Agricultural reuse of the digestate from low-cost tubular digesters in rural Andean communities.
This research aimed at assessing the properties of guinea pig manure digestate from low-cost tubular digesters for crops fertilization in rural Andean communities. To this end, field trials were carried out to evaluate the effect of the digestate on two common Andean crops: potato (Solanum tuberosum) and forage (Lolium multiflorum and Trifolium pratense L.). The potato yield (20-25 tha(-1)) increased by 27.5% with digestate, by 15.1% with pre-compost and by 10.3% with the mixture, compared to the control. The forage yield (20-21 tha(-1)) increased by 1.4% with digestate - 50% dose, and by 8.8% with digestate - 100% dose and digestate - 150% dose, compared to the control. The results suggest that the digestate is an appropriate substitute of manure pre-compost for potato fertilization. The results with forage indicate that it can be applied in a range of doses, according to the amount produced by the digester. Currently, manure is either used for cooking or as fertilizer. With low-cost tubular digesters implementation, it could be used to feed the digester, using the digestate for crops fertilization and biogas for cooking; improving household living conditions and protecting the environment. Since soil properties in rural Andean communities differ from experimental layouts, the effect of fertilizers should be re-evaluated in-situ in future research studies.


Regulation of IkappaBalpha expression involves both NF-kappaB and the MAP kinase signaling pathways.
IkappaBalpha is an inhibitor of the nuclear transcription factor NF-kappaB. Binding of IkappaBalpha to NF-kappaB inactivates the transcriptional activity of NF-kappaB. Expression of IkappaBalpha itself is regulated by NF-kappaB, which provides auto-regulation of this signaling pathway. Here we present a mouse model for monitoring in vivo IkappaBalpha expression by imaging IkappaBalpha-luc transgenic mice for IkappaBalpha promoter driven luciferase activity. We demonstrated a rapid and systemic induction of IkappaBalpha expression in the transgenic mice following treatment with LPS. The induction was high in liver, spleen, lung and intestine and lower in the kidney, heart and brain. The luciferase induction in the liver correlated with increased IkappaBalpha mRNA level. Pre-treatment with proteasome inhibitor bortezomib dramatically suppressed LPS-induced luciferase activity. The p38 kinase inhibitor SB203580 also showed moderate inhibition of LPS-induced luciferase activity. Analysis of IkappaBalpha mRNA in the liver tissue showed a surprising increase of the IkappaBalpha mRNA after bortezomib and SB203580 treatments, which could be due to increased IkappaBalpha mRNA stability. Our data demonstrate that regulation of IkappaBalpha expression involves both the NF-kappaB and the p38 signaling pathways. The IkappaBalpha-luc transgenic mice are useful for analyzing IkappaBalpha expression and the NF-kappaB transcriptional activity in vivo.


Impact of a risk-based prevention policy on neonatal group B streptococcal disease.
Neonatal group B streptococcal infections can be prevented by intrapartum antibiotic prophylaxis. Beginning in 1992, women with obstetric risk factors at University of Miami-Jackson Memorial Medical Center were targeted to receive intrapartum antibiotic prophylaxis. We evaluated these preventive efforts. A case was defined as isolation of group B streptococci from a sterile site in an infant <7 days old born during the study period, 1992-1995. We reviewed systematic samples of women with preterm delivery and prolonged rupture of membranes to assess use of intrapartum antibiotic prophylaxis. Group B streptococcal cases declined from 1.7 cases/1000 live births to 0.2 cases/1000 live births (Poisson regression, P =.002). Intrapartum antibiotic prophylaxis use increased from 13% of preterm deliveries in 1992 to 42% in 1995, and from 20% of deliveries with prolonged rupture of membranes in 1992 to 72% in 1995 (chi2 test for linear trend P =.007 and P <.001, respectively). Provision of intrapartum antibiotic prophylaxis on the basis of risk factors was associated with decreased group B streptococcal disease.


Postcoital contraception with dl-norgestrel/ethinyl estradiol combination: six years experience in a student medical clinic.
Postcoital contraception with ethinyl estradiol/dl-norgestrel in combination has been available to women students attending the University of British Columbia since 1974. This paper reports on the side effects, cycle control and efficacy, for a six-year period (1979-1985). In this sample of women 50% reported side effects of nausea alone or nausea with vomiting. Length of the menstrual cycle was shortened in women who took the medication prior to the expected day of ovulation. The number of pregnancies reported was significantly (p less than 0.002) less than the number expected had the medication not been taken. Some women took the medication even though there was a possibility of conception earlier in the cycle and this might account for four of the failures. The mode of action of the postcoital medication remains unsolved making it difficult to understand possible reasons for the other 14 failures.


Reduction of oxidative stress and apoptosis in hyperlipidemic rabbits by ellagic acid.
Oxidative stress is one of the major risk factors for coronary artery disease. Ellagic acid is a phenolic compound present in fruits and nuts, and has been found to have antioxidative property. Twenty-four New Zealand white (NZW) rabbits were assigned randomly into four dietary groups. The normal group was fed regular rabbit chow, and the cholesterol group was fed a high fat and cholesterol diet. The ellagic acid (E) group and probucol group were fed the same diet as the cholesterol group plus the addition of 1% (w/w diet) ellagic acid and probucol, respectively. Oxidative stress [as measured by plasma lipids, oxygen free radicals and thiobarbituric acid reactive substances (TBARS)] increased in the cholesterol group compared with the normal group; however, it decreased in the probucol and E groups compared with the cholesterol group. Forty-five percent of the intimal surface of the thoracic aorta was covered with atherosclerotic lesions in the cholesterol group, but only 2-3% was covered in the E and probucol groups. The aortic level of 8-(OH)dG and the expression of caspase-8, caspase-9 and Fas ligand were also suppressed after ellagic acid supplement. These results indicated that ellagic acid could prevent atherosclerosis via suppression of oxidative stress and apoptosis in hyperlipidemic rabbits.


Smoking cessation services and shared decision-making practices among lung cancer screening facilities: A cross-sectional study.
Little is known about how screening facilities are meeting the requirements for the reimbursement of lung cancer screening from the Centers for Medicare & Medicaid Services (CMS), including 1) the collection and submission of data to the CMS-approved registry (American College of Radiology [ACR] Lung Cancer Screening Registry), 2) the verification of a counseling and shared decision-making (SDM) visit having occurred as part of the written order for lung cancer screening with low-dose computed tomography, and 3) the offering of smoking cessation interventions. The authors identified facilities in a southwestern state that were listed by either the ACR Lung Cancer Screening Registry or the GO2 Foundation Centers of Excellence. To select facilities, they used 2 purposive sampling approaches: maximum variation sampling and snowball sampling. They surveyed facilities from February to November 2019. There were 87 facilities contacted, and a total of 63 facilities representing 32 counties across Texas completed the survey. Nearly all facilities used Lung-RADS to classify nodules (92%; n = 58) and submitted data to a CMS-approved registry (92%; n = 57). Most facilities verified that the counseling and SDM visit had occurred (86%; n = 54). Although slightly more than half of the facilities reported always providing self-help cessation materials (68%; n = 42), similar or higher proportions of facilities reported that they never referred smokers to onsite cessation services (68%; n = 42) or quitlines (77%; n = 47), provided cessation counseling (81%; n = 50), or recommended medications (85%; n = 52). In general, screening facilities are meeting CMS requirements for screening, but they are struggling to offer smoking cessation interventions other than providing self-help materials.


Tyzzer's disease in wild-trapped muskrats in British Columbia.
A diagnosis of Tyzzer's disease (Bacillus piliformis infection) was made in a group of recently-trapped muskrats (Ondatra zibethica). The major lesions consisted of enteritis and focal necrosis of the liver, with organisms resembling B. piliformis in hepatocytes on the periphery of these foci. The outbreak was associated with recent capture, housing, and the use of sulfaquinoxaline-medicated feed.


Expanding the Living Donor Pool "Second Act": Laparoscopic Donor Nephrectomy and ABO-Incompatible Kidney Transplantation Improve Donor Recruitment.
To safely expand our living donor pool, we recently decided to work on 3 areas: analysis of causes of exclusion of potential donors, the results of which we recently published, introduction of laparoscopic donor nephrectomy (LDN), and ABO-incompatible (ABOi) transplantation. We sought to determine the impact of the new strategy on living donor recruitment and transplantation during over a 10-year period at a single institution. From January 2005 to September 2014, we evaluated 131 living donors. Of these, 80 (61%) were genetically related, 51 (39%) unrelated, 119 (91%) ABO compatible (ABOc), 12 ABOi (9%). The analysis was divided into 2 eras: era 1, 2005-2010 (n = 53) included the use of open lumbotomy and acceptance of ABOc only; and era 2, 2011-2014 (n = 78), which saw the introduction of LDN and ABOi transplantation. Forty-five (34%) potential candidates successfully donated, 67 (51%) were excluded, and 19 (15%) were actively undergoing evaluation. Overall, 53 potential donors were evaluated in era 1 (8.8 donors/year), 78 in era 2 (19.5 donors/year). There were fewer excluded donors in era 2 vs era 1 (62% era 1 vs 44% era 2), and living donor kidney transplantation (LDKT) significantly increased in era 2 vs era 1 (3.3/year era 1 vs 7.1/year era 2). The establishment of an ABOi LDKT program led to a 15% increase of evaluations in era 2 (12/78 donors). LDN along with ABOi LDKT allowed for an improvement in recruitment of living donors and corresponding LDKT.


[Establishment of an animal model of osteochondral defect by arthroscope in TMJ].
To create an animal model of osteochondral defect in temporomandibular joint (TMJ) by arthroscope to minimize the surgical injury. Subchondral drilling on the anterior slope of condyle and posterior slope of eminence were performed on 12 rhesus monkeys (24 joints) by arthroscope. The osteochondral defect models of TMJ were successfully made on 12 monkeys (24 joints). There are fewer injuries and bias in the animal models of TMJ osteochondral defect by arthroscope than by open surgery.


12-year old adolescent with super morbid obesity, treated with laparoscopic one anastomosis gastric bypass (LOAGB/BAGUA): A case report after 5-year follow-up.
The prevalence of morbid obesity among adolescents has being on the increased in the recent decades specifically in developed countries around the world. In Europe, Spain has the highest prevalence of obese adolescents with more than 18% of the population of children and adolescents. There is evidence that the only effective and permanent treatment for morbid obesity and the comorbidities is surgical treatment, however there exists many controversies about which treatment is the best for obese adolescents. We report a case of a 12 year old patient with super obesity (58.5 kg/m(2) of BMI) and metabolic syndrome who underwent LOAGB/BAGUA and monitored during the last 5 year. The patient after five years follow-up maintains a 22.4 kg/m(2) of BMI. We consider that LOAGB/ BAGUA could be an effective and safe procedure as a treatment of obesity and comorbidities as well, for adolescent patients.


