Function of Fe(III)-minerals in the enhancement of anammox performance exploiting integrated network and metagenomics analyses.
Iron is a recognized physiological requirement for microorganisms but, for anaerobic ammonium oxidation (anammox) bacteria, its role extends well beyond that of a nutritional necessity. In this study, the function of two typical Fe(III)-minerals (ferrihydrite and magnetite) in anammox processes was evaluated in the absence/presence of Fe(II) by integrated network and metagenomics analyses. Results showed that Fe-(III) minerals addition increased the activity of cellular processes and pathways associated with granule formation, enabling the peak values of particle size to increase by 144% and 115%, respectively. Notably, ferrihydrite (5 mM) enhanced nitrogen removal by 4.8% and 4.1%, respectively, in the short-term and long-term absence of Fe(II). Ferrihydrite also promoted the retention of anammox bacteria affiliated with phylum Planctomycetes in the reactor, contributing to an 11% higher abundance with ferrihydrite amendment when compared with the control (without iron additions) in the short-term absence of Fe(II). Network-based analyses revealed that ferrihydrite facilitated the microbial community to form densely clustered and complex topologies to improve resistance to environmental disturbance (i.e., Fe(II) deficiency), and effectively increased the underlying cooperation and facilitation in the community. Metagenomic analysis revealed that there was limited promotion of anammox central metabolism by the extra addition of Fe(III)-minerals in the presence of Fe(II), highlighting the poor utilization of Fe(III)-minerals by anammox bacteria under Fe(II) sufficiency. This study deepens our understanding of the function of Fe(III)-minerals in anammox systems at the community and functional level, and provides a fundamental basis for developing Fe-based anammox enhancement technologies.


Overexpressed BAG3 is a potential therapeutic target in chronic lymphocytic leukemia.
Bcl-2-associated athanogene 3 (BAG3), a member of BAG family, is shown to sustain cell survival and underlie resistance to chemotherapy in human neoplastic cells. We aimed to determine the exact role and underlying mechanisms of BAG3 in human chronic lymphocytic leukemia (CLL). One hundred human CLL samples and 20 normal B-cell samples from healthy controls were collected. We measured the BAG3 expression in these cells and explored its relationship with known prognostic factors for CLL. The roles of BAG3 in cell apoptosis and migration were evaluated by small interfering RNA-mediated knockdown of BAG3 in primary CLL cells. We showed that BAG3 expression level was increased in CLL cells compared with normal B cells. Moreover, BAG3 expression was particularly upregulated in CD38 positive, unmutated immunoglobulin heavy-chain patients and those with lymphadenopathy and/or splenomegaly. Importantly, patients with increased BAG3 expression level have poor overall survival in subgroups with positive ZAP-70 or those without any "p53 abnormality". In addition, knocking down of BAG3 expression resulted in increased apoptotic ratio and decreased migration in primary CLL cells. Our data indicate that BAG3 is a marker of poor prognostic in specific subgroups of CLL patients and may be a potential therapeutic target for this disease.


Fragmented mitochondrial genomes of seal lice (family Echinophthiriidae) and gorilla louse (family Pthiridae): frequent minichromosomal splits and a host switch of lice between seals.
The mitochondrial (mt) genomes of 15 species of sucking lice from seven families have been studied to date. These louse species have highly dynamic, fragmented mt genomes that differ in the number of minichromosomes, the gene content, and gene order in a minichromosome between families and even between species of the same genus. In the present study, we analyzed the publicly available data to understand mt genome fragmentation in seal lice (family Echinophthiriidae) and gorilla louse, Pthirus gorillae (family Pthiridae), in particular the role of minichromosome split and minichromosome merger in the evolution of fragmented mt genomes. We show that 1) at least three ancestral mt minichromosomes of sucking lice have split in the lineage leading to seal lice, 2) one minichromosome ancestral to primate lice has split in the lineage to the gorilla louse, and 3) two ancestral minichromosomes of seal lice have merged in the lineage to the northern fur seal louse. Minichromosome split occurred 15-16 times in total in the lineages leading to species in six families of sucking lice investigated. In contrast, minichromosome merger occurred only four times in the lineages leading to species in three families of sucking lice. Further, three ancestral mt minichromosomes of sucking lice have split multiple times independently in different lineages of sucking lice. Our analyses of mt karyotypes and gene sequences also indicate the possibility of a host switch of crabeater seal louse to Weddell seals. We conclude that: 1) minichromosome split contributes more than minichromosome merger in mt genome fragmentation of sucking lice, and 2) mt karyotype comparison helps understand the phylogenetic relationships between sucking louse species.


Low levels of antibodies against common viruses associate with anti-citrullinated protein antibody-positive rheumatoid arthritis; implications for disease aetiology.
Infection by common viruses has long been discussed in the aetiology of a number of autoimmune diseases, including rheumatoid arthritis (RA). However, studies investigating this hypothesis in RA show conflicting results. These studies often lack well-matched control populations, and many do not include data on autoantibodies, genetic risk factors and other environmental factors, which are known to contribute to disease only in subgroups of patients. In the present study, we have therefore examined the role of Epstein-Barr virus (EBV), cytomegalovirus (CMV) and parvovirus B19 (B19) in RA aetiology, by analysing anti-viral antibodies in relation to anti-citrullinated protein antibodies (ACPA), smoking, HLA-DRB1 shared epitope (SE) alleles, and clinical parameters, in both RA patients and matched controls. Anti-viral antibodies were measured by ELISA in serum samples from 990 RA patients and 700 controls from the Swedish population-based Epidemiological Investigation of RA (EIRA) cohort. Data on ACPA, smoking, SE, inflammation (C-reactive protein) and disease activity score in 28 joints (DAS28) was obtained from the EIRA database. Fisher's exact test, the chi-squared test, and the Mann-Whitney U test were used to calculate differences in anti-viral antibody frequencies and levels; unconditional logistic regression was used to determine the association of anti-viral antibodies with different RA subsets. Antibodies against all viruses were highly prevalent in EIRA, with no major differences detected between ACPA-positive RA, ACPA-negative RA and controls. However, both anti-B19 and anti-EBV IgG levels were significantly lower in ACPA-positive RA compared to controls, and there were significant interactions between low levels of anti-B19 and anti-EBV antibodies and SE in the development of ACPA-positive RA. We could not detect an association between RA and elevated anti-viral antibody levels, for any of the three common viruses, EBV, CMV or B19. On the contrary, our study demonstrated association between low anti-EBV/anti-B19 antibody levels and ACPA-positive RA, in particular when HLA-DRB1 SE was present. These data could potentially suggest that high anti-viral antibody levels would be protective against ACPA-positive RA. Further investigations are required to address the mechanisms behind these findings.


Differences in Overall and Cancer-specific Survival of Patients Presenting With Chromophobe Versus Clear Cell Renal Cell Carcinoma: A Propensity Score Matched Analysis.
To investigate prognostic parameters for the oncological outcome of patients treated for chromophobe renal cell carcinoma (chRCC) in comparison with patients treated for clear cell RCC (ccRCC) using propensity score matching for survival analysis. From 1969 to 2009, we identified 1010 from 3567 patients with RCC. Survival was analyzed using Kaplan-Meier estimate for histological subtypes including 109 chRCC and 901 ccRCC. Uni- and multivariate Cox regression was used to analyze prognostic factors for overall survival (OS) and cancer-specific survival (CSS). Propensity score matching was performed to adjust for differences in patient characteristics among histological subgroups. The median follow-up was 61 months (range 0-289). chRCC showed longer OS (5 year, 90.1%; 10 year, 74.2%; 15 year, 61.4%) and CSS (94.2%, 89.7%, 89.7%) compared with ccRCC (OS 75.7%, 54.9%, 46.1% and CSS 84.7%, 75.4%, 72.2%; P = .002). Multivariate Cox regression revealed histology as a significant prognostic factor. Propensity score matching showed a difference in 72.4% (OS) and 87.2% (CSS) of matching attempts confirming the significant impact of histology. Univariate Cox regression showed nephron sparing surgery, no metastasis and no symptoms at presentation, age <65, eosinophilic features, low American Society of Anesthesiologists score, and Charlson Comorbidity Index to be beneficial for CSS. Only age at surgery, metastasis at presentation, and American Society of Anesthesiologists and Charlson Comorbidity Index scores were significant factors for OS in chRCC patients. ChRCC appears to have a favorable outcome compared with ccRCC. Even after adjustment for differences in characteristics known to have an influence on survival by propensity score matching, histology remains a significant prognostic factor.


Ciclosporin A in bilateral auto-immune chronic posterior uveitis associated with macular oedema: a Long-term Observational Safety and Efficacy Study.
A non-interventional, longitudinal, retrospective follow-up study to assess CsA-induced nephrotoxicity (IN) and its reversibility after withdrawal in patients exhibiting a bilateral chronic posterior uveitis (CPU) associated with cystoid macular oedema (CMO) in at least one eye. Data from medical records between 1986 and 2013. Primary outcome was the renal tolerance during and after CsA treatment assessed by plasma creatinine concentration and glomerular filtration rate (GFR) estimated by Chronic Kidney Disease Epidemiology (CKD-Epi) formula. Secondary outcomes were CsA through concentration, occurrence of cancers and ophthalmologic efficacy assessed by three parameters including CMO, vitreous inflammation, and best-corrected visual acuity BVCA changes. One hundred forty-three patients were followed for renal tolerance. Underlying diseases were Birdshot retinochoroiditis (n = 67), Behçet disease (n = 9), probable sarcoidosis (n = 23), sympathetic ophthalmia (n = 3), idiopathic (n = 41). After CsA discontinuation in 115 patients (mean treatment duration of 5.9 ± 3.8 years) mean plasma creatinine concentration was 82.2 ± 14.2 µmol/L versus 82.1 ± 14.1 µmol/L at baseline, mean GFR was 79.4 ± 13.9 mL/min versus 82.5 ± 14.3 mL/min at baseline, with no significant difference (respectively p = 0.91 and p = 0.09). Blood pressure did not significantly change during follow-up. CMO was completely resorbed in at least one eye, in 70.8% patients (n = 72) at 6 months, in 71.4% patients (n = 49) at 10 years and in 54.2% patients (n = 24) at 20 years. BCVA did not statistically change over time. Early and long-term monitoring of renal tolerance and dual adjustment of CsA doses in inflammatory stages of CPU were associated with reversible CsA IN. CsA could be effective in the treatment of CMO in CPU patients.


Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches.
Aging drives the genetic and epigenetic changes that result in a decline in hematopoietic stem cell (HSC) functioning. Such changes lead to aging-related hematopoietic/immune impairments and hematopoietic disorders. Understanding how such changes are initiated and how they progress will help in the development of medications that could improve the quality life for the elderly and to treat and possibly prevent aging-related hematopoietic diseases. Here, we review the most recent advances in research into HSC aging and discuss the role of HSC-intrinsic events, as well as those that relate to the aging bone marrow niche microenvironment in the overall processes of HSC aging. In addition, we discuss the potential mechanisms by which HSC aging is regulated.


Clinical results with subcutaneous implants containing 3-keto desogestrel.
Eight healthy women using one Silastic implant of 30 mm length filled with 3-keto desogestrel, the active metabolite of desogestrel, were studied for 36-664 days. The release rate of 3-keto desogestrel was quite constant and around 30 micrograms/day. No ovulations occurred. One woman was amenorrheic, while the others had different bleeding patterns, often with periods of spotting. No other side effects were recorded. The mean plasma levels of 3-keto desogestrel were 0.9 nmol/l after 1 month and 0.5 nmol/l after 12 months. 3-Keto desogestrel was less effective than testosterone, estradiol or levonorgestrel in displacing 3H-dihydrotestosterone from SHBG. It is concluded that contraception with 3-keto desogestrel delivered through an implant is a promising method for further investigation. With a single implant we found a duration of at least one year.


Metaheuristic secured transmission in Telecare Medical Information System (TMIS) in the face of post-COVID-19.
The outbreak of novel corona virus had led the entire world to make severe changes. A secured healthcare data transmission has been proposed through Telecare Medical Information System (TMIS) based on metaheuristic salp swarm. Patients need proper medical remote treatments in this Post-COVID-19 time from their quarantines. Secured transmission of medical data is a significant challenge of digitally overwhelmed environment. The objective is to impart the patients' data by encryption with confidentiality and integrity. Eavesdroppers can carry sniffing and spoofing in order to deluge the data. In this paper, a novel scheme on metaheuristic salp swarm based intelligence has been sculptured to encrypt electrocardiograms (ECG) for data privacy. Metaheuristic approach has been blended in cryptographic engineering to address the TMIS security issues. Session key has been derived from the weight vector of the fittest salp from the salp population. The exploration and exploitation control the movements of the salps. The proposed technique baffles the eavesdroppers by the key strength and other robustness factors. The results, thus obtained, were compared with some existing classical techniques with benchmark results. The proposed MSE and RMSE were 28,967.85, and 81.17 respectively. The time needed to decode 128 bits proposed session key was 8.66 × 1052 years. The proposed cryptographic time was 8.8 s.


Evidence for In utero hematogenous transmission of group B beta-hemolytic streptococcus.
The presumed ascending route of group B beta-hemolytic streptococcus (GBS) infection from the colonized maternal genital tract is well accepted. This case report proposes a hematogenous, selective infection of one unruptured amniotic sac over the other ruptured amniotic sac in a twin gestation in a patient with known GBS vaginal colonization. This is a case report of GBS sepsis in twin B with intact membranes. Twin A, with 28 h of ruptured membranes, failed to show any signs of infection. The pathology of the placenta confirmed chorioamnionitis in twin B and the absence of infection in twin A. The presence of culture-positive GBS sepsis in the twin with the unruptured amniotic sac, as well as the absence of GBS infection in the twin with the ruptured sac, suggests an alternative means of infection for GBS infection, such as hematogenous transplacental transmission.


Spray freezing into liquid versus spray-freeze drying: influence of atomization on protein aggregation and biological activity.
Protein aggregation and enzyme activity were compared for reconstituted lysozyme particles produced by two cryogenic technologies, spray freezing into liquid (SFL) and spray-freeze drying (SFD). The particles were characterized by enzyme activity measurements, scanning electron microscopy (SEM), light scattering, X-ray photoelectron spectroscopy (XPS) and BET specific surface area analysis. Highly porous microparticle aggregates of protein nanoparticles, observed by SEM, were produced by both processes. The smaller degree of protein aggregation and smaller losses in enzyme activity for the SFL process relative to the SFD process were due primarily to the spraying step. The higher stability of the SFL versus SFD powders was consistent with the smaller surface excess of lysozyme measured by XPS in SFL, resulting from the reduced time of exposure to the air-water interface during atomization. For pure lysozyme, the degree of aggregation and enzyme activity were comparable for lyophilization and SFL, despite the much larger particle surface area for SFL.


Molecular dynamics simulations.
Molecular dynamics simulations have become a standard tool for the investigation of biomolecules. Simulations are performed of ever bigger systems using more realistic boundary conditions and better sampling due to longer sampling times. Recently, realistic simulations of systems as complex as transmembrane channels have become feasible. Simulations aid our understanding of biochemical processes and give a dynamic dimension to structural data; for example, the transformation of harmless prion protein into the disease-causing agent has been modeled.


SproutAngio: an open-source bioimage informatics tool for quantitative analysis of sprouting angiogenesis and lumen space.
Three-dimensional image analyses are required to improve the understanding of the regulation of blood vessel formation and heterogeneity. Currently, quantitation of 3D endothelial structures or vessel branches is often based on 2D projections of the images losing their volumetric information. Here, we developed SproutAngio, a Python-based open-source tool, for fully automated 3D segmentation and analysis of endothelial lumen space and sprout morphology. To test the SproutAngio, we produced a publicly available in vitro fibrin bead assay dataset with a gradually increasing VEGF-A concentration ( https://doi.org/10.5281/zenodo.7240927 ). We demonstrate that our automated segmentation and sprout morphology analysis, including sprout number, length, and nuclei number, outperform the widely used ImageJ plugin. We also show that SproutAngio allows a more detailed and automated analysis of the mouse retinal vasculature in comparison to the commonly used radial expansion measurement. In addition, we provide two novel methods for automated analysis of endothelial lumen space: (1) width measurement from tip, stalk and root segments of the sprouts and (2) paired nuclei distance analysis. We show that these automated methods provided important additional information on the endothelial cell organization in the sprouts. The pipelines and source code of SproutAngio are publicly available ( https://doi.org/10.5281/zenodo.7381732 ).


Parents who spent more hours in intensive care units with their low birthweight newborn infant did not achieve autonomous care faster.
We examined the correlation between how long it took the parents of very low birthweight infants, born weighing up to 1500 g, to provide different kinds of autonomous care in a neonatal intensive care unit (NICU). This prospective observational was conducted in the NICU of a Spanish hospital from 10 January 2020 to 3 May 2022. The unit had 11 beds single-family rooms and provided eight beds in an open bay room. The study examined breastfeeding, patient safety, participation in rounds, pain prevention and cleanliness. We studied 96 patients and their parents and there was no correlation between any type of care and the time it took parents to provide it autonomously. Parents in the single-family room cohort spent a median of 9.5 h per day between them in the NICU, while the parents in the open bay room spent 7.0 h with their infants (p = 0.03). However, parents in the single-family room group were able to recognise pain faster (p = 0.02). Parents in single-family rooms spent more time in the NICU and recognised pain faster but did not achieve autonomous care faster than parents in the open bay group.


Analytical methods and stability assessment of liquid yeast derived sucrase.
Two independent analytical methods for determining the activity and stability profile of liquid yeast derived sucrase (YS) were established and validated in order to conduct preliminary stability studies as a function of temperature. The methods included a hexokinase-based (HK) enzymatic assay for determining the formation of glucose upon hydrolysis of sucrose by YS, and a direct polarimetric procedure to quantitate YS hydrolysis of sucrose. Both assays were validated with respect to YS dilution, incubation time, sucrose or glucose concentration, linearity of response and within- and between-day variability. A preliminary stability study was conducted over a 24 week period with liquid YS samples stored at -20, 4, 30, 40 and 50 degrees C. Enzymatic activity was monitored as a function of time using both the HK and polarimetric assays. Liquid YS samples stored at -20, 4 and 30 degrees C retained 100% activity after 24 weeks storage, while the samples stored at 40 degrees C lost approximately 70% activity over the same storage period and samples stored at 50 degrees C lost approximately 95% activity after 12 weeks storage. The two methods of analysis gave consistent results over the course of the study.


A highly efficient gene-targeting system for Aspergillus parasiticus.
To establish a system that greatly increases the gene-targeting frequency in Aspergillus parasiticus. The ku70 gene, a gene of the nonhomologous end-joining (NHEJ) pathway, was replaced by the nitrate reductase gene (niaD) in A. parasiticus RHN1 that accumulates O-methylsterigmatocystin (OMST). The NHEJ-deficient strain, RHDeltaku70, produced conidia, sclerotia and OMST normally. It had identical sensitivity as RHN1 to the DNA-topoisomerase I complex inhibitor, camptothecin, and the DNA-damaging agent, melphalan. For targeting an aflatoxin biosynthetic pathway gene, adhA, partial restriction enzyme recognition sequences in its flanking regions were manipulated to create homologous ends for integration. Using a linearized DNA fragment that contained Aspergillus oryzae pyrithiamine resistance gene (ptr) marker the adhA-targeting frequency in RHDeltaku70 reached 96%. The homologous recombination pathway is primarily responsible for repair of DNA damages in A. parasiticus. The NHEJ-deficient RHDeltaku70, easy creation of homologous ends for integration, and the ptr-based selection form a highly efficient gene-targeting system. It substantially reduces the time and workload necessary to obtain knockout strains for functional studies. The developed system not only streamlines targeted gene replacement and disruption but also can be used to target specific chromosomal locations like promoters or intergenic regions. It will expedite the progresses in the functional genomic studies of A. parasiticus and Aspergilllus flavus.


Study of the relationship between psoriasis and the polymorphic site C677T of methylenetetrahydrofolate reductase.
In order to investigate 5,10-methylenetetrahydrofolate reductase (MTHFR)'s polymorphic changes in psoriasis vulgaris. We detected mutation of site C677V of MTHFR in 39 psoriastics by PCR-RFLP. Genotype frequencies of the psoriastics were C/C=20.15%, C/T=48.72% and T/T=30.77%; the allelic frequencies were C=0.4487 and T=0.5513. Homozygous mutant (TT) of the psoriastics was significantly different from the normal control group by X2 test. C677V mutant of MTHFR might be related with psoriasis.


Origins of smile and laughter: a preliminary study.
To present fundamental data, spontaneous smiles and spontaneous laughs (smiles accompanied by vocal sounds) were cross-sectionally observed in 10 newborn infants and longitudinally observed in six infants. Unilateral spontaneous smiles were more common than bilateral smiles in neonates, but by 2 months almost all spontaneous smiles were bilateral. All spontaneous laughs were bilateral. "Spontaneous smile" and "Spontaneous laugh" might be different behaviors from the beginning.


