Microsatellite primers in the endangered quillwort Isoetes hypsophila (Isoetaceae) and cross-amplification in I. sinensis.
The first microsatellite primers were developed for Isoetes hypsophila, an endangered quillwort species endemic to the Qinghai-Tibetan Plateau in China, to further describe its genetic variability and population structure. We also examined their cross-amplification in a congeneric species, I. sinensis. Using the Fast Isolation by AFLP of Sequences COntaining Repeats (FIASCO) protocol, nine microsatellite loci were isolated and characterized in 32 samples from four natural populations of I. hypsophila. The primers amplified di- and hexanucleotide repeats with three to 11 alleles per locus. Seven of nine primers were cross-amplified in I. sinensis with two to seven alleles per locus. The microsatellite loci primers will be useful for studies of genetic diversity and gene flow in natural populations of Isoetes species.


Oral lesions in the chicken: behavioural responses following nociceptive stimulation.
The behaviour of normal birds and birds with ulcerated buccal lesions was described following oral stimulation with Acetylcholine chloride (ACh) and Bradykinin (BK). Both groups of birds showed normal oral behaviour but a number of birds with oral lesions showed a behaviour pattern which had been previously seen in our laboratory following nociceptive stimulation. The birds remained motionless in a crouch-like stance with the head pulled into the body and a significantly reduced number of alert head movements. The onset and duration of this immobility response was compared with reports of pain in humans in the blister-base test using similar concentrations of ACh and BK. It was concluded that nocifensive responses of the chicken fulfil many of the requirements for the definition of pain in animals.


Effects of Different Laying Hen Species on Odour Emissions.
Odour is one of the main environmental concerns in the laying hen industry and may also influence animal health and production performance. Previous studies showed that odours from the laying hen body are primarily produced from the microbial fermentation (breakdown) of organic materials in the caecum, and different laying hen species may have different odour production potentials. This study was conducted to evaluate the emissions of two primary odorous gases, ammonia (NH3) and hydrogen sulphide (H2S), from six different laying hen species (Hyline, Lohmann, Nongda, Jingfen, Xinghua and Zhusi). An in vitro fermentation technique was adopted in this study, which has been reported to be an appropriate method for simulating gas production from the microbial fermentation of organic materials in the caecum. The results of this study show that Jingfen produced the greatest volume of gas after 12 h of fermentation (p < 0.05). Hyline had the highest, while Lohmann had the lowest, total NH3 emissions (p < 0.05). The total H2S emissions of Zhusi and Hyline were higher than those of Lohmann, Jingfen and Xinghua (p < 0.05), while Xinghua exhibited the lowest total H2S emissions (p < 0.05). Of the six laying hen species, Xinghua was identified as the best species because it produced the lowest total amount of NH3 + H2S (39.94 µg). The results for the biochemical indicators showed that the concentration of volatile fatty acids (VFAs) from Zhusi was higher than that for the other five species, while the pH in Zhusi was lower (p < 0.01), and the concentrations of ammonium nitrogen (NH4+), uric acid and urea in Xinghua were lower than those in the other species (p < 0.01). Hyline had the highest change in SO42- concentration during the fermentation processes (p < 0.05). In addition, the results of the correlation analysis suggested that NH3 emission is positively related to urease activities but is not significantly related to the ureC gene number. Furthermore, H2S emission was observed to be significantly related to the reduction of SO42- but showed no connection with the aprA gene number. Overall, our findings provide a reference for future feeding programmes attempting to reduce odour pollution in the laying hen industry.


The effect of 6-hydroxydopamine on the antinociceptive action of morphine.
The role of brain catecholamines in the antinociceptive action of morphine was investigated. Intraventricular 6-hydroxydopamine which depleted brain noradrenaline in the rat had no effect on morphine's antinociceptive action but combined treatment with pargyline and 6-hydroxydopamine to further deplete brain dopamine potentiated morphine's action. It was also shown that when dopamine receptors were blocked, the antinociceptive action of morphine was potentiated whereas alpha- and beta-adrenoceptor antagonists had no effect. 6-Hydroxydopamine had two effects in mice tested on the hot-plate. It produced a hyperalgesia and antagonized the antinociceptive action of morphine. This antagonism of morphine appeared to be the result of the depletion of noradrenaline rather than dopamine. Intraventricular injection of both catecholamines restored the antinociceptive action of morphine in 6-hydroxydopamine-treated mice but dopamine was ineffective in the presence of a dopamine beta-hydroxylase inhibitor. It is suggested that the antinociceptive action of morphine is expressed by noradrenergic neurones in the mouse and by both noradrenergic and dopaminergic neurones in the rat.


Evolution in action through hybridisation and polyploidy in an Iberian freshwater fish: a genetic review.
The Iberian minnow Leuciscus alburnoides represents a complex of diploid and polyploid forms with altered modes of reproduction. In the present paper, we review the recent data on the origin, reproductive modes, and inter-relationships of the various forms of the complex, in order to predict its evolutionary potential. The complex follows the hybrid-origin model suggested for most other asexual vertebrates. Diploid and triploid females from the southern river basins exhibit reproductive modes that cannot be conveniently placed into the categories generally recognised for these vertebrate complexes, which imply continuous shifting between forms, where genomes derived from both parental ancestors are cyclically lost, gained or replaced. Replacement of nuclear genomes allow the introduction of novel genetic material, that may compensate for the disadvantages of asexual reproduction. Contrasting with most other vertebrate complexes, L. alburnoides males are fertile and play an important role in the dynamics of the complex. Moreover, diploid hybrid males may have initiated a tetraploidization process, when a diploid clonal sperm fertilised a diploid egg. This direct route to tetraploidy by originating fish with the right constitution for normal meiosis (symmetric), may eventually lead to a new sexually reproducing polyploid species. This case-study reinforces the significance of hybridisation and polyploidy in evolution and diversification of vertebrates.


Effective Connectivity of the Fronto-Parietal Network during the Tangram Task in a Natural Environment.
Although the neural basis underlying visuospatial reasoning has been widely explored by neuroimaging techniques, the brain activation patterns during naturalistic visuospatial reasoning such as tangram remains unclear. In this study, the directional functional connectivity of fronto-parietal networks during the tangram task was carefully inspected by using combined functional near-infrared spectroscopy (fNIRS) and conditional Granger causality analysis (GCA). Meanwhile, the causal networks during the traditional spatial reasoning task were also characterized to exhibit the differences with those during the tangram task. We discovered that the tangram task in a natural environment showed enhanced activation in the fronto-parietal regions, particularly the frontal cortex. In addition, a strong directional connectivity from the right prefrontal cortex to left angular gyrus was detected for the complex spatial reasoning condition of spatial reasoning task, whereas no effective connectivity was identified between the frontal and parietal cortices during the tangram task. Further correlation analyses showed that the behavioral performance in the spatial reasoning rather than the tangram task manifested the relationship with the connectivity between the frontal and parietal cortex. Our findings demonstrate that the tangram task measures a different aspect of the visuospatial reasoning ability which requires more trial-and-error strategies and creative thinking rather than inductive reasoning. In particular, the frontal cortex is mostly involved in tangram puzzle-solving, whereas the interaction between frontal and parietal cortices is regulated by the hands-on experience during the tangram task.


Electron microprobe analysis of frog skin epithelium: evidence for a syncytial sodium transport compartment.
For elucidation of the functional organization of frog skin epithelium with regard to transepithelial Na transport, electrolyte concentrations in individual epithelial cells were determined by electron microprobe analysis. The measurements were performed on 1-micron thick freeze-dried cryosections by an energy-dispersive X-ray detecting system. Quantification of the electrolyte concentrations was achieved by comparing the X-ray intensities obtained in the cells with those of an internal albumin standard. The granular, spiny, and germinal cells, which constitute the various layers of the epithelium, showed an identical behavior of their Na and K concentrations under all experimental conditions. In the control, both sides of the skin bathed in frog Ringer's solution, the mean cellular concentrations (in mmole/kg wet wt) were 9 for Na and 118 for K. Almost no change in the cellular Na occurred when the inside bathing solution was replaced by a Na-free isotonic Ringer's solution, whereas replacing the outside solution by distilled water resulted in a decrease of Na to almost zero in all layers. Inhibition of the transepithelial Na transport by ouabain (10(-4) M) produced in increase in Na to 109 and a decrease in K to 16. The effect of ouabain on the cellular Na and K concentrations was completely cancelled when the Na influx from the outside was prevented, either by removing Na or adding amiloride (10(-4) M). When, after the action of ouabain, Na was removed from the outside bathing solution, the Na and K concentration in all layers returned to control values. The latter effect could be abolished by amiloride. The other cell types of the epithelium showed under some experimental conditions a different behavior. In the cornified cells and the light cells, which occurred occasionally in the stratum granulosum, the electrolyte concentrations approximated those of the outer bathing medium under all experimental conditions. In the mitochondria-rich cells, the Na influx after ouabain could not be prevented by adding amiloride. In the gland cells, only a small change in the Na and K concentrations could be detected after ouabain. The results of the present study are consistent with a two-barrier concept of transepithelial Na transport. The Na transport compartment comprises all living epithelial layers. Therefore, with the exception of some epithelial cell types, the from skin epithelium can be regarded as a functional syncytium for Na.


Management of psychiatric in-patient violence: patient ethnicity and use of medication, restraint and seclusion.
Significant ethnic differences have been found previously on a forensic unit in the management of psychiatric patients after a violent incident. To study the management of violent incidents on all general wards in a large psychiatric hospital in South London. The main question is whether there are differences in the management of Black patients involved in violent incidents compared with White patients and, if so, what are the factors leading to it? All recorded violent incidents (1515 in total) on 14 general wards over three years (1994, 1996, 1998) were analysed using mixed logistic regression to estimate the odds ratio that the corresponding management decision (emergency medication, physical restraint, seclusion) was taken for Black patients compared with White patients after controlling for covariates and unobserved heterogeneity between subjects. Black patients were more likely than White patients to be given emergency medication and to be secluded after a violent incident, but not to be physically restrained. However, differences disappeared when the odds ratios were adjusted for other variables. Racial 'stereotyping' was unlikely to have played a major direct role in determining nurses' responses.


