Why does a steep caudal-rostral gradient exist in glycine content in the brain?
Glycine is an important amino acid in the central nervous system. Interestingly, the content of glycine is about 9 times higher in the spinal cord grey matter than in the telencephalon. And this kind of caudal to rostral gradient is never seen in any other neurotransmitters. However, the cause of this phenomenon remains unknown. In the present report, I, thus, postulate the following theory. Glycine has dual roles as a neurotransmitter, one is the agonist for inhibitory glycine receptors (GlyRs), and the other is a co-agonist for excitatory NMDA receptors (NMDARs). Inhibitory GlyRs are concentrated in the lower brain and the affinity of glycine to GlyRs is low, leading to the high content of glycine in the lower brain. In contrast, in the upper brain, there are little glycinergic neurons and the affinity of glycine to NMDARs is very high, leading to the low content of glycine in the forebrain. These different roles of glycine as a neurotransmitter between in the upper brain and in the lower brain make this steep caudal-rostral gradient in glycine content.


Intussusception mimicking rectal prolapse.
We report a 10-week-old boy with a prolapsing colocolic intussusception mimicking rectal prolapse. Rectal prolapse of ileocolic intussusception has been well-described, but colocolic intussusception presenting as rectal prolapse is unique.


Development of a PCR-compatible enrichment medium for Yersinia enterocolitica: amplification precision and dynamic detection range during cultivation.
A Yersinia PCR-Compatible Enrichment (YPCE) medium was developed, which removes the necessity for sample pretreatment before PCR-based detection of Yersinia enterocolitica. The medium was designed through a sequence of independent screening and factorial design experiments to study the PCR inhibition and growth characteristics of medium components. The compatibility of the YPCE medium was evaluated using real-time PCR. The real-time PCR assay, based on the fluorescent double-stranded DNA binding dye SYBR green, generated approximately a 4-log linear range of amplification and in the range of 10(5)-10(8) (CFU/ml), the coefficient of variation <5%. When a background flora was present at concentrations > or = 10(6) (CFU/ml), the DNA amplification was influenced and a change in the log-linear slope leading to a lower amplification efficiency was observed. To study the dynamic detection range and relative amplification precision during enrichment. Y. enterocolitica and background flora were inoculated at various concentrations. It was possible to detect inoculation concentrations of 10(1) (CFU/ml) Y. enterocolitica in the presence of at least an inoculation concentration of 10(3) (CFU/ml) of an undefined background flora and the optimal conditions for sample withdrawal was in the range of 9 to 18 h enrichment. The YPCE medium can, especially for swab samples, form part of a simple analysis procedure allowing high throughput PCR.


N-Isovalerylalanine and N-isovalerylsarcosine: two new minor metabolites in isovaleric acidemia.
Besides N-isovalerylglycine, isovaleric, 3-hydroxyisovaleric, 4-hydroxyisovaleric, methylsuccinic, mesaconic, 3-hydroxyisoheptanoic and N-isovalerylglutamic acids the excretion of hitherto unreported N-isovalerylalanine and N-isovalerylsarcosine, two minor but characteristic constituents of the organic acid profile in isovaleric acidemia, is described. The new metabolites are assumed to be formed from isovaleryl-CoA by action of the enzyme glycine N-acylase on alanine and sarcosine, respectively.


Congenital candidiasis.
Congenital candidiasis presents with a variety of clinical features. We report two neonates with congenital candidiasis characterized by diffuse erythematous papules associated with pneumonia and respiratory distress. Candida pseudohyphae were identifiable in skin scrapings. Systemic cultures were negative, but urine and sputum cultures grew Candida albicans. After prompt systemic antifungal therapy, the infants were discharged from hospital with no overt complications. This report highlights the presence of characteristic skin lesions associated with candidal infection, occurring within 24 hours of birth. This is an important observation which could help in the early diagnosis of congenital candidal infection.


Impact of Rotavirus Vaccination on Childhood Hospitalization for Seizures.
Rotavirus vaccine (RV) might reduce the risk of hospitalization due to childhood seizures (CS). We aimed to identify and assess variations in the incidence of hospitalizations for CS among children <5 years of age before and after RV introduction. Annual hospitalization rates for any kind of CS, before and after RV introduction in 2007, were calculated using the official surveillance system for hospitalization data. Our study cohort totaled 6149 children <5 years of age admitted to the hospital between 2003 and 2013 with any kind of CS (780.3* + 779.0* + 333.2* + 345* ICD-9-CM code). The annual hospitalization rates for any kind of CS in children <5 years of age were correlated with RV coverage (r = -0.673; P = 0.033) and rotavirus acute gastroenteritis admission rates (ρ = 0.506; P = 0.001), with decrease rates ranging from 16.2% (95% confidence interval: 8.3-23.5%) in 2007 to 34.0% (27.3-40.1%) in 2010, as compared with the median rate of the pre-vaccination period (2003 to 2006). Similarly, for convulsions (780.3*ICD-9-CM code), the decrease seen in children <5 years of age was significantly correlated with the increase in RV coverage (r = -0.747; P = 0.013) and rotavirus acute gastroenteritis admission rates (ρ = 0.543; P < 0.001), with decrease rates ranging from 18.7% (9.6-26.8%) in 2007 to 42.5% (35.3-48.9%) in 2012. Significant results were also obtained for infants <12 months and infants 1-2 years of age. In the remaining age groups or diagnostic categories analyzed, changes were either not significant or not related to vaccination changes or rotavirus acute gastroenteritis admission rates. Our results show that rotavirus vaccination may have a significant impact in the decrease in seizure-related hospitalizations in childhood. This additional benefit of rotavirus vaccination seems more marked in the youngest infants.


The mechanism and biomarker function of Cavin-2 in lung ischemia-reperfusion injury.
Lung Ischemia Reperfusion injury(LIRI) is one of the most predominant complications of ischemic lung disease. Cavin-2 emerged as a regulator of a variety of cellular processes, including endocytosis, lipid homeostasis, signal transduction and tumorigenesis, but the function of Cavin-2 in LIRI is unknown. The purpose of this study was to determine the predictive potential of Cavin-2 in protecting lung ischemia-reperfusion injury and its corresponding mechanisms. We found the strong relationship between Cavin-2 and multiple immune-related genes by deep learning method. To reveal the mechanism of Cavin-2 in LIRI, the LIRI SD rat model was constructed to detect the expression of Cavin-2 in the lung tissue of SD rats after LIRI, and the expression of Cavin-2 in lung cell lines was also detected. The expression of IL-6, IL-10 and MDA in cells after Cavin-2 over-expression or knockdown was examined under hypoxic conditions. The expression levels of p-AKT, p-STAT3 and p-ERK1/2 were measured in over-expressing Cavin-2 cells under hypoxic-ischemia conditions, and then the corresponding blockers of AKT, STAT3 and ERK1/2 were given to verify, whether they play a protective role in LIRI. After hypoxia, the expression of Cavin-2 in rat lung tissues was significantly increased, and the cellular activity and IL-10 in Cavin-2 over-expressing cells were significantly higher than that of the control group, while IL-6 and MDA were significantly lower than that of the control group, while the above results were reversed in Cavin-2 knockdown cells; Meanwhile, the phosphorylation levels of AKT, STAT3, and ERK1/2 were significantly increased in Cavin-2 over-expression cells after hypoxia. When AKT, STAT3, and ERK1/2 specific blockers were given, they lost their protective effect against LIRI. Cavin-2 shows biomarker potential in protecting lung from ischemia-reperfusion injury through the survivor activating factor enhancement (SAFE) and reperfusion injury salvage kinase (RISK) pathway.


[The role of age-related and adaptive changes in the vascular wall in atherogenesis in light of the theory of Academician I. V. Davydovskiĭ on atherosclerosis].
Aorta and coronary arteries (1053 and 386 cases, respectively) were evaluated in young persons. It is shown that atherosclerotic developments in the vessels are largely determined by hyperplastic involvement of the intima due to age-related vascular rearrangement and the hemodynamic factor. For aorta, these are represented by rhythmic structures which seem to give rise to the majority of the fibrous plaques. The findings are in consistence with I. V. Davydovsky's conceptions on age-related and adaptation changes in the vascular wall emerging during various human vital activities and supposed to underlie the development of atherosclerosis.


Visible light driven α-Fe2O3 nanorod photocatalyst.
α-Fe2O3 nanorods are controlled prepared by a facile hydrothermal process followed by a calcination treatment. The experiment results indicate that the morphology of the as-obtained product depends greatly on the quantity of NaOH. The photocatalytic performances of the as-prepared samples were evaluated by photocatalytic decolorization of Congo red solution at ambient temperature. The results indicate that the photocatalytic activity of the α-Fe2O3 nanorods is superior to α-Fe2O3 nanoparticles and microplates, revealing the versatile potential applications of the product in wastewater purifications.


Variations of nursing teamwork by hospital, patient unit, and staff characteristics.
The aim of this cross-sectional study was to examine the relationship among hospital, patient units, and staff characteristics and nursing teamwork. Using multiple linear regression analysis, we found that nursing role, shift, absenteeism, perceived adequacy of staffing, and unit type were significant predictors of teamwork.


The management of chronic granulomatous disease.
Chronic granulomatous disease (CGD) is a primary immunodeficiency disease which results from absence of the NADPH oxidase in the professional phagocytic cells neutrophils, monocytes, macrophages and eosinophils. Deficiency of this oxidase renders the patient liable to infection by bacteria and fungi, and, as the name of the disease suggests, to chronic granulomatous inflammation. These patients present with a great variety of infections and other complications of their disease, which often tax the clinical and therapeutic skill of the doctors responsible for their care. Collectively we look after, or advise on the management of, over 100 of these subjects, and have developed experience in the diagnosis and management of the infections and other clinical problems they present. We thought that it might be timely to provide guidelines for their management based upon this experience. The numbers of patients are still relatively small, and the clinical presentations very varied, so it is impossible to provide clear statistical proof of the veracity of this advice. It does, however, reflect the working practise of the physicians caring for many of these patients in Europe.


Rehabilitation engineering technology and the arthritis patient.
Patients with arthritis and related disorders experience major limitations in their abilities to do work in the environment. The selective and appropriate use of technical aids and new forms of advanced technology can resolve dysfunctions of mobility, self-care, and manipulation of objects in the environment. This paper reviews the state of the art of various technologies for the disabled and points out specific applications and limitations to the patient with arthritis.


