High veno-arterial carbon dioxide gradient is not predictive of worst outcome after an elective cardiac surgery: a retrospective cohort study.
Alteration of tissue perfusion is a main contributor of organ dysfunction. In cardiac surgery, the importance of organ dysfunction is associated with worse outcome. Central venous-arterial difference in CO2 tension (ΔCO2) has been proposed as a global marker of the adequacy of tissue perfusion in shock states. We hypothesized that ΔCO2 could be increased in case of postoperative organ failure or worse outcome. In this monocentric retrospective cohort study, we retrieved, from our database, 220 consecutive patients admitted in intensive care after an elective cardiac surgery. Four time points were formed: ICU admission, and 6, 24 and 48 h after. A ΔCO2 below 6 mmHg defined the normal range values. The SOFA score, intensive care unit and hospital length of stay, hospital and 6-month mortality rate were recorded. We compared patient with low ΔCO2 (<6 mmHg) and high ΔCO2 (≥6 mmHg). We included 55 (25 %) and 165 patients in low and high ΔCO2 groups, respectively. The SOFA score, the hospital and 6 months mortality rate were higher in patients with low ΔCO2. Surprisingly, we did not find results previously published in other surgical settings. In cardiac surgery, ΔCO2 has a low predictive value of outcome.


Exploring the role of gut microbiota in obesity and PCOS: Current updates and future prospects.
Polycystic ovary syndrome (PCOS) is a common endocrine gynecological disorder, and the specific pathogenesis of PCOS has not been elucidated. Obesity is a current major public health problem, which is also vital to PCOS. It can exacerbate PCOS symptoms via insulin resistance and hyperandrogenemia. The treatment of PCOS patients depends on the prevailing symptoms. Lifestyle interventions and weight loss remain first-line treatments for women with PCOS. The gut microbiota, which is a current research hot spot, has a substantial influence on PCOS and is closely related to obesity. The present study aimed to elucidate the function of the gut microbiota in obesity and PCOS to provide new ideas for the treatment of PCOS.


Lyme disease: laboratory issues.
This article describes the laboratory modalities available to confirm the diagnosis of Lyme borreliosis. Use and limitations of these methods are discussed. Current guidelines for the use of recommended serologic methods and discussion of newer methods also are provided.


Intestinal regulation of body iron.
A significant proportion of the world's population suffers from iron deficiency or iron overload. These disorders arise primarily from defects in the gastrointestinal absorption of iron. The intestinal mucosal cell plays a key role in this process because it lies at the interface between the gastrointestinal lumen which supplies its iron and body compartments which control its behaviour. The concentration of mucosal ferritin is closely linked to absorption, but it is still not clear whether it plays an active or a passive role. Transferrin also has been detected in the mucosal cell, but firm evidence that it participates in the absorptive process is lacking. Deficiencies in the luminal phase are responsible for the high global prevalence of iron deficiency which is predominantly dietary in origin. Much information has accumulated in recent years on dietary factors that enhance or impair iron absorption but their quantitative importance as determinants of iron status remains to be determined.


Soluble heparin-binding lectins from human brain: purification, specificity and relationship to an heparin-binding growth factor.
1. An heparin-binding lectin activity was detected in soluble extracts of human brain. Three polypeptide chains were purified by affinity chromatography on heparin-Sepharose. Their Mrs estimated by polyacrylamide gel electrophoresis were 13,000, 14,500 and 16,000. 2. Several glycosaminoglycans were potent inhibitors of their hemagglutination activity. 3. From the pool of purified lectins three peaks were separated by reversed-phase high-performance liquid chromatography. They were indistinguishable by activity criteria (hemagglutination, stimulation of endothelial cell growth), and immunological relationship was found between one of them and acidic fibroblast growth factor (aFGF).


Immune reconstitution and survival of patients with parvovirus B19 related pure red cell aplasia after haplo-PBSCT.
Parvovirus B19 (PvB19) infection and PvB19 related pure red cell aplasia (PRCA) in recipients with allogeneic hematopoietic stem cell transplantation have been reported sporadically. However, clinical studies with large sample sizes are lacking, especially in patients undergoing HLA-haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). In addition, clinical features, immune reconstitution, and outcomes of these patients are not clear. We conducted a retrospective analysis of 164 patients who received haplo-PBSCT with low-dose anti-thymocyte globulin (ATG) plus low-dose posttransplant cyclophosphamide (PTCy)-based regimen as graft-versus-host disease (GVHD) prophylaxis. We analyzed the incidence of PvB19 related PRCA and compared the clinical characteristics, immune reconstitution, incidence of GVHD, relapse rate, and survival between patients with and without PvB19 related PRCA. A total of 14 (8.5%) recipients developed PvB19 related PRCA after a median of 5.3 months after haplo-PBSCT. These patients with PvB19 related PRCA had slower immune reconstitution, but similar incidences of GVHD, relapse rate, and overall survival compared with recipients without PvB19 related PRCA. PvB19 related PRCA indicated relative delayed and poor immune reconstitution of the recipients early after haplo-PBSCT. PvB19 related PRCA had no effects on GVHD, relapse, and survival.


Patterns and Trends in the Use of Medications for COPD Control in a Cohort of 9476 Colombian Patients, 2017-2019.
Chronic obstructive pulmonary disease (COPD) affects approximately 174 million people worldwide. The objective was to determine the trends of COPD medication use in a group of Colombian patients. This was a retrospective study on prescription patterns of bronchodilators and other medications used in COPD from a population database with follow-up at 12 and 24 months. Patients older than 18 years of age of any sex with a COPD diagnostic code between 2017 and 2019 were included. Sociodemographic variables, medications, treatment schedules for COPD, comorbidities, comedications, and the specialty of the prescriber were considered. Data from 9476 people with COPD was evaluated. The mean age was 75.9 ± 10.7 years, 50.1% were male, and 86.8% were prescribed by a general practitioner. A total of 57.9% had comorbidities, most often hypertension (44.4%). At the baseline measurement, on average, they received 1.6 medications/patient, mainly short-acting antimuscarinics (3784; 39.9%), followed by short-acting β-agonists (2997, 31.6%) and inhaled corticosteroids (ICS) (2239, 23.6%); more than half (5083, 53.6%) received a long-acting bronchodilator. Prescription of triple therapy (antimuscarinic, β-agonist, and ICS) went from 645 (6.8%) at baseline to 1388 (20.6%) at the 12-month mark. This group of patients with COPD treated in Colombia frequently received short-acting bronchodilators and ICS, but a growing proportion are undergoing controlled therapy with long-acting bronchodilators, a situation that can improve the indicators of morbidity, exacerbations, and hospitalization.


PCR-free telomerase assay using chronocoulometry coupled with hexaammineruthenium(III) chloride.
An electrochemical method based on chronocoulometry coupled with hexaammineruthenium chloride (RuHex) is proposed for simple and rapid assay of telomerase without relying on PCR and gel electrophoresis. Thus, DNA extended by telomerase in extracts of as small as 5-1,000 HeLa cells on the TS primer-immobilized electrodes was quantified successfully. This method is suitable for quick screening of drug candidates which inhibit telomerase. When 10 compounds were tested, the multiplicity of extension (x in (TTAGGG)(x)) varied from 11 to 0, suggesting that there is more than one mechanism of inhibition. IC(50) values of telomerase inhibitors TMPyP4 and PIPER were determined as 5.5 and 15 μM, respectively, though their mechanisms of inhibition are different. This method is capable of discriminating two possible mechanisms of telomerase inhibition: direct binding of inhibitors to telomerase and indirect inhibition through their binding to the quadruplex generated by telomerase. As this method is easy and quick to run, it will be useful for high-throughput screening of drug candidates which inhibit telomerase.


Biological effects of some natural and chemical compounds on the potato tuber moth, Phthorimaea operculella Zell. (Lepidoptera:Gelechiidae).
The olfactory reaction of larvae and moths was investigated towards 18 oils (6 natural oils and 12 commercial chemical oils). Some of these oils such as peppermint and camphor (natural oils) and eugenol and camphene (commercial oils) were repellent to both larvae and moths. Other oils such as strawberry and d-limonene were attractive to both larvae and moths. Some of the repellent oils were, therefore, tested for their effect on certain biological aspects of the insects. Eugenol and peppermint oils, each at the 0.01% conc., caused a significant depression in the fecundity of moth and decreased the percentage of egg hatchability. Eugenol oil was much more effective than peppermint oil at 1%. Dried (leaves, fruits or seeds) powder of 14 different plants species were tested in different concentrations with talcum powder (carrier material) against egg deposition. The results indicated that dried powders of Allium cepa, Curcuma longa, Colocasia antiqurum, Ocimum basilicum. Dodonaea viscose and Thuja orientalis played a highly significant role in reducing egg deposition. The most impressive effect was displayed by powders of D. viscose and A. cepa, which caused the highest depression in egg deposition as well as in the emerging offsprings. Ethanolic extracts of 11 plants indicated that extracts of Pithuranthos tortosus and Iphiona scabra caused the maximum inhibition of egg hatchability, followed by C. longa, Citrullus colocynthia and T. orientalis. Ethanolic extracts of Schinus terebenthiflius (leaves) and I. scabra caused the highest depression in the deposited eggs, as they played a remarkable role as ovipositor deterrents. The majority of the plant extracts at 1% conc. could protect potato tubers at different intervals according to the calculated tuber damage index as follows: Iphiopna > Pithuranthos > Curcuma > Schinus (fruits) Thuja > Schinus (leaves) > Dodonaea > Citrullus.


Alterations of mammalian oocyte meiosis I with divalent cations and calmodulin.
Experiments using a Ca2+/Mg2+, serum free media were carried out aimed at clarifying proposed effects of these divalent cations on in vitro meiotic maturation of mouse and cow oocytes. Agents known to perturb intracellular Ca2+ or calmodulin were also studied. Total absence of both cations restricts both oocyte species from completing meiosis I. Media containing Mg2+ and no Ca2+ permitted some maturation in both species. Absence or small amounts of Mg2+ in the media containing control amounts of Ca2+ was much more inhibitory for the cow than the mouse oocyte. Studies of mouse oocyte maturation with Verapamil, Epinephrine and A23187 demonstrated an inhibition of maturation perhaps by the intracellular Ca2+ changes these agents are alleged to induce. A dependency of mouse oocyte maturation on active Ca-Calmodulin complexes was suggested by the calmodulin inhibitor studies.