Amplitude modulation of nuclear Ca2+ signals in human skeletal myotubes: a possible role for nuclear Ca2+ buffering.
Video-rate confocal microscopy of Indo-1-loaded human skeletal myotubes was used to assess the relationship between the changes in sarcoplasmic ([Ca(2+)](S)) and nuclear ([Ca(2+)](N)) Ca(2+) concentration during low- and high-frequency electrostimulation. A single stimulus of 10 ms duration transiently increased [Ca(2+)] in both compartments with the same time of onset. Rate and amplitude of the [Ca(2+)] rise were significantly lower in the nucleus (4.0- and 2.5-fold, respectively). Similarly, [Ca(2+)](N) decayed more slowly than [Ca(2+)](S) (mono-exponential time constants of 6.1 and 2.5 s, respectively). After return of [Ca(2+)] to the prestimulatory level, a train of 10 stimuli was applied at a frequency of 1 Hz. The amplitude of the first [Ca(2+)](S) transient was 25% lower than that of the preceding single transient. Thereafter, [Ca(2+)](S) increased stepwise to a maximum that equalled that of the single transient. Similarly, the amplitude of the first [Ca(2+)](N) transient was 20% lower than that of the preceding single transient. In contrast to [Ca(2+)](S), [Ca(2+)](N) then increased to a maximum that was 2.3-fold higher than that of the single transient and equalled that of [Ca(2+)](S). In the nucleus, and to a lesser extent in the sarcoplasm, [Ca(2+)] decreased faster at the end of the stimulus train than after the preceding single stimulus (time constants of 3.3 and 2.1 s, respectively). To gain insight into the molecular principles underlying the shaping of the nuclear Ca(2+) signal, a 3-D mathematical model was constructed. Intriguingly, quantitative modelling required the inclusion of a satiable nuclear Ca(2+) buffer. Alterations in the concentration of this putative buffer had dramatic effects on the kinetics of the nuclear Ca(2+) signal. This finding unveils a possible mechanism by which the skeletal muscle can adapt to changes in physiological demand.


Apoptosis signalling is essential and precedes protein degradation in wasting skeletal muscle during catabolic conditions.
Activation of skeletal muscle proteolysis leads to wasting in many types of catabolic/chronic diseases. Protein breakdown is basically accomplished by the activation of the ubiquitin-proteasome system. Interestingly, several publications have shown that DNA fragmentation also occurs in skeletal muscle tissue during catabolism. The present review suggests that activation of apoptosis precedes protein breakdown associated with muscle wasting. In addition, the role of the different proteolytic systems and their relation with apoptosis is emphasized. Altogether, the data presented could be used for the design of new approaches for the treatment of muscle wasting diseases.


Cannabis Use and Prospective Long-Term Association with Anxiety: A Systematic Review and Meta-Analysis of Longitudinal Studies: Usage du cannabis et association prospective à long terme avec l'anxiété: une revue systématique et une méta-analyse d'études longitudinales.
Cannabis use is proposed as a risk factor for psychosis and is associated with depressive disorders. However, the relationship between recreational cannabis use and its longitudinal implications on anxiety conditions is less studied. The aim of this investigation is to systematically evaluate published literature and perform a meta-analysis of the data. A systematic search was performed of MEDLINE, Embase, and PsychINFO from inception to May 31, 2020, in addition to a hand search. Longitudinal studies that evaluated the relationship of cannabis use and development of anxiety were included. Where applicable, adjusted odds ratios (ORs) were extracted, pooled, and evaluated using random-effects meta-analysis. After screening of unique abstracts (n = 6835), the final evaluation included 24 studies, of which 10 reported ORs that were analyzed quantitatively. Cannabis use was significantly associated with increased odds of developing any anxiety conditions (OR = 1.25; 95% CI, 1.01 to 1.54). Cannabis use was not significantly associated with developing generalized anxiety disorder, panic disorder, or social anxiety disorder. Review of studies not reporting OR revealed mixed results but are suggestive of a link between cannabis use and increased rates/severity of anxiety. Published evidence suggests that cannabis use is likely associated with increased risk of anxiety in the long term but variability of study designs precludes declaration of a causal relationship. Awareness of this association is of relevance for both clinical practice and mental health policy implementation.


Injection practice in Kaski district, Western Nepal: a community perspective.
Previous studies have shown that unsafe injection practice is a major public health problem in Nepal but did not quantify the problem. The present community-based study was planned to: 1) quantify injection usage, 2) identify injection providers, 3) explore differences, if any, in injection usage and injection providers, and 4) study and compare people's knowledge and perception about injections between the urban and rural areas of Kaski district. A descriptive, cross-sectional mixed-methods study was conducted from July to November 2012, using a questionnaire based survey and focus group discussions (FGDs). A semi-structured questionnaire advocated by the World Health Organization was modified and administered to household heads and injection receivers in selected households and the FGDs were conducted using a topic guide. The district was divided into urban and rural areas and 300 households from each area were selected. Twenty FGDs were held. In 218 households (36.33%) [99 in urban and 119 in rural] one or more members received at least one injection. During the three month recall period, 258 subjects (10.44%) reported receiving injection(s) with a median of two injections. The average number of injections per person per year was calculated to be 2.37. Health care workers (34.8%), staff of medical dispensaries (37.7%), physicians (25.2%), and traditional healers (2.3%) were consulted by the respondents for their basic health care needs and for injections. Compared to urban respondents, more rural respondents preferred injections for fever (p < 0.001). People preferred injections due to injections being perceived by them as being powerful, fast-acting, and longer lasting than oral pills. More than 82% of respondents were aware of, and named, at least one disease transmitted by using unsterile syringes during injection administration or when syringes are shared between people. Less preference for injections and high awareness about the association between injections and injection-borne infections among the general population is encouraging for safe injection practice. However, respondents were not aware of the importance of having qualified injection providers for safe injections and were receiving injections from unqualified personnel.


Chromium and manganese levels in biological samples of normal and night blindness children of age groups (3-7) and (8-12) years.
This study was designed to compare the levels of chromium (Cr) and manganese (Mn) in scalp hair, blood, and urine of night blindness in children age ranged (3-7) and (8-12) years of both genders, comparing them to sex- and age-matched controls. A microwave-assisted wet acid digestion procedure, was developed as a sample pretreatment, for the determination of Cr and Mn in biological samples of night blindness children. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, blood and urine. The digests of all biological samples were analyzed for Cr and Mn by electrothermal atomic absorption spectrometry. The results indicated significantly higher levels of Cr, whilst low level of Mn in the biological samples (blood and scalp hair) of male and female night blindness children, compared with control subjects of both genders. These data present guidance to clinicians and other professional investigating deficiency of Mn and excessive level of Cr in biological samples (scalp hair and blood) of night blindness children.


Telehealth in Nursing Education: A Systematic Review.
Telehealth encompasses a broad variety of technologies and methods to deliver virtual medical, health, and education services. This systematic review examined the research completed in the past 10 years to determine the prevailing state of the science related to nursing education and telehealth. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was followed. The criteria for inclusion were nursing education research related to telehealth in an academic setting. A total of 13 articles met the inclusion criteria. A lack of rigorous research design, valid and reliable instrumentation, and measurable outcomes were noted. This review found a lack of research focused on nursing education associated with telehealth. One article validating 14 nursing telehealth entrustable professional activities with 52 corresponding competencies was found to have the potential to guide curricular integration, measure outcomes, and build a program of telehealth nursing education research. [J Nurs Educ. 2021;60(11):633-635.].


Physical, functional, nutritional and antioxidant properties of foxtail millet in Bangladesh.
The nutritional and phytochemical content of foxtail millet (Cetaria italica) makes it a viable food grain. In this study, we looked at foxtail millet in Bangladesh and analyzed its nutritional value, functional and physical characteristics. In addition, methanol, ethanol, and acetone: water: acetic acid (70: 29.50: 0.50) extracts of foxtail millet flour (FMF) were analyzed for their antioxidant properties (total phenolic and flavonoid content, total antioxidant capacity, ferric reducing antioxidant power (FRAP) assay, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity). According to this study, foxtail millet has favorable physiological and functional properties. FMF had protein at 11.65 ± 0.45 g/100 g, fat at 3.48 ± 0.04 g/100 g, carbohydrates at 75.33 ± 0.53 g/100 g, and crude fiber at 2.21 ± 0.03 g/100 g. Calcium was found at 47 ± 0.48 mg/100 g, iron at 4.59 ± 0.14 mg/100 g, potassium at 393 ± 15.87, sodium at 27.4 ± 1.21, magnesium at 45.40 ± 2.22, manganese at 0.71 ± 0.02, copper at 0.58 ± 0.04 and zinc at 2.30 ± 0.18 mg/100 g. The total flavonoid content (TFC) of the methanolic extract (68.26 ± 1.51 mg quercetin equivalents (QE)/100 g) was significantly (p < 0.05) higher than the extract of acetone: water: acetic acid. Total antioxidant capacity (TAC) (169.40 ± 3.45 mg ascorbic acid equivalents (AAE)/100 g) and total phenolic content (TPC) (51.35 ± 1.35 mg gallic acid equivalents (GAE)/100 g) of the methanolic extracts were significantly (p < 0.05) higher than others. The ascending order of DPPH free radical scavenging activity of FMF extract is as follows: acetone: acetic acid: water < ethanol < methanol. In the ferric reducing antioxidant power (FRAP) test, the reducing power of FMF extracts increased with the rise in sample concentration. Foxtail millet has potential as a functional food that could influence rural residents' diets and health.


Increased calcium influx mediates increased cardiac stiffness in hyperthyroid rats.
Cardiac remodeling (hypertrophy and fibrosis) and an increased left ventricular diastolic stiffness characterize models of hypertension such as the SHR and DOCA-salt hypertensive rats. By contrast, hyperthyroidism induces hypertrophy and hypertension, yet collagen expression and deposition is unchanged or decreased, whereas diastolic stiffness is increased. We determined the possible role of increased calcium influx in the development of increased diastolic stiffness in hyperthyroidism by administering verapamil (15 mg/[kg x d] orally) to rats given triiodothyronine (T3) (0.5 mg/[kg x d] subcutaneously for 14 d). Administration of T3 significantly increased body temperature (control: 36.7 +/- 0.2 degrees C; T3: 39.6 +/- 0.2 degrees C), left ventricular wet weight (control: 2.09 +/- 0.02 mg/kg; T3 3.07 +/- 0.07 mg/kg), systolic blood pressure (control: 128 +/- 5 mmHg; T3: 156 +/- 4 mmHg), and left ventricular diastolic stiffness (control: 20.6 +/- 2.0; T3: 28.8 +/- 1.4). Collagen content of the left ventricle was unchanged. Contractile response to noradrenaline in thoracic aortic rings was reduced. Relaxation in response to acetylcholine (ACh) was also reduced in T3-treated rats, whereas sodium nitroprusside response was unchanged. Verapamil treatment of hyperthyroid rats completely prevented the increased diastolic stiffness and systolic blood pressure while attenuating the increased body temperature and left ventricular weight; collagen content remained unchanged. ACh response in thoracic aortic rings was restored by verapamil. Thus, in hyperthyroid rats, an increased calcium influx is a potential mediator of the increased diastolic stiffness independent of changes in collagen.


