ABCA1 rs1883025 polymorphism and risk of age-related macular degeneration.
To evaluate the association of the ABCA1 rs1883025 polymorphism and susceptibility to age-related macular degeneration (AMD). A systematic search of the PubMed, EMBASE, and ISI web of science databases was performed to identify eligible published studies without language restrictions up to September 2015. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were estimated under different genetic models using meta-analytic methods. Stratified analysis and sensitivity analysis were performed to explore potential sources of heterogeneity. A total of 12 articles with 25,445 cases and 36,460 controls were eligible in this meta-analysis. The ABCA1 rs1883025 variant showed significant association with the lower risk of overall AMD under the allelic model (OR= 0.81, 95 % CI=0.74-0.89). Stratified analysis based on ethnicity demonstrated a strong association between rs1883025 polymorphism and AMD in the Caucasian population, but not in Asian population. For late AMD, the ABCA1 rs1883025 variant was observed to have a significant association with the lower risk of this disease (OR = 0.81, 95 % CI, 0.72-0.91). In early-stage AMD, significant associations of the rs1883025 polymorphism with lower risk of early AMD were observed in different genetic models (OR ranging from 0.45 to 0.65, all P < 0.05). The present meta-analysis indicated that the T allelic in rs1883025 variant was significantly associated with the risk of developing AMD, particularly at the early stage. The associations of the ABCA1 locus with AMD risk in various populations need further exploration.


Rapid detection of herpes simplex virus using a combination of human fibroblast cell cultures and peroxidase-antiperoxidase staining.
A method for rapid detection of Herpes simplex virus (HSV), using a combination of human fibroblast cell cultures with peroxidase-antiperoxidase (HF-PAP) staining after 18-24 hours of incubation was developed. The sensitivity of the HF-PAP, compared with viral isolation using primary rabbit kidney and human fibroblast cells, was 88.4% with 20.7% of clinical Herpes isolates detected by HF-PAP before any signs of cytopathic effect (CPE) of HSV were present. The specificity of the new procedure was 98.8%, and overall 739 of 761 specimens (97.1%) were identified correctly by HF-PAP. This system can be used to confirm preliminary or questionable CPE. All of the specimens that exhibited possible CPE at 18-24 hours and from which the virus eventually was isolated were also positive by HF-PAP. However, this method was less sensitive for specimens with smaller amounts of virus. Thus, this method provides a rapid and improved, although not foolproof, means of HSV detection.


Distribution of Chironomidae in a semiarid intermittent river of Brazil.
The effects of the intermittency of water flow on habitat structure and substrate composition have been reported to create a patch dynamics for the aquatic fauna, mostly for that associated with the substrate. This study aims to describe the spatial distribution of Chironomidae in an intermittent river of semiarid Brazil and to associate assemblage composition with environmental variables. Benthic invertebrates were sampled during the wet and dry seasons using a D-shaped net (40 cm wide and 250 μm mesh), and the Chironomidae were identified to genus level. The most abundant genera were Tanytarsus, Polypedilum, and Saetheria with important contributions of the genera Procladius, Aedokritus, and Dicrotendipes. Richness and density were not significantly different between the study sites, and multiple regression showed that the variation in richness and density explained by the environmental variables was significant only for substrate composition. The composition of genera showed significant spatial segregation across the study sites. Canonical Correspondence Analysis showed significant correspondence between Chironomidae composition and the environmental variables, with submerged vegetation, elevation, and leaf litter being important predictors of the Chironomidae fauna. This study showed that Chironomidae presented important spatial variation along the river and that this variation was substantially explained by environmental variables associated with the habitat structure and river hierarchy. We suggest that the observed spatial segregation in the fauna results in the high diversity of this group of organisms in intermittent streams.


Diagnostic options for blunt abdominal trauma.
Physical examination, laboratory tests, ultrasound, conventional radiography, multislice computed tomography (MSCT), and diagnostic laparoscopy are used for diagnosing blunt abdominal trauma. In this article, we investigate and evaluate the usefulness and limitations of various diagnostic modalities on the basis of a comprehensive review of the literature. We searched commonly used databases in order to obtain information about the aforementioned diagnostic modalities. Relevant articles were included in the literature review. On the basis of the results of our comprehensive analysis of the literature and a current case, we offer a diagnostic algorithm. A total of 86 studies were included in the review. Ecchymosis of the abdominal wall (seat belt sign) is a clinical sign that has a high predictive value. Laboratory values such as those for haematocrit, haemoglobin, base excess or deficit, and international normalised ratio (INR) are prognostic parameters that are useful in guiding therapy. Extended focused assessment with sonography for trauma (eFAST) has become a well established component of the trauma room algorithm but is of limited usefulness in the diagnosis of blunt abdominal trauma. Compared with all other diagnostic modalities, MSCT has the highest sensitivity and specificity. Diagnostic laparoscopy is an invasive technique that may also serve as a therapeutic tool and is particularly suited for haemodynamically stable patients with suspected hollow viscus injuries. MSCT is the gold standard diagnostic modality for blunt abdominal trauma because of its high sensitivity and specificity in detecting relevant intra-abdominal injuries. In many cases, however, clinical, laboratory and imaging findings must be interpreted jointly for an adequate evaluation of a patient's injuries and for treatment planning since these data supplement and complement one another. Patients with blunt abdominal trauma should be admitted for clinical observation over a minimum period of 24 h since there is no investigation that can reliably rule out intra-abdominal injuries.


Development and validation of direct dry loop mediated isothermal amplification for diagnosis of Trypanosoma evansi.
Non-tsetse transmitted Trypanosoma evansi infection (Surra) is one of the most important diseases of camels in north and east Africa and of buffalo and cattle in Asia. Early, accurate and feasible diagnosis is a crucial step towards the control of Surra. Dry format of loop-mediated isothermal amplification (LAMP) diagnostics for the detection of T. evansi was developed, where the detection limit was determined as to equivalent to one parasite per reaction. The assay was validated by testing blood from 48 camels clinically diagnosed to have Surra, which all tested negative microscopically and revealed 43 (89.6%) to be positive for T. evansi when tested by the dry-LAMP. Furthermore, DNA extracted from a randomly selected subset of 20 of these blood samples were then subjected to RoTat1.2-PCR (TaKara Ex Taq), with 14 matching results, with six that were positive by dry-LAMP and negative by PCR. The kappa value of dry-LAMP applied to direct blood was 0.4211, indicating moderate agreement to RoTat 1.2-PCR. In addition, 103 genomic DNA extracted from camels' blood were tested by both dry-LAMP and RoTat1.2-PCR revealed 67 matching results and 31 positive by dry-LAMP and negative by PCR and a further five positives by PCR and negative by dry-LAMP. This novel dry-LAMP method is more sensitive than conventional PCR, direct (without DNA extraction step), is user friendly and does not require cold chain or highly trained personnel.


Dental abnormalities in eight captive giant pandas (Ailuropoda melanoleuca) in China.
Dental data from eight adult giant pandas (Ailuropoda melanoleuca) (four females and four males) were collected at the Beijing Zoo from February 2009 to July 2010. Examination findings were recorded in dental charts. All the pandas had different degrees of tooth wear. Incisors, canines and second premolars had the most abnormalities. Five animals had caries; molars were the most affected. Chip fractures were found in seven teeth (incisor, canine and premolar) of five pandas; two had complicated fractures of their canines. Premolars and other teeth were missing in three pandas. Different degrees of dental plaque and calculus were found in all animals. Two pandas had mild gingivitis; the depth of periodontal pockets in all pandas was normal (0-2 mm). Five pandas had abnormal tooth mobility. Samples of dental plaque were collected for microbial culture. Two hundred and fifty-three bacterial strains belonging to 48 species of 23 genera were isolated. Streptococcus, Moraxella, Peptostreptococcus and Porphyromonas were the dominant genera. Further research with larger sample sizes of free-ranging and captive giant pandas will be required in order to demonstrate the absence of the premolar tooth, tooth fractures and the relatively low prevalence of periodontal disease in captive giant pandas.


Graciousness, Elegance, and Firmness: Ballet and the Constitution of a Protective Environment for Peripheral Masculinities in Brazil.
Due to its graceful and light movements, its clothing, and body postures, ballet is tied to characteristics that are socially perceived as feminine. The aim of this paper is to describe the way men live and interact within the classic ballet environment, a way that is deemed deviant according to Western heteronormative norms of gender and sexuality. The overall idea was to delineate the masculinity that surrounds and is built in this space, and how ballet operates to build the identities of these individuals. The research was done through direct observation in a ballet school linked to one of the oldest and most important ballet institutions in Brazil. The main idea expressed is that ballet acts as a protective environment for young men who break out of heteronormativity. It is believed that men subvert social norms in this environment because that is where behaviors that escape hegemonic masculinity are more acceptable, gain representativeness and legitimacy.


A combined bioinformatics, experimental and clinical approach to identify novel cardiac-specific heart failure biomarkers: is Dickkopf-3 (DKK3) a possible candidate?
Cardiac specificity provides an advantage in correlating heart failure (HF) biomarker plasma levels with indices of cardiac function and remodelling, as shown for natriuretic peptides. Using bioinformatics, we explored the cardiac specificity of secreted proteins and investigated in more detail the relationship of Dickkopf-3 (DKK3) gene expression and DKK3 plasma concentrations with cardiac function and remodelling in (pre)clinical studies. The cardiac specificity of secreted proteins was determined using RNAseq data for a large panel of organs and tissues. This showed that natriuretic peptides (NPPA and NPPB) are highly cardiac-specific (>99%), whereas other HF biomarkers, including galectin-3 (Gal-3, LGALS3) and growth differentiation factor-15 (GDF-15), lack cardiac specificity (<4%). DKK3 was cardiac-enriched (44%), warranting further investigation. In three different HF mouse models, cardiac Dkk3 expression was altered, but DKK3 plasma concentrations were not. In humans, DKK3 plasma concentrations were higher in HF patients (n = 2090) in comparison with age- and sex-matched controls without HF (n = 240) (46.4 ng/mL vs. 36.3 ng/mL; P < 0.001). Multivariate regression analysis revealed that DKK3 was strongly associated with HF risk factors and comorbidities, including age, kidney function and atrial fibrillation. After correction for existing prediction models, DKK3 did not independently predict HF outcome [all-cause mortality/HF hospitalization, hazard ratio 1.13 (0.79-1.61) per DKK3 doubling; P = 0.503]. Of actively secreted HF biomarkers, only natriuretic peptides showed high cardiac specificity. Despite a cardiac specificity of 44%, secreted DKK3 had limited additional diagnostic and prognostic value.


