The influence of shape and charge on protein corona composition in common gold nanostructures.
With increasing importance of gold nanoparticles (AuNPs) in the medical field, the understanding of their interactions in biological environments is essential. It is known that the exposure to biological fluids of particles in the nanometric range leads to accumulation of proteins on the particle surface proximity, generating the so-called protein corona. This fact can completely change the properties of AuNPs, thus drastically influencing the characteristics and intended purpose of the particles. Therefore, deep insight on the formation and composition of this protein corona is of extreme importance. Between the different factors that can alter the corona formation, our study focuses on the influence of the shape and particle surface charge. In detail, four different shapes of nanometrical scale (spheres, rods, stars and cages) of comparable size were used, all of them stabilized with three different heterofunctionalized poly(ethylene glycol) thiol (R-PEG-SH) linkers (R = OCH3, COOH or NH2) to check the effect of charge as well. After incubation with human serum, abundant proteins were identified via liquid chromatography-electrospray ionization-tandem mass spectroscopy (LC ESI MS/MS) and compared in terms of their relative abundance. On the basis of statistical evaluations, the shape of our AuNPs showed a greater influence than the surface charge. Especially, cage-shaped AuNPs showed a lower amount of total corona proteins. This shape showed differences in the abundances of individual proteins like albumin, vitronectin and members of the complement system. These results indicate that nanocages could present an improved biocompatibility compared with the other shapes due to the high curvature areas and dense ligation on the flat surfaces that could hinder opsonisation and fast removal by the immune system.


Update: cholera--Western Hemisphere, 1992.
Epidemic cholera continues to spread throughout Central and South America (Figure 1). This report updates the surveillance of this problem during 1992.


The current state of carnivore cognition.
The field of animal cognition has advanced rapidly in the last 25 years. Through careful and creative studies of animals in captivity and in the wild, we have gained critical insights into the evolution of intelligence, the cognitive capacities of a diverse array of taxa, and the importance of ecological and social environments, as well as individual variation, in the expression of cognitive abilities. The field of animal cognition, however, is still being influenced by some historical tendencies. For example, primates and birds are still the majority of study species in the field of animal cognition. Studies of diverse taxa improve the generalizability of our results, are critical for testing evolutionary hypotheses, and open new paths for understanding cognition in species with vastly different morphologies. In this paper, we review the current state of knowledge of cognition in mammalian carnivores. We discuss the advantages of studying cognition in Carnivorans and the immense progress that has been made across many cognitive domains in both lab and field studies of carnivores. We also discuss the current constraints that are associated with studying carnivores. Finally, we explore new directions for future research in studies of carnivore cognition.


Counterselection of prokaryotic ribosomal RNA during reverse transcription using non-random hexameric oligonucleotides.
Ribosomal RNA (rRNA) is the major component in total RNA extracts, interfering with the synthesis of cDNA corresponding to messenger RNA (mRNA). In this study, we present a novel strategy for selectively discriminating against rRNA and favoring mRNA from prokaryotes during synthesis of cDNA by reverse transcriptase. Our technique is based on the fact that rRNA sequences, in many species, are G+C rich relative to the genome at large, and highly conserved among prokaryotes. The sequence TTTT is therefore rarely found in rRNA sequences. However, TTTT priming sites are found at a much higher frequency in protein-encoding gene sequences. We designed specific hexamers (HD/DHTTTT) to prime reverse transcription reactions resulting in a selective synthesis of cDNA corresponding to mRNA from prokaryotic total RNA extractions.


Evaluation of the 3M™ Petrifilm™ Rapid E. coli/Coliform Count Plate for the Enumeration of E. coli and Coliforms: Collaborative Study, First Action: 2018.13.
The 3M™ Petrifilm™ Rapid E. coli/Coliform Count Plate is a selective and differential sample-ready-culture medium designed for the rapid enumeration of Escherichia coli (E. coli) and coliforms in the food and beverage industries. The 3M Petrifilm Rapid E. coli/Coliform Count Plate was compared to the U.S. Food and Drug Administration Bacteriological Analytical Manual (BAM) Chapter 4 Enumeration of Escherichia coli and the Coliform Bacteria, the International Organization of Standards (ISO) 4832:2006 Microbiology of food and animal feeding stuffs - Horizontal method for the enumeration of coliforms-Colony-count technique, and ISO 16649-2:2017 Microbiology of food and animal feeding stuffs-Horizontal method for the enumeration of beta-glucuronidase-positive Escherichia coli-Part 2 Colony-count technique at 44 degrees C using bromo-4-chloro-3- indolyl beta-D-glucuronide methods for the enumeration of E. coli and coliforms in dry dog kibble. The candidate method was evaluated using two diluents, Butterfield's phosphate buffered diluent and peptone salt solution, in a paired study design with each reference method in a multi-laboratory collaborative study following the current AOAC Validation Guidelines. Three target contamination levels and an uninoculated control level were evaluated. The candidate and reference methods were not statistically different at each contamination level. Reproducibility values obtained during the collaborative study were similar between the candidate and reference methods. These results demonstrate that the candidate method is equivalent to the reference methods. 3M Petrifilm Rapid E. coli/Coliform Count Plate was recommended for Official First Action status for enumeration of E. coli and coliforms in a broad range of foods and environmental surfaces.


Adult zebrafish in CNS disease modeling: a tank that's half-full, not half-empty, and still filling.
The zebrafish (Danio rerio) is increasingly used in a broad array of biomedical studies, from cancer research to drug screening. Zebrafish also represent an emerging model organism for studying complex brain diseases. The number of zebrafish neuroscience studies is exponentially growing, significantly outpacing those conducted with rodents or other model organisms. Yet, there is still a substantial amount of resistance in adopting zebrafish as a first-choice model system. Studies of the repertoire of zebrafish neural and behavioral functions continue to reveal new opportunities for understanding the pathobiology of various CNS deficits. Although some of these models are well established in zebrafish, including models for anxiety, depression, and addiction, others are less recognized, for example, models of autism and obsessive-compulsive states. However, mounting data indicate that a wide spectrum of CNS diseases can be modeled in adult zebrafish. Here, we summarize recent findings using zebrafish CNS assays, discuss model limitations and the existing challenges, as well as outline future directions of research in this field.


Surgical Prevention of Weight Regain and Type 2 Diabetes Recurrence in 3 Different Bariatric Operations and Their Differential Long-Term Outcome: An 8-Year Prospective Observational Study.
Comparative data on long-term outcomes of mechanistically different bariatric operations are scarce. In this prospective, observational study, consecutive patients with severe obesity were studied using a predefined reoperation algorithm to determine long-term health outcomes after bariatric surgery (BS): adjustable gastric banding (AGB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion (BPD). All patients were assessed for mortality, postoperative weight loss, rate of reoperation, comorbidities, and quality of life (QoL) 8 years after surgery. Between 1996 and 2008, 2364 Swiss patients, with a mean body mass index of 43 ± 7 kg/m2 (mean ± SD) underwent AGB (n = 1404), RYGB (n = 790), or BPD (n = 170). Two thousand two hundred twenty-eight (94%) were followed for 8 years after BS. Eight-year mortality of the whole study group was 34.3 per 104 person-years. Percent excessive weight loss at 8 years was 56.7 ± 1.4% (95% confidence interval) in AGB, 62.5 ± 2.4% in RYGB and 64.8+-3.0% in BPD. The rate of major reoperation was highest in AGB and significantly lower in RYGB and BPD (63.4 vs 54.3 vs 47.2 per 103 person-years, P < 0.001). Remission of comorbidities was observed across all 3 groups, with key improvement (P < 0.01) in esophagitis in the RYGB group, and type 2 diabetes (T2D) (>60%) in procedures involving duodenal exclusion. Total improvement in QoL was similar between the 3 types of operations but was strongly correlated with weight loss preservation (P < 0.001). BS, at the expense of a high reoperation rate but low procedural mortality, considerably improves the QoL and results in sustained remission of comorbidities, especially T2D using a predefined reoperation algorithm developed to prevent weight regain and operation-specific complications.


Using RNA-Seq to Identify Reference Genes of the Transition from Brown to White Adipose Tissue in Goats.
Brown adipose tissues have unique non-shivering thermogenesis functions, can be found in newborn ruminate animals, and then are gradually replaced by white adipose tissues in adulthood. For the purpose of exploring the intrinsic mechanism underlying the conversion process from brown (BAT) to white adipose tissue (WAT), it is necessary to utilize Quantitative PCR (qPCR) to study gene expression profiling. In this study, we identified reference genes that were consistently expressed during the transformation from goat BAT to WAT using RNA-seq data. Then, twelve genes were evaluated as candidate reference genes for qPCR in goat perirenal adipose tissue using three tools (geNorm, Normfinder, and BestKeeper). In addition, the selected reference genes were used to normalize the gene expression of PGC-1α and GPAT4. It was found that traditional reference genes, such as GAPDH, RPLP0, HPRT1, and PPIA were not suitable for target gene normalization. In contrast, CTNNB, PFDN5, and EIF3M, selected from RNA sequencing data, showed the least variation and were recommended as the best reference genes during the transformation from BAT to WAT.


Association of IL-17A promoter region SNP-rs2275913 with urinary bladder cancer.
Urinary bladder cancer (UBC) is the fourth most common cancer among men and tenth most common cancer in women. This study investigated an association of interleukins -17A promoter region single nucleotide polymorphism (SNP)-rs2275913 with UBC in Pakistani population. Population-based study was designed with 127 UBC patients and 100 healthy individuals. Only UBC Patients were included and other diseases hepatitis or any other malignancy/cancer were excluded from the study. Polymerase chain reaction Restriction fragment length polymorphism technique was used to genotype the rs2275913 SNP in patients and control. Linear regression analysis was performed on the genotype data and allelic frequency data. Online statistical tool was used to calculate ratio of odds. Linear regression analysis showed that there was no association between rs2275913 SNP and UBC patients in the dominant model (OR = 0.815, CI = 0.415-1.6), recessive model (OR = 0.389, CI = 0.014-5.565), codominant model (OR = 0.376, CI=0.013-5.420) and (OR = 0.855, CI = 0.427-1.713). Moreover, among the UBC samples, low-grade non-muscle invasive UBC samples dominant model (OR = 0.722, CI = 0.316-1.637), recessive model (OR = 0.000, CI = 0.000-5.864), codominant model (OR = 0.864, CI = 0.030-12.668), and (OR = 0.788, CI = 0.341-1.806) did also not show any association. When same analysis was performed for high-grade muscle invasive UBC, dominant (OR = 0.936, CI = 0.403-2.155), recessive model (OR = 0.875, CI = 0.031-12.696), and codominant model (OR = 0.864, CI = 0.030-12.668,), and (OR = 0.942, CI = 0.394-2.232) did not show any association. Results revealed that rs2275913 did not show any associated with the high risk of UBC in Pakistani population. Some limitations of the studies are firstly, the samples size and other are detailed information on UBC and role of inflammation.