Antecedents of disruptive behaviours involving radiographers at central hospitals in Harare Metropolitan Province, Zimbabwe.
Although disruptive behaviours (DBs) are universal in healthcare, each healthcare setting, profession or department presents unique DBs antecedents. Gaining better insights into the antecedents of DBs is crucial in order to put together a tailor-made program designed to raise awareness, establish accountability, and provide resources to mitigate their impact. There are, however, a few studies exploring antecedents of DBs involving radiographers, more so in low resource settings like Africa. The aim of the study was to determine the antecedents of DBs involving radiographers employed by central hospitals in Harare Metropolitan Province, Zimbabwe. A descriptive cross-sectional survey was carried out from January to March 2021 at central hospitals in Harare Metropolitan Province, Zimbabwe. A self-administered questionnaire was used to capture the views of 100 randomly selected radiographers. There was a significant agreement that the following are antecedents of DBs: frustration due to poor working conditions (Mean = 3.93.p < .0005); long waiting times for patients (Mean = 3.91.p < .0005); a sense of privilege and status for those at the top (Mean = 3.87.p < .0005); burnout or fatigue (Mean = 3.79.p < .0005); narcissism (Mean = 3.79.p < .0005); differences in communication styles (Mean = 3.68.p < .0005); divergence of opinions or thoughts (Mean = 3.59.p < .0005); personal conflicts or family problems (Mean = 3.57.p < .0005); self-protection against feelings of inadequacy (Mean = 3.42.p < .0005); dysfunctional organizational culture (Mean = 3.38.p < .0005) and cultural, generational or gender bias (Mean = 3.32.p < .0005). This study identifies the antecedents of DBs involving radiographers at central hospitals in Harare Metropolitan Province. It is crucial that any attempts at finding solutions to address the behaviours should be based on evidence of the antecedents in the setting concerned. This will help in the understanding of the antecedents of DBs involving radiographers so that context specific interventions to address these behaviours are formulated.


A model of an inflammatory bowel disease population-based registry: The Forlì experience (1993-2013).
The article presents a population-based registry designed to estimate incidence and prevalence of inflammatory bowel disease (IBD) in the area of Forlì (north-eastern Italy). The registry included all patients with IBD ulcerative colitis (UC) and Crohn's disease (CD) in the Forlì area from 1993 to 2013. A data manager matched records from various sources. Seven hundred ninety-one patients were registered during the study period, 564 (71.3%) with UC and 227 (28.7%) with CD. The standardized annual incidence rate for UC was 12.8 per 100,000 females (95% CI 11.1-14.4) and 15.7 per 100,000 males (95% CI 13.9-17.5). That of CD was 7.0 per 100,000 for females (95% CI 5.7-8.3) and 5.4 per 100,000 males (95% CI 4.3-6.4). The prevalence of CD and UC on 1 January 2014 was 109.2 per 100,000 inhabitants (95% CI 94.3-124.2) and 266.4 per 100,000 inhabitants (95% CI 243.4-289.7), respectively. Although further studies are needed, the data suggest that incidence and prevalence of IBD in Italy are underestimated.


Anionic sites in the myelin sheath as shown by cationized ferritin.
The distribution of anionic sites in the myelin sheath of sciatic nerves of rabbits was studied using cationized ferritin. Ferritin molecules were observed on the cytoplasmic sides of the myelin lamellae stratified in paranodes and Schmidt-Lanterman clefts. In the compact myelin, ferritin molecules have not been found in the tissue sections. They have been observed on membranes of the myelin fraction. The significance of the localization of negatively charged groups on the cytoplasmic side of membranes is discussed.


Plant lyophilisate carrying S-HBsAg as an oral booster vaccine against HBV.
A formulation of a defined antigen dosage together with an appropriate and convenient immunisation regime are the main problems of a plant-derived oral vaccine against HBV. Both factors have to be mutually adjusted to ensure efficacious vaccination and to minimise the risk of oral tolerance acquisition. As based on previous research, solely oral immunisation appears to be of limited effectiveness, but a combined immunisation scheme via injection priming and oral boosting can be proposed. Thus, the previously optimised plant lyophilisate with accumulated S-HBsAg was orally administered in a series of mouse immunisation trials. The impact of various S-HBsAg oral dosages and concentrations on the induction of an active immune response was studied. Immunisation via i.m. priming followed by double oral boosting in 6-week intervals was comparably efficient as standard i.m. vaccination. Among the tested dosages, 2× 5 or 200 ng triggered effective and exclusively systemic responses. Mucosal adjuvants CTB or quillaja bark saponins as well as alhydrogel either had no or a negative effect on immune response, which indicates that a low-dosed plant lyophilisate as an oral booster vaccine may not require exogenous adjuvants. Additionally, a positive effect of S-HBsAg encapsulation in lyophilised cells on immune response stimulation was confirmed by comparison with the antigen released in the plant extract. The low-dosed plant lyophilisate with concentrated S-HBsAg was proven as an effective and convenient oral booster vaccine. Results of immunisation via a mixed injection-oral route provide the foundation for research on further standardisation of a plant-derived oral vaccine against HBV and details of immune response together with effects for health condition.


COVID-19 outbreak and rural household food security in the Western Democratic Republic of the Congo.
Although global assessments of the initial impacts of the coronavirus disease (COVID-19) have focused on income, jobs, and health conditions, this study constitutes one of the first studies that assessed the impact of COVID-19 on food security in DRC and established the short-term implications of the COVID-19 outbreak on rural households' food security in DRC. In addition, the study recommendations contributed to shaping government interventions toward the pandemic in the Country. The study used data from four western provinces of the country on 1339 households. Our results show that 80 % of households experienced an increase in food prices, 61 % a noticeable decrease in the availability of food, and 54 % a decrease in their dietary diversity. Due to changes in food availability, dietary diversity, and food accessibility imposed by the COVID-19 outbreak, >70 % of households experienced either a decrease in the consumption of meat, milk, fish, and cereals or an increase in their consumption of traditional vegetables. In addition, COVID-19 significantly affected food security dimensions in larger households, households with a greater number of members aged 35 years and above, households headed by women, households where members participate in associations or cooperatives, households that depend on crop sales as the major source of income, and in poorer households. These findings highlight the significant implications of the COVID-19 outbreak on household food security in western DRC and underscore the need for emergency interventions to strengthen the resilience of rural people and accelerate their recovery and other long-term measures toward sustainable and inclusive development.


The roles of stem cell memory T cells in hematological malignancies.
Adoptive cell therapy (ACT) is rapidly migrating from bench to clinical therapy for hematological malignancies. Recently, a new subtype of memory T cells, stem cell memory T (TSCM) cells, was shown to be one of the most favorable subsets for ACT. TSCM has high self-renewal capacity and is associated with superior T cell engraftment, persistence, and antitumor immunity. In this review, we focused on the characteristics of antigen-specific TSCM cells and discussed their potential for immunotherapy targeting hematological malignancies.


Good democratic governance can combat COVID-19 - excess mortality analysis.
Some studies claim that democracy is in crisis during the current pandemic while authoritarian countries better combat COVID-19 because they face no tradeoff between freedom and health. These claims, however, are usually supported by unreliable reported data; furthermore, they often overlook an important variation in government effectiveness that is likely to interact with different political regimes. In this paper, I use as the dependent variable more reliable data, excess mortality, which is available for 152 countries, and analyze the interaction effect between regime type and government effectiveness. The results reveal that democratic countries with higher government effectiveness are likely to reduce excess mortality. Democratic countries thus need not give up freedom; they need to improve government effectiveness to combat COVID-19.


Use and long-term outcomes of implantable cardioverter-defibrillators, 1990 to 2009.
Automated implantable cardioverter-defibrillators (ICDs) have become standard therapy for patients at high risk for sudden cardiac death. Linked data allow examination of trends in use and long-term survival after ICD implantation in an adult population. Linked state-wide person-based data on hospital admissions and deaths from 1980 to 2009 were used to identify incident cases of ICD implantation. Population rates were calculated using census data. Kaplan-Meier techniques were used to describe cumulative survival. Cox regression models were used to determine the factors associated with the outcomes. Between 1988 and 2009, 1593 devices were implanted in patients in Western Australia, rising from 2 in 1988 to 245 in 2009; standardized population rates rose from 0.8 in 100000 in 1995 to 14.9 in 100000 in 2009. Mean age rose from 52.6 (SD 11.6) to 64.1 (11.4) years. Ventricular tachycardia (23%), cardiomyopathy (18%), and heart failure (16%) were the most frequent principal diagnoses. Ischemic heart disease was present in 49% of patients. Five-year cumulative survival was 0.74 (SE 0.01), and at 10 years, 0.53 (SE 0.03); median survival was 11.3 years. Readmission within a year, older age, heart failure, device complications, and chronic ischemic heart disease were associated with poorer survival. Implantable cardioverter-defibrillator use in adults at risk for sudden cardiac death has grown rapidly. Readmission within 12 months of discharge is associated with worse medium and long-term mortality. Survival for most patients younger than 65 years exceeds 10 years and 5 years for those aged ≥75 years.


Correction: Turner et al. Steatitis in Cold-Stunned Kemp's Ridley Sea Turtles (Lepidochelys kempii). Animals 2021, 11, 898.
In the original publication [...].


The New Satisfaction with Life and Treatment Scale (SLTS-7) in Patients with Parkinson's Disease.
The satisfaction with life and, in particular, with treatment in Parkinson's disease (PD) is understudied. To explore a new 7-item rating tool assessing satisfaction with life and treatment (SLTS-7) in PD. In this cross-sectional, multi-center study, including patients screened for advanced therapies, psychometric characteristics of the SLTS-7 were analyzed. An exploratory factor analysis identified the underlying factorial structure of the SLTS-7. 117 patients were included, and the data quality of the SLTS-7 was excellent (computable data 100%), and acceptability measures satisfied standard criteria. Besides the global assessment (item 1), the exploratory factor analysis produced item 2 (physical satisfaction) as an independent item and two factors among the remaining items: items 3-5 (psycho-social satisfaction), and items 6 and 7 (treatment satisfaction). Cronbach's alpha was 0.89, indicative of high internal consistency. The SLTS-7 total score correlated moderately with motor symptoms and weakly with non-motor symptoms total scores. SLTS-7 showed the highest correlations with the European Quality of Life with 5 items (EQ-5D) visual analog scale (0.43-0.58, p < 0.01), indicating a moderate convergent validity. The SLTS-7 significantly increased with higher non-motor symptoms burden levels (p = 0.002). Life satisfaction in PD covers three specific aspects, namely physical, psycho-social, and treatment satisfaction. The new SLTS-7 is a valid, reliable, and easy-to-use tool to assess satisfaction with life and treatment in patients with PD screened for advanced therapies. Longitudinal studies analyzing the effect of advanced PD treatment on life and treatment satisfaction are warranted.


