Inheritance and expression of the cry1Ab gene in Bt ( Bacillus thuringiensis) transgenic rice.
The inheritance and expression patterns of the cry1Ab gene were studied in the progenies derived from different Bt ( Bacillus thuringiensis) transgenic japonica rice lines under field conditions. Both Mendelian and distorted segregation ratios were observed in some selfed and crossed F(2) populations. Crosses between japonica intra-subspecies had no significant effect on the segregation ratios of the cry1Ab gene, but crossing between japonica and indicainter-subspecies led to distorted segregation of the cry1Ab gene in the F(2)population. Field-release experiments indicated that the cry1Ab gene was stably transmitted in an intact manner via successive sexual generations, and the concentration of the Cry1Ab protein was kept quantitatively stable up to the R(6)generation. The cry1Ab gene, driven by the maize ubiquitinpromoter, displayed certain kinds of spatial and temporal expression patterns under field conditions. The content of the Cry1Ab protein varied in different tissues of the main stems, the primary tillers and the secondary tillers. Higher levels of the Cry1Ab protein were found in the stems, leaves and leaf sheaths than in the roots, while the lowest level was detected in grains at the maturation stage. The content of the Cry1Ab protein in the leaves peaked at the booting stage and was lowest at the heading stage. Furthermore, the Cry1Ab content of cry1Ab expression in different tissues of transgenic rice varied individually with temperature.


Flexural properties and surface finishing of acetal resin denture clasps.
This study examined flexural properties of acetal resin to determine the appropriate design for an acetal resin removable partial denture clasp. The effectiveness of various acetal resin polishing procedures was also evaluated using scanning electron microscopy. Loads of up to 1,500 g were applied to cylindrical acetal resin specimen lengths of 5, 10, and 15 mm, and the degree of deflection of the specimen tip was measured. Specimens were 2 mm and 1.5 mm in diameter with a round cross-section (R2 and R1.5, respectively), as well as 2 mm in diameter and half-round in cross-section. Half-round specimens were loaded with their flat surface vertical and then horizontal (HRV and HRH, respectively). Contour plots showing load and deflection for varying lengths of resin were developed for each cross-sectional type based on specimen length, and the stiffness was calculated. Additional acetal resin specimens underwent polishing techniques including tungsten carbide burs, aluminium oxide stones, abrasive impregnated rubber points, and "Polish-D." Polished specimens were examined with scanning electron microscopy to compare surface roughness. For the 5-mm-length specimens, the median stiffness values decreased in the following order: R2 > HRV > HRH > R1.5. The median stiffness values for the 10-mm and 15-mm lengths followed a similar trend. At each length, the R2 specimen was generally at least twice as stiff as other designs. Regarding polishing, the smoothest surface was seen on the specimen that was polished with the rubber point followed by "Polish-D." To have stiffness similar to a cast cobalt-chromium clasp 15 mm long and 1 mm in diameter, a suitable acetal resin clasp must be shorter (approximately 5 mm) with greater cross-sectional diameter (approximately 1.4 mm). To obtain a smooth surface, the acetal resin clasp should be polished with a rubber point followed by a material such as "Polish-D."


Earl Wood--a research career noted for development of novel instruments driven by the power of the indicator dilution concept.
During World War 2, Earl Wood was charged with elucidating the biomedical factors in acceleration-induced loss of consciousness experienced by pilots in high-performance aircraft. For this, he developed devices for measurement and recording of blood pressure and tissue blood content. Those data lead to the design and fabrication of successful countermeasures to acceleration-induced loss of consciousness with an inflatable "G-suit" and "M1" breath-holding maneuver. After World War 2, he utilized and modified these instruments and made use of indicator dilution techniques by continuous intracardiac blood sampling to greatly increase the specificity and sensitivity of diagnosis of intracardiac anatomic and functional abnormalities in patients with congenital heart disease. This contributed to the greatly increased success rate of open-heart surgery in the 1950s. In the 1960s, he built on the then recently available video-coupled electronic X-ray image intensifier to develop X-ray fluoroscopy-based recording of indicator dilution signals in all cardiac chambers and surrounding great vessels without the need for placing catheter tips at those locations for blood sampling. However, these blood flow-related data were of limited value, as they were not measured concurrent with myocardial functional demand for perfusion. In the 1970s, he overcame this limitation by developing a high-speed multislice X-ray imaging scanner to provide tomographic images of concurrent dynamic cardiac anatomy and the indicator dilution-based estimates of blood flow distributions. On his retirement at age 70 in 1982, he had accomplished his 2 decade-old goal of the ability to make accurate concurrent, minimally invasive, and indicator dilution-based measurement of cardiovascular structure to function relationships.


Toxic effects of systemic retinoids on meibomian glands.
Systemic use of retinoids is common in the treatment of various dermatological disorders. Blepharitis and conjunctivitis have been reported in 20-45% of the patients following systemic treatment with 13-cis-retinoic acid. Our purpose was to study the histopathological changes in the eyelids caused by long-term systemic treatment of female New Zealand rabbits with isotretinoin (2 mg/kg) and etretinate (2 mg/kg). The histopathological evaluation showed degenerative changes in the meibomian gland acini, leading to cell necrosis and a decrease in the basaloid cells lining the acini walls. No evidence of acute or chronic inflammatory reaction was noted.


Cochrane Collaboration helping unravel tangled web woven by international research.
Although there are sceptics and critics, the Cochrane Collaboration continues to grow exponentially. With centres in nine countries, its common goal is to create, maintain and disseminate systematic reviews of randomized controlled trials in an effort to bring clinicians the most current, accurate evidence about medical treatments available around the world. The future of the collaboration will depend largely on whether the methodology of their reviews can be shown to be valid and to produce consistently relevant and timely reviews.


Measuring Medication Adherence in a Population-Based Asthma Administrative Pharmacy Database: A Systematic Review and Meta-Analysis.
Limited studies have systematically reviewed the literature to identify and compare the various database methods and optimal thresholds for measuring medication adherence specific to adolescents and adults with asthma. In the present study, we aim to identify the methods and optimal thresholds for measuring medication adherence in population-based pharmacy databases. We searched PubMed, Embase, International Pharmaceutical Abstracts (IPA), Web of Science, Google Scholar, and grey literature from January 1, 1998, to March 16, 2021. Two independent reviewers screened the studies, extracted the data, and assessed the quality of the studies. A quantitative knowledge synthesis was employed. Thirty-eight (38) retrospective cohort studies were eligible. This review identified 20 methods for measuring medication adherence in adolescent and adult asthma administrative health records. Two measures namely the medication possession ratio (MPR) and proportion of days covered (PDC) were commonly reported in 87% of the literature included in this study. From the meta-analysis, asthma patients who achieved adherence threshold of "0.75-1.00" [OR: 0.56, 95% CI: 0.41 to 0.77] and ">0.5" [OR: 0.71, 95% CI: 0.54 to 0.94] were less likely to experience asthma exacerbation. Despite their limitations, the PDC and the MPR still remain the most common measures for assessing adherence in asthma pharmacy claim databases. The evidence synthesis showed that an adherence threshold of at least 0.75 is optimal for classifying adherent and non-adherent asthma patients.


Role of oral teriflunomide in the management of multiple sclerosis.
The landscape of the treatment of relapsing-remitting multiple sclerosis is changing fast. Several oral treatments have shown benefit and generate much interest because of the convenience of their administration. Two oral compounds, fingolimod and teriflunomide, have been approved in relapsing-remitting multiple sclerosis, while others have completed Phase III trials and are awaiting review for registration. Teriflunomide is a pyrimidine synthesis inhibitor with selective immunomodulatory and immunosuppressive properties that have shown consistent efficacy in clinical trials, and a good safety profile. This paper provides an overview of the mechanisms of action and efficacy and safety results from clinical trials with this drug. The role of teriflunomide in the treatment of relapsing-remitting multiple sclerosis is discussed.


Agricultural origins and the isotopic identity of domestication in northern China.
Stable isotope biochemistry (delta(13)C and delta(15)N) and radiocarbon dating of ancient human and animal bone document 2 distinct phases of plant and animal domestication at the Dadiwan site in northwest China. The first was brief and nonintensive: at various times between 7900 and 7200 calendar years before present (calBP) people harvested and stored enough broomcorn millet (Panicum miliaceum) to provision themselves and their hunting dogs (Canis sp.) throughout the year. The second, much more intensive phase was in place by 5900 calBP: during this time both broomcorn and foxtail (Setaria viridis spp. italica) millets were cultivated and made significant contributions to the diets of people, dogs, and pigs (Sus sp.). The systems represented in both phases developed elsewhere: the earlier, low-intensity domestic relationship emerged with hunter-gatherers in the arid north, while the more intensive, later one evolved further east and arrived at Dadiwan with the Yangshao Neolithic. The stable isotope methodology used here is probably the best means of detecting the symbiotic human-plant-animal linkages that develop during the very earliest phases of domestication and is thus applicable to the areas where these connections first emerged and are critical to explaining how and why agriculture began in East Asia.


Aspirin resistance, an emerging, often overlooked, factor in the management of patients with coronary artery disease.
Aspirin is the most widely used medication in patients with cardiovascular disease. It has had a greater effect on patients with cardiovascular disease than any other drug. With the importance of aspirin now known for decades, it is recently becoming clearer that some patients do not derive as great a benefit from this "wonder drug" secondary to their resistance to its effects. Aspirin resistance, its prevalence, its identification, and how to overcome or avert it with other medications then becomes a central topic of discussion as important, if not more so, than the importance of aspirin itself as a cornerstone in the treatment of patients with cardiovascular disease. This review explores the current understanding of the mechanism of aspirin resistance with regard to its prevalence and the magnitude of its clinical significance. It also examines the therapeutic implications of a diagnosis of aspirin resistance.


