Pulmonary Hypertension: The Hidden Danger for Newborns.
Despite growing awareness of the clinical importance of pulmonary hypertension (PH) in preterm infants, uncertainty persists regarding the different clinical settings in which abnormalities of pulmonary vascular growth, function, and structure contribute to high morbidity and mortality, and potential interventions to improve outcomes are uncertain. A major gap for improving outcomes of preterm infants with PH has been the limited characterization of the distinct settings of PH and related disease-specific mechanisms in preterm infants that represent diverse pulmonary vascular phenotypes of prematurity. In comparison with term newborns, preterm infants have a higher risk for developing hypoxemia due to suprasystemic levels of PH in preterm infants shortly after birth or persistent pulmonary hypertension of the newborn (PPHN). Variable and milder levels of PH have also been demonstrated in preterm infants without evidence of severe hypoxemic respiratory failure, suggesting delayed vascular transition of the lung which is associated with higher risks of mortality and developing bronchopulmonary dysplasia (BPD). In addition, early echocardiographic signs of PH at day 7 are strongly associated with the subsequent diagnosis of BPD, late PH, and respiratory disease throughout early childhood. In infants with evolving or established BPD, PH that persists beyond the first few months of life in preterm infants is associated with high mortality. Recent data further show that PVD can persist and cause PH in prematurely born adults. Overall, more precise characterization and studies of diverse pulmonary vascular phenotypes in preterm infants will be likely to improve the development of therapeutic strategies to optimize care of preterm infants with PH.


Seminal antioxidant capacity in pre- and postoperative varicocele.
In order to explore the impact of surgical treatment on antioxidant defense system in varicocele (VAR), we evaluated seminal total antioxidant capacity (TAC) in 25 patients affected by VAR, in 14 patients studied 10-24 months after varicocelectomy (post-VAR) and separated into normo- and oligospermic groups, and in 24 non-VAR control patients with seminal parameters matched to patients with VAR in the oligo- and normospermic groups (7 subjects with idiopathic oligospermia and 17 normal fertile subjects). TAC was measured in seminal plasma with the system H(2)O(2)-metamyoglobin as a source of radicals, which interact with a chromogen 2,2',-azinobis (3-ethylbenzothiazoline-6-sulphonate) (ABTS), generating a radical cation spectroscopically detectable. The presence of antioxidants induces a lag time in the production of ABTS cation proportional to the concentration of antioxidant compounds. When whole groups of patients were analyzed, lag values were significantly higher in VAR vs non-VAR controls (mean +/- SEM, 106.6 +/- 8.8 seconds vs 78.7 +/- 8.8 seconds) but were not modified by surgery (mean +/- SEM, 105.8 +/- 8.6 seconds). In groups separated according to seminal parameters, oligospermic VAR presented significantly higher lag values than oligospermic controls. Finally, when exploring a possible association of TAC with seminal parameters, we found a significant correlation between lag and sperm motility only in patients with VAR who were in the normospermic group (r = 0.65, P <.01). This correlation was not yet manifest post-VAR. In conclusion, surgical treatment does not seem to modify absolute values of TAC but influences its fine regulation and relationships with sperm motility.


Cardiac event rate in a lifestyle modification program for patients with chronic coronary artery disease.
Several clinical trials have shown that intensive lifestyle modification programs have a significant impact on cardiovascular risk factors. This paper is a retrospective analysis to determine the effect of participation in a 2-year lifestyle management program on long-term clinical outcome in patients outside the setting of a clinical trial. Patients with angiographically confirmed coronary artery disease (CAD) enrolled in a 2-year program of exercise training, dietary counseling, stress management, and therapeutic education. They were accepted into the program from 1991 through December 2002. Follow-up after completion of the program ranged from 10 to 2 years. In all, 134 patients enrolled in the program; of these, 77 completed the program and 57 failed to do so. Those who completed the program improved their effort tolerance and reached recommended goals for serum lipid and blood pressure levels. The cumulative event rate (cardiac death, myocardial infarction, and stroke) over 10 years in the patients who completed the program was 1.5%. The corresponding event rate in patients who dropped out was 18% (p < 0.02). It is suggested that patients who complete a 2-year lifestyle modification program appear to have a favorable prognosis over an extended period of time.


Current status of Phytophthora in Australia.
Among the most economically relevant and environmentally devastating diseases globally are those caused by Phytophthora species. In Australia, production losses in agriculture and forestry result from several well-known cosmopolitan Phytophthora species and infestation of natural ecosystems by Phytophthora cinnamomi have caused irretrievable loss to biodiversity especially in proteaceous dominated heathlands. For this review, all available records of Phytophthora in Australia were collated and curated, resulting in a database of 7 869 records, of which 2 957 have associated molecular data. Australian databases hold records for 99 species, of which 20 are undescribed. Eight species have no records linked to molecular data, and their presence in Australia is considered doubtful. The 99 species reside in 10 of the 12 clades recognised within the complete phylogeny of Phytophthora. The review includes discussion on each of these species' status and additional information provided for another 29 species of concern. The first species reported in Australia in 1900 was Phytophthora infestans. By 2000, 27 species were known, predominantly from agriculture. The significant increase in species reported in the subsequent 20 years has coincided with extensive surveys in natural ecosystems coupled with molecular taxonomy and the recognition of numerous new phylogenetically distinct but morphologically similar species. Routine and targeted surveys within Australian natural ecosystems have resulted in the description of 27 species since 2009. Due to the new species descriptions over the last 20 years, many older records have been reclassified based on molecular identification. The distribution of records is skewed toward regions with considerable activity in high productivity agriculture, horticulture and forestry, and native vegetation at risk from P. cinnamomi. Native and exotic hosts of different Phytophthora species are found throughout the phylogeny; however, species from clades 1, 7 and 8 are more likely to be associated with exotic hosts. One of the most difficult challenges to overcome when establishing a pest status is a lack of reliable data on the current state of a species in any given country or location. The database compiled here for Australia and the information provided for each species overcomes this challenge. This review will aid federal and state governments in risk assessments and trade negotiations by providing a comprehensive resource on the current status of Phytophthora species in Australia. Citation: Burgess TI, Edwards J, Drenth A, et al. 2021. Current status of Phytophthora in Australia. Persoonia 47: 151-177. https://doi.org/10.3767/persoonia.2021.47.05.


The impact of delayed graft function on the long-term outcome of renal transplantation.
Recent studies provide conflicting conclusions regarding the impact of delayed graft function (DGF) on the long-term outcome of renal transplantation. Some centres report DGF as an independent risk factor for reduced long-term graft and patient survival, while others report no impact on long-term outcome. Further scrutiny of data from these studies reveals differences in the definition of DGF, definition of long-term outcome, and statistical methods that may partly explain the variability. The commonest definition of DGF is the need for dialysis in the first week post-transplant, but this may be less informative than definitions that consider DGF as a continuous variable such as time to achieving creatinine clearance > 10ml/min. Acute rejection (AR) occurs more commonly in patients with DGF and variability in the impact of DGF may also relate to strategies to detect and treat AR during DGF. Centres with a vigilant strategy are likely to note a lower impact of DGF because the associated long-term adverse impact of AR is minimised. Furthermore, many centres reduce the dose of calcineurin inhibiting drugs and/or use polyclonal antibody therapy during DGF but the long-term impact of this strategy is unclear. Newer agents such as humanised anti-IL2 monoclonal antibodies and rapamycin may have a role, but controlled studies are required to define the optimal immunosuppressive regimen for patients with DGF. In the meantime, measures to minimise ischaemic damage to the transplant kidney and intensive surveillance for AR with weekly renal biopsy in patients with DGF are recommended.


A computational strategy for finding novel targets and therapeutic compounds for opioid dependence.
Opioids are widely used for treating different types of pains, but overuse and abuse of prescription opioids have led to opioid epidemic in the United States. Besides analgesic effects, chronic use of opioid can also cause tolerance, dependence, and even addiction. Effective treatment of opioid addiction remains a big challenge today. Studies on addictive effects of opioids focus on striatum, a main component in the brain responsible for drug dependence and addiction. Some transcription regulators have been associated with opioid addiction, but relationship between analgesic effects of opioids and dependence behaviors mediated by them at the molecular level has not been thoroughly investigated. In this paper, we developed a new computational strategy that identifies novel targets and potential therapeutic molecular compounds for opioid dependence and addiction. We employed several statistical and machine learning techniques and identified differentially expressed genes over time which were associated with dependence-related behaviors after exposure to either morphine or heroin, as well as potential transcription regulators that regulate these genes, using time course gene expression data from mouse striatum. Moreover, our findings revealed that some of these dependence-associated genes and transcription regulators are known to play key roles in opioid-mediated analgesia and tolerance, suggesting that an intricate relationship between opioid-induce pain-related pathways and dependence may develop at an early stage during opioid exposure. Finally, we determined small compounds that can potentially target the dependence-associated genes and transcription regulators. These compounds may facilitate development of effective therapy for opioid dependence and addiction. We also built a database (http://daportals.org) for all opioid-induced dependence-associated genes and transcription regulators that we discovered, as well as the small compounds that target those genes and transcription regulators.


Opportunities and challenges of fatty acid conjugated therapeutics.
Instability, poor cellular uptake and unfavorable pharmacokinetics and biodistribution of many therapeutic molecules require modification in their physicochemical properties. The conjugation of these APIs with fatty acids has demonstrated an enhancement in their lipophilicity and stability. The improvement in the formulations that resulted from the conjugation of a drug with a fatty acid includes increased half-life, enhanced cellular uptake and retention, targeted tumor delivery, reduced chemoresistance in cancer, and improved blood-brain-barrier (BBB) penetration. In this review, various therapeutic molecules, including small molecules, peptides and oligonucleotides, that have been conjugated with fatty acid have been thoroughly discussed along with various conjugation strategies. The application of nano-system based delivery is gaining a lot of attention due to its ability to provide controlled drug release, targeting and reducing the extent of side effects. This review also covers various nano-carriers that have been utilized for the delivery of fatty acid drug conjugates. The enhanced lipophilicity of the drug-fatty acid conjugate has shown to enhance the affinity of the drug towards these carriers, thereby increasing the entrapment efficiency and formulation performance.


