Parenting style in childhood and mortality risk at older ages: a longitudinal cohort study.
Parenting style is associated with offspring health, but whether it is associated with offspring mortality at older ages remains unknown. We examined whether childhood experiences of suboptimal parenting style are associated with increased risk of death at older ages. Longitudinal cohort study of 1964 community-dwelling adults aged 65-79 years. The association between parenting style and mortality was inverse and graded. Participants in the poorest parenting style score quartile had increased risk of death (hazard ratio (HR) = 1.72, 95% CI 1.20-2.48) compared with those in the optimal parenting style score quartile after adjustment for age and gender. Full adjustment for covariates partially explained this association (HR = 1.49, 95% CI 1.02-2.18). Parenting style was inversely associated with cancer and other mortality, but not cardiovascular mortality. Maternal and paternal parenting styles were individually associated with mortality. Experiences of suboptimal parenting in childhood are associated with increased risk of death at older ages.


The diets of Hispaniolan colubrid snakes : I. Introduction and prey genera.
Approximately 1590 Hispaniolan colubrid snakes representing six genera and eight species were examined for prey remains (Alsophis cantherigerus, Antillophis parvifrons, Darlingtonia haetiana, Hypsirhynchus ferox, Ialtris dorsalis, Uromacer catesbyi, U. frenatus, and U. oxyrhynchus). The snakes were collected at many localities over a span of 80 years.Of 426 prey items, 77.9% were lizards (of which 69.6% were anoles), 19% frogs, 2.6% birds and mammals, and 0.5% other snakes. Darlingtonia was the only snake that did not exploit lizards; it fed exclusively on Eleutherodactylus frogs, including egg clutches. Disregarding Darlingtonia, there is no size class of Hispaniolan colubrids between 20-90 cm SVL that does not prey primarily on Anolis. Certain prey genera are added to, or deleted from, diets depending on snake size, but the data suggest that snake SVL alone does little to dictate what prey genera (or groups) are eaten. Shannon-Wiener values (H') indicate that Darlingtonia has the narrowest trophic niche, while Alsophis and Ialtris have the widest. Values of H' are not correlated with snake SVL, but highly significant (P<0.001) correlations exist between H' and mid-body circumference, head width, and snout width, and these characters may be indicators of trophic generalists and specialists. Anolis lizards are the most ubiquitous and conspicuous vertebrates on Hispaniola, and it is not surprising that they are widely exploited as a food source. Although as some snake species grow larger, anoles play a decreasingly important role in their diets, there is no evidence to suggest that they are ever abandoned as a food source by any Hispaniolan colubrid of any size.Secretive lizards of low vagility are eaten almost exclusively by wide ranging foragers (Alsophis, Antillophis); very active prey (Ameiva) is taken by sit-and-wait strategists (Hysirhynchus, U. frenatus). Those snakes which exploit the most prey groups are active foragers. Uromacer catesbyi exhibits both foraging modes, and predictably, eats diurnally active (anoles) and diurnally quiescent (hylid frogs) prey with almost equal frequency.Within Maglio's cantherigerus species assemblage, in which an Alsophis cantherigerus-like snake was ancestral to the other species, and in which longsnouted Uromacer are the most morphologically derived, there is an obvious trend toward trophic specialization on Hispaniola. The West Indies have provided an ideal natural laboratory for the investigation of many aspects of vertebrate ecology, and an arena in which to test theories of island biogeography. The most extensively studied West Indian vertebrates have been the lizards of the iguanid genus Anolis. Conversely, the ecology of West Indian snakes has been largely ignored. This is surprising in light of the fact that much has been written about Anolis predation, but little has been written about predators of Anolis; snakes may be important, frequent consumers of anoles.Hispaniola is physiographically and ecologically the most diverse of the Greater Antilles and, concomitantly, it has the most diverse snake fauna, including six colubrid genera containing 11 described species. It has rich frog and lizard faunas, but only two endemic mammals. Study of the diets of Hispaniola's colubrid snakes was undertaken to gain initial insights into the ecology of the snakes and to determine 1) what the snakes eat; 2) what relationships exist between snake diet and snake size as well as head and body proportions; 3) what relationships exist between snake foraging mode and prey type and size; 4) if anoles, as the most ubiquitous and conspicuous vertebrates on Hispaniola, comprise an important source of food; 5) if significant geographical differences in diet exist, expecially on satellite islands; 6) if "north island" and "south island" (sensu Williams 1961) Anolis ecomorphs are preyed upon by the same snake species in similar proportions; 7) if snakes are selective or opportunistic predators.This paper, the first in a series that will address all of the above topics, will briefly describe methods, snake species and prey genera. Prey genera are analyzed in terms of what snake taxa prey upon them, what size classes of snakes prey upon them, and prey genera diversity versus snake size and proportions.


Measurement of aortic blood velocity in acute myocardial infarction by Doppler ultrasound.
Aortic blood velocity was measured by a transcutaneous continuous wave Doppler technique in thirty-five patients with proven acute myocardial infarction. Measurements were made on the first and seventh day following admission to hospital. Group I comprised 21 patients who had sustained a first myocardial infarction of moderate size, uncomplicated by hypoperfusion. Group II comprised 14 patients who had had a large rise in cardiac enzymes, a previous myocardial infarction or were clinically hypoperfused. The mean value for peak aortic velocity for Group I on Day 1 was 88 +/- 12.9 cm/s. This was significantly lower than the mean value of 101.8 +/- 23.1 cm/s for a group of 85 normal subjects. By Day 7 the mean value for Group I of 105.1 +/- 19.8 cm/s was not significantly different from normal. For Group II patients on Day 1 the mean value for peak aortic velocity was 67.9 +/- 11.7 cm/s and was significantly lower than that for both Group I and the normal group. By the seventh day the mean value for Group II was 76.5 +/- 17.1 cm/s which was not significantly different from Day 1.


Minimally invasive video-assisted thyroidectomy for the early-stage differential thyroid carcinoma.
Minimally invasive video-assisted thyroidectomy (MIVAT), the modified Miccoli's thyroid surgery, is the most widespread minimally invasive technique and has been widely used for treatment of thyroid disease. This study aimed to verify the potential benefits of the modified Miccoli's thyroid surgery, determine the feasibility of the MIVAT for early-stage differential thyroid carcinoma and evaluate the likelihood of the surgical method as a standard operation for early malignant thyroid carcinoma. A total of 135 patients were retrospectively compared which included two groups of patients: the first group underwent the conventional thyroidectomy; the other group underwent MIVAT. Patients with thyroid nodule smaller than 20 mm and without previous neck surgery were included while those with wide-ranging and distant metastases of cervical tissues, or any suspected thyroid nodal metastases were excluded for analysis. MIVAT and the central compartment (level VI) lymph nodes dissection (LND) were considered as a new treatment method for this retrospective study. In addition to the comparison of surgical outcomes between the new treatment and the conventional thyroid surgery, other surgical parameters including operative time, operative volume of hemorrhage, incisional length, postoperative volume of drainage, length of hospitalization, accidence of hoarse voice, accidence of bucking, accidence of hypocalcemia and peak angle of cervical axial rotation were also compared. Out of 135 patients, 111 patients underwent conventional thyroid surgery and 24 patients underwent MIVAT plus level VI LND for treatment of early-stage differential malignant carcinoma. Patients who received the new surgical treatment had significantly shorter incisional length (3.1 cm vs. 6.9 cm, p < 0.0001), shorter operative time (109 min vs. 139 min, p = 0.014) and fewer operative hemorrhage (29.5 ml vs. 69.7 ml, p < 0.0001) when compared to the conventional treatment. Postoperative peak angle of cervical axial rotation of patients treated with MIVAT was less than those treated with conventional surgery (L: 31.5° vs. 39.0°, p < 0.0001; R: 31.5° vs. 38.0°, p < 0.0001). Incisional wound infection, postoperative hoarse voice, bucking and hypocalcemia were not observed in all patients. Postoperative analgetica was not required as well. Compared with conventional thyroid surgery for early-stage differential thyroid carcinoma, the new surgical treatment could be considered as an alternative surgical method for treatment of early-stage thyroid carcinoma since it was feasible, safe and clinically effective with better surgical and cosmetic outcomes.


Draft Genome Sequence of Magnetospirillum sp. Strain SO-1, a Freshwater Magnetotactic Bacterium Isolated from the Ol'khovka River, Russia.
Here, we present the draft genome sequence of Magnetospirillum sp. strain SO-1, a freshwater magnetotactic spirillum isolated from the sediments of the Ol'khovka River, Russia.


Changes in plasma thrombomodulin antigen in rabbit developing endotoxin-induced disseminated intravascular coagulation and the effect of heparin.
Soluble thrombomodulin (TM) antigen level was 1.64 +/- 0.64 microgram/ml (n = 18, mean +/- S.D.) in plasma of normal male rabbits as measured by enzyme immunoassay, and the antigen consisted of subspecies of 94, 83 and 51 kd. When disseminated intravascular coagulation (DIC) was induced by intravenous infusion of endotoxin into rabbits, the TM antigen level in plasma was elevated to about 1.5 times of the control value, and an increase in the 83 kd subspecies as well as the appearance of new subspecies of 76 and 48 kd was observed concomitantly with disappearance of the 94 kd subspecies in plasma. Elevation of the antigen level and disappearance of the 94 kd subspecies caused by infusion of endotoxin were reduced by simultaneous infusion of heparin. Addition of leukocytes stimulated with endotoxin plus FMLP to cultured endothelial cells induced release of TM antigen to the medium accompanying cell injury as measured by 51Cr release, which was prevented by treatment with heparin. It was suggested that the increase in plasma TM antigen level in parallel with the generation of DIC reflected endothelial injury of rabbits, and that the elevation of TM antigen and the endothelial cell injury were prevented by heparin treatment.


Synthesis of new sulfonate and phosphonate derivatives for cation-independent mannose 6-phosphate receptor targeting.
The cation-independent mannose 6-phosphate receptor (CI-M6PR) is essential for the endocytosis of proteins bearing the mannose 6-phosphate (M6P) recognition marker. This study described the synthesis of M6P and M6S analogs presenting greater affinity for CI-M6PR than their natural compounds. Moreover, the finding of their lack of cytotoxicity for human cells and of their increased stability in human serum supports the high potential of these isosteric derivatives in therapies requiring CI-M6PR targeting.