Prevalence and socio-demographic correlates of major depressive episode in rural and urban areas of Beijing, China.
This study aimed to determine the 12-month and lifetime prevalence of major depressive episode (MDE) and their socio-demographic correlates in both the urban and rural areas of Beijing, China. A total of 4767 adults were randomly selected and interviewed in Beijing using the Composite International Diagnostic Interview (CIDI 1.0). Basic socio-demographic and clinical data were collected during the interviews. The overall 12-month prevalence of MDE was 3.2%; 2.8% and 3.8% for men and women, respectively. The overall lifetime prevalence of MDE was 5.3%; 4.4% and 6.3% for men and women, respectively. Being older than 25 years of age was independently associated with increased risk of MDE. Sixteen point three percent of the subjects with lifetime MDE attempted suicide while the rate of suicide attempts was only 0.2% in subjects without MDE. The percentage of subjects with MDE who received any type of treatment from medical practitioners was 33.1%; of them, only 5.4% sought help from mental health professionals. National epidemiologic surveys are needed to further explore the prevalence of MDE in China. The low percentage of subjects treated for MDE constitutes a major public health problem that should be urgently addressed.


Effects of long-term exposure to high temperature on growth performance, chemical composition, hematological and histological changes, and physiological responses in hybrid catfish [♂Clarias gariepinus (Burchell, 1822) ×♀C. macrocephalus (Günther, 1864)].
The anthropogenic and climate-driven rise in water temperature is expected to have an effect on the physiological functions of ectothermic species. In the present study, hybrid catfish were subjected to three different temperatures (27, 32, and 37 °C) for 50 days to examine the effect of long-term exposure to high temperatures on growth and physiological parameters. The results showed that acclimation temperature improves growth and feed utilization with a quadratic effect (P < 0.05). The highest performance was observed at 32 °C, but fish acclimated at 37 °C decreased growth and feed utilization. In addition, skin darkening was observed in fish acclimated with increasing temperatures. Fat content of whole-body, liver, and dorsal muscle of fish was decreased by increasing temperatures (P < 0.05). Higher temperature levels significantly increased in all blood parameters (P < 0.05), except for high-density lipoprotein cholesterol, which was quadratically decreased (P = 0.004). Fish acclimated with increasing temperature also altered gill and liver histology such as gill shortening, hyperplasia and edema in the connective tissue, severe hyperplasia of epithelial cells, and desquamation, hepatocyte vacuolization, nuclei displacement, and pyknotic hepatic cells. While mucus cells were periphery distributed in the subcutaneous skin. In addition, cuboidal shape-like of club cells and melanophores were also observed in fish acclimated at 37 °C resulting in increased epithelial layer thickness. After fish subjected to increasing temperature exhibited an increase in the number of operculum movement and number of gasping for air (P < 0.05) in all acclimated groups. While fish challenged at 37 °C showed higher critical thermal maximum (CTmax, 41.33 °C) than those of the other groups. Overall, the maximum temperature (37 °C) may rick to hybrid catfish. To prevent physiological damage to the fish, as well as reduction of growth and productivity, the temperature in the aquaculture setting should be kept below 37 °C.


rac-Diethyl 5-oxo-2-[(2,4,4-trimethyl-pentan-2-yl)amino]-4,5-dihydro-pyrano[3,2-c]chromene-3,4-dicarboxyl-ate.
The title compound, C(26)H(33)NO(7), comprises a racemic mixture of asymmetric mol-ecules containing one stereogenic centre. The dihedral angle between the mean planes of the fused pyran ring and the coumarin ring system is 8.12 (14)°. The mol-ecular structure features a short N-H⋯O contact, which generates an S(6) ring motif. The crystal packing are stabilized by C-H⋯O inter-actions.


Opposite effects of insulin and glucagon in acute hormonal control of hepatic lipogenesis.
Conditions for the isolation of rat hepatocytes that are responsive to insulin with regard to fatty acid synthesis were explored. Cells prepared according to the procedure of Ingebretsen and Wagle require the presence of fetal calf serum for insulin expression. Cells isolated by the Seglen method are the preparation of choice, since they respond to insulin in a simple, well-defined medium and, moreover, show much higher basal rates of fatty acid synthesis. In the latter cells isolated from fed male rats, the rate of fatty acid synthesis, as determined by tritium incorporation from [3H]H2O at 37 degrees C, is enhanced within 30 min after addition of insulin to the incubation medium; with glucagon, it is depressed. In the presence of insulin, the cellular content of malonyl coenzyme A is noticeably increased, whereas the concentrations of pyruvate, lactate, and citrate are not markedly affected. Glucagon, on the other hand, decreases the concentrations of all four intermediates. The activity of acetyl-CoA carboxylase is stimulated and depressed after addition of insulin and glucagon, respectively. In all conditions tested, the activity of acetyl-CoA carboxylase correlates with the rate of fatty acid synthesis, which in turn correlates with the cellular level of malonyl-CoA.


Occupational burn injuries.
The epidemiology of occupational burns injuries in a well-defined population is analysed. Although a total of 371 persons sustained an injury, only a few were inpatients and just one required anti-shock treatment. The mean burn surface area was 0.66 per cent and 14 patients had full thickness burn injuries. There were no deaths. Men were found to be more prone than women to injury, especially young workers. The distribution by categories of work and causes of burn are illustrated. Scalds and contact burns were dominant, particularly in restaurants. The work by the National Labour Inspection is acknowledged.


Subacute ruminal acidosis (SARA) in grazing Irish dairy cows.
Subacute ruminal acidosis (SARA) is a significant production disease of dairy cattle. Previous concerns have been raised over the occurrence of SARA in pasture-fed dairy cattle and the potential consequences of laminitis and lameness. Highly digestible perennial rye grass contains high concentrations of rapidly fermentable carbohydrate and low concentrations of physical effective fibre that may result in SARA. This study conducted a point prevalence survey of rumen health status in grazing Irish dairy cattle fed predominantly perennial rye grass-based pasture. The survey assessed rumen fluid, animal health status, milk production data and pasture composition. A total of 144 cows between 80 and 150 days in milk were sampled on 12 farms. Eleven percent of cows were classified as affected with SARA (pH < or = 5.5), 42% were marginal (pH 5.6-5.8) and 47% were normal (pH>5.8). The study showed that low rumen pH is prevalent in grazing Irish dairy cattle consuming perennial rye grass-based pasture and raises concerns regarding effective pasture utilisation and possible consequences for animal health.


Management of an unusual sciatica.
Extraforaminal entrapment of the L5 nerve root is uncommon, and its management can sometimes be very challenging. We present the case of a 57-year-old female, complaining of a sciatica in her left leg, for 3 years, with no response to any kind of conservative treatment. MRI and CT scan revealed the presence of a large L5S1 strictly lateral osteophyte compressing the left L5 root in its extraforaminal path. The patient underwent a left anterior retroperitoneal approach with assistance from a vascular surgeon given the very close relation between the osteophyte and the left common iliac vein, lying just on top of it, osteophyte was removed in one piece with the use of an osteotome after retraction of the vessels. The patient progressively recovered from her left sciatic pain with a satisfactory clinical result at 1 year. Literature is sparse on the treatment of extraforaminal entrapment of the L5 nerve root; the current case shows a successful treatment strategy with the use of an anterior approach for direct vision of the lesion and good control of the vessels.


Primary renal lymphoma presenting with hypertension.
Primary renal lymphoma (PRL) is a rare lymphoma which usually presents with hematuria, flank pain, abdominal mass, and weight loss. PRL is more diagnosed in adults than children. We describe an asymptomatic child who presented with hypertension and was subsequently diagnosed with primary renal lymphoma. This case represents an atypical presentation for PRL.


Rates of workplace aggression in the emergency department and nurses' perceptions of this challenging behaviour: A multimethod study.
Over the last 10 years, the rate of people presenting with challenging behaviour to emergency departments (EDs) has increased and is recognised as a frequent occurrence facing clinicians today. Challenging behaviour often includes verbal aggression, physical aggression, intimidation and destruction of property. The aim of this research was to (i) identify the characteristics and patterns of ED-reported incidents of challenging behaviour and (ii) explore emergency nurses' perceptions of caring for patients displaying challenging behaviour. This was a multi-method study conducted across two metropolitan Sydney district hospitals. Phase 1 involved a 12-month review of the hospital's incident management database. Phase 2 involved a survey of emergency nurses' perceptions of caring for patients displaying challenging behaviour. Over 12 months there were 34 incidents of aggression documented and the perpetrators were often male (n=18; 53.0%). The average age was 34.5 years. The majority of reported incidents (n=33; 90.1%) involved intimidation, verbal assault and threatening behaviour. The median time between patient arrival and incident was 109.5min (IQR 192min). The median length of stay for patients was 302.5min (IQR 479min). There was no statistical difference between day of arrival and time of actual incident (t-test p=0.235), length of stay (t-test p=0.963) or ED arrival to incident time (t-test p=0.337). The survey (n=53; 66.2%) identified the average ED experience was 12.2 years (SD 9.8 years). All participants surveyed had experienced verbal abuse and/or physical abuse. Participants (n=52) ranked being spat at (n=37; 71.1%) the most difficult to manage. Qualitative survey open-ended comments were analysed and organised thematically. The survey identified three themes which were (i) increasing security, (ii) open access and (iii) rostering imbalance. The study provides insight into emergency nurses' reported perceptions of patients who display challenging behaviour. All emergency nurse participants reported being regularly exposed to challenging behaviour and this involved both physical and verbal abuse. This was in contrast to a low incident hospital reporting rate. ED clinicians need to be better supported with targeted educational programmes, appropriate ED architecture and reporting mechanism that are not onerous.


High-performance liquid chromatography of 2-mercaptopropionylglycine and its metabolite 2-mercaptopropionic acid in plasma and urine after treatment with thiopronine.
2-Mercaptopropionic acid has been identified as a normal metabolite of 2-mercaptopropionylglycine (thiopronine) when this drug was given to humans and dogs. A high-performance liquid chromatographic method was developed to resolve the derivatives of these two thiols and thus enable simultaneous determination of the two compounds in plasma and urine.


