Evidence for up-regulated low density lipoprotein receptor in human lung adenocarcinoma cell line A549.
Human lung adenocarcinoma cell line A549 was studied with respect to the metabolism of human low density lipoprotein (LDL) and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR) activity. After incubation in medium containing lipoprotein-deficient serum (LPDS) for 24 h, the A549 cell line expresses a single class of high affinity LDL binding sites (KD at 37 degrees C of 15.1 +/- 0.7 nM and capacity of 118 +/- 2.8 ng/mg cell protein) and an HMGR activity of 111.4 +/- 7 pmol/min/mg cell protein. After binding, the LDLs were internalized and degraded by a common saturable process. The HMGR activity was higher in A549 cells than in fibroblasts but LDL affinity and binding capacity were similar in both cell types. However, in the presence of lipoproteins, A549 cells showed a two-fold higher binding capacity than fibroblasts. When the cells were deprived of cholesterol, the amount of LDLR sites increased but the extent of stimulation was lower in A549 than in fibroblast cells (2.5-fold versus six-fold respectively). This increase was accompanied by a similar increase in the specific LDLR mRNA cellular levels (two-fold versus six-fold respectively). When cells were deprived of exogenous and endogenous cholesterol (biosynthesis blocked by compactin), the binding capacity and the LDLR mRNA levels were yet again increased in A549 cells but not in fibroblasts. Taken together these results suggest that the level of expression of the LDLR is up-regulated in A549 cells compared to fibroblasts.


The effect of polyethylene glycol on mammalian nerve impulses.
Polyethylene glycol (PEG) is a polymeric compound used as a vehicle for depot steroid preparations such as methylprednisolone acetate and triamcinolone diacetate injected into the epidural or intrathecal space to relieve low back pain. There have been reports of neurodysfunction associated with these injections, and it has been postulated that the PEG vehicle is the offending agent. Studies supporting such a possibility have, however, relied upon concentrations of PEG higher than those used clinically (3%) or have used PEG in combination with other drugs. Using an in vitro rabbit sheathed-nerve preparation, we investigated the effects of a 1-hr exposure to different concentrations (3-40%) of PEG in Liley solution on the transmission of impulses of the A, B, and C nerve fibers. The 3% and 10% PEG had no effect on mean amplitudes of the compound action potentials (CAPs) nor did they significantly decrease conduction velocity. Twenty percent PEG slightly depressed and 30% markedly decreased CAPs. Both 20% and 30% PEG significantly slowed the conduction velocities of A, B, and C nerve fibers. Forty percent PEG abolished CAPs. With washout CAPs recovered to at least 80% of their baseline levels, and conduction velocities returned toward baseline levels. The pH of the Liley solution decreased with an increasing concentration of PEG, from 7.4 in the control Liley solution to 6.45 in the solution of 40% PEG.(ABSTRACT TRUNCATED AT 250 WORDS)


Changes in opioid prescribing after implementation of mandatory registration and proactive reports within California's prescription drug monitoring program.
In 2016, California updated its prescription drug monitoring program (PDMP), adding two key features: automated proactive reports to prescribers and mandatory registration for prescribers and pharmacists. The effects of these changes on prescribing patterns have not yet been examined. We aimed to evaluate the joint effect of these two PDMP features on county-level prescribing practices in California. Using county-level quarterly data from 2012 to 2017, we estimated the absolute change associated with the implementation of these two PDMP features in seven prescribing indicators in California versus a control group comprising counties in Florida and Washington: opioid prescription rate per 1000 residents; patients' mean daily opioid dosage in milligrams of morphine equivalents[MME]; prescribers' mean daily MME prescribed; prescribers' mean number of opioid prescriptions per day; percentage of patients getting >90 MME/day; percentage of days with overlapping prescriptions for opioids and benzodiazepines; multiple opioid provider episodes per 100,000 residents. Proactive reports and mandatory registration were associated with a 7.7 MME decrease in patients' mean daily opioid dose (95 %CI: -11.4, -2.9); a 1.8 decrease in the percentage of patients prescribed high-dose opioids (95 %CI: -2.3, -0.9); and a 6.3 MME decrease in prescribers' mean daily dose prescribed (95 %CI: -10.0, -1.3). California's implementation of these two PDMP features was associated with decreases in the total quantity of opioid MMEs prescribed, and indicators of patients prescribed high-dose opioids compared to states that had PDMP's without these features. Rates of opioid prescribing and other high-risk prescribing patterns remained unchanged.


Parents' resolution of their child's diagnosis: A scoping review.
This scoping review focused on parents' resolution of their reactions to receiving a diagnosis for their child, based on Marvin and Pianta's model and Reaction to Diagnosis Interview (RDI). We aimed to map the populations examined, the prevalence of parents' narrated resolution, and what is known about its outcomes and determinants. A structured search identified 47 peer-reviewed papers published between 1992-2021. All employed the RDI and most had a cross-sectional design. Studies focused on a wide range of children's health and mental health diagnoses. Days to years after receiving the diagnosis, RDI narratives of 18.43% to 72.49% of the parents (44% on average) indicated lack of resolution. Studies reported associations between unresolved narratives and children's insecure attachment, higher parenting stress, and poorer parental health. However, findings on the associations of narrated resolution with parents' representations of their child, sensitivity, and psychological symptoms were equivocal, and findings on factors that may shape narrated resolution were limited. To advance the understanding of parents' narrated resolution and its effects, we recommend researchers employ prospective and longitudinal designs, evaluate narrated resolution as a continuous phenomenon, focus on outcomes derived from attachment theory, and systematically sample families from heterogenous cultures.


Occurrence, formation, environmental fate and risks of environmentally persistent free radicals in biochars.
Biochars are used globally in agricultural crop production and environmental remediation. However, environmentally persistent free radicals (EPFRs), which are stable emerging pollutants, are generated as a characteristic feature during biomass pyrolysis. EPFRs can induce the formation of reactive oxygen species, which poses huge agro-environmental and human health risks. Their half-lives and persistence in both biochar residues and in the atmosphere may lead to potentially adverse risks in the environment. This review highlights the comprehensive research into these bioreactive radicals, as well as the bottlenecks of biochar production leading up to the formation and persistence of EPFRs. Additionally, a way forward has been proposed, based on two main recommendations. A global joint initiative to create an all-encompassing regulations policy document that will improve both the technological and the quality control aspects of biochars to reduce EPFR generation at the production level. Furthermore, environmental impact and risk assessment studies should be conducted in the extensive applications of biochars in order to protect the environmental and human health. The highlighted key research directions proposed herein will shape the production, research, and adoption aspects of biochars, which will mitigate the considerable concerns raised on EPFRs.


The Gray Area of Freezing of Gait Annotation: A Guideline and Open-Source Practical Tool.
Freezing of gait, a disabling episodic symptom, is difficult to assess as the exact begin- and endpoint of an episode is not easy to specify. This hampers scientific and clinical progress. The current golden standard is video annotation by two independent raters. However, the comparison of the two ratings gives rise to non-overlapping, gray areas. To provide a guideline for dealing with these gray areas. We propose a standardized procedure for handling the gray areas based on two parameters, the tolerance and correction parameter. Furthermore, we recommend the use of positive agreement, negative agreement, and prevalence index to report interrater agreement instead of the commonly used intraclass correlation coefficient or Cohen's kappa. This theoretical guideline was implemented in an open-source practical tool, FOGtool (https://github.com/helenacockx/FOGtool). This paper aims to contribute to the standardization of freezing of gait assessment, thereby improving data sharing procedures and replicability of study results.


Integrated sample processing and counting microfluidic device for microplastics analysis.
The presence of microplastics is widespread in the ocean, freshwater, soil, or even in the human body. The current microplastics analysis method involves a relatively complicated sieving, digestion filtration, and manual counting process, which is both time-consuming and requires experienced operation personnel. This study proposed an integrated microfluidic approach for the quantification of microplastics from river water sediment and biosamples. The proposed two-layer PMMA-based microfluidic device is able to conduct the sample digestion, filtration and counting processes inside the microfluidic chip with the preprogrammed sequence. For demonstration, samples from river water sediment and fish gastrointestinal tract were analyzed, result indicate the proposed microfluidic device is able to perform the quantification of microplastics from river water and biosamples. Compared with the conventional approach, the proposed microfluidic-based sample processing and quantification method for microplastics are simple, low-cost and with low demand for laboratory equipments, the self-contained system also has the application potential for the continuous on-site inspection of microplastics.


[Features of the construction of the scanning system of tomographs SRT-1000 and SRT-1000M].
The article may serve as a handbook for the user of the second generation computed X-ray tomographs for human brain examination.


Implantation of a stent graft in the right pulmonary artery enables radical resection of a central endothelial sarcoma of the left pulmonary artery.
In a patient with a huge endothelial sarcoma of the left pulmonary artery, we report successful implantation of a stent graft in the right pulmonary artery, including the pulmonary arterial trunk. This preoperative measure enabled a safe and radical left-sided pneumonectomy, including the tumor and the central parts of the left pulmonary artery. No major blood loss occurred, and neither use of a heart-lung machine nor cardiopulmonary bypass was necessary.


[Simultaneous bilateral humeral head disclocation and acetabular fracture. A rare manifestation after hypoglycemia-induced seizures].
Seizures can cause severe musculoskeletal injuries and posterior shoulder dislocation is a typical result of a seizure. Bilateral posterior shoulder dislocation is rare and acetabular fractures caused by a seizure are also a rarity. We present the case of a 48-year-old man with simultaneous bilateral posterior shoulder fracture dislocations and bilateral acetabular fractures as a result of hypoglycemia-induced seizures.


Indole-3-carbinol ameliorated the thioacetamide-induced hepatic encephalopathy in rats.
Indole-3-carbinol (I3C) is reported to have hepatic and neuroprotective properties. However, the I3C role in the protection of the liver and brain in the pathological condition of hepatic encephalopathy has not been investigated. Therefore, in the present study, we have assessed the hepatic and neuroprotective roles of I3C against thioacetamide (TAA)- induced hepatic encephalopathy in Wistar rats. TAA (300 mg/kg) was intraperitoneally administered to Wistar rats to induce hepatic encephalopathy. The elevated levels of ammonia in the blood, liver, and brain were substantially lowered by I3C treatment (25, 50, and 100 mg/kg, oral, 7 days). I3C significantly ameliorated the TAA-induced liver dysfunction by decreasing the alanine transaminase, aspartate transaminase, and alkaline phosphatase enzymes and reduced the elevated cytochrome P4502E1 (CYP2E1) activity in the liver and brain. Further, I3C alleviated mitochondrial dysfunction and oxidative stress in the brain. I3C treatment improved the anti-inflammatory cytokine interleukin (IL)- 10 while reducing inflammatory cytokines such as tumor necrosis factor-1 and IL-6 in hepatic encephalopathy rats. I3C reduced the levels of apoptotic indicators mediated by the mitochondria, including cytochrome c, caspase 9, and caspase 3. Concurrently, I3C mitigated the liver and brain histological abnormalities in hepatic encephalopathy rats. Therefore, the present study concluded that the I3C protected the liver and brain from TAA-induced hepatic encephalopathy injury by inhibiting CYP2E1 enzyme activity and decreasing ammonia, oxidative stress, inflammation, and apoptosis. The present study provides preclinical validation of I3C use as hepatic and neuroprotective for hepatic encephalopathy management.