Impact of human papillomavirus vaccination on the clinical meaning of cervical screening results.
Women previously vaccinated against human papillomavirus (HPV) type 16 and 18 are now reaching the age (21 years) at which cervical-cancer screening is recommended in the U.S. The impact of HPV vaccination on risks of cervical precancer following a positive and negative screen among women aged 21-24 years who just started routine cervical screening are not well described. Therefore, three-year absolute and relative (RR) cumulative risks of cervical intraepithelial neoplasia grade 2 or more severe diagnoses (≥CIN2) and grade 3 or more severe diagnoses (≥CIN3) were estimated for women undergoing cervical screening at Kaiser Permanente Northern California. Risks were estimated in women aged 21-24 years (n = 75,008) undergoing cervical screening since late 2006, 6 months after HPV vaccination became available; women were categorized vaccinated at ages <18, 18-20, and 21-24 years and compared to those who were unvaccinated. Three-year risks were estimated for normal, low-grade, and high-grade cytology results. Three-year risks of ≥CIN2 and ≥CIN3 for unvaccinated women following low-grade cytology were 10.89% for and 3.70%, respectively. By comparison, Three-year risks of ≥CIN2 and ≥CIN3 were 5.26% (RR = 0.48, 95%CI = 0.24-0.99) and 0.99% (RR = 0.27, 95%CI = 0.06-1.13), respectively, for women vaccinated under the age of 18 years. Three-year ≥CIN2 and ≥CIN3 risks were lower for those HPV vaccinated at younger age for any screening result (ptrend ≤ 0.01 for all comparisons). These data support initiating cervical screening at an older age or changing the management of a low-grade cytology result in women aged 21-24 years who were vaccinated against HPV younger than age of 18 years.


Detection of tuberculosis using digital chest radiography: automated reading vs. interpretation by clinical officers.
A busy urban health centre in Lusaka, Zambia. To compare the accuracy of automated reading (CAD4TB) with the interpretation of digital chest radiograph (CXR) by clinical officers for the detection of tuberculosis (TB). A retrospective analysis was performed on 161 subjects enrolled in a TB specimen bank study. CXRs were analysed using CAD4TB, which computed an image abnormality score (0-100). Four clinical officers scored the CXRs for abnormalities consistent with TB. We compared the automated readings and the readings by clinical officers against the bacteriological and radiological results used as reference. We report here the area under the receiver operating characteristic curve (AUC) and kappa (κ) statistics. Of 161 enrolled subjects, 97 had bacteriologically confirmed TB and 120 had abnormal CXR. The AUCs for CAD4TB and the clinical officers were respectively 0.73 and 0.65-0.75 in comparison with the bacteriological reference, and 0.91 and 0.89-0.94 in comparison with the radiological reference. P values indicated no significant differences, except for one clinical officer who performed significantly worse than CAD4TB (P < 0.05) using the bacteriological reference. κ values for CAD4TB and clinical officers with radiological reference were respectively 0.61 and 0.49-0.67. CXR assessment using CAD4TB and by clinical officers is comparable. CAD4TB has potential as a point-of-care test and for the automated identification of subjects who require further examinations.


[Fractionation of eukaryotic DNA in a pulsating electrical field. I. Detection and properties of discrete DNA fragments].
The fractionation of eukaryotic DNA by field inversion gel electrophoresis results in the appearance of discrete DNA-fragments. The set of these fragments is similar to that of different eukaryotic representatives and consists of various chromosomal DNAs, unified by size. The physical properties of DNA-fragments suggest that they can form multimeric structures due to the presence of sticky ends flanking discrete fragments. We suppose that the set of discrete DNA-fragments results in a specific cleavage of intact nuclear DNA and can reflect different levels of chromatin structural organization.


Cancer-associated oxidoreductase ERO1-α drives the production of tumor-promoting myeloid-derived suppressor cells via oxidative protein folding.
Endoplasmic reticulum disulfide oxidase ERO1-α plays a role in the formation of disulfide bonds in collaboration with protein disulfide isomerase. Disulfide bond formation is required for the proper conformation and function of secreted and cell surface proteins. We found that ERO1-α was overexpressed in a variety of tumor types; therefore, we examined its role in tumor growth. In BALB/c mice, knockdown of ERO1-α within 4T1 mouse mammary gland cancer (KD) cells caused retardation of in vivo tumor growth compared with tumor growth of scrambled control (SCR) cells. In contrast, when ERO1-α-overexpressed 4T1 (OE) cells were compared with mock control cells, OE cells showed augmented tumor growth. However, differences in tumor growth were not observed among four groups of nude mice, suggesting that expression of ERO1-α diminished antitumor immunity. We observed dense peritumoral granulocytic infiltrates in tumors of wild-type 4T1 and SCR cells but not KD cells, and these cells were identified as polymorphonuclear myeloid-derived suppressor cells (MDSCs). In addition, production of G-CSF and CXCL1/2, which have intramolecular disulfide bonds, from KD cells was significantly decreased compared with that from SCR cells. In contrast, OE cells produced a larger amount of these molecules than did mock cells. These changes were regulated at the posttranscriptional level. These results suggest that overexpression of ERO1-α in the tumor inhibits the T cell response by recruiting polymorphonuclear MDSCs via regulation of MDSC-prone cytokines and chemokines.


Vagal Afferent Innervation of the Airways in Health and Disease.
Vagal sensory neurons constitute the major afferent supply to the airways and lungs. Subsets of afferents are defined by their embryological origin, molecular profile, neurochemistry, functionality, and anatomical organization, and collectively these nerves are essential for the regulation of respiratory physiology and pulmonary defense through local responses and centrally mediated neural pathways. Mechanical and chemical activation of airway afferents depends on a myriad of ionic and receptor-mediated signaling, much of which has yet to be fully explored. Alterations in the sensitivity and neurochemical phenotype of vagal afferent nerves and/or the neural pathways that they innervate occur in a wide variety of pulmonary diseases, and as such, understanding the mechanisms of vagal sensory function and dysfunction may reveal novel therapeutic targets. In this comprehensive review we discuss historical and state-of-the-art concepts in airway sensory neurobiology and explore mechanisms underlying how vagal sensory pathways become dysfunctional in pathological conditions.


Haemochromatosis HFE gene polymorphisms as potential modifiers of hereditary nonpolyposis colorectal cancer risk and onset age.
Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by germline mutations in DNA mismatch repair genes; however, variation in disease expression suggests that there are potential modifying factors. Polymorphisms of the HFE gene, which cause the iron overload disorder hereditary haemochromatosis, have been proposed as potential risk factors for the development of colorectal cancer (CRC). To understand the relationship between HNPCC disease phenotype and polymorphisms of the HFE gene, a total of 362 individuals from Australia and Poland with confirmed causative MMR gene mutations were genotyped for the HFE C282Y and H63D polymorphisms. A significantly increased risk of developing CRC was observed for H63D homozygotes when compared with combined wild-type homozygotes and heterozygotes (hazard ratio = 2.93, p = 0.007). Evidence for earlier CRC onset was also observed in H63D homozygotes with a median age of onset 6 years earlier than wild type or heterozygous participants (44 vs. 50 years of age). This effect was significant by all tests used (log-rank test p = 0.026, Wilcoxon p = 0.044, Tarone-Ware p = 0.035). No association was identified for heterozygosity of either polymorphism and limitations on power-prevented investigation of C282Y homozygosity or compound C282Y/H63D heterozygosity. In the Australian sample only, women had a significantly reduced risk of developing CRC when compared with men (hazard ratio = 0.58, p = 0.012) independent of HFE genotype for either single nucleotide polymorphisms. In conclusion, homozygosity for the HFE H63D polymorphism seems to be a genetic modifier of disease expression in HNPCC. Understanding the mechanisms by which HFE interrelates with colorectal malignancies could lead to reduction of disease risk in HNPCC.


Denatured muscle grafts for nerve repair in an experimental model of nerve damage in leprosy. 2. Recovery of peripheral peptide-containing nerves assessed by quantitative immunohistochemical study.
A marked depletion of neuropeptide-immunoreactive nerves, a consequence of the nerve damage which is commonly found in leprosy, has been reported in peripheral tissues of leprosy patients and of a leprosy animal model. The aim of this study was to investigate peripheral reinnervation following a denatured autologous muscle graft in an animal model of leprosy nerve damage. Possible reinnervation of the foot-pad skin was studied by immunohistochemistry using antisera to the neuronal marker protein gene product 9.5 (PGP), the neuropeptides calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and the C-flanking peptide of neuropeptide Y (CPON). The extent of the reinnervation process was assessed by image analysis quantification at different time points. At 8 weeks after muscle grafting, there were small numbers of immunoreactive nerves (p < 0.05). At 12, 16, and 20 weeks postoperatively there was a gradual increase in all immunostaining. At 20 weeks, no significant difference was found for PGP-, CGRP-, and SP-immunoreactive nerves in the epidermal and subepidermal layers compared to control (contralateral) tissue. In experimental tissue the recovery of immunoreactive nerves around sweat glands took longer (up to 12 weeks) than in other skin compartments, but after that time the recovery was rapid and at 20 weeks no difference was measured for VIP-immunoreactive nerves in comparison with controls. Around blood vessels, the recovery of CGRP- and CPON-immunoreactive fibers was slow, and at 20 weeks a difference with control samples (p < 0.01) was noted. In the same area, there was no significant difference for PGP immunoreactivity between controls and tissues at 20 weeks. In contrast, the immunoreactive nerve bundles in the dermis showed a faster recovery than nerves in other skin areas, with amounts similar to controls at 20 weeks. The significant recovery of immunoreactive nerves, in particular of those containing sensory neuropeptide, is consistent with the described functional recovery.


Masticatory function and histogenesis of the middle and upper face in chimpanzees (Pan troglodytes).
Evidence has been offered suggesting that masticatory function is an important factor governing development of the supraorbital region. Data have also been provided showing that a mechanism which enables rapid skeletal growth to occur is present in the supraorbital region in the form of fine cancellous woven bone tissue. That Browridge morphogenesis is linked with masticatory function is not a novel interpretation. On the contrary, numerous investigators have offered a variety of evidence in support or refutation of this notion [Toldt, 1914; Weidenreich, 1941, 1946; Endo, 1966, 1970; Moss and Young, 1960]. This study differs from most previous efforts, however, in that it specifically identifies some of the factors and mechanisms; i.e., bite forces and bone tissues involved in growth and development of the upper facial skeleton and the masticatory system. The nature of the relationships among these developmental and functional phenomena remains to be experimentally demonstrated.


