotron In-Line Phase Contrast Imaging.
X-ray phase contrast imaging generates contrast from refraction of X-rays, enhancing soft tissue contrast compared to conventional absorption-based imaging. Our goal is to develop a contrast agent for X-ray in-line phase contrast imaging (PCI) based on ultrasound microbubbles (MBs), by assessing size, shell material, and concentration. Polydisperse perfluorobutane-core lipid-shelled MBs were synthesized and size separated into five groups between 1 and 10 μm. We generated two size populations of polyvinyl-alcohol (PVA)-MBs, 2-3 μm and 3-4 μm, whose shells were either coated or integrated with iron oxide nanoparticles (SPIONs). Microbubbles were then embedded in agar at three concentrations: 5 × 107, 5 × 106 and 5 × 105 MBs/ml. In-line phase contrast imaging was performed at the Canadian Light Source with filtered white beam micro-computed tomography. Phase contrast intensity was measured by both counting detectable MBs, and comparing mean pixel values (MPV) in minimum and maximum intensity projections of the overall samples. Individual lipid-MBs 6-10 μm, lipid-MBs 4-6 μm and PVA-MBs coated with SPIONs were detectable at each concentration. At the highest concentration, lipid-MBs 6-10 μm and 4-6 μm showed an overall increase in positive contrast, whereas at a moderate concentration, only lipid-MBs 6-10 μm displayed an increase. Negative contrast was also observed from two largest lipid-MBs at high concentration. These data indicate that lipid-MBs larger than 4 μm are candidates for PCI, and 5 × 106 MBs/ml may be the lowest concentration suitable for generating visible phase contrast in vivo. Identifying a suitable MB for PCI may facilitate future clinical translation.


Biological properties of lithium-containing surface pre-reacted glass fillers as direct pulp-capping cements.
Surface pre-reacted glass fillers (S-PRG) can release different types of ions and in our previous study, we modified these fillers with lithium chloride (S-PRG/Li-100 mM) to induce reparative dentin formation by activating the Wnt/β-catenin signaling pathway. Here, we assessed the biological performance of S-PRG/Li-100 mM and compared it with that of mineral trioxide aggregate (MTA) and S-PRG without additives. In vivo studies were conducted on male Wistar rats using Masson's trichrome staining in pulp-capped molars. The test materials were implanted subcutaneously to evaluate their capacity for vascularization and biocompatibility. The ability of the test materials to form apatite was tested by immersing them in simulated body fluid. Rhodamine-B staining was conducted to assess their sealing ability in bovine teeth, while their antibacterial activity was evaluated against Streptococcus mutans and Lactobacillus casei in terms of colony-forming units and by live/dead staining. Masson's trichrome staining and tissue-implantation tests confirmed the biocompatibility of S-PRG/Li-100 mM and it was similar to that of MTA and S-PRG; inflammation regression was observed 14 days after operation in the subcutaneous tissues. S-PRG/Li-100 mM promoted the formation of apatite on its surface. Both the S-PRG groups showed higher sealing capability and bactericidal/bacteriostatic activity against oral bacterial biofilms than MTA. Lithium-containing surface pre-reacted glass cements exhibit better antibacterial and sealing capabilities than MTA, suggesting their potential as high-performance direct pulp-capping materials.


Mitochondrial dysfunction and the inflammatory response.
Inflammation has been linked to multiple degenerative and acute diseases as well as the aging process. Moreover, mitochondrial alterations play a central role in these processes. Mitochondria have an important role in pro-inflammatory signaling; similarly, pro-inflammatory mediators may also alter mitochondrial function. Both of these processes increase mitochondrial oxidative stress, promoting a vicious inflammatory cycle. Additionally, damage-associated molecular patterns derived from mitochondria could contribute to inflammasome formation and caspase-1 activation, while alterations in mitochondrial autophagy may cause inflammation. Strategies aimed at controlling excessive oxidative stress within mitochondria may represent both preventive and therapeutic interventions in inflammation.