Pseudoaneurysm of the ascending thoracic aorta years after aortic valve replacement.
Aortic pseudoaneurysm (PSA) formation post aortic valve replacement is one of the rare and devastating complications if left untreated. Aortic PSA can occur few weeks or month after surgery. The spectrum of symptoms varies from dyspnea, wide pulse pressure, and chest pain. However, in rare cases, aortic root PSA could be asymptomatic. Aortic PSA mortality could be as high as 70%, if left untreated. Therefore, High clinical suspicion and prompt surgical intervention is imperative. In this case, the patient presented with dyspnea years after Bentall procedure, and imaging studies revealed para-aortic PSA that was treated surgically.


A randomized trial comparing heater probe plus thrombin with heater probe plus placebo for bleeding peptic ulcer.
This multicenter, double-blind, controlled trial compared the efficacy of combined endoscopic hemostatic treatment using the heater probe plus thrombin injection with that of the heater probe plus placebo injection as treatment for peptic ulcers with active bleeding or nonbleeding visible vessels. Efficacy was defined in terms of primary hemostasis, prevention of rebleeding, and need for urgent surgery. Two hundred forty-seven patients presenting with major peptic ulcer bleeding were randomized to heater probe plus thrombin or to heater probe plus placebo. The groups were well matched for all risk categories including age, endoscopic stigmata, shock, and severity of comorbid diseases. Endoscopic therapy was applied using the heater probe followed by injection of thrombin or placebo. Successful primary hemostasis was achieved in 97% of patients. Rebleeding developed in 19 (15%) of thrombin plus heater probe patients and 17 (15%) of placebo plus heater probe patients. Emergency surgery was necessary in 16 and 13 patients, respectively. Eight patients in the thrombin group had adverse events compared with 4 in the placebo group. Eight (6%) of thrombin plus heater probe patients and 14 (12%) of placebo plus heater probe patients died (P = 0.21). The combination of thrombin and the heater probe does not confer an additional benefit over heater probe and placebo as endoscopic treatment for bleeding peptic ulcer. Our trial does not support the use of this combination of hemostatic therapy.


At risk in two worlds: injury mortality among indigenous people in the US and Australia, 1990-92.
This paper outlines the commonalties and unique differences in injury experience among the indigenous people in the United States and Australia. Injury mortality rates among Indigenous people in the United States and Australia are approximately 2-3 times greater than rates for the non-Indigenous population in each country. Motor vehicle-related injuries accounted for one-third of the injury deaths for Native Americans and Australian Aboriginals. Suicide accounted for more deaths in Native Americans (15.5 per 100,000) than it did for Australian Aboriginals (11.1 per 100,000), whereas the injury death rate in Australian Aboriginals due to poisoning was almost twice that of Native Americans. Culturally appropriate interventions tailored to specific local settings and problems will be necessary to reduce injury mortality among Indigenous people.


Net power output and thermal efficiency data for single and double flash cycles of Cerro Prieto geothermal power plants.
The data presented below is the thermodynamic simulation and mathematical model development for the single and double flash cycles of Cerro Prieto geothermal power plants. For more insight into analysis thermodynamic, please see "thermodynamic simulation and mathematical model for single and double flash cycles of Cerro Prieto geothermal power plants" [1]. The datasets contained in this paper are thermodynamic simulations obtained in Aspen Hysys software, the data described represents the net power output and thermal efficiency for Cerro Prieto geothermal power plants, located in Mexicali, México. A single flash and double flash cycle have been selected for power generation at this facility. The single flash net power output and the thermal efficiency data includes eight main parameters: Well temperature (°C), Separator pressure (kPa), Condenser pressure (kPa), Turbine's power (kW), Phase Fraction, Mass Flow (kg/h), Energy input (kW) and Energy output (kW). Whereas the double flash net power output and the thermal efficiency data includes eight main parameters: Well temperature (°C), High-pressure separator (kPa), Low-pressure separator (kPa), Condenser pressure (kPa), Turbine's power (kW), Phase Fraction, Mass Flow (kg/h), Energy Input (kW) and Energy output (kW).


Magnetic resonance imaging as an adjunctive diagnostic aid in patient selection for endosseous implants: preliminary study.
The use of magnetic resonance imaging as an adjunctive aid to determine the amount of bone available and the anatomic limitations for the placement of endosseous dental implants is introduced. Advantages and disadvantages are discussed. The results suggest that magnetic resonance imaging can provide, without the need for a reformatting software program, adequate information concerning the amount of bone and anatomic limitations for placement of endosseous implants in the mandible and maxilla.


Canolol and its derivatives: A novel bioactive with antioxidant and anticancer properties.
The health and safety concerns associated with synthetic antioxidants has resulted in an urgent search for natural sources of antioxidants. Such antioxidants are not only convenient but may also have important therapeutic properties. Oilseed crops, for example, are rich in phenolic compounds some of which exhibit powerful antioxidant properties that have broad applications in both the food and feed industry. Often, the concentration of these phenolic compounds is affected by many processing conditions including temperature, pressure, pH, and extracting solvents. Hence it is important to optimize processing conditions to obtain maximum levels of those antioxidants with superior antioxidant activity. Oilseeds, such as canola and mustard, are rich sources of sinapates and kaempferol derivatives. When subjected to different processing conditions, including pressurized temperature, sinapates are converted to vinyl phenol derivatives, of which the major one is canolol. This chapter will focus on the nature of canolol and its applications in food and medicine.


Increasing extracellular calcium improves conduction in partially demyelinated rat fimbria in vitro.
1. We have tested the effect of changed concentrations of Ca2+ upon demyelination-induced conduction block in rat fimbria in vitro. 2. In a rat fimbria containing a region of acute focal demyelination induced by in vitro microinjection of lysophosphatidyl chloride (LPC) 6 days earlier, raising bath [Ca2+] to 4.4 mM improved conduction through the damaged area, while lowering it to 0.25 mM depressed conduction. 3. A contrary effect, consistent with the well-known effects of extracellular calcium ion on voltage-sensitive channels, was seen in non-lesioned preparations.


The developmental response of flesh flies (Diptera: Sarcophagidae) to tropical seasons : Variation in generation time and diapause in east africa.
In a tropical environment near the equator in Nairobi, Kenya, flesh fly development is nearly continuous throughout the year with only a few individuals being channeled into pupal diapause during the coldest months. Two species reared in a field cage completed 7 generations/year. Generation time for nondiapause flies varied from 41 to 62 days.


Dopamine-resistant hypotension and severe retinopathy of prematurity.
To examine the relationship between the cause or severity of hypotension and the development of severe ROP (sROP) (≥stage 3 or stage 2 with plus disease in zone I or II). Infants (<28 weeks' gestation, n = 242) were observed for hypotension and treated with a standardized hypotension-treatment protocol. Hypotension was classified as resulting from one of the following causes: (1) culture-positive infection and/or necrotizing enterocolitis; (2) patent ductus arteriosus ligation; or (3) "idiopathic" (no cause identified other than prematurity), and as being either dopamine responsive or dopamine resistant. Cortisol levels were measured for infants with dopamine-resistant hypotension. Eye examinations were performed until the retinopathy of prematurity resolved or the vasculature matured. Multivariable logistic regression analysis was performed to determine the relationship between the cause/severity of hypotension and sROP. Overall, 66% of infants developed hypotension (41% were dopamine responsive and 25% were dopamine resistant). sROP developed in 19% of infants. "Idiopathic" dopamine-resistant hypotension was the only cause significantly related to sROP. Of the infants with dopamine-resistant hypotension, 66% had low serum cortisol (≤10 μg/dL). Low cortisol, in the presence of dopamine-resistant hypotension, was significantly associated with sROP and accounted for the relationship between "idiopathic" hypotension and sROP. When low cortisol was included in statistical models, other known risk factors, such as immature gestation, were no longer significantly related to sROP. Low cortisol, in the presence of dopamine-resistant hypotension, has the greatest magnitude of association with sROP.


Preoperative Volume-Based PET Parameter, MTV2.5, as a Potential Surrogate Marker for Tumor Biology and Recurrence in Resected Pancreatic Cancer.
This study aims to evaluate the role of volume-based positron emission tomography parameters as potential surrogate markers for tumor recurrence in resected pancreatic cancer. Between January 2008 and October 2012, medical records of patients who underwent surgical resection for pancreatic ductal adenocarcinoma and completed ¹⁸F-fluorodeoxyglucose positron emission tomography/CT as a part of preoperative staging work-up were retrospectively reviewed. Not only clinicopathologic variables but also positron emission tomography parameters such as SUVmax, MTV2.5 (metabolic tumor volume), and TLG (total lesion glycolysis) were obtained. Twenty-six patients were women and 31 were men with a mean age of 62.9 ± 9.1 years. All patients were preoperatively determined to resectable pancreatic cancer except 1 case with borderline resectability. R0 resection was achieved in all patients and 45 patients (78.9%) received postoperative adjuvant chemotherapy with or without radiation therapy. Median overall disease-free survival was 12.8 months with a median overall disease-specific survival of 25.1 months. SUVmax did not correlate with radiologic tumor size (P = 0.501); however, MTV2.5 (P = 0.001) and TLG (P = 0.009) were significantly associated with radiologic tumor size. In addition, MTV2.5 (P < 0.001) and TLG (P < 0.001) were significantly correlated with a tumor differentiation. There were no significant differences in TLG and SUVmax according to lymph node ratio; only MTV2.5 was related to lymph node ratio with marginal significance (P = 0.055). In multivariate analysis, lymph node ratio (Exp [β] = 2.425, P = 0.025) and MTV2.5 (Exp[β] = 2.273, P = 0.034) were identified as independent predictors of tumor recurrence following margin-negative resection. Even after tumor size-matched analysis, MTV2.5 was still identified as significant prognostic factor in resected pancreatic cancer (P < 0.05). However, preoperative neoadjuvant treatment attenuated adverse oncologic impact of high preoperative MTV2.5 (P = 0.210). Preoperatively determined volume-based PET parameter, MTV2.5, can potentially be used as a surrogate marker to estimate tumor biology and tumor recurrence. Individual treatment strategies for pancreatic cancer can be suggested based on patients' preoperative MTV2.5.


