Relationship between prophage induction and transformation in Haemophilus influenzae.
The interaction between transformation and prophages of HP1c1, S2, and a defective phage of Haemophilus influenzae has been investigated by measurement of (i) the effect of prophage on transformation frequency and (ii) the effect of transformation on phage induction. The presence of any of the prophages does not appreciably alter transformation frequencies in various Rec(+) and Rec(-) strains. However, exposure of competent lysogens to transforming deoxyribonucleic acid (DNA) may induce phage but only in Rec(+) strains, which are able to integrate transforming DNA into their genome. Transformation of Rec(+) lysogens with DNA irradiated with ultraviolet (UV) light causes the production of even more phage than results from unirradiated DNA, but this indirect UV induction is not as effective as direct induction by UV irradiation of lysogens. Both types of UV induction are influenced by the repair capacity of the host. Wild-type cells contain a prophage and can be induced by transformation to produce a defective phage, which kills a small fraction of the cells. Defective phage in wild-type cells are also induced by H. parainfluenzae DNA, and a much larger fraction of the cells is killed. Strain BC200, which is highly transformable but is not inducible for defective phage, is not killed by H. parainfluenzae DNA, suggesting that wild-type cells are killed by killed by this DNA because of phage induction. A minicell-producing mutant, LB11, has been isolated. Some phage induction occurs in this strain when the cells are made competent, unlike the wild type. A large majority of LB11 cells surviving the competence regime are killed by exposure to transforming DNA.


The Pharmacogenetics of Statin Therapy on Clinical Events: No Evidence that Genetic Variation Affects Statin Response on Myocardial Infarction.
Background: The pharmacogenetic effect on cardiovascular disease reduction in response to statin treatment has only been assessed in small studies. In a pharmacogenetic genome wide association study (GWAS) analysis within the Genomic Investigation of Statin Therapy (GIST) consortium, we investigated whether genetic variation was associated with the response of statins on cardiovascular disease risk reduction. Methods: The investigated endpoint was incident myocardial infarction (MI) defined as coronary heart disease death and definite and suspect non-fatal MI. For imputed single nucleotide polymorphisms (SNPs), regression analysis was performed on expected allelic dosage and meta-analysed with a fixed-effects model, inverse variance weighted meta-analysis. All SNPs with p-values <5.0 × 10-4 in stage 1 GWAS meta-analysis were selected for further investigation in stage-2. As a secondary analysis, we extracted SNPs from the Stage-1 GWAS meta-analysis results based on predefined hypotheses to possibly modifying the effect of statin therapy on MI. Results: In stage-1 meta-analysis (eight studies, n = 10,769, 4,212 cases), we observed no genome-wide significant results (p < 5.0 × 10-8). A total of 144 genetic variants were followed-up in the second stage (three studies, n = 1,525, 180 cases). In the combined meta-analysis, no genome-wide significant hits were identified. Moreover, none of the look-ups of SNPs known to be associated with either CHD or with statin response to cholesterol levels reached Bonferroni level of significance within our stage-1 meta-analysis. Conclusion: This GWAS analysis did not provide evidence that genetic variation affects statin response on cardiovascular risk reduction. It does not appear likely that genetic testing for predicting effects of statins on clinical events will become a useful tool in clinical practice.


Head imaging abnormalities in dihydropyrimidine dehydrogenase deficiency.
Dihydropyrimidine dehydrogenase (DPD) deficiency is a rare autosomal recessive disorder of pyrimidine metabolism. Patients may present with a wide range of neurological symptoms during the first years of life. Head imaging abnormalities have been reported only rarely and include diffuse cerebral atrophy and white-matter hyperintensity. The pathogenesis of the white-matter abnormalities is unknown, although environmental factors and altered energy metabolism may be involved. To further understanding of the spectrum of brain abnormalities associated with DPD deficiency, we report a 17-month-old girl, born to a consanguineous Pakistani couple, who had a history of encephalopathy, prolonged hypoventilation, developmental delay and failure to thrive. Head MRI showed prominent sulci and abnormal T2 prolongation in the cerebral white matter and brainstem. Thus, DPD deficiency may feature prominent brain abnormalities involving the cerebral white matter and brainstem. Anoxic stress may have contributed to the clinical presentation and brain findings in this case. In order to define more clearly the contribution of DPD deficiency to the pathogenesis of these MRI abnormalities, we recommend performing detailed analysis of urine pyrimidine metabolites in patients who have such findings.


Catalyst-free photo-induced aerobic radical synthesis of lactams from N-alkenyl trichloroacetamides in 2-methyltetrahydrofuran as the radical initiator under violet light.
The first violet light-mediated synthesis of γ- and δ-lactams from N-alkenyl trichloroacetamides is reported in tetrahydrofuran or 2-methyltetrahydrofuran alone. These catalyst and additive-free reactions are achieved with non-anhydrous solvents and under an air atmosphere where the solvent serves as the radical initiator.


Celebrating the 50th Issue of Qatar Medical Journal: Editorial Letter.
It is with great pride that we celebrate the 50th issue of Qatar Medical Journal (QMJ) that has achieved significant growth recently. Our mission is to encourage authors to submit high-quality and innovative research promoting medical advancements. In the past two years, manuscripts submissions have tripled in number and were enriched by a more diverse pool of authors with global representation, resulting in an increase in the number of published issues moving from being a biannual to a triannual journal. Additionally, the number of articles published in an issue has doubled. QMJ continues to be an open-access peer-reviewed journal, publishing original research work, reviews, editorials, and case reports that are particularly relevant to medicine and free of charge to authors. It is indexed in several renowned and highly ranked platforms such as PubMed Central, Scopus, Scimago, Google Scholar, and the Directory of Open Access Journals. It was also recently indexed in the World Health Organization's Index Medicus for the Eastern Mediterranean Region (IMEMR). We look forwards to becoming the highest-rated medical journal, in terms of impact factor, regionally.


β Decays as Sensitive Probes of Lepton Flavor Universality.
Nuclear β decays as well as the decay of the neutron are well-established low-energy probes of physics beyond the standard model (SM). In particular, with the axial-vector coupling of the nucleon g_{A} determined from lattice QCD, the comparison between experiment and SM prediction is commonly used to derive constraints on right-handed currents. Further, in addition to the CKM element V_{us} from kaon decays, V_{ud} from β decays is a critical input for the test of CKM unitarity. Here, we point out that the available information on β decays can be reinterpreted as a stringent test of lepton flavor universality (LFU). In fact, we find that the ratio of V_{us} from kaon decays over V_{us} from β decays (assuming CKM unitarity) is extremely sensitive to LFU violation (LFUV) in W-μ-ν couplings thanks to a CKM enhancement by (V_{ud}/V_{us})^{2}∼20. From this perspective, recent hints for the violation of CKM unitarity can be viewed as further evidence for LFUV, fitting into the existing picture exhibited by semileptonic B decays and the anomalous magnetic moments of muon and electron. Finally, we comment on the future sensitivity that can be reached with this LFU violating observable and discuss complementary probes of LFU that may reach a similar level of precision, such as Γ(π→μν)/Γ(π→eν) at the PEN and PiENu experiments or even direct measurements of W→μν at an FCC-ee.


Determination of Atomoxetine Hydrochloride in Biological Fluids Using Potentiometric Carbon Paste Electrode Modified by TiO2 Nanoparticles.
Endeavors to improve the limit of detection for atomoxetine-selective electrode were documented. Simple potentiometric carbon paste electrodes (CPEs) based on atomoxetine-derivatized with tetraphenylborate (ATM-TPB) or phosphotungstic acid (ATM-PTA) as ion-pairs decorated with TiO2 nanoparticles and sodium tetraphenylborate (Na-TPB) as additives were most useful. Parameters affecting the performance of the electrodes were investigated, such as paste composition, type of plasticizers, kind of electroactive materials and interfering species. The electrodes were notable for bringing down the detection limit to 8.0 x 10-7 M and 9.2 x 10-7 M, wide linear ranges 1.1 x 10-6-1.0 x 10-2 M and 1.75×10-6-1.00×10-2 M, slope 58.7±0.5 mV/decade and 67.2±0.8 mV/decade, respectively. Importantly, the potential reading became more stable and rapidly attained in the presence of additives. The selectivity for the drug over other species such as inorganic and organic cations, as well as different excipients that are likely incorporated in pharmaceutical preparations was high making their effect negligible on the response of the electrodes. The sensors, as indicator electrodes, were successfully applied for determination of the drug in pharmaceutical preparation, urine and serum with good accuracy, excellent recovery and efficiency.


Strongyloides stercoralis, the hidden worm. Epidemiological and clinical characteristics of 70 cases diagnosed in the North Metropolitan Area of Barcelona, Spain, 2003-2012.
The nematode Strongyloides stercoralis has a very particular autoinfection life-cycle which leads to chronic infections remaining undetected for decades. However, hyperinfection can occur in patients receiving immunotherapy resulting in high mortality rates. The main objective of this study was to assess the results of a 10-year multicenter surveillance program performed in an area with dense immigration in Barcelona, Spain. From January 2003 to December 2012, all individuals with Strongyloides stercoralis infection attending the four centers with diagnostic capability in the North Metropolitan area of Barcelona were recorded. The annual detection rate was 0.2 new diagnosed cases x10 000 inhabitants/year and 1 case x10 000 immigrants/year. Many patients were immigrants (63; 90.0%), asymptomatic (45; 64.3%) and with a high eosinophil count (63; 90.0%). Immunosuppression was present in 11 (15.7%) patients, among whom two (2.8%) cases of disseminated hyperinfection were recorded. Ivermectin was prescribed in 45 (76.3%) and albendazole in 14 (23.7%). Following treatment seven patients (11.9%) receiving albendazole presented relapse, that is, albendazole failed to clear the parasite in 50% of these drug-treated patients (p < 0.001). During the study period, 90% of the cases of Strongyloides stercoralis diagnosed could be considered as imported by immigrants, most being asymptomatic and with eosinophilia. The infection is probably largely underestimated and population-based studies are needed to determine its true prevalence. Meanwhile, diagnosis must be based on active investigation of the helminth (serology and feces culture), especially in immunocompromised patients. The implementation of pre-immunosuppression protocols with the aim of identifying Strongyloides stercoralis is encouraged with empirical treatment with ivermectin being recommended in sites without diagnostic facilities.