Endoscopic argon laser photocoagulation of small sessile colonic polyps.
The availability of flexible quartz wave ¿uides allowing introduction of argon laser energy through endoscopes suggests the possibility of ablation of colonic mucosal lesions by this technique. To ascertain the effects of the argon laser on the colon, penetration depth and perforation studies were conducted in dogs. At 250 joules/cm2 energy density, less than 50% muscularis externa injury was noted in 29 of 42 lesions. No perforation was noted. Healing was complete in 8 days. The time required for deliberate perforation with the catheter firmly pressed against the wall of a distended inflated colon using 2 W argon laser applied continuously was 41 +/- 13 sec, N = 53. In a human study of 15 small sessile polyps ablated by laser and the colon examined 4 days later at colectomy, no penetration of the laser beneath the submucosa was noted. In 11 patients with Gardner's syndrome 211 polyps have been removed in 18 treatments without complication. These encouraging results suggest the continued study of this endoscopic modality in the treatment of mucosal lesions of the colon.


Oxidative Allylic Esterification of Alkenes by Cooperative Selenium-Catalysis Using Air as the Sole Oxidant.
A new metal-free catalysis protocol for the oxidative coupling of nonactivated alkenes with simple carboxylic acids has been established. This method is predicated on the cooperative interaction of a diselane and a photoredox catalyst, which allows for the use of ambient air or pure O2 as the terminal oxidant. Under the title conditions, a range of both functionalized and nonfunctionalized alkenes can be readily converted into the corresponding allylic ester products with good yields (up to 89%) and excellent regioselectivity as well as good functional group tolerance.


Early-life weight gain is associated with non-atopic asthma in childhood.
Previous studies suggest the association between early-life weight gain and asthma. It remains unclear whether early-life weight gain is associated with atopic or non-atopic asthma. This study aimed to investigate whether early-life weight gain is associated with atopic or non-atopic asthma. Included in this study were 1343 singleton-birth children (761 boys, 57%) born between January 2010 and December 2011 participating in the Longitudinal Investigation of Global Health in Taiwanese Schoolchildren (LIGHTS) cohort were evaluated by a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and interviewed by pediatricians between July 1, 2016 and May 31, 2018 at the mean age of 6.4 years. Weight gain z-scores during the first 6, 12, and 18 months of life were classified into 4 groups: slow (below -0.67), on track (-0.67 to 0.67), rapid (0.67 to 1.28), and extremely rapid (above 1.28). The main outcomes were atopic and non-atopic asthma. Asthma was defined as having physician-diagnosed asthma and the presence of wheeze or asthma exacerbations in the last 12 months. Atopy was determined by Phadiatop Infant. The extremely rapid weight gain group of children during the first 6, 12, and 18 months of life was significantly associated with an increased risk of non-atopic asthma (adjusted odd ratio [AOR], 2.14, 95% confidence interval [CI], 1.01-4.53 for the first 6 months; AOR, 2.86, 95% CI, 1.34-6.14 for the first 12 months; AOR, 3.26, 95% CI 1.49-7.15 for the first 18 months) compared with the on track group. No significant association was found in atopic asthma. A sex-stratified analysis revealed the association of early-life weight gain with non-atopic asthma was statistically significant only in boys (AOR, 4.24, 95% CI, 1.44-12.50). Extremely rapid weight gain during the first 6-18 months of life was significantly associated with 2.1- to 3.3-fold increased risk of non-atopic asthma, with a more pronounced risk found in boys.


Efficacy of novel antimicrobials against clinical isolates of opportunistic amebas.
We examined the effects of the macrolide antimicrobial agent azithromycin and phenothiazine compounds against clinical isolates of Acanthamoeba spp. and Balamuthia mandrillaris, opportunistic pathogens of human beings and other animals. Acanthamoeba growth was inhibited in vitro at 1, 5, and 10 micrograms/ml of azithromycin, but not the macrolides, erythromycin, and clarithromycin. In experiments attempting to simulate in vivo conditions, azithromycin protected monolayers of rat glioma cells from destruction by Acanthamoeba at a concentration of 0.1 microgram/ml, and delayed destruction at concentrations of 0.001 and 0.01 microgram/ml. We concluded that the minimal inhibitory concentration of azithromycin was 0.1 microgram/ml. Our results, however, suggested that the drug was amebastatic but not amebicidal, since ameba growth eventually resumed after drug removal. The phenothiazines (chlorpromazine, chlorprothixene, and triflupromazine) inhibited Acanthamoeba growth by 70-90% at 5 and 10 micrograms/ml, but some of these compounds were toxic for rat glioma cells at 10 micrograms/ml. Azithromycin was not very effective against B. mandrillaris in an in vitro setting, but was amebastatic in tissue culture monolayers at concentrations of 0.1 microgram/ml and higher. Balamuthia amebas showed in vitro sensitivity to phenothiazines. Ameba growth was inhibited 30-45% at 5 micrograms/ml in vitro, but completely at 5 micrograms/ml in the rat glioma model. In spite of their potential as antiamebic drugs in Balamuthia infections, toxicity of phenothiazines limits their use in clinical settings.


Effects of new intravascular contrast agents on [Ca2+]i transients and contraction in cultured ventricular myocytes.
We examined the effects of four kinds of intravascular contrast agents (amidtrizoic acid, iohexol, iopamidol, and ioxaglic acid) on [Ca2+]i transients (indo-1 fluorescence) and cell contraction (video motion analyzer), using cultured chick embryo ventricular myocytes. Exposure of ventricular myocytes to amidtrizoic acid (a conventional contrast agent) reduced the [Ca2+]i transients and the sensitivity of the contractile elements to [Ca2+]i. Ioxaglic acid (a low osmotic contrast agent) also reduced the [Ca2+]i transients, but did not significantly change the sensitivity of the contractile elements to [Ca2+]i. Neither iohexol nor iopamidol (nonionic contrast agents) reduced the [Ca2+]i transients, but both significantly decreased the sensitivity of the contractile elements to [Ca2+]i. A marked negative inotropic effect of amidtrizoic acid was caused by both calcium binding and hypertonicity. The less marked depression of contractility produced by ioxaglic acid is possibly the result of calcium binding, but is not caused by hypertonicity. The negative inotropism produced by nonionic contrast agents (iohexol and iopamidol) was due to hypertonicity, but not due to alterations in the [Ca2+]i transients. Exposure of ventricular myocytes to nonionic contrast agents (iohexol and iopamidol) slowed decay in the [Ca2+]i transients with increased end-diastolic [Ca2+]i. After washing out the nonionic contrast agents, these parameters returned to control levels. On the other hand, exposure to amidtrizoic acid decreased end-diastolic [Ca2+]i without changing decay time in the [Ca2+]i transients. After washing out amidtrizoic acid, there was a prolongation of half decay time in [Ca2+]i transients with a significant increase in end-diastolic [Ca2+]i and cell position. Diastolic dysfunction just after washout of amidtrizoic acid was possibly caused by an increase in [Na+]i due to sodium influx during exposure to the contrast agent.


Immunohistochemical and electron microscopic demonstration of vascular innervation in the mammalian brainstem.
Ultrastructural morphological relationship between microvessels and neural elements containing serotonin-like immunoreactivity, substance P and methionine-enkephalin like immunoreactivity were studied in the monkey and cat brain. A close relationship between serotonin-like immunoreactive dendritic processes, enkephalin-like immunoreactive profiles and capillary basement membrane was observed; they were usually separated by a double layer of glial membrane. More importantly, serotonin and substance P-like immunoreactive dendritic profiles are reported in close approximation with capillary basement membrane with no glial limitans at the site of contact. These intimate morphological associations may be the basis for neural regulation of tonicity, permeability and chemosensor function in the brain microvasculature.


DMSO Delays Alzheimer Disease Causing Aβ-induced Paralysis in C. elegans Through Modulation of Glutamate/Acetylcholine Neurotransmission.
Alzheimer's disease (AD), a prevalent neurodegenerative disease with progressive dementia and neurotransmission (NT)-dysfunction-related complications in older adults, is known to be caused by abnormal Amyloid-β (Aβ) peptide and associated amyloid plaques in the brain. Drugs to cure AD are not in sight. Two major excitatory neurotransmitters, glutamate (Glu) and acetylcholine (ACh), and their signaling systems are implicated in AD. To determine the effect of various NT-altering compounds including fenobam, quisqualic acid, and dimethyl sulfoxide (DMSO) in the protection against Aβ toxicity. Further, to identify the potential mechanism through which the protection happens. The well-known C. elegans AD model, CL4176, in which human Aβ expression is turned on upon a temperature shift to 25 °C that leads to paralysis, was screened for protection/delay in paralysis because of Αβ toxicity. While screening the compounds, dimethyl sulfoxide (DMSO), a universal solvent used to solubilize compounds, was identified to provide protection. Aldicarb and levamisole assays were performed to identify the contribution of ACh neurotransmission in Αβ toxicity protection by DMSO. One percent and two percent DMSO delayed paralysis by 48% and 90%, respectively. DMSO was dominant over one of the Glu-NT pathway-related compounds, Fenobam-Group I mGluR antagonist. But DMSO provided only 30% to 50% protection against Quisqualic acid, the Glu-agonist. DMSO (2%) delayed ACh-NT, both presynaptic acetylcholine esterase inhibitor (AchEi)-aldicarb and postsynaptic-iAChR-agonst-levamisole induced paralysis, by ∼70% in CL4176. DMSO seems to be altering Ca2+ ion permeability essential for NT as EthyleneDiamine Tetra-Acetic acid (EDTA) and DMSO provided similar aldicarb resistance either combined or alone in wildtype worms. But postsynaptic Ca2+ depletion by EDTA could reverse DMSO-induced levamisole hypersensitivity. Surprisingly, the absence of FOrkhead boXO (FOXO) transcription factor homolog, daf-16 (loss-of-function mutant), a critical transcription factor in the reduced IIS-mediated longevity in C. elegans, abolished DMSO-mediated AldR. DMSO and Fenobam protect against Aβ toxicity through modulation of NT.


Heat stability of Proteobacterial PII protein facilitate purification using a single chromatography step.
The P(II) proteins comprise a family of widely distributed signal transduction proteins that integrate the signals of cellular nitrogen, carbon and energy status, and then regulate, by protein-protein interaction, the activity of a variety of target proteins including enzymes, transcriptional regulators and membrane transporters. We have previously shown that the P(II) proteins from Azospirillum brasilense, GlnB and GlnZ, do not alter their migration behavior under native gel electrophoresis following incubated for a few minutes at 95°C. This data suggested that P(II) proteins were either resistant to high temperatures and/or that they could return to their native state after having been unfolded by heat. Here we used (1)H NMR to show that the A. brasilense GlnB is stable up to 70°C. The melting temperature (Tm) of GlnB was determined to be 84°C using the fluorescent dye Sypro-Orange. P(II) proteins from other Proteobacteria also showed a high Tm. We exploited the thermo stability of P(II) by introducing a thermal treatment step in the P(II) purification protocol, this step significantly improved the homogeneity of A. brasilense GlnB and GlnZ, Herbaspirillum seropedicae GlnB and GlnK, and of Escherichia coli GlnK. Only a single chromatography step was necessary to obtain homogeneities higher than 95%. NMR(1) and in vitro uridylylation analysis showed that A. brasilense GlnB purified using the thermal treatment maintained its folding and activity. The purification protocol described here can facilitate the study of P(II) protein family members.