Assessment of the impacts of climatic variability and anthropogenic stress on hydrologic resilience to warming shifts in Peninsular India.
Most parts of the world are witnessing climatic warming and the trend is expected to increase in the future. It is important to assess the response of watershed hydrology to this warming. Moreover, human interactions and climatic variability influence the water balance of a catchment. We perform contribution analysis along with resilience study using Budyko framework and two parameters (dynamic deviation and modified elasticity), in-order to comprehend the involvement of anthropogenic stress and climatic variance on partitioning of precipitation and their relation with hydrologic resilience to warming shifts across 55 catchments in peninsular India. Here, 23 catchments have displayed hydrologic resilience (low departure and high elasticity) to climatic warming shifts. Only 37.14% of anthropogenic dominated catchments (higher contribution from human activities in runoff changes) were found to be resilient whereas 58.82% of climate dominated catchments had resilience attributes. Most of the catchments on western and extreme southern part of India were not hydrologic resilient. Extensive human interactions tend to depart the catchment from expected hydrological functioning under critical climatic conditions (Warming in our study) that lead to declining of hydrological resilience.


Differences of Escherichia coli isolated from different organs of the individual sheep: molecular typing, antibiotics resistance, and biofilm formation.
Despite numerous studies on Escherichia coli (E. coli) from sheep, there have been few reports on the characterization of E. coli isolates from various organs of individual sheep until now. The present study conducted molecular typing, antibiotics resistance, biofilm formation, and virulence genes on E. coli isolated from 57 freshly slaughtered apparently healthy sheep carcasses, gallbladders, fecal samples, and mesenteric lymph nodes (MLNs). The results demonstrated that the detection rate of R1 LPS core type in E. coli isolated from fecal samples (70.83%) was higher than that from other organs, but the detection rate of antibiotic resistance genes was lower (P < 0.05). The predominant phylogenetic group of E. coli isolated from the carcasses was group B1 (93.33%), and the detection rate of multidrug-resistance phenotype (80%) and the resistance rate of E. coli was higher than that from other organs (P < 0.05). Interestingly, the intensity of biofilm formation of E. coli isolated from MLNs was higher than that from other organs (P < 0.05). However, except for ibeB, the detection rates of virulence genes did not differ in E.coli isolated from different organs. In conclusion, differences were noted in these parameters of E. coli isolated from different organs of individual sheep. Therefore, the data may contain considerable mistakes concerning the actual situation in the host if we only analyze the data of E. coli isolated from feces or carcasses.


The translational repressor Cup associates with the adaptor protein Miranda and the mRNA carrier Staufen at multiple time-points during Drosophila oogenesis.
In Drosophila melanogaster, Cup acts as a translational regulator during oocyte maturation and early embryogenesis. In this report, we show that Cup associates with Miranda, an adaptor protein involved in localization of specific mRNA complexes in both neuroblasts and oocytes. miranda and cup also interact genetically, since reducing miranda activity worsens the oogenesis defects associated with different cup mutant alleles. miranda mRNA is first detected within the cytoplasm of egg chambers during early oogenesis, coincidentally with very low levels of Miranda protein. We furthermore show that Cup interacts with Staufen, a protein involved in mRNA localization during oogenesis and nervous system development, and the two proteins co-localize within the posterior cytoplasm of late oocytes. Our results substantiate the idea that Cup is a multi-functional protein cooperating with different protein partners to direct egg chamber development at multiple time-points.


A highly selective fluorogenic probe for the detection and in vivo imaging of Cu/Zn superoxide dismutase.
Copper/zinc superoxide dismutase (Cu/Zn SOD) is an essential enzyme that protects tissue from oxidative damage. Herein we report the first fluorogenic probe (SODO) for the detection and in vivo imaging of Cu/Zn SOD. SODO represents a unique chemical probe for translational imaging studies of Cu/Zn SOD in inflammatory disorders.


Arming antibodies: prospects and challenges for immunoconjugates.
Immunoconjugates--monoclonal antibodies (mAbs) coupled to highly toxic agents, including radioisotopes and toxic drugs (ineffective when administered systemically alone)--are becoming a significant component of anticancer treatments. By combining the exquisite targeting specificity of mAbs with the enhanced tumor-killing power of toxic effector molecules, immunoconjugates permit sensitive discrimination between target and normal tissue, resulting in fewer toxic side effects than most conventional chemotherapeutic drugs. Two radioimmunoconjugates, ibritumomab tiuxetan (Zevalin) and tositumomab-131I (Bexxar), and one drug conjugate, gemtuzumab ozogamicin (Mylotarg), are now on the market. For the next generation of immunoconjugates, advances in protein engineering will permit greater control of mAb targeting, clearance and pharmacokinetics, resulting in significantly improved delivery to tumors of radioisotopes and potent anticancer drugs. Pre-targeting strategies, which separate the two functions of antibody-based localization and delivery or generation of the toxic agent into two steps, also promise to afford superior tumor targeting and therapeutic efficacy. Several challenges in optimizing immunoconjugates remain, however, including poor intratumoral mAb uptake, normal tissue conjugate exposure and issues surrounding drug potency and conditional release from mAb carriers. Nonetheless, highly promising results from preclinical models will continue to drive the clinical development of this therapeutic class.


Regulation of nuclear scaffold protease activity by calcium.
Recent investigations have disclosed protease activity which is intimately associated with the nuclear scaffold. This protease activity shows a marked selectivity for lamins A/C, and from them may produce the 46-kDa NTPase thought to participate in nucleocytoplasmic RNA transport. Preliminary characterizations suggested that the protease activity might require Ca2+. In this report, we present evidence showing that nuclear scaffold protease activity is stringently regulated by Ca2+ within the physiologic range. Further, calmodulin antagonists such as calmidazolium and chlorpromazine produce marked inhibition of the protease activity, suggesting modulation by calmodulin or calmodulin-like factors.


Projections from the rostral mesencephalic reticular formation to the spinal cord. An HRP and autoradiographical tracing study in the cat.
Eye and head movements are strongly interconnected, because they both play an important role in accurately determining the direction of the visual field. The rostral brainstem includes two areas which contain neurons that participate in the control of both movement and position of the head and eyes. These regions are the caudal third of Field H of Forel, including the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal with adjacent reticular formation (INC-RF). Lesions in the caudal Field H of Forel in monkey and man result in vertical gaze paralysis. Head tilt to the opposite side and inability to maintain vertical eye position follow lesions in the INC-RF in cat and monkey. Projections from these areas to extraocular motoneurons has previously been observed. We reported a study of the location of neurons in Field H of Forel and INC-RF that project to spinal cord in cat. The distribution of these fiber projections to the spinal cord are described. The results indicate that: 1. Unlike the neurons projecting to the extra-ocular muscle motoneurons, the major portion of the spinally projecting neurons are not located in the riMLF or INC proper but in adjacent areas, i.e. the ventral and lateral parts of the caudal third of the Field H of Forel and in the INC-RF. A few neurons were also found in the nucleus of the posterior commissure and ventrally adjoining reticular formation. 2. Neurons in caudal Field H of Forel project, via the ventral part of the ventral funiculus, to the lateral part of the upper cervical ventral horn. This area includes the laterally located motoneuronal cell groups, innervating cleidomastoid, clavotrapezius and splenius motoneurons. At lower cervical levels labeled fibers are distributed to the medial part of the ventral horn. Projections from the caudal Field H of Forel to thoracic or more caudal spinal levels are sparse. 3. Neurons in the INC-RF, together with a few neurons in the area of the nucleus of the posterior commissure, project bilaterally to the medial part of the upper cervical ventral horn, via the dorsal part of the ventral funiculus. This area includes motoneurons innervating prevertebral flexor muscles and some of the motoneurons of the biventer cervicis and complexus muscles. Further caudally, labeled fibers are distributed to the medial part of the ventral horn (laminae VIII and adjoining VII) similar to the projections of Field H of Forel. A few INC-RF projections were observed to low thoracic and lumbosacral levels.(ABSTRACT TRUNCATED AT 400 WORDS)


Reversal, maintenance or progression: what happens to the liver after a virologic cure of hepatitis C?
A sustained virological response (SVR) from HCV (synonymous with virological cure) leads to decreased mortality, morbidity and improved quality of life, as well as a reduced incidence of liver disease progression, including liver failure, cirrhosis and hepatocellular carcinoma. Large clinical trials comparing pre- and post-treatment liver biopsies demonstrate improvements in inflammation as well as fibrosis score following SVR. However, a small subset of patients display persistent hepatic inflammation and/or progress to cirrhosis despite SVR. In addition to conferring a risk of fibrosis progression, advanced fibrosis pre-treatment is a major risk factor for post-SVR hepatocellular carcinoma. In this review, we discuss the mechanisms of fibrosis regression uncovered using experimental fibrosis models and highlight potential mechanisms in those few patients with fibrosis progression despite SVR. We also introduce current concepts of fibrosis-dependent tumorigenesis post-SVR in patients with advanced disease. This article forms part of a symposium in Antiviral Research on "Hepatitis C: next steps toward global eradication."


Searching for Certainty During a Pandemic: A Longitudinal Investigation of the Moderating Role of Media Consumption on the Development of Posttraumatic Stress Symptoms During COVID-19.
The current study longitudinally examined the moderating effects of consuming different types of media ( i.e. , formal [news] and informal [social media, WhatsApp]) in the association among COVID-19-related worries, intolerance of uncertainty (IU), and posttraumatic stress symptoms (PTSSs). Data were collected at two time points during July and September 2020, with approximately 60 days between measurements. Results showed that both COVID-19-related worries and IU were found to be positively associated with PTSSs. An interaction with formal media consumption was found, so that when one's formal media consumption was high, he or she were most vulnerable to the aforementioned effects on the development of PTSSs. Our findings point to the interactive effects of both COVID-19 worries and IU with media consumption on the development of PTSSs. Although media consumption might provide information during uncertainty, it may also intensify PTSSs during times of crisis. Implications and limitations are discussed.