DICROCOELIUM DENDRITICUM INFECTION IN A PATIENT WITH CHRONIC SCHISTOSOMIASIS HAEMATOBIUM.
Infection with Dicrocoelium dendriticum in humans is seldom to be reported in Egypt. This liver fluke, which commonly infects ruminants, has a complex life cycle with two intermediate hosts; the land snail and the ant. Human infection occurs by accidental ingestion of the second intermediate host. The present reported a patient suffered from recurrent acute chole-cystitis with chronic urinary schistosomiasis whose Kato stool examination showed Dicroceolium dendriticum eggs. He was successfully treated with Mirazid.


Idiopathic constipation associated with impaired urethrovesical and sacral reflex function.
Sixteen chronically constipated women (age range 20-66 years) and 29 healthy control subjects (age range 22-53 years) underwent neurophysiological assessment of the integrity of pelvic spinal reflexes. The results were compared with videourodynamic studies and multiport anorectal manometry combined with external anal sphincter electromyography. The neurophysiological assessment consisted of electrical stimulation of the dorsogenital nerve, while recording any evoked reflex activity in the external anal and urethral sphincters with concentric needle and surface electrodes. Of these constipated women, 75 per cent had absence of one or more evoked sacral reflexes (compared with 20 per cent of healthy controls, P less than 0.05). Sensory thresholds and motor unit potentials in the external anal sphincter were similar in healthy and constipated women. Nine (56 per cent) constipated women displayed urodynamic abnormalities (increased bladder capacity, acontractile bladder and genuine stress incontinence). Only 38 per cent of constipated women perceived a desire to defaecate during rectal distension with up to 100 ml, compared with 95 per cent of normal subjects (P less than 0.0005). Moreover, 73 per cent of constipated women did not relax the external anal sphincter during defaecation, compared with 12 per cent of controls (P = 0.001). Taking into account the possible significance of our data in relation to previous findings it is suggested that the integration of sensory information within the sacral cord may be impaired in chronic idiopathic constipation.


Women physicians receive lower Press Ganey patient satisfaction scores in a multicenter study of outpatient gynecology care.
Emerging data suggest that patient satisfaction data are subject to inherent biases that negatively affect women physicians. This study aimed to describe the association between the Press Ganey patient satisfaction survey and physician gender in a multi-institutional study of outpatient gynecologic care. This was a multisite, observational, population-based survey study using the results of Press Ganey patient satisfaction surveys from 5 unrelated community-based and academic medical institutions with outpatient gynecology visits between January 2020 and April 2022. The primary outcome variable was the likelihood to recommend a physician, and individual survey responses served as the unit of analysis. Patient demographic data were collected through the survey, including self-reported age, gender, and race and ethnicity (categorized as White, Asian, or Underrepresented in Medicine, which groups together Black, Hispanic or LatinX, American Indian or Alaskan Native, and Hawaiian or Pacific Islander). Bivariate comparisons between demographics (physician gender, patient and physician age quartile, patient and physician race) and likelihood to recommend were assessed using generalized estimating equation models clustered by physician. Odds ratios, 95% confidence intervals, and P values for these analyses are reported, and results were considered statistically significant at P<.05. Analysis was performed using SAS, version 9.4 (SAS Institute Inc., Cary, NC). Data were obtained from 15,184 surveys for 130 physicians. Most physicians were women (n=95 [73%]) and White (n=98 [75%]), and patients were also predominantly White (n=10,495 [69%]). A little over half of all visits were race-concordant, meaning that both patient and physician reported the same race (57%). Women physicians were less likely to receive a topbox survey score (74% vs 77%) and in the multivariate model had 19% lower odds of receiving a topbox score (95% confidence interval, 0.69-0.95). Patient age had a statistically significant relationship with score, with patients aged ≥63 years having >3-fold increase in odds of providing a topbox score (odds ratio, 3.10; 95% confidence interval, 2.12-4.52) compared with the youngest patients. After adjustment, patient and physician race and ethnicity showed similar effects on the odds of a topbox likelihood-to-recommend score, with Asian physicians and Asian patients having lower odds of a topbox likelihood-to-recommend score when compared with White physicians and patients (odds ratio: 0.89 [95% confidence interval, 0.81-0.98] and 0.62 [95% confidence interval, 0.48-0.79], respectively). Underrepresented in medicine physicians and patients showed significantly increased odds of a topbox likelihood-to-recommend score (odds ratio: 1.27 [95% confidence interval, 1.21-1.33] and 1.03 [95% confidence interval, 1.01-1.06], respectively). The physician age quartile was not significantly associated with odds of a topbox likelihood-to-recommend score. Women gynecologists were 18% less likely to receive top patient satisfaction scores compared with men in this multisite, population-based survey study using the results of Press Ganey patient satisfaction surveys. The results of these questionnaires should be adjusted for bias given that they provide data currently being used to understand patient-centered care.


Highly-Tunable Intrinsic Room-Temperature Ferromagnetism in 2D van der Waals Semiconductor Crx Ga1- x Te.
The combination of semiconductivity and tunable ferromagnetism is pivotal for electrical control of ferromagnetism and next-generation low-power spintronic devices. However, Curie temperatures (TC ) for most traditional intrinsic ferromagnetic semiconductors (≤200 K) and recently discovered two-dimensional (2D) ones (<70 K) are far below room temperature. 2D van der Waals (vdW) semiconductors with intrinsic room-temperature ferromagnetism remain elusive considering the unfavored 2D long-range ferromagnetic order indicated by Mermin-Wagner theorem. Here, vdW semiconductor Crx Ga1- x Te crystals exhibiting highly tunable above-room-temperature ferromagnetism with bandgap 1.62-1.66 eV are reported. The saturation magnetic moment (Msat ) of Crx Ga1- x Te crystals can be effectively regulated up to ≈5.4 times by tuning Cr content and ≈75.9 times by changing the thickness. vdW Crx Ga1- x Te ultrathin semiconductor crystals show robust room-temperature ferromagnetism with the 2D quantum confinement effect, enabling TC 314.9-329 K for nanosheets, record-high for intrinsic vdW 2D ferromagnetic semiconductors. This work opens an avenue to room-temperature 2D vdW ferromagnetic semiconductor for 2D electronic and spintronic devices.


Epoxide derivatives of pipecolic acid and proline are inhibitors of pipecolate oxidase.
The cis-4,5-epoxide derivative of L-pipecolic acid (2S,4S,5R-epoxypipecolic acid, cis-3) was synthesized and found to serve as an excellent substrate for L-pipecolate oxidase (L-PO) and also to cause time-dependent, irreversible inactivation of the enzyme. Data are presented showing this compound is a mechanism-based inhibitor of L-PO, whereas 2S,3R,4S-epoxyproline acts as a reversible inhibitor.


Single leg hopping in children with fetal alcohol spectrum disorder: Dynamic postural stability and kinematics.
This study compared dynamic postural stability (DPS) and lower limb kinematics during single leg hopping (SLH) performed by typically-developed children from urban and rural settings and children with Fetal Alcohol Spectrum Disorder (FASD) from a rural setting. Typically-developed nine-year-old children from an urban (n = 27) and rural setting (n = 14) (controls), and nine-year-old children with FASD from a rural setting (n = 14) (cases) performed SLH and landing on a pressure mat. Motion analysis systems described 1) Spatiotemporal and centre of pressure parameters (COP) and lower limb sagittal plane kinematics. Descriptive results are presented in median and ranges and differences between groups were determined by Kruskal-Wallis and Mann-Whitney U statistical tests. The level of significance was p < 0.05. During hopping, the urban controls had longer stance and swing times (p < 0.001) than the rural groups. The urban controls remained in greater hip flexion compared to the case group (p = 0.02). The urban controls landed in more plantarflexion at initial foot contact (IFC) than the cases (p < 0.001) and the rural controls (p = 0.03). The rural groups landed with greater knee extension at IFC than the urban controls (cases p = 0.04; rural controls p < 0.001). During the landing motion, the urban controls moved into more hip flexion compared to the cases (p = 0.015) and the rural controls (p = 0.026). The cases displayed greater COP anteroposterior values during landing compared to both control groups, but the case group displayed the fastest time to stability. The different hopping strategies observed provides an indication of the movement capabilities of these groups.


[Retrospective analysis of 1354 autopsies in cases of death caused by trauma].
1,354 deaths due to traumatic causes arising in 1976-1985 among patients admitted to the Molinette Hospital, Turin were analysed. The causes were divided into 5 major groups with to monitoring the course of the pathologies concerned over time. The results confirm an increase in deaths from septic shock that reflects increased recourse to surgery and the application of resuscitation manoeuvres and equipment, but a decrease in death due to haemorrhagic shock. These two pathologies represent the major lines for future research aimed at improving the prognosis in traumatic lesions.


Intrathecal application of autologous bone marrow cell preparations in Parkinsonian syndromes.
A growing number of patients is treated with intrathecal application of autologous bone marrow cells (aBMCs), but clinical data are completely lacking in movement disorders. We provide first clinical data on efficacy and safety of this highly experimental treatment approach in parkinsonian syndromes. Retrospective data collection from patients with parkinsonism who spontaneously sought cell treatment. The application procedure was neither recommended nor performed by the authors. We report 17 patients with parkinsonian syndromes (Parkinson's disease [PD], n = 7; multiple system atrophy [MSA], n = 7; various, n = 3) who received intrathecal application of aBMCs. We did not observe any changes in motor function, activities of daily living, global clinical impression, or antiparkinsonian medication after a median observation period of 10 months. Two patients reported a worsening of parkinsonian symptoms, but the intervention was otherwise safe and well-tolerated. Intrathecal application of aBMCs in uncontrolled conditions produces no clinical benefit in parkinsonian syndromes.


Environmental Factors and Genetic Parameters of Beef Traits in Fleckvieh Cattle Using Field and Station Testing.
The goal of this study was to analyze the genetic and environmental factors of selected meat yield indicators in Fleckvieh cattle in the Czech Republic, through the application of station (S) and field (F) testing methods. Data collected from fattened bulls were analyzed for F (n = 9378) and for S (n = 6346). In the F method and the S method, the values of the main meat yield indicators were as follows: carcass weight 402.91 kg (F), 339.37 kg (S); carcass daily gain 626.05 g/day (F), 609.74 g/day (S); SEUROP carcass classification 2.73 (F), 2.19 (S). Environmental factors were found to have a significant impact on the selected meat yield indicators; their heritability ranged from 0.14 (SEUROP classification) to 0.33 (dressing percentage). The genetic trend was significantly positive only in relation to those meat yield traits, which had a positive link to the size or weight of the animal. The genetic correlation between observations obtained in the S and F methods of testing was very high in relation to the carcass daily gain (0.8351) and carcass weight (0.8244), while slightly lower correlations were calculated for the SEUROP classification. A genetic evaluation of the degree of fatness is not routinely performed in Fleckvieh populations, and the newly established heritability for this trait ranges between 0.17-0.20. The genetic correlation between beef yield indicators and the exterior trait of muscularity was also established, and shows a strong link to the net daily gain, the SEUROP classification and body weight (0.79-0.97). The aim of the study was to evaluate the genetic and environmental effects on meat yield and also estimate genetic parameters for new traits. We can also state, based on the results, that a strong positive genetic trend is confirmed, especially in traits related to the size or weight of animals. This result can be used in breeding programs of dual-purpose cattle, where we can genetically improve the meat and milk yield through the body size.


