Influence of dipyridamole on the fatty acid composition of the main lipid classes of chick serum.
We have studied the effects of dipyridamole treatment on the fatty acid composition of the main lipid classes of chick serum bearing in mind the relationship between platelet aggregation and eicosanoids production from arachidonic acid. In the free fatty acids, percentages of MUFA and n-6 PUFA fell. The effects of dipyridamole appeared to be less pronounced in triglyceride fraction, but more so in serum phospholipids and cholesterol esters. The percentage of arachidonic acid was significantly reduced by dipyridamole, as well as that of different n-3 PUFA present in phospholipid fraction. The percentage of linoleic acid in serum cholesterol esters was significantly lowered by dipyridamole, whereas that of arachidonic acid did not change significantly. Our results suggest that decreased arachidonic acid in the serum phospholipids and linoleic acid in all lipid classes may be of importance in order to dipyridamole participation in several pathologies characterized by an imbalance in the production of vasodilator and vasoconstrictor prostanoids.


Increased nitrate reductase A activity as a sign of membrane alteration in early blocked asporogenous mutants of Bacillus subtilis.
Nitrate reductase (Nar) activity, and its regulation, have been studied in B. subtilis and Spo0 mutants derived from it. The mutants are blocked at the stage zero of sporulation. The only Nar detected was the membrane-bound Nar A, which has been solubilized and purified. The enzyme itself, and its regulation, seem to be the same in Spo+ and Spo0 strains. Under all conditions tested, however, the mutants were hyperproducers of Nar A. Whether produced by a Spo+ or a Spo0 strain, the purified enzyme has the same Km on nitrate, and the same heat inactivation kinetics. In situ in membrane vesicles of a Spo+ strain, it displays the same Km and its thermoinactivation is exponential. In mutant vesicles, however, two Km's are observed, one normal and one five times higher, and thermoinactivation follows an initial period of activation. The higher Km disappears after heat activation. The Spo0 mutation studied seems to result in a modification of the membrane, such that insertion of Nar A in the modified membrane confers to the enzyme new allotopic properties. Additional and abnormal enzyme-binding sites may be created as a result of the mutation and these may be normalized during heat activation.


A Review of Electronic Devices to Assess Inhaler Technique.
Multiple electronic devices exist that provide feedback on the accuracy of patient inhaler technique. Our purpose is to describe the inhaler technique feedback provided by these devices, including specific technique steps measured, how feedback is displayed, target of feedback (patient, provider, researcher), and compatibility with inhaler type (metered-dose inhaler [MDI], diskus, etc.). We identified eight devices that provide feedback on inhaler technique. Only one device assessed all evidence-based MDI technique steps. Most devices provide limited real-time feedback to patients, if any feedback at all. Technologies to assess inhaler technique are advancing and hold great potential for improving patient inhaler technique. Many devices are limited in their ability to detect all evidence-based technique steps and provide real-time user-friendly feedback to patients and providers. Usability tests with patients and providers could identify ways to improve these devices to improve their utility in clinical settings.


Threshold effects of COVID-19-confirmed cases on change in pollutants changes: evidence from the Chinese top ten cities.
A more comprehensive understanding of the impact of the COVID-19 pandemic on changes in pollution could serve us to better deal with the environmental challenges caused by the pandemic. Existing studies mainly focused on the linear impact of the pandemic on the pollutants without considering the impact of other factors. To fill the research gap, the nonlinear relationship between pandemic and pollutants with considering the temperature factor was explored by developing panel threshold regression approach. In the proposed approach, the number of confirmed cases was set as explanatory variable, concentrations of NO2 and PM2.5 were set as explained variables, temperature was used as threshold variable, and other air pollution indicators were used as control variables. The results showed that there is a threshold effect between the changes in confirmed COVID-19 cases and the concentrations of PM2.5 and NO2, confirming the impact of the pandemic on pollutions was nonlinear. The results also show that the negative impact of pandemic on pollution increased when the temperature was rising. This work had theoretical and practical significance. The nonlinear research perspective of this article provided a methodological reference for exploring the relationship between epidemic and pollutant-related variables. Furthermore, this study expanded the scope of application of the threshold panel regression model and enriched the quantitative analysis of epidemics and pollutants.


Soft Tissue Sarcoma of Lower Extremity: Functional Outcome and Quality of Life.
Few studies have focused on patient-related factors in analyzing long-term functional outcome and health-related quality of life (HRQoL) in patients with postoperative lower extremity soft tissue sarcoma (STS). The purpose of this study was to investigate factors associated with postoperative functional outcome and HRQoL in patients with lower extremity STS. This cross-sectional study was performed in a tertiary referral center using the Toronto Extremity Salvage Score (TESS), Quality-of-Life Questionnaire (QLQ)-C30 and 15 Dimension (15D) measures. Functional outcome and HRQoL data were collected prospectively. All patients were treated by a multidisciplinary team according to a written treatment protocol. A total of 141 patients who had undergone limb-salvage surgery were included. Depending on the outcome measure used, 19-51% of patients were completely asymptomatic and 13-14% of patients had an unimpaired HRQoL. The mean score for TESS, 15D mobility score, and QLQ-C30 Physical Functioning scale were 86, 0.83, and 75, respectively, while the mean score for 15D was 0.88, and 73 for QLQ-C30 QoL. Lower functional outcome was statistically significantly associated with higher age, higher body mass index (BMI), and the need for reconstructive surgery and radiotherapy, while lower HRQoL was statistically significantly associated with higher age, higher BMI, and reconstructive surgery. Functional outcome and HRQoL were generally high in this cross-sectional study of patients with STS in the lower extremity. Both tumor- and treatment-related factors had an impact but patient-related factors such as age and BMI were the major determinants of both functional outcome and HRQoL.


New Faculty Orientation for Nurse Educators: Offerings and Needs.
The purpose of this study was to identify the common elements for new faculty orientation (NFO) programs and then replicate two previous studies regarding NFO offerings and needs. Using a descriptive survey research design, a 40-item survey was developed based on Morin and colleagues' surveys and disseminated via the Qualtrics platform. The survey addressed nurse faculty orientation offerings and needs. Some form of orientation was offered to 61% of the respondents. Only 14% identified a person responsible for orienting new faculty to their nursing program, 15% said no one person was accountable, and 69% reported they did not know who was responsible. The top three categories to be included in an orientation program were educational environment, academic environment, and social milieu. NFO programs attended by nursing faculty may not be as comprehensive or effective as they could be. [J Nurs Educ. 2021;60(5):273-276.].


Association between depression in chronic phase and future clinical outcome of patients with schizophrenia.
Depression in schizophrenia is an important symptom. We investigated whether depression and suicidal symptoms in the chronic phase are related to remote future clinical outcomes in patients with schizophrenia and whether psychotropics improved clinical outcomes. The subjects included 462 outpatients of working age (15 to 64 years old) with schizophrenia treated at Okayama University Hospital from January 2010 to December 2011. We investigated the relationship between the Clinical Global Impression-Severity score at the last visit (average 19.2 years) and the existence of previous depression, suicidal ideas, and suicide attempts. We adjusted by several possible confounders including medical history using multiple regression analysis or logistic regression analysis. Of 462 patients, 168 (36.4%) presented with depression 2 years after schizophrenia onset. A history of suicidal ideas and attempts was related to worse clinical outcome. In males, a history of depression was related to worse clinical outcome, but not in females. Lithium carbonate was related to better clinical outcome in all schizophrenia patients with depression, especially in males. Treatment with antidepressants was related to better clinical outcome only in males. A history of depression or suicidal symptoms in the chronic phase predicted the future worse clinical outcome in patients with schizophrenia. The administration of lithium carbonate or antidepressants might be recommended, especially to male schizophrenia patients with depression.


[Risk of contamination by pipetting bacterial culture broth with "Pasteur pipettes" (author's transl)].
Our experiments have shown that the cotton plug located at the top end of a "Pasteur pipette" allows aerosol to escape upon aspiration of a bacterial culture broth and may be the cause of contamination. In the following, we propose the use of a bacteriological filter system which insures greater safety.


Capillary basement membrane in retina, kidney, and muscle of diabetic dogs and galactosemic dogs and its response to 5 years aldose reductase inhibition.
Capillary basement membrane thickening has been compared in retina, renal glomerulus, and leg muscle of dogs alloxan-diabetic 5 years and dogs experimentally galactosemic 5 years, and the effects of inhibition of aldose reductase have been examined. Basement membrane in each site became thickened as a result of either galactosemia or diabetes, but showed appreciable variation among the sites. The thickening of basement membrane in retina and muscle of galactosemic animals was similar in quantity and appearance to that seen in the diabetics, notwithstanding large differences between the two animal models with respect to tissue polyol concentrations and nonenzymatic glycation of hemoglobin and plasma protein. Aldose reductase inhibition was without influence on capillary basement membrane thickening in each tissue from dogs diabetic or galactosemic 5 years, despite substantial polyol path inhibition.


Hepatitis B vaccine containing surface antigen and selected preS1 and preS2 sequences. 2. Immunogenicity in poor responders to hepatitis B vaccines.
The immunogenicity of a yeast-derived recombinant hepatitis B virus (HBV) vaccine containing surface antigen (S) and selected preS1 and preS2 sequences (S-L*) was compared with that of a vaccine containing S alone (Engerix-B) in 32 healthy adults with a previous history of poor response (anti-HBs < 10 mIU ml-1) after at least three consecutive monthly doses of hepatitis B vaccines. The poor responders were randomized to receive three additional 20-microgram doses of either S-L* or Engerix-B in a double-blind fashion according to a 0-, 1-, 2-month schedule. In vivo humoral and in vitro lymphoproliferative responses to the S and preS regions were monitored. Although the addition of the selected preS sequences to S did not enhance the in vivo humoral anti-HBs response, the administration of the three additional vaccine doses, irrespective of their preS content, induced seroprotective anti-HBs levels in most vaccinees (29/32, 91%). In vitro proliferative responses to HBV surface antigens were only observed in subjects displaying anti-HBs titers > 1000 mIU ml-1 after the third additional vaccine dose.