The effects of vesicle toxin from the sea anemone Bunodosoma cangicum on the behavior of a freshwater shrimp, Palaemon argentinus, and shore crab, Neohelice granulata.
Sea anemones of the genus Bunodosoma possess along their body column, longitudinally arranged brown-colored vesicles. We have shown that in B. cangicum, these warty structures contain a mixture of potent toxins. This work highlights the neuro-inhibitory effects exhibited by two decapod crustacean species exposed to the extracts from these vesicles. For this, we use the unrefined toxin in doses, exposure times, and different exposure pathways. The findings show that at least one neuro-inhibitory compound is present and remains active regardless of the exposure method or dose tested. This toxin affects neuro-motor pathways but not neuro-sensory pathways. Shrimp exposed to toxin could continue to perceive and track food pellets but could not secure and consume their ration. Of six anatomical reflexes tested under the toxin's influence, voluntary movements of the mouthparts were impacted most commonly. Interestingly, all subject animals recovered from the toxin exposure within 2 h. Finally, we propose Reflexive Action Analysis (RAMP) as a tool to evaluate the potency of other neurotoxic or neuro-inhibitory compounds in crustacea. This work is the first to show the neuro-inhibitory activity of extracts from these sea anemone columnar vesicle structures and the first to evaluate these effects using RAMP reflex analysis.


Platelet transfusion refractoriness caused by a mismatch in HLA-C antigens.
HLA-C antigens have been thought to be of little significance in determining the efficacy of platelet transfusions. However, six alloimmunized patients were encountered who were refractory to platelet transfusions because of anti-HLA-Cw3, -Cw3, -Cw7, or -Cw8. Between 1995 and the present, 88 patients with hematologic malignancies became refractory to random-donor platelet transfusions due to HLA antibodies. HLA-A- and HLA-B-compatible platelet transfusions were successful in boosting platelet levels with 82 of the patients. This study concerns the remaining six HLA-immunized patients who were refractory to HLA-A- and HLA-B-compatible platelet transfusions. The response to the platelet transfusions was assessed by calculating both 1- and 24-hour posttransfusion CCIs for each transfusion. The average CCI(1 hour) and CCI(24 hours) in all patients were 20.0 and 12.8 for HLA-A-, HLA-B-, and HLA-C-compatible transfusions and were 1.4 and 1.2 for HLA-A- and HLA-B-compatible but HLA-C-incompatible transfusions, respectively (p < 0.001). These findings clearly indicate that matching of the HLA-C antigens is also required in some alloimmunized patients to obtain the effectiveness of platelet transfusions.


Alterations in corneal biomechanics underlie early stages of autoimmune-mediated dry eye disease.
Autoimmune-mediated dry eye disease is a pathological feature of multiple disorders including Sjögren's syndrome, lupus and rheumatoid arthritis that has a life-long, detrimental impact on vision and overall quality of life. Although late stage disease outcomes such as epithelial barrier dysfunction, reduced corneal innervation and chronic inflammation have been well characterized in both human patients and mouse models, there is little to no understanding of early pathological processes. Moreover, the mechanisms underlying the loss of cornea homeostasis and disease progression are unknown. Here, we utilize the autoimmune regulatory (Aire)-deficient mouse model of autoimmune-mediated dry eye disease in combination with genome wide transcriptomics, high-resolution imaging and atomic force microscopy to reveal a potential extracellular matrix (ECM)-biomechanical-based mechanism driving cellular and morphological changes at early disease onset. Early disease in the Aire-deficient mouse model is associated with a mild reduction in tear production and moderate immune cell infiltration, allowing for interrogation of cellular, molecular and biomechanical changes largely independent of chronic inflammation. Using these tools, we demonstrate for the first time that the emergence of autoimmune-mediated dry eye disease is associated with an alteration in the biomechanical properties of the cornea. We reveal a dramatic disruption of the synthesis and organization of the extracellular matrix as well as degradation of the epithelial basement membrane during early disease. Notably, we provide evidence that the nerve supply to the cornea is severely reduced at early disease stages and that this is independent of basement membrane destruction or significant immune cell infiltration. Furthermore, diseased corneas display spatial heterogeneity in mechanical, structural and compositional changes, with the limbal compartment often exhibiting the opposite response compared to the central cornea. Despite these differences, however, epithelial hyperplasia is apparent in both compartments, possibly driven by increased activation of IL-1R1 and YAP signaling pathways. Thus, we reveal novel perturbations in corneal biomechanics, matrix organization and cell behavior during the early phase of dry eye that may underlie disease development and progression, presenting new potential targets for therapeutic intervention.


Sonography of brain abscesses complicating Citrobacter neonatal meningitis.
The incidence of cerebral complications from citrobacter meningitis is high, and these problems are often difficult to diagnose clinically. Cranial sonography provides the ideal imaging modality to detect the early complications of meningitis and the problems that may occur during or after treatment. Early and serial use of cranial sonography should help to preserve brain tissue and minimize the long-term neurologic deficits that arise from this disease.


An empirical approach to the "Trump Effect" on US financial markets with causal-impact Bayesian analysis.
In this paper, we have tested the existence of a causal relationship between the arrival of the 45th presidency of United States and the performance of American stock markets by using a relatively novel methodology, namely the causal-impact Bayesian approach. In effect, we have found strong causal relationships which, in addition to satisfying the classical Granger Causality linear test, have been quantified in absolute and relative terms. Our findings should be included in the context of one of the main markets anomalies, the so-called "calendar effects". More specifically, when distinguishing between the subperiods of pre- and post-intervention, data confirm that the "US presidential cycle" represents a process of high uncertainty and volatility in which the behavior of the prices of financial assets refutes the Efficient-Market Hypothesis.


GABRP Promotes the Metastasis of Pancreatic Cancer by Activation of the MEK/ERK Signaling Pathway.
Pancreatic cancer remains the common cancer with the worst prognosis because of its late diagnosis and extensive metastasis. This study aimed to investigate the effects of GABRP on pancreatic cancer metastasis and the molecular mechanism. The expression of GABRP was measured using the quantitative real-time PCR and western blot. The biological behaviors of cancer cells were assessed using the cell counting kit-8, Transwell assay, and western blot. The regulation of GABRP on the MEK/ERK pathway was detected by western blot. The results indicated that GABRP was overexpressed in pancreatic cancer tissues and cells. Knockdown of GABRP suppressed cell viability, invasion, migration, and epithelial-mesenchymal transition (EMT), whereas GABRP overexpression facilitated these biological behaviors. Inactivation of the MEK/ERK pathway reversed the effects on cellular processes induced by GABRP. Moreover, silencing of GABRP inhibited tumor growth. In conclusion, GABRP promoted the progression of pancreatic cancer by facilitating cell metastasis and tumor growth via activating the MEK/ERK pathway. The findings suggest that GABRP has the potential to be a therapeutic target for the metastatic pancreatic cancer.


Use of machine learning to classify high-risk variants of uncertain significance in lamin A/C cardiac disease.
Variation in lamin A/C results in a spectrum of clinical disease, including arrhythmias and cardiomyopathy. Benign variation is rare, and classification of LMNA missense variants via in silico prediction tools results in a high rate of variants of uncertain significance (VUSs). The goal of this study was to use a machine learning (ML) approach for in silico prediction of LMNA pathogenic variation. Genetic sequencing was performed on family members with conduction system disease, and patient cell lines were examined for LMNA expression. In silico predictions of conservation and pathogenicity of published LMNA variants were visualized with uniform manifold approximation and projection. K-means clustering was used to identify variant groups with similarly projected scores, allowing the generation of statistically supported risk categories. We discovered a novel LMNA variant (c.408C>A:p.Asp136Glu) segregating with conduction system disease in a multigeneration pedigree, which was reported as a VUS by a commercial testing company. Additional familial analysis and in vitro testing found it to be pathogenic, which prompted the development of an ML algorithm that used in silico predictions of pathogenicity for known LMNA missense variants. This identified 3 clusters of variation, each with a significantly different incidence of known pathogenic variants (38.8%, 15.0%, and 6.1%). Three hundred thirty-nine of 415 head/rod domain variants (81.7%), including p.Asp136Glu, were in clusters with highest proportions of pathogenic variants. An unsupervised ML method successfully identified clusters enriched for pathogenic LMNA variants including a novel variant associated with conduction system disease. Our ML method may assist in identifying high-risk VUS when familial testing is unavailable.


Effects of iron deficiency on respiration of hamster cheek-pouch epithelium in vitro.
Iron-deficiency anaemia was induced in hamsters by feeding a low-iron diet coupled with weekly bleeding. Respiration, assessed by measuring oxygen uptake, was significantly reduced (p less than 0.002) in cheek-pouch epithelia from iron-deficient animals. To relate data on oxygen consumption to cell numbers, the cell densities of the basal and maturation compartments were measured. The cell density of the maturation compartment in iron-deficient animals was significantly reduced (p less than 0.05), whereas that of the basal cell compartment was marginally higher than in control animals. However, the cell density of the tissue as a whole was similar in both groups. Thus, the reduced oxygen consumption in iron deficiency was not due to a reduction in cell numbers. Although there was a significant reduction in epithelial volume in the iron-deficient group, this was not sufficient to account for the reduced oxygen uptake in cheek-pouch epithelia from these animals. It is concluded that iron-deficiency anaemia affects cell respiration directly, probably by interfering with the amounts and/or functions of iron-containing enzymes or cytochromes in the electron-transport chain.


Effect of whole body vibration on the rat brain content of serotonin and plasma corticosterone.
To investigate the effects of whole body vibration on the central nervous system, rats were exposed to various whole body vibrations and changes in whole brain levels of Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were then determined. Changes in plasma corticosterone levels were also determined and related to the changes in the whole brain levels of 5-HT and 5-HIAA. The dose-related changes in the 5-HT and 5-HIAA levels were observed as acceleration increased from 0.4G to 5.0G. Changes in vibration frequency also affected the 5-HT and 5-HIAA levels of brain: they were significantly elevated at a frequency of 20 Hz (P less than 0.05). Plasma corticosterone levels increased as acceleration increased from 0.4G to 5.0G. As the vibration frequency was changed from 5 Hz to 30 Hz, plasma corticosterone levels also rose significantly (P less than 0.05) but the extent of elevation was approximately the same at each frequency. The correlation between brain 5-HT and plasma corticosterone levels with increasing acceleration (r = 0.93, P less than 0.01) was significant.


A case of methamphetamine use disorder treated with the antibiotic drug minocycline.
Methamphetamine (METH) use is one of the major public health concerns worldwide. Long-term use of METH induces not only dependence but also psychosis which is associated with METH-induced brain damage, including neuroinflammation produced by activated microglia. We report the case of a female patient whose psychotic symptoms in METH use disorder were successfully improved by anti-inflammatory drug minocycline therapy. Although the precise mechanism(s) underlying the efficacy of minocycline in METH use disorder are currently unclear, minocycline appears to be a good candidate for future investigation clinical trials for medication development in METH using populations.