Resource utilization and cost analyses of home-based palliative care service provision: the Niagara West End-of-Life Shared-Care Project.
Increasing emphasis is being placed on the economics of health care service delivery - including home-based palliative care. This paper analyzes resource utilization and costs of a shared-care demonstration project in rural Ontario (Canada) from the public health care system's perspective. To provide enhanced end-of-life care, the shared-care approach ensured exchange of expertise and knowledge and coordination of services in line with the understood goals of care. Resource utilization and costs were tracked over the 15 month study period from January 2005 to March 2006. Of the 95 study participants (average age 71 years), 83 had a cancer diagnosis (87%); the non-cancer diagnoses (12 patients, 13%) included mainly advanced heart diseases and COPD. Community Care Access Centre and Enhanced Palliative Care Team-based homemaking and specialized nursing services were the most frequented offerings, followed by equipment/transportation services and palliative care consults for pain and symptom management. Total costs for all patient-related services (in 2007 $CAN) were $1,625,658.07 - or $17,112.19 per patient/$117.95 per patient day. While higher than expenditures previously reported for a cancer-only population in an urban Ontario setting, the costs were still within the parameters of the US Medicare Hospice Benefits, on a par with the per diem funding assigned for long-term care homes and lower than both average alternate level of care and hospital costs within the Province of Ontario. The study results may assist service planners in the appropriate allocation of resources and service packaging to meet the complex needs of palliative care populations.


Polyglycerol coatings of glass vials for protein resistance.
Proteins are surface active molecules which undergo non-specific adsorption when getting in contact with surfaces such as the primary packaging material. This process is critical as it may cause a loss of protein content or protein aggregation. To prevent unspecific adsorption, protein repellent coatings are of high interest. We describe the coating of industrial relevant borosilicate glass vials with linear methoxylated polyglycerol, hyperbranched polyglycerol, and hyperbranched methoxylated polyglycerol. All coatings provide excellent protein repellent effects. The hyperbranched, non-methoxylated coating performed best. The protein repellent properties were maintained also after applying industrial relevant sterilization methods (≥200 °C). Marginal differences in antibody stability between formulations stored in bare glass vials and coated vials were detected after 3 months storage; the protein repellent effect remained largely stable. Here, we describe a new material suitable for the coating of primary packaging material of proteins which significantly reduces the protein adsorption and thus could present an interesting new possibility for biomedical applications.


NLR, d-NLR and PLR can be affected by many factors.
We have read the article by Yang et al, entitled "The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients" with great interest. The authors emphasized that the NLR (Neutrophil to lymphocyte ratio) is an independent prognostic biomarker for COVID-19 patients. First of all, we congratulate the authors for their valuable contribution to the literature in these difficult conditions. However, we would like to add on a few cases that need more attention.


Dental caries status is associated with arteriosclerosis in patients on hemodialysis.
We previously found that worse dental caries status was associated with high pulse pressure among patients on hemodialysis, indicating that such patients might have arteriosclerosis. In this study, we used abdominal computed tomography to evaluate arteriosclerosis in patients on hemodialysis and investigated the association between arteriosclerosis and dental caries status. We also prospectively examined risk factors associated with 2-year prognosis. The dental caries and periodontal disease statuses of 80 patients on hemodialysis were evaluated using the decayed, missing, or filled teeth (DMFT) index, and periodontal pocket depth, respectively. The aortic calcification index was semiquantitatively measured using computed tomography images of the abdominal aorta. Clinical data were also analyzed after all patients on hemodialysis provided written, informed consent to participate in the study. Regression analysis demonstrated a significant correlation between the DMFT and aortic calcification indexes. Multiple regression analysis showed that the DMFT index was significantly correlated with the aortic calcification index, following adjustment for age, sex, and dialysis period. Thirteen of the 80 patients died during the 2-year follow-up period; logistic regression analysis showed that mortality rate was significantly associated with the aortic calcification index, but not the DMFT index. However, periodontal pocket depth was not correlated with the aortic calcification index. These findings suggest that worse dental caries status could be associated with arteriosclerosis among patients on hemodialysis, which may indirectly affect the prognosis of arteriosclerosis in these patients.


Minimally invasive versus open central pancreatectomy: Systematic review and meta-analysis.
This systematic review and meta-analysis aimed to give an overview on the postoperative outcome after a minimally invasive (ie, laparoscopic and robot-assisted) central pancreatectomy and open central pancreatectomy with a specific emphasis on the postoperative pancreatic fistula. For benign and low-grade malignant lesions in the pancreatic neck and body, central pancreatectomy may be an alternative to distal pancreatectomy. Exocrine and endocrine insufficiency occur less often after central pancreatectomy, but the rate of postoperative pancreatic fistula is higher. An electronic search was performed for studies on elective minimally invasive central pancreatectomy and open central pancreatectomy, which reported on major morbidity and postoperative pancreatic fistula in PubMed, Cochrane Register, Embase, and Google Scholar until June 1, 2021. A review protocol was developed a priori and registered in PROSPERO as CRD42021259738. A meta-regression was performed by using a random effects model. Overall, 41 studies were included involving 1,004 patients, consisting of 158 laparoscopic minimally invasive central pancreatectomies, 80 robot-assisted minimally invasive central pancreatectomies, and 766 open central pancreatectomies. The overall rate of postoperative pancreatic fistula was 14%, major morbidity 14%, and 30-day mortality 1%. The rates of postoperative pancreatic fistula (17% vs 24%, P = .194), major morbidity (17% vs 14%, P = .672), and new-onset diabetes (3% vs 6%, P = .353) did not differ significantly between minimally invasive central pancreatectomy and open central pancreatectomy, respectively. Minimally invasive central pancreatectomy was associated with significantly fewer blood transfusions, less exocrine pancreatic insufficiency, and fewer readmissions compared with open central pancreatectomy. A meta-regression was performed with a random effects model between minimally invasive central pancreatectomy and open central pancreatectomy and showed no significant difference for postoperative pancreatic fistula (random effects model 0.16 [0.10; 0.24] with P = .789), major morbidity (random effects model 0.20 [0.15; 0.25] with P = .410), and new-onset diabetes mellitus (random effects model 0.04 [0.02; 0.07] with P = .651). In selected patients and in experienced hands, minimally invasive central pancreatectomy is a safe alternative to open central pancreatectomy for benign and low-grade malignant lesions of the neck and body. Ideally, further research should confirm this with the main focus on postoperative pancreatic fistula and endocrine and exocrine insufficiency.


The 'vapour-phase' migration of styrene from general purpose polystyrene and high impact polystyrene into cooking oil.
General purpose and high impact polystyrene (GPPS and HIPS, respectively) are used in many food packaging applications. In some packaging configurations, where there is no direct contact of a liquid surface with the polymer, 'vapour-phase' migration of styrene monomer from the polymer with subsequent absorption into food is thought to be a significant mode of transfer. Correlation of residual styrene concentrations in polystyrene with vapour-phase styrene migration is of interest in order to predict potential consumer exposure to styrene from food-packaging applications of this configuration. Studies of the migration of styrene from GPPS and HIPS into air with subsequent absorption of the monomer into cooking oil, 'vapour-phase' migration, was determined in a sealed system. The results showed that for both polymers the amount of styrene migrating from the polystyrene and being absorbed by the oil was proportional to the square root of the time of exposure. The diffusion coefficients calculated for the vapour-phase migration of styrene from both polymers were found to be in good agreement with the diffusion coefficients previously determined for the 'liquid-phase' migration of styrene from similar polymers where the polymers were completely submerged in the cooking oil. These results indicate that the styrene concentrations measured in both experiments were attributable to the intrinsic diffusion of styrene from polystyrene, and that contact with cooking oil did not accelerate migration in previous experiments.


Correlation between Hashimoto's thyroiditis and polycystic ovary syndrome: A systematic review and meta-analysis.
A growing body of research suggests that patients with polycystic ovary syndrome (PCOS) may be at increased risk of developing Hashimoto's thyroiditis (HT), and having both conditions can make the condition worse. However, current research views are not uniform. Therefore, to explore the link between PCOS and HT, we conducted this study. From the establishment of the database to August 2022, we searched 2 databases to study the correlation between Hashimoto's and polycystic ovary syndrome. Two authors independently screened the articles for eligibility, and three authors extracted relevant data. Statistical analysis was performed using STATA16.0 software. A total of 20 studies were included, including 7 case-control studies and 13 cross-sectional studies. A total of 13 countries and 7857 participants were embraced. Studies have demonstrated that both PCOS patients have an increased risk of HT, and meanwhile, HT patients also have an increased risk of PCOS compared with controls. The study also incorporated that the prevalence of HT in PCOS patients in India and Turkey was higher than in other countries, and the prevalence of HT in PCOS patients in South America was higher than in Asia and Europe. In conclusion, our study illustrates that there is a correlation between PCOS and HT, and it is necessary to further study the underlying mechanism between PCOS and HT. At the same time, it is of great significance to regularly screen PCOS patients for HT risk and HT patients for PCOS risk. https://www.crd.york.ac.uk/prospero/, identifier CRD 42022351168.


Effects of dietary molybdenum on nematode and host during Trichostrongylus vitrinus infection in lambs.
The addition of molybdenum (0.05 mmol kg-1 dry matter) to the diet of lambs exposed for four weeks to a trickle (2500 third stage larvae per day) infection with Trichostrongylus vitrinus reduced the number and length of adult worms retrieved from the small intestine 11 days later: both effects were particularly marked in female worms from female lambs (P less than 0.01). Worms from lambs given molybdenum contained less proteinase enzyme activity and secreted less proteinases in culture irrespective of the sex of the host. Pathogenicity was not attenuated by molybdenum. Damage to the intestinal mucosa was severe in both dietary groups but infected females given molybdenum developed lower plasma albumin concentrations and lighter dressed carcases than those not given molybdenum. Neither the effects on the parasite nor those on the host could be attributed simply to molybdenum-induced copper depletion, using conventional measures of copper status. Molybdenum may be toxic to T vitrinus but may also facilitate or enhance the inflammatory process limiting larval establishment or increasing parasite rejection.