Chromosomal instability and alteration of telomere repeat sequences.
The very end of the chromosome is called the telomere and is composed of DNA repeat sequences and associated proteins. Genetic and biochemical analyses of this complex, the telosome, lead to the hypothesis that transcription and DNA replication are submitted to position effects mediated by the telomere proximity. Telomere length reduction and alterations of the telomeric chromatin assembly might explain the chromosome instability which occurs during the senescence and the immortalization process in vitro. A particular polymerase, the telomerase, is able to lengthen the telomeres. A telomerase activity was characterized in yeast, Tetrahymena, but also in transformed and in germline cells. We reviewed the involvement of telomeres in the aging process. We proposed that the short size of the telomere repeat at each chromosome could direct the loss of heterozygosity, thus telomere length could play a role in individual and tissular susceptibility to develop cancer. Antitelomerase strategy for cancer therapy is attractive but limited by the short decrease of the telomere length at each cell division.


Probability of rainstorm and flood disasters due to extreme precipitation in Fen River Basin, China.
Analysis of the probability of extreme precipitation events leading to rainstorm and flood disasters can aid in disaster prevention policy development. Using daily precipitation data from 16 meteorological stations from 1960 to 2019, we calculated eight extreme precipitation indices to analyze the spatio-temporal characteristics of extreme precipitation in the Fen River Basin (FRB) through ensemble empirical mode decomposition and Kriging interpolation. Extreme precipitation events and disasters were defined based on a combination of the antecedent precipitation index (API) and extreme precipitation on the event day and classified; extreme precipitation and the API were ranked from small to large and classified into dry, wet, and moderate (mod) precipitation periods, respectively, yielding nine extreme precipitation event categories. The probability of disasters caused by different types of extreme precipitation events was calculated using a binomial distribution. The results are as follows: (1) between 1960 and 2019, except for extreme precipitation period length, which continuously increased, the extreme precipitation indices changed from a downward to an upward trend since the 1980s. All extreme precipitation indices showed similar interannual variation over short periods and different interdecadal variation over long periods. (2) The extreme precipitation indices showed latitudinal and zonal spatial divergence patterns, but different spatial characteristics were observed around the 1980s. (3) More than 70% of extreme precipitation events in the midstream and downstream fell into four categories: "dry-dry," "dry-mod," "mod-dry," and "mod-mod." (4) A single category VII (VIII) extreme precipitation event in the midstream (downstream) had a maximum probability of causing disaster of 14%. When more than four extreme precipitation events occurred in a year, the probability of one disaster was the highest and that of four or more disasters was < 0.1%. The probability of rainstorm and flood disasters increased gradually with increasing frequency of annual extreme precipitation events.


Heterologous vaccination (ChAdOx1 and BNT162b2) induces a better immune response against the omicron variant than homologous vaccination.
The ongoing COVID-19 pandemic has seen the emergence of numerous novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. In this study, we compared the efficacy of three different forms of immunization against the wild-type, delta, and omicron variants of the virus: two doses of the BNT or AZ vaccine (BNT/BNT or AZ/AZ) as homologous vaccination, three doses of AZ/AZ/BNT as heterologous vaccination, and naturally occurring immunization in severe COVID-19 cases. We collected serum samples from vaccine recipients (67 receiving BNT/BNT, 111 receiving AZ/AZ, and 18 receiving AZ/AZ/BNT) and 46 patients who were admitted to the hospital with severe COVID-19. Blood samples were taken one month after the last injection and the efficacy of the vaccination was determined using the surrogate virus neutralization test (sVNT), with a positive result defined as an inhibition rate of over 30%. Serum samples from COVID-19 patients were taken at various points during their hospitalization and tested for inhibition rates. Our results indicated that there was no notable difference in the levels of neutralizing antibodies (nAb) in vaccine recipients and patients against the wild-type and delta variants. However, when it came to the omicron variant, the vaccine recipients had significantly lower nAb titers. Among the vaccine recipients, those who received a booster dose of BNT after their first two doses of AZ (AZ/AZ/BNT) demonstrated the highest level of protection against the omicron variant at 44.4%, followed closely by the COVID-19 patients. In analyzing the serial samples taken from hospitalized COVID-19 patients, we observed that their inhibition rates against the wild-type and delta variants improved over time, while the inhibition rate against the omicron variant decreased. In conclusion, our findings suggest that heterologous booster vaccination after primary vaccination produces higher nAb titers and provides a higher level of protection against the omicron variant compared to primary vaccination alone. This protective effect was similar to that observed in patients with severe COVID-19.


Leuco-erythroblastosis following withdrawal from glucocorticoid therapy.
Leuco-erythroblastosis has many known associations (Burkett, Cox and Fields, 1965; Weick, Hagedorn and Linman, 1974; Retief, 1964), but the only ones related to drug therapy are the well established response to haematinics (Burkett et al., 1965) and one possible case following anti-epileptic therapy (Retief, 1964). The case described below is of leuco-erythroblastosis following steroid withdrawal in a young man with primary polymyositis.


Management of Alcohol Withdrawal Syndrome in Patients with Alcoholic Liver Disease.
Alcohol withdrawal syndrome (AWS) is a common condition that is seen in treatment-seeking patients with Alcohol use disorder (AUD) and alcoholic liver disease (ALD). AWS, which typically starts within 4-6 h of the last alcohol use, can range from mild symptoms such as insomnia, tremors, and autonomic hyperactivity to more severe symptoms such as seizures and delirium tremens. Clinical Institute Withdrawal Assessment Scale-Alcohol Revised (CIWA-Ar) is the most commonly used scale to assess AWS in clinical practice. The presence of moderate withdrawal as indicated by a score of more than 8 is an indication for pharmacotherapy. Lorazepam and oxazepam are preferred agents for the management of AWS in the setting of ALD. In severe ALD, benzodiazepines should be used cautiously with monitoring due to the risk of excessive sedation or precipitating hepatic encephalopathy.


Development and retention of phenotypically specialized cells in pituitary allografts in the hamster (Mesocricetus auratus).
We used immunohistochemistry to identify cells present in pituitary allografts in the hamster. Hypophyses removed from neonatal hamsters or adenohypophyses removed from adult females were placed beneath renal capsules of hypophysectomized adult females. Serum PRL, LH, and GH concentrations were measured at two, five and eight weeks after placement of allografts. Allografts were removed after eight weeks and stained for cells containing PRL, LH, FSH, GH, or ACTH. Allografts did not release LH or GH. Those of adult adenohypophyseal tissue released significantly more PRL. The morphology of allografts of neonatal hypophyseal tissue resembled that of the adult adenohypophysis in situ. Lactotrophs, corticotrophs, somatotrophs and LH-cells were observed; very few FSH-cells were present. Allografts of adult adenohypophyseal tissue contained pituitary cells, numerous cavities, often enclosing lymphoid cells, and fibrous tissue. Atypical lactotrophs were the numerically dominant cells in these allografts; all other cells were present. The LH-cells outnumbered FSH-cells. These observations suggest that: (a) development of normal adenohypophyseal morphology can occur in an ectopic position; (b) intracellular hormones are present in cells in an ectopic site; (c) development and retention of intracellular FSH is more dependent on occupation of the normal position of the adenohypophysis than is retention of intracellular LH; and (d) release of PRL occurs from atypical cells in allografts of adult adenohypophyseal tissue.


Influence of Imidazolium Ionic Liquids on Dehydrogenase Activity of Activated Sludge Microorganisms.
Imidazolium salts are one of the most often used and investigated groups of ionic liquids (ILs). The research concerning their ecotoxicity comprised many test organisms representing different trophic levels; however, their impact on mixed cultures of microorganisms such as activated sludge has been hardly ever investigated. Thus, in this work, the effect of imidazolium ionic liquids on dehydrogenase activity of activated sludge was estimated. Three activated sludges of different properties and origin were tested. It occurred that 1-alkyl-3-methyl imidazolium bromides do not inhibit dehydrogenase activity of sludge, if the alkyl chain contains up to six carbon atoms. The values of IC50 for these ILs were above 100 mg l(-1). At the same time, the inhibitory effect on dehydrogenase activity of activated sludge increases with the increase in chain length of the alkyl substituent. The degree of inhibition of dehydrogenase activity of sludge microorganisms is dependent on activated sludge properties.


9-[(Z)-2-(4,4,5,5-Tetra-methyl-1,3,2-dioxaborolan-2-yl)ethen-yl]-9H-carbazole.
The title compound, C20H22BNO2, has a polarized π-system due to resonance between N-C(H)=C(H)-B and ionic N+=C(H)-C(H)=B- canonical structures. The dihedral angles between the ethenyl plane (r.m.s. deviation for C2H2 = 0.0333 Å) with the ethenyl-C(NC2-pyrrole) plane (r.m.s. deviation CNC2 0.0423 Å) and the ethenyl-C(BO2-1,3,2-dioxaborolane) plane (r.m.s. deviation BCO2 0.0082 Å) are 45.86 (8) and 37.47 (8)°, respectively, and are greater than those found for the previously reported E-isomer [Hatayama & Okuno (2012 ▸) Acta Cryst. E68, o84]. In comparison with the E-isomer, the reduced planarity of Z-isomer results in a decrease of the contribution of the N+=C(H)-C(H)=B- canonical structure.