The neurological outcome of radiotherapy versus surgery in patients with metastatic spinal cord compression presenting with myelopathy.
While radiotherapy is generally an acceptable treatment for metastatic spinal cord compression, surgical intervention is controversial due to the invasiveness and diversity of diseases in the patients being considered. The ideal treatment, therefore, depends on the situation, and the most acute treatment possible is necessary in patients presenting with myelopathy. We compared the neurological outcomes between radiotherapy and surgery in patients with metastatic spinal cord compression presenting with myelopathy. A total 54 patients with metastatic spinal cord compression presenting with myelopathy treated in our institution between 2006 and 2016 were analyzed retrospectively. Twenty patients were selected by radiotherapy alone (radiation group), and 36 patients were selected by decompression and stabilization surgery with or without radiotherapy (surgery group). The neurological outcomes and complications were compared between the two treatment groups. Seven patients initially in the radiation group underwent surgery because of a substantial decline in their motor strength during radiotherapy. One of the remaining 13 patients (8%) in the radiation group and 30 of the 34 patients (88%) in the surgery group showed improvement in their neurological symptoms (P < 0.01). One patient (8%) in the radiation group and 21 patients (62%) in the surgery group were ambulatory after treatment (P < 0.01). There were no major complications related to radiotherapy, but surgery-related complications occurred in 9 of 34 (26%) patients, and 6 (18%) patients needed reoperation. Surgical decompression and stabilization may be required to improve the neurological function in patients with metastatic spinal cord compression presenting with myelopathy. However, the high rate of complications associated with surgery should be taken into consideration.


Comparison of four sequential methods allowing for early stopping of comparative clinical trials.
Phase III trials aim to assess whether a new treatment has superior efficacy than a standard treatment. Sequential methods, such as the sequential probability ratio test (SPRT), the triangular test (TT) and so-called one-parameter boundaries (OPB), now allow early stopping of such trials, both in the case of efficacy (alternative hypothesis; H(1)) and in the case of lack of efficacy (null hypothesis; H(0)). We compared the statistical properties of the SPRT and the TT, and of OPB with Pocock (OPB(Delta=0.5)) and O'Brien and Fleming (OPB(Delta=0)) type boundaries, in the setting of one-sided comparative trials with normal response. We studied the type I error (alpha), power (1-beta), average sample number (ASN) and 90th percentile (P90) of the number of patients required to reach a conclusion using simulations. The four tests were also compared with the corresponding single-stage design (SSD). All sequential tests display alpha and 1-beta close to nominal values and, as compared with SSD, allow important decreases in ASN: for example, -48%, -42%, -40% and -31% under H(0) and H(1) for SPRT, TT, OPB(Delta=0.5) and OPB(Delta=0) respectively. For situations between H(0) and H(1), ASNs of all sequential tests were still smaller than the sample size required by SSD, with the TT displaying the largest decrease (-25%). The P90s of the TT and OPB(Delta=0) under H(0) and H(1) were smaller than the P90s of the SPRT and OPB(Delta=0.5), which were similar to the sample size required by SSD. If all sequential tests display approximately similar features, the TT is the most appealing regarding decreases in sample size, especially for situations between H(0) and H(1).


Double-stranded ribonucleic acid in viruses of Penicillium citrinum.
The nucleic acid content of two viral populations in a strain of Penicillium citrinum is shown to be double-stranded ribonucleic acid, resolved through polyacrylamide gel electrophoresis into 10 size groups ranging from 1.17 to 3.98 megadaltons.


One baby, four parents: assisted reproduction for two couples in New Zealand.
Egg donation by another woman in New Zealand and elsewhere has become a successful solution for childless couples who want to have a baby. In vitro fertilization (IVF) was first undertaken in New Zealand in 1983 (1). Approximately 5 in 100 couples have IVF in New Zealand, and 450 IVF babies are born each year (2). In this article, two women and two men who underwent this assisted reproductive process describe, in question-and-answer format, their experiences from their initial meeting and proposal, evaluation, egg retrieval and implantation, and pregnancy, to the birth of a healthy infant. Petra is the egg donor and genetic mother and Adam is her husband, Donna is the recipient and biological mother, and Erich is her husband and the genetic/biological father. Lorelai, the baby, was born on 27 November 2009 in Auckland, New Zealand.


Silver nanowire catalysts on carbon nanotubes-incorporated bacterial cellulose membrane electrodes for oxygen reduction reaction.
Silver nanowires have unique electrical, thermal and optical properties, which support their potential application in numerous fields including catalysis, electronics, optoelectronics, sensing, and surface-enhanced spectroscopy. Especially, their application such as catalysts for alkaline fuel cells (AFCs) have attracted much interest because of their superior electrical conductivity over that of any metal and their lower cost compared to Pt. In this study, multiwalled carbon nanotubes (MWCNTs)-incorporated bacterial cellulose (BC) membrane electrode with silver nanowire catalyst was prepared. First, acid-treated MWCNTs were incorporated into BC membranes and then freeze-dried after solvent exchange to tert-butanol in order to maintain the 3D-network macroporous structure. Second, silver nanowires synthesized by polyol process were introduced onto the surface of the MWCNTs-incorporated BC membrane through easy vacuum filtration. Finally, thermal treatment was carried out to confirm the effect of the PVP on the silver nanowire catalysts toward oxygen reduction reaction. The electrode with thermally treated silver nanowire had great electrocatalytic activity compared with non-treated one. These results suggest that the MWCNTs-incorporated BC electrode with silver nanowire catalysts after thermal treatment could be potentially used in cathodes of AFCs.


Migraine-Associated TRESK Mutations Increase Neuronal Excitability through Alternative Translation Initiation and Inhibition of TREK.
It is often unclear why some genetic mutations to a given gene contribute to neurological disorders and others do not. For instance, two mutations have previously been found to produce a dominant negative for TRESK, a two-pore-domain K+ channel implicated in migraine: TRESK-MT, a 2-bp frameshift mutation, and TRESK-C110R. Both mutants inhibit TRESK, but only TRESK-MT increases sensory neuron excitability and is linked to migraine. Here, we identify a new mechanism, termed frameshift mutation-induced alternative translation initiation (fsATI), that may explain why only TRESK-MT is associated with migraine. fsATI leads to the production of a second protein fragment, TRESK-MT2, which co-assembles with and inhibits TREK1 and TREK2, two other two-pore-domain K+ channels, to increase trigeminal sensory neuron excitability, leading to a migraine-like phenotype in rodents. These findings identify TREK1 and TREK2 as potential molecular targets in migraine and suggest that fsATI should be considered as a distinct class of mutations.


Photoperiodism in birds.
Birds show a circadian rhythm in melatonin secretion and, as expected, the pattern of output changes with photoperiod. Somewhat surprisingly then, in view of the mechanisms in mammals, birds do not seem to use this seasonal message in the photoperiodic control of reproduction. Some further experiments are needed, however, because in birds the pineal gland is not the only source of melatonin. Another difference from mammals is that birds detect the photoperiodic light not with the retina but by brain photoreceptors, which probably lie in the hypothalamus. An action spectrum for these receptors has now been obtained for the quail and this shows a peak absorption at 492 nm, suggesting that the photoreceptor is rhodopsin-based. The sensitivity of the brain receptors to 500 nm light was calculated at 2 X 10(4) photons mm-2s-1. For light to induce the photoperiodic response it must be interpreted by the bird's clock as a long day. This happens if the light falls 12-20 h after dawn and coincides with a rhythm of photosensitivity. The subsequent neuroendocrine response to the light signal is both precise and relatively long-term. A single 4 h light pulse initiates a wave of gonadotropin secretion lasting for 10 days. The light stimulus can be replaced by a brief (2 min) daily electrical stimulus given to the hypothalamus 10-12 h after dawn. Over the next few years it should be possible to disentangle further the neural processes involved.


Behavioral impact of maternal allergic-asthma in two genetically distinct mouse strains.
Recent population-based studies of expecting mothers identified a unique profile of immune markers that are associated with an increased risk of having a child diagnosed with autism spectrum disorder (ASD). This immune profile, including increased levels of maternal and placental interleukin (IL)-4 and IL-5, is consistent with an immune response found in an allergic-asthma phenotype. Allergies and asthma reflect an imbalance in immune responses including polarization towards T-helper type 2 (TH2) responses, with both genetic susceptibility and environmental factors affecting this T-cell polarization. Mouse strains provide a known and controlled source of genetic diversity to explore the role of genetic predisposition on environmental factors. In particular, the FVB background exhibits a skew towards TH2-mediated allergic-asthma response in traditional models of asthma whereas the C57 strain exhibits a more blunted TH2 polarized phenotype resulting in an attenuated allergic-asthma response. C57BL/6J (C57) and the sighted FVB.129P2-Pde6b(+) Tyr(c-ch)/Ant (FVB/Ant) lines were selected based on their characteristic high sociability and differing sensitivity to TH2-mediated stimuli. Based on the distinct allergy-sensitive immune responses of these two strains, we hypothesized that unique developmental consequences would occur in offspring following maternal allergy-asthma exposure. Female C57 and FVB/Ant dams were primed/sensitized with an exposure to ovalbumin (OVA) before pregnancy, then exposed to either aerosolized OVA or PBS-vehicle throughout gestation. Sera from pregnant dams were analyzed for changes in cytokine profiles using multiplex-arrays and offspring were assessed for changes in autism-like behavioral responses. Analysis of maternal sera revealed elevated IL-4 and IL-5 in OVA-treated dams of both strains but only C57 mice expressed increased levels of IL-1β, IL-6, TNFα, and IL-17. Behavioral assessments revealed strain-dependent changes in juvenile reciprocal social interaction in offspring of maternal allergic asthma dams. Moreover, mice of both strains showed decreased repetitive grooming and increased marble burying behavior when born to OVA-exposed dams. Together, these findings support the important role genetic predisposition plays in the effects of maternal immune activation and underscore differences in ASD-like behavioral outcomes across mouse strains.


Marketing activities of vape shops across racial/ethnic communities.
There has been a surge in the number of vape shops in the USA. Research on the marketing practices of e-cigarette manufacturers is scarce and even less known are the practices of vape shop retailers. Past research on tobacco marketing has shown differences in the amount and content of marketing material, based on a community's demographic profile. This study examined marketing strategies in vape shops and explored differences among vape shops located in communities that differ by ethnic composition. Data was gathered in 2014 from a pilot-study on vape shops (n=77) in Los Angeles, which documented the characteristics of shops through employee interviews and in-store observations. Data were collected from shops located in communities that were predominantly, African-American (n=20), Hispanic (n=17), Korean (n=18), or non-Hispanic White (n=22). Sixty-one percent of vape shops had advertisements (print ads and posters) for e-cigarettes and 84% offered discounts. Vape shops in Hispanic communities were more likely to have ethnic specific marketing material compared to shops in other communities. All the shops provided customers with free samples, however those in Korean and non-Hispanic White communities had a significantly higher prevalence of customer accessible free samples. Vape shop marketing practices differed by ethnic community. A large majority of shops provided free samples to their customers, a practice which is now banned by the FDA. It will be important to monitor how vape shops will adjust their marketing strategy because of this ban. Future research should expand on the findings presented here to provide regulators with further crucial information.