Induction of tumor regression by intratumoral STING agonists combined with anti-programmed death-L1 blocking antibody in a preclinical squamous cell carcinoma model.
Cyclic dinucleotides (CDNs) are bacterial intracellular messengers that have demonstrated antitumor activity in melanoma and breast tumors, although their role in immunotherapy of head and neck squamous cell cancers (HNSCCs) has not been well investigated. We measured primary tumor growth rates, mechanism of antitumor activity, and efficacy of programmed death-L1 blockade combinatorial therapy in SCCFVII tumor-bearing C3H/HeOUJ mice undergoing intratumoral injections with RR-cyclic-di-guanine (synthetic CDG), CDG (natural cyclic-di-guanine), R848 (TLR 7/8 agonist), or phosphate buffered saline (PBS, control). Intratumoral CDN treatment groups showed decreased tumor size and enhanced splenocyte Th1 response when compared to the PBS treatment control group (p < .05). The RR-CDG tumor microenvironment showed upregulated interferon (IFN)-γ+CD8+ and programmed death-L1. Combining programmed death-L1 blocking antibody with RR-CDG induced regression of established tumors. This study demonstrates the antitumor effects of CDNs in a HNSCC cell line. These preclinical data strongly support the future clinical development of intratumoral CDN in patients with HNSCC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1086-1094, 2017.


Kiwifruit-derived supplements increase stool frequency in healthy adults: a randomized, double-blind, placebo-controlled study.
The worldwide growth in the incidence of gastrointestinal disorders has created an immediate need to identify safe and effective interventions. In this randomized, double-blind, placebo-controlled study, we examined the effects of Actazin and Gold, kiwifruit-derived nutritional ingredients, on stool frequency, stool form, and gastrointestinal comfort in healthy and functionally constipated (Rome III criteria for C3 functional constipation) individuals. Using a crossover design, all participants consumed all 4 dietary interventions (Placebo, Actazin low dose [Actazin-L] [600 mg/day], Actazin high dose [Actazin-H] [2400 mg/day], and Gold [2400 mg/day]). Each intervention was taken for 28 days followed by a 14-day washout period between interventions. Participants recorded their daily bowel movements and well-being parameters in daily questionnaires. In the healthy cohort (n = 19), the Actazin-H (P = .014) and Gold (P = .009) interventions significantly increased the mean daily bowel movements compared with the washout. No significant differences were observed in stool form as determined by use of the Bristol stool scale. In a subgroup analysis of responders in the healthy cohort, Actazin-L (P = .005), Actazin-H (P < .001), and Gold (P = .001) consumption significantly increased the number of daily bowel movements by greater than 1 bowel movement per week. In the functionally constipated cohort (n = 9), there were no significant differences between interventions for bowel movements and the Bristol stool scale values or in the subsequent subgroup analysis of responders. This study demonstrated that Actazin and Gold produced clinically meaningful increases in bowel movements in healthy individuals.


Detection of Pepino mosaic virus isolates from tomato by one-step reverse transcription loop-mediated isothermal amplification.
Loop-mediated isothermal amplification (LAMP) of DNA is a novel technique for the amplification of DNA under isothermal conditions. For the first time, we applied this method to develop a simple and sensitive tool for the detection of Pepino mosaic virus (PepMV). PepMV is an emerging pathogen that causes yield and quality losses in tomato crops. Specific RT-LAMP primers for PepMV detection were designed based on triple gene block sequences. The reaction was performed in a single tube at 65 °C for 30 min. The RT-LAMP assay is easy to perform and inexpensive, and it may be applied in the rapid and specific diagnosis of PepMV.


Consistency and Variation in School-Level Youth Sports Traumatic Brain Injury Policy Content.
The purpose of the study was to examine the consistency and variation in content of high school written traumatic brain injury (TBI) policies in relation to the three key tenets of youth sports TBI laws. A content analysis was conducted on written TBI policies retrieved from 71 high schools currently participating in High School Reporting Information Online. Each policy was independently analyzed by two trained coders. The number and percent of the policies reflecting the three key tenets of state youth sports TBI laws were described and compared on policy enforcement (i.e., strictness of language), policy description (i.e., details and definitions of the requirements), and policy implementation steps (i.e., specific steps for implementing the requirements). Direct quotes were identified to support quantitative findings. All 71 high school TBI policies contained at least two of the three main TBI law tenets, where 98.6% (n = 70) included the return to play tenet, 83.1% (n = 59) included the removal from play tenet, and 59.2% (n = 42) specified the distribution of TBI information sheets to student-athletes and their parents. Nearly half of the policies (49.3%, n = 35) required parents' signature while only 39.4% (n = 28) required students' signature on the TBI information sheet. The language exhibited wide variance across the 71 TBI policies regarding policy enforcement, policy description, and policy implementation specifications. All 71 TBI policies covered at least two of the three youth sports TBI law tenets, but with considerable variation. Future research should assess variations by schools within the same state and their impact on TBI rates in school athletics.


Phosphorylation of fructose bisphosphate aldolase in Trypanosoma brucei.
Methods were developed for in vivo labelling of trypanosome proteins with inorganic phosphate and the labelling of fructose bisphosphate aldolase and variant surface glycoprotein was investigated. It was found that the large pool size of phosphate in trypanosomes precludes detailed kinetic analyses. Aldolase contains low levels of phosphoserine but the function of this phosphorylation has yet to be determined.


Disappearance of cocaine from human hair after abstinence.
In this work the study of the disappearance of cocaine in hair is reported. The subject of the study is a woman who stopped the consumption of cocaine after a period of drug abuse of over 1 year. Hair samples were collected over a period of 10 months. During this time the absence of cocaine intake was monitored by the toxicological analysis of urine, performed every 2 days. After decontamination with methanol, the hair sample, cut in two segments (0-1.5 and 1.5-3 cm from the hair root) was added with cocaine-D(3) (internal standard), hydrolyzed and extracted with chloroform/isopropanol (9:1). The extract was evaporated to dryness, reconstituted in 25 microl of ethyl acetate and analyzed by GC-MS in SIM mode. The obtained results show that the incorporation of cocaine in hair decreased during the first 3 months after the last consumption and after this period of time no cocaine was found in the hair sections closest to the root.


Determinants of Clinical Behavior and Prognosis in Cushing's Disease: A Quest for Useful Biomarkers.
Cushing's disease (CD) is the most common cause of endogenous hypercortisolemia. The clinical management of this condition is complex and entails multiple therapeutic strategies, treatment of chronic comorbidities, and lifelong surveillance for recurrences and complications. The identification of robust, practical, and reliable markers of disease behavior and prognosis could potentially allow for a tailored and cost-efficient management of each patient, as well as for a reduction of the medical procedure-associated stress. For this purpose, multiple clinical, biochemical, imaging, histopathological, molecular, and genetic features have been evaluated over the years. Only a handful of them, however, have been sufficiently validated for their application in the routine care of patients with CD. This review summarizes the current status of the established and potential biomarkers of CD, bases for their use, proposed and/or established utility, as well as advantages and barriers for their implementation in the clinic. (Rev Invest Clin. 2022;74(5):244-57).


Surgical management of refractory venous stasis ulceration.
A 15-year experience with 27 patients, 20 to 75 years of age, with refractory venous stasis ulcers is presented. All patients had been managed with support hose, elevation, elastic wraps, Unna's paste boots, and graduated compression stockings. Because of multiple recurrences of their ulcers, the patients were offered surgical treatment to reduce the venous hypertension in the areas of ulceration. The 27 patients had 32 modified Linton procedures. Five had bilateral procedures. At the time of operation, 18 limbs had medial malleolar ulcers, five had bimalleolar ulcers, four had lateral ulcers, three had posterior ulcers, and two patients were free of ulcer. Medial incisions were used in 20 limbs, lateral incisions in six, medial and lateral incisions in three, and midposterior incisions in three. Split-thickness skin grafts were placed on six limbs the day of surgery and on 22 limbs 4 to 7 days later. Postoperative complications included deep venous thrombosis in two, partial flap necrosis in three, and cellulitis of the lower leg in three patients. Follow-up has ranged from 6 months to 10 years. During the most recent clinic visits, 21 limbs were completely healed, whereas six limbs had a recurrence of the ulcer. Five patients have been lost to follow-up. The good long-term results in 78% of the cases indicate that patients with recurrent venous stasis ulcers may receive lasting benefit from modified Linton procedures.


Effectiveness of "OralDETECT": a Repetitive Test-enhanced, Corrective Feedback Method Competency Assessment Tool for Early Detection of Oral Cancer.
Early diagnosis of oral cancer results in less aggressive treatment and improves the quality of life and overall 5-year survival rate. Well-trained dental professionals can play a crucial role in the early detection of oral cancers. The present study aims to determine the effectiveness of the training program "OralDETECT", a spaced repetitive, test-enhanced learning tool with a corrective feedback mechanism for early detection of oral cancer. Thirty-two dentists and 259 dental students from three Malaysian dental schools were involved in this study. All participants were trained and calibrated to recognize oral potentially malignant disorders (OPMD) and oral cancer using "OralDETECT", which is comprised of a series of pre-test, lecture, post-tests and review sessions. The percentage of correct answers (scores) for each test given by the participants was calculated and analysed using a paired t test. It was found that the overall percentage of diagnostic accuracy for both dental professionals and student groups increased to above 80% from the pre-tests to the final post-tests. There was a significant improvement in overall scores between the pre-tests and all three post-tests for the dental professional groups and the student groups. The diagnostic accuracy for individual OPMD and lesions suspicious of oral cancer also increased to above 80% for both groups. The results of our study demonstrate that the "OralDETECT" is an efficient and effective competency tool which can be used to train dental professionals and students for the early detection of OPMD and oral cancer.