Cross-sectional study evaluating the seroprevalence of SARS-CoV-2 antibodies among healthcare workers and factors associated with exposure during the first wave of the COVID-19 pandemic in New York.
Estimate the seroprevalence of SARS-CoV-2 antibodies among New York City Health and Hospitals (NYC H+H) healthcare workers during the first wave of the COVID-19 pandemic, and describe demographic and occupational factors associated with SARS-CoV-2 antibodies among healthcare workers. Descriptive, observational, cross-sectional study using a convenience sample of data from SARS-CoV-2 serological tests accompanied by a demographic and occupational survey administered to healthcare workers. A large, urban public healthcare system in NYC. Participants were employed by NYC H+H and either completed serological testing at NYC H+H between 30 April 2020 and 30 June 2020, or completed SARS-CoV-2 antibody testing outside of NYC H+H and were able to self-report results from the same time period. SARS-CoV-2 serostatus, stratified by key demographic and occupational characteristics reported through the demographic and occupational survey. Seven hundred and twenty-seven survey respondents were included in analysis. Participants had a mean age of 46 years (SD=12.19) and 543 (75%) were women. Two hundred and fourteen (29%) participants tested positive or reported testing positive for the presence of SARS-CoV-2 antibodies (IgG+). Characteristics associated with positive SARS-CoV-2 serostatus were Black race (25% IgG +vs 15% IgG-, p=0.001), having someone in the household with COVID-19 symptoms (49% IgG +vs 21% IgG-, p<0.001), or having a confirmed COVID-19 case in the household (25% IgG +vs 5% IgG-, p<0.001). Characteristics associated with negative SARS-CoV-2 serostatus included working on a COVID-19 patient floor (27% IgG +vs 36% IgG-, p=0.02), working in the intensive care unit (20% IgG +vs 28% IgG-, p=0.03), being employed in a clinical occupation (64% IgG +vs 78% IgG-, p<0.001) or having close contact with a patient with COVID-19 (51% IgG +vs 62% IgG-, p=0.03). Results underscore the significance that community factors and inequities might have on SARS-CoV-2 exposure for healthcare workers.


Pregnant adolescents and nurses perspectives on accessibility and utilization of maternal and child health information in Ohangwena Region, Namibia.
Adolescent reproductive health is still a challenge in Low and Middle Income Come Countries (LMICs). However, the reasons for the inability of most pregnant adolescent girls to access and utilize maternal and child health information (MCHI) are not well-documented. This is despite the policy guidelines promoting the provision of this necessary information to pregnant adolescents in order to prepare them for delivery. This provision is one of the strategies envisaged to improve their attendance of ANC visits and their maternal and child health. Data were generated from 12 adolescent pregnant girls aged 15 to 19 years and eight nurses from four different health centres in the Ohangwena Region of Namibia, using semi-structured in-depth interviews. The study was conducted over the period of three months (December 2018 to March 2019). The data were grouped into clusters aided by NVivo computer software version 12. Data were organized and condensed in small units, prior to being coded, categorized, and finally grouped into main themes and sub-themes. Results revealed that long travel hours to reach the nearest clinics was amongst the leading challenges affecting accessibility and utilization of MCHI for pregnant adolescent girls. This was exacerbated by poor support with transport fare, poor road infrastructure and non-availability of transport, and these factors were key barriers to accessibility and utilization of clinic services. Other barriers pertained to the family dynamics, such as disclosing the pregnancy to the family members prior to commencing antenatal care (ANC) visits and harsh treatment from family members after the disclosure. The pregnant adolescent girls were concerned about their inability to access and utilize MCHI, thereby making them susceptible to maternal complications. Health educational interventions should prioritize both the adolescent girls and their families for proper support, especially since the reactions of families on the pregnancy of their adolescent girls often negatively affect accessibility and utilization of maternal and child health services. Moreover, further research on adolescents' needs during pregnancy should be expanded to include their parents, in order to better inform policymakers.


Correction: On-chip stool liquefaction via acoustofluidics.
Correction for 'On-chip stool liquefaction via acoustofluidics' by Shuaiguo Zhao et al., Lab Chip, 2019, 19, 941-947, DOI: .


Effect of indomethacin and adrenocorticotrophic hormone on renal function in man: an experimental model of inappropriate antidiuresis.
The effect of prostaglandin synthesis inhibition on basal and ACTH-stimulated adrenal and renal function was investigated in normal volunteers. Data were collected during control and experimental study periods (13 days each). Adrenocorticotrophic hormone (Cosyntropin, 80 U/day) was administered i.v. on days 8 and 9 of each period. Indomethacin (150 mg/day) was given on days 5 through 13 of the experimental period. The subjects ate a constant diet containing 9 mEq of sodium, 100 mEq of potassium, and 2,500 ml of fluid daily. Indomethacin markedly inhibited urinary PGE excretion and plasma PGE concentration. The effect of ACTH alone as compared to the effect of ACTH and indomethacin showed: plasma sodium concentration, 139 +/- 1 vs. 131 +/ 3 mEg/liter (P less than 0.01, mean +/- SEM); plasma osmolality, 287 +/- 3 vs. 270 +/- 3 mOsm/liter (P less than 0.01); free water clearance, 97 +/- 66 vs. -1100 +/- 380 ml/24hr (P less than 0.01); urine volume, 2,000 +/- 60 vs. 950 +/- 200 ml/day (P less than 0.01); and urine osmolality 282 +/- 12 vs. 720 +/- 144 mOsm/liter (P less than 0.01). We conclude that the effects of ACTH and prostaglandin synthesis inhibition interact to result in inappropriate antidiuresis.


Characterizing superspreading events and age-specific infectiousness of SARS-CoV-2 transmission in Georgia, USA.
It is imperative to advance our understanding of heterogeneities in the transmission of SARS-CoV-2 such as age-specific infectiousness and superspreading. To this end, it is important to exploit multiple data streams that are becoming abundantly available during the pandemic. In this paper, we formulate an individual-level spatiotemporal mechanistic framework to integrate individual surveillance data with geolocation data and aggregate mobility data, enabling a more granular understanding of the transmission dynamics of SARS-CoV-2. We analyze reported cases, between March and early May 2020, in five (urban and rural) counties in the state of Georgia. First, our results show that the reproductive number reduced to below one in about 2 wk after the shelter-in-place order. Superspreading appears to be widespread across space and time, and it may have a particularly important role in driving the outbreak in rural areas and an increasing importance toward later stages of outbreaks in both urban and rural settings. Overall, about 2% of cases were directly responsible for 20% of all infections. We estimate that the infected nonelderly cases (<60 y) may be 2.78 [2.10, 4.22] times more infectious than the elderly, and the former tend to be the main driver of superspreading. Our results improve our understanding of the natural history and transmission dynamics of SARS-CoV-2. More importantly, we reveal the roles of age-specific infectiousness and characterize systematic variations and associated risk factors of superspreading. These have important implications for the planning of relaxing social distancing and, more generally, designing optimal control measures.


Longer looks for language: Novel labels lengthen fixation duration for 2-year-old children.
The language infants hear guides their visual attention; infants look more to objects when they are labeled. However, it is unclear whether labels also change the way infants attend to and encode those objects-that is, whether hearing an object label changes infants' online visual processing of that object. Here, we examined this question in the context of novel word learning, asking whether nuanced measures of visual attention, specifically fixation durations, change when 2-year-olds hear a label for a novel object (e.g., "Look at the dax") compared with when they hear a non-labeling phrase (e.g., "Look at that"). Results confirmed that children visually process objects differently when they are labeled, using longer fixations to examine labeled objects versus unlabeled objects. Children also showed robust retention of these labels on a subsequent test trial, suggesting that these longer fixations accompanied successful word learning. Moreover, when children were presented with the same objects again in a silent re-exposure phase, children's fixations were again longer when looking at the previously labeled objects. Finally, fixation duration at first exposure and silent re-exposure were correlated, indicating a persistent effect of language on visual processing. These effects of hearing labels on visual attention point to the critical interactions involved in cross-modal learning and emphasize the benefits of looking beyond aggregate measures of attention to identify cognitive learning mechanisms during infancy.


Antimutagenic and anticarcinogenic activity of tea polyphenols.
Tea is the most popular beverage, consumed by over two thirds of the world's population. Tea is processed differently in different parts of the world to give green (20%), black (78%) or oolong tea (2%). Green tea is consumed mostly in Japan and China. The antimutagenic and anticarcinogenic activities of green tea are extensively examined. The chemical components of green and black tea are polyphenols, which include EC, ECG, EGC, EGCG and TFs. This article reviews the epidemiological and experimental studies on the antimutagenicity and anticarcinogenicity of tea extracts and tea polyphenols. In Japan, an epidemiological study showed an inverse relationship between habitual green tea drinking and the standardized mortality rates for cancer. Some cohort studies on Chanoyu (Japanese tea ceremony) women teachers also showed that their mortality ratio including deaths caused by malignant neoplasms were surprisingly low. The antimutagenic activity against various mutagens of tea extracts and polyphenols including ECG and EGCG has been demonstrated in microbial systems (Salmonella typhimurium and Escherichia coli), mammalian cell systems and in vivo animal tests. The anticarcinogenic activity of tea phenols has been shown in experimental animals such as rats and mice, in transplantable tumors, carcinogen-induced tumors in digestive organs, mammary glands, hepatocarcinomas, lung cancers, skin tumors, leukemia, tumor promotion and metastasis. The mechanisms of antimutagenesis and anticarcinogenesis of tea polyphenols suggest that the inhibition of tumors may be due to both extracellular and intracellular mechanisms including the modulation of metabolism, blocking or suppression, modulation of DNA replication and repair effects, promotion, inhibition of invasion and metastasis, and induction of novel mechanisms.


Evolution of the albumin: alpha-fetoprotein ancestral gene from the amplification of a 27 nucleotide sequence.
The genes for alpha-fetoprotein and albumin arose by duplication of an ancestral gene that contained three genetic domains. These domains were generated by the triplication of a primordial genetic domain composed of five exons or subdomains. That the primordial domain itself arose by amplification of a simpler sequence is suggested by nucleotide sequence homologies among the subdomains of the mouse alpha-fetoprotein gene. A detailed analysis of these homologies reveals that each of the five subdomain families contains remnants of a 27-base-long repeat from which the entire alpha-fetoprotein coding sequence has been assembled. A consensus sequence for the 27 nucleotide repeat is derived, and the positions of the repeats within each subdomain are described. A model is proposed for the evolution of the primordial domain by the amplification and divergence of the 27 base-pair sequence, along with the condensation of the repeats into subdomains separated by intervening sequences. It is postulated that the role of intervening sequences may be to limit sequence amplification in genes such as alpha-fetoprotein and albumin whose protein products cannot tolerate size variation.


[Blood lead level in Switzerland in 1985: results of the MONICA survey].
New federal regulations regarding air pollution will soon impose catalysator equipped cars and unleaded fuel. In order to evaluate whether these measures affect the blood lead content in the Swiss population, there will be lead measurements in all three MONICA sample surveys. In the first survey, based on representative population samples, blood lead level was measured in the cantons of Vaud and Fribourg. Results based on 1774 lead measurements indicate a mean blood lead level significantly higher for males than females: 0.63 and 0.44 micromol/l. Work condition as measured by socio-professional category is only related to blood lead among males, while the living environment (community size) is only associated with female blood lead levels. Workers in agriculture and inhabitants of small communes have the lowest blood lead level. In addition, alcohol and tobacco consumption show a strong direct association with blood lead levels and are the two most important potentially confounding factors regarding the relation between blood lead levels and environmental lead pollution.