ANMCO POSITION PAPER: cardio-oncology in the COVID era (CO and CO).
The COVID-19 pandemic and its impact on patients with cancer and cardiovascular disease have confirmed the particular vulnerability of these populations. Indeed, not only a higher risk of contracting the infection has been reported but also an increased occurrence of a more severe course and unfavourable outcome. Beyond the direct consequences of COVID-19 infection, the pandemic has an enormous impact on global health systems. Screening programmes and non-urgent tests have been postponed; clinical trials have suffered a setback. Similarly, in the area of cardiology care, a significant decline in STEMI accesses and an increase in cases of late presenting heart attacks with increased mortality and complication rates have been reported. Health care systems must therefore get ready to tackle the 'rebound effect' that will likely show a relative increase in the short- and medium-term incidence of diseases such as heart failure, myocardial infarction, arrhythmias, and cardio- and cerebrovascular complications. Scientific societies are taking action to provide general guidance and recommendations aimed at mitigating the unfavourable outcomes of this pandemic emergency. Cardio-oncology, as an emerging discipline, is more flexible in modulating care pathways and represents a beacon of innovation in the development of multi-specialty patient management. In the era of the COVID-19 pandemic, cardio-oncology has rapidly modified its clinical care pathways and implemented flexible monitoring protocols that include targeted use of cardiac imaging, increased use of biomarkers, and telemedicine systems. The goal of these strategic adjustments is to minimize the risk of infection for providers and patients while maintaining standards of care for the treatment of oncologic and cardiovascular diseases. The aim of this document is to evaluate the impact of the pandemic on the management of cardio-oncologic patients with the-state-of-the-art knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease (COVID-19) in order to optimize medical strategies during and after the pandemic.


Gestational diabetes: an evaluation of serum fructosamine as a screening test in a high-risk population.
To evaluate the value of serum fructosamine as a screening test for gestational diabetes mellitus (GDM). 849 pregnant women underwent the one-step 75 g oral glucose tolerance test (OGTT) for universal screening of GDM. The fasting serum fructosamine (cFruc) was assessed using the area under the receiver operating characteristic curve (AUC). The GDM diagnostic criteria used were those of the American Diabetes Association; however, the cFruc performance was also evaluated using criteria of the World Health Organization, Australian (ADIPS), European (EASD) and International Association of Diabetes and Pregnancy Study Groups (IADPSG). 113 (13.3%) women had GDM. The AUC of the cFruc was 0.60 (95% CI 0.54-0.66). A cFruc threshold of 237 μmol/l achieved an acceptable sensitivity of 85.8% (95% CI 78.0-91.0%), but the associated specificity remained poor at 23.4% (95% CI 20.0-27.0%) with a positive predictive value of just 14.7%. Overall, over 4 out of 5 pregnant women, being over this cutoff, would need the confirmatory OGTT. No cFruc threshold reached acceptable likelihood ratios to rule-in or rule-out GDM. The AUC for cFruc remained unacceptable independent of the diagnostic criteria. Despite all the advances in technology, serum fructosamine is a poor test to screen for GDM.


Spawning aggregations of checkered snapper (Lutjanus decussatus) and blackspot snapper (L. fulviflamma): seasonality, lunar-phase periodicity and spatial distribution within spawning ground.
Snappers (family Lutjanidae) are important fisheries target species and some species are known to form spawning aggregations at particular spawning grounds. The present study investigated the ecological characteristics of fish aggregations of two snapper species (checkered snapper Lutjanus decussatus and blackspot snapper L. fulviflamma) that form at a particular site. Specifically, the aims were to clarify (1) seasonality and lunar-phase periodicity of fish aggregation formation, (2) fine-scale spatial distribution of fish density (spatial variations of fish density at intervals of several-tens meters) within the aggregation site, (3) size and age frequency distributions of fishes in the aggregation site, (4) gonad development, (5) to compare fish abundance between inside and outside the aggregation site, and (6) to verify that fish aggregations of the two snapper species were spawning aggregation. Underwater observations using a 600 m × 5 m transect revealed that greater fish abundance of Lutjanus decussatus was found monthly between May and October, and clear positive peaks in the fish abundance were found only around the last-quarter moon. This lunar-related periodicity in the increase of fish abundance was confirmed by a time-series analysis (correlogram). Within the aggregation site, L. decussatus showed a relatively uniform distribution. In contrast, greater fish abundance of L. fulviflamma was found monthly between April and October, and clear positive peaks in the fish abundance were found around the last-quarter moon (April, May, June and October) or new moon (July, August and September). This lunar-related periodicity was also confirmed by correlogram. Lutjanus fulviflamma showed a relatively clumped distribution within the aggregation site. Most females of the two species in the aggregation site had hydrated eggs, indicating that the two species form aggregations for reproduction. The two species, although occurring simultaneously, are considered to form aggregations of conspecifics only. For L. decussatus, average fork length and age of males and females were 229.2 mm and 243.9 mm and 9.4 years and 8.1 years, respectively. For L. fulviflamma, average fork length and age of males and females were 233.9 mm and 246.9 mm and 6.8 years and 8.1 years, respectively. Fish abundance inside the aggregation site was 266.8-fold and 141557.1-fold greater than those outside the aggregation site for L. decussatus and L. fulviflamma, respectively. These results showed that (1) fish aggregation formation of the two snapper species was predictably repeated in particular months and lunar-phase, (2) it was predictably found at the particular site, (3) the fish abundance in the aggregation site markedly exceeded the fish abundance outside the aggregation site, and (4) the two species form aggregations for reproduction. Therefore, it is suggested that the fish aggregations for the two species can be regarded as spawning aggregations.


[Properties of hepatitis A virus particles produced during infection in vitro].
Four types of virus-specific particles with different sedimentation coefficients and buoyant densities in CsCl were shown to be accumulated in hepatitis A virus (strain HAS-15) infected fetal rhesus monkey kidney cells (FRhK-4 line). Unlike the mature virions (155S, 1.34 g/cm3), cell-associated isosedimenting 92 S-particles (buoyant densities of 1.30 and 1.20 g/cm3) proved to be sensitive to lipase action. Particles of all four types were shown to contain similar sets of polypeptides, and, with the exception of "empty" 1.30 g/cm3-particles, appeared to be "full" under the immune electron microscopic examination. The viral RNA was unequivocally identified by the molecular hydridization test only in the mature virions.


Eye movements in patients in early psychosis with and without a history of cannabis use.
It is unclear whether early psychosis in the context of cannabis use is different from psychosis without cannabis. We investigated this issue by examining whether abnormalities in oculomotor control differ between patients with psychosis with and without a history of cannabis use. We studied four groups: patients in the early phase of psychosis with a history of cannabis use (EPC; n = 28); patients in the early phase of psychosis without (EPNC; n = 25); controls with a history of cannabis use (HCC; n = 16); and controls without (HCNC; n = 22). We studied smooth pursuit eye movements using a stimulus with sinusoidal waveform at three target frequencies (0.2, 0.4 and 0.6 Hz). Participants also performed 40 antisaccade trials. There were no differences between the EPC and EPNC groups in diagnosis, symptom severity or level of functioning. We found evidence for a cannabis effect (χ2 = 23.14, p < 0.001), patient effect (χ2 = 4.84, p = 0.028) and patient × cannabis effect (χ2 = 4.20, p = 0.04) for smooth pursuit velocity gain. There was a large difference between EPC and EPNC (g = 0.76-0.86) with impairment in the non cannabis using group. We found no significant effect for antisaccade error whereas patients had fewer valid trials compared to controls. These data indicate that impairment of smooth pursuit in psychosis is more severe in patients without a history of cannabis use. This is consistent with the notion that the severity of neurobiological alterations in psychosis is lower in patients whose illness developed in the context of cannabis use.


Crisflash: open-source software to generate CRISPR guide RNAs against genomes annotated with individual variation.
CRISPR/Cas9 system requires short guide RNAs (sgRNAs) to direct genome modification. Most currently available tools for sgRNA design operate only with standard reference genomes, and are best suited for small-scale projects. To address these limitations, we developed Crisflash, a software tool for fast sgRNA design and potential off-target discovery, built for performance and flexibility. Crisflash can rapidly design CRISPR guides against any sequenced genome or genome sequences, and can optimize guide accuracy by incorporating user-supplied variant data. Crisflash is over an order of magnitude faster than comparable tools, even using a single CPU core, and efficiently and robustly scores the potential off-targeting of all possible candidate CRISPR guide oligonucleotides. https://github.com/crisflash. Supplementary data are available at Bioinformatics online.


Recent developments in MrBUMP: better search-model preparation, graphical interaction with search models, and solution improvement and assessment.
Increasing sophistication in molecular-replacement (MR) software and the rapid expansion of the PDB in recent years have allowed the technique to become the dominant method for determining the phases of a target structure in macromolecular X-ray crystallography. In addition, improvements in bioinformatic techniques for finding suitable homologous structures for use as MR search models, combined with developments in refinement and model-building techniques, have pushed the applicability of MR to lower sequence identities and made weak MR solutions more amenable to refinement and improvement. MrBUMP is a CCP4 pipeline which automates all stages of the MR procedure. Its scope covers everything from the sourcing and preparation of suitable search models right through to rebuilding of the positioned search model. Recent improvements to the pipeline include the adoption of more sensitive bioinformatic tools for sourcing search models, enhanced model-preparation techniques including better ensembling of homologues, and the use of phase improvement and model building on the resulting solution. The pipeline has also been deployed as an online service through CCP4 online, which allows its users to exploit large bioinformatic databases and coarse-grained parallelism to speed up the determination of a possible solution. Finally, the molecular-graphics application CCP4mg has been combined with MrBUMP to provide an interactive visual aid to the user during the process of selecting and manipulating search models for use in MR. Here, these developments in MrBUMP are described with a case study to explore how some of the enhancements to the pipeline and to CCP4mg can help to solve a difficult case.