Assessing emergency obstetric and newborn care: can performance indicators capture health system weaknesses?
Regular monitoring and assessment of performance indicators for emergency obstetric and newborn care can help to identify priorities to improve health services for women and newborns. The aim of this study was to perform a district wide assessment of emergency obstetric and newborn care performance and identify ways for improvement. Facility assessment of 13 dispensaries, four health centers and one district hospital in a rural district in Tanzania was performed in two data collection periods in 2014. Assessment included a facility walk-through to observe facility infrastructure and interviews with facility in-charges to assess available services, staff and supplies. In addition facility statistics were collected for the year 2013. Results were discussed with district representatives. Approximately 65% of expected births took place in health facilities and 22% of women with complications were treated in facilities expected to provide emergency care. None of the facilities was, however, able to perform at the expected level for emergency obstetric and newborn care since not all required signal functions could be provided. Inadequate availability of essential drugs such as uterotonics, antibiotics and anticonvulsants as well as lack of ability to perform vacuum extraction and blood transfusion limited performance. Performance of emergency obstetric and newborn care in Magu District was not in accordance with expected guidelines and highly influenced by lack of available resources and an insufficiently functioning health care system. Improving assessment approaches, to look beyond the signal functions, can capture weaknesses in the system and will help to understand poor performance and identify locally applicable ways for improvement.


Complete genome sequence analysis of a novel Staphylococcus phage StAP1 and proposal of a new species in the genus Silviavirus.
Bacteriophage StAP1 was isolated from a soil sample infecting Staphylococcus aureus and S. xylosus. Its genome was found to be 135,502 base pairs (bp) long with 30.00 mol% G+C content and 192 open reading frames. While no tRNA encoding genes were identified, 7 mobile elements were found to interrupt five StAP1 open reading frames. Comparative genomic and proteomic analysis consistently supports the establishment of a new species in the genus Silviavirus.


Prevalence of enteropathogenic and enterotoxigenic Escherichia coli in children with and without diarrhoea in Esteli, Nicaragua.
In Esteli, Las Segovias, Nicaragua, the frequency of isolations of enteropathogenic (EPEC), and enterotoxigenic E. coli (ETEC) was investigated in 100 children with (n = 50) and without diarrhoea (n = 50). EPEC was found to be significantly (p < 0.05) more frequent in diarrhoeal (16%) than in healthy children (4%). Detailed analyses revealed that 6 serotypes of E. coli were involved. Isolation of ETEC was not statistically significantly different (p > 0.05) in diarrhoeal (28%) and healthy children (16%). Determination of the susceptibility of isolated E. coli indicated a high level of resistance to common antimicrobial drugs. These resistant strains of E. coli might become a health problem in this part of Nicaragua.


Advancing evolution: Bacteria break down gene silencer to express horizontally acquired genes.
Horizontal gene transfer advances bacterial evolution. To benefit from horizontally acquired genes, enteric bacteria must overcome silencing caused when the widespread heat-stable nucleoid structuring (H-NS) protein binds to AT-rich horizontally acquired genes. This ability had previously been ascribed to both anti-silencing proteins outcompeting H-NS for binding to AT-rich DNA and RNA polymerase initiating transcription from alternative promoters. However, we now know that pathogenic Salmonella enterica serovar Typhimurium and commensal Escherichia coli break down H-NS when this silencer is not bound to DNA. Curiously, both species use the same protease - Lon - to destroy H-NS in distinct environments. Anti-silencing proteins promote the expression of horizontally acquired genes without binding to them by displacing H-NS from AT-rich DNA, thus leaving H-NS susceptible to proteolysis and decreasing H-NS amounts overall. Conserved amino acid sequences in the Lon protease and H-NS cleavage site suggest that diverse bacteria degrade H-NS to exploit horizontally acquired genes.


Lymphocyte subpopulations in blood and cerebrospinal fluid from patients with subacute sclerosing panencephalitis.
Lymphocyte subpopulations in peripheral blood (PB) and cerebrospinal fluid (CSF) from 26 children affected with subacute sclerosing panencephalitis (SSPE) and from 13 controls with various neurological diseases without any immunological implication were examined for surface markers. SSPE patients were found to have significantly lower %s of E-rosette forming cells (RFC) (T lymphocytes) and of EA-RFC (TG lymphocytes, suppressor T cells) in both CSF and PB. No difference was found in EAC-RFC (B lymphocytes) either in CSF or PB. The low EA-RFC values can be explained by genetic factors, immune complexes or virus infection, and they could account for the hypersynthesis of oligoclonal immunoglobulins in the central nervous system. Longitudinal studies performed in 6 SSPE patients during isoprinosine therapy revealed a time-dependent decrement of the %s of E- and EA-RFC in CSF. It cannot be affirmed whether this is related to the disease or to the therapy.


Multi-focal oral non-Hodgkin's lymphoma in an AIDS patient.
Cases of non-Hodgkin's lymphoma (NHL) occurring in immunosuppressed patients, including those who are infected with the human immunodeficiency virus, may develop in areas other than the lymph nodes. In AIDS-associated NHL, about 5% of cases of extranodal NHL are intra-oral. This case report describes the presentation of malignant non-Hodgkin's lymphoma in the mouth of a man who had AIDS. The lesion arose on separate occasions at three distinct sites, spontaneously regressing at each site prior to appearing at another intra-oral site.


Characterization of hemoglobin adduct formation in mice and rats after administration of [14C]butadiene or [14C]isoprene.
Occupational exposures to 1,3-butadiene or isoprene occur through their use in the manufacture of rubber and other related polymer products. The purpose of this study was to determine if butadiene or isoprene administration would result in the formation of adducts with blood hemoglobin (Hb), and if such adducts can be used as a measure of previous exposure(s). Male B6C3F1 mice and male Sprague-Dawley rats were injected intraperitoneally with 1, 10, 100, or 1000 mumol [14C]butadiene or 0.3, 3.0, 300, 1000, or 3000 mumol [14C]isoprene per kilogram body weight. Animals were killed 24 hr later. Globin was isolated from blood samples and was analyzed for 14C by liquid scintillation spectroscopy. Hb adduct formation was linearly related to administered doses up to 100 mumol [14C]butadiene or 500 mumol [14C]isoprene per kilogram body weight for mice and rats, respectively. For [14C]butadiene, the efficiency of Hb adduct formation in mice and rats within the linear response range was 0.177 +/- 0.003 and 0.407 +/- 0.019 (pmol of 14C-adducts/mg globin)/(mumol of retained [14C]butadiene/kg body wt), respectively (mean +/- SE; n = 18). For [14C]isoprene, these values for mice and rats were 0.158 +/- 0.035 and 0.079 +/- 0.016 (pmol of 14C-adducts/mg globin)/(mumol of retained [14C]isoprene/kg body wt), respectively (mean +/- SE; n = 12). Hb adducts also accumulated linearly after repeated daily administration of 100 mumol [14C]butadiene or 500 mumol [14C]isoprene per kilogram body wt to mice and rats, respectively, for 3 days. [14C]Butadiene-derived Hb adducts in blood showed lifetimes of approximately 24 and approximately 65 days for mice and rats, respectively, which correlate with the reported lifetimes for red blood cells in these rodent species. Thus, levels of butadiene- or isoprene-derived adducts on Hb in circulating blood may be a useful measure of prior repeated exposures to these compounds.


Real-time PCR for rapid genotyping of angiotensin-converting enzyme insertion/deletion polymorphism.
To develop a real-time PCR technique for detection of the insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) gene. Three primers were designed for performing real-time PCR in the presence of SYBR Green I as flurochrome followed by melting curve analysis. Forty human genomic DNA that have been genotyped by two-rounds of conventional PCR were used for evaluation of this technique. Melting curve analysis indicated the melting peak at 73.9 degrees C and 76.2 degrees C corresponding to the presence of I and D alleles, respectively. Comparable genotyping results were obtained by both conventional and real-time PCR. Besides, the mistyping of ID allele individuals by the first run of conventional PCR were accurately genotyped by single-tube real time PCR. The real-time PCR method presented in this study provides a rapid and sensitive way for genotyping of ACE gene that may be suitable for large-scale clinical and epidemiologic study.


Mechanomyographic response to transcranial magnetic stimulation from biceps brachii and during transcutaneous electrical nerve stimulation on extensor carpi radialis.
Transcranial magnetic stimulation (TMS) elicits short latency excitatory responses in the target muscles, termed motor evoked potential (MEP). When TMS is delivered during a voluntary contraction, the MEP is followed by a period of silence called silent period (SP). These MEP parameters are in general recordable by electromyography (EMG). Mechanomyography (MMG) on the other hand is the mechanical counterpart of EMG. Thus, this study has been conducted to observe whether the MEP parameters from MMG signals showed similar trait of EMG recordings. Five normal healthy male subjects were included in this study. The subjects were required to perform right biceps brachii muscles contraction at diverse graded of load level at 5, 10, 20, 30, 40, 60, and 100% maximum voluntary contraction (MVC). MEPs by single pulse TMS on left hemisphere were obtained from both EMG electrode and MMG accelerometer at rest and at different levels of predetermined load level. MEP amplitude and area obtained both from EMG and MMG record were increased with the increase of muscle contraction with a maximum of 60% MVC. With increasing the level of contraction there was a shortening of onset latency and decreasing in the length of silent period in both EMG and MMG signals. We also recorded the EMG- and MMG-MEP from the right extensor carpi radialis muscle during transcutaneous electric nerve stimulation in order to observe neural changes in sensory stimulation from both EMG and MMG responses. The EMG-MEP was not visible in electrical artifact whereas it was obvious in MMG responses. In accordance with other study, this study showed that the voluntary contraction of biceps brachii muscle influenced the MEP parameter which are moreover obtainable by MMG even in electrical noise may provide insight for future study.


Close to the Bone: Tissue-Specific Checkpoint Immunotherapy Evasion.
Primary or secondary resistance to immune checkpoint therapy is often analyzed in primary tumors rather than metastases. In this issue of Cell, Jiao et al. show that the site of metastatic diffusion matters and bones empower a particularly hostile environment.


Plant cell cycle regulators: Mitogen-activated protein kinase, a new regulating switch?
Cell cycle is essential for the maintenance of genetic material and continuity of a species. Its regulation involves a complex interplay between multiple proteins with diverse molecular functions such as the kinases, transcription factors, proteases and phosphatases. Every step of this cycle requires a certain combination of these protein regulators which paves the way for the next stage. It is now evident that plants have their own unique features in the context of cell cycle regulation. Cell cycle in plants is not only necessary for maintenance of its physio-morphological parameter but it also regulates traits important for mankind like grain or fruit size. This makes it even more important to understand how plants regulate its cell cycle amidst various a/biotic stresses it is subjected to during its lifetime. The association of MAPK signaling pathways with every major developmental and stress response pathways in plants raises the question of its potential role in cell cycle regulation. There are number of cell cycle regulating proteins with putative sites for MAPK phosphorylation. The MAPK signaling pathway may directly or in a parallel pathway regulate the plant cell cycle. Unraveling the role of MAPK in cell cycle will open up new arenas to explore.