Conservation of Three-Dimensional Structure of Lepidoptera and Trichoptera L-Fibroins for 290 Million Years.
The divergence of sister orders Trichoptera (caddisflies) and Lepidoptera (moths and butterflies) from a silk-spinning ancestor occurred around 290 million years ago. Trichoptera larvae are mainly aquatic, and Lepidoptera larvae are almost entirely terrestrial-distinct habitats that required molecular adaptation of their silk for deployment in water and air, respectively. The major protein components of their silks are heavy chain and light chain fibroins. In an effort to identify molecular changes in L-fibroins that may have contributed to the divergent use of silk in water and air, we used the ColabFold implementation of AlphaFold2 to predict three-dimensional structures of L-fibroins from both orders. A comparison of the structures revealed that despite the ancient divergence, profoundly different habitats, and low sequence conservation, a novel 10-helix core structure was strongly conserved in L-fibroins from both orders. Previously known intra- and intermolecular disulfide linkages were accurately predicted. Structural variations outside of the core may represent molecular changes that contributed to the evolution of insect silks adapted to water or air. The distributions of electrostatic potential, for example, were not conserved and present distinct order-specific surfaces for potential interactions with or modulation by external factors. Additionally, the interactions of L-fibroins with the H-fibroin C-termini are different for these orders; lepidopteran L-fibroins have N-terminal insertions that are not present in trichopteran L-fibroins, which form an unstructured ribbon in isolation but become part of an intermolecular β-sheet when folded with their corresponding H-fibroin C-termini. The results are an example of protein structure prediction from deep sequence data of understudied proteins made possible by AlphaFold2.


FI-chemiluminometric study of thiazides by on-line photochemical reaction.
The present manuscript deals with a simple and sensitive flow-injection method for the chemiluminescent determination of thiazides. The method is based on the on-line photodegradation and chemiluminescent determination of the resulting photo-fragments. The on-line photodegradation is performed in basic medium by using a photoreactor consisting of a 550cm long x 0.8mm ID piece of PTFE tubing helically coiled around an 8W low-pressure mercury lamp. The determination of the photo-irradiated thiazides is performed by a chemiluminescent oxidative reaction with Ce(IV) in sulphuric acid medium. A heterogeneous group of thiazides (indapamide, metolazone, hydroflumethiazide, chlorthalidone and bendroflumethiazide) has been studied. Hydrochlorothiazide was selected as a test substance. The "on-line" photochemical reaction approach allows the sensitive chemiluminescent determination of thiazides which do not present native chemiluminescence in the absence of sensitizers such as Rhodamine 6G. Linear calibration graphs were typically over the range 0.5-12 microgml(-1) (indapamide, metolazone, hydroflumethiazide and chlorthalidone); and over the range 0.5-5 microgml(-1) (hydrochlorothiazide). Limits of detection ranged between 0.005 microgml(-1) (hydrochlorothiazide) and 0.06 microgml(-1) (bendroflumethiazide). The relative standard deviation for the test substance was 2.0% for 2 microgl(-1) of the drug (n = 11) and the throughput was 65 h(-1) in all cases. The assessment of the photodegradation step on the molecular structure of thiazides was established by recording UV and fluorimetric spectra. The viability of the on-line photoinduced fluorescent determination of hydroflumethiazide and bendroflumethiazide was confirmed. The method was also applied to the determination of hydrochlorothiazide in commercially available formulation.


Reduction in T LCO and survival in a clinical population.
How best to express the level of transfer factor of the lung for carbon monoxide (T LCO) has not been properly explored. We used the most recent clinical data from 13 829 patients (54% male; 10% non-European ancestry; median age 60.5 years, range 20-97 years; median survival 3.5 years, range 0-20 years) to determine how best to express T LCO function in terms of its relationship to survival. The proportion of subjects of non-European ancestry with Global Lung Function Initiative (GLI) T LCO z-scores above predicted was reduced, but was significantly increased between -1.5 and -3.5, suggesting the need for ethnicity-appropriate equations. Applying GLI forced vital capacity (FVC) ethnicity methodology to GLI T LCO z-scores removed this ethnic bias and was used for all subsequent analysis. T LCO z-scores using the GLI equations were compared with Miller's USA equations with median T LCO z-scores being -1.43 and -1.50 for GLI and Miller equations, respectively (interquartile range -2.8 to -0.3 and -2.4 to -0.7, respectively). GLI T LCO z-scores gave the best Cox regression model for predicting survival. A previously proposed six-tier grading system for level of lung function did not show much separation in survival risk in the less-severe grades. A new four-tier grading based on z-scores of -1.645, -3 and -5 showed better separation of risk with hazard ratio for all-cause mortality of 2.0, 3.4 and 6.6 with increasing severity. Applying GLI FVC ethnicity methodology to GLI T LCO predictions to remove ethnic bias together with a new four-tier z-score grading best relates T LCO function to survival.


Dominating Antiaromatic Character of as-Indacene Decides Overall Properties of a Formally Aromatic Dicyclopenta[c]fluorenothiophene.
Dicyclopenta[c]fluorenothiophene 5 was synthesized as the isoelectronic polycyclic heteroarene analogue of an as-indacenodifluorene with a (4n + 2)π-electron perimeter. Single-crystal and 1H NMR analyses indicated a quinoidal ground state for 5, which was supported by theoretical calculations while suggesting a degree of antiaromaticity of the as-indacene subunit greater than that for s-indacenodifluorene 3. The dominant antiaromaticity for 5 was evidenced by the broad weakly intense absorption tail reaching the near-IR region, four-stage redox amphotericity, and small HOMO-LUMO energy gap.


Timing of G-CSF administration based on the circadian rhythm in patients with ovarian cancer.
The aim of this study was to determine the relationship between the timing of granulocyte colony-stimulating factor (G-CSF) administration and its efficacy in patients with chemotherapy-induced granulocytopenia. Twenty patients in whom chemotherapy-induced leukopenia developed after the first course were enrolled in this prospective study. Subjects were randomly divided in two groups according to G-CSF injection time as follows: at 7:00 am and 7:00 pm. Before the G-CSF injection, the plasma G-CSF level for all patients was significantly lower at 7:00 am than that at 7:00 pm. After the injection, plasma G-CSF level did not differ between the two groups. The nadir of the leukocyte was 2,554 +/- 379/mm3 (granulocyte 1,530 +/- 689) for the group injected at 7:00 am, and 2,300 +/- 426/mm3 (granulocyte 1,203 +/- 848) for the group injected at 7:00 pm. The duration of leukocytes less than 2,000/mm3 and granulocytes less than 1,000/mm3 were 2.8 +/- 1.8 days and 3.2 +/- 1.8 days, respectively. Those differences were not significant. The present study showed the circadian rhythm of G-CSF levels in patients with ovarian cancer with chemotherapy-induced granulocytopenia, but there was no remarkable difference depending on administration time.


Growth hormone (GH)-releasing activity of chicken GH-releasing hormone (GHRH) in chickens.
Two peptides with sequence similarities to growth hormone releasing hormone (GHRH) have been identified by analysis of the chicken genome. One of these peptides, chicken (c) GHRH-LP (like peptide) was previously found to poorly bind to chicken pituitary membranes or to cloned and expressed chicken GHRH receptors and had little, if any, growth hormone (GH)-releasing activity in vivo or in vitro. In contrast, a second more recently discovered peptide, cGHRH, does bind to cloned and expressed cGHRH receptors and increases cAMP activity in transfected cells. The possibility that this peptide may have in vivo GH-releasing activity was therefore assessed. The intravenous (i.v.) administration of cGHRH to immature chickens, at doses of 3-100 μg/kg, significantly increased circulating GH concentrations within 10 min of injection and the plasma GH levels remained elevated for at least 30 min after the injection of maximally effective doses. The plasma GH responses to cGHRH were comparable with those induced by human (h) or porcine (p) GHRH preparations and to that induced by thyrotropin releasing hormone (TRH). In marked contrast, the i.v. injection of cGHRH-LP had no significant effect on circulating GH concentrations in immature chicks. GH release was also increased from slaughterhouse chicken pituitary glands perifused for 5 min with cGHRH at doses of 0.1 μg/ml or 1.0 μg/ml, comparable with GH responses to hGHRH1-44. In contrast, the perifusion of chicken pituitary glands with cGHRH-LP had no significant effect on GH release. In summary, these results demonstrate that cGHRH has GH-releasing activity in chickens and support the possibility that it is the endogenous ligand of the cGHRH receptor.


Recurrent pulmonary emboli with characteristic histopathology.
We report a unique case of recurrent thromboembolism and its histological findings that were revealed in an autopsy. Although it is well known that repeating thrombosis presents organization and recanalization, we also observed rare findings of thickening of the bronchial artery and fixation of the valve of the lower extremity vein in this case.


Inequality, perception biases and trust.
This paper studies the effect of income (wealth) inequality on interpersonal trust. We propose a theoretical framework that links trust, trustworthiness and inequality. The key feature is that agents do not necessarily observe the entire income distribution but base their assessment on reference groups (i.e. they might hold a biased view of reality). In this framework the negative impact of inequality on interpersonal trust is related to the individual-specific perception of inequality. This has important implications for the empirical analyses since researchers typically do not observe perceptions but only objective measures of inequality (e.g. the Gini coefficient). We show that the use of the latter is appropriate only under restrictive assumptions and in general will result in an underestimation of the true effect. An unbiased estimate of the effect of inequality on trust can be obtained with a measure of individual-specific perceptions of inequality. Survey data support our framework. Perceptions of higher inequality exert a strong negative effect on trust. The online version contains supplementary material available at (10.1007/s10888-021-09490-x).


Multi-Level and Intersectional Stigma Experienced by Black Transgender Women in Chicago: a Qualitative Study to Inform Sociostructural Interventions for Reducing Stigma and Improving Health Outcomes.
Stigma contributes to health disparities including increased HIV vulnerability among minority communities. Black transgender women experience multiple forms of stigma (e.g., anticipated, experienced), which can result in poor HIV-related outcomes. We utilized an adapted social ecological model (ASEM) to better understand the levels at which stigma is encountered and its impact on lived experience, particularly related to making healthcare decisions. Semi-structured interviews and two focus groups (n = 38) were conducted with Black transgender women and Black transfeminine individuals in Chicago from 2016 to 2017. Participants were asked about discrimination in the community, healthcare experiences, and their thoughts and decision-making process with their healthcare provider regarding HIV pre-exposure prophylaxis. We conducted thematic analysis and organized our findings based on the levels of the ASEM: individual, interpersonal, organizational, community, and structural. Participants experienced and anticipated stigma at each ASEM level. Stigma was not experienced in isolation: stigma experienced at one level caused anticipated stigma at other levels and internalized stigma leading to negative self-image. In each case, stigma adversely impacted health outcomes (e.g., medication nonadherence, disengagement from care). Stigma within healthcare settings, medication-related stigma, and stigma directed at appearance and identity are particularly detrimental to shared decision-making with a healthcare provider. Recognizing and valuing Black transgender women's experience with stigma are essential for developing social and structural interventions that may work collaboratively across multiple levels of lived experience to reduce stigma and healthcare disparities faced by Black transgender women.