Short and long alteplase dwells in dysfunctional hemodialysis catheters.
Hemodialysis catheter dysfunction (CD) is the inability to attain adequate blood pump speeds (BPS) and is attributed to thrombus or catheter malposition; alteplase (TPA) is often given in a variety of dwell times to treat CD. The purpose of this study was to determine if TPA dwell time affects short- or long-term catheter patency rates. Sixty hemodialysis (HD) patients with CD, as defined by BPS of < 250 mL/min, were randomized to receive either 1- or > 48-hr (to subsequent HD run) TPA dwell. The primary outcomes were catheter patency (BPS of > 250 mL/min) at the subsequent HD run and catheter patency at 2 weeks. The secondary outcome was the time from study entry to the next catheter intervention (including subsequent TPA installation). After TPA installation, a 78% overall catheter patency rate was observed at the subsequent HD run, falling to 48% patency at 2 weeks. There is no statistically significant difference between the short and long TPA dwell groups for catheter patency at the subsequent HD run (76.9% vs. 79.4%) or at 2 weeks (42.3% vs. 52.9%). Multivariate analysis demonstrates that the use of TPA on two or more previous occasions is a predictor of TPA failure both at the subsequent HD run and at 2 weeks. TPA installation achieves a median catheter function time of only 14 days, after which CD reoccurs. This study demonstrates that although patency for the next HD run can be achieved with either short or long TPA dwell, neither is reliable in terms of long-term patency. Strategies that employ TPA for CD are temporary and allow a 2-week window during which more definitive therapies for HD access should be sought.


Anti-inflammatory and analgesic activities of Neolamarckia cadamba and its bioactive monoterpenoid indole alkaloids.
Neolamarckia cadamba has been used traditionally to treat inflammation, fever, and pruritus in the Dai ethnopharmacy in Yunnan province, P.R. China. However, according to literature survey, the action basis of anti-inflammatory and analgesic activities of this plant were rarely reported, which accounts for the original intentions of this investigation. The study aimed to investigate the anti-inflammatory and analgesic action of methanolic extract (ME), ethyl acetate (EA), and aqueous (AQS) fractions of N. cadamba and further explore the accurate compounds responsible for the activities of EA fraction. The in vivo anti-inflammatory and analgesic activities of ME, EA, and AQS fractions at the doses of 200 and 400 mg/kg and two major constituents (compounds 5 and 7) at 50 and 100 mg/kg via intragastrically administrated, respectively, were evaluated by carrageenan-induced paw edema and acetic acid-stimulated writhing animal models. Aspirin (ASP) was used as the positive control at the dose of 200 mg/kg. The monoterpenoid indole alkaloids (MIAs) in EA fraction were phytochemically studied utilizing chromatographic techniques, and their structures and absolute configurations were established on the basis of multiple spectroscopic analyses and quantum computational chemistry method. Moreover, the in vitro anti-inflammatory activities of all the isolates were assessed by suppressing releases of LPS-activated inflammatory mediators (TNF-α, IL-1β, and COX-2) in RAW 264.7 macrophage cells at a concentration of 10 μg/mL. Dexamethasone (DXM) was used as the positive control. Three fractions (ME, EA, and AQS) significantly ameliorated the paw edema caused by carrageenan and reduced the number of writhing induced by acetic acid in comparison to the control group at the doses of 200 and/or 400 mg/kg (in vivo). Subsequent phytochemical investigation of EA fraction led to the structural characterization of four new monoterpenoid indole alkaloids, neocadambines A-D (1-4), as well as eight known analogues (5-12). Neocadambine A possesses a novel 14-nor-MIA skeleton that could be derived from the corynantheine-type MIAs via oxidative cleavage of C3-C14 bond and subsequently degradation of C14. Moreover, the structure of a bioactive known MIA, cadambine acid (6), was reassigned by analysis of its NMR spectroscopic data. Further biological assays revealed that the major constituent 3β-dihydrocadambine (7) significantly relieved the paw edema and decreased the number of writhing at 100 mg/kg in vivo. In addition, most of the isolates displayed remarkable in vitro anti-inflammatory effects by inhibiting the secretion of aforementioned inflammatory mediators (COX-2, IL-1β, and TNF-α) at a concentration of 10 μg/mL, and compounds 4, 7, and 9 showed better anti-inflammatory effects than that of positive control, dexamethasone. This study further validated the anti-inflammatory and analgesic activities of N. cadamba, and revealed that monoterpenoid indole alkaloids could partly contribute to the efficacy of this ethnodrug. The major constituent 3β-dihydrocadambine (7) showed significant anti-inflammatory activities both in vitro and in vivo, which suggested that it could be a promising anti-inflammatory lead compound. Our findings provided scientific justification to support the traditional application of N. cadamba for treating inflammatory and nociceptive disorders.


Circulating ghrelin and GLP-1 are not affected by habitual diet.
Ghrelin and glucagon-like peptide-1 (GLP-1) are gut hormones known to induce hunger and satiety, respectively. Current knowledge about the effects of different macronutrients on circulating ghrelin and GLP-1 comes mainly from acute test meals, whereas little is known about the effects of chronic dietary intake on gut hormone secretion. This study was designed to examine whether 8-week habituation to diets with different percentages of carbohydrate and fat would affect serum ghrelin, GLP-1, and subjective hunger in a postabsorptive state and in response to a standard liquid mixed meal. Sixty-one overweight men and women were provided all food for 8 weeks of either a higher-carbohydrate/lower-fat diet (High-CHO/Low-FAT; 55% CHO, 18% PRO, 27% FAT) or a lower-carbohydrate/higher-fat diet (Low-CHO/High-FAT; 43% CHO, 18% PRO, 39% FAT). After overnight fasts at baseline and week 8, participants consumed a standard liquid meal (7 kcals/kg, 58.6% CHO, 17.4% PRO, 24% FAT). Blood was sampled before the meal and at 15, 60, 90, 120, 180, and 240 min to determine total serum ghrelin and active GLP-1. Hunger was assessed by a visual analog scale. Mixed models were used to evaluate whether the temporal patterns of total serum ghrelin and active GLP-1 differed with diet. Although both diet groups reported greater hunger after 8 weeks (p=0.03), circulating ghrelin and GLP-1 were not affected by acclimation to different macronutrients. Habituation to different diets does not appear to influence fasting ghrelin, fasting GLP-1, or responses of these gut hormones to a standard meal.


Effect of TIPA on mechanical properties and hydration properties of cement-lithium slag system.
Effect of triisopropanolamine (TIPA) on compressive strength and hydration properties of cement-lithium slag (LS, 30%) paste was studied. The results demonstrated that the addition of TIPA is advantageous for compressive strength at 7 d, 28 d and 60 d. The reason was related to the pore complexity and hydration process of cement and LS. TIPA reduced the total porosity, and increased the fractal dimension, making the pore structure more complicated. In addition, TIPA promoted the pozzolanic reaction of LS and the hydration of cement, expediting the formation of C-S(A)-H gel. TIPA accelerated the dissolution of aluminate ions, silicate ions and ferric ions in the pore solution, thereby accelerating the pozzolanic reaction of LS. During the hydration of cement-LS paste, TIPA facilitated the conversion of ettringite to the AFm-like phase and produced more C-A-S-H gel by promoting the dissolution of aluminate ions.


Defining the relationship between ovarian hormones and migraine headache.
(1) To determine whether the attack characteristics of migraine differ between different intervals of the menstrual cycle; (2) To ascertain whether the "rate of change,""magnitude of change," or "total burden" of urinary hormone metabolites correlates with headaches outcome measures during different intervals of the menstrual cycle. The mechanisms through which migraines are influenced by ovarian hormones remain unclear. No previous studies until now have identified "hormonally defined" time intervals within the female menstrual cycle and compared headache outcome measures among these intervals in female migraineurs. Daily headache diary data were obtained from 21 female migraineurs during three native menstrual cycles. Daily urine samples were collected and later assayed for estrogen and progesterone metabolites. Seven 3-day time intervals were identified within each menstrual cycle based on urine hormone measurements. Primary (headache index) and secondary (disability index, headache severity, and headache frequency) outcome measures were compared between intervals using the mixed model approach. "Rates of change,""magnitude of change," and the "total burden" of ovarian hormones were estimated from urine hormone metabolites and correlated with headache outcome measures. The headache index was significantly different across different intervals of the menstrual cycle (P values <.001) and was higher during menstrual intervals (first 6 days of the menstrual cycle) than during mid-cycle and mid-luteal intervals (P < .002). Similarly, secondary outcome measures were highest during the menstrual intervals. "Higher burdens" of urinary progesterone metabolites were positively correlated with headache outcome measures during the luteal intervals of the menstrual cycle. "Rates of change" and the "magnitude of change" of urinary hormone metabolites did not correlate with headache outcome measures. Migraine headache is more severe, disabling, and frequent during the menstrual intervals of the female reproductive cycle than during mid-luteal or mid-cycle intervals. Progesterone metabolites may play a role in modulating migraine headaches during luteal intervals of the menstrual cycle.


First introduction of dengue virus type 3 in Niger, 2022.
Dengue fever is the most important mosquito-borne viral disease of humans, with a significant disease burden in tropical and subtropical countries. The disease is caused by four distinct dengue virus (DENV) serotypes, DENV-1 to -4, all of which belong to the family Flaviviridae, genus Flavivirus. Approximately 3.6 billion people live in areas where they are at risk of transmission of DENVs, resulting in up to 390 million infections and 96 million symptomatic cases annually. Although the disease is highly endemic in the West Africa region, little is known about the prevalence and distribution of DENVs in Niger. We hereby report the first laboratory-confirmed case of dengue in Niger.


The impact of aerosol box on tracheal intubation during the COVID-19 pandemic: a systematic review.
This study aimed to summarize the effect of the aerosol box on tracheal intubation in patients with COVID-19. According to the PRISMA guidelines, a systematic search was performed to identify relevant literature on the 'impact of the aerosol box on tracheal intubation during the COVID-19 pandemic' in different electronic databases up to March 2021. Based on a set of predefined inclusion and exclusion criteria, 447 articles were screened. Finally, 20 articles were included in the current systematic review. The findings showed that the use of aerosol box during intubation could reduce droplet contamination on the healthcare workers but not necessarily aerosols. An increase in the time of intubation with the aerosol box was also observed in 9 out of 12 studies (75%); however, three studies reported no significant difference in the time of intubation with and without the aerosol box. Most studies (8 out of 9, 89%) were also shown that intubation with the aerosol box may lead to more difficulty. The proceduralist and other healthcare workers involved in airway management of COVID-19 infected patients should decide whether to apply the aerosol box with caution, balancing between benefits and risks, especially in difficult airway circumstances.


