MicroRNA-32 and MicroRNA-548a Promote the Drug Sensitivity of Non-Small Cell Lung Cancer Cells to Cisplatin by Targeting ROBO1 and Inhibiting the Activation of Wnt/β-Catenin Axis.
The roles of microRNA (miR)-32 and miR-548a in non-small cell lung cancer (NSCLC) have been studied. But their influences on NSCLC cells to cisplatin (DDP) resistance remain elusive. This study estimated the mechanisms of miR-32 and miR-548a in NSCLC cells to DDP. Differentially expressed miRs in DDP-sensitive and resistant tissues were screened out using a GSE56036 chip. Then the predictive efficacies of miR-32 and miR-548a on DDP resistance were analyzed in NSCLC patients. The target mRNAs of miR-548a and miR-32 were predicted. miR-548a and miR-32 were knocked down to assess the influences of miR-32 and miR-548a on NSCLC growth. DDP-resistant cells were constructed and miR-32 and miR-548a expression was detected in resistant cells. After miR-32 and miR-548a knockdown, the IC50 value of DDP was detected. Then, the activation level of Wnt/β-catenin pathway was detected. The roles of miR-32 and miR-548a in NSCLC growth in vivo were detected by tumorigenesis experiment. miR-32 and miR-548a were poorly expressed in DDP-resistant NSCLC. miR-32 and miR-548a mimic enhanced the DDP sensitivity of NSCLC cells. Both miR-32 and miR-548a targeted ROBO1, and overexpression of ROBO1 inhibited the promotion of miR-32 and miR-548a mimic on DDP sensitivity. ROBO1 activated the Wnt/β-catenin pathway, thus enhancing the DDP resistance. miR-32 and miR-548a target ROBO1 and inhibit Wnt/β-catenin activation, thus promoting the drug sensitivity of NSCLC cells to DDP.


Heterogeneity of high-density lipoprotein in cord blood and its postnatal change.
Several subclasses of HDL are demonstrated to have different roles in atherosclerosis based on adult studies, but the significance of HDL heterogeneity in the fetus and neonate has not been clarified. It has been described that the cholesterol supply from apoE-rich HDL is essential for central nerve system neuron growth. Sixty-five healthy, term, appropriate for gestational age neonates (38 males and 27 females) were included in the study. Serum lipoprotein analyses were performed by HPLC with gel permeation columns, which classified HDL into 5 subgroups (i.e., very large, large, medium, small, and very small) on the basis of particle size. Apolipoprotein A-I, B, and E were also determined by turbidimetric immunoassay. Cord blood has higher very large and very small HDL-cholesterol levels. Cord blood apolipoprotein E was not uniformly distributed in the HDL subclasses, with a strong association with very large HDL-cholesterol levels (males, r=0.548, p<0.001; females, r=0.631, p<0.01). However, the association disappeared by 1 month of age in males; in females, the association remained during the neonatal period. These results suggest that HDL may play the role of a dominant cholesterol carrier in the human fetus, and very large HDL-cholesterol have some contribution to the neurodevelopment in the fetus and neonates because of the close relationship with apolipoprotein E levels.


Psychological Predictors of Satisfaction after Lumbar Surgery for Lumbar Spinal Stenosis.
A retrospective study of prospectively collected clinical data. To identify preoperative psychological factors associated with patient satisfaction after surgery for lumbar spinal stenosis (LSS). Associations between depressive symptoms, anxiety, and worse surgical outcome or patient dissatisfaction have been reported in LSS patients. However, the influence of preoperative pain catastrophizing and fear-avoidance beliefs on postoperative satisfaction is not well understood. LSS patients who underwent decompression surgery with or without fusion were included. Clinical outcomes were measured before surgery and 6 months postoperatively using the Zurich Claudication Questionnaire (ZCQ); Visual Analog Scale (VAS) of low back pain, leg pain, and leg numbness; Japanese Orthopaedic Association Back Pain Evaluation Questionnaire; and the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36). The Hospital Anxiety and Depression Scale (HADS), Pain Catastrophizing Scale, and Pain Anxiety Symptoms Scale were used to evaluate psychological status before surgery. Patients were classified as satisfied or dissatisfied with surgery based on a ZCQ satisfaction subscale cutoff score of 2.5. The satisfied and dissatisfied groups contained 128 and 29 patients, respectively. Six months postoperatively, outcome scores for the dissatisfied group were unchanged or worse than preoperative scores (p>0.05). Multivariate logistic regression analysis showed significant associations between dissatisfaction and preoperative low back pain VAS score ≥ median (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.10-0.74; p=0.01), preoperative mental health SF-36 score ≥ median (OR, 0.26; 95% CI, 0.08-0.89; p=0.03), and preoperative anxiety HADS score ≥ median (OR, 3.95; 95% CI, 1.16-13.46; p=0.03). Preoperative less severe low back pain, lower mental health, and higher anxiety are associated with patient dissatisfaction with lumbar surgery, not depression, pain catastrophizing, or fear-avoidance beliefs. Pre- and postoperative psychological status should be assessed carefully and managed appropriately.


Effect of berry-based supplements and foods on cognitive function: a systematic review.
In the current decade, a growing body of evidence has proposed the correlation between diet and cognitive function or dementia in the ageing population. This study was designed to appraise discoveries from the randomized controlled trials to confirm the effects of berry-based supplements or foods on cognitive function in older adults. PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, EMBASE, Google Scholar, and ProQuest as well as SID, Magiran, and Iranmedex electronic databases were explored for human interventional studies up to March 2021. In total, eleven articles were identified using frozen blueberry (n = 4 studies), blueberry concentrate (n = 2), beverage (n = 3), capsule (n = 1), extract and powder (n = 1). These studies had been performed among older people with no recognized cognitive impairment or mild cognitive impairment (MCI). The primary outcomes included global cognitive function, psychomotor function, learning and memory, working memory capacity, executive functions, and brain perfusion/activity. To our knowledge, this is the first systematic review of available clinical trials on the effects of berry-based supplements and foods on cognitive performances as well as brain perfusion parameters among the elderly with normal cognition or MCI. Existing evidence concludes that berry-based supplements and foods have beneficial effects on resting brain perfusion, cognitive function, memory performance, executive functioning, processing speed, and attention indices.


Association of life satisfaction with disability-free survival: role of chronic diseases and healthy lifestyle.
this article investigates the association between life satisfaction and disability-free survival, and explores the roles of chronic diseases and healthy lifestyle in this association. a cohort of 2,116 functionally independent adults aged ≥60 was followed up to 12 years. At baseline, life satisfaction was assessed with the Life Satisfaction Index A (LSI-A). Disability-free survival was defined as the survival till the first occurrence of either death, dementia or physical disability. Information on lifestyle factors was collected via questionnaire. Chronic diseases were ascertained through clinical examinations at baseline and each follow-up. Data were analysed using Cox proportional hazard regression models and Laplace regression. over follow-up, 1,121 participants died, developed dementia, or became disabled. High LSI-A versus Low LSI-A had a lower risk of death, dementia and physical disability (hazard ratio [HR] 0.79, 95% confidence intervals [CI] 0.67-0.94), and had a longer disability-free period by 1.73 (95% CI 0.18-3.32) years. In mediation analysis, accumulation of chronic diseases mediated 17.8% of the association between LSI-A and disability-free survival. In joint effect analysis, participants with high LSI-A and a favourable lifestyle profile had a HR of 0.53 (95% CI 0.41-0.69) for the composite endpoint, and lived 3.2 (95% CI 1.35-5.11) disability-free years longer than those with low life satisfaction and an unfavourable lifestyle profile. high life satisfaction is independently associated with longer disability-free survival. This association is partially mediated by a lower burden of chronic diseases and is reinforced by healthy lifestyle.


Fitting an ex-Gaussian function to examine costs in event-based prospective memory: evidence for a continuous monitoring profile.
Event-based prospective memory (PM) tasks require individuals to remember to perform a deferred action when a target event occurs. PM task requirements can slow ongoing task responses on non-target trials ('costs') under conditions where the defining features of targets are non-focal to the ongoing task, which is indicative that individuals have allocated some form of cognitive control process to the PM task. Recent fits of the ex-Gaussian mathematical function to non-target trial response distributions by prior studies have indicated that these control processes are transiently allocated. In the current paper, fits of the ex-Gaussian function to data reported by Loft and Humphreys (2012) demonstrate a shift in the entire response time distribution (μ) and an increase in skew (τ) for a non-focal PM condition required to remember to make a PM response if presented with category exemplars, compared to a control condition. This change in μ is indicative of a more continuous PM monitoring profile than that reported by prior studies. In addition, within-subject variability in μ was reliably correlated with PM accuracy, suggesting that these control processes allocated on a regular basis were functional to PM accuracy. In contrast, when the ongoing task directed attention to the defining features of targets (focal PM) there was a trend level increase in μ, but the within-subject variability in μ was not correlated with PM accuracy, consistent with the theoretical premise that focal PM tasks are not as dependent on cognitive control as non-focal PM tasks.


Biodiversity and conservation of sharks in Pacific Mexico.
Mexico is home to a broad biodiversity of shark species, and more than half of the sharks in Mexican waters are distributed in the Mexican Pacific, with over 62 species recorded. This high biodiversity is the result of numerous and diverse marine and coastal environments, including the dynamic Mexican seas, where circulation and spatial variation of oceanic currents is complex, and the seasonal variation of isotherms can be substantial. In the Mexican Pacific we can distinguish some patterns of species distribution, with temperate water and subtropical species found in the northern regions, and tropical conditions and species found in the south. Due to the blending of cold and warm waters, however, we can find a mixture of subtropical and tropical sharks in northern regions seasonally, off the west coast of the Baja California Peninsula and in the Gulf of California, and these areas contain the highest shark species richness. In this chapter we described the shark species biodiversity occurring in the Mexican Pacific, review their conservation status in a regional and global context, and summarize the main conservation measures and issues associated with their management.


Effects of tubocurarine and eserine on the axon-Schwann cell relationship in the squid nerve fibre.
The effects of eserine and D-tubocurarine on the axon and Schwann cell membrane potentials have been studied in the giant nerve fibre of the squid.1. The addition of eserine at concentrations of up to 10(-4)M to the external sea-water medium has no appreciable effects on either the Schwann cell electrical potential of unstimulated nerve fibres or on the resting and action potentials of the axon.2. However, eserine at a concentration of 10(-9)M prolongs the long-lasting Schwann cell hyperpolarizations which follow the conduction of impulse trains by the axon.3. Higher concentrations of eserine (10(-7), 10(-4)M) decrease and block the long-lasting effects of nerve impulse train conduction.4. D-tubocurarine at concentrations of up to 10(-5)M has no appreciable effect on the resting and action potentials of the axon.5. However, D-tubocurarine at a concentration of 10(-9)M blocks completely the hyperpolarizing effects of nerve impulse trains on the Schwann cell electrical potential.6. In addition to its blocking action, D-tubocurarine induces transient hyperpolarizations in the Schwann cells of unstimulated nerve fibres both in intact fibres and in slitted preparations.7. These findings suggest that a cholinergic system, which may be located at the axon-Schwann cell boundary, is involved in the genesis of the long-lasting Schwann cell hyperpolarization caused by the conduction of nerve impulse trains by the axon.