1.32 ± 0.11 Ma age for underwater remains constrain antiquity and longevity of the Dominican primate Antillothrix bernensis.
Endemic New World monkeys are an important element of the extinct mammal faunas of the Caribbean's Greater Antilles. Here we report the first geochronometric evidence that the primate Antillothrix bernensis existed in the Dominican Republic during the Pleistocene, based on the uranium-series age of carbonate speleothem that encased a tibia when it was collected in a flooded cave. Three-dimensional geometric morphometrics of laser-scanned living and extinct samples provide evidence to support the hypothesis that this specimen and other Dominican primate tibial remains belong to that same species. U-Th dating of the host cave carbonate returns ages consistently at the 600 ka upper limit of the technique. However, U-Pb, capable of resolving ages of greater antiquity, is more robust in this context, returning a secure age of 1.32 ± 0.11 Ma, which is the oldest chronometric age recorded for a Hispaniolan mammal. While its origins and manner and time of arrival are obscure, the morphometric studies are consistent with phylogenetic analyses that place A. bernensis within the pitheciid clade of the platyrrhines. The species apparently endured for over 1 million years during the climatic perturbations of the Pleistocene, as a frugivorous climbing quadruped, one of two known primate species occupying the hazard prone island of Hispaniola.


MR imaging of hemorrhagic brain lesions: a comparison of dual-echo gradient- and spin-echo and fast spin-echo techniques.
Our objective was to assess the usefulness of the dual-echo gradient- and spin-echo (GRASE) technique in revealing acute hemorrhagic brain lesions and compare GRASE and fast spin-echo techniques for revealing acute hemorrhagic lesions and image artifacts. Thirty-two consecutive patients with acute intracranial hemorrhage underwent dual-echo GRASE (TEeff1/TEeff2, 35/85) and fast spin-echo (25/110) imaging. The techniques were matched for TR (3032 msec), spatial resolution, and acquisition time. Two neuroradiologists reviewed the images independently, documenting the number, size (<1, >1, or 1 cm in diameter), location, and signal characteristics (hypointense versus hyperintense compared with brain) of detectable lesions. These observers also compared matched T2- and proton density-weighted GRASE and fast spin-echo images for paramagnetic lesion conspicuity, diamagnetic susceptibility artifacts, chemical shift artifacts along the phase- and frequency-encoding directions, and artifactual CSF hyperintensity in the thin curvilinear cortical sulci and the Virchow-Robin spaces on only the proton density-weighted images. The average number and conspicuity of dark (paramagnetic) lesions were significantly greater on GRASE than on fast spin-echo images (p < .05 and p < .001, respectively). We found no significant difference in the average number of bright lesions revealed by either technique (p > .1). Chemical shift artifacts along the phase-encoding directions were more prominent on GRASE than on fast spin-echo imaging. Chemical shift artifacts along the frequency-encoding directions and artifactual CSF hyperintensity were more prominent on fast spin-echo than on GRASE imaging. No visually apparent difference was found in the degree of diamagnetic susceptibility artifacts seen with the two techniques. Dual-echo GRASE imaging can be helpful in the examination of patients with suspected acute brain hemorrhage.


Effect of probiotics on body weight and body-mass index: a systematic review and meta-analysis of randomized, controlled trials.
To assess the efficacy of probiotic therapies on body weight and BMI using a meta-analysis of randomized, controlled trials. Twenty studies with 25 trials (1931 participants with age over 18 years) were included. The pooled WMD was calculated by random effects model. Probiotic consumption significantly reduced body weight by 0.59 kg (95% CI, 0.30-0.87) and BMI by 0.49 kg/m(2) (95% CI, 0.24-0.74). A greater reduction in BMI was found with multiple species of probiotics. Subgroup analysis of trials with intervention duration ≥8 weeks found a more significant reduction in BMI. Limiting analysis to trials with a baseline BMI ≥25 kg/m(2) showed a greater reduction in BMI. Consuming probiotics could reduce body weight and BMI, with a potentially greater effect when multiple species of probiotics were consumed, the duration of intervention was ≥8 weeks, or the objects were overweight.


Maternal anxiety during the transition to parenthood: a prospective study.
This prospective study used both self-report (STAI) and clinical diagnostic interview (MINI-Plus) to examine the course of maternal anxiety across the transition to parenthood. The study also assessed i) the validity of the STAI for antenatal use in an Australian sample and ii) the relative utility of the MINI-Plus and STAI scales as antenatal measures of risk for postnatal anxiety and mood disorders. Participants were 100 women recruited during routine antenatal assessment at a major obstetric hospital in Sydney. An antenatal screening instrument (ANRQ) identified half the sample as being at "high risk" for developing postnatal anxiety and/or depression. Participants completed the STAI during the third trimester of pregnancy and the MINI-Plus was administered during pregnancy and during the seventh postnatal month to assess anxiety and depression meeting DSM-IV criteria. The data indicated considerable stability in anxiety and depression from pregnancy through the postnatal period, as assessed by both diagnostic interview and maternal self-report. Antenatal anxiety meeting diagnostic criteria and antenatal trait anxiety exceeding a cut-off score of 40 on the STAI were both found to be significant predictors of postnatal anxiety and mood disorders (p-values<.05). Further analyses revealed that the measures were equivalent in their predictive utility. Finally, the STAI state and trait anxiety scales demonstrated a reasonable estimation of antenatal clinical state when tested against the MINI-Plus diagnostic interview during pregnancy. The findings from this study suggest that antenatal anxiety as assessed by either clinical interview or maternal self-report is an important predictor of postnatal anxiety and mood disorders. The validity of the STAI scales for use during pregnancy was also demonstrated for the first time in an Australian sample.


The 4R's Framework of Nutritional Strategies for Post-Exercise Recovery: A Review with Emphasis on New Generation of Carbohydrates.
Post-exercise recovery is a broad term that refers to the restoration of training capacity. After training or competition, there is fatigue accumulation and a reduction in sports performance. In the hours and days following training, the body recovers and performance is expected to return to normal or improve. ScienceDirect, PubMed/MEDLINE, and Google Scholar databases were reviewed to identify studies and position declarations examining the relationship between nutrition and sports recovery. As an evidence-based framework, a 4R's approach to optimizing post-exercise recovery was identified: (i) Rehydration-a fundamental process that will depend on the athlete, environment and sports event; (ii) Refuel-the consumption of carbohydrates is not only important to replenish the glycogen reserves but also to contribute to the energy requirements for the immune system and tissue reparation. Several bioengineered carbohydrates were discussed but further research is needed; (iii) Repair-post-exercise ingestion of high-quality protein and creatine monohydrate benefit the tissue growth and repair; and (iv) Rest-pre-sleep nutrition has a restorative effect that facilitates the recovery of the musculoskeletal, endocrine, immune, and nervous systems. Nutritional consultancy based on the 4R's is important for the wise stewardship of the hydration, feeding, and supplementation strategies to achieve a timely recovery.


Post-traumatic hydrocephalus.
Surgical treatment of ventricular dilatation following severe head trauma (GCS <8) remains controversial due to the difficulty to distinguish brain atrophy-related ventriculomegaly from active, symptomatic ventricular dilatation. Consequently, the reported incidence of post-traumatic hydrocephalus in literature varies greatly from 0.7-29%. The presence of ventricular dilatation following severe head trauma should be considered and demands investigation, based also on satisfactory results obtained with cerebrospinal fluid (CSP) shunting, Ninety-eight patients with post-traumatic hydrocephalus undergoing CSF shunting were selected for this study among 4,044 patients with severe head trauma treated from 1972 to 1999 at the Department of Neurosurgery at the City Hospital of Verona. Patients included 82 (84%) males and 16 (16%) women, ranging from one month to 83 years (mean age; 39 years). In 24 (24%) cases, the brain trauma lesion was single, while in 74 (76%) cases the patient suffered multiple cranio-cerebral lesions. The total number of lesions was 230 including 214 (93%) supratentorial and 16 (7%) posterior cranial fossa (PCF) lesions. Seventy-nine operations were performed on 59 (60%) patients. The onset of hydrocephalus was immediate after trauma in 14 (14%) cases, whereas a delayed onset was observed within 30 days in 44 (45%) cases, between one-four months in 30 (31%) cases and between four-six months in 10 (10%) cases. Of the 98 patients in this study, 15 were treated with an external CSF shunt and 83 underwent internal CSF shunting. Long-term results of the 15 patients with external shunts demonstrated good recovery in 13% while 87% of cases resulted in death. In the 83 cases of internal shunts, despite severe preoperative conditions (75% in coma or persistent coma), the results were as follows: good recovery in 37 (45%) patients, partial disability in nine (11%), persistent coma in 29 (35%) and death in seven (8%) cases. Post-traumatic hydrocephalus is a complication that must always be considered in cases of severe head trauma (GCS <8) in young patients presenting added neurological deficits, ceased clinical improvement (ceased improvement after initial improvement), increased hypertonia, surgical flap tension or CSF accumulation. The results of this study suggest the necessity to treat post-traumatic ventricular dilatation with aggressive surgery and CSF shunting, based on favorable outcome seen even in coma and persistent coma patients.


GP78 Cooperates with Dual-Specificity Phosphatase 1 To Stimulate Epidermal Growth Factor Receptor-Mediated Extracellular Signal-Regulated Kinase Signaling.
GP78 is an autocrine motility factor (AMF) receptor (AMFR) with E3 ubiquitin ligase activity that plays a significant role in tumor cell proliferation, motility, and metastasis. Aberrant extracellular signal-regulated kinase (ERK) activation via receptor tyrosine kinases promotes tumor proliferation and invasion. The activation of GP78 leads to ERK activation, but its underlying mechanism is not fully understood. Here, we show that GP78 is required for epidermal growth factor receptor (EGFR)-mediated ERK activation. On one hand, GP78 interacts with and promotes the ubiquitination and subsequent degradation of dual-specificity phosphatase 1 (DUSP1), an endogenous negative regulator of mitogen-activated protein kinases (MAPKs), resulting in ERK activation. On the other hand, GP78 maintains the activation status of EGFR, as evidenced by the fact that EGF fails to induce EGFR phosphorylation in GP78-deficient cells. By the regulation of both EGFR and ERK activation, GP78 promotes cell proliferation, motility, and invasion. Therefore, this study identifies a previously unknown signaling pathway by which GP78 stimulates ERK activation via DUSP1 degradation to mediate EGFR-dependent cancer cell proliferation and invasion.