Interpretation of metameric architecture in dominant shrubs of the Chilean matorral.
The seasonal progression of phenophases in 21 shrub species of the Chilean matorral was analyzed. Five "modules" or basic units that are responsible for the aboveground architecture of the plants were characterized. These modules appear to be organized in seven different spatial arrangements. In drought-deciduous species a module type with an "absolute short shoot" with limited apical growth, leafy or spiny, predominated. In evergreen species "long shoot" and "temporal leafy short shoot" module types were more frequent. The spatial arrangement of morphologically different modules and the temporal sequence of their formation allow a dynamic interpretation of the modular architecture of the plants.


EGFR mutation status in Middle Eastern patients with non-squamous non-small cell lung carcinoma: A single institution experience.
Epidermal growth factor receptor (EGFR) represents an important molecular target in the treatment of lung adenocarcinomas; many anti-EGFR therapies are approved as first line and second-line treatment in patients having metastatic lung adenocarcinomas. The occurrence of this mutation varies in terms of race; it is around 10% in Caucasians and can reach 30% in Asians. Its prevalence in our Middle Eastern region is not well known. Patients diagnosed with non-squamous non-small cell lung carcinomas between March 2013 and March 2015 were included. This study was conducted at Hôtel-Dieu de France University Hospital, a tertiary medical center in Lebanon. EFGR mutations were analyzed using real time PCR technique on the Rotor-Gene Q using Scorpions and ARMS technologies. The following data was collected: the patients' characteristics (age, gender, smoking status, stage), the samples' characteristics (histology subtype, TTF-1 and Napsin A immunostainings, the site and the adequacy and the type of the sample), and the mutational EGFR status (presence and type of mutation). These variables were analyzed using SPSS 20. 201 patients were included. The mean age was 65.2 years [31-87]; 40.2% were females. 78.1% of the included patients were smokers or ex-smokers. 12.9% of patients had a localized disease, 17.4% a locally advanced disease and 69.7% a metastatic disease. Adenocarcinoma was the main histologic subtype found in 90.5% of patients, followed by large cell carcinoma (3.5%), adenosquamous carcinoma (3.0%) and non-small cell carcinoma not otherwise specified (3.0%). 11.9% of patients had an EGFR mutation: 48% of them presented a deletion on exon 19, 40.0% a L858R mutation on exon 21, 4.0% a G719X mutation in exon 18, 4.0% an insertion in exon 20, and 4% a T790M mutation in exon 20. The presence of an EGFR mutation was significantly associated with the female gender (two-third) (p<0.05) and the non-smoking status (two-third) (p<0.05). The prevalence of EGFR mutation (11.9%) detected in our Lebanese population is similar to that observed in the Caucasian population. This mutation is also significantly more frequent in females and non-smokers.


Follow-up of hypertension after aortic coarctation stent implantation based on safe and effective re-intervention: a retrospective cohort study.
Stent implantation for aortic coarctation (CoA) is associated with anatomical and hemodynamic advantages. Although the anatomy is corrected after the intervention, patients often still suffer from hypertension during the follow-up. Its risk factors remain unclear. There are only a few studies on the long-term follow-up of hypertension after stenting. This study aimed to investigate the factors influencing systemic hypertension after CoA by transcatheter stent placement. A total of 82 patients (native CoA: 37; men: 53) who underwent stent implantation for CoA at a median age of 123 months (range, 40 days-44 years) between January 2004 and September 2012 were included in this study. Patients with native or recurrent CoA after surgery, simple CoA or complex CoA associated with other cardiac anomalies were recruited in this study. Only stents that were expandable to adult size were implanted. After the initial stent implantation, the patients were followed up for 76.7 months (range, 6-151 months). Those who met the indications for a re-intervention underwent a balloon dilatation or stent implantation to relieve restenosis and alleviate the hypertension caused by restenosis. Patients with hypertension were treated with anti-hypertensive agents. In the initial intervention, 87 stents were implanted in 82 patients. Seventy-two patients (87.8%) were diagnosed with hypertension before treatment, but only 23 (28.0%) patients had hypertension at the last follow-up, which is a number significantly lower than that before the intervention (P<0.001). Cox regression analysis showed that age at stent implantation was significantly correlated with the incidence of hypertension, which indicates that the younger the patient receiving the intervention, the lower the incidence of hypertension. Moreover, the incidence of hypertension in follow-up is related to the diagnosis. It was higher in the patients with simple CoA than those with complex CoA. There was no significant correlation between native CoA and recurrent CoA. The incidence of hypertension after CoA stent implantation was significantly lower than that before the intervention. Age at stent implantation is an essential influencing factor for paradoxical hypertension after CoA stent implantation. Complex CoA in patients was related to a significantly lower prevalence of follow-up hypertension.


Molecular and functional expression of voltage-operated calcium channels during osteogenic differentiation of human mesenchymal stem cells.
We used the patch-clamp technique and RT-PCR to study the molecular and functional expression of VOCCs in undifferentiated hMSCs and in cells undergoing osteogenic differentiation. L-type Ca2+ channel blocker nifedipine did not influence alkaline phosphatase activity, calcium, and phosphate accumulation of hMSCs during osteogenic differentiation. This study suggests that osteogenic differentiation of hMSCs does not require L-type Ca2+ channel function. During osteogenic differentiation, mesenchymal stem cells from human bone marrow (hMSCs) must adopt the calcium handling of terminally differentiated osteoblasts. There is evidence that voltage-operated calcium channels (VOCCs), including L-type calcium channels, are involved in regulation of osteoblast function. We therefore studied whether VOCCs play a critical role during osteogenic differentiation of hMSCs. Osteogenic differentiation was induced in hMSCs cultured in maintenance medium (MM) by addition of ascorbate, beta-glycerophosphate, and dexamethasone (ODM) and was assessed by measuring alkaline phosphatase activity, expression of osteopontin, osteoprotegerin, RANKL, and mineralization. Expression of Ca2+ channel alpha1 subunits was shown by semiquantitative or single cell RT-PCR. Voltage-activated calcium currents of hMSCs were measured with the whole cell voltage-clamp technique. mRNA for the pore-forming alpha1C and alpha1G subunits of the L-type and T-type Ca2+ channels, respectively, was found in comparable amounts in cells cultured in MM or ODM. The limitation of L-type Ca2+ currents to a subpopulation of hMSCs was confirmed by single cell RT-PCR, where mRNA for the alpha1C subunits was detectable in only 50% of the cells cultured in MM. Dihydropyridine-sensitive L-type Ca2+ currents were found in 13% of cells cultured in MM and in 12% of the cells cultured in ODM. Under MM and ODM culture conditions, the cells positive for L-type Ca2+ currents were significantly larger than cells without Ca2+ currents as deduced from membrane capacitance; thus, current densities were comparable. Addition of the L-type Ca2+ channel blocker nifedipine to the culture media did not influence alkaline phosphatase activity and the extent of mineralization. These results suggest that, in the majority of hMSCs, Ca2+ entry through the plasma membrane is mediated by some channels other than VOCCs, and blockade of the L-type Ca2+ channels does not affect early osteogenic differentiation of hMSCs.


Methods for separation of long-acting thyroid stimulator (LATS) from sera containing LATS and TSH.
Methods were devised for separation of long-acting thyroid-stimulator (LATS) from TSH in serum containing both thyroid stimulators by using Rivanol, concanavalin A (con A), or staphylococcal protein A. When 3-5 volumes of 0.5% Rivanol solution were mixed to serum containing TSH or LATS activity, LATS activity remained mainly with IgG in the supernatant fraction. On the contrary, TSH activity was precipitated. When 10 mg con A was added to 1 ml test serum, almost all TSH activity was precipitated, but LATS activity remained in the supernatant fraction, which consisted mainly of IgG and albumin. Almost all LATS activity and part of the TSH activity were precipitated by addition of more than 7.5% polyethylene glycol (PEG), which was therefore not useful for separation of the stimulators in serum. Affinity chromatography on staphylococcal protein A-Sepharose was also found to separate the two thyroid stimulators in serum. By this method LATS-immunoglobulin bound to the protein A column, but no binding of the biologic and immunologic activity of TSH was observed. The protein A method seems the most useful of these four methods for complete separation of both stimulators.


Antioxidant and antibacterial polyelectrolyte wound dressing based on chitosan/hyaluronan/phosphatidylcholine dihydroquercetin.
Antioxidant and antimicrobial wound dressings are the most favorable for acute and chronic wounds treatment. Herein, we formulated a multifunctional polyelectrolyte wound dressing membrane on the basis of chitosan (Ch) and hyaluronan (HA) enhanced by phosphatidylcholine dihydroquercetin (PCDQ). Physicochemical properties and microstructures of fabricated films were investigated adopting Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA) and scanning electron microscope (SEM). Furthermore, water uptakes, wettability profiles, surface roughness, and mechanical characteristics of the developed membranes were studied. The developed wound dressing revealed free radical scavenging potency, hemocompatibility with a tendency to enhance blood clotting. Furthermore, incorporation of PCDQ significantly promoted the antibacterial and anti-inflammatory activities of Ch/HA/PCDQ. Moreover, Ch/HA/PCDQ films exhibited cellular compatibility towards mouse fibroblast cells. The capability of Ch/HA/PCDQ to promote wound healing was evaluated using adult Wistar albino female rats. The in vivo findings demonstrated that Ch/HA/PCDQ films significantly ameliorated mouse full-thickness wounds as evidenced by a reduction in the wound area. Moreover, histological examinations of wounds dressed with Ch/HA/PCDQ illustrated a prominent re-epithelialization compared with wounds handled with the cotton gauze and Ch/HA dressings, exposing the efficiency of PCDQ. These findings emphasized that a Ch/HA/PCDQ membrane has outstanding potential for wound healing and skin regeneration.


Regulators of G1 cyclin-dependent kinases and cancers.
The mammalian cell cycle can be divided into four phases: G1 (gap phase 1), S (DNA synthesis), G2 (gap phase 2), and M (mitosis). Progression through each phase of the cell cycle is delicately controled by the activity of different cyclin-dependent kinases (CDKs) and their regulatory subunits known as cyclins. CDK2, CDK4, CDK6 and their associated cyclins control the G1 to S phase transition. The association of CDK4 or CDK6 with D-type cyclins is critical for G1 phase progression, whereas the CDK2-cyclin E complex is important for initiation of the S phase. Cancer can originate from dysregulation of these regulators. A variety of intrinsic and extrinsic signals were recently identified to regulate these G1 or G1/S CDKs and cyclins. Here we discuss the regulators of these protein kinases at different mechanistic level with a hope that these insights can be applied to develop therapeutic strategies for cancer treatment.