Surgical treatment of melanoma metastases to the small bowel: A single cancer referral center real-life experience.
Treatment of metastatic melanoma has rapidly changed during the last years, and patients often require a multidisciplinary approach to achieve effective results. We aimed to assess the survival benefit achieved through surgical approach to patients with small bowel (SB) metastases from cutaneous melanoma, to emphasize the potential role of surgery in association with novel therapies. Ninety consecutive patients with cutaneous melanoma diagnosed as having resectable SB metastases from 1995 to 2015 were retrospectively investigated. Median age at surgery of melanoma metastases was 53.4 years. Among 30 patients who had a curative-intent resection, the 5- and 10-year survival rates were 61% and 54%, respectively, while among 60 patients treated with a palliative surgery the corresponding rates were both 4%. Among 29 patients, for whom the interval time between the occurrence of SB metastases and the previous surgical event on GI tract was ≥36 months, the 5-year overall survival rate was 42%; for 56 patients who had an interval time <36 months the corresponding survival rate was 14%. Within the whole series, an absence of any residual disease after surgery (R0) was a factor affecting better survival, regardless of the evidence of metastases in other organs. Our observational data showed that surgical treatment for patients with SB metastases from melanoma might increase survival, but further studies are needed to confirm this finding. In the age of novel available therapies, the increase in survival time given by surgery may offer important chances for patients to benefit from systemic therapies.


Lack of tolerance and morphine-induced cross-tolerance to the analgesia of chimeric peptide of Met-enkephalin and FMRFa.
Chimeric peptide of Met-enkephalin and FMRFa (YGGFMKKKFMRFa-YFa), a kappa-opioid receptor specific peptide, did not induce tolerance and cross-tolerance effects to its analgesic action on day 5 after pretreatment with either YFa or morphine for 4 days. However, pretreatment with YFa for 4 days led to the development of cross-tolerance to the analgesic effects of morphine and also 4 days of pretreatment of morphine resulted in the expression of tolerance to its own analgesic effects. Similar expression of tolerance and cross-tolerance were also observed when YFa was compared with the kappa receptor agonist peptide dynorphin A(1-13) [DynA(1-13)]. Cross-tolerance effects between YFa and DynA(1-13) analgesia were also not observed on day 5. Interestingly, when YFa and DynA(1-13) were tested for their analgesic effects for 5 days, reduction in analgesia on day 3 was observed in case of DynA(1-13) whereas YFa maintained its analgesia for 5 days. Thus, chimeric peptide YFa may serve as a useful probe to understand pain modulation and expression of tolerance and cross-tolerance behavior with other opioids.


Development of a Wet-Granulated Sourdough Multiple Starter for Direct Use.
The search for sourdough starters for the direct production of baked goods with all the advantages of biological sourdough fermentation is still a crucial issue. In this study, 43 Lactic Acid Bacteria strains isolated from mature sourdoughs were evaluated for features of technological interest and tested for fermentation ability. Three microbial combinations were selected and used to produce bread. Based on GC-MS and sensory analysis, bread made by using the three combinations of strains was characterized by a more complex aroma profile with the prevalence of VOCs typical of sourdough bread. To set up the best way to keep microbial viability upon drying, the three combinations were subject to freeze-drying and wet granulation, with the latter being used for the first time for food starters' stabilization. Wet granulation ensured optimal strains' viability. Surprisingly, the height attained by mature sourdoughs when inoculated with wet granulated starters was constantly higher than the height reached by sourdoughs made with the same starters as fresh cells. The microbial combination E75-B72 exhibited the best performances and may represent a starter able to ensure sourdough bread production in 16 h of fermentation at 28 °C.


Ten years of progress in the Hokkaido birth cohort study on environment and children's health: cohort profile--updated 2013.
The Hokkaido Study on Environment and Children's Health is an ongoing cohort study that began in 2002. The study consists of two prospective birth cohorts, the Sapporo cohort (n = 514) and the Hokkaido large-scale cohort (n = 20,940). The primary goals of this study are to first examine the potential negative effects of perinatal environmental chemical exposures on birth outcomes, including congenital malformations and growth retardation; second, to evaluate the development of allergies, infectious diseases and neurodevelopmental disorders and perform longitudinal observations of the children's physical development to clarify the causal relationship between these outcomes and environmental chemicals; third, to identify individuals genetically susceptible to environmental chemicals; finally, to identify the additive effects of various environmental factors in our daily life, such as secondhand smoke exposure or low folate intake during early pregnancy. In this paper, we introduce our recent progress in the Hokkaido study with a cohort profile updated in 2013. For the last ten years, we followed pregnant women and their offspring, measuring various environmental chemicals, i.e., PCB, OH-PCB and dioxins, PFCs (Perfluorinated Compounds), Organochlorine pesticides, Phthalates, bisphenol A and mercury. We discovered that the concentration of toxic equivalents (TEQ) of dioxin and other specific congeners of PCDF or PCDD have effects on birth weight, infants' neurodevelopment and immune function. There were significant gender differences in these effects; our results suggest that male infants have more susceptibility to those chemical exposures than female infants. Interestingly, we found maternal genetic polymorphisms in AHR, CYP1A1 or GSTs that significantly modified the dioxin concentrations in maternal blood, suggesting different dioxin accumulations in the bodies of individuals with these genotypes, which would lead to different dioxin exposure levels. These genetic susceptibility factors influenced the body size of children born from mothers that either smoked or were passively exposed to tobacco smoke. Further studies investigating the correlation between epigenetics, the effects of intrauterine exposure to environmental chemicals and developmental factors related to health and disease are warranted.


Orcein staining of leukocytes.
An Orcein staining method has been developed which stains mature and immature leukocytes in blood films and bone-marrow smears. Two different patterns of staining are obtained depending upon whether staining is or is not preceded by oxidation. In the latter case, all granulocytes and some monocytes show granular reddish-brown cytoplasmic staining. When prior oxidation is used, the staining is in the form of fine grey or black cytoplasmic granules. All lymphocytes, by both techniques, are negative. It is suggested that Orcein stains sulphated mucosubstances, possibly chondroitin sulphate, which in granulocytes is concentrated in their primary granules.


Volumes of hippocampal subfields suggest a continuum between schizophrenia, major depressive disorder and bipolar disorder.
There is considerable debate as to whether the continuum of major psychiatric disorders exists and to what extent the boundaries extend. Converging evidence suggests that alterations in hippocampal volume are a common sign in psychiatric disorders; however, there is still no consensus on the nature and extent of hippocampal atrophy in schizophrenia (SZ), major depressive disorder (MDD) and bipolar disorder (BD). The aim of this study was to verify the continuum of SZ - BD - MDD at the level of hippocampal subfield volume and to compare the volume differences in hippocampal subfields in the continuum. A total of 412 participants (204 SZ, 98 MDD, and 110 BD) underwent 3 T MRI scans, structured clinical interviews, and clinical scales. We segmented the hippocampal subfields with FreeSurfer 7.1.1 and compared subfields volumes across the three diagnostic groups by controlling for age, gender, education, and intracranial volumes. The results showed a gradual increase in hippocampal subfield volumes from SZ to MDD to BD. Significant volume differences in the total hippocampus and 13 of 26 hippocampal subfields, including CA1, CA3, CA4, GC-ML-DG, molecular layer and the whole hippocampus, bilaterally, and parasubiculum in the right hemisphere, were observed among diagnostic groups. Medication treatment had the most effect on subfields of MDD compared to SZ and BD. Subfield volumes were negatively correlated with illness duration of MDD. Positive correlations were found between subfield volumes and drug dose in SZ and MDD. There was no significant difference in laterality between diagnostic groups. The pattern of hippocampal volume reduction in SZ, MDD and BD suggests that there may be a continuum of the three disorders at the hippocampal level. The hippocampus represents a phenotype that is distinct from traditional diagnostic strategies. Combined with illness duration and drug intervention, it may better reflect shared pathophysiology and mechanisms across psychiatric disorders.


Results of Pulmonary Resection: Other Epithelial Malignancies.
This article summarizes the interdisciplinary work, survival, prognostic factors, and prognostic groups for lung metastases from breast cancer and renal cell cancer. Furthermore, the prevalence of lymph node metastases and the importance of a systematic lymph node dissection in metastasectomy of breast cancer and renal cell cancer for a true R0 resection are discussed.


Aging disrupts circadian gene regulation and function in macrophages.
Aging is characterized by an increased vulnerability to infection and the development of inflammatory diseases, such as atherosclerosis, frailty, cancer and neurodegeneration. Here, we find that aging is associated with the loss of diurnally rhythmic innate immune responses, including monocyte trafficking from bone marrow to blood, response to lipopolysaccharide and phagocytosis. This decline in homeostatic immune responses was associated with a striking disappearance of circadian gene transcription in aged compared to young tissue macrophages. Chromatin accessibility was significantly greater in young macrophages than in aged macrophages; however, this difference did not explain the loss of rhythmic gene transcription in aged macrophages. Rather, diurnal expression of Kruppel-like factor 4 (Klf4), a transcription factor (TF) well established in regulating cell differentiation and reprogramming, was selectively diminished in aged macrophages. Ablation of Klf4 expression abolished diurnal rhythms in phagocytic activity, recapitulating the effect of aging on macrophage phagocytosis. Examination of individuals harboring genetic variants of KLF4 revealed an association with age-dependent susceptibility to death caused by bacterial infection. Our results indicate that loss of rhythmic Klf4 expression in aged macrophages is associated with disruption of circadian innate immune homeostasis, a mechanism that may underlie age-associated loss of protective immune responses.


Eating disorders among athletes. Research and recommendations.
Research indicates that certain athletes, particularly those in sports that emphasize leanness to enhance performance or appearance (e.g., gymnastics, wrestling, figure skating, diving, and ballet), are at risk for eating disorders. Little is known about the risk for eating disorder symptoms in weight and strength training. It is concluded that, even when mild variants of eating disorders are observed in athletes, they should be given immediate attention because they may severely compromise health and performance. Practical recommendations are made for coaches and trainers to identify the physical, psychological, and behavioral symptoms of eating disorders. Finally, suggestions are made for addressing eating disorders in athletes.