DRAMAtic transforms in magic angle spinning recoupling NMR: The Bessel function pathway.
In magic angle spinning (MAS) NMR recoupling experiments, the extraction of multiple couplings or a coupling distribution from the observed dephasing signals remains a challenging problem. At least for REDOR experiments, the REDOR transform solves this problem, enabling the simultaneous measurement of multiple dipolar couplings. Focusing on the quadrupolar dephasing observed in QUADRAMA experiments as a representative example, we demonstrate that the same analytical form used for the mathematical description of REDOR dephasing also describes the dephasing observed in a wide variety of MAS NMR recoupling experiments. This fact immediately extends REDOR transform techniques to a much broader suite of recoupling experiments than had previously been realized, including those of DRAMA, MELODRAMA and QUADRAMA. As an illustration, we use the DRAMAtic transform to provide the first inversion of a QUADRAMA dephasing signal to extract the quadrupole coupling distribution. Using a complete elliptic integral of the first kind, we further develop a novel expression for the Pake-spun powder patterns of the corresponding recoupled lineshapes. Our methods and results reinforce the central role that Bessel functions can play in simplifying the integrals that define both the dephasing signals in the time domain, and their Fourier transforms in the frequency domain.


Phase-specific healthcare costs of cervical cancer: estimates from a population-based study.
There is a lack of evidence on the economic burden of managing cervical cancer in the public payer Canadian setting. We used individual patient-level data to obtain a comprehensive estimate of the cost of managing cervical cancer in the province of Ontario, identifying main cost drivers and predictors of increased costs. The cost-of-illness technique was used to estimate the incremental costs associated with cervical cancer in 4 phases: prediagnosis, initial care, continuing care, and terminal care. All patients with cervical cancer diagnosed between 2005 and 2009 in the province of Ontario were propensity-score matched to 5 noncancer controls on birth year, income quintile, rurality, comorbidities, and patterns of healthcare utilization pattern during the 2 years before cancer diagnosis. Both cases and the noncancer comparison group were followed to death or March 31, 2013. Costs for all healthcare services paid for by the Ontario Ministry of Health and Long-term Care during the follow-up period were estimated by the use of linked administrative data. Incremental costs for managing cervical cancer were calculated through generalized estimating equations. Predictors of greater health costs were explored using multivariate quantile regression models. All costs were presented in 2012 Canadian dollars ($1.00CDN = $1.00USD). The total incremental costs for managing cervical cancer were $362 in the pre-diagnosis phase, $15,722 in the initial phase, $3924 per year in the continuing phase, and $52,539 in the terminal phase. Inpatient care accounted for 34%, 28%, and 52% of total healthcare cost in the initial, continuing, and terminal phase, respectively. Physician services ranked first in the continuing phase (30%) and second in the initial (26%) and terminal (13%) phases. Advanced age, advanced cancer stage at diagnosis, and comorbidities were significant predictors of greater costs in most care phases. Aggregate costs of care for cervical cancer are substantial and vary by cancer stage, phase of care, patient age at diagnosis, and comorbidities before diagnosis. These estimates can serve as baseline data in economic analyses that aim to evaluate interventions for managing cervical cancer.


Effects of an experimental increase in prey abundance upon the reproductive rates of two orb-weaving spider species (Araneae: Araneidae).
A field experiment was performed to determine if food is a limited resource for adult females of two species of orb-weaving spiders, Mecynogea lemniscata and Metepeira labyrinthea. Spiders built webs after being added to open experimental units located in a mixed deciduous-pine forest in Maryland, USA. Each unit was a frame supporting dead branches of the type used by both species for anchoring webs. Spiders on half the units were exposed to natural prey densities only, while each spider on the other units was given laboratory-reared flies in order to increase prey availability above natural levels. Supplemental feeding continued for 2.5 months. At the end of the experiment all egg sacs were removed from the units.Providing additional prey did not increase the survival rate on the units (net effect of mortality, emigration and immigration). However, both species responded to additional prey by significantly increasing the number of eggs produced per female, indicating that food was a limited resource for these species. Median egg production per female increased from 34 to 62 for Mecynogea lemniscata and from 65 to 145 for Metepeira labyrinthea. Egg weight was not affected.Feeding rates and nearest neighbor distances were determined for spiders in non-experimental populations, which permitted evaluation of the experiment's naturalness. The effects of food supply upon the reproductive rates of the two species are discussed in relation to their numerical response and population dynamics.


The nose in children with unilateral cleft lip and palate.
Surgeons and orthodontists are still challenged to achieve 'better' noses for children with a unilateral cleft or lip, alveoulus and palate (UCLP). Various aspects are discussed: infant anatomy and later changes, developmental mechanics, cleft syndrome in animals with surgically produced facial clefts, untreated patients with congenital clefts, the radical primary correction of the UCLP nose, the unsolved problems in secondary rhinoplasty and suggestions for scientific communication.


High-throughput protein production and purification at the Seattle Structural Genomics Center for Infectious Disease.
The establishment of an efficient and reliable protein-purification pipeline is essential for the success of structural genomic projects. The SSGCID Protein Purification Group at the University of Washington (UW-PPG) has established a robust protein-purification pipeline designed to purify 400 proteins per year at a rate of eight purifications per week. The pipeline was implemented using two ÄKTAexplorer 100 s and four ÄKTAprimes to perform immobilized metal-affinity chromatography (IMAC) and size-exclusion chromatography. Purifications were completed in a period of 5 d and yielded an average of 53 mg highly purified protein. This paper provides a detailed description of the methods used to purify, characterize and store SSGCID proteins. Some of the purified proteins were treated with 3C protease, which was expressed and purified by UW-PPG using a similar protocol, to cleave non-native six-histidine tags. The cleavage was successful in 94% of 214 attempts. Cleaved proteins yielded 2.9% more structures than uncleaved six-histidine-tagged proteins. This 2.9% improvement may seem small, but over the course of the project the structure output from UW-PPG is thus predicted to increase from 260 structures to 318 structures. Therefore, the outlined protocol with 3C cleavage and subtractive IMAC has been shown to be a highly efficient method for the standardized purification of recombinant proteins for structure determination via X-ray crystallography.


Cytogenetic investigations in a family with ataxia telangiectasia.
Cytogenetic findings on a family with ataxia telangiectasia (A-T) in which three of four sibs were affected are described. The affected individuals had approximately twice the level of spontaneous chromosome breakage of a normal control, while the parents and the normal sib had no significant increase. Lymphocytes from all three A-T homozygotes showed specific stable chromosomal rearrangements involving chromosomes 7 and 14. All of these abnormalities involved breakage at the usual four sites associated with A-T (7p14, 7q35, 14q12, and 14q32). Two rearrangements detected in the eldest and most severely affected patient were clones, one of which [t(14;14)(p11;q12)] is not commonly found in A-T cells. No chromosomal rearrangements were encountered in lymphocytes from the control, the parents, or the normal sib. Lymphocytes from the A-T patients also were found to be 7-11 times more sensitive to the induction of chromatid aberrations by X-irradiation than control cells. Lymphocytes from the parents and normal sib showed a moderately increased frequency of X-ray induced aberrations compared with that of the control.


Expression of Nrf2 and its downstream gene targets in hibernating 13-lined ground squirrels, Spermophilus tridecemlineatus.
Mammalian hibernation is associated with wide variation in heart rate, blood flow, and oxygen delivery to tissues and is used as a model of natural ischemia/reperfusion. In non-hibernators, ischemia/reperfusion is typically associated with oxidative stress but hibernators seem to deal with potential oxidative damage by enhancing antioxidant defenses in an anticipatory manner. The present study assesses the role of the Nrf2 transcription factor in the regulation of antioxidant defenses during hibernation. Nrf2 mRNA and protein expression were enhanced in selected organs of 13-lined ground squirrels, Spermophilus tridecemlineatus during hibernation. Furthermore, Nrf2 protein in heart was elevated by 1.4-1.5 fold at multiple stages over a torpor-arousal bout including during entry, long term torpor, and early arousal. Levels returned to euthermic values when squirrels were fully aroused in interbout. Protein levels of selected downstream target genes under Nrf2 control were also measured via immunoblotting over the torpor-arousal cycle in heart. Cu/Zn superoxide dismutase and aflatoxin aldehyde reductase levels increased significantly during entry into torpor and then gradually declined falling to control levels or below in fully aroused animals. Heme oxygenase-1 also showed the same trend. This suggests a role for Nrf2 in regulating the antioxidant defenses needed for hibernation success. Heart nrf2 was amplified by PCR and sequenced. The deduced amino acid sequence showed high identity with the sequence from other mammals but with selected unique substitutions (e.g., proline residues at positions 111 and 230) that might be important for conformational stability of the protein at near 0 degrees C body temperatures in the torpid state.


Aspects of the biology of Ostertagia ostertagi in relation to the genesis of ostertagiasis.
Adaptations such as the capacity of free-living stages to survive environmental stress, inhibition and density-dependent effects on population size and fecundity show O. ostertagi to be a consummate parasite of cattle in temperate environments. Knowledge of these adaptations, within an animal management context, provides the key to understanding the occurrence of disease and a basis for control of parasite numbers. Substantial infections do arise from low egg contamination rates of pastures. Discontinuities in rates of infection are caused by poorly predicted seasonal events such as the effects on eggs of oxygen-deficient environments, fluctuating temperatures and the absence of sufficient moisture for migration of infective larvae from faeces to herbage. Time delays of several months between pasture contamination and availability of infection are therefore common. Ingestion of large numbers of larvae, over a short period early in the grazing season, gives rise to Type I disease or subclinical infections which decrease liveweight gains. In some ecotypes, environmentally induced inhibition leads to the accumulation of large populations of early 4th stage parasites within the host. These populations, under poorly defined conditions, can mature synchronously to produce severe diarrhoea, debility and even death in a proportion of mature cattle--the Type II disease.