Mortality of urban and rural young children with cerebral palsy in Bangladesh.
Bangladesh has a high child mortality rate. However, little is known about the outcome for young children who have cerebral palsy (CP). Ninety-two children with CP with a mean age of 3 years 3 months at entry into the study were followed for up to 3 years as part of an intervention study. Eight children died: two of 49 (4%) from an urban area and six of 43 (14%) from a rural area. Extrinsic factors such as infections and drug reactions preceded all the deaths, but those who died were mostly severely malnourished and among the more severely disabled of the total group. Eighty-nine percent of rural children in the study were from low-income families. Intervention programmes for severely disabled children in developing countries must include primary health care and feeding programmes as well as rehabilitation services to address both the needs of the child and empowerment of the mother and the family.


Watermelon responds to organic fertilizer by enhancing root-associated acid phosphatase activity to improve organic phosphorus utilization.
Organic fertilizer is commonly used to increase crop yields and improve soil quality. However, it is unclear whether crops adapt to organic fertilizer by regulating metabolic pathways that are involved in nutrient utilization. In this study, we focused on the organic phosphorus (Po) in organic fertilizer and, using watermelon, investigated changes in gene expression and metabolic pathways in response to organic fertilizer and the combination of chemical fertilizer and organic fertilizer (chemical fertilizer 70% and organic fertilizer 30%, based on phosphorus supply). Purple acid phosphatase (PAP) gene expression was upregulated in leaves and roots of watermelon grown in organic fertilizer alone and in the combination of chemical/organic fertilizer, resulting in enhanced phosphatase activity in roots. When the ratio of chemical to organic fertilizer was 85/15, root-associated acid phosphatase (APase) activity increased over chemical fertilizer alone. This formulation also resulted in increased inorganic phosphate (Pi) concentration in roots and leaves, and the upregulation of the secretory APase genes ClaPAP10/12/15/26, and ClaPAP18 in roots. In conclusion, watermelon responds to organic fertilizer by upregulating expression of secretory ClaPAP genes, subsequently enhancing root-associated APase activity further improving the hydrolysis of phosphomonoesters, and ultimately facilitating Po utilization by roots. The mechanisms of P utilization by roots comprise the enhancement of APase and phytase activity, absorption of small Po molecules, uptake of Pi, and the increase of lateral root number when organic fertilizer is applied to the plants. These findings help to establish the mechanisms by which plants respond to organic fertilizer by regulating metabolic pathways at the transcriptional level.


Association between Haemagglutination inhibiting antibodies and protection against clade 6B viruses in 2013 and 2015.
The epidemiology of the pandemic A(H1N1) virus has been changing as population immunity continues to co-evolve with the virus. The impact of genetic changes in the virus on human's susceptibility is an outstanding important question in vaccine design. In a community-based study, we aim to (1) determine the genetic characteristics of 2009-2015 pandemic H1N1 viruses, (2) assess antibody response following natural infections and (3) assess the correlation of A/California/07/09 antibody titers to protection in the 2013 and 2015 epidemics. In a household transmission study, serum specimens from 253 individuals in Managua, Nicaragua were analyzed. Combined nose and throat swabs were collected to detect RT-PCR confirmed influenza infection and virus sequencing. Hemagglutination inhibition assays were performed and the protective titer for circulating H1N1pdm was determined. Clade 6B pandemic H1N1 viruses predominated in Nicaragua during the 2013 and 2015 seasons. Our household transmission study detected a household secondary attack rate of 17% in 2013 and 33% in 2015. Infected individuals, including vaccinees, showed an apparent antibody response to A/California/07/09. Baseline titers of A/California/07/09 antibodies were found to associate with protection in both seasons. A titer of ≥1:40 correlated to a 44% protection in children, a 29% protection in adults 15-49years old and a 51% protection in adults 50-85years old. In 2013 and 2015, antibody titers to A/California/07/09 associated with an infection risk reduction amongst exposed household contacts. This is consistent with a detectable vaccine effectiveness reported in a number of studies. Genetic changes in clade 6B viruses might have led to a reduced immunity in some whereas others might have been less affected. The use of human serologic data is important in virus characterization and if performed in a timely manner, could assist in vaccine strain selection.


Abnormal DNA methylation analysis of leucine-rich glioma-inactivated 1 antibody encephalitis reveals novel methylation-driven genes related to prognostic and clinical features.
Aberrant DNA methylation occurs commonly during pathogenesis of neuroimmunological diseases and is of clinical value in various encephalitis subtypes. However, knowledge of the impact of DNA methylation changes on pathogenesis of leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis remains limited. A total of 44 cytokines and 10 immune checkpoint moleculars (ICMs) in the serum of patients with LGI1 encephalitis and healthy donors (HDs) were measured to evaluate the association of them with clinical parameters. Genome-wide DNA methylation profiles were performed in peripheral blood mononuclear cell (PBMC) from LGI1 encephalitis patients and HDs using reduced representation bisulfite sequencing (RRBS) and validated for the methylation status by pyrosequencing. MicroRNA profiles were acquired in serum exosome by small RNA sequencing. Targeted cytokines expression was assessed at the presence or absence of miR-2467-5p in PBMCs and the culture media, and the binding of miR-2467-5p and its targeted genes was validated by luciferase assay. There existed significant difference in 22 cytokines/chemokines and 6 ICMs between LGI1 encephalitis patients and HDs. Decreased PDCD1 with increased ICAM1 could predict unfavorable prognosis in one-year follow-up for LGI1 encephalitis patients. Fifteen of cytokines/chemokines and ICMs presented DNA-methylated changes in the promoter and gene body using RRBS in which five were verified as methylation status by pyrosequencing, and the methylation level of CSF3, CCL2, and ICAM1 was conversely associated with their expression in PBMCs. By combining RRBS data with exosome-derived microRNA sequencing, we found that hypomethylated-driven hsa-miR-2467-5p presented elevated expression in serum exosomes and PBMCs in LGI1 encephalitis. Mechanically, miR-2467-5p significantly induced reduced expression of CSF3 and PDCD1 by binding with their 3`UTR while enhanced CCL15 expression, but not significantly correlated with peripheral blood CD19 + B cell proportion of LGI1 encephalitis patients. Our results provided convincing evidence for DNA methylation changes, microRNA profiles in serum exosome for LGI1 encephalitis, and we also identified several novel cytokines related to clinical features in which some represented epigenetic modification of methylated-driven pattern and microRNA modulation. Our study contributed to develop treatment for epigenetic pathogenesis in LGI1 encephalitis.


The application of convolution neural network based cell segmentation during cryopreservation.
For most of the cells, water permeability and plasma membrane properties play a vital role in the optimal protocol for successful cryopreservation. Measuring the water permeability of cells during subzero temperature is essential. So far, there is no perfect segmentation technique to be used for the image processing task on subzero temperature accurately. The ice formation and variable background during freezing posed a significant challenge for most of the conventional segmentation algorithms. Thus, a robust and accurate segmentation approach that can accurately extract cells from extracellular ice that surrounding the cell boundary is needed. Therefore, we propose a convolutional neural network (CNN) architecture similar to U-Net but differs from those conventionally used in computer vision to extract all the cell boundaries as they shrank in the engulfing ice. The images used was obtained from the cryo-stage microscope, and the data was validated using the Hausdorff distance, means ± standard deviation for different methods of segmentation result using the CNN model. The experimental results prove that the typical CNN model extracts cell borders contour from the background in its subzero state more coherent and effective as compared to other traditional segmentation approaches.


Client preferences for HIV Care Coordination Program features in New York City: latent class analysis of a discrete choice experiment.
The PROMISE study, launched in 2018, evaluates the implementation of revisions to the HIV Care Coordination Program (CCP) designed to minimize persistent disparities in HIV outcomes among high-need persons living with HIV in New York City. We conducted a discrete choice experiment (DCE) assessing the preferences of CCP clients to inform improvements to the program's design. Clients chose between two hypothetical CCP options that varied across four program attributes: help with antiretroviral therapy (ART) adherence (directly observed therapy [DOT] vs. remind via phone/text vs. adherence assessment), help with primary care appointments (remind and accompany vs. remind and transport vs. remind only), help with issues other than primary care (coverage and benefits vs. housing and food vs. mental health vs. specialty medical care) and visit location (meet at home vs. via phone/video vs. program visit 30 or 60 minutes away). The latent class analysis identified different preference patterns. A choice simulation was performed to model client preferences for hypothetical CCPs as a whole. One hundred and eighty-one CCP clients from six sites implementing the revised CCP completed the DCE January 2020-March 2021. Most clients had stable housing (68.5%), reported no problem substance use in the last 3 months (72.4%) and achieved viral suppression (78.5) with only 26.5% receiving DOT within a CCP. 77.3% of responses were obtained before the COVID-19 pandemic. Preferences clustered into three groups. Visit location and ART adherence support were the most important attributes. Group 1 (40%) endorsed telehealth for visit location; telehealth for ART adherence support; and help with securing housing/food; Group 2 (37%) endorsed telehealth for visit location; telehealth for ART adherence support; and staff reminding/arranging appointment transportation; Group 3 (23%) endorsed staff meeting clients at program location and staff working with clients for medication adherence. In the choice simulation, Basic and Medium hypothetical CCPs were endorsed more than Intensive CCPs. This DCE revealed a strong preference for telehealth and a relatively low preference for intensive services, such as DOT and home visits; preferences were heterogeneous. The findings support differentiated care and remote service delivery options in the NYC CCP, and can inform improvements to CCP design.