TSPO-Detectable Chronic Active Lesions Predict Disease Progression in Multiple Sclerosis.
In the multiple sclerosis (MS) brain, chronic active lesions can be detected using MRI- and PET-based methods. In this study, we investigated whether the frequency of TSPO-PET-detectable chronic active lesions associates with disease progression measured using the Expanded Disability Status Scale (EDSS) at 5-year follow-up. Chronic lesion-associated innate immune cell activation was evaluated using TSPO-PET in 82 patients with MS. Chronic lesions were categorized into rim-active, inactive, and overall active lesion subtypes based on innate immune cell activation patterns in the lesion core and at the 2-mm perilesional rim. Logistic regression was used to identify best predictors of progression. Twenty-one patients experienced disability progression during the follow-up. These patients had a significantly higher proportion of rim-active lesions (p < 0.001) and a significantly lower proportion of inactive lesions (p = 0.001) compared with nonprogressed patients. The results were similar in the patient group having no relapses during the follow-up (60 patients, 14 experienced progression). In logistic regression modeling, the categorized variable "patients with >10% rim-active lesions and ≤50% inactive lesions of all chronic lesions" predicted disease progression in the entire cohort (OR = 26.8, p < 0.001) and in the group free of relapses (OR = 34.8, p = 0.002). The results show that single TSPO-PET-based in vivo lesion phenotyping of chronic MS lesions provides a strong predictor for MS disease progression. This emphasizes the significance of chronic active lesions in disability accumulation in MS.


Survey of Atypical Antipsychotic Medication Use by Child and Adolescent Psychiatrists.
Atypical antipsychotics could be replacing traditional antipsychotics in the treatment of childhood disorders. A postal survey was conducted of Child Psychiatrists in a region of the United Kingdom to evaluate their use of atypical antipsychotics for psychotic and non-psychotic conditions. 97% of respondents reported prescribing atypical antipsychotics and at least 65% did so for non-psychotic indications although several concerns were raised. Differences in prescribing and monitoring practices between Community and Specialist services were noted. Atypical antipsychotics appear to play a significant role in current child psychiatry practice. Further discussions and research needs to occur about their use and guidelines produced.


Impact of mashing protocol on the formation of fermentable sugars from millet in gluten-free brewing.
The production of fermentable sugars (FS) in gluten-free (GF) brewing is hindered by the high starch gelatinization temperatures of GF malts and lower diastatic power compared to barley malt. Our previous work has demonstrated that starch gelatinization was the primary hurdle, and when decoupled from a single mash phase, high concentrations of FS could be produced. However, more research was required to improve the applicability of GF brewing. In this study, millet was used as a model GF malt demonstrating that despite the low α-amylase and β-amylase activities compared to barley malt ∼ 90 % of the FS (∼110 g/L) could be produced within 40 min. Limitations to enzyme extraction and separation due to coarse milling and lautering initially limited FS by ∼ 30 g/L, requiring additional processing or exogenous enzyme supplements that improved fermentable sugar generation by ∼ 20 g/L. Overall, millet is a promising brewing ingredient, provided appropriate mashing procedures are implemented.


OlsG (Sinac_1600) Is an Ornithine Lipid N-Methyltransferase from the Planctomycete Singulisphaera acidiphila.
Ornithine lipids (OLs) are phosphorus-free membrane lipids widespread in bacteria but absent from archaea and eukaryotes. In addition to the unmodified OLs, a variety of OL derivatives hydroxylated in different structural positions has been reported. Recently, methylated derivatives of OLs were described in several planctomycetes isolated from a peat bog in Northern Russia, although the gene/enzyme responsible for the N-methylation of OL remained obscure. Here we identify and characterize the OL N-methyltransferase OlsG (Sinac_1600) from the planctomycete Singulisphaera acidiphila. When OlsG is co-expressed with the OL synthase OlsF in Escherichia coli, methylated OL derivatives are formed. An in vitro characterization shows that OlsG is responsible for the 3-fold methylation of the terminal δ-nitrogen of OL. Methylation is dependent on the presence of the detergent Triton X-100 and the methyldonor S-adenosylmethionine.


Channels formed by M2 peptides of a putative glutamate receptor subunit of locust.
A cDNA encoding part of a polypeptide (Loc1) that exhibits similarity to the corresponding portion of the rat GluR1 subunit has been identified by screening an amplified locust cDNA library. This polypeptide is deduced to be missing about 200 amino acids of the amino-terminus and about 100 amino acids of the carboxy-terminus. cDNAs encoding two other glutamate receptor-like polypeptides (Loc2 and Loc3), which both exhibit good sequence homology with Loc1, have also been identified. So far, there is no evidence for 'flip' and 'flop' variants of Loc1, 2 and 3. A 27-mer peptide including the M1 sequence of Loc1 and a 25-mer peptide including the M2 sequence of this putative glutamate receptor subunit have been synthesised and incorporated into artificial bilayers. Channel openings, of minimum conductance 20 pS, were seen more frequently with the M2 peptide. These studies are designed to lead to the isolation of full-length cDNAs for Loc1, 2 and 3 and to the electrophysiological characterisation of their ion transport properties.


Effects of endothelin on the cardiovascular system and on smooth muscle preparations in different species.
(1) The actions of porcine endothelin (ET), an endothelium-derived vasoconstrictor peptide, have been investigated in several in vitro smooth and cardiac muscle preparation as well as on the blood pressure of anaesthetized rats and rabbits. (2) In isolated visceral smooth muscles (guinea pig ileum, rat colon and uterus, rabbit jejunum) ET caused a long-lasting contraction which persisted after repeated rinsing. ET did not interfere with the spontaneous phasic activity of the rabbit jejunum or with contractions evoked by histamine or carbachol. (3) ET contracted isolated blood vessels (portal vein of guinea-pig and rat). In isolated perfused organs (rabbit ear, guinea-pig lung, rat mesentery and hindpaw) ET led to a long-lasting vasoconstriction. In the isolated perfused guinea-pig lung ET caused vaso- and bronchoconstriction. (4) ET produced a long-lasting positive inotropic effect in spontaneously beating isolated guinea-pig atria. The positive inotropic action of strophanthin was augmented in the presence of ET. (5) In the isolated perfused guinea-pig and rat hearts the prominent effect of ET was a long-lasting coronary vasoconstriction. (6) Pithed rats responded to i.v. injection of ET with a long-lasting increase in blood pressure. In pentobarbitone anaesthetized rats pretreated either with atropine, with guanethidine plus atropine, or with guanethidine plus atropine plus indomethacin, the long-lasting increase in blood pressure was smaller than in pithed rats whereas the initial short-lasting decrease in blood pressure was more pronounced; in pentobarbitone anaesthetized rabbits endothelin caused bronchoconstriction, a decrease in blood pressure and a pronounced increase in central venous pressure possibly resulting from pulmonary or coronary artery constriction or a combination of both effects.(ABSTRACT TRUNCATED AT 250 WORDS)


Pediatric pearls from the AAD Annual Meeting.
This article summarizes novel pediatric dermatology clinical pearls and emerging literature highlights compiled from the 2017 Annual Meeting of the American Academy of Dermatology in Orlando, Florida.


[The specific features of microbiocenoses in children living under conditions of anthropogenic pressing].
The specific features of enteric and nasopharyngeal microbiocenoses and the species composition of bifidobacteria have been studied in children living in the industrial towns of the Irkutsk Region under the existing anthropogenic load. Ambient air pollution is characterized and a presumptive human health risk assessed.


Electrical low-frequency stimulation induces homotopic long-term depression of nociception and pain from hand in man.
Electrical low-frequency stimulation (LFS) of cutaneous afferents evokes long-term depression (LTD) of nociception. In vitro studies suggest a sole homosynaptic effect on the conditioned pathway. The present study addresses homotopy of LTD in human nociception and pain. In 30 healthy volunteers, nociceptive Adelta fibers were electrically stimulated by a concentric electrode. Test stimulation (0.125 Hz) was alternately applied unilateral to radial and ulnar side of right hand dorsum (ExpUni) or bilateral to radial side of right and left hand dorsum (ExpBi). Conditioning LFS (1 Hz, 1,200 pulses) was applied to radial side of right hand dorsum. Somatosensory evoked cortical vertex potentials (SEP) were recorded, and volunteers rated stimulus intensity. After homotopic LFS, SEP amplitude (ExpUni: -34.6%; ExpBi: -33.6%) and pain rating (ExpUni: -44.1%; ExpBi: -29.1%) significantly decreased. Amplitude reduction after heterotopic LFS did not differ from habituation effects in Control experiment without LFS. Heterotopic pain perception was not affected. The electrophysiological and psychophysical study on synaptic plasticity in healthy man demonstrates homotopic organization of LTD. Homotopy is probably due to a homosynaptic effect at first nociceptive synapse, but descending inhibitory systems may also be involved. These experiments may help to judge the potency of LTD for future therapy in chronic pain.


O-GlcNAcylation of Raptor transduces glucose signals to mTORC1.
The mechanistic target of rapamycin complex 1 (mTORC1) regulates metabolism and cell growth in response to nutrient levels. Dysregulation of mTORC1 results in a broad spectrum of diseases. Glucose is the primary energy supply of cells, and therefore, glucose levels must be accurately conveyed to mTORC1 through highly responsive signaling mechanisms to control mTORC1 activity. Here, we report that glucose-induced mTORC1 activation is regulated by O-GlcNAcylation of Raptor, a core component of mTORC1, in HEK293T cells. Mechanistically, O-GlcNAcylation of Raptor at threonine 700 facilitates the interactions between Raptor and Rag GTPases and promotes the translocation of mTOR to the lysosomal surface, consequently activating mTORC1. In addition, we show that AMPK-mediated phosphorylation of Raptor suppresses Raptor O-GlcNAcylation and inhibits Raptor-Rags interactions. Our findings reveal an exquisitely controlled mechanism, which suggests how glucose coordinately regulates cellular anabolism and catabolism.


Optical coherence tomography: an emerging technology for biomedical imaging and optical biopsy.
Optical coherence tomography (OCT) is an emerging technology for performing high-resolution cross-sectional imaging. OCT is analogous to ultrasound imaging, except that it uses light instead of sound. OCT can provide cross-sectional images of tissue structure on the micron scale in situ and in real time. Using OCT in combination with catheters and endoscopes enables high-resolution intraluminal imaging of organ systems. OCT can function as a type of optical biopsy and is a powerful imaging technology for medical diagnostics because unlike conventional histopathology which requires removal of a tissue specimen and processing for microscopic examination, OCT can provide images of tissue in situ and in real time. OCT can be used where standard excisional biopsy is hazardous or impossible, to reduce sampling errors associated with excisional biopsy, and to guide interventional procedures. In this paper, we review OCT technology and describe its potential biomedical and clinical applications.