Purification and characterization of dihydroorotase from Pseudomonas putida.
Dihydroorotase was purified to homogeneity from Pseudomonas putida. The relative molecular mass of the native enzyme was 82 kDa and the enzyme consisted of two identical subunits with a relative molecular mass of 41 kDa. The enzyme only hydrolyzed dihydro-L-orotate and its methyl ester, and the reactions were reversible. The apparent Km and Vmax values for dihydro-L-orotate hydrolysis (at pH 7.4) were 0.081 mM and 18 mumol min-1 mg-1, respectively; and those for N-carbamoyl-DL-aspartate (at pH 6.0) were 2.2 mM and 68 mumol min-1 mg-1, respectively. The enzyme was inhibited by metal ion chelators and activated by Zn2+. However, excessive Zn2+ was inhibitory. The enzyme was inhibited by sulfhydryl reagents, and competitively inhibited by N-carbamoylamino acids such as N-carbamoylglycine, with a Ki value of 2.7 mM. The enzyme was also inhibited non-competitively by pyrimidine-metabolism intermediates such as dihydrouracil and orotate, with a Ki value of 3.4 and 0.75 mM, respectively, suggesting that the enzyme activity is regulated by pyrimidine-metabolism intermediates and that dihydroorotase plays a role in the control of pyrimidine biosynthesis.


Impact of vitamin D supplementation during a resistance training intervention on body composition, muscle function, and glucose tolerance in overweight and obese adults.
The impact of vitamin D supplementation in overweight and obese adults during resistance training on body composition, muscle function, and glucose tolerance was investigated. Twenty-three overweight and obese (age: 26.1±4.7 y; BMI: 31.3±3.2 kg/m(2); 25-hydroxyvitamin D: 19.3±7.2 ng/mL) adults were recruited for participation in a double-blind, placebo-controlled trial. Participants were randomly divided into vitamin D (VitD, 4000 IU/d; 5 females, 5 males) and placebo (PL; 7 females, 6 males) groups. Both groups completed 12 weeks of resistance training. 25-hydroxyvitamin D, parathyroid hormone, body composition, and glucose tolerance were assessed at baseline and 12 weeks. Muscle function (strength and power) was assessed at baseline, 4, 8, and 12 weeks. During the intervention, 25-hydroxyvitamin D increased and parathyroid hormone decreased in the VitD group (P<0.05). Peak power was significantly increased at 4 weeks in the VitD group only (P<0.05). Regression analysis revealed an inverse association between the change in 25-hydroxyvitamin D with the change in waist-to-hip ratio (R(2)=0.205, P=0.02). No other improvements were observed with supplementation. Vitamin D supplementation in overweight and obese adults during resistance training induced an early improvement in peak power, and elevated vitamin D status was associated with reduced waist-to-hip ratio. NCT01199926.


Early angiogenesis detected by PET imaging with 64Cu-NODAGA-RGD is predictive of bone critical defect repair.
Therapies using stem cells may be applicable to all fields of regenerative medicine, including craniomaxillofacial surgery. Dental pulp stem cells (DPSCs) have demonstrated in vitro and in vivo osteogenic and proangiogenic properties. The aim of the study was to evaluate whether early angiogenesis investigated by nuclear imaging can predict bone formation within a mouse critical bone defect. Two symmetrical calvarial critical-sized defects were created. Defects were left empty or filled with i) DPSC-containing dense collagen scaffold, ii) 5% hypoxia-primed DPSC-containing dense collagen scaffold, iii) acellular dense collagen scaffold, or iv) left empty. Early angiogenesis assessed by PET using 64Cu-NODAGA-RGD as a tracer was found to be correlated with bone formation determined by micro-CT within the defects from day 30, and to be correlated to the late calcium apposition observed at day 90 using 18F-Na PET. These results suggest that nuclear imaging of angiogenesis, a technique applicable in clinical practice, is a promising approach for early prediction of bone grafting outcome, thus potentially allowing to anticipate alternative regenerative strategies. STATEMENT OF SIGNIFICANCE: Bone defects are a major concern in medicine. As life expectancy increases, the number of bone lesions grows, and occurring complications lead to a delay or even lack of consolidation. Therefore, to be able to predict healing or the absence of scarring at early times would be very interesting. This would not "waste time" for the patient. We report here that early nuclear imaging of angiogenesis, using 64Cu-NODAGA-RGD as a tracer, associated with nuclear imaging of mineralization, using 18F-Na as a tracer, is correlated to late bone healing objectivized by classical histology and microtomography. This nuclear imaging represents a promising approach for early prediction of bone grafting outcome in clinical practice, thus potentially allowing to anticipate alternative regenerative strategies.


Greater age-related changes in white matter morphometry following early life stress: Associations with internalizing problems in adolescence.
Early life stress (ELS) is associated with increased risk for internalizing disorders and variations in gray matter development. It is unclear, however, whether ELS affects normative age-related changes in white matter (WM) morphology, and if such maturational differences are associated with risk for internalizing psychopathology. We conducted comprehensive interviews in a cross-sectional sample of young adolescents (N = 156; 89 F; Ages 9-14) to assess lifetime exposure to stress and objective cumulative ELS severity. We used diffusion-weighted imaging to measure WM fixel-based morphometry and tested the effects of age and ELS on WM fiber density and cross-section (FDC), and associations between WM FDC and internalizing problems. Age was positively associated with FDC in all WM tracts; greater ELS severity was related to stronger age-WM associations in several association tracts connecting the frontal lobes with limbic, parietal, and occipital regions, including bilateral superior and inferior longitudinal and uncinate fasciculi (UF). Among older adolescents with greater ELS severity, a higher UF FDC was associated with fewer internalizing problems. Greater ELS severity predicted more mature WM morphometry in tracts implicated in emotion regulation and cognitive processing. More phenotypically mature UF WM may be adaptive against internalizing psychopathology in adolescents exposed to ELS.


Acute experimental glomerulonephritis induced by the glomerular deposition of circulating polymeric IgA-concanavalin A complexes.
The perfusion of polymeric or secretory IgA-Concanavalin A complexes into the aorta of rats led to a mannose-dependent binding of both IgA and lectin to the glomerular capillary wall, as shown by double immunolocalization experiments, by quantitative analysis of the amount of radiolabelled complexes bound per g of kidney, and by blocking experiments with the corresponding carbohydrate. Rats injected with amounts of those complexes as low as 500 micrograms developed, one hour later, a focal and segmental proliferative glomerulonephritis characterized by the deposition of injected complexes and of rat C3 and rat fibrin/fibrinogen in most glomeruli; focal thrombosis and small areas of necrosis in 10 to 15% of glomeruli, confined to the periphery of a single lobule of the tuft and segmental infiltration of these glomeruli by polymorphonuclear leucocytes and platelets. At the same time, many mesangial cells exhibited a hyperactive appearance, and red blood cells were noted in tubular lumens. In contrast, rats similarly injected with either monomeric IgA-ConA complexes, multimeric or secretory IgA-peanut agglutinin complexes or polymeric or monomeric IgA aggregates of comparable apparent molecular weight did not develop obvious glomerular lesions within one hour. The data indicate that performed polymeric IgA-ConA complexes can specifically bind to glomerular structures in vivo and trigger acute glomerular lesions locally, analogous to those observed in some glomerular diseases associated with a cryoglobulinaemia.


Overweight and obesity in native-American adolescents: comparing nonreservation youths with African-American and Caucasian peers.
Previous studies have consistently shown that, compared to national standards, Native Americans across all age groups are disproportionately overweight or obese. Although most available data on rates of obesity in this group come from studies conducted on reservations, the proportion of Native Americans residing on reservation lands is rapidly declining. This study examines the prevalence of overweight and obesity in a population of Midwestern adolescents in public school settings and contrasts Caucasian and African-American adolescents with Native-American youths of the same age. Data were derived from a secondary analysis of an anonymous health-risk survey. Height, weight, and ethnicity were ascertained through self-report. The results call into question whether rates of overweight or obesity in Native-American adolescents are disproportionate relative to those for Caucasian and African-American adolescents. Cumulative comparisons of all overweight and obese adolescents in the sample (n = 5,655) show significant differences among ethnic groups, but age-specific comparisons do not yield a consistent pattern, especially for Native-American girls. To compare the entire sample to national weight standards, we plotted mean body mass index (BMI) for each ethnic group by age against NHANES II reference data. Age-specific BMI means for Native-American and Caucasian girls fell largely below the NHANES II reference data. We present several explanations for these results. Given the study limitations, further objective study of the weight status of Native-American children and adolescents in direct comparison with other ethnic groups is recommended.


Natural photoredox catalysts promote light-driven lytic polysaccharide monooxygenase reactions and enzymatic turnover of biomass.
Lytic polysaccharide monooxygenases (LPMOs) catalyze oxidative cleavage of crystalline polysaccharides such as cellulose and chitin and are important for biomass conversion in the biosphere as well as in biorefineries. The target polysaccharides of LPMOs naturally occur in copolymeric structures such as plant cell walls and insect cuticles that are rich in phenolic compounds, which contribute rigidity and stiffness to these materials. Since these phenolics may be photoactive and since LPMO action depends on reducing equivalents, we hypothesized that LPMOs may enable light-driven biomass conversion. Here, we show that redox compounds naturally present in shed insect exoskeletons enable harvesting of light energy to drive LPMO reactions and thus biomass conversion. The primary underlying mechanism is that irradiation of exoskeletons with visible light leads to the generation of H2O2, which fuels LPMO peroxygenase reactions. Experiments with a cellulose model substrate show that the impact of light depends on both light and exoskeleton dosage and that light-driven LPMO activity is inhibited by a competing H2O2-consuming enzyme. Degradation experiments with the chitin-rich exoskeletons themselves show that solubilization of chitin by a chitin-active LPMO is promoted by light. The fact that LPMO reactions, and likely reactions catalyzed by other biomass-converting redox enzymes, are fueled by light-driven abiotic reactions in nature provides an enzyme-based explanation for the known impact of visible light on biomass conversion.


HIV-Specific T Cell Responses Are Highly Stable on Antiretroviral Therapy.
HIV infection induces a robust T cell response that is sustained by high viremia, but falls following the onset of antiretroviral therapy (ART). Relatively little has been reported on the subsequent stability of the HIV-specific T cell response in individuals on durable therapy. Such data are critical for powering clinical trials testing T cell-based immunotherapies. In a cross-sectional study, HIV-specific T cell responses were detectable by ex vivo interferon (IFN)-γ ELISpot (average ∼1,100 spot-forming units [SFUs]/106 peripheral blood mononuclear cells) in persons living with HIV (PLWH; n = 34), despite median durable ART suppression of 5.0 years. No substantial association was detected between the summed HIV-specific T cell response and the size of the replication-competent HIV reservoir. T cell responses were next measured in participants sampled weekly, monthly, or yearly. HIV-specific T cell responses were highly stable over the time periods examined; within-individual variation ranged from 16% coefficient of variation (CV) for weekly to 27% CV for yearly sampling. These data were used to generate power calculations for future immunotherapy studies. The stability of the HIV-specific T cell response in suppressed PLWH will enable powered studies of small sizes (e.g., n = 6-12), facilitating rapid and iterative testing for T cell-based immunotherapies against HIV.