Urban versus rural residency and pancreatic cancer survival: A Danish nationwide population-based cohort study.
It is unknown whether urban versus rural residency affects pancreatic cancer survival in a universal tax-financed healthcare system. We conducted a nationwide, population-based cohort study of all patients diagnosed with pancreatic cancer in Denmark from 2004-2015. We used nationwide registries to collect information on characteristics, comorbidity, cancer-directed treatment, and vital status. We followed the patients from pancreatic cancer diagnosis until death, emigration, or 1 October 2017, whichever occurred first. We truncated at five years of follow up. We stratified patients into calendar periods according to year of diagnosis (2004-2007, 2008-2011, and 2012-2015). We used Cox proportional hazards model to compute hazard ratios (HRs) with associated 95% confidence intervals (CIs) of death, comparing patients in urban and rural areas. HRs were adjusted for age, sex, comorbidity, tumor stage, and localization. In a sub-analysis, we also adjusted for cancer-directed treatment. We included 10,594 patients diagnosed with pancreatic cancer. Median age was 71 years (inter-quartile range: 63-78 years), and half were men. The majority (61.7%) lived in an urban area at the time of diagnosis. When adjusting for potential confounders, we observed a better survival rate among pancreatic cancer patients residing in urban areas compared with rural areas (adjusted HR: 0.92; 95% CI: 0.87-0.98). When taking treatment into account, the association was unclear (adjusted HR: 0.96; 95% CI: 0.88-1.04). Pancreatic cancer patients residing in urban areas had a slightly better survival rate compared with patients in rural areas.


Should Torsion Balance Technique Continue to be Taught to Pharmacy Students?
Objective. To determine the types of balances used in compounding pharmacies: torsion or digital. Methods. A survey was mailed to the pharmacist-in-charge at 698 pharmacies, representing 47% of the pharmacies in Missouri as of July 2013. The pharmacies were randomly selected and stratified by region into eight regions to ensure a representative sample. Information was gathered regarding the type and use of balances and pharmacists' perspectives on the need to teach torsion balance technique to pharmacy students. Results. The response rate for the survey was 53.3%. Out of the total responses received, those pharmacies having a torsion balance, digital balance or both were 46.8%, 27.4% and 11.8%, respectively. About 68.3% of respondents compound prescriptions. The study showed that 52% of compounding pharmacies use torsion balances in their practice. Of those with a balance in their pharmacy, 65.6% favored continuation of torsion balance instruction. Conclusions. Digital balances have become increasingly popular and have replaced torsion balances in some pharmacies, especially those that compound a significant number of prescriptions. The results of this study indicate that torsion balances remain integral to compounding practice. Therefore, students should continue being taught torsion balance technique at the college.


Are salty liquid food flavorings in vitro antitumor substances?
The objective of this study was to evaluate the antiproliferative, cytotoxic and genotoxic potential of salty liquid synthetic flavorings of Butter, Cheddar Cheese and Onion. The antiproliferative potential (2.9-1500 µg/mL) was assessed by MTT assay after 72h using the human tumor lines SF-295 (glioblastoma), OVCAR-8 (ovarian), HCT-116 (colon) and HL-60 (promyelocytic leukemia) and primary cultures of murine Sarcoma 180 (S180) and peripheral blood mononuclear cells (PBMC). Allium cepa bulbs were exposed to growing respective doses (1 mL and 2 mL). Only Butter and Cheddar flavorings revealed cytotoxic activity on cancer cells, with IC50 values ranging from 125.4 µg/mL (Cheddar - HCT-116) to 402.6 µg/mL (Butter - OVCAR-8). Butter flavoring was the most cytotoxic on PBMC (136.3 µg/mL) and increased cell division rate in relation to the mitotic index but did not cause cellular aberrations. Onion and Cheddar flavorings reduced the mitotic index after 24h and 48h exposure, but only Onion flavoring resulted in cellular aberrations and mitotic spindle abnormalities, such as anaphase and telophase bridges, micronucleated cells, conchicine-metaphases and amplifications. So, Butter, Onion and/or Cheddar flavorings caused significant changes in the division of meristematic cells of A. cepa and presented cytotoxic action even on decontrolled proliferating human tumor cells.


The 5' terminal uracil of let-7a is critical for the recruitment of mRNA to Argonaute2.
Small RNAs modulate gene expression by forming a ribonucleoprotein complex with Argonaute proteins and directing them to specific complementary sites in target nucleic acids. However, the interactions required for the recruitment of the target nucleic acid to the ribonucleoprotein complex are poorly understood. In the present manuscript we have investigated this question by using let-7a, Argonaute2 and a fully complementary mRNA target. Importantly, we have found that recombinant Argonaute2 is sufficient to direct let-7a guided cleavage of mRNA. Thus this model system has allowed us to investigate the mechanistic basis of silencing in vitro and in vivo. Current models suggest that Argonaute proteins bind to both the 5' and 3' termini of the guide RNA. We have found that the termini of the let-7a microRNA are indeed critical, since circular let-7a does not support mRNA cleavage. However, the 5' end is the key determinant, since its deletion abrogates activity. Surprisingly, we have found that alteration of the 5' terminal uracil compromises mRNA cleavage. Importantly, we have found that substitution of this base has little effect upon the formation of the binary let-7a-Argonaute2 complex, but inhibits the formation of the ternary let-7a-Argonaute2-mRNA complex. Thus we conclude that the interaction of the 5' uracil base with Argonaute2 plays a critical and novel role in the recruitment of mRNA.


Antagonistic genetic correlations for milking traits within the genome of dairy cattle.
Genome-wide association studies can be applied to identify useful SNPs associated with complex traits. Furthermore, regional genomic mapping can be used to estimate regional variance and clarify the genomic relationships within and outside regions but has not previously been applied to milk traits in cattle. We applied both single SNP analysis and regional genomic mapping to investigate SNPs or regions associated with milk yield traits in dairy cattle. The de-regressed breeding values of three traits, total yield (kg) of milk (MLK), fat (FAT), and protein (PRT) in 305 days, from 2,590 Holstein sires in Japan were analyzed. All sires were genotyped with 40,646 single-nucleotide polymorphism (SNP) markers. A genome-wide significant region (P < 0.01) common to all three traits was identified by regional genomic mapping on chromosome (BTA) 14. In contrast, single SNP analysis identified significant SNPs only for MLK and FAT (P < 0.01), but not PRT in the same region. Regional genomic mapping revealed an additional significant region (P < 0.01) for FAT on BTA5 that was not identified by single SNP analysis. The additive whole-genomic effects estimated in the regional genomic mapping analysis for the three traits were positively correlated with one another (0.830-0.924). However, the regional genomic effects obtained by using a window size of 20 SNPs for FAT on BTA14 were negatively correlated (P < 0.01) with the regional genomic effect for MLK (-0.940) and PRT (-0.878). The BTA14 regional effect for FAT also showed significant negative correlations (P < 0.01) with the whole genomic effects for MLK (-0.153), FAT (-0.172), and PRT (-0.181). These negative genomic correlations between loci are consistent with the negative linkage disequilibrium expected for traits under directional selection. Such antagonistic correlations may hamper the fixation of the FAT increasing alleles on BTA14. In summary, regional genomic mapping found more regions associated with milk production traits than did single SNP analysis. In addition, the existence of non-zero covariances between regional and whole genomic effects may influence the detection of regional effects, and antagonistic correlations could hamper the fixation of major genes under intensive selection.


Inhibition of defocus-induced myopia in chickens.
To determine the effect of wearing a lens with a unique peripheral optical design on the development and progression of defocus-induced myopia in newly hatched chickens. Eighty-five newly hatched chickens underwent bilateral retinoscopy and A-scan ultrasound to determine their refractive error and axial length. They were randomly divided into Control and two Test groups, in which each chicken was fitted with a goggle-lens over the right eye, with the left eye remaining untreated. The Control group wore a lens of power -10.00 diopters (D) of standard spherical optical design. The two Test lenses both had a central optical power -10.00 D, but used different peripheral myopia progression control (MPC) designs. For all groups, retinoscopy was repeated on days 3, 7, 10, and 14; ultrasound was repeated on day 14. On day 0 there was no statistical difference in refractive error (mean +6.92 D) or axial length (mean 8.06 mm) between Test and Control groups or treated and untreated eyes (all P 0.05). At day 14, 37 (43.5%) of 85 chickens had not experienced goggle detachment and were included in the final analyses. in this cohort there was a significant refractive difference between the treated eyes of the control group (n = 17) and those of test 1 (n = 14) and Test 2 (N = 6) groups (both P <0.01): Control -4.65 ± 2.11 D, Test 1 +4.57 ± 3.11 D, Test 2 +1.08 ± 1.24 D (mean ± SEM). There was also a significant axial length difference (both P < 0.01): Control 10.55 ± 0.36 mm, Test 1 9.99 ± 0.14 mm, Test 2 10.17 ± 0.18 mm. Use of these unique MPC lens designs over 14 days caused a significant reduction in the development of defocus-induced myopia in chickens; the degree of reduction appeared to be design specific.


[Morphological and dimensional changes of the magnetic resonance imaging in the carpal tunnel (pre- and postoperatively)].
Carpal tunnel syndrome is the most common compression neuropathy of the upper limb, and the release of the median nerve is the surgical treatment that is carried out. There are several surgical techniques used to treat this condition; However, this virtual cavity, which we call the carpal tunnel, undergoes several morphological and dimensional changes, prior to surgery and after surgery using the various techniques that the surgeon has a predilection for. Observational, prospective and longitudinal study conducted in the period from March to November 2009. We studied patients of both sex, with a diagnosis of carpal tunnel syndrome, who underwent MRI pre and post-surgery studies, to which measurements and analysis of it were made. We evaluated 25 patients with an average of 40 years, 14 female patients and 11 male, finding a palmar displacement of the nerve after surgery with a diameter of 6.2 mm, maintaining changes from the oval to a circular shape. There are morphological and dimensional changes, evaluated by magnetic resonance after the release, for which the favorable clinical response after surgery is related; however, we found a larger diameter of the nerve due to the fact that they underwent neurolysis.