Cardiopulmonary and gas exchange responses to acute strenuous exercise at 1,270 meters in sickle cell trait.
The impact of strenuous exercise and environmental hypoxia on sickle cell trait (SCT) remains controversial. To determine if these factors induce cardiopulmonary and gas exchange abnormalities in SCT, healthy, young black male volunteers, 25 with SCT (HbAS) and 16 control subjects (HbAA), were evaluated during incremental and steady-state exercise tests using a cycle ergometer at 1,270 meters and 24 degrees C. Peak incremental exercise values for power (242 +/- 7 versus 253 +/- 10 watts), oxygen consumption (3.08 +/- 0.1 versus 3.26 +/- 0.14 liters/minute), heart rate (188 +/- 2 versus 189 +/- 3 beats/minute), minute ventilation (129 +/- 4.6 versus 144 +/- 7.7 liters/minute), oxygen pulse (16.4 +/- 0.5 versus 17.3 +/- 0.8 ml/beat), and respiratory exchange ratio (1.31 +/- 0.01 versus 1.33 +/- 0.02) revealed no significant differences (p less than 0.05) between the SCT and control groups, respectively. Peak incremental exercise values for arterial oxygen tension (82 +/- 1.7 versus 82 +/- 2.2 mm Hg), arterial carbon dioxide tension (32 +/- 0.7 versus 31 +/- 0.9 mm Hg), and alveolar-arterial oxygen pressure differences (19 +/- 1.4 versus 21 +/- 1.9 mm Hg) were similar for the SCT and control groups, respectively. Steady-state exercise results corroborate incremental exercise findings. It is concluded that cardiopulmonary and gas exchange responses to a brief period of strenuous exercise performed at low altitude at 24 degrees C in a well-characterized SCT sample of recruits were within normal limits and comparable to those of a carefully selected control sample.


[Significance and application of nuclear matrix protein 22 in detecting bladder cancer].
To investigate the significance of nuclear matrix protein 22 (NMP22) in the detection of bladder cancer. The level of NMP22 was measured in the urine of 90 patients (40 patients with bladder cancer and 50 patients with non-bladder cancer) by ELISA and compared with urinic cytology (UC). The level of NMP22 in bladder cancer group was significantly higher than that of control group, and it was not influenced by hematuria. The sensitivity of NMP22 was high, but the specificity was lower than that of UC. NMP22 can be used to screen and follow up bladder cancer with high sensitivity.


Accelerated Chemical Thermodynamics of Uranium Extraction from Seawater by Plant-Mimetic Transpiration.
The extraction of uranium from seawater, which is an abundant resource, has attracted considerable attention as a viable form of energy-resource acquisition. The two critical factors for boosting the chemical thermodynamics of uranium extraction from seawater are the availability of sufficient amounts of uranyl ions for supply to adsorbents and increased interaction temperatures. However, current approaches only rely on the free diffusion of uranyl ions from seawater to the functional groups within adsorbents, which largely limits the uranium extraction capacity. Herein, inspired by the mechanism of plant transpiration, a plant-mimetic directional-channel poly(amidoxime) (DC-PAO) hydrogel is designed to enhance the uranium extraction efficiency via the active pumping of uranyl ions into the adsorbent. Compared with the original PAO hydrogel without plant-mimetic transpiration, the uranium extraction capacity of the DC-PAO hydrogel increases by 79.33% in natural seawater and affords the fastest reported uranium extraction average rate of 0.917 mg g-1 d-1 among the most state-of-the-art amidoxime group-based adsorbents, along with a high adsorption capacity of 6.42 mg g-1 within 7 d. The results indicate that the proposed method can enhance the efficiency of solar-transpiration-based uranium extraction from seawater, particularly in terms of reducing costs and saving processing time.


Sexual function after modified radical hysterectomy (Piver II/Type B) vs. classic radical hysterectomy (Piver III/Type C2) for early stage cervical cancer. A prospective study.
When cervical cancer is detected at an early stage (International Federation of Gynecology and Obstetrics [FIGO] IA2-IB1), it can be successfully treated by radical surgery alone. Considering that most patients are young and sexually active at the moment of diagnosis and the long life expectancy of survivors after the treatment, quality of life (QoL) and sexual function are important issues for cancer survivors and caregivers. However, only a few studies have examined the QoL and sexual function in disease-free cervical cancer survivors, and there are no studies in the literature comparing prospectively sexual function after different types of radical hysterectomy. To compare sexual function in two groups of early stage cervical cancer survivors treated by radical surgery alone, undergoing two different types of radical hysterectomy. Patients treated by radical hysterectomy with systematic lymphadenectomy for early stage cervical cancer (FIGO IA2-IB1) have been enrolled and divided in two groups with regard to type of radical hysterectomy performed; S1: modified radical hysterectomy (Piver II/Type B), S2: classic radical hysterectomy (Piver III/ Type C2). Twenty-four months after surgery we assessed the sexual function using the European Organization for Research and Treatment of Cancer Cervix Cancer Module Questionnaire, which is a validated system for the assessment of disease- and treatment-specific issues that affect the QoL and sexual functioning of women who are treated for cervical cancer. Of the 31 patients enrolled in the S1 group and 46 in the S2 group, 23 and 33 patients have been included, respectively. We observed significant differences between the two groups in terms of symptom experience, sexual/vaginal functioning, sexual activity, and sexual enjoyment. There was not any significant difference regarding lymphedema, peripheral neuropathy, and sexual worry. Survivors of early stage cervical cancer treated by modified radical hysterectomy (Piver II/ Type B) have a better sexual function than those operated by classic radical hysterectomy (Piver III/ Type C2).


Computed tomography guided radiofrequency ablation of multifocal osteoid osteoma.
Osteoid osteoma is a benign osteoblastic tumor characterized mostly by presence of one nidus, butvery infrequentlyniduses can be multiple. Radiofrequency ablation is a well-established treatment method for this disease. We report a case of a 19-year-old male patient with bifocal osteoid osteoma which was partially missed on the initial magnetic resonance imaging and treated successfully with two sessions of radiofrequency ablation. Following the second session of ablation, the pain resolved immediately and the patient remains pain-free for 6 months since the procedure. Our case report underlines the fact that although very rare, multifocal osteoid osteomas do exist and its niduses can be obscured during the magnetic resonance imaging due to the edema. It emphasizes the role of the initial computed tomography evaluation.


Elucidating the origins of multimode vibrational coherences of polyatomic molecules induced by intense laser fields.
Strong-field laser-molecule interaction forms much of the basis for initiating and probing ultrafast quantum dynamics. Previous studies aimed at elucidating the origins of vibrational coherences induced by intense laser fields have been confined to diatomic molecules. Furthermore, in all cases examined to date, vibrational wave packet motion is found to be induced by R-selective depletion; wave packet motion launched by bond softening, though theoretically predicted, remains hitherto unobserved. Here we employ the exquisite sensitivity of femtosecond extreme ultraviolet absorption spectroscopy to sub-picometer structural changes to observe both bond softening-induced vibrational wave packets, launched by the interaction of intense laser pulses with iodomethane, as well as multimode vibrational motion of the parent ion produced by strong-field ionization. In addition, we show that signatures of coherent vibrational motion in the time-dependent extreme ultraviolet absorption spectra directly furnish vibronic coupling strengths involving core-level transitions, from which geometrical parameters of transient core-excited states are extracted.Nuclear dynamics of polyatomic molecules involves multiple degrees of freedom and is challenging to explore. Here the authors study the internuclear distance-dependent depletion and bond-softening induced vibrational wavepacket dynamics of CH3I molecules using femtosecond XUV transient absorption spectroscopy.


Outcome in Men with a Screen-detected Abdominal Aortic Aneurysm Who are not Fit for Intervention.
Abdominal aortic aneurysm (AAA) screening in Gloucestershire has been ongoing for 25 years. The aim of this study was to review the outcome of a cohort of men with a large (> 5.4 cm) screen-detected AAA who did not have early intervention for their AAA. A prospectively maintained database was interrogated for a 10-year interval from 2001 to 2011. Men who did not have their large AAA repaired within 3 months of the diagnosis were identified. The reasons for initial nonintervention and subsequent outcomes were identified from a combination of hospital case notes and general practitioner records. Of 334 men referred, 59 (median age 71 years, range 62-83 years) did not have intervention within 3 months (initial nonintervention rate 17.6%). The reasons included placed back on surveillance after assessment (n = 34); immediately discharged (n = 12); required further investigations (n = 5); died before complete assessment (n = 3); and incomplete follow-up (n = 5). Sixteen men had delayed AAA repair with no perioperative mortality. Overall mortality in the study was 14/34 (nine from ruptured AAA, the rest from medical conditions). Two further men survived repair of a ruptured AAA. The overall rate of ruptured AAA was 11/59 (18.6%). Information from studies such as these can be used to help plan treatment of men with a large AAA and to compare performance of vascular units.


[Post-operative necrotising enterocolitis. One case cured by hyperbaric oxygenotherapy (author's transl)].
About one case of necrotising enterocolitis following an extra-peritoneal and aseptic operation, it seems that a post-operative ileus, by the ischemia of mucous membrane and the swarming of anerobics that it involves, seems to be responsable of this dreadful complication. The macroscopic and deceiver aspect of intestine to an early re-operation can impeed this diagnosis. The hyperbaric oxygenotherapy seems to be a perceptible adjuvant treatment.


Anacystis mutants with different tolerances to DCMU-type herbicides show differences in architecture and dynamics of the photosynthetic apparatus, depending on site and mode of the amino acid exchanges in the D 1 protein.
Mutants of Anacystis R 2 with different amino acid exchanges in positions 255 and/or 264 in copy I of the psbA gene, leading to different tolerances to DCMU-type herbicides, are compared with the respective wild type concerning pigmentation and incorporation of 35S into the D 1 protein upon growth in the presence of [35S]methionine. All mutants have shade-type appearance compared to the wild type, although to different extents depending on site and mode of the amino acid exchange in the D 1 protein. Except for 3 mutants, there is no correlation between shade-type appearance on one hand and resistance towards a certain inhibitor on the other hand. Not only the molar ratio of phycocyanin (PC) to chlorophyll (Chl) is higher in all mutants compared to the respective wild type, but also the rate of synthesis of the D 1 protein. On the background of different levels of total 35S incorporation within 18 min, D 1 synthesis can be related to shade adaptation. Degradation of the D 1 protein remains to be thoroughly studied in this context. No reproducible differences in whole chain electron transport were observed between mutants and wild type.