Modeling the potential impact of pre-exposure prophylaxis for HIV among men who have sex with men in Cameroon.
Men who have sex with men (MSM) are consistently burdened by HIV at higher levels than other adults. While HIV prevention programs for MSM are growing in coverage and quality, HIV incidence remains high. In response, pre-exposure prophylaxis (PrEP) was introduced in 2019 to support HIV risk reduction among MSM in Cameroon. Understanding how PrEP initiation programs will change the HIV prevalence among MSM in Cameroon is important to developing effective programs. This study uses a mathematical model to simulate population-level HIV transmission among MSM in the cities of Yaoundé and Douala, Cameroon. PrEP is incorporated into the model at rates that equal 25%, 50%, or 75% coverage after twenty years to assess the potential effects on HIV prevalence among MSM, requiring annual initiation rates of 2.5%, 6.8%, and 17.2% for Yaoundé and 2.2%, 5.6%, and 13.4% for Douala, respectively. The data utilized for this model are from a cross sectional study which recruited MSM through respondent-driven sampling of MSM in two major cities in Cameroon: Yaoundé and Douala. The model estimated an HIV prevalence of 43.2% among MSM, annual HIV diagnoses of 300 per 10,000 MSM and antiretroviral therapy (ART) coverage of 53.9% in Yaoundé. In Douala, estimated prevalence is 26.5% among MSM, 167 per 10,000 MSM annual diagnoses and ART coverage of 72.0%. Standalone PrEP interventions aimed at 50% coverage at the end of a 20-year program would reduce the prevalence from 43.2% to 35.4% in Yaoundé and from 26.5 to 20.1% in Douala. Combining PrEP with a 10% increase in HIV testing would decrease the number of MSM living with HIV and unaware of their status from 9.8 to 6.0% in Yaoundé and from 8.7 to 4.6% in Douala. PrEP would be beneficial in reducing prevalence even at varying initiation and coverage levels. Combination of PrEP and increased HIV testing further decreased the number of undiagnosed MSM. This study supports the utility of implementing PrEP as part of comprehensive HIV prevention programming among MSM in Cameroon.


Primary pancreatic hydatid cyst: a case report and literature review.
Hydatid cysts are parasitic zoonoses that often occur in the liver. Pancreatic hydatid cysts are very rare and are usually misdiagnosed as pancreatic cystadenomas. At present, surgical resection combined with albendazole administration is the standard treatment for pancreatic hydatid cysts. However, making accurate preoperative diagnoses and avoiding intraoperative cystic rupture are challenges for surgeons. A 28-year-old woman from the pastoral area presented to the surgical office complaining of abdominal pain and new-onset jaundice that began 9 days earlier. An enhanced computed tomography scan demonstrated a 6.0 × 5.3 cm pancreatic head cystic mass that compressed the common bile duct and induced choledochectasia. The preoperative diagnosis was pancreatic head cystadenoma, and laparotomic pancreaticoduodenectomy was initiated successfully. The intra- and postoperative diagnosis was pancreatic hydatid cyst. The patient was discharged uneventfully 7 days after the operation. A 1-year course of albendazole (15 mg/kg/day) was admitted. Pancreatic hydatid cysts are rare and often misdiagnosed as other types of cysts. History of living in an area in which the causative organism is endemic and positive anti-echinococcus IgG antibody status could help with the diagnosis. Radical resection combined with oral albendazole administration is the standard treatment for pancreatic hydatid cysts. Avoiding perioperative cystic rupture and abdominal echinococcosis implantation metastasis is crucial for the success of the operation.


Report from the 2nd Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes and Cardiovascular Disease (D&CVD) EASD Study Group.
The 2nd Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes and Cardiovascular Disease (D&CVD) EASD Study Group was held on the 20th-21st October 2016 in Munich. This second Summit was organized in light of recently published CVOTs on diabetes, with the aim of serving as a reference meeting for discussion on this topic. Along with presentations on the results of the most recently published CVOTs, panel discussions on trial implications for reimbursement and the perspective of cardiologists and/or nephrologists, as well as on CVOTs weaknesses and potentials constituted the heart of the program. Future activities of the D&CVD EASD Study Group in 2017 include an annual meeting in Milano and the 3rd CVOT Summit on Diabetes of the D&CVD EASD Study Group, in Munich ( http://www.dcvd.org ).


Outcomes of free vascularized fibular graft for post-traumatic osteonecrosis of the femoral head.
Osteonecrosis of the femoral head (ONFH) can occur after traumatic injuries of the hip. Surgical treatment with total hip arthroplasty (THA) may not produce lifelong viability in younger patients. Free vascularized fibular graft (FVFG) has become a reliable method to delay or even avoid THA in this patient population by aiming to correct loss of viable bone through vascularized autologous bone transfer. The purpose of this study was to evaluate the longevity and outcomes of FVFG for traumatic hip injuries resulting in ONFH. We performed a retrospective review of our institutional database of patients who had undergone FVFG from 1980-2006 for post-traumatic ONFH and had a minimum follow-up of 5 years. Data collected included demographics, pre-operative Urbaniak ONFH staging, Harris Hip scores (HHS), SF-12 scores, and conversion to THA. Seventy-two hips in 68 patients met inclusion criteria. Mean follow-up was 11.6 years (range 5.1-33.2 years). Etiology included femoral neck fracture in 36 patients (61%), hip dislocation in 7 (12%), trauma without fracture or dislocation in 11 (19%), and femoral neck nonunion in 5 (8%). The most common stage at presentation was stage IV (48 patients). Graft survival at final follow-up (mean 10.9 years) was 64%, with mean time to conversion to THA of 8.4 years in those that did not survive (36%). There was no difference between THA conversion rates in hips with pre-collapse (Stage I and II) versus impending or post-collapse (Stage III or IV) lesions (p = 0.227). In hips with surviving grafts at final follow-up, mean HHS improved from 56.7 to 77.3 (SD 24.57, range 69-93), a mean improvement of 20.6 (p < 0.001). Our study reveals improvement in HHS in surviving FVFG and an acceptable overall THA conversion rate at mid to long term follow-up in Urbaniak stage I through IV hips. FVFG remains a viable option for treatment in younger patients with pre- and post-collapse (stage IV) ONFH lesions secondary to hip trauma.


Lack of association between XPG Asp1104His and XPF Arg415Gln polymorphism and breast cancer risk: a meta-analysis of case-control studies.
The xeroderma pigmentosum group G (XPG or ERCC5) and group F (XPF or ERCC4) play an important role in DNA repair, and produce dual incision 3' and 5' to the damaged nucleotide fragment. Several polymorphisms in the XPF and XPG gene have been described, including the commonly occurring Asp1104His in XPG and Arg415Gln in XPF. The published data on the association between these polymorphisms and breast cancer remained controversial. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A total of 17 studies were identified to the meta-analysis, including 5,235 cases and 5,685 controls for XPG Asp1104His (from ten studies) and 3,910 cases and 3,985 controls for XPF Arg415Gln (from seven studies). Overall, no significantly elevated breast cancer risk was found in all genetic models when all studies were pooled into the meta-analysis (for XPG Asp1104His Asp/His vs. Asp/Asp: OR 1.02, 95% CI 0.94-1.11; His/His vs. Asp/Asp: OR 0.96, 95% CI 0.83-1.11; dominant model: OR 1.01, 95% CI 0.94-1.09; and for XPF Arg415Gln Arg/Gln vs. Arg/Arg: OR 1.00, 95% CI 0.89-1.12; Gln/Gln vs. Arg/Arg: OR 2.40, 95% CI 0.62-9.22; dominant model: OR 1.03, 95% CI 0.90-1.18). In stratified analyses, we observed an overall OR of 5.20 (95% CI 2.08-12.95) for breast cancer developing risk in the Caucasian ethnicity, comparing Gln/Gln type to wild-type Arg/Arg for Arg415Gln polymorphism. In conclusion, this meta-analysis suggests that XPG Asp1104His polymorphism is not associated with increased breast cancer risk, and XPF Arg415Gln may be a low-penetrant risk factor in the Caucasian ethnicity for developing breast cancer.


Comparison of corneal and aqueous humor penetration of moxifloxacin, gatifloxacin and levofloxacin during keratoplasty.
Achieving high antibiotic concentrations is important for preventing and treating postoperative infections. However, no study has simultaneously compared the achieved concentrations of moxifloxacin, gatifloxacin, and levofloxacin in the human cornea and aqueous humor. The authors therefore performed a randomized study to determine the concentrations of 0.5% moxifloxacin, 0.3% gatifloxacin, and 0.5% levofloxacin in the corneal tissue and aqueous humor after topical instillation in patients undergoing penetrating keratoplasty. Patients who required penetrating keratoplasty were eligible for this study. The topical preparations of 0.5% moxifloxacin, 0.3% gatifloxacin, and 0.5% levofloxacin used in the study were preservative free (Japanese formulations). Patients were randomly assigned to one of three sequential drug groups, in which each drug was administered three times before surgery. In each administration cycle, the patients received two drops of each drug at 2-minute intervals. Samples of corneal tissue and aqueous humor were collected during surgery. The concentrations of each drug in the samples were determined by high-performance liquid chromatography. A total of 63 patients across eight centers in Japan were enrolled in the study. Overall, 61 corneal and 58 aqueous humor samples were evaluated. The concentration (mean±standard deviation) of moxifloxacin in corneal tissues was 12.66±8.93 μg/g, which was significantly higher than that of gatifloxacin (4.71±3.39 μg/g; P<0.0001) and levofloxacin (5.95±4.02 μg/g; P<0.0001). The mean concentration of moxifloxacin in aqueous humor samples was 1.40±1.17 μg/mL, which was significantly higher than that of gatifloxacin (0.65±0.80 μg/mL; P=0.0001) and levofloxacin (0.89±0.86 μg/mL; P<0.05). The sequence of drug administration did not significantly affect the results. These results show that 0.5% moxifloxacin achieved superior ocular concentration than both 0.3% gatifloxacin and 0.5% levofloxacin.


High success rates for the use of sofosbuvir/ombitasvir/paritaprevir/ritonavir + ribavirin and sofosbuvir/simeprevir/daclatasvir + ribavirin in retreatment of chronic hepatitis C infection after unsuccessful sofosbuvir/daclatasvir therapy: a real-life experience.
The aim of this work was assessment of the efficacy and tolerability of two different regimens for retreatment of hepatitis C virus (HCV) patients who failed to respond to SOF/DCV-based therapy. This prospective study included 104 HCV patients who failed to respond to SOF/DCV-based therapy. Patients were randomly allocated to two groups. Efficacy and tolerability were assessed. The 12-week sustained virological response (SVR12) rates were 96% and 94.4% in groups B and A, respectively, with no significant difference (p = 1.000). Most adverse events reported were mild to moderate, with no deaths during the study. Multi-target direct-acting antiviral (DAA) combinations are efficient for retreatment of HCV patients after failure of SOF/DCV-based therapy in real-world management.ClinicalTrials.gov identifier: NCT02992457.