The contribution of social and environmental factors to race differences in dental services use.
Dental services use is a public health issue that varies by race. African Americans are less likely than whites to make use of these services. While several explanations exist, little is known about the role of segregation in understanding this race difference. Most research does not account for the confounding of race, socioeconomic status, and segregation. Using cross-sectional data from the Exploring Health Disparities in Integrated Communities Study, we examined the relationship between race and dental services use. Our primary outcome of interest was dental services use within 2 years. Our main independent variable was self-identified race. Of the 1408 study participants, 59.3% were African American. More African Americans used dental services within 2 years than whites. After adjusting for age, gender, marital status, income, education, insurance, self-rated health, and number of comorbidities, African Americans had greater odds of having used services (odds ratio = 1.48, 95% confidence interval 1.16, 1.89) within 2 years. Within this low-income racially integrated sample, African Americans participated in dental services more than whites. Place of living is an important factor to consider when seeking to understand race differences in dental service use.


Psychological sub-types among persons with HIV infection: an empirical study.
Cluster analysis was utilized to derive sub-types from a group of 53 males with HIV infection based on scores from several psychological measures. Measures administered included the Beck Depression Inventory, Life Orientation Test, Rosenberg Self-Esteem Test and the Internal Control Index. Three sub-types were identified: (1) average performing sub-type (2) severely dysfunctional sub-type, and (3) highly adaptive sub-type. All three sub-types showed different levels and patterns of test performance. Results are discussed in terms of sub-type characteristics and potential treatment issues.


Effect of a Rapidly Degrading Presolidified 10 kDa Chitosan/Blood Implant and Subchondral Marrow Stimulation Surgical Approach on Cartilage Resurfacing in a Sheep Model.
Objective This study tested the hypothesis that presolidified chitosan-blood implants are retained in subchondral bone channels perforated in critical-size sheep cartilage defects, and promote bone repair and hyaline-like cartilage resurfacing versus blood implant. Design Cartilage defects (10 × 10 mm) with 3 bone channels (1 drill, 2 Jamshidi biopsy, 2 mm diameter), and 6 small microfracture holes were created bilaterally in n = 11 sheep knee medial condyles. In one knee, 10 kDa chitosan-NaCl/blood implant (presolidified using recombinant factor VIIa or tissue factor), was inserted into each drill and Jamshidi hole. Contralateral knee defects received presolidified whole blood clot. Repair tissues were assessed histologically, biochemically, biomechanically, and by micro-computed tomography after 1 day ( n = 1) and 6 months ( n = 10). Results Day 1 defects showed a 60% loss of subchondral bone plate volume fraction along with extensive subchondral hematoma. Chitosan implant was resident at day 1, but had no effect on any subsequent repair parameter compared with blood implant controls. At 6 months, bone defects exhibited remodeling and hypomineralized bone repair and were partly resurfaced with tissues containing collagen type II and scant collagen type I, 2-fold lower glycosaminoglycan and fibril modulus, and 4.5-fold higher permeability compared with intact cartilage. Microdrill holes elicited higher histological ICRS-II overall assessment scores than Jamshidi holes (50% vs. 30%, P = 0.041). Jamshidi biopsy holes provoked sporadic osteonecrosis in n = 3 debrided condyles. Conclusions Ten kilodalton chitosan was insufficient to improve repair. Microdrilling is a feasible subchondral marrow stimulation surgical approach with the potential to elicit poroelastic tissues with at least half the compressive modulus as intact articular cartilage.


A sensitive method for the determination of Sulfonamides in seawater samples by Solid Phase Extraction and UV-Visible spectrophotometry.
The authors have developed a sensitive spectrophotometric method for determination of sulfonamide derivatives such as sulfanilamide (SAA), sulfadiazine (SDZ), sulfacetamide (SCT) sulfamethoxazole (SMX), sulfamerazine (SMR), sulfadimethoxine (SDX), sulfamethiazole (SMT) and Sulfathiazole (STZ). This method is based on the Bratton-Marshall reaction, which involves the diazotization of sulfonamides with sodium nitrite under acidic conditions, followed by coupling with N-(1-naphtyl) ethylenediamine dihydrochloride (NED) to form a pink colored compound. Therefore, the Bratton-Marshall method was modified by optimizing the reaction conditions, which allows us to determine a low concentration range of sulfonamides compared to the reported methods. The limits of detection and quantification obtained were 0.019-0.05 and 0.06-0.16μgmL-1, respectively. In comparison with other reported methods using different coupling agents, the proposed method was found to be the most simple and sensitive for sulfonamides determination. In this paper, the modified method was successfully employed for the determination of sulfonamides in drinking water, seawater and pharmaceutical and veterinary formulations. The purpose of this work is to optimize and develop a simple method for extraction and concentration of sulfonamides present as residues in seawater and their quantification with the recommended spectrophotometric method. Solid phase extraction (SPE) of sulfonamides from seawater samples was evaluated using Oasis HLB cartridges (3mL, 540mg). The recovery efficiency was investigated in the sulfonamides concentration range comprised between 0.19 and 126ngmL-1. The ease of use of this extraction method makes it very useful for routine laboratory work.


[Fronto-striatal correlations in normal and pathologic aging of the human brain].
In psychically healthy persons of three age groups (30-40, 50-60, 80-90 years), as well as in those suffering from Alzheimer's disease (50-60 years) right and left hemispheres formations, including into a single functional system (fields 8, 10, 47 and the nucleus caudatus) have been investigated. Using the series of frontal paraffin sections 20 mcm thick, stained after Nissl and Bielschowsky methods, cyto-glioarchitectonics and neuronal composition of the structures mentioned have been studied. In 0.001 mm3 of the brain substance, in cortical layers II and V and in the nucleus caudatus head density of neurons, perineuronal glia, neurons with lipofuscin, size of the neurons have been calculated. Various degree of manifestation of morphological changes is revealed in different stages of the single functional system. These changes are directly proportional to the organizational level of the structures studied and depend on the stage of the process, on accompanying diseases and individual peculiarities of the person. They are more intensive in the frontal fields and weaker in the nucleus caudatus. At Alzheimer's disease they are more distinct in the associative fields 10 and 47, at normal ageing--in the motor structures--in the field 8 and then in the nucleus caudatus. Spreading of the pathological process occurs with a predominant damage of neurons of cholinergic origin.


Caloric restriction and brain function.
In addition to extending lifespan, animal research shows that specific diets benefit brain functioning. Indeed, it has been proven that caloric restriction prevents age-related neuronal damage. What are those mechanisms involved in the effects of caloric restriction on brain functioning? Could caloric restriction be proposed in the future to prevent or treat neurodegenerative disorders such as Alzheimer's disease? Is there a future for caloric restriction interventions in adults? Hypotheses linking caloric restriction to cognitive capability include anti-inflammatory mechanisms, reduction of neural oxidative stress, promotion of synaptic plasticity, induction of various stress and neurotrophic/neuroprotective factors. Caloric restriction may also prevent beta-amyloid neuropathology in Alzheimer transgenic models. Finally, both exercise and caloric restriction enhance neurogenesis via different mechanisms suggesting that their combination may decrease the risk of neurodegenerative disease. It is now well established that caloric restriction could be used to promote successful brain aging. Data from randomized controlled trials in humans are limited. No positive effect on cognitive impairment was found probably due to methodological limitations. The long-term effects of caloric restriction in adults must be clarified before engaging in such preventive strategy. Additional animal studies must be conducted in the future to test the effects of 'multidomain' interventions (caloric restriction plus regular exercise) on age-related cognitive decline.


In vivo assessment of intratumoral aspirin injection to treat hepatic tumors.
To study the antineoplastic efficacy of 10% aspirin intralesional injection on VX2 hepatic tumors in a rabbit model. Thirty-two male rabbits (age: 6-9 wk; body weight: 1700-2500 g) were inoculated with VX2 hepatic tumor cells (10(4) cells/rabbit) via supra-umbilical median laparotomy. On day 4 post-implantation, when the tumors were about 1 cm in diameter, the rabbits were randomly divided into the following groups (n = 8 each group) to assess early (24 h) and late (7 d) antineoplastic effects of intratumoral injection of 10% bicarbonate aspirin solution (experimental groups) in comparison to intratumoral injection of physiological saline solution (control groups): group 1, 24 h control; group 2, 24 h experimental; group 3, 7 d control; group 4, 7 d experimental. The serum biochemistry profile (measurements of glycemia, alkaline phosphatase, gamma-glutamyl transferase, aspartate aminotransferase, and alanine aminotransferase) and body weight measurements were obtained for all animals at the following time points: D0, before tumor implant; D4, day of treatment; D5, day of sacrifice for groups 1 and 2; D11, day of sacrifice for groups 3 and 4. Gross assessments of the abdominal and thoracic cavities were carried out upon sacrifice. The resected liver tissues, including hepatic tumors, were qualitatively (general morphology, signs of necrosis) and quantitatively (tumor area) assessed by histopathological analysis. Gross examination showed no alterations, besides the left hepatic lobe tumors, had occurred in the thoracic and abdominal cavities of any animal at any time point evaluated. However, the features of the tumor foci were distinctive between the groups. Compared to the control groups, which showed normal unabated tumor progression, the aspirin-treated groups showed imprecise but limited tumor boundaries and a general red-white coloration (indicating hemorrhaging) at 24 h post-treatment, and development of yellow-white areas of a cicatricial aspect at 7 d after treatment. At all time points evaluated, all except one biochemical parameters tested within the reference range (P > 0.05); a significant increase was detected in the alkaline phosphatase level of the control group 3 on D11 (P < 0.05). At 24 h post-treatment, the aspirin-treated groups showed extensive coagulation necrosis accompanied by a remarkable absence of viable tumor foci; at 7 d after treatment, the tumors had completely disappeared in these animals and fibrous necrotic nodules had developed. In contrast, throughout the study course, the tumors of the control groups remained unchanged, showing tumor nodules without necrosis at the time point corresponding to 24 h post-treatment and increased amounts of tumor nodules at the time point corresponding to 7 d post-treatment. Quantitative analysis of the remaining tumor area revealed that the aspirin-treated groups had significantly smaller tumor foci at 24 h post-treatment (8.5% ± 0.7%) and at 7 d after treatment (11.0% ± 4.2%), compared to those in the control groups (24 h: 98.5% ± 1.5% and 7 d: 94.0% ± 2.7%; both, P < 0.005). Intralesional injection of a 10% aspirin solution causes destruction of VX2 hepatic tumors in rabbits without evidence of relapse at 7 d after treatment administration.