Prognosis in children with traumatic injuries referring to the emergency department.
Trauma may lead to serious complications in children patients. The purpose of this study was to investigate prognosis in children with traumatic injuries. This cross-sectional study was conducted on all of the children (<18 years old) who had suffered traumatic injuries and transferred to the emergency department of Imam Hussein Hospital by emergency medical services. After selecting the children, a checklist including information such as demographic characteristics, trauma type, consciousness level, and final outcome was recorded. Finally, the data were analyzed using t-test, Chi-square test and ANOVA. In total of 564 children were investigated. Among them, 70% were males, and 33.2% were in the age range of 5-12 years. The mechanism of injuries in 97.9% of the cases was blunt trauma. The most common chief complaint among the affected children was nausea. The majority of them had stable vital signs and normal neurological tests results. However, 1.06% of them died during hospitalization. The results indicated that the final outcome in the children affected by traumatic injuries is significantly related to the type of trauma, the location of traumatic event, the vehicle used to transport them to emergency departments and their Glasgow coma scale score (p < 0.05). Considering the young age of the child patients and over half of trauma happened at home, it is important to raise parents' awareness about the risky places and activities, which were likely to result in traumatic injuries for children.


Membrane degradation of covered stents in the upper gastrointestinal tract: frequency and clinical significance.
To evaluate the frequency, clinical significance, and predictive factors of membrane degradation of covered stents in the upper gastrointestinal (UGI) tract. From 1996 to 2006, 166 stents were removed from 151 patients. Indications for stent removal included temporary stent placement for esophageal cancer before radiation therapy or radiation-chemotherapy (n = 53), stent migration (n = 40), temporary stent placement for a benign UGI stricture (n = 32), pain (n = 21), recurrent obstruction (n = 16), incomplete stent expansion (n = 1), recurrent transesophageal fistula (n = 2), and aspiration (n = 1). Removed stents were examined to evaluate possible causes of membrane degradation. Multivariate analysis was performed to determine the predictive factors of membrane degradation. Degradation of the covering membrane occurred in 14 of the 166 stents (8%). Recurrent obstruction due to tumor ingrowth (n = 7) and reopening of the transesophageal fistula (n = 1) through the degraded membrane occurred in eight stents (5%). At multivariate logistic regression analysis, the type of covering membrane (P = .018), stricture location (P = .006), and duration of stent placement (P = .002) were significantly associated with degradation of the covering membrane. Degradation of the covering membrane after stent placement in the UGI tract is not an uncommon event, and recurrent obstruction or fistula can occur through the degraded membrane. A polyurethane membrane is not biostable and dissolves over time, particularly in the gastroduodenal area.


Effects of Dexmedetomidine on Systemic Inflammation and Postoperative Complications in Laparoscopic Pancreaticoduodenectomy: A Double-blind Randomized Controlled Trial.
Laparoscopic pancreaticoduodenectomy (LPD) may induce intense inflammatory response which might be related to the patient's outcomes. Clinical dexmedetomidine (DEX) has been widely used for opioid-sparing anesthesia and satisfactory sedation. The objective of this study was to investigate the influence of DEX on inflammatory response and postoperative complications in LPD. Ninety-nine patients undergoing LPD were randomly assigned to two groups: normal saline (NS) and DEX. The primary outcome was the neutrophil-to-lymphocyte ratio (NLR) differences postoperatively within 48 h. Secondary outcomes were postoperative complications, the length of postoperative hospital stay and the incidence of ICU admission. Other outcomes included anesthetics consumption and intraoperative vital signs. NLR at postoperative day 2 to baseline ratio decreased significantly in the DEX group (P = 0.032). Less major complications were observed in the DEX group such as pancreatic fistula, delayed gastric emptying and intra-abdominal infection (NS vs. DEX, 21.7% vs. 13.6%, P = 0.315; 10.9% vs. 2.3%, P = 0.226; 17.4% vs. 11.4%, P = 0.416, respectively) though there were no statistical differences. Three patients were transferred to the ICU after surgery in the NS group, while there was none in the DEX group (P = 0.242). The median postoperative hospital stay between groups were similar (P = 0.313). Both intraoperative propofol and opioids were less in the DEX group (P < 0.05). Intraoperative DEX reduced the early postoperative inflammatory response in LPD. It also reduced the use of narcotics that may related to reduced major complications, which need additional research further.


Ozone, nitrogen dioxide and lung cancer: a review of some recent issues and problems.
Lung cancer in man is a common disease. There is some recent concern that oxidant air pollutants might be a contributing risk factor. Experimental data show that ozone and NO2 increase incidence and multiplicity of lung tumors in strain A mice; however, the data are not always statistically significant. Also it depends on experimental design whether ozone enhances or inhibits the development of lung tumors in mice. Similarly, ozone and nitrogen dioxide enhance lung colonization by cancer cells injected intravenously following exposure to the air pollutants, whereas NO2 kills lung metastases if cells are injected prior to exposure. Both ozone and NO2 modulate the proliferation of pulmonary neuroendocrine cells, the precursor cells for small cell lung cancer. It is concluded that there is little evidence to implicate ozone or NO2 directly as pulmonary carcinogens, but that they might modify and influence the carcinogenic process in the lung.


Compensatory feeding response of the slug Sarasinula plebeia to dietary dilution.
Like many polyphagous herbivores, individuals of Sarasinula plebeia (Fischer) (Soleolifera: Veronicellidae) consume a variety of plant species that may differ in nutritional content. In this study we determined the ability of these slugs to compensate for such variation in diet composition. Dilution with water of an agar-based diet containing commercial guinea pig food or carrot root to obtain dry weights (dw) of 90, 70, 40 and 10% of diet fresh weight (fw), caused immature slugs to consume increasingly more fresh weight of food [as much as 4.7-(guinea pig) to 6.1-fold (carrot) more]. Dry weight consumption and body mass-relative dry weight consumption rate also increased at intermediate dilutions, buth with further dilution, dry weight intake declined despite the greater fresh weight consumption. At each dilution level, slugs fed the guinea pig diet consumed from ca. 5-to 6.4-fold more fresh weight than the carrotfed slugs. The former grew substantially, with their final biomass and body mass-relative growth rate varying curvilinearly with diet % dw. If these slugs had not fed more but instead maintained the same fresh weight consumption as slugs in the 90% dw tretments, without altering food utilization efficiencies, then their biomass gain in the 70, 40 and 10% dw treatments would have been only about 62, 43, and 21%, respectively, of the values actually attained. In contrast, carrot-fed slugs did not grow and were only able to maintain their initial biomass. For each diet, slug tissue water (% fw) was highest in the most diluted treatment but did not differ significantly among the other dilution levels. Approximate digestibility of the carrot diet was highest at intermediate dilution levels (ca. 75% of ingested food was digested and absorbed); for the guinea pig diet, this efficiency declined linearly from about 66% to 59% with increased dilution. For slugs that grew (i.e., those fed the guinea pig diet), effeciences of converting digested (29-52%) and ingested (18-33%) food to dry biomass were both curvilinearly related to diet % dw. Thus, S. plebeia, like many other herbivores, has the capacity to increase food consumption substantially inresponse to reduced dietary nutrient level, allowing the slugs to cope with variable nutrient content in their food plants.


[Effect of theophylline and isoprenaline on N-acetylation activity in the rat liver].
The activity of N-acetyltransferase is shown to significantly rise after administration of theophylline and isoprenaline, but not of propranolol and N-acetylderivate of para-aminosalicylic acid to form during 30 minutes at a constant rate that increases following addition of cyclic AMP to the incubation medium. The capacity of the rat to acetylate paraaminosalicylic acid did not change under the effect of the mentioned agents.


Linking aberrant glycosylation of plasma glycoproteins with progression of myelodysplastic syndromes: a study based on plasmonic biosensor and lectin array.
Aberrant glycosylation of glycoproteins has been linked with various pathologies. Therefore, understanding the relationship between aberrant glycosylation patterns and the onset and progression of the disease is an important research goal that may provide insights into cancer diagnosis and new therapy development. In this study, we use a surface plasmon resonance imaging biosensor and a lectin array to investigate aberrant glycosylation patterns associated with oncohematological disease-myelodysplastic syndromes (MDS). In particular, we detected the interaction between the lectins and glycoproteins present in the blood plasma of patients (three MDS subgroups with different risks of progression to acute myeloid leukemia (AML) and AML patients) and healthy controls. The interaction with lectins from Aleuria aurantia (AAL) and Erythrina cristagalli was more pronounced for plasma samples of the MDS and AML patients, and there was a significant difference between the sensor response to the interaction of AAL with blood plasma from low and medium-risk MDS patients and healthy controls. Our data also suggest that progression from MDS to AML is accompanied by sialylation of glycoproteins and increased levels of truncated O-glycans and that the number of lectins that allow discriminating different stages of disease increases as the disease progresses.


Chompy: an infestation of MITE-like repetitive elements in the crocodilian genome.
Interspersed repeats are a major component of most eukaryotic genomes and have an impact on genome size and stability, but the repetitive element landscape of crocodilian genomes has not yet been fully investigated. In this report, we provide the first detailed characterization of an interspersed repeat element in any crocodilian genome. Chompy is a putative miniature inverted-repeat transposable element (MITE) family initially recovered from the genome of Alligator mississippiensis (American alligator) but also present in the genomes of Crocodylus moreletii (Morelet's crocodile) and Gavialis gangeticus (Indian gharial). The element has all of the hallmarks of MITEs including terminal inverted repeats, possible target site duplications, and a tendency to form secondary structures. We estimate the copy number in the alligator genome to be approximately 46,000 copies. As a result of their size and unique properties, Chompy elements may provide a useful source of genomic variation for crocodilian comparative genomics.


Selective recruitment of Adh genes for distinct enzymatic functions in Petunia hybrida.
Alcohol dehydrogenase (ADH) activity in plants is generally associated with glycolytic fermentation, which facilitates cell survival during episodes of low-oxygen stress in water-logged roots as well as chronically hypoxic regions surrounding the vascular core. Work with tobacco and potato has implicated ADH activity in additional metabolic roles, including aerobic fermentation, acetaldehyde detoxification and carbon reutilization. Here a combination of approaches has been used to examine tissue-specific patterns of Adh gene expression in order to provide insight into the potential roles of alcohol dehydrogenases, using Petunia hybrida, a solanaceous species with well-characterized genetics. A reporter-gene study, relying on the promoters of Adh1 and Adh2 to drive expression of the gene for a green fluorescent protein derivative, mgfp5, revealed unexpectedly complex patterns of GFP fluorescence in floral tissues, particularly the stigma, style and nectary. Results of GC-MS analysis suggest the association of ADH with production of aromatic compounds in the nectary. Overall the results demonstrate selective recruitment of Adh gene family members in tissues and organs associated with diverse ADH functions.