Determination of lead in blood by graphite furnace atomic absorption spectrometry--a critique.
Graphite furnace atomic absorption spectrometry (GFAAS) is increasingly becoming the method of choice for the determination of Pb in blood. The major GFAAS methods that have been published to date include: (i) direct introduction of the sample into the furnace; (ii) dilution with water, Triton X-100 or acid; (iii) deproteinization with nitric acid; (iv) matrix modification; and (v) solvent extraction. This review focuses on the difficulties associated with each of these methods, and highlights recent attempts to overcome matrix interferences and improve the accuracy and precision of Pb determination in blood using modern furnace technology, especially the stabilized temperature platform furnace.


Childhood maltreatment and lead levels in middle adulthood: A prospective examination of the roles of individual socio-economic and neighborhood characteristics.
Lead is a common environmental hazard because of its past use as an additive to gasoline and household paint. Some evidence suggests that children with histories of child abuse and neglect are at elevated risk for residence in communities and households with less desirable characteristics and high levels of exposure to environmental hazards and toxins. To understand whether childhood maltreatment leads to higher levels of household dust lead and blood lead in adulthood and the extent to which characteristics of a person's physical environment or individual level socio-economic status (SES) (based on unemployment, poverty, and receipt of public assistance) contribute to understanding the relationship. A large prospective cohort design study in which abused and neglected children (ages 0-11) were matched with non-maltreated children and assessed in adulthood. Objective and subjective neighborhood characteristics were assessed at approximate age 40 and household dust lead (cleaned and less often cleaned) and blood lead levels were measured at age 41. Blood was collected through venipuncture by a registered nurse as part of a medical status exam. Childhood maltreatment predicted higher levels of dust lead in less often cleaned household places, residence in worse neighborhoods defined by objective (census tract data) and subjective (reports of physical disorder and lack of social cohesion and control), and higher levels of poverty, receiving public assistance, and unemployment. Only objective neighborhood characteristics mediated the relationship between childhood maltreatment and dust lead level in adulthood. There were also significant paths from objective neighborhood disadvantage and individual level SES to higher levels of blood lead. Thirty years after their childhood experiences, individuals with documented histories of childhood maltreatment are at higher risk for living in environments as adults with elevated lead levels that may impact other aspects of their lives and compromise their health.


Vascular endothelial growth factor is an in vivo survival factor for tumor endothelium in a murine model of colorectal carcinoma liver metastases.
Recent studies have suggested that vascular endothelial growth factor (VEGF), in addition to its proangiogenic properties, also functions as a survival factor for endothelial cells. The authors hypothesized that inhibition of VEGF activity by blockade of VEGF receptor-2 (R-2) function prevents angiogenesis and decreases tumor growth in colon carcinoma liver metastases. Spleens of mice were injected with human colon carcinoma cells producing liver metastases. After 7 days of tumor growth, groups of mice received either antibody to VEGFR-2 (DC101) or phosphate-buffered saline (control). In a follow-up experiment, a similar treatment regimen was followed except that mice were sacrificed at 1-week intervals to assess the time course of endothelial cell and tumor cell apoptosis. After 21 days of therapy, the authors observed a significant decrease in vessel counts in liver metastases from human colon carcinoma in nude mice after therapy with VEGFR-2 antibody. Tumor cell apoptosis was increased significantly in the tumors of mice receiving DC101. Temporal studies with immunofluorescent double staining for the microvasculature and apoptotic cells revealed an increase in endothelial cell apoptosis that preceded an increase in tumor cell apoptosis. In vitro, treatment of human umbilical vein endothelial cells with antibody to VEGFR-2 produced a > 2.5-fold increase in endothelial cell apoptosis. Therapy targeting the VEGFR-2 inhibited tumor growth in a murine model of colon carcinoma liver metastasis. Surprisingly, this therapy did not only inhibit angiogenesis but also led to endothelial cell death. These findings suggest that VEGF, via VEGFR-2 signaling, functions as a survival factor for tumor endothelial cells in liver metastases from colon carcinoma.


Use of thiol-ene click chemistry to modify mechanical and thermal properties of polyhydroxyalkanoates (PHAs).
In order to diversify the number of applications for poly[(R)-3-hydroxyalkanoates] (PHAs), methods must be developed to alter their physical properties so they are not limited to aliphatic polyesters. Recently we developed Escherichia coli LSBJ as a living biocatalyst with the ability to control the repeating unit composition of PHA polymers, including the ability to incorporate unsaturated repeating units into the PHA polymer at specific ratios. The incorporation of repeating units with terminal alkenes in the side chain of the polymer allowed for the production of random PHA copolymers with defined repeating unit ratios that can be chemically modified for the purpose of tailoring the physical properties of these materials beyond what are available in current PHAs. In this study, unsaturated PHA copolymers were chemically modified via thiol-ene click chemistry to contain an assortment of new functional groups, and the mechanical and thermal properties of these materials were measured. Results showed that cross-linking the copolymer resulted in a unique combination of improved strength and pliability and that the addition of polar functional groups increased the tensile strength, Young's modulus, and hydrophilic profile of the materials. This work demonstrates that unsaturated PHAs can be chemically modified to extend their physical properties to distinguish them from currently available PHA polymers.


Stable C &N isotopes in 2100 Year-B.P. human bone collagen indicate rare dietary dominance of C4 plants in NE-Italy.
C4 plants (e.g. maize, millet), part of our current diet, are only endemic of reduced areas in South-Europe due to their need of warm climates. Since the first vestiges of agriculture in Europe remains of C4 plants were recorded but their overall proportion in the human diet remains unknown. Therefore, isotopic (δ13C and δ15N) composition of bone collagen from the skeletal remains (human and animals) of a Celtic population, Cenomani Gauls, from Verona (3rd to 1st century BC) in the NE Italy provide a new perspective on this matter. The δ13C collagen values of 90 human skeletal individuals range between -20.2‰ and -9.7‰ (V-PDB) with a mean value of -15.3‰. As present day C4 plants have δ13C values around -11‰, which is equivalent to -9.5‰ for samples of preindustrial age, the less negative δ13C values in these individuals indicate a diet dominated by C4 plants. This palaeodietary study indicates that some European populations predominantly consumed cultivated C4 plants 2100 year B.P. This is supported by the paleobotanical records and ancient Roman sources (e.g. Pliny the Elder), which indicate that millet was a staple food in South-Europe.


Antibacterial Activities of Endophytic Fungi Isolated from Mentha cordifolia Leaves and Their Volatile Constituents.
A total of 17 endophytic fungal isolates were obtained from the leaves of Mentha cordifolia Opiz (Lamiaceae). Seven isolates were identified to the level of genus by using taxonomically relevant morphological traits. Colletotrichum and Phoinopsis species were dominant among these strains. All strains were separated from M cordifolia leaf for the first time. The ethyl acetate extracts of all endophytic fungi were tested for antibacterial activity against Salmonella typhimurium TISTR 1166 and Pseudomonas aeruginosa TISTR781. Most endophytes exhibited antibacterial activity. Ustilago sp. MFLUCC15-1024 presented the highest inhibition zone diameter with a MIC of 31.25 μg/mL against the tesfed pathogens. The chemical composition of the ethyl acetate extract of this strain was investigated using gas chromatography-mass spectrometry. Twenty-one components were identified. 2-Phenylethanol (38.7%), E-ligustilide (12.4%), a-eudesmol (10.2%), β-vetivone (4.6%), β-ylangene (3.7%) and verbanol (3.4%) were the major components of the extract. The strong antibacterial activity of Ustilago sp. MFLUCC15-1024 ethyl acetate extract may be attributed to the presence of a high concentration of bioactive compounds including phenyl ethyl alcohol, E-ligustilide and a-eudesmol. The results indicate that there is high diversity of endophytic fungi in M cordifolia leaf, and that Ustilago sp. MFLUCC l5-1024 strain could be an excellent resource of natural antibacterial compounds.


Effect of season on weaned piglet mortality during transport greater than 8 h under Canadian conditions.
North American swine producers commonly transport piglets away from sow farms at weaning. However, limited information on factors associated with piglet mortality during these transports is available. The objectives of this study were to identify transport characteristics that were associated with the occurrence of in-transit mortality (≥1 piglet found dead on arrival) and/or associated with increased rates of in-transit mortality using records of weaned piglet transport voluntarily provided by Canadian swine companies. Following cleaning and validation, records of 810 long duration (>8 h to <28 h) weaned piglet (min.: 4.2, max.: 7.7 kg) transports conducted between 2016 and 2017 by four companies were available to investigate risk factors for the occurrence of in-transit mortality. Transports originated in Ontario, Saskatchewan, or Alberta and 30% of transports had one or more mortality events recorded. Season of transport was significant in the final logistic regression model; the odds of a transport having mortality occur was greater during the winter (December, January, February) compared to the spring (March, April, May) (OR=1.8; 95% CI: 1.13-2.96; P = 0.013), summer (June, July, August) (OR= 2.1; 95% CI: 1.28-3.34; P = 0.003) and fall (September, October, November) (OR=2.2; 95% CI: 1.36-3.62; P = 0.001), with no differences observed between the other seasons. Additionally, records from 755 long duration weaned piglet (min.: 4.2, max.: 7.9 kg) transports conducted between 2014 and 2017 by a single company was used to identify risk factors for increased rates of in-transit mortality. Transports originated in Saskatchewan or Alberta and 44.9% of transports had one or more mortality events recorded with in-transit mortality rates ranging from 0.00% to 6.16%. Season of transport was again significant in the final negative binomial regression model. The rate of piglet death in-transit was increased in all seasons compared to the summer with winter transport having the highest predicted rate of in-transit mortality. Transports conducted during the winter had a rate of in-transit mortality nearly five times greater compared to transports conducted during the summer (IRR= 4.94; 95% CI: 3.11-7.87; P = 0.000) and approximately three times greater compared to transports conducted during the fall (IRR=2.7; 95% CI: 1.73-4.30; P = 0.000) and spring (IRR=3.1; 95% CI: 1.96-4.99; P = 0.000). These results suggest that winter transport in Western Canada is an area of opportunity to reduce in-transit mortality during long duration weaned piglet transport. Research investigating transport practices that may mitigate the effects of extreme cold (e.g., space allowance, bedding provision) would be useful for informing specific recommendations for this age group.