Quantitative real-time polymerase chain reaction (qRT-PCR) restriction fragment length polymorphism (RFLP) method for monitoring highly conserved transgene expression during gene therapy.
Evaluation of the transfer efficiency of a rat heme oxygenase-1 (HO-1) transgene into mice requires differentiation of rat and mouse HO-1. However, rat and mouse HO-1 have 94% homology; antibodies and enzyme activity cannot adequately distinguish HO-1. We designed a quantitative real-time polymerase chain reaction (qRT-PCR) method to monitor HO-1 transcription relative to a housekeeping gene, GAPDH. The ratio of rat and mouse HO-1 mRNA could be estimated through restriction fragment length polymorphism (RFLP) analysis of the PCR products. In vitro, murine AML12 hepatocytes were transfected with rat HO-1. After 40 h, the total HO-1 mRNA was enriched 2-fold relative to control cells, and rat HO-1 comprised 84% of HO-1 cDNA. In vivo, the rat HO-1 transgene was cloned into a Sleeping Beauty transposase (SB-Tn) construct and was injected hydrodynamically into a mouse model of sickle cell disease (SCD). After 21 days, there was a 32% enrichment of HO-1 mRNA relative to control mice and the rat transgene comprised 88% of HO-1 cDNA. After 21 days, HO-1 protein expression in liver was increased 2.5-fold. In summary, qRT-PCR RFLP is a useful and reliable method to differentiate the transgene from host gene transcription, especially when the host and transgene protein are identical or highly homologous. This method has translational applications to the design, delivery, and monitoring of gene-therapy vectors.


[Treatment strategies in anxiety disorders--an update].
Anxiety disorders are persistent impairing diseases, with often chronic course and suffering from symptoms throughout a life-span. The medication with the most evidence of efficacy is the benzodiazepines having a low incidence of side effects but may cause physical dependence, withdrawal and sedation. The use of these drugs should be limited to the acute treatments during the first several weeks in combination with an SSRI or and SNRI for the treatment of the acute phase. After three to four weeks, when antidepressants become effective, benzodiazepine dose should be tapered over a one week period. Among the antidepressants, the SSRI and the SNRI are considered a first-line therapy because of their favourable side effect spectrum compared to tricyclic antidepressants. However, the association with side effects such as nausea, sweating, sexual dysfunction and gastrointestinal problems and insomnia may be intolerable for a number of patients. Combining antidepressants and benzodiazepine therapy or medication treatment and psychotherapy may lead to an increase in improvement in patients not responding to one treatment approach alone. The most effective treatment for managing the recurrent symptoms of this chronic disorder are still unknown and other studies and approaches are in need as remission rates are still only about 40%.


Comparison of assays for the determination of entomogenous nematode infectivity.
Injection, contact, and soil assays were used to compare infectivity of Heterorhabditis bacteriophora strain HP88 and Steinernema carpocapsae strain All to final instar Galleria mellonella larvae. Under comparable assay conditions, H. bacteriophora produced less Galleria mortality and showed greater within-assay variability in infectivity than S. carpocapsae. Injection of individual S. carpocapsae or H. bacteriophora infective juveniles into Galleria indicated that a comparatively greater percentage of S. carpocapsae was capable of initiating infection. In addition to nematode species, other major components of variability in assay estimations of nematode infectivity were number of nematodes used in the assay, assay type, date of the assay, and possibly, Galleria age.


NucMap: a database of genome-wide nucleosome positioning map across species.
Dynamics of nucleosome positioning affects chromatin state, transcription and all other biological processes occurring on genomic DNA. While MNase-Seq has been used to depict nucleosome positioning map in eukaryote in the past years, nucleosome positioning data is increasing dramatically. To facilitate the usage of published data across studies, we developed a database named nucleosome positioning map (NucMap, http://bigd.big.ac.cn/nucmap). NucMap includes 798 experimental data from 477 samples across 15 species. With a series of functional modules, users can search profile of nucleosome positioning at the promoter region of each gene across all samples and make enrichment analysis on nucleosome positioning data in all genomic regions. Nucleosome browser was built to visualize the profiles of nucleosome positioning. Users can also visualize multiple sources of omics data with the nucleosome browser and make side-by-side comparisons. All processed data in the database are freely available. NucMap is the first comprehensive nucleosome positioning platform and it will serve as an important resource to facilitate the understanding of chromatin regulation.


Patient Perception of Depressive Symptoms in Rheumatic Diseases: A Cross-sectional Survey.
The presented study aimed to explore the presence and the self-identification of depressive symptoms among patients with rheumatic musculoskeletal diseases (RMDs) through the use of the Patient Health Questionnaire (PHQ-9). Between June and October 2019, patients from the regional association for people with RMDs in Lombardy, Italy (ALOMAR), were invited to participate in a cross-sectional online survey. Participants completed PHQ-9 along with a survey about their perception of depressive symptoms. Patients were stratified according to PHQ-9 score as follows: not depressed (<4), subclinical or mild depression (5-9), moderate depression (10-14), moderately severe depression (10-14), and severe depression (20-27). Descriptive statistics and analyses of variance were used to explore data. Of the 192 RMD patients who completed PHQ-9, 35 (18.2%) were not depressed, 68 (35.4%) had subclinical or mild depression, 42 (21.9%) had moderate depression, 30 (15.6%) had moderately severe depression, and 17 (8.9%) had severe depression. Contrary to the above findings, only 16 respondents (8.3%) reported that they experienced depressive symptoms, and only 7 of the 16 were being followed by a psychiatrist. Respondents with higher PHQ-9 scores tended to have concomitant fibromyalgia, to be younger, and to be overweight. The current results indicate the overall burden of depressive symptoms in RMD patients. While clinical depression (PHQ-9 >10) was detected in 41.2% of respondents, only 8.3% reported that they experience depressive symptoms. Routine screening of RMD patients for depression is therefore critical.


Clinical experience with GRF.
Growth hormone releasing factor (GRF) is one of two main releasing hormones which control pituitary hGH production and release. This activity is retained even when the length of the GRF polypeptide is reduced to the 29 N-terminal residues. This 29-residue polypeptide has been chemically synthesized, and testing in healthy volunteers elicited secretion of hGH to a maximum level of about 40 ng/ml. In a trial of children with various disorders, the maximum hGH response was reached within 60 minutes; those children with hGH deficiency showed much lower responses than those with other disorders not related to hGH deficiency. The frequency of false-positive tests was low, and it is proposed that GRF testing could provide a useful additional tool in the diagnosis of hGH deficiency.


Molecular beacons immobilized within suspended core optical fiber for specific DNA detection.
We propose and experimentally demonstrate a new class of sensor for specific DNA sequences based on molecular beacons (MB) immobilized on the internal surfaces of suspended core optical fibers (SCF). MBs, a type of hairpin structured DNA probe, are attached on the surface of the SCF core using a fuzzy nanoassembly process used in conjunction with a biotin-streptavidin-biotin surface attachment strategy. The proposed DNA sensor detects complementary DNA sequences (cDNA) while discriminating sequences differing from the target by just one base. This enables the detection of DNA in unprecedentedly small sample volumes (nL scale) and is, to the best of our knowledge, the first specific DNA detection using a DNA probe immobilized within a microstructured optical fiber.


Regulation of dorsal in cultured cells by Toll and tube: tube function involves a novel mechanism.
We described previously a transient cotransfection assay that allows us to study regulation of the Drosophila Dorsal protein (dl) in cultured cells. For example, we showed that over-expression of the Toll transmembrane receptor was sufficient to cause relocalization of dl from the cytoplasm to the nucleus. Here we present data that the tube protein, shown previously by genetic studies to act downstream of Toll, can function in a novel way to enhance dl activity. In the absence of dl, or when dl is cytoplasmic, tube is also found in the cytoplasm of transfected cells. But when dl is localized to the nucleus, so is tube. tube can then function to enhance reporter gene expression, either by cooperation with dl or as a GAL4-tube fusion protein. tube thus appears capable of acting both as a chaperon or escort for dl as it moves to the nucleus, and then as a transcriptional coactivator. We also show that the intracytoplasmic domain of Toll, and specifically the region sharing homology with the interleukin-1 receptor, is sufficient to induce dl-tube nuclear translocation.


First cases in the Czech Republic of the Hallervorden-Spatz disease resulting from mutation in the pantothenate kinase 2 gene.
Hallervorden-Spatz disease (HSD) was and is known as a rare disorder primarily characterized by progressive extrapyramidal dysfunction and dementia alongside optic nerve atrophy or retinal degeneration and pyramidal signs. The rate of occurence of HSD is thus far unknown. Progress in DNA diagnostics stirred up a nomenclature and from HSD, or, perhaps better put, the Hallervorden-Spatz syndrome, crystallized the pantothenate kinase-associated neurodegeneration (PKAN) as a clearly defined entity on the level of DNA. In this paper, we present our first results and experience in the diagnosis of PKAN in the Czech Republic and discuss questions related to differential diagnosis.


Stimulatory heterotrimeric GTP-binding protein inhibits hydrogen peroxide-induced apoptosis by repressing BAK induction in SH-SY5Y human neuroblastoma cells.
Heterotrimeric stimulatory GTP-binding protein (G(s)) stimulates adenylate cyclases to activate the cAMP signaling pathway. Although the cAMP pathway has been reported to be involved in apoptosis, the role of the G(s)-cAMP signaling pathway during reactive oxygen species (ROS)-mediated apoptosis, which is involved in the resistance of cancer cells to chemotherapy and radiation, is not clearly understood. Thus, in this study we aimed to investigate the role of the alpha subunit of G(s) (Galpha(s)) in the ROS-induced apoptosis of cancer cells. The stable expression of constitutively active Galpha(s) (Galpha(s)QL) inhibited the hydrogen peroxide-induced apoptosis of SH-SY5Y human neuroblastoma cells and reduced the hydrogen peroxide-induced increase in Bak and the decrease in Bcl-x(L) protein expression. Exogenous Bak expression abolished these inhibitory effects of Galpha(s)QL, but Bak small interfering RNA decreased hydrogen peroxide-induced apoptosis. Galpha(s) repressed hydrogen peroxide-induced Bak expression by inhibiting the transcription of Bak mRNA, which resulted from the inhibition of the hydrogen peroxide-induced activation of transcription factors such as AP1, NF-kappaB, and NFAT. Moreover, Galpha(s) also inhibited the hydrogen peroxide-induced binding of AP1, NF-kappaB, and NFAT to the Bak promoter. Furthermore, hydrogen peroxide-induced apoptosis was reduced by treating cells with prostaglandin E(2), which activates Galpha(s), but this was augmented by CCPA, which activates Galpha(i) causing a decrease in cAMP levels. From the results, we conclude that Galpha(s) protects neuroblastoma cells from hydrogen peroxide-induced apoptosis by repressing Bak induction, which is mediated by the inhibition of the hydrogen peroxide-induced activations of AP1, NF-kappaB, and NFAT through cAMP-PKA-CREB signaling system.