EpCAM-Targeted 3WJ RNA Nanoparticle Harboring Delta-5-Desaturase siRNA Inhibited Lung Tumor Formation via DGLA Peroxidation.
Knocking down delta-5-desaturase (D5D) expression by D5D small interfering RNA (siRNA) has been reported that could redirect the cyclooxygenase-2 (COX-2)-catalyzed dihomo-γ-linolenic acid (DGLA) peroxidation from producing prostaglandin E2 to 8-hydroxyoctanoic acid (8-HOA), resulting in the inhibition of colon and pancreatic cancers. However, the effect of D5D siRNA on lung cancer is still unknown. In this study, by incorporating epithelial cell adhesion molecule (EpCAM) aptamer and validated D5D siRNA into the innovative three-way junction (3WJ) RNA nanoparticle, target-specific accumulation and D5D knockdown were achieved in the lung cancer cell and mouse models. By promoting the 8-HOA formation from the COX-2-catalyzed DGLA peroxidation, the 3WJ-EpCAM-D5D siRNA nanoparticle inhibited lung cancer growth in vivo and in vitro. As a potential histone deacetylases inhibitor, 8-HOA subsequently inhibited cancer proliferation and induced apoptosis via suppressing YAP1/TAZ nuclear translocation and expression. Therefore, this 3WJ-RNA nanoparticle could improve the targeting and effectiveness of D5D siRNA in lung cancer therapy.


Stable Solid Electrolyte Interphase In Situ Formed on Magnesium-Metal Anode by using a Perfluorinated Alkoxide-Based All-Magnesium Salt Electrolyte.
Passivation of the Mg anode surface in conventional electrolytes constitutes a critical issue for practical Mg batteries. In this work, a perfluorinated tert-butoxide magnesium salt, Mg(pftb)2 , is codissolved with MgCl2 in tetrahydrofuran (THF) to form an all-magnesium salt electrolyte. Raman spectroscopy and density function theory calculation confirm that [Mg2 Cl3 ·6THF]+ [Mg(pftb)3 ]- is the main electrochemically active species of the electrolyte. The proper lowest unoccupied molecular orbital energy level of the [Mg(pftb)3 ]- anion enables in situ formation of a stable solid electrolyte interphase (SEI) on Mg anodes. A detailed analysis of the SEI reveals that its stability originates from a dual-layered organic/inorganic hybrid structure. Mg//Cu and Mg//Mg cells using the electrolyte achieve a high Coulombic efficiency of 99.7% over 3000 cycles, and low overpotentials over ultralong-cycle lives of 8100, 3000, and 1500 h at current densities of 0.5, 1.0, and 2.0 mA cm-2 , respectively. The robust SEI layer, once formed on a Mg electrode, is also shown highly effective in suppressing side-reactions in a TFSI- -containing electrolyte. A high Coulombic efficiency of 99.5% over 800 cycles is also demonstrated for a Mg//Mo6 S8 full cell, showing great promise of the SEI forming electrolyte in future Mg batteries.


Altered functional connectivity during spatial working memory in children with heavy prenatal alcohol exposure.
Individuals prenatally exposed to alcohol often have impaired spatial working memory (SWM). This study examines functional connections of frontal and parietal regions that support SWM in children with and without prenatal alcohol exposure. Children ages 10 to 16 with histories of heavy prenatal alcohol exposure (AE group; n = 18) and controls (CON group; n = 19) underwent functional magnetic resonance imaging (fMRI) while performing a SWM task. Whole brain task-related functional connectivity of bilateral dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) seed regions were estimated for each participant using a psychophysiological interaction approach. Children in the AE group were less accurate than children in the CON group when performing the SWM task (p = 0.008). Positive coupling between bilateral DLPFC seeds and regions within the fronto-parietal network was observed in the CON group, whereas the AE group showed negative connectivity. In contrast to the CON group, the AE group showed positive connectivity between PPC seeds and frontal lobe regions. Across seeds, decreased negative coupling with regions outside the fronto-parietal network (e.g., left middle occipital gyrus) were observed in the AE group relative to the CON group. Functional data clusters were considered significant at p < 0.05. Overall findings suggest that localized alterations in neural activity, aberrant fronto-parietal network synchrony, and poor coordination of neural responses with regions outside of this network may help explain SWM deficits in individuals with a history of heavy prenatal alcohol exposure.


Successful treatment of lathosterolosis: A rare defect in cholesterol biosynthesis-A case report and review of literature.
Lathosterolosis is a rare autosomal recessive disorder of cholesterol biosynthesis. It is caused by defects in the SC5D (sterol C5-desaturase) gene which encodes for the 3-beta-hydroxysteroid-delta-5-desaturase (also called sterol-C5-desaturase or lathosterol dehydrogenase). Only six cases have been described in the literature, but it is possible that a number of patients with milder forms of the condition might have been missed. Lathosterolosis manifests as microcephaly, bilateral cataracts, dysmorphism, limb anomalies, and developmental delay/intellectual disability. Liver involvement is variable and can range from normal liver function tests to portal fibrosis and cirrhosis. Diagnosis is made by demonstration of specific mutations in the SC5D gene and by plasma sterol analysis to confirm elevated lathosterol levels. In this report, we describe a girl with transaminitis in association with developmental delay/intellectual disability, facial dysmorphism, limb anomalies, and bilateral cataracts. Fibroscan showed severe liver fibrosis. Plasma sterol analysis and exome sequencing confirmed the diagnosis of lathosterolosis. Simvastatin treatment resulted in lowering of plasma lathosterol levels, improvement in transaminitis, and liver fibrosis grade, suggesting that children with this condition should be actively treated in order to prevent progression of liver disease.


Connections and consequences in complex systems: insights from a case study of the emergence and local impact of crisis resolution and home treatment services.
In this article the broad contours of a complexity perspective are outlined. Complexity ideas are then drawn on to frame an empirical examination of the connections running between different levels of organisation in health and social care, and to underpin investigation into the intended and unintended local system consequences of service development. Data are used from a study conducted in the UK's mental health field. Here, macro-level policy has led to the supplementing of longstanding community mental health teams by newer, more specialised, services. An example includes teams providing crisis resolution and home treatment (CRHT) care as an alternative to hospital admission. Using an embedded case study design, where 'the case' examined was a new CRHT team set in its surrounding organisational environment, ethnographic data (with interviews predominating) were generated in a single site in Wales over 18 months from the middle of 2007. In a large-scale context favourable to local decision-making, and against a background of a partial and disputed evidence base, the move to establish the new standalone service was contested. Whilst users valued the work of the team, and local practitioners recognised the quality of its contribution, powerful effects were also triggered across the locality's horizontal interfaces. Participants described parts of the interconnected system being closed to release resources, staff gravitating to new crisis services leaving holes elsewhere, and the most needy service users being cared for by the least experienced workers. Some community mental health team staff described unexpected increases in workload, and disputes over eligibility for crisis care with implications for system-wide working relations. Detailed data extracts are used to illustrate these connections and consequences. Concluding lessons are drawn on the use of evidence to inform policy, on the significance of local contexts and system interfaces, and on anticipating the unexpected at times of change.


Editorial Commentary: Patient Reported Outcomes Measurement Information System (PROMIS) May Be Our Promise for the Future.
Collection of patient-reported outcome data in orthopaedic surgery is more important than ever. A recent research article compares the Patient Reported Outcomes Measurement Information System to several general health and shoulder-specific scoring systems in patients with preoperative rotator cuff pathology. This study addresses important concepts such as validity, reliability, floor/ceiling effects, and "decreased question burden" or questionnaire brevity that orthopaedic surgeons should consider when they collect patient-reported outcome data. It is vitally important that orthopaedic surgeons become actively involved in data collection efforts.


Periaqueductal gray neurons project to spinally projecting GABAergic neurons in the rostral ventromedial medulla.
The analgesic effects of morphine are mediated, in part, by periaqueductal gray (PAG) neurons that project to the rostral ventromedial medulla (RVM). Although much of the neural circuitry within the RVM has been described, the relationship between RVM neurons and PAG input and spinal output is not known. The objective of this study was to determine whether GABAergic output neurons from the PAG target RVM reticulospinal neurons. Immunocytochemistry and confocal microscopy revealed that PAG neurons project extensively to RVM neurons projecting to the spinal cord, and two-thirds of these reticulospinal neurons appear to be GABAergic (contain GAD67 immunoreactivity). The majority (71%) of PAG fibers that contact RVM reticulospinal GAD67-immunoreactive neurons also contained GAD67 immunoreactivity. Thus, there is an inhibitory projection from PAG to inhibitory RVM reticulospinal neurons. However, there were also PAG projections to the RVM that did not contain GAD67 immunoreactivity. Additional experiments were conducted to determine whether the heterogeneity in this projection can be explained by the electrophysiological character of the RVM target neurons. PAG projections to electrophysiologically defined and juxtacellularly filled ON, OFF, and Neutral cells in the RVM were examined. Similar to the pattern reported above, both GAD67- and non-GAD67-immunoreactive PAG neurons project to RVM ON, OFF, and Neutral cells in the RVM. These inputs include a GAD67-immunoreactive projection to a GAD67-immunoreactive ON cell and non-GAD67 projections to GAD67-immunoreactive OFF cells. This pattern is consistent with PAG neurons producing antinociception by direct excitation of RVM OFF cells and inhibition of ON cells.


The NHS leads positive change for BME people in the workplace.
At the end of last month, I attended the launch of Race in the Workplace: The McGregor-Smith Review.


Avian influenza rapidly induces antiviral genes in duck lung and intestine.
Ducks are the natural reservoir of influenza A and survive infection by most strains. To characterize the duck immune response to influenza, we sought to identify innate immune genes expressed early in an infection. We used suppressive subtractive hybridization (SSH) to construct 3 libraries enriched in differentially expressed genes from lung RNA of a duck infected with highly pathogenic avian influenza virus A/Vietnam/1203/04 (H5N1), or lung and intestine RNA of a duck infected with low pathogenic avian influenza A/mallard/BC/500/05 (H5N2) compared to a mock-infected duck. Sequencing of 1687 clones identified a transcription profile enriched in genes involved in antiviral defense and other cellular processes. Major histocompatibility complex class I (MHC I), interferon induced protein with tricopeptide repeats 5 (IFIT5), and 2'-5' oligoadenylate synthetase-like gene (OASL) were increased more than 1000-fold in relative transcript abundance in duck lung at 1dpi with highly pathogenic VN1203. These genes were induced much less in lung or intestine following infection with low pathogenic BC500. The expression of these genes following infection suggests that ducks initiate an immediate and robust response to a potentially lethal influenza strain, and a minimal response to a low pathogenic strain.