Topical application with conjugated linoleic acid ameliorates 2, 4-dinitrofluorobenzene-induced atopic dermatitis-like lesions in BALB/c mice.
Atopic dermatitis (AD) is a multifactorial chronic inflammatory skin disease characterized by skin barrier dysfunction, eczematous lesions, pruritus, and abnormal immune responses. In this study, we assessed the therapeutic effect of topical applied conjugated linoleic acid (CLA) on a murine AD model that was developed by repetitive applications of 2, 4-dinitrofluorobenzene (DNFB). 2% or 5% CLA could markedly ameliorate AD-like skin lesions, scratching behaviour and skin inflammation as evidenced by the reduced inflammatory blood cells, IgE and Th2-related cytokine levels, and the infiltration of mast cells and inflammatory cells to the dermal tissues. Moreover, topical application with CLA modulated skin barrier repair including maintaining a balanced skin pH and increasing skin hydration, partially mediated by upregulating skin barrier-related protein, filaggrin (FLG). In addition, topical CLA significantly dose-dependently inhibited pro-inflammatory cytokines including interleukin (IL)-6, IL-1β, tumour necrosis factor (TNF)-α and pro-inflammatory enzyme expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in inflamed mice skin. Its anti-inflammatory effect was associated with the inhibition of DNFB-stimulated IκBα and NF-κB p65 phosphorylation in mouse skin. Taken together, our results suggest that locally applied CLA exerts potentially protective effects against AD lesional skin at least in part, due to regulation of skin barrier function and inflammatory response.


Planar thermal Hall effect of topological bosons in the Kitaev magnet α-RuCl3.
The honeycomb magnet α-RuCl3 has attracted considerable interest because it is proximate to the Kitaev Hamiltonian whose excitations are Majoranas and vortices. The thermal Hall conductivity κxy of Majorana fermions is predicted to be half-quantized. Half-quantization of κxy/T (T, temperature) was recently reported, but this observation has proven difficult to reproduce. Here, we report detailed measurements of κxy on α-RuCl3 with the magnetic field B ∥ a (zigzag axis). In our experiment, κxy/T is observed to be strongly temperature dependent between 0.5 and 10 K. We show that its temperature profile matches the distinct form expected for topological bosonic modes in a Chern-insulator-like model. Our analysis yields magnon band energies in agreement with spectroscopic experiments. At high B, the spin excitations evolve into magnon-like modes with a Chern number of ~1. The bosonic character is incompatible with half-quantization of κxy/T.


POSITION OF IN-THE-BAG POSTERIOR CHAMBER INTRAOCULAR LENSES RELATIVE TO THE LIMBUS: Applications to Scleral-Sutured Lenses.
To characterize the true position of in-the-bag intraocular lenses (IOLs) relative to the limbus using ultrasound biomicroscopy and estimate scleral-sutured IOL positioning. This prospective single-center study included 70 eyes of 41 patients with in-the-bag posterior chamber IOLs. Four vertical ultrasound biomicroscopy captures were performed in each eye in the superior, inferior, nasal, and temporal quadrants. Postoperative biometric data were collected. The primary outcome was the vertical distance of the in-the-bag IOL from the sclerocorneal limbus. Secondary outcomes included anterior shift and refractive change of a theoretical scleral-sutured IOL using sclerotomies at 2.5 mm and 3 mm posterior to the limbus. A total of 265 ultrasound biomicroscopy images were analyzed, including 64 superior, 69 inferior, 66 nasal, and 66 temporal. The true in-the-bag IOL position measured as distance posterior to the sclerocorneal limbus was 4.23 ± 0.56 mm superiorly, 4.22 ± 0.46 mm inferiorly, 3.95 ± 0.48 mm nasally, and 3.86 ± 0.52 mm temporally. The anterior shift of a theoretical scleral-sutured IOL was 0.60 mm for a 3-mm sclerotomy and 0.93 mm for a 2.5-mm sclerotomy, resulting in a theoretical myopic shift of 0.45 diopter (D) and 0.79 D, respectively, assuming a 15-D IOL. Larger biometric measurements correlated with a more posterior in-the-bag position. True in-the-bag IOL position was found to be more posterior than estimates of scleral-sutured IOLs. Additional corrections in scleral-sutured IOL calculations may improve refractive outcomes.


A 45-year follow-up study of adolescent schizophrenia. Part II: Age of disease onset, type of onset of the disorder and presence of developmental burden in the context of disease course and long-term social functioning of patients.
Research on predictors of adolescent schizophrenia, especially that based on long-term follow-up studies, is rare in the literature. In our analysis, we examine the relationships of the age of disease onset, type of onset of the disorder and the presence of developmental burden with clinical and social indicators of the disease course. A total of 69 patients hospitalized at an average age of 16 years (time point 0) due to schizophrenia (retrospectively re-diagnosed according to ICD-10 criteria) and re-examined 5 years later (time point 1 - personal examination of 41 individuals) were re-evaluated for clinical and social parameters 45 years after initial hospitalization (time point 2 - personal examination of 21 individuals). Besides personal examination, other methods of data collection were also used, including hospital queries. The hidden type of onset of schizophrenia revealed numerous and various correlations with both the symptomatic picture and the clinical course of schizophrenia, and with distant social functioning of the subjects, translating into a classical Bleuler symptomatic picture, weaker response to treatment, and worse functioning in personal and professional life. The presence of significant separations in childhood proved to be a factor conducive to insight and less intense psychopathology in the distant course of schizophrenia. The family burden of schizophrenia correlated with the catatonic picture in the future and with more hospitalizations and earlier death. The hidden type of onset of schizophrenia is the most important predictor of its later course.


Toward a biophysical understanding of the salt stress response of individual plant cells.
We present and explore a kinetic model of ion transport across and between the membranes of an isolated plant cell with an emphasis on the cell's response to salt (Na(+)) stress. The vacuole, cytoplasm and apoplast are treated as concentric regions separated by tonoplast and plasma membranes. The model includes the transport of Na(+), K(+), Cl(-) and H(+) across both membranes via primary active proton pumps, secondary active antiporters and symporters, as well as passive ion channels. In addition, water transport is included, allowing us to investigate both the osmotic and ionic components of salt stress. The model's predictions of steady state and transient cytosolic pH and Na(+) concentrations were found to be quantitatively comparable to measured experimental values. Through an extensive simulation study we have identified and characterized scenarios in which individual transport processes (H(+) pumps, Na(+)/H(+) antiporters and channels involved in the transport of Na(+)) and their combinations have major effects on the level of Na(+) in each of the cell compartments. This systematic study emulates the effects of overexpressing and inhibiting transporter genes by genetic modification and hence we have compared our simulations with observations from experiments conducted on transgenic plants. The simulations suggest that overexpressing tonoplast Na(+)/H(+) antiporter genes and tonoplast H(+) pump genes lead to an increase in the storage of Na(+) in the vacuole (helping the cell to maintain water uptake under salt stress), with only a transient influence on the cytoplasmic Na(+) concentration. The model predicts effects of varying the expression of transporter genes (individually or in combination) which have yet to be investigated in experiments. For example, our findings indicate that simultaneously overexpressing plasma membrane and tonoplast Na(+)/H(+) antiporter genes would lead to improvements in both ionic and osmotic stress tolerance. The results demonstrate the importance of simultaneously modelling the transport of Na(+) across both the tonoplast and plasma membrane, a task not undertaken previously.


Systemic adverse events following intraarticular corticosteroid injections for the treatment of juvenile idiopathic arthritis: two patients with dermatologic adverse events and review of the literature.
Intraarticular corticosteroid injections are an important part of the treatment for juvenile idiopathic arthritis due to the ability to achieve high concentration of the medication in the affected joint, while minimizing potential systemic adverse effects. There may be some systemic absorption of corticosteroids resulting in systemic adverse events. Our aim was to demonstrate the potential of adverse events due to the systemic absorption of intraarticular corticosteroids through presentation of 2 case reports, a review of our practices and a systematic review of the literature. We reviewed the intraarticular injections performed at our 3 centers in 2010 and 2011 for the prevalence of systemic adverse events. We searched PubMed for articles in English on systemic adverse effects of intraarticular corticosteroid injection in children, using numerous keywords, as well as review articles and textbooks on juvenile rheumatoid/idiopathic arthritis up to and including December 2011. We report the development of severe acneiform rashes in 2 adolescents with juvenile idiopathic arthritis following bilateral knee intraarticular injections of triamcinolone hexacetonide. The prevalence of systemic adverse events at our centers was in 4/179 (2.2%) injections, the 2 cases reported above, 1 case of insomnia in a 2-year-old child and 1 case of cushingoid features following injection of 21 joints. While in the literature there are some reports of general "Cushing-like" appearances, there are only very few reports of specific skin and other organ/system adverse effects resulting from systemic corticosteroid absorption. It is important to recognize the potential of rare adverse events that are attributable to the systemic absorption of intraarticular corticosteroids in children.


Tetany by transfusion of small volume of blood: a rare case report.
A requisition for two units of packed red blood cells was received for a 54 year female, known case of genitourinary carcinoma. After transfusion of approximately 15-20 ml of blood, a call was received from resident in charge of radiotherapy ward stating that patient had clenching of hands along with circumoral tingling and paresthesias in her limbs. Her investigations showed decreased serum potassium and calcium levels but serum magnesium levels were not available. Multiple electrolyte disturbances probably precipitated tetany even by small volume of blood transfusion. We therefore recommend careful monitoring of electrolytes, including magnesium, before starting blood transfusion.


What happens when drivers face hazards on the road?
The current study aims to obtain knowledge about the nature of the processes involved in Hazard Perception, using measurement techniques to separate and independently quantify these suspected sub-processes: Sensation, Situation Awareness (recognition, location and projection) and decision-making. It applies Signal Detection Theory analysis to Hazard Perception and Prediction Tasks. To enable the calculation of Signal Detection Theory parameters, video-recorded hazardous vs. quasi-hazardous situations were presented to the participants. In the hazardous situations it is necessary to perform an evasive action, for instance, braking or swerving abruptly, while the quasi-hazardous situations do not require the driver to make any evasive manoeuvre, merely to carry on driving at the same speed and following the same trajectory. A first Multiple Choice Hazard Perception and Prediction test was created to measure participants' performance in a What Happens Next? Task. The sample comprised 143 participants, 47 females and 94 males. Groups of non-offender drivers (learner, novice and experienced) and offender drivers (novice and experienced) were recruited. The Multiple Choice Hazard Perception and Prediction test succeeded in finding differences between drivers according to their driving experience. In fact, differences exist with regard to the level of hazard discrimination (d' prime) by drivers with different experience (learner, novice and experienced drivers) and profile (offenders and non-offenders) and these differences emerge from Signal Detection Theory analysis. In addition, it was found that experienced drivers show higher Situation Awareness than learner or novice drivers. On the other hand, although offenders do worse than non-offenders on the hazard identification question, they do just as well when their Situation Awareness is probed (in fact, they are as aware as non-offenders of what the obstacles on the road are, where they are and what will happen next). Nevertheless, when considering the answers participants provided about their degree of cautiousness, experienced drivers were more cautious than novice drivers, and non-offender drivers were more cautious than offender drivers. That is, a greater number of experienced and non-offender drivers chose the answer "I would make an evasive manoeuvre such as braking gradually".