MiR-320a acts as a prognostic factor and Inhibits metastasis of salivary adenoid cystic carcinoma by targeting ITGB3.
Salivary Adenoid cystic carcinoma (SACC) patients with local invasion and lung metastasis are often resistant to conventional therapy such as operation, chemotherapy and radiotherapy. To explore the underling mechanisms, we studied the roles of miRNA in regulating invasiveness of SACC cells. MicroRNA profiling was done in SACC cells with microarray. MiRNA mimics or antisense oligonucleotide was transfected and invasiveness of SACC cells was evaluated by adhesion assay and transwell assay. The target gene of miRNA was identified by luciferase reporter assay and "rescue" experiment. Tumor metastasis was evaluated by BALB/c-nu mice xenografts. MiRNA and its target gene expression were identified by in-situ hybridization and immunohistochemistry respectively, in 302 patients from affiliated hospitals of Sun Yat-sen University and in 148 patients from affiliated hospitals of Central South University, and correlated to the clinicopathological status of the patients. MiR-320a was down-regulated in high lung metastatic ACCM and SACC-LM cells compared with the corresponding low metastatic ACC2 and SACC-83 cells, and inhibited adhesion, invasion and migration of SACC cells by targeting integrin beta 3 (ITGB3). In vivo, enforced miR-320a expression suppressed metastasis of SACC xenografts. In the two independent sets, miR-320a was downregulated in primary SACCs with metastasis compared to those without metastasis, and low expression of this miRNA predicts poor patient survival and rapid metastasis. Multivariate analysis showed that miR-320a expression was an independent indicator of lung metastasis. MiR-320a inhibits metastasis in SACCs by targeting ITGB3 and may serve as a therapeutic target and prognostic marker in salivary cancers.


Evaluating the capacity of the distress thermometer to detect high fear of cancer recurrence.
Fear of cancer recurrence (FCR) is common and burdensome to patients, but often remains undetected. Oncology professionals report need for tools to improve FCR detection in routine care. Oncology care guidelines recommend the Distress Thermometer (DT) for distress screening, but it has not been validated for FCR. This study evaluated the capacity of the DT and accompanying problem list to detect FCR. Amalgamated data of two studies with 149 breast cancer and 74 colorectal cancer survivors were used. We evaluated the Dutch DT including the DT score, problem list fears item and emotional domain score using Receiver Operating Characteristic analyses. The Dutch Cancer Worry Scale-6 (CWS-6) was used as reference measure, with validated cut-off scores ≥10 and ≥12 for high FCR. Sensitivity, specificity, negative and positive predictive values were calculated. The DT score showed poor performance in discriminating between low and high FCR. The recommended cut-off ≥4 had low sensitivity (65% for CWS-6≥10; 72% for CWS-6 ≥12) and specificity (67% and 58%). No other cut-off had an acceptable combination of sensitivity and specificity. The fears item had low sensitivity (29% and 44.9%) and high specificity (95% and 94%). The emotional domain score had fair performance in discriminating between low and high FCR but there was no cut-off with acceptable sensitivity and specificity. The DT as currently recommended in oncology care guidelines is not suitable to effectively detect FCR in routine care. To improve patients access to psychosocial care, it should be investigated how FCR-specific measures can be integrated in oncology practice.


Differential effects of reproductive and hormonal state on basic fibroblast growth factor and glial fibrillary acid protein immunoreactivity in the hypothalamus and cingulate cortex of female rats.
Morphological changes in astrocytes occur in a number of brain regions including the hypothalamus and hippocampal regions as a function of hormonal and reproductive state. Because basic fibroblast growth factor has been shown to play an important role in morphological changes in astrocytes, we investigated whether basic fibroblast growth factor immunoreactivity would also be influenced by reproductive state and circulating gonadal steroids. To do this we compared astrocytic basic fibroblast growth factor and glial fibrillary acid protein immunoreactivity in hypothalamic nuclei and the cingulate cortex, area 2 among groups of cycling, late pregnant and lactating rats as well as in ovariectomized and ovariectomized hormone-replaced females. Significant differences in both basic fibroblast growth factor and glial fibrillary acid protein immunoreactivity were observed across groups in the supraoptic nucleus, parvocellular paraventricular nucleus, medial preoptic area of the hypothalamus and cingulate cortex 2. The pattern of change in basic fibroblast growth factor and glial fibrillary acid protein immunoreactivity varied across regions both in direction and magnitude. For example, although in the supraoptic nucleus ovariectomized rats had lower levels of basic fibroblast growth factor-ir than cycling females, this pattern was reversed within cingulate cortex. Overall the results of this study suggest that reproductive and hormonal states are associated with robust changes in basic fibroblast growth factor and glial fibrillary acid protein immunoreactivity in a number of brain areas but that the changes observed vary in magnitude as well as direction from one brain region to another.


Corrigendum: Decreased interfacial dynamics caused by the N501Y mutation in the SARS-CoV-2 S1 spike:ACE2 complex.
[This corrects the article DOI: 10.3389/fmolb.2022.846996.].


Early aspirin use and the development of cardiac allograft vasculopathy in pediatric heart transplant recipients: A pediatric heart transplant society analysis.
Cardiac allograft vasculopathy (CAV) remains a leading cause of graft loss in pediatric heart transplant (HTx) recipients. Adult literature suggests that aspirin (ASA) use in the early post-HTx period may reduce the risk of CAV. This study aimed to determine the impact of early ASA use on the development of CAV in pediatric HTx recipients. All subjects <17 years of age at time of primary HTx who survived ≥3 years without evidence of CAV were identified for inclusion from the Pediatric Heart Transplant Society database (1996-2019). Early ASA use was defined as ASA started within the first 3 years post-HTx and was classified as continuous or intermittent. Frequency of ASA use was described across centers. Kaplan-Meier method assessed freedom from CAV and overall graft survival. Multiphase parametric hazard analyses and propensity score matched analysis were used to identify independent risk factors. 3,011 patients were included with 387 (13%) receiving continuous ASA, 676 (22%) receiving intermittent ASA, and 1,948 (65%) receiving no ASA. ASA use was highly variable across centers (0%-100%). At baseline patients receiving continuous ASA therapy demonstrated inferior graft survival (p < 0.001) and worse freedom from CAV (p = 0.002), but with lower CAV grades (p = 0.05). In multiphase parametric hazard modeling continuous ASA use was not independently associated with CAV, but remained associated with inferior graft survival. Propensity-matched sub-analysis between continuous and no ASA groups demonstrated no difference in freedom from CAV or overall graft loss. ASA use varies widely across pediatric HTx centers. Early ASA use did not reduce the risk of CAV or graft loss in pediatric heart transplant recipients.


Cognitive dysfunction and the 25-item National Eye Institute Visual Function Questionnaire.
Visual function and cognitive impairment are interrelated; however, little is known about the impact of modifying treatable vision impairment on the development of cognitive dysfunction. This study examines the relationship between cognition and self-reported visual function using the National Eye Institute's Visual Function Questionnaire (NEI VFQ). Participants completed the NEI VFQ 25-Item questionnaire as well as the Mini-Mental State Examination (MMSE). Additionally, all participants were assigned a consensus clinical diagnosis based on established criteria. We used a general linear model and analysis of variance approach to compare means between multiple groups. A significant association between overall composite score on the NEI VFQ and total MMSE score was revealed (P = 0.04). On average, for every 1-point increase in MMSE score, the overall composite score increased by 0.40 units (95% confidence interval: 0.03-0.77). Reduced visual function should raise concerns about cognitive decline and prompt additional assessment.


Photoluminescent Properties of Phosphor Based on Perovskite CsPbBr3 Nanocrystals Combined with Violet Leds.
The characteristics of an LED lighting system consisting of a commercial violet LED and a green phosphor based on CsPbBr3 nanocrystals are studied in the context of development of LED illumination sources with antibacterial effects but without harmful effects on human health. The internal efficiency of the nanocrystalline phosphor in a silicone compound was found to exceed 40%, dropping noticeably because of heating for an electric current of ~0.1 A (phosphor excitation intensity ~0.1 W/mm2). This undesirable feature can be diminished by using a remote phosphor design for the illuminators and by using chemical techniques to improve the thermal stability of the nanocrystals.


Assessing the necessity of a family of genes that encode small proteins in Dictyostelium discoideum development.
Dictyostelium discoideum's genome encodes for a large class of small proteins that are developmentally regulated. We deleted six of the genes that encode these proteins to determine if they play an essential role in Dictyostelium discoideum development. Deletion of these genes had no significant effect on Dictyostelium discoideum development. These results suggest that the selected genes do not play an essential role in Dictyostelium discoideum development.


Dietary carbohydrate decreases 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesterol synthesis in rat liver.
Diets high in carbohydrate and low in fat led to a decrease in the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in livers of healthy, reverse light-cycled rats. The effect on reductase was due both to a decline in expressed enzyme activity and to a decrease in total number of enzyme molecules. Inhibition of reductase activity was paralleled by a fall in hepatic cholesterolgenesis and by an increase in triglyceride formation. Thus, a reduction in endogenous cholesterol synthesis may explain the serum cholesterol-lowering effect of high carbohydrate, low fat diets in man.


Comprehensive Post Orthognathic Surgery Orthodontics: Complications, Misconceptions, and Management.
Post orthognathic surgery patient management is critical for high-quality and predictable outcomes. Surgeons and orthodontists must have the knowledge and ability to implement postsurgical management protocols and strategies to provide the best care and outcomes possible. This article presents basic concepts, philosophies, treatment protocols, risks, and potential complications associated with postsurgical patient management. Postsurgical orthodontic goals are to maximize the occlusal fit and provide predictable means to retain the occlusion. Aggressive orthodontic mechanics may be required to provide the best occlusal fit. Complications can occur, but early recognition of complications and implementation of corrective tactics should minimize adverse outcomes.


Genetic engineering of carotenoid formation in tomato fruit and the potential application of systems and synthetic biology approaches.
The health benefits conferred by numerous carotenoids have led to attempts to elevate their levels in foodstuffs. Tomato fruit and its products contain the potent antioxidant lycopene and are the predominant source of lycopene in the human diet. In addition, tomato products are an important source of provitamin A (beta-carotene). The presence of other health promoting phytochemicals such as tocopherols and flavonoids in tomato has led to tomato and its products being termed a functional food. Over the past decade genetic/metabolic engineering of carotenoid biosynthesis and accumulation has resulted in the generation of transgenic varieties containing high lycopene and beta-carotene contents. In achieving this important goal many fundamental lessons have been learnt. Most notably is the observation that the endogenous carotenoid pathways in higher plants appear to resist engineered changes. Typically, this resistance manifests itself through intrinsic regulatory mechanisms that are "silent" until manipulation of the pathway is initiated. These mechanisms may include feedback inhibition, forward feed, metabolite channelling, and counteractive metabolic and cellular perturbations. In the present article we will review progress made in the genetic engineering of carotenoids in tomato fruit, highlighting the limiting regulatory mechanisms that have been observed experimentally. The predictability and efficiency of the present engineering strategies will be questioned and the potential of more Systems and Synthetic Biology approaches to the enhancement of carotenoids will be assessed.


