What is the purpose of ultra-processed food? An exploratory analysis of the financialisation of ultra-processed food corporations and implications for public health.
In recent decades there has been a global rise in consumption of ultra-processed foods (UPFs) to the detriment of population health and the environment. Large corporations that have focused heavily on low-cost manufacturing and extensive marketing of UPFs to maximise profits have driven this dietary transition. The same corporations claim to serve the interests of multiple 'stakeholders', and that they are contributing to sustainable development. This paper aimed to test these claims by examining the degree to which UPF corporations have become 'financialised', focusing on the extent to which they have prioritised the financial interests of their shareholders relative to other actors, as well as the role that various types of investors have played in influencing their governance. Findings were used to inform discussion on policy responses to improve the healthiness of population diets. We adopted an exploratory research design using multiple methods. We conducted quantitative analysis of the financial data of U.S. listed food and agricultural corporations between 1962 and 2021, share ownership data of a selection of UPF corporations, and proxy voting data of a selection of investors between 2012 and 2022. We also conducted targeted narrative reviews using structured and branching searches of academic and grey literature. Since the 1980s, corporations that depend heavily on manufacturing and marketing UPFs to generate profits have been increasingly transferring money to their shareholders relative to their total revenue, and at a level considerably higher than other food and agricultural sectors. In recent years, large hedge fund managers have had a substantial influence on the governance of major UPF corporations in their pursuit of maximising short-term returns. In comparison, shareholders seeking to take steps to improve population diets have had limited influence, in part because large asset managers mostly oppose public health-related shareholder proposals. The operationalisation of 'shareholder primacy' by major UPF corporations has driven inequity and undermines their claims that they are creating 'value' for diverse actors. Measures that protect population diets and food systems from the extractive forces of financialisation are likely needed as part of efforts to improve the healthiness of population diets.


Antibodies against an acid extract from a single campylobacter strain in hospitalized campylobacter patients.
An acid glycine extract from a single Campylobacter jejuni strain was used as the antigen in the enzyme immunoassay (EIA). Elevated values indicating the presence of specific IgM and/or IgG antibodies were found in 73% of 52 patients hospitalized for campylobacter infection. A further 6% of the patients who had lower EIA values in paired serum samples showed at least a 20% change in EIA values. The same sera had been studied earlier for agglutinating antibodies using four reference campylobacter strains. 74% of the patients had shown elevated titres and a further 17% four-fold changes of lower titres in paired sera.


Effects of left recurrent laryngeal neurectomy, prosthetic laryngoplasty, and subtotal arytenoidectomy on upper airway pressure during maximal exertion.
Upper airway pressure was measured with a nasotracheal catheter system and a portable pressure transducer in 10 normal horses during maximal exercise before and after left recurrent laryngeal neurectomy. Measurements were repeated 16 weeks after prosthetic laryngoplasty (5 horses) or subtotal arytenoidectomy (5 horses). During maximal exertion, prosthetic laryngoplasty was more effective than subtotal arytenoidectomy in reversing the increases in upper airway pressure that followed left recurrent laryngeal neurectomy.


Leber hereditary optic neuropathy. Electron microscopy and molecular genetic analysis of a case.
Leber hereditary optic neuropathy (LHON) is a mitochondrial genetic disorder characterized by bilateral central visual loss typically in early adulthood. Few histopathologic studies, including ultrastructural and molecular genetic analysis, have been reported. Ocular tissue was obtained postmortem from an 81-year-old woman with LHON from the Queensland 1 pedigree characterized by mutations at nucleotide positions 4160 and 14484. Routine histopathologic studies, electron microscopy, electron-probe analysis, and molecular genetic analysis were performed. Marked atrophy of the nerve fiber and retinal ganglion cell layers and optic nerves was present. Results of electron microscopic examination demonstrated 1.2 microns electron-dense, double-membrane-bound inclusions, consisting of calcium by electron-probe analysis, in retinal ganglion cells. The optic nerve was homoplasmic for mutations 4160 and 14484. Optic nerve and inner retinal atrophy in LHON may be a result of metabolic mitochondrial dysfunction leading to intramitochondrial calcification. Homoplasmy for mitochondrial mutations 4160 and 14484 in the leukocyte/platelet fraction of whole blood may correlate with homoplasmy in the optic nerve.


Bioimpedance spectroscopy for the estimation of fat-free mass in end-stage renal disease.
BACKGROUND #ENTITYSTARTX00026; AIMS: Bioimpedance spectroscopy may provide reliable estimates of fat-free mass in end-stage renal disease patients. We aimed to evaluate the ability of bioimpedance spectroscopy to estimate fat-free mass in end-stage renal disease patients using dual-energy X-ray absorptiometry as a reference. METHODS: Fat-free mass measured by bioimpedance spectroscopy was compared to fat-free mass measured by dual-energy X-ray absorptiometry in 16 end-stage renal disease patients on hemodialysis, 12 undialysed end-stage renal disease patients and 23 control subjects. RESULTS: Methods were highly correlated for fat-free mass in all subject groups (r = 0.87, P < 0.001). Mean bioimpedance spectroscopy measures of fat-free mass were not different from the dual-energy X-ray absorptiometry measures in any subject group. Individual comparisons revealed wide limits of agreement between methods in hemodialysis (11.6 to -9.72 kg) and undialysed patients (10.95 to -14.73 kg). CONCLUSIONS: Although bioimpedance spectroscopy estimates of fat-free mass in the end-stage renal disease patient groups were not different from dual-energy X-ray absorptiometry and the methods were highly correlated, there was great individual variability. From these data it is clear that future studies are warranted before bioimpedance spectroscopy can be recommended as a valid clinical tool for assessing fat-free mass in end-stage renal disease patients.


Lessons Learned from a Two-Round Delphi-based Scenario Study.
The Delphi technique is a suitable methodology for structuring group communication to answer current and prospective research questions within several rounds. The method is used in many disciplines and characterized by anonymity, iteration, controlled feedback, and statistical "group response" (Rowe & Wright, 2001). This technical paper presents practical details and lessons learned from a two-round Delphi-based scenario study in which projections (Delphi statements, questions or hypotheses) were developed with findings from expert interviews and an expert workshop. This Delphi study provides answers to future-related questions for which other research methods are inappropriate. This is depicted as a five-step process, making it easy to follow and replicable, for example to help first-time Delphi-method researchers. In doing so, the authors aim to provide the community with valuable technical insights and guidance for studies applying the Delphi technique both to prospective questions and in other research settings.•Conducting a Delphi study can be a slow process with respect to receiving feedback from the panelists. Planning an appropriate period for distributing the questionnaire may produce a higher return rate. A sufficient time buffer should be incorporated into project planning.•Projections that create dissent among the panelists may provide valuable results.•Data analytics, software programs and online social networks can support researchers, save time and resources, and provide further insights in the process of conducting a Delphi study.


Differential gene expression signatures between colorectal cancers with and without KRAS mutations: crosstalk between the KRAS pathway and other signalling pathways.
KRAS mutation is an important predictive marker in determining resistance to anti-Epidermal Growth Factor Receptor (EGFR) antibody therapies. In order to clarify whether not only KRAS related signalling pathways but also other signalling pathways are altered in patients with colorectal cancers (CRCs) with KRAS mutations, we examined the differences in the gene expression signatures between CRCs with and without KRAS mutation. One-hundred and thirteen patients who underwent a surgical resection of a primary CRC were examined. KRAS mutational status was determined using the Peptide Nucleic Acid (PNA)-clamp real-time polymerase chain reaction (PCR) TaqMan assay. Gene expression profiles were compared between CRCs with and without KRAS mutation using the Human Genome GeneChip array U133. Among 113 CRCs, KRAS mutations were present in 35 tumours (31%). We identified 30 genes (probes) that were differentially expressed between CRCs with and without KRAS mutation (False Discovery Rate (FDR), p<0.01), by which we were able to predict the KRAS status with an accuracy of 90.3%. Thirty discriminating genes included TC21, paired-like homeodomain 1 (PITX1), Sprouty-2, dickkopf homologue 4 (DKK-4), SET and MYND domain containing 3 (SMYD3), mitogen-activated protein kinase kinase kinase 14 (MAP3K14) and c-mer Proto-oncogene tyrosine kinase (MerTK). These genes were related to not only KRAS related signalling pathway but also to other signalling pathways, such as the Wnt-signalling pathway, the NF-kappa B activation pathway and the TGF-beta signalling pathway. KRAS mutant CRCs exhibited a distinct gene expression signature different from wild-type KRAS CRCs. Using human CRC samples, we were able to show that there is crosstalk between the KRAS-mediated pathway and other signalling pathways. These results are necessary to be taken into account in establishing chemotherapeutic strategies for patients with anti-EGFR-refractory KRAS mutant CRCs.


Ne2, a typical CC-NBS-LRR-type gene, is responsible for hybrid necrosis in wheat.
Hybrid necrosis, caused by complementary genes Ne1 and Ne2, is a serious barrier for combining desirable traits from different genotypes of wheat, affecting the full utilisation of heterosis. To date, both Ne1 and Ne2 are still not isolated although they were documented decades ago. We report here the map-based cloning and functional characterisation of Ne2, encoding a coiled coil-nucleotide-binding site-leucine-rich repeat (CC-NBS-LRR) protein. Homozygous frameshift mutations generated using the CRISPR/Cas9 approach confirmed the Ne2-inducing hybrid necrosis in wheat. Upregulated expression of Ne2 induced by Ne1 and excess hydrogen peroxide accumulation are associated with the necrosis formation. Genetic analyses of a Ne2 allele (Ne2m ) and leaf rust resistance gene LrLC10/Lr13 revealed that they might be the same gene. Furthermore, we demonstrated that the frequency of the Ne2 allele was much lower in landraces (2.00%) compared with that in modern cultivars (13.62%), suggesting that Ne2 allele has been partially applied in wheat genetic improvement. Our findings open opportunities of thoroughly investigating the molecular mechanism of hybrid necrosis, selecting Lr13 and simultaneously avoiding hybrid necrosis in wheat breeding through marker-assisted selection.