Risk factors for death in a cohort of patients with and without healthcare-associated infections in Finnish acute care hospitals.
We evaluated risk factors for death among hospitalised patients with healthcare-associated infections (HCAIs) using the McCabe classification and Charlson index to predict mortality. The study consisted of a cohort of 703 patients with HCAIs and 7531 patients without HCAI in acute care hospitals participating in the Finnish national prevalence survey in 2005. We used Centers for Disease Control and Prevention definitions for HCAIs and recorded the McCabe classification for comorbidity. We used the date from the prevalence survey and the patient's national identity code in order to retrieve data from the National Hospital Discharge Registry on discharge diagnoses (International Classification of Diseases-10 codes) for the Charlson index and the dates of death from the National Population Information System. Of all inpatients, 425 (5.2%) died within 28 days from the prevalence survey date; the death rate was higher in HCAI patients than in those without HCAI (9.8% vs 4.7%, P<0.001). In the multivariate regression analysis age >65 years, intensive care, McCabe classification and Charlson index, gastrointestinal system infection and pneumonia/other lower respiratory tract infections were independent predictors for death. The survival analysis, when adjusted by McCabe class or Charlson index, showed that HCAI reduced survival only among patients without severe underlying diseases. Certain types of HCAI increased the risk of death. The McCabe classification had advantages over the Charlson index as a predictor of death, because it was easier to collect from a prevalence survey.


Sera from Cameroon recognize proteins of Plasmodium falciparum isolates from geographically diverse areas of the world.
Immunological reactions of clinically-defined sera collected from 176 children and adults (3 to 63 years of age) living in malaria endemic regions of Cameroon were evaluated by ELISA, growth inhibition studies and immunoprecipitation assays using different parasite isolates from geographically diverse areas. The proportions of sera positive by ELISA and with positive growth inhibitory activity tended to increase with increased age. SDS-PAGE analyses of immunoprecipitates using [35S]methionine labelled parasite polypeptides revealed that a wide range of proteins was recognized by the sera. There were many similarities in the patterns of antigens immunoprecipitated in the different isolates, particularly when immune sera were used. Variability in response was more evident in sera collected from children. These findings suggest that strains may share components which generate protective immunity.


Oxalate homeostasis.
Oxalate homeostasis is maintained through a delicate balance between endogenous sources, exogenous supply and excretion from the body. Novel studies have shed light on the essential roles of metabolic pathways, the microbiome, epithelial oxalate transporters, and adequate oxalate excretion to maintain oxalate homeostasis. In patients with primary or secondary hyperoxaluria, nephrolithiasis, acute or chronic oxalate nephropathy, or chronic kidney disease irrespective of aetiology, one or more of these elements are disrupted. The consequent impairment in oxalate homeostasis can trigger localized and systemic inflammation, progressive kidney disease and cardiovascular complications, including sudden cardiac death. Although kidney replacement therapy is the standard method for controlling elevated plasma oxalate concentrations in patients with kidney failure requiring dialysis, more research is needed to define effective elimination strategies at earlier stages of kidney disease. Beyond well-known interventions (such as dietary modifications), novel therapeutics (such as small interfering RNA gene silencers, recombinant oxalate-degrading enzymes and oxalate-degrading bacterial strains) hold promise to improve the outlook of patients with oxalate-related diseases. In addition, experimental evidence suggests that anti-inflammatory medications might represent another approach to mitigating or resolving oxalate-induced conditions.


Involvement of Abnormal p-α-syn Accumulation and TLR2-Mediated Inflammation of Schwann Cells in Enteric Autonomic Nerve Dysfunction of Parkinson's Disease: an Animal Model Study.
The study was designed to investigate the pathogenesis of gastrointestinal (GI) impairment in Parkinson's disease (PD). We utilized 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg) and probenecid (250 mg/kg) to prepare a PD mice model. MPTP modeling was first confirmed. GI motility was measured using stool collection test and enteric plexus loss was also detected. Intestinal phosphorylated α-synuclein (p-α-syn), inflammation, and S100 were assessed using western blotting. Association between Toll-like receptor 2(TLR2) and GI function was validated by Pearson's correlations. Immunofluorescence was applied to show co-localizations of intestinal p-α-syn, inflammation, and Schwann cells (SCs). CU-CPT22 (3 mg/kg, a TLR1/TLR2 inhibitor) was adopted then. Success in modeling, damaged GI neuron and function, and activated intestinal p-α-syn, inflammation, and SCs responses were observed in MPTP group, with TLR2 related to GI damage. Increased p-α-syn and inflammatory factors were shown in SCs of myenteron for MPTP mice. Recovered fecal water content and depression of inflammation, p-α-syn deposition, and SCs activity were noticed after TLR2 suppression. The study investigates a novel mechanism of PD GI autonomic dysfunction, demonstrating that p-α-syn accumulation and TLR2 signaling of SCs were involved in disrupted gut homeostasis and treatments targeting TLR2-mediated pathway might be a possible therapy for PD.


Low expression of KLF17 is associated with tumor invasion in esophageal carcinoma.
KLF17 belongs to the Sp/KLF zinc-finger protein family as a regulator in tumor development. However, its expression and biologic function has remained unclear in EC. The esophageal carcinoma tissue samples and adjacent normal tissues were obtained from the Second Hospital of Hebei Medical University. Immunohistochemistry, Western blot, and transfection were applied to evaluate the expression and clinical significance of KLF17 in esophageal cancer. In this study, we showed that KLF17 was overexpressed in esophageal normal samples compared to the cancer. Moreover, KLF17 was upregulated at lymph node non-metastatic cancer tissues when compared to metastatic cancer tissues. KLF17 overexpression decreased EC cell proliferation, migration and invasion ability. In contrast, the knockdown of KLF17 increased EC cell proliferation, migration and invasion ability. These results suggest that KLF17 inhibits tumor development and may serve as a potential therapeutic target.


Effects of the modified excision combined with bidirectional photodynamic therapy on refractory hidradenitis suppurativa: a retrospective study.
To describe the clinical features of refractory hidradenitis suppurativa (HS) patients (Hurley stageII and stage III) and evaluate the efficacy of combined treatment of the modified excision with bidirectional photodynamic therapy (PDT). A retrospective, multicenter study was conducted in 35 refractory HS patients. They were treated with the modified excision combined with bidirectional PDT. The outcomes, patients' satisfaction, adverse effects, and the Dermatology Life Quality Index (DLQI) were observed. There were more males than females (6:1). The axilla was the most frequently affected region (37.5%). All patients had experienced treatment failures before and had good response to our combined therapy (clearance rate > 75%). The average time required for complete wound healing was 11 days. After 1 year of follow-up, no significant recurrence was observed. The DLQI decreased significantly after the combined treatment. The comprehensive evaluation of scar and the deformation showed good cosmetic results after treatment. Reversible adverse events such as small patchy blackness, necrosis, or ulcer in the tip of the flap occurred in six patients (17.1%). Of the 35 patients, 30 were very satisfied with the treatment. This case series finds that the modified excision combined with bidirectional PDT may hold promise for radical treatment of Hurley stage II and stage III.


Weight loss and side-effects of liraglutide and lixisenatide in obesity and type 2 diabetes mellitus.
Glucagon-like peptide-1 receptor agonist (GLP-1 RA) is used to treat obesity or type 2 diabetes mellitus (DM). We compared weight loss and side-effects between patients with and without DM using GLP-1 RA. This was a retrospective cohort study based on electronic medical records. Patients were categorized into three groups: liraglutide without DM (LiRa_NL), liraglutide with DM (LiRa_DM), and lixisenatide with DM (LiXi_DM). Six-month outcomes were evaluated for weight loss, side-effect types, and onset discontinuation of GLP-1 RA. We enrolled 356 (190 LiRa_NL, 95 LiRa_DM, and 71 LiXi_DM) patients (women, 72.5 %; mean age, 43.7 ± 12.7 years; mean body mass index, 30.7 ± 5.2 kg/m2). The mean glycated hemoglobin (HbA1c) participants were 7.7 ± 2.1 %. Average weight loss was 2.9 ± 0.3 kg. The change in HbA1c was lower in the LiXi_DM group than in the LiRa_DM group (- 1.1 ± 0.2 % vs. - 0.4 ± 0.1 %, P < 0.05). The LiRa_DM group showed a more effective weight loss (- 3.0 ± 0.4 kg) than the LiXi_DM group (- 0.9 ± 0.4 kg) (P < 0.05). Approximately 30 % of the patients reported experiencing side-effects, with gastrointestinal side-effects being the most frequent (20.5 %). The median side-effect onset was 1.9 ± 0.1 months from first treatment. The rate of GLP-1 RA discontinuation was 72.8 %. Discontinuation rates due to side-effects were 75.7 %, 68.9 %, and 64.4 % in the LiRa_NL, LiRa_DM, and LiXi_DM groups, respectively. The LiRa_NL group showed the most weight loss, although the discontinuation rate was high. Most side-effects occurred at 1-2 months. When prescribing GLP-1 RA, education concerning side-effects and discontinuation is needed to enhance treatment adherence.


Soluble biomarkers development in osteoarthritis: from discovery to personalized medicine.
Specific soluble biomarkers could be a precious tool for diagnosis, prognosis and personalized management of osteoarthritic (OA) patients. To describe the path of soluble biomarker development from discovery to clinical qualification and regulatory adoption toward OA-related biomarker qualification. This review summarizes current guidance on the use of biomarkers in OA in clinical trials and their utility at five stages, including preclinical development and phase 1 to phase 4 trials. It also presents all the available regulatory requirements. The path through the adoption of a specific soluble biomarker for OA is steep but is worth the challenge due to the benefit that it can provide.


Chemometrics-assisted analysis of chemical impurity profiles of tabun nerve agent using comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry.
A route determination strategy through non-targeted screening of chemical attribution signatures was developed to identify tabun samples from three different synthetic routes. The CAS profiles of tabun samples were obtained by comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometer (GC×GC-TOFMS). The structures of 109 CAS were identified by NIST library and mass spectrometry fragment analysis. A few identified compounds could be traced to impurities in precursor compounds used in tabun synthesis. Based on the gas chromatography/mass spectrometry peak data of the selected CAS, partial least squares-discriminant analysis (PLS-DA) was used to extract the chemical attribution signatures of the characteristic compounds. The trained PLS-DA model performed well, with the lowest specificity and sensitivity values of 1.000 and 0.882, respectively. The performance of the PLS-DA model was further verified by unknown sample test set. The model demonstrated its ability to differentiate all the unknown tabun samples. The stability of chemical attribution signatures from different time periods was also investigated, and was further evaluated.