Regeneration of pancreatic insulin-producing cells by in situ adaptive cell conversion.
The impaired ability to produce or respond to insulin, a hormone synthetized by the pancreatic β-cells, leads to diabetes. There is an excruciating need of finding new approaches to protect or restore these cells once they are lost. Replacement and ex vivo directed reprogramming methods have an undeniable therapeutic potential, yet they exhibit crucial flaws. The in vivo conversion of adult cells to functional insulin-producing cells is a promising alternative for regenerative treatments in diabetes. The stunning natural transdifferentiation potential of the adult endocrine pancreas was recently uncovered. Modulating molecular targets involved in β-cell fate maintenance or in general differentiation mechanisms can further potentiate this intrinsic cell plasticity, which leads to insulin production reconstitution.


[Effect of berberin hydrochloride on blood concentration of cyclosporine A in cardiac transplanted recipients].
To observe the clinic effect of combined use of berberin hydrochloride (Ber) with cyclosporine A (CsA) on the blood concentration of CsA in heart transplanted recipients. The blood concentration of CsA, liver-renal function and blood lipids in 22 heart transplanted recipients, who received Ber-CsA combined therapy, were measured. The whole blood steady state concentration of CsA, C0 and C2, in recipients after being treated with Ber-CsA significantly increased than those before applying Ber-CsA (P < 0.01), with the mean increment of 26% and 18% respectively; the dosage of CsA used decreased in 21 patients by 25-100 mg/d; and the Ber-CsA showed no significant effect on liver-renal function or blood lipids (P > 0.05). Combined use of CsA with Ber could markedly increase the blood concentration of CsA in heart transplanted recipients and reduce the dosage of CsA required, save the fee for medical service, and shows no obvious adverse reaction.


Potential effectiveness and safety of antiviral agents in children with coronavirus disease 2019: a rapid review and meta-analysis.
The COVID-19 outbreak presents a new, life-threatening disease. Our aim was to assess the potential effectiveness and safety of antiviral agents for COVID-19 in children. Electronic databases (MEDLINE, Embase, Web of Science, the Cochrane library, CBM, CNKI, and Wanfang Data) from their inception to March 31, 2020 were searched for randomized controlled trials (RCTs), clinical controlled trials and cohort studies of interventions with antiviral agents for children (less than 18 years of age) with COVID-19. A total of 23 studies with 6,008 patients were included. There was no direct evidence and all of evidence were indirect. The risks of bias in all studies were moderate to high in general. The effectiveness and safety of antiviral agents for children with COVID-19 is uncertain: For adults with COVID-19, lopinavir/ritonavir had no effect on mortality [risk ratio (RR) =0.77; 95% confidence interval (CI), 0.45 to 1.30]. Arbidol and hydroxychloroquine (HCQ) had no benefit on probability of negative PCR test (RR =1.27; 95% CI, 0.93 to 1.73; RR =0.93; 95% CI, 0.73 to 1.18) respectively. For adults with SARS, interferon was associated with reduced corticosteroid dose [weighted mean difference (WMD) = -0.14 g; 95% CI, -0.21 to -0.07] but had no effect on mortality (RR =0.72; 95% CI, 0.28 to 1.88); ribavirin did not reduce mortality (RR =0.68; 95% CI, 0.43 to 1.06) and was associated with high risk of severe adverse reactions; and oseltamivir had no effect on mortality (RR =0.87; 95% CI, 0.55 to 1.38). Ribavirin combined with interferon was also not effective in adults with MERS and associated with adverse reactions. There is no evidence showing the effectiveness of antiviral agents for children with COVID-19, and the clinical efficacy of existing antiviral agents is still uncertain. We do not suggest clinical routine use of antivirals for COVID-19 in children, with the exception of clinical trials.


Real-World Sarilumab Use and Rule Testing to Predict Treatment Response in Patients with Rheumatoid Arthritis: Findings from the RISE Registry.
Clinical trial findings may not be generalizable to routine practice. This study evaluated sarilumab effectiveness in patients with rheumatoid arthritis (RA) and tested the real-world applicability of a response prediction rule, derived from trial data using machine learning (based on C-reactive protein [CRP] > 12.3 mg/l and seropositivity [anticyclic citrullinated peptide antibodies, ACPA +]). Sarilumab initiators from the ACR-RISE Registry, with ≥ 1 prescription on/after its FDA approval (2017-2020), were divided into three cohorts based on progressively restrictive criteria: Cohort A (had active disease), Cohort B (met eligibility criteria of a phase 3 trial in RA patients with inadequate response/intolerance to tumor necrosis factor inhibitors [TNFi]), and Cohort C (characteristics matched to the phase 3 trial baseline). Mean changes in Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) were evaluated at 6 and 12 months. In a separate cohort, predictive rule was tested based on CRP levels and seropositive status (ACPA and/or rheumatoid factor); patients were categorized into rule-positive (seropositive with CRP > 12.3 mg/l) and rule-negative groups to compare the odds of achieving CDAI low disease activity (LDA)/remission and minimal clinically important difference (MCID) over 24 weeks. Among sarilumab initiators (N = 2949), treatment effectiveness was noted across cohorts, with greater improvement noted for Cohort C at 6 and 12 months. Among the predictive rule cohort (N = 205), rule-positive (vs. rule-negative) patients were more likely to reach LDA (odds ratio: 1.5 [0.7, 3.2]) and MCID (1.1 [0.5, 2.4]). Sensitivity analyses (CRP > 5 mg/l) showed better response to sarilumab in rule-positive patients. In real-world setting, sarilumab demonstrated treatment effectiveness, with greater improvements in the most selective population, mirroring phase 3 TNFi-refractory and rule-positive RA patients. Seropositivity appeared a stronger driver for treatment response than CRP, although optimization of the rule in routine practice requires further data.


Δ(5)-Cholenoyl-amino acids as selective and orally available antagonists of the Eph-ephrin system.
The Eph receptor-ephrin system is an emerging target for the development of novel anti-angiogenic therapies. Research programs aimed at developing small-molecule antagonists of the Eph receptors are still in their initial stage as available compounds suffer from pharmacological drawbacks, limiting their application in vitro and in vivo. In the present work, we report the design, synthesis and evaluation of structure-activity relationships of a class of Δ(5)-cholenoyl-amino acid conjugates as Eph-ephrin antagonists. As a major achievement of our exploration, we identified N-(3β-hydroxy-Δ(5)-cholen-24-oyl)-L-tryptophan (UniPR1331) as the first small molecule antagonist of the Eph-ephrin system effective as an anti-angiogenic agent in endothelial cells, bioavailable in mice by the oral route and devoid of biological activity on G protein-coupled and nuclear receptors targeted by bile acid derivatives.


A Bidentate Iodine(III)-Based Halogen-Bond Donor as a Powerful Organocatalyst*.
In contrast to iodine(I)-based halogen bond donors, iodine(III)-derived ones have only been used as Lewis acidic organocatalysts in a handful of examples, and in all cases they acted in a monodentate fashion. Herein, we report the first application of a bidentate bis(iodolium) salt as organocatalyst in a Michael and a nitro-Michael addition reaction as well as in a Diels-Alder reaction that had not been activated by noncovalent organocatalysts before. In all cases, the performance of this bidentate XB donor distinctly surpassed the one of arguably the currently strongest iodine(I)-based organocatalyst. Bidentate coordination to the substrate was corroborated by a structural analysis and by DFT calculations of the transition states. Overall, the catalytic activity of the bis(iodolium) system approaches that of strong Lewis acids like BF3 .


Characterizing the elderly homeless: a 10-year study in Israel.
Since 1980s there is a noticeable change in the homeless population in Western countries. Some researchers titled the change as the "new" homeless that are distinctly different than the "skid row" population described in the past. Among the "new" homeless there are increasing numbers of elderly subjects. The elderly homeless are a fragile and vulnerable group that suffers from high rates of physical and mental problems as well as increased mortality. The aim of the present study was to characterize the "new" elderly homeless. Over a 10-year period each homeless 65 years of age and older was assessed by a psychiatrist. The project was undertaken in Tel-Aviv, Israel, and was feasible due to close co-operation between the Municipal Welfare Department and mental health consultants. The Structured Clinical Interview for DSM-IV (SCID) was the main diagnostic tool. Ninety-eight subjects of 2567 homeless persons located and contacted were elderly (3.8%). Mean age for the elderly sub-group was 71.7+/-5.3 years and the great majority were male 94/98 (95.9%). In 44/98 (44.9%), a formal DSM-IV axis I psychiatric disorder was diagnosed, most common being dementia (15/44) and schizophrenia (15/44). A significant minority of 13/44 (29.5%) were diagnosed and treated prior to becoming homeless. Physical co-morbidity was found in nearly 2/3 subjects. Following intensive case-management by social workers, 35/44 (79.5%) subjects were successfully placed in permanent housing. The main conclusion is that the "new" elderly homeless are typically males suffering from frequent psychiatric morbidity and physical co-morbidity. Intensive case-management succeeded in achieving return to permanent housing in the majority of subjects.


An electrochemical PAH-modified aptasensor for the label-free and highly-sensitive detection of saxitoxin.
Saxitoxin (STX), is one of the most dangerous and widespread paralytic shellfish toxins, causing a severe threat to the ecosystem and human health. So, it is important and highly essential to develop novel techniques for STX detection in a convenient, desirable, and low-cost manner. Herein, this study developed an electrolyte-insulator-semiconductor (EIS) sensor covered with a layer-by-layer prepared, positively-charged weak polyelectrolyte layer of poly (allylamine hydrochloride) (PAH) for the label-free detection of STX. The specific aptamer (Apt) sensitive to STX was electrostatically adsorbed onto the PAH layer. This leads to a preferentially flat orientation of the Apt within the Debye length, thus yielding a reduced charge-screening influence and a higher sensor signal. Each step of sensor surface modification, i.e. PAH adsorption, immobilization of Apt, and attachment of STX, was monitored by capacitance-voltage (C-V) and constant-capacitance (ConCap) measurements. Furthermore, atomic force microscopy (AFM) was employed to characterize the surface morphology and roughness of the PAH layer. Fluorescence microscopy was used to confirm the effective immobilization of Apt onto the PAH-modified EIS sensor. The results showed that the detection range of this aptasensor for STX detection was 0.5-100 nM and the detection limit was as low as 0.05 nM. Furthermore, this aptasensor showed good selectivity and 9 days' stability. The mussel tissue extraction test suggested that this aptasensor can be used to detect STX in real samples. This aptasensor provides a convenient approach for moderate, rapid, and label-free detection of marine biological toxins.