[The role of magnetic stimulation in diagnosis of the peripheral nervous system].
Magnetic stimulation has recently been introduced as a new method for stimulation of neuronal tissues. Up to now most investigators were emphasized the advantages of this method for the investigation of the central nervous system. With this paper we want to show that magnetic stimulation may also be useful for the examination of the peripheral nervous system. Both, magnetic and electrical stimulation, seem to employ the same stimulation mechanisms in the nervous tissue. The results obtained with both methods should therefore be comparable. By measuring EMG-latencies after electrical and magnetic stimulation (Fig. 1) the exact site of magnetic stimulation can be determined. Magnetic stimulation offers major advantages over electrical stimulation: 1) Magnetic stimulation is a painless method even when high stimulus intensities are used. 2) Magnetic stimulation can reach deep neuronal structures that are not easily accessible using electrical stimulation (Fig. 2, Fig. 3). 3) Using a wide range of stimulus intensities (Fig. 4, Fig. 5) magnetic stimulation provides a much better descrimination of different components of the compound muscle action potential than electrical stimulation. Magnetic stimulation seems to be a promising new method for the electrodiagnostic examination of pain- sensitive patients, especially when deep-lying peripheral nerves have to be investigated.


Characterization of FcalphaR-triggered Ca(2+) signals: role in neutrophil NADPH oxidase activation.
Human neutrophil IgA receptors (FcalphaR) trigger phagocytosis of IgA-opsonized particles and activate the NADPH oxidase complex ultimately leading to pathogen destruction. Signal transduction events triggered by FcalphaR have not been investigated in the context of NADPH oxidase activation. In this study, we show that crosslinking FcalphaR triggers the release of Ca(2+) from an intracellular store that was unchanged by the addition of extracellular EGTA. This was in contrast to the thapsigargin-triggered Ca(2+) signal, which activates store-operated Ca(2+) entry pathways (SOCP) and is sensitive to extracellular EGTA. Buffering extracellular Ca(2+) with EGTA had no effect on FcalphaR-triggered NADPH oxidase activation, suggesting that SOCP was not required for activation by FcalphaR. EGTA inhibited thapsigargin-triggered NADPH oxidase activation but had no effect on PMA-triggered responses. The intracellular Ca(2+) chelator BAPTA caused dose-dependent inhibition of both FcalphaR-triggered and thapsigargin-triggered NADPH oxidase activation but had no effect on PMA-triggered responses. Our data demonstrate that FcalphaR-triggered NADPH oxidase activation is dependent on the release of Ca(2+) from an intracellular store, but is independent of SOCP.


[In vitro uptake of fluoride from South African fluoride gel dentifrices].
An increasingly difficult situation in obtaining imported products has led to the development of a locally-manufactured topical fluoride gel. In order to evaluate the anticariogenic potential of the gel an in vitro study was conducted to compare the fluoride (F) uptake into the enamel from the locally-manufactured gel with that of two overseas products. Sound, unerupted third molar teeth were used in the study. One half of the buccal surface of each tooth was used as a control and the remaining half for conducting the experiment. Enamel biopsies (0.5 N HCLO4 3,143 mm2; 15 sec) were conducted prior to the F treatment (control halves) as well as 24 hours after F treatment (experimental halves). The fluoride concentrations ([F]) of the etching solutions were analyzed according to the potentiometric analytical method. The calcium concentrations were determined by means of a flame spectrophotometer. The [F] of the control halves of the teeth were used as a reference to determine the actual F uptake in the experimental halves after F treatment. The results obtained from the study showed that the teeth treated with the locally-manufactured F gel, revealed a significant uptake of fluoride in the enamel as well as an increased resistance to acid dissolution. Only one of the imported products showed a statistically significant higher fluoride uptake than the acidulated South African manufactured phosphate fluoride gel. There was a favourable overall comparison of the locally manufactured F gel with that of the overseas products.


Including lifestyle medicine in undergraduate medical curricula.
Currently, there is no model to integrate the discipline of lifestyle medicine (LM) into undergraduate medical education. Furthermore, there are no guidelines, validated assessment tools, or evaluation or implementation plans in place. The World Health Organization predicts that by 2020, two-thirds of disease worldwide will be the result of poor lifestyle choices. Fewer than 50% of US primary care physicians routinely provide specific guidance on nutrition, physical activity, or weight control. We are establishing a plan to integrate LM into medical school education in collaboration with the investing stakeholders, including medical school deans and students, medical curriculum developers and researchers, medical societies, governing bodies, and policy institutes. Three planning and strategy meetings are being held to address key areas of focus - with a particular interest in nutrition, physical activity, student self-care, and behavior change - to develop specific implementation guidelines and landmarks. After the first two meetings, the proposed areas of focus were determined to be: 1) supporting of deans and key personnel, 2) creation of federal and state policy commitments, 3) use of assessment as a driver of LM, 4) provision of high-quality evidence-based curricular material on an easily navigated site, and 5) engaging student interest. Implementation strategies for each focus area will be addressed in an upcoming planning meeting in early 2015. This initiative is expected to have important public health implications by efficiently promoting the prevention and treatment of non-communicable chronic disease with a scalable and sustainable model to educate physicians in training and practice.


The ACTive Intervention in Hospice Interdisciplinary Team Meetings: Exploring family caregiver and hospice team communication.
This paper presents the theoretical framework and rationale for the ACTive intervention which proposes the use of video technology to facilitate patient and family participation in hospice interdisciplinary team meetings where plans of care are determined. It is surmised that patient and family involvement will improve communication and compliance in hospice care. An analysis of data from a pilot project of the ACTive intervention was conducted to explore active participation among family caregivers and the hospice team. Through the use of videophone technology caregivers participated in video-recorded team meetings. The actual communication behaviors of caregivers and team members were analyzed for active participation. Findings revealed that team-prompted caregiver participation was most common, however, team use of supportive talk in this context was considerably less frequent. The study also found that the team's use of active participation behaviors elicits caregiver active participation behaviors. The results of this study suggest the intervention was an effective way to involve family caregivers as active participants in the designing of care for their loved one. Findings also suggest that hospice staff would benefit from education and training on best practices for communicating with caregivers in the team meeting setting.


Copper in Glucose Intolerance, Cognitive Decline, and Alzheimer Disease.
Trace metal dyshomeostasis has been linked to loss of cognitive performance. In particular, a disturbance in the regulation of copper (Cu), characterized by an increase in circulating Cu not bound to ceruloplasmin (non-Cp Cu), is thought to play a role in the development of Alzheimer disease (AD) and other neurodegenerative diseases in the aging population. Non-Cp Cu is redox active and its toxicity is thought to result from its ability to accelerate oxidative stress and advanced glycation endproduct (AGE) formation, leading to extracellular matrix damage in tissues including the brain. Cognitive loss is increasingly recognized to be a feature of type 2 diabetes and the increased AGE formation characteristic of diabetes may play a role in the development of this complication. There also is evidence for copper dyshomeostasis in type 2 diabetes, and therefore this could contribute to the cognitive deterioration associated with this disease. Demonstrating that disturbances of copper homeostasis correlate with an increased rate of cognitive decline in type 2 diabetes patients, and that they correlate with an increased rate of conversion from prediabetes to diabetes would bring almost immediate benefits in the clinical community in terms of treatment efficacy, AD prevention, and cost savings.


Mr-Proadm Elevation Upon Icu Admission Predicts the Outcome of Septic Patients and is Correlated with Upcoming Fluid Overload.
Among septic patients admitted to the intensive care unit (ICU), early recognition of those with the highest risk of death is of paramount importance. We evaluated the prognostic value of Procalcitonin (PCT), mid regional-proadrenomedullin (MR-proADM), copeptine and CT-proendothelin 1 (CT-ProET 1) concentrations. This was a prospective cohort study, which included 173 septic patient admitted to one ICU. Blood samples for biomarker measurements were obtained upon admission and on day 5. The predictive value of each biomarker regarding the risk of death at day 28 was assessed. The fluid balance was evaluated from admission to day 5. All cause ICU mortality was 36.4%. All the biomarkers except CT-ProET-1 were significantly more elevated in the non-survivors than in the survivors upon day 1. This was especially true for MR-proADM (8.6 [5.9] vs. 4.4 [3.9] nmol/L; P < 0.0001) and for the CT-proET-1/MR-proADM ratio (52.9 [22.4] vs. 31.3 [26.6] arbitrary units; P < 0.0001). The best AUROCC values on day 1 were obtained with MR-ProADM and the CT-proET-1/MR-proADM ratio as well (0.75 [0.67-0.85] and 0.82 [0.75-0.89]; 95% CI, respectively). An improved accuracy was achieved on day 5. Moreover, MR-ProADM baseline levels and fluid balance over the 5-day period following ICU admission were strongly correlated (Rho = 0.41; P < 0.001). In patients admitted to the ICU with sepsis, MR-ProADM on admission was the best predictor of short-term clinical outcome if compared with others. This could be related to its ability to predict fluid sequestration.


Ultrastructure and electrical activity of the rat neurohypophysis.
Ultrastructural and electrophysiological studies of the rat neurohypophysis was carried out following stimulation to cause vasopressin release. Unit activity was investigated with microelectrodes, filtered, integrated, and recorded simultaneously with blood pressure in a polygraph. The basal unit activity was challenged by perfusing the hypothalamus and pituitary gland with hypertonic, hypotonic, and isotonic solutions through the internal carotid and by bleeding. Posterior lobes were fixed in osmium tetroxide and stained with uranyl acetate for electron microscopy. Single unit activity from the neural lobe showed mostly a continuous pattern of activity with a rate of discharge (RD) of 7 to 30 pulses per 10 s during control periods. Following hypertonic stimulation, out of 20 units studied, 35% increased, 10% decreased, and 55% did not change their RD. The effect of bleeding was studied in 34 units. Following the withdrawal of 1 ml of blood from the jugular vein, 29% increased, 32% decreased, and 38% did not change their RD. It is concluded that the existence in the neurohypophysis of fibers which are excited or inhibited by stimuli known to cause vasopressin release supports the hypothesis of the existence of a modulatory mechanism for neuropeptide release in the neural lobe.


