Immunological studies of uveitis. 2. Immune complex containing retinal S antigen in patient with chronic intractable uveitis.
A case of chronic uveitis resistant to steroid treatment was reported where plasma exchange therapy, in contrast, had a remarkable effect on reducing the cystoid macular edema and retinal phlebitis. The removed plasma showed an elevated level of immune complex, and Western blotting demonstrated that this immune complex in the plasma contained retinal S antigen.


COOH-terminal processing of polypeptide D1 of the photosystem II reaction center of Scenedesmus obliquus is necessary for the assembly of the oxygen-evolving complex.
Mutant LF-1 of the green alga Scenedesmus obliquus has been described by Metz and co-workers (Metz, J. G., Pakrasi, H., Seibert, M., and Arntzen, C. J. (1986) FEBS Lett. 205, 269-274) to be inactive for light-driven oxygen evolution, despite a functional Photo-system II reaction center. A polypeptide, D1, implicated in the ligation of the primary photoreactants of photosystem II, was shown to migrate with an apparent higher molecular mass on LDS-PAGE in the mutant than in the wild-type (WT) strain. We show here that polypeptide D1 is synthesized in a precursor form in Scenedesmus WT. Following synthesis and insertion into the thylakoid membrane, a 1.5-2-kDa oligopeptide is clipped off with a half-time of 1-2 min, yielding the mature 34-kDa form of the polypeptide. No processing of polypeptide D1 from mutant LF-1 was observed to take place. We show here that polypeptide D1 of LF-1 displays an identical proteolytic fingerprint pattern to the precursor D1 polypeptide of the wild-type strain. These both have molecular masses about 1.5-2 kDa higher than that of the mature WT polypeptide. A polyclonal antibody elicited by a synthetic oligopeptide (14-mer), predicted from the psbA gene nucleotide sequence to be homologous to the COOH terminus of the precursor D1 of spinach, cross-reacts only with D1 of mutant LF-1 and not with mature D1 of spinach, Chlamydomonas, or of Scenedesmus WT. This observation demonstrates that the greater molecular mass of polypeptide D1 from mutant LF-1 and of Scenedesmus WT precursor D1 is derived from a COOH-terminal extension. We conclude that the LF-1 mutant lacks the appropriate nuclear-encoded protease which processes polypeptide D1 at its COOH terminus from the precursor to the mature form. Such processing would appear to be a necessary step toward the stable incorporation of manganese into the oxygen-evolving site.


Cyclin D1 immunohistochemical staining to separate benign from malignant mesothelial proliferations.
The separation of benign from malignant mesothelial proliferations is a morphologically difficult problem. Mutations/deletions of components of the Hippo pathway are frequent in malignant mesotheliomas, and one downstream effect of aberrant Hippo signaling is increased production of cyclin D1. We examined expression of cyclin D1 nuclear staining in two tissue microarrays containing 52 reactive epithelial mesothelial proliferations, 51 reactive spindle cell mesothelial proliferations, 54 epithelial mesotheliomas, and 22 sarcomatous/desmoplastic mesotheliomas. When present, cyclin D1 staining was always strong, hence the arrays were scored as 0, 1-25%, 26-50%, 51-75%, and 76-100% staining. Both arrays showed a similar pattern. Reactive epithelial proliferations generally showed no staining (42/52 cases) or 1-25% staining (10/52 cases) with no cases showing >25% staining. Overall for reactive epithelial proliferations the maximum staining was 14.8% and mean 1.1 ± 2.9%. For epithelial mesotheliomas 39/54 (72%) cases demonstrated >25% staining, with 8/54 in the 26-50% staining range, 9/54 in the 51-75% range, and 22/54 in the >75% range. Combinations of staining using cyclin D1 >50% plus BAP1 or MTAP loss in epithelial mesotheliomas produced about a 10% increase in sensitivity. Reactive spindle cell proliferations showed a broader range of staining with 27/51 in the 1-25% range, 5/51 in the 26-50% range, and 1/51 >50%. Eleven of 22 sarcomatous/desmoplastic mesotheliomas scored 50% or greater. We conclude that for epithelial mesothelial proliferations, the finding of >50% of tumor cells staining supports a diagnosis of epithelial mesothelioma with 100% specificity but only modest (57%) sensitivity.


Case Report: Unilateral Cranial Nerve VI Palsy Secondary to Intracranial Hypotension.
Intracranial hypotension is a condition that occurs from a cerebrospinal fluid leak. Various visual symptoms have been associated with this condition. Cranial nerve VI (CN VI) palsies are the most common ocular manifestation, as the abducens nerve is prone to injury because of its intracranial anatomical course. This case report presents a CN VI palsy secondary to intracranial hypotension from ventriculoperitoneal shunt overfiltration. Diagnosis, treatment, and management considerations are discussed. No identifiable health information was included in this case report. A 70-year-old White man was referred to the eye clinic for evaluation of binocular horizontal diplopia. The patient had a recent history of a left ventriculoperitoneal shunt for a persistent cerebrospinal fluid leak after complex mastoid surgery. The patient was also symptomatic for positional headaches, which improved in a recumbent position. He was diagnosed with a left CN VI palsy secondary to intracranial hypotension from a ventriculoperitoneal shunt overfiltration. The patient was followed up by neurosurgery for shunt adjustments to resolve the overfiltration. Binocular horizontal diplopia was managed conservatively with Fresnel prism. Intracranial hypotension should be considered in patients presenting with cranial nerve palsies and positional headaches. Obtaining neuroimaging and comanaging with neurology or neurosurgery are advised to make prompt diagnosis and treatment. Careful clinical monitoring and conservative diplopia therapy are recommended as visual symptoms improve upon resolution of the cerebrospinal fluid leak.