New developments in the preoperative evaluation and perioperative management of coronary artery disease in patients undergoing vascular surgery.
Preoperative evaluation and perioperative management of cardiac disease in patients undergoing vascular surgery (VS) is important for patients and vascular surgeons. Recent evidence has emerged that has allowed us to develop contemporary paradigms for evaluating and managing coronary artery disease in VS patients perioperatively. The utility of stress testing, the role of preoperative coronary revascularization, the optimal use of beta-blockers and statins, and the role of antiplatelet therapy in VS patients were reviewed in the literature. The revised Lee cardiac risk index, based on the number of risk factors (high-risk surgery, ischemic heart disease, congestive heart failure, cerebrovascular disease, insulin-dependent diabetes mellitus, renal failure, hypertension, and age >75) quantitates cardiac risk. Stress testing is not predictive of myocardial ischemia/infarction (MI) or death and is only recommended in patients with unstable angina or an active arrhythmia. Stress testing for patients with 0 to 2 risk factors delays VS up to 3 weeks. In high-risk patients (>or=3 risk factors), it helps to identify patients who may develop myocardial ischemia and would benefit from a 30-day period to optimize medical therapy before VS. Stress testing and coronary catheterization do not predict which coronary artery to revascularize to prevent MI or death. Revascularization does not decrease MI or death rates at 1 month or 6 years. Although beta-blocker treatment decreases cardiac risk with VS, timing and dosage (titration) influence outcomes, improper usage may increase stroke and death rate, and not all VS patients should be taking these drugs. Patients with >or=1 risk factor should be considered to begin a low dose beta-blocker 1 month before VS. Preoperative statin use sharply decreases MI, stroke, and death perioperatively and long-term postoperatively. Routine stress testing should not be performed before VS. The Lee index should be used to stratify risk in patients undergoing VS. Patients with >or=3 risk factors or active cardiac conditions should undergo stress testing, if VS can be delayed. All VS patients, except those with 0 risk factors, should be considered for a beta-blocker (bisoprolol, 2.5-5 mg/d started 1 month before VS, titrated to a pulse <70 beats/min and a systolic blood pressure >or=120 mm Hg). Intermediate risk factors may not require aggressive heart rate control but simply maintenance on a low-dose beta-blocker. Statins should be started (ideally 30 days) before all VS using long-acting formulations such as fluvastatin (80 mg/d) for patients unable to take oral medication.


Case-control study of primary human herpesvirus 6 infection in children with febrile seizures.
Human herpesvirus 6 (HHV-6) has been demonstrated to be the causative agent in roseola infantum. It has been suggested that HHV-6 may have neurotropic properties and be involved in the pathogenesis of febrile seizures in infants. We describe a case-control study to examine the hypothesis that acute HHV-6 infection occurs more commonly in children with febrile seizures than in controls. Patients presenting with a first or second febrile seizure between 6 months and 2 years of age were entered in the study. Control patients did not have a seizure but had similar inclusion and exclusion criteria. Specimens were obtained for HHV-6 viral serology and polymerase chain reaction in the acute stage and approximately 2 weeks later. A diagnosis of HHV-6 infection was based on HHV-6-specific IgM and IgG serology and HHV-6 polymerase chain reaction of peripheral blood mononuclear cells and saliva. Eighty-six patients (45 with febrile seizures; 41 controls) were enrolled. The HHV-6 infection status could be determined in only 68 patients (35 with febrile seizures; 33 controls). Acute HHV-6 infection was identified in 15 of 35 febrile seizure patients and in 15 of 33 controls. Evidence of past HHV-6 infection was demonstrated in 13 febrile seizure patients and in 8 controls. The incidence of primary HHV-6 infection is similar in patients with febrile seizures and age-matched controls. HHV-6 does not seem to be a major factor in the pathogenesis of first and second febrile seizures.


Quenching of a no-insulation high-temperature superconducting magnet.
We report details on the quenching incident of an 18 T high-temperature superconducting (HTS) magnet, which occurred in December 2020. It has been received that the no-insulation (NI) design of an HTS magnet is relatively safe in quenching. However, the NI design could not completely prevent the magnet from quenching and damaging the associated system. Due to significant vibrations and fast energy dissipation during quenching, the magnet and the detector components are seriously damaged. The manufacturer inspected the magnet after the incident and repaired it in the spring of 2021. The magnet showed stable and consistent performance after the repair. It is evident that the NI-HTS magnet still requires quench protection circuits to secure the magnet and associated system.


Indirect parental effects on offspring viability by egg-derived fluids in an external fertilizer.
The capacity for parents to influence offspring phenotypes via nongenetic inheritance is currently a major area of focus in evolutionary biology. Intriguing recent evidence suggests that sexual interactions among males and females, both before and during mating, are important mediators of such effects. Sexual interactions typically extend beyond gamete release, involving both sperm and eggs, and their associated fluids. However, the potential for gamete-level interactions to induce nongenetic parental effects remains under-investigated. Here, we test for such effects using an emerging model system for studying gamete interactions, the external fertilizer Mytilus galloprovincialis. We employed a split-ejaculate design to test whether exposing sperm to egg-derived chemicals (ECs) from a female would affect fertilization rate and offspring viability when those sperm were used to fertilize a different female's eggs. We found separate, significant effects of ECs from non-fertilizing females on both fertilization rate and offspring viability. The offspring viability effect indicates that EC-driven interactions can have nongenetic implications for offspring fitness independent of the genotypes inherited by those offspring. These findings provide a rare test of indirect parental effects driven exclusively by gamete-level interactions, and to our knowledge the first evidence that such effects occur via the gametic fluids of females.


Neighborhood binary speckle pattern for deformation measurements insensitive to local illumination variation by digital image correlation.
Speckle pattern-based characteristics of digital image correlation (DIC) restrict its application in engineering fields and nonlaboratory environments, since serious decorrelation effect occurs due to localized sudden illumination variation. A simple and efficient speckle pattern adjusting and optimizing approach presented in this paper is aimed at providing a novel speckle pattern robust enough to resist local illumination variation. The new speckle pattern, called neighborhood binary speckle pattern, derived from original speckle pattern, is obtained by means of thresholding the pixels of a neighborhood at its central pixel value and considering the result as a binary number. The efficiency of the proposed speckle pattern is evaluated in six experimental scenarios. Experiment results indicate that the DIC measurements based on neighborhood binary speckle pattern are able to provide reliable and accurate results, even though local brightness and contrast of the deformed images have been seriously changed. It is expected that the new speckle pattern will have more potential value in engineering applications.


A genome-wide analysis reveals no nuclear dobzhansky-muller pairs of determinants of speciation between S. cerevisiae and S. paradoxus, but suggests more complex incompatibilities.
The Dobzhansky-Muller (D-M) model of speciation by genic incompatibility is widely accepted as the primary cause of interspecific postzygotic isolation. Since the introduction of this model, there have been theoretical and experimental data supporting the existence of such incompatibilities. However, speciation genes have been largely elusive, with only a handful of candidate genes identified in a few organisms. The Saccharomyces sensu stricto yeasts, which have small genomes and can mate interspecifically to produce sterile hybrids, are thus an ideal model for studying postzygotic isolation. Among them, only a single D-M pair, comprising a mitochondrially targeted product of a nuclear gene and a mitochondrially encoded locus, has been found. Thus far, no D-M pair of nuclear genes has been identified between any sensu stricto yeasts. We report here the first detailed genome-wide analysis of rare meiotic products from an otherwise sterile hybrid and show that no classic D-M pairs of speciation genes exist between the nuclear genomes of the closely related yeasts S. cerevisiae and S. paradoxus. Instead, our analyses suggest that more complex interactions, likely involving multiple loci having weak effects, may be responsible for their post-zygotic separation. The lack of a nuclear encoded classic D-M pair between these two yeasts, yet the existence of multiple loci that may each exert a small effect through complex interactions suggests that initial speciation events might not always be mediated by D-M pairs. An alternative explanation may be that the accumulation of polymorphisms leads to gamete inviability due to the activities of anti-recombination mechanisms and/or incompatibilities between the species' transcriptional and metabolic networks, with no single pair at least initially being responsible for the incompatibility. After such a speciation event, it is possible that one or more D-M pairs might subsequently arise following isolation.


Polarized secretion of tyrosine-sulphated proteins and free tyrosine O-sulphate by filter-grown Madin-Darby canine kidney (MDCK) cells.
Filter-grown Madin-Darby canine kidney (MDCK) cells labelled for 24 h with [35S]sulphate were found to secrete macromolecules [35S]sulphated on their carbohydrate moieties predominantly into the basolateral medium, whereas the tyrosine-[35S]sulphated proteins synthesized were predominantly secreted into the apical medium. In contrast with the predominant apical secretin of tyrosine-[35S]sulphated proteins, the free tyrosine O-[35S]sulphate (Tyr[35S]) was released mostly into the basolateral medium. A time-lapse study using prelabelled MDCK cells incubated in fresh medium revealed that, during the 48 h time course monitored, the release of tyrosine-[35S]sulphated proteins into the apical medium was faster and quantitatively greater than that into the basolateral medium. During the same time there was a concomitant release, predominantly into the basolateral medium, of the free Tyr[35S] derived from the degradation of tyrosine-[35S]sulphated proteins. An endocytotic degradation experiment was performed to demonstrate the endocytosis of tyrosine-sulphated proteins and their degradation to generate free TyrS. It was found that free Tyr[35S] was generated and released when an apically secreted (or basolaterally secreted) tyrosine-[35S]sulphated protein preparation was added to the apical medium (or the basolateral medium) of unlabelled filter-grown MDCK cells. In both cases, the free Tyr[35S] generated was predominantly released into the basolateral medium similar to the results obtained in the time-lapse study.