Bovine milk-derived cells express transcriptome markers of pluripotency and secrete bioactive factors with regenerative and antimicrobial activity.
The bovine mammary stem/progenitor cell secretome stimulates regeneration in vitro and contains proteins associated with antimicrobial defense. This has led to the exploration of the secretome as a biologic treatment for mastitis, a costly inflammation of the udder commonly caused by bacteria. This study reports on a population of bovine mammary stem/progenitor cells isolated non-invasively from milk (MiDCs). MiDCs were characterized by immunophenotyping, mammosphere formation assays, and single cell RNA sequencing. They displayed epithelial morphology, exhibited markers of mammary stem/progenitor cells, and formed mammospheres, like mammary gland tissue-isolated stem/progenitor cells. Single cell RNA sequencing revealed two sub-populations of MiDCs: epithelial cells and macrophages. Functionally, the MiDC secretome increased fibroblast migration, promoted angiogenesis of endothelial cells, and inhibited the growth of mastitis-associated bacteria, including antibiotic-resistant strains, in vitro. These qualities of MiDCs render them a source of stem cells and stem cell products that may be used to treat diseases affecting the dairy industry, including mastitis.


Ultra-sensitive film sensor based on Al2O3-Au nanoparticles supported on PDDA-functionalized graphene for the determination of acetaminophen.
An electrochemical sensor of acetaminophen based on poly(diallyldimethylammonium chloride) (PDDA)-functionalized reduced graphene-loaded Al2O3-Au nanoparticles coated onto glassy carbon electrode (Al2O3-Au/PDDA/reduced graphene oxide (rGO)/glass carbon electrode (GCE)) were prepared by layer self-assembly technique. The as-prepared electrode-modified materials were characterized by scanning electron microscopy, X-ray powder diffraction, and Fourier transform infrared spectroscopy. The electrocatalytic performances of Al2O3-Au/PDDA/rGO-modified glassy carbon electrode toward the acetaminophen were investigated by cyclic voltammetry and differential pulse voltammetry. The modified electrodes of graphene oxide (GO)/GCE, PDDA/rGO/GCE, and Al2O3-Au/PDDA/rGO/GCE were constructed for comparison and learning the catalytic mechanism. The research showed Al2O3-Au/PDDA/rGO/GCE having good electrochemical performance, attributing to the synergetic effect that comes from the special nanocomposite structure and physicochemical properties of Al2O3-Au nanoparticles and graphene. A low detection limit of 6 nM (S/N = 3) and a wide linear detection range from 0.02 to 200 μM (R (2) = 0.9970) was obtained. The preparation of sensor was successfully applied for the detection of acetaminophen in commercial pharmaceutical pills. Graphical abstract Schematic diagram of synthesis of Al2O3-Au/PDDA/rGO/GCE.


Mathematical modelling of SARS-CoV-2 variant outbreaks reveals their probability of extinction.
When a virus spreads, it may mutate into, e.g., vaccine resistant or fast spreading lineages, as was the case for the Danish Cluster-5 mink variant (belonging to the B.1.1.298 lineage), the British B.1.1.7 lineage, and the South African B.1.351 lineage of the SARS-CoV-2 virus. A way to handle such spreads is through a containment strategy, where the population in the affected area is isolated until the spread has been stopped. Under such circumstances, it is important to monitor whether the mutated virus is extinct via massive testing for the virus sub-type. If successful, the strategy will lead to lower and lower numbers of the sub-type, and it will eventually die out. An important question is, for how long time one should wait to be sure the sub-type is extinct? We use a hidden Markov model for infection spread and an approximation of a two stage sampling scheme to infer the probability of extinction. The potential of the method is illustrated via a simulation study. Finally, the model is used to assess the Danish containment strategy when SARS-CoV-2 spread from mink to man during the summer of 2020, including the Cluster-5 sub-type. In order to avoid further spread and mink being a large animal virus reservoir, this situation led to the isolation of seven municipalities in the Northern part of the country, the culling of the entire Danish 17 million large mink population, and a bill to interim ban Danish mink production until the end of 2021.


Hemodynamic and catecholamine response to a rapid increase in isoflurane or sevoflurane concentration during a maintenance phase of anesthesia in humans.
The purpose of this study was to compare hemodynamic and catecholamine changes due to a sudden increase in inhalation anesthetic concentrations (isoflurane and sevoflurane) during surgery. Thirty patients aged 40-70 years scheduled for lower abdominal surgery were anesthetized with either isoflurane or sevoflurane with nitrous oxide and epidural block. During surgery the isoflurane or sevoflurane concentration was kept at 0.5 minimum alveolar concentration (MAC) (end-tidal concentration) for 15 min. Then the isoflurane or sevoflurane concentration (inhalation concentration) was changed to 1.5 MAC and maintained at that level for 10 min. Thereafter, it was decreased to 0.5 MAC for 10 min. Blood pressure, heart rate, and plasma concentrations of epinephrine and norepinephrine were measured. The blood pressure decreased significantly in both groups after increasing the anesthetic concentration, and it increased after decreasing the concentration. The decrease in systolic blood pressure was significantly larger in the isoflurane group. The heart rate increased significantly after increasing the anesthetic concentration only in the isoflurane group. Plasma concentrations of epinephrine and norepinephrine increased significantly in the isoflurane group, whereas the epinephrine concentration (but not the norepinephrine concentration) decreased in the sevoflurane group. During surgery a sudden increase in isoflurane concentration induced larger changes in hemodynamics and sympathetic nerve activity than sevoflurane.


Viroporins from RNA viruses induce caspase-dependent apoptosis.
The virus-encoded viroporins are known to modify membrane permeability and play an essential role in virus budding. Here, a comparative analysis of the membrane permeabilization capacity of a number of viroporins was performed in baby hamster kidney cells. Synthesis of 6K protein from Sindbis virus, E from mouse hepatitis virus, M2 from influenza A virus, and 2B and 3A from poliovirus enhanced membrane permeability to different extents. We show that two proteins from hepatitis C virus, p7 and NS4A, also display viroporin activity to a level comparable to 6K protein. In addition to their capacity to disrupt ionic cellular homeostasis and promote bacterial cell lysis, the expressed viroporins were able to induce cell death. Degradation of internucleosomal DNA and generation of apoptotic bodies were observed upon viroporin expression. Consistently, cleavage of translation initiation factor 4GI and poly-(ADP-ribose) polymerase indicated activation of effector caspase-3. We found that poliovirus 2B localizes partially in mitochondria and induces an anomalous perinuclear distribution of these organelles. Mitochondria morphology was also altered after expression of other viroporins. Finally, detection of cytochrome c release from mitochondria suggests involvement of the mitochondrial pathway in viroporin-induced apoptosis. These findings suggest that viroporins induce caspase-dependent programmed cell death.


Changing the Conversation about The Ethics of Genomics and Health Disparities Research with American Indian and Alaska Native Communities: A Report from the Field.
"Changing the conversation" around genomic research with U.S. tribal communities may lead to new pathways to address persistent health disparities. Restoring trustworthiness between researchers and communities entails a willingness to listen to Indigenous voices, being flexible, and refining existing policies and frameworks to adapt to communities' needs.


Nitric oxide, prostacyclin and cyclic nucleotide formation in externally stented porcine vein grafts.
Non-restrictive, porous, external stents inhibit neointima formation in porcine vein grafts. Since the mechanisms underlying these effects are unknown we investigated the impact of this external stent on factors known to inhibit vascular smooth muscle cell proliferation: prostacyclin (PGI2), nitric oxide (NO), cAMP and cGMP formation in different regions of stented and unstented porcine vein grafts. Paired stented and unstented saphenous vein-carotid artery interposition grafting was carried out in Landrace pigs. One month after surgery, the vessels were excised and the formation of PGI2, cAMP and cGMP determined using radioimmunoassay and nitric oxide synthase (NOS) distribution studied using autoradiography and histochemistry. There were no significant differences between PGI2, cAMP and cGMP (nitroprusside-stimulated) formation in the medial/intimal regions of grafts of stented vein graft and ungrafted saphenous vein whereas all were significantly reduced in unstented vein graft. A23187-stimulated cGMP formation (mediated by NO release) and NOS content was significantly greater in the medial/intimal region of stented and unstented vein graft compared to ungrafted saphenous vein, indicating induction of endothelial NOS (eNOS) in both types of graft. This normalisation of the PGI2-cAMP axis and guanylyl cyclase activity in the medial/intimal region may contribute to the beneficial impact of the external stent on vein graft thickening. The increase in eNOS in both stented and unstented vein grafts mitigates against this isoform as playing a role in mediating the inhibitory effect of the stent on neointima formation. In the adventitia of both stented and unstented grafts there was an increase in PGI2, cAMP and cGMP formation compared to ungrafted saphenous vein, the production being greater in the stented compared to the unstented graft. In the adventitia of stented veini grafts, NOS, detected with NAPDH diaphorase staining, was associated with microvessels as well as with inflammatory cells. Taken together, these data are suggestive of a role for PGI2 and NO in promoting microangiogenesis in the adventitia of stented vein grafts which may in turn minimize graft hypoxia, an established contributory factor to neointima formation.


The psychological effects of reporting extreme violence: a study of Kenyan journalists.
To assess the psychological health of journalists in Kenya who have reported on, and been exposed to, extreme violence. Descriptive. Psychological responses were elicited to two stressors, the ethnic violence surrounding the disputed 2007 general election and the Al-Shabab attack on the Westgate Mall in Nairobi. A representative sample of 90 Kenyan journalists was enrolled. Newsrooms of two national news organizations in Kenya. Symptoms of post-traumatic stress disorder (Impact of Event Scale-revised), depression (Deck Depression inventory-revised) and general psychological wellbeing (General Health Questionnaire). Of the 90 journalists approached 57 (63.3%) responded. Journalists covering the election violence (n = 23) reported significantly more PTSD type intrusion (p = 0.027) and arousal (p = 0.024) symptoms than their colleagues (n = 34) who had not covered the violence. Reporting the Westgate attack was not associated with increased psychopathology. Being wounded (n = 11) emerged as the most robust independent predictor of emotional distress. Journalists covering the ethnic violence compared to colleagues who did not were not more likely to receive psychological counselling. These data, the first of their kind from an African country, replicate findings over a decade old from Western media, namely that journalists asked to cover life-threatening events may develop significant symptoms of emotional difficulties and fail to receive therapy for them. Good journalism, a pillar of civil society, depends on healthy journalists. It is hoped that these data act as a catalyst encouraging news organisations sending journalists into harm's way to look out for their psychological health in doing so.