An investigation into the use of cuprous chloride for the removal of radioactive iodide from aqueous solutions.
Cuprous chloride (CuCl) was examined as a precipitant to remove iodide (I(-)) from aqueous solutions. The effects of the dosage of CuCl, reaction time, initial concentrations of I(-) and bicarbonate (HCO3(-)) on I(-) removal were investigated. The results showed that the optimized removal efficiency of I(-) reached approximately 95.8% when the dosage was 150 mg/L, the initial I(-) concentration ranged from 5 to 40 mg/L and the reaction time was 15 min. The removal efficiency decreased from 95.8% to 76.0% with the addition of HCO3(-) at a concentration in the range of 0-107 mg/L. Furthermore, the dissociation of CuCl, the disproportionation reaction of Cu(+), the precipitation of cuprous iodide (CuI) and cuprous oxide (Cu2O), and the formations of copper sulfide (CuxS, 1≤x<2) were identified as the primary reactions using the PHREEQC software and the measurements of water quality parameters under various conditions. X-rays photoelectron spectroscopy (XPS) analysis was performed before and after the reaction, helping to elucidate the reaction mechanism. This study can provide a promising method to address radioactive I(-) pollution in water.


A novel M-superfamily conotoxin with a unique motif from Conus vexillum.
Cone snails are tropical marine mollusks that envenomate prey with a complex mixture of neuropharmacologically active compounds for the purpose of feeding and defence, each evolved to act in a highly specific manner on different parts of the nervous system. Here, we report the peptide purification, molecular cloning, chemical synthesis, and functional characterization of a structurally unique toxin isolated from the venom of Conus vexillum. The novel peptide, designated Vx2, was composed of 21 amino acid residues cross-linked by 3 disulfide bonds (WIDPSHYCCCGGGCTDDCVNC). Intriguingly, its mature peptide sequence shows low level of similarity with other identified conotoxins, and its unique motif (-CCCGGGC-) was not reported in other Conus peptides. However, its signal peptide sequence shares high similarity with those of the M-superfamily conotoxins. Hence, Vx2 could be classified into a new family of the M-superfamily.


Deep Learning-based Recurrence Prediction in Patients with Non-muscle-invasive Bladder Cancer.
Non-muscle-invasive bladder cancer (NMIBC) is characterized by frequent recurrence of the disease, which is difficult to predict. To combine digital histopathology slides with clinical data to predict 1- and 5-yr recurrence-free survival of NMIBC patients using deep learning. Data of patients undergoing a transurethral resection of a bladder tumor between 2000 and 2018 at a Dutch academic medical center were selected. Corresponding histological slides were digitized. A three-step approach was used to predict 1- and 5-yr recurrence-free survival. First, a segmentation network was used to detect the urothelium on the digital histopathology slides. Second, a selection network was trained for the selection of patches associated with recurrence. Third, a classification network, combining the information of the selection network with clinical data, was trained to give the probability of 1- and 5-yr recurrence-free survival. The accuracy of the deep learning-based model was compared with a multivariable logistic regression model using clinical data only. In the 1- and 5-yr follow-up cohorts, 359 and 281 patients were included with recurrence rates of 27% and 63%, respectively. The areas under the curve (AUCs) of the model combining digital histopathology slide data with clinical data were 0.62 and 0.76 for 1- and 5-yr recurrence predictions, respectively, which were higher than those of the model using digital histopathology slide data only (AUCs of 0.56 and 0.72, respectively) and the multivariable logistic regression (AUCs of 0.58 and 0.57, respectively). In our population, the deep learning-based model combining digital histopathology slides and clinical data enhances the prediction of recurrence (within 5 yr) compared with models using clinical data or image data only. By combining histopathology images and patient record data using deep learning, the prediction of recurrence in bladder cancer patients is enhanced.


Nedd4-2 up-regulation is associated with ACE2 ubiquitination in hypertension.
Angiotensin-converting enzyme 2 (ACE2) is a critical component of the compensatory renin-angiotensin system that is down-regulated during the development of hypertension, possibly via ubiquitination. However, little is known about the mechanisms involved in ACE2 ubiquitination in neurogenic hypertension. This study aimed at identifying ACE2 ubiquitination partners, establishing causal relationships and clinical relevance, and testing a gene therapy strategy to mitigate ACE2 ubiquitination in neurogenic hypertension. Bioinformatics and proteomics were combined to identify E3 ubiquitin ligases associated with ACE2 ubiquitination in chronically hypertensive mice. In vitro gain/loss of function experiments assessed ACE2 expression and activity to validate the interaction between ACE2 and the identified E3 ligase. Mutation experiments were further used to generate a ubiquitination-resistant ACE2 mutant (ACE2-5R). Optogenetics, blood pressure telemetry, pharmacological blockade of GABAA receptors in mice expressing ACE2-5R in the bed nucleus of the stria terminalis (BNST), and capillary western analysis were used to assess the role of ACE2 ubiquitination in neurogenic hypertension. Ubiquitination was first validated as leading to ACE2 down-regulation, and Neural precursor cell-expressed developmentally down-regulated protein 4-2 (Nedd4-2) was identified as a E3 ligase up-regulated in hypertension and promoting ACE2 ubiquitination. Mutation of lysine residues in the C-terminal of ACE2 was associated with increased activity and resistance to angiotensin (Ang)-II-mediated degradation. Mice transfected with ACE2-5R in the BNST exhibited enhanced GABAergic input to the paraventricular nucleus (PVN) and a reduction in hypertension. ACE2-5R expression was associated with reduced Nedd4-2 levels in the BNST. Our data identify Nedd4-2 as the first E3 ubiquitin ligase involved in ACE2 ubiquitination in Ang-II-mediated hypertension. We demonstrate the pivotal role of ACE2 on GABAergic neurons in the maintenance of an inhibitory tone to the PVN and the regulation of pre-sympathetic activity. These findings provide a new working model where Nedd4-2 could contribute to ACE2 ubiquitination, leading to the development of neurogenic hypertension and highlighting potential novel therapeutic strategies.


Characteristics, formation, and sources of PM2.5 in 2020 in Suzhou, Yangtze River Delta, China.
Here we present seasonal chemical characteristics, formations, sources of PM2.5 in the year 2020 in Suzhou, Yangtze River Delta, China. Expectedly, organic matter (OM) found to be the most dominant component of PM2.5, with a year-average value of 10.3 ± 5.5 μg m-3, followed by NO3- (6.7 ± 6.5 μg m-3), SO42- (3.3 ± 2.5 μg m-3), NH4+ (3.2 ± 2.8 μg m-3), EC (1.1 ± 1.3 μg m-3), Cl- (0.57 ± 0.56 μg m-3), Ca2+ (0.55 ± 0.91 μg m-3), K+ (0.2 ± 1.0 μg m-3), Na+ (0.18 ± 0.45 μg m-3), and Mg2+ (0.09 ± 0.15 μg m-3). Seasonal variations of PM2.5 showed the highest average value in spring, followed by winter, fall, and summer. Meanwhile, the formation mechanisms of the major PM2.5 species (NO3-, SO42-, and OM) varied in seasons. Interestingly, NO2 may have the highest conversion rate to NO3- in spring, which might be linked with the nighttime chemistry due to the high relative humidity. Moreover, OM in summer was mainly produced by the daytime oxidation of volatile organic compounds, while local primary organic aerosols might play a significant role in other seasons. Source apportionment showed that the more-aged PM2.5 contributed significantly to the PM2.5 mass (42%), followed by the dust-related PM2.5 (38%) and the less-aged PM2.5 (21%). Potential contribution source function (PSCF) results indicated that aged PM2.5 were less affected by transportation than dust-related PM2.5.


Role of Immediate Postoperative Prolactin Measurement in Female Prolactinoma Patients: Predicting Long-Term Remission After Complete Tumor Removal.
Transsphenoidal surgery is one of the important treatment options in the management of prolactinomas; however, complete resection of the tumor does not always lead to endocrinological remission. While many studies have investigated preoperative factors associated with surgical outcome, little has been known about the relationship between postoperative factors and long-term surgical outcomes; moreover, there is no consistency in results. The aim of this study was to demonstrate the reliability of immediate postoperative prolactin levels as predictors of long-term outcomes. A total of 105 female patients who underwent complete removal of their histologically confirmed prolactinomas were included, and their medical records were retrospectively reviewed. To evaluate the predictability of immediate postoperative prolactin levels for long-term remission, prolactin levels were measured at 2, 6, 12, 18, 24, 48, and 72 h after surgery. From the 105 included patients, 95 (90.5%) and 10 (9.5%) belonged to the remission and non-remission groups, respectively. A significant difference was observed in the prolactin level measured 6 h after surgery between the remission and non-remission groups, and this difference stayed apparent until 72 h after surgery. We derived a cut-off value for every postoperative time point that showed a significant relationship with disease remission. Our study suggests that immediate postoperative measurement of prolactin levels is a reliable predictor of long-term remission and can contribute to early identification of patients who require adjuvant treatment after surgery.


A technical aid to performance of neurolytic lumbar sympathectomy.
The injection of ten ml of air into the retroperitoneal space outlines the anterior margin of the psoas muscle. This been found to be useful, using an Image Intensifier, for the accurate location of needle tips in the performance of neurolytic lumbar sympathectomy.


Allosteric switching of agonist/antagonist activity by a single point mutation in the interluekin-1 receptor antagonist, IL-1Ra.
The pleiotropic pro-inflammatory cytokine interleukin (IL)-1β has co-evolved with a competitive inhibitor, IL-1 receptor antagonist (IL-1Ra). IL-1β initiates cell signaling by binding the IL-1 receptor (IL-1R) whereas IL-1Ra acts as an antagonist, blocking receptor signaling. The current paradigm for agonist/antagonist functions for these two proteins is based on the receptor-ligand interaction observed in the crystal structures of the receptor-ligand complexes. While IL-1Ra and IL-1β are structurally homologous, IL-1Ra engages only two of the three extracellular domains of the receptor, whereas IL-1β engages all three. We find that an allosteric functional switch exists within a highly conserved pocket of residues, residues 111-120. This region is maintained across all IL-1 family members and serves as a hydrophobic mini-core for IL-1β folding. A key difference across species is a conserved aromatic residue at position 117 in IL-1β, versus a conserved cysteine in IL-1Ra at the analogous position, 116. We find that the replacement of C116 with a phenylalanine switches the protein from an antagonist to an agonist despite the distant location of C116 relative to receptor interaction sites. These results suggest new ways to develop designer cytokine activity into the β-trefoil fold and may be of general use in regulation of this large family of signaling proteins.