[Packing: current concepts of "life-saving" surgery].
Abdominal packing is a lifesaving technique for temporary control of severe injury and it is used in Damage Control Surgery schedule. Technically bleeding from abdominal cavity can generally be achieved by applying pressure with several large abdominal packs. It's possible too applying packs in organ-specific techniques (early abdominal packing). A wide review of the literature has allowed to emphasize the most common problem of this technique, the adequacy of the particular indications, their evolution, timing, the results in general and particular which multiple critical situations and not always predictable when an intensive diagnostic and methodological approach is necessary in. The principal indications are when complex anatomic lesions are diagnosed with not ruleable hemorrhages, in presence of metabolic failure--like hypothermia < 35 degrees C, acidosis > 7.2, coagulopathy PTT > 16 seconds: these three derangements become established quickly in the exsanguinating trauma patient and, once established, form a vicious circle which may be impossible to overcome. The results are encouraging and we can evaluate a median survival of the 60%, certainly superior to the obtainable survival with immediate surgical repair. Immediate failures are substantially due to bleeding, especially in "underpacking" case, and remote: these last can be premises, fundamentally septic and bound at the time of stay (above the 72 hours) and associated by the coexistence of lesions; in these situations is possible a MOF syndrome due to excessive intraabdominal pressure (overpacking) or to an abdominal compartment syndrome.


Aryl hydrocarbon receptor modulates stroke-induced astrogliosis and neurogenesis in the adult mouse brain.
The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor activated by environmental agonists and dietary tryptophan metabolites for the immune response and cell cycle regulation. Emerging evidence suggests that AHR activation after acute stroke may play a role in brain ischemic injury. However, whether AHR activation alters poststroke astrogliosis and neurogenesis remains unknown. We adopted conditional knockout of AHR from nestin-expressing neural stem/progenitor cells (AHRcKO) and wild-type (WT) mice in the permanent middle cerebral artery occlusion (MCAO) model. WT mice were treated with either vehicle or the AHR antagonist 6,2',4'-trimethoxyflavone (TMF, 5 mg/kg/day) intraperitoneally. The animals were examined at 2 and 7 days after MCAO. The AHR signaling pathway was significantly upregulated after stroke. Both TMF-treated WT and AHRcKO mice showed significantly decreased infarct volume, improved sensorimotor, and nonspatial working memory functions compared with their respective controls. AHR immunoreactivities were increased predominantly in activated microglia and astrocytes after MCAO compared with the normal WT controls. The TMF-treated WT and AHRcKO mice demonstrated significant amelioration of astrogliosis and microgliosis. Interestingly, these mice also showed augmentation of neural progenitor cell proliferation at the ipsilesional neurogenic subventricular zone (SVZ) and the hippocampal subgranular zone. At the peri-infarct cortex, the ipsilesional SVZ/striatum, and the hippocampus, both the TMF-treated and AHRcKO mice demonstrated downregulated IL-1β, IL-6, IFN-γ, CXCL1, and S100β, and concomitantly upregulated Neurogenin 2 and Neurogenin 1. Neural cell-specific AHR activation following acute ischemic stroke increased astrogliosis and suppressed neurogenesis in adult mice. AHR inhibition in acute stroke may potentially benefit functional outcomes likely through reducing proinflammatory gliosis and preserving neurogenesis.


A comparison of US and Norwegian regulation of coumarin in tobacco products.
This paper examines policy processes regarding why the USA and Norway have not regulated coumarin in tobacco. A qualitative analysis of all tobacco industry documents regarding coumarin since the 1950s from the 1998 US Master Settlement Agreement and subsequent legal settlements. Additional data were collected from newspaper reports, general internet search engines, journal articles, scholarly reports, court cases, statutes, regulations, and informal correspondence with tobacco control experts in Norway. An overview, summary, and analysis of all documents related to coumarin. In the USA from 1954 until 1985 when coumarin was reportedly removed from domestic cigarettes, but not from pipe tobacco until 1996, and not at all from imported Indian bidi cigarettes, regulatory efforts were stymied. In Norway, from 1973 to the present, the tobacco industry has never disclosed whether its tobacco products contain coumarin. In both the USA and Norway, the extreme delay and lack of vigorous evidence gathering and significant remedies were caused by tobacco industry assertions that revealing tobacco additives was a violation of trade secrets, and by weak regulatory authority and efforts to regulate coumarin. Vigorous and expeditious regulatory investigations and remedies for harmful additives in tobacco, such as coumarin, can protect the public health. Astute insider and outsider political advocacy by health advocates is required to hold elected officials and civil servants publicly accountable for failing to enact disclosure laws and to engage in effective regulatory efforts.


Indigo-A New Tribological Substance Class for Non-Toxic and Ecological Gliding Surfaces on Ice, Snow, and Water.
The biogenic substance E-indigo can form supramolecular, hydrophobic structures using self-organization. These structures show a low coefficient of friction as a gliding layer against polar surfaces. The formation of primary particles with platelet morphology based on hydrogen-bonded E-indigo molecules is ideal to produce the gliding layer. Structures with excellent gliding properties can be achieved by means of directed friction and high pressure, as well as through tempering. The resulting hard, thin gliding layer of E-indigo does not easily absorb dirt and, thus, prevents a rapid increase in friction. Field tests on snow, with cross-country skis, have shown promising results in comparison to fluorinated and non-fluorinated waxes. Based on quantitative structure-activity relationship (QSAR) data for E-indigo, and its isomers and tautomers, it has been demonstrated that both the application and abrasion of the thin indigo layers are harmless to health, and are ecologically benign and, therefore, sustainable.


Assessment of the household availability of oral rehydration salt in rural Botswana.
Diarrhea contributed for 17.6% of under-five deaths in Botswana. Oral rehydration salt (ORS) therapy has been the cornerstone in the control of morbidity and mortality secondary to diarrheal diseases. The study was aimed at assessing the household availability of ORS following the nationwide campaign of availing ORS at household level. A cross sectional community based study was conducted in August 2012. EPI random walk method was used to identify households. Data was collected using interviewers' administered structured questionnaire. SPSS software was used in data entry and analysis. Oral Rehydration Salt (ORS) was available in 50.8% of the households with under-five children. Information on ORS is well disseminated whereas only three-fourth of informed participants had adequate knowledge of ORS preparation. The sources of information were predominantly the Child Welfare Clinic (88.8%). Being grandmother as a care taker was a negative predictor of household availability of ORS (AOR 0.25, 95% CI 0.09-0.69) while respondents who are knowledgeable about ORS preparation were more likely to have ORS available at home (AOR 1.92, 95% CI 1.10-3.34). The campaign has brought a significant coverage in terms of availability of ORS. The health education and community sensitization efforts need to go beyond health facilities via other means like the media and community based approaches. Approaches aimed at improving the knowledge of care takers on the importance of ORS, its preparation, correct use and restocking are of paramount importance. Availing community based outlet for ORS is an alternative to enhance accessibility.


Consensus statement for perioperative care in total hip replacement and total knee replacement surgery: Enhanced Recovery After Surgery (ERAS®) Society recommendations.
Background and purpose - There is a large volume of heterogeneous studies across all Enhanced Recovery After Surgery (ERAS®) components within total hip and total knee replacement surgery. This multidisciplinary consensus review summarizes the literature, and proposes recommendations for the perioperative care of patients undergoing total hip replacement and total knee replacement with an ERAS program.Methods - Studies were selected with particular attention being paid to meta-analyses, randomized controlled trials, and large prospective cohort studies that evaluated the efficacy of individual items of the perioperative treatment pathway to expedite the achievement of discharge criteria. A consensus recommendation was reached by the group after critical appraisal of the literature.Results - This consensus statement includes 17 topic areas. Best practice includes optimizing preoperative patient education, anesthetic technique, and transfusion strategy, in combination with an opioid-sparing multimodal analgesic approach and early mobilization. There is insufficient evidence to recommend that one surgical technique (type of approach, use of a minimally invasive technique, prosthesis choice, or use of computer-assisted surgery) over another will independently effect achievement of discharge criteria.Interpretation - Based on the evidence available for each element of perioperative care pathways, the ERAS® Society presents a comprehensive consensus review, for the perioperative care of patients undergoing total hip replacement and total knee replacement surgery within an ERAS® program. This unified protocol should now be further evaluated in order to refine the protocol and verify the strength of these recommendations.


Plasma and White Blood Cells Show Different miRNA Expression Profiles in Parkinson's Disease.
Parkinson's disease (PD) diagnosis is based on the assessment of motor symptoms, which manifest when more than 50% of dopaminergic neurons are degenerated. To date, no validated biomarkers are available for the diagnosis of PD. The aims of the present study are to evaluate whether plasma and white blood cells (WBCs) are interchangeable biomarker sources and to identify circulating plasma-based microRNA (miRNA) biomarkers for an early detection of PD. We profiled plasma miRNA levels in 99 L-dopa-treated PD patients from two independent data collections, in ten drug-naïve PD patients, and in unaffected controls matched by sex and age. We evaluated expression levels by reverse transcription and quantitative real-time PCR (RT-qPCR) and combined the results from treated PD patients using a fixed effect inverse-variance weighted meta-analysis. We revealed different expression profiles comparing plasma and WBCs and drug-naïve and L-dopa-treated PD patients. We observed an upregulation trend for miR-30a-5p in L-dopa-treated PD patients and investigated candidate target genes by integrated in silico analyses. We could not analyse miR-29b-3p, normally expressed in WBCs, due to the very low expression in plasma. We observed different expression profiles in WBCs and plasma, suggesting that they are both suitable but not interchangeable peripheral sources for biomarkers. We revealed miR-30a-5p as a potential biomarker for PD in plasma. In silico analyses suggest that miR-30a-5p might have a regulatory role in mitochondrial dynamics and autophagy. Further investigations are needed to confirm miR-30a-5p deregulation and targets and to investigate the influence of L-dopa treatment on miRNA expression levels.


Reliability in the oxide vertical-cavity surface-emitting lasers exposed to electrostatic discharge.
Electrostatic discharge(ESD) damage is known as a major source affecting the lifetime of oxide VCSEL. We investigated how ESD damage threshold voltage depends on the size, thickness, and composition of the oxide aperture by measuring the change of output power and reverse leakage current after ESD. ESD damage threshold voltage increased with the size of the oxide aperture, regardless of the thickness and the composition of the oxide aperture. However, damaged devices with thinner oxide layers showed relatively longer lifetime in the reliability test. The reliability data also showed that the VCSELs exposed to ESD have steeper power declines in reliability test than normal devices. This may be due to the defects formed in the active medium by ESD.