Saliva as a possible tool for the SARS-CoV-2 detection: A review.
Salivary tests for the new coronavirus (SARS-CoV-2) diagnosis have been suggested as alternative methods for the nasopharyngeal and oropharyngeal tests. Two reviewers independently performed a search in the following electronic databases: PubMed, Medline, Cochrane Library, Web of Science, Embase and Scopus to identify cross-sectional and cohort studies that used saliva samples for SARS-CoV-2 detection. The search strategy was: ("saliva") and ("SARS-CoV-2" or "coronavirus" or "COVID-1"). A total of 363 studies were identified and 39 were selected for review. Salivary samples for SARS-CoV-2 detection was as consistent and sensitive as the nasopharyngeal swabs in most studies, having been effective in detecting asymptomatic infections previously tested negative in nasopharyngeal samples. Viral nucleic acids found in saliva obtained from the duct of the salivary gland may indicate infection in that gland. Live viruses could be detected in saliva by viral culture. Salivary samples show great potential in SARS-CoV-2 detection and may be recommended as a simple and non-invasive alternative.


Anterior C2-C3 fixation with screws: proposal of a new technique and comparative mechanical assays.
The technical difficulties involved in the anterior fixation of the C2-C3 vertebral segment by means of plates and screws, related to retraction of the structures around the vertebral segment, appropriate exposure of the site and positioning of the screws and plate, motivated the development of a new modality of fixation of this segment using only screws. Fixation of the C2-C3 vertebral segment according to the technique proposed requires less exposure of the vertebral segment and does not involve the technical difficulties of standard fixation with plates and screws. In order to study the mechanical properties of this new modality of vertebral fixation, mechanical tests were performed comparing the proposed technique (fixation solely with screws positioned in the craniocaudal direction) and routinely used fixation (H plate and screws). The tests were performed using 80 cervical spine segments from Landrace pigs aged 5 months. The vertebral segments fixed by the two techniques were divided into experimental groups of ten specimens each and submitted to mechanical tests of flexion, extension, lateral bending and rotation in a universal testing machine. The mechanical properties used to compare the results were the load necessary to produce a pre-established deformation and stiffness. No significant differences were observed between the values obtained for the production of the pre-established deformation in the flexion and rotation tests. In the extension and lateral bending tests, the mean values obtained for vertebral segments fixed only with screws were significantly higher. Analysis of stiffness showed no significant difference in the flexion, rotation and lateral bending tests, whereas in the extension tests, the mean values for the group fixed only with screws were significantly higher. The results of the mechanical tests performed showed that fixation of the C2-C3 segment only with screws was not inferior from a mechanical point of view when compared to fixation with H plates of the Orozco type.


Is stronger better? Influence of a strength phase followed by a hypertrophy phase on muscular adaptations in resistance-trained men.
Although used by resistance-trained individuals, it is unknown if increasing muscle strength prior to hypertrophy training leads to greater muscle growth and strength gains. We investigated muscle thickness and maximum strength in 26 resistance-trained men who were randomly assigned to either: STHT, consisted in a 3-week strength-oriented training period (4x1-3 repetition maximum [RM]) prior to a 5-week hypertrophy-oriented period (4x8-12RM), or HT, which comprised an 8-week hypertrophy-oriented training period. Vastus lateralis muscle thickness, and back squat and leg-press 1-RM were assessed at pre, third week, and after 8 weeks of training. When pre-to-post changes are compared, STHT induced greater muscle growth (p = 0.049; 95%CI = 0.15-3.2%; d = 0.81) and strength gains in the back squat (p = 0.015; 95%CI = 1.5-13%; d = 1.05) and leg-press 45° (p = 0.044; 95%CI = 0.16-9.9%; d = 0.79) compared to HT. Our results support the use of a period to increase muscle strength prior to an HT to increase muscle thickness and maximum strength in resistance-trained men.


Functional and environmental performance of plant-produced crumb rubber asphalt mixtures using the dry process.
Incorporating crumb rubber (CR) using the dry process, directly in the asphalt mixture rather than into the bituminous binder requires no plant retrofitting, and therefore is the most practical industrial method for CR incorporation into asphalt mixtures. Nevertheless, very few large scale studies have been conducted. This work uses a holistic approach and reports on the functional and environmental performance of asphalt mixtures with different concentrations of CR fabricated employing the dry process in asphalt plants. Gaseous emissions were monitored during the production and laboratory leaching tests simulating the release of pollutants during rain, was conducted to evaluate the toxicology of both the CR material alone and the modified asphalt mixtures. In addition, laboratory compacted samples were tested to assess their fatigue behavior. Furthermore, noise relevant surface properties of large roller compacted slabs were evaluated before and after being subjected to a load simulator (MMLS3) to evaluate their resistance to permanent deformation. The results confirm that comparable performance can be achieved with the incorporation of CR using the dry process for high performance surfaces such as semi-dense asphalt, which usually require the use of polymer modified binders. Environmental performance improvement can be achieved by a washing step of the CR material that could remove polar CR additives which have commonly been used as vulcanization accelerator during rubber production.


Disclosure to physicians of CAM use by breast cancer patients: findings from the Women's Healthy Eating and Living Study.
Physician awareness of their patients' use of complementary and alternative medicine (CAM) is crucial, particularly in the setting of a potentially life-threatening disease such as cancer. The potential for harmful treatment interactions may be greatest when a patient sees a CAM practitioner--perceived as a physician-like authority figure--but does not disclose this to their physician. Therefore, this study investigated the extent of nondisclosure in a large cohort of cancer patients. CAM use in participants of the UCSD Women's Healthy Eating and Living (WHEL) Study, a multicenter study of the effect of diet and lifestyle on disease-free and overall survival in women aged 18-70 years who had completed treatment for invasive breast cancer between 1995 and 2000, is investigated. Data regarding CAM use and disclosure were collected via a telephone-administered questionnaire in 2003-2004. This questionnaire asked about different CAM modalities, including those requiring a "skilled CAM practitioner" (acupuncturist, chiropractor, homeopath, or naturopath) for administration. Demographic data were obtained at the WHEL baseline clinic interview. Modality-specific disclosure rates were determined and a comparison of demographic variables of disclosers versus nondisclosers was conducted using 2 tests for categorical variables, and t tests for continuous variables. Of 3088 total WHEL participants, 2527 completed the CAM questionnaire. Of these, 2017 reported using some form of CAM. Of these, 300 received treatment from an acupuncturist, chiropractor, homeopath, or naturopath and also provided information on whether or not they disclosed this care to their conventional physician. The highest disclosure rate was for naturopathy (85%), followed by homeopathy (74%), acupuncture (71%), and chiropractic (47%). Among demographic characteristics, only education (P=.047) and study site (P=.039) were associated with disclosure. College graduates and postgraduates, in particular, were more likely to disclose CAM use to their physicians than those with lesser education. Overall, moderately high rates of physician disclosure of CAM use for all modalities except chiropractic were observed. Education and study site associations suggest that disclosure may be greater when CAM use is more prevalent and possibly more socially accepted. These findings underscore the importance of open, destigmatized patient--physician communication regarding CAM use.


Turn-on fluorescence of ruthenium pyrene complexes in response to bovine serum albumin.
Two novel pyrene triphenylphosphine ruthenium conjugates act as fluorescent turn-on beacons for serum albumin, being non-fluorescent in aqueous media but exhibiting strong emission upon binding to BSA. The selective cytotoxicity of the compounds against tumour cells is enhanced upon irradiation by UV-light, paving the way for application in photodynamic therapy under two-photon excitation.


Melatonin and insulin modulates the cellular biochemistry, histoarchitecture and receptor expression during hepatic injury in diabetic rats.
Aims; The present study was designed to ameliorate the integrated efficacy of exogenous melatonin and insulin on tissue biochemical, serological, histopathological architecture and receptor expression of melatonin (MT1, MT2) and insulin receptor (IR) expression against the hepatic injury in diabetic rats. Materials and Method; the rats were randomly allocated into nine different experimental groups. Diabetes was induced by streptozotocin (15 mg/kg) for 6 days. Rats having blood glucose level above 250 mg/dl were considered as diabetic. Animals euthanized after 4 weeks, blood and liver samples were collected to perform various biochemical, serological, histopathological and receptor expression of melatonin (MT1, MT2) and insulin receptor (IR). Key findings; Diabetic rats revealed significant increase in lipid peroxidation (LPO) of liver tissue, liver function tests (ALT, AST and ALP), increase in serum cholesterol, LDL, VLD, but decrease in HDL level. Further, diabetic rats exhibited significant decrement in antioxidative enzymatic system (GSH, SOD, CAT, GR, GPX, G6PDH and GST), total tissue protein and glycogen content. Histomicrograph of liver of diabetic rats resulted in vacuolization indicating cellular damages as well as upregulation in liver MT1, MT2 and IR protein expression. However, the combined therapy (Melatonin and insulin treatment) revealed significant recovery and restoration in biochemical, cellular architecture of liver cells and receptor expression pattern of MT1, MT2 and IR. Significance; It may establish a synergistic action of melatonin and insulin, which might be a novel evidence for clinicians to combat the hepatic complication along with controlling diabetes.


Spatial and temporal patterns of granivorous ant seed predation in patchy cereal crop areas of central Spain.
Patterns of granivorous ant seed predation in extensive cereal croplands of central Spain were investigated by measuring seed removal rates on artificial seed patches. Sampling was designed to cope with the seasonal and daily foraging cycle of ant colonies. Simultaneously with removal rates, I measured seed availability, habitat physiognomy at two spatial scales (landscape and microhabitat), weather variables (temperature and rainfall), and distance to the nearest ant nest. Ant seed predation was concentrated on shrublands, and associated with places with high covers of shrubs, chamaephytes and stones. These results were in close agreement with those obtained by analyzing the spatial distribution of granivorous ant nests (Díaz 1991). Moreover, there was a close relationship between seed removal rates and distance to the nearest ant nest, that fitted the predictions of the optimal foraging model developed by Reyes-López (1987). Seasonal and daily patterns of ant foraging activity seemed to depend more on endogenous factors than on environmental variation. I conclude that ants were not able to track the spatial and temporal variation of their food resources in these man-modified habitats, so that their potential to interact with other members of the granivore system is greatly reduced by human activities.