Older Adults' Biobehavioral Fall Risks Were Affected by the COVID-19 Pandemic: Lessons Learned for Future Fall Prevention Research to Incorporate Multilevel Perspectives.
Examining the impact of coronavirus disease 2019 (COVID-19) pandemic on fall risks may provide insight into how multilevel factors as described in National Institute of Nursing Research's (NINR's) draft strategic plan can guide future fall prevention research. This article describes the affect of COVID-19 on fall risks from the perspective of older adults who live in assisted living facilities (ALFs), and explores the needs and approaches to implement fall prevention interventions at individual, social, community, and policy levels. Exploratory survey study. Participants from a fall prevention study at 2 ALFs in Oregon were invited to the study. Survey questions asked about COVID experience, and changes in fall risks and day-to-day activities in Spring 2020. Quantitative responses were analyzed using descriptive statistics and Cohen's d effect sizes. Qualitative responses were analyzed using conventional content analysis. Thirteen participants (age: M = 87.08, standard deviation = 6.52) responded. More participants reported feeling unsteady compared to pre-COVID data (38% vs. 62%), while the proportion of those worried about falling remained the same at 38%. Participants reported negligible decreases in importance of fall prevention and small decreases in confidence of fall prevention (Cohen's d = -0.13 and -0.21, respectively). The themes related to the affect of COVID on fall risks were: not to worry about fall risks but be cautious and physical activity is important, but it's hard during COVID. Impact of COVID on day-to-day activities were: varying degrees of concern for COVID, lack of social and community support, and finding unique ways to cope with COVID. These individual-level perspectives suggest that older adults were at increased risk for falling. Results exemplify the influence of broader-level factors (e.g., social, community, and policy) on individual biobehavioral factors (e.g., fall risks and health behaviors), and illustrate the value of examining multilevel factors in future fall prevention research.


Outcomes of Mitral Valve Repair Versus Replacement in the Elderly.
This study evaluated outcomes of mitral valve surgery (MVS) in the elderly. Patients 75 years or older undergoing MVS at a single center between 2010 and 2018 were included. Patients were stratified into mitral valve repair (MVr) or replacement (MVR). The primary outcome was mortality. Secondary outcomes included postoperative complications, readmissions, and freedom from at least moderate mitral regurgitation. Multivariable Cox regression was used for risk adjustment. A subanalysis of isolated, non-reoperative MVS for degenerative disease was also performed. Elderly patients (n = 472) underwent MVS, 301 (64%) with MVr and 171 (36%) with MVR. The majority of cases (68%) were performed for degenerative etiologic process. Survival was similar between MVr and MVR at 1 year (84% versus 86%; P = .40) and 5 years (64% versus 64%; P = .59). Postoperative complications were also comparable. Freedom from readmission was lower in the MVR cohort at 1 year (57% versus 68%; P = .02) and 5 years (33% versus 43%; P = .02). In isolated MVS for degenerative etiologic process, there was no difference in early or late mortality between MVr and MVR, although readmissions were lower with MVr. Overall, freedom from mitral valve reoperation was comparable, and the freedom from at least moderate regurgitation was 86% at 5 years in the MVr group. This study indicates that the outcomes of elderly patients undergoing MVS are acceptable with approximately 64% survival at 5 years. Our data suggest that MVr in the elderly may not confer a survival advantage but can be performed with durable results.


Investigation of random telegraph signal in two junction layouts of proton irradiated CMOS SPADs.
This paper focuses on the understanding of the Random Telegraph Signal (RTS) in Single-Photon Avalanche Diodes (SPAD). We studied the RTS of two different SPAD layouts, designed and implemented in a 150-nm CMOS process, after proton irradiation. The two structures are characterized by different junction types: the first structure is constituted by a P+/Nwell junction, while the second is formed by a Pwell/Niso junction. RTS occurrence has been measured in about one thousand SPAD pixels and the differences addressed in two layouts are motivated and discussed. Hypotheses on the RTS origin are drawn by analyzing the RTS time constants and the RTS occurrence evolution as a function of the annealing temperature.


Visible light-driven photocatalytic dye degradation under natural sunlight using Sn-doped CdS nanoparticles.
Herein, cadmium sulfide (CdS) nanoparticles (NPs) and different concentrations (1-5 and 10 wt %) of Sn-doped CdS NPs were prepared by a chemical precipitation method using PVP as a capping agent. The synthesized NPs were characterized using various characteristic techniques such as XRD, SEM, TEM, Raman spectroscopy, UV-Vis, and photoluminescence to investigate structural, morphological, and optical properties. Optical band gap of CdS has been tuned by substitution of Sn with different concentrations. Pure CdS and Sn-doped CdS NPs were used for the photocatalytic degradation of methylene blue (MB) dye under direct sunlight irradiation. The photocatalytic activity of the Sn-doped CdS NPs is attributed to the interface actions between Sn and CdS, which significantly decreases the recombination of a photogenerated electron-hole pair. The degradation efficiencies were found to be 91.39% and 97.56% within 180 min for pure CdS and Sn-doped CdS NPs, respectively. Among the catalysts, 4% Sn-doped CdS NPs exhibit best photocatalytic degradation efficiency after 180 min of irradiation.


Role of bacille Calmette-Guérin in preventing tuberculous infection.
Rural community in South India. To determine the role of bacille Calmette-Guérin (BCG) in preventing tuberculous infection in children. A prevalence survey was undertaken in 1999-2001 in a representative rural population in Tiruvallur District in South India using cluster sampling. Tuberculin testing was performed among all children aged <15 years, and all adults aged 15 years were questioned about chest symptoms and underwent radiography, followed by sputum examinations, if indicated. In children living in households with a tuberculosis case, the proportion with evidence of tuberculous infection was 35.5% of 200 in the absence of a BCG scar and 27.0% of 100 in its presence, a reduction of 24% (P = 0.14). In very young children (age <5 years), the corresponding proportions were 29.1% of 55 and 11.9% of 42, a reduction of 59%; the difference was statistically significant (P = 0.048). There is a possible role for BCG in preventing tuberculous infection in very young children.


Design and characterization of high-affinity synthetic peptides as bioreceptors for diagnosis of cutaneous leishmaniasis.
Cutaneous leishmaniasis (CL) is one of the illnesses caused by Leishmania parasite infection, which can be asymptomatic or severe according to the infecting Leishmania strain. CL is commonly diagnosed by directly detecting the parasites or their DNA in tissue samples. New diagnostic methodologies target specific proteins (biomarkers) secreted by the parasite during the infection process. However, specific bioreceptors for the in vivo or in vitro detection of these novel biomarkers are rather limited in terms of sensitivity and specificity. For this reason, we here introduce three novel peptides as bioreceptors for the highly sensitive and selective identification of acid phosphatase (sAP) and proteophosphoglycan (PPG), which have a crucial role in leishmaniasis infection. These high-affinity peptides have been designed from the conservative domains of the lectin family, holding the ability to interact with the biological target and produce the same effect than the original protein. The synthetic peptides have been characterized and the affinity and kinetic constants for their interaction with the targets (sAP and PPG) have been determined by a surface plasmon resonance biosensor. Values obtained for KD are in the nanomolar range, which is comparable to high-affinity antibodies, with the additional advantage of a high biochemical stability and simpler production. Pep2854 exhibited a high affinity for sAP (KD = 1.48 nM) while Pep2856 had a good affinity for PPG (KD 1.76 nM). This study evidences that these peptidomimetics represent a novel alternative tool to the use of high molecular weight proteins for biorecognition in the diagnostic test and biosensor devices for CL.


Serum cardiovascular-related metabolites disturbance exposed to different heavy metal exposure scenarios.
Health effects induced by heavy metal components of particulate matter need further research. A total of 32 healthy volunteers were recruited to walk for 4 h in two different exposure scenarios in Wuhan from May 1 to Jun 30, 2019. Metabolomics technology was used to identify serum cardiovascular-related metabolites disturbance, and the health risk assessment model was employed to assess the non-carcinogenic and carcinogenic risks associated with airborne heavy metals. The results showed that the average mass concentrations of Co, Ni, Cd, Cu, Ag and Ba in PM10 from May 1 to Jun 30, 2019 were 0.22, 0.49, 11.53, 2.23, 34.47 and 4.19 ng/m3, respectively, and were 0.86, 128.47, 291.85, 291.94, 98.55 and 422.62 ng/m3 in PM2.5, respectively. Healthy young adults briefly exposed to heavy metals were associated with serum cardiovascular-related metabolites disturbance, including increased SM(d18:1/17:0) and Sphingomyelin, and decreased GlcCer(d16:1/18:0) and Galabiosylceramide, simultaneously accompanied by activation of the sphingolipid metabolism pathway. Non-carcinogenic and carcinogenic risks of airborne heavy metals via the inhalation route were observed, Ni and Cd most influenced to potential health risks. Findings indicated exposure to increment of heavy metals may increase health risks by causing cardiovascular-related metabolites disturbance via activating the sphingolipid metabolism pathway.


Temporal relationship between insemination and sperm penetration in immature rats, with special reference to the effect of incubation of spermatozoa.
Superovulated immature rats (24 to 25 days old) were inseminated with epididymal sperm before or after ovulation and their eggs were examined at various times. When inseminated before ovulation, the interval between insemination and sperm penetration was 7 to 9 hours; the sperm penetration began approximately 2 hours after the first appearance of eggs in the oviducts and ceased 4 to 6 hours later. When inseminated after ovulation, the interval between insemination and sperm penetration was 5 to 6 hours; sperm penetration started 5 to 9 hours after ovulation and the proportion of penetrated eggs was not increased 4 hours later. The fertilizing capacity of sperm in the immature female tract lasted for 10 to 14 hours, which is shorter than in the mature animals, and sperm penetration occurred 2 to 10 hours after ovulation. The proportion of eggs fertilized, however, was not higher than 55%. A significant greater number of eggs was penetrated by more than one sperm but the number of polyspermic eggs was not increased when insemination was delayed. Epididymal sperm were incubated for various lengths of time and similarly inseminated into the uterine horns of immature rats. The fertilizing capacity of sperm could be maintained in culture for 10 hours but the proportion of fertilized eggs decreased sharply after incubation for 8 hours. Although rat epididymal sperm in a concentrated form could not be capacitated in vitro, they could be capacitated after incubation by intrauterine insemination.