Transduction persists in rod photoreceptors after depletion of intracellular calcium.
We have examined the role of Ca++ in phototransduction by manipulating the intracellular Ca++ concentration in physiologically active suspensions of isolated and purified rod photoreceptors (OS-IS). The results are summarized by the following. Measurement of Ca++ content using arsenazo III spectroscopy demonstrates that incubation of OS-IS in 10 nM Ca++-Ringer's solution containing the Ca++ ionophore A23187 reduces their Ca++ content by 93%, from 1.3 to 0.1 mol Ca++/mol rhodopsin. Virtually the same reduction can be accomplished in 10 nM Ca++-Ringer's without ionophore, presumably via the plasma membrane Na/Ca exchange mechanism. Hundreds of photoresponses can be obtained from the Ca++-depleted OS-IS for at least 1 h in 10 nM Ca++-Ringer's with ionophore. The kinetics and light sensitivity of the photoresponse are essentially the same in the presence or absence of the ionophore in 10 nM Ca++. The addition of A23187 in 1 mM Ca++-Ringer's results in a Ca++ influx that rapidly suppresses the dark current and the photoresponse. This indicates that there is an intracellular site at which Ca++ can modulate the light-regulated conductance. Both the current and photoresponse can be restored if intracellular Ca++ is reduced by lowering the external Ca++ to 10 nM. During the transition from high to low Ca++, the response duration becomes shorter, which suggests that it can be regulated by a Ca++-dependent mechanism. If the dark current and the photoresponse are suppressed by adding A23187 in 1 mM Ca++-Ringer's, the subsequent addition of the cyclic GMP phosphodiesterase inhibitor isobutylmethylxanthine can restore the current and photoresponse. This implies that under conditions where the rod can no longer control its intracellular Ca++, the elevation of cyclic GMP levels can restore light regulation of the channels. The persistence of normal flash responses under conditions where intracellular Ca++ levels are reduced and perturbed suggests that changes in the intracellular Ca++ concentration do not cause the closure of the light-regulated channel.


Rhizosphere shapes the associations between protistan predators and bacteria within microbiomes through the deterministic selection on bacterial communities.
The assembly of bacterial communities in the rhizosphere is well-documented and plays a crucial role in supporting plant performance. However, we have limited knowledge of how plant rhizosphere determines the assembly of protistan predators and whether the potential associations between protistan predators and bacterial communities shift due to rhizosphere selection. To address this, we examined bacterial and protistan taxa from 443 agricultural soil samples including bulk and rhizosphere soils. Our results presented distinct patterns of bacteria and protistan predators in rhizosphere microbiome assembly. Community assembly of protistan predators was determined by a stochastic process in the rhizosphere and the diversity of protistan predators was reduced in the rhizosphere compared to bulk soils, these may be attributed to the indirect impacts from the altered bacterial communities that showed deterministic process assembly in the rhizosphere. Interestingly, we observed that the plant rhizosphere facilitates more close interrelationships between protistan predators and bacterial communities, which might promote a healthy rhizosphere microbial community for plant growth. Overall, our findings indicate that the potential predator-prey relationships within the microbiome, mediated by plant rhizosphere, might contribute to plant performance in agricultural ecosystems.


Abnormal behavior and associated risk factors in captive baboons (Papio hamadryas spp.).
Abnormal behavior, ranging from motor stereotypies to self-injurious behavior, has been documented in captive nonhuman primates, with risk factors including nursery rearing, single housing, and veterinary procedures. Much of this research has focused on macaque monkeys; less is known about the extent of and risk factors for abnormal behavior in baboons. Because abnormal behavior can be indicative of poor welfare, either past or present, the purpose of this study was to survey the presence of abnormal behavior in captive baboons and to identify potential risk factors for these behaviors with an aim of prevention. Subjects were 144 baboons (119 females, 25 males) aged 3-29 (median = 9.18) years temporarily singly housed for research or clinical reasons. A 15-min focal observation was conducted on each subject using the Noldus Observer® program. Abnormal behavior was observed in 26% of the subjects, with motor stereotypy (e.g., pace, rock, swing) being the most common. Motor stereotypy was negatively associated with age when first singly housed (P < 0.005) while self-directed behavior (e.g., hair pull, self-bite) was positively associated with the lifetime number of days singly housed (P < 0.05) and the average number of blood draws per year (P < 0.05). In addition, abnormal appetitive behavior was associated with being male (P < 0.05). Although the baboons in this study exhibited relatively low levels of abnormal behavior, the risk factors for these behaviors (e.g., social restriction, routine veterinary procedures, and sex) appear to remain consistent across primate species.


Selective Atrophy of the Vastus Medialis: Does It Exist in Women With Nontraumatic Patellofemoral Pain?
A commonly cited theory related to the pathomechanics of patellofemoral pain (PFP) states that atrophy of the vastus medialis (VM) muscle leads to lateral tracking of the patella. However, isolated atrophy of the VM or atrophy of the quadriceps muscle group as a whole, has not been consistently reported in this population. To compare individual and total quadriceps muscle volumes between women with nontraumatic PFP and women without PFP as measured on magnetic resonance imaging scans. Cross-sectional study; Level of evidence, 3. A total of 52 women with nontraumatic PFP and 64 women without PFP between the ages of 18 and 45 years participated. Magnetic resonance imaging scans of the thigh were obtained from the anterior inferior iliac spine to the tibial plateau. Individual quadriceps muscle cross-sectional area measurements were obtained from each image, and muscle volumes for the VM, vastus lateralis, vastus intermedius, and rectus femoris were calculated. Muscle volume measurements were expressed in absolute values and normalized to body mass. Separate 2-way mixed-factorial analysis of variance (group × muscle) were used to compare absolute and normalized individual muscle volumes between groups. Independent t tests were used to compare absolute and normalized total quadriceps volumes between groups. There was no difference in absolute and normalized individual muscle volumes between individuals with and those without PFP. Additionally, absolute and normalized total muscle volumes did not differ between groups. Our findings do not support the concept of preferential atrophy of the VM or generalized quadriceps atrophy in women with nontraumatic PFP.


Operon prediction by comparative genomics: an application to the Synechococcus sp. WH8102 genome.
We present a computational method for operon prediction based on a comparative genomics approach. A group of consecutive genes is considered as a candidate operon if both their gene sequences and functions are conserved across several phylogenetically related genomes. In addition, various supporting data for operons are also collected through the application of public domain computer programs, and used in our prediction method. These include the prediction of conserved gene functions, promoter motifs and terminators. An apparent advantage of our approach over other operon prediction methods is that it does not require many experimental data (such as gene expression data and pathway data) as input. This feature makes it applicable to many newly sequenced genomes that do not have extensive experimental information. In order to validate our prediction, we have tested the method on Escherichia coli K12, in which operon structures have been extensively studied, through a comparative analysis against Haemophilus influenzae Rd and Salmonella typhimurium LT2. Our method successfully predicted most of the 237 known operons. After this initial validation, we then applied the method to a newly sequenced and annotated microbial genome, Synechococcus sp. WH8102, through a comparative genome analysis with two other cyanobacterial genomes, Prochlorococcus marinus sp. MED4 and P.marinus sp. MIT9313. Our results are consistent with previously reported results and statistics on operons in the literature.


Salmonellae in fish meal plants: relative amounts of contamination at various stages of processing and a method of control.
Previous studies have shown that Menhaden fish meal, a common ingredient of animal feeds, is frequently contaminated with salmonellae. Animals that eat contaminated feed may become infected. If they, in turn, are eaten by humans, they may be a means by which salmonellae are introduced into the human population. Epidemiological studies of the fish-meal industry were carried out to determine the sources of salmonellae in fish meal and the factors affecting the persistence and survival of salmonellae during the processing of fish meal. Examination of 190 fish immediately after they came from the Gulf of Mexico revealed no salmonellae, but salmonellae were frequently isolated from samples of fish taken from the boats when they arrived at the plants. Salmonellae were also frequently isolated from dockside water at each of the plants. Approximately 50% of the samples taken in the raw fish processing areas were contaminated with salmonellae. The percentage of samples yielding salmonellae decreased progressively through the various sequences of processing, but more than 15% of the samples taken from the finished products were also positive. Salmonellae were isolated from the raw area of the plant most frequently while the plant was operating and less frequently when the plant was idle, whereas in the processing area of the plant the reverse was true. Salmonellae appeared to survive and multiply in the processing area of the plant while the plant was idle, which resulted in contamination of the first portion of each day's production. Salmonellae in the processed fish meal were reduced to nondetectable levels by reprocessing the first 45 min of each day's production.


Optimal timing of extubation in preterm infants.
In neonatal intensive care, endotracheal intubation is usually performed as an urgent or semi-urgent procedure in infants with critical or unstable conditions related to progressive respiratory failure. Extubation is not. Patients undergoing extubation are typically stable, with improved respiratory function. The key elements to facilitating extubation are to recognize improvement in respiratory status, promote weaning of mechanical ventilation, and accurately identify readiness for removal of the endotracheal tube. Therefore, extubation should be a planned and well-organized procedure. In this review, we will appraise the evidence for existing predictors of extubation readiness and provide patient-specific, pathophysiology-derived strategies to optimize the timing and success of extubation in neonates, with a focus on extremely preterm infants.


Carbohydrate-binding modules: fine-tuning polysaccharide recognition.
The enzymic degradation of insoluble polysaccharides is one of the most important reactions on earth. Despite this, glycoside hydrolases attack such polysaccharides relatively inefficiently as their target glycosidic bonds are often inaccessible to the active site of the appropriate enzymes. In order to overcome these problems, many of the glycoside hydrolases that utilize insoluble substrates are modular, comprising catalytic modules appended to one or more non-catalytic CBMs (carbohydrate-binding modules). CBMs promote the association of the enzyme with the substrate. In view of the central role that CBMs play in the enzymic hydrolysis of plant structural and storage polysaccharides, the ligand specificity displayed by these protein modules and the mechanism by which they recognize their target carbohydrates have received considerable attention since their discovery almost 20 years ago. In the last few years, CBM research has harnessed structural, functional and bioinformatic approaches to elucidate the molecular determinants that drive CBM-carbohydrate recognition. The present review summarizes the impact structural biology has had on our understanding of the mechanisms by which CBMs bind to their target ligands.


Studies in porphyria. I. A defect in the reductive transformation of natural steroid hormones in the hereditary liver disease, acute intermittent porphyria.
A variety of 5beta steroid metabolites derived from hormones natural to man are potent inducers experimentally of delta-aminolevulinate synthetase, the rate-limiting enzyme in porphyrin-heme formation. This mitochondrial enzyme is found at high levels of activity in the livers of patients with the genetic disease, acute intermittent porphyria (AIP). In this study the metabolism of (14)C-labeled testosterone was examined in AIP patients to determine whether there was a disproportionate conversion of the hormone to its 5beta, compared to its 5alpha metabolite. The results indicate that AIP subjects do generate a substantially greater than normal fraction of 5beta metabolite from this steroid; the excessive degree of ring A reduction of testosterone taking place via the 5beta pathway in the porphyric patients averages 350% greater than in the nonporphyric subjects. In one asymptomatic AIP patient the disproportionate generation of 5beta metabolite from the hormone reached a level 10 times the normal mean. Studies with a second (14)C-labeled hormone, dehydroisoandrosterone, whose metabolism in man resembles that of testosterone, confirmed the derangement in reductive transformation of steroids found in the individuals carrying the genetic lesion of AIP. These findings define a new endocrine abnormality in AIP patients and raise the possibility that endogenously derived 5beta steroids may contribute by an induction mechanism to the increased levels of hepatic delta-aminolevulinate synthetase activity found in AIP patients.