Isolation of the polar and lateral flagellum-defective mutants in Vibrio alginolyticus and identification of their flagellar driving energy sources.
Vibrio alginolyticus has two types of flagella (polar and lateral) in one cell. We isolated mutants with only a polar flagellum (Pof+ Laf-) or only lateral flagella (Pof- Laf+). Using these mutants, we demonstrated that the energy sources of the lateral and polar flagellar motors in V. alginolyticus are H+ and Na+ motive forces, respectively, as in the related species V. parahaemolyticus.


Relative selectivity of some conformationally constrained tryptamine analogs at 5-HT1, 5-HT1A and 5-HT2 recognition sites.
In an attempt to define pharmacophoric differences between 5-HT1, 5-HT1A and 5-HT2 recognition sites, a number of rigid analogs were studied and compared to analogous free chain tryptamines. Racemic partial ergolines RU 27849 and RU 28306 showed reduced potency at all 5-HT1 sites, but were at least equipotent to analogous tryptamines at the 5-HT2 site. A nonergoline-like constrained analog of tryptamine was similar in potency to RU 27849 at all 5-HT1 sites, but showed a 4-fold enhancement in potency over RU 27849 and tryptamine at the 5-HT2 site. At all 3 sites, 3-(tetrahydropyridyl) indoles (unless substituted at the indole 2-position) were the most potent rigid analogs studied and represent the most promising class for the development of selective compounds.


A fever workup guideline.
Fever is a common clinical problem in patients hospitalized with trauma. When an infection is suspected, it is important to identify the source of fever and begin definitive care before more severe morbidity occurs. An undirected approach with "pan cultures" has resulted in a high rate of negative cultures obtained and has increased patient care costs. By developing and using an evidence-based fever workup guideline, this institution was able to evaluate and identify infections and reduce costs.


RNA-binding proteins in regulating mRNA stability and translation: roles and mechanisms in cancer.
RNA-binding proteins (RBPs) are key players in cellular physiology through posttranscriptional regulation of the expression of target RNA transcripts. By modulating the processing, stability and translation of cancer-related messenger RNA (mRNA) transcripts, a large set of RBPs play essential roles in various types of cancers. Perturbations in RBP activity have been causally associated with cancer development, tumor metabolism, drug resistance, cancer stem cell self-renewal, and tumor immune evasion. Here, we summarize the recent advances in cancer pathological roles and mechanisms of RBPs in regulating mRNA stability and translation with an emphasis on the emerging category of RNA modification-associated RBPs. The functional diversity of RBPs in different types of cancers and the therapeutic potential of targeting dysregulated RBPs for cancer treatment are also discussed.


CORRELATIONS BETWEEN INTELLIGENCE, HEAD CIRCUMFERENCE AND HEIGHT: EVIDENCE FROM TWO SAMPLES IN SAUDI ARABIA.
This study was based on two independent studies which in total consisted of 1812 school pupils aged 6-12 years in Saudi Arabia. Study I consisted of 1591 school pupils (609 boys and 982 girls) attending state schools, and Study II consisted of 211 boys with learning disabilities. Intelligence (measured using the Standard Progressive Matrices Plus for Study I and the Standard Progressive Matrices for Study II), head size and height were measured for the two samples. The results showed that intelligence was statistically significantly correlated with head circumference (r=0.350, p<0.001 for Study I and r=0.168, p<0.05 for Study II) and height (r=0.271, p<0.001 for Study I and r=0.178, p<0.05 for Study II).


Numerical solution of structured population models. I. Age structure.
Numerical methods are presented for a general age-structured population model with demographic rates depending on age and the total population size. The accuracy of these methods is established by solving problems for which alternate solution techniques are available and are used for comparison. The methods reliably solve test problems with a variety of dynamic behavior. Simulations of a blowfly population exhibit cyclic fluctuations, whereas a simulated squirrel population reaches a stable age distribution and stable equilibrium population size. Life-history attributes are easily studied from the computed solutions, and are discussed for these examples. Recovery of a stressed population back to equilibrium is examined by computing the transition in age structure, and the transient behavior of other properties of the population such as the per capita growth rate, the average age, and the generation length.


One step synthesis of highly crystalline and high coercive cobalt-ferrite nanocrystals.
Highly crystalline and almost monodisperse spinel cobalt-ferrite nanocrystals are synthesized in a one step process, which has very high coercivity at 10 K and exhibits superparamagnetic behaviour at 300 K.


Aromatherapy in Palliative Care: A Single-Institute Retrospective Analysis Evaluating the Effect of Lemon Oil Pads against Nausea and Vomiting in Advanced Cancer Patients.
Aromatherapy is regularly used in the University Hospital Krems's palliative care unit. In a retrospective analysis, we investigated whether there were improvements in nausea and vomiting in patients with advanced cancers over a time span of 24 months. Data collection used the medical records of patients who were institutionally approved to receive routine aroma applications for alleviating nausea and vomiting. The efficacy of using lemon oil pads was tested with one-dimensional chi-squared tests. Sixty-six patients received 222 applications of lemon oil on cotton pads; no data were available for 17 applications. The adequate relief of nausea and vomiting was reported for 149 (73%) applications, whereas no symptom control was seen for 56 (27%) applications. For the 56 applications without symptom control, first- and second-line rescue medications were successful in 53 and 3 cases, respectively. The use of aromatherapy with lemon oil pads against nausea and vomiting was feasible for 73% of all applications. All patients who did not benefit from aromatherapy had effective symptom control with a rescue medication. Large randomized prospective trials are necessary to evaluate the benefit of the use of lemon oil pads against nausea and vomiting in patients with advanced cancer.


[Preoperative irradiation, cisplatin sensitization and radical surgery of primarily operable carcinomas of the oral cavity. Results of a prospective DOSAK treatment study].
165 patients with carcinomas of the oral cavity or oropharynx, clinically appearing operable, were treated between 1985 and 1987 within the framework of a prospective multicenter study. The treatment concept consisted in preoperative irradiation with 32 Gy, cisplatin sensitization with 5 X 20 mg per m2 body surface area and subsequent radical removal of the primary tumor and the regional cervical lymph nodes. Regarding recurrence and survival rates the patient data were analyzed using one- and multi-dimensional statistical methods. The observed survival rates were compared with those assessed with the aid of the treatment-dependent prognosis index TPI (Platz et al. 1982). After 1 years the survival rates under the selected combination therapy were 12% and after 2 years 19% above the assessed survival rates under radical surgery alone.


Detection of the ethyl- and pentyl-radical adducts of alpha-(4-pyridyl-1- oxide)-N-tert-butylnitrone in rat-liver microsomes treated with ADP, NADPH and ferric chloride.
HPLC-EPR analyses of the reaction mixtures of microsomal suspensions incubated with ADP, ferric chloride, NADPH and alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) were performed. In the elution pattern of the reaction mixture, three peaks (peaks 1, 2 and 3) were detected. The radical adducts (1 and 3) were identified as being the pentyl- and ethyl-radical adducts of 4-POBN by comparing their retention times with those of the authentic radical adducts.


Vertical Stratification in Urban Green Space Aerobiomes.
Exposure to a diverse environmental microbiome is thought to play an important role in "educating" the immune system and facilitating competitive exclusion of pathogens to maintain human health. Vegetation and soil are key sources of airborne microbiota--the aerobiome. A limited number of studies have attempted to characterize the dynamics of near surface green space aerobiomes, and no studies to date have investigated these dynamics from a vertical perspective. Vertical stratification in the aerobiome could have important implications for public health and for the design, engineering, and management of urban green spaces. The primary objectives of this study were to: a) assess whether significant vertical stratification in bacterial species richness and evenness (alpha diversity) of the aerobiome occurred in a parkland habitat in Adelaide, South Australia; b) assess whether significant compositional differences (beta diversity) between sampling heights occurred; and c) to preliminarily assess whether there were significant altitudinal differences in potentially pathogenic and beneficial bacterial taxa. We combined an innovative columnar sampling method at soil level, 0.0, 0.5, 1.0, and 2.0m, using passive petri dish sampling to collect airborne bacteria. We used a geographic information system (GIS) to select study sites, and we used high-throughput sequencing of the bacterial 16S rRNA gene to assess whether significant vertical stratification of the aerobiome occurred. Our results provide evidence of vertical stratification in both alpha and beta (compositional) diversity of airborne bacterial communities, with diversity decreasing roughly with height. We also found significant vertical stratification in potentially pathogenic and beneficial bacterial taxa. Although additional research is needed, our preliminary findings point to potentially different exposure attributes that may be contingent on human height and activity type. Our results lay the foundations for further research into the vertical characteristics of urban green space aerobiomes and their implications for public health and urban planning. https://doi.org/10.1289/EHP7807.


Barbed compared with standard suture: effects on cellular composition and proliferation of the healing wound in the ovine uterus.
To compare cellular composition (fibroblasts vs. smooth muscle cells) and proliferation in uterine healing wounds after application of barbed compared with standard suture in a sheep model. Randomized trial (Canadian Task Force classification I) using each animal as its own control. Certified animal research facility. Population or sample. 23 non-pregnant ewes. A myometrial incision was created with the harmonic scalpel in each horn of the bicornuate uterus. The incisions were randomly allocated to be closed using either polyglactin 210 (Vicryl®) or barbed suture. Three months later, uterine tissues were collected, fixed and used for determination of cellular composition and proliferation using histochemistry (Masson trichrome staining) and immunohistochemistry (staining of smooth muscle cell actin and Ki67, a marker of proliferating cells) followed by image analysis. Evaluation and comparison of the cellular composition and proliferation of uterine wounds after application of barbed vs. standard suture. The ratio between connective tissue elements and smooth muscle cells, expression of smooth muscle cell actin and labeling index were similar in wounds after application of barbed compared with standard suture, but were different (p < 0.0001-0.05) in wounds than in non-wounded areas in uterus. Both barbed and standard sutures had similar effects on cellular composition and proliferation of uterine wounds in an animal model.


Delayed hypersensitivity to PPD-S following BCG vaccination in African children--an 18-month field study.
BCG vaccine given to young Gambian children produced a conversion rate, measured by delayed hypersensitivity to PPD-S, which increased with improving nutritional status. Retesting when nutrition had improved showed a considerable loss of delayed hypersensitivity in all nutritional groups. This may be the result of enhanced macrophage microbicidal acitvity at the time the BCG was administered. BCG is not likely to be very effective if given to malnourished children or to those who are undergoing repeated antigenic stimulation.