Pesticide-loaded colloidal nanodelivery systems; preparation, characterization, and applications.
The fast developments in pesticide-loaded nanodelivery systems over the last decade have inspired many companies and research organizations to highlight potential applications by employing encapsulation approaches in order to protect the agricultural crops. This approach is being used to retard the indiscriminate application of conventional pesticides, as well as, to make ensure the environmental safety. This article shed light on the potential of colloidal delivery systems, particularly controlled releasing profiles of several pesticides with enhanced stability and improved solubility. Colloidal nanodelivery systems, being efficient nanoformulations, have the ability to boost up the pest-control competence for prolonged intervals thru averting the early degradation of active ingredients under severe ecofriendly circumstances. This work is thus aimed to provide critical information on the meaningful role of nanocarriers for loading of pesticides. The smart art of pesticide-loaded nanocarriers can be more fruitful owing to the use of lower amount of active ingredients with improved efficiency along with minimizing the pesticide loss. Also, the future research gaps regarding nano-pesticide formulations, such as role of nanomaterials as active ingredients are discussed briefly. In addition, this article can deliver valuable information to the readers while establishing novel pesticide-loaded nanocarriers for a wide range of applications in the agriculture sectors.


[History of human African trypanosomiasis in Moyen-Chari (Chad)].
The authors give on historical record of the focus of the sleeping disease in Moyen-Chari (South of Chad) from 1914 to 1989. Over such a period, they describe the fighting means used to control this endemic disease.


Early umbilical cord clamping contributes to elevated blood lead levels among infants with higher lead exposure.
To investigate whether infant iron status, modified by umbilical cord clamping time and infant feeding mode, affected infant blood lead concentration at 6 months of age. Participants were a subset of women and their infants randomized to receive early (10 seconds) or delayed (2 minutes) umbilical cord clamping and were monitored to 6 months postpartum in Mexico City. Iron and lead status was analyzed in maternal, placental, and 6-month infant blood samples. Baseline maternal lead exposure data and infant feeding data at 2, 4, and 6 months were collected. In the total sample, maternal blood lead concentration, infant ferritin, and breast-feeding practices predicted infant blood lead concentration. Among infants with higher placental blood lead concentration and breast-fed infants not receiving any iron-fortified formula or milk at 6 months, early clamping increased infant blood lead concentration, an effect mediated in part via decreased infant iron status. Early cord clamping, by decreasing infant iron status, contributes to higher blood lead concentrations at 6 months of age among infants at high risk.


Sustainable production of genistin from glycerol by constructing and optimizing Escherichia coli.
Genistin is one of the bioactive isoflavone glucosides found in legumes, which have great nutraceutical and pharmaceutical significance. The market available isoflavones are currently produced by direct plant extraction. However, its low abundance in plant and structural complexity hinders access to this phytopharmaceutical via plant extraction or chemical synthesis. Here, the E. coli cell factory for sustainable production of genistin from glycerol was constructed. First, we rebuilt the precursor genistein biosynthesis pathway in E. coli, and its titer was then increased by 668% by identifying rate-limiting steps and applying an artificial protein scaffold system. Then de novo production of genistin from glycerol was achieved by functional screening and introduction of glycosyl-transferases, UDP-glucose pathway and specific genistin efflux pumps, and 48.1 mg/L of genistin was obtained. A further engineered E. coli strain equipped with an improved malonyl-CoA pathway, alternative glycerol-utilization pathways, acetyl-CoA carboxylase (ACC), and CRISPR interference (CRISPRi) mediated regulation produced up to 137.8 mg/L of genistin in shake flask cultures. Finally, 202.7 mg/L genistin was achieved through fed-batch fermentation in a 3-L bioreactor. This study represents the de novo genistin production from glycerol for the first time and will lay the foundation for low-cost microbial production of glucoside isoflavones. In addition, the multiphase workflow may provide a reference for engineering the biosynthetic pathways in other microbial hosts as well, for green manufacturing of complex natural products.


The importance of antegrade completion angiography in aortobifemoral bypass limb revision.
Aortobifemoral bypass is a durable arterial reconstruction with well-defined failure modes. Management of graft limb thrombosis requires restoration of inflow and correction of any causative outflow lesions. Successful, minimally invasive inflow restoration with catheter thrombectomy can become problematic if assessment of technical adequacy is deficient or reveals causal lesions within the graft body. We describe a case illustrating the potential shortfall of retrograde graft limb completion angiography in depicting neointimal flaps, the benefit of antegrade angiography in depicting these flaps, and a novel utilization of a standard endovascular method to correct flaps that involve the graft body.


Hypoxia induces H19 expression through direct and indirect Hif-1α activity, promoting oncogenic effects in glioblastoma.
H19 expression is elevated in many human tumors including glioblastomas, suggesting an oncogenic role for the long noncoding RNA; yet the upregulation of H19 in glioblastomas remains unclear. Here we report that hypoxia significantly stimulated H19 expression in glioblastoma cell lines, which was related to hypoxia-inducible factors 1α (Hif-1α). Hif-1α promoted H19 expression in U87 and U251 cells. Meanwhile PTEN is an advantageous factor to affect H19 expression, through attenuating Hif-1α stability. Hif-1α also positively correlates with H19 in human glioblastoma samples depending on PTEN status. ChIP and luciferase reporter assays showed that Hif-1α induced H19 transcription through directly binding to the H19 promoter. Furthermore, Hif-1α upregulated specific protein 1 (SP1) expression in glioblastomas cells in vitro and in vivo, and SP1 also strongly interacted with the H19 promoter to promote H19 expression under hypoxia. We also showed that H19 acts as a molecular sponge that binds miR-181d, relieving inhibition of β-catenin expression. Therefore, H19 participates in hypoxia-driven migration and invasion in glioblastoma cells. In summary, our results uncover the mechanisms that stimulate H19 expression under hypoxia to promote malignant effects in glioblastomas and suggest H19 might be a promising therapeutic target.


Pseudoarthrosis after anterior cervical discectomy and fusion: rate of occult infections and outcome of anterior revision surgery.
Pseudoarthrosis after anterior cervical discectomy and fusion (ACDF) is relatively common and can result in revision surgery. The aim of the study was to analyze the outcome of patients who underwent anterior revision surgery for pseudoarthrosis after ACDF. From 99 patients with cervical revision surgery, ten patients (median age: 48, range 37-74; female: 5, male: 5) who underwent anterior revision surgery for pseudoarthrosis after ACDF with a minimal follow up of one year were included in the study. Microbiological investigations were performed in all patients. Computed tomography (CT) scans were used to evaluate the radiological success of revision surgery one year postoperatively. Clinical outcome was quantified with the Neck Disability Index (NDI), the Visual Analog Scale (VAS) for neck and arm pain, and the North American Spine Society Patient Satisfaction Scale (NASS) 12 months (12-60) after index ACDF surgery. The achievement of the minimum clinically important difference (MCID) one year postoperatively was documented. Occult infection was present in 40% of patients. Fusion was achieved in 80%. The median NDI was the same one year postoperatively as preoperatively (median 23.5 (range 5-41) versus 23.5 (7-40)), respectively. The MCID for the NDI was achieved 30%. VAS-neck pain was reduced by a median of 1.5 points one year postoperatively from 8 (3-8) to 6.5 (1-8); the MCID for VAS-neck pain was achieved in only 10%. Median VAS-arm pain increased slightly to 3.5 (0-8) one year postoperatively compared with the preoperative value of 1 (0-6); the MCID for VAS-arm pain was achieved in 14%. The NASS patient satisfaction scale could identify 20% of responders, all other patients failed to reach the expected benefit from anterior ACDF revision surgery. 60% of patients would undergo the revision surgery again in retrospect. Occult infections occur in 40% of patients who undergo anterior revision surgery for ACDF pseudoarthrosis. Albeit in a small cohort of patients, this study shows that anterior revision surgery may not result in relevant clinical improvements for patients, despite achieving fusion in 80% of cases. Retrospective study, level III.


Evaluation of the cancer risk from PAHs by inhalation: Are current methods fit for purpose?
There is ample evidence from occupational studies that exposure to a mixture of Polycyclic Aromatic Hydrocarbons (PAHs) is causally associated with an increased incidence of lung cancers. In both occupational atmospheres and ambient air, PAHs are present as a mixture of many compounds, but the composition of the mixture in ambient air differs from that in the occupational atmosphere, and varies in time and space in ambient air. Estimates of cancer risk for PAH mixtures are based upon unit risks which derive from extrapolation of occupational exposure data or animal model data, and in the case of the WHO use one compound, benzo[a]pyrene as a marker for the entire mixture, irrespective of composition. The U.S. EPA has used an animal exposure study to derive a unit risk for inhalation exposure to benzo[a]pyrene alone, and there have been a number of rankings of relative carcinogenic potency for other PAHs which many studies have used to calculate a cancer risk from the PAHs mixture, frequently incorrectly by adding the estimated relative risks of individual compounds, and applying the total "B[a]P equivalent" to the WHO unit risk, which already applies to the entire mixture. Such studies are often based upon data solely for the historic US EPA group of 16 compounds which do not include many of the apparently more potent carcinogens. There are no data for human cancer risk of individual PAHs, and conflicting evidence of additivity of PAH carcinogenicity in mixtures. This paper finds large divergences between risk estimates deriving from the WHO and U.S. EPA methods, as well as considerable sensitivity to the mixture composition, and assumed PAH relative potencies. Of the two methods, the WHO approach appears more likely to provide reliable risk estimates, but recently proposed mixture-based approaches using in vitro toxicity data may offer some advantages.


Distance-dependent distribution thresholding in probabilistic tractography.
Tractography is widely used in human studies of connectivity with respect to every brain region, function, and is explored developmentally, in adulthood, ageing, and in disease. However, the core issue of how to systematically threshold, taking into account the inherent differences in connectivity values for different track lengths, and to do this in a comparable way across studies has not been solved. By utilising 54 healthy individuals' diffusion-weighted image data taken from HCP, this study adopted Monte Carlo derived distance-dependent distributions (DDDs) to generate distance-dependent thresholds with various levels of alpha for connections of varying lengths. As a test case, we applied the DDD approach to generate a language connectome. The resulting connectome showed both short- and long-distance structural connectivity in the close and distant regions as expected for the dorsal and ventral language pathways, consistent with the literature. The finding demonstrates that the DDD approach is feasible to generate data-driven DDDs for common thresholding and can be used for both individual and group thresholding. Critically, it offers a standard method that can be applied to various probabilistic tracking datasets.