Sources of informal financial support among adolescent and young adult cancer survivors: a mixed methods analysis from the HIAYA CHAT study.
The purpose of this exploratory sequential mixed methods study was to describe the sources of informal financial support used by adolescent and young adult (AYA) cancer survivors and how financial toxicity and demographic factors were associated with different types and magnitudes of informal financial support. This analysis is part of a larger health insurance literacy study that included pre-trial interviews and a randomized controlled trial (RCT) for AYA cancer survivors. Eligible study participants were 18 years of age, diagnosed with cancer as an AYA (15-39 years), insured, and for the RCT sample less than 1 year from diagnosis. Interview audio was transcribed, quality checked, and thematically analyzed. RCT baseline and follow-up surveys captured informal financial support use. Chi-squared and Fisher's exact tests were used to assess differences in informal financial support type use and frequency by financial toxicity and AYA demographics. A total of N = 24 and N = 86 AYAs participated in pre-trial interviews and the RCT respectively. Interview participants reported a variety of informal financial support sources including savings, community, family/friends, and fundraisers. However, only half of participants reported their informal financial support to be sufficient. High financial toxicity was associated with the most types of informal financial support and a higher magnitude of use. The lowest income group accessed informal financial supports less frequently than higher income groups. Our study demonstrates that AYA survivors experiencing financial toxicity frequently turn to informal sources of financial support and the magnitude is associated with financial toxicity. However, low-income survivors, and other at-risk survivors, may not have access to informal sources of financial support potentially widening inequities.


Relevance of sensitization to legumes in peanut-allergic children.
Legume consumption has increased during the two past decades. In France, legumes are responsible for 14.6% of food-related anaphylaxis in children, with peanut as the main allergen (77.5%). Few studies have demonstrated cross-reactivities between peanut and other legumes. The aim of this study was to determine prevalence and relevance of sensitization to legumes in peanut-allergic children. All children, aged of 1-17 years, admitted to the Pediatric Allergy Department of the University Hospital of Nancy between January 1, 2017 and February 29, 2020 with a confirmed peanut allergy (PA) and a documented consumption or sensitization to at least one other legume were included. Data were retrospectively collected regarding history of consumption, skin prick tests, specific immunoglobulin E (IgE), prior allergic reactions, and oral food challenges for each legume. Among the 195 included children with PA, 122 were sensitized to at least one other legume (63.9%). Main sensitizations were for fenugreek (N = 61, 66.3%), lentil (N = 38, 42.2%), soy (N = 61, 39.9%), and lupine (N = 63, 34.2%). Among the 122 sensitized children, allergy to at least one legume was confirmed for 34 children (27.9%), including six children who had multiple legume allergies (4.9%). Lentil, lupine, and pea were the main responsible allergens. Half of allergic reactions to legumes other than peanut were severe. The high prevalence of legume sensitization and the frequent severe reactions reported in children with PA highlight that tolerated legume consumption should be explored for each legume in the case of PA, and sensitization should be investigated if not.


Fas ligand downregulation with antisense oligonucleotides in cells and in cultured tissues of normal skin epidermis and basal cell carcinoma.
Fas ligand (FasL), a member of the tumor necrosis factor family, induces apoptosis upon interaction with Fas-receptor-expressing cells. FasL normally plays an important immune regulatory role, but it can also cause severe skin diseases if overexpressed and it may serve some tumors for immune evasion. Thus, in situ inhibition of FasL expression with antisense oligonucleotides in patients may be a novel approach to overcome its pathogenic role. We designed and evaluated 15 phosphorothioate antisense oligonucleotides directed against different regions of the human FasL mRNA. They exhibited different inhibitory activities on FasL expression in HEK293 cells. The most potent antisense oligonucleotide, ASO8, specifically downregulated 90% FasL expression at the protein level and 80% at the mRNA level. FasL downregulation reduced the effector function of HEK293 cells toward Fas receptor positive target cells. Further studies demonstrated that ASO8 efficiently inhibited FasL synthesis in split skin and basal cell carcinoma tissue. Our results show that the modulation of FasL expression by antisense oligonucleotides is possible in cells as well as tissue and indicate that antisense oligonucleotides may provide a promising strategy for the therapy of FasL-mediated disorders.


The interaction of sexual orientation and provider-patient communication on sexual and reproductive health in a sample of U.S. women of diverse sexual orientations.
Our goal was to examine associations among provider-patient communication, past-year contraceptive use and lifetime sexually transmitted infection. Data were analyzed cross-sectionally from 22,554 women in the Growing Up Today Study and Nurses' Health Study 3 between the follow-up period of 1996-2020. We used multivariable Poisson regression models adjusted for race/ethnicity, age in years, study cohort, and region of residence to obtain risk ratio (RR) associations and 95% confidence intervals (CI). Provider-patient communication was associated with higher likelihood of using all methods of past-year contraceptive use (RRs ranging from 1.11 to 1.63) and lifetime STI diagnosis (RRs ranging from 1.18 to 1.96). Completely heterosexual women with no same-sex partners (referent) were 13% more likely than lesbians and 4% less likely than other groups to report a provider ever discussed their SRH. Significant interactions emerged between sexual minority status and provider-patient communication. Sexual minority women whose providers discussed their SRH were less likely to report contraceptive non-use in the past year (p < .0001). Provider-patient communication may benefit sexual minority women's contraceptive practices and engagement with STI testing. Differences in provider-patient SRH discussion by sexual orientation indicate lesbian women are not receiving the same attention in clinical encounters.


A brain penetration after Taser injury: controversies regarding Taser gun safety.
We report the case of a 27 year old man who was injured by a Taser gun device which penetrated the frontal part of the skull and damaged the underlying frontal lobe. Cerebral penetration was revealed by a brain CT scan. A neurosurgical procedure was required to remove the dart from the skull and brain and the evolution was successful allowing discharge of the patient one week later. There were no additional lesions, particularly electrifying lesion, as only one probe had penetrated the skull. We also observed the length of a Taser dart is sufficient to allow brain penetration. Fortunately, no infection or neurological complication occurred following brain injury. This case study underlines the potential risk induced by the use of Taser stun gun. Although generally regarded as a safe alternative, serious injuries have however been reported and questions regarding the safety of the device still remains unresolved.


Association between air pollutants and neural tube defects during pregnancy in Lanzhou, China: a time series analysis.
Few studies have evaluated the association between air pollutants and neural tube defects (NTDs). Moreover, the existing research ignores the lag effect of air pollution on health and provides inconsistent epidemiological evidence. We aim to estimate the association between air pollution and NTDs during the first trimester of pregnancy and identify specific susceptible windows. Birth data was collected from the Birth Defects Surveillance Network in Lanzhou from September 1, 2014, to December 31, 2019. Air quality and meteorological data were collected from ambient air monitoring stations and China Meteorological Data Network. The log connection function of the Poisson distribution function is used to establish a DLNM model to estimate the exposure-effect relationship and exposure-lag relationship association between air pollutants levels and NTDs. There were 320,787 perinatal infants in Lanzhou from September 1, 2014, to December 31, 2019, and 486 cases of NTDs (1.5‰). The result indicates that exposure to inhalable particles (PM10) at lag 2-4 weeks was significantly associated with the risk of NTDs, with the most significant impact at the lag 2 week (RR=1.048, 95%CI, 1.015-1.084). Exposure to fine particulate matter (PM2.5) at the lag 2 week was significantly associated with the risk of NTDs, with the most significant impact at the lag 2 week (RR=1.077, 95%CI, 1.004-1.155). Exposure to sulfur dioxide (SO2) and nitrogen dioxide (NO2) at lag 3-6weeks was significantly associated with the risk of NTDs, with the most significant impact at the lag 4 week (RR=1.220, 95%CI, 1.105-1.348; RR=1.143, 95%CI, 1.048-1.245). This study provides further evidence that exposure to air pollutants in the first trimester of pregnancy significantly increases the risk of neural tube defects.


A comparison of epidural infusions in the combined spinal/epidural technique for labor analgesia.
We compared the clinical effects of three epidural infusions initiated after subarachnoid medication was administered as part of the combined spinal/epidural technique for labor analgesia. Fifteen minutes after administering subarachnoid fentanyl 25 microg and 1 mL of bupivacaine 0.25%, and 5 min after an epidural test dose of 3 mL of bupivacaine 0.25%, women were randomized to receive an epidural infusion of saline, bupivacaine 0.125%, bupivacaine 0.0625%, or bupivacaine 0.04% with epinephrine 1:600,000. All epidural infusions were started at 10 mL/h, and all except the Saline Group also received fentanyl 2 microg/mL. The end point of the study was delivery or request for additional medication for analgesia. We found that time until request for additional analgesia was longest in women who received bupivacaine 0.125% (median duration, 300 min) versus saline (median duration, 118 min) (P = 0.0001) and was intermediate for bupivacaine 0.0625% and bupivacaine 0.04% (median duration, 162 and 180 min, respectively) (P = 0.0001 versus saline). Women who received bupivacaine 0.125% had the most motor block. We conclude that all the bupivacaine-based infusions we tested maintained the analgesia from subarachnoid medication longer than saline, with the longest duration, but the most motor block, from bupivacaine 0.125%. In this prospective, randomized, and double-blinded study we found that initiating an epidural infusion of bupivacaine 0.125% with fentanyl 2 microg/mL at 10 mL/h 15 min after subarachnoid fentanyl 25 microg with 1 mL of bupivacaine 0.25%, followed by an epidural test dose of 3 mL of bupivacaine 0.25%, maintained the analgesia for longer but with more motor block than with either bupivacaine 0.04% or bupivacaine 0.0625%.


Combining diffusion kurtosis imaging and clinical data for predicting the extramural venous invasion of rectal adenocarcinoma.
The aim of this study is to investigate the diagnostic ability of diffusion kurtosis imaging (DKI) -derived parameters combining with clinical data as risk factors for EMVI's involvement status in rectal adenocarcinoma. Preoperative MR examination including DKI and conventional diffusion-weighted imaging (DWI) was performed on 154 rectal adenocarcinoma patients enrolled in this respective study. Kmean, Dmean, and apparent diffusion coefficient (ADC) values were calculated. Clinical information, serum tumor markers, MR and pathological assessment of EMVI were recorded. The Shapiro-Wilk test, two-sample t-test, Mann-Whitney U test, Spearman's rank-order correlation, univariate and multivariate logistic regression analyses were used for statistical analysis. Receiver operating characteristic (ROC) curve analyses were performed to identify risk factors in EMVI involvement. Of the 154 patients, pEMVI-positive rectal tumors had significantly higher Kmean values, lower ADCmean values compared to pEMVI-negative rectal tumors. Kmean values positively correlated with mrEMVI scores, whereas ADCmean values showed a negative correlation with mrEMVI scores. However, there was no significant correlation between the Dmean values and the mrEMVI scores. Univariate analysis demonstrated increased Kmean values, decreased ADCmean values, nodal involvement, an advanced tumor stage, and a G2 tumor grade were significantly related to the pEMVI of rectal adenocarcinoma. The multivariate analysis demonstrated that the Kmean values, lymph node involvement and an advanced tumor stage (T3) were independent risk factors for EMVI. The potential for diffusion kurtosis imaging as a biomarker for evaluating the EMVI of rectal cancer is feasible, especially given DKI's capability of detecting tumor heterogeneity noninvasively.