IKK regulation and human genetics.
The IKK kinase complex is the core element of the NF-κB cascade. It is essentially made of two kinases (IKKα and IKKβ) and a regulatory subunit, NEMO/IKKγ. Additional components may exist, transiently or permanently, but their characterization is still uncertain. In this review, we will focus on the NEMO molecule, and describe the results which have been obtained, and the hypotheses which have been proposed, to explain how NEMO controls the activation of the IKK complex. NEMO is one of the very few non-redundant components of the NF-κB cascade, and the localization of the gene that encodes it on the X chromosome suggests it is likely to be the target of mutations leading to pathologies: this is indeed the case, and we will also present the current status of our knowledge regarding NEMO-associated pathologies.


Periphyton as an important source of methylmercury in Everglades water and food web.
Periphyton is ubiquitous in Florida Everglades and has a profound effect on mercury (Hg) cycling. Enhanced methylmercury (MeHg) production in periphyton has been well documented, but the re-distribution of MeHg from periphyton remains unknown. In this study, periphyton, sediments, surface water, periphyton overlying water, and periphyton porewater were collected from Everglades for analyzing the distribution of MeHg and total Hg (THg). Results showed that there were no significant differences in THg and MeHg in different types of periphyton, but they all displayed higher MeHg levels than sediments. MeHg distribution coefficients (logkd) in periphyton were lower than in sediments, suggesting that periphyton MeHg could be more labile entering aquatic cycling and bioaccumulation. In water, the more the distance of water samples taken from periphyton, the lower the MeHg and dissolved organic carbon concentrations were detected. In extracellular polymeric substances of periphyton, MeHg in colloidal fractions was significantly higher than that in capsular fractions. It was estimated that approximately 10% (or 1.35 kg) of periphyton MeHg were passed on to mosquitofish entering the food web during wet season, contributing 73% of total Hg stocked in mosquitofish. These results revealed the importance of periphyton on water MeHg distribution and MeHg bioaccumulation in Everglades.


Perturbation in linker histone content has no effect on the cell cycle but affects the cell size of suspension grown tobacco BY-2 cells.
Histone H1, a key structural element of eukaryotic chromosomes can be perturbed in plants in vivo by overexpression or by a change in the proportion of native H1 variants (Prymakowska-Bosak M., Przewloka M., Iwkiewicz J., Egierszdorff S., Kuras M., Chaubert N., Gigot C., Spiker S., Jerzmanowski A., Histone H1 overexpressed to high level in tobacco affects certain developmental programs but has limited effect on basal cellular functions, Proc. Natl. Acad. Sci. U.S.A. 93 (1996) 10250-10255; Prymakowska-Bosak M., Slusarczyk J., Przewloka M., Kuras M., Lichota J., Kilianczyk B., Jerzmanowski A., Linker Histones Play a Role in Male Meiosis and the Development of Pollen Grains in Tobacco, Plant Cell 11 (1999) 2317-2330). In order to analyze the possible causes of the specific phenotypic changes observed in whole plants we employed a simpler system of tobacco BY-2 cell line. We show that the BY-2 cells engineered to overexpress a major variant of Arabidopsis H1 or with the level of native major variants of H1 decreased by antisense strategy maintain the normal ability to grow and the normal length of the cell cycle. In the cells with perturbed H1 histones no change was observed in the organization of mitotic spindle or actin filaments of the cytoskeleton. The only visible phenotypic change occurred in cells overexpressing H1 that showed an increased frequency of cells with unusually large size. This phenotype was correlated with subtle but reproducible changes in the organization of cortical microtubules.


Purification and properties of bovine liver lysosomal adenosine 5'-phosphosulphate sulphohydrolase. A non-specific enzyme with pyrophosphatase and phosphodiesterase activities.
Bovine liver lysosomal adenosine 5'-phosphosulphate sulphohydrolase (EC 22.214.171.124) was purified to apparent homogeneity. The molecular weight of the enzyme was 53 000 by sodium dodecyl sulphate polyacrylamide gel electrophoresis and 56 000 by BioGel P-150 gel filtration. The substrate specificity of the enzyme was studied. The several substrates towards which the enzyme preparation showed high activity were used to establish that a single enzyme was responsible for the different activities. This multiple specificity provides a possible explanation of the physiological role of lysosomal adenosine 5'-phosphosulphate sulphohydrolase.


Synthesis of Drosophila melanogaster alcohol dehydrogenase in yeast.
Expression systems for the heterologous expression of Drosophila melanogaster alcohol dehydrogenase (ADH) in Saccharomyces cerevisiae have been designed, analyzed and compared. Four different yeast/Escherichia coli shuttle vectors were constructed and used to transform four different yeast strains. Expression was detectable in ADH- yeast strains, from either a constitutive promoter, yeast ADH1 promoter (ADCp), or a regulated promoter, yeast GALp. The highest amount of D. melanogaster ADH was obtained from a multicopy plasmid with the D. melanogaster Adh gene expressed constitutively under the control of yeast ADCp promoter. The D. melanogaster enzyme was produced in cell extracts, as assessed by Coomassie blue staining and Western blotting after polyacrylamide-gel electrophoresis and it was fully active and able to complement the yeast ADH deficiency. Results show that D. melanogaster ADH subunits synthesized in yeast are able to assemble into functional dimeric forms. The synthesized D. melanogaster ADH represents up to 3.5% of the total extracted yeast protein.


Utilization patterns, outcomes and costs of a simplified acute malnutrition treatment programme in Burkina Faso.
Access to treatment for acute malnutrition remains a challenge, in part due to the fragmentation of treatment programmes based on case severity. This paper evaluates utilization patterns, outcomes and associated costs for treating acute malnutrition cases among a cohort of children in Burkina Faso. This study is a secondary analysis of a proof-of-concept trial, called Optimizing treatment for acute Malnutrition (OptiMA), conducted in Burkina Faso in 2016. A total of 4958 eligible children whose mid-upper arm circumference (MUAC) was less than 125 mm or with oedema were followed weekly and given ready-to-use therapeutic foods (RUTF). We evaluated the service utilization and outcomes among patients and estimated resource use and variable cost per patient, and examined factors driving variation in resource use. Children with lower initial MUAC level grew faster but required more time to recover than those with higher initial MUAC level. They also had higher rates of death, default and nonresponse. The simplified OptiMA approach for treating acute malnutrition achieved high rates of recovery overall (84%), especially among less severe cases, with modest quantities of RUTF. The average overall variable cost per child admitted was US$38.0 (SD: 20.5) half of which was accounted for by the cost of RUTF. Cost per recovered case was correlated with case severity, ranging from US$35.1 to US$132.8. If simplified integrated programmes using severity-based RUTF dosing can increase access to treatment at earlier, less severe stages of acute malnutrition, they can help avoid more serious and costlier cases.


PDE5 inhibitors and permanent visual loss.
Nonarteritic anterior ischemic optic neuropathy (NAION), a form of optic nerve stroke, has received attention as the result of a possible rare association with PDE5 inhibitors (PDE5i). The possible mechanism of the PDE5i interaction with NAION is unclear, and the sporadic case reports do not seem to shed light on this topic. There is little guidance on this subject for the patient and clinician alike. Nonetheless, clinicians are being deluged with queries, without definitive answers. At this juncture, an ophthalmologic evaluation is discretionary, and appears to be based on either patient desire, patient risk factor profile, or clinician instinct. The scientific literature is scant as well. Several case reports exist to date, without clear vision for the future study of this disease. Robert Tomsak, a noted neuro-ophthalmologist, discusses NAION here.


Persistent hypercoagulation associated with heterotopic ossification in patients with spinal cord injury long after injury has occurred.
Three patients are presented with traumatic spinal cord injury (SCI) complicated by acute heterotopic ossification (HO), and concurrent deep vein thrombosis 15 months, 18 months and 22 years after SCI, accompanied by persistent hypercoagulation. The diagnosis of HO preceded deep vein thrombosis in all three patients. All were treated with etidronate disodium and therapeutic heparin followed by oral anticoagulation. As these patients were not acutely injured, the questions arose as to what predisposed them to deep vein thrombosis and when was the appropriate time to discontinue anticoagulation. Over a course of 3 years following deep vein thrombosis, these patients were monitored for evidence of hypercoagulation by D-dimer assay, plasma fibrinogen estimation, and rate of whole blood clotting by Sonoclot coagulation analyzer. The activity of acute HO was assessed by three-phase bone scan. A steady state of hypercoagulation, reflected by an increase in all three parameters, ran parallel to the extent of acute HO for the entire observation period. Moreover, hypercoagulation was persistently greater during increased acute HO activity even when the warfarin-induced prothrombin time ratio was 1.2-1.5. In addition, as acute heterotopic ossification activity decreased, the test values returned to near normal during warfarin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


Characterization of calcitonin gene-related peptide (CGRP) receptors in guinea pig basilar artery.
The vasomotor effects of calcitonin gene-related peptide (CGRP) analogs have been studied in circular segments of guinea pig basilar artery in vitro. Five CGRP agonists induced concentration-dependent relaxations of pre-contracted vessels with the following order of potency: alpha-rCGRP greater than or equal to beta-rCGRP greater than or equal to alpha-hCGRP greater than beta-hCGRP greater than [Tyr0]CGRP with maximum responses between 80 and 87%. The magnitude of responses to calcitonin was low (12%) but with the same potency as the CGRP analogs. hCGRP(8-37) (10(-6) M), a CGRP antagonist, induced a parallel shift of alpha-rCGRP- and alpha-hCGRP-induced relaxations but not of beta-rCGRP and beta-hCGRP. Another putative antagonist [Tyr0]CGRP28-37 (10(-6) M) had no antagonistic effect on dilator responses to the CGRP agonists. The results suggests two types of CGRP responses in the guinea pig basilar artery: alpha-CGRP induced relaxation is blocked by the antagonist hCGRP(8-37), while the equally strong dilator response to beta-CGRP is not antagonized. It is therefore possible that the guinea pig basilar artery is equipped with CGRP-1 receptors sensitive to hCGRP(8-37) and CGRP-2 receptors being sensitive to beta-CGRP but not antagonized by hCGRP(8-37).