Baseline striatal and nigral interneuronal protein levels in two distinct mice strains differ in accordance with their MPTP susceptibility.
Epidemiological studies reveal an ethnicity-based bias in prevalence of Parkinson's disease (PD), deriving from the differences that exist between Caucasians and African or Asian populations. Experimental mice models provide a scope to analyse the cellular mechanisms of differential susceptibility to PD. C57BL/6J mice, for instance, are more susceptible to MPTP-induced Parkinsonism whereas CD-1 mice are resistant. In PD-pathogenesis, interneuronal contribution is also likely, although they comprise only 5-10% of the striatal cells. The interneurons harbour calcium binding proteins, like calretinin (Cal-R) and parvalbumin (PV), which are crucial in Ca2+ homeostasis for preventing calcium-induced excitotoxicity. GAD-67-immunoreactive interneurons are the other prominent set of GABAergic interneurons. In PD, dopamine loss up-regulates GAD-67 expression in striatal projection neurons and other basal ganglia circuit. We studied the possible contribution of interneurons in determining variable susceptibility by assessing the expression of calretinin, PV and GAD-67 in both striatum and substantia nigra pars compacta (SNpc) in two distinct mice strains, i.e. C57BL/6J and CD-1 under normal conditions, using unbiased stereology for quantification of immunoreactive cells and immunoblotting. The vulnerable C57BL/6J had lesser basal parvalbumin expression in both nigra and striatum whereas the calretinin levels were low only in the striatum. GAD-67 expression showed no perceptible differences in the striatum or SNpc of either of the strains. Differential expression of calcium buffering/binding proteins under normal physiological condition proffers a role for interneurons in the differential susceptibility to PD. Thus, even the baseline susceptibility indices i.e. without using the neurotoxin; can provide vital mechanistic insights into PD pathogenesis.


Dietary phytochemicals and their potential effects on obesity: a review.
The incidence of obesity is rising at an alarming rate and is becoming a major public health concern with incalculable social costs. Indeed, obesity facilitates the development of metabolic disorders such as diabetes, hypertension, and cardiovascular diseases in addition to chronic diseases such as stroke, osteoarthritis, sleep apnea, some cancers, and inflammation-bases pathologies. In this review we summarize the progresses made in our understanding of obesity, including the role of inflammation process, the recently understood endocrine function of adipose tissue, as well as passive roles of processes of energy storage and adipogenesis related to fat cell lifecycle: differentiation, maturation, and apoptosis. In addition, the article discusses the anti-obesity potential of dietary phytochemicals and analyzes their mechanisms of action, e.g. induction of apoptosis and lipolysis and inhibition of inflammation.


Microbiome modulation after severe acute kidney injury accelerates functional recovery and decreases kidney fibrosis.
Targeting gut microbiota has shown promise to prevent experimental acute kidney injury (AKI). However, this has not been studied in relation to accelerating recovery and preventing fibrosis. Here, we found that modifying gut microbiota with an antibiotic administered after severe ischemic kidney injury in mice, particularly with amoxicillin, accelerated recovery. These indices of recovery included increased glomerular filtration rate, diminution of kidney fibrosis, and reduction of kidney profibrotic gene expression. Amoxicillin was found to increase stool Alistipes, Odoribacter and Stomatobaculum species while significantly depleting Holdemanella and Anaeroplasma. Specifically, amoxicillin treatment reduced kidney CD4+T cells, interleukin (IL)-17 +CD4+T cells, and tumor necrosis factor-α double negative T cells while it increased CD8+T cells and PD1+CD8+T cells. Amoxicillin also increased gut lamina propria CD4+T cells while decreasing CD8+T and IL-17+CD4+T cells. Amoxicillin did not accelerate repair in germ-free or CD8-deficient mice, demonstrating microbiome and CD8+T lymphocytes dependence for amoxicillin protective effects. However, amoxicillin remained effective in CD4-deficient mice. Fecal microbiota transplantation from amoxicillin-treated to germ-free mice reduced kidney fibrosis and increased Foxp3+CD8+T cells. Amoxicillin pre-treatment protected mice against kidney bilateral ischemia reperfusion injury but not cisplatin-induced AKI. Thus, modification of gut bacteria with amoxicillin after severe ischemic AKI is a promising novel therapeutic approach to accelerate recovery of kidney function and mitigate the progression of AKI to chronic kidney disease.


Life-threatening human herpes virus-6 infection in early childhood: presenting symptom of a primary immunodeficiency?
To report two previously healthy children with a life-threatening course of human herpes virus type 6 (HHV-6) infection and prolonged pediatric intensive care treatment. Case reports. A 16 bed pediatric intensive care unit at a tertiary care children's hospital. Two children with life-threatening HHV-6 disease. Both children were mechanically ventilated because of respiratory failure. A detailed viral and immunologic workup was performed and treatment with antiviral medication started. Polymerase chain reaction assays of plasma, cerebrospinal fluid, bronchoalveolar lavage, and lung biopsies yielded HHV-6 in both patients. Immunophenotyping and lymphocyte stimulation tests with both mitogens and antigens indicated an immunodeficiency in both patients. HHV-6 infection should be considered in infants and young children with respiratory failure or meningo-encephalitis without clear causative agent or failure to respond to empirical treatment. A thorough immunologic workup and early start with antiviral therapy in any patient with a life-threatening course of HHV-6 infection is mandatory, because a severe HHV-6 infection can be the first indication of a primary immunodeficiency.


Vitamin D Status and Health Outcomes in School Children in Northern Ireland: Year One Results from the D-VinCHI Study.
(1) Background: Vitamin D status has never been investigated in children in Northern Ireland (UK). (2) Methods: Children (4-11 years) (n = 47) were recruited from November 2019 to March 2020 onto the cross-sectional study. Anthropometry was assessed. Plasma 25-hydroxyvitamin D (25(OH)D) was analysed. Vitamin D intake, parental knowledge and perceptions, participant habits, physical activity and sedentary behaviour were established via questionnaire. Muscle strength was assessed via isometric grip strength dynamometry and balance via dominant single-leg and tandem stance. Parathyroid hormone, bone turnover markers (OC, CTX and P1NP), glycated haemoglobin and inflammatory markers (CRP, IFN-γ, IL-10, IL-12p70, IL-13, IL-1β, IL-2, IL-4, IL-6, IL-8 and TNF-α) were analysed. (3) Results: Mean (SD) 25(OH)D was 49.17 (17.04) nmol/L (n = 47); 44.7% of the children were vitamin D sufficient (25(OH)D >50 nmol/L), 48.9% were insufficient (25-50 nmol/L) and 6.4% were deficient (<25 nmol/L). 25(OH)D was positively correlated with vitamin D intake (µg/day) (p = 0.012, r = 0.374), spring/summer outdoor hours (p = 0.006, r = 0.402) and dominant grip strength (kg) (p = 0.044, r = 0.317). Vitamin D sufficient participants had higher dietary vitamin D intake (µg/day) (p = 0.021), supplement intake (µg/day) (p = 0.028) and spring/summer outdoor hours (p = 0.015). (4) Conclusion: Over half of the children were vitamin D deficient or insufficient. Wintertime supplementation, the consumption of vitamin D rich foods and spring/summer outdoor activities should be encouraged to minimise the risk of vitamin D inadequacy.


[Familical cleft foot--a clinical study over 4 generations (author's transl)].
Within this paper a family is being described in which foot deformities are shown over four generations. During two generations cleft foot is found as well as a syndaktylism. The cases are demonstrated clinically, by photographs and also by X-ray. The question of inheritance is being discussed in comparison with the existing literature, also taking into account the coexistence of cleft foot and syndaktylism.


High-efficiency hyperfluorescent white light-emitting diodes based on high-concentration-doped TADF sensitizer matrices via spatial and energy gap effects.
Despite the success of monochromatic hyperfluorescent (HF) organic light-emitting diodes (OLEDs), high-efficiency HF white OLEDs (WOLEDs) are still a big challenge. Herein, we demonstrate HF WOLEDs with state-of-the-art efficiencies, featuring a quasi-bilayer emissive layer (EML) composed of an ultrathin (0.1 nm) blue fluorescence (FL) emitter (TBPe) layer and a layer of thermally activated delayed fluorescence (TADF) sensitizer matrix heavily doped with a yellow FL emitter (TBRb, 3%). Based on an asymmetric high-energy-gap TADF sensitizer host (PhCzSPOTz), such an "ultrathin blue emitting layer (UTBL)" strategy endowed the HF WOLEDs with a record power efficiency of ∼80 lm W-1, approaching the level of fluorescent tubes. Transient photoluminescence (PL) and electroluminescence (EL) kinetics demonstrate that the spatial separation of TBPe from the TADF sensitizer and TBRb, and the large energy gap between the latter two effectively suppress triplet leakage, in addition to suppressing triplet diffusion in the PhCzSPOTz matrix with anisotropic intermolecular interactions. These results provide a new insight into the exciton allocation process in HF white light-emitting systems.


Neonatal lupus erythematosus associated with unilateral pectoralis major atrophy.
Neonatal lupus erythematosus (NLE), in most cases, presents with cardiac and dermatological manifestation due to transferred IgG auto antibodies (anti Ro/SSA and anti La/SSB) from the mother. Some unusual associations with myelopathy, vasculopathy, transient myasthenia gravis, congenital nephrotic syndrome, chondrodysplasia punctata etc. are also reported. Here, the authors present a case of NLE with isolated left sided pectoralis major muscle atrophy, which has not been reported earlier.