Celiac plexus block: a reappraisal.
The neurolytic celiac plexus block is an established, well-developed procedure and the most widely applicable of all the neurolytic pain blocks. It optimizes palliative treatment for cancer of the upper abdominal viscera. Several techniques have been proposed in an attempt to increase success rates, reduce morbidity, and enhance technical accuracy. However, the assessment of the results and effectiveness of the block have been controversial. A survey was made of pertinent English language literature on the anatomic and technical problems, indications, advantages, complications, and outcomes related to the neurolytic celiac plexus block as well as the neurolytic solutions and radiologic guidance used. The successful relief of the pain of pancreatic cancer and other abdominal malignancies can be expected in 85% and 73% of patients, respectively. Following the block, many patients can be weaned from opioids or at least have their dose reduced. The half-life of the celiac plexus block seems to be more than 4 weeks. The probability of patients remaining completely pain-free diminishes with increases survival time. The technique selected should be appropriate to the available and the extent of malignancy, since the analgesic results seem to be independent of the principal techniques used. Serious complications are extremely rare. However, critical analysis revealed major deficiencies in all of the reports reviewed. Neurolytic celiac plexus block alone is capable of providing complete pain relief until death in a few cases and, therefore, should be considered as an adjuvant treatment in the analgesic strategy. Combination palliative therapy is necessary in most cases. Failure of the block may be attributed to tumor metastasizing beyond the nerves that conduct pain via the celiac plexus and the component nerves that form it. Concomitant pain of somatic origin (frequently observed in upper gastrointestinal cancer because of significant peritoneal involvement) requires other therapeutic measures.


[Silencing the target rhoptry neck protein (RON) gene responsible for the invasion of Toxoplasma gondii with siRNA transfection].
Toxoplasma gondii is a coccidian protozoan that causes toxoplasmosis is a common disease in Turkey as well as all over the world. It causes various clinical symptoms depending on the immune system status, age, or location of the disease. There is an organelle called the apical complex at the anterior end of the parasite. Rhoptry Neck Proteins (RONs), a component of this organelle, play a critical role in the formation of "moving junction" and parasitophorous vacuoles during host cell invasion. On the other hand, interfering RNA (iRNA) treatment options developed in recent years have emerged. With small iRNAs (siRNA) it is also possible to treat and control parasitic diseases, too. From here it is thought to use this method against toxoplasmosis. Within the scope of the project, it is aimed to silence RON1 gene the target invasion molecules of T.gondii with siRNA transfection. In the study, the negative control group constitute HeLa cells, the positive control group constitute HeLa cells infected with T.gondii tachyzoites and the experimental group constitute HeLa cells infected with T.gondii tachyzoites after siRNA transfection were used. Samples were collected in each study group at 30 seconds, 1 minute, 5 minutes, 15 minutes, 30 minutes, 1 hour, 6 hours, 12 hours, 24 hours, 36 hours and 48 hours. In order to calculate the proportional change of the parasite loads between control groups and experimental groups, RNA and protein isolations were performed from these samples for real time polymerase chain reaction (qRt-PCR) and WB analyzes, respectively. The statistical difference between control groups and experimental groups was calculated. Significant difference in gene expression in experiments with siRNA1 (p< 0.0055), siRNA2 (p< 0.0003), siRNA3 (p<0.0001), siRNA4 (p< 0.0001), siRNA5 (p< 0.0001), siRNA6 (p< 0.0001), siRNA7 (p< 0.0182), siRNA9 (p< 0.0011) and siRNA10 (p< 0.0004) but there was no significant difference statistically in the experiment with siRNA8 (p< 0.4049) was detected. Thus, it has been detected that invasion was inhibited due to the lack of production of parasite antigen in the cell lysate belongs to experimental groups at WB assays with anti-T.gondii RON1 and total anti-T.gondii antibodies resulting in silencing of the RON1 gene. The suppression of the TgRON1 gene expression by this method is a promising step in the development of anti-toxoplasmosis vaccines and therapeutic agents.


Knowledge, Attitudes and Practices of Parents and Pediatricians Regarding Antibiotic Use among Children: Differences in Relation to the Level of Education of the Parents in the Republic of Srpska Bosnia and Herzegovina.
Antibiotics are often misused, especially for the treatment of upper respiratory tract infections (URTIs) in children, where their use is unnecessary and leads to antimicrobial resistance. This study sought to explore the knowledge, attitudes and practices (KAP) of parents and pediatricians on the use of antibiotics among children and whether the level of education of parents has an impact on their KAP. The research was carried out among 1459 parents of children under 6 years of age and among 18 pediatricians. Sixty percent of pediatricians (61.1%) were prescribed antibiotics daily in their practice. Most of the surveyed parents (98.4%) state that doctors are their main source of information when deciding on the use of antibiotics in the treatment of their children. Parents with a higher level of education use television less often as a source of information when making this decision compared to parents with a lower level of education (p = 0.039, i.e., p = 0.003). The majority of parents (80.7%) knew that Panklav (amoxicillin/clavulanic acid) is an antibiotic, while 52.5% identified Pancef (cefixime) as an antibiotic. Parents with a higher level of education correctly identified antibiotics significantly more often (p < 0.001). This study shows that in the Republic of Srpska, parents have adequate knowledge about antibiotics, especially those with a higher level of education, who show better KAP when it comes to antibiotic use.


The Ethics of Cloud Computing.
Cloud computing is rapidly gaining traction in business. It offers businesses online services on demand (such as Gmail, iCloud and Salesforce) and allows them to cut costs on hardware and IT support. This is the first paper in business ethics dealing with this new technology. It analyzes the informational duties of hosting companies that own and operate cloud computing datacentres (e.g., Amazon). It considers the cloud services providers leasing 'space in the cloud' from hosting companies (e.g., Dropbox, Salesforce). And it examines the business and private 'clouders' using these services. The first part of the paper argues that hosting companies, services providers and clouders have mutual informational (epistemic) obligations to provide and seek information about relevant issues such as consumer privacy, reliability of services, data mining and data ownership. The concept of interlucency is developed as an epistemic virtue governing ethically effective communication. The second part considers potential forms of government restrictions on or proscriptions against the development and use of cloud computing technology. Referring to the concept of technology neutrality, it argues that interference with hosting companies and cloud services providers is hardly ever necessary or justified. It is argued, too, however, that businesses using cloud services (e.g., banks, law firms, hospitals etc. storing client data in the cloud) will have to follow rather more stringent regulations.


A Point of View About Fluency.
This article presents several potential concerns with the common usage of the term fluency in the study of stuttering and people who stutter (or, as many speakers now prefer, stutterers). Our goal is to bridge gaps between clinicians, researchers, and stutterers to foster a greater sense of collaboration and understanding regarding the words that are used and meanings that are intended. We begin by reviewing the history of the term fluency. We then explore its usage and current connotations to examine whether the term meaningfully describes constructs that are relevant to the study of the stuttering condition. By highlighting current research and perspectives of stutterers, we conclude that the term fluency (a) is not fully inclusive, (b) encourages the use of misleading measurement procedures, (c) constrains the subjective experience of stuttering within a false binary categorization, and (d) perpetuates a cycle of stigma that is detrimental to stutterers and to the stuttering community as a whole. We recommend that researchers and clinicians cease referring to stuttering as a fluency disorder and simply refer to it as stuttering. Furthermore, we recommend that researchers and clinicians distinguish between moments of stuttering (i.e., what stutterers experience when they lose control of their speech or feel stuck) and the overall lived experience of the stuttering condition.


First molecular detection and characterization of herpesvirus and poxvirus in a Pacific walrus (Odobenus rosmarus divergens).
Herpesvirus and poxvirus can infect a wide range of species: herpesvirus genetic material has been detected and amplified in five species of the superfamily Pinnipedia; poxvirus genetic material, in eight species of Pinnipedia. To date, however, genetic material of these viruses has not been detected in walrus (Odobenus rosmarus), another marine mammal of the Pinnipedia clade, even though anti-herpesvirus antibodies have been detected in these animals. In February 2013, a 9-year-old healthy captive female Pacific walrus died unexpectedly at L'Oceanografic (Valencia, Spain). Herpesvirus was detected in pharyngeal tonsil tissue by PCR. Phylogenetic analysis revealed that the virus belongs to the subfamily Gammaherpesvirinae. Poxvirus was also detected by PCR in skin, pre-scapular and tracheobronchial lymph nodes and tonsils. Gross lesions were not detected in any tissue, but histopathological analyses of pharyngeal tonsils and lymph nodes revealed remarkable lymphoid depletion and lymphocytolysis. Similar histopathological lesions have been previously described in bovine calves infected with an alphaherpesvirus, and in northern elephant seals infected with a gammaherpesvirus that is closely related to the herpesvirus found in this case. Intracytoplasmic eosinophilic inclusion bodies, consistent with poxviral infection, were also observed in the epithelium of the tonsilar mucosa. To our knowledge, this is the first molecular identification of herpesvirus and poxvirus in a walrus. Neither virus was likely to have contributed directly to the death of our animal.