Brain structure and symptom dimension relationships in obsessive-compulsive disorder: a voxel-based morphometry study.
Obsessive-compulsive disorder (OCD) is a clinically heterogenous disorder characterized by temporally stable symptom dimensions. Past inconsistent results from structural neuroimaging studies of OCD may have resulted from the effects of these specific symptom dimensions as well as other socio-demographic and clinical variables upon gray matter (GM) volume. GM volume was measured in 25 adult OCD patients and 20 adult healthy controls using voxel-based morphometry (VBM), controlling for age and total brain GM volume. Univariate and multivariate regression analyses were carried out between regions of GM difference and age, age of onset, medication load, OCD severity, depression severity, and separate symptom dimension scores. Significant GM volumetric differences in OCD patients relative to controls were found in dorsal cortical regions, including bilateral BA6, BA46, BA9 and right BA8 (controls>patients), and bilateral midbrain (patients>controls). Stepwise regression analyses revealed highly significant relationships between greater total OCD symptom severity and smaller GM volumes in dorsal cortical regions and larger GM volumes in bilateral midbrain. Greater age was independently associated with smaller GM volumes in right BA6, left BA9, left BA46 and larger GM volumes in right midbrain. Greater washing symptom severity was independently associated with smaller GM volume in right BA6, while there was a trend association between greater hoarding symptom severity and lower GM volume in left BA6. The sample was relatively small to examine the relationship between symptom scores and GM volumes. Multiple patients were taking medication and had comorbid disorders. These analyses suggest dorsal prefrontal cortical and bilateral midbrain GM abnormalities in OCD that appear to be primarily driven by the effects of total OCD symptom severity. The results regarding the relationship between GM volumes and symptom dimension scores require examination in larger samples.


Mid-pass whole genome sequencing enables biomedical genetic studies of diverse populations.
Historically, geneticists have relied on genotyping arrays and imputation to study human genetic variation. However, an underrepresentation of diverse populations has resulted in arrays that poorly capture global genetic variation, and a lack of reference panels. This has contributed to deepening global health disparities. Whole genome sequencing (WGS) better captures genetic variation but remains prohibitively expensive. Thus, we explored WGS at "mid-pass" 1-7x coverage. Here, we developed and benchmarked methods for mid-pass sequencing. When applied to a population without an existing genomic reference panel, 4x mid-pass performed consistently well across ethnicities, with high recall (98%) and precision (97.5%). Compared to array data imputed into 1000 Genomes, mid-pass performed better across all metrics and identified novel population-specific variants with potential disease relevance. We hope our work will reduce financial barriers for geneticists from underrepresented populations to characterize their genomes prior to biomedical genetic applications.


Before and beyond the precautionary principle: epistemology of uncertainty in science and law.
The precautionary principle has become, in European regulation of science and technology, a general principle for the protection of the health of human beings, animals, plants, and the environment. It requires that "[w]here there are threats of serious or irreversible damage, lack of full scientific certainty shall not be used as a reason for postponing cost-effective measures to prevent environmental degradation". By focusing on situations of scientific uncertainty where data are lacking, insufficient, or inconclusive, the principle introduced a shift from a neutral legal attitude towards science to a bias in favor of safety, and a shift from the paradigm of science certain and objective to the awareness that the legal regulation of science involves decisions about values and interests. Implementation of the precautionary principle is highly variable. A crucial question still needs to be answered regarding the assumption that scientific certainty is a 'normal' characteristic of scientific knowledge. The relationship between technoscience and society has moved into a situation where uncertain knowledge is the rule. From this perspective, a more general framework for a democratic governance of science is needed. In democratic society, science may still have a special authoritative voice, but it cannot be the ultimate word on decisions that only the broader society may make. Therefore, the precautionary model of scientific regulation needs to be informed by an 'extended participatory model' of the relationship between science and society.


Impact of the 2020 COVID-19 Pandemic on Ambulatory Hepatitis C Testing.
Coronavirus disease 2019 (COVID-19) has led to unprecedented modifications to healthcare delivery in the U.S. To preserve resources in preparation for a COVID-19 surge, Boston Medical Center (BMC) implemented workflows to decrease ambulatory in-person visits effective March 16th, 2020. Telemedicine was incorporated into clinical workflows and much preventive care, including Hepatitis C (HCV) testing, was not routinely performed. To explore the impact that the COVID-19 rapid restructuring response has had on HCV testing and identification hospital-wide and in ambulatory settings. BMC utilizes reflex confirmatory testing for HCV. When a sample is HCV Ab positive, it is automatically reflexed for confirmatory RNA and genotype testing. HCV test results for patients were collected daily. We compared unique patient tests for 3.5 month periods before and after March 16th, 2020. Descriptive statistics showed total tests and total new HCV RNA+ before versus after, both hospital-wide and in ambulatory clinics alone. Mean daily tests completed were compared. Hospital-wide, total HCV testing decreased by 49.6%, and new HCV+ patient identification decreased by 42.1%. In ambulatory clinics, testing decreased by 71.9%, and new HCV+ identification decreased by 63.3%. Hospital-wide, mean daily tests decreased by 22.9 tests per day (95% CI: 17.9-28.0, P < .001), and mean daily new HCV+ identification decreased by 0.36 (95% CI: 0.20-0.53, P < .001). In ambulatory clinics, mean daily tests decreased by 22.1 tests per day (95% CI: 17.5-26.7, P < .001) and mean daily HCV+ decreased by 1.40 (95% CI: 1.03-1.76, P < .001). The COVID-19 systematic emergency response led to decreased HCV testing and identification, and in this regard telemedicine acts as a barrier to HCV care. Other public health initiatives must be monitored in the context of telemedicine workflows. Continued monitoring of HCV screening trends is vital, and adaptive approaches to work toward the goal of HCV elimination are needed.


Evaluating the response to locoregional and systemic treatment for hepatocellular carcinoma.
Evaluating the response to different treatments is a decisive factor in the clinical management of patients with hepatocellular carcinoma because it can determine the efficacy of the treatment and because it can detect the recurrence of treated tumors or the appearance of new lesions that can be candidates for new treatments. When locoregional treatments that induce necrosis or molecular therapies are applied, the treated lesions usually change their behavior on imaging studies. It is important to point out that the size of the lesions does not usually decrease, at least initially, and some lesions can even appear to increase in size. For this reason, it is essential to know the mechanisms of action for each treatment applied and the spectrum of findings that these treatments can cause in the different imaging techniques used to assess the response.


Prevalence of inducible paroxysmal supraventricular tachycardia during esophageal electrophysiologic study in patients with unexplained stroke.
The relationships between stroke and atrial tachycardia or atrial fibrillation were previously reported. Electrophysiological study is one of the means, used to detect and evaluate these atrial tachyarrhythmias. But, some other arrhythmias as paroxysmal supraventricular tachycardia, can be induced during electrophysiologic study and their significance in stroke is unknown. The aim of the study was to assess the significance of inducible paroxysmal supraventricular tachycardia (PSVT) in stroke. One hundred thirty seven patients, aged 61+/-12 years had unexplained stroke (group I) and were compared to 60 subjects aged 45+/-18.5 years without stroke and history of tachycardia (group II); Holter monitoring (HM), echocardiogram and esophageal electrophysiologic study (EPS) in basal state and after isoproterenol were performed. Heart disease was noted in 19 group I patients (14%) and 10 group II patients (17%). In group I, atrial fibrillation or tachycardia (AF-AT) was induced in 20 patients (15%) and PSVT was induced in 19 patients (14%) aged 66+/-12 years. In group II, AF/AT was induced in 3 patients (5%); no group II patient had induced PSVT. After 3+/-1 years, in group I, one of 98 patients without induced arrhythmias had new strokes and 2 had AF; 5 patients with induced AT/AF developed AF; 5 patients with induced PSVT had PSVT's, requiring ablation in 4 of them; 1 died from a new stroke; one had a second non-fatal stroke and 3 patients developed AF (16%). In group II, there were no events. In 14% of patients with unexplained stroke, PSVT was inducible during esophageal electrophysiologic study. Further studies are warranted to assess the significance of this finding in patients with unexplained stroke.


Avian epidermal differentiation. II. Adaptive response of permeability barrier to water deprivation and replenishment.
Zebra Finches are the epitome of desert-adapted avian species; i.e. they are able to survive without drinking water for over a year. Whereas transepidermal water loss (TEWL) in naked Zebra Finch nestlings is lower than in adults, and desert adaptation is accompanied by intercellular deposition of epidermal multigranular body (MGB) contents, MGB secretion is reduced as nestlings mature into feathered adults, indicative of less stringent barrier requirements. Here, removal of drinking water resulted in increased intercellular deposition of MGB contents, and TEWL progressively decreased. In contrast, MGB intercellular deposition decreased when birds were rehydrated, with TEWL returning towards normal within 5 days of rehydration. Finally, water-deprivation caused significant changes in epidermal lipid composition that returned toward control levels with rehydration. These studies show that adult Zebra Finches adapt to xeric stress by increased secretion of multigranular bodies resulting in reduced TEWL.


The VersaJet for Breast-Reduction Surgery: Operator Beware.
Modern techniques for breast-reduction surgery depend on large surface de-epithelialization. The current gold standard technique involves the use of a scalpel for sharp debridement and is a time-consuming process that is labor-intensive and often requires an assistant to stabilize the breast. Surgeons who perform breast-reduction surgery continue to search for instruments and innovations that may reduce the time and effort required for successful de-epithelialization. One such innovation is the use of the VersaJet Hydrosurgery system. The purpose of this article is to highlight an important complication that may result from the use of this device. The authors describe their experience with the VersaJet Hydrosurgery System in reduction mammoplasty of 28 breasts. The authors experienced several complications characterized by the formation of epithelial inclusion cysts requiring reoperation. The VersaJet Hydrosurgery system may lead to quicker speeds of de-epithelialization as compared with traditional methods but poses a risk of epidermal cyst formation.