Pubovaginal sling and pelvic prolapse repair in women with occult stress urinary incontinence: effect on postoperative emptying and voiding symptoms.
To determine the perioperative morbidity of performing a concurrent pubovaginal sling with prolapse repair in women with occult (or potential) stress incontinence, particularly on voiding dysfunction and emptying. We reviewed the charts of 38 women with grade 3-4 pelvic prolapse and occult stress incontinence. All patients underwent video urodynamic testing with the prolapse unreduced and again with the prolapse reduced with a pessary or packing. The abdominal leak point pressure was determined. Appropriate surgical repair of all components of the prolapse was performed concurrently with pubovaginal sling placement. The outcomes were measured with respect to the time to spontaneous voiding, permanent urinary retention, development of stress incontinence or de novo urge incontinence, resolution of urge incontinence, and perioperative complications. The mean age was 72 years, and the mean follow-up was 15 months (range 6 to 39). The mean time required before spontaneous voiding resumed without the need for catheterization was 11.8 days (range 2 to 46). No patient developed permanent urinary retention. Two (9.5%) of 21 women without preoperative urge incontinence developed de novo urge incontinence. However, existing urge incontinence resolved in 45%. One woman developed a suprapubic wound infection, which resolved with conservative management. Stress incontinence occurred in 2 women (7%) at 4 and 19 months postoperatively. Clinically significant prolapse (uterine) developed in 1 patient 2 years after surgery. Simultaneous pubovaginal sling placement for women with occult stress incontinence undergoing repair of a large pelvic prolapse is effective in preventing postoperative stress incontinence and has little negative effect on postoperative bladder emptying. It should be considered in all women with occult stress incontinence undergoing prolapse repair.


Signal transduction pathways for serotonin as an intestinal secretagogue.
This review presents a signal transduction pathways for serotonin (5-hydroxytryptamine, 5-HT) as an intestinal secretagogue and some recently published related findings. 5-HT is a secretagogue in the small and large intestine of all studied species including pig and man. 5-HT mediates intestinal secretion through activation of at least the epithelial 5-HT2, and neuronal 5-HT3, and 5-HT4 receptors in the submucosal plexus, including a reflex arc. 5-HT activates both a cholinergic and a non-cholinergic pathway in its secretory response. Intracellular mediators include at least eicosanoids (prostaglandin E2), calcium, phosphoinositols (1,4,5-inositol trisphosphate) and maybe nitric oxide and cyclic nucleotides. Pig small intestine appears to be an appropriate model for the human small intestine with respect to the signal transduction pathways for 5-HT as an intestinal secretagogue. Species and segmental differences in the signal transduction pathways for 5-HT as an intestinal secretagogues are discussed together with related news on 5-HT receptors, 5-HT antagonists in clinical use, the enteric nervous system, and intracellular mediators.


Identification of a haptoglobin-hemoglobin complex in human blood plasma.
Blood plasma metalloproteins that contain copper (Cu), iron (Fe), zinc (Zn) and/or other metals/metalloids are potential disease biomarkers because the bloodstream is in permanent contact with organs. Their quantification and/or the presence of additional metal-entities or the absence of certain metalloproteins in blood plasma (e.g. in Wilson's disease) may provide insight into the dyshomeostasis of the corresponding metal (s) to gain insight into disease processes. The first step in investigating if the determination of plasma metalloproteins is useful for the diagnosis of diseases is their definitive qualitative identification. To this end, we have added individual highly pure Cu, Fe or Zn-containing metalloproteins to plasma (healthy volunteer) and analyzed this mixture by size-exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic spectrometer (ICP-AES), simultaneously monitoring the emission lines of Cu, Fe and Zn. The results clearly identified ceruloplasmin (Cp), holo-transferrin (hTf), and α2-macroglobulin (α2M), which verifies our previous assignments. Interestingly, another major Fe-peak in plasma was identified as a haptoglobin (Hp)-hemoglobin (Hb) complex. This Hp-Hb complex is formed after Hb, which is released during the hemolysis of erythrocytes, binds to the plasma protein Hp. The Hp-Hb complex formation is known to be one of the strongest interactions in biochemistry (Kd≈1pmol/L) and is critical because it prevents kidney toxicity of free Hb. Hence, the simultaneous determination of Cp, hTf, α2M and the Hp-Hb complex in plasma in <25min has the potential to provide new insight into disease processes associated with the bioinorganic chemistry of Cu, Fe and Zn.


Further observations on the nature of prosopagnosia.
Two new cases of prosopagnosia are described and compared with pertinent clinical material from the English language literature. The interpretation of this disorder most compatible with the clinical data appears to us to be that there is an underspecification of visuoperceptive information preventing both the formation of significant face images and the retrieval of well-known face memoranda existing within a relatively intact visual remote memory store. Failure of formation of immediate memoranda of similarly complex visual images is also commonly observed but does not seem to be a requirement for the symptom of prosopagnosia. Conceptualizing this abnormality as simply a material specific visual agnosia of images beyond the classifier level would still appear to be acceptable if less informative.


Sediment methane production within eutrophic reservoirs: The importance of sedimenting organic matter.
While temperate reservoirs can be a significant source of atmospheric methane (CH4), knowledge of the role they play in global emissions of the gas remains limited in line with extreme temporal and spatial variability noted both within and between reservoirs. There is also still no clear identification of the environmental factors influencing the emission of this gas to the atmosphere. This article presents the results of research into the influence of sedimenting matter on CH4 emission from the surface of different zones of reservoirs. The research were conducted in 2018-2019 within Maziarnia and Nielisz Reservoirs - two artificial bodies of water of eutrophic status both located in SE Poland. Their diffusive CH4 fluxes at the water-air interface were measured using the "static chamber" method, while sediment traps monitored the rate of accumulation of sedimenting matter in bottom sediments (US). The CH4 fluxes noted at the reservoirs proved highly variable, both temporally and spatially, ranging from 0.02 to over 2500 mmol/m2·d. Determined accumulation indexes were in turn in the 13.61-618.49 g/m2·d range. Nevertheless, CH4 flux was found to correlate significantly with sedimentation index (US), with highest observed values for both reservoirs noted in river zone, while the lowest characterise the lacustrine zone. On this basis, it was hypothesised that sedimentation index may prove a useful tool in estimating CH4 emissions from reservoirs, with the reverse relationship also likely to apply. Furthermore, the key factor found to be responsible for the aforementioned temporal and spatial variations in CH4 emissions is primary production, whose subsequent sedimentation supplies sediments with easily-degradable organic matter. The results presented here contribute to an understanding of environmental factors that may influence spatial variation in CH4 production and can be useful to serve determinate of potential methods by which to reduce emissions this gas from managed systems such as reservoirs.


Low transferrin saturation is associated with impaired fasting glucose and insulin resistance in the South Korean adults: the 2010 Korean National Health and Nutrition Examination Survey.
The associations of transferrin saturation with diabetes have not been well evaluated and conflicting results have been reported. The purpose of this study is to examine the association of iron indices (serum ferritin and transferrin saturation) with risk of impaired fasting glucose and insulin resistance. We conducted a cross-sectional study in 2413 individuals (1150 men and 1263 women) aged 20-50 years who participated in the 2010 Korean National Health and Nutrition Examination Survey. Participants were free of diabetes, malignancy, liver cirrhosis, chronic renal failure, anaemia, pregnancy and menopause. Fasting plasma glucose, insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) were measured as the outcomes. Impaired fasting glucose was more prevalent in the highest compared with the lowest serum ferritin quartile among men (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.20-3.24) after adjustment for multiple covariates. Following the same adjustment, impaired fasting glucose was less prevalent in the highest compared with the lowest transferrin saturation quartile among men (OR, 0.45; 95% CI, 0.25-0.80) and women (OR, 0.33; 95% CI, 0.14-0.77). Moreover, a higher ferritin level was significantly associated with higher HOMA-IR after adjusting for confounders in men. Lower transferrin saturation was also significantly associated with higher insulin levels and HOMA-IR in both sexes. Lower transferrin saturations were associated with an increased risk of impaired fasting glucose and insulin resistance among general South Korean population.


A cellular and proteomic approach to assess proteins extracted from cryopreserved human amnion in the cultivation of corneal stromal keratocytes for stromal cell therapy.
Human corneal stromal keratocytes propagated in culture media supplemented with human amnion extract (AME) can correct early corneal haze in an animal model. Clinical application of cultivated keratocytes is limited by infectious disease screening before amnion products can be used in humans. It remains unclear if AME from cryopreserved versus fresh human amnion can support human keratocyte propagation, and which components of the extract promote keratocyte growth. Three placentas were collected for the preparation of fresh and cryopreserved amnion tissues followed by homogenization and protein extraction. AME protein profiles were studied using isobaric tagging for relative and absolute quantitation (iTRAQ) proteomics. Enriched gene ontology (GO) terms and functional classes were identified. Primary human keratocytes from 4 donor corneas were cultured in media supplemented with fresh AME (F-AME) or cryopreserved AME (C-AME). Cell viability, proliferation and keratocyte marker expression were examined by confocal immunofluorescence and flow cytometry. AME proteomics revealed 1385 proteins with similar expression levels (between 0.5- and 2-fold) between F- and C-AME, while 286 proteins were reduced (less than 0.5-fold) in C-AME. Enriched GO term and biological pathway analysis showed that those proteins with comparable expression between F-AME and C-AME were involved in cell metabolism, epithelial-mesenchymal transition, focal adhesion, cell-extracellular matrix interaction, cell stress regulation and complement cascades. Human corneal stromal keratocytes cultured with F-AME or C-AME showed similar morphology and viability, while cell proliferation was mildly suppressed with C-AME (P > 0.05). Expression of aldehyde dehydrogenase 3A1 (ALDH3A1) and CD34 was similar in both cultures. AME from cryopreserved amnion had limited influence on keratocyte culture. It is feasible to use protein extract from cryopreserved amnion to propagate human keratocytes for potential translational applications.


Novel therapeutics for Stargardt disease.
Stargardt disease, an inherited macular dystrophy caused by mutations in the ABCA4 gene encoding a retinal transporter protein, is the most prevalent form of macular degeneration in children. Patients with Stargardt disease develop severe vision loss within their first or second decades of life, which progresses to irreversible decreased visual acuity in almost all cases. Presently, there are no standard treatments for Stargardt disease. However, encouraging progress has been made in the development of innovative approaches to preventing vision loss in Stargardt patients. Among the promising treatment candidates include ALK-001, fenretinide, and A1120 as pharmacological agents to modulate the visual cycle, StarGenTM as a vector for supplementation of a functional ABCA4 gene, and stem-cell transplantation of hESC-RPE cells for regeneration of the retinal pigment epithelium. This study aims to systematically review and summarize evidence concerning the most up-to-date developments in pharmacologic, gene, and stem-cell therapies as novel therapeutic strategies to improve vision for patients with Stargardt disease.