Classification of scanning electron microscope images of pharmaceutical excipients using deep convolutional neural networks with transfer learning.
Convolutional Neural Networks (CNNs) are image analysis techniques that have been applied to image classification in various fields. In this study, we applied a CNN to classify scanning electron microscopy (SEM) images of pharmaceutical raw material powders to determine if a CNN can evaluate particle morphology. We tested 10 pharmaceutical excipients with widely different particle morphologies. SEM images for each excipient were acquired and divided into training, validation, and test sets. Classification models were constructed by applying transfer learning to pretrained CNN models such as VGG16 and ResNet50. The results of a 5-fold cross-validation showed that the classification accuracy of the CNN model was sufficiently high using either pretrained model and that the type of excipient could be classified with high accuracy. The results suggest that the CNN model can detect differences in particle morphology, such as particle size, shape, and surface condition. By applying Grad-CAM to the constructed CNN model, we succeeded in finding particularly important regions in the particle image of the excipients. CNNs have been found to have the potential to be applied to the identification and characterization of raw material powders for pharmaceutical development.


Real-world treatment patterns and survival outcomes for advanced non-small cell lung cancer in the pre-immunotherapy era in Portugal: a retrospective analysis from the I-O Optimise initiative.
As part of the multinational I-O Optimise research initiative, this retrospective cohort study of patients with advanced non-small cell lung cancer (NSCLC) evaluated real-world treatment patterns and survival prior to immunotherapy reimbursement in Portugal. This study utilized a database held by IPO-Porto, Portugal's largest oncology hospital. Adult patients diagnosed with stage IIIB or IV NSCLC from January 2012 to December 2016 at IPO-Porto, with follow-up to June 2017, were included. Treatment analyses were performed from 2015 onwards. Kaplan-Meier methods were used for overall survival (OS). Factors associated with OS and systemic anti-cancer therapy (SACT) treatment were assessed using multivariate statistical models. Of 1524 patients diagnosed with NSCLC at IPO-Porto, 1008 patients had advanced disease (stage IIIB: 10.1%, 154/1524, stage IV: 56.0%, 854/1524). For those with advanced disease, median age was 65 years (range: 21-92) and 75.6% (762/1008) were male. Median OS (interquartile range [IQR]) was 11.4 (5.2-26.9) months for stage IIIB and 6.3 (2.4-15.0) months for stage IV. Factors associated with decreased risk of death included female sex and epidermal growth factor receptor gene (EGFR)/anaplastic lymphoma kinase gene (ALK) mutations/rearrangements; factors associated with increased risk of death included older age and stage IV disease. Among patients diagnosed in 2015 or 2016, 75.8% (297/392) received ≥1 line of SACT. Platinum-based chemotherapy was the most common first-line therapy (non-squamous cell carcinoma [NSQ]: 72.9%; squamous cell carcinoma [SQ] 87.3%, 55/63; patients with EGFR/ALK mutations/rearrangements primarily received tyrosine kinase inhibitors). The likelihood of receiving SACT was lower in older patients and those diagnosed with stage IV disease. Patients not receiving SACT had poor survival outcomes (median OS [IQR]: NSQ, 1.8 [1.1-3.1] months; SQ, 2.3 (1.3-3.4) months), while median OS (IQR) in SACT-treated patients was 12.6 (6.1-24.5) months for NSQ and 10.3 (5.7-15.9) months for SQ. This real-world data analysis from a large Portuguese oncology hospital demonstrates a high disease burden for advanced NSCLC in the pre-immunotherapy era, with nearly one-quarter of patients not receiving SACT. Even in patients receiving SACT, median survival was only about 1 year.


Separation principles of cycling temperature capillary electrophoresis.
High throughput means to detect and quantify low-frequency mutations (<10(-2) ) in the DNA-coding sequences of human tissues and pathological lesions are required to discover the kinds, numbers, and rates of genetic mutations that (i) confer inherited risk for disease or (ii) arise in somatic tissues as events required for clonal diseases such as cancers and atherosclerotic plaque.While throughput of linear DNA sequencing methods has increased dramatically, such methods are limited by high error rates (>10(-3) ) rendering them unsuitable for the detection of low-frequency risk-conferring mutations among the many neutral mutations carried in the general population or formed in tissue growth and development. In contrast, constant denaturing capillary electrophoresis (CDCE), coupled with high-fidelity PCR, achieved a point mutation detection limit of <10(-5) in exon-sized sequences from human tissue or pooled blood samples. However, increasing CDCE throughput proved difficult due to the need for precise temperature control and the time-consuming optimization steps for each DNA sequence probed. Both of these problems have been solved by the method of cycling temperature capillary electrophoresis (CTCE). The data presented here provide a deeper understanding of the separation principles involved in CTCE and address several elements of a previously presented two-state transport model.


Scalable chromatography-based purification of virus-like particle carrier for epitope based influenza A vaccine produced in Escherichia coli.
Virus-like particles (VLPs) are promising molecular structures for the design and construction of novel vaccines, diagnostic tools, and gene therapy vectors. Size, oligomer assembly and repetitiveness of epitopes are optimal features to induce strong immune responses. Several VLP-based vaccines are currently licensed and commercialized, and many vaccine candidates are now under preclinical and clinical studies. In recent years, the development of genetically engineered recombinant VLPs has accelerated the need for new, improved downstream processes. In particular, a rapid low cost purification process has been identified as a remaining key challenge in manufacturing process development. In the present study we set up a size-exclusion chromatography-based, scalable purification protocol for the purification of a VLP-based influenza A vaccine produced in Escherichia coli. Recombinant VLPs derived from the RNA bacteriophage MS2 displaying an epitope from the ectodomain of Matrix 2 protein from influenza A virus were produced and purified. The 3 steps purification protocol uses a recently developed multimodal size-exclusion chromatography medium (Capto™ Core 700) in combination with detergent extraction and size-exclusion polishing to reach a 89% VLP purity with a 19% yield. The combination of this downstream strategy following production in E. coli would be suited for production of VLP-based veterinary vaccines targeting livestock and companion animals where large amounts of doses must be produced at an affordable price.


A Prospective Study Investigating Blood Patch Pleurodesis for Postoperative Air Leaks After Pulmonary Resection.
Prolonged air leaks (PALs) after lung resection are one of the most common complications in thoracic surgery. Several options are available to treat PALs. The autologous blood patch pleurodesis is commonly used but has not been thoroughly investigated. We conducted a prospective randomized study including all consecutive patients with PALs after pulmonary resections. Patients were randomized to either having received pleurodesis by injecting 100 mL autologous blood at d 5 and 6 (Group A) or being placed under observation (Group B). Patients from either group undergoing revisions were further investigated by a post hoc analysis and formed Group C. A total of 24 patients were included: 10 patients were randomized to group A and 14 to group B. Six patients (3 from each group) underwent surgical revision and were included in Group C. Groups A and B did not differ in baseline characteristics. The median time to drainage removal was 9 d (range: 5-23 d) in Group A; 9 d (range: 2-20 d) in Group B; and 6 d in Group C (range: 3-10 d), (A/B versus C, P < 0.04; A versus B was not significant). There is no evidence indicating a benefit for blood patch pleurodeses in patients undergoing lung resections and presenting with postoperative PALs for more than 5 d. An early operative closure of postoperative air leakage seems to be more effective.


Design of an S-scheme photo-catalyst utilizing a Cu-doped perovskite and MOF-5 for simultaneous degradation of organic pollutants under LED light irradiation: Application of EXRSM method for spectra separation and BBD-RSM modeling.
Heterojunction photo-catalysts have attracted significant attention in solar energy conversion due to their ability to reduce suppressing electron-hole pairs and improve catalytic capability. Herein, we designed an S-scheme photo-catalyst by encapsulating a Cu-doped perovskite inside the pores of MOF-5 for the first time, exhibiting excellent efficiency in a pollutant degradation process. The pristine MOF cannot act in the visible light region because of its wide bandgap. However, the encapsulation modified its bandgap and but also increased its photo-catalytic activity. Simultaneous photo-degradation of two organic contaminants, methylene blue (MB) and paracetamol (PA), was investigated to evaluate the catalytic activity of this composite. As a challenge, the UV-vis spectra of PA strongly overlapped with MB in a binary mixture preventing direct measurement of its concentration without previous separation via conventional methodologies. Hence, we used a simple and fast technique called the extended ratio subtraction method (EXRSM) to separate their absorption spectra. The statistical investigations established that it could resolve the issue of signal overlapping. Also, a statistical approach, Box-Behnken (BBD-RSM), was used to model and optimize the degradation process providing a better way to explain the effect and interactions of main parameters on degradation efficiency. Now, an empirical model for each pollutant can make a relationship between them. The photo-degradation yield was obtained at 67.12% and 87.96% for PA and MB, respectively, under optimum conditions. Furthermore, the kinetics and mechanism of reaction were investigated, and the results revealed that it follows a pseudo-first-order model for each pollutant.


Triage of ASC-H: A meta-analysis of the accuracy of high-risk HPV testing and other markers to detect cervical precancer.
Women with a cytological diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) are usually immediately referred for colposcopy. However, triage may reduce the burden of the diagnostic workup and prevent overtreatment. A meta-analysis was conducted to assess the accuracy of high-risk human papillomavirus (hrHPV) testing and testing for other molecular markers for the detection of grade 2 cervical intraepithelial neoplasia or worse (CIN2+) or grade 3 cervical intraepithelial neoplasia or worse (CIN3+) in women with ASC-H. An additional question that was assessed was whether triage would be useful in light of the relatively high pretriage probability of underlying precancer. The pooled absolute sensitivity and specificity of the Hybrid Capture 2 (HC2) assay for CIN2 + (derived from 19 studies) were 93% (95% confidence interval [CI], 89%-95%) and 45% (95% CI, 41%-50%), respectively. p16(INK4a) staining (only 3 studies) had similar sensitivity (93%; 95% CI, 75%-100%) but superior specificity (specificity ratio, 1.69) to HC2 for CIN2+. Testing for paired box 1 gene methylation (only 1 study) showed a superior specificity of 95% (specificity ratio, 2.08). The average pretest risk was 34% for CIN2 + and 20% for CIN3+. A negative HC2 result decreased this to 8% and 5%, respectively, whereas a positive result upgraded the risk to 47% and 28%, respectively. Because of the high probability of precancer with a diagnosis of ASC-H, the utility of triage is limited. The usual recommendation for referring women with ASC-H for colposcopy is not altered by a positive triage test, whatever test is used. A negative hrHPV DNA or p16(INK4a) test may allow repeat testing, but this recommendation will depend on local decision thresholds for referral.