Comparison of anatomical locations of cutaneous melanoma in men and women: a population-based study in France.
Identification of differences in melanoma location between the sexes could lead to sex-specific preventive measures. To compare precise melanoma location and side in men and women. The location of 1542 incident melanomas diagnosed during the period 2004-2011 in the French Champagne-Ardenne region (1·3 million inhabitants) was recorded using a regional registry and questionnaires sent to physicians. Men and women were compared for frequency of tumours on the head and neck; trunk; upper limb; lower limb; hand and foot. For each location, more precise sublocations were recorded. The laterality (right vs. left) was studied for head/neck and limb tumours. Melanomas predominated on the lower limb in women (32·2% vs. 9·3% in men; P < 0·01) and on the trunk in men (41·8% vs. 14·9%; P < 0·01), while the proportion of upper limb and head/neck tumours was similar in both sexes. Hand and foot melanomas predominated in women (10·3% vs. 6·3%; P < 0·01), with a sex-related distribution between sublocations. Within the head and neck location, 75·1% of tumours in women were located in the central area vs. 53·7% in the peripheral area in men (P < 0·01). Head and neck melanomas were more frequently right-sided in women and left-sided in men (P = 0·04), with the left/right ratio reaching 1·58 in men vs. 0·61 in women for peripheral tumours (P < 0·01). No difference in laterality was observed for other locations. Sex differences in occupational and leisure time ultraviolet exposure, clothing (including shoes), hairstyle, and side and photo exposure in cars could explain these results. General preventive messages could be completed by sex-specific advice for melanoma prevention.


Natural products, extracts and formulations comprehensive therapy for the improvement of motor function in alcoholic liver disease.
Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide that afflicts human health. With the in-depth study of the disease, its pathogenesis has gradually become clear. Although great breakthroughs have been made in the research of ALD, the research and development of drugs related to ALD has lagged behind seriously. However, natural products have always inspired the development of drugs. Meanwhile, there is evidence that some natural products can also play a certain role in the treatment of ALD. Thus, we reviewed the natural products, extracts and formulations with potential anti-ALD activities by consulting the relevant data in the databases of PubMed, Web of Science and CNKI databases, in order to elucidate the regulated mechanism of these natural products. Sum up, the insights provided in present review will be needed for further exploration of botanical drugs in the development of ALD therapy.


Doppler echocardiographic measurement of mitral flow volume: validation of a new method in adult patients.
Instantaneous intracardiac flow volumes can be calculated as the product of instantaneous flow velocity and instantaneous orifice area. This was accounted for in a new method of measuring stroke volume and cardiac output in the mitral orifice by pulsed Doppler echocardiography. This method was compared with simultaneous thermodilution in 30 adult patients in sinus rhythm without substantial atrioventricular or pulmonary valve abnormalities. The mitral orifice was assimilated to a conduit with 1) an ellipse-shaped inlet and outlet, 2) the same (and constant) long axis for the inlet and outlet ellipses (that is, the mediolateral anulus diameter measured on apical four chamber views), and 3) a varying outlet short axis (that is, the mitral anteroposterior leaflet separation derived from left parasternal M-mode recordings). This method design avoided the need for a short-axis view of the whole circumference of the mitral outlet orifice, which is difficult to obtain in many adult patients. The mitral flow velocity was recorded from the apex under two-dimensional guidance, within the mitral canal, close to the outlet section. Integration of instantaneous mitral leaflet separation multiplied by instantaneous flow velocity was performed using Simpson's rule. In addition to the proposed "instantaneous orifice area" method (method A), a "mean orifice area" method (method B) was also compared with thermodilution. In this simplified method, mitral flow was the product of mean orifice area and the diastolic mitral velocity integral, both derived from the same recordings as for method A.(ABSTRACT TRUNCATED AT 250 WORDS)


An assessment of the existence of muscle synergies during load perturbations and intentional movements of the human arm.
A cross-correlation analysis was performed on EMG activities in elbow and shoulder flexors evoked by force perturbations acting in different directions on the forearm and during intentionally generated movements with the purpose of characterizing the temporal relationships between patterns of activation of different muscles. Qualitatively it was found that the shape of the cross-correlation function differed from one experimental condition to the next. A principal component analysis permitted a quantitative assessment of this point. In general it was found that two principal components could account for the data. Furthermore when the cross-correlograms are represented in principal component space, there was no clustering of the data points. Several possible definitions of 'muscle synergies' are discussed from the perspective of this finding. It is concluded that the most restrictive definition is incompatible with the data. Less restrictive definitions, while compatible with the data, do not lead to a simplification of the control problem.


Cephalosporin therapy in intraabdominal infections. A multicenter randomized, comparative study of cefotetan, moxalactam, and cefoxitin.
Three broad-spectrum cephalosporins (cefotetan, moxalactam, and cefoxitin) proved effective in this randomized, prospective trial for treatment of 303 surgical patients with moderately severe regional peritonitis.


Complexus cordis
The science-based study of the heart has allowed us to know its structure and function deeply, through the fragmentation and analysis of its parts, following the guidelines that so many achievements have given to us. However, at the time of reassembling those analyzed fragments, we realize that something is missing; the simply sum of the parts is not equal to everything. Thus, for decades, numerous scientists have studied novel strategies that allow us understanding, every natural phenomena from a more inclusive, open and integrative models, which closely address to interactions rather than components. In this way, we can observe how, the behavior of many variables usually transgress the conventional plane and moves towards non-linearity and fractality, making a complex tissue that will maintain its structure while thermodynamically viable. Thus, this document shows the way how, the non-linear study of complex cardiovascular dynamics, begins to give us answers to many questions that the clinical cardiologist poses every day.


Author Correction: Whole exome sequencing reveals rare variants linked to congenital pouch colon.
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.


Emerging roles of cytosolic phosphoenolpyruvate kinase 1 (PCK1) in cancer.
Although it was traditionally believed that gluconeogenesis enzymes were absent from cancers that did not originate in gluconeogenic organs, numerous investigations have shown that they are functionally expressed in a variety of tumors as mediators of shortened forms of Gluconeogenesis. One of the isomers of PEPCK, the first-rate limiting enzyme in gluconeogenesis, is PCK 1, which catalyzes the conversion of oxaloacetate (OAA) and GTP into PEP, CO2, and GDP. It is also known as PEPCK-C or PCK1, and it is cytosolic. Despite being paradoxical, it has been demonstrated that, in addition to its enzymatic role in normal metabolism, this enzyme also plays a role in tumors that arise in gluconeogenic and non-gluconeogenic organs. According to newly available research, it has metabolic and non-metabolic roles in tumor progression and development. Thus, this review will give insight into PCK1 relationship, function, and mechanism in or with different types of cancer using contemporary findings.


Cystectomy for patients with Hunner-type interstitial cystitis at a tertiary referral center in Japan.
To evaluate the outcomes of partial and total cystectomy in patients with refractory Hunner-type interstitial cystitis (HIC). Patients with end-stage HIC who underwent supratrigonal partial cystectomy with augmentation ileocystoplasty (PC-CP) or total cystectomy with ileal conduit (TC-IC) were identified retrospectively. Changes in the 11-point numerical rating scale of bladder pain and in 7-grade quality of life (QOL) scores were evaluated. Changes in the O'Leary and Sant's Symptom Index (OSSI) and O'Leary and Sant's Problem Index (OSPI) were analyzed in patients with PC-CP. Peri- and postoperative complications and patient satisfaction with overall outcomes were examined. Four patients (one female) underwent PC-CP and 13 (nine females) underwent TC-IC. Bladder pain persisted in three PC-CP patients, but resolved completely in all TC-IC patients. Pain scale and QOL scores improved significantly in patients with TC-IC (P < .01), but not in those with PC-CP. OSSI/OSPI scores did not improve significantly in patients with PC-CP. Three PC-CP patients required clean intermittent catheterization due to voiding dysfunction or persistent pain. Two TC-IC patients developed stricture of the ureteroileal anastomosis, resulting in permanent placement of a ureteral stent in one case and nephrostomy in the other. Satisfaction rate was higher in the TC-IC than in the PC-CP group (76.9% vs 25.0%, P < .05). TC-IC provided reliable pain relief and improved QOL in patients with end-stage HIC, but the small case number and limited methodology restrict interpretation of the results. Further studies are needed to identify appropriate candidates and optimal surgical procedures.


Deep membrane insertion of prion protein upon reduction of disulfide bond.
The membrane may play a role in the pathogenesis of the prion protein (PrP). Cytoplasmic expression of PrP causes the conversion of PrP to a self-perpetuating PrP(Sc)-like conformation and the interaction of polypeptide chain with the hydrophobic core of the membrane is believed to be closely correlated with neurodegeneration. However, it is still elusive what factors govern the membrane interaction of PrP. Here, we show that PrP penetrates deeply into the membrane when the single disulfide bond is reduced, which results in membrane disruption and leakage. The proteinase K treatment and the fluorescence quenching assays showed that a predicted transmembrane domain of PrP penetrates into the membrane when the disulfide bond was reduced. Therefore, the oxidation state of PrP might be an important factor that influences its neurotoxicity or pathogenesis.


Modic type I change may predict rapid progressive, deforming disc degeneration: a prospective 1-year follow-up study.
This prospective magnetic resonance imaging (MRI) study in chronic low-back pain (CLBP) patients evaluated the natural course of degenerative lumbar spine changes in relation to Modic 1 type changes (M1) within 1 year. From 3,811 consecutive CLBP patients referred to lumbar spine MRI 54 patients with a large M1 were selected using strict exclusion criteria to exclude specific back disorders. Follow-up MRI was obtained within 11-18 months. At baseline M1 was associated with an adjacent endplate lesion in 96% of the cases. In follow-up, an unstable M1 was associated both with an increase of endplate lesions, decrease of disc height and change in disc signal intensity, most found at L4/5 or L5/S1. In disc spaces without M1, progression of degenerative changes was rare. Endplate deformation, decreasing disc height and change of disc signal intensity appear essential features of accelerated degenerative process associated with M1.