Facilitating and inhibiting factors for long-term involvement of patients at outcome conferences--lessons learnt from a decade of collaboration in OMERACT: a qualitative study.
Several studies have provided insights into the conditions for successful patient involvement in health research. We recently demonstrated that long-term engagement with people with rheumatic conditions in international outcome research led to significant changes in the research agenda in the field of rheumatology. This article explores facilitating and inhibiting factors for long-term involvement of patients as collaborative partners at five Outcome Measures in Rheumatology (OMERACT) conferences. Responsive evaluation, starting with a thematic document analysis of conference proceedings and the grey literature, followed by 38 qualitative interviews. Interview transcripts were subjected to inductive content analysis. 5 international OMERACT conferences between 2002 and 2012. Patient delegates (n=16) and professional delegates representing researchers (n=14), pharmaceutical industry and regulators (n=2). Combined review of the document analysis and interview data revealed five main facilitators and three main barriers. Patient engagement as full participants at OMERACT conferences was enhanced by: strong leadership commitment and the presence of change agents, a clear selection procedure, an inclusive consensus-based conference design, individualised and self-organised support, an interactive and encouraging moderation style during discussion groups. Barriers were related to the intensity of the conference programme, scepticism among researchers and doubts about the representativeness of the patient group. This study concludes that developing a sustainable structure for funding, selection and support of patient delegates, as well as adjusting conference design and moderation style, contributes not only towards facilitating direct dialogue between all stakeholders but also towards enhancing mutual understanding and the successful incorporation of the patient perspective in an outcome conference such as OMERACT.


Effects of 6-times-weekly versus 3-times-weekly hemodialysis on depressive symptoms and self-reported mental health: Frequent Hemodialysis Network (FHN) Trials.
Patients undergoing maintenance hemodialysis frequently exhibit poor mental health. We studied the effects of frequent in-center and nocturnal hemodialysis on depressive symptoms and self-reported mental health. 1-year randomized controlled clinical trials. Hemodialysis centers in the United States and Canada. 332 patients were randomly assigned to frequent (6-times-weekly) compared with conventional (3-times-weekly) hemodialysis in the Frequent Hemodialysis Network (FHN) Daily (n = 245) and Nocturnal (n = 87) Trials. The Daily Trial was a trial of frequent (6-times-weekly) compared with conventional (3-times-weekly) in-center hemodialysis. The Nocturnal Trial assigned patients to either frequent nocturnal (6-times-weekly) hemodialysis or conventional (3-times-weekly) hemodialysis. Self-reported depressive symptoms and mental health. Beck Depression Inventory and the mental health composite score and emotional subscale of the RAND 36-Item Health Survey at baseline and 4 and 12 months. The mental health composite score is derived by summarizing these domains of the RAND 36-Item Health Survey: emotional, role emotional, energy/fatigue, and social functioning scales. In the Daily Trial, participants randomly assigned to frequent compared with conventional in-center hemodialysis showed no significant change over 12 months in adjusted mean Beck Depression Inventory score (-1.9 ± 0.7 vs -0.6 ± 0.7; P = 0.2), but experienced clinically significant improvements in adjusted mean mental health composite (3.7 ± 0.9 vs 0.2 ± 1.0; P = 0.007) and emotional subscale (5.2 ± 1.6 vs -0.3 ± 1.7; P = 0.01) scores. In the Nocturnal Trial, there were no significant changes in the same metrics in participants randomly assigned to nocturnal compared with conventional hemodialysis. Trial interventions were not blinded. Frequent in-center hemodialysis, as compared with conventional in-center hemodialysis, improved self-reported general mental health. Changes in self-reported depressive symptoms were not statistically significant. We were unable to conclude whether nocturnal hemodialysis yielded similar effects.


The zone-based approach for selection of tympanoplasty technique.
At the outset of surgery, the extent of a tympanic membrane defect is judged including any additional loss of area that may result from disease extirpation or removal of the mucocutaneous junction. There are, three tiers of complexity when deciding upon which technique should be used for repair. Limited central perforations are defects amenable to a standard underlay technique. The Zone Based Approach is applied for marginal perforations whereby the specific technique is selected based on the zone of the defect. The zones and specific techniques are detailed. There are however, still a significant number of patients who have scarce residual tympanic membrane, or keratin matrix adherently involving the undersurface requiring sacrifice. These situations prove poor for either standard underlay or the zone based techniques. The total tympanic membrane reconstruction (TT MR) technique was developed specifically to avoid these complications as well as facilitate extirpation of the more extensive inflammatory and neoplastic pathologies commonly encountered, yet still amenable to intact canal wall mastoidectomy approaches.


Hypercalcemia associated with mineral oil-induced sclerosing paraffinomas.
Granuloma-forming diseases such as sarcoidosis are associated with extrarenal synthesis of 1,25-dihydroxyvitamin D [1,25(OH)₂D]. We describe a case of extensive skin lesions associated with mineral oil injections in which we provide evidence for cutaneous granuloma synthesis of 1,25(OH)₂D in the pathogenesis of the patient's hypercalcemia. Analysis of expression of the 25(OH)D-1a-hydroxylase (1-a OHase [CYP27b1]) was carried out by immunohistochemical analysis of involved skin. In involved skin, expression of CYP27b1 was found in the dermis, where it is not normally expressed. Successful management of hypercalcemia was achieved with glucocorticoids. Hypercalcemia associated with mineral oil induced skin lesions is likely driven by unregulated expression of CYP27b1 by inflammatory monocytes and macrophages infiltrating the dermis.


Improved Low-Rank Filtering of Magnetic Resonance Spectroscopic Imaging Data Corrupted by Noise and B₀ Field Inhomogeneity.
To improve the signal-to-noise ratio (SNR) of magnetic resonance spectroscopic imaging (MRSI) data. A low-rank filtering method recently proposed for denoising MRSI data is extended by: 1) incorporating tissue boundary constraints to enable local low-rank filtering, and 2) integrating B0 field inhomogeneity correction by rank-minimization to make the low-rank model more effective. The proposed method was validated using both simulated and in vivo MRSI data. Its denoising performance is also compared with an upper bound based on the constrained Cramér-Rao lower bound for low-rank filtering. Low-rank filtering can effectively improve the SNR of MRSI data corrupted by both noise and B0 field inhomogeneity. The proposed low-rank filtering method will enhance the practical utility of high-resolution MRSI, where SNR has been a limiting factor.


The biosynthetic pathway of pyrimidine (deoxy)nucleotides: a sensor of oxygen tension necessary for maintaining cell proliferation?
Culture experiments on Ehrlich ascites tumor cells revealed that a low oxygen tension (about 20% in normoxic atmosphere) induced an increase in the length of the growth cycle. The relative growth of aerobic control cells after transfer to the second in vitro passage was 145% within 24 h, and reduced to 50% at 1% O2 and about 30% at 0.1% O2. The increase in protein and DNA content of these hypoxic cultures was equally impaired. Also, the cell cycle traverse as analyzed by flow cytometry was affected predominantly at the G1/early S stage. Uptake of labeled thymidine into acid-insoluble material of hypoxic cells was below that of controls whereas incorporation of uridine exceeded that of normoxic controls. Supplementation of cells cultured under 0.1 and 1% O2 with 0.1 mM uridine or 0.1 mM deoxycytidine + 0.01 mM deoxyadenosine and deoxyguanosine improved all growth parameters; deoxynucleosides were more effective than uridine in cells under 0.1% O2 whereas in cells cultured under 1% O2 similar effects of both were observed. This points to an insufficient supply of nucleic acid precursors even under moderate limitations of oxygen tension and not only under strict hypoxia. Whereas a 12-h cultivation time at 0.1% O2 hardly impaired cell growth after reoxygenation, a cultivation time of 24 h considerably reduced the cellular capability to recover. This was alleviated by addition of (deoxy)nucleosides from the beginning of hypoxic culture. The results are interpreted as supporting the concept that the biosynthetic pathway of pyrimidine (deoxy)nucleotides--because of two oxygen-dependent enzymes, dihydroorotate dehydrogenase and ribonucleotide reductase--is a potential transducer of environmental limitations in oxygen tension to the proliferative capacity of cells.


Frog liver dolichols: separation and quantitative determination related to seasonality.
1. The liver of female frogs shows a significantly higher dolichol content in May (134 micrograms/g) than in November (90 micrograms/g). The male frog liver (134 micrograms/g May; 119 micrograms/g November) does not show any significant change. 2. The rat liver does not show any significant change in dolichol content from May to November (30 micrograms/g). 3. The dolichyl-phosphate level was the same in male and female frog livers and in the rat liver. 4. Data is given of the distribution of dolichols according to the number of their isoprene residues.


The effect of histidine ammonia-lyase on some murine tumours.
The histidine ammonia-lyase from bacterial strain CAMR 5315 was partially purified to assess its effect on the growth of murine tumours. This strain was selected as the source after an extensive screening programme for histidine ammonia-lyases. The enzyme was partially purified by ammonium sulphate fractionation, chromatography on DEAE-cellulose and Sephadex G-150. The enzyme reduced circulating L-histidine levels in Wistar rats and in mice persisted with a half-life of 6-7 h. Neither LDH virus nor chemical modification with ethylacetimidate increased the half-life as observed with L-asparaginase and L-glutaminase. The enzyme was tested in mice against Ehrlich carcinoma, L5178Y lymphoblastic leukaemia, Mc/S sarcoma, B16 melanoma, P8157 mastocytoma, P1798 lymphosarcoma and the Gardner 6C3HED lymphosarcoma. The only tumours to show sensitivity to the enzyme were the Mc/S sarcoma against which a 65% increase in life span was observed at the highest enzyme dose, 1000 U/kg on alternate days over 14 days and the Ehrlich ascites carcinoma where cures were obtained at 250 U/kg on alternate days over 14 days, but only at inocula levels of 10(5) and 10(3) cells/animal respectively.


Fibroblast activation protein imaging in atrial fibrillation: a proof-of-concept study.
To evaluate the feasibility of using radiolabeled fibroblast activation protein inhibitor (FAPI) PET/CT imaging to assess activated fibroblasts in the atria of individuals with AF and to identify factors contributing to enhanced atrial activity. We constructed left atrial appendage (LAA) pacing beagle dog AF models (n = 5) and conducted 18F-FAPI PET/CT imaging at baseline and eight weeks after pacing. Right atrial (RA) specimens were collected from these models. Additionally, 28 AF patients and ten age- and sex-matched healthy volunteers underwent 18F-FAPI PET/CT imaging. RA of AF beagles showed increased 18F-FAPI uptake. Among AF patients, 18 out of 28 (64.3%) exhibited enhanced atrial FAPI activity. No atrial 18F-FAPI uptake was observed in the sham beagle and healthy volunteers. In animal RA specimens, 18F-FAPI activity correlated positively with FAP mRNA (r = .98, P = .002) and protein (r = .82, P = .03) levels, as well as collagen I mRNA expression (r = .85, P = .02). B-type natriuretic peptide levels were associated with atrial 18F-FAPI activity (OR = 3.01, P = .046). This proof-of-concept study suggests that 18F-FAPI PET/CT imaging may be a feasible method for evaluating activated fibroblasts in the atria of AF patients.