Islet product characteristics and factors related to successful human islet transplantation from the Collaborative Islet Transplant Registry (CITR) 1999-2010.
The Collaborative Islet Transplant Registry (CITR) collects data on clinical islet isolations and transplants. This retrospective report analyzed 1017 islet isolation procedures performed for 537 recipients of allogeneic clinical islet transplantation in 1999-2010. This study describes changes in donor and islet isolation variables by era and factors associated with quantity and quality of final islet products. Donor body weight and BMI increased significantly over the period (p<0.001). Islet yield measures have improved with time including islet equivalent (IEQ)/particle ratio and IEQs infused. The average dose of islets infused significantly increased in the era of 2007-2010 when compared to 1999-2002 (445.4±156.8 vs. 421.3±155.4×0(3) IEQ; p<0.05). Islet purity and total number of β cells significantly improved over the study period (p<0.01 and <0.05, respectively). Otherwise, the quality of clinical islets has remained consistently very high through this period, and differs substantially from nonclinical islets. In multivariate analysis of all recipient, donor and islet factors, and medical management factors, the only islet product characteristic that correlated with clinical outcomes was total IEQs infused. This analysis shows improvements in both quantity and some quality criteria of clinical islets produced over 1999-2010, and these parallel improvements in clinical outcomes over the same period.


Measuring drinking patterns: the experience of the last half century.
While there were earlier surveys of drinking behaviour, the modern tradition of these surveys dates back 50 years ago, and by the 1970s encompassed a number of countries. The paper reviews developments in the modern tradition of drinking surveys. One major tradition asks respondents about very recent drinking occasions, while the other asks the respondent to summarize the behavior over a longer period. While earlier analyses differentiated between frequency of drinking and quantity per occasion, this tradition was swamped by analyses in terms of an overall volume of drinking. Now, however, there is a renewed emphasis on patterns of drinking. Current developments in characterizing drinking patterns are summarized, with the conclusion that frequency of drinking at all, and frequency of heavier drinking occasions, are dimensions important both in terms of the social meaning of drinking and of the relation to potential consequences of drinking.


Mechanisms by Which Ranolazine Terminates Paroxysmal but Not Persistent Atrial Fibrillation.
Ranolazine inhibits Na+ current (INa), but whether it can convert atrial fibrillation (AF) to sinus rhythm remains unclear. We investigated antiarrhythmic mechanisms of ranolazine in sheep models of paroxysmal (PxAF) and persistent AF (PsAF). PxAF was maintained during acute stretch (N=8), and PsAF was induced by long-term atrial tachypacing (N=9). Isolated, Langendorff-perfused sheep hearts were optically mapped. In PxAF ranolazine (10 μmol/L) reduced dominant frequency from 8.3±0.4 to 6.2±0.5 Hz (P<0.01) before converting to sinus rhythm, decreased singularity point density from 0.070±0.007 to 0.039±0.005 cm-2 s-1 (P<0.001) in left atrial epicardium (LAepi), and prolonged AF cycle length (AFCL); rotor duration, tip trajectory, and variance of AFCL were unaltered. In PsAF, ranolazine reduced dominant frequency (8.3±0.5 to 6.5±0.4 Hz; P<0.01), prolonged AFCL, increased the variance of AFCL, had no effect on singularity point density (0.048±0.011 to 0.042±0.016 cm-2 s-1; P=ns) and failed to convert AF to sinus rhythm. Doubling the ranolazine concentration (20 μmol/L) or supplementing with dofetilide (1 μmol/L) failed to convert PsAF to sinus rhythm. In computer simulations of rotors, reducing INa decreased dominant frequency, increased tip meandering and produced vortex shedding on wave interaction with unexcitable regions. PxAF and PsAF respond differently to ranolazine. Cardioversion in the former can be attributed partly to decreased dominant frequency and singularity point density, and prolongation of AFCL. In the latter, increased dispersion of AFCL and likely vortex shedding contributes to rotor formation, compensating for any rotor loss, and may underlie the inefficacy of ranolazine to terminate PsAF.


Collective bargaining and organized nurses: correlation of support and participation.
The objective of this article was to list identified personal characteristics which are intrinsic to the respondents, irrespective of their profession or employment, and which influence their viewpoints and participation in collective bargaining. Little information is reported in the nursing literature which points out the similarities of nurses to other subsets of society. The belief systems of various sub-group affiliations can have greater influence on one's opinions than one's socialization to professional values or exposure to particular environments. The current investigation was of an explorative nature. Moreover, as with many surveys, the applicability of findings is limited to the respondent population. No significant correlations were identified for nurses who are financially dependent on the income from their position, union membership of a family member, hospital size, shift worked or full-time/part-time employment status. The identified correlates of participation in collective bargaining as seniority in bargaining units and employment, hierarchical employment position and involvement in the organizing campaign were consistent with findings regarding blue collar unionists. Perception and militance correlates of age, seniority in the profession and the bargaining unit, race, religion, sex, employment position, membership in the professional association prior to collective bargaining, involvement in the initial organizing campaign and geographic location are also supportive of previous findings. The major finding of this investigation was that a tendency toward negative perceptions was associated with a proclivity toward militance. This was particularly true for the professional model of collective bargaining.(ABSTRACT TRUNCATED AT 250 WORDS)


Sequence diversity, metal specificity, and catalytic proficiency of metal-dependent phosphorylating DNA enzymes.
Although DNA has not been found responsible for biological catalysis, many artificial DNA enzymes have been created by "in vitro selection." Here we describe a new selection approach to assess the influence of four common divalent metal ions (Ca(2+), Cu(2+), Mg(2+), and Mn(2+)) on sequence diversity, metal specificity, and catalytic proficiency of self-phosphorylating deoxyribozymes. Numerous autocatalytic DNA sequences were isolated, a majority of which were selected using Cu(2+) or Mn(2+) as the divalent metal cofactor. We found that Cu(2+)- and Mn(2+)-derived deoxyribozymes were strictly metal specific, while those selected by Ca(2+) and Mg(2+) were less specific. Further optimization by in vitro evolution resulted in a Mn(2+)-dependent deoxyribozyme with a k(cat) of 2.8 min(-1). Our findings suggest that DNA has sufficient structural diversity to facilitate efficient catalysis using a broad scope of metal cofactor utilizing mechanisms.


A Novel AKR1C3 Specific Prodrug TH3424 With Potent Antitumor Activity in Liver Cancer.
Overexpression of AKR1C3, an aldo-keto reductase, was recently discovered in liver cancers. In this study, an inverse correlation between AKR1C3 expression and survival of patients with liver cancer was observed. AKR1C3 inhibitors, however, failed to suppress liver cancer cell growth. The prodrug TH3424, which releases a DNA alkylating reagent upon reduction by AKR1C3, was developed to target tumors with overexpression of AKR1C3. TH3424 showed specific killing of liver cancer cells with AKR1C3 overexpression both in vitro and in vivo. In patient-derived mouse xenograft models, TH3424 at doses as low as 1.5 mg/kg eliminated liver tumors with no apparent toxicity. Therefore, TH3424 is a promising drug candidate for liver cancer and other types of cancers overexpressing AKR1C3.


Standard Water Generating Vials for Lipophilic Compounds.
The study of non-polar compounds in aqueous environments has always been challenging due to their poor solubility in aqueous media. The low affinity of non-polar compounds toward polar solutions facilitates their attachment to glassware, which results in unstable sample concentrations. To address this challenge, and to enable the preparation of a stable mixture of hydrophobic compounds in an aquatic environment, we introduce an in-vial standard water generating system consisting of a vial containing appropriate aqueous solution and a polydimethylsiloxane thin film spiked with target compounds. In this system, a solution with a stable analyte concentration is attained once equilibrium between the thin-film and aqueous solution has been achieved. The developed standard water system was studied using endocannabinoids and phospholipids as model hydrophobic compounds of biological importance, with results indicating that the concentration of hydrophobic compounds in water can remain stable over multiple days. The results also showed that analytes released from the thin film can compensate for analyte loss due to extractions with solid-phase microextraction fibers, thereby re-establishing equilibrium. Thus, the vial is suitable for the repeatable generation of non-polar standards for routine analysis and quality control. The results of this work show that the developed system is stable and reproducible and therefore appropriate for studies requiring the measurement of free concentrations and accurate quantification.


Oseltamivir use in pregnancy: Risk of birth defects, preterm delivery, and small for gestational age infants.
Influenza infection during pregnancy increases risks for adverse outcomes for both mother and fetus. For this reason, treatment for infection or postexposure prophylaxis with a neuraminidase inhibitor, such as oseltamivir, may be needed. Between 2009 and 2017, the Organization of Teratology Information Specialists (OTIS) MotherToBaby Pregnancy Studies enrolled pregnant women in the United States and Canada who were or were not treated with oseltamivir in a prospective cohort study. Data were collected on major birth defects, spontaneous abortion, preterm delivery, and small for gestational age birth size. Crude relative risks (RRs) or hazard ratios (HRs) were estimated together with 95% confidence intervals (CIs) for these outcomes. There were 716 subjects available for analysis; 112 were exposed to oseltamivir sometime in pregnancy and 604 were unexposed. 2/30 (6.7%) first-trimester-exposed pregnancies resulted in a fetus or infant with one or more major birth defects compared to 48/604 (7.9%) in the unexposed cohort (RR 0.84, 95% CI 0.19, 2.80). There were no spontaneous abortions reported. Risk of preterm delivery was not elevated in exposed versus comparison women (HR 0.65, 95% CI 0.26, 1.63). RRs for small for gestational age infants on weight, length, and head circumference following oseltamivir exposure anytime in pregnancy ranged from 0.70 to 1.30 with all 95% CIs including 1. We found no evidence of increased risks with oseltamivir for any of the outcomes evaluated. While numbers are small, these data are reassuring for pregnant women who need to be treated for infection or for postexposure prophylaxis.