Genome-wide identification and characterization of gibberellin metabolic and signal transduction (GA MST) pathway mediating seed and berry development (SBD) in grape (Vitis vinifera L.).
Grape is highly sensitive to gibberellin (GA), which is crucial during seed and berry development (SBD) either by itself or by interacting with other hormones, such as auxin, Abscisic acid (ABA), and Cytokinin (CK). However, no systematic analysis of GA metabolic and signal transduction (MST) pathway has been undertaken in grapevine. In this study, total endogenous GA3 content significantly decreased during SBD, and a total of 48 known genes in GA metabolic (GAM; 31) and signal transduction (ST; 17) pathways were identified in this process. In the GAM pathway, out of 31 genes, VvGA20ox1-1, VvGA3ox4-1, and VvGA2ox1-1 may be the major factors interacting at the green-berry stage (GBS) accompanied with higher accumulation rate. GA biosynthesis was greater than GA inactivation at GBS, confirming the importance of seeds in GA synthesis. The visible correlation between endogenous GA3 content and gene expression profiles suggested that the transcriptional regulation of GA biosynthesis pathway genes was a key mechanism of GA accumulation at the stone-hardening stage (SHS). Interestingly, we observed a negative feedback regulation between VvGA3oxs-VvGAI1-4, VvGA2oxs-VvGAI1-4, and VvGID1B-VvGAI1-4 in maintaining the balance of GA3 content in berries. Moreover, 11 miRNAs may be involved in the modulation of GA MST pathway by mediating their target genes, such as VvGA3ox, VvGID1B, and VvGAMYB. Many genes in auxin, ABA, and CK MST pathways were further identified and found to have a special pattern in the berry, and the crosstalk between GA and these hormones may modulate the complex process during SBD through the interaction gene network of the multihormone pathway. Lastly, based on the expression characterization of multihormone MST pathway genes, a proposed model of the GA-mediated multihormone regulatory network during SBD was proposed. Our results provided novel insights into GA-mediated regulatory networks during SBD in grape. The complexity of GA-mediated multihormone ST in SBD was also elucidated, thereby providing valuable information for future functional characterizations of specific genes in grape.


Therapeutic strategies for the treatment of stroke.
Acute ischaemic stroke is a major health problem with no effective treatments apart from the thrombolytic recombinant tissue plasminogen activator (rt-PA), which must be given within 3h of stroke onset. However, rt-PA increases the risk of symptomatic intracranial haemorrhage and is administered to <5% of stroke patients. New perfusion-enhancing compounds are in development but the risk:benefit ratio remains to be determined. Many neuroprotective drugs have been studied but all those that reached clinical development have failed to demonstrate efficacy. However, adherence to recently published guidelines on preclinical development has resulted in one novel compound (NXY-059) demonstrating efficacy in a Phase III trial, providing encouragement for the validity of the concept of neuroprotection. There are a variety of new neuroprotective compounds in the early stages of investigation and some could prove clinically effective, provided appropriate preclinical development guidelines are observed.


Allograft adenovirus nephritis accompanied by Crohn's disease in a kidney transplant recipient: a novel case report.
Excessive immunosuppression after kidney transplantation (KT) is often encountered in patients undergoing therapy for anti-rejection or autoimmune disease that requires further treatment using immunosuppressive medications (IMs), including biologic agents. We report a novel case wherein a kidney transplant recipient developed severe acute allograft injury and hemorrhagic cystitis at 4.5 years after KT due to adenovirus nephritis after treatment with infliximab for Crohn's disease. The diagnosis was made based on adenovirus immunohistochemistry staining and urine polymerase chain reaction tests. The patient was successfully treated by reducing IMs and administration of immunoglobulin even though allograft function was eventually partially recovered. When new immunosuppressive agents, particularly biologic agents, are initiated for other diseases in addition to maintenance IMs, the following points need to be regarded: (1) pay attention to opportunistic infections even in the late phase of KT, and (2) maintain communication with other specialists who prescribe biologics to ensure appropriate administration of IMs.


The nubbin sign on computed tomography and sonography.
The loss of parenchyma in the lower pole of a kidney with a duplicated collecting system may mimic a mass on urography ("the nubbin sign"). Computed tomographic findings of this entity are diagnostic. The diagnosis may be difficult to make using sonography alone.


T cell immunomodulation by clinically used allogeneic human cancellous bone fragments: a potential novel immunotherapy tool.
Multipotential stromal cells (MSCs) demonstrate strong immunomodulation capabilities following culture expansion. We have previously demonstrated that human cancellous bone fragments (CBFs) clinically used as viable allografts for spinal fusion have resident MSCs that exhibit T cell immunomodulation after monolayer expansion. This study investigated the immunomodulatory ability of these CBFs without MSC culture-expansion. CD4 positive T cells were induced to proliferate using CD3/CD28 stimulation and added to CBFs at different ratios of T cells per gram of CBF. A dose-dependent suppressive effect on T cell proliferation was evident and correlated with increased culture supernatant levels of TGF-ß1, but not PGE2. CBF-driven immunosuppression was reduced in co-cultures with TGF-ß neutralising antibodies and was higher in cell contact compared to non-contact cultures. CBF gene expression profile identified vascular cell adhesion molecule-1, bone marrow stromal antigen 2/CD317 and other interferon signalling pathway members as potential immunomodulatory mediators. The CD317 molecule was detected on the surface of CBF-resident cells confirming the gene expression data. Taken together, these data demonstrate that human clinically used CBFs are inherently immunomodulatory and suggest that these viable allografts may be used to deliver therapeutic immunomodulation for immune-related diseases.


Supercritical fluid chromatographic analysis for on-line monitoring of hexane removal from soybean oil miscella using liquid carbon dioxide.
Liquid carbon dioxide (L-CO2) can be used to separate hexane from hexane/soybean oil (SBO) mixtures (i.e., miscella). An on-line supercritical fluid chromatographic (SFC) method was developed to monitor this separation. L-CO2 (25 degrees C and 9.31 MPa) was passed through 50 mL of a 25% (w/w) hexane miscella and then directed on-line through a SFC injector. After passing 300-L expanded CO2, the hexane concentrations in the L-CO2 were 0.05% and 0.04% for n-hexane and isohexane, respectively and the residual hexane concentrations in the SBO were 3.8 and 3.3 ppm, respectively. This technique provided real time on-line monitoring of the hexane separation process.


Aging and the thyroid. Decreased requirement for thyroid hormone in older hypothyroid patients.
In 84 patients, aged 23 to 84, with primary hypothyroidism, the daily dose of thyroxine needed to lower the serum thyrotropin level into the normal range was significantly less in older patients than in younger ones (p less than 0.01). Most of the difference between middle-aged (40 to 60 years) and older patients (greater than 60 years) was due to a decrease in the required dose in men; there was no difference in the dose needed by women in these age groups. Previous hyperthyroidism did not affect the dose of thyroxine required; it is unlikely that residual autonomous thyroid tissue affected the dose. Although the wide range of doses needed precludes use of these data in calculating a dose of thyroxine for an individual patient, doses of 100 micrograms per day or less were common in patients over age 40, and a few patients over age 60 needed 50 micrograms per day or less. Thus, (1) there is a sound physiologic basis for the common practice of using low doses of thyroxine, e.g., 25 micrograms per day, as initial therapy in older hypothyroid patients and (2) it may be reasonable to reassess the dose of thyroxine after several years in older patients.


Contemporary study of multiple sclerosis disability in South East Wales.
A contemporary understanding of disability evolution in multiple sclerosis (MS) is an essential tool for individual disease management and planning of interventional studies. We have used prospectively collected longitudinal data to analyse disability progression and variation in a British MS cohort. Cox proportional hazards regression was used to estimate hazard of Expanded Disability Status Scale (EDSS) 4.0 and 6.0. A continuous Markov model was used to estimate transitional probabilities for individual EDSS scores. Models were adjusted for age at MS onset, sex and disease-modifying treatments (DMTs) exposure. 2135 patients were included (1487 (70%) female, 1922 (89%) relapsing onset). 865 (41%) had used DMTs. Median time to EDSS 4.0 and 6.0 was 18.2 years (95% CI 16.3 to 20.2) and 22.1 years (95% CI 20.5 to 24.5). In the Markov model, the median time spent at EDSS scores of <6 (0.40-0.98 year) was shorter than the time spent at EDSS scores of ≥6 (0.87-4.11 year). Hazard of change in EDSS was greatest at EDSS scores <6 (HR for increasing EDSS: 1.02-1.33; decreasing EDSS: 0.34-1.27) compared with EDSS scores ≥6 (HR for increasing EDSS: 0.08-0.61; decreasing EDSS: 0.18-0.54). These data provide a detailed contemporary model of disability outcomes in a representative population-based MS cohort. They support a trend of increasing time to disability milestones compared with historical reference populations, and document disability variation with the use of transitional matrices. In addition, they provide essential information for patient counselling, clinical trial design, service planning and offer a comparative baseline for assessment of therapeutic interventions.


Novel Drugs and Radiotherapy in Relapsed Lymphomas: Abscopal Response and Beyond.
Combined modality has represented a mainstay of treatment across many lymphoma histologies, given their sensitivity to both multi-agent chemotherapy and intermediate-dose radiotherapy. More recently, several new agents, including immunotherapies, have reshaped the therapeutic panorama of some lymphomas. In parallel, radiotherapy techniques have witnessed substantial improvement, accompanied by a growing understanding that radiation itself comes with an immune-mediated effect. Six decades after a metastatic lesion regression outside the irradiated field was first described, there is increasing evidence that a combination of radiotherapy and immunotherapy could boost an abscopal effect. This review focuses on the mechanisms underlying this interaction in the setting of lymphomas, and on the results of pivotal prospective studies. Furthermore, the available evidence on the concomitant use of radiotherapy and small molecules (i.e., lenalidomide, venetoclax, and ibrutinib), as well as brentuximab vedotin, and chimeric antigen receptor (CAR) T-cell therapy, is summarized. Currently, combining radiotherapy with new agents in patients who are affected by lymphomas appears feasible, particularly as a bridge to anti-CD19 autologous CAR T-cell infusion. However, more studies are required to assess these combinations, and preliminary data suggest only a synergistic rather than a curative effect.