Response of young patients with probable ICD-11 complex PTSD to treatment with developmentally adapted cognitive processing therapy.
Background: ICD-11 features Complex Posttraumatic Stress Disorder (CPTSD) as a new diagnosis. To date, very few studies have investigated CPTSD in young patients, and there is a need for evidence on effective treatment. Objective: The present study evaluates the applicability of developmentally adapted cognitive processing therapy (D-CPT) for CPTSD in young patients in a secondary analysis of the treatment condition of a randomized controlled trial (RCT) investigating the efficacy of D-CPT. Methods: The D-CPT treatment group in the original study included 44 patients (14-21 years) with DSM-IV PTSD after childhood abuse. We used the ICD-11 algorithm to divide the sample into a probable CPTSD and a non-CPTSD group. We performed multilevel models for interviewer-rated and self-rated PTSD symptoms with fixed effects of group (CPTSD, non-CPTSD) and time (up to 12 months follow-up) and their interaction. Treatment response rates for both groups were calculated. Results: Nineteen (43.2%) patients fulfilled criteria for probable ICD-11 CPTSD while 25 (56.8%) did not. Both CPTSD and non-CPTSD groups showed symptom reduction over time. The CPTSD group reported higher symptom severity before and after treatment. Linear improvement and treatment response rates were similar for both groups. D-CPT reduced symptoms of disturbances in self-regulation in both groups. Discussion: Both, patients with and without probable ICD-11 CPTSD seemed to benefit from D-CPT and the treatment also reduced disturbances in self-regulation. Conclusion: This study presents initial evidence of the applicability of D-CPT in clinical practice for young patients with CPTSD. It remains debatable whether CPTSD implies different treatment needs as opposed to PTSD.


Evaluation of the short-term stability of specimens for clinical laboratory testing.
A major concern in both the laboratory-medicine and research communities is the quality of human specimens for analysis. However, there is insufficient scientific evidence regarding optimal conditions for handling and storing routine specimens, especially those in liquid form. Thus, we investigated the stability of clinically relevant samples stored under various conditions. Ten clinical laboratories in Japan conducted analyses of the stability of post-clinical (left over after analysis) test samples in relation to temperature and storage duration. We examined serum, whole blood, and urine samples submitted to each laboratory for routine testing. In this study, at least 5 samples for each of 35 tests were analyzed at each laboratory. After completion of routine testing, specimens with sufficient residual volume and values between LL-R/2 (lower limit of reference interval) and UL+R/2 (upper limit) were divided into 300 μL aliquots, where R=UL - LL. Aliquots of serum specimens were stored at either room temperature (23°C), 4°C, -20°C, or -80°C without light exposure. Aliquots of whole blood and urine specimens were stored at either 23°C or 4°C. The storage time was either 1, 3, or 7 days. Average differences between pre- and post-storage test results were evaluated for each laboratory test by two-way ANOVA. F-values for between-day variations were used for judging the statistical significance of storage-related changes in test values, whereas the ratio of between-day SD to between-individual SD (one-fourth of reference interval) was used to indicate the practical significance of the change. Sample denaturation is clearly temperature- and storage-duration dependent for almost all analytes. In general, specimens were most susceptible to denaturation at 23°C, then 4°C, -20°C, and -80°C. This study confirmed the accumulated routine, practice-based, detailed knowledge regarding specimen stability and will help to ensure the reliability of laboratory test results.


Socioeconomic inequality in recent adverse all-cause mortality trends in Scotland.
Gains in life expectancies have stalled in Scotland, as in several other countries, since around 2012. The relationship between stalling mortality improvements and socioeconomic inequalities in health is unclear. We calculate the difference, as percentage change, in all-cause, all-age, age-standardised mortality rates (ASMR) between 2006 and 2011 (period 1) and between 2012 and 2017 (period 2), for Scotland overall, by sex, and by Scottish Index of Multiple Deprivation (SIMD) quintile. Linear regression is used to summarise the relationship between SIMD quintile and mortality rate change in each period. Between 2006 and 2011, the overall ASMR fell by 10.6% (138/100 000), by 10.1% in women, and 11.8% in men, but between 2012 and 2017 the overall ASMR fell by only 2.6% (30/100 000), by 3.5% in women, and by 2.0% in men. Within the most deprived quintile, the overall ASMR fell by 8.6% (143/100 000) from 2006 to 2011 (7.2% in women; 9.8% in men), but rose by 1.5% (21/100 000) from 2012 to 2017 (0.7% in women; 2.1% in men).The socioeconomic gradient in ASMR improvement more than quadrupled, from 0.4% per quintile in period 1, to 1.7% per quintile in period 2. From 2012 to 2017, socioeconomic gradients in mortality improvement in Scotland were markedly steeper than over the preceding 6 years. As a result, there has not only been a slowdown in overall reductions in mortality, but a widening of socioeconomic mortality inequalities.


Ursolic Acid in Cancer Treatment and Metastatic Chemoprevention: From Synthesized Derivatives to Nanoformulations in Preclinical Studies.
Cancer metastasis has emerged as a major public health threat that causes majority of cancer fatalities. Traditional chemotherapeutics have been effective in the past but suffer from low therapeutic efficiency and harmful side-effects. Recently, it has been reported ursolic acid (UA), one of the naturally abundant pentacyclic triterpenes, possesses a wide range of biological activities including anti-inflammatory, anti-atherosclerotic, and anti-cancer properties. More importantly, UA has the features of low toxicity, liver protection and the potential of anti-cancer metastasis. This article aimed at reviewing the great potential of UA used as a candidate drug in the field of cancer therapy relating to suppression of tumor initiation, progression and metastasis. Selective searches were conducted in Pubmed, Google Scholar and Web of Science using the keywords and subheadings from database inception to December 2017. Systemic reviews are summarized here. UA has exhibited chemopreventive and therapeutic effects of cancer mainly through inducing apoptosis, inhibiting cell proliferation, preventing tumor angiogenesis and metastatic. UA nanoformulations could enhance the solubility and bioavailability of UA as well as exhibit better inhibitory effect on tumor growth and metastasis. The information presented in this article can provide useful references for further studies on making UA a promising anti-cancer drug, especially as a prophylactic metastatic agent for clinical applications.


Antiangiogenic agent sunitinib transiently increases tumor oxygenation and suppresses cycling hypoxia.
Structural and functional abnormalities in tumor blood vessels impact the delivery of oxygen and nutrients to solid tumors, resulting in chronic and cycling hypoxia. Although chronically hypoxic regions exhibit treatment resistance, more recently it has been shown that cycling hypoxic regions acquire prosurvival pathways. Angiogenesis inhibitors have been shown to transiently normalize the tumor vasculatures and enhance tumor response to treatments. However, the effect of antiangiogenic therapy on cycling tumor hypoxia remains unknown. Using electron paramagnetic resonance imaging and MRI in tumor-bearing mice, we have examined the vascular renormalization process by longitudinally mapping tumor partial pressure of oxygen (pO(2)) and microvessel density during treatments with a multi-tyrosine kinase inhibitor sunitinib. Transient improvement in tumor oxygenation was visualized by electron paramagnetic resonance imaging 2 to 4 days following antiangiogenic treatments, accompanied by a 45% decrease in microvessel density. Radiation treatment during this time period of improved oxygenation by antiangiogenic therapy resulted in a synergistic delay in tumor growth. In addition, dynamic oxygen imaging obtained every 3 minutes was conducted to distinguish tumor regions with chronic and cycling hypoxia. Sunitinib treatment suppressed the extent of temporal fluctuations in tumor pO(2) during the vascular normalization window, resulting in the decrease of cycling tumor hypoxia. Overall, the findings suggest that longitudinal and noninvasive monitoring of tumor pO(2) makes it possible to identify a window of vascular renormalization to maximize the effects of combination therapy with antiangiogenic drugs.


Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 1. Michael acceptor structure-activity studies.
The structure-based design, chemical synthesis, and biological evaluation of peptide-derived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds incorporate various Michael acceptor moieties and are shown to irreversibly bind to HRV serotype 14 3CP with inhibition activities (kobs/[I]) ranging from 100 to 600 000 M-1 s-1. These inhibitors are also shown to exhibit antiviral activity when tested against HRV-14-infected H1-HeLa cells with EC50's approaching 0.50 microM. Extensive structure-activity relationships developed by Michael acceptor alteration are reported along with the evaluation of several compounds against HRV serotypes other than 14. A 2.0 A crystal structure of a peptide-derived inhibitor complexed with HRV-2 3CP is also detailed.


The maternal origin of indigenous domestic chicken from the Middle East, the north and the horn of Africa.
Indigenous domestic chicken represents a major source of protein for agricultural communities around the world. In the Middle East and Africa, they are adapted to hot dry and semi-dry areas, in contrast to their wild ancestor, the Red junglefowl, which lives in humid and sub-humid tropical areas. Indigenous populations are declining following increased demand for poultry meat and eggs, favouring the more productive exotic commercial breeds. In this paper, using the D-loop of mitochondrial DNA as a maternally inherited genetic marker, we address the question of the origin and dispersal routes of domestic chicken of the Middle East (Iraq and Saudi Arabia), the northern part of the African continent (Algeria and Libya) and the Horn of Africa (Ethiopia). The analysis of the mtDNA D-loop of 706 chicken samples from Iraq (n = 107), Saudi Arabia (n = 185), Algeria (n = 88), Libya (n = 23), Ethiopia (n = 211) and Pakistan (n = 92) show the presence of five haplogroups (A, B, C, D and E), suggesting more than one maternal origin for the studied populations. Haplogroup E, which occurred in 625 samples, was the most frequent in all countries. This haplogroup most likely originates from the Indian subcontinent and probably migrated following a terrestrial route to these different countries. Haplotypes belonging to haplogroup D were present in all countries except Algeria and Libya, it is likely a legacy of the Indian Ocean maritime trading network. Haplogroup A was present in all countries and may be of commercial origin. Haplogroup B was found only in Ethiopia. Haplogroup C was only detected in the South-Western region of Saudi Arabia and in Ethiopia. The results support a major influence of the Indian subcontinent on the maternal diversity of the today's chicken populations examined here. Most of the diversity occurs within rather than between populations. This lack of phylogeographic signal agrees with both ancient and more recent trading networks having shaped the modern-day diversity of indigenous chicken across populations and countries.


IRONSperm: Sperm-templated soft magnetic microrobots.
We develop biohybrid magnetic microrobots by electrostatic self-assembly of nonmotile sperm cells and magnetic nanoparticles. Incorporating a biological entity into microrobots entails many functional advantages beyond shape templating, such as the facile uptake of chemotherapeutic agents to achieve targeted drug delivery. We present a single-step electrostatic self-assembly technique to fabricate IRONSperms, soft magnetic microswimmers that emulate the motion of motile sperm cells. Our experiments and theoretical predictions show that the swimming speed of IRONSperms exceeds 0.2 body length/s (6.8 ± 4.1 µm/s) at an actuation frequency of 8 Hz and precision angle of 45°. We demonstrate that the nanoparticle coating increases the acoustic impedance of the sperm cells and enables localization of clusters of IRONSperm using ultrasound feedback. We also confirm the biocompatibility and drug loading ability of these microrobots, and their promise as biocompatible, controllable, and detectable biohybrid tools for in vivo targeted therapy.