Corpus callosum hematoma, as a rare complication of COVID-19.
A 46-year-old gentleman had a complicated course of COVID-19 pneumonia. Despite the recovery of the respiratory status, he developed corpus callosum hematoma and critical illness neuropathy/myopathy. The clinical situation became more complicated by developing pulmonary embolism that required anticoagulation. Fortunately, the patient made a good recovery.


[Resolution of the XV Congress. All-Russian public organization "Russian Society of Surgeons named after Academician V.S. Saveliev" 26 October 2023 Moscow, Russia].
Resolution of the XV Congress. All-Russian public organization "Russian Society of Surgeons named after Academician V.S. Saveliev" 26 October 2023 Moscow, Russia.


Major-effect candidate genes identified in cultivated strawberry (Fragaria × ananassa Duch.) for ellagic acid deoxyhexoside and pelargonidin-3-O-malonylglucoside biosynthesis, key polyphenolic compounds.
Strawberries are rich in polyphenols which impart health benefits when metabolized by the gut microbiome, including anti-inflammatory, neuroprotective, and antiproliferative effects. In addition, polyphenolic anthocyanins contribute to the attractive color of strawberry fruits. However, the genetic basis of polyphenol biosynthesis has not been extensively studied in strawberry. In this investigation, ripe fruits from three cultivated strawberry populations were characterized for polyphenol content using HPLC-DAD-MSn and genotyped using the iStraw35k array. GWAS and QTL analyses identified genetic loci controlling polyphenol biosynthesis. QTL were identified on four chromosomes for pelargonidin-3-O-malonylglucoside, pelargonidin-3-O-acetylglucoside, cinnamoyl glucose, and ellagic acid deoxyhexoside biosynthesis. Presence/absence of ellagic acid deoxyhexoside and pelargonidin-3-O-malonylglucoside was found to be under the control of major gene loci on LG1X2 and LG6b, respectively, on the F. × ananassa linkage maps. Interrogation of gene predictions in the F. vesca reference genome sequence identified a single candidate gene for ellagic acid deoxyhexoside biosynthesis, while seven malonyltransferase genes were identified as candidates for pelargonidin-3-O-malonylglucoside biosynthesis. Homologous malonyltransferase genes were identified in the F. × ananassa 'Camarosa' genome sequence but the candidate for ellagic acid deoxyhexoside biosynthesis was absent from the 'Camarosa' sequence. This study demonstrated that polyphenol biosynthesis in strawberry is, in some cases, under simple genetic control, supporting previous observations of the presence or absence of these compounds in strawberry fruits. It has also shed light on the mechanisms controlling polyphenol biosynthesis and enhanced the knowledge of these biosynthesis pathways in strawberry. The above findings will facilitate breeding for strawberries enriched in compounds with beneficial health effects.


Validity of self-reported pregnancy delivery weight: an analysis of the 1988 National Maternal and Infant Health Survey. NMIHS Collaborative Working Group.
This study examined the validity of self-reported delivery weight among 3,518 respondents to the 1988 National Maternal and Infant Health Survey. Self-reported delivery weight was ascertained from a mail survey administered during the postpartum period. Measured delivery weight was obtained by abstraction of medical records from the hospital of delivery. On average, a woman's reported delivery weight was 2.82 pounds (1 pound = 0.45 kg) less than her measured delivery weight (p < 0.001). The level of underreporting increased significantly with increases in prepregnancy body mass index, current body mass index, pregnancy weight gain, and weight change from delivery to recall. Reporting error also increased among women who were non-White, less educated, and unmarried; whose pregnancy was unintended; and who initiated prenatal care late, responded late to the survey questionnaire, became pregnant again before responding, and reported a delivery weight ending in zero. When reported delivery weight was used to calculate weight gain and was categorized into typical weight gain categories, 30-40% of women were classified incorrectly. An empirical evaluation of how this misclassification might impact epidemiologic analyses indicated that associations between weight gain and birth weight were attenuated when weight gain was based on reported delivery weight rather than on measured delivery weight.


The Pyrazolo[3,4-d]pyrimidine Derivative, SCO-201, Reverses Multidrug Resistance Mediated by ABCG2/BCRP.
ATP-binding cassette (ABC) transporters, such as breast cancer resistance protein (BCRP), are key players in resistance to multiple anti-cancer drugs, leading to cancer treatment failure and cancer-related death. Currently, there are no clinically approved drugs for reversal of cancer drug resistance caused by ABC transporters. This study investigated if a novel drug candidate, SCO-201, could inhibit BCRP and reverse BCRP-mediated drug resistance. We applied in vitro cell viability assays in SN-38 (7-Ethyl-10-hydroxycamptothecin)-resistant colon cancer cells and in non-cancer cells with ectopic expression of BCRP. SCO-201 reversed resistance to SN-38 (active metabolite of irinotecan) in both model systems. Dye efflux assays, bidirectional transport assays, and ATPase assays demonstrated that SCO-201 inhibits BCRP. In silico interaction analyses supported the ATPase assay data and suggest that SCO-201 competes with SN-38 for the BCRP drug-binding site. To analyze for inhibition of other transporters or cytochrome P450 (CYP) enzymes, we performed enzyme and transporter assays by in vitro drug metabolism and pharmacokinetics studies, which demonstrated that SCO-201 selectively inhibited BCRP and neither inhibited nor induced CYPs. We conclude that SCO-201 is a specific, potent, and potentially non-toxic drug candidate for the reversal of BCRP-mediated resistance in cancer cells.


Isolation, purification and characterization of an extracellular L-asparaginase produced by a newly isolated Bacillus megaterium strain MG1 from the water bodies of Moraghat forest, Jalpaiguri, India.
An extracellular L-asparaginase was isolated and purified from Bacillus megaterium MG1 to apparent homogeneity. The purification procedure involved a combination of ammonium sulfate precipitation, ion-exchange chromatography, and gel filtration techniques, resulting in a purification factor of 31.52 fold with a specific activity of 215 U mg-1. The molecular mass of the purified enzyme was approximately 47 kDa on SDS-PAGE and 185 kDa on native PAGE gel as well as in gel filtration column chromatography, revealing that the enzyme was a homotetramer. The Km and Vmax values of the purified enzyme were calculated to be 2.0 ⅹ 10-4 M and 1.198 mM s-1. Maximum enzyme activity was observed over a wide range of temperature and pH values with an optimum temperature of 37°C and pH 8.5. SDS and metal ions such as Fe2+, Cu2+, Mg2+, Co2+, Mn2+, and Ca2+ decreased the enzyme activity remarkably, whereas the addition of Na+ and K+ led to an increase in activity. The insensitivity of the protein in the presence of EDTA suggested that the enzyme might not essentially be a metalloprotein. Its marked stability and activity in organic solvents and reducing agents suggest that this asparaginase is highly suitable as a biotechnological tool with industrial applications.


Altered pontine taste processing in a rat model of obesity.
The increased palatability of modern diet contributes to eating beyond homeostatic need and in turn to the growing prevalence of obesity. How palatability is coded in taste-evoked neural activity and whether this activity differs between obese and lean remains unknown. To investigate this, we used extracellular single-unit recording in the second central gustatory relay, the pontine parabrachial nucleus while stimulating the tongue with various concentrations of sucrose (0.01-1.5 M) in Otsuka Long Evans Tokushima Fatty (OLETF) rats, lacking CCK-1R. The analyses included a total of 179 taste-responsive neurons in age-matched prediabetic, obese OLETF and lean Long Evans Tokushima Otsuka (LETO) controls. Compared with LETO, we found more NaCl-, and fewer sucrose-responsive neurons (67 vs. 47% and 14 vs. 32%), and an overall reduced response magnitude to sucrose in the OLETF rats. Further, in the obese rats there was a rightward shift in sucrose concentration-response functions relative to lean controls with a higher response-threshold (0.37+/-0.05 vs. 0.23+/-0.2 M, P<0.05) and maximal neural response to higher sucrose concentrations (0.96+/-0.07 vs. 0.56+/-0.5 M, P<0.001). These findings demonstrate altered central gustatory processing for sucrose in obese OLETF rat and further support the notion that palatability is encoded in the across neuron pattern.


Platelet-derived growth factor receptor-tyrosine kinase inhibitor, imatinib, is effective for treating pulmonary hypertension induced by pulmonary tumor thrombotic microangiopathy.
Pulmonary hypertension (PH) induced by pulmonary tumor thrombotic microangiopathy (PTTM) can be fatal because its rapid progression confounds diagnosis, and it is difficult to control with therapy. Here we describe a woman with symptomatic PTTM-PH accompanying gastric cancer that was suspected from perfusion scintigraphy. PTTM-PH was diagnosed by gastroesophageal endoscopy and lung biopsy after partial control of PH using the platelet-derived growth factor (PDGF) receptor (PDGFR) tyrosine kinase inhibitor, imatinib. Treatment with sildenafil and ambrisentan further decreased PH, and she underwent total gastrectomy followed by adjuvant TS-1 chemotherapy. PH did not recur before her death from metastasis. Postmortem histopathology showed recanalized pulmonary arteries where the embolized cancer masses disappeared. PDGF-A, -B, and PDGFR-α, β expression was detected in cancer cells and proliferating pulmonary vascular endothelial cells. Thus, PTTM-PH was successfully controlled using a combination of imatinib, drugs to treat pulmonary arterial hypertension, and cancer management.


A Comparison of Red Fluorescent Proteins to Model DNA Vaccine Expression by Whole Animal In Vivo Imaging.
DNA vaccines can be manufactured cheaply, easily and rapidly and have performed well in pre-clinical animal studies. However, clinical trials have so far been disappointing, failing to evoke a strong immune response, possibly due to poor antigen expression. To improve antigen expression, improved technology to monitor DNA vaccine transfection efficiency is required. In the current study, we compared plasmid encoded tdTomato, mCherry, Katushka, tdKatushka2 and luciferase as reporter proteins for whole animal in vivo imaging. The intramuscular, subcutaneous and tattooing routes were compared and electroporation was used to enhance expression. We observed that overall, fluorescent proteins were not a good tool to assess expression from DNA plasmids, with a highly heterogeneous response between animals. Of the proteins used, intramuscular delivery of DNA encoding either tdTomato or luciferase gave the clearest signal, with some Katushka and tdKatushka2 signal observed. Subcutaneous delivery was weakly visible and nothing was observed following DNA tattooing. DNA encoding haemagglutinin was used to determine whether immune responses mirrored visible expression levels. A protective immune response against H1N1 influenza was induced by all routes, even after a single dose of DNA, though qualitative differences were observed, with tattooing leading to high antibody responses and subcutaneous DNA leading to high CD8 responses. We conclude that of the reporter proteins used, expression from DNA plasmids can best be assessed using tdTomato or luciferase. But, the disconnect between visible expression level and immunogenicity suggests that in vivo whole animal imaging of fluorescent proteins has limited utility for predicting DNA vaccine efficacy.