Chronic inflammation is correlated with percentage of body fat independent of the burden of infection.
The aim of this population-based study was to investigate the association of the percentage of body fat (BF) and high-sensitivity C-reactive protein (hs-CRP) when the infectious burden was adjusted for. A total of 1,546 subjects were randomly selected. BF was determined using bioelectrical impedance analysis. Sera were analyzed for IgG antibodies to Chlamydia pneumoniae, herpes simplex virus type 1, Helicobacter pylori, and cytomegalovirus using ELISA. Measurement of C-reactive protein (CRP) by a high-sensitivity CRP assay was performed. A linear relationship between an increase in the number of pathogens and CRP concentrations was observed (p = 0.007). Age-adjusted serum hs-CRP levels were correlated with percentage of BF in men (r = 0.28, p < 0.0001) and women (r = 0.37, p < 0.0001). In multiple regression analyses, hs-CRP showed significant correlations with percentage of BF after controlling for age, sex, cardiovascular risk factors, and the infectious burden was divided into two, three, and four pathogens [(β = 0.24, p < 0.0001), (β = 0.2 1, p < 0.0001), and (β = 0.23, p = <0.0001), respectively]. In conclusion, there was a strong association between hs-CRP and percentage of body fat independent of viral and bacterial pathogens that had been previously associated with coronary artery disease as well as carotid atherosclerosis.


Conditioned culture for protoplasts isolated from chrysanthemum: an efficient approach.
An efficient approach was described for the culture of protoplasts isolated from chrysanthemum, and factors affecting the plating efficiency, defined as the number of protoplasts developing microcolonies divided by the number of cultured protoplasts, were investigated here. A yield of 4.86+/-0.22x10(5) mesophyll protoplasts per gram fresh weight were achieved by an enzymolysis procedure. The viability of fresh isolated protoplasts was 64.5+/-8.2% as confirmed by Evans blue staining. Sustained cell division and microcolony formation from the protoplasts were supported by modified Murashige and Skoog medium, complemented with 1:4 diluted conditioned medium harvested from three different callus suspension cultures. Results showed that the plating efficiency was obviously influenced by various concentrations of agarose and antibiotic, and significantly increased by conditioned medium harvested from chrysanthemum suspensions, while the other two species had a positive effect generally. Results also indicated that the growth-stimulative effect was reduced when the conditioned medium was stored for 6-14 days prior to use, suggesting the unstable characteristic of conditioning factors.


The water economy of South American desert rodents: from integrative to molecular physiological ecology.
Rodents from arid and semi-arid habitats live under conditions where the spatial and temporal availability of free water is limited, or scarce, thus forcing these rodents to deal with the problem of water conservation. The response of rodents to unproductive desert environments and water deficits has been intensively investigated in many deserts of the world. However, current understanding of the cellular, systemic and organismal physiology of water economy relies heavily on short-term, laboratory-oriented experiments, which usually focus on responses at isolated levels of biological organization. In addition, studies in small South American mammals are scarce. Indeed xeric habitats have existed in South America for a long time and it is intriguing why present day South American desert rodents do not show the wide array of adaptive traits to desert life observed for rodents on other continents. Several authors have pointed out that South American desert rodents lack physiological and energetic specialization for energy and water conservation, hypothesizing that their success is based more on behavioral and ecological strategies. We review phenotypic flexibility and physiological diversity in water flux rate, urine osmolality, and expression of water channels in South American desert-dwelling rodents. As far as we know, this is the first review of integrative studies at cellular, systemic and organismal levels. Our main conclusion is that South American desert rodents possess structural as well as physiological systems for water conservation, which are as remarkable as those found in "classical" rodents inhabiting other desert areas of the world.


Biosynthesis of zinc oxide nanoparticles using leaf extracts of Alchornea laxiflora and its tyrosinase inhibition and catalytic studies.
Zinc oxide nanoparticles (ZnO-NPs) were synthesized using a simple, low cost and safe method involving aqueous leaf extracts of Alchornea laxiflora and a zinc precursor salt. The nanoparticles were characterized by ultraviolet-visible (UV-vis), Fourier transform (FT-IR) spectroscopy, Energy dispersive X-ray (EDX), X-ray diffraction (XRD) and Scanning electron microscope (SEM). They were evaluated for their potentials as tyrosinase inhibitors and as catalysts in the degradation of Congo red dye. The UV-vis spectra gave characteristic surface Plasmon bands within the range 276-456 nm. The band gap energies of the ZnO-NPs were of the range, 2.50-3.67 ev. The SEM results showed average sizes of 29 nm and 38 nm for particles obtained using 1 mL and 2 mL of the plant extracts respectively. EDX plot showed the elemental compositions of the nanoparticles with zinc and oxygen being pronounced. The ZnO nanoparticles exhibited good photocatalytic efficiency of 87 % degradation of Congo red (CR) dye molecules in 60 min, They also showed good anti-tyrosinase ability with an IC50 of 66.28 μg/mL. Overall the biogenic ZnO nanoparticles are promising materials for dual applications as photocatalysts in the degradation of Congo red dye and as tyrosinase inhibitors.


The burden of brain tumor: a single-institution study on psychological patterns in caregivers.
Quality of life and well-being in caregivers are usually partly neglected since all attention is focused on patients and the way they react to the illness. Carers also usually neglect their own needs, especially when the illness of the patient is as complex as a brain tumor. The aim of this study is to investigate how caregivers deal with a diagnosis of brain tumor in their relatives and how they manage their quality of life and psychosocial well-being. One hundred primary caregivers of patients with brain tumors were interviewed and were asked to fill in self-administered questionnaires detecting multidimensional levels of quality of life, anxiety, depression, and psychosocial reaction to the patient's illness. Data were related with some functional and psychosocial information collected about the patient's disease. Caregivers try to react to the illness of their relatives by mobilizing their physical reaction and growing their self-esteem, but they live with a clinically significant impairment of their quality of life, and experience a deep level of anxiety and depression. The caregivers' burden appears mainly in their ability to provide care and in financial strain. The length of disease and the functional status of patients significantly influence caregivers' psychosocial well-being. Despite the appearance they want to show their affected relatives, caregivers suffer from deep limitation in their quality of life. The relevance of caregivers' burden suggests the importance of psychological support to improve reaction to the illness.


Effect of livingstonepotato (Plectranthus esculenthus N.E.Br) on hyperglycemia, antioxidant activity and lipid metabolism of streptozotocin induced diabetic rats.
The effect of livingstone potato (Plectranthus esculenthus N.E.Br) on serum glucose, glycated hemoglobin (HbA1C), serum triglyceride, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), hepatic malic enzyme (ME), isocitrate dehydrogenase (IDH) and catalase activities of Streptozotocin induced diabetic rats were investigated using standard techniques. The atherogenic index (AI) and coronary risk index (CRI) of the rats were calculated as the ratios of LDL to HDL and total cholesterol to HDL, respectively. The serum glucose of the non-diabetic, diabetic control and diabetic rats given livingstone potato incorporated feeds (test feed) were 92.58 ± 3.97, 352.30 ± 4.88 and 165.50 ± 7.88 mg/dl, respectively. Intake of the test feed by the diabetic rats of group 3, resulted in significant (P < 0.05) decrease of their serum glucose, HbA1c, triglyceride, cholesterol, LDL, VLDL, AI and CRI but significant increase (P < 0.05) of hepatic levels of ME, IDH, catalase and serum HDL compared with the diabetic control rats that had significant alteration of these parameters (P < 0.05) compared with the non-diabetic rats. The feed intakes of the non-diabetic, diabetic control and diabetic rats given the test feed were 133.34 ± 1.32, 137.84 ± 5.77 and 146.38 ± 4.33 g/rat/week by the last week of experimentation. The diabetic control rats recorded significant loss of weight (P < 0.05) compared with the non diabetic rats despite increased feed intake. Chemical analysis of the standard and test feeds showed that the standard rat feed contained 15.00 ± 0.78% protein, 7.24 ± 1.20% fat, 31.55 ± 2.62% carbohydrates, energy value of 290.65 ± 4.77 kcal/100 g, 10% crude fiber and 0.12 ± 0.04 mg Gallic Acid Equivalent while the test feed contained 40.10 ± 0.16% carbohydrates, 17.22 ± 0.40% protein, 22.16 ± 0.34% fat, energy value of 428.70 ± 2.12 kcal/100 g, 8.51 ± 0.16% crude fiber, 1.3 ± 0.2 mg Gallic Acid Equivalent/g of sample and strong antioxidant activity comparable to standard quercetin. The study shows the potentials of livingstone potato in the management of diabetes and hyperlipidemia.


Physiologically Based Pharmacokinetic Model to Assess the Influence of Blinatumomab-Mediated Cytokine Elevations on Cytochrome P450 Enzyme Activity.
Blinatumomab is a CD19/CD3 bispecific T-cell engager (BiTE®) antibody construct for treatment of leukemia. Transient elevation of cytokines (interleukin (IL)-6, IL-10, interferon-gamma (IFN-γ)) has been observed within the first 48 hours of continuous intravenous blinatumomab infusion. In human hepatocytes, blinatumomab showed no effect on cytochrome P450 (CYP450) activities, whereas a cytokine cocktail showed suppression of CYP3A4, CYP1A2, and CYP2C9 activities. We developed a physiologically based pharmacokinetic (PBPK) model to evaluate the effect of transient elevation of cytokines, particularly IL-6, on CYP450 suppression. The predicted suppression of hepatic CYP450 activities was <30%, and IL-6-mediated changes in exposure to sensitive substrates of CYP3A4, CYP1A2, and CYP2C9 were <twofold and lasted <1 week. Model verification indicated that IL-6 was the key cytokine suppressing CYP450 activities; the duration of cytokine elevation was a major determinant of magnitude of suppression. This study shows the utility of PBPK modeling for risk assessment of cytokine-mediated drug interactions.


A cluster of microvillous inclusion disease in the Navajo population.
We report 4 unrelated patients with characteristic microscopic findings of microvillous inclusion disease (MID) with early-onset phenotype. All 4 patients came from the Navajo reservation in northern Arizona. A literature search revealed a fifth unrelated Navajo child with MID. The unusually high incidence in this population indicates that a founder effect might be responsible for an increased frequency of this rare genetic disorder in the Navajo. It is recommended that all Navajo infants presenting with severe diarrhea during early infancy undergo investigation for MID.


Mechanism of action of potato carboxypeptidase inhibitor (PCI) as an EGF blocker.
The epidermal growth factor receptor (EGFR) signal transduction pathway plays a prominent role in the development of carcinomas, and is an interesting target for antitumoral therapy. We have previously described how potato carboxypeptidase inhibitor (PCI), a 39-amino acid protease inhibitor with a T-Knot motif, binds to EGFR receptor and inhibits the activation of receptor protein tyrosine kinase. In this paper it is shown that PCI interferes with EGFR activation through inhibition of receptor dimerization and receptor transphosphorylation induced by epidermal growth factor (EGF) and by transforming growth factor alpha (TGF-alpha). Moreover, PCI blocks the formation and activation of ErbB1/ErbB-2 heterodimers that have a prominent role in carcinoma development. As a result of these effects, PCI interferes in the EGFR signal transduction pathway by reversing the effects of EGF on the growth of two tumoral cell lines, A431 and MDA-MB-453, and promotes EGFR down-regulation. These results show that PCI acts as an EGF/TGF-alpha antagonist, which suggests its therapeutic potential in the treatment of carcinomas.