Complications of phacoemulsification.
Charles Kelman performed the first phacoemulsification operation in 1967, but it was not until 1971 that the technique had been sufficiently refined to allow its use by others. Now over 2,000 surgeons have been trained in the technique, and more than 100,000 cases have been performed. However, extended follow-up in any given series has been difficult because of the wide geographic distribution of patients, and interpretation is hampered by the frequent insertion of intraocular lenses in these patients. The present series attempts to carefully document operative and postoperative complications encountered in a consecutive series of patients whose senile cataracts were treated by phacoemulsification.


Use of fumaric acid as a feed additive in quail's nutrition: its effect on growth rate, carcass, nutrient digestibility, digestive enzymes, blood metabolites, and intestinal microbiota.
To investigate the effects of dietary fumaric acid (FUA) on performance, carcasses, nutrient digestibility, blood metabolites, digestive enzymes, and cecal microbiota in Japanese quail chicks. Three hundred unsexed Japanese quail (1-wk-old) were randomly assigned to 5 groups. Supplementation of FUA in the diet of Japanese quail chicks exhibited a significant improvement in growth performance through the different experimental periods studied compared with those receiving unsupplemented one. The digestibility of crude protein (CP) and metabolizable energy (ME) were improved with 10 and 15 g/kg FUA, respectively. Apart from lipase enzyme, birds fed 5 and 15 g/kg FUA recorded higher activity of amylase. There were no significant changes among experimental groups on the relative weights of carcass, gizzard, heart, and dressing. Dietary supplementation of FUA at different levels (P> 0.05) increased total protein (TP) and globulin (GLB) concentrations and A/G % compared with control group. A significant (P < 0.01) decrease in plasma low density lipoprotein (LDL) and total cholesterol (TC) levels and increase in high density lipoprotein (HDL) concentrations were observed in chicks fed with FUA containing diets. Immunoglobulin G (IgG) (P = 0.0026) and M (IgM) (P = 0.0007) levels were greater in groups treated with either 10 or 15 g FUA/kg diet. A significant increase in plasma Ca concentration was noticed in chicks received 15 g FUA/ kg compared with the other groups. Quail chicks received diets containing FUA at different levels exhibited reduced cecal count of coliform, E. coli, and Salmonella as compared with control group. In conclusion, supplementation of fumaric acid (especially 15 g/kg diet) in quail chick diets improved their growth, digestibility of nutrients, immune response, antioxidant status, digestive enzyme, and intestinal health.


[Results after fracture of the os calcis (author's transl)].
A double study over a period of 40 years was undertaken--from 1935 to 1954 in Berlin and from 1955 to 1976 in Salzgitter--including a total of 393 fractures of the os calcis. The results of different types of treatment are presented. It is the type and severity of the fractures, not the way of treatment which determines the outcome. 161 patients have been followed clinically and radiologically at least 5 years after fracture of the os calcis. Third degree fractures were objectively and subjectively less favourable regardless of therapy. Active surgical treatment should be post-poned and consist in fusion of the subtalar joint.


Medical and Surgical Advancements in the Management of Cystic Fibrosis Chronic Rhinosinusitis.
The purpose of this review is to provide otolaryngologists with the most up-to-date advancements in both the medical and surgical management of CF-related sinus disease. Recent studies have supported more aggressive CRS management, often with a combination of both medical and surgical therapies. Comprehensive treatment strategies have been shown to reduce hospital admissions secondary to pulmonary exacerbations in addition to improving CRS symptoms. Still, current management strategies are lacking in both high-level evidence and standardized guidelines. The unified airway model describes the bi-directional relationship between the upper and lower airways as a single functional unit and suggests that CRS may play a pivotal role in both the development and progression of lower airway disease. Current strategies for CF CRS focus primarily on amelioration of symptoms with antibiotics, nasal saline and/or topical medicated irrigations, and surgery. However, there are no definitive management guidelines and there remains a persistent need for additional studies. Nevertheless, otolaryngologists have a significant role in the overall management of CF, which requires a multi-disciplinary approach and a combination of both surgical and medical interventions for optimal outcomes of airway disease. Here we present a review of currently available literature and summarize medical and surgical therapies best suited for the management of CF-related sinus disease.


Pattern of extremity gunshot injuries seen in Lagos University Teaching Hospital, Lagos, Nigeria.
The rising incidence of gunshot injuries (GSI) remains one of the leading causes of death, long hospitalization and economic losses worldwide. This study was undertaken due to rising incidence of civilian GSI in Lagos, Nigeria. To determine the epidemiological characteristics of extremity gunshot injuries in Lagos, Nigeria. This three year crossectional study of extremity gunshot injuries was conducted at the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria between 1st January 2000 and 31st December 2002. Two hundred and fifty four patients with extremity gunshot injuries presented with 240 analyzed. Those brought in dead (BID) were excluded from the study. Ninety-five percent of the patients were males. One hundred and twenty six patients (52.5%) were in the 21-40 years age group. The patients were shot mainly (75%) at night and mostly (80%) by armed robbers. Shot guns were used in shooting 47.5% of patients. The study showed that young adult males were more affected by GSI. Most of the shootings occurred at night by armed robbers.


Modification of human hemoglobin by covalent association with soluble dextran.
Stroma-free Hb solutions present some drawbacks when used as erythrocyte substitutes, mainly because the protein has a short in vivo half-life, due to its small hydrodynamic volume. Covalent coupling of oxyHb with dialdehyde-dextran (Mw congruent to 40 000; Mn congruent to 25 000) leads to adducts whose properties depend upon the pH of the condensations. At pH less than 9.6, many labile imine linkages are formed and the conjugates have a high molecular weight at the end of the reaction. In contrast, the final products obtained as pH increases from 9.6 to 10 contain a low-molecular-weight adduct in an increasing ratio; in this case the bond between dextran and Hb is stable and this stability is assumed to result from the rearrangement of a specific imine linkage formed at an NH2 site of Hb, into a ketoamine group (Amadori rearrangement). Dextran-Hb conjugates have oxygen-binding properties characterized by increased oxygen affinity, and decreased subunit cooperativity and alkaline Bohr effect, relative to unconjugated Hb. These differences become less as the time of condensation reaction decreases and seem to be due to modification of amine groups involved in the salt bridges that stabilize the deoxy form of the protein. Taking into account their oxygen-binding characteristics, the low-molecular-weight conjugates can be regarded as potential erythrocyte substitutes.


Nanoemulsion: an advanced mode of drug delivery system.
An advanced mode of drug delivery system has been developed to overcome the major drawbacks associated with conventional drug delivery systems. This review gives a detailed idea about a nanoemulsion system. Nanoemulsions are nano-sized emulsions, which are manufactured for improving the delivery of active pharmaceutical ingredients. These are the thermodynamically stable isotropic system in which two immiscible liquids are mixed to form a single phase by means of an emulsifying agent, i.e., surfactant and co-surfactant. The droplet size of nanoemulsion falls typically in the range 20-200 nm. The main difference between emulsion and nanoemulsion lies in the size and shape of particles dispersed in the continuous phase. In this review, the attention is focused to give a basic idea about its formulation, method of preparation, characterization techniques, evaluation parameters, and various applications of nanoemulsion.


Automated calibration and in-line measurement of product quality during therapeutic monoclonal antibody purification using Raman spectroscopy.
Current manufacturing and development processes for therapeutic monoclonal antibodies demand increasing volumes of analytical testing for both real-time process controls and high-throughput process development. The feasibility of using Raman spectroscopy as an in-line product quality measuring tool has been recently demonstrated and promises to relieve this analytical bottleneck. Here, we resolve time-consuming calibration process that requires fractionation and preparative experiments covering variations of product quality attributes (PQAs) by engineering an automation system capable of collecting Raman spectra on the order of hundreds of calibration points from two to three stock seed solutions differing in protein concentration and aggregate level using controlled mixing. We used this automated system to calibrate multi-PQA models that accurately measured product concentration and aggregation every 9.3 s using an in-line flow-cell. We demonstrate the application of a nonlinear calibration model for monitoring product quality in real-time during a biopharmaceutical purification process intended for clinical and commercial manufacturing. These results demonstrate potential feasibility to implement quality monitoring during GGMP manufacturing as well as to increase chemistry, manufacturing, and controls understanding during process development, ultimately leading to more robust and controlled manufacturing processes.


Inflammatory markers and risk of hip fracture in older white women: the study of osteoporotic fractures.
Hip fractures are the most devastating consequence of osteoporosis and impact 1 in 6 white women leading to a two- to threefold increased mortality risk in the first year. Despite evidence of inflammatory markers in the pathogenesis of osteoporosis, few studies have examined their effect on hip fracture. To determine if high levels of inflammation increase hip fracture risk and to explore mediation pathways, a case-cohort design nested in a cohort of 4709 white women from the Study of Osteoporotic Fractures was used. A random sample of 1171 women was selected as the subcohort (mean age 80.1 ± 4.2 years) plus the first 300 women with incident hip fracture. Inflammatory markers interleukin-6 (IL-6) and soluble receptors (SR) for IL-6 (IL-6 SR) and tumor necrosis factor (TNF SR1 and TNF SR2) were measured, and participants were followed for a median (interquartile range) of 6.3 (3.7, 6.9) years. In multivariable models, the hazard ratio (HR) of hip fracture for women in the highest inflammatory marker level (quartile 4) was 1.64 (95% confidence interval [CI], 1.09-2.48, p trend = 0.03) for IL-6 and 2.05 (95% CI, 1.35-3.12, p trend <0.01) for TNF SR1 when compared with women in the lowest level (quartile 1). Among women with 2 and 3-4 inflammatory markers in the highest quartile, the HR of hip fracture was 1.51 (95% CI, 1.07-2.14) and 1.42 (95% CI, 0.87-2.31) compared with women with zero to one marker(s) in the highest quartile (p trend = 0.03). After individually adjusting for seven potential mediators, cystatin-C (a biomarker of renal function) and bone mineral density (BMD) attenuated HRs among women with the highest inflammatory burden by 64% and 50%, respectively, suggesting a potential mediating role. Older white women with high inflammatory burden are at increased risk of hip fracture in part due to poor renal function and low BMD.