MMP-7 affects peritoneal ultrafiltration associated with elevated aquaporin-1 expression via MAPK/ERK pathway in peritoneal mesothelial cells.
Peritoneal membrane dysfunction and the resulting ultrafiltration failure are the major disadvantages of long-term peritoneal dialysis (PD). It becomes increasingly clear that mesothelial cells play a vital role in the pathophysiological changes of the peritoneal membrane. Matrix metalloproteinases (MMPs) function in the extracellular environment of cells and mediate extracellular matrix turnover during peritoneal membrane homeostasis. We showed here that dialysate MMP-7 levels markedly increased in the patients with PD, and the elevated MMP-7 level was negatively associated with peritoneal ultrafiltration volume. Interestingly, MMP-7 could regulate the cell osmotic pressure and volume of human peritoneal mesothelial cells. Moreover, we provided the evidence that MMP-7 activated mitogen-activated protein kinases (MAPKs)-extracellular signal-regulated kinase 1/2 (ERK) pathway and subsequently promoted the expression of aquaporin-1 (AQP-1) resulting in the change of cell osmotic pressure. Using a specific inhibitor of ERK pathway abrogated the MMP-7-mediating AQP-1 up-regulation and cellular homeostasis. In summary, all the findings indicate that MMP-7 could modulate the activity of peritoneal cavity during PD, and dialysate MMP-7 might be a non-invasive biomarker and an alternative therapeutic target for PD patients with ultrafiltration failure.


Awareness of hepatitis C infection among men who have sex with men in Flanders, Belgium.
Over the past decade an increasing incidence of hepatitis C (HCV) has been observed in different countries among HIV-positive men who have sex with men (MSM). We conducted an online survey in the Dutch speaking part of Belgium among MSM to assess awareness of transmission routes and prevention measures for HCV. A 37 question online survey was conducted via two well known websites in Belgium for MSM. Out of 333 responders, only 57% of men self reporting high-risk sexual behaviour considered themselves at risk for HCV. Only 48.2% knew there is no protective vaccine against HCV. Forty eight (16.6%) men were convinced they were protected for HCV by a vaccine. One third of men considered personal hygiene as an efficient way of HCV prevention. Over half of the responders never received any information about HCV, but almost all would find it useful. The online survey among MSM in Flanders, Belgium suggests that awareness of transmission routes and prevention measures for HCV is low and that there is an urgent need for more information.


Genetic predispositions for thromboembolism as a possible etiology for gastroschisis.
Occlusion of the omphalomesenteric artery in utero, leading to disruption of the umbilical ring with subsequent herniation of intestines, has been proposed as the mechanism by which gastroschisis occurs. We hypothesized that affected fetuses have a predisposition to arterial or venous thromboembolism. Thirty-one children born with gastroschisis were tested for Factor V Leiden, prothrombin, and methylene tetrahydrofolate reductase (MTHFR) mutations. Fifty-two appropriately grown term neonates whose mothers were matched by maternal age and race served as control neonates. Of children with gastroschisis, 6.45% were heterozygous for Factor V Leiden. No infants with gastroschisis had prothrombin gene mutations. Thirty-six percent of affected infants were heterozygous, and 16% were homozygosity for MTHFR. Among control infants, 42% were heterozygous, and 14% were homozygous for MTHFR. The mutation rate for MTHFR did not differ in children with and without gastroschisis when mothers were matched by race and age.


Randomized clinical trial comparing outcomes after fentanyl or ketamine-dexmedetomidine analgesia in thoracolumbar spinal surgery in dogs.
Opioids are widely used for perioperative pain control in dogs undergoing spinal surgery, but alternatives may be required because data suggest that opioids exacerbate inflammation in the injured spinal cord and veterinary access to opioids may become more restricted in the future. To compare recovery of ambulation and other functions between spinal cord-injured dogs receiving peri-operative fentanyl and those receiving a ketamine-dexmedetomidine combination. A total of 102 client-owned dogs undergoing decompressive surgery for thoracolumbar intervertebral disc herniation. Randomized clinical trial. Dogs were randomized 1:1 to fentanyl or a ketamine-dexmedetomidine combination for intra and postoperative analgesia. Primary outcome was time to recovery of ambulation; secondary outcomes were the postoperative Colorado Acute Pain Scale, the short-form Glasgow Composite Measure Pain Scale, time to recovery of voluntary urination and time to unassisted eating. No difference was found in time to recovery of ambulation between groups (adjusted sub-hazard ratio, 0.83; 95% confidence interval [CI], 0.55-1.24; P = .36) or in pain scores (Colorado: χ2 = 14.74; P = .32; Glasgow: χ2 = 6.61; P = .76). Differences in time to recovery of eating and urination were small but favored ketamine-dexmedetomidine (adjusted odds ratios, 3.31; 95% CI, 1.53-7.16; P = .002 and 2.43; 95% CI, 1.00-5.96; P = .05, respectively). There was no evidence that, at the doses used, fentanyl impaired ambulatory outcome after surgery for thoracolumbar intervertebral disc herniation in dogs. Pain control appeared similar between groups. Secondary outcomes suggested minor benefits associated with ketamine-dexmedetomidine. The ketamine-dexmedetomidine combination appears to be a reasonable alternative to peri-operative opioids.


Sentinel lymph node biopsy using intraoperative indocyanine green fluorescence imaging navigated with preoperative CT lymphography for superficial esophageal cancer.
The sentinel lymph node (SLN) concept has been gaining attention for gastrointestinal neoplasms but remains controversial for esophageal cancer. This study evaluated the feasibility of SLN identification using intraoperative indocyanine green (ICG) fluorescence imaging (IGFI) navigated by preoperative computed tomographic lymphography (CTLG) to treat superficial esophageal cancer. Subjects comprised 20 patients clinically diagnosed with superficial esophageal cancer. Five minutes after endoscopic submucosal injection of iopamidol around the primary lesion using a four-quadrant injection pattern with a 23-gauge endoscopic injection sclerotherapy needle, three-dimensional multidetector computed tomography was performed to identify SLNs and lymphatic routes. ICG solution was injected intraoperatively around the tumor. Fluorescence imaging was obtained by infrared ray electronic endoscopy. Thoracoscope-assisted standard radical esophagectomy with lymphadenectomy was performed to confirm fluorescent lymph nodes detected by CTLG. Lymphatic vessels and SLNs were identified preoperatively using CTLG in all cases. Intraoperative detection rates were 100% using CTLG and 95% using IGFI. Lymph node metastases were found in four cases, including one false-negative case with SLNs occupied by bulky metastatic tumor that were not enhanced with both methods. The other 19 cases, including three cases of metastatic lymph nodes, were accurately identified by both procedures. Preoperative CTLG visualized the correct number and site of SLNs in surrounding anatomy during routine computed tomography to evaluate distant metastases. Referring to CTLG, SLNs were identified using IGFI, resulting in successful SLN navigation and saving time and cost. This method appears clinically applicable as a less-invasive method for treating superficial esophageal cancer.


Hypoglycemia with intensive insulin therapy after cardiac surgery: predisposing factors and association with mortality.
Intensive insulin therapy has become a major therapeutic target in cardiac surgery patients. It has been associated, however, with an increased risk of hypoglycemia compared with conventional insulin therapy. Our study sought to identify the factors predisposing to hypoglycemia with intensive insulin therapy and investigate its effect on early clinical outcomes after cardiac surgery. A concurrent cohort study of 2,538 consecutive patients undergoing cardiac surgery (coronary artery bypass grafting, valve, or bypass grafting and valve surgery) from January 2005 to March 2010 was carried out. Multivariable logistic regression analysis and propensity score matching were used (1) to identify the risk factors for developing hypoglycemia (blood glucose < 60 mg/dL) after cardiac surgery and (2) to compare major morbidity, operative mortality, and actuarial survival between patients in whom hypoglycemia developed (n = 77) and those in whom it did not (n = 2461). The propensity score-adjusted sample included 61 patients in whom hypoglycemia developed and 305 patients in whom it did not (1 to 5 matching). Risk factors for hypoglycemia included female gender (odds ratio [OR] = 2.3, 95% confidence intervals [CI] = 1.4-3.7; P < .001), diabetes (OR = 2.8, CI = 1.7-4.5; P < .001), hemodialysis (OR = 3.0, CI = 1.3-6.8; P = .009), intraoperative blood product transfusion (OR = 2.0, CI = 1.2-3.4; P = .010), and earlier date of surgery (years of surgery, 2005-2007; OR = 2.1, CI = 1.2-3.7; P = .007) . Hypoglycemia increased the risk for operative mortality in univariate (hypoglycemic 10% vs normoglycemic patients 2%; P < .001) but not in propensity score- adjusted analysis (OR= 2.5, 0.9-6.7; P = .11). The propensity score-adjusted analysis demonstrated a significant increase in hemorrhage-related reexploration (P = .048), pneumonia (P < .001), reintubation (P < .001), prolonged ventilatory support (P < .001), hospital length of stay (P < .001), and intensive care unit length of stay (P < .001) for the hypoglycemic compared with normoglycemic patients. Five-year actuarial survival was similar in the compared patient groups (hypoglycemic 75% vs normoglycemic 75%; P = .22). Hypoglycemia with intensive insulin therapy is independently associated with increased risk for respiratory complications and prolonged hospital and intensive care unit lengths of stay after cardiac surgery. In our study, hypoglycemia was not independently associated with increased risk of death.


Synthesis and inhibitory activity of 4-alkynyl and 4-alkenylquinazolines: identification of new scaffolds for potent EGFR tyrosine kinase inhibitors.
The present study identified several 4-alkynyl and 4-alkenylquinazolines that serve as novel and potent EGFR tyrosine kinase inhibitors. The IC(50) values of these compounds are in the nanomolar range. In addition, the 4-(4-phenylbut-1-yn/en-yl)quinazolines provided scaffolds for potent enzyme inhibition. Chiral discrimination was observed to occur in one of the 4-alkynylquinazoline derivatives with the (R)-isomer being more than 150 times as potent as the (S)-isomer.


Phosphate utilization and alkaline phosphatase activity in Anacystis nidulans (Synechococcus).
Anacystis nidulans (Synechococcus) was maintained in a medium of low phosphate concentration (0.1 mM) and grew with a normal doubling time of 5 hrs at 30 degrees C. Such cultures had a normal pigment composition and alkaline phosphatase was detectable at low specific activities only. The onset of phosphate-limited growth occurred when the phosphate concentration in the medium fell to a value below 4 muM (the limit of accurate determination by the assay method used ) and resulted in increases in alkaline phosphatase activity, reaching a final 10 to 15 fold increase in specific activity after a period of several hours. Marked changes in the overall pigment composition occurred in this period of growth restriction. The addition of phosphate to such cultures resulted in a halt in synthesis of the enzyme and the restoration of normal pigmentation before growth resumed at the normal rate. Several oraganic phosphate esters could replace inorganic phosphate for growth and were also hydrolyzed by the partially purified enzyme, but growth rates were characteristically lower and the specific activity only 3 to 4 fold higher than in cultures grown in phosphate excess. Studies with the partially purified enzyme suggested that it differed in some of its properties from other alkaline phosphatases described in the literature.