Solitary bronchial amyloid presenting with haemoptysis.
Pulmonary amyloidosis can be classified into tracheobronchial diffuse alveolar-septal and nodular parenchymal forms. Tracheobronchial amyloidosis can be further subdivided into diffuse and focal varieties. The latter is rare. We report a patient with a focal intrabronchial deposit of amyloid who presented with haemoptysis. The haemoptysis ceased following bronchoscopic removal of this deposit.


Vitamin D receptor gene polymorphism: association with Crohn's disease susceptibility.
The vitamin D receptor (VDR) gene represents a strong positional candidate susceptibility gene for inflammatory bowel disease (IBD). The VDR gene maps to a region on chromosome 12 that has been shown to be linked to IBD by genome screening techniques. It is the cellular receptor for 1,25(OH)(2) vitamin D(3) (calcitriol) which has a wide range of different regulatory effects on the immune system. IBD is characterised by activation of the mucosal immune system. To determine if polymorphisms in the VDR gene are associated with susceptibility to IBD SUBJECTS: European Caucasoids: 158 patients with ulcerative colitis, 245 with Crohn's disease, and 164 cadaveric renal allograft donor controls. Single nucleotide polymorphisms (TaqI, ApaI, and FokI) in VDR were typed in patients with Crohn's disease, ulcerative colitis, and controls by polymerase chain reaction with sequence specific primers. There were significantly more homozygotes for the TaqI polymorphism at codon 352 of exon 8 (genotype "tt") among patients with Crohn's disease (frequency 0.22) than patients with ulcerative colitis (0.12) or controls (0.12) (odds ratio 1.99; 95% confidence interval 1.14-3.47; p=0.017). This study provides preliminary evidence for a genetic association between Crohn's disease susceptibility and a gene that lies within one of the candidate regions determined by linkage analysis.


Neuron/target plasticity in the peripheral gustatory system.
Taste bud volume on the anterior tongue in adult rats is matched by an appropriate number of innervating geniculate ganglion cells. The larger the taste bud, the more geniculate ganglion cells that innervate it. To determine if such a match is perturbed in the regenerated gustatory system under different dietary conditions, taste bud volumes and numbers of innervating neurons were quantified in adult rats after unilateral axotomy of the chorda tympani nerve and/or maintenance on a sodium-restricted diet. The relationship between taste bud size and innervation was eliminated in rats merely fed a sodium-restricted diet; individual taste bud volumes were smaller than predicted by the corresponding number of innervating neurons. Surprisingly, the relationship was disrupted in a similar way on the intact side of the tongue in unilaterally sectioned rats, with no diet-related differences. The mismatch in these groups was due to a decrease in average taste bud volumes and not to a change in numbers of innervating ganglion cells. In contrast, individual taste bud volumes were larger than predicted by the corresponding number of innervating neurons on the regenerated side of the tongue; again, with no diet-related differences. However, the primary variable responsible for disrupting the function on the regenerated side was an approximate 20% decrease in geniculate ganglion cells available to innervate taste buds. Therefore, the neuron/target match in the peripheral gustatory system is susceptible to surgical and/or dietary manipulations that act through multiple mechanisms. This system is ideally suited to model sensory plasticity in adults.


Sedative and anticonvulsant effects of adenosine analogs in mouse and rat.
The behavioral and physiological effects of L-phenylisopropyladenosine, cyclohexyladenosine and 2-chloroadenosine were examined in mice and rats. These analogs of adenosine are agonists which bind with high affinity to putative central A1 receptors in vitro. Relatively low doses of these drugs administered i.p. produced marked sedation and hypothermia; higher doses resulted in an almost complete cessation of spontaneous motor activity as well as some ataxia. These analogs also antagonized seizures elicited by a variety of convulsants with different mechanisms of action. The differences observed in the anticonvulsant potencies of the analogs suggest that these effects are not produced by the interaction of these drugs with a single class of adenosine receptor. In particular, 2-chloroadenosine and cyclohexyladenosine appear to be more related to each other pharmacologically than to L-phenylisopropyladenosine. Because some of the anticonvulsant actions of L-phenylisopropyladenosine are not reversed by the adenosine antagonist theophylline, and are not shared by the other analogs, these may reflect actions mediated by other, perhaps nonpurinergic receptors. Although benzodiazepines also have sedative, hypothermic and anticonvulsant properties, responses to benzodiazepines can be clearly dissociated from responses to the adenosine agonists.


The "Race" Toward Diversity, Inclusion, and Equity in Pathology: The Johns Hopkins Experience.
With 3.8% black trainees in 2012, pathology had significantly fewer trainees from groups underrepresented in medicine compared to other specialties. To address this, faculty in the Johns Hopkins Department of Pathology established an outreach program and funded rotation for students underrepresented in medicine and from disadvantaged groups. The aims were to increase exposure to the field and improve diversity, inclusion, and equity in pathology. A 1-month rotation for students underrepresented in medicine was established in 2013. Rotation schedules tailored to each rotator's interests included resident conferences and individual faculty meetings. In 2016, a proactive outreach program was established. Faculty visited historically black medical schools and underrepresented in medicine student groups at other institutions, where they gave a "Careers in Pathology" presentation targeted to second- and third-year medical students. Faculty also attended underrepresented in medicine student conferences and participated in high school student programs to further expand the underrepresented in medicine pipeline into medicine and pathology. Since 2016, fourteen outreach presentations have been delivered. The number of rotators increased from 1 in 2013 to 18 in July 2019. Rotators self-identified as African, African American, Hispanic, and Native American. Most were second- to fourth-year medical students, and 1 was a pathology resident. Six rotators are currently pathology residents, and others are strongly considering applying to pathology. The outreach efforts account for the success of our rotation, which, in turn, has had a positive impact on interest in pathology. However, we recognize barriers to retention and intend to incorporate additional professional development activities to further address equity.


No Association between the Plasmodium vivax crt-o MS334 or In9pvcrt Polymorphisms and Chloroquine Failure in a Pre-Elimination Clinical Cohort from Malaysia with a Large Clonal Expansion.
Increasing reports of resistance to a frontline malaria blood-stage treatment, chloroquine (CQ), raises concerns for the elimination of Plasmodium vivax. The absence of an effective molecular marker of CQ resistance in P. vivax greatly constrains surveillance of this emerging threat. A recent genetic cross between CQ sensitive (CQS) and CQ resistant (CQR) NIH-1993 strains of P. vivax linked a moderate CQR phenotype with two candidate markers in P. vivax CQ resistance transporter gene (pvcrt-o): MS334 and In9pvcrt. Longer TGAAGH motif lengths at MS334 were associated with CQ resistance, as were shorter motifs at the In9pvcrt locus. In this study, high-grade CQR clinical isolates of P. vivax from a low endemic setting in Malaysia were used to investigate the association between the MS334 and In9pvcrt variants and treatment efficacy. Among a total of 49 independent monoclonal P. vivax isolates assessed, high-quality MS334 and In9pvcrt sequences could be derived from 30 (61%) and 23 (47%), respectively. Five MS334 and six In9pvcrt alleles were observed, with allele frequencies ranging from 2 to 76% and 3 to 71%, respectively. None of the clinical isolates had the same variant as the NIH-1993 CQR strain, and none of the variants were associated with CQ treatment failure (all P > 0.05). Multi-locus genotypes (MLGs) at 9 neutral microsatellites revealed a predominant P. vivax strain (MLG6) accounting for 52% of Day 0 infections. The MLG6 strain comprised equal proportions of CQS and CQR infections. Our study reveals complexity in the genetic basis of CQ resistance in the Malaysian P. vivax pre-elimination setting and suggests that the proposed pvcrt-o MS334 and In9pvcrt markers are not reliable markers of CQ treatment efficacy in this setting. Further studies are needed in other endemic settings, applying hypothesis-free genome-wide approaches, and functional approaches to understand the biological impact of the TGAAGH repeats linked to CQ response in a cross are warranted to comprehend and track CQR P. vivax.


Long-Acting Local Anesthetics for Total Knee Arthroplasty: Past, Present, and Future.
Pain management remains a challenge in the optimization of outcomes after total knee arthroplasty. Multimodal analgesia is commonplace for modern elective joint replacement, combining various medications and anesthetics along the pain pathway. Local analgesics have the advantage of avoiding systemic effects and offering concentrated local delivery of medications. Long-acting local anesthetics provide the added advantage of providing sustained pain relief when other treatment options may no longer be effective. It is important to provide an update on current local analgesic strategies available with a review of the current literature, outlining the potential benefits and unique considerations of each treatment. Novel medications in development targeting pain management following total knee arthroplasty are possible options in the future.


Effects of a high-fat low-carbohydrate diet under different energy conditions on glucose homeostasis and fatty liver development in rats and on gluconeogenesis in the isolated perfused liver.
The beneficial effects of high-fat low-carbohydrate (HFLC) diets on glucose metabolism have been questioned and their effects on liver metabolism are not totally clear. The aim of this work was to investigate the effects of an HFLC diet under different energy conditions on glucose homeostasis, fatty liver development, and hepatic gluconeogenesis using the isolated perfused rat liver. HFLC diet (79% fat, 19% protein, and 2% carbohydrates in Kcal%) was administered to rats for 4 weeks under three conditions: ad libitum (hypercaloric), isocaloric, and hypocaloric (energy reduction of 20%). Fasting blood glucose levels and total fat in the liver were higher in all HFLC diet rats. Oral glucose tolerance was impaired in isocaloric and hypercaloric groups, although insulin sensitivity was not altered. HFLC diet also caused marked liver metabolic alterations: higher gluconeogenesis rate from lactate and a reduced capacity to metabolize alanine, the latter effect being more intense in the hypocaloric condition. Thus, even when HFLC diets are used for weight loss, our data imply that they can potentially cause harmful consequences for the liver.