Interstitial Lung Disease in 2020: A History of Progress.
Interstitial lung diseases (ILDs) are heterogenous and complex chronic lung diseases that even today are challenging to diagnose and classify. The terminology and mechanistic understanding of specific ILDs have evolved substantially over the last centuries and decades, and clinicians, pathologists, radiologists, and researchers are continuously working to untangle the various ILDs of differing causes. Despite many drawbacks and negative clinical trials, the unremitting work of ILD researchers have resulted in great therapeutic successes over the last decade. In this chapter, the authors present historical aspects of ILD and build a foundation to understand current and emerging concepts in ILD.


[Patient safety and risk management].
Patient safety is the latest issue in the present stage of the German health care system, characterized by costs and quality both resulting in value of care. Patient safety defined as "absence of adverse events" represents an important problem, because 10% of in-house patients experience an adverse event, which in nearly 50% of the cases is due to an error (preventable adverse event). Threats and near misses are errors without a consecutive adverse event, much more common and better to integrate in the concept of risk management, which is based on thorough analysis and prevention of errors in medicine. Chart reviews show adverse events in between 3% and 11% of hospital patients, studies with direct observation result in higher estimates (17.7%). Nosocomial infections occur in 3-5%, adverse drug events in 0.17-6.5%, and adverse medical device events in up to 8% of patients. Medication errors (ordering, dosing, distribution) are present in up to 50% of all drug applications. Adverse drug events are important reasons for hospital admissions (3.2-10.8% of all admitted patients), other consequences of adverse drug events are severe disability and death. Mortality of adverse drug events is estimated between 0.04% and 0.95% of all patients. The introduction of risk management in the German health care system is one option to prevent a malpractice crisis similar to the situation in the US health care system in the 1990s. Errors are not to be considered only individual but also organizational failures. Critical incident report systems (CIRS) can help to increase the knowledge about errors, near misses and adverse events, so that prevention of errors can take place. On the organizational level, it is an issue of leaderchip to convince the members of the organization that prevention of errors has a higher priority than punishing and blaming. The medical and other professions, on the other side, have to change their self-understanding from the zero mistake philosophy to accepting errors as common events. This understanding is a prerequisite that analysis can be performed. The participation of patients should be strengthened, because public disclosure is an important issue, although the scientific evidence for real improvement in health care resulting from public disclosure is still inconclusive.


Distribution of the LETS protein (fibronectin) in rat cerebellum. An in vitro and in vivo developmental study.
The distribution of the large, external, transformation-sensitive (LETS; fibronectin) protein was investigated in rat cerebellum, both in vitro and in vivo, by biochemical and immunocytochemical methods. Biochemical analyses indicated that LETS protein is not demonstrable on the surfaces of cerebellar neurons from postnatal rats maintained in cell culture for varying periods of time, but is present on the surfaces of at least some fraction of the total nonneuronal cell population in vitro. Indirect immunofluorescence microscopy with an anti-LETS antiserum substantiated these observations and further indicated that LETS-bearing cells of cerebellum maintained in vitro are probably of endothelial and fibroblastic origin. The LETS protein is arranged in a reticular network of filaments spanning the surfaces of the cells, and the filaments are often extensively interdigitated with each other. At all stages of development investigated (two days postnatal to adult) LETS antigen was observed in vivo to be primarily localized in the meninges covering the surface of the cerebellum and between folia, and in the walls of blood vessels within the tissue. Neuroblasts and neurons of the external and internal granule layers of the cerebellum, respectively, were negative for the presence of LETS antigen.


Genetic map of artichoke × wild cardoon: toward a consensus map for Cynara cardunculus.
An integrated consensus linkage map is proposed for globe artichoke. Maternal and paternal genetic maps were constructed on the basis of an F(1) progeny derived from crossing an artichoke genotype (Mola) with its progenitor, the wild cardoon (Tolfa), using EST-derived SSRs, genomic SSRs, AFLPs, ten genes, and two morphological traits. For most genes, mainly belonging to the chlorogenic acid pathway, new markers were developed. Five of these were SNP markers analyzed through high-resolution melt technology. From the maternal (Mola) and paternal (Tolfa) maps, an integrated map was obtained, containing 337 molecular and one morphological markers ordered in 17 linkage groups (LGs), linked between Mola and Tolfa. The integrated map covers 1,488.8 cM, with an average distance of 4.4 cM between markers. The map was aligned with already existing maps for artichoke, and 12 LGs were linked via 31 bridge markers. LG numbering has been proposed. A total of 124 EST-SSRs and two genes were mapped here for the first time, providing a framework for the construction of a functional map in artichoke. The establishment of a consensus map represents a necessary condition to plan a complete sequencing of the globe artichoke genome.


Long-term changes in bone mass after partial gastrectomy in a well-defined population and its relation to tobacco and alcohol consumption.
We studied the long-term effect of partial gastrectomy on bone metabolism in a well defined population of gastrectomized patients compared to an age- and sex-matched group with unoperated peptic ulcers (controls). We selected 61 individuals between 61 and 70 years old at the time of investigation who had been operated on at the same surgical department an average of 20 years earlier. Compared to unoperated ulcer patients, we found reduced bone mass of the distal forearm in the operated groups. The serum level of calcidiol was significantly reduced in Billroth I (BI) operated women and insignificantly lower in the other operated groups. In men, ionized and total calcium was reduced, and 24-hour excretion of hydroxyproline in the urine as increased (p < 0.05). Biochemical signs of osteomalacia were found in one gastrectomized patient only. There were no significant differences between operated and unoperated patients in serum levels of alkaline phosphatases, iPTH, calcitriol, or the 24-hour urine calcium/creatinine excretion, even though there was a trend toward lower 24-hour urine calcium/creatinine ratio and increased levels in iPTH in the operated groups. There was no correlation between the daily alcohol consumption or cumulative tobacco consumption and bone mineral content in each group. Gastrectomized women smoked much more than control women, and smoking may be a determinant factor for the bone loss, as it is in healthy persons. Operated patients had a lower intake of milk products. All patients were exposed to sunlight for more than 3 hours/week. It is suggested that osteopenia after gastrectomy might be caused by calcium depletion rather than lack of vitamin D. The consumption of tobacco but not of alcohol was connected to bone loss.


T and B cell development in pituitary deficient insulin-like growth factor-II transgenic dwarf mice.
Treatment of mice with IGF-I stimulates T and B cell development. We showed that overexpression of IGF-II in transgenic FVB/N mice only stimulated T cell development. In the present study, we further addressed the in vivo effects of IGF-II in the absence of IGF-I to get more insight into the potential abilities of IGF-II to influence T and B cell development. To this end, we studied lymphocyte development in IGF-II transgenic Snell dwarf mice that are prolactin, GH and thyroid-stimulating hormone deficient and as a consequence show low serum IGF-I levels. We showed that T cell development was stimulated to the same extent as in IGF-II transgenic FVB/N mice. Furthermore, IGF-II increased the number of nucleated bone marrow cells and the number of immature B cells without having an effect on the number of mature B cells in spleen and bone marrow. Our data show that IGF-II has preferential effects on T cell development compared with B development, and that these preferential effects also occur in the absence of measurable IGF-I levels.


Aerobic Gram-negative Bacillary Pneumonia.
Gram-negative bacilli (GNB) are a common cause of severe hospital-acquired pneumonia. Due to changes in the health care environment and selective antimicrobial pressure, these bacteria also are becoming a more common cause of pneumonia in venues outside of the traditional hospital setting and are increasingly resistant to antimicrobial agents. Risk factors for acquisition of GNB allow the clinician to efficiently identify patients who are likely to have pneumonia due to these pathogens. Available diagnostic techniques have a limited capacity to accurately detect GNB pulmonary infection. Yet, a pathogen specific diagnosis and knowledge of local resistance patterns are quintessential elements in formulating an effective treatment plan. This article reviews the epidemiologic characteristics, pathogenesis, and current management issues of GNB pneumonia.


Pathological mechanisms and crosstalk among different forms of cell death in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder characterized by a profound immune dysregulation and the presence of a variety of autoantibodies. Aberrant activation of programmed cell death (PCD) signaling and accelerated cell death is critical in the immunopathogenesis of SLE. Accumulating cellular components from the dead cells and ineffective clearance of the dead cell debris, in particular the nucleic acids and nucleic acids-protein complexes, provide a stable source of self-antigens, which potently activate auto-reactive B cells and promote IFN-I responses in SLE. Different cell types display distinct susceptibility and characteristics to a certain type of cell death, while different PCDs in various cells have mutual and intricate connections to promote immune dysregulation and contribute to the development of SLE. In this review, we discuss the role of various cell death pathways and their interactions in the pathogenesis of SLE. An in depth understanding of the interconnections among various forms cell death in SLE will lead to a better understanding of disease pathogenesis, shedding light on the development of novel therapeutic targets.


Contamination from 131I, 103Ru, and 239Np in the eluate of 99Mo-99mTc generators loaded with (n, gamma)-produced 99Mo.
Iodine-131, ruthenium-103, and neptunium-239 are present as contaminants in the eluate of 99Mo-99mTc generators loaded with 99Mo prepared by thermal-neutron irradiation of enriched 98Mo. The elution pattern of each of these contaminants is determined, together with the amounts found in the eluate of all generators tested over a 7-month period.


Preparation and characterization of polycaprolactone/chitosan-g-polycaprolactone/hydroxyapatite electrospun nanocomposite scaffolds for bone tissue engineering.
Chitosan (CS) and poly (ε-caprolactone) (PCL) are two most usable polymers in biomedical applications. In this study, chitosan has been modified and incorporated with poly (ε-caprolactone) to fabricate bone tissue engineering scaffold. Moreover, hydroxyapatite nanoparticles were added to enhance bioactivity and mechanical properties of scaffold. Bulk and fibrous comparative results showed significant effect of fiber diameter and distribution on mechanical properties. Moreover, the incorporation of chitosan-g-poly (ε-caprolactone) (CS-g-PCL) significantly decreases fiber diameter of pure PCL scaffold. Furthermore, both CS-g-PCL and nHA enhance mineralization and degradation of the scaffold soaked in simulated body fluid (SBF) and phosphate buffered saline (PBS), respectively. In vitro cytocompatibility assays also confirmed high cell viability and proliferation on the samples. Taken together, the results suggest that the microfabricated nanocomposite scaffolds could be used in bone tissue engineering.