Retrofascial nontuberculous psoas abscess.
Psoas abscess is usually associated with tuberculous spondylitis, but also occurs in relation to inflammatory bowel disease. We present 17 cases of primary pyogenic psoas abscess seen during a 10 year period at the King Fahd Hospital, Al-Khobar. There were 13 males and 4 females with a mean age of 24.9 years (range one to 55 years). Five patients had sickle cell disease. The average delay in presentation was 4.5 weeks (range 2 to 9 weeks). Pyrexia and a painful hip with a flexion deformity were the most obvious signs. The sedimentation rate and white cell count were markedly raised in every case. Staphylococci were cultured in 10 and anaerobic streptococci, salmonella and E coli in 2 each. Ultrasonography, CT and MR imaging were used to confirm the diagnosis. Early recognition and drainage are important to ensure a rapid recovery.


Activation of p21CIP1/WAF1 gene expression and inhibition of cell proliferation by overexpression of hepatocyte nuclear factor-4alpha.
The F9 murine embryonal carcinoma cell line provides an attractive system for studying epithelial differentiation and antiproliferative processes. We have recently established F9 cells expressing doxycycline-inducible hepatocyte nuclear factor (HNF)-4alpha and shown that HNF-4alpha triggers the gene expression of tight-junction molecules, occludin, claudin-6, and claudin-7, as well as formation of functional tight junctions and polarized epithelial morphology (Exp. Cell Res. 286, [2003] 288). Since these events were very similar to those induced by retinoids, we investigated whether HNF-4alpha, like retinoid receptors, was involved in the control of cell proliferation. We herein show that HNF-4alpha up-regulates expression of the p21 gene, but not the p15, p16, p18, p19, or p27 gene, in a p53-independent manner, and inhibits cell growth in F9 cells. Similar results were observed in rat lung endothelial cells, in which expression of HNF-4alpha is conditionally induced by doxycycline. Furthermore, we demonstrate, by reporter assay, that HNF-4alpha significantly elevates the transcriptional activity of the p21 promoter. Since, HNF-4alpha is expressed not only in the liver but also in organs containing epithelial cells, such as kidney, intestine, pancreas, and stomach, it might also play critical roles in the regulation of epithelial morphogenesis and proliferation in these organs.


Sclerostin Neutralizing Antibody Treatment Enhances Bone Formation but Does Not Rescue Mechanically Induced Delayed Healing.
During bone healing, tissue formation processes are governed by mechanical strain. Sost/sclerostin, a key Wnt signaling inhibitor and mechano-sensitive pathway, is downregulated in response to mechanical loading. Sclerostin neutralizing antibody (SclAb) increases bone formation. Nevertheless, it remains unclear whether sclerostin inhibition can rescue bone healing in situations of mechanical instability, which otherwise delay healing. We investigated SclAb's influence on tissue formation in a mouse femoral osteotomy, stabilized with rigid or semirigid external fixation. The different fixations allowed different magnitudes of interfragmentary movement during weight bearing, thereby influencing healing outcome. SclAb or vehicle (veh) was administeredand bone healing was assessed at multiple time points up to day 21 postoperatively by in vivo micro-computed tomography, histomorphometry, biomechanical testing, immunohistochemistry, and gene expression. Our results show that SclAb treatment caused a greater bone volume than veh. However, SclAb could not overcome the characteristic delayed healing of semirigid fixation. Indeed, semirigid fixation resulted in delayed healing with a prolonged endochondral ossification phase characterized by increased cartilage, lower bone volume fraction, and less bony bridging across the osteotomy gap than rigid fixation. In a control setting, SclAb negatively affected later stages of healing under rigid fixation, evidenced by the high degree of endosteal bridging at 21 days in the rigid-SclAb group compared with rigid-veh, indicating delayed fracture callus remodeling and bone marrow reconstitution. Under rigid fixation, Sost and sclerostin expression at the gene and protein level, respectively, were increased in SclAb compared with veh-treated bones, suggesting a negative feedback mechanism. Our results suggest that SclAb could be used to enhance overall bone mass but should be carefully considered in bone healing. SclAb may help to increase bone formation early in the healing process but not during advanced stages of fracture callus remodeling and not to overcome delayed healing in semirigid fixation. © 2018 American Society for Bone and Mineral Research.


Contrasting adaptive genetic consequences of stream insects under changing climate.
Freshwater biodiversity undergoes degradation due to climate change. Researchers have inferred the effects of climate change on neutral genetic diversity, assuming the fixed spatial distributions of alleles. However, the adaptive genetic evolution of populations that may change the spatial distribution of allele frequencies along environmental gradients (i.e., evolutionary rescue) have largely been overlooked. We developed a modeling approach that projects the comparatively adaptive and neutral genetic diversities of four stream insects, using empirical neutral/ putative adaptive loci, ecological niche models (ENMs), and a distributed hydrological-thermal simulation at a temperate catchment under climate change. The hydrothermal model was used to generate hydraulic and thermal variables (e.g., annual current velocity and water temperature) at the present and the climatic change conditions, projected based on the eight general circulation models and the three representative concentration pathways scenarios for the two future periods (2031-2050, near future; 2081-2100, far future). The hydraulic and thermal variables were used for predictor variables of the ENMs and adaptive genetic modeling based on machine learning approaches. The increases in annual water temperature in the near- (+0.3-0.7 °C) and far-future (+0.4-3.2 °C) were projected. Of the studied species, with different ecologies and habitat ranges, Ephemera japonica (Ephemeroptera) was projected to lose rear-edge habitats (i.e., downstream) but retain the adaptive genetic diversity owing to evolutionary rescue. In contrast, the habitat range of the upstream-dwelling Hydropsyche albicephala (Trichoptera) was found to remarkably decline, resulting in decreases in the watershed genetic diversity. While the other two Trichoptera species expanded their habitat ranges, the genetic structures were homogenized over the watershed and experienced moderate decreases in gamma diversity. The findings emphasize the evolutionary rescue potential, depending on the extent of species-specific local adaptation.


An assessment of the potency related to Cannabis-based products in the South African market.
It was the aim of this study to analyse a portion of the South African cannabis-based products market and provide a detailed overview of their THC and CBD profiles. To date, no data of this kind exists in South Africa. Samples were submitted to a contract laboratory. A total of 840 samples were analysed in duplicate (1680 datapoints in total) and reported in an anonymous format. Samples were categorised into 7 different types: Edible, Extract, Infusion, Liquid, Other, Plant material, and Solid. Each category was divided into the following weight by percentage concentration levels:<0.1 wt.-%, 0.1 wt.-% to 1 wt.-% and finally>1 wt.-%. Both HPLC-UV, as well as, GC-MS was employed for analysis with the datasets combined. The results indicated that high amounts of THC are present in most of the cannabis-based products in South Africa. This is of concern due to the health implications of these products, and the current South African legislation related to CBD and THC. Medicines and controlled substance regulators as well as the South African public will be informed about the current state of cannabis-based products in South Africa.


EWI2 and its relatives in Tetraspanin-enriched membrane domains regulate malignancy.
Experimental studies on immunoglobulin superfamily (IgSF) member EWI2 reveal that it suppresses a variety of solid malignant tumors including brain, lung, skin, and prostate cancers in animal models and inhibits tumor cell movement and growth in vitro. While EWI2 appears to support myeloid leukemia in mouse models and maintain leukemia stem cells. Bioinformatics analyses suggest that EWI2 gene expression is downregulated in glioblastoma but upregulated in melanoma, pancreatic cancer, and liver cancer. The mechanism of action for EWI2 is linked to its inhibition of growth factor receptors and cell adhesion proteins through its associated tetraspanin-enriched membrane domains (TEMDs), by altering the cell surface clustering and endolysosome trafficking/turnover of these transmembrane proteins. Recent studies also show that EWI2 modulates the nuclear translocation of ERK and TFEB to change the activities of these gene expression regulators. For EWI2 relatives including FPRP, IgSF3, and CD101, although their roles in malignant diseases are not fully clear and remain to be determined experimentally, FPRP and IgSF3 likely promote the progression of solid malignant tumors while CD101 seems to modulate immune cells of tumor microenvironment. Distinctive from other tumor regulators, the impacts of EWI subfamily members on solid malignant tumors are likely to be context dependent. In other words, the effect of a given EWI subfamily member on a tumor probably depends on the molecular network and composition of TEMDs in that tumor. Collectively, EWI2 and its relatives are emerged as important regulators of malignant diseases with promising potentials to become anti-cancer therapeutics and cancer therapy targets.


The utility of routine pouchogram before ileostomy reversal in children and adolescents following ileal pouch anal anastomosis.
Pouchograms are used to assess the integrity of the ileal pouch anal anastomosis (IPAA) in patients who have undergone restorative proctocolectomy. Its benefits have been questioned, and there are no data to support the routine use in children. We retrospectively reviewed the charts of 26 patients who had an IPAA and pouchogram at our institution between 2001 and 2009. Each patient also underwent an examination under anesthesia to assess the integrity of the IPAA on the day of the ileostomy closure. The mean age of the patients was 13.8 (± 0.7) years. The pouchogram was performed at a median of 6 weeks after the IPAA (range, 4-20 weeks). The findings were normal in 26 (89.7%) and demonstrated stricture in 2 (6.9%) and leak in 1 (3.4%). History was suggestive and physical examination was confirmatory in these 3 problematic cases. A contrast enema is not routinely required to evaluate the integrity of the IPAA before ileostomy reversal in pediatric patients. Complications can be detected by history and rectal examination before ileostomy closure. We recommend the use of contrast enema only in symptomatic patients where a leak is suspected, thereby limiting radiation exposure and inconvenience.


Competition between chemoattractants causes unexpected complexity and can explain negative chemotaxis.
Negative chemotaxis, where eukaryotic cells migrate away from repellents, is important throughout biology, for example, in nervous system patterning and resolution of inflammation. However, the mechanisms by which molecules repel migrating cells are unknown. Here, we use predictive modeling and experiments with Dictyostelium cells to show that competition between different ligands that bind to the same receptor leads to effective chemorepulsion. 8-CPT-cAMP, widely described as a simple chemorepellent, is inactive on its own and only repels cells when it acts in combination with the attractant cAMP. If cells degrade either competing ligand, the pattern of migration becomes more complex; cells may be repelled in one part of a gradient but attracted elsewhere, leading to populations moving in different directions in the same assay or converging in an arbitrary place. More counterintuitively still, two chemicals that normally attract cells can become repellent when combined. Computational models of chemotaxis are now accurate enough to predict phenomena that have not been anticipated by experiments. We have used them to identify new mechanisms that drive reverse chemotaxis, which we have confirmed through experiments with real cells. These findings are important whenever multiple ligands compete for the same receptors.