Relationship between readiness for and processes of change in a sample of alcohol dependent males.
Previous research (Isenhart, 1997) has shown a relationship between pre-treatment stages of change and outcome. The objective of this project was to evaluate whether certain processes of change measures predicted stages of change measures. A stepwise multiple regression model used Contemplation, Determination, and Action scores as dependent variables and process of change scores and measures of alcohol dependence severity and pre-treatment alcohol consumption as independent variables. The only process of change scale consistently correlated with the Contemplation, Determination, and Action scales was Self-reevaluation. Self-reevaluation was negatively correlated with Contemplation and positively correlated with Determination and Action. These results suggest that as patients become more discouraged and frustrated with their alcohol use, they experience less ambivalence, are more likely to acknowledge that a problem exists, and are more willing to take action to address that problem. Implications and limitations of these findings are provided and inconsistencies between previous studies and these results are discussed.


[Soft tissue and bone defects of the tibia. Treatment with pedicled muscle transfer and a microvascular anastomosed myocutaneous flap].
The free tissue transfer by microvascular anastomoses has opened new dimensions in reconstructive surgery. However a free microvascular myocutaneous flap should only be used in case of a local pedicled flap being impossible. In treating complicated defects of soft tissue and bones a clear cut gradation of therapeutic steps has to be observed: 1. control of wound infection, 2. wound debridement, 3. soft tissue repair, 4. bone reconstruction.


Iron excess affects release of neutrophil extracellular traps and reactive oxygen species but does not influence other functions of neutrophils.
Neutrophils apply several antimicrobial strategies including degranulation, phagocytosis, the generation of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs) to fight pathogens. Iron is considered to be an invaluable constituent of host immune defense and plays a dual role in immunity. It is a well-known component of antimicrobial proteins and is a necessary microelement for pathogen survival. The aim of this study was to broaden the knowledge regarding the impact of iron on the function of neutrophils. Neutrophils from healthy blood donors and patients with mild iron-deficiency anemia and HL-60 cells differentiated toward granulocyte-like cells were incubated with Fe2+ , Fe3+ or holo-transferrin (holo-Tf). Moreover, we isolated murine neutrophils of HFE gene knockout (KO) mice and mice fed iron-deficient, iron-equivalent and high-iron diets. We analyzed the release of NETs, phagocytosis, degranulation of azurophilic granules, ROS release, bactericidal activity of granulocytes against Escherichia coli and neutrophil elastase (NE) activity. We show that holo-Tf inhibits the release of NETs stimulated by phorbol 12-myristate 13-acetate by inhibiting NE activity. Studies performed in mice models reveal that iron overload inhibits the release of NETs and ROS production in neutrophils isolated from HFE KO mice and mice fed a high-iron diet. No impact of a low-iron diet on neutrophil phagocytosis, ROS production or release of NETs was observed. Our study underscores the physiological significance of iron in neutrophil function, specifically in the release of NETs.


Tapeworms.
Dogs and cats become infected with tapeworms by ingesting intermediate hosts that contain encysted juvenile tapeworms called larvae. The dog or cat is said to be the definitive host because it shelters the sexually reproductive, egg-producing stage of the tapeworm. The intermediate hosts, which are vertebrates in the case of Taenia and Mesocestoides and insects in the case of Dipylidium and Hymenolepis, become infected by ingesting unhatched but infective tapeworm eggs discharged in the feces of the dog or cat. The relatively less common Diphyllobothrium and Spirometra tapeworms discharge eggs that are undeveloped when passed in the feces and must fall into water to undergo development to the coracidium stage. Diphyllobothrium and Spirometra may have two or three aquatic intermediate hosts in series. The first of these, a copepod, ingests the free-swimming coracidium or ciliated oncosphere that has hatched from the egg. The final intermediate host containing the larva (plerocercoid) infective for the dog or cat is an aquatic vertebrate (fish, frog, water snake). Thus, dogs and cats become infected with tapeworms by eating uncooked meat or fish or by ingesting certain insects. These intermediate hosts are infected with juvenile tapeworms called larvae, which are the infective form for the dog or cat. The intermediate hosts, in turn, become infected by ingesting tapeworm eggs discharged in the feces of the dog or cat or, in the case of Diphyllobothrium and Spirometra, by ingesting coracidia that have subsequently developed in and hatched from such eggs. By far the most common tapeworms of dogs and cats in North America are D. caninum, T. pisiformis, and T. hydatigena. Therefore, the most common sources of tapeworm infection are, respectively, fleas, wild rabbits, and the uncooked meat and offal of ruminants and swine. Whenever a dose of tapeworm remedy is administered or dispensed, the client should be informed of these potential sources of reinfection. There is considerable overlap in the spectra of activity of currently available cestocides. Mebendazole, fenbendazole, niclosamide, bunamidine, and praziquantel are all effective against Taenia spp. Bunamidine is the drug of choice against Spirometra, Diphyllobothrium, and Mesocestoides. Praziquantel is the drug of choice against Echinococcus and Dipylidium.


The predictive validity of the Strengths and Difficulties Questionnaire for child attention-deficit/hyperactivity disorder.
We need accurate screening measures for attention-deficit/hyperactivity disorder (ADHD) to ensure that children with the disorder are referred for assessment without raising concern for children with normal behaviour. The Strengths and Difficulties Questionnaire (SDQ) provides hyperactivity-inattention (HI), conduct, emotional and peer problem subscales and impact scores that may be used for screening. The aim of the study was to investigate the predictive validity of the Danish version of the parent SDQ HI subscale at the child age of 7 years for subsequent clinically diagnosed ADHD (age 8-15 years). Participants were part of the Danish National Birth Cohort (N = 51,096), and children with ADHD were identified through the Danish National Health registries (n = 943). Receiver operating characteristic analysis showed that the screening accuracy for the HI scores was good (area under the curve = .84). With Cox multivariate regression analysis, we found that SDQ HI subscale scores ≥ 7 with impact gave a nearly 14-fold [hazard ratio (HR) = 13.59] increased risk for ADHD, while conduct and emotional problems indicated low risk (HRs of 1.62 and 1.67, respectively). For the HI subscale to be a sensitive measure for ADHD, a low cutoff (4) was needed, but gave many false screening positives (PPV = .02). Although the diagnostic accuracy of the parent version of the SDQ HI subscale for predicting ADHD was good, our results question the feasibility of screening the general child population for ADHD with only the parent SDQ HI subscale.


Non-pyramidal hippocampal projection neurons: a light and electron microscopic study.
Following injections of horseradish peroxidase conjugated with wheat germ agglutinin into the medial nucleus accumbens of the rat, a large number of projecting pyramidal neurons in the hippocampus were retrogradely labelled. In addition to this major projection, a few retrogradely labelled cells were tentatively identified at the light microscopic level as non-pyramidal neurons. These presumptive non-pyramidal neurons were found in all hippocampal layers, although they were mainly outside the stratum pyramidale, in the stratum oriens. Ultrastructurally, in serial sections, the non-pyramidal nature of 20 of these neurons was confirmed by their characteristic features such as deeply indented nuclei, occasional intranuclear inclusions, and symmetric and asymmetric synaptic contacts with their somata. Possible transmitters used by these neurons are discussed.


Lack of alpha-adrenergic component in the chronotrophic action of serotonin on isolated atrium of hamster.
Effects of serotonin on alpha-adrenergic receptors of isolated hamsters' atria preparation were investigated. The positive chronotropic effect of serotonin on isolated atria of the hamster is not related with postsynaptic alpha-adrenergic receptors.


[Development and study of three-dimensional CT scanning system for dental cast measurement and analysis].
To develop a computer assisted CT scanning system for 3D dental cast measurement and to study its reliability. 20 dental stone casts were scanned by helical CT and captured a series digital sliced radiographs of them. The program which was developed by Visual C 6.0 language and run under the Windows surroundings rebuilt the 3D graphics and measured the coordinate of the dental cast. These dental casts were scanned and measured to test the reliability of the system, contrasting with manual measurement. There was no significant difference between 3D CT scanning and manual measurement (P > 0.05). The system is a valuable computer assisted system for clinical diagnosis and treatment of malocclusion.


Establishment of bovine trophoblast stem cells.
Here, we report that a chemical cocktail (LCDM: leukemia inhibitory factor [LIF], CHIR99021, dimethinedene maleate [DiM], minocycline hydrochloride), previously developed for extended pluripotent stem cells (EPSCs) in mice and humans, enables de novo derivation and long-term culture of bovine trophoblast stem cells (TSCs). Bovine TSCs retain developmental potency to differentiate into mature trophoblast cells and exhibit transcriptomic and epigenetic (chromatin accessibility and DNA methylome) features characteristic of trophectoderm cells from early bovine embryos. The bovine TSCs established in this study will provide a model to study bovine placentation and early pregnancy failure.


mTORC1/rpS6 and mTORC2/PKC regulate spermatogenesis through Arp3-mediated actin microfilament organization in Eriocheir sinensis.
Mammalian target of rapamycin (mTOR) is a crucial signaling protein regulating a range of cellular events. Numerous studies have reported that the mTOR pathway is related to spermatogenesis in mammals. However, its functions and underlying mechanisms in crustaceans remain largely unknown. mTOR exists as two multimeric functional complexes termed mTOR complex 1 (mTORC1) and mTORC2. Herein, we first cloned ribosomal protein S6 (rpS6, a downstream molecule of mTORC1) and protein kinase C (PKC, a downstream effector of mTORC2) from the testis of Eriocheir sinensis. The dynamic localization of rpS6 and PKC suggested that both proteins may be essential for spermatogenesis. rpS6/PKC knockdown and Torin1 treatment led to defects in spermatogenesis, including germ cell loss, retention of mature sperm and empty lumen formation. In addition, the integrity of the testis barrier (similar to the blood-testis barrier in mammals) was disrupted in the rpS6/PKC knockdown and Torin1 treatment groups, accompanied by changing in expression and distribution of junction proteins. Further study demonstrated that these findings may result from the disorganization of filamentous actin (F-actin) networks, which were mediated by the expression of actin-related protein 3 (Arp3) rather than epidermal growth factor receptor pathway substrate 8 (Eps8). In summary, our study illustrated that mTORC1/rpS6 and mTORC2/PKC regulated spermatogenesis via Arp3-mediated actin microfilament organization in E. sinensis.