Comparative study of therapeutic effects of short- and long-acting loop diuretics in outpatients with chronic heart failure (COLD-CHF).
Loop diuretics have two different classes with different duration of activity: short-acting such as furosemide (duration of activity, 6h) and long-acting such as azosemide (duration of activity, 10-12h). We conducted a multicenter, randomized, controlled trial in order to compare the therapeutic effects of azosemide, a long-acting loop diuretic, and furosemide, a short-acting one, on neurohumoral factors and cardiac function in outpatients with chronic heart failure (CHF). We enrolled 98 patients with CHF who were receiving furosemide and an angiotensin-converting enzyme inhibitor, and they were randomly divided into furosemide (n=49) and azosemide (n=49) groups. The furosemide group continued furosemide at the same dosage, and the azosemide group switched from furosemide to azosemide. At baseline and after 3 months, we measured body weight, and levels of brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), norepinephrine, active renin, creatinine, blood urea nitrogen, sodium, potassium, and hematocrit. Chest X-ray and echocardiography were also performed. Body weight and plasma levels of BNP and ANP significantly decreased after 3 months in the azosemide group compared to the furosemide group. There were no significant differences in changes of levels of creatinine, blood urea nitrogen, sodium, potassium, hematocrit, norepinephrine, and active renin after 3 months between the furosemide and azosemide groups. Echocardiography and chest X-ray did not demonstrate significant differences between the two groups. Long-acting azosemide is suggested to be useful for the improvement of neurohumoral factors compared with short-acting furosemide in patients with CHF.


The intracellular effects of non-ionic amphiphilic cyclodextrin nanoparticles in the delivery of anticancer drugs.
The aim of this study was to develop nanoparticles made of the amphiphilic cyclodextrin heptakis (2-O-oligo(ethyleneoxide)-6-hexadecylthio-)-beta-CD (SC16OH) entrapping docetaxel (Doc) and establish their in vivo potential. Doc-loaded SC16OH nanoparticles were prepared by the emulsion-solvent evaporation technique and fully characterized for size, zeta potential, amount of entrapped drug, release rate and degradation rate. Spherical vesicular nanoparticles displaying a hydrodynamic radius of about 95 nm which did not change upon storage as an aqueous dispersion, a negative zeta potential and entrapment efficiency of Doc very close to 100% were produced. DSC study highlighted the crystalline nature of SC16OH, unloaded and Doc-loaded SC16OH nanoparticles which resulted in their very slow dissolution during release stage and well-modulated release of entrapped Doc for about 8 weeks. Doc-loaded SC16OH nanoparticles were not hemolytic toward red blood cells as compared to a commercial Doc formulation (Taxotere) which shows a dose-dependent toxicity. After exposure of HEp-2 cells to equivalent doses of free Doc and Doc-loaded SC16OH nanoparticles, superior cell killing and cell damage were observed for nanoparticles. Finally, cell damage was attributed to aberrant mitosis which was found to be significantly higher for HEp-2 cells treated with Doc-loaded SC16OH nanoparticles as compared to free Doc likely due to the ability of nanoparticles to slowly release the drug allowing prolonged cell arrest in mitosis. Taken together, these results highlights a great potential of nanoparticles based on SC16OH in solid tumors therapy.


[Effect of an ultrahigh-frequency electromagnetic field on the heat conductivity of experimental biological tissue].
It has been established that heat conductivity was markedly increased after UHF-irradiation. The combined use of UHF-irradiation and cryogenic destruction is 30-40 times as effective as cryogenic destruction alone.


Effect of a lung recruitment maneuver by high-frequency oscillatory ventilation in experimental acute lung injury on organ blood flow in pigs.
The objective was to study the effects of a lung recruitment procedure by stepwise increases of mean airway pressure upon organ blood flow and hemodynamics during high-frequency oscillatory ventilation (HFOV) versus pressure-controlled ventilation (PCV) in experimental lung injury. Lung damage was induced by repeated lung lavages in seven anesthetized pigs (23-26 kg). In randomized order, HFOV and PCV were performed with a fixed sequence of mean airway pressure increases (20, 25, and 30 mbar every 30 minutes). The transpulmonary pressure, systemic hemodynamics, intracranial pressure, cerebral perfusion pressure, organ blood flow (fluorescent microspheres), arterial and mixed venous blood gases, and calculated pulmonary shunt were determined at each mean airway pressure setting. The transpulmonary pressure increased during lung recruitment (HFOV, from 15 +/- 3 mbar to 22 +/- 2 mbar, P < 0.05; PCV, from 15 +/- 3 mbar to 23 +/- 2 mbar, P < 0.05), and high airway pressures resulted in elevated left ventricular end-diastolic pressure (HFOV, from 3 +/- 1 mmHg to 6 +/- 3 mmHg, P < 0.05; PCV, from 2 +/- 1 mmHg to 7 +/- 3 mmHg, P < 0.05), pulmonary artery occlusion pressure (HFOV, from 12 +/- 2 mmHg to 16 +/- 2 mmHg, P < 0.05; PCV, from 13 +/- 2 mmHg to 15 +/- 2 mmHg, P < 0.05), and intracranial pressure (HFOV, from 14 +/- 2 mmHg to 16 +/- 2 mmHg, P < 0.05; PCV, from 15 +/- 3 mmHg to 17 +/- 2 mmHg, P < 0.05). Simultaneously, the mean arterial pressure (HFOV, from 89 +/- 7 mmHg to 79 +/- 9 mmHg, P < 0.05; PCV, from 91 +/- 8 mmHg to 81 +/- 8 mmHg, P < 0.05), cardiac output (HFOV, from 3.9 +/- 0.4 l/minute to 3.5 +/- 0.3 l/minute, P < 0.05; PCV, from 3.8 +/- 0.6 l/minute to 3.4 +/- 0.3 l/minute, P < 0.05), and stroke volume (HFOV, from 32 +/- 7 ml to 28 +/- 5 ml, P < 0.05; PCV, from 31 +/- 2 ml to 26 +/- 4 ml, P < 0.05) decreased. Blood flows to the heart, brain, kidneys and jejunum were maintained. Oxygenation improved and the pulmonary shunt fraction decreased below 10% (HFOV, P < 0.05; PCV, P < 0.05). We detected no differences between HFOV and PCV at comparable transpulmonary pressures. A typical recruitment procedure at the initiation of HFOV improved oxygenation but also decreased systemic hemodynamics at high transpulmonary pressures when no changes of vasoactive drugs and fluid management were performed. Blood flow to the organs was not affected during lung recruitment. These effects were independent of the ventilator mode applied.


Effects of polyethylene glycol attachment on physicochemical and biological stability of E. coli L-asparaginase.
L-asparaginase obtained from E. coli strains is an important enzyme widely used in leukemia treatment. However, hypersensitivity reactions must be considered a relevant adverse effect of asparaginase therapy. One approach to reduce the hypersensitivity reactions caused by this enzyme is to change its physicochemical and biological properties by means of polyethylene glycol (PEG) conjugation, resulting in a less immunogenic enzyme with much longer half-time of plasmatic life. This work investigated the factors that could interfere in PEG-enzyme's stability. The complexation did not affect the range of pH activity and stability was improved in acid medium remaining stable during 1 h at pH 3.5. The PEG-enzyme exhibited activity restoration capacity (32% after 60 min) when subjected to temperatures of 65 degrees C in physiological solution. The PEG-enzyme in vitro assays showed a very high stability in a human serum sample, keeping its activity practically unchanged during 40 min (strength to non-specific antibodies or proteases in serum). An increase of PEG-enzyme catalytic activity during the lyophilization was observed. The process of modification of L-asparaginase with PEG improved both physicochemical and biological stability.


Global gene expression analysis reveals a subtle effect of DEHP in human granulosa cell line HGrC1.
Di(2-ethylhexyl) phthalate (DEHP) is an endocrine disruptor that exerts anti-steroidogenic effects in human granulosa cells; however, the extent of this effect depends on the concentration of DEHP and granulosa cell models used for exposure. The objective of this study was to identify the effects of low- and high-dose DEHP exposure in human granulosa cells. We exposed human granulosa cell line HGrC1 to 3 nM and 25 μM DEHP for 48 h. The whole genome transcriptome was analyzed using the DNBSEQ sequencing platform and bioinformatics tools. The results revealed that 3 nM DEHP did not affect global gene expression, whereas 25 µM DEHP affected the expression of only nine genes in HGrC1 cells: ABCA1, SREBF1, MYLIP, TUBB3, CENPT, NUPR1, ASS1, PCK2, and CTSD. We confirmed the downregulation of ABCA1 mRNA and SREBP-1 protein (encoded by the SREBF1 gene), both involved in cholesterol homeostasis. Despite these changes, progesterone production remained unaffected in low- and high-dose DEHP-exposed HGrC1 cells. The high concentration of DEHP decreased the levels of ABC1A mRNA and SREBP-1 protein and prevented the upregulation of STAR, a protein involved in progesterone synthesis, in forskolin-stimulated HGrC1 cells; however, the observed changes were not sufficient to alter progesterone production in forskolin-stimulated HGrC1 cells. Overall, this study suggests that acute exposure to low concentration of DEHP does not compromise the function of HGrC1 cells, whereas high concentration causes only subtle effects. The identified nine novel targets of high-dose DEHP require further investigation to determine their role and importance in DEHP-exposed human granulosa cells.


A highly efficient scheme for library preparation from single-stranded DNA.
Although methods for sequencing library preparation from double-stranded DNA are well established, those from single-stranded DNA (ssDNA) have not been well studied. Further, the existing methods have limitations in efficiency and yield. Therefore, we developed a highly efficient procedure for sequencing library preparation from ssDNA. In this method, the first adaptor tagging of ssDNA is performed using terminal deoxyribonucleotidyl transferase (TdT)-assisted adenylate connector-mediated ssDNA (TACS) ligation, which we reported recently. After complementary strand synthesis using the adaptor-tagged ssDNA, second adaptor tagging via Vaccinia virus topoisomerase I (VTopoI or TOPO)-based adaptor ligation is performed. With additional steps for degradation, repression, and removal of the adaptor dimer, the proposed TACS-TOPO scheme realizes adaptor dimer-free sequencing library preparation from ssDNA samples of 24 pg. The TACS-TOPO scheme was successfully applied to cell-free DNA analysis with amplification-free library preparation from 50 µL of human serum. A modified TACS-TOPO scheme was also applied to DNA extracted from ancient human bones, bringing two to eight times more library yields than those using a conventional library preparation protocol. The procedures for preparing VTopoI and its complex with a double-stranded oligonucleotide adaptor are also described. Overall, the proposed TACS-TOPO scheme can facilitate practical and sensitive sequencing analysis of ssDNA.


Integration of urban science and urban climate adaptation research: opportunities to advance climate action.
There is a growing recognition that responding to climate change necessitates urban adaptation. We sketch a transdisciplinary research effort, arguing that actionable research on urban adaptation needs to recognize the nature of cities as social networks embedded in physical space. Given the pace, scale and socioeconomic outcomes of urbanization in the Global South, the specificities and history of its cities must be central to the study of how well-known agglomeration effects can facilitate adaptation. The proposed effort calls for the co-creation of knowledge involving scientists and stakeholders, especially those historically excluded from the design and implementation of urban development policies.