The impact of the first UK COVID-19 lockdown on presentations with psychosis to mental health services for older adults: An electronic health records study in South London.
Social distancing restrictions in the COVID-19 pandemic may have had adverse effects on older adults' mental health. Whereby the impact on mood is well-described, less is known about psychotic symptoms. The aim of this study was to compare characteristics associated with psychotic symptoms during the first UK lockdown and a pre-pandemic comparison period. In this retrospective observational study we analysed anonymised records from patients referred to mental health services for older adults in South London in the 16-week period of the UK lockdown starting in March 2020, and in the comparable pre-pandemic period in 2019. We used logistic regression models to compare the associations of different patient characteristics with increased odds of presenting with any psychotic symptom (defined as hallucinations and/or delusion), hallucinations, or delusions, during lockdown and the corresponding pre-pandemic period. 1991 referrals were identified. There were fewer referrals during lockdown but a higher proportion of presentations with any psychotic symptom (48.7% vs. 42.8%, p = 0.018), particularly hallucinations (41.0% vs. 27.8%, p < 0.001). Patients of non-White ethnicity (adjusted odds ratio (OR): 1.83; 95% confidence interval (CI): 1.13-2.99) and patients with dementia (adjusted OR: 3.09; 95% CI: 1.91-4.99) were more likely to be referred with psychotic symptoms during lockdown. While a weaker association between dementia and psychotic symptoms was found in the pre-COVID period (adjusted OR: 1.55; 95% CI: 1.19-2.03), interaction terms indicated higher odds of patients of non-White ethnicity or dementia to present with psychosis during the lockdown period. During lockdown, referrals to mental health services for adults decreased, but contained a higher proportion with psychotic symptoms. The stronger association with psychotic symptoms in non-White ethnic groups and patients with dementia during lockdown suggests that barriers in accessing care might have increased during the COVID-19 pandemic.


Correction to: Comparative study on anti-oxidative and anti-inflammatory properties of hydroponic ginseng and soil-cultured ginseng.
[This corrects the article DOI: 10.1007/s10068-018-0450-x.].


Evaluation of staging criteria for disposition and airway intervention in emergency department angioedema patients.
Angioedema is a nonpitting edema that can lead to death secondary to airway obstruction. Previously, a staging system based on localization of the angioedema was proposed for risk stratification of likelihood of need for admission or airway intervention. This study aims to evaluate a staging system based on angioedema localization as a method of predicting need for admission or airway intervention. This was a retrospective chart review of angioedema cases that presented to an academic emergency department (ED) from August 1, 2006, to January 31, 2018. Data were collected on location of swelling, treatment setting, and medical and procedural interventions. Cases were categorized by modified Ishoo criteria, defined as follows: 1, lips, face, periorbital, extremities, total body/diffuse swelling; 2, soft palate, posterior pharynx; 3, tongue; 4, larynx. Predictive probability of disposition by stage was then compared. A total of 320 patients were included in this study (median age, 44 years; 54.4% female). Stage 4 was more likely to require intensive care unit care without (probability 17%) and with (67%) airway intervention compared with stage 1 without (2.5%) and with (0.1%) airway intervention. Conversely, stage 1 was more likely to be treated in ED and discharged (85%) compared with stage 4 (0%). Stage 4 was also more likely to require airway intervention (67%) compared with other stages (1, 0.1%; 2, 8.6%; 3, 16%). Higher-stage patients were more likely to require higher levels of care and airway intervention. Thus, the staging system appears to be a valid method of predicting risk among ED angioedema patients.