The Brain Chart of Aging: Machine-learning analytics reveals links between brain aging, white matter disease, amyloid burden, and cognition in the iSTAGING consortium of 10,216 harmonized MR scans.
Relationships between brain atrophy patterns of typical aging and Alzheimer's disease (AD), white matter disease, cognition, and AD neuropathology were investigated via machine learning in a large harmonized magnetic resonance imaging database (11 studies; 10,216 subjects). Three brain signatures were calculated: Brain-age, AD-like neurodegeneration, and white matter hyperintensities (WMHs). Brain Charts measured and displayed the relationships of these signatures to cognition and molecular biomarkers of AD. WMHs were associated with advanced brain aging, AD-like atrophy, poorer cognition, and AD neuropathology in mild cognitive impairment (MCI)/AD and cognitively normal (CN) subjects. High WMH volume was associated with brain aging and cognitive decline occurring in an ≈10-year period in CN subjects. WMHs were associated with doubling the likelihood of amyloid beta (Aβ) positivity after age 65. Brain aging, AD-like atrophy, and WMHs were better predictors of cognition than chronological age in MCI/AD. A Brain Chart quantifying brain-aging trajectories was established, enabling the systematic evaluation of individuals' brain-aging patterns relative to this large consortium.


Drug-induced metabolic bone disease.
Drug-induced metabolic bone disease via modification of resorption, formation, and mineralization is responsible for a spectrum of disorders classified as osteoporosis, osteomalacia, and adynamic bone disease. Bone disease and the coincident risk of fracture and disability are well-documented with use of glucocorticoids, L-thyroxine, ethanol, tobacco, anticonvulsants, neuroleptics, and chemotherapeutic agents. Physician awareness of these risks highlights the need for close monitoring of dosages and drug interactions and allows for intervention with nutritional support, antiresorptive agents, and proformation agents.


Interconnectedness of global hemostasis assay parameters in simultaneously evaluated thrombin generation, fibrin generation and clot lysis in normal plasma.
Fluorogenic thrombin generation (TG) assays and turbidity-based fibrin generation (FG)- and fibrinolysis (FL)-resistance assays have been sought to assess bleeding and clotting disorders. Theoretically, TG, FG and FL tests should provide overlapping information because thrombin is responsible for FG and induces protection from FL. The relationships between TG, FG and FL parameters remain poorly investigated, partly because existing experimental systems do not permit simultaneous detection of both TG and FG in the same sample of plasma, and are instead tested in separate experiments. We evaluated the potential benefits of a combined TG/FG/FL assay by testing responses of normal plasma to a wide range of tissue factor (TF) and tissue plasminogen activator (tPA) concentrations. Correlations between multiple parameters extracted from the TG and FG/FL curves were also compared. Rate of FG correlated well with TG peak height at all TF concentrations, but correlations between TG and FL parameters depended on the TF concentration. Without thrombomodulin, all FG/FL parameters at high TF could be predicted from TG parameters and no FL protection was observed. With thrombomodulin and high TF, TF-dependent FL protection did not correlate with TF-dependent TG. The fluorogenic thrombin substrate did not interfere with optical density readings, and meaningful tPA concentrations did not interfere with TG readings. In normal plasma, TG, FG and FL parameters may provide interchangeable information. Evaluation of FL-resistance may provide additional data under special assay conditions, but the value of this information should be studied under disease conditions.


Exceptionally high Cd levels and other trace elements in eggshells of American oystercatcher (Haematopus palliatus) from the Bahía Blanca Estuary, Argentina.
Concentrations of six trace metals were determined in the eggshells of American oystercatchers (Haematopus palliatus) from the Bahía Blanca estuary, Argentina. All metals measured in selected samples presented concentrations above the detection limit. Means found for Cu, Pb, Cr, Zn and Ni were as follow: 2.02±0.52, 7.23±2.33, 0.78±0.03, 2.22±1.13 and 6.05±0.89mg/kg dw. The mean concentrations of Cd found were surprisingly high: 13.28±3.38mg/kg dw. Previous studies made on prey items of the American oystercatchers showed low to medium concentrations of the six trace metals. This may indicate a possible transfer of the metals that are available in the environment through food chains. Our study indicates that American oystercatchers sequester heavy metals in their eggshells. Therefore the eggshells may be useful as biomonitors for trace metal contamination in the Bahía Blanca estuary.


Dimensional structure of the Hamilton Depression Rating Scale in patients with obsessive-compulsive disorder.
Comorbid depression is frequent in obsessive-compulsive disorder (OCD) and is acknowledged as a major confound in biological and neurocognitive investigations in OCD. The aim of the present study was to assess the distribution of depressive symptoms in a large OCD sample (n=162) and to analyze the dimensional structure of the Hamilton Depression Rating Scale (HDRS) in OCD. Major depressive disorder according to DSM-IV criteria was apparent in approximately one third of the patients. Frequent symptoms were depressed mood, reduced ability to work, anxiety symptoms and guilt feelings. HDRS scores were submitted to a varimax-rotated factor analysis. In accordance with studies conducted with depressed samples, multi-dimensional solutions suggesting three to six factors emerged. Subsequent confirmatory factor analysis revealed satisfactory fit indices for a four-factorial solution comprising core depressive symptoms, sleep disturbance, anxiety and gastrointestinal problems. Aggression-related obsessions as well as the overall severity of obsessions were related to core depressive symptoms. Anxiety symptoms were associated with excessive rituals. Greater recognition of depressive sub-components may help to raise the replicability of empirical findings in OCD research as there is evidence from both depression and OCD samples that distinct depressive syndromes have different biological correlates.


Simvastatin suppresses osteoblastic expression of Cyr61 and progression of apical periodontitis through enhancement of the transcription factor Forkhead/winged helix box protein O3a.
In this study, the role of transcription factor Forkhead/winged helix box protein O3a (FoxO3a) in Cyr61 expression and its modulation by simvastatin were investigated in cultured murine osteoblasts and a rat model of induced apical periodontitis. We also examined the effects of simvastatin on the synthesis of chemokine CCL2 and chemotaxis of macrophages in vitro. We assessed tumor necrosis factor (TNF)-α-stimulated expression of Cyr61 and phosphorylated inactive FoxO3a (p-FoxO3a) in MC3T3-E1 murine osteoblasts by Western analysis. Forced expression of FoxO3a by lentiviral-based gene transduction was performed, and its effect on Cyr61 expression was evaluated. The modulation of CCL2 secretion and macrophage chemotaxis by simvastatin were examined by enzyme-linked immunosorbent assay and transwell migration assay, respectively. In a rat model of induced apical periodontitis, the relation between disease progression and osteoblastic expression of Cyr61, p-FoxO3a, and CCL2 and macrophage recruitment were studied by radiographic and immunohistochemistry analyses. Western blot analysis showed enhanced expression of Cyr61 and p-FoxO3a after TNF-α treatment in a time-dependent manner. Simvastatin significantly counteracted the actions of TNF-α. Forced expression of FoxO3a reduced TNF-α-stimulated Cyr61 synthesis. Simvastatin and FoxO3a diminished TNF-α-induced CCL2 secretion and macrophage recruitment, whereas Cyr61 partially restored the stimulating action. In rat periapical lesions, simvastatin significantly attenuated bone resorption, reduced osteoblastic expressions of Cyr61, p-FoxO3a, and CCL2, and suppressed macrophage recruitment. Simvastatin may alleviate periapical lesions by enhancing FoxO3a activity to suppress the synthesis of Cyr61 in osteoblasts. Moreover, the downstream effector mechanism of Cyr61 may involve CCL2 production and macrophage recruitment.


Quantitative structure-activity relationships for the mutagenicity of propylene oxides with Salmonella.
A quantitative structure-activity relationship approach was used to investigate the mutagenicity of a series of seventeen-monosubstituted propylene oxides in Salmonella typhimurium strains TA100 and TA1535. Mutagenicity in strain TA100, using a liquid suspension assay, was found to correlate with chemical reactivity, as measured by the rates of reaction with two model bionucleophiles, nicotinamide and 4-(4-nitrobenzyl)pyridine. However, since the reactivity of three of the epoxides did not correlate to their Taft sigma * values, as a measure of the electronic effects of substituent groups, neither was their mutagenicity predicted by this substituent constant. The relative mutagenicity for the propylene oxides was different in the liquid suspension assay than that determined by the standard plate incorporation assay and also differed between the two bacterial strains. The assay differences were attributed to epoxide stability. The differences between strains was observed to be due to the response of the error-prone repair system, found only in TA100, to the stronger alkylating agents.


A scalable and reproducible manufacturing process for Phlebotomus papatasi salivary protein PpSP15, a vaccine candidate for leishmaniasis.
Cutaneous leishmaniasis is a parasitic and neglected tropical disease transmitted by the bites of sandflies. The emergence of cutaneous leishmaniasis in areas of war, conflict, political instability, and climate change has prompted efforts to develop a preventive vaccine. One vaccine candidate antigen is PpSP15, a 15 kDa salivary antigen from the sandfly Phlebotomus papatasi that facilitates the infection of the Leishmania parasite and has been shown to induce parasite-specific cell-mediated immunity. Previously, we developed a fermentation process for producing recombinant PpSP15 in Pichia pastoris and a two-chromatographic-step purification process at 100 mL scale. Here we expand the process design to the 10 L scale and examine its reproducibility by performing three identical process runs, an essential transition step towards technology transfer for pilot manufacture. The process was able to reproducibly recover 81% of PpSP15 recombinant protein with a yield of 0.75 g/L of fermentation supernatant, a purity level of 97% and with low variance among runs. Additionally, a freeze-thaw stability study indicated that the PpSP15 recombinant protein remains stable after undergoing three freeze-thaw cycles, and an accelerated stability study confirmed its stability at 37 °C for at least one month. A research cell bank for the expression of PpSP15 was generated and fully characterized. Collectively, the cell bank and the production process are ready for technology transfer for future cGMP pilot manufacturing.


Cloning and expression of a hybrid Streptomyces clavuligerus cefE gene in Penicillium chrysogenum.
A hybrid cefE gene was constructed by juxtaposing promoter sequences from the Penicillium chrysogenum pcbC gene to the open reading frame of the Streptomyces clavuligerus cefE gene. In S. clavuligerus the cefE gene codes for the enzyme penicillin N expandase [also known as deacetoxycephalosporin C synthetase (DAOCS)]. To insert the hybrid cefE gene into P. chrysogenum the vector pPS65 was constructed; pPS65 contains the hybrid cefE gene and the Aspergillus nidulans amdS gene. The amdS gene encodes acetamidase and provides for dominant selection in P. chrysogenum. Protoplasts of P. chrysogenum were transformed with pPS65 and selected for the ability to grow on acetamide medium. Extracts of cells cultivated in penicillin production medium were analyzed for penicillin N expandase activity. Penicillin N expandase activity was detected in approximately one-third of the transformants tested. Transformants WG9-69C-01 and WG9-61L-03 had the highest specific activities of penicillin N expandase: 4.3% and 10.3%, respectively, relative to the amount of penicillin N expandase in S. clavuligerus. Untransformed P. chrysogenum exhibited no penicillin N expandase activity. Analysis of the penicillin V titer revealed that WG9-61L-03 produced titers equal to that of the recipient strain while the amount of penicillin V produced in WG9-69C-01 was reduced by five fold.