Histological Analysis of Carotid Plaques: The Predictors of Stroke Risk.
The morphology and histological structure of the atherosclerotic plaque seem critical to its stability. Our study aimed to identify the epidemiological, morphological and histological parameters associated with stable and unstable plaques. The study included 280 plaques harvested from 269 consecutive patients. Epidemiological and demographic data were recorded as well as the histological features of plaque, i.e. calcifications, myxoid changes, bleeding into plaque, presence of thrombus, inflammation, macrophages, giant cell reaction, siderophages, neovascularization and plaque ossification. All specimens were classified according to the American Heart Association (AHA). Monofactorial analysis identified three significant histological predictors for the symptomatic plaque: a plaque with a large necrotic core (odds ratio, OR=2.0, p = 0.03), thrombosis (OR=3.7, p = 0.01) and the formation of foamy macrophages (OR=2.0, p = 0.01). Multifactorial logistic regression revealed that the presence of foamy macrophages (OR=1.9, p = 0.03) and thrombosis (OR=3.5, p = 0.02) were significant predictors of symptomatic stenosis. Symptomatic plaques were significantly more frequently classified as AHA type VI than AHA type IV-V compared to asymptomatic ones (OR=1.8, p = 0.03). Our study shows that no single histological feature, except for the presence of foamy macrophages and thrombosis on the plaque, is predictive of plaque instability. Rather, a complex plaque structure (AHA type VI) is predictive of plaque instability. Our findings should be kept in mind during the assessment of non-invasive imaging and stroke risk estimation.


SARS-CoV-2 Antibody Seroprevalence in Industry Workers in Split-Dalmatia and Šibenik-Knin County, Croatia.
To examine seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in industry workers population sample. From 23 to April 28, 2020, we conducted serological testing for antibodies (Immunoglobulin G (IgG) and Immunoglobulin M (IgM)) on 1494 factory employees living in the Split-Dalmatia and Šibenik-Knin County (Croatia). We detected antibodies in 1.27% of participants (95% confidence interval [CI] 0.77-1.98%). In Split facility 13/1316 (0.99%, 95% CI 0.53-1.68%) of participants were tested positive, of which 13/1079 (1.20%, 95% CI 0.64-2.05%) of those living outside the facility and 0/237 (0%, 95% CI 0-1.26%) of those living inside the facility. In Knin facility, 6/178 (3.37%, 95% CI 1.25-7.19%) participants were tested positive for antibodies. The study showed relatively small SARS-CoV-2 antibody seroprevalence in the DIV Group population sample.


Ineffectiveness of hypothalamic serotonin to block neuropeptide Y-induced feeding.
A variety of recent research has suggested that the feeding associated with enhanced neuropeptide Y (NPY) activity within the hypothalamus may operate in part by interacting antagonistically with other neural processes responsive to serotonin (5-hydroxytryptamine or 5-HT). To test this possibility further, experiments were performed to determine if the magnitude of feeding produced by injecting NPY into the paraventricular nucleus (PVN) or the perifornical hypothalamus (PFH) was diminished by coinjections of 5-HT into these two sites or peripheral injections of the 5-HT agonist, d-fenfluramine. Adult male Sprague-Dawley rats were implanted unilaterally with stainless steel cannulae aimed to terminate either in the PVN or the PFH. In both studies, NPY (235 pmol) produced significant feeding in both sites either 1 or 2 h after injection when compared to saline. This enhanced feeding response was significantly greater in the PFH 2 h after injection (40% in the central study; 70% in the peripheral study). Coinjection of 5-HT (6.3, 12.5, or 25.0 nmol) into either site had no effect on the induction of this NPY-induced feeding response. However, peripherally injected d-fenfluramine (0.32, 0.63, or 1.25 mg/kg) produced strong dose-dependent attenuation both 1- and 2-h food intake elicited by 235 pmol NPY in either site, with the PFH being proportionately more sensitive to this effect. Viewed together, these results suggest that the feeding-suppressant effects of systemic fenfluramine on hypothalamic NPY-induced feeding may operate largely via peripheral mechanisms and/or central ones that have little to do with its 5-HT agonistic effects within the PVN or PFH.


Verification of elicitor efficacy of lipopolysaccharides and peptidoglycans on antibacterial peptide gene expression in Bombyx mori.
We verified the efficacy of lipopolysaccharide (LPS) in activating the cecropin B gene (CecB) in an immune-competent Bombyx mori cell line. Strong activation of CecB by the LPSs from Escherichia coli, Pseudomonas aeruginosa, and Salmonella minnesota were completely eliminated after digestion of the LPSs with muramidase. The results clearly indicate that a polymer form of PGN in the LPSs elicited CecB. An oligonucleotide microarray screen revealed that none of the 16,000 genes on the array were activated by LPS in the cells. In contrast, E. coli PGN strongly elicited five antibacterial peptide genes and numerous other genes, and PGN from Micrococcus luteus activated only several genes. Semi-quantitative RT-PCR revealed that all antibacterial genes activated by both PGNs, but the extents were 10-100 times higher with E. coli PGN. Similarly, higher elicitor activity of E. coli than M. luteus was indicated using peptidoglycan recognition protein gene, which is involved in pro-phenol oxidase cascade.


Detection of endogenous Snf1 and its activation state: application to Saccharomyces and Candida species.
The stress-response Snf1 protein kinase of Saccharomyces cerevisiae serves as a powerful model for studies of the eukaryotic Snf1/AMP-activated protein kinase (AMPK) family. Central to studies of Snf1 are methods that determine its activation state under various physiological and genetic conditions. Here, we have developed a convenient and sensitive method for immunoblot analysis of endogenous yeast Snf1 and its activation-loop threonine (Thr210) phosphorylation. The method employs readily obtainable reagents and yields results that faithfully reflect the environmental and genetic conditions tested. Using our method, we have obtained evidence that Snf1 remains stress-regulated in reg1 Delta cells, revealing the existence of a Snf1 signalling mechanism(s) that is independent of Reg1-PP1 phosphatase. In addition to strains of common laboratory S. cerevisiae backgrounds, we have applied the method to two pathogenic Candida species, C. glabrata and C. albicans. We have detected proteins whose gel mobilities, immune properties and regulation patterns are consistent with those expected for the corresponding Snf1 homologues. Because Snf1 activation is a sensitive marker of several types of stress, including artifactual stresses associated with common cell harvesting and protein extraction procedures, the convenient and efficient protein extraction method described here should be advantageous for SDS-PAGE and immunoblot analyses of stress-regulated and other proteins from various yeast species.


Psychopathology in children and adolescents with epilepsy: an investigation of predictive variables.
This epidemiological study was aimed at determining the prevalence of behavioral and emotional problems in a UK community-based population of children and adolescents with epilepsy aged 4-17 using a postal questionnaire survey. The intent was to identify, through this survey, those epilepsy-related and demographic factors predictive of the presence of psychopathology and diminished health-related quality of life, and to distinguish whether such factors differ for differing types of psychopathology. Outcomes were measured using the Strengths and Difficulties Questionnaire (SDQ), Moods and Feelings Questionnaire (MFQ), Impact of Paediatric Epilepsy Scale (IPES), and Quality of Life in Epilepsy Inventory for Adolescents (QOLIE-AD-48). Information was obtained from main carers for 56 children (25 males and 31 females, mean age=12 years, SD=3 years 9 months, range=5-17). Parent report identified that 23 (47.9%, 95% confidence interval [CI] 34.5-61.7%) children met psychiatric caseness criteria and 32 (61.5%, 95% CI 48-73.5%) had chronic distress and social impairment. Regression analyses identified seizure severity as a risk factor for emotional problems and depression (odds ratio [OR]=1.09, P<0.05), whereas cognitive impairment was associated with behavioral problems, specifically conduct problems (OR=14.0, P<0.05), hyperactivity/inattention (OR=9.4, P<0.01), and peer problems (OR=28.5, P<0.01). Cognitive impairment and high seizure frequency were significantly related to increased IPES scores (R(2)=0.33, P<0.001) and diminished QOLIE-AD-48 scores (R(2)=0.39, P<0.01). In conclusion, children with epilepsy experience considerable psychopathology and reduced quality of life. Epilepsy-related factors appear more closely associated with emotional well-being, and cognitive factors with behavior problems.


Trnp1 regulates expansion and folding of the mammalian cerebral cortex by control of radial glial fate.
Evolution of the mammalian brain encompassed a remarkable increase in size of the cerebral cortex, which includes tangential and radial expansion. However, the mechanisms underlying these key features are still largely unknown. Here, we identified the DNA-associated protein Trnp1 as a regulator of cerebral cortex expansion in both of these dimensions. Gain- and loss-of-function experiments in the mouse cerebral cortex in vivo demonstrate that high Trnp1 levels promote neural stem cell self-renewal and tangential expansion. In contrast, lower levels promote radial expansion, with a potent increase of the number of intermediate progenitors and basal radial glial cells leading to folding of the otherwise smooth murine cerebral cortex. Remarkably, TRNP1 expression levels exhibit regional differences in the cerebral cortex of human fetuses, anticipating radial or tangential expansion. Thus, the dynamic regulation of Trnp1 is critical to control tangential and radial expansion of the cerebral cortex in mammals.


Dependence of electrical activity of the amygdaloid complex on level of motivation and emotional state of the dog.
The effect of an increment in the power of the rhythmic activity of the amygdala during changes in the level of motivation in conditions of the dominance of alimentary or defensive motivation, irrespective of type, was discovered on the basis of spectral analysis of prolonged recordings of electrosubcorticograms of the amygdaloid complexes of three dogs. The resonance characteristics of the system responsible for the generation of this rhythm remain unchanged in the process, which allows explanation of the increase in the spectral peak by an increase in the inflow of afferent impulse activity into the amygdala. Summation of the influences of each of them is not observed in the presence of competing motivations, while a more complex influence on rhythm in the amygdala emerges.


Absence of a pharmacokinetic interaction between digoxin and levofloxacin.
Levofloxacin, a broad-spectrum fluoroquinolone, may enhance digoxin bioavailability by eliminating intestinal flora that metabolize digoxin. Moreover, levofloxacin, which is eliminated primarily by glomerular filtration and active tubular secretion, may alter the elimination rate of digoxin. Because of the narrow therapeutic index of digoxin, it is important to evaluate the potential for interaction with levofloxacin when administered concomitantly. This was a placebo-controlled, randomized, double-blind, two-phase crossover study. Twelve healthy subjects (six males and six females) received 500 mg twice/day oral doses of levofloxacin or placebo for 6 days and a single oral dose of 0.4 mg digoxin on the morning of study day 5 along with levofloxacin or placebo. There was no significant effect of levofloxacin on the pharmacokinetics (Cmax, AUC, and other disposition parameters) of oral digoxin. Steady-state levofloxacin absorption and disposition kinetics were also similar in the presence or absence of digoxin. Results of this study suggest that an important pharmacokinetic interaction between levofloxacin and digoxin is unlikely to occur when administered concomitantly.