An innovative method of nasal chemical cautery in active anterior epistaxis.
We present a method to cauterize an actively bleeding source in anterior epistaxis. In our experience, this method is efficient, provides full control of the bleeding, and ensures precise cautery of the bleeding source with minimal usage of chemical cautery sticks.


Histamine 4 receptor promotes expression of costimulatory B7.1/B7.2 molecules, CD28 signaling and cytokine production in stress-induced immune responses.
Recently, the expression of histamine 4 receptor (H4R) on neurons was reported, however its function in cells within the central nervous system (CNS) remains poorly understood. To this end, we used the H4R agonist, 4-methylhistamine (4-MeH), and the H4R antagonist, JNJ77777120 (JNJ), to investigate the function of H4R signaling in immune cells in a murine model of chronic stress. Treatment of stressed mice with 4-MeH resulted in an increase in the proportion of lymphocyte subsets (CD3(+), CD8(+), CD28(+), and CD4(+)CD28(+)) and cells expressing the co-stimulatory molecules CD80(+) (B7.1) and CD86(+) (B7.2) in heparinized blood as compared to normal control (NC) and stressed control (SC) groups. We also observed that as compared to NC and SC mice, 4-MeH-treated mice showed greater production of IL-2(+), IL-6(+), IL-9(+), IL-21(+), and IL-27(+) cytokines in the spleen and by splenic CD4(+) T cells. Furthermore, 4-MeH treatment of stressed mice led to an increase in the levels of serum Th1/Th17 cytokines and corticosterone, and a decrease in Th2 cytokines. Treatment of chronically-stressed mice with 4-MeH also augmented expression of IL-6, IL-21, NF-κB p65, and STAT3 mRNA. Moreover, Western blot analyses confirmed increased protein expression of NF-κB, iNOS, and STAT3 expression following 4-MeH treatment of chronically-stressed mice as compared to controls. These proteins provide a novel relevant targets for the manipulation of chronic stress induced immune regulation. In striking contrast, treatment of stressed mice with the H4R antagonist, JNJ, resulted in a substantial reduction in all of the aforementioned effects upon immune cell percentages and cytokine production.


The influence of seabird manuring on the phosphorus status of Marion Island (Subantarctic) soils.
Manuring by penguins, wandering albatrosses and burrowing petrel and prion species substantially enhances P concentrations in Marion Island soils and plants. Non-manured soils contain low levels of plant-available P on a soil volume basis but the evidence suggests that the island soils are primarily deficient in N rather than P.


Ornithine decarboxylase activity during neonatal development of the rat ventral prostate.
The relationship between ornithine decarboxylase activity and growth has been examined in ventral prostates from rats aged 2--60 weeks. The incorporation of [125I]iododeoxyuridine in vitro was used to assess DNA-synthetic activity. During 2--7 weeks post-partum ornithine decarboxylase activity/prostrate and the protein content and wet weight increased exponentially. In contrast, the incorporation of [125I]iododeoxyuridine/prostate fell during the first 4 weeks. This decline was reversed at about the time when the systemic concentrations of gonadal androgens start to rise. After 10 weeks post-partum the incorporation of [1252]iododeoxyuridine/prostate and ornithine decarboxylase activity/prostate levelled off, whereas the DNA and protein content of the prostate continued to increase at a slow rate.


An epifluidic electronic patch with spiking sweat clearance for event-driven perspiration monitoring.
Sensory neurons generate spike patterns upon receiving external stimuli and encode key information to the spike patterns, enabling energy-efficient external information processing. Herein, we report an epifluidic electronic patch with spiking sweat clearance using a sensor containing a vertical sweat-collecting channel for event-driven, energy-efficient, long-term wireless monitoring of epidermal perspiration dynamics. Our sweat sensor contains nanomesh electrodes on its inner wall of the channel and unique sweat-clearing structures. During perspiration, repeated filling and abrupt emptying of the vertical sweat-collecting channel generate electrical spike patterns with the sweat rate and ionic conductivity proportional to the spike frequency and amplitude over a wide dynamic range and long time (> 8 h). With such 'spiking' sweat clearance and corresponding electronic spike patterns, the epifluidic wireless patch successfully decodes epidermal perspiration dynamics in an event-driven manner at different skin locations during exercise, consuming less than 0.6% of the energy required for continuous data transmission. Our patch could integrate various on-skin sensors and emerging edge computing technologies for energy-efficient, intelligent digital healthcare.


High dose esomeprazole as an anti-inflammatory agent in sepsis: Protocol for a randomized controlled trial.
Sepsis is caused by dysregulated immune responses due to infection and still presents high mortality rate and limited efficacious therapies, apart from antibiotics. Recent evidence suggests that very high dose proton pump inhibitors might regulate major sepsis mediators' secretion by monocytes, which might attenuate excessive host reactions and improve clinical outcomes. This effect is obtained with doses which are approximately 50 times higher than prophylactic esomeprazole single daily administration and 17 times higher than the cumulative dose of a three day prophylaxis. We aim to perform a randomized trial to investigate if high dose esomeprazole reduces organ dysfunction in patients with sepsis or septic shock. This study, called PPI-SEPSIS, is a multicenter, randomized, double blind, placebo-controlled clinical trial on critically ill septic patients admitted to the emergency department or intensive care unit. A total of 300 patients will be randomized to receive high dose esomeprazole (80 mg bolus followed by 12 mg/h for 72 h and a second 80 mg bolus 12 h after the first one) or equivolume placebo (sodium chloride 0.9%), with 1:1 allocation. The primary endpoint of the study will be mean daily Sequential Organ Failure Assessment (SOFA) score over 10 days. Secondary outcomes will include antibiotic-free days, single organ failure severity, intensive care unit-free days at day 28, and mortality. This trial aims to test the efficacy of high dose esomeprazole to reduce acute organ dysfunction in patients with septic shock. This trial was registered on ClinicalTrials.gov with the trial identification NCT03452865 in March 2018.


Early and late hemodynamic evaluation after cardiac transplantation: a study of 28 cases.
Right heart catheterization was performed in 28 patients 1 week and 6 to 24 months after orthotopic cardiac transplantation. All patients were receiving cyclosporine and methylprednisolone orally. At early catheterization, right heart pressures as well as pulmonary capillary wedge pressure still remained above normal values in the majority of patients. Systemic arterial hypertension was already present in 29% of the patients and cardiac index was usually in the normal range, without any inotropic support. Results of late catheterization showed continuing improvement with return of right heart pressures to normal values in most but not all patients. Systemic arterial hypertension was noted in nearly all patients and is likely to be the result of hypervolemia secondary to cyclosporine-induced sodium retention. The increase in cardiac index, which was above normal values in 39% of the patients, was also consistent with hypervolemia in the setting of cardiac denervation. Thus, cardiac function at rest is satisfactory at short- and long-term assessment after cardiac transplantation, but the development and persistence of systemic arterial hypertension associated with cyclosporine use are a matter of concern in such patients.


Laparoscopic cholecystectomy causes less sleep disturbance than open abdominal surgery.
The aim of this study was to examine subjective sleep quality before and after laparoscopic vs open abdominal surgery. Twelve patients undergoing laparoscopic cholecystectomy and 15 patients undergoing laparotomy were evaluated with the aid of a sleep questionnaire from 4 days before until 4 weeks after surgery. Following laparoscopic surgery, total sleep time increased during the 1st week after the operation compared with preoperative values (p = 0.02), whereas sleep duration during weeks 2, 3, and 4 did not differ from the times reported preoperatively. Following laparotomy, sleep duration increased during the 1st, 3rd, and 4th weeks after the operation compared with preoperative values (p < 0.05). All patients experienced postoperative circadian sleep disturbance, with significantly more sleep during the daytime compared with preoperative values; the disturbance was present 1 week after laparoscopy and 4 weeks after laparotomy. After laparotomy, total sleep time increased and there was a change in diurnal sleep distribution. These sleep alterations were less pronounced after laparoscopic cholecystectomy. Thus, sleep architecture was disturbed for ?4 weeks after major abdominal surgery but for only 1 week after laparoscopic cholecystectomy.


Is the "red flag" referral pathway effective in diagnosing colorectal carcinoma?
In 2000-2004 there were, on average, 93 8 new cases of colorectal cancer (CRC) diagnosed per annum in Northern Ireland, accounting for 13.9% of all cancers. The two week "red flag" referral system aims to detect 90% of patients with CRC for prompt treatment. The aim of this study is to examine the impact of the "red flag" referral system on identification of patients with CRC, time to treatment and stage of disease. A random sample of 200 patients referred via the "red flag" system was identified from the local cancer patient tracker database. Data pertaining to demographics, time to hospital appointment, appropriateness of referral and diagnosis were collected. For patients identified with CRC, the stage of disease and time to first definitive treatment were also documented. Of the 200 patients, 56% were female. The age range was 27-93 years. Eighty three percent were seen within 14 days of referral. Referrals adhered to the guidelines in 45% of cases. There were 4 pancreatic cancers, 1 endometrial cancer, 1 ovarian cancer and 1 myelodysplasia diagnosed. Three patients were diagnosed with CRC (1.5%). Of these, 1 was palliative and the remaining 2 commenced definitive management within 6 days of decision to treat. The "red flag" referral system does not appear to be effective in identifying patients with CRC but did identify patients with other types of cancer. Less than half of the referrals adhered to the guidelines. A review of this system should be undertaken.


Study of the effect of trans fatty acids from ruminants on blood lipids and other risk factors for cardiovascular disease.
The intake of trans fatty acids (TFA) from industrially hydrogenated vegetable oils (iTFA) is known to have a deleterious effect on cardiovascular health, the effects of TFA from ruminants (rTFA) are virtually unknown. The purpose of the present study was to compare the effects of rTFA and iTFA on plasma LDL concentrations and other cardiovascular disease risk factors in healthy subjects. In a double-blind, randomized crossover controlled study, 38 healthy men were fed each of 4 experimental isoenergetic diets lasting 4 wk each. The 4 diets were high in rTFA (10.2 g/2500 kcal), moderate in rTFA (4.2 g/2500 kcal), high in iTFA (10.2 g/2500 kcal), and low in TFA from any source (2.2 g/2500 kcal) (control diet). Plasma LDL-cholesterol concentrations were significantly higher after the high- rTFA diet than after the control (P = 0.03) or the moderate- rTFA (P = 0.002) diet. Plasma LDL-cholesterol concentrations also were significantly (P = 0.02) higher after the iTFA diet than after the moderate-rTFA diet. Plasma HDL-cholesterol concentrations were significantly (P = 0.02) lower after the high-rTFA diet than after the moderate-rTFA diet. Finally, all risk factors were comparable between the control and the moderate-rTFA diets. These results suggest that, whereas a high dietary intake of TFA from ruminants may adversely affect cholesterol homeostasis, moderate intakes of rTFA that are well above the upper limit of current human consumption have neutral effects on plasma lipids and other cardiovascular disease risk factors.