Integrative prescreening in analysis of multiple cancer genomic studies.
In high throughput cancer genomic studies, results from the analysis of single datasets often suffer from a lack of reproducibility because of small sample sizes. Integrative analysis can effectively pool and analyze multiple datasets and provides a cost effective way to improve reproducibility. In integrative analysis, simultaneously analyzing all genes profiled may incur high computational cost. A computationally affordable remedy is prescreening, which fits marginal models, can be conducted in a parallel manner, and has low computational cost. An integrative prescreening approach is developed for the analysis of multiple cancer genomic datasets. Simulation shows that the proposed integrative prescreening has better performance than alternatives, particularly including prescreening with individual datasets, an intensity approach and meta-analysis. We also analyze multiple microarray gene profiling studies on liver and pancreatic cancers using the proposed approach. The proposed integrative prescreening provides an effective way to reduce the dimensionality in cancer genomic studies. It can be coupled with existing analysis methods to identify cancer markers.


Maintenance use of antidepressants in Dutch general practice: non-guideline concordant.
There is hardly evidence on maintenance treatment with antidepressants in primary care. Nevertheless, depression guidelines recommend maintenance treatment i.e. treatment to prevent recurrences, in patients with high risk of recurrence, and many patients use maintenance treatment with antidepressants. This study explores the characteristics of patients on maintenance treatment with antidepressants in general practice, and compares these characteristics with guideline recommendations for maintenance treatment. We used data (baseline, two-year and four-year follow-up) of primary care respondents with remitted depressive disorder (≥6 months) from the Netherlands Study of Depression and Anxiety (n = 776). Maintenance treatment was defined as the use of an antidepressant for ≥12 months. Multilevel logistic regression was used to describe the association between sociodemographic, clinical and care characteristics and use of maintenance treatment with antidepressants. Older patients, patients with a lower education, those using benzodiazepines or receiving psychological/psychiatric care and patients with a concurrent history of a dysthymic or anxiety disorder more often received maintenance treatment with antidepressants. Measurements were not made at the start of an episode, but at predetermined points in time. Diagnoses were based on interview (CIDI) data and could therefore in some cases have been different from the GP diagnosis. Since patients with chronic or recurrent depression do not use maintenance treatment with antidepressants more often, characteristics of patients on maintenance treatment do not fully correspond with guideline recommendations. However, patients on maintenance treatment appear to be those with more severe disorder and/or more comorbidity.


Chromosomal distribution of two multigene families and the unusual occurrence of an X1X1X2X2/X1X2Y sex chromosome system in the dolphinfish (Coryphaenidae): an evolutionary perspective.
Dolphinfishes (Coryphaenidae) are pelagic predators distributed throughout all tropical and subtropical oceans and are very important for commercial, traditional, and sport fishing. This small family contains the Coryphaena hippurus and Coryphaena equiselis species whose chromosomal aspects remain unknown, despite recent advances in cytogenetic data assimilation for Perciformes. In this study, both species were cytogenetically analyzed using different staining techniques (C-, Ag-, and CMA3 banding) and fluorescence in situ hybridization, to detect 18S rDNA and 5S rDNA. C. hippurus females exhibit 2n = 48 chromosomes, with 2m+4sm+42a (NF = 54). In C. equiselis, where both sexes could be analyzed, females displayed 2n = 48 chromosomes (2m+6sm+40a) and males exhibited 2n = 47 chromosomes (3m+6sm+38a) (NF = 56), indicating the presence of X1X1X2X2/X1X2Y multiple sex chromosomes. Sex-chromosome systems are rare in Perciformes, with this study demonstrating the first occurrence in a marine pelagic species. It remains unknown as to whether this system extends to other populations; however, these data are important with respect to evolutionary, phylogenetic, and speciation issues, as well as for elucidating the genesis of this unique sex system.


The role of military service in preventing depression in China: evidence from a nationally representative longitudinal survey.
Despite recognition in the West that military veterans experience more mental health issues than the general population, little research has focused on this subject in China. This study examined the associations between male veterans' military experience and depression in China. A sample of 12,914 men including 669 veterans was included in the final analysis and propensity score matching, multivariable regressions and fixed effect model were used. The military experience was associated with a lower likelihood of depression in male veterans. In the subgroup analysis, military experience was associated with a lower likelihood of depression among married and urban male veterans. Military experience was also associated with a lower likelihood of depression in both "junior college and above" and "below junior college" groups. In contrast, evidence was lacking regarding the associations between military experience and depression for unmarried and rural veterans. Individual characteristics could influence the relationship between military experience and depression in male veterans, and the mental health of veterans should be paid more attention and guaranteed.


Evolution of insulin resistance in New Zealand obese mice.
The etiology of non-insulin-dependent diabetes mellitus (NIDDM) is not known. Hyperglycemia is due to increased hepatic glucose production (HGP), decreased glucose uptake, and impaired insulin secretion. It is unknown if these defects are coinherited or if one precedes and causes the others. The aim of this study was to determine the earliest defects in the evolution of the syndrome in the New Zealand obese (NZO) mouse, a polygenic model of NIDDM. NZO and control NZC mice were studied at 4-5 and 20 wk of age. Glucose turnover and glucose uptake in individual tissues were measured basally and during a hyperinsulinemic clamp. First-phase insulin secretion was measured after an intravenous glucose load. HGP was higher in the NZO mice both basally and during the clamp at both ages. At 4-5 wk of age, there was evidence of insulin insensitivity in brown adipose tissue, soleus, diaphragm, red quadriceps, and red gastrocnemius but not in heart, white quadriceps, and white gastrocnemius. In 20-wk-old mice, insulin responsiveness was decreased in white and brown adipose tissue and soleus muscle but not in heart, diaphragm, red and white quadriceps, and red and white gastrocnemius. First-phase insulin secretion (percentage rise above basal) 3 min after the glucose bolus was impaired in NZO mice at both ages. We conclude that hepatic glucose overproduction, brown adipose tissue and skeletal muscle insulin resistance, and impaired first-phase insulin secretion are all early abnormalities in the NZO mouse.


A 12-month survey of gastrointestinal helminth infections of cervids kept in two zoos in Belgium.
Infections with helminths are a major health issue in captive and wild deer. In this study, fecal egg count patterns and clinical signs associated with gastrointestinal nematodes were assessed for 12 mo in nine cervid herds kept under different husbandry conditions at two sites. At site 1, an urban zoo, fecal egg counts remained low and no clinical signs of parasitic gastroenteritis were seen in the herds of fallow deer (Dama dama), Dybowski's deer (Cervus nippon dybowski), pudu (Pudu pudu), and reindeer (Rangifer tarandus tarandus). Helminth infection at this site may have been successfully prevented by daily dung removal of the small sandy-soil enclosures, and applying routine anthelmintic treatment was not justified. At site 2, a wild animal park, involved species were red deer (Cervus elaphus hippelaphus), Nelson's elk (Cervus elaphus nelsoni), Père David's deer (Elaphurus davidianus), European elk (Alces alces alces), and reindeer (Rangifer tarandus tarandus). Nematode eggs were frequently encountered in herds of red deer, Nelson's elk, and European elk, which were kept on larger, grassy enclosures that were irregularly cleaned. The trimodal pattern of fecal egg counts in herds from the wild animal park, consisting of a small spring rise in June, a peak in October, and a small rise in February, indicates that infective larvae on pastures are the main source of infection. In addition, routine anthelmintic treatment with fenbendazole in April and July limited egg shedding, but reinfection rapidly occurred. In two European elk and one reindeer, increasing fecal egg counts were associated with loss of fecal consistency and reduced appetite. Three genera and three species of nematodes were recovered at necropsy of one red deer and three Nelson's elk: Spiculopteragia spiculoptera, Trichostrongylus spp., Nematodirus filicollis, Capillaria spp., Oesophagostomum radiatum, and Trichuris spp., with total worm counts between 950 and 8,700.


Temporal dynamics of two-photon-pumped amplified spontaneous emission in slab organic crystals.
We have studied the ultrafast dynamics of two-photon-pumped amplified spontaneous emission (ASE) from a single crystal by the time-resolved fluorescence upconversion technique. With the increase of two-photon pump intensities, the emission decay time is dramatically shortened by 30 times (from 3ns to approximately 87 ps), and the energy migration rate is acutely enhanced when ASE occurs. The stripe length is also found to play an important role in the formation of the ASE. Meanwhile, the gain coefficient is evaluated to be 15cm(-1) for 560nm at an excitation intensity of 2.3mJ/pulse/cm(2) by the variable stripe length technique.


Prevalence of avian influenza viruses, Borrelia garinii, Mycobacterium avium, and Mycobacterium avium subsp. paratuberculosis in waterfowl and terrestrial birds in Slovakia, 2006.
The prevalence of Borrelia, Mycobacteria and avian influenza virus (AIV) infections, together with the distribution of different AIV subtypes, was studied in migratory waterfowl and terrestrial birds trapped in three localities in Slovakia during 2006. Samples obtained from waterfowl captured in the Senianske Ponds area of Eastern Slovakia showed the highest diversity of AIV isolates. A total of 13 different subtypes were detected in 19 samples from this location (H1N2, H2N2, H3N2, H6N6, H7N6, H9N2, H9N5, H9N6, H10N5, H10N6, H12N6, H13N6, and H16N6). H3N5 virus was detected in 50% of passerines testing positive for AIV in the Parizske Wetlands, with H7N2, H9N2, H9N5, H12N1, and H13N2 infections also recorded at this locality. H9N5 virus predominated in passerines captured at Trnava Ponds, with isolates H1N6, H6N5, H7N2, H7N6, H10N3, and H10N6 also detected at this location. There were five cases where different AIV infections were detected in oropharyngeal and cloacal samples originating from the same bird (H13N6 and H1N2; H10N5 and H12N6; H9N5 and H6N5; H10N6 and H7N6; and H9N2 and H3N5 in the oropharynx and cloaca, respectively). Between 21% and 52% of captured birds tested positive for Borrelia burgdorferi sensu lato, with the proportion infected depending on bird species and locality. Samples were characterized by polymerase chain reaction-restriction fragment length polymorphism analysis and identified as Borrelia garinii species (either B/B' or R/R' pattern). Mycobacteria were detected in 42% and 26% of waders captured at Senianske Ponds and marsh-dwelling passerines captured in the Parizske Wetlands, respectively. Interestingly, forest-dwelling passerine species caught in the Trnava Ponds region were tested negative for Mycobacteria.