DNA damaging agents and DNA repair: From carcinogenesis to cancer therapy.
Cancer genome instability arises from diverse defects in DNA-repair machinery, which make cancer cells more susceptible to DNA targeting agents. The interrelation between DNA repair deficiency and the increased effect of DNA targeting agents highlights the double-strand break (DSB) repair, which comprises the homologous recombination (HR) and non-homologous end joining (NHEJ) pathways. The DNA targeting agents are classified into two major groups: non-covalent DNA binding agents and covalent DNA-reactive agents. Although these agents have well-known limitations, such as resistance and secondary carcinogenesis risk, they are extremely important in today's real-life cancer therapy in combination with targeted therapy and immunotherapy. Indeed, DNA targeting drugs are promising therapeutics with a precise application through the background of cancer-specific DNA repair failure. In the current review, the mechanisms of action of diversified DNA-targeting agents, as well as the modulation of DNA repair pathways to increase the DNA-damaging drugs efficacy are presented. Finally, DNA-targeting-based therapies are discussed considering risks, resistance and its uses in the medicine precision era.


The effect of intravenous nutrition on muscle mass and exercise capacity in perioperative patients.
This study was undertaken to compare the efficacy of four different types of perioperative intravenous nutritional support. Fifty-five patients undergoing routine major surgery were studied. They were prospectively assigned to one of four study groups. Group 1 received formal total parenteral nutrition (90 g amino acids, 3,000 calories as glucose, per day); Group 2, 100 g glucose per day; Group 3, 90 g amino acids per day; and Group 4, peripheral parenteral nutrition (90 g amino acids plus 1,600 calories, 60 percent as fat per day). Group 1 was maintained on therapy for 3 weeks and the other groups for 8 days. Nitrogen balance, maintenance of body cell mass, serum albumin levels, and maintenance of exercise capacity were measured. Patients receiving peripheral parenteral nutrition maintained their nutritional parameters, as did those receiving total parenteral nutrition. These infusions were both markedly superior to those receiving glucose alone or those receiving amino acids alone. Nitrogen balance was not correlated with maintenance of function, but maintenance of body cell mass was correlated with maintenance of exercise capacity (r = 0.66, p less than or equal to 0.01). We conclude that perioperative peripheral parenteral nutrition, in contradistinction to hypocaloric infusions of glucose or amino acids, is capable of maintaining postoperative muscle mass and function close to preoperative levels after major surgery, and in situations of relatively mild surgical stress, approaches the efficacy of total parenteral nutrition in this regard. A significant correlation exists between changes in body cell mass determined from isotope dilution and changes in the exercise capacity of large muscle masses.


[Significance of deficient bacterial colonization in the pathogenesis of mucosal lesions in experimental blind loop syndrome].
A complete evaluation of the bacterial flora in jejunal self-filling blind loops was performed. The results show a significant increase in bacteria of the genera E. coli, Streptococcus and Bacteroides. In further experiments, jejunal self-filling blind loops were created in germ-free animals. In spite of the germ-free state the mucosa displayed marked hyperplasia. The same was true when the blind loops had been contaminated with aerobic bacteria. These results demonstrate that other factors in addition to bacterial overgrowth contribute to the mucosal damage observed in self-filling blind loops.


Causes of Death Among Patients With Metastatic Prostate Cancer in the US From 2000 to 2016.
Owing to improved survival among US patients with prostate cancer (PC), patients tend to live long enough after a PC diagnosis for non-cancer-related comorbidities to be associated with their overall survival. Although studies have investigated causes of death among patients with localized PC, data are lacking regarding causes of death among patients with metastatic PC. To assess causes of death among US patients with metastatic PC from 2000 to 2016. This retrospective cohort study used data from the Surveillance, Epidemiology, and End Results Program database to analyze a sample of 26 168 US men who received a diagnosis of metastatic PC from January 1, 2000, to December 31, 2016. Data were analyzed from February 2 to July 28, 2020. Diagnosis of metastatic PC. Standardized mortality ratios (SMRs) for different causes of death were calculated by dividing the observed number of deaths from each cause of death by the expected number of deaths in the age-matched US male population for the same period, adjusting for age and race/ethnicity. Of 26 168 patients with metastatic PC included in the analysis, 48.9% were aged 50 to 70 years (mean age at diagnosis, 70.83 years); 74.5% were White individuals, and 72.7% received a diagnosis of stage M1b metastatic PC. A total of 16 732 patients (63.9%) died during the follow-up period. The mean age at death was 74.13 years. Most deaths (59.0%) occurred within the latency period of 2 years after diagnosis of metastatic PC, whereas 31.6% occurred 2 to 5 years after diagnosis and 9.4% occurred more than 5 years after diagnosis. Of the total deaths, 13 011 (77.8%) were from PC, 924 (5.5%) were from other cancers, and 2797 (16.7%) were from noncancer causes. During all latency periods, the most common noncancer causes of death were cardiovascular diseases (SMR, 1.34; 95% CI, 1.26-1.42), chronic obstructive pulmonary disease (SMR, 1.19; 95% CI, 1.03-1.36), and cerebrovascular diseases (SMR, 1.31; 95% CI, 1.13-1.50). In this cohort study, deaths from noncancer causes, including cardiovascular disease, constituted a substantial number of deaths among men with metastatic PC. Therapy and follow-up should be tailored to the needs of each patient with metastatic PC, and counseling regarding future health risks should be provided.


A model of cytochrome P-450-centered hepatic dysfunction in drug metabolism induced by cobalt-protoporphyrin administration.
Cobalt-protoporphyrin treatment disrupts cytochrome P-450-centered drug metabolism and is known to decrease significantly the cytochrome P-450 content of the liver. This study assesses further the correlations between biochemical and functional changes induced by Co-protoporphyrin. Specifically, it confirmed the fall in cytochrome P-450 levels in liver and demonstrated that both NADPH-cytochrome P-450 reductase and NADH-cytochrome b5 reductase activities decreased in a dose-dependent manner, albeit to a lesser degree, upon Co-protoporphyrin administration. Furthermore, plasma clearance of the marker drug aminopyrine fell off abruptly with a minimal decrease in cytochrome P-450 content, and then monotonically with its further depletion. Both aminopyrine and caffeine demethylation, as measured by the amount of radiolabeled CO2 exhaled, also decreased with diminishing cytochrome P-450 content. With aminopyrine the decrease was abrupt but with caffeine biphasic, consistent with preferential isozyme depletion. The drop in oxidative drug metabolism measured by these two in vivo techniques occurred in the absence of organellar damage to hepatocytes, as observed by electron microscopy. In vitro studies of aminopyrine metabolism in microsomes prepared from rats with and without Co-protoporphyrin injection proved to be consistent with the in vivo studies. Moreover aminopyrine Vmax decreased and Km increased with decreasing cytochrome P-450 content, suggesting preferential isozyme depletion. Furthermore, the changes in aminopyrine intrinsic clearance predicted by the in vitro Vmax and Km values agreed with those measured by in vivo plasma clearance. Taken together, these data suggest that Co-protoporphyrin treatment can be used to produce a model of altered cytochrome P-450-centered drug metabolism, as measured consistently by several techniques. However, this model appears to be more complex than one involving nonspecific depletion of cytochrome P-450 alone, and may be influenced also by concomitant changes in the electron transport chain or other aspects of hepatic metabolism.


Recurrent stroke in a case of left atrial myxoma masquerading vasculitis.
We report a case of left atrial myxoma presenting as recurrent neurological deficits with absent peripheral pulses mimicking systemic vasculitis. Due to absence of cardiac signs and symptoms, there was one year delay in diagnosis from initial symptom. Left atrial myxomas are rare but treatable cause of recurrent stroke.


MDMX Regulates Transcriptional Activity of p53 and FOXO Proteins to Stimulate Proliferation of Melanoma Cells.
The tumor suppressor protein p53 has an important role in cell-fate determination. In cancer cells, the activity of p53 is frequently repressed by high levels of MDMX and/or MDM2. MDM2 is a ubiquitin ligase whose activity results in ubiquitin- and proteasome-dependent p53 degradation, while MDMX inhibits p53-activated transcription by shielding the p53 transactivation domain. Interestingly, the oncogenic functions of MDMX appear to be more wide-spread than inhibition of p53. The present study aimed to elucidate the MDMX-controlled transcriptome. Therefore, we depleted MDMX with four distinct shRNAs from a high MDMX expressing uveal melanoma cell line and determined the effect on the transcriptome by RNAseq. Biological function analyses indicate the inhibition of the cell cycle regulatory genes and stimulation of cell death activating genes upon MDMX depletion. Although the inhibition of p53 activity clearly contributes to the transcription regulation controlled by MDMX, it appeared that the transcriptional regulation of multiple genes did not only rely on p53 expression. Analysis of gene regulatory networks indicated a role for Forkhead box (FOX) transcription factors. Depletion of FOXO proteins partly prevented the transcriptional changes upon MDMX depletion. Furthermore, depletion of FOXO proteins relatively diminished the growth inhibition upon MDMX knockdown, although the knockdown of the FOXO transcription factors also reduces cell growth. In conclusion, the p53-independent oncogenic functions of MDMX could be partially explained by its regulation of FOXO activity.


HBV/A and HBV/C genotype predominance among patients with chronic hepatitis B virus infection in Cebu City, Philippines.
Chronic Hepatitis B virus (HBV) infection causes significant morbidity and mortality with widespread global distribution. Different genotypes display variations in pathogenesis, disease behavior, and treatment response. HBV/B and HBV/C are prevalent in Asia, but minimal data come from the Philippines. This study is aimed to determine the HBV genotypes of Filipino patients with Chronic HBV infection seen in Cebu City, Philippines and describe the age, sex, viral activity, alanine aminotransferase (ALT) levels and viral load patterns by genotype. Case series with prospective mode of data collection. Gastroenterology specialty clinics, Cebu City, Philippines. Patients with Chronic HBV infection seen in 2008. MANEUVERS: Chronic HBV infection was defined as HBsAg(+) for >6 months with persistent/intermittent ALT/aspartate aminotransferase levels (AST) elevations. Hepatitis panel and biochemical tests determined disease activity. Ultrasound documented liver cirrhosis with corresponding hypoalbuminemia and prolonged Prothrombin time. Hepatitis C virus (HCV) co-infection was a reactive anti-HCV test. Hepatocellular carcinoma was diagnosed by ultrasound or computed tomography (CT) scan with alpha-feto protein (AFP) > 500 ng/L. COBAS Taqman HBV Test(®) determined HBV-DNA level. Polymerase chain reaction (PCR) genotyping was done using type-specific primers. This study analyzed data from 50 patients, where 74% were males, and median age was 31 years (IR 25-40 years.). Chronic active hepatitis was seen in 76.6%. Only 18% had ALT levels >2 × ULN. Viral loads >20,000 IU/L were reported in 71% of HBeAg(+) patients. Viral loads >2,000 IU/L were seen in 73% of HBeAg(-) patients. Predominant genotypes identified were HBV/A (28%) and HBV/C (26%). No significant correlation between genotype and age (p = 0.92) and ALT levels (p = 0.58) was determined. Consistently high-DNA titers were reported for 83% of HBV/C patients and for all patients with >1 HBV genotypes. Hepatocelullar carcinoma was noted for one patient with HBV/A. Two patients with liver cirrhosis had HBV/C. Possible significant associations between genotype and some patient-related parameters could not be determined due to scarcity of subjects. HBV/A and HBV/C genotypes are equally predominant among Filipino patients with Chronic HBV infection seen in two specialty clinics in Cebu City, Philippines.