Uncovering the Transcriptional Correlates of Hub Connectivity in Neural Networks.
Connections in nervous systems are disproportionately concentrated on a small subset of neural elements that act as network hubs. Hubs have been found across different species and scales ranging from C. elegans to mouse, rat, cat, macaque, and human, suggesting a role for genetic influences. The recent availability of brain-wide gene expression atlases provides new opportunities for mapping the transcriptional correlates of large-scale network-level phenotypes. Here we review studies that use these atlases to investigate gene expression patterns associated with hub connectivity in neural networks and present evidence that some of these patterns are conserved across species and scales.


[Diagnostic efforts for the detection of chlamydia trachomatis infections in Iceland 1982-1994.].
The results of diagnostic testing for the detection of Chlamydial infections in Iceland during the years 1982 to 1994 were reviewed. During those 13 years 123,461 laboratory tests were performed in 101,574 examinations. These examinations were positive in 14,462 instances. The first diagnostic test to be introduced was cell culture in 1982. From then on the number of examinations and the number of positive examinations increased steadily until 1988, when positive examinations reached a peak at approximately 570 cases per 100,000 inhabitants. In 1990 a sharp decline in both the total number of examinations and positive results was observed. The percentage of positive examinations declined during the study period. In 1991 and 1992 the number of examinations, the number of positive examinations and the percentage of positive examinations increased but the number of positive tests declined again in 1993. In 1994 the polymerase chain reaction assay (PCR) replaced the much less sensitive Chlamydiazyme(R) assay and the number of positive examinations rose again although the number of tests declined. The dramatic reduction in prevalence experienced in Sweden does not seem to have taken place in Iceland. In Sweden a substantial effort was made to screen asymptomatic populations. In Iceland the screening of asymptomatic patients increased from the beginning of the study period until 1988 but declined thereafter. Screening of asymptomatic populations as well as contact tracing may be important for bringing about a significant reduction of the prevalence of sexually transmitted infections caused by Chlamydia trachomatis.


Measuring coping in people with amyotrophic lateral sclerosis using the Coping Index-ALS: A patient derived, Rasch compliant scale.
The progressively disabling and terminal nature of ALS/MND imposes major coping demands on patients. We wished to improve the psychometric properties of our previously published MND-Coping Scale, so that parametric analyses were valid, and to make it simpler for patients to complete and clinicians to score. After a new qualitative analysis of 26 patients with ALS/MND, the draft Coping Index-ALS (CI-ALS) was administered to 465 additional patients, alongside COPE-60, General Perceived Self Efficacy scale, and WHOQOL-BREF. Validity of the CI-ALS was assessed using the Rasch model. External validity was checked against comparator measures. Thirteen centres contributed 465 patients, mean age 64.9 years (SD 10.8), mean disease duration 28.4 months (SD 37.5). The CI-ALS-Self and CI-ALS-Others both satisfied Rasch model expectations and showed invariance across age, gender, marital status and type of onset. Expected correlations were observed with comparator scales. A nomogram is available to convert the raw scores to interval level measures suitable for parametric analysis. Coping abilities in ALS/MND can now be measured using a simple 21 item self-report measure, offering two subscales with a focus of 'coping by self ' and 'coping with others'. This allows clinicians to identify individuals with poor coping and facilitates research on interventions that may improve coping skills.


Recent advances in multifunctional silica-based hybrid nanocarriers for bioimaging and cancer therapy.
In recent years, there has been a considerable research focus on integrating cancer cell imaging and therapeutic functions into single nanoscale platforms for better treatment of cancer. This task could often be achieved by incorporating multiple components into a hybrid nanosystem. In this minireview, we highlight different types of silica-based hybrid nanosystems and their recent applications as integrated multifunctional platforms for cancer imaging and treatment. The discussions are divided into several sections focusing on various types of materials employed to integrate with silica, which include silica-metallic nanoparticle based hybrid nanocarriers, silica-gold nanoparticle based hybrid nanocarriers, silica-quantum dot based hybrid nanocarriers, silica-upconversion nanoparticle based hybrid nanocarriers, silica-carbon based hybrid nanocarriers, and organosilica nanocarriers. Therapeutic agents loaded in such hybrids include chemodrugs, proteins, DNA/RNA and photosensitizers. For targeted delivery into tumor sites, targeting ligands such as antibodies, peptides, aptamers, and other small molecules are grafted on the surface of the nanocarriers. At the end of the review, a brief summary and research outlook are presented. This minireview aims to provide a quick update of recent research achievements in the field.


Subgroup analysis of the relationship between polycyclic aromatic hydrocarbons and rheumatoid arthritis: Data from the National Health and Nutrition Examination Survey, 2003-2014.
The present study examined potential effect modifiers between polycyclic aromatic hydrocarbon (PAH) exposure and the development of rheumatoid arthritis (RA) and elucidated the relationship between PAHs and RA in subgroups using data from the National Health and Nutrition Examination Survey (NHANES) (2003-2014). The relatedness between eight PAH metabolites and RA in the whole population and different subgroups was tested using multivariable logistic regression analyses. This study included 6297 participants, including 400 RA patients and 5897 non-RA control participants, with full data. Compared to the lowest quartiles, risk of RA was increased in population with the highest quartiles of 1-hydroxynaphthalene (1-NAP), 2-NAP, 2-hydroxyfluorene (2-FLU), and 3-FLU in a bias factor corrected model. The associations between urinary PAH metabolites and RA were prominent in female, young and middle-aged, obese, smoking and alcohol-consuming populations in the subgroup analysis. Our results demonstrated that PAH exposure was related to RA, and the relationship between urinary PAH metabolites and RA differed between subgroups and depended on specific PAH metabolites.


Provokable bilateral vertebral artery compression diagnosed with transcranial Doppler.
Head and neck movements may cause vascular compression that produces a syndrome of vertebrobasilar insufficiency. Vertebrobasilar circulation was examined noninvasively in two patients who were able to provoke these symptoms repeatedly on demand. Blood flow velocities in the basilar artery (case 1) and both posterior cerebral arteries (both cases) were measured continuously by transcranial Doppler sonography while the patients voluntarily performed the offending maneuvers and reproduced their symptoms. The provocative maneuvers evoked an immediate and precipitous drop in blood flow velocity, producing symptoms within seconds. Upon relief, the blood flow velocities showed a transient overshoot before returning to baseline values. These observations indicate that the symptoms of vertebrobasilar insufficiency were due to real reductions in blood flow and demonstrate the usefulness of transcranial Doppler sonography to diagnose bilateral extracranial vertebral artery compression.


Inter-decadal variability of phytoplankton biomass along the coastal West Antarctic Peninsula.
The West Antarctic Peninsula (WAP) is a climatically sensitive region where periods of strong warming have caused significant changes in the marine ecosystem and food-web processes. Tight coupling between phytoplankton and higher trophic levels implies that the coastal WAP is a bottom-up controlled system, where changes in phytoplankton dynamics may largely impact other food-web components. Here, we analysed the inter-decadal time series of year-round chlorophyll-a (Chl) collected from three stations along the coastal WAP: Carlini Station at Potter Cove (PC) on King George Island, Palmer Station on Anvers Island and Rothera Station on Adelaide Island. There were trends towards increased phytoplankton biomass at Carlini Station (PC) and Palmer Station, while phytoplankton biomass declined significantly at Rothera Station over the studied period. The impacts of two relevant climate modes to the WAP, the El Niño-Southern Oscillation and the Southern Annular Mode, on winter and spring phytoplankton biomass appear to be different among the three sampling stations, suggesting an important role of local-scale forcing than large-scale forcing on phytoplankton dynamics at each station. The inter-annual variability of seasonal bloom progression derived from considering all three stations together captured ecologically meaningful, seasonally co-occurring bloom patterns which were primarily constrained by water-column stability strength. Our findings highlight a coupled link between phytoplankton and physical and climate dynamics along the coastal WAP, which may improve our understanding of overall WAP food-web responses to climate change and variability.This article is part of the theme issue 'The marine system of the West Antarctic Peninsula: status and strategy for progress in a region of rapid change'.


Functional Capacity Past Age 40 in Patients With Congenital Ventricular Septal Defects.
Background Ventricular septal defects (VSD), when treated correctly in childhood, are considered to have great prognoses, and the majority of patients are discharged from follow-up when entering their teens. Young adults were previously found to have poorer functional capacity than healthy peers, but the question remains whether functional capacity degenerates further with age. Methods and Results A group of 30 patients with surgically closed VSDs (51±8 years) with 30 matched, healthy control participants (52±9 years) and a group of 30 patients with small unrepaired VSDs (55±12 years) and 30 matched control participants (55±10 years) underwent cardiopulmonary exercise testing using an incremental workload protocol and noninvasive gas measurement. Peak oxygen uptake was lower in participants with closed VSDs than matched controls (24±7 versus 34±9 mL/min per kg, P<0.01) and with unrepaired VSDs than matched controls (26±5 versus 32±8 mL/min per kg, P<0.01). Patients demonstrated lower oxygen uptake from exercise levels at 20% of maximal workload compared with respective control groups (P<0.01). Peak ventilation was lower in patients with surgically closed VSDs than control participants (1.0±0.3 versus 1.4±0.4 L/min per kg, P<0.01) but similar in patients with unrepaired VSDs and control participants (P=0.14). Exercise capacity was 29% lower in older patients with surgically closed VSDs than healthy peers, whereas younger patients with surgically closed VSDs previously demonstrated 18% lower capacity compared with peers. Older patients with unrepaired VSDs reached 21% lower exercise capacity, whereas younger patients with unrepaired VSDs previously demonstrated 17% lower oxygen uptake than healthy peers. Conclusions Patients with VSDs demonstrate poorer exercise capacity than healthy peers. The difference between patients and control participants increased with advancing age-and increased most in patients with operated VSDs-compared with previous findings in younger patients. Results warrant continuous follow-up for these simple defects.