Hypoaminoacidemia underpins glucagon-mediated energy expenditure and weight loss.
Glucagon analogs show promise as components of next-generation, multi-target, anti-obesity therapeutics. The biology of chronic glucagon treatment, in particular, its ability to induce energy expenditure and weight loss, remains poorly understood. Using a long-acting glucagon analog, G108, we demonstrate that glucagon-mediated body weight loss is intrinsically linked to the hypoaminoacidemia associated with its known amino acid catabolic action. Mechanistic studies reveal an energy-consuming response to low plasma amino acids in G108-treated mice, prevented by dietary amino acid supplementation and mimicked by a rationally designed low amino acid diet. Therefore, low plasma amino acids are a pre-requisite for G108-mediated energy expenditure and weight loss. However, preventing hypoaminoacidemia with additional dietary protein does not affect the ability of G108 to improve glycemia or hepatic steatosis in obese mice. These studies provide a mechanism for glucagon-mediated weight loss and confirm the hepatic glucagon receptor as an attractive molecular target for metabolic disease therapeutics.


Epibulbar choristomas containing lacrimal tissue. Clinical distinction from dermoids and histologic evidence of an origin from the palpebral lobe.
Three new cases of epibulbar choristomas, all containing lacrimal tissue, are presented and compared with those reported previously in the literature. The first and second cases were unilateral, complex choristomas, consisting of ectopic lacrimal tissue, smooth muscle, and cartilage; the first case was also remarkable for the presence of lesional tissue in the peripheral cornea and evidence of progressive growth during puberty. The third case was a bilateral, complex choristoma, manifesting epibulbar lacrimal tissue, cartilage, and smooth muscle; also associated were bilateral optic nervehead colobomas and a uniocular focus of posterior scleral cartilage demonstrated by computed tomography (CT) scanning. On clinical examination, all three lesions displayed highly vascularized thickenings of the conjunctiva with diagnostically useful gelatinous elevations, which corresponded microscopically to lobules of lacrimal tissue. In addition, all three cases had the interesting diagnostic feature of superficial corneal scarring or sclerosis, with a fine vascularity adjacent to the conjunctival lesional tissue. Electron microscopy of the third case demonstrated completely normal cytoarchitecture of the lacrimal tissue. Because of the frequent presence of Müller's smooth muscle in epibulbar lacrimal choristomas, the authors propose that these lesions represent embryologic ectopias or overly extensive field effects of the palpebral lobe of the lacrimal gland.


Value of urine/serum Neutrophil gelatinase-associated lipocalin ratio in distinguishing acute kidney injury from chronic kidney disease.
This study was performed to test the hypothesis that neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker would be helpful for differentiation acute kidney injury (AKI) from chronic kidney disease (CKD) in kidney malfunction patients from the nephrology department. This retrospective study included 355 patients admitted from the nephrology department with modification of diet in renal disease estimated glomerular filtration rate (MDRD eGFR) < 60 ml/min/1.73 m2. The subjects were categorized into AKI group (n = 204) and CKD group (n = 151). A propensity-matched analysis, incorporating 17 variables, was performed to control potential selection bias. Urinary NGAL (uNGAL) level in the AKI group was higher than in the CKD group (372.10 (170.10-690.63) vs 88.10 (52.00-238.80), P < 0.001), but there was no significant difference in serum NGAL (sNGAL). Both sNGAL and uNGAL had a correlation with MDRD eGFR in total patients, AKI patients, and CKD patients. The propensity-matched analysis enrolled 75 patients in each group. In matched AKI group, sNGAL was lower (401.20 (239.10-616.00) vs 468.50 (305.00-709.40), P = 0.049) and uNGAL was elevated (284.00 (136.90-690.90) vs 203.70 (69.20-596.00), P = 0.032), compared with the matched CKD group. In all patients (n = 355), the ratio of uNGAL and sNGAL (u/s NGAL), fractional excretion of NGAL (Fe NGAL) discriminated AKI from CKD (area under the curve, 0.803 and 0.790, respectively). After stratified kidney function, the sub-analyses found that u/s NGAL and Fe NGAL were shown to differ substantially between the AKI group and CKD group (all P < 0.01). The u/s NGAL ratio always had the highest AUC area in the sub-analyses. u/s NGAL might be helpful to discriminate AKI from CKD in kidney malfunction patients admitted to the nephrology department. Further confirmatory studies might be warranted.


Comparing triage evaluation of adult dyspneic patients between emergency nurses and doctors using simulated scenarios.
Although registered nurses frequently perform triaging in many emergency departments (EDs), little is known regarding the agreement between nurses and doctors in triaging dyspneic patients. The aim of our study was to compare the effectiveness of trained ED nurses with doctors in the evaluation of dyspneic patients at triage using the SimMan 3G simulator. We compared eight nurses who underwent a structured training/accreditation program with eight doctors. Two assessors evaluated them through seven common and/or important cardiorespiratory simulated scenarios. Each scenario had an evaluation instrument that scored participants on triage assessment and management. Each nurse was also surveyed over a six-point Likert scale (0-5) on their confidence in triaging dyspneic patients after the study. Data was analyzed using descriptive statistics with statistical significance set at p<0.05. There were no statistically significant differences between the mean assessment or management scores across all scenarios between doctors versus nurses (p ranging from 0.070 to 0.798). Six nurses felt they could evaluate ED dyspneic patients alone (score of 4) and the remainder with supervision (score of 2-3). Trained ED nurses; when compared to doctors; could triage and evaluate dyspneic patients effectively on a simulator.


Ultrasound-guided intraoperative electron beam radiation therapy: A phantom study.
To develop the method for ultrasound (US)-guided intra-operative electron beam radiation therapy (IOERT). We first established the simulation, planning, and delivery methods for US-guided IOERT and constructed appropriate hardware (the multi-function applicator, accessories, and US phantom). We tested our US-guided IOERT method using this hardware and the Monte Carlo simulation IOERT treatment planning system (TPS). The IOERT TPS used a compensator to build the conformal dose distribution. Then, we used the TPS to evaluate the effect of setup uncertainty on target coverage by introducing phantom setup error ranging from 0 mm to 10 mm to the plans with and without the compensator. The simulation, planning, and delivery methods for US-guided IOERT were introduced and validated on a phantom. A complete technique for US-guided IOERT was established. Target coverage decreased by about 12% and 29% as the phantom setup error increased to 5 mm and 10 mm for the plans with compensator, respectively. Without compensator, the corresponding target coverage decreases were 2% and 13%, respectively. In our study, we developed the multi-function applicator, US Phantom, and TPS for IOERT. The procedures included not only dose distribution planning, but also intraoperative US imaging, which provided the information necessary during surgery to improve IOERT quality assurance. Target coverage was more sensitive to setup errors with compensator compared to no compensator. Further studies are needed to validate the clinical efficacy of this US-guided IOERT method.


3D microstructural study of selachimorph enameloid evolution.
Enameloid, the hyper-mineralized tissue covering shark teeth is a complex structure resulting from both ameloblast and odontoblast activity. The way these two types of cells interact to set up this tissue is not fully understood and results in the formation of subunits in the enameloid: the Single Crystallite Enameloid (SCE) and the Bundled Crystallite Enameloid (BCE). Using the Focused Ion Beam Nanotomography (FIB-nt), 3D images were produced to assess the relationship between the SCE and BCE of one fossil and one recent neoselachian shark teeth. 3D analysis of crystallite bundles reveals a strong connection between the crystallites forming the SCE and those forming the bundles of the Radial Bundle Enameloid (RBE), a component of the BCE, although it has been suggested that SCE and BCE have a different origin: epithelial for the SCE and mesenchymal for the BCE. Another significant result of the use of FIB-nt is the visualization of frequent branching among the radial bundles forming the RBE, including horizontal link between adjacent bundles. FIB-nt demonstrates therefore a strong potential to decipher the complex evolution of hyper-mineralised tissue in shark teeth, and, therefore, to better understand the evolution of tooth structure among basal Gnathostomes.


Case study: ancient DNA recovered from pleistocene-age remains of a Florida armadillo.
Warm, humid regions are not ideal for long-term DNA preservation. Consequently, little ancient DNA research has been carried out involving taxa that lived in, for example, tropical and subtropical regions. Those studies that have isolated ancient DNA from warm environments have mostly been limited to the most recent several thousand years. Here, we discuss an ancient DNA experiment in which we attempt to amplify mitochondrial DNA from remains of armadillo, glyptodont, and pampathere from sites in Florida, USA, all believed to be around 10,000-12,000 years old. We were successful in recovering DNA from only one of these samples. However, based on the amount and distribution of DNA damage, the ancient DNA recovered was well-preserved despite the age and preservation environment. In this case study chapter, we discuss the experimental procedure we used to characterize the DNA from the Floridian samples, focusing on challenges of working with ancient specimens from warm environments and steps taken to confirm the authenticity of the recovered sequence.


Ambient air pollution and daily emergency department visits for asthma in Edmonton, Canada.
As demonstrated by many studies, emergency department (ED) visits for asthma can be associated with air pollution exposures. The aim of this study was to examine and assess the potential relations between ED visits for asthma and the concentrations of ambient air pollutants. Generalized linear mixed model was applied to study 62,563 ED visits for asthma (ICD-9: 493) in Edmonton, Canada. Two age groups, with 10 years of age as a separator, were considered by gender and season of the year: all (I-XII), warm (IV-IX) and cold (X-III). The percentage increase in daily ED visits for asthma was 17.8% (95% CI: 7.1-29.5) and 13.8% (95% CI: 3.3-25.3) for females below 10 years of age, in the period of IV-IX, for current day and 1-day lagged exposure to ozone (O(3)), respectively. The percentage increase was 19.2% (95% CI: 11.4-27.6) for males below 10 years of age, in the period of IV-IX, for 2-day lagged exposure to nitrogen dioxide (NO(2)). The findings provide support for the hypothesis that ED visits for asthma are associated with exposure to O(3). This study underlines the significant role of air pollutants as triggering asthma attacks.