Myocardial ischemia in patients with hypertrophic cardiomyopathy: contribution of inadequate vasodilator reserve and elevated left ventricular filling pressures.
To study the mechanism and hemodynamic significance of myocardial ischemia in hypertrophic cardiomyopathy, 20 patients (nine with resting left ventricular outflow tract obstruction greater than or equal to 30 mm Hg) with a history of angina pectoris and angiographically normal coronary arteries underwent a pacing study with measurement of great cardiac vein flow, lactate and oxygen content, and left ventricular filling pressure. Compared with 28 control subjects without hypertrophic cardiomyopathy, their resting coronary blood flow was higher (91 +/- 27 vs 66 +/- 17 ml/min; p less than .001) and their coronary resistance was lower (1.13 +/- 0.38 vs 1.55 +/- 0.45 mm Hg/ml/min; p less than .001). Left ventricular end-diastolic pressure (16 +/- 6 vs 11 +/- 3 mm Hg; p less than .001) and pulmonary arterial wedge pressure (13 +/- 5 vs 7 +/- 3 mm Hg; p less than .001) were significantly higher in patients with hypertrophic cardiomyopathy. During pacing, coronary flow rose in both groups, although coronary and myocardial hemodynamics differed greatly. In contrast to the linear increase in flow in control subjects up to heart rate of 150 beats/min (66 +/- 17 to 125 +/- 28 ml/min), patients with hypertrophic cardiomyopathy demonstrated an initial rise in flow to 133 +/- 31 ml/min at an intermediate heart rate of 130 beats/min. At this point, 12 of 20 patients developed their typical chest pain. With continued pacing to a heart rate of 150 beats/min, mean coronary flow fell to 114 +/- 29 ml/min (p less than .002), with 18 of 20 patients experiencing their typical chest pain and metabolic evidence of myocardial ischemia. This fall in coronary flow was associated with a substantial rise in left ventricular end-diastolic pressure (30 +/- 9 mm Hg immediately after peak pacing). In the 14 patients whose coronary flow actually fell from intermediate to peak pacing, the rise in left ventricular end-diastolic pressure in the same interval was greater than that of the six patients whose flow remained unchanged or increased (11 +/- 8 vs 2 +/- 2 mm Hg; p less than .01). In addition, despite metabolic and hemodynamic evidence of myocardial ischemia, the arteriovenous O2 difference actually narrowed at peak pacing. Thus most patients with hypertrophic cardiomyopathy achieved maximum coronary vasodilation and flow at modest increases in heart rate. Elevation in left ventricular filling pressure, probably related to ischemia-induced changes in ventricular compliance, was associated with a decline in coronary flow.(ABSTRACT TRUNCATED AT 400 WORDS)


Deep transformers and convolutional neural network in identifying DNA N6-methyladenine sites in cross-species genomes.
As one of the most common post-transcriptional epigenetic modifications, N6-methyladenine (6 mA), plays an essential role in various cellular processes and disease pathogenesis. Therefore, accurately identifying 6 mA modifications is necessary for a deep understanding of cellular processes and other possible functional mechanisms. Although a few computational methods have been proposed, their respective models were developed with small training datasets. Hence, their practical application is quite limited in genome-wide detection. To overcome the existing limitations, we present a novel model based on transformer architecture and deep learning to identify DNA 6 mA sites from the cross-species genome. The model is constructed on a benchmark dataset and explored a feature derived from pre-trained transformer word embedding approaches. Subsequently, a convolutional neural network was employed to learn the generated features and generate the prediction outcomes. As a result, our predictor achieved excellent performance during independent test with the accuracy and Matthews correlation coefficient (MCC) of 79.3% and 0.58, respectively. Overall, its performance achieved better accuracy than the baseline models and significantly outperformed the existing predictors, demonstrating the effectiveness of our proposed hybrid framework. Furthermore, our model is expected to assist biologists in accurately identifying 6mAs and formulate the novel testable biological hypothesis. We also release source codes and datasets freely at https://github.com/khanhlee/bert-dna for front-end users.


Radiofrequency treatment alters cancer cell phenotype.
The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease. Here, we report that pancreatic cancer cell phenotype was altered in response to a physical method for cancer therapy, a non-invasive radiofrequency (RF) treatment, which is currently being developed for human trials. We provide a battery of tests to explore these phenotype characteristics. Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment. These may have consequences for tissue architecture, for diffusion of anti-cancer therapeutics and cancer cell susceptibility within the tumor. Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. We also report, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. Additionally, we provide evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment.


A Novel Inorganic Sulfur Compound Metabolizing Ferroplasma-Like Population Is Suggested to Mediate Extracellular Electron Transfer.
Mining and processing of metal sulfide ores produces waters containing metals and inorganic sulfur compounds such as tetrathionate and thiosulfate. If released untreated, these sulfur compounds can be oxidized to generate highly acidic wastewaters [termed 'acid mine drainage (AMD)'] that cause severe environmental pollution. One potential method to remediate mining wastewaters is the maturing biotechnology of 'microbial fuel cells' that offers the sustainable removal of acid generating inorganic sulfur compounds alongside producing an electrical current. Microbial fuel cells exploit the ability of bacterial cells to transfer electrons to a mineral as the terminal electron acceptor during anaerobic respiration by replacing the mineral with a solid anode. In consequence, by substituting natural minerals with electrodes, microbial fuel cells also provide an excellent platform to understand environmental microbe-mineral interactions that are fundamental to element cycling. Previously, tetrathionate degradation coupled to the generation of an electrical current has been demonstrated and here we report a metagenomic and metatranscriptomic analysis of the microbial community. Reconstruction of inorganic sulfur compound metabolism suggested the substrate tetrathionate was metabolized by the Ferroplasma-like and Acidithiobacillus-like populations via multiple pathways. Characterized Ferroplasma species do not utilize inorganic sulfur compounds, suggesting a novel Ferroplasma-like population had been selected. Oxidation of intermediate sulfide, sulfur, thiosulfate, and adenylyl-sulfate released electrons and the extracellular electron transfer to the anode was suggested to be dominated by candidate soluble electron shuttles produced by the Ferroplasma-like population. However, as the soluble electron shuttle compounds also have alternative functions within the cell, it cannot be ruled out that acidophiles use novel, uncharacterized mechanisms to mediate extracellular electron transfer. Several populations within the community were suggested to metabolize intermediate inorganic sulfur compounds by multiple pathways, which highlights the potential for mutualistic or symbiotic relationships. This study provided the genetic base for acidophilic microbial fuel cells utilized for the remediation of inorganic sulfur compounds from AMD.


Soliton-induced relativistic-scattering and amplification.
Solitons are of fundamental importance in photonics due to applications in optical data transmission and also as a tool for investigating novel phenomena ranging from light generation at new frequencies and wave-trapping to rogue waves. Solitons are also moving scatterers: they generate refractive index perturbations moving at the speed of light. Here we found that such perturbations scatter light in an unusual way: they amplify light by the mixing of positive and negative frequencies, as we describe using a first Born approximation and numerical simulations. The simplest scenario in which these effects may be observed is within the initial stages of optical soliton propagation: a steep shock front develops that may efficiently scatter a second, weaker probe pulse into relatively intense positive and negative frequency modes with amplification at the expense of the soliton. Our results show a novel all-optical amplification scheme that relies on soliton induced scattering.


[Outcomes after surgical repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries: a series of 104 cases].
Objective: To examine the early and midterm surgical outcome of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA/VSD/MAPCA) using revised surgical strategies. Methods: A retrospective analysis of clinical data, surgical methods, and follow-up results was performed of 104 cases of PA/VSD/MAPCA in Department of Cardiovascular Surgery, Guangzhou Women and Children's Medical Center from January 2017 to September 2022. There were 55 males and 49 females, aged (M(IQR)) 33.9 (84.0) months (range: 0.5 to 209.6 months) at the first surgical procedures. The anatomical classification included 89 cases of type B and 15 cases of type C. The number of major aortopulmonary collateral arteries was 4.2 (3.0) (range: 1 to 8). The Kaplan-Meier method was used for survival estimation. Results: In the first stage of surgery, 50 patients underwent a complete primary repair, 12 patients underwent partial repair, 32 patients underwent palliative right ventricular-pulmonary artery connection, and only 10 patients chose the Blalock-Taussig shunt. There were 10 cases of early death. In the second stage, 14 patients underwent complete repair and 4 patients underwent partial repair with no early death. The interval between the two surgeries was 19 (10) months (range: 9 to 48 months). Finally, during the 40 (34) months follow-up period, a total of 64 patients were complete repair and the right/left ventricular pressure ratio after complete repair was 0.63±0.16 (range: 0.36 to 1.00). Survival analysis showed that survival rates at 1 and 5 years after first-stage surgery were both 89.4% (95%CI: 83.5% to 95.3%). At 28 (34) months (range: 1 to 67 months) of follow-up after complete repair, the survival analysis showed that the survival rates at 1 and 5 years were both 95.2% (95%CI: 89.9% to 100%). Conclusions: Using combined approaches tailored to individual patients and optimized unifocalization strategy, the complete repair rate at one stage and the cumulative complete repair rate at 5 years improved significantly with a lower right/left ventricular pressure ratio and satisfactory early and intermediate survival.


Variation in multiple paternity in natural populations of a free-spawning marine invertebrate.
For free-spawning marine invertebrates, fertilization processes control the genetic diversity of offspring. Each egg can potentially be fertilized by a sperm from a different male, and hence genetic diversity within a brood varies with levels of multiple paternity. Yet, few studies have characterized the frequency of multiple paternity in natural spawns. We analysed patterns of multiple paternity in two populations of the colonial ascidian Botryllus schlosseri using microsatellites. Because previous studies have shown that at moderate to high population densities, competition among male-phase B. schlosseri colonies results in the nearest male dominating the paternity of a brood, we specifically tested the effect of population density on patterns of paternity. Paternity was estimated using three multilocus indices: minimum number of fathers, counts of sperm haplotypes, and effective paternity (K(E)). Multiple paternity was evident in more than 92% of the broods analysed, but highly variable, with a few broods displaying unequal contributions of different males. We found no effect of population density on multiple paternity, suggesting that other factors may control paternity levels. Indirect benefits from increasing the genetic diversity of broods are a possible explanation for the high level of multiple paternity in this species.