Possibilities for transborder cooperation in breast cancer care in Europe: a comparative analysis regarding the content, quality and evidence use of breast cancer guidelines.
To encourage transborder cooperation in breast cancer care in Europe, we explored possibilities with the German-Dutch border area as an example. Evidence-based breast cancer guidelines were searched and compared on the: (1) methodological quality (with AGREE (Appraisal of Guidelines for Research and Evaluation)), (2) content of recommendations and (3) evidence use. The methodological quality of the German (n=2) and Dutch guidelines (n=2) was generally sufficient and comparable, although the applicability and the editorial independence were not clearly documented in the Dutch guidelines. Regarding the content analysis, German recommendations were taken as a reference point, because of the highest AGREE scores. Twenty-one of 25 recommendations discussed in both guidelines were corresponding and 4 were different, 32 were not mentioned in the Dutch guideline. The guidelines shared little evidence (< or =11%). We conclude that there are possibilities to encourage transborder cooperation. The clinical context of our results should be examined by measuring the actual care in both countries preferably with quality indicators.


Immersed membrane bioreactors: an overview with special emphasis on anaerobic bioprocesses.
Immersed membrane bioreactor (IMBR) has emerged as a novel potential technology which is considered globally as potent technology, primarily for wastewater treatment. It offers quality improvement in effluents treatment compared to other technological systems. It also offers potential benefits for the bioprocesses where product formation and separation is desired simultaneously in a compact container. This review gives insight for the wide range applications of IMBR focussing on anaerobiosis. It discusses the significance, advantages and drawbacks of IMBR against the conventional methods, highlighting the external membrane bioreactors. While the commercial significance of IMBR is obvious for industrial and municipal wastewater treatment, the current focus is shifting on other applications such as anaerobic bioprocesses. Though the IMBR technology is generally considered hand-in-hand as sustainable technology, the major bottleneck in its application at commercial scale for wastewater treatment seems its economic feasibility and compatibility. Among the technical issues, the membrane fouling is considered as a major problem for which several strategies have been developed to overcome the problem, though there is no complete or universal solution to this problem.


Short-term retention effect of rehabilitation using head position-based electrotactile feedback to the tongue: influence of vestibular loss and old-age.
Our objective was to evaluate whether the severity of vestibular loss and old-age (>65) affect a patient's ability to benefit from training using head-position based, tongue-placed electrotactile feedback. Seventy-one chronic dizzy patients, who had reached a plateau with their conventional rehabilitation, followed six 1-h training sessions during 4 consecutive days (once on days 1 and 4, twice on days 2 and 3). They presented bilateral vestibular areflexia (BVA), bilateral vestibular losses (BVL), unilateral vestibular areflexia or unilateral vestibular losses and were divided into two age-subgroups (≤65 and >65). Posturographic assessments were performed without the device, 4h before and after the training. Patients were tested with eyes opened and eyes closed (EC) on static and dynamic (passively tilting) platforms. The studied posturographic scores improved significantly, especially under test conditions restricting either visual or somatosensory input. This 4-h retention effect was greater in older compared to younger patients and was proportional to the degree of vestibular loss, patients with increased vestibular losses showing greater improvements. In bilateral patients, who constantly fell under dynamic-EC condition at the baseline, the therapy effect was expressed by disappearance of falls in BVL and significant prolongation in time-to-fall in BVA subgroups. Globally, our data showed that short training with head-position based, tongue-placed electrotactile biofeedback improves balance in chronic vestibulopathic patients some 16.74% beyond that achieved with standard balance physiotherapy. Further studies with longer use of this biofeedback are needed to investigate whether this approach could have long-lasting retention effect on balance and quality of life.


The innervation of synovium of human osteoarthritic joints in comparison with normal rat and sheep synovium.
To study whether osteoarthritis (OA) in the knee is associated with a change of the innervation pattern in the synovial layer. In synovial tissue from the normal knee joint of rat and sheep we studied the presence of vessels and of nerve fibres using transmission electron microscopy and immunohistochemistry. Synovial material was also obtained from patients who underwent total knee replacement surgery. This material was examined for inflammatory changes, and the presence of vessels and nerve fibres was assessed. The synovium in the parapatellar region of the normal knee joint of rat and sheep exhibited a dense capillary and neuronal network. It was entered by calcitonin gene-related peptide containing sensory fibres and tyrosine hydroxylase-positive sympathetic nerve fibres. Synovial material from patients with knee OA exhibited different degrees of inflammation. Synovial material without inflammation exhibited a similar vascular and neuronal network as the normal knee joint from rat and sheep. However, in synovium with inflammatory changes we found a significant decrease of nerve fibres in depth ranges close to the synovial lining layer depending on the degree of inflammation whereas deeper regions were less affected. Inflammatory changes in the synovium of OA joints are associated with a massive destruction of the capillary and neuronal network which is present in normal synovium. Due to the disappearance of the sensory fibres it is unlikely that OA pain is initiated directly in the synovium. The loss of normally innervated vascularisation may have multiple consequences for the physiological functions of the synovium.


Neurotoxicity test validation, positive controls and proficiency: are chemicals necessary?
The USEPA neurotoxicity guidelines require the use of positive control data in support of toxicology studies submitted to the Agency and emphasize the use of chemicals to accomplish this requirement. These guidelines, though, propose a number of different rationales for the use of chemicals as positive control agents. We re-evaluated the potential roles of positive control data in addressing three questions: 1) what does the test measure? 2) is the performing laboratory proficient in the use of the test? 3) do the complementary data submitted in support of neurotoxicity studies conducted with the test material provide enough context for the interpretation of the biological significance of an effect? While, for most types of guideline neurotoxicity tests, the use of test chemicals has been emphasized for positive control testing, the use of non-chemical procedures (i.e., systematic manipulation of the experimental parameters of a test, which poses less risk of adverse effects to the test animals) should be strongly considered as a potential alternative.


Immunological detection of a cysteine protease in the skin and other tissues.
Monospecific antibody directed to cysteine protease of 2-day-old rat epidermis recently characterized as being different from the proteases previously reported was produced in rabbits. By immunofluorescence microscopy and immunoperoxidase staining with an avidin-biotin-peroxidase method the protease was found to be present in the epidermis of rodents of different ages as well as that of humans, but not in the dermis. The staining in germinative cells was more intense than in cells in the superficial layers. It appeared as irregular patches in the nuclei and stained more diffusely in the cytoplasm where small granular components, strongly stained, were identified. The staining patterns in granular cells showed accumulation of the antigen in a granular form. The morphology and distribution of granules resembled those of keratohyalin-like granules in the nucleus and dense homogeneous deposits in the cytoplasm. In cornified cells the reaction product was localized by the plasma membrane where concentration of the dense homogeneous deposits occurred, suggesting that the cysteine protease is one component of the unique and characteristic structure of differentiated keratinocytes. In addition, the cysteine protease antigen having the same molecular weight as the epidermal enzyme was detected in liver, kidney and lung indicating a wider tissue distribution of the protease. The significance of the protease in regulation of cellular functions remains to be investigated.


Investigating pathogenic SNP of PKCι in HCV-induced hepatocellular carcinoma.
Hepatocellular carcinoma is a leading cause of cancer-related deaths due to its complexity in diagnosis, chemo-resistance, and aggressive nature. Identifying pathogenic single nucleotide polymorphism (SNP) in protein kinase C iota (PKCι) can be a potential biomarker in the prognosis and treatment of HCC. This study investigated the association between a SNP in PRKCI and the Pakistani population's hepatocellular carcinoma (HCC) risk. Obtained samples were first evaluated for ALT measurements and viral load quantification through reverse transcriptase-PCR. The PKCι nsSNP rs1199520604 was evaluated computationally by multiple consensus bioinformatics tools for predicting its potential deleterious effects. Its association with hepatitis C virus- (HCV) mediated HCC was then investigated through ARMS-PCR (Amplification Refractory Mutation System Polymerase Chain Reaction). SNP analysis of rs1199520604 was performed in 100 cases and 100 controls. Variant rs1199520604's homozygous T genotype is a risk factor allele for the HCV-induced HCC (odds ratio: 4.13, relative risk: 2.01, P-value < 0.0001). The heterozygous genotype is determined to protect HCV patients from HCC development (P < 0.001). The study highlighted the disease association of variant rs1199520604 with HCV-induced HCC in the Pakistani populations. This variant, after further validation through high-throughput investigation on a larger cohort, has the potential to be translated at the clinical level.


The effect of therapeutic ultrasound on repair of the achilles tendon (tendo calcaneus) of the rat.
The purpose of this study was to evaluate the effects of therapeutic ultrasound (US) on the healing process in the Achilles tendon (Tendo calcaneus) of Wistar rats after tenotomy. Sonication was performed at a frequency of 1 MHz, an intensity of 0.5 W/cm(2) (SATA), for 5 min, over a period of 14 consecutive days in two modalities (n = 15); in both continuous and pulsed modes. The control group was divided into tenotomized, mock-sonicated and nontenotomized tendons (n = 15). On the 15th postoperative day, the tendons were removed and analyzed by using the polarized light microscopy, with the purpose of detecting and measuring the organization of collagen fibers through birefringence. The results showed a high birefringence for the tendons treated using the pulsed mode (p < 0.001), revealing the best organization and aggregation of collagen bundles. Sonication in the continuous mode induced a decrease (p = 0.047) in the ability to quicken the healing process. These findings suggest that US therapy is beneficial in the early healing process of tendons when the pulsed mode is used.


Macromolecular crowding limits growth under pressure.
Cells that grow in confined spaces eventually build up mechanical compressive stress. This growth-induced pressure (GIP) decreases cell growth. GIP is important in a multitude of contexts from cancer, to microbial infections, to biofouling, yet our understanding of its origin and molecular consequences remains limited. Here, we combine microfluidic confinement of the yeast Saccharomyces cerevisiae, with rheological measurements using genetically encoded multimeric nanoparticles (GEMs) to reveal that growth-induced pressure is accompanied with an increase in a key cellular physical property: macromolecular crowding. We develop a fully calibrated model that predicts how increased macromolecular crowding hinders protein expression and thus diminishes cell growth. This model is sufficient to explain the coupling of growth rate to pressure without the need for specific molecular sensors or signaling cascades. As molecular crowding is similar across all domains of life, this could be a deeply conserved mechanism of biomechanical feedback that allows environmental sensing originating from the fundamental physical properties of cells.