Treating Center Volume and Congenital Diaphragmatic Hernia Outcomes in California.
To examined outcomes for infants born with congenital diaphragmatic hernias (CDH), according to specific treatment center volume indicators. A population-based retrospective cohort study was conducted involving neonatal intensive care units in California. Multivariable analysis was used to examine the outcomes of infants with CDH including mortality, total days on ventilation, and respiratory support at discharge. Significant covariables of interest included treatment center surgical and overall neonatal intensive care unit volumes. There were 728 infants in the overall CDH cohort, and 541 infants (74%) in the lower risk subcohort according to a severity-weighted congenital malformation score and never requiring extracorporeal membrane oxygenation. The overall cohort mortality was 28.3% (n = 206), and 19.8% (n = 107) for the subcohort. For the lower risk subcohort, the adjusted odds of mortality were significantly lower at treatment centers with higher CDH repair volume (OR, 0.41; 95% CI, 0.23-0.75; P = .003), ventilator days were significantly lower at centers with higher thoracic surgery volume (OR, 0.56; 9 5% CI, 0.33-0.95; P = .03), and respiratory support at discharge trended lower at centers with higher neonatal intensive care unit admission volumes (OR, 0.51; 9 5% CI, 0.26-1.02; P = .06). Overall and surgery-specific institutional experience significantly contribute to optimized outcomes for infants with CDH. These data and follow-on studies may help inform the ongoing debate over the optimal care setting and relevant quality indicators for newborn infants with major surgical anomalies.


Nutritional screening of elderly patients: a health improvement approach to practice.
Almost 60% of elderly care in-patients are at risk of malnutrition. Malnourished patients have poorer clinical outcomes and this is a key factor with respect to prolonging the length of stay. Since 2003, the Malnutrition Universal Screening Tool (MUST) has been advocated as a method for identifying these at-risk patients. Screening should take place on admission; however, the Trust has set a stretch target of aiming to document the score accurately within 6 h of admission. Three 'care of the elderly' wards participated in the project. Each month, the timeliness (within 6 h of admission) and accuracy (compared to a dietician assessment) of the MUST scores on the wards were reviewed. Plan-Do-Study-Act cycles were used to rapidly test changes in the ward areas. Tests included a study day, one-to-one ward-based nutrition training, a focus on the use of alternative anthropometric measurements, the development of a training pack and the identification of the challenges for undertaking accurate and timely assessments. Baseline data identified that a MUST was documented in <60% of patients within 6 h of admission and that only 70% were accurate. After implementation of the change package, all the wards achieved an improvement and documented MUST within 6 h of admission; one ward achieved 90% accuracy in the scores. Ward teams receiving training and monthly feedback of their results creates ownership, momentum and maintains enthusiasm for striving to reach stretch targets. The team continues to work on improving accurate nutritional screening across the Trust by using quality improvement methodologies.


Sex steroid ablation enhances hematopoietic recovery following cytotoxic antineoplastic therapy in aged mice.
Cytotoxic antineoplastic therapy is widely used in the clinic as a treatment for malignant diseases. The treatment itself, however, leads to long-term depletion of the adaptive immune system, which is more pronounced in older patients, predominantly due to thymic atrophy. We and others have previously shown that withdrawal of sex steroids is able to regenerate the aged thymus and enhance recovery from autologous and allogeneic hematopoietic stem cell transplant. In this study we have examined the effects of sex steroid ablation (SSA) on the recovery of lymphopoiesis in the bone marrow (BM) and thymus following treatment with the chemotherapeutic agent cyclophosphamide (Cy) in middle-aged and old mice. Furthermore, we have also examined the impact of this regeneration on peripheral immunity. SSA enhanced the recovery of BM resident hematopoietic stem cells and lymphoid progenitors and promoted lymphopoiesis. Interestingly, Cy alone caused a profound increase in the recently described common lymphoid progenitor 2 (CLP-2) population in the BM. In the thymus, SSA caused a profound increase in cellularity as well as all intrathymic T-lineage progenitors including early T-lineage progenitors (ETPs) and non-canonical T cell progenitors such as the CLP-2. We also found that these transferred into numerical increases in the periphery with enhanced B and T cell numbers. Furthermore, these lymphocytes were found to have an enhanced functional capacity with no perturbation of the TCR repertoire. Taken together, these results provide the basis for the use of SSA in the clinic to enhance treatment outcomes from cytotoxic antineoplastic therapy.


The underlying mechanism for the PARP and BRCA synthetic lethality: clearing up the misunderstandings.
Poly (ADP-ribose) polymerase (PARP) inhibitors effectively kill tumours defective in the BRCA1 or BRCA2 genes through the concept of synthetic lethality. It is suggested that PARP inhibitors cause an increase in DNA single-strand breaks (SSBs), which are converted during replication to irreparable toxic DNA double-strand breaks (DSBs) in BRCA1/2 defective cells. There are a number of recent reports challenging this model. Here, alternative models that are not mutually exclusive are presented to explain the synthetic lethality between BRCA1/2 and PARP inhibitors. One such model proposes that PARP inhibition causes PARP-1 to be trapped onto DNA repair intermediates, especially during base excision repair. This may in turn cause obstruction to replication forks, which require BRCA-dependent homologous recombination to be resolved. In another model, PARP is directly involved in catalysing replication repair in a distinct pathway from homologous recombination. Experimental evidence supporting these novel models to explain the PARP-BRCA synthetic lethality are discussed.


Estimating non-response bias in a survey on alcohol consumption: comparison of response waves.
According to 'the continuum of resistance model' late respondents can be used as a proxy for non-respondents in estimating non-response bias. In the present study, the validity of this model was explored and tested in three surveys on alcohol consumption. The three studies collected their data by means of mailed questionnaires on alcohol consumption whereby two studies also performed a non-response follow-up. Comparisons of early respondents, late respondents and non-respondents in one study showed some support for 'the continuum of resistance model', although another study could not confirm this result. Comparison of alcohol consumption between three time response groups showed no significant linear pattern of differences between response waves. The hypothesis that late respondents are more similar to non-respondents than early respondents, could not be confirmed or rejected. Repeated mailings are effective in obtaining a greater sample size, but seem ineffective in improving the representativeness of alcohol consumption surveys.


Injury-Induced Inhibition of Bystander Neurons Requires dSarm and Signaling from Glia.
Nervous system injury and disease have broad effects on the functional connectivity of the nervous system, but how injury signals are spread across neural circuits remains unclear. We explored how axotomy changes the physiology of severed axons and adjacent uninjured "bystander" neurons in a simple in vivo nerve preparation. Within hours after injury, we observed suppression of axon transport in all axons, whether injured or not, and decreased mechano- and chemosensory signal transduction in uninjured bystander neurons. Unexpectedly, we found the axon death molecule dSarm, but not its NAD+ hydrolase activity, was required cell autonomously for these early changes in neuronal cell biology in bystander neurons, as were the voltage-gated calcium channel Cacophony (Cac) and the mitogen-activated protein kinase (MAPK) signaling cascade. Bystander neurons functionally recovered at later time points, while severed axons degenerated via α/Armadillo/Toll-interleukin receptor homology domain (dSarm)/Axundead signaling, and independently of Cac/MAPK. Interestingly, suppression of bystander neuron function required Draper/MEGF10 signaling in glia, indicating glial cells spread injury signals and actively suppress bystander neuron function. Our work identifies a new role for dSarm and glia in suppression of bystander neuron function after injury and defines two genetically and temporally separable phases of dSarm signaling in the injured nervous system.


Assessment of physical function and participation in chronic pain clinical trials: IMMPACT/OMERACT recommendations.
Although pain reduction is commonly the primary outcome in chronic pain clinical trials, physical functioning is also important. A challenge in designing chronic pain trials to determine efficacy and effectiveness of therapies is obtaining appropriate information about the impact of an intervention on physical function. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) and Outcome Measures in Rheumatology (OMERACT) convened a meeting to consider assessment of physical functioning and participation in research on chronic pain. The primary purpose of this article is to synthesize evidence on the scope of physical functioning to inform work on refining physical function outcome measurement. We address issues in assessing this broad construct and provide examples of frequently used measures of relevant concepts. Investigators can assess physical functioning using patient-reported outcome (PRO), performance-based, and objective measures of activity. This article aims to provide support for the use of these measures, covering broad aspects of functioning, including work participation, social participation, and caregiver burden, which researchers should consider when designing chronic pain clinical trials. Investigators should consider the inclusion of both PROs and performance-based measures as they provide different but also important complementary information. The development and use of reliable and valid PROs and performance-based measures of physical functioning may expedite development of treatments, and standardization of these measures has the potential to facilitate comparison across studies. We provide recommendations regarding important domains to stimulate research to develop tools that are more robust, address consistency and standardization, and engage patients early in tool development.


Does a lack of perceptual expertise prevent participants from forming reliable first impressions of "other-race" faces?
[Correction Notice: An Erratum for this article was reported online in Journal of Experimental Psychology: General on Feb 27 2023 (see record 2023-48793-001). The original article is being made available open access under the CC-BY license following the University of Nottingham opt-in to the Jisc/APA Read and Publish agreement. The correct copyright is "© 2022 The Author(s)" and the CC-BY license disclaimer is below. All versions of this article have been corrected. "Open Access funding provided by Birkbeck, University of London: This work is licensed under a Creative Commons Attribution 4.0 International License (CC-BY). This license permits copying and redistributing the work in any medium or format, as well as adapting the material for any purpose, even commercially."] Many studies investigating first impressions from faces employ stimulus sets that comprise only White faces. It is argued that participants lack the necessary perceptual expertise to provide reliable trait evaluations when viewing faces from ethnicities that differ from their own. In combination with a reliance on White and WEIRD participants, this concern has contributed to the widespread use of White face stimuli in this literature. The present study sought to determine whether concerns about the use of so-called other-race faces are justified by assessing the test-retest reliability of trait judgments made about same- and other-race faces. In two experiments conducted on 400 British participants, we find that White British participants made reliable trait judgments about Black faces, and Black British participants made reliable trait judgments about White faces. It is important that future work be conducted to determine how widely these results generalize. Considering our findings, however, we suggest (a) that the default assumption in future first impressions research should be that participants-particularly those recruited from diverse communities-are able to form reliable first impressions of other-race faces and (b) that faces of color be included in stimulus sets whenever possible. (PsycInfo Database Record (c) 2023 APA, all rights reserved).