Pattern of spatial distribution in Drosophila melanogaster.
The effect of temperature and sex on spatial distribution of Drosophila melanogaster adults was studied in a specially designed apparatus. It was observed that individuals tend to aggregate in sections of the sphere independently of sex and temperature. Nevertheless, decrease in temperature increase aggregation. The mobility of both males and females indicates a negative geotactic tendency.


Pathological reporting of cystectomy lymph nodes: a retrospective analysis of experience in Paris.
Pathological evaluation of pelvic lymph node (LN) dissection (PLND) is important for management of cystectomy patients. However, challenges such as unclear interobserver variability of LN counting remain. Here, we assess interobserver variability of LN measures and their clinical utility, with a focus on variant histology. We retrieved radical cystectomy cases with PLND between 2010 and 2016 and reevaluated pathological parameters; number of total and metastatic LN, LN density (LND), length of metastatic LN and metastases, extranodal extension (ENE). We report 96 patients: median age of 71a, 34 cases pN+, 36 cases with any extent of variant histology, median follow-up 10 months. Perivesical LN were only rarely identified, but frequently metastatic (4/9). Variant histology (34 cases) frequently exhibited LN metastasis (53% of pN+ cases). Interobserver variance was poor for total LN (kappa = 0.167), excellent for positive LN (0.85) and pN staging (0.96), and mediocre for LND (0.53). ROC analysis suggests that both LND and the sum of LN metastasis length may predict outcome (AUC 0.83 and 0.75, respectively). Our study confirms the notion of LND as a prognostic measure, but cautions due to strong interobserver variance of LN counts. The sum length of LN metastases could be a measure that is independent of LN counts. We find that microscopically identified perivesical LN merit particular attention. In summary, our study highlights current challenges in pathological reporting of PLND, confirms previous observations and forms a basis for further studies.


Pharmacokinetics of Exosomes-An Important Factor for Elucidating the Biological Roles of Exosomes and for the Development of Exosome-Based Therapeutics.
Exosomes are small membrane vesicles containing lipids, proteins, and nucleic acids. Recently, researchers have uncovered that exosomes are involved in various biological events, such as tumor growth, metastasis, and the immune response, by delivering their cargos to exosome-receiving cells. Moreover, exosomes are expected to be used in therapeutic treatments, such as tissue regeneration therapy and antitumor immunotherapy, because exosomes are effective delivery vehicles for proteins, nucleic acids, and other bioactive compounds. To elucidate the biological functions of exosomes, and for the development of exosome-based therapeutics, the pharmacokinetics of exosomes is important. In this review, we aim to summarize current knowledge about the pharmacokinetics and biodistribution of exosomes. The pharmacokinetics of exogenously administered exosomes is discussed based on the tissue distribution, types of cells taking up exosomes, and key molecules in the pharmacokinetics of exosomes. In addition, recent progress in the methods to control the pharmacokinetics of exosomes is reviewed.


A fuzzy rule-based multi-criterion approach for a cooperative green supplier selection problem.
Multi-criterion decision-making models are widely used in supplier selection problems. This study contributes to a green supplier selection problem considering the green manufacturing, green transportation, and green procurement. This study contributes to reverse logistics, eco-design, reusing, recycling, and remanufacturing with their high impact on the industries. In addition to the logistics costs and transportation costs, the carbon emissions are considered. With regard to the game theory, this paper uses a cooperative green supplier selection model. If transportation requirements of two or more companies are combined, it will help manufacturers to have less [Formula: see text] emissions with lower cost. After creating the optimization model to consider the uncertainty, this cooperative game theory model is established in a fuzzy environment. In this regard, a fuzzy rule-based (FRB) system is deployed and the set of fuzzy IF-THEN rules is considered. The proposed FRB model is contributed for the first time in the area of green supplier selection problem. Finally, some sensitivity analyses are conducted in a numerical example to evaluate the proposed model. With regard to the findings, although the cost of CO2 emission of horizontal cooperation is increased, the cost saving of companies is increased. It means our total cost is optimal in a logistic network using the cooperative game theory. The results also indicate that horizontal cooperation in logistic network causes less cost and benefits for each company.


Risk Factor Analysis for Type 2 Diabetes Patients About Hypoglycemia Using Continuous Glucose Monitoring: Results from a Prospective Observational Study.
Introduction: To determine the relationship between hypoglycemia and glucose variability in outpatients with type 2 diabetes mellitus (T2DM). Materials and Methods: The study participants were 999 outpatients with T2DM who used the FreeStyle Libre Pro for continuous glucose monitoring (FLP-CGM). Hypoglycemia was defined as glucose level of <3.0 mM, and the frequency of episodes and duration of hypoglycemia were evaluated by comparing patients who did or did not achieve time-below-range <3.0 mM (TBR<3.0) of <1% of the time. The association of TBR<3.0 and long% coefficient of variation (%CV) with medications used was examined using multivariate analysis with a proportional odds model. Results: The average TBR<3.0 was 0.33% (4.75 min). The TBR<3.0 >1% group comprised 71/999 patients. Patients of the TBR<3.0 >1% group had lower body mass index, longer disease duration, and poorer renal function. For the TBR<3.0 >1% group, the predicted cutoff values were 7.19 mM average glucose (AG), and 30.30% for %CV. When AG <7.19 mM and %CV >30.30% were considered as hypoglycemic risk factors, the frequency and duration of hypoglycemia increased as the risk factor values increased. In multivariate analysis, sulfonylurea (SU) use, insulin use, and low blood glucose index correlated significantly with increased length of TBR<3.0 and %CV, even after adjustment for concomitant diabetes medications. Conclusion: In T2DM, maintaining TBR<3.0 <1% requires to keep AG >7.2 mM and %CV <30%, in addition to comprehensive management of CGM metrics. Since SU and insulin use is associated with prolonged TBR<3.0 and increased %CV, their doses should be adjusted to avoid excessive fall in AG and raising %CV.


Complex effects of two presumably antagonistic endocrine disrupting compounds on the goldfish Carassius aumtus: a comprehensive study with multiple toxicological endpoints.
We studied the effects of endocrine disrupting compounds nonylphenol (NP) and letrozole (LE) on the male goldfish Carassius aumtus. Exposure to NP (20 μg l(-1)) alone caused a significant up-regulation in the expression of aromatase, estrogen receptors and vitellogenin (VTG) genes, an increase in hepatic and plasma VTG concentration, but no obvious testicular impairment. Exposure to LE (1 mg kg(-1)) alone resulted in a significant decline in aromatase activity, reduced levels of plasma 17β-estradiol (E2), and enhanced sperm maturation. Co-exposure with LE (1 mg kg(-1)) could only partially affect some of the estrogenic effects caused by NP (20 μg l(-1)) (i.e. expression of hepatic and brain estrogen receptor genes, hepatic VTG concentration), but inhibit other estrogenic effects (i.e. brain and testicular aromatase activity, plasma E2). In addition, co-exposure resulted in impairment of liver mitochondria (i.e. detachment of ridges from the membrane, and uneven distribution of the cytoplasm with clusters of glycogen granules), but did not cause significant damage to the testes (i.e. the morphology, the spermatogonia and spermatozoa densities). Our results clearly showed that nonylphenol and letrozole co-exposure could induce profound effects on fish, and highlighted the importance of adopting multiple toxicological endpoints when evaluating the combined effects of endocrine disrupting compounds.


Plague in Lushoto district, Tanzania, 1980-1988.
Rodents were live-trapped in selected plague-inflicted villages from June 1980 to March 1988. Flea infestation rates were determined and the animals were serologically tested for plague. Clinically suspected and clinically healthy people in the affected areas were similarly tested for plague antibodies. Of 1596 rodent sera tested, 91 (5.7%) were positive for plague. These were mostly from Rattus rattus, Mastomys natalensis, Otomys spp. and Pelomys fallax. A total of 1772 fleas, of which Dinopsyllus lypusus, Xenopsylla brasiliensis and Ctenophthalmus calceatus comprised the largest proportion, was collected from the captured rodents. Total flea indices ranged from 0.67 to 1.12 fleas per rodent. A total of 2809 human cases and a mortality rate of 10.2% were recorded in 1980-1988. It was concluded that most rodent species in the area were suitable reservoirs of plague and that D. lypusus, X. brasiliensis and C. calceatus were probably responsible for transmitting the pathogen. Lack of effective quarantine measures during outbreaks was partly responsible for the spread of the disease to many villages, while inadequate rodent and flea control and poor sanitary measures could be responsible for continued outbreaks of plague in the area.


Kinetic study of cis-dichloroethylene (cis-DCE) and vinyl chloride (VC) dechlorination using green rusts formed under varying conditions.
Abiotic degradation of cis-dichloroethylene (cis-DCE) and vinyl chloride (VC) was investigated using Fe hydroxides obtained by hydrolyzing Fe(II) salts over a pH range of 7.7-8.0. Within this narrow pH range, a green rust (GR) precipitated. The dechlorination reactivity of the resulting GR precipitates increased with the dissolved Fe(II) concentration remaining in solution after precipitation. Controls run using only the dissolved Fe(II) supernatant were not reactive, suggesting the relative amount of Fe(II) on the surface of precipitated GRs was the causative agent in the relative reactivity. To test this, a series of GR batches with varying dissolved Fe(II) concentrations were prepared by acid-base titration and examined for cis-DCE and VC dechlorination kinetics under reducing conditions. X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analyses of these batches were performed to characterize the bulk mineralogy and the excess surface Fe(II), respectively. Cis-DCE and VC dechlorination results along with solid phase characterization show that different surface Fe(II)/Fe(III) compositions are responsible for the different reactivity of GRs formed within the GR precipitation zone.