The effect of a novel vaginal ring delivering oestradiol acetate on climacteric symptoms in postmenopausal women.
Evaluate the efficacy and acceptability of a novel vaginal ring delivering oestradiol acetate (Menoring) versus oral oestradiol for relief of climacteric symptoms in postmenopausal women. Prospective, multicentre, randomised, double-blind, comparator-controlled, parallel group study. Twenty-one centres in the United Kingdom. Postmenopausal women, aged <65 years experiencing > or =20 hot flushes/night sweats per week for two consecutive weeks. Patients received a vaginal ring releasing oestradiol acetate at a rate equivalent to 50 microg/day in addition to placebo tablets (vaginal ring group) or oral oestradiol 1 mg/day in addition to placebo vaginal ring (oral group) for 24 weeks. For patients with inadequate control of vasomotor symptoms, dosage was doubled at 12 weeks. Non-hysterectomised women received norethisterone 1 mg/day for 12 days in each 28 day cycle. Efficacy was assessed by change in climacteric symptoms measured by the Greene Climacteric Scale, as well as mean change in frequency of hot flushes/night sweats. A total of 159 patients were enrolled (84 vaginal ring, 75 oral). Significant improvement (P < 0.05) in mean total Greene Climacteric Scale scores in both treatment groups was observed at 12 and 24 weeks and for every subscale score including anxiety, depression and sexual dysfunction (P < 0.05). In both groups, frequency of hot flushes/night sweats was significantly reduced (P < 0.001) at 12 and 24 weeks. No significant between-group differences were noted at 12 or 24 weeks. The oestradiol vaginal ring significantly improved climacteric symptoms as measured by Greene Climacteric Scale scores and reduced the frequency of hot flushes/night sweats. Efficacy and safety of vaginal ring oestradiol were comparable with those of oral therapy. Patient evaluations of oestradiol vaginal ring tolerability and acceptability were excellent.


A Cox proportional-hazards model with time-dependent covariates to evaluate the relationship between body-condition score and the risks of first insemination and pregnancy in a high-producing dairy herd.
The objective of this study was to determine the relationship between body-condition score and postpartum reproductive efficiency in dairy cattle. Data on body-condition score, reproduction, diseases, and production from 1404 lactations of 639 cows, calving between January 1984 and November 1996 on a commercial farm, were used. The Cox proportional-hazards model with time-dependent covariates was used to qualify the relationship between body-condition score on a scale of 1 to 5 and risks of first insemination and pregnancy. Cows with body condition at calving < 3 had lower first-insemination risks. Loss of body-condition score between calving and 45 days after calving was associated with increased days open and days-to-first insemination. Cows with body-condition scores < 2 after Day 45 and before first insemination were less likely to be inseminated and become pregnant compared with cows that had higher body condition. Milk yield, mastitis, lameness, milk fever and genital infection were associated with a reduction in reproductive efficiency. The results indicated that loss of body-condition and actual body-condition scores before conception or first insemination or both can be used as a prognosis for days open and days-to-first insemination in dairy herds.


Study of spin-lattice and spin-spin relaxation times of 1H, 2H, and 17O in muscular water.
Spin-lattice (T1) and spin-spin (T2) relaxation times of proton, deuteron, and oxygen-17 in muscle water have been measured at 9.21 MHz in the temperature range of 0 degree--40 degrees C. The values of the apparent activation energy for the three nuclei are (in kJ . mol-1) 9.1, 19, and 18 for 1/T1, and -1.3, 4.2, and 14 for 1/T2, respectively. The relatively small values for T2 for 1H and 2H and their low apparent activation energies are attributed to hydrogen exchange between water and proteins; this exchange does not affect the 17O relaxation. Quantitative calculations on deuteron T1 and oxygen-17 T1 and T2 have been made. The effect of surface-induced anisotropy on a minor fraction of water molecules is considered in some detail, and a new expression for its spectral density similar to that of liquid crystalline systems is applied in the calculation. It is suggested that water on the surfaces of macromolecules has a rotational correlation time of tau c approximately 1 x 10(-9) S, with a time constant of tau x approximately 3 x 10(-7) S, which is characteristic of the relaxation of the local structure.