Association of Weight Loss Maintenance and Weight Regain on 4-Year Changes in CVD Risk Factors: the Action for Health in Diabetes (Look AHEAD) Clinical Trial.
Short-term weight loss improves cardiovascular disease (CVD) risk factors. We sought to determine the longer-term effects of maintaining weight loss or, conversely, regaining weight. We used data from Action for Health in Diabetes (Look AHEAD), a randomized trial of intensive lifestyle intervention (ILI) compared to a control condition in overweight/obese individuals with type 2 diabetes. ILI participants were grouped according to weight change patterns, as follows: 1) no weight loss (±3% at years 1 and 4); 2) moderate weight loss (3-8% at years 1 and 4); 3) large weight loss (8-20% at years 1 and 4); 4) moderate loss/full regain (3-8% at year 1/±3% at year 4); 5) large loss/full regain (8-20% at year 1/± 3% year 4); and 6) large loss/partial regain (8-20% at year 1/3-8% at year 4) and changes in CVD risk factors were compared. Adjusting for baseline differences and medication use, larger weight losses produced greater improvements in HbA1c, systolic blood pressure, HDL cholesterol, and triglycerides at years 1 and 4 (all P ≤ 0.02). Despite maintenance of weight loss, HbA1c levels worsened between years 1 and 4, and remained below baseline only in those with large weight losses. We found no negative associations of losing and regaining weight relative to not having lost weight. Moreover, those who had large initial weight loss but full regain of weight had greater improvements in HbA1c levels at year 4 than those with smaller or no initial weight loss. Larger initial weight loss should be encouraged in individuals with type 2 diabetes, despite the possibility of regain.


Molecular characterization and expression analysis of elongation factors 1A and 2 from the Pacific white shrimp, Litopenaeus vannamei.
Elongation factors (EF) are abundant cell proteins that play important roles in the metabolism of all multicellular organisms. Here we describe a functional analysis of elongation factor 1-alpha (EF1A) and elongation factor 2 (EF2), from the Pacific white shrimp, Litopenaeus vannamei. Full-length cDNAs of genes corresponding to EF1A and EF2 were obtained that were 1547 and 2729 bp long, with open reading frames encoding 461 and 846 amino acids, respectively. The deduced amino acid sequences of L. vannamei EF1A and EF2 showed high similarity with those from mice, humans, chickens and other shrimps. RT-PCR analysis indicated that mRNA transcripts of EF1A and EF2 are strongly (but differentially) expressed in haemocytes and gill tissue, and at varying levels in other examined tissues, of the shrimps. Levels of both EF1A and EF2 transcripts increased when shrimps were challenged by pH and cadmium stress, but reached maximal levels after different exposure periods. These results indicate that EF1A and EF2 may play distinct, essential roles in the repair of cellular damage induced by pH and cadmium stress.


Glucose variability and mood in people with type 1 diabetes using ecological momentary assessment.
Mood fluctuations related to blood glucose excursions are a commonly reported source of diabetes-distress, but research is scarce. We aimed to assess the relationship between real-time glucose variability and mood in adults with type 1 diabetes (T1D) using ecological momentary assessments. In this prospective observational study, participants wore a masked continuous glucose monitor and received prompts on their smartphone 6 times a day to answer questions about their current mood (Profile Of Mood States (POMS)-SF (dimensions: Anxiety, Depressive symptoms, Anger, Fatigue, Vigor)) for 14 days. Mixed model analyses examined associations over time between daily Coefficient of Variation (CV) of blood glucose and mean and variability (CV) of POMS scores. Further, within-person differences in sleep and nocturnal hypoglycemia were explored. 18 people with T1D (10 female, mean age 44.3 years) participated. A total of 264 out of 367 days (70.2%) could be included in the analyses. No overall significant associations were found between CV of blood glucose and mean and CV of POMS scores, however, nocturnal hypoglycemia moderated the associations between CV of blood glucose and POMS scales (mean Fatigue Estimate 1.998, p < .006, mean Vigor Estimate -3.308, p < .001; CV Anger Estimate 0.731p = 0.02, CV Vigor Estimate -0.525, p = .006). We found no overall relationship between real-time glycemic variability and mood per day. Further research into within-person differences such as sleep and nocturnal hypoglycemia is warranted.


Leadership and followership in the healthcare workplace: exploring medical trainees' experiences through narrative inquiry.
To explore medical trainees' experiences of leadership and followership in the interprofessional healthcare workplace. A qualitative approach using narrative interviewing techniques in 11 group and 19 individual interviews with UK medical trainees. Multisite study across four UK health boards. Through maximum variation sampling, 65 medical trainees were recruited from a range of specialties and at various stages of training. Participants shared stories about their experiences of leadership and followership in the healthcare workplace. Data were analysed using thematic and narrative analysis. We identified 171 personal incident narratives about leadership and followership. Participants most often narrated experiences from the position of follower. Their narratives illustrated many factors that facilitate or inhibit developing leadership identities; that traditional medical and interprofessional hierarchies persist within the healthcare workplace; and that wider healthcare systems can act as barriers to distributed leadership practices. This paper provides new understandings of the multiple ways in which leadership and followership is experienced in the healthcare workplace and sets out recommendations for future leadership educational practices and research.


Plants boost pyrrhotite-driven nitrogen removal in constructed wetlands.
Pyrrhotite is a promising electron donor for autotrophic denitrification. Using pyrrhotite as the substrate in constructed wetlands (CWs) can enhance the nitrogen removal performance in carbon-limited wastewater treatment. However, the role of plants in pyrrhotite-integrated CW is under debate as the oxygen released from plant roots may destroy the anoxic condition for autotrophic denitrification. This study compared pyrrhotite-integrated CWs with and without plants and identified the effects of plants' presence in nitrogen removal, pyrrhotite oxidized dissolution, and microbial community. The results show that plants enhanced the TN removal significantly (from 41.6 ± 3.9 % to 97.1 ± 2.6 %). Plants can accelerate the PAD in CW through the strengthening of pyrrhotite dissolution. Enriched functional (Thiobacillus and Acidiferrobacter) and a more complex bacterial co-occurrence network has been found in CW with plants. This study identified the role of plants in PAD acceleration, providing an in-depth understanding of pyrrhotite in CW systems.


Secular Trends of Stroke Epidemiology in Örebro, Sweden, 2017 Compared to the Trends in 1999: A Population-Based Study.
A stroke incidence study in -Örebro, situated in Southern Sweden, that was carried out in 1999 showed high incidence rates. Since then, in many Western countries, declining incidence rates have been observed. The main purpose of this study is to examine whether there have been any changes in stroke incidence in the city of -Örebro between 1999 and 2017. Secondary purposes are to show trends in stroke severity, length of stay and case fatality (CF). The criterion of an "ideal" stroke incidence study was used in both the 1999 and the present investigation. These criteria include uniform diagnostics, case ascertainment including strokes managed outside the hospital, and the use of several overlapping sources, prospective design, well-defined denominator, and a large population. The overall stroke incidence rate of first ever stroke (adjusted to the 2013 European population) dropped from 346/100,000 (95% CI 314-380) to 168/100,000 (95% CI 148-190). Stroke severity declined from a median of 6 to 4 points on the National Institute of Health Stroke scale. CF within 28 days also declined from 19 to 16% (n.s.). Median length-of-stay in hospital was 16 days in 1999, and 10 days in 2017. Twenty-one per cent of all kinds of stroke were recurrent (not included in the above results). During the years between 1999 and 2017, there have been reductions in stroke incidence, severity and mortality. The explanation is most likely to be found in the prevalence of risk factors and how they are treated. The use of antihypertensives and statins has increased, corresponding to lower levels of blood pressure and cholesterol in the population. The use of anticoagulants in patients with atrial fibrillation has increased. Cigarette smoking has decreased. These are encouraging results that show that preventive medication and public health measures work in practice.


Membrane insertion of the bacterial signal transduction protein ToxR and requirements of transcription activation studied by modular replacement of different protein substructures.
The Vibrio cholerae protein ToxR is an integral membrane protein that acts as a transcription activator in response to environmental signals; it controls expression of toxin genes ctxA and ctxB, along with a variety of other genes related to pathogenicity. Here it is shown that: (i) ToxR has a modular architecture and that activation of transcription starting at the ctx promoter depends strictly on dimerization of the periplasmic ToxR domain; (ii) the transmembrane (TM) region of ToxR is sufficient as a topogenic signal but not for stable membrane anchoring of the protein; (iii) the TM region has no special function in signal transduction and (iv) a proline residue located within the TM region minimizes background transcription activation, most plausibly by reducing TM-TM interaction. Possible applications of ToxR as a technical tool for analysing protein-protein interactions between pairs of arbitrary TM domains are discussed.


Influence of parenteral immunization in rabbits on the penetrability of oral mucosa for macromolecules.
It should not be overlooked that serum-derived antibodies may normally play an important role in mucosal homeostasis conducive to health. Thus, protection against at least some bacterial components may be an antibody-mediated function during the initial phase of gingivitis (21). Nevertheless, Auer demonstrated in 1920 that mild inflammation can be severely aggravated by local accumulation of serum-derived antibodies combined with a systemic supply of the corresponding antigen (2); subsequent studies have shown that this holds true also when the antigen is topically applied (11,14). Theoretically, the initial gingival lesion is an ideal situation for the development of a so-called "Auer-phenomenon", due to continuous supply of antigens from dental plaque and food. This possible hazard of circulating antibodies must be taken into account when immunoprophylaxis is attempted by parenteral vaccines.


Cytochalasin D does not produce net depolymerization of actin filaments in HEp-2 cells.
The altered morphology, disappearance or 'disruption' of actin filaments (microfilaments) in cells treated with cytochalasin has sometimes been attributed to depolymerization of filamentous actin (F-actin) to its globular subunit (G-actin), but attempts to confirm that mechanism have been inconclusive. Treatment of purified actin filaments with cytochalasin B (CB) decreased their viscosity, consistent with depolymerization, which was not, however, revealed by electron microscopy, although the filaments appeared abnormal. CB also increased the ATP-ase activity of F-actin, suggesting that it had been destabilized, while actin filaments in the acrosomal process were not depolymerized. CB or cytochalasin D (CD) can dissolve actin gels (reviewed in ref. 7, see also refs 8 and 9) without depolymerizing their filaments. The 'disrupted' actin structures in CD-treated cells bound heavy meromysin, indicating that at least some of the cellular actin was filamentous. Using a rapid assay for G- and F-actin in cell extracts, based on the inhibition of DNase I, we have found that neither short-nor long-term exposure of HEp-2 cells to CD produce net depolymerization of actin filaments.