Concurrent destruction strategy: NaNO2-catalyzed, trichlorophenol-coupled degradation of p-nitrophenol using molecular oxygen.
Oxidative degradation of p-nitrophenol (PNP) was investigated with NaNO(2) as the catalyst and dioxygen as the oxidizing agent in the presence of trichlorophenol (TCP). Although degradation of PNP alone was proved to be inefficient toward the NaNO(2)-mediated oxidative degradation system, when PNP in combination with TCP was used as the substrate, NaNO(2) showed relatively high catalytic activity for eradicating both PNP and TCP with molecular oxygen. Reaction conditions to the degradation system, e.g., temperatures, reaction time, pH, NaNO(2) and TCP concentrations were optimized. PNP could be highly efficiently degraded in the NaNO(2)/TCP/O(2) system (more than 99% removal for PNP) and the TOC removal of the mixture of PNP and TCP could reach 71% at 150 degrees C, 0.5 MPa oxygen pressure. Degradation products were determined, and 93% carbon atom was clarified. A plausible overall mechanism for the formation of active species is described, in which peroxylnitrite was believed to be a dominating active intermediate being responsible for destroying the substrates, PNP and TCP. The novel NaNO(2)-based concurrent oxidation system for PNP and TCP provides a potential application in treatment of multi-component industrial effluents.


The effects of potentiality education on potentiality and job satisfaction among psychiatric nurses in Taiwan.
This study evaluated the effects of a potentiality education program on potentiality and job satisfaction among psychiatric nurses. This quasiexperimental study recruited 59 psychiatric nurses, of whom 26 were assigned to an experimental group, based on their interest in participating in the program, and 33 to a control group. The results indicated that the scores for job satisfaction were significantly higher in the experimental group than in the control group. Specifically, potentiality education promoted job satisfaction but had no significant influence on potentiality. PRACTICE APPLICATION: Increasing nurses' potentiality could help them to successfully cope with their large workload and the various challenges of their job.


LncRNA LINC00470 promotes proliferation through association with NF45/NF90 complex in hepatocellular carcinoma.
Increasing evidence demonstrates that long noncoding RNAs (lncRNAs) play an important role in the development and progression of human cancers. LncRNA LINC00470 has been reported to function as an oncogene in glioblastoma. Until now, the roles and underlying mechanisms of LINC00470 in the progression of hepatocellular carcinoma (HCC) remain unclear. Here, we found that LINC00470 was upregulated in HCC cells and tissues. High-level LINC00470 was significantly correlated with bigger tumor size, advanced TNM stage and poor prognosis in patients with HCC. Functional studies showed that knockdown of LINC00470 expression inhibited HCC cell proliferation and cell cycle progression, while overexpression of LINC00470 showed the opposite effects. Further investigation suggested that LINC00470 was associated with NF45/NF90 complex and increased its interaction with cyclin E1 mRNA, thus inhibiting the degradation of cyclin E1 mRNA. Additionally, knockdown of cyclin E1 in LINC00470-overexpressed cells abolished its promotive effects on HCC cell proliferation. In summary, our findings suggest that targeting LINC00470 could be a potential therapeutic approach in treating HCC patients.


Model of pattern formation in marsh ecosystems with nonlocal interactions.
Smooth cordgrass Spartina alterniflora is a grass species commonly found in tidal marshes. It is an ecosystem engineer, capable of modifying the structure of its surrounding environment through various feedbacks. The scale-dependent feedback between marsh grass and sediment volume is particularly of interest. Locally, the marsh vegetation attenuates hydrodynamic energy, enhancing sediment accretion and promoting further vegetation growth. In turn, the diverted water flow promotes the formation of erosion troughs over longer distances. This scale-dependent feedback may explain the characteristic spatially varying marsh shoreline, commonly observed in nature. We propose a mathematical framework to model grass-sediment dynamics as a system of reaction-diffusion equations with an additional nonlocal term quantifying the short-range positive and long-range negative grass-sediment interactions. We use a Mexican-hat kernel function to model this scale-dependent feedback. We perform a steady state biharmonic approximation of our system and derive conditions for the emergence of spatial patterns, corresponding to a spatially varying marsh shoreline. We find that the emergence of such patterns depends on the spatial scale and strength of the scale-dependent feedback, specified by the width and amplitude of the Mexican-hat kernel function.


Cerebral blood flow, metabolic rate, and cross-brain oxygen consumption in brain injury.
In six deeply comatose children, the relationships of intracranial pressure, cerebral perfusion pressure, cerebral blood flow, cross-brain oxygen consumption, and metabolic rate to outcome were studied sequentially during therapy. Intracranial pressure, cross-brain oxygen consumption, and metabolic rate values were significantly different in the three children who survived compared with those in the three who died. The differences in cross-brain oxygen consumption and metabolic rate occurred in the presence of clinically acceptable values for intracranial and cerebral perfusion pressures. Cross-brain oxygen consumption and metabolic rate may be important indicators of degree of neuronal injury, and of outcome.


False-positive imaging of In-111 labeled monoclonal antibody conjugate CYT-103 in a patient with metastatic colorectal carcinoma.
In-111 satumomab whole-body imaging is used in the evaluation of patients with colorectal carcinoma. The authors report a case of false-positive In-111 localization in a nonfunctional adrenal adenoma in a patient with metastatic colon carcinoma.


Diagnostic potential of salivary interleukin-17, RANKL, and OPG to differentiate between periodontal health and disease and discriminate stable and unstable periodontitis: A case-control study.
Limitations of the conventional diagnostic techniques urged researchers to seek novel methods to predict, diagnose, and monitor periodontal disease. Use of the biomarkers available in oral fluids could be a revolutionary surrogate for the manual probing/diagnostic radiograph. Several salivary biomarkers have the potential to accurately discriminate periodontal health and disease. This study aimed to determine the diagnostic sensitivity and specificity of salivary interleukin (IL)-17, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), RANKL/OPG for differentiating (1) periodontal health from disease and (2) stable and unstable periodontitis. Participants with periodontitis (n = 50) and gingivitis (n = 25), both diseases represented the cases, and subjects with healthy periodontium (n = 15) as a control were recruited for this study. Periodontitis cases were further equally subdivided into stable and unstable. Whole unstimulated salivary sample were collected from all participants. Periodontal parameters including bleeding on probing, probing pocket depth, clinical attachment loss, and number of missing teeth were recorded. The protein levels of salivary IL-17, RANKL, and OPG were determined by using enzyme-linked immunosorbent assays technique. Salivary IL-17, OPG, RANKL, and RANKL/OPG showed high sensitivity and specificity to differentiate periodontal health from gingivitis and periodontitis. Similar pattern was observed in discriminating stable and unstable periodontitis. Salivary IL-17 and RANKL showed a good accuracy to differentiate gingivitis from periodontitis. However, OPG and RANKL/OPG did not exhibit enough sensitivity and specificity to differentiate the latter conditions. Salivary IL-17, RANKL, OPG, and RANKL/OPG system are potential candidates for differentiating periodontal health and disease and discriminate stable and unstable periodontitis.


Young men who have sex with men's awareness, acceptability, and willingness to participate in HIV vaccine trials: Results from a nationwide online pilot study.
New cases of human immunodeficiency virus (HIV) among young men who have sex with men (YMSM) underscore the need to examine their willingness to use biomedical prevention methods, including an acceptable and efficacious HIV vaccine. We examined whether YMSM's vaccine altruism and vaccine-related socials concerns factors were associated with HIV vaccine acceptability across two vaccine efficacy scenarios, and their awareness and willingness to participate in HIV vaccine research. This secondary analysis uses data from a mHealth trial with YMSM at heightened HIV risk (N = 137; 50% racial/ethnic minority; M = 21.7 years). Most YMSM (91.2%) had tested for HIV, and 17.5% (N = 24) reported a prior STI.We used paired-samples t-test to compare differences in efficacy acceptability (50% vs 85%), followed by multivariable regressions examining whether vaccine attitudes (altruism and social concerns) were associated with vaccine acceptability and awareness and willingness to participate in HIV vaccine trials. We controlled for age, education, race/ethnicity, prior HIV testing, and STI diagnosis in our analyses. Acceptability for the HIV vaccine with 85% efficacy (M = 8.86; SD = 1.76) was greater than acceptability in the 50% efficacy scenario (M = 7.60; SD = 2.58). Altruistic attitudes were associated with greater vaccine acceptability at 50% (β = 0.62) and 85% (β = 0.59) efficacy. Higher educational attainment was negatively associated with a vaccine with 50% efficacy (β = -0.20, but not for 85% efficacy. Greater vaccine-related social concerns were negatively associated with HIV vaccine research awareness (AOR = 0.38 (95% CI: 0.22, 0.67). Willingness to participate in a HIV vaccine trial was positively associated with age (β = 0.18) and altruism (β = 0.60), and negatively associated with education (β = -0.21). YMSM find HIV vaccines as an acceptable prevention modality and are willing to participate in HIV vaccine trials. Findings highlight the need to consider YMSM's altruistic and social concerns attitudes in HIV vaccine research and explore how to leverage these attitudes in research campaigns. ClinicalTrials.gov Identifier: NCT02842060.


Intestinal cholesterol embolism resulting from intra-aortic balloon pumping: a case report.
Intra-aortic balloon pumping is used in elective percutaneous coronary intervention for increasing coronary blood flow. However, intra-aortic balloon pumping may decrease visceral blood flow and cause mesenteric ischemia by visceral artery obstruction. We report the case of a 79-year-old Asian man in whom elective percutaneous coronary intervention was performed with intra-aortic balloon pumping. He died from mesenteric ischemia 25 hours after the procedure. Microscopic findings showed that intra-aortic balloon pumping had detached the aortic plaque, breaking it into systemic emboli, leading to subsequent intestinal ischemia and necrosis. We conclude that intra-aortic balloon pumping can cause an intestinal cholesterol embolism.


IL-17A promotes the migration and invasiveness of cervical cancer cells by coordinately activating MMPs expression via the p38/NF-κB signal pathway.
IL-17A plays an important role in many inflammatory diseases and cancers. We aimed to examine the effect of IL-17A on the invasion of cervical cancer cells and study its related mechanisms. Wound healing and matrigel transwell assays were used to examine the effect of IL-17A on cervical cancer cell migration and invasion by a panel of cervical cancer cell lines. The levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) were investigated using western blotting. The activity of p38 and nuclear factor-kappa B (NF-κB) signal pathway was detected too. Here, we showed that IL-17A could promote the migration and invasion of cervical cancer cells. Further molecular analysis showed that IL-17A could up-regulate the expressions and activities of MMP2 and MMP9, and down-regulate the expressions of TIMP-1 and TIMP-2. Furthermore, IL-17A also activates p38 signal pathway and increased p50 and p65 nuclear expression. In addition, treatment of cervical cancer cells with the pharmacological p38/NF-κB signal pathway inhibitors, SB203580 and PDTC, potently restored the roles of invasion and upregulation of MMPs induced by IL-17A. IL-17A could promote the migration and invasion of cervical cancer cell via up-regulating MMP2 and MMP9 expression, and down-regulating TIMP-1 and TIMP-2 expression via p38/NF-κB signal pathway. IL-17A may be a potential target to improve the prognosis for patients with cervical cancer.