Apios americana Medik flowers polysaccharide (AFP) alleviate Cyclophosphamide-induced immunosuppression in ICR mice.
Immunosuppression refers to the suppression of the immune response. The immune function of immunocompromised people is not enough to resist bacterial, viral, fungal and other infections, leading to a series of diseases. A large number of experimental data show that polysaccharide compounds are immune modulators, which can enhance the body immunity with little toxic. Meanwhile, it can reduce the side effects of commonly used immunosuppressants, such as cytotoxicity, decreased ability of the body to fight infection, and inhibition of the reproduction of bone marrow hematopoietic cells. It can be used as oral or injectable drugs. In this study, a purified polysaccharide was primarily extracted from the flowers of Apios americana Medik (AAM), which can improve the immunosuppression induced by cyclophosphamide (CTX). The immunoenhancement effect of AFP was evaluated by measuring the body weight, immune organ index, cytokine secretion and antibody generated levels of CTX-induced mice. Our results showed that AFP could significantly improve the above immune indexes, which indicated AFP could alleviate immunosuppression induced by CTX. The study provided a theoretical basis for the promotion, development and application of AAM as a newly introduced food material.


Human leukocyte antigens associated with hyperthyroid Graves ophthalmology in Japanese patients.
To evaluate the association of human leukocyte antigen (HLA) types in Japanese patients with Graves ophthalmopathy. Japanese patients with severe ophthalmopathy (48 patients) and patients without ophthalmopathy (46 patients) were selected prospectively from 234 consecutive patients with hyperthyroid Graves disease. The criteria for severe ophthalmopathy were proptosis of 19 mm or more, or a 3-mm difference in exophthalmometry measurement between the two eyes, or diplopia at the primary eye position. The criteria for the absence of ophthalmopathy were proptosis of 16 mm or less, no diplopia, no lid retraction, and no thickening of extraocular muscles. Serologic HLA typing of class I and II antigens was performed in the two patient groups. The frequency of each HLA antigen in the two patient groups was compared to that in 767 unrelated normal healthy Japanese controls. The frequencies of HLA-DR14 and DQ1 were significantly higher in the patient group with severe ophthalmopathy (35% and 75%, respectively) than in healthy controls (4% and 43%, respectively; corrected P < .05), and also greater than in the patient group without ophthalmopathy (13% and 55%, respectively; P < .01). On the other hand, the frequencies of HLA-B35, B54, DR4, and DQ4 were significantly higher in the patient group without ophthalmopathy (23%, 23%, 43%, and 30%, respectively) than in the patient group with severe ophthalmopathy (13%, 15%, 25%, and 19%, respectively; P < .01). HLA-DR14 and DQ1 antigens may be genetic markers of predisposition to the development of severe ophthalmopathy. In addition, HLA-B35, B54, DR4, and DQ4 may be genetic markers of resistance to severe ophthalmopathy. Variation in the severity of ophthalmopathy associated with Graves disease may depend, in part, on the presence or absence of particular HLA antigens.


Comprehensive literature review of the outcome, modifications, and alternatives to double-stapled low pelvic colorectal anastomosis.
The double-stapled technique is widely used for creation of colorectal anastomosis after anterior resection of the rectum. Anastomotic leak has been recognized as one of the serious complications of low pelvic colorectal anastomosis. The present review aimed to illustrate the collective outcome of double-stapled technique, risk factors for anastomotic leak, and the modifications and alternatives of double-stapled technique. A comprehensive review of PubMed/Medline, Scopus, and Web of Science was conducted to search articles that entailed patients who underwent low anterior resection with double-stapled low pelvic anastomosis. The main outcome measures were anastomotic leak and complication rates of double-stapled technique and its technical modifications. Overall, the median anastomotic leak rate across 25 studies was 7.3% (range: 0.7%-24.5%). The most commonly reported predictors of anastomotic leak after double-stapled technique were low tumor location, multiple stapler firings, male sex, longer operation time, and perioperative blood transfusion. Several modifications of the double-stapled technique were described and include hand-sewn colonic J-pouch, vertical division of the rectum, transanal reinforcement of anastomosis, transanal pull-through with single stapling technique, elimination of dog-ears using sutures, the natural orifice intracorporeal anastomosis with extraction of specimen procedure, and transanal transection and single-stapled. The median rate of anastomotic leak after double-stapled technique was less than 8%; however, it showed a wide range from less than 1% to approximately 25%. This wide variation might be related to additional risk factors of anastomotic leak, namely low tumor location and multiple stapler firings. Several techniques were described to modify the double-stapled technique to try to reduce the incidence of anastomotic leak.


Assessment of the Effectiveness of Glaucoma Treatment Using MicroPulse Transscleral Cyclophotocoagulation in Patients with Glaucoma Who Have Previously Undergone Vitreoretinal Surgery.
This retrospective study aimed to assess the effectiveness of using MicroPulse transscleral cyclophotocoagulation (µP-TSCPC) in patients who had previously undergone pars plana vitrectomy (PPV), depending on the endotamponade used. For the study, a total of 60 patients were enrolled who underwent PPV followed by tμP-TSCPC as a result of an increase in intraocular pressure (IOP) over the norm of 21 mmHg. In this group of patients, 20 received silicone oil endotamponade during PPV, 20 received sulfur hexafluoride gas SF6, and in another 20 a differentiated balanced salt solution (BSS) was used. The main indications for conducting PPV were (1) retinal detachment (silicone oil endotamponade was used; n = 12); (2) dislocation/subluxation of the patient's own or artificial intraocular lens (balanced salt solution (BSS) endotamponade was used; n = 11); (3) the presence of an epiretinal membrane and/or a macular hole (BSS endotamponade was used; n = 9, or SF6; n = 20); and (4) hemorrhage into the vitreous chamber (silicone oil endotamponade was used; n = 8). The choice of endotamponade used during PPV was not found to determine the effectiveness of µP-TSCPC treatment. The effectiveness of µP-TSCPC in patients after PPV depended, above all, on the etiology of the disease, for which PPV was previously performed. The lowest effectiveness of µP-TSCPC was noted in cases where the reason for conducting PPV was hemorrhage into the vitreous chamber and silicone oil endotamponade was used, while the highest effectiveness was noted in cases where PPV was conducted owing to the presence of an epiretinal membrane and/or a macular hole and SF6 endotamponade was used.


Superior left ventricle in combination with inferior right ventricle: presenting with balanced hemodynamics and mild symptoms in a late adolescent.
We describe a case of superoinferior ventricles with an unusual superior location of the left ventricle and inferior location of the right ventricle. The patient was a 17-year-old boy who had been admitted for paroxysmal supraventricular tachycardia with pre-excitation syndrome. The cardiac anomaly was first recognized after admission, and the pre-excitation syndrome, eventually, was treated successfully by radiofrequency catheter ablation. This case featured a segmental set notation {S, D, S} with concordant atrioventricular and ventriculoarterial alignments. Persistent left superior vena cava was the only associated defect. To the best of our knowledge, there has been only 1 other reported case of superoinferior ventricles in which the left ventricle was in the superior position. In our case, the patient's hemodynamics were sufficiently normal that he had reached adolescence with only minor adverse events.


Analysis of serial CT scans to assess template and catheter movement in prostate HDR brachytherapy.
As prostate high-dose-rate (HDR) brachytherapy becomes more prevalent, varying amounts of catheter displacement have been noted. To investigate the constancy of catheter position and its impact on dose distribution, we analyzed serial dosimetric CT scans. The data from 50 patients were analyzed. During initial CT treatment planning, transverse images of the implant volume were collected, and all structures were digitized into the Nucletron Brachytherapy Planning System. Digitally reconstructed radiographs were generated with rendering of the catheter tips, ischial tuberosity, and perineal template. The distance from each catheter tip to the template and to the ischial tuberosity was measured. The distance between the ischial tuberosity and the template was similarly measured. A second CT set was obtained at different intervals and compared with the first measurement to assess catheter and/or template movement. In 10 patients, the second CT set was obtained before the third fraction in both 2-mm and 5-mm slice sequences, and the latter was used to re-create the HDR plan. Although no interfraction catheter movement relative to the template was found, the template-catheter unit moved in a caudal direction between HDR fractions. The amount of displacement was time dependent: 2 mm before the second fraction, 8 mm before the third, and 10 mm before the fourth. When comparing the first HDR treatment with the third, median decreases in the following dosimetric parameters were noted: dose to 90% of the prostate volume, 35% (r = 0-60); minimal dose to the base, 35% (r = 17-65); and maximal dose to 1 cm(3), 13% (r = 3-19%). The interstitial catheters did not slip within the template and were not caudally displaced independently but rather in conjunction with the template. The displacement occurred in a time-dependent fashion, and, without redress, significant dosimetric changes are encountered by the third fraction.


Stimulatory effect of glutamine on human monocyte activation as measured by interleukin-6 and soluble interleukin-6 receptor release.
The activation state of murine peritoneal macrophages is shown to depend on extracellular glutamine concentration. However, there are no studies on the effect of glutamine concentration on the activation state of human monocytes. We studied the effect of extracellular glutamine concentration on interleukin (IL-6) and soluble IL-6 receptor (sIL-6R) production by activated monocytes. Monocytes separated by density gradient centrifugation and adherence to glass from buffy coats obtained from healthy donors were activated by 1 pg/ml or 1 ng/ml lipopolysaccharide (LIPS) and incubated for 48 h in 0, 0.1, 0.2, 0.6 and 2.0 mM glutamine. Levels of IL-6 and sIL-6R in culture medium were measured by immunoassay. The extracellular glutamine concentration had a significant effect on IL-6 secretion by activated human monocytes. The mean levels of IL-6 in 0.1 mM glutamine were only marginally higher (P = 0.54) compared to those in the absence of glutamine. A minimum of 0.2 mM glutamine was required to reach the maximal production of IL-6. At all glutamine concentrations the higher concentration of LPS (1 ng/ml) induced higher mean levels of IL-6 than the lower one (1 pg/ml). Glutamine concentration did not affect sIL-6R production. Our results indicate that very low levels of glutamine in plasma may impair the activation of human monocytes as measured by IL-6 secretion.