Elastic cationic liposomes for vitamin C delivery: Development, characterization and skin absorption study.
The influence of hydrophilic surfactants acting on the membrane elasticity of liposomes on the skin absorption of vitamin C is investigated. The purpose of encapsulation inside cationic liposomes is to improve the skin delivery of vitamin C. The properties of elastic liposomes (ELs) are compared to that of conventional liposomes (CLs). ELs are formed by the addition of the "edge activator" Polysorbate 80 to the CLs composed of soybean lecithin, cationic lipid DOTAP (1,2-dioleoyl-3-trimethylammoniopropane chloride), and cholesterol. The liposomes are characterized by dynamic light scattering and electron microscopy. No toxicity is detected in human keratinocyte cells. Evidences of Polysorbate 80 incorporation into liposome bilayers and of the higher flexibility of ELs are given by isothermal titration calorimetry and pore edge tension measurements in giant unilamellar vesicles. The presence of a positive charge in the liposomal membrane increases the encapsulation efficacy by approximately 30% for both CLs and ELs. Skin absorption of vitamin C from CLs, ELs and a control aqueous solution measured in Franz cells shows a high delivery of vitamin C into each skin layer and the acceptor fluid from both liposome types. These results suggest that another mechanism drives skin diffusion, involving interactions between cationic lipids and vitamin C depending on the skin pH.


[N-nitroso compounds in the food products in regions with a high stomach cancer morbidity].
The content of cancerogenous N-nitrosamines (NA) was examined in food marketed in the regions with the increased gastric carcinoma incidence. The food was analyzed by means of the fluorescent technique. Some of food products, such as lard, corned beef, dried mushrooms were found to be contaminated with volatile NA, while vegetable and milk products contained negligible amounts of NA or did not contain them at all.


Population pharmacokinetic and pharmacodynamic modeling of capecitabine and its metabolites in breast cancer patients.
The present study was performed to examine relationships between systemic exposure of capecitabine metabolites (5-FU, 5'-DFCR and 5'-DFUR) and toxicity or clinical response in patients with metastatic breast cancer. A population pharmacokinetic model for capecitabine and its three metabolites was built. Typical parameter values, characteristics of random distributions, associated with parameters, and covariates impact were estimated. Area under the curve (AUC) were computed for 5-FU and compared with grades of toxicity. Pharmacokinetic modeling was based on data collected on the first treatment cycle. Toxicity was assessed on the two first treatment cycles. The study was conducted in 43 patients. The population pharmacokinetic model (a one-compartment model per compound) was able to capture the very complex absorption process of capecitabine. Statistically significant covariates were cytidine deaminase, alkaline phosphatase and dihydrouracilemia (UH2)/uracilemia (U) ratio. UH2/U ratio was the most significant covariate on 5-FU elimination and CDA on the transformation of 5'-DFCR in 5'-DFUR. A trend was observed between 5-FU AUC and thrombopenia toxicity grades, but not with other toxicities. Best clinical response was not linked to systemic exposure of capecitabine metabolites. In our study, we propose a model able to describe, meanwhile, and its main metabolites, with a complex absorption process and inclusion of enzyme activity covariates such as CDA and UH2/U ratio. Trial registration Eudract 2008-004136-20, 2008/11/26.


Intensive diet instruction by registered dietitians improves weight-loss success.
Multiple factors influence long-term weight-loss success, as shown by the National Weight Control Registry. We evaluated the influence of two of those factors, diet instruction by a registered dietitian (RD) and frequency of weigh-in visits, on initial weight-loss success. Twenty-six overweight subjects with a baseline body mass index of 33.2+/-3.7 and a mean age of 43+/-12 years were enrolled in a weight-loss study. The 11-week weight loss period included 33 total visits, with weekly RD-instructed classes with a weigh-in, and 22 semiweekly related weigh-in visits without an RD present. Classes covered topics in the areas of energy restriction, dietary change, exercise, and behavior modification. Subjects were enrolled at different time points within the class topic rotation but all completed the 11-week program. The mean weight loss for all subjects was 3.8+/-2.8 kg (P<0.001). Weight loss (%) was significantly correlated with attendance of RD-instructed classes (r=0.451, P=0.021) but not attendance at weigh-ins that did not include RD-instructed classes (r=0.329, P=0.101). We conclude that RD-led dietary instruction was more beneficial than frequent weigh-in visits alone in promoting weight loss.


Pachydermoperiostosis: a rare mimicker of acromegaly.
Pachydermoperiostosis is a very rare osteoarthrodermopathic disorder whose clinical and radiographic presentations may mimic those of acromegaly. In the evaluation of patients with acromegaloid appearances, pachydermoperiostosis should be considered as a differential diagnosis. In this article, we report a 17-year-old boy who presented with 2-year history of acral enlargement and facial appearance changes associated with joint pain and excessive sweating. He had been investigated extensively for acromegaly, and the final diagnosis was pachydermoperiostosis. There is a broad range of differential diagnosis for acromegaloid features such as acromegaly, pseudoacromegaly with severe insulin resistance, Marfan's syndrome, McCune-Albright and a rare condition called pachydermoperiostosis.Once a patient is suspected to have acromegaly, the first step is biochemical testing to confirm the clinical diagnosis, followed by radiologic testing to determine the cause of the excess growth hormone (GH) secretion. The cause is a somatotroph adenoma of the pituitary in over 95 percent of cases.The first step is measurement of a serum insulin-like growth factor 1 (IGF1). A normal serum IGF1 concentration is strong evidence that the patient does not have acromegaly.If the serum IGF1 concentration is high (or equivocal), serum GH should be measured after oral glucose administration. Inadequate suppression of GH after a glucose load confirms the diagnosis of acromegaly.Once the presence of excess GH secretion is confirmed, the next step is pituitary magnetic resonance imaging (MRI).Atypical presentation warrants revision of the diagnosis. This patient presented with clubbing with no gigantism, which is expected in adolescent acromegalics as the growth spurt and epiphyseal plate closure have not taken place yet.


Transport of 2-deoxy-D-[3H]glucose in microvessels isolated from bovine cerebral cortex.
Microvessels were isolated from a bovine cortex and the transport of glucose was investigated by using 2-deoxy-D-[3H]glucose (2-DG). The apparent Km for 2-DG transport was 118 microM and therefore indicates a significant high affinity for the substrate. The inhibition of 2-DG uptake by D-glucose showed an apparent Ki of 222 microM. Other sugars, e.g., 3-methyl-D glucose and D-fructose, also inhibited the 2-DG uptake by 60.6 and 36.0%, respectively. Phloretin (1 X 10(-3) M) inhibited the 2-DG transport more than phlorizin (83.7 vs. 53.8%). Ouabain (1 and 5 X 10(-4) M) did not inhibit the uptake of 2-DG but 2,4-dinitrophenol (1 X 10(-4) M) did (78.0%). The uptake of 2-DG could not be demonstrated in homogenized microvessels. Adenine nucleotides (conc. 2 mM) had various effects on the 2-DG uptake by microvessels. ATP inhibited the uptake by 20.7%, ADP was virtually without effect, and AMP stimulated the uptake of 2-DG by 8.5%. It was also found that the decrease of adenylate energy charge favors the uptake of 2-DG. All these findings suggest that, in cerebral microvessels of a bovine cortex, 2-DG is apparently transported by a specific, carrier-mediated transport system.


Signal enhancement in DNA microarray using dye doped silica nanoparticles: application to human papilloma virus (HPV) detection.
DNA microarray is a powerful tool for the parallel of nucleic acids and other biologically significant molecules. In this communication we report an easy and cheap synthesis route for incorporating organic dyes into monodisperse inorganic silica nanoparticles and their application on the detection of carcinogenic risky Human Papilloma Virus using DNA microarray technology. We correlate our system with conventional direct dyes and commercial quantum dots, with a promising increase in optical signal, and a related decrease of the limit of detection, thus giving a remarkable improvement in this technique towards early diagnosis of diseases and trace level detection of dangerous biological contaminants.


A review on lactoferrin as a proton pump inhibitor.
Lactoferrin (Lf) is a versatile natural milk-derived protein that exhibits multiple interesting biological activities. Since it is safe for human administration and currently manufactured using low cost and well-established large-scale processes, the Lf scientific community has been devoted at dissecting its mechanisms of action towards its more rational and efficient use for various applications. Emerging literature has identified proton pumping ATPases as molecular targets of Lf in different cellular models linked to distinct activities of this natural protein. Information on this subject has not been systematically analysed before, hence herein we review the current state of art on the effect of Lf on proton pumping ATPases. Though structurally different, we propose that Lf holds a proton pump inhibitor (PPI)-like activity based on the functional resemblance with the classical inhibitors of the stomach H+/K+-ATPase. The downstream events and outcomes of the PPI-like activity of Lf, as well as its impact for the development of improved Lf applications are also discussed.


The effect of lead and cadmium on liver, kidney, and brain levels of cadmium, copper, lead, manganese, and zinc, and on erythrocyte ALA-D activity in mice.
Lead and cadmium were administered intraperitoneally, singly and jointly, to the mice. The levels of cadmium, copper, manganese, lead and zinc were determined in liver, kidney and brain by atomic absorption spectrophotometric technique and delta-aminolevulinic acid dehydratase (ALA-D) activity was determined in erythrocytes. The tissue levels of some of these metals were found significantly altered by cadmium and lead both, but cadmium was found to have no effect on blood on ALA-D activity.


Reproducibility of peroneal motor nerve conduction measurement in older adults.
While neuropathy is common in the elderly, nerve conduction (NC) reproducibility in older adults is not well-established. We sought to evaluate intraobserver reproducibility of peroneal motor NC measures in a diverse sample of older adults. We measured peroneal motor NC amplitude and velocity in a subset of participants (mean age=82.9±2.7, n=62, 50% female, 51.6% black, 35.5% DM) in the Health, Aging, and Body Composition Study. Using coefficients of variation (CVs), intraclass correlation coefficients (ICCs), and Bland Altman Plots, we compared two sets of measurements taken by the same examiner hours apart on the same day. Low CVs (2.15-4.24%) and moderate to high ICCs (0.75-0.99) were observed. No systematic variation was found across measures. Despite small numbers in some subgroups, we found no differences in reproducibility by diabetes, race or study site. NC measures have moderate to high intraobsever reproducibility in older adults and are not affected by diabetes, race, or gender. These data provide evidence to support use of these measures in aging research.