Repeated Exposure to High-THC Cannabis Smoke during Gestation Alters Sex Ratio, Behavior, and Amygdala Gene Expression of Sprague Dawley Rat Offspring.
Because of the legalization of Cannabis in many jurisdictions and the trend of increasing Δ9-tetrahydrocannabinol (THC) content in Cannabis products, an urgent need exists to understand the impact of Cannabis use during pregnancy on fetal neurodevelopment and behavior. To this end, we exposed female Sprague Dawley rats to Cannabis smoke daily from gestational day 6 to 20 or room air. Maternal reproductive parameters, offspring behavior, and gene expression in the offspring amygdala were assessed. Body temperature was decreased in dams following smoke exposure and more fecal boli were observed in the chambers before and after smoke exposure in dams exposed to smoke. Maternal weight gain, food intake, gestational length, litter number, and litter weight were not altered by exposure to Cannabis smoke. A significant increase in the male-to-female ratio was noted in the Cannabis-exposed litters. In adulthood, male and female Cannabis smoke-exposed offspring explored the inner zone of an open field significantly less than control offspring. Gestational Cannabis smoke exposure did not affect behavior on the elevated plus maze test or social interaction test in the offspring. Cannabis offspring were better at visual pairwise discrimination and reversal learning tasks conducted in touchscreen-equipped operant conditioning chambers. Analysis of gene expression in the adult amygdala using RNA sequencing revealed subtle changes in genes related to development, cellular function, and nervous system disease in a subset of the male offspring. These results demonstrate that repeated exposure to high-THC Cannabis smoke during gestation alters maternal physiological parameters, sex ratio, and anxiety-like behaviors in the adulthood offspring.


Parenteral Copper Administration at the Beginning of a Fixed-Time Artificial Insemination Protocol in Beef Cattle: Effect on Ovarian Function and Pregnancy Rates.
The aim of this study was to evaluate the association between plasma copper (Cu) concentration and ovarian function during a fixed-time artificial insemination (FTAI) protocol and the effect of parenteral Cu administration (100 mg) at the start of such protocol (day 0) on area of preovulatory follicle (APF); area of corpus luteum (ACL), plasma estradiol (E2), and progesterone (P4) concentrations; CL blood flow (CLBF); and pregnancy rate in beef heifers and cows. In cows, plasma Cu concentration on days 0 and 7 correlated positively with APF. Copper administration increased plasma Cu concentration and decreased APF and plasma E2 concentration (day 9), without modifying ACL, plasma P4 concentration, and CLBF (day 16) in cows. Pregnancy rate was higher in Cu-supplemented cattle on day 41 after FTAI as compared with controls (58.76 and 45.28%, respectively). In conclusion, Cu administration at the beginning of the FTAI protocol increased pregnancy rate in beef heifers and cows, modifying APF and plasma E2 concentration in the latter.


Chinese school adolescents' stress experience and coping strategies: a qualitative study.
Stress in adolescence is associated with adverse mental health outcomes. Coping resources have been proved by literature to have buffering effects on the impact of stress on mental health. It is imperative to understand the stress and coping strategies of adolescents. However, to date, there has been a scarce of qualitative examination of stress and coping strategies in adolescents in a Chinese population. This study aimed to understand the stress experience and coping strategies of high school students in China. This study adopted a qualitative design involving three focus group interviews. A purposive sampling method was used to recruit high school students who were enrolled in grades 10 to 11, and their teachers, at a Chinese high school which resulted in 20 students and 9 teacher participants. Data were analysed using inductive thematic analysis. A total of 4 themes were identified: (i) sources of stress; (ii) impacts of stress (iii) coping strategies used by students; and (iv) recommendations for stress management programs. Students experienced excessive stress in their daily lives. The primary source of stress came from high expectations for academic achievement. Other sources of stress were peer relationships and family issues. The stress had negative impacts on students' emotions, sleep, study, and mental wellbeing. The students demonstrated various coping strategies, with the most common being avoidant coping. Students and teachers agreed that the coping strategies were not effective in reducing stress in the long run and that more coping skills training was needed. This study is the first to assess the perceptions of Chinese high school students and their teachers regarding adolescent stress experiences and coping strategies. Chinese high school students experienced significant stress in their daily lives and demonstrated unhelpful coping strategies. Participants demonstrated consensus that they did not have the skills to cope. There is a demonstrated need for interventions that focus on increasing coping skills in this population.


The usefulness of the Revised Psychoeducational Profile for the assessment of preschool children with pervasive developmental disorders.
Data from the Psychoeducational Profile-Revised (PEP-R) were analysed in a sample of 46 children, aged from 1.7 to 5.11 years, of whom 21 had autistic disorder (AD) and 25 had pervasive developmental disorder not otherwise specified (PDD-NOS). Analysis with a t-test for independent samples revealed a significant difference (p < 0.05) between children with AD and those with PDD-NOS on both developmental and behavioural PEP-R scales, supporting the utility of the PEP-R in discriminating between two diagnostic groups. This study emphasizes the effectiveness of the PEP-R as a tool for the early assessment of children with pervasive developmental disorders.


The connection between language and the world: a paradox of the linguistic turn?
Alex Gillespie and Flora Cornish draw on the dialogic turn as they consider that, in order to interpret the meaning of an utterance, it is necessary to emphasize its contextual nature. Among other aspects, they address what context is and what is being done while speaking. Taking these two issues as point of departure, it is worth pondering on (1) what revolves around language and what the status of nonlinguistic semiotic systems is for the philosophers of language, (2) Umberto Eco's critique of the Philosophy of Language, which has not problematized the pre-linguistic relationship with things, and (3) how ontogenesis may shed light on this scheme where linguistic and nonlinguistic aspects are inevitably interrelated. I will reflect on the pragmatic aspects in adult-child communication at its pre-linguistic level. I will underscore the key role played by the object as a complex referent and as a tool for communication.


In-hospital outcome of post-cardiotomy extracorporeal life support in adult patients: the 2007-2017 Maastricht experience.
The use of post-cardiotomy extracorporeal life support (PC-ECLS) has increased worldwide over the past years but a concurrent decrease in survival to hospital discharge has also been observed. We analysed use and outcome of PC-ECLS at the Maastricht University Medical Center. A retrospective study of a single-centre PC-ECLS cohort. Patient characteristics and in-hospital outcomes were evaluated. Patients who underwent PC-ECLS due to intra- or peri-operative cardiogenic shock or cardiac arrest were included. Descriptive statistics were analysed and frequency analysis and testing of group differences were performed. Eighty-six patients who received PC-ECLS between October 2007 and June 2017 were included. The mean age of the population was 65 years (range, 31-86 years), and 65% were men. Survival rates were calculated and PC-ECLS management data and complications were assessed. Pre-ECLS procedures were isolated coronary artery bypass grafting (CABG) (22%), isolated valve surgery (16%), thoracic aorta surgery (4%), a combination of CABG and valve surgery (21%) or other surgery (24%). PC-ECLS was achieved via central cannulation in 17%, peripheral cannulation in 65%, or by a combination in 17%. The median duration of PC-ECLS was 5.0 days (IQR, 6.0 days). Weaning was achieved in 49% of patients, and 37% survived to discharge. Post-operative bleeding (overall rate, 42%) showed a trend towards a reduced rate over more recent years. Our experience confirms an increased use of PC-ECLS during the last 10 years and shows that, by carefully addressing patient management and complications, survival rat e may be satisfactory, and improved outcome may be achieved in such a challenging ECLS setting.


The structure and function of catalytic domains within inositol polyphosphate 5-phosphatases.
Phosphoinositide signaling pathways regulate many essential cellular functions including proliferation, differentiation and survival, cytoskeletal organization, and vesicular trafficking. The inositol polyphosphate 5-phosphatases regulate the cellular levels of several bioactive phosphoinositide species. This review describes the structure and function of the 5-phosphatase and Sac1 catalytic domains of these enzymes. The crystal structure of the 5-phosphatase domain has been solved and shares homology with members of the AP endonuclease family. The phosphoinositide polyphosphatase activity of the Sac1 domain, found in some inositol polyphosphate 5-phosphatases, is defined by a motif, CX5 R(T/S), also found in both protein and lipid phosphatases.


The effect of COVID-19-related school closures on students' well-being: Evidence from Danish nationwide panel data.
We study the effect of the temporary closure of Danish schools as a result of the COVID-19 pandemic in spring 2020 on students' reported levels of well-being and test whether the effect varies among students of different socioeconomic status. To this end, we draw on panel data from the mandatory annual nationwide Danish Student Well-being Survey (DSWS) and exploit random variation in whether students answered the 2020 survey before or during the spring lockdown period. This enables us to compare reported levels of student well-being for selected measures - whether students "like school" and whether they "feel lonely" - among students in grades 6-9 to their responses from previous years. We use an event-study design with individual as well as year, month, and grade fixed effects. Our results indicate, firstly, that students' well-being with respect to liking school improved during the lockdown, even if students who answered during vs. before the lockdown were not on parallel trends in terms of previous levels of reported well-being. Secondly, school closures seemed to not affect students' reported levels of loneliness. Thirdly, the spring lockdown might have had a more positive impact among students of lower socioeconomic status.