Visible-Light-Driven, Radical-Triggered Tandem Cyclization of o-Hydroxyaryl Enaminones: Facile Access to 3-CF2 /CF3-Containing Chromones.
A practical and straightforward synthetic route to construct a variety of 3-CF2/CF3-containing chromones via photoredox catalysis was developed. This novel protocol features a visible-light-induced radical-triggered tandem cyclization.


A macrophage-endothelial immunoregulatory axis ameliorates septic acute kidney injury.
The most common cause of acute kidney injury (AKI) in critically ill patients is sepsis. Kidney macrophages consist of both F4/80hi and CD11bhi cells. The role of macrophage subpopulations in septic AKI pathogenesis remains unclear. As F4/80hi macrophages are reported to contribute to immunomodulation following injury, we hypothesized that selective depletion of F4/80hi macrophages would worsen septic AKI. F4/80hi macrophages were depleted via diphtheria toxin injection in CD11cCre(+)/CX3CR1dtr/wt (F4/80 MKO mice) compared to CD11cCre(-)/CX3CR1dtr/wt (F4/80 MWT) mice. F4/80 MWT and F4/80 MKO mice were subjected to sham or cecal ligation and puncture to induce sepsis. Compared to F4/80 MWT mice, F4/80 MKO mice displayed worsened septic AKI at 24 hours as measured by serum creatinine and histologic injury scoring. Kidneys from F4/80 MKO mice elaborated higher kidney interleukin-6 levels. Mechanistically, single cell RNA sequencing identified a macrophage-endothelial cell immunoregulatory axis that underlies interleukin-6 expression. F4/80hi macrophages expressed interleukin-1 receptor antagonist and limited interleukin-6 expression in endothelial cells. In turn, anti-interleukin-6 therapy ameliorated septic AKI in F4/80 MKO mice. Thus, F4/80hi macrophages express interleukin-1 receptor antagonist and constrain interleukin-6 generation from endothelial cells to limit septic AKI, representing a targetable cellular crosstalk in septic AKI. These findings are particularly relevant owing to the efficacy of anti-interleukin-6 therapies during COVID-19 infection, a disease associated with high rates of AKI and endothelial dysfunction.


Alternative splicing of a barley gene results in an excess-tillering and semi-dwarf mutant.
An excess-tillering semi-dwarf gene Hvhtd was identified from an EMS-induced mutant in barley and alternative splicing results in excess-tillering semi-dwarf traits. Tillering and plant height are important traits determining plant architecture and grain production in cereal crops. This study identified an excess-tillering semi-dwarf mutant (htd) from an EMS-treated barley population. Genetic analysis of the F1, F2, and F2:3 populations showed that a single recessive gene controlled the excess-tillering semi-dwarf in htd. Using BSR-Seq and gene mapping, the Hvhtd gene was delimited within a 1.8 Mb interval on chromosome 2HL. Alignment of the RNA-Seq data with the functional genes in the interval identified a gene HORVU2Hr1G098820 with alternative splicing between exon2 and exon3 in the mutant, due to a G to A single-nucleotide substitution at the exon and intron junction. An independent mutant with a similar phenotype confirmed the result, with alternative splicing between exon3 and exon4. In both cases, the alternative splicing resulted in a non-functional protein. And the gene HORVU2Hr1G098820 encodes a trypsin family protein and may be involved in the IAA signaling pathway and differs from the mechanism of Green Revolution genes in the gibberellic acid metabolic pathway.


Assessing the evidence for organised cancer screening programmes.
The aim of this study was to review the evidence in the literature for organised cancer screening programmes. A Medline search for publications related to organised cancer screening programmes and their components was done. While there is a broad descriptive literature on various cancer screening programmes, there are few published studies that evaluate the impact of organised cancer screening. Most of the evidence to date is from Scandinavian cervical and breast cancer screening programmes. There is a moderate amount of literature that evaluates specific components of cancer screening programmes (such as quality control and recruitment). There is a substantial body of literature on organised cancer screening programmes. However, the studies tend to describe organised screening programmes rather than evaluate their effectiveness relative to opportunistic screening. Furthermore, most studies focus on individual components of organised screening programmes, rather than on the programmes as a whole. More research is needed that directly compares organised with opportunistic cancer screening.


Preferential expression of the vasoactive intestinal peptide (VIP) receptor VPAC1 in human cord blood-derived CD34+CD38- cells: possible role of VIP as a growth-promoting factor for hematopoietic stem/progenitor cells.
Primitive hematopoietic progenitor cells such as severe combined immunodeficiency- repopulating cells and long-term culture-initiating cells are enriched in CD34+CD38- cells derived from various stem cell sources. In this study, to elucidate the features of such primitive cells at the molecular level, we tried to isolate genes that were preferentially expressed in umbilical cord blood (CB)-derived CD34+CD38- cells by subtractive hybridization. The gene for VPAC1 receptor, a receptor for the neuropeptide vasoactive intestinal peptide (VIP), was thereby isolated and it was shown that this gene was expressed in both CD34+CD38- and CD34+CD38+ CB cells and that the expression levels were higher in CD34+CD38- CB cells. Next, we assessed the effects of VIP on the proliferation of CD34+ CB cells using in vitro culture systems. In serum-free single-cell suspension culture, VIP enhanced clonal growth of CD34+ CB cells in synergy with FLT3 ligand (FL), stem cell factor (SCF), and thrombopoietin (TPO). In serum-free clonogenic assays, VIP promoted myeloid (colony-forming unit-granulocyte/macrophage (CFU-GM)) and mixed (CFU-Mix) colony formations. Furthermore, in Dexter-type long-term cultures, VIP increased colony-forming cells at week 5 of culture. These results suggest that VIP functions as a growth-promoting factor of CB-derived hematopoetic progenitor cells.


The consistency of circadian blood pressure and heart rate patterns over three months in women employed in sedentary office jobs.
The purpose of this study was to evaluate the consistency of the circadian patterns of blood pressure (BP) and heart rate (HR) variation over a three-month time frame in women employed outside the home. The subjects were 157 healthy women of varying ethnicity (age = 38.2 ± 8.9) who all worked in similar positions at two major medical centers in New York City. Each wore an ambulatory BP monitor during the course of three mid-week work days approximately one month apart. Hourly BPs and HRs were calculated from 9 am to 6 am the following morning and compared among the three days using anova and t tests. The results indicate that there were virtually no differences in the mean hourly levels of any parameter during the waking period across the three days of assessment. However, mean hourly levels of systolic BP significantly declined from 12 pm to 4 am (P < .04, P = .001, P < .001, P = .001, P = .009, respectively) on the third assessment day compared to the first. Because BP and HR respond to environmental demands in an allostatic fashion, the consistency in the waking patterns of BP and HR variation suggest that the patterns of demands on a workday are reasonably stable in this sample of women. The decline in systolic pressures from 12 pm to 4 am over the three assessments may indicate an improving ability to sleep with the monitor over time.


[Paraganglioma of spermatic cord].
Paragangliomas can exist anywhere in the distribution of neural crest derived cells. In the spermatic cord, they are exceedingly rare. We report a case of histologically discovery, occurring in a man of 50 years who had a para-testicular mass, painless, firm without other signs associated. In view of this observation and a review of the literature, we propose to establish the epidemiological profile and study the prognostic and the clinicopathologic features of this tumor.


The Unacceptable Morbidity of Negative Laparoscopic Appendicectomy.
One of the most common acute conditions managed by general surgeons is acute appendicitis. Laparoscopic appendicectomy (LA) is the surgical technique used by many surgeons. The aims of this study were to define our unit's negative appendicectomy rate and compare the outcomes associated with removal of a normal appendix with those for acute appendicitis in patients having LA. A single-centre retrospective case note review of patients undergoing LA for suspected acute appendicitis was performed. Patients were divided into positive and negative appendicectomy groups based on histology results. The positive group was subdivided into uncomplicated and complicated (perforated and/or gangrenous) appendicitis. Outcomes were compared between groups. There were 1413 patients who met inclusion criteria, 904 in the positive group and 509 in the negative group, an overall negative appendicectomy rate of 36.0%. Morbidity rates (6.3% vs. 6.9%; P = 0.48) and types of morbidity were the same for negative appendicectomy and uncomplicated appendicitis. There was no significant difference in complication severity (all P > 0.17) or length of stay (2.3 vs. 2.6 days; P = 0.06) between negative appendicectomy and uncomplicated appendicitis groups. Patients with complicated appendicitis had a significantly higher morbidity rate compared to negative and uncomplicated groups (20.1% vs. 6.3% and 20.1% vs. 6.9%; both P < 0.001). The morbidity of negative LA is the same as LA for uncomplicated appendicitis. The morbidity of LA for complicated appendicitis is significantly higher. The selection criteria for LA in our unit needs to be reviewed to address the high negative appendicectomy rate and avoid unnecessary surgery and its associated morbidity.