Carrier models for the simulation of Hodgkin's disease: a review with some extensions.
Epidemiologists have unearthed a good deal of both anecdotal and statistical evidence to suggest that Hodgkin's disease might be a transmissible entity. This paper critically reviews those findings which have led to the building of a single-region carrier model capable of making deterministic simulations for the temporal incidence of Hodgkin's disease. The results of fitting this model to the monthly incidence of the disease in Greater Manchester between 1962 and 1976 are discussed in relation to the plausibility of the equilibria associated with the more realistic solutions. In the light of this evaluation, the specification of the model is extended to include multi-region settings with more complex infective mechanisms. Finally, the improvements that accrue from adopting a stochastic modelling style are outlined.


Unravelling the ultramafic rock-driven serpentine soil formation leading to the geo-accumulation of heavy metals: An impact on the resident microbiome, biogeochemical cycling and acclimatized eco-physiological profiles.
In the present study, we have underpinned the serpentine rock, serpentinized ultramafic soil and rhizosphere's microbial communities, signifying their heavy metals-exposed taxa signatures and functional repertoires in comparison to non-serpentine soils. The results revealed that the serpentine rock embedded soil highlighted the geo-accumulation of higher amount of Cr and Ni impacting soil microbial diversity negatively by metal stress-driven selection. Biolog Ecoplate CLPP defined a restricted spectrum of C-utilization in the higher heavy metal-containing serpentine samples compared to non-serpentine. The linear discriminant analysis (LDA) score identified a higher abundance of Desulfobacterota, Opitutales, and Bacteroidales in low Cr and Ni-stressed non-serpentine-exposed samples. Whereas the abundance of Propionibacteriales and Actinobacteriota were significantly enriched in the serpentine niche. Further, the C, N, S, Fe, and methane biogeochemical cycles linked functional members were identified, and showing higher functional diversity in low Cr and Ni concentration-containing rhizosphere JS-soils. The Pearson correlation coefficient (r) value confirmed the abundance of functional members linked to specific biogeochemical cycle, positively correlated with relevant pathway enrichment. Ultimately, this study highlighted the heavy metal stress within a serpentine setting that could limit the resident microbial community's metabolic diversity and further select the bacteria that could thrive in the serpentine-associated heavy metal-stressed soils. These acclimatized microbes could pave the way for the future applications in the soil conservation and management.


Undergraduate nursing students' use of video technology in developing confidence in clinical skills for practice: A systematic integrative literature review.
This review examines the current evidence of the effectiveness of the use of video or video podcast technology produced either commercially or in-house in developing nursing students' confidence in clinical skills for practice. The ability of graduates to provide safe, quality, nursing care is the core of any nursing education curriculum. Developing teaching and learning strategies to enhance skills development and confidence is challenging for educators, particularly with contemporary and diverse student populations requiring student-centred, technology-enhanced learning. An integrative review framework. A systematic search was conducted using the following eight databases: CINAHL, MEDLINE, ProQuest, PubMed, ERIC, Scopus, EMBASE, and Google Scholar. Selection criteria included: published in English, involving undergraduate nursing students, measuring confidence in relation to skills development, and using video or video podcasts. Four studies met the inclusion criteria, with six themes identified. Four themes emerged: Pedagogy; Skills performance and competency; Student satisfaction and confidence in relation to skills development; Technical constraints. Two additional themes related to the impetus for introducing video podcasts: first, time as an institutional, curricular, and academic/student challenge; and second, meeting the generational needs of students. This review demonstrates that video technology teaching methods and traditional teaching methods used in conjunction with each other create the most positive learning environment. Although video technology methods provide a flexible teaching option for the contemporary student population, developing and delivering videos in a clinical skills program need to be conceptualised within an appropriate pedagogical approach to ensure a purposeful and meaningful learning experience. Whilst student confidence was embedded within other evaluations, it is not clearly reviewed or understood; therefore, further research is required in this area.


Stability, flow alignment and a phase transition of the lipidic cubic phase during continuous flow injection.
Continuous flow injection is a key technology for serial crystallography measurements of protein crystals suspended in the lipidic cubic phase (LCP). To date, there has been little discussion in the literature regarding the impact of the injection process itself on the structure of the lipidic phase. This is despite the fact that the phase of the injection matrix is critical for the flow properties of the stream and potentially for sample stability. Here we report small-angle X-ray scattering measurements of a monoolein:water mixture during continuous delivery using a high viscosity injector. We observe both an alignment and modification of the LCP as a direct result of the injection process. The orientation of the cubic lattice with respect to the beam was estimated based on the anisotropy of the diffraction pattern and does not correspond to a single low order zone axis. The solvent fraction was also observed to impact the stability of the cubic phase during injection. In addition, depending on the distance traveled by the lipid after exiting the needle, the phase is observed to transition from a pure diamond phase (Pn3m) to a mixture containing both gyriod (Ia3d) and lamellar (Lα) phases. Finite element modelling of the observed phase behaviour during injection indicates that the pressure exerted on the lipid stream during extrusion accounts for the variations in the phase composition of the monoolein:water mixture.


Metabolic engineering of Bacillus subtilis for high-level production of uridine from glucose.
As an intermediate in drug synthesis, uridine has practical applications in the pharmaceutical field. Bacillus subtilis is used as a host to boost uridine yield by manipulating its uridine biosynthesis pathway. In this study, we engineered a high-uridine-producing strain of B. subtilis by modifying its metabolic pathways in vivo. Overexpression of the aspartate ammonia-lyase (ansB) gene increased the relative transcriptional level of ansB in B. subtilis TD320 by 13·18 times and improved uridine production to 15·13 g l-1 after 72-h fermentation. Overexpression of the putative 6-phosphogluconolactonase (ykgB) gene increased uridine production by the derivative strain TD325 to 15·43 g l-1 . Reducing the translation of the amido phosphoribosyl transferase (purF) gene and inducing expression of the subtilisin E (aprE) gene resulted in a 1·99-fold increase in uridine production after 24 h shaking. Finally, uridine production in the optimal strain B. subtilis TD335, which exhibited reduced urease expression, reached 17·9 g l-1 with a yield of 314 mg of uridine g-1 glucose. To our knowledge, this is the first study to obtain high-yield uridine-producing B. subtilis in a medium containing only three components (80 g l-1 glucose, 20 g l-1 yeast powder, and 20 g l-1 urea).


Tissue vibration in prolonged running.
The impact force in heel-toe running initiates vibrations of soft-tissue compartments of the leg that are heavily dampened by muscle activity. This study investigated if the damping and frequency of these soft-tissue vibrations are affected by fatigue, which was categorized by the time into an exhaustive exercise. The hypotheses were tested that (H1) the vibration intensity of the triceps surae increases with increasing fatigue and (H2) the vibration frequency of the triceps surae decreases with increasing fatigue. Tissue vibrations of the triceps surae were measured with tri-axial accelerometers in 10 subjects during a run towards exhaustion. The frequency content was quantified with power spectra and wavelet analysis. Maxima of local vibration intensities were compared between the non-fatigued and fatigued states of all subjects. In axial (i.e. parallel to the tibia) and medio-lateral direction, most local maxima increased with fatigue (supporting the first hypothesis). In anterior-posterior direction no systematic changes were found. Vibration frequency was minimally affected by fatigue and frequency changes did not occur systematically, which requires the rejection of the second hypothesis. Relative to heel-strike, the maximum vibration intensity occurred significantly later in the fatigued condition in all three directions. With fatigue, the soft tissue of the triceps surae oscillated for an extended duration at increased vibration magnitudes, possibly due to the effects of fatigue on type II muscle fibers. Thus, the protective mechanism of muscle tuning seems to be reduced in a fatigued muscle and the risk of potential harm to the tissue may increase.


Prevalence of non-motor symptoms and their association with quality of life in cervical dystonia.
Non-motor symptoms (NMS) are commonly present along with motor impairment in patients with cervical dystonia (CD) and have a significant impact on health-related quality of life (HRQoL). However, the prevalence of NMS and their association with dystonia are still unclear. The aim of our study was to assess the prevalence of depression, anxiety, fatigue, apathy, pain, sleep problems, and excessive daytime sleepiness (EDS) in CD using different evaluation approaches and to explore their association with HRQoL relative to that of motor symptoms. We enrolled 102 Slovak patients with CD. The severity of both motor and non-motor symptoms was assessed using validated scales. HRQoL was determined by the 36-item Short Form Health Survey (SF-36). Association of NMS with poor HRQoL was assessed using multiple regressions. The most frequent NMS in our sample were sleep impairment (67.3%), anxiety (65.5%), general and physical fatigue (57.5% and 52.9%, respectively), depression (47.1%), mental fatigue (31.4%), apathy (30.4%), reduced activity (29.4%), EDS (20.2%), and reduced motivation (18.6%). Univariate analysis showed that NMS, but not motor symptoms, were significantly linked to poor HRQoL, with EDS being most commonly associated with poor HRQoL, followed by disrupted sleep, depression, and fatigue. The prevalence of NMS among patients with CD is high, and some NMS are strongly associated with poor HRQoL, while motor impairment was not associated with the severity of NMS or poor HRQoL. Actively diagnosing and treating NMS should therefore be a routine part of the clinical management of patients with CD.


Comparison of the effects of peripherally administered kisspeptins.
Kisspeptins are structurally closely related peptides derived from the Kiss1 gene that have been demonstrated to stimulate the hypothalamo-pituitary gonadal axis. The natural peptide products derived from post-translational processing of the kisspeptin precursor have not been elucidated. We examined the acute effect on serum levels of free testosterone in the adult male mouse after systemic administration of kisspeptins with different lengths of both human and mouse origin. Mouse kisspeptin-10 and -52 dose-dependently increased serum testosterone, and both peptides showed similar potency and efficacy. Human kisspeptin-10 and kisspeptin-54 evoked robust increase in serum testosterone, with the same potency as for mouse kisspeptins. Other members of the RFRP family of peptides, i.e. RFRP-1 and -3 were inactive. Time-course experiments revealed that the longer forms had a slower onset of action, and the long human form also a more prolonged effect. The effect of the peripherally administered mouse kisspeptin-10 could be totally blocked by the GnRH antagonist acyline. Finally, peripherally administered mouse kisspeptin-10 had no effect on Fos induction in GnRH cells. These data show that all peptides tested are active and supports the concept that their effect is mediated by a target upstream of the pituitary, such as the median eminence.