Ebselen alters cellular oxidative status and induces endoplasmic reticulum stress in rat hippocampal astrocytes.
Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is an organoselenium radical scavenger compound, which has strong antioxidant and anti-inflammatory effects. Because of its properties, it may be protective against injury to the nervous tissue. However, evidence suggests that its glutathione peroxidase activity could underlie certain deleterious actions on cell physiology. In this study we have analyzed the effect of ebselen on rat hippocampal astrocytes in culture. Cellular oxidative status, cytosolic free-Ca(2+) concentration ([Ca(2+)]c), setting of endoplasmic reticulum stress and phosphorylation of glial fibrillary acidic protein and major mitogen-activated protein kinases were analyzed. Our results show that ebselen induced a concentration-dependent increase in the generation of reactive oxygen species in the mitochondria. We observed a concentration-dependent increase in global cysteine oxidation and in the level of malondialdehyde in the presence of ebselen. We also detected increases in catalase, glutathione S-transferase and glutathione reductase activity. Ebselen also evoked a concentration-dependent increase in [Ca(2+)]c. Moreover, we observed a concentration-dependent increase in the phosphorylation of the unfolded protein response markers, eukaryotic translation initiation factor 2α and X-box binding protein 1. Finally, ebselen also induced an increase in the phosphorylation of glial fibrillary acidic protein, SAPK/JNK, p38 MAPK and p44/42 MAPK. Our results provide strong evidence that implicate endoplasmic reticulum stress and activation of crucial mitogen-activated protein kinases in an oxidative damage of cells in the presence of ebselen. The compound thus might exert deleterious actions on astrocyte physiology that could compromise their function.


Utilization of Anabaena sp. in CO₂ removal processes: modelling of biomass, exopolysaccharides productivities and CO₂ fixation rate.
This paper focuses on modelling the growth rate and exopolysaccharides production of Anabaena sp. ATCC 33047, to be used in carbon dioxide removal and biofuels production. For this, the influence of dilution rate, irradiance and aeration rate on the biomass and exopolysaccharides productivity, as well as on the CO(2) fixation rate, have been studied. The productivity of the cultures was maximum at the highest irradiance and dilution rate assayed, resulting to 0.5 g(bio) l(-1) day(-1) and 0.2 g(eps) l(-1) day(-1), and the CO(2) fixation rate measured was 1.0 gCO(2) l(-1) day(-1). The results showed that although Anabaena sp. was partially photo-inhibited at irradiances higher than 1,300 μE m(-2) s(-1), its growth rate increases hyperbolically with the average irradiance inside the culture, and so does the specific exopolysaccharides production rate. The latter, on the other hand, decreases under high external irradiances, indicating that the exopolysaccharides metabolism hindered by photo-damage. Mathematical models that consider these phenomena have been proposed. Regarding aeration, the yield of the cultures decreased at rates over 0.5 v/v/min or when shear rates were higher than 60 s(-1), demonstrating the existence of thus existence of stress damage by aeration. The behaviour of the cultures has been verified outdoors in a pilot-scale airlift tubular photobioreactor. From this study it is concluded that Anabaena sp. is highly recommended to transform CO(2) into valuable products as has been proved capable of metabolizing carbon dioxide at rates of 1.2 gCO(2) l(-1) day(-1) outdoors. The adequacy of the proposed equations is demonstrated, resulting to a useful tool in the design and operation of photobioreactors using this strain.


Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons.
CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic domains. In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na(+) channel-mediated dendritic spikes are efficiently initiated by waveforms mimicking synaptic events. CA3 pyramidal neuron dendrites showed a high Na(+)-to-K(+) conductance density ratio, providing ideal conditions for active backpropagation and dendritic spike initiation. Dendritic spikes may enhance the computational power of CA3 pyramidal neurons in the hippocampal network.


A case control study of needlescopic herniotomy versus open herniotomy in children.
Since the inception of laparoscopy, it has been explored in many fields of surgery, like in the abdomen, hernia, thorax, etc., Laparoscopic hernioplasty in adults is being practiced by many surgeons nowadays. However, the role of laparoscopic inguinal hernia repair in pediatric patients is not well-established, even though it is being explored as an alternative to open herniotomy procedure. In the present study, laparoscopic needlescopic hernia repair was compared with the conventional open herniotomy procedure. The study was a case-control study conducted in a tertiary care hospital in northeast India during 2018-2021. A total of 25 patients underwent needlescopic hernia repair, the outcome of which was compared by collecting data of 25 more patients who earlier underwent open herniotomy repairs. The laparoscopic needlescopic repair took a longer operative time as compared to the open technique with a smaller-sized incision. Laparoscopic needlescopic hernia repair is a safe and feasible procedure with a similar outcome to open herniotomy but with a smaller scar.


Adriana Briscoe.
Interview with Adriana Briscoe, who studies how color vision impacts ecological interactions between butterflies, host plants, and the environment at the University of California, Irvine.


Investigation of Temperature-Responsive Tocosomal Nanocarriers as the Efficient and Robust Drug Delivery System for Sunitinib Malate Anti-Cancer Drug: Effects of MW and Chain Length of PNIPAAm on LCST and Dissolution Rate.
In this study, for the first time, the coated tocosome by blend of chitosan, CS, and poly(N-isopropylacrylamide), PNIPAAm, was developed as the efficient and robust drug delivery system with improved drug encapsulation efficiency, extended stability, proper particle size and industrial upscaling for Sunitinib malate anti-cancer drug. Tocosome was synthesized by using Mozafari method as a scalable and robust method and without the need for organic solvents. The effects of tocosome composition and drug concentration on the stability, particle size of tocosome, zeta potential, encapsulation efficacy and loading of drug into it were investigated by Taguchi method, and optimum composition was selected for combining with the polymeric blend. Homopolymer of PNIPAAm was synthesized by two different polymerization methods, including free radical and reversible addition-fragmentation chain transfer (RAFT). Effects of molecular weight (MW) and chain length of the polymers on lower critical solution temperature (LCST) were examined. The developed nanocarrier in this research, CS-Raft-PNIPAAm-tocosome, indicated LCST value beyond 37°C (about 45°C) and this is suitable for hyperthermia and spatio-temporal release of drug particles.


A polymorphism of the metabotropic glutamate receptor mGluR7 (GRM7) gene is associated with schizophrenia.
Glutamate dysfunction has been implicated in the pathophysiology of schizophrenia. The metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors. GRM7, the gene that encodes mGluR7, is expressed in many regions of the human central nervous system. The GRM7 gene is located on human chromosome 3p26, which has been suggested by linkage analysis to contain a susceptibility locus for schizophrenia. We screened for mutations in all exons, exon/intron junctions, and promoter regions of the GRM7 gene in Japanese patients with schizophrenia and evaluated associations between the detected polymorphisms and schizophrenia. We examined the influence of one polymorphism associated with schizophrenia on the expression of GRM7 by dual-luciferase assay in transfected cells. Twenty-five polymorphisms/mutations were detected in GRM7. Case-control analysis revealed a potential association of a synonymous polymorphism (371T/C, rs3749380) in exon 1 with schizophrenia in our case-control study of 2293 Japanese patients with schizophrenia and 2382 Japanese control subjects (allelic p=0.009). Dual-luciferase assay revealed suppression of transcription activity by exon 1 containing this polymorphism and a statistically significant difference in the promoter activity between the T and C alleles. Our results support the possible association of a GRM7 gene polymorphism with genetic susceptibility to schizophrenia.


Development of a droplet digital PCR for pertussis toxin locus copy number determination in a genetically-modified Bordetella pertussis strain.
To improve pertussis toxin (PT) yield in B. pertussis strains for vaccine production a genetically-engineered strain (gdPT 191-134 strain) with a second copy of the genetically detoxified PT (gdPT) locus was developed. The consistency of the production and genetic stability of the strain when used for vaccine production must be established. We developed two simplex ddPCR assays with PCR systems for ptxA, the target gene present in two copies, and pgm, the reference gene present as a single copy. The ddPCR assay had sufficient precision to discriminate the copy number of the PT locus accurately in two B. pertussis strains: one copy in the parent, non-genetically-engineered strain and two copies in the gdPT 191-134 strain. Using the ddPCR assays, we were able to show that the ratio of the ptxA to pgm genes decreased during serial culture passages, due to the loss of PT locus, which in turn, resulted in lower levels of PT production over time. We were then able to assess culture conditions that improved the stability of the double locus, as shown by non-significant reduction in gdPT toxin yield.


Electrocatalysis in Room Temperature Sodium-Sulfur Batteries: Tunable Pathway of Sulfur Speciation.
Benefiting from the merits of natural abundance, low cost, and ultrahigh theoretical energy density, the room temperature sodium-sulfur (RT NaS) batteries are regarded as one of the promising candidates for the next-generation scalable energy storage devices. However, the uncontrollable sulfur speciation pathways severely hinder its practical applications. Recently, various strategies have been employed to tune the conversion pathways of sulfur, such as physical confinement, chemical inhibition, and electrocatalysis. Herein, the recent advances in electrocatalytic effects manipulate sulfur speciation pathways in advanced RT NaS electrochemistry are reviewed, including the promotion of the nearly full conversion of long-chain polysulfides, short-chain polysulfides, and small sulfur molecules. The underlying catalytic modulation mechanism that fundamentally tunes the electrochemical pathway of sulfur species is comprehensively summarized along with the design strategies for catalytic active centers. Furthermore, the challenge and potential solutions to realize the quasi-solid conversion of sulfur are proposed to accelerate the real application of RT NaS batteries.


The effects of hemolyzed blood on pulmonary and systemic arterial pressure and heart rate of the dog.
The injection of hemolyzed blood into the venous system of the dog produced a rise in the pulmonary arterial pressure and a fall in the systemic arterial pressure. There were variable changes in the heart rate. Comparison with serotonin injections indicated that the above responses were produced by factors other than serotonin.