Aerosolized Beractant in neonatal respiratory distress syndrome: A randomized fixed-dose parallel-arm phase II trial.
There is increasing research into novel techniques of administering surfactant to preterm infants (PTIs) with respiratory distress syndrome (RDS) receiving non-invasive respiratory support (NIRS). Although aerosolized surfactant (AS) is promising in PTIs receiving NIRS, the optimal surfactant dose and formulation, drug-device combination and patient profile is not known. The objective of this randomized clinical trial was to investigate the feasibility, safety, efficacy and impact of four dosing schedules of AS using two nebulizers in PTIs with RDS stratified by gestational age (GA). PTIs with RDS receiving pre-defined NIRS for ≤8 h were assigned to 4 A S dosing schedules and 2 nebulizers within three GA strata (I = 240/7-286/7, II = 290/7-326/7, III = 330/7-366/7 weeks). There was no contemporaneous control group; at the recommendation of the Data Monitoring Committee, data was collected retrospectively for control infants. Of 149 subjects that received AS, the median age at initiation of the 1st dose and duration was 5.5 and 2.4 h respectively. There were 29 infants in stratum I, and 60 each in strata II and III. Of infants <32 weeks GA, 94% received caffeine prior to AS. Fifteen infants (10%) required intubation within 72 h; the rates were not significantly different between GA strata, dosing schedules and nebulizers for infants who received aerosolized surfactant. Compared to retrospective controls, infants who received AS were less likely to need intubation within 72 h in both the intention-to-treat (32% vs. 11%) and the per-protocol (22% vs. 10%) analyses (p < 0.05) with GA stratum specific differences. AS was well tolerated by infants and clinical caregivers. Commonest adverse events included surfactant reflux from nose and mouth (18%), desaturations (11%), and increased secretions (7%). We have demonstrated the feasibility, absence of serious adverse events and short-term efficacy of four dosing schedules of AS in the largest Phase II clinical trial of PTIs 24-36 weeks' GA with RDS receiving NIRS (ClinicalTrials.gov NCT02294630). The commonest adverse events noted were surfactant reflux and desaturations; no serious adverse effects were observed. Infants who received AS were less likely to receive intubation within 72 h compared to historical controls. AS is a promising new therapy for PTIs with RDS.


Pain perception: modification of threshold of intolerance and cortical potentials by cutaneous stimulation.
Cutaneous electrical stimulation temporarily raises the threshold of intolerance for pain elicited by electric shock. Similar stimulation suppresses the somatosensory cortical evoked potential.


Epstein-Barr Virus Infection in the Development of Neurological Disorders.
Epstein-Barr Virus (EBV) is a ubiquitous human herpesvirus that contributes to the etiology of diverse human cancers and auto-immune diseases. EBV establishes a relatively benign, long-term latent infection in over 90 percent of the adult population. Yet, it also increases risk for certain cancers and auto-immune disorders depending on complex viral, host, and environmental factors that are only partly understood. EBV latent infection is found predominantly in memory B-cells, but the natural infection cycle and pathological aberrations enable EBV to infect numerous other cell types, including oral, nasopharyngeal, and gastric epithelia, B-, T-, and NK-lymphoid cells, myocytes, adipocytes, astrocytes, and neurons. EBV infected cells, free virus, and gene products can also be found in the CNS. In addition to the direct effects of EBV on infected cells and tissue, the effect of chronic EBV infection on the immune system is also thought to contribute to pathogenesis, especially auto-immune disease. Here, we review properties of EBV infection that may shed light on its potential pathogenic role in neurological disorders.


Prediction of Portal Vein Thrombosis Following Hepatectomy for Perihilar Cholangiocarcinoma: Efficacy of Postoperative Portal Vein Diameter Ratio and Angle.
Portal vein thrombosis (PVT) is a life-threatening complication after hepatectomy. However, the relationship between postoperative PVT and morphometric features of the PV has not been fully elucidated yet. A total of 81 patients who underwent hepatectomy for perihilar cholangio-carcinoma (PHCC) were studied. We investigated the diameters and angles of PV using pre- and postoperative computed tomography (CT) reconstructed by SYNAPSE VINCENT®. The incidence of PVT after hepatectomy was 11.1%. There were significant differences with respect to the remnant liver PV diameter (p=0.015), the diameter ratio (p=0.001), and the postoperative PV angle (p=0.001) between patients with and without PVT. Multivariate analysis revealed that a postoperative PV angle of less than 90° (p=0.008) and a diameter ratio of less than 45% (p=0.041) were independent risk factors for PVT. A postoperative PV angle of less than 90° and diameter ratio of less than 45% eventually lead to PVT after hepatectomy for PHCC.


Exploring a Fused 2-(Thiophen-2-yl)thieno[3,2-b]thiophene (T-TT) Building Block to Construct n-Type Polymer for High-Performance All-Polymer Solar Cells.
In the field of all-polymer solar cells, exploring new electron-donating units (D) to match with electron-accepting units (A) is an important subject to promote the performance of D-A-type polymer acceptors. Herein, we developed a fused D unit 2-(thiophen-2-yl)thieno[3,2-b]thiophene (T-TT) derivated from the famous 2-(2-(thiophen-2-yl)vinyl)thiophene (TVT) unit. With classical naphthalene diimide (NDI) as A unit, the new D-A polymer PNDI-T-TT exhibits enhanced absorption coefficient, electron mobility, and miscibility with donor polymer in comparison with the analogous PNDI-TVT polymer. These advantages can be attributed to the enlarged conjugation and reduced rotamers due to the fused T-TT unit, leading to a stronger intermolecular interaction. When blending with the donor polymer PBDB-T, both NDI-based polymers can form better interpenetrating nanostructures than the corresponding blend films with the donor polymer J71. Finally, PBDB-T/PNDI-T-TT device achieves a power conversion efficiency of 6.1%, which is much higher than that of PBDB-T/PNDI-TVT device (4.24%). These results demonstrate that n-type polymer based on fused T-TT unit can ameliorate the absorption coefficient, molecular aggregation, and charge-carrier mobility and consequently achieve an improved photovoltaic performance in comparison with the classic TVT unit.


Physiological articular contact kinematics and morphological femoral condyle translations of the tibiofemoral joint.
The changes of tibiofemoral articular cartilage contact locations during knee activities represent a physiological functional characteristic of the knee. However, most studies reported relative motions of the tibia and femur using morphological flexion axes. Few data have been reported on comparisons of morphological femoral condyle motions and physiological tibiofemoral cartilage contact location changes. This study compared the morphological and physiological kinematic measures of 20 knees during an in vivo weightbearing single leg lunge from full extension to 120° of flexion using a combined MRI and dual fluoroscopic imaging system (DFIS) technique. The morphological femoral condyle motion was measured using three flexion axes: trans-epicondylar axis (TEA), geometric center axis (GCA) and iso-height axis (IHA). At low flexion angles, the medial femoral condyle moved anteriorly, opposite to that of the contact points, and was accompanied with a sharp increase in external femoral condyle rotation. At 120° of flexion, the morphological measures of the lateral femoral condyle were more posteriorly positioned than those of the contact locations. The data showed that the morphological measures of femoral condyle translations and axial rotations varied with different flexion axes and did not represent the physiological articular contact kinematics. Biomechanical evaluations of the knee joint motion should include both morphological and physiological kinematics data to accurately demonstrate the functionality of the knee.


In situ boron-doped cellulose-based biochar for effective removal of neonicotinoids: Adsorption mechanism and safety evaluation.
Biochar materials have been widely employed for adsorption of pollutants, which necessitates further consideration of their efficiency and safety in environmental remediation. In this study, a porous biochar (AC) was prepared through the combination of hydrothermal carbonization and in situ boron doping activation to effectively adsorb neonicotinoids. The adsorption process was shown to be a spontaneous endothermic physical adsorption process, where the predominant interaction forces between the acetamiprid and AC were electrostatic and hydrophobic interactions. The maximum adsorption capacity was 227.8 mg g-1for acetamiprid and the safety of AC was verified by simulating the situation where the aquatic organism (D. magna) was exposed to the combined system (AC & neonicotinoids). Interestingly, AC was observed to reduce the acute toxicity of neonicotinoids owing to the reduced bioavailability of acetamiprid in D. magna and the newly generated expression of cytochrome p450. Thus, it enhanced the metabolism and detoxification response in D. magna, which reducing the biological toxicity of acetamiprid. This study not only demonstrates the potential application of AC from a safety perspective, but also provides insight into the combined toxicity caused by biochar after adsorption of pollutants at the genomic level, which fills the gap in related research.


[Calcific uremic arteriolopathy. a case report and review of the literature].
Calcific uremic arteriolopathy is defined as a syndrome consisting of ischemic skin ulceration due to calcification of the wall of the arterioles of the subcutaneous tissue as a result of hyperparathyroidism in uremic patients. A 55-year old female patient, hypertense, with heart failure and kidney failure treated with hemodialysis, who presented lower limb pain and hypercalcemia. On physical examination, skin lesions with symmetrical peripheral pulses present in the limbs. Laboratory tests revealed hypercalcemia, hyperphosphatemia, and very high parathyroid hormone levels. Parathyroidectomy was performed and biopsy of skin lesions, the patient having a torpid course causing exitus. Autopsy was performed, with histologic features characteristic of calcific uremic arteriolopathy. Calcific calcium uremic arteriolopathy or calciphylaxis is a complex and variable disease that is difficult to diagnose and whose treatment is complicated. Despite the efforts of the investigators, there are still many questions regarding its pathogenesis. This acts as an incentive for further research to establish the most appropriate actions to take to maintain an adequate quality of life for the patients and avoid complications that trigger death in some cases.


Does age matter? - A MRI study on peritumoral edema in newly diagnosed primary glioblastoma.
Peritumoral edema is a characteristic feature of malignant glioma related to the extent of neovascularisation and to vascular endothelial growth factor (VEGF) expression.The extent of peritumoral edema and VEGF expression may be prognostic for patients with glioblastoma. As older age is a negative prognostic marker and as VEGF expression is reported to be increased in primary glioblastoma of older patients, age-related differences in the extent of peritumoral edema have been assessed. In a retrospective, single-center study, preoperative magnetic resonance imaging (MRI) scans of steroid-naïve patients (n = 122) of all age groups were analysed. Patients with clinically suspected, radiologically likely or known evidence of secondary glioblastoma were not included.Extent of brain edema was determined in a metric quantitative fashion and in a categorical fashion in relation to tumor size. Analysis was done group-wise related to age. Additionally, tumor size, degree of necrosis, superficial or deep location of tumor and anatomic localization in the brain were recorded. The extent of peritumoral edema in patients >65 years (ys) was not different from the edema extent in patients ≤ 65 ys (p = 0.261). The same was true if age groups ≤ 55 ys and ≥ 70 ys were compared (p = 0.308). However, extent of necrosis (p = 0.023), deep tumor localization (p = 0.02) and frontal localisation (p = 0.016) of the tumor were associated with the extent of edema. Tumor size was not linearly correlated to edema extent (Pearson F = 0.094, p = 0.303) but correlated to degree of necrosis (F = 0.355, p < 0.001, Spearman-Rho) and depth of tumor (p < 0.001). In a multifactorial analysis of maximum edema with the uncorrelated factors age, regional location of tumor and degree of necrosis, only the extent of necrosis (p = 0.022) had a significant effect. Age at diagnosis does not determine degree of peritumoral edema, and tumor localization in the white matter is associated with greater extent of edema. The area of necrosis is reflective of volume of edema. In summary, the radiographic appearance of a glioblastoma at diagnosis does not reflect biology in the elderly patient.