Hysteroscopic resection vs ultrasound-guided dilation and evacuation for treatment of cesarean scar ectopic pregnancy: a randomized clinical trial.
Cesarean scar ectopic pregnancy is a type of ectopic pregnancy in which the fertilized egg is implanted in the muscle or fibrous tissue of the scar after a previous cesarean delivery. The condition can be catastrophic if not managed on time and can lead to significant morbidity and mortality. Several approaches have been studied for the management of cesarean scar ectopic pregnancy in women who opted for termination of pregnancy with no consensus on the best treatment modality reached so far. This study aimed to compare the success rate of hysteroscopic resection vs ultrasound-guided dilation and evacuation for the treatment of cesarean scar ectopic pregnancy. This was a parallel group, nonblinded, randomized clinical trial conducted at a single center in Italy. Women with singleton gestations at <8 weeks and 6 days of gestation were included in the study. Inclusion criteria were women with a cesarean scar ectopic pregnancy with positive embryonic heart activity who opted for termination of pregnancy. Patients were randomized 1:1 to receive either hysteroscopic resection (ie, intervention group) or ultrasound-guided dilation and evacuation (ie, control group). Both groups received 50 mg/m2 of methotrexate intramuscularly at the time of randomization (day 1) and another dose at day 3. A third dose of methotrexate was planned in case of persistence of positive fetal heart activity at day 5. Participants received either ultrasound-guided dilation and evacuation or hysteroscopic resection from 1 to 5 days after the last dose of methotrexate. Hysteroscopic resection was performed under spinal anesthesia using a 15 Fr bipolar mini-resectoscope. Dilation and evacuation were performed by vacuum aspiration with a Karman cannula, followed by sharp curettage, if necessary, under ultrasound guidance. The primary outcome was the success rate of the treatment protocol, defined as no further treatment required until the complete resolution of the cesarean scar ectopic pregnancy. Resolution of the cesarean scar ectopic pregnancy was evaluated based on decline of beta-hCG and the absence of residual gestational material in the endometrial cavity. Treatment failure was defined as the necessity for further treatment required until the complete resolution of the cesarean scar ectopic pregnancy. A sample size calculation indicated that 54 participants were required to test the hypothesis RESULTS: A total of 54 women were enrolled and randomized. Number of previous cesarean deliveries ranged from 1 to 3. Overall, 10 women received a third dose of methotrexate with 7 of 27 (25.9%) participants in the hysteroscopic resection group and 3 of 27 (11.1%) in the dilation and evacuation group. The success rate was 100% (27/27) in the hysteroscopic resection group and 81.5% (22/27) in the dilation and evacuation group (relative risk, 1.22; 95% confidence interval, 1.01-1.48). Additional procedures were required in 5 cases of the control group, namely 3 hysterectomies, 1 laparotomic uterine segmental resection, and 1 hysteroscopic resection. The length of stay in the hospital was 9.0±2.9 days in the intervention group and 10.0±3.5 days in the control group (mean difference, -1.00 days; 95% confidence interval, -2.71 to 0.71). No cases of admission to intensive care unit or maternal death were reported. Hysteroscopic resection was associated with an increased success rate in the treatment of cesarean scar ectopic pregnancy when compared with ultrasound-guided dilation and evacuation.


Designing interventions in psychosocial research.
There is little guidance in the literature on how to design cost-effective interventions for preventing or treating psychosocial health care problems. Four sources of information are described for developing interventions that are based on a strong theoretical and empirical foundation: (1) an explicit theory for intervention, (2) supporting descriptive data, (3) an evaluation of possible intervention strategies that are consistent with the theory and the supporting data, and (4) focus groups to examine the feasibility and external validity of the intervention before formal testing.


Diarrhea-Predominant and Constipation-Predominant Irritable Bowel Syndrome: Current Prescription Drug Treatment Options.
Irritable bowel syndrome (IBS) is a heterogenous disease with a variety of therapeutic options, including eight prescription drugs approved for use in IBS in the USA. Choosing among the myriad treatment options requires attention to patient preferences both on clinical outcomes and costs associated with treatment. We performed a narrative review of the literature to summarize these important determinants of treatment choice including: labeled indications; clinical profiles of efficacy, safety, and tolerability of prescription drugs; and cost-effectiveness for diarrhea-predominant IBS drugs (IBS-D: alosetron, eluxadoline, and rifaximin) and constipation-predominant IBS drugs (IBS-C: linaclotide, lubiprostone, plecanatide, tegaserod, and tenapanor). We then review the standard model of shared decision-making aimed at guiding an informed, patient-centered discussion to integrate comparative clinical and cost outcomes toward choosing an IBS treatment in practice.


Evaluation of an Immunochromatographic Lateral Flow Assay (OXA-48 K-SeT) for Rapid Detection of OXA-48-Like Carbapenemases in Enterobacteriaceae.
We evaluated an immunochromatographic lateral flow assay to detect OXA-48-like carbapenemases (OXA-48 K-SeT) in Enterobacteriaceae (n = 82). One hundred percent sensitivity and specificity were observed using bacteria recovered from both solid medium and spiked blood culture bottles, and the results were obtained in <10 min.


Second malignancies in the context of lenalidomide treatment: an analysis of 2732 myeloma patients enrolled to the Myeloma XI trial.
We have carried out the largest randomised trial to date of newly diagnosed myeloma patients, in which lenalidomide has been used as an induction and maintenance treatment option and here report its impact on second primary malignancy (SPM) incidence and pathology. After review, 104 SPMs were confirmed in 96 of 2732 trial patients. The cumulative incidence of SPM was 0.7% (95% confidence interval (CI) 0.4-1.0%), 2.3% (95% CI 1.6-2.7%) and 3.8% (95% CI 2.9-4.6%) at 1, 2 and 3 years, respectively. Patients receiving maintenance lenalidomide had a significantly higher SPM incidence overall (P=0.011). Age is a risk factor with the highest SPM incidence observed in transplant non-eligible patients aged >74 years receiving lenalidomide maintenance. The 3-year cumulative incidence in this group was 17.3% (95% CI 8.2-26.4%), compared with 6.5% (95% CI 0.2-12.9%) in observation only patients (P=0.049). There was a low overall incidence of haematological SPM (0.5%). The higher SPM incidence in patients receiving lenalidomide maintenance therapy, especially in advanced age, warrants ongoing monitoring although the benefit on survival is likely to outweigh risk.


Racial/ethnic health disparities among children with special health care needs in Boston, Massachusetts.
Little is known about the factors that contribute to racial/ethnic disparities among children with special health care needs (CSHCN). To quantify the contributions of determinants of racial/ethnic disparities in health and health care among CSHCN in Boston, Massachusetts. A sample of 326 Black, Latino, and white CSHCN was drawn from the Boston Survey of Children's Health, a city-wide representative sample of children. The study implemented Oaxaca-Blinder-style decomposition techniques to examine the relative contributions of health resources and child-, family-, and neighborhood-level factors to disparities in four outcomes: health status, barriers to medical care, oral health status, and utilization of preventive dental care. White CSHCN had a greater likelihood of having very good/excellent health and oral health and were less likely to experience barriers to care than Black CSHCN. Compositional differences on predictors explained 63%, 98%, and 80% of these gradients, respectively. Group variation in household income, family structure, neighborhood support, and exposure to adverse childhood experiences accounted for significant portions of the Black-white gaps in health and access. White CSHCN were also more likely to have very good/excellent health and oral health compared to Latino CSHCN. Differences on predictors accounted for about 86% and 80% of these gaps, respectively. Household income, adverse childhood experiences, and household language emerged as significant determinants of Latino-white disparities. Racial/ethnic health disparities among CSHCN are explained by relatively few determinants. Several of the contributing factors that emerged from the analysis and could be targeted by public health and policy interventions.


Removal of Cr(VI) from aqueous solution using chitosan-g-poly(butyl acrylate)/silica gel nanocomposite.
The present work deals with the preparation of the novel sorbent, glutaraldehye crosslinked silica gel/chitosan-g-poly(butyl acrylate) (Cs-g-PBA/SG) nanocomposite by sol-gel method for removal of toxic chromium ion. Prepared nanosorbent was then characterized by FTIR, XRD, DLS, SEM, BET isotherm for its formation and suitability. Its sorption capacity and sorption isotherms were brought under batch mode to suit the optimal parameters viz., contact time, pH, adsorbent dose and initial metal ion concentration which influence the sorption. The theoretical modeling such as Langmuir and Freundlich isotherm adsorption were applied to describe isotherm constants. Equilibrium data agreed well with the Langmuir isotherm model (R(2)=0.9763) with maximum adsorption capacity of 55.71 (mg/g). The kinetic studies showed that the adsorption follows the pseudo-second-order kinetics (R(2)=0.9999). From the results, it was concluded that Cs-g-PBA/SG nanocomposite is an excellent biosorbent for Cr removal from wastewater.


Biosecurity practices on foie gras duck farms, Southwest France.
On-farm biosecurity can be assessed by analyzing patterns of practices to better tailor technical advice to producers. Given their close contact with environmental and wildlife disease reservoirs, free-range duck farms are exposed to multiple risk factors of pathogen exposure that are rare or absent in indoor production. The recurrent emergence of Highly Pathogenic Avian Influenza (HPAI) viruses in Southeast Asia and Europe has emphasized the importance of farm-level biosecurity on free-range duck farms. This study was conducted on 46 French duck farms. The farms were visited and an 80-question survey was administered to assess biosecurity practices. Patterns of practices were explored with multiple correspondence analysis and hierarchical cluster analysis. Farms were assigned to one of three clusters in which specific farm types were overrepresented: farms specialized in rearing to grow-out phases and open-circuit full cycle (i.e., all production phases on the farm) farms in cluster 1, closed-circuit full cycle farms in cluster 2, and farms specialized in gavage in cluster 3. Differences in practices might be linked with differences in production constraints. This study provides a baseline assessment of biosecurity practices on foie gras duck farms in Southwest France and will help efforts to adapt biosecurity programs to farm types.


Phase de-synchronization effects auditory gating in the ventral striatum but not auditory cortex.
The underlying mechanisms and involved brain areas in sensory gating of repetitive auditory stimuli remain unclear. Especially, the influence of the auditory cortex and the role of temporal precision are under debate. Our first objective was to analyze gating dynamics of local field potentials in the primary auditory cortex and the ventral striatum in an animal experiment, particularly, assessing the influence of the cortex. The second aim was to follow the hypothesis that auditory gating results from phase de-synchronization of evoked potentials in response to the second auditory stimulus. Local field potentials were recorded simultaneously in the auditory cortex and ventral striatum of awake Mongolian gerbils (n=15) during stimulation with trains of frequency-modulated tones. Gating was analyzed by amplitude ratios of the auditory potentials evoked by the first two stimuli in a train, as well as by time-frequency analyses and between-area phase coupling. The strength of auditory gating in the striatum was found to exceed that in the primary auditory cortex by more than 50%. While total-signal-power was comparable between areas, energy in the striatum was primarily expressed in the non-phase-locked fraction. At the same time, energy in the auditory cortex remained phase-locked to the stimuli. Furthermore, we also observed a between-area phase unlocking during sound presentations. Phase de-synchronization appears to be the candidate mechanism behind attenuation of responses to identical repetitive stimuli in the ventral striatum. We conclude that a direct inhibitory response suppression by the auditory cortex plays a minor role in this process.


Human ependymomas reveal frequent deletions on chromosomes 6 and 9.
Ependymomas are glial tumors of the brain and spinal cord. Genetic aberrations associated with the development of these tumors have not been fully identified yet. In previous cytogenetic and comparative genomic hybridization studies, multiple genomic imbalances in ependymomas were found, including partial or whole chromosome losses (1p, 4q, 6q, 9, 10, 11, 13, 16, 17, 19q, 20q and 22q). The aim of this study was to map particularly the commonly affected regions in ependymomas. Thirty-three pairs of matched normal and tumor specimens from ependymoma patients were genotyped using 34 polymorphic microsatellite markers distributed over 15 chromosomes. Loss of heterozygosity (LOH) was found in 26 of 33 tumors (78.8%). The most frequent LOHs were found on the long arms of chromosomes 6 (30.3%) and 9 (27.3%). LOH was also detected on 3p14 (13.3%), 10q23 (10.3%) and 11q (18.2%). Because of the high percentage of LOH on chromosome 6 and 9, we conclude that important tumor suppressor genes are situated on these two chromosomes.