Increasing plasma lysophosphatidylcholine levels in patients with regular dextran sulfate lipoprotein apheresis.
Previously we found a highly significant increase of phosphatidylethanolamines (PE) in response to acute lipoprotein apheresis (LA) with whole blood dextran sulfate adsorption (DSA) in contrast to the overall tendency of reduction of lipid metabolites of all lipid classes in post-apheresis plasma. Therefore, the aim of the present study was to analyze long-term modifications of the plasma lipidomic profile in patients with repeated DSA apheresis. Nine patients weekly treated with DSA were followed for 40 weeks. Pre- and post-apheresis levels of routine lipid parameters and lipidomic profiles of five apheresis sessions were assessed. The main finding of the present study was a progressive increase of pre- and post-apheresis plasma lysophosphatidylcholine (LPC) levels, which doubled in concentration at the end of the 40 week observation period. LPC metabolites which mainly contributed to this increase were LPC 20:4 > 18:0 > 18:1 > 16:0 > 20:3 > 18:2. These data indicate that long-term application of DSA technology may be associated with a continuous increase in LPC levels. Possible pro- or anti-atherogenic consequences should be elucidated in further studies.


Glutathione S-transferase activity in follicular fluid from women undergoing ovarian stimulation: role in maturation.
Female infertility involves an emotional impact for the woman, often leading to a state of anxiety and low self-esteem. The assisted reproduction techniques (ART) are used to overcome the problem of infertility. In a first step of the in vitro fertilization therapy women are subjected to an ovarian stimulation protocol to obtain mature oocytes, which will result in competent oocytes necessary for fertilization to occur. Ovarian stimulation, however, subjects the women to a high physical and psychological stress, thus being essential to improve ART and to find biomarkers of dysfunction and fertility. GSH is an important antioxidant, and is also used in detoxification reactions, catalysed by glutathione S-transferases (GST). In the present work, we have investigated the involvement of GST in follicular maturation. Patients with fertility problems and oocyte donors were recruited for the study. From each woman follicles at two stages of maturation were extracted at the preovulatory stage. Follicular fluid was separated from the oocyte by centrifugation and used as the enzyme source. GST activity was determined based on its conjugation with 3,4-dichloronitrobenzene and the assay was adapted to a 96-well microplate reader. The absorbance was represented against the incubation time and the curves were adjusted to linearity (R(2)>0.990). Results showed that in both donors and patients GST activity was significantly lower in mature oocytes compared to small ones. These results suggest that GST may play a role in the follicle maturation by detoxifying xenobiotics, thus contributing to the normal development of the oocyte. Supported by FIS/FEDER (PI11/02559), Gobierno Vasco (Dep. Educación, Universiades e Investigación, IT687-13), and UPV/EHU (CLUMBER UFI11/20 and PES13/58). The work was approved by the Ethics Committee of the UPV/EHU (CEISH/96/2011/RUIZLARREA), and performed according to the UPV/EHU and IVI-Bilbao agreement (Ref. 2012/01).


Mediastinal foregut duplication cysts.
Foregut duplication cysts are rare congenital anomalies of enteric origin. In majority of the patients, the diagnosis is made in infancy. The authors report 4 cases of mediastinal foregut duplication cyst in children diagnosed on CT/MRI and confirmed on histopathology. In none of the cases the cysts had intraspinal extension nor heterotopic gastric mucosa.


Data in the activities of caspases and the levels of reactive oxygen species and cytochrome c in the •OH-induced fish erythrocytes treated with alanine, citrulline, proline and their combination.
The present study explored the effects of alanine (Ala), citrulline (Cit), proline (Pro) and their combination (Ala10Pro4Cit1) on the activities of caspases and levels of reactive oxygen species (ROS) and cytochrome c in hydroxyl radicals (•OH)-induced carp erythrocytes. The data displayed that •OH induced the increases in the activities of caspase-3, caspase-8 and caspase-9 and the levels of ROS and cytochrome c in carp erythrocytes. However, Ala, Cit, Pro and Ala10Pro4Cit1 effectively suppressed the •OH-induced increases in the activities of caspase-3, caspase-8 and caspase-9 and the levels of ROS and cytochrome c in carp erythrocytes. Furthermore, the activities of caspase-3, caspase-8 and caspase-9 and the levels of ROS and cytochrome c were gradually decreased with increasing concentrations of Ala, Cit, Pro and Ala10Pro4Cit1 (0.175-1.400 mM) in the •OH-induced carp erythrocytes. These data demonstrated that the 50% inhibitory doses (ID50) of Ala10Pro4Cit1 on the activities of caspase-8, caspase-9 and caspase-3 and levels of ROS and cytochrome c were respectively estimated to be the minimum values among amino acids examined so far. The 5% inhibitory doses (ID5) of Ala, Cit, Pro and Ala10Pro4Cit1 on the activities of caspase-8, caspase-9 and caspase-3 and levels of ROS and cytochrome c were estimated to be at their physiological concentrations in mammalian. Our research article for further interpretation and discussion from these data in Li et al. (2016) [1].


Multicenter study of re-irradiation using carbon-ions for head and neck malignancies after photon radiotherapy.
The goal of this multicenter retrospective study of patients with head and neck malignancies was to evaluate the efficacy and safety of carbon-ion (C-ion) radiotherapy (RT) after photon RT. We enrolled 56 patients with head and neck malignancies who underwent re-irradiation (re-RT) using C-ions between November 2003 and March 2019, treated previously with photon RT. The tumors at re-RT were located in the sinonasal cavities (n = 20, 35.7%), skull base (n = 12, 21.4%), and orbit (n = 7, 12.5%). The tumors at the initial RT were located in the sinonasal cavities (n = 13, 23.2%), skull base (n = 9, 16.1%), and orbit (n = 9, 16.1%). The median period between the initial RT and re-RT was 41 (4-568) months. The most common histology of re-RT was squamous cell carcinoma (n = 11, 19.6%). The most commonly used protocol was 57.6 Gy (relative biological effectiveness) in 16 fractions (n = 23, 41.1%). Surgery preceded re-RT in three patients (5.4%). One patient with malignant melanoma received concurrent chemotherapy. The 2-year local control, progression-free survival, and overall survival rates were 66.5%, 36.9%, and 67.9%, respectively. The median follow-up time was 28 months. Two patients (3.6%) developed grade ≥ 3 acute toxicities, and 14 (25.0%) developed grade ≥ 3 late toxicities. A single patient had confirmed grade 5 dermatitis with infection. Re-RT using C-ions for head and neck malignancies after photon RT is an effective treatment with tolerable toxicity.


Therapeutic management of primary immunodeficiency in older patients.
Primary immunodeficiency disease (PID) has traditionally been viewed as a group of illnesses seen in the paediatric age group. New advances in diagnosis and treatment have led to an increase in the number of elderly PID patients. However, there is lack of research evidence on which to base clinical management in this group of patients. Management decisions often have to be based therefore on extrapolations from other patient cohorts or from younger patients. Data from the European Society for Immunodeficiencies demonstrates that the vast majority of elderly patients suffer from predominantly antibody deficiency syndromes. We review the management of PID disease in the elderly, with a focus on antibody deficiency disease.


Transcatheter coil occlusion of residual shunt in a patient with recurrent cryptogenic stroke after PFO percutaneous closure.
A significant association has been suggested between a residual shunt and the risk of cerebral ischemic recurrences after transcatheter patent foramen ovale (PFO) closure. We report the use of a detachable coil to treat a residual shunt in a patient who had a recurrent cerebral ischemic event after transcatheter closure of a PFO.


Growth and metabolism of selected strains of probiotic bacteria, in maize porridge with added malted barley.
A fermented probiotic maize porridge with high energy density and low viscosity was prepared, using maize flour and barley malt. The porridge was fermented with four probiotic strains (grown separately): Lactobacillus reuteri, Lb. acidophilus (LA5 and 1748) and Lb. rhamnosus GG. These strains were inoculated at two levels; to obtain approx. 7 or 6 log cfu g(-1) in the porridge at 0 h. The porridge was fermented for 24 h at 37 degrees C, and analysed for viable cell count, pH, organic acids, volatile aromatic compounds and sugar content. The inoculated cell concentration was shown to be particularly important during the first hours of the fermentation period, showing a delayed production of most metabolites in porridge inoculated with approx. 6 log cfu g(-1). Most strains reached maximum cell count after 12-h fermentation (7.2-8.2 log cfu g(-1)), with a pH below 4.0. Depending on the strain, lactic acid was produced in amounts ranging from 1360 to 4000 mg kg(-1). Lb. reuteri metabolised succinate, while pyruvate and small amounts of diacetyl were detected in porridge inoculated with Lb. acidophilus LA5 and Lb. acidophilus 1748. High amounts of diacetyl (6 mg kg(-1)) and acetoin (27 mg kg(-1)) were detected in porridge inoculated with Lb. rhamnosus GG. Porridge inoculated with Lb. acidophilus LA5 and Lb. acidophilus 1748, contained acetaldehyde, while both Lb. reuteri and Lb. rhamnosus GG reduced the acetaldehyde to ethanol. Lb. reuteri utilised both maltose and glucose as carbohydrate sources, while Lb. acidophilus LA5, Lb. acidophilus 1748 and Lb. rhamnosus GG utilised only glucose.


Structure of Intergenic Spacer IGS1 of Ribosomal Operon from Schistidium Mosses.
The structure of the intergenic spacer 1 (IGS1) of the ribosomal operon from 12 species of Schistidium mosses was studied. In the IGS1 sequences of these species, three conserved regions and two areas of GC- and A-enriched repeats were identified. All of the studied mosses have a conserved pyrimidine-enriched motif at the 5'-end of IGS1. Species-specific nucleotide substitutions and insertions were found in the conserved areas. The repeated units contain single nucleotide substitutions that make unique the majority of repeated units. The positions of such repeats in IGS1 are species-specific, but their number can vary within the species and among operons of the same specimen. The comparison of IGS1 sequences from the Schistidium species and from representatives of ten other moss genera revealed the presence of common conserved motifs with similar localization. Presumably, these motifs are elements of termination of the pre-rRNA transcription and processing of rRNA.


Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, blocks lysosomal cholesterol trafficking in macrophages.
Certain steroids having an oxo group at the C-17 or C-20 position such as pregnenolone and dehydroisoandrosterone inhibit the cholesterol transport from lysosomes to other cellular sites. Taking advantage of the fact that the inhibition is reversed upon removal of the steroids, we studied the factors that control the cholesterol transport from lysosomes to other cellular sites in macrophages. Macrophages that accumulated unesterified cholesterol in their lysosomes were prepared by incubating cells with liposomes containing cholesterol and phosphatidylserine in the presence of a steroid inhibitor. These cells were chased by means of steroid washout, and then the effects of various pharmacological agents on the subsequent metabolism of cholesterol were examined. When the cells were chased in the absence of the agents, some of the cholesterol was converted to cholesteryl esters in the cells, and others were desorbed into the medium as unesterified forms, suggesting recovery of lysosomal cholesterol trafficking. Among the agents tested, bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, completely blocked both cholesterol esterification and cholesterol desorption at 10 nM. Moreover, agents that neutralize the lysosomal proton gradient, such as ammonium chloride and chloroquine, also reduced both of the processes. Fluorescent microscopic examination of bafilomycin A1-treated cells revealed extensive filipin-cholesterol staining of perinuclear lysosomes. From these data, we conclude that acidic pH is required for the efflux of cholesterol from lysosomes to other cellular sites.


Phylogenetic and morphological diversity of novel soil cercomonad species with a description of two new genera (Nucleocercomonas and Metabolomonas).
Cercomonads are important components of microbial food webs in soils and aquatic sediments. Here, we investigated the general morphology, behaviour, life cycle and 18S rDNA phylogeny of cercomonad cultures from a German grassland soil habitat. We describe ten new species including two new genera from 23 strains. Three Cercomonas, two Eocercomonas and three Paracercomonas species are described. Based on large phylogenetic distance and distinct morphology, we erect two novel clade B genera near the root of the cercomonad tree. Nucleocercomonas nov. gen. bears a number of characters unusual for cercomonads: Its anterior flagellum is extremely long, it mostly does not glide, and in its most frequent life stage the cell body does not attach to the substratum, but produces unattached pseudopodia. Furthermore, it has a unique nucleus with a peripheral nucleolus that attaches to the nuclear envelope opposite the basal body connection. Metabolomonas nov. gen. is extremely metabolic. It is characterized by a very high beating frequency of the anterior flagellum, fast gliding, rapid changes in shape and strong cytoplasmic streams. A new genus Brevimastigomonas is erected for the previously described species Paracercomonas anaerobica. The general morphology of cercomonad species often does not correspond with their phylogenetic position: closely related species may have a very different morphology.


Plasma-activated water: An alternative disinfectant for S protein inactivation to prevent SARS-CoV-2 infection.
SARS-CoV-2 is a highly contagious virus and is causing a global pandemic. SARS-CoV-2 infection depends on the recognition of and binding to the cellular receptor human angiotensin-converting enzyme 2 (hACE2) through the receptor-binding domain (RBD) of the spike protein, and disruption of this process can effectively inhibit SARS-CoV-2 invasion. Plasma-activated water efficiently inactivates bacteria and bacteriophages by causing damage to biological macromolecules, but its effect on coronavirus has not been reported. In this study, pseudoviruses with the SARS-CoV-2 S protein were used as a model, and plasma-activated water (PAW) effectively inhibited pseudovirus infection through S protein inactivation. The RBD was used to study the molecular details, and the RBD binding activity was inactivated by plasma-activated water through the RBD modification. The short-lived reactive species in the PAW, such as ONOO-, played crucial roles in this inactivation. Plasma-activated water after room-temperature storage of 30 days remained capable of significantly reducing the RBD binding with hACE2. Together, our findings provide evidence of a potent disinfection strategy to combat the epidemic caused by SARS-CoV-2.


Cardiovascular disease risk in long-term breast cancer survivors: A population-based cohort study.
Breast cancer survival is increasing, making late effects such as cardiovascular disease (CVD) more relevant. The purpose of this study was to evaluate incident CVD following breast cancer diagnosis among long-term survivors and to investigate possible risk factors for CVD. A population-based cohort of 6641 breast cancer survivors diagnosed between 1997 and 2009 who survived at least 10 years was identified within the Utah Cancer Registry. In addition, 36,612 cancer-free women from the general population, matched by birth year and state, were identified within the Utah Population Database. Cox proportional hazards models were used to calculate CVD hazard ratios (HRs) for >10 to 15 and >15 years. Long-term breast cancer survivors had an increased risk of newly diagnosed diseases of the circulatory system (HR, 1.32; 99% confidence interval [CI], 1.00-1.75) from 10 to 15 years following cancer diagnosis compared with the general population. No increased CVD risks were observed after 15 years. Breast cancer survivors with Charlson Comorbidity Index score ≥2 had a significantly higher risk of diseases of the circulatory system (HR, 2.64; 95% CI, 1.08-6.45) beyond 10 years following breast cancer diagnosis. Similarly, older age, obesity, lower education, and family history of CVD and breast cancer were risk factors for heart and circulatory system diseases among long-term breast cancer survivors. Risk of CVD compared to the general population was moderate among this cohort of long-term breast cancer survivors between 10 to 15 years since cancer diagnosis. Awareness of CVD risks is important for breast cancer survivors.


A bio-what? Medical companions' perceptions towards biosimilars and information needs in rheumatology.
Patient perceptions influence biosimilar uptake in non-mandatory transitions. Companions (support people) are often actively involved in the patient's medical journey and are likely to have unique perceptions of biosimilars, which may shape patient attitudes. This study explores the congruence between patient and companion perceptions towards biosimilars and their information needs. Patients taking bio-originators for rheumatic diseases (59% for rheumatoid arthritis) and their companions received an explanation about biosimilars. Participants (N = 78) completed questionnaires assessing their familiarity with biosimilars, perceptions, concerns, and benefits of being accompanied. Contingency tables and paired sample t-tests were used to explore differences in familiarity, confidence in knowledge, and perceptions. Intra-class correlation coefficients were calculated to assess the degree of congruence for perceptions towards biosimilars. Companions were significantly less familiar with biosimilars (p = 0.014, Cramer's V = 0.28) and reported lower confidence in their knowledge (p = 0.006, Cohen's d = 0.47) than patients. Companions and patients had moderate to good congruency for perceptions toward confidence in biosimilar use and safety, efficacy, and side-effect expectations (intra-class correlation coefficients ranging from 0.75 to 0.81). Companions and patients were most concerned about safety and effectiveness. Companions also reported concerns about cost savings driving the transition, while patients had concerns about uncertainty and testing. Patients reported the ability for discussion, improved understanding, and validation as benefits of being accompanied. Companions and patients have similar levels of perceptions and expectations towards biosimilars but report some unique information needs. Future educational interventions should involve companions and address their concerns to help improve biosimilar acceptance.


Ex vivo elimination of neoplastic T-cells from human marrow using an anti-Mr 41,000 protein immunotoxin: potentiation by ASTA Z 7557.
ASTA Z 7557 potentiated the ex vivo efficiency of a T-cell directed immunotoxin containing pokeweed antiviral protein (PAP). We used an immunotoxin of pan-T monoclonal antibody 3-A1 directed against p41 antigen expressed both on normal and leukemic T-cells. Treatment with 3A1-PAP in combination with ASTA Z 7557 produced 7-8 logs elimination of target lymphoblastic leukemia cells. Our data suggest that this new strategy shows potential for more effective ex vivo marrow purging in autologous marrow transplantation for acute lymphoblastic leukemia.


Central diabetes insipidus in pediatric patients with Langerhans cell histiocytosis: Results from the JLSG-96/02 studies.
We analyzed central diabetes insipidus (CDI) development in pediatric patients with Langerhans cell histiocytosis (LCH) treated according to the Japan LCH Study Group (JLSG) regimen, which is the combination chemotherapy including cytarabine (Ara-C). Retrospective data from 317 patients (multisystem disease (MS), n = 206; multiple focal bone (MFB), n = 111) treated according to the JLSG-96/02 regimens were analyzed. The median follow-up duration was 10.6 years (range, 0.1-21.1). A total of 50/317 (15.8%) patients developed CDI (MFB, n = 4; MS, n = 46). Of the 50 cases, CDI was already present at the time of LCH diagnosis (pre-CDI) in 25, and it newly developed after the diagnosis and initiation of treatment (post-CDI) in the other 25 cases. The cumulative incidence of post-CDI at 10-year calculated by Kaplan-Meier analysis was 9.0% for total and 12.0% for MS patients. A positive correlation with LCH lesions at the CNS risk sites at diagnosis was found in pre-CDI cases (17/164 vs 8/171; P = 0.0359), but not in post-CDI cases (14/129 vs 11/163; P = 0.254). Multivariate analysis showed that relapse at the CNS risk sites was significantly associated with post-CDI development (hazard ratio: 4.70; 95% CI, 1.29-17.1, P < 0.05). In the JLSG-96/02 studies, CDI developed in 15.8% of the cohort in which half as pre- and the other half as post-CDI. Relapse, particularly at the CNS risk sites, was linked with the development of post-CDI.


Differentiation and characterization of the cytoplasmic and nuclear deoxyribonucleic acid polymerases from baby hamster kidney cells.
Distinct DNA polymerase activities have been found in the cytoplasmic and nuclear fractions of a baby hamster kidney cell line. They were separated by chromatography on DEAE-cellulose and partially purified by ammonium sulfate fractionation, DNA - cellulose and linear sucrose gradients. The cytoplasmic DNA polymerase exhibited an S-coefficient of 6.95 S in 0.15 M NaCl and its activity was highly sensitive to inhibition by N-ethylmaleimide and elevated temperatures, regardless of the presence of DNA template or other cofactors. It was stimulated by monovalent salts in the order of NH4 Cl greater than KCl greater than NaCl greater than CsCl greater than LiCl (inhibitory). The DNA polymerase extracted from nuclei sedimented with an S-value of 3.47 S, was resistant to inactivation by N-ethylmaleimide, and maximally stimulated by NaCl, while also being inhibited by LiCl. For optimal activity, both DNA polymerase activities required a divalent cation, with MgCl2 being more effective than MnCl2. Although the optimal pH values for the two enzyme activities differed slightly, glycine - NaOH buffer induced an alkaline shift of 1.5 pH units in the optimum of both enzymes. This was accompanied by an increase in the effectiveness of MnCl2 relative to MgCl2 for the cytoplasmic DNA polymerase.