Full-length transcriptome analysis provides new insights into the early bolting occurrence in medicinal Angelica sinensis.
Angelica sinensis (Oliv.) Diels root part is an integral component of traditional Chinese medicine, widely prescribed to improve blood circulation and blood stasis. However, early bolting of A. sinensis compromises the quality of the roots and hence is a major limitation for yield of medicinal materials. To date, little information about the molecular mechanisms underlying bolting is available for this important medicinal plant. To identify genes putatively involved in early bolting, we have conducted the transcriptome analysis of the shoot tips of the early-bolting plants and non-bolting (normal) plants of A. sinensis, respectively, using a combination of third-generation sequencing and next-generation sequencing. A total of 43,438 non-redundant transcripts were collected and 475 unique differentially expressed genes (DEGs) were identified. Gene annotation and functional analyses revealed that DEGs were highly involved in plant hormone signaling and biosynthesis pathways, three main flowering pathways, pollen formation, and very-long-chain fatty acids biosynthesis pathways. The levels of endogenous hormones were also changed significantly in the early bolting stage of A. sinensis. This study provided new insights into the transcriptomic control of early bolting in A. sinensis, which could be further applied to enhance the yield of medicinally important raw materials.


Above the Clavicle: A Simplified Screening Method for Asymptomatic Blunt Cerebral Vascular Injury.
Blunt cerebrovascular injury (BCVI) is an increasingly detected pattern in trauma with significant morbidity, putting patients at risk for subsequent stoke. Complex screening protocols exist to determine who should undergo CT angiography of the neck (CTAN) to evaluate for BCVI. Once identified, stroke incidence may be reduced with appropriate treatment across grades. We hypothesize that an expanded and simplified method for identifying patients with clinical suspicion for BCVI based upon injury above the clavicle (ATC) will illustrate a previously undiagnosed cohort of patients. A single-institution retrospective review of adult (age ≥18 years) blunt trauma patients with BCVI from January 1, 2010 to December 31, 2019 was conducted at a tertiary academic medical center. Patients undergoing CTAN were divided into 2 groups based upon qualification by either the expanded Denver criteria or clinical evidence of any injury ATC. A total of 219 patients were diagnosed with BCVI (25 566 blunt trauma admissions, .9% incidence). Seventeen patients (8%) who did not satisfy expanded Denver were diagnosed with BCVI by ATC, most commonly undergoing CTAN due to facial trauma (n = 8). There were no differences in distribution of carotid artery injuries (CAI) and vertebral artery injuries (VAI) in the expanded Denver criteria group compared to the ATC group. CTAN for blunt trauma with any injury ATC is an easy-to-use screening tool and may be seamlessly included with initial whole-body imaging.


Phospholipid binding and biophysical activity of pulmonary surfactant-associated protein (SAP)-35 and its non-collagenous COOH-terminal domains.
Surfactant-associated protein of Mr = 35,000, SAP-35, is the major glycoprotein present in mammalian pulmonary surfactants. In this study, canine SAP-35 and several of its COOH-terminal peptides were purified and characterized by amino acid composition and NH2-terminal sequencing analysis. These proteins were then studied in terms of their specific lipid-binding characteristics and surface activity when combined with a synthetic phospholipid mixture, SM, chosen as an approximation of lung surfactant phospholipids. Purified, delipidated SAP-35 bound SM strongly. In contrast, SAP-21 (a non-collagenous fragment generated by collagenase digestion) bound phospholipid weakly; SAP-18 (an acidic COOH-terminal fragment comprising residues Gly-118 to Phe-231) did not bind phospholipid, demonstrating the importance of hydrophobic amino acid residues Gly-81 to Val-117 and the NH2-terminal collagenous domain in interaction of the SAP-35 with phospholipids. In surface activity experiments, purified SAP-35 enhanced the adsorption of SM phospholipids in terms of both rate and overall surface tension lowering. However, the adsorption facility of the SM-SAP-35 mixture did not approach that of either whole surfactant or the surfactant extract preparations, calf lung surfactant extract or surfactant-TA, used in exogenous surfactant replacement therapy for the neonatal respiratory distress syndrome. In addition, the dynamic surface activity of the SM-SAP-35 mixture was well below that of natural surfactant or surfactant extracts. This was also true of mixtures of SM phospholipids combined with the SAP-18 and SAP-21 fragments of SAP-35.


Influence of GSTM1 and GSTT1 genotypes and confounding factors on the frequency of sister chromatid exchange and micronucleus among road construction workers.
In the present study, we have investigated the influence of polymorphism of GSTM1 and GSTT1 genes and confounding factors such as age, sex, exposure duration and consumption habits on cytogenetic biomarkers. Frequency of sister chromatid exchanges (SCEs), high frequency cell (HFC) and cytokinesis blocked micronuclei (CBMN) were evaluated in peripheral blood lymphocytes of 115 occupationally exposed road construction workers and 105 unexposed individuals. The distribution of null and positive genotypes of glutathione-S transferase gene was evaluated by multiplex PCR among control and exposed subjects. An increased frequency of CBMN (7.03±2.08); SCE (6.95±1.76) and HFC (6.28±1.69) were found in exposed subjects when compared to referent (CBMN - 3.35±1.10; SCE - 4.13±1.30 and HFC - 3.98±1.56). These results were found statistically significant at p<0.05. When the effect of confounding factors on the frequency of studied biomarkers was evaluated, a strong positive interaction was found. The individuals having GSTM1 and GSTT1 null genotypes had higher frequency of CBMN, SCE and HFC. The association between GSTM1 and GSTT1 genotypes and studied biomarkers was found statistically significant at p<0.05. Our findings suggest that individuals having null type of GST are more susceptible to cytogenetic damage by occupational exposure regardless of confounding factors. There is a significant effect of polymorphism of these genes on cytogenetic biomarkers which are considered as early effects of genotoxic carcinogens.


Differential impacts of salinity on antibiotic resistance genes during cattle manure stockpiling are linked to mobility potentials revealed by metagenomic sequencing.
Livestock manure is an important source of antibiotic resistance genes (ARGs), and its salinity level can change during stockpiling. To understand how the salinity changes affect the fate of ARGs, cattle manure was adjusted of salinity and stockpiled in laboratory microcosms at low (0.3% salt), moderate (3.0%) and high salinity levels (10.0%) for 44 days. Amongst the five ARGs (tetO, blaTEM, sul1, tetM, and ermB) and the first-class integrase (intI1) monitored by qPCR, the relative abundance of tetO and blaTEM exhibited no clear trend in response to salinity levels, while that of sul1, tetM, ermB and intI1 showed clear downward trends over time at the lower salinity levels (0.3% and 3%) but not at the high salinity level (10%). Metagenomic contig construction of cattle manure samples revealed that sul1, tetM and ermB genes were more likely to associate with mobile genetic elements (MGEs) than tetO and blaTEM, suggesting that their slower decay at higher salinity levels was either caused by horizontal gene transfer or co-selection of ARGs and osmotic stress resistant determinants. Further analysis of metagenomic contigs showed that osmotic stress resistance can also be located on MGEs or in conjunction with ARGs.


An extremely rare case of large Delphian node metastasis preceding primary laryngeal cancer.
To present an extremely rare case of large Delphian node metastasis preceding primary laryngeal cancer. A 74-year-old male who noted a mass on the lower anterior neck and consulted our department immediately. The mass rapidly grew to 6cm from 2cm in diameter within 2 months after the initial presentation. Fiberoptic laryngoscopy was unremarkable. Surgical excision of the lesion showed well differentiated squamous cell carcinoma with invasion into the surrounding tissues. Postoperative radiotherapy was added. During follow-up after those treatments, thickening of the right vocal cord was observed, which gradually became more apparent. Total laryngectomy was performed 13 months after the initial operation. Delphian node metastasis is included in the differential diagnosis in a case of rapidly increasing mass in the anterior neck.


Initial and long-term effects of cloxazolam with intractable epilepsy.
Cloxazolam has been used mainly as an anxiolytic agent. The present study was designed to evaluate the effectiveness of cloxazolam as an add-on antiepileptic drug in patients with intractable epilepsy. A total of 32 patients with intractable epilepsy were treated with cloxazolam: 13 with generalized epilepsy, 15 with focal epilepsy, and 4 with undetermined type of epilepsy. The initial effects were evaluated at 1 month after reaching a maintenance dose (0.3-0.5 mg/kg). The long-term effects were investigated at 2 years after reaching a maintenance dose. With cloxazolam, seizure frequency was reduced by ≥ 50% in 19/32 patients (59%) during initial therapy and in 6/23 patients (26%) during long-term therapy. Two became seizure free throughout the cloxazolam therapy. During initial therapy, 8/32 patients (25%) developed 11 episodes of adverse events during the initial therapy, including 5 with drowsiness, 3 with hyperactivity, 2 with irritability, and 1 with loss of appetite. During long-term therapy, 2/23 (9%) developed drowsiness. The mean dose of cloxazolam in patients with an effective response was 0.30 ± 0.18 mg/kg for initial therapy and 0.26 ± 0.20 mg/kg for long-term therapy. Seven of the 19 effective responders developed tolerance (37%). Cloxazolam is an effective and safe antiepileptic drug for intractable epilepsy.


Manzamine alkaloids: isolation, cytotoxicity, antimalarial activity and SAR studies.
The infectious disease Malaria is caused by different species of the genus Plasmodium. Resistance to quinoline antimalarial drugs and decreased susceptibility to artemisinin-based combination therapy have increased the need for novel antimalarial agents. Historically, natural products have been used for the treatment of infectious diseases. Identification of natural products and their semi-synthetic derivatives with potent antimalarial activity is an important method for developing novel antimalarial agents. Manzamine alkaloids are a unique group of β-carboline alkaloids isolated from various species of marine sponge displaying potent antimalarial activity against drug-sensitive and -resistant strains of Plasmodium. In this review, we demonstrate antimalarial potency, cytotoxicity and antimalarial SAR of manzamine alkaloids.