Transcriptomic analysis of bisphenol AF on early growth and development of zebrafish (Danio rerio) larvae.
Bisphenol AF (BPAF), an alternative to bisphenol A, is widely detected in aquatic environments. Owing to health concerns, the toxic effects of BPAF on organisms are drawing attention. The present study aims to evaluate the toxicity of BPAF, combining the results of omics techniques and experiment. Employing transcriptome sequencing (RNA-seq), we obtained 391, 648, 512, and 545 differentially expressed genes (DEGs) in 0.1, 1, 10, and 100 μg/L BPAF-exposed zebrafish larvae, respectively. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealed the early development, stimulus-response, and MAPK signaling pathway were significantly affected by BPAF. In addition, five hub genes (fgf3, fgf4, map2k1, myca, and casp3b) were highlighted as the key genes in MAPK signaling pathway using the protein-protein interaction network. Therefore, the RNA-seq results showed that early development and stimulus-response were the main processes affected by BPAF, which was consistent with our morphological and pathological results. The hatching rate of zebrafish embryos in 1 and 10 μg/L BPAF groups was significantly inhibited, and the oxidative stress indexes, including the level of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and lipid peroxidation (LPO), were significantly increased by the 100 μg/L BPAF treatment. Moreover, the activity of alkaline phosphatase (AKP) was significantly decreased in all BPAF exposure groups. In conclusion, exposure to BPAF at environmental relevant concentrations affected the early development and immune system of zebrafish larvae by modulating MAPK signaling pathway, and our results provide solid evidence for the future studies on the toxicity of bisphenols.


Multidrug-resistant Pseudomonas aeruginosa infections pose growing threat to health care-associated infection control in the hospitals of Southern China: a case-control surveillance study.
Multidrug-resistant Pseudomonas aeruginosa (MDRPA) is one of the most common agents among health care-associated infections. There is a lack of data on the clinical features of MDRPA from Southern China. A case-control surveillance study of P aeruginosa was conducted based on surveillance from July 2008-December 2012, in 5 hospitals of Guangzhou, China. Data were analyzed by univariate analysis and multivariate logistic regression using Stata 13 (StataCorp, College Station, TX). Of the 348 P aeruginosa strains, the prevalence of MDRPA was 54%, and it has increased over time. Isolates of P aeruginosa showed increased resistance to most antimicrobials during this time period. Independent risk factors were tracheal intubation insertion (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.16-4.23; P = .02) and use of carbapenem (odds ratio [OR], 3.36; 95% confidence interval [CI], 1.75-6.47; P < .01). The distribution of MDRPA infections was uneven among the 5 hospitals (P = .01). Being infected with MDRPA strains resulted in longer duration of hospitalization (39 vs 24 days) and higher mortality (49% vs 20%). The infections of MDRPA were severe issues. More stringent measures should be applied for those with independent predictors of MDRPA infections because they may induce adverse clinical outcomes.


[Perforations in neoplasms of the colon].
The authors show their experience about the surgical treatment of colonic perforations in course of neoplastic disease. Their casuistry is compared with those of other centres.


Factors influencing surfactant composition in the newborn infant.
In order to evaluate the surfactant maturation of the neonate, tracheal aspirates were analyzed in 84 newborn infants with 12h of birth. Using 2-dimensional thin-layer chromatography, 9 different phospholipids were identified. Dynamic surface tension measurements were performed with a modified Wilhelmy balance. Five different groups of infants with typical phospholipid patterns were characterized: i.e., 1. Normal term newborn. 2. RDS in the preterm infant. 3. Acceleration of lung maturity in preterm infants without RDS. 4. Retardation in term infants with RDS. 5. Therapeutic induction of pulmonary maturity in preterm infants following maternal glucocorticoid administration. Mature lung effluent contains high concentrations of phosphatidylcholine (PC) and phsophatidylglycerol (PG). In infants with RDS, PC is low and PG absent. Accelerated lung maturity was observed after chronic prenatal stress, such as prolonged rupture of the membranes, chronic vaginal bleeding, and maternal hepatitis or drug addiction. Retardation of pulmonary maturity was seen in infants with alpha-1-AT-deficiency, maternal diabetes and maternal hypothyroidism. Administration of methylprednisolone to the mother 24 h to 72h before birth induced both the synthesis of PC and PG in the preterm infants, resulting in an almost full-term phospholipid pattern as early as 31 weeks of gestation. The significance of these factors on the pathogenesis of RDS is discussed.


Treatment of autoimmune hepatitis: a review of current and evolving therapies.
Autoimmune hepatitis (AIH) is an immune-mediated necroinflammatory condition of the liver. Presentation can vary from the asymptomatic individual with abnormal liver function test to fulminant liver failure. The diagnosis is based on the combination of biochemical, autoimmune, and histological parameters, and exclusion of other liver diseases. Standard therapy consists of a combination of corticosteroids and azathioprine, which is efficacious in 80% of patients. Alternative therapies are increasingly being explored in patients who do not respond to the standard treatment and/or have unacceptable adverse effects. This review examines the role of alternative drugs (second-line agents) available for AIH treatment non-responders. These agents include budesonide, mycophenolate mofetil, cyclosporin, tacrolimus, 6-mercaptopurine, 6-thioguanine, rituximab, ursodeoxycholic acid, rapamycin, and methotrexate. In addition, the risk of opportunistic infections and malignancies are discussed. A treatment algorithm is proposed for the management of patients with AIH treatment non-responders.


Use of PTFE stent grafts for hemodialysis-related central venous occlusions: intermediate-term results.
To assess the safety and effectiveness of a polytetrafluoroethylene (PTFE) encapsulated nitinol stents (Bard Peripheral Vascular, Tempe, AZ) for treatment of hemodialysis-related central venous occlusions. Study design was a single-center nonrandomized retrospective cohort of patients from May 2004 to August 2009 for a total of 64 months. There were 14 patients (mean age 60 years, range 50-83 years; 13 male, 1 female). All patients had autogenous fistulas. All 14 patients had central venous occlusions and presented with clinical symptoms of the following: extremity swelling (14%, 2 of 14), extremity and face swelling (72%, 10 of 14), and face swelling/edema (14%, 2 of 14). There was evidence of access dysfunction with decreased access flow in 36% (5 of 14) patients. There were prior interventions or previous line placement at the site of the central venous lesion in all 14 patients. Results were assessed by recurrence of clinical symptoms and function of the access circuit (National Kidney Foundation recommended criteria). Sixteen consecutive straight stent grafts were implanted in 14 patients. Average treated lesion length was 5.0 cm (range, 0.9-7 cm). All 14 patients had complete central venous occlusion (100% stenosis). The central venous occlusions were located as follows: right subclavian and brachiocephalic vein (21%, 3 of 14), right brachiocephalic vein (36%, 5 of 14), left brachiocephalic vein (36%, 5 of 14), and bilateral brachiocephalic vein (7%, 1 of 14). A total of 16 PTFE stent grafts were placed. Ten- or 12-mm-diameter PTFE stent grafts were placed. The average stent length was 6.1 cm (range, 4-8 cm). Technical (deployment), anatomic (<30% residual stenosis), clinical (resolution of symptoms), and hemodynamic (resolution of access dysfunction) success were 100%. At 3, 6, and 9 months, primary patency of the treated area and access circuit were 100% (14 of 14). This PTFE encapsulated stent graft demonstrates encouraging intermediate-term patency results for central vein occlusions. Further prospective studies with long-term assessment and larger patient populations will be required.


Superior in vitro activity of carbapenems over anti-methicillin-resistant Staphylococcus aureus (MRSA) and some related antimicrobial agents for community-acquired MRSA but not for hospital-acquired MRSA.
Eighty-eight strains of Panton-Valentine leukocidin (PVL)-positive and -negative community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and 152 strains of hospital-acquired MRSA (HA-MRSA) were examined for susceptibility to carbapenems, oxacillin, and other antimicrobial agents. CA-MRSA strains were more susceptible to carbapenems (MIC(90), 1-4 microg/ml) than HA-MRSA strains (MIC(90), 32-64 microg/ml). Among the carbapenems examined, CA-MRSA strains were most susceptible to imipenem (MIC(50), 0.12 microg/ml; MIC(90), 1 microg/ml). A similar tendency was observed with oxacillin, but less markedly (MIC(90): 32 microg/ml for CA-MRSA and > or =256 microg/ml for HA-MRSA). This difference was also observed between CA-MRSA and HA-MRSA in susceptibility levels to cephems, erythromycin, clindamycin, and levofloxacin, but not to ampicillin, vancomycin, teicoplanin, linezolid, and arbekacin. The data indicate that, in terms of MIC(50) or MIC(90) values, CA-MRSA is 64-256 times more susceptible to imipenem than HA-MRSA, and for CA-MRSA, some carbapenems, e.g., imipenem, show better in vitro activity than anti-MRSA or some related agents.


A DNA repair disorder caused by de novo monoallelic DDB1 variants is associated with a neurodevelopmental syndrome.
The DNA damage-binding protein 1 (DDB1) is part of the CUL4-DDB1 ubiquitin E3 ligase complex (CRL4), which is essential for DNA repair, chromatin remodeling, DNA replication, and signal transduction. Loss-of-function variants in genes encoding the complex components CUL4 and PHIP have been reported to cause syndromic intellectual disability with hypotonia and obesity, but no phenotype has been reported in association with DDB1 variants. Here, we report eight unrelated individuals, identified through Matchmaker Exchange, with de novo monoallelic variants in DDB1, including one recurrent variant in four individuals. The affected individuals have a consistent phenotype of hypotonia, mild to moderate intellectual disability, and similar facies, including horizontal or slightly bowed eyebrows, deep-set eyes, full cheeks, a short nose, and large, fleshy and forward-facing earlobes, demonstrated in the composite face generated from the cohort. Digital anomalies, including brachydactyly and syndactyly, were common. Three older individuals have obesity. We show that cells derived from affected individuals have altered DDB1 function resulting in abnormal DNA damage signatures and histone methylation following UV-induced DNA damage. Overall, our study adds to the growing family of neurodevelopmental phenotypes mediated by disruption of the CRL4 ubiquitin ligase pathway and begins to delineate the phenotypic and molecular effects of DDB1 misregulation.


Complete Genome Sequences of Mycobacterium smegmatis Phages NihilNomen and Carlyle, Isolated in Las Vegas, Nevada.
We present the complete genomes of the Mycobacterium smegmatis phages Carlyle and NihilNomen, isolated from soil in Las Vegas, Nevada. The phages were isolated and annotated by undergraduate students enrolled in the Phage Discovery course offered by the School of Life Sciences at the University of Nevada Las Vegas.