Glaucoma: Management and Future Perspectives for Nanotechnology-Based Treatment Modalities.
Glaucoma, being asymptomatic for relatively late stage, is recognized as a worldwide cause of irreversible vision loss. The eye is an impervious organ that exhibits natural anatomical and physiological barriers which renders the design of an efficient ocular delivery system a formidable task and challenge scientists to find alternative formulation approaches. In the field of glaucoma treatment, smart delivery systems for targeting have aroused interest in the topical ocular delivery field owing to its potentiality to oppress many treatment challenges associated with many of glaucoma types. The current momentum of nano-pharmaceuticals, in the development of advanced drug delivery systems, hold promises for much improved therapies for glaucoma to reduce its impact on vision loss. In this review, a brief about glaucoma; its etiology, predisposing factors and different treatment modalities has been reviewed. The diverse ocular drug delivery systems currently available or under investigations have been presented. Additionally, future foreseeing of new drug delivery systems that may represent potential means for more efficient glaucoma management are overviewed. Finally, a gab-analysis for the required investigation to pave the road for commercialization of ocular novel-delivery systems based on the nano-technology are discussed.


Bronchial carcinoid tumor: A case report.
Bronchial carcinoid tumors are rare, slow growing, malignant neuroendocrine tumors and account for less than 2% of all lung tumors. Early diagnosis is extremely important as the main stay of treatment is surgical excision. We present a rare case of bronchial typical carcinoid tumor in a 22-year-old female who presented with a complaint of intermittent productive cough with bloody sputum of 3 weeks' duration associated with wheezing, low grade intermittent fever and loss of appetite. She was being treated as bronchial asthma for 10 years prior to her current presentation. Right lung bi-lobectomy with regional lymph node resection was done and she was discharged home in good condition. Majority of typical carcinoids are located in the central airways leading to bronchial obstruction with recurrent pneumonia, chest pain, wheezing and hemoptysis. Due to such nonspecific presentation most patients are misdiagnosed or diagnosed late. Both typical and atypical Carcinoids have similar radiologic features and definitive diagnosis relies on bronchoscopic tissue biopsy. Although hilar and mediastinal lymph nodes are the most common metastatic sites for typical carcinoids most lymphadenopathies are caused by a reactive inflammatory reaction. Bronchial carcinoids are rare, malignant neuroendocrine tumors with complete surgical resection being the only curative management. Thus patients with recurrent respiratory symptoms despite optimum medical treatment should be thoroughly investigated for accurate and early diagnosis The outcome of typical carcinoids with lymph node metastasis is excellent with complete resection but close follow up is mandatory when dealing with larger tumors.


Minimal alteration of pulmonary function after lobectomy in lung cancer patients with chronic obstructive pulmonary disease.
The aim of this study was to evaluate the influence of chronic obstructive pulmonary diseases (COPD) on postoperative pulmonary function and to elucidate the factors for decreasing the reduction of pulmonary function after lobectomy. We conducted a retrospective chart review of 521 patients who had undergone lobectomy for lung cancer at Chiba University Hospital between 1990 and 2000. Forty-eight patients were categorized as COPD, defined as percentage of predicted forced expiratory volume at 1 second (FEV1) less than or equal to 70% and percentage of FEV1 to forced vital capacity less than or equal to 70%. The remaining 473 patients were categorized as non-COPD. Although all preoperative pulmonary function test data and arterial oxygen tension were significantly lower in the COPD group, postoperative arterial oxygen tension and FEV1 were equivalent between the two groups, and the ratio of actual postoperative to predicted postoperative FEV1 was significantly better in the COPD group (p < 0.001). With multivariable analysis, COPD and pulmonary resection of the lower portion of the lung (lower or middle-lower lobectomies) were identified as independent factors for the minimal deterioration of FEV1. Actual postoperative FEV1 was 15% lower and higher than predicted, respectively, in the non-COPD patients with upper portion lobectomy and the COPD patients with lower portion lobectomy. Finally, we created a new equation for predicting postoperative FEV1, and it produced a higher coefficient of determination (R(2)) than the conventional one. The postoperative ventilatory function in patients with COPD who had lower or middle-lower lobectomies was better preserved than predicted.


[Long-term exposure to PM2.5 from automobile exhaust results in reproductive dysfunction in male rats].
To explore the effects of long-term exposure to particulate matter 2.5 (PM2.5) from automobile exhaust on the reproductive function of Sprague Dawley (SD) rats. Forty-five male SD rats, weighing 80 - 94 g and aged 28 days, were randomly assigned to receive intra-tracheal administration of 0.9% normal saline (control group, n = 15), PM2. 5 at 2 μg per 100 g body weight per day (low-dose PM2.5 group, n = 15), and PM2.5 at 16 μg per 100 g body weight per day (high-dose PM2.5 group, n = 15), qd, for 60 successive days. After the last 24-hour exposure, 10 rats were taken from each group for copulation with normal female ones, while the others were sacrificed, their testes removed for sperm count and deformity, pathological examination, and determination of the Connexin43 expression. The conception rate was significantly decreased in the low- and high-dose PM2.5 groups as compared with that of the control (70% and 50% vs 100%), and so were the sperm count and quality. The rats in the PM2.5-exposed groups showed significantly disordered histological structure of the seminiferous tubules, reduced sperm count in the testicular lumen, some exfoliated secondary spermatocytes, downregulated Connexin43 expression in the testis, and damaged blood-testis barrier. Long-term exposure to PM2.5 from automobile exhaust damages the reproductive function of male SD rats.


Estrogen receptor binding material in blood of patients after clomiphene citrate administration: determination by a radioreceptor assay.
The aim of the current study was to assess whether clomiphene citrate (CC) and/or active metabolites are present at presumed time of ovulation, nidation, or steroid-sensitive organogenesis, in serum of patients receiving CC for induction of ovulation. A radioreceptor assay, based on competitive replacement of 3H-estradiol on the rat uterus estrogen receptor, by ligands present in serum of patients after CC administration, was developed. Ligands reached maximal concentration 4 to 5 hours after a single dose of CC was administered, and declined with a half-life of 4.5 to 10 hours. In patients receiving CC on day 5 to day 9 in the cycle, ligands are still present on day 14 in the cycle and in some patients on day 22 of the cycle, but no ligands were detected 60 days after CC treatment.


Synthesis and activity of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors.
A series of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors was discovered. Several compounds such as 15 and 20 showed good hNET potency. Compounds 15 and 20 also displayed excellent selectivity at hNET that appeared superior to those of reboxetine and atomoxetine (4 and 5).


Interactions between the protein-epigallocatechin gallate complex and nanocrystalline cellulose: A systematic study.
In this work, the noncovalent interactions between the protein-epigallocatechin gallate (protein-EGCG) complex and nanocrystalline cellulose (NCC) were systematically investigated. Rheological properties, including large amplitude oscillation shear (LAOS), transient rheology, and conventional rheology of the mixture were also evaluated. As obtained, flexible myofibrillar protein-epigallocatechin gallate (MP-EGCG) and rigid ovalbumin-epigallocatechin gallate (Ova-EGCG) follow different rules in the stability of the regulatory system because of the difference in noncovalent interactions, triggering different rheological responses of the complexes. Additionally, MP-EGCG/NCC showed an obvious strain overshoot during LAOS flow, which could not be obtained in Ova-EGCG/NCC. Notably, the fibrous MP-EGCG network was the factor that dominated the formation of a more stable suspension system with strong hydrogen bonding, dipole-dipole interactions and/or van der Waals forces. This study can provide some ideas for the future study of the interaction between protein-polyphenol complexes and polysaccharides.


Regional anesthesia for ambulatory surgery.
Ambulatory surgery is increasing at unprecedented rates with more complex procedures being performed. This article reviews the benefits of the use of regional anesthesia during ambulatory surgeries. Regional anesthesia, by putting the anesthetic at the surgical site, provides ideal conditions for ambulatory surgery and provides a smooth, predictable post-operative course.


Glycoproteins in bacterial membranes. In vivo labeling of the sugar portion of energy-transducing ATPase and a low-molecular-weight fraction fromMicrococcus lysodeikticus membranes.
The energy-transducing ATPase and a low-molecular-weight fraction ofMicrococcus lysodeikticus membranes incorporated(14)C label fromD-[U-(14)C]glucose fed to the bacteria in synthetic medium. The specific radioactivity of the sugar portion of the ATPase and low-molecular-weight fraction was, respectively, 2.65 and 2.88 times that of their amino acids. Glucose and mannose in approximately equimolar amounts were identified as the main sugars of the glycoprotein ATPase, thus confirming previous structural studies. Glucose, galactose, and mannose (1:1:2) were identified as the main sugars of the low-molecular-weight glycopeptides. These results confirm and extend the notion that glycoprotein are constituents of prokaryotic membranes.


Covariation of diet and gut microbiome in African megafauna.
A major challenge in biology is to understand how phylogeny, diet, and environment shape the mammalian gut microbiome. Yet most studies of nonhuman microbiomes have relied on relatively coarse dietary categorizations and have focused either on individual wild populations or on captive animals that are sheltered from environmental pressures, which may obscure the effects of dietary and environmental variation on microbiome composition in diverse natural communities. We analyzed plant and bacterial DNA in fecal samples from an assemblage of 33 sympatric large-herbivore species (27 native, 6 domesticated) in a semiarid East African savanna, which enabled high-resolution assessment of seasonal variation in both diet and microbiome composition. Phylogenetic relatedness strongly predicted microbiome composition (r = 0.91) and was weakly but significantly correlated with diet composition (r = 0.20). Dietary diversity did not significantly predict microbiome diversity across species or within any species except kudu; however, diet composition was significantly correlated with microbiome composition both across and within most species. We found a spectrum of seasonal sensitivity at the diet-microbiome nexus: Seasonal changes in diet composition explained 25% of seasonal variation in microbiome composition across species. Species' positions on (and deviations from) this spectrum were not obviously driven by phylogeny, body size, digestive strategy, or diet composition; however, domesticated species tended to exhibit greater diet-microbiome turnover than wildlife. Our results reveal marked differences in the influence of environment on the degree of diet-microbiome covariation in free-ranging African megafauna, and this variation is not well explained by canonical predictors of nutritional ecology.


Sequence homology between retroviral reverse transcriptase and putative polymerases of hepatitis B virus and cauliflower mosaic virus.
In infected cells, the RNA genomes of RNA tumour viruses are copied into DNA by a virus-encoded reverse transcriptase enzyme. This transfer of information from RNA into DNA was thought to be a unique feature of RNA tumour viruses, but recent results suggest it may be a more general strategy. Hepatitis B virus (HBV) has a double-stranded DNA genome, and it has recently been shown that the minus DNA strand of the HBV genome is copied from a plus-strand RNA template, leading to the suggestion that reverse transcription is central to the life cycle of HBV. More recently it has been suggested that the replication cycle of a plant virus, cauliflower mosaic virus (CaMV), includes a reverse transcription step. We report here the existence of amino acid sequence homology between retroviral reverse transcriptase and the putative polymerases of HBV and CaMV.