Cloning and nucleotide sequence of a linear DNA plasmid from Xanthophyllomyces dendrorhous (Phaffia rhodozyma).
Extrachromosomal elements were found in a strain of X. dendrorhous, and were characterized as linear DNA forming two well defined groups, pPh1 with 3 high-copy-number molecules, pPh11 (6.9 kb), pPh12 (5.7), pPh13 (4.7), and pPh2 with 2 low-copy-number molecules, pPh21 (3.6 kb), pPh22 (3.0). A 4077 bp fragment from pPh13 was cloned in pUC18 (pDK1) and sequenced (accession no. AJ 278,424). Seven putative ORF and some possible regulator sequences were defined.


Human Data Science.
Most data science is about people, and opinions on the value of human data differ. The author offers a synthesis of overly optimistic and overly pessimistic views of human data science: it should become a science, with errors systematically studied and their effects mitigated-a goal that can only be achieved by bringing together expertise from a range of disciplines.


Determinants of person-centered maternity care at the selected health facilities of Dessie town, Northeastern, Ethiopia: community-based cross-sectional study.
Person-centered maternity care is providing care that is respectful and responsive to individual women's preferences, needs, and values and ensuring that their values guide all clinical decisions during childbirth. Although person-centered health care is one of the factors that increase client satisfaction and increased health service utilization in Ethiopia, little is known about predictors of person-centered maternity care. Therefore, the aim of this study was to identify the determinant factors of person-centered maternity care among mothers who gave birth in selected health facilities in Dessie town, Northeastern, Ethiopia. A community-based cross-sectional study was conducted with a total of 317 study participants at Dessie town selected by a simple random sampling technique. The data was coded and entered Epi-data version 4.4 and analyzed using SPSS version 23. Descriptive statistics was presented using tables and figures. Multivariable linear regression analysis was used to identify factors associated with Person-Centered Maternity Care. Two sides P-value < 0.05 was taken to declare statistically significant. Overall, 310 study participants participated with a response rate of 97.8%. In multivariable linear regression, rural residence (β = -4.12; 95% CI: -7.60, -0.67), family average monthly income ≤ 3000 birr (β = -6.20, 95% CI: -9.40, -3.04), night time delivery(β = -2.98, 95%CI: -5.90, -0.06), dead fetus outcome during delivery (β = -12.7; 95% CI: -21.80, -3.50), and 2-7 days health facility length of stay (β = -5.07, 95% CI: -9.20, -0.92) were significantly decreased Person Center Maternity Care score, whereas private health institution delivery (β = 14.13, 95% CI: 7.70, 20.60) is significantly increased Person centered maternity care score. This study revealed that most of the factors that affect person-centered maternity care are modifiable factors. Therefore, Primary attention should be given to improve the quality of care through effective communication between clients and providers at each level of the health care delivery system to increase the uptake of high-quality facility-based births.


Structural systems biology and multiscale signaling models.
We review current advances in experimental as well as computational modeling and simulation approaches to structural systems biology, whose overall aim is to build quantitative models of signaling networks while retaining the crucial elements of molecular specificity. We briefly discuss the current and emerging experimental and computational methods, particularly focusing on hybrid and multiscale methods, and highlight several applications in cell signaling with quantitative and predictive capabilities. The scope of such models range from delineating protein-protein interactions to describing clinical implications.


Validity and interrater reliability of a regional mock oral board examination.
There have been decreasing pass rates recently on the American Board of Surgery Certifying Examination (ABSCE). General surgery residents from the University of Pittsburgh Medical Center, the West Penn Allegheny Health System, the Conemaugh Health System, and Mercy Hospital participate in a mock oral board examination, which is similar to the ABSCE. The aims of the study are to compare examinee performance on the mock oral boards with the ABSCE and to evaluate the interrater reliability of examiner pairs. In this retrospective study from 2003 to 2010, outcomes on the mock oral boards and the first attempt of the ABSCE for chief residents were compared for the 4 regional residency programs. Interrater reliability for examiner pairs was evaluated with agreement and kappa statistics. Nonparametric statistics were performed, with α = 0.05. A total of 32 of 38 (84.2%) chief residents passed the mock oral boards. The median score for each of the 3 rooms was 6 (clear pass). A total of 37 of 38 (97.4%) residents passed the ABSCE. The sensitivity of the mock oral boards was 83.8%, with a positive predictive value of 96.9%, and an accuracy of 81.6%. A total of 25 of 47 (53.2%) examiner pairs were from the same residency institution, whereas 22 of 47 (46.8%) were from different institutions. The median agreement was 100% (interquartile range (IQR) [100% - 100%]). The median kappa statistic was 1.00 (IQR [0.38-1.00]). The Mann-Whitney U tests showed no difference in agreement or kappa for examiner pairs from the same or from different institutions (p> 0.05). The mock oral boards have substantial sensitivity and positive predictive value in relation to the ABSCE. There are also very high levels of interrater agreement and interrater reliability. This regional mock oral board examination is valuable for ABSCE preparation.


[Not Available].
The results support the view that apart from the pathogenic and allergological relevance of microbial emissions from garbage, secondary fungal metabolites, and thus toxicological aspects, deserve further attention.


Oxycodone-acetaminophen versus celecoxib for postoperative pain in knee osteoarthritis patients after total knee arthroplasty: a randomized, controlled study.
Oxycodone-acetaminophen is a synergic combination of semisynthetic opioid agonis and analgesic/antipyretic agent, which improves analgesic efficacy. This randomized, controlled study intended to evaluate the analgesic efficacy and tolerance of oxycodone-acetaminophen compared to celecoxib alone in post-total knee arthroplasty (TKA) knee osteoarthritis patients. One hundred and six knee osteoarthritis patients were randomized into oxycodone-acetaminophen group (N = 54) and celecoxib group (N = 52) at a 1:1 ratio. Each patient orally received oxycodone-acetaminophen (5 mg/325 mg, four times per day) or celecoxib (200 mg, twice per day) from 2 h to day (D) 3 after TKA; meanwhile, each patient received 2-day patient-controlled analgesia (PCA). The primary outcome was pain visual analog scale (VAS) score at rest; other assessments were the secondary outcomes. Pain VAS scores at rest at D1, D2, D3, and pain VAS scores at flexion at D0.5, D1, D2, D3 were lower in oxycodone-acetaminophen group compared to celecoxib group (all P < 0.050). Besides, extra (P < 0.001) and total (P < 0.001) PCA consumption were declined in oxycodone-acetaminophen group compared with celecoxib group. Furthermore, patients' satisfaction score at D3 (P = 0.012) and D7 (P = 0.043) was higher in oxycodone-acetaminophen group versus celecoxib group. Hospital for special surgery knee score (HSS) at preoperation, M1, and M3 did not differ between the two groups (all P > 0.050). The incidences of all adverse events were not varied between oxycodone-acetaminophen and celecoxib groups (all P > 0.050). Oxycodone-acetaminophen exerts superior analgesic efficacy, patients' satisfaction, and similar tolerance compared to celecoxib in post-TKA knee osteoarthritis patients.


Four novel algal virus genomes discovered from Yellowstone Lake metagenomes.
Phycodnaviruses are algae-infecting large dsDNA viruses that are widely distributed in aquatic environments. Here, partial genomic sequences of four novel algal viruses were assembled from a Yellowstone Lake metagenomic data set. Genomic analyses revealed that three Yellowstone Lake phycodnaviruses (YSLPVs) had genome lengths of 178,262 bp, 171,045 bp, and 171,454 bp, respectively, and were phylogenetically closely related to prasinoviruses (Phycodnaviridae). The fourth (YSLGV), with a genome length of 73,689 bp, was related to group III in the extended family Mimiviridae comprising Organic Lake phycodnaviruses and Phaeocystis globosa virus 16 T (OLPG). A pair of inverted terminal repeats was detected in YSLPV1, suggesting that its genome is nearly complete. Interestingly, these four putative YSL giant viruses also bear some genetic similarities to Yellowstone Lake virophages (YSLVs). For example, they share nine non-redundant homologous genes, including ribonucleotide reductase small subunit (a gene conserved in nucleo-cytoplasmic large DNA viruses) and Organic Lake virophage OLV2 (conserved in the majority of YSLVs). Additionally, putative multidrug resistance genes (emrE) were found in YSLPV1 and YSLPV2 but not in other viruses. Phylogenetic trees of emrE grouped YSLPVs with algae, suggesting that horizontal gene transfer occurred between giant viruses and their potential algal hosts.


A comparative study on the pharmacokinetics of a traditional Chinese herbal preparation with the single herb extracts in rats by LC-MS/MS method.
The Er-Mu preparation (EMP) is a well-known traditional Chinese prescription that has been clinically employed for the treatment of asthma and bronchial inflammation for hundreds of years. Neomangiferin, mangiferin, peimine, peiminine, timosaponin BII and timosaponin AIII are the major active ingredients of EMP for their anti-inflammatory or anti-asthmatic effects. The aim of this study was to investigate the pharmacokinetics of the target compounds from the recipe of EMP and the single herb extracts of Anemarrhenae asphodeloides Bge. (ARR) and Fritillariae cirrhosae D.Don (FCB), and the influence of compatibility on the pharmacokinetics of the main active ingredients. The rats were randomly assigned to three groups and orally administered with the recipe of EMP and the single herb extracts of ARR and FCB, respectively. The concentrations of the target compounds in rat plasma were determined by an optimal liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS) and multiple reaction monitoring (MRM) with a multi-switching monitoring mode coupled with simple protein precipitation method, and the main pharmacokinetic parameters were estimated. Significant differences (p<0.05) were found in the pharmacokinetic parameters of neomangiferin, mangiferin, peimine and peiminine between the single ARR or FCB extract and the combination treatment (p<0.05). The developed HPLC-ESI-MS method by switching positive and negative ESI sources in a single run was successfully applied to study the pharmacokinetics of six compounds in SD rat, which was powerful in terms of sensitivity, selectivity, time savings and solvent consumption in the quantitative analysis of complex herbal medicines. It was surmised that formula compatibility could significantly influence the pharmacokinetics of EMP and our study has preliminarily elucidated the priority in the compatible administration of EMP based on pharmacokinetic studies.


The binaural interaction component in human ABR is stable within the 0- to 1-ms range of interaural time differences.
The effect of unilaterally delayed acoustic stimuli on binaural interaction was studied in 12 subjects with normal hearing. Auditory brainstem response (ABR) was obtained in the midline between the forehead and the neck, and click stimuli were unilaterally delayed at 0.2-ms intervals in the 0- to 1-ms range. Binaural interaction was evaluated by measuring the beta wave in the binaural difference waveform, i.e. the remainder after subtracting the binaurally evoked registration from the sum of the two monaural registrations. Computation of the binaural difference waveform showed the beta wave amplitude to be relatively stable throughout the 0- to 1-ms range of interaural time differences. This finding suggests stable binaural interaction within the range of interaural time differences where binaural click stimuli induce a binaurally fused intracranial image.