Residential Mobility and Lung Cancer Risk: Data-Driven Exploration Using Internet Sources.
Frequent relocation has been linked to health decline, particularly with respect to emotional and psychological wellbeing. In this paper we investigate whether there is an association between frequent relocation and lung cancer risk. For the initial investigation we used web crawling and tailored text mining to collect cancer and control subjects from online data sources. One data source includes online obituaries. The second data source includes augmented LinkedIn profiles. For each data source, the subjects' spatiotemporal history is reconstructed from the available information provided in the obituaries and from the education and work experience provided in the LinkedIn profiles. The study shows that lung cancer subjects have higher mobility frequency than the control group. This trend is consistent for both data sources.


Intra-abdominal adhesions: cellular mechanisms and strategies for prevention.
Postoperative intra-abdominal adhesions represent a serious clinical problem. In this review, we have focused on recent progress in the cellular and humoral mechanisms underpinning adhesion formation, and have reviewed strategies that interfere with these pathways as a means to prevent their occurrence. Current and previous English-language literature on the pathogenesis of adhesion formation was identified. As the burden of surgical disease in the world population increases, and the frequency of reoperation increases, prevention of adhesion formation has become a pressing goal in surgical research.


Association of bacterial infection and red blood cell transfusion after coronary artery bypass surgery.
Previous studies have shown an association between red blood cell transfusions (RBC) and bacterial infections following coronary artery bypass graft (CABG) surgery. We sought to assess whether there is an independent effect of RBC on the incidence of bacterial infections. This was a prospective cohort study of 533 CABG patients over a 7-month period. Subjects were followed from time of CABG until 30 days postoperatively. Data were collected on patient and treatment characteristics, surgical management, and transfusion incidence. Seventy-five (14.1%) of 533 patients developed a bacterial infection. After controlling for patient and disease characteristics, invasive treatments, surgical time, and the transfusion of other substances, the adjusted rates of bacterial infection were 4.8% for no RBC transfusion, 15.2% with one to two units, 22.1% with three to five units, and 29.0% with greater than or equal to six units, (p(trend) < 0.001). Diabetes was the only patient or disease factor significantly associated with bacterial infection (p < 0.001). RBC transfusions were independently associated with a higher incidence of post-CABG bacterial infections. The risk of infection increased in proportion to the number of units of RBC transfused.


Diabetes and mitochondrial bioenergetics: alterations with age.
Several studies have been carried out to evaluate the alterations in mitochondrial functions of diabetic rats. However, some of the results reported are controversial, since experimental conditions, such as aging, and/or strain of animals used were different. The purpose of this study was to evaluate the metabolic changes in liver mitochondria, both in the presence of severe hyperglycaemia (STZ-treated rats) and mild hyperglycaemia (Goto-Kakizaki (GK) rats). Moreover, metabolic alterations were evaluated both at initial and at advanced states of the disease. We observed that both models of type 1 and type 2 diabetes presented alterations on respiratory chain activity. Because of continual severe hyperglycaemia, 9 weeks after the induction of diabetes, the respiratory function declined in STZ-treated rats, as observed by membrane potential and respiratory ratios (RCR, P/O, and FCCP-stimulated respiration) assessment. In contrast, GK rats of 6 months age presented increased respiratory ratios. To localize which respiratory complexes are affected by diabetes, enzymatic respiratory chain activities were evaluated. We observed that succinate dehydrogenase and cytochrome c oxidase activities were significantly augmented both in STZ-treated rats and GK rats of 6 months age. Moreover, H(+)-ATPase activity was also significantly increased in STZ-treated rats with 3 weeks of diabetes and in GK rats of 6 months age as compared to controls. Therefore, these results clearly suggest that both animal models of diabetes present some metabolic adjustments in order to circumvent the deleterious effects promoted by the high glucose levels typical of the disease.


Biological dressings for the management of enteric fistulas in the open abdomen: a preliminary report.
Biological dressings can be effective tools in the management of enteric fistulas, which are the nemesis of exposed viscera. Retrospective review of medical records. University-affiliated level I trauma center. Patients with open abdominal cavities and coexistent intestinal fistulas who were treated between January 1, 1999, and July 1, 2006. Application of biological dressings to fistula sites within open abdominal cavities during serial fascial closure. Biological dressings included cadaveric skin, human acellular dermal matrix, and fibrin sealant. Enteric fistula closure and healing of the abdominal wound. During the 6 years under review, there were 69 patients with open abdomens. Of these patients, 7 (10%) developed enteric fistulas and underwent application of biological dressings. In 5 patients, fistulas closed and the abdominal wound healed after application of biological dressings. One additional patient healed after fistula resection. Biological dressing treatment and fistula resection both failed in 1 patient. There was no morbidity or mortality attributable to the intervention. Intestinal fistulas significantly complicate the management of patients with open abdomens. In this case series, biological dressings were effective in achieving fistula closure. A prospective multi-institutional study is required to confirm these preliminary encouraging results.


Effects of Kinesio Taping on peak torque and muscle activity in women with low back pain presenting fears and beliefs related to physical activity.
KT is an elastic taping that has been widely used as an adjunct to conventional physiotherapy. The purpose of this study was to evaluate the effects of Kinesio Taping on peak torque, muscle fatigue index and muscle activity of erector spinae in women with low back pain presenting fears and beliefs related to physical activity. This is a pilot controlled clinical trial. The subjects were divided into two groups according to the Fear Beliefs Avoidance Questionnaire (FABQ): Group A (Patients with no fears and/or beliefs related to physical activity) and Group B (Patients with fears and/or beliefs related to physical activity). The Kinesio Taping was applied in "I" in order to facilitate erector spinae. An isokinetic dynamometer and a surface electromyography were used to evaluate the outcomes. The evaluations were performed without and with the KT. Sample of 16 women equally divided into two groups with similar characteristics regarding age, weight, height, body mass index, functional capacity and pain levels in the evaluations without and with Kinesio Taping. There were within-groups and between-groups differences in the peak torque (p ≤ .05), with better results in the Group B. No differences were found on muscle fatigue index and muscle activity in both groups (p > .05). It was concluded that Kinesio Taping had immediate effects in the peak torque of the erector spinae of women with nonspecific chronic low back pain presenting fears and beliefs related to physical activity. It is suggested that such results occurred by placebo effect. NCT: RBR-5xh3ch.


Usefulness of real-time myocardial perfusion imaging to evaluate alterations of myocardial blood flow in patients with stable angina pectoris undergoing elective percutaneous coronary interventions.
Release of cardiac enzymes has been reported in patients with stable angina who undergo elective percutaneous coronary intervention (PCI) and has been associated with adverse clinical outcomes. The aim of the present study was to investigate whether impaired microvascular integrity can be detected using myocardial contrast echocardiography in patients undergoing elective PCI, and whether it is related to the extent of postprocedural troponin T elevation. We investigated consecutive patients with stable angina (n = 19) who were scheduled for elective angioplasty with stent placement. Myocardial contrast echocardiography was performed before and 2 to 4 hours and 24 hours after coronary intervention. Contrast images were analyzed visually and quantitatively measuring the peak signal intensity (A) and the slope of the signal intensity rise (beta) in 16 myocardial segments. The product of A x beta was calculated in each segment to estimate the regional myocardial blood flow. Troponin T was collected serially before and 2 to 4 hours and 24 hours after PCI. Five patients (26%) had elevated troponin T 24 hours after PCI (range 0.03 to 0.46 microg/L). Eight patients (42%), including all 5 patients with elevated troponin T levels, demonstrated impaired microvascular integrity 2 to 4 hours after PCI in >or=2 myocardial segments (range 2 to 4) within the perfusion territory of the target vessel. Of the 11 patients without evidence of impaired myocardial perfusion by myocardial contrast echocardiography, none had elevated troponin T levels at follow-up. Quantitative analysis of myocardial blood flow showed that impaired perfusion after PCI was partially reversible. Thus, A x beta had decreased significantly at 2 to 4 hours after PCI (3.4 +/- 1.6 vs 8.8 +/- 3.4 dB/s baseline, p <0.01), reincreased after 24 hours (6.4 +/- 2.3 dB/s at 24 hours vs 3.4 +/- 1.6 dB/s at 2 to 4 hours, p <0.01), but did not return to baseline (8.8 +/- 3.4 dB/s at baseline vs 6.4 +/- 2.3 dB/s at 24 hours, p <0.01). The perfusion defect size 2 to 4 hours after PCI was closely related to the troponin T levels after 24 hours (r(2) = 0.80, p <0.0001). In conclusion, impaired microvascular integrity is partially present in patients with stable angina who undergo elective PCI, is partially reversible, and is closely related to the release of troponin T. Because judgment of interventional success has shifted downstream to tissue level perfusion, myocardial contrast echocardiography may be useful to monitor such alterations in myocardial tissue perfusion.


A novel small-molecule inhibitor of influenza A virus acts by suppressing PA endonuclease activity of the viral polymerase.
The RNA-dependent RNA polymerase of influenza A virus comprises conserved and independently-folded subdomains with defined functionalities. The N-terminal domain of the PA subunit (PA(N)) harbors the endonuclease function so that it can serve as a desired target for drug discovery. To identify a class of anti-influenza inhibitors that impedes PA(N) endonuclease activity, a screening approach that integrated the fluorescence resonance energy transfer based endonuclease inhibitory assay with the DNA gel-based endonuclease inhibitory assay was conducted, followed by the evaluation of antiviral efficacies and potential cytotoxicity of the primary hits in vitro and in vivo. A small-molecule compound ANA-0 was identified as a potent inhibitor against the replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2, in cell cultures. Combinational treatment of zanamivir and ANA-0 exerted synergistic anti-influenza effect in vitro. Intranasal administration of ANA-0 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. In summary, ANA-0 shows potential to be developed to novel anti-influenza agents.


ACTN3 R577X and other polymorphisms are not associated with elite endurance athlete status in the Genathlete study.
Homozygosity for a premature stop codon at amino acid position 577 in the alpha-actinin-3 (ACTN3) gene leads to α-actinin-3 deficiency. This genotype is observed in approximately 18% of Caucasians. The ACTN3 R577X polymorphism has been previously associated with indicators of physical performance in several, but not all, studies. We examined the prevalence of R577X (rs1815739) and two additional haplotype tagging single nucleotide polymorphisms (htSNPs) of the ACTN3 gene (rs1791690 and rs2275998) in the Genathlete study comprising 316 male elite endurance athletes (VO2max 79.0+3.5 ml · kg(-1) · min(-1); mean +/- s) from North America, Finland, and Germany and 304 sedentary controls (VO2max 40.1+7.0 ml · kg(-1) · min(-1) matched by country of origin. The distribution of genotype and allele frequencies between the two groups was tested by Pearson chi-square and/or Fischer exact test. The prevalence of the 577X homozygote genotype was similar in endurance athletes and controls (20% and 17.5%, respectively). The resulting odds ratio for endurance performance in 577X homozygotes compared with 577R-allele carriers was 1.24 (95%CI 0.82-1.87, P = 0.3). The genotype distribution of the two htSNPs and haplotype frequencies did not differ significantly between athletes and controls. In conclusion, our findings indicate that ACTN3 R577X and other SNPs in ACTN3 are not genetic determinants of endurance performance in Caucasian males.