A nomogram model to predict the venous thromboembolism risk after surgery in patients with gynecological tumors.
Venous thromboembolism (VTE) is a common post-surgical complication of gynecological malignant tumors that has serious implications on the prognosis and quality-of-life of patients. However, there exists only a few recognized specific evaluation models for the occurrence of VTE after gynecological malignant tumor surgery. We aimed to establish a nomogram model that could predict the probability of post-surgical VTE in patients with gynecological malignancies. We collected the clinical information of 673 patients who underwent surgery for gynecological malignant tumor in our hospital between January 2014 and May 2020. To reduce bias from confounding factors between groups, a 1:1 ratio propensity score matching (PSM) method was performed; meanwhile, univariate and multivariate analyses were applied to analyze the risk factors of VTE after surgeries. A nomogram prediction model was accordingly established and internally validated. The predictors contained in the nomogram model included age, D-dimer value, body mass index (BMI), and surgical approach. The C-index of the model was 0.721 (95% confidence interval: 0.644-0.797), with good discrimination and calibration effect. The internally verified C-index value was 0.916. Decision curve analysis confirmed that the nomogram model was clinically useful when the incidence of thrombosis in patients was 10-75%. Considering the risk factors of VTE after surgery for gynecological malignant tumor, a high-performance nomogram model was established and then validated to provide individual risk assessment and guide treatment decisions.


Mate tea prevents oxidative stress in the blood and hippocampus of rats with acute or chronic ethanol administration.
The aim of this study was to evaluate the influence of acute and chronic intake of mate tea on the effects elicited by acute and chronic administration of ethanol. Oxidative stress was evaluated by measuring thiobarbituric acid-reactive substances (TBARS), as well as the activities of the antioxidant enzymes, catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) in the hippocampus and blood of rats. Male Wistar rats were randomly assigned to four groups, for both acute and chronic treatment: (1) control group, (2) treated group, (3) intoxicated group, (4) and intoxicated group treated with mate tea. Both ethanol administrations significantly increased TBARS in plasma and hippocampus of rats and altered antioxidant enzyme activities, changes which were reverted by mate tea administration. Data indicate that acute and chronic ethanol administration induced oxidative stress in hippocampus and blood and that mate tea treatment was able to prevent this situation.


Transoral Robotic Retropharyngeal Lymph Node Dissection in Nasopharyngeal Carcinoma With Retropharyngeal Lymph Node Recurrence.
Nasopharyngeal carcinoma (NPC) patients with retropharyngeal lymph node (RPLN) recurrence typically undergo reirradiation and experience severe radiotoxicity. Salvage open surgery is challenging because gaining access to the retropharyngeal space is complex and risky. Thus, only several centers can perform this procedure, and complications are common. We applied transoral robotic surgery RPLN dissection (TORS-RPLND) to NPC patients with RPLN recurrence to address the problem with open surgery. From March 2017 to October 2020, 10 NPC patients with RPLN recurrence underwent TORS-RPLND using the da Vinci Si/Xi Surgical System. We applied the balloon occlusion test to protect the internal carotid artery, induction chemotherapy to shrink large tumors preoperatively, and ultrasound positioning to effectively locate unrecognizable RPLNs during surgery. Clinical characteristics, complications, and survival outcome data were retrospectively collected. Of 10 patients, 8 underwent en bloc resection via TORS-RPLND, and the remaining 2 patients were converted to open surgery because we failed to identify the RPLN during TORS. After introducing intraoperative ultrasound positioning, no such failure occurred. The mean operative time and intraoperative blood loss were 297 ± 120 min and 40 ± 43 ml, respectively. All surgical margins were negative. TORS-related complications were mild, and the most severe one was grade 3 dysphagia in one patient who underwent conversion to open surgery (10%). With a median follow-up of 19 months, only 1 (10%) patient developed cervical recurrence. TORS-RPLND is feasible, safe, and effective in the treatment of NPC patients with RPLN recurrence, especially with the help of intraoperative ultrasound positioning. 4 Laryngoscope, 131:E1895-E1902, 2021.


A comparison of hospital and community-acquired infective endocarditis.
The epidemiology, clinical features, microbiology and outcome of 30 episodes of nosocomial endocarditis occurring over a 13-year period were reviewed and compared with 148 cases of community-acquired endocarditis. Twenty-eight patients (93%) had been in hospital for > 1 week and 10 patients (33%) for > 1 month when they developed endocarditis. Left-sided infection was most frequent; only 3 cases involved the tricuspid valve. Compared with community-acquired infection, patients tended to be older, had a greater incidence of congestive cardiac failure (p = 0.001) or hypotension (p = 0.0008) at presentation and were more likely to have bacteremia after an invasive procedure (83 vs 31%; p < 0.00001). Intravascular devices were the presumed source of bacteremia in 11 cases (37%); the same organism was isolated from both the blood and the suspected source of infection. Staphylococcus aureus was the most frequent causative organism, accounting for 17 episodes (57%), including 4 (13%) due to methicillin-resistant strains. Nosocomial endocarditis had a significantly higher mortality than did community-acquired infection (40 vs 18%; p = 0.02). Eight patients (27%) needed valve replacement. Proper adherence to protocols for management of intravascular devices and appropriate antimicrobial prophylaxis before procedures may have prevented endocarditis in 15 of 30 patients.


Perioperative fluid management and associated complications in children receiving kidney transplants in the UK.
Intravenous fluid administration is an essential part of perioperative care for children receiving a kidney transplant. There is a paucity of evidence to guide optimal perioperative fluid management. This study aimed to identify the volume of perioperative fluids administered across 5 UK paediatric kidney transplant centres and explore associations between fluid volume administered, graft function, and fluid-related adverse events. Data were collected from five UK paediatric kidney transplant centres on perioperative fluid volumes administered, and incidence of pulmonary oedema, systemic hypertension, and requirement for intensive care support. Children < 18 years of age who received a kidney-only transplant between 1st January 2020 and 31st December 2021 were included. Complete data from 102 children were analysed. The median total volume of fluid administered in 72 h was 377 ml/kg (IQR 149 ml/kg) with a high degree of variability. A negative relationship between total fluid volume administered and day 7 eGFR was noted (p < 0.001). Association between urine volume post-transplant and day 7 eGFR was also negative (p < 0.001). Adverse events were frequent but no significant difference was found in the fluid volume administered to those who developed an adverse event, vs those who did not. This study describes a high degree of variability in perioperative fluid volumes administered to children receiving kidney transplants. Both fluid volume and urine output were negatively associated with short-term graft function. These data contrast traditional interpretation of high urine output as a marker of graft health, and highlight the need for prospective clinical trials to optimise perioperative fluid administration for this group. A higher resolution version of the Graphical abstract is available as Supplementary information.


Modulation of high mannose levels in N-linked glycosylation through cell culture process conditions to increase antibody-dependent cell-mediated cytotoxicity activity for an antibody biosimilar.
The regulatory approval of a biosimilar product is contingent on the favorable comparability of its safety and efficacy to that of the innovator product. As such, it is important to match the critical quality attributes of the biosimilar product to that of the innovator product. The N-glycosylation profile of a monoclonal antibody (mAb) can influence effector function activities such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity. In this study, we describe efforts to modulate the high-mannose (HM) levels of a biosimilar mAb produced in a Chinese hamster ovary cell fed-batch process. Because the HM level of the mAb was observed to impact ADCC activity, it was desirable to match it to the innovator mAb's levels. Several cell culture process related factors known to modulate the HM content of N-glycosylation were investigated, including osmolality, ammonium chloride (NH4 Cl) addition, glutamine concentration, monensin addition, and the addition of alternate sugars and amino sugars to the feed medium. The process conditions evaluated varied in impact on HM levels, process performance and product quality. One condition, the addition of alternate sugars and amino sugars to feed medium, was identified as the preferred method for increasing HM levels with minimal disruptions to process performance or other product quality attributes. Interestingly, a secondary interaction between sugar and amino sugar supplemented feeds and osmolality was observed during process scale-up. These studies demonstrate sugar and amino sugar concentrations and osmolality are critical variables to evaluate to match HM content in biosimilar and their innovator mAbs.


Selective trigeminal root section via an endoscopic transpyramidal retrolabyrinthine approach.
Present experience supports the view that endoscopic access to the cerebellopontine angle has proved an easy and safe therapeutic (selective trigeminal root section in cases of Vth nerve neuralgia) and diagnostic (inspection in cases of otherwise undetectable tumours) method, offering the advantages of little surgical risk and high effectiveness.


Spirulina platensis mediated biosynthesis of Cuo Nps and photocatalytic degradation of toxic azo dye Congo red and kinetic studies.
The current research is designed to synthesis Copper oxide nanoparticles (CuO NPs) using Cyanobacterium in greener way. The NPs were synthesized using Spirulina platensis. The method is adopted for the less toxic, less cost and environment friendly method. The synthesized CuO NPs are capped and stabilized by the natural substance of S. platensis including flavonoids, phenolic and acid groups of the microorganism which was confirmed by the GC-MS analysis. Majorly, beta-ionone, p-cumic aldehyde, phytol compounds are identified by GC-MS and it may also involve in the preparation of NPs. Further, the characterization has been carried out using UV-Vis spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction, Scanning electron microscope (SEM), transmission electron microscope (TEM). All the analytical techniques are confirmed the formation of NPs. The formed NPs are showed significant peaks in XRD analysis which further compared with literature. Functional group analysis showed -OH group compounds in extract and it might involve in the formation of NPs. The photo catalytic activity of CuO NPs was showed significant photo degradation of Congo red (CR) dye. The consideration of intense peak, the size of CuO NPs was calculated and found to be 15.2 nm with spherical shape as resulted in morphological identification. The results are showed good photocatalytic activity, since the peak appeared at 230 and 495 nm corresponding to the benzene and azo group of Congo Red were gradually decreased with increase of time. The reaction was found to have nature of pseudo first order reaction. The rate constant was calculated and was found to be - k = 0.3459, which indicates the Congo red degradation was 0.3459 per minute. This study will be a base for budding researchers for their isolation of S. platensis active compounds and with the help of secondary metabolites (active compounds) CuO NPs were synthesized which further acted has degradation agent against Congo red.


Linking early maternal input during shared reading to later theory of mind through receptive language and executive function: A within- and between-family design.
This study explored whether early maternal input during shared reading predicted later theory of mind (ToM) understanding through children's receptive language and executive function (EF). Maternal input plays a prominent role in the development of children's language skills, which are crucial for both EF and ToM development. There is also an abundance of behavioral evidence suggesting a directional link from EF to ToM. This relation raises the possibility of a cognitive cascade in which maternal input during shared reading promotes ToM development sequentially through receptive language and EF. The sample included 656 children clustered within 328 ethnically and sociodemographically diverse families. The shared reading sessions occurred when the younger and older siblings were 1.5 and 4 years old, respectively. Receptive language, EF, and ToM were measured when the siblings were approximately 5 years old to account for age differences. Multilevel modeling using Bayesian estimation was used to account for the effect of family-wide confounds (i.e., shared between the siblings in the family) while isolating child-specific processes (i.e., unique to each child within the family). The results supported two indirect paths from shared reading to children's ToM: one through receptive language alone and another that operated sequentially through receptive language and EF. These paths were observed only at the family level. These findings emphasize the importance of maternal input during early shared reading for cognitive development and suggest a cascade from maternal input to ToM via language and EF during the preschool period.