Structural characterization and developability assessment of sustained release hydrogels for rapid implementation during preclinical studies.
Sustained-release formulations are important tools to convert efficacious molecules into therapeutic products. Hydrogels enable the rapid assessment of sustained-release strategies, which are important during preclinical development where drug quantities are limited and fast turnaround times are the norm. Most research in hydrogel-based drug delivery has focused around synthesizing new materials and polymers, with limited focus on structural characterization, technology developability and implementation. Two commercially available thermosensitive hydrogel systems, comprised of block copolymers of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PLGA) and poly(lactide-co-caprolactone)-b-poly(ethyleneglycol)-b-poly(lactide-co-caprolactone) (PLCL), were evaluated during this study. The two block copolymers described in the study were successfully formulated to form hydrogels which delayed the release of lysozyme (> 20 days) in vitro. Characterization of formulation attributes of the hydrogels like Tsol-gel temperature, complex viscosity and injection force showed that these systems are amenable to rapid implementation in preclinical studies. Understanding the structure of the gel network is critical to determine the factors controlling the release of therapeutics out of these gels. The structures were characterized via the gel mesh sizes, which were estimated using two orthogonal techniques: small angle X-ray scattering (SAXS) and rheology. The mesh sizes of these hydrogels were larger than the hydrodynamic radius (size) of lysozyme (drug), indicating that release through these gels is expected to be diffusive at all time scales rather than sub-diffusive. In vitro drug release experiments confirm that diffusion is the dominating mechanism for lysozyme release; with no contribution from degradation, erosion, relaxation, swelling of the polymer network or drug-polymer interactions. PLGA hydrogel was found to have a much higher complex viscosity than PLCL hydrogel, which correlates with the slower diffusivity and release of lysozyme seen from the PLGA hydrogel as compared to PLCL hydrogel. This is due to the increased frictional drag experienced by the lysozyme molecule in the PLGA hydrogel network, as described by the hydrodynamic theory.


The role of diagnostic ultrasonography in varicocele evaluation.
Twenty-one patients with the clinical diagnosis of varicocele were evaluated with static and superficial organ scanners. The sonogram was able to image the dilated scrotal veins in all of these cases. The small, clinically subtle varicocele could be demonstrated only with high-resolution, dedicated real-time small-parts scanners, whereas larger lesions could also be imaged with B-mode contact equipment. Varicoceles are a well-documented cause of male infertility amenable to surgical treatment. From this study it is felt that ultrasonography can accurately detect varicoceles. It can be used as a screening procedure so that only those men requiring therapy need undergo more extensive and complicated diagnostic procedures.


Does an electrocardiogram add predictive value to the rose angina questionnaire for future coronary heart disease? 10-year follow-up in a Middle East population.
To evaluate the power of abnormal resting ECG versus Rose Questionnaire angina and its additive value in predicting 10-year coronary heart disease (CHD) risk in an Iranian urban population with high prevalence of CHD. There were 5101 subjects ≥30 years (2900 women), free of CHD at baseline; they were categorised in to four groups according to their Rose Angina and ECG status for ischaemia as Rose-/ECG-, Rose+/ECG-, Rose-/ECG+ and Rose+/ECG+. HR of CHD was estimated using Cox regression analysis, given Rose-/ECG- as the reference. The authors used Akaike information criterion, C-index and integrated discrimination improvement indices to evaluate the prognostic value of ECG when would be added to Rose Questionnaire. During follow-up, 387 CHD events (169 women) were observed. Multivariate analysis showed a HR of 2.59 (95% CI 1.71 to 3.91) and 2.26 (1.48 to 3.44) for Rose+/ECG- group in men and women, respectively. These figures for Rose-/ECG+ were 1.36 (0.90 to 2.05) in men and 2.09 (1.40 to 3.12) in women. There was no any interaction between Rose Questionnaire and gender to predict incident CHD, in age-adjusted analysis. Akaike information criterion, C-index and relative integrated discrimination improvement did not show any difference between models including Rose alone and Rose plus ECG to predict CHD events especially in men. Rose Questionnaire as a simple screening tool is equally important to predict incident CHD in both genders. Adding abnormal ECG to angina did not culminate in higher risk for future CHD events.


High temperature combined with drought affect rainfed spring wheat and barley in South-Eastern Russia: I. Phenology and growth.
Heat stress, when combined with drought, is one of the major limitations to food production worldwide, especially in areas that use rainfed agriculture. As the world population continues to grow, and water resources for the crop production decline and temperature increases, so the development of heat- and drought-tolerant cultivars is an issue of global concern. In this context, four barley and two wheat genotypes were evaluated in south-eastern Russia to identify heat- and drought-tolerant genotypes for future breeding programmes by identifying suitable sowing times for specific genotypes. High temperature stress, when combined with drought during late sowing, decreased the days to visible awns, days to heading and days to ripe harvest, finally negatively affecting the growth and development of plants and resulting in a lower plant population m(-2), tillers plant(-1), plant height and dry matter production m(-2). On the other hand, low temperature in combination with early sowing increased the number of days to germination, reduced seedling stand establishment and tillering capacity, finally affecting the growth and development of the crops. Compared to overall performance and optimum sowing date, barley genotypes 'Zernograd.770' and 'Nutans', and wheat genotype 'Line4' performed best in both late (high temperature with drought) and early (low temperature) stress conditions.


Thermal behaviour and stability in Olanzapine.
The stability and thermal behaviour of two anhydrate phases and a new mixed water:DMSO solvate of Olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno-[2,3-b][1,5]benzodiazepine) are studied by different methods: differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and Raman scattering (RS). Single crystal structural data for the latter phase are presented, confirming the presence of the (Olanzapine)(2) dimer as the structural building unit of all known phases of the drug, either anhydrate or solvated. An apparent interconversion between both solid state forms is shown to be an artifact and explained in terms of a melting-recrystallization process.


Description of a cellulose-binding domain and a linker sequence from Aspergillus fungi.
A family I cellulose-binding domain (CBD) and a serine- and threonine-rich linker peptide were cloned from the fungi Aspergillus japonicus and Aspergillus aculeatus. A glutathione S-transferase (GST) fusion protein comprising GST and a peptide linker with the CBD fused to its C-terminus, was expressed in Escherichia coli. The renatured GST-CBD recovered from inclusion bodies had a molecular mass of 36.5 kDa which agrees with the 29 kDa of the GST plus the calculated 7.5 kDa of the linker with the CBD. The isolated GST-CBD protein adsorbed to both bacterial microcrystalline cellulose and carboxymethyl cellulose. Deletion of the linker peptide caused a decrease in cellulose adsorbance and a higher sensitivity to protease digestion.


Successful management of massive lamotrigine extended-release intoxication in a dog.
A 3-year-old spayed female Siberian Husky presented for evaluation following ingestion of approximately 429 mg/kg of lamotrigine extended-release. She demonstrated severe neurologic and cardiac signs and was treated with lipid emulsion, anticonvulsants, antiarrhythmics and aggressive decontamination and supportive care. She was successfully discharged from the hospital 5 days later.


ent-Abietane-type diterpenoids from the roots of Euphorbia ebracteolata with their inhibitory activities on LPS-induced NO production in RAW 264.7 macrophages.
Ten ent-abietane diterpenoids (1-10), including four new (1-4) and six known ones (5-10) were isolated from the roots of Euphorbia ebracteolata. Their structures were determined by 1D, 2D NMR, and HRESIMS. Compounds 2, 4, and 7 exhibited significant inhibitory activities on lipopolysaccharide (LPS)-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 0.69, 1.97, and 0.88μM, respectively. A primary structure-activity relationship was also discussed.


Association between the month of starting a weight management program and weight change in people at high risk of type 2 diabetes: A prospective cohort study.
Weight loss is one of the most common New Year's resolutions, but it is unclear whether attempting to lose weight in January is more successful than attempting it at other times of the year. In this prospective cohort study from the English National Health Service (NHS) Diabetes Prevention Program, adults with nondiabetic hyperglycemia were enrolled in a structured behavioral weight management program. Repeated measures models assessed the mean difference between baseline and follow-up weight adjusting for monthly variation in weight among those with ≥1 weight measurement. Among 85,514 participants with a mean baseline BMI of 30.3 kg/m2 (range: 13.4 to 84.2), mean weight change at the end of the program after an average 7.9 (SD: 4.5) sessions over 6.4 (SD: 5.6) months was -2.00 kg (95% CI: -2.02 to -1.97 kg) or -2.33% (95% CI: -2.35% to -2.32%). Compared with participants starting in January, participants starting in other months lost less weight, ranging between 0.28 kg (95% CI: 0.10 to 0.45 kg) less weight in those starting in March and 0.71 kg (95% CI: 0.55 to 0.87 kg) less weight in those starting in November. April and May were the only exceptions, in which the estimates followed the same direction but were not statistically significant. Higher session attendance mediated the effects, with participants starting in January attending, on average, 0.2 to 0.7 more sessions than those starting in other months. People starting a weight management program in January lost 12% to 30% more weight than people starting it at other times of the year.


Farnesol attenuates lipopolysaccharide-induced neurodegeneration in Swiss albino mice by regulating intrinsic apoptotic cascade.
Neuronal apoptosis occurs as a sequel of oxidative stress associated with various neuropathies. In this study, we have investigated the protective effect of farnesol, a sequisterpene on lipopolysaccharide (LPS) induced neurodegeneration through modulation of intrinsic apoptotic cascade in the cortex and hippocampus of Swiss albino mice. Intraperitoneal (i.p.) injection of LPS (250 μg/kg b.wt. for 7 days) resulted in elevated levels of lipid peroxidation, protein carbonyls and 8-Hydroxydeoxyguanosine (8OHdG), with subsequent depletion in the antioxidant status and severe histological aberrations. These anomalies were accompanied by increased expressions of pro-apoptotic Bax, caspase-3 and p53 with decrease in anti-apoptotic Bcl-2. Farnesol treatment (100mg/kg b.wt.) ameliorated LPS-induced oxidative stress by enhancing the antioxidant defense system as evident from the increased levels of SOD, CAT, GSH and GST and exhibited protected cellular morphology manifested from histopathological and nissl staining analyses. Farnesol treatment also reduced the expulsion of cytochrome c from mitochondria and downregulated caspase 3 activation as revealed by immunoblot analysis. Furthermore, farnesol treatment reduced the expression of Bax and antagonized LPS-induced decrease in anti-apoptotic Bcl-2. Results of this study show that farnesol exerts neuroprotective effect by regulating intrinsic apoptotic cascade through its antioxidant effect during LPS-induced neurodegeneration.