"Fatigue on rest" and associated symptoms (headache, vertigo, blurred vision, nausea, tension and irritability) due to locally asymptomatic, unerupted, impacted teeth.
"Fatigue on Rest", headache, vertigo and the feeling of loss of balance, blurred vision, nausea, tension and irritability, were found to be prevalent amongst patients who had locally asymptomatic, unerupted impacted teeth. A comparative pressure sign was developed, which, when positive, confirmed the relationship between the impacted teeth and the medical symptoms. Removal of the impactions resulted in the alleviation of the symptoms. Stress and psychogenic factors are considered as trigger mechanisms, rather than as basic causes of the symptoms.


Angiotensin-I-converting enzyme and its correlation with human follicular fluid steroids.
Angiotensin-I-converting enzyme (ACE) is a peptidyl-dipeptide hydrolase which splits off the dipeptide His-Leu from the decapeptide angiotensin I and thus converts it to angiotensin II. We determined ACE activity in human preovulatory follicular fluid to further establish the intraovarian activity of the renin angiotensin system. Follicular fluids (n = 18) were obtained from eight patients undergoing in vitro fertilization (IVF) and embryo transfer (ET). ACE activity in follicular fluid and serum was determined by fluorescent spectrophotometry. The median follicular fluid ACE activity was 1.12 (range: 0.19-1.56) nmol/min/ml. This value was significantly lower than ACE activity in serum, 1.50 (range: 1.22-1.57) nmol/min/ml (P less than 0.001). In contrast to this 3:4 ratio between follicular fluid and serum ACE when expressed per ml fluid, the values were very similar when expressed per mg of protein: 0.025 vs. 0.023 nmol/min/mg in follicular fluid and serum, respectively. Correlations were sought between follicular fluid ACE activity and both serum and follicular fluid E2 and P4. A highly significant correlation (P less than 0.0005, r = 0.73) was found between ACE activity in follicular fluid and follicular fluid P4. The presence of significant ACE activity in human follicular fluid further supports the local-ovarian activity of the renin angiotensin cascade.


Effect of vitamin B6 on the synthesis and degradation of aspartate aminotransferase in chicken embryo fibroblasts.
The effect of pyridoxal depletion and supplementation on the intracellular level of mitochondrial and cytosolic aspartate aminotransferase in cultured chicken embryo fibroblasts was examined. No apoenzyme was detected in cells grown in the presence of pyridoxal, and the specific activity of total enzyme did not vary profoundly from primary to quaternary cultures. Under pyridoxal depletion, up to 40% apoenzyme was found in tertiary cultures which was entirely due to the mitochondrial isoenzyme. Cytosolic apoenzyme was never detected. Total aspartate aminotransferase relative to total protein was increased 2-fold in secondary cultures; only the mitochondrial isoenzyme contributed to the increased specific activity. The cytosolic isoenzyme decreased steadily and was below the limit of detection in quaternary cultures. The changes are attributed to an increased and decreased synthesis of mitochondrial and cytosolic isoenzyme, respectively. No induction of either isoenzyme was observed after incubating the cells with different hormones and substrates. In secondary cultures, no degradation of mitochondrial isoenzyme could be detected under pyridoxal deficiency or supplementation during 4.4 days, an interpassage duration. The cytosolic aspartate aminotransferase was degraded initially with an apparent half-life of approximately 0.9 day under both sets of conditions. The pronounced stability of mitochondrial aspartate aminotransferase, even though one-third of it was present as apoenzyme, excludes the formation of the apoform to be the rate-limiting step in its degradation. The present results show that pyridoxal affects the synthesis of mitochondrial and cytosolic aspartate aminotransferase, but differently.