Photocatalytic degradation of ciprofloxacin by MMT/CuFe2O4 nanocomposite: characteristics, response surface methodology, and toxicity analyses.
The photocatalytic degradation of ciprofloxacin (CIP) was examined by loading spinel ferrite copper (CuFe2O4) nanoparticles onto montmorillonite (MMT) under irradiation using UV light. The laboratory parameters were optimized using response surface methodology (RSM), and maximum efficiency (83.75%) was achieved at a pH of 3, CIP concentration of 32.5 mg/L, MMT/CuFe2O4 dose of 0.78 g/L, and irradiation time of 47.50 min. During the photocatalysis process, the experiments on radical trapping demonstrated the generation of hydroxyls (•OH), superoxide (•O2-) radical, electrons (e-), and holes (h+). A low rate drop (below 10%) in the CIP degradation during the six consecutive reaction cycles corroborated the remarkable recyclability and stability of the MMT/CuFe2O4. The acute toxicity of the treated solution was determined using Daphnia Magna, by applying photocatalysis, which was indicative of a marked decline in the toxicity. Comparing the findings of the degradation using UV and the degradation process using visible light represented results with close resemblance to each other at the end of the reaction time. Besides, under UV and visible light, the particles in reactor are easily activated when the pollutant mineralization exceeded 80%.


Factor VII activating protease (FSAP) is not essential in the pathophysiology of angioedema in patients with C1 inhibitor deficiency.
Excessive bradykinin (BK) generation from high molecular weight kininogen (HK) by plasma kallikrein (PK) due to lack of protease inhibition is central to the pathophysiology of hereditary angioedema (HAE). Inadequate protease inhibition may contribute to HAE through a number of plasma proteases including factor VII activating protease (FSAP) that can also cleave HK. To investigate the interaction between FSAP and C1 inhibitor (C1Inh) and evaluate the potential role of FSAP in HAE with C1Inh deficiency. Plasma samples from 20 persons with HAE types 1 or 2 in remission were studied and compared to healthy controls. We measured and compared antigenic FSAP levels, spontaneous FSAP activity, FSAP generation potential, activation of plasma pre-kallikrein (PPK) by FSAP, and the formation of FSAP-C1Inh and FSAP-alpha2-antiplasmin (FSAP-α2AP) complexes. Furthermore, we measured HK cleavage and PK activation after activation of endogenous pro-FSAP and after addition of exogenous FSAP. In plasma from HAE patients, there is increased basal FSAP activity compared to healthy volunteers. HAE plasma exhibits decreased formation of FSAP-C1Inh complexes and increased formation of FSAP-α2AP complexes in histone-activated plasma. Although exogenous FSAP can cleave HK in plasma, this was not seen when endogenous plasma pro-FSAP was activated with histones in either group. PK was also not activated by FSAP in plasma. In this study, we established that FSAP activity is increased and the pattern of FSAP-inhibitor complexes is altered in HAE patients. However, we did not find evidence suggesting that FSAP contributes directly to HAE attacks.


Basement membrane proteoglycans: from cellar to ceiling.
The biology of basement membrane proteoglycans extends far beyond the original notion of anionic filters. These complex molecules have dual roles as structural constituents of basement membranes and functional regulators of several growth-factor signalling pathways. As such, they are involved in angiogenesis and, consequently, in tumour progression and their partial or total absence causes several congenital defects that affect the musculoskeletal, cardiovascular and nervous systems. New findings indicate a potential functional coupling between the intricate make-up of basement membrane proteoglycans and their ability to control important biological processes.


An assessment of computational methods for obtaining structural information of moderately flexible biomolecules from ion mobility spectrometry.
When utilized in conjunction with modeling, the collision cross section (Ω) from ion mobility spectrometry can be used to deduce the gas phase structures of analyte ions. Gas phase conformations are determined computationally, and their Ω calculated using an approximate method, the results of which are compared with experimental data. Though prior work has focused upon rigid small molecules or large biomolecules, correlation of computational and experimental Ω has not been thoroughly examined for analytes with intermediate conformational flexibility, which constitute a large fraction of the molecules studied in the field. Here, the computational paradigm for calculating Ω has been tested for the tripeptides WGY, YGW, and YWG (Y = tyrosine, W = tryptophan, G = glycine). Experimental data indicate that Ω(exp) (YWG) > Ω(exp) (WGY) ≈ Ω(exp) (YGW). The energy distributions of conformations obtained from tiers of simulated annealing molecular dynamics (SAMD) were analyzed using a wide array of density functionals. These quantum mechanical energy distributions do not agree with the MD data, which leads to structural differences between the SAMD and DFT conformations. The latter structures are obtained by reoptimization of the SAMD geometries, and are the only suite of structures that reproduce the experimental trend in analyte separability. In the absence of fitting Lennard Jones potentials that reproduce experimental results for the Trajectory Method, the Exact Hard Sphere Scattering method produced numerical values that are in best agreement with the experimental cross sections obtained in He drift gas.


Dermoscopic features of cutaneous leishmaniasis.
Previous studies have demonstrated that dermoscopy improves accuracy in diagnosing pigmented and non-pigmented tumors. Recently, there has been increasing evidence that dermoscopy can also be useful in the diagnosis of some skin infections. We sought to describe the dermoscopic features of cutaneous leishmaniasis. Dermoscopic examination (using the Derm Lite FOTO, 3Gen) of 144 CL lesions in 82 patients was performed. This study was conducted in the Imam Reza and Ghaem hospitals (Mashhad, Iran) from October 2010 to September 2011. We observed the following dermoscopic features: generalized erythema (81.9%), white starbursts (60.4%), yellow hue (43.8%), yellow teardrop-like structures (41.7%), central ulcers (59%), hyperkeratosis (33.3%), and milia-like cysts (4.9%). We also observed vascular structures, including dotted vessels (61.1%), hairpin vessels (37.5%), linear irregular vessels (30.6%), comma-shaped vessels (29.9%), glomerular vessels (22.9%), arborizing telangiectasia (10.4%), and corkscrew vessels (4.2%). Biopsy and pathologic evaluation were not performed due to ethical considerations. Important vascular patterns seen in melanocytic and non-melanocytic tumors were frequently observed in this infection. Dermoscopy may be a promising tool to predict the clinical course in cases of cutaneous leishmaniasis.


Metabolic syndrome and cognitive deficits in the Greek cohort of Epirus Health Study.
Metabolic syndrome is considered an important risk factor for cognitive decline and dementia. However, the evidence in middle-aged individuals is still conflicting. The aim of the study was to explore the association between metabolic syndrome and its individual components with cognitive function and to investigate possible interaction between sex, age and genetic predisposition for metabolic syndrome and Alzheimer's disease in a middle-aged Greek cohort. A total of 2,077 healthy adults (mean age: 46.7 years) were included in the primary cross-sectional analysis and 305 of them in secondary prospective analyses. Metabolic syndrome was defined by the revised National Cholesterol Education-Adult Treatment Panel III and the International Diabetes Federation criteria. Cognitive function was measured primarily with the Trail Making, Verbal fluency and Logical Memory test, and in secondary prospective analyses with online versions of Posner cueing task, an emotional recognition task, Corsi block-tapping task and Stroop task. Multivariable linear regressions showed an association of metabolic syndrome with lower performance in attention (β=1.62 seconds, 95% CI=0.20, 3.04) and memory (β=-0.62 words, 95% CI=-1.19, -0.05) that could be driven by associations with elevated fasting glucose and abdominal obesity. Similar associations were observed in the secondary prospective analyses. In summary, metabolic syndrome was associated with cognitive deficits in domains related with the cognitive profile of vascular cognitive impairment.


Redescription of Isospora vanriperorum Levine, 1982 (Apicomplexa: Eimeriidae) from the Northern Cardinal, Cardinalis cardinalis (L.) (Passeriformes: Cardinalidae), in North Texas, USA.
Little is known about the coccidian parasites of North American birds of the family Cardinalidae. A single isosporan, Isospora vanriperorum was previously described over 40 years ago from the northern cardinal, Cardinalis cardinalis from Hawaii. Since then, it was also reported in the green-winged saltator, Saltator similis from Brazil but the identification was invalidated recently. Feces were collected in July 2022 from two C. cardinalis found dead in Lamar County, Texas, USA. One sample contained oöcysts representing I. vanriperorum. Oöcysts are spheroidal to subspheroidal with a smooth uni-layered wall, measure (L × W) 23.8 × 22.4 µm and have a length/width (L/W) ratio of 1.04; a micropyle and oöcyst residuum are absent but polar granule(s) are present. Sporocysts are ovoidal and measure 15.5 × 10.5 µm, L/W 1.5; a knob-like Stieda body and a rounded sub-Stieda body are present. The sporocyst residuum is more often composed of various-sized granules dispersed between and across the sporozoites; it is less often in a compact rounded mass. This isosporan has now been reported from the northern cardinal for the second time but most importantly, from the mainland USA for the first time.


Effect of ranitidine and indomethacin on nocturnal gastric acidity in normal subjects.
To assess the effect of indomethacin on gastric acidity and to identify a potential pharmacodynamic interaction between indomethacin and ranitidine, we measured nocturnal acidity on half-hourly aliquots of gastric contents from 10 volunteers on the seventh day of four dosing regimens given in a randomized double-blind manner. These were indomethacin (50 mg t.d.s.) and ranitidine (300 mg in the evening) together or alone with matching placebos. Median nocturnal acidity on placebo was 41.7 mmol/L (range 67.6-25.1 mmol/L) and was 39.8 mmol/L (63.1-24.0 mmol/L) on indomethacin (N.S.). During ranitidine dosing it was 0.4 mmol/L (21.3-0.0 mmol/L) without and 0.8 mmol/L (43.7-0.0 mmol/L) with concurrent indomethacin, representing 99 and 98% decreases in gastric acidity (P less than 0.01) compared with placebo. Indomethacin did not increase overnight gastric acidity and did not influence the suppression of acidity produced by ranitidine. It is unlikely that the ulcerogenic potential of indomethacin is explicable by an effect on gastric acidity.