Testing of some permitted food colours for the induction of gene conversion in diploid yeast.
12 permitted food colours in use were screened for geno-toxicity. Mitotic gene conversion in Saccharomyces cerevisiae was used as the end-point. Each food colour was tested in stationary-phase as well as log-phase cells but without microsomal activation. These food colours did not cause any increase in mitotic gene conversion in diploid yeast BZ 34.


N-acetylcysteine protects human periodontal ligament fibroblasts from pyroptosis and osteogenic differentiation dysfunction through the SIRT1/NF-κB/Caspase-1 signaling pathway.
This study was aimed to determine whether N-acetylcysteine (NAC) could inhibit lipopolysaccharides / adenosine triphosphate (ATP)-induced pyroptosis and alleviate the damage of osteogenic differentiation in human periodontal ligament fibroblasts (hPDLFs). Furthermore, this study detected whether NAC acted effectively by modulating the silent information regulator 2 homolog 1 (SIRT1)/ the nuclear factor-κB (NF-κB)/Caspase-1 signaling pathway in hPDLFs. Cell Counting Kit-8 assay was employed to determine the appropriate concentration of NAC for the follow-up experiments. To explore the effect and the underlying mechanisms of NAC on pyroptosis and osteogenic differentiation in hPDLFs, intracellular reactive oxygen species levels were detected using 2',7'-Dichlorodihydrofluorescein Diacetate kits. Moreover, SIRT1 inhibitor, SIRT1 activator, NF-κB inhibitor and Caspase-1 inhibitor were applied, the incidence of pyroptosis was detected by flow cytometry, the osteogenic differentiation of hPDLFs was observed using alkaline phosphatase and alizarin red staining, Real-time quantitative polymerase chain reaction and Western Blot were used to detect the expression of relevant factors, the release of interleukin-1β, interleukin-18 and lactate dehydrogenase were detected by Enzyme-linked immunosorbent assay. The results demonstrated that NAC protected hPDLFs from lipopolysaccharides/ATP-induced damage, alleviating pyroptosis and osteogenic differentiation dysfunction. Moreover, NAC abrogated the inhibition of SIRT1 activity by scavenging reactive oxygen species, thereby reduced pyroptosis and osteogenic differentiation dysfunction by inhibiting the NF-κB/Caspase-1signaling pathway. NAC could inhibit pyroptosis and osteogenic differentiation dysfunction of hPDLFs by scavenging reactive oxygen species to regulate the SIRT1/NF-κB/Caspase-1 signaling axis.


Behavioral and physiological effects of a single injection of rat interferon-alpha on male Sprague-Dawley rats: a long-term evaluation.
Interferon-alpha (IFN-alpha) is a cytokine used as a first line of defense against diseases such as cancer and hepatitis C. However, reports indicate that its effectiveness as a treatment is countered by central nervous system (CNS) disruptions in patients. Our work explored the possibility that it may also cause long-term behavioral disruptions by chronicling the behavioral and physiological disturbances associated with a single injection of vehicle, 10, 100, or 1,000 units of IFN-alpha in male Sprague-Dawley rats (n = 5/dose). Following 1 day of locomotor baseline collection, we monitored sickness behaviors (ptosis, piloerection, lethargy, and sleep), food and water intake, body weight, temperature, and motor activity. Observations were recorded 4 days prior to and 4 days following the IFN-alpha injection. Temperature and sickness behaviors were recorded three times daily at 9:00, 15:00, and 21:00 h, and all other indices, once daily. On the injection day, temperature values were highest in the animals receiving the 10-unit IFN-alpha dose 15 min and 13 h post-injection. In the case of sickness behaviors, a significant increase was observed in piloerection in all IFN-alpha groups at each time point measured, while the scores of the rats in the vehicle condition remained unchanged between pre- and post-injection days. Analyses of overall sickness behaviors during morning and night observation periods indicated increased scores in all IFN-alpha groups following injection. Cumulatively, these data suggest that a single IFN-alpha exposure may elicit long-term behavioral disruptions and that its consequences should be thoroughly investigated for its use in clinical populations.


Sarcoidosis rates in BCG-vaccinated and unvaccinated young adults: A natural experiment using Danish registers.
Sarcoidosis may have an infectious trigger, including Mycobacterium spp. The Bacille Calmette-Guérin (BCG) vaccine provides partial protection against tuberculosis and induces trained immunity. We examined the incidence rate (IR) of sarcoidosis in Danish individuals born during high BCG vaccine uptake (born before 1976) compared with individuals born during low BCG vaccine uptake (born in or after 1976). We performed a quasi-randomized registry-based incidence study using data from the Danish Civil Registration System and the Danish National Patient Registry between 1995 and 2016. We included individuals aged 25-35 years old and born between 1970 and 1981. Using Poisson regression models, we calculated the incidence rate ratio (IRR) of sarcoidosis in individuals born during low BCG vaccine uptake versus high BCG vaccine uptake, adjusting for age and calendar year (separately for men and women). The IR of sarcoidosis was increased for individuals born during low BCG vaccine uptake compared with individuals born during high BCG vaccine uptake, which was largely attributed to men. The IRR of sarcoidosis for men born during low BCG vaccine uptake versus high BCG vaccine uptake was 1.22 (95% confidence interval [CI] 1.02-1.45). In women, the IRR was 1.08 (95% CI 0.88-1.31). In this quasi-experimental study that minimizes confounding, the time period with high BCG vaccine uptake was associated with a lower incidence rate of sarcoidosis in men, with a similar effect seen in women that did not reach significance. Our findings support a potential protective effect of BCG vaccination against the development of sarcoidosis. Future interventional studies for high-risk individuals could be considered.


Field safety and efficacy of an orally administered combination of sarolaner, moxidectin and pyrantel (Simparica Trio®) for the prevention of angiostrongylosis in dogs presented as veterinary patients.
Infection with the cardiopulmonary nematode Angiostrongylus vasorum may cause severe disease in dogs, therefore prophylactic treatments are necessary to prevent infection in dogs at risk. A clinical field study was conducted to demonstrate the efficacy and safety of an oral combination of sarolaner, moxidectin and pyrantel (Simparica Trio®) for the prevention of A. vasorum infection in dogs (prevention study). A survey study was conducted concurrently to determine the infection pressure in the same areas. Prevention and survey studies were both conducted at the same veterinary clinics in endemic hot spots for A. vasorum in Denmark and Italy. The prevention study was a randomized, placebo controlled, double masked study where 622 client-owned dogs were treated and tested at 30 days intervals for 10 months. In the survey study 1628 dogs that were at risk of infection and/or were suspected to be infected were tested by fecal and/or serological methods, and the percent of dogs positive for A. vasorum was calculated. In the prevention study, there were no adverse events related to treatment with Simparica Trio®. Two placebo-treated animals became infected with A. vasorum during the 10-month study period, while none of the dogs in the combination product-treated group became infected. In the survey study, 12.2% of the study dogs were found positive to A. vasorum, indicating high exposure to the parasite during the period of the prevention study. Monthly oral treatment with the combination of sarolaner, moxidectin and pyrantel (Simparica Trio®) was 100% effective in the prevention of natural infection with A. vasorum in dogs in highly endemic areas. In endemic areas, A. vasorum occurrence in dogs at risk is considerable.


[Biochemical test for the presence of pepsinogen-pepsin for the diagnosis of stomach cancer metastases].
In metastases and malignant tumors arising from gastric mucous membrane irrespective of their localization the method of electrophoresis and enzyme-electroporesis in agar gel demonstrates the presence of rapidly moving anode fractions I, II, and III corresponding to pepsinogen-pepsin isoforms of normal gastric mucosa but lacking proteolytic activity.


A rare case of femoral artery saccular aneurysm caused by tuberculosis in a male patient: A case report and review of literature.
Tuberculosis (TB) is still a major global health issue. In over 75 % of all cases of mycotic aneurysm, TB spreads directly by eroding through the vascular wall. Aortic and innominate arteries are frequently the sites of tubercular aneurysms, primarily due to contiguous dissemination from pulmonary infection sites. We report a case of a saccular aneurysm at the distal common femoral artery associated with tuberculosis. A 34-year-old man had the chief complaint of a voluminous pulsatile mass in the left thigh. We found a bruit on auscultation examination at the site of the mass. A computed tomography (CT) angiography showed a saccular aneurysm at the distal common femoral artery and stenosis at the proximal femoral profunda artery. A chest CT scan was conducted, and the result showed a ground-glass appearance and multiple enlarged lymph nodes. The patient was treated surgically by resection of the aneurysm and reconstruction with an inter-positional saphenous vein graft. Later, he was treated with a drug regimen for tuberculosis by pulmonologist. The patient was discharged with no post-operative complications. Patients with femoral artery aneurysms are at high risk of rupture and death by exsanguination. It can be a severe complication of tuberculosis, especially in immunocompromised patients. Although this was a very rare case, all surgeons must be aware. A combination of medical and surgical intervention is imperative. Careful clinical care postoperatively is mandatory because of the risk of repetitive anastomotic aneurysms and recurrent aneurysms in another vessel.


The relationship between life-sustaining treatment limitation and organ donation in Swedish intensive care: A nationwide register study.
Life-sustaining treatment limitation (LSTL) on the intensive care unit (ICU) may affect the rate of organ donation after brain death (DBD). The primary aim of this study was to examine whether there is a relationship between LSTL and DBD. Furthermore, we aimed to determine the rate of LSTL involved in ICU deaths and to describe technical and procedural characteristics of LSTL on Swedish ICUs. This was an observational cohort study on all ICU deaths (n = 13 156) in Sweden between 2014 and 2017. We analysed differences in DBD rates between deaths in ICU with and those without LSTL, using descriptive statistics and logistic regression. After excluding 1084 deaths on specialised ICUs and units not registering goals of treatment, the study population comprised 12 072 deaths including 615 DBDs, of which 7865 had LSTL, 1706 had no LSTL and 2501 had no stated goals of treatment. The final cohort on which the relationship between DBD and LSTL was analysed comprised 9571 deaths including 419 DBDs. When no LSTL was documented, the rate of organ donation was 9.5% compared to 3.3% when LSTL was documented (P < .001). LSTL was associated with a lower DBD rate after adjusting for patient- and ICU-related factors (OR 0.41, 95% CI 0.31-0.53, P < .001). There was an inverse relationship between LSTL and DBD amongst patients who died on the ICU. This relationship remained after adjusting for factors known to influence organ donation. The reason remains to be determined.