A facile low-cost enzymatic paper-based assay for the determination of urine creatinine.
Creatinine is one of many markers used to investigate kidney function. This paper describes a low-cost enzymatic paper-based analytical device (enz-PAD) for determining urine creatinine. The disposable dead volumes of creatinine enzyme reagents from an automatic analyser cassette were utilised. Whatman No. 3 paper was cut into long rectangular shapes (4×40 mm(2)) on which the enzyme reagents, R1 and R2, were adsorbed in two consecutive regions. The assay was performed by immersing test strips into urine samples contained in microwells to allow creatinine in the sample to react with immobilised active ingredients and, then, traverse via capillary action to the detection area where chromogen products accumulated. The method is based on hydrogen peroxide (H2O2) formation via creatinine conversion using creatininase, creatinase, and sarcosine oxidase. The liberated H2O2 reacts with 4-aminophenazone and 2,4,6-triiodo-3-hydroxybenzoic acid to form quinoneimine with a pink-red colour at the detection zone. The linear range of the creatinine assay was 2.5-25 mg dL(-1) (r(2)=0.983), and the detection limit was 2.0 mg dL(-1). The colorimetric enz-PAD for the creatinine assay was highly correlated with a conventional alkaline picrate method when real urine samples were evaluated (r(2)=0.977; n=40). This simple and nearly zero-cost paper-based device provides a novel alternative method for screening urinary creatinine and will be highly beneficial for developing countries.


[The shell of the quail's egg: ultrastructural and crystallographic study (author's transl)].
The egg-shell of Japanese quail was studied by several techniques. Semithin sections (1 micron thick) of non-decalcified shell were observed by normal and polarized light microscopy. Thin sections of non-decalcified shell, examined by transmission electron microscopy, permitted us to observe the forms and dimensions of crystals of calcite within different layers of the shell: mammilary layer, layer of cones, palissade layer and surface crystal layer. There appears to be two distinct zones in the layer of cones as well as in the superficial crystal layer. Electron microdiffraction revealed the orientation of calcite crystals in the columns. Some crystal defects (twins?) were described and the possibility of their artefactual formation during ultramicrotomy is discussed. Localization of Ca, Mg, P and S were made by X-ray microanalysis of semithin sections. This technique shows that shell membranes, and chiefly the true cuticle, are also mineralized but, in these layers, minerals are not crystallized. Otherwise the distribution of Mg is not uniform throughout the shell thickness; it is less concentrated in the external zone of the layer of cones. These results together with observation of developing shells by scanning electron microscopy allowed us to propose a scheme for shell organization of the quail egg. This organization was related with decalcification which occurs during hatching.


Selective, novel spleen tyrosine kinase (Syk) inhibitors suppress chronic lymphocytic leukemia B-cell activation and migration.
Syk is a protein tyrosine kinase that couples B-cell receptor (BCR) activation with downstream signaling pathways, affecting cell survival and proliferation. Moreover, Syk is involved in BCR-independent functions, such as B-cell migration and adhesion. In chronic lymphocytic leukemia (CLL), Syk becomes activated by external signals from the tissue microenvironment, and was targeted in a first clinical trial with R788 (fostamatinib), a relatively nonspecific Syk inhibitor. Here, we characterize the activity of two novel, highly selective Syk inhibitors, PRT318 and P505-15, in assays that model CLL interactions with the microenvironment. PRT318 and P505-15 effectively antagonize CLL cell survival after BCR triggering and in nurse-like cell-co-cultures. Moreover, they inhibit BCR-dependent secretion of the chemokines CCL3 and CCL4 by CLL cells, and leukemia cell migration toward the tissue homing chemokines CXCL12, CXCL13, and beneath stromal cells. PRT318 and P505-15 furthermore inhibit Syk and extracellular signal-regulated kinase phosphorylation after BCR triggering. These findings demonstrate that the selective Syk inhibitors PRT318 and P505-15 are highly effective for inhibition of CLL survival and tissue homing circuits, and support the therapeutic development of these agents in patients with CLL, other B-cell malignancies and autoimmune disorders.