Empowering fisherwomen leaders helped reduce the effects of the COVID-19 pandemic on fishing communities: Insights from Brazil.
Small-scale fishers in the developing world have been particularly affected by the COVID-19 pandemic given that they belong to one of the most socioeconomically vulnerable groups. In Brazil, one of the countries most affected by the pandemic, it was expected early on that the economy and wellbeing of fishers would be negatively impacted, yet fishers were expected to show some adaptive and coping mechanisms. To assess whether this was the case, 40 fishers, who are also leaders of fishing associations representing over 80 thousand fishers throughout the country, were interviewed. Results revealed that female leaders appraised the economic and health / wellbeing impacts to be harsher on fishers than men did. Moreover, fishers on the coast were found to be better able to adapt than those inland, although both had low levels of adaptive capacity. The nature of coping and adaptive mechanisms was also found to be different between locations. Whereas leaders from coastal associations stated that most of the adaptive responses occurred in the post-harvest sector (e.g., changes to the types of sales and changes to supply chain actors), leaders from inland communities stated that the changes that occurred related specifically to fishing (e.g., decrease in effort and changes in fishing grounds). These findings suggest that: 1) women may be better prepared to respond to COVID-19 because their appraisal may be more realistic than men, 2) the historic vulnerability of fishing communities may limit their adaptative capacity, and 3) coastal fishers have likely found ways to maintain part of their trade, contrary to inland fishers. Thus, to better help small-scale fisheries to cope with this particular pandemic or other large disruptive impacts, it would be recommended to invest in women in leadership roles while also guaranteeing that fishers have the minimal conditions to cope with and adapt to impacts. The latter can be done by assuring emergency cash transfers for the duration of the impact, as with the still ongoing pandemic, and investing in building fisher resilience for future shocks.


Overproduction of poly(β-malic acid) (PMA) from glucose by a novel Aureobasidium sp. P6 strain isolated from mangrove system.
After over 100 strains of Aureobasidium spp isolated from mangrove system were screened for their ability to produce poly(β-malic acid) (PMA), it was found that Aureobasidium sp. P6 strain among them could produce high level of Ca(2+)-PMA. Fourteen percent glucose and 6.5 % CaCO3 in the medium were the most suitable for Ca(2+)-PMA production. Then, 100.7 g/l of Ca(2+)-PMA was produced using Aureobasidium sp. P6 strain within 168 h at flask level. During 10-l batch fermentation, when the medium contained 12.0 % glucose, 98.7 g/l of Ca(2+)-PMA in the culture and 14.7 g/l of cell dry weight were obtained within 156 h, leaving 0.34 % reducing sugar in the fermented medium. When glucose concentration in the fermentation medium was 14.0 %, 118.3 g/l of Ca(2+)-PMA in the culture and 16.4 g/l of cell dry weight were obtained within 168 h, leaving 0.4 % reducing sugar in the fermented medium. After purification of Ca(2+)-PMA from the culture and acid hydrolysis of the pure Ca(2+)-PMA, analysis of HPLC showed that Aureobasidium sp. P6 strain only produced two main components of Ca(2+)-PMA and minor amount of calcium malate and that the hydrolysate of PMA was mainly composed of calcium malate. This is the first time to report that the novel yeast strain Aureobasidium sp. P6 strain isolated from the mangrove systems can produce such high amount of Ca(2+)-PMA.


[Principles in the organization of voluntary certifying system for studies and services in pathologic anatomy].
The aim of voluntary certification is to improve the quality of pathology service and to implement it under the Russian Federation's laws and existing standards. The noncommercial organization "Voluntary Certifying System for Postmortem Studies" has been set up, which includes expert groups comprising highly skilled specialists.


Effects of intra-amygdalar thyrotropin releasing hormone (TRH) and its antagonism by atropine and benzodiazepines during stress ulcer formation in rats.
Bilateral intra-amygdalar (i/am) microinjections of TRH (1 and 10 micrograms) and physostigmine (10 micrograms) into the central nucleus (CEA) aggravated cold restraint stress (3 hr at 4 degrees C) induced gastric ulcer formation in rats, whereas atropine (1, 5 and 10 micrograms) attenuated this phenomenon. Similar stress ulcer reducing effects were seen with chlordiazepoxide (CDP, 10 mg/kg, IP) and midazolam (1, 3 and 10 micrograms, i/am). Pretreatment of rats with atropine or CDP antagonized the ulcerogenic effects of both TRH and physostigmine. Further, when administered intra-CEA, midazolam neutralized the effects of TRH in a dose-related manner. These results are discussed in light of TRH-acetylcholine-benzodiazepine/GABA interactions within the amygdaloid complex during stress ulcer formation.


Fetal gender specific expression of tandem-repeat galectins in placental tissue from normally progressed human pregnancies and intrauterine growth restriction (IUGR).
The tandem-repeat type galectins, which comprise of gal-4, -6, -8, -9, and -12, form a sub-family of galectins. Gal-6 is expressed only in rodents, whereas the other four galectins, tandem-repeat galectins, are also detectable in human tissue. The placental expression of individual members of the tandem-repeat gal family is increasingly known, however, systematic, comparative analysis especially in the human placenta from normal or pathological pregnancies is still lacking. Within this study, third trimester placentas obtained at delivery (n = 14 IUGR, n = 15 controls, equally divided in placentas from male and female fetuses) were analyzed for the expression of gal-4, -8, -9 and -12 by immunohistology and immunofluorescence, data were obtained by using a semiquantitative scoring system. Double immune-fluorescence with trophoblast specific markers was used to identify co-expression in the decidua. We identified dysregulation of tandem repeat galectins in IUGR placentas with a strong connection to the fetal gender. We identified a significantly lower expression of gal-4 and gal-9 in villous trophoblast tissue of IUGR placentas with male fetuses and a downregulation of gal-4 and gal-8 in extravillous trophoblast (EVT) from IUGR and male fetuses. Conversely, expression of gal-9 and gal-12 was higher in EVT of IUGR cases in placentas with female fetuses. Double immunofluorescence using cytokeratin-7 confirmed the expression of tandem-repeat galectins in EVT. The human placenta expresses tandem-repeat type galectins in villous trophoblasts, EVT, endothelial cells and decidual stromal cells. Summarizing all effects, there is significant down-regulation of gal-4, -8 and gal-9 in the IUGR trophoblast of male fetuses. In contrast, in IUGR pregnancies with female fetus gal-9 and gal-12 are upregulated in the EVT and in endothelial cells in the cases of gal-12. Therefore we propose a fetal-gender specific action of tandem repeat galectins in IUGR placentas.


Matrix metalloproteinase-2 expression correlates with cavernous sinus invasion in pituitary adenomas.
The aim of this study was to evaluate the relationship between expression of matrix metalloproteinase-2 (MMP-2) and cavernous sinus invasion in pituitary adenoma. Tissue samples from 54 pituitary adenomas were examined for expression of MMP-2 protein by immunohistochemistry. In sixteen tumors, the expression of MMP-2 mRNA was also examined by RT-PCR. Immunostaining was semiquantatively scored based on intensity (0-3) and distribution (0-3). There were 34 women and 20 men, with a mean age of 49.9 years (range 18-76). There were 12 tumors with cavernous sinus invasion, and 42 noninvasive cases. The MMP-2 score of pituitary adenomas with cavernous sinus invasion (3.9 +/- 0.5) was significantly higher than those without invasion (2.3 +/- 0.2; P < 0.01). There was no difference in MMP-2 score between macroadenomas (3.0 +/- 0.3) and microadenomas (2.1 +/- 0.4; P > 0.05), and also, no difference between the functioning adenomas (2.8 +/- 0.3) and non-functioning adenomas (2.8 +/- 0.3; P > 0.05). We found no correlation between the MMP-2 score and the Ki-67 labeling index (r2 = -0.05; P = 0.72). MMP-2 mRNA expression was also intense in invasive pituitary adenomas and was significantly higher in invasive pituitary adenomas than those without invasion (68.2 +/- 15.3; 21.8 +/- 8.2; P < 0.05). This study suggests that MMP-2 may be associated with aggressiveness and invasion in pituitary adenoma but is not related to tumor size or secretory function. MMP-2 may be a useful tool for assessing the invasive potential.


TFEB inhibition induces melanoma shut-down by blocking the cell cycle and rewiring metabolism.
Melanomas are characterised by accelerated cell proliferation and metabolic reprogramming resulting from the contemporary dysregulation of the MAPK pathway, glycolysis and the tricarboxylic acid (TCA) cycle. Here, we suggest that the oncogenic transcription factor EB (TFEB), a key regulator of lysosomal biogenesis and function, controls melanoma tumour growth through a transcriptional programme targeting ERK1/2 activity and glucose, glutamine and cholesterol metabolism. Mechanistically, TFEB binds and negatively regulates the promoter of DUSP-1, which dephosphorylates ERK1/2. In melanoma cells, TFEB silencing correlates with ERK1/2 dephosphorylation at the activation-related p-Thr185 and p-Tyr187 residues. The decreased ERK1/2 activity synergises with TFEB control of CDK4 expression, resulting in cell proliferation blockade. Simultaneously, TFEB rewires metabolism, influencing glycolysis, glucose and glutamine uptake, and cholesterol synthesis. In TFEB-silenced melanoma cells, cholesterol synthesis is impaired, and the uptake of glucose and glutamine is inhibited, leading to a reduction in glycolysis, glutaminolysis and oxidative phosphorylation. Moreover, the reduction in TFEB level induces reverses TCA cycle, leading to fatty acid production. A syngeneic BRAFV600E melanoma model recapitulated the in vitro study results, showing that TFEB silencing sustains the reduction in tumour growth, increase in DUSP-1 level and inhibition of ERK1/2 action, suggesting a pivotal role for TFEB in maintaining proliferative melanoma cell behaviour and the operational metabolic pathways necessary for meeting the high energy demands of melanoma cells.