SCARB1 in extracellular vesicles promotes NPC metastasis by co-regulating M1 and M2 macrophage function.
Distant metastasis is currently the main factor affecting the prognosis of nasopharyngeal carcinoma (NPC), and understanding the mechanisms of metastasis and identifying reliable therapeutic targets are critical for improving prognosis and achieving clinical translation. Macrophages, as important immune cells in the tumor microenvironment (TME), have been shown to regulate metastasis. And extracellular vesicles (EVs) secreted by stromal cells and tumor cells play the important role in intercellular communication in the tumor microenvironment. However, the role of NPC-EVs on macrophages and their function in regulating macrophages to affect metastasis has not been fully clarified. In this study, we report that NPC-EVs can be uptake by macrophages and alter macrophage polarization, for the first time, we identified the genes implicated in these regulatory functions: SCARB1, HAAO, and CYP1B1. Moreover, we found that SCARB1 was positively associated with metastasis and poor prognosis of NPC. Interestingly, we found that SCARB1-rich EVs promoted M1 macrophages ferroptosis to decrease M1 macrophages infiltration by upregulating the HAAO level while decreasing phagocytosis of M2 macrophages by upregulating the CYP1B1 level. Finally, we identified the SCARB1-binding gene KLF9, which is involved in the transcription of HAAO and CYP1B1. Our findings showed that SCARB1-EVs promoted metastasis by co-regulating M1 and M2 macrophage function. The related mechanism will provide a new therapeutic strategy to help patients with NPC improve their prognosis.


Stress tolerance of five willow clones after irrigation with different amounts of landfill leachate.
Short-rotation willow (Salix sp.) coppice, a commercial crop grown for energy purposes, is used for phytoremediation of landfill leachate in Sweden. However, the leachate's chemical composition can cause plant damage mainly due to high NaCl and NH4 concentrations. A pot experiment was conducted in order to quantify the growth responses of five different willow clones ("78-183", "Jorr", "Loden", "Olof", "Tora") to irrigation with different leachate mixtures (corresponding to 240, 180, and 120 mg Cl l(-1)) and to assess the applicability of leaf length and leaf fluctuating asymmetry as stress indicators. A series of plant traits (shoot, root and leaf dry weight, leaf area, leaf length and leaf fluctuating asymmetry) were measured. The irrigation with leachate resulted in reduced relative growth rates but there were no clear differences between the different concentrations. The clones "Jorr" and "Loden" performed best in terms of differences in relative growth rate between control and leachate treatments. Leaf length appeared to be a useful stress diagnostic tool for use in situ showing a high correlation to growth, whereas fluctuating asymmetry showed no such correlation. Higher N, lower P and higher Na concentrations in plant stems treated with leachate than control plants were observed.


The envelope proteins of bovine leukemia virus: purification and sequence analysis.
Two proteins, termed gp60 and p30, have been purified to homogeneity from bovine leukemia virus (BLV) using controlled pore glass and reverse-phase liquid chromatography (RPLC). gp60 was shown to be a glycoprotein by identification of glucosamine on the amino acid analyzer. Antiserum prepared to gp60 recognized in addition to gp60 a 52,000-Da polypeptide in some virus preparations, but did not cross-react with p30. The amino and carboxyl termini of gp60 were found to be tryptophan and arginine, respectively, and a 38-residue amino-terminal sequence of gp60 (NH2TrpArgXSerLeuSerLeuGlyAsnGlnGlnTrpMetThrAlaTyrAsnGlnGluAlaLys PheSerIleSerIleAspGlnIleLeuGluAlaHisAsnGlnSerProPhe-) was obtained. A 12-residue amino-terminal sequence for p30 (NH2SerProValAlaAlaLeuThrLeuGlySerAlaLeu) was also obtained. The p30 sequence showed substantial homology to the transmembrane proteins of both types B and C retroviruses and also to a deduced sequence of the 3' region of the env gene of human T-cell leukemia virus. From these results and from elution behavior of these proteins on RPLC, it was concluded that gp60 and p30 are the BLV env gene-encoded surface glycoprotein and transmembrane protein, respectively.


Retraction: Temperature-regulated polymerization and swelling/collapsing/flocculation properties of hybrid nanospheres with magnetic cores and thermo/pH-sensitive nanogel shells.
[This retracts the article DOI: 10.1039/C3RA43919D.].


Origins of the BOLD changes due to synaptic activity at astrocytes abutting arteriolar smooth muscle.
We have recently provided a detailed model that links glutamatergic synaptic activity to volume and blood flow changes in nearby arterioles [Bennett, M.R., Farnell, L., Gibson, W.G., 2008. Origin of blood volume change due to glutamatergic synaptic activity at astrocytes abutting on arteriolar smooth muscle cells. J. Theor. Biol. 250, 172-185]. This neurovascular coupling model is used in the present work to predict changes in deoxyhemoglobin (Hbr) in capillaries, arterioles, venules and veins due to glutamatergic synaptic activity and hence the changes in the blood oxygen level dependent (BOLD) signals recorded by functional magnetic resonance imaging. The model provides a quantitative account of Hbr changes observed in each of the vascular compartments following stimulation of somatosensory cortex and visual cortex and of the BOLD signal following stimulation of motor and visual cortex.


Tumor necrosis factor-associated susceptibility to type 1 diabetes is caused by linkage disequilibrium with HLA-DR3 haplotypes.
Tumor necrosis factor-α (TNF-α) is an important proinflammatory cytokine involved in the pathogenesis of autoimmune type 1 diabetes (T1D). The TNF gene locus is located in the major histocompatibility complex (MHC) class III region and its genetic polymorphisms have been reported to be associated with T1D. However, it is not clear whether these associations are primary or caused by their linkage disequilibrium with other predisposing genes within the MHC. We have tested 2 TNF-α single nucleotide polymorphisms at positions -308G/A and -238G/A in the 5' untranslated region and a (GT)n microsatellite TNFa in the North Indian healthy population and T1D patients with known HLA-A-B-DR-DQ haplotypes. The allele frequencies of TNFa5, -308A, and -238G were determined to be significantly increased among patients compared with controls. Although the observed positive association of -238G was caused by its presence on all 3 DR3(+) groups, namely, B8-DR3-DQ2, B50-DR3-DQ2, and B58-DR3-DQ2 haplotypes associated with T1D in this population, the increase of the -308A allele was caused by its association with the latter 2 haplotypes. On the other hand, TNF -308G occurred on B8-DR3 haplotypes along with -238G and TNFa5 alleles, particularly in T1D patients with late disease onset (at >20 years of age). These results indicate that TNF associations with T1D are caused by their linkage disequilibrium with specific HLA-DR3-DQ2 haplotypes in the Indian population. Because polymorphisms in the promoter region regulate TNF expression levels (e.g., -308A), they retain crucial immunological significance in the development of T1D and its management.


Nr4a1 promotes renal interstitial fibrosis by regulating the p38 MAPK phosphorylation.
Renal interstitial fibrosis (RIF) is a common pathway to end-stage renal disease regardless of the initial etiology. Currently, the molecular mechanisms for RIF remains not fully elucidated. Nuclear receptor subfamily 4 group A member 1(Nr4a1), a member of the NR4A subfamily of nuclear receptors, is a ligand-activated transcription factor. The role of Nr4a1 in RIF remains largely unknown. In this study, we determined the role and action mechanism of Nr4a1 in RIF. We used unilateral ureteral obstruction (UUO) mice and transforming growth factor (TGF)-β1-treated human renal proximal tubular epithelial cells (HK-2 cells) as in vivo and in vitro models of RIF. A specific Nr4a1 agonist Cytosporone B (Csn-B) was applied to activate Nr4a1 both in vivo and in vitro, and Nr4a1 small interfering RNA was applied in vitro. Renal pathological changes were evaluated by hematoxylin and eosin and Masson staining, and the expression of fibrotic proteins including fibronectin (Fn) and collagen-I (Col-I), and phosphorylated p38 MAPK was measure by immunohistochemical staining and western blot analysis. The results showed that Nr4a1 was upregulated in UUO mouse kidneys, and was positively correlated with the degree of interstitial kidney injury and the levels of fibrotic proteins. Csn-B treatment aggravated UUO-induced renal interstitial fibrosis, and induced p38 MAPK phosphorylation. In vitro, TGF-β induced Nr4a1 expression, and Nr4a1 downregulation prevented TGF-β1-induced expression of Fn and Col-I and the activation of p38 MAPK. Csn-B induced fibrotic proteins expression and p38 MAPK phosphorylation, and moreover Csn-B induced fibrotic proteins expression was abrogated by treatment with p38 MAPK inhibitor SB203580. We provided further evidence that Csn-B treatment promoted cytoplasmic accumulation of Nr4a1. The findings in the present study indicate that Nr4a1 promotes renal fibrosis potentially through activating p38 MAPK kinase.


Bone morphometrics and tetracycline marking patterns in young growing American alligators (Alligator mississippiensis).
Nine young American alligators (Alligator mississippiensis) were injected at monthly intervals with tetracycline to determine the bone apposition rate and the resorption patterns over a 3-mo period. The periosteal apposition rate increased progressively over the 3-mo period from 2.99 microns/day to 5.94 microns/day. Endosteal apposition rate was much slower with incomplete tetracycline lines being observed on the endosteum. This suggests that most modeling-resorptive activities occur on the endosteal envelope.


Strain Engineering to Modify the Electrochemistry of Energy Storage Electrodes.
Strain engineering has been a critical aspect of device design in semiconductor manufacturing for the past decade, but remains relatively unexplored for other applications, such as energy storage. Using mechanical strain as an input parameter to modulate electrochemical potentials of metal oxides opens new opportunities intersecting fields of electrochemistry and mechanics. Here we demonstrate that less than 0.1% strain on a Ni-Ti-O based metal-oxide formed on superelastic shape memory NiTi alloys leads to anodic and cathodic peak potential shifts by up to ~30 mV in an electrochemical cell. Moreover, using the superelastic properties of NiTi to enable strain recovery also recovers the electrochemical potential of the metal oxide, providing mechanistic evidence of strain-modified electrochemistry. These results indicate that mechanical energy can be coupled with electrochemical systems to efficiently design and optimize a new class of strain-modulated energy storage materials.


Advances in Pediatric Small Bowel Imaging.
Technological advances for visualizing the small bowel have significantly grown over the past few decades. Balloon-assisted enteroscopy has come to the forefront of these innovations, and has been found to be safe and effective in children with small bowel ailments. The expanding body of research into balloon-assisted enteroscopy will continue to refine the current knowledge base of this technique, along with a growing assessment of the long-term benefits of such interventions.