Temporal expression analysis of angiogenesis-related genes in brain development.
The current knowledge on molecular pathogenesis of cerebral vascular malformations (CVM), which are believed to arise during development, is very limited. To unravel the molecular mechanisms involved in CVMs, a detailed understanding of the brain vascular development at molecular level is crucial. In this study, we aimed to explore the temporal and comparative expression profile of angiogenesis-related genes in the establishment of brain vasculature. Expression of a total of 113 angiogenesis-related genes during murine brain development has been analyzed using low-density array systems designed for angiogenesis-related genes. Bai1 (brain specific angiogenesis inhibitor-1), a recently identified novel anti-angiogenic gene, has been selected for further characterization. We found that 62 out of 113 analyzed genes have expression in brain development at varying levels. Nineteen of these were differentially expressed between embryonic and postnatal stages (>1.5 fold). Bai1 is strongly expressed on growing blood vessels of cerebral cortex and hippocampus, partially expressed in the lateral regions of striatum, but mostly absent on the thalamus. By showing the comparative expression analysis of angiogenesis-related genes throughout brain development, the data presented here will be a crucial addition to further functional studies on cerebrovascular research.


A Supramolecular Complex of C60 -S with High-Density Active Sites as a Cathode for Lithium-Sulfur Batteries.
The well-known "shuttle effect" of the intermediate lithium polysulfides (LiPSs) and low sulfur utilization hinder the practical application of lithium-sulfur (Li-S) batteries. Herein, we describe a novel C60 -S supramolecular complex with high-density active sites for LiPS adsorption that was formed by a simple one-step process as a cathode material for Li-S batteries. Benefiting from the cocrystal structure, 100 % of the C60 molecules in the complex can offer active sites to adsorb LiPSs and catalyze their conversion. Furthermore, the lithiated C60 cores promote internal ion transport inside the composite cathode. At a low electrolyte/sulfur ratio of 5 μL mg-1 , the C60 -S cathode with a sulfur loading of 4 mg cm-2 exhibited a high capacity of 809 mAh g-1 (3.2 mAh cm-2 ). The development of the C60 -S supramolecular complex will inspire the invention of a new family of S/fullerenes as cathodes for high-performance Li-S batteries and extend the application of fullerenes.


Timing of hormone therapy, type of menopause, and coronary disease in women: data from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation.
The aim of this study was to assess the relationship of the timing of hormone therapy (HT) use with angiographic coronary artery disease (CAD) and cardiovascular disease (CVD) events in women with natural versus surgical menopause. We studied 654 postmenopausal women undergoing coronary angiography for the evaluation of suspected ischemia. Timing and type of menopause, HT use, and quantitative angiographic evaluations were obtained at baseline, and the women were followed for a median of 6 years for CVD events. Ever users of HT had a significantly lower prevalence of obstructive CAD compared with never users (age-adjusted odds ratio, 0.41 [0.28-0.60]). Women with natural menopause initiating HT before age 55 years had lower CAD severity compared with never users (age-adjusted β [SE] = -6.23 [1.50], P < 0.0001), whereas those initiating HT at age 55 years or more did not differ statistically from never users (-3.34 [2.13], P = 0.12). HT use remained a significant predictor of obstructive CAD when adjusted for a "healthy user" model (odds ratio, 0.44 [0.30-0.73]; P = 0.002). An association between HT and fewer CVD events was observed only in the natural menopause group (hazard ratio [95% CI], 0.60 [0.41-0.88]; P = 0.009) but became nonsignificant when adjusted for the presence or severity of obstructive CAD. Using the quantitative measurements of the timing and type of menopause and HT use, earlier initiation of HT was associated with less angiographic CAD in women with natural but not surgical menopause. Our data suggest that the effect of HT use on reduced cardiovascular event rates is mediated by the presence or absence of angiographic obstructive atherosclerosis.


Identification of atrial fibrillation drivers by means of concentric ring electrodes.
The prevalence of atrial fibrillation (AF) has tripled in the last 50 years due to population aging. High-frequency (DFdriver) activated atrial regions lead the activation of the rest of the atria, disrupting the propagation wavefront. Fourier based spectral analysis of body surface potential maps have been proposed for DFdriver identification, although these approaches present serious drawbacks due to their limited spectral resolution for short AF epochs and the blurring effect of the volume conductor. Laplacian signals (BC-ECG) from bipolar concentric ring electrodes (CRE) have been shown to outperform the spatial resolution achieved with conventional unipolar recordings. Our aimed was to determine the best DFdriver estimator in endocardial electrograms and to assess the BC-ECG capacity of CRE to quantify AF activity non-invasively. 31 AF episodes were simulated using realistic tridimensional models of the atria electrical activity and torso. Periodogram and autoregressive (AR) spectral estimators were computed and the percentile (P90th, P95th and P98th) to impose on the dominant frequencies (DFs) across whole atria to define the best DFdriver estimator evaluated. The identification of DFdriver on DFs from BC-ECG and unipolar surface signals with conventional disc electrodes was compared. The best DFdriver estimator was P95th and AR order 100. BC-ECG signals allowed better detection of AF activity than unipolar signals, with a significantly greater percentage of electrode locations in which DFdriver was identified (p-value 0.0095). The use of BC-ECG signals for body surface Laplacian potential mapping with CRE could be helpful for better AF diagnosis, prognosis and ablation procedures than those with conventional disk electrodes.


Relationships between adenosine, cyclic nucleotides, and xanthines in asthma.
Methylxanthines have been used for the treatment of asthma for more than 60 years, but their mechanism of action is poorly understood. Their ability to inhibit cyclic adenosine monophosphate phosphodiesterase has attracted much attention. However, this is clearly demonstrable only in high doses and is more likely to be related to toxicity. An alternative mechanism is antagonism of adenosine receptors in the lung. Adenosine has been shown to be released in asthma and cause bronchoconstriction in patients with asthma. Its effects are selectively inhibited by concentrations of theophylline that do not block histamine-induced bronchoconstriction. Neither phosphodiesterase inhibition nor adenosine receptor antagonism explains the action of enprofylline in asthma. Consequently, additional actions of methylxanthines are likely to contribute to their beneficial effects. They may include adrenaline release from the adrenal medulla, an effect on cell calcium distribution, inhibition of the generation of contractile prostaglandins, and an improvement of diaphragmatic contractility.


Primitive abscess of the great epiploon: clinical case and literature review.
The primitive abscess of the great epiploon often poses a pre-operative diagnosis problem. The clinical picture associates an abdominal pain and an inflammatory syndrome. The diagnosis is essentially based on the imaging data and the exploratory laparoscopy. The treatment consists in performing a drainage of the abscess and an epiploic resection "on demand" preserving healthy tissues, as well as giving antibiotics. The patient has been treated successfully by coelioscopy and a partial epiploic resection was performed with uncomplicated post-operative outcome. The primitive abscess of the great epiploon remains a rare pathology of uncertain etiology. The coelioscopy is the best method to rectify or to comfirm pre-operative diagnosis and to perform treatment avoiding the inconveniences of the laparotomy.


Factors associated with insomnia among frontline nurses during COVID-19: a cross-sectional survey study.
Research predominantly suggests that nurses are at high risk of developing psychopathology. The empirical data show that the occurrence rate of problem-related sleep quality among clinical nurses is high. Therefore, this study was conducted to address the lack of information on the relationship between the coronavirus disease 2019 (COVID-19) pandemic and insomnia. A convenience sample of nurses (n = 680) completed an online survey that included the Insomnia severity index, the COVID-19-related psychological distress scale, the general health questionnaire, neuroticism, dysfunctional beliefs, attitudes about sleep scale, and difficulties in emotion regulation scale. The results showed that 35.8% (n = 253) of nurses were classified as individuals with moderate to severe clinical insomnia. The results showed that the psychological distress generated by COVID-19 predicted insomnia (β = .47, SE = 0.02, P < .001, t = 13.27, 95% CI 0.31-0.46). Additionally, the association is mediated by psychopathology vulnerabilities, emotion dysregulation, dysfunctional beliefs about sleep, and neuroticism. Moreover, female nurses exhibited higher levels of insomnia (Cohen's d = .37), neuroticism (Cohen's d = 30), psychopathology vulnerability (Cohen's d = .26), and COVID-19-related psychological distress (Cohen's d = .23). The present study's findings help to explain how pandemic consequences can be associated with insomnia. Additionally, the findings make a significant contribution to better understanding the role of neuroticism, emotion dysregulation, beliefs, and psychopathology vulnerability in the development of insomnia among nurses. The findings suggest the potential influence of cognitive behavioral therapy for insomnia (CBT-I) and transdiagnostic integrated therapies that could be incorporated into therapeutic programs designed to develop as a way of inhibiting or preventing insomnia among clinical nurses.


Cross-linking, carboxymethylation and hydroxypropylation treatment to sorghum dietary fiber: Effect on physicochemical, micro structural and thermal properties.
The effect of cross-linking (CL), carboxymethylation (CM), and hydroxypropylation (HP) on the physicochemical, micro-structural, and thermal properties of sorghum dietary fiber (SODF) was studied. Results reflected that all three modifications significantly (p < 0.05) increased the water absorption capacity, swelling capacity, oil absorption capacity, and soluble dietary fiber content of SODF with CM being the most effective treatment. The CM significantly (p < 0.05) improved the solubility (9.9 %), whereas CL (4.65 %) and HP (2.79 %) significantly reduced the solubility of native SODF. The color analysis reflected the decrease in L* value after all modifications, indicating an increase in brown color of SODF. XRD analysis reflected an increase in crystallinity value (14.47 to 17.94 %) of SODF after modifications, resulting in increased thermal stability of modified SODF. The DSC results revealed the increased decomposition temperature of cross-linked and hydroxypropylated dietary fiber showing improved thermal stability of these types of modified fibers. The changes in thermal, physicochemical, and microstructural properties of SODF after modification could be ascribed to the changes in structure and chemical composition as reflected from SEM, XRD, and FTIR analysis.


Intraoral osseous choristoma: report of case.
A case of oral osseous choristoma of the buccal vestibule is presented. Of 27 reported cases, including this one, 24 occurred in the dorsum of the tongue, one in the ventral aspect of the tongue, and two in the buccal mucosa. There have been no recurrences reported after local excision.