The Jena Eyewitness Research Stimuli (JERS): A database of mock theft videos involving two perpetrators, presented in 2D and VR formats with corresponding 2D and 3D lineup images.
Empirical investigations into eyewitness identification accuracy typically necessitate the creation of novel stimulus materials, which can be a challenging and time-consuming task. To facilitate this process and promote further research in this domain, we introduce the new Jena Eyewitness Research Stimuli (JERS). They comprise six video sequences depicting a mock theft committed by two different perpetrators, available in both two-dimensional (2D) and 360° format, combined with the corresponding lineup images presented in 2D or three-dimensional (3D) format. Images of one suspect and eight fillers are available for each lineup. We evaluated lineup fairness by using mock eyewitness paradigm and noted a Tredoux's E of 4.687 for Perpetrator 1 and 5.406 for Perpetrator 2. Moreover, no bias towards the perpetrators was observed in the lineups. We incorporated 360° videos and 3D lineup images to encourage the adoption of innovative data formats in experimental investigations of eyewitness accuracy. In particular, compatibility with Virtual Reality (VR) makes JERS a promising tool for advancing eyewitness research by enabling researchers to construct controlled environments that offer observers an immersive experience. JERS is freely accessible for the use of academic purposes via the Open Science Framework (OSF).


Nutrition and Allergic Diseases.
The development of IgE-mediated allergic diseases is influenced by many factors, including genetic and environmental factors such as pollution and farming, but also by nutrition. In the last decade, substantial progress has been made in our understanding of the impact that nutrition can have on allergic diseases. Many studies have addressed the effect of breastfeeding, pre-, pro- and synbiotics, vitamins and minerals, fiber, fruit and vegetables, cow's milk, and n-3 fatty acids, on the development of allergies. In addition, nutrition can also have indirect effects on allergic sensitization. This includes the diet of pregnant and breastfeeding women, which influences intrauterine development, as well as breastmilk composition. These include the diet of pregnant and breastfeeding women that influences intrauterine development as well as breastmilk composition, effects of food processing that may enhance allergenicity of foods, and effects via modulation of the intestinal microbiota and their metabolites. This editorial review provides a brief overview of recent developments related to nutrition and the development and management of allergic diseases.


Effects of Shock Waves on Expression of IL-6, IL-8, MCP-1, and TNF-α Expression by Human Periodontal Ligament Fibroblasts: An In Vitro Study.
Extracorporeal shock wave therapy (ESWT) can modulate cell behavior through mechanical information transduction. Human periodontal ligament fibroblasts (hPDLF) are sensible to mechanical stimulus and can express pro-inflammatory molecules in response. The aim of this study was to evaluate the impacts of shock waves on interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor-alpha (TNF-α) expression by hPDLF. After being treated by shock waves with different parameters (100-500 times, 0.05-0.19 mJ/mm(2)), cell viability was tested using CCK-8. IL-6, IL-8, MCP-1, and TNF-α gene expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and IL-6 and IL-8 protein was measured by enzyme-linked immunosorbent assay (ELISA) at different time points. Shock waves with the parameters used in this study had no significant effects on the viability of hPDLF. A statistical inhibition of IL-6, IL-8, MCP-1, and TNF-α expression during the first few hours was observed (P<0.05). Expression of IL-8 was significantly elevated in the group receiving the most pulses of shock wave (500 times) after 4 h (P<0.05). At 8 h and 24 h, all treated groups demonstrated significantly enhanced IL-6 expression (P<0.05). TNF-α expression in the groups receiving more shock pulses (300, 500 times) or the highest energy shock treatment (0.19 mJ/mm(2)) was statistically decreased (P<0.05) at 24 h. Under the condition of this study, a shock wave with energy density no higher than 0.19 mJ/mm(2) and pulses no more than 500 times elicited no negative effects on cell viability of hPDLF. After a uniform initial inhibition impact on expression of inflammatory mediators, a shock wave could cause dose-related up-regulation of IL-6 and IL-8 and down-regulation of TNF-α.


Papillary thyroid cancer coexisting with thyroid tuberculosis: A case report.
The current study presents the case of a 56-year-old female, with thyroid nodules showing signs of malignancy under B-mode ultrasonography, who was admitted to Shaoxing People's Hospital. A histopathological examination revealed the coexistence of papillary thyroid cancer (PTC) and thyroid tuberculosis (TB). A total thyroidectomy and selective neck dissection (left side, levels III, IV and VI) were performed. This report presents a rare case showing the malignant growth of thyroid nodules and the development of thyroid TB, which implicates the possible role of mycobacterial infection in the tumorigenesis of PTC.


Thrombospondin promotes cell-substratum adhesion.
The physiological role of the platelet-secreted protein thrombospondin (TSP) is poorly understood, although it has been postulated to be involved in platelet aggregation and cellular adhesion. In this report, TSP isolated from human platelets was found to promote, in vitro, the cell-substratum adhesion of a variety of cells, including platelets, melanoma cells, muscle cells, endothelial cells, fibroblasts, and epithelial cells. The adhesion-promoting activity of TSP was species independent, specific, and not due to contamination by fibronectin, vitronectin, laminin, or platelet factor 4. The cell surface receptor for TSP is protein in nature and appears distinct from that for fibronectin.


Depletion of plasma membrane cholesterol dampens hydrostatic pressure and shear stress-induced mechanotransduction pathways in osteoblast cultures.
The preferential association of cholesterol and sphingolipids within plasma membranes forms organized compartments termed lipid rafts. Addition of caveolin proteins to this lipid milieu induces the formation of specialized invaginated plasma membrane structures called caveolae. Both lipid rafts and caveolae are purported to function in vesicular transport and cell signaling. We and others have shown that disassembly of rafts and caveolae through depletion of plasma membrane cholesterol mitigates mechanotransduction processes in endothelial cells. Because osteoblasts are subjected to fluid-mechanical forces, we hypothesize that cholesterol-rich plasma membrane microdomains also serve the mechanotransduction process in this cell type. Cultured human fetal osteoblasts were subjected to either sustained hydrostatic pressure or laminar shear stress using a pressure column or parallel-plate apparatus, respectively. We found that sustained hydrostatic pressure induced protein tyrosine phosphorylation, activation of extracellular signal-regulated kinase (ERK)1/2, and enhanced expression of c-fos in both time- and magnitude-dependent manners. Similar responses were observed in cells subjected to laminar shear stress. Both sustained hydrostatic pressure- and shear stress-induced signaling were significantly reduced in osteoblasts pre-exposed to either filipin or methyl-beta-cyclodextrin. These mechanotransduction responses were restored on reconstitution of lipid rafts and caveolae, which suggests that cholesterol-rich plasma membrane microdomains participate in the mechanotransduction process in osteoblasts. In addition, mechanical force-induced phosphoproteins were localized within caveolin-containing membranes. These data support the concept that lipid rafts and caveolae serve a general function as cell surface mechanotransduction sites within the plasma membrane.


Time-Dependent Effects of Acute Exercise on University Students' Cognitive Performance in Temperate and Cold Environments.
Background: Few studies have examined the acute exercise-induced changes in cognitive performance in different thermal environments and the time course effects. Objective: Investigate the time-dependent effects of acute exercise on university students' processing speed, working memory and cognitive flexibility in temperate and cold environments. Method: Twenty male university students (age 23.5 ± 2.0 years) with moderate physical activity level participated in a repeated-measures within-subjects design. Processing speed, working memory and cognitive flexibility were assessed using CogState test battery at baseline (BASE), followed by a 45-min rest (REST), immediately after (EX) and 30 min after (POST-EX) 30-min moderate-intensity treadmill running in both temperate (TEMP; 25°C) and cold (COLD; 10°C) environments. Mean skin temperature (MST) and thermal sensation (TS) were also recorded. Two-way repeated measures ANOVA was performed to analyze each variable. Spearman's rho was used to identify the correlations between MST, TS and cognitive performance. Results: Reaction time (RT) of processing speed and working memory decreased immediately after exercise in both conditions (processing speed: p = 0.003; working memory: p = 0.007). The facilitating effects on processing speed disappeared within 30 min after exercise in TEMP (p = 0.163) and COLD (p = 0.667), while improvements on working memory remained 30 min after exercise in TEMP (p = 0.047), but not in COLD (p = 0.663). Though RT of cognitive flexibility reduced in both conditions (p = 0.003), no significance was found between EX and REST (p = 0.135). Increased MST and TS were significantly associated with reductions in processing speed RT (MST: r = -0.341, p < 0.001; TS: r = -0.262, p = 0.001) and working memory RT (MST: r = -0.282, p < 0.001; TS: r = -0.2229, p = 0.005), and improvements in working memory accuracy (MST: r = 0.249, p = 0.002; TS: r = 0.255, p = 0.001). Conclusion: The results demonstrate different time-dependent effects of acute exercise on cognition in TEMP and COLD. Our study reveals facilitating effects of exercise on university students' processing speed and working memory in both environments. However, in contrast to TEMP, effects on working memory in COLD are transient.


Soil Sample Preservation Strategy Affects the Microbial Community Structure.
Sample preservation is a critical procedure in any research that relies on molecular tools and is conducted in remote areas. Sample preservation options include low and room temperature storage, which require freezing equipment and specific buffering solutions, respectively. The aim of the present study was to investigate whether DNA/RNA Shield 1x from Zymo Research and DESS (Dimethyl sulfoxide, Ethylenediamine tetraacetic acid, Saturated Salt) solution performed similarly to snap freezing in liquid nitrogen. Soil samples were stored for 1 month in each of the buffers and without any solution at a range of temperatures: -20, +4, and +23°C. All treatments were compared to the "optimal treatment", namely, snap freezing in liquid nitrogen. The quality and quantity of DNA were analyzed, and the microbial community structure was investigated in all samples. The results obtained indicated that the quantity and integrity of DNA was preserved well in all samples; however, the taxonomic distribution was skewed in samples stored without any solution at ambient temperatures, particularly when analyses were performed at lower taxonomic levels. Although both solutions performed equally well, sequencing output and OTU numbers in DESS-treated samples were closer to those snap frozen with liquid nitrogen. Furthermore, DNA/RNA Shield-stored samples performed better for the preservation of rare taxa.