Dosage of colloidal bismuth subcitrate in duodenal ulcer healing and clearance of Campylobacter pylori.
Sixty consecutive patients with endoscopically proven duodenal ulcers were given colloidal bismuth subcitrate tablets either as 120 mg q.d.s. or 240 mg b.d., in a randomized single-blind study. The efficacy of each regimen was determined by endoscopic examination and antral biopsy at 4 weeks; if the ulcer remained unhealed, treatment was continued and endoscopy repeated at 8 weeks. The ulcer-healing efficacy of the two regimens was identical; however, in the four times daily group only 27% remained Campylobacter pylori positive after 8 weeks of treatment compared with 58% of the twice-daily group. Similarly, only 21% of twice daily patients were free of histological gastritis compared with 42% of the four times daily patients.


Outcome and clinical-biological characteristics of patients with advanced breast cancer undergoing removal of ovarian/pelvic metastases.
Patients with metastatic breast cancer to the ovary, without tumor debulking and after systemic therapy, have a 5-year survival rate < 10%. We analyzed a series of 37 patients, operated in one institution over 10 years, for both the primary tumor (PT) and ovarian/pelvic metastases (OPM). Estrogen receptors (ER), progesterone receptors (PgR), HER-2 and Ki-67 were determined. Patients were predominantly young: 27 (73%) patients were < 50 years. Average ER/PgR expression did not change significantly between PT (mean ER = 66%, PgR = 35%) and OPM (mean ER = 67%, PgR = 28%). Median time to OPM was 42 months (range 0-176); 5-year OS after OPM was 51% (95% confidence interval 32% to 67%). When combining ER and PgR status, patients with ER > 50% on both PT and OPM and with PgR > 50% on PT and/or OPM (good prognosis, 11 patients) had a better outcome versus0 patients with ER and PgR ≤ 50% on both PT and OPM (bad prognosis, eight patients) and also versus the remaining patients (intermediate prognosis, 18 patients), P value = 0.010. Patients with OPM from breast cancer show a favorable prognosis after tumor debulking, whether it was radical or not, especially when a high expression of ER and PgR is present in both PT and OPM.


Predictors of mortality in younger and older patients with heart failure and preserved or reduced left ventricular ejection fraction.
Although half of elderly patients with heart failure have preserved left ventricular ejection fraction (LVEF), little is known about predictors of mortality in this group. We reviewed the charts of 400 patients hospitalized at an academic medical center in 1999 with a principal discharge diagnosis of heart failure. Patients were divided into 4 groups on the basis of age > or =75 or <75 years and the presence of preserved or reduced LVEF. Vital status was ascertained as of October 2001. A total of 373 patients (mean age 69.1 years, 56.0% female, 47.5% nonwhite) underwent echocardiography to assess LVEF. Of these, 216 patients were <75 years of age (81 with preserved LVEF [group 1, 21.7%] and 135 with reduced LVEF [group 2, 36.2%]), and 157 were > or =75 years of age (81 with preserved LVEF [group 3, 21.7%] and 76 with reduced LVEF [group 4, 19.6%]). After a mean follow-up of 25 months, independent predictors of mortality among the 4 groups differed substantially: group 1, male sex, prescription of a calcium-channel blocker, and diuretic dose at discharge; group 2, blood urea nitrogen (BUN), lower hemoglobin level, and not being prescribed a beta-blocker at discharge; group 3, BUN; and group 4, older age, history of myocardial infarction, severity of reduced LVEF, and diuretic dose. In patients with heart failure, predictors of mortality vary by age and by the presence of preserved or reduced LVEF. Traditional predictors of mortality in patients with reduced LVEF may not apply to elderly patients with preserved LVEF.


Evaluation of side effects of mechanical cleaning with an anionic detergent on granite cladding tiles.
One of the aims of Goal 11 of the UN's 2030 Agenda for Sustainable Development is to make human settlements sustainable. Some effort should therefore focus on developing maintenance strategies for buildings. Polished granite cladding tiles are very popular for use as flooring material in private and public buildings. These tiles are often treated by mechanical cleaning with detergents and scrubbers, and anionic detergents without chelating agents are usually used to prevent damaging the material. In this study, the anionic detergent Teepol® was applied to granite tiles in order to determine the effect of the treatment on the surface properties of this stone, i.e. appearance, colour, gloss, roughness and hydrophobicity. The results obtained were explained by scanning electron microscopy observations, which enabled characterisation of the microtexture of the surfaces, chemical contamination and any damage to the different granite-forming minerals. The results were compared with those obtained for tiles cleaned by the same mechanical procedure but with tap water in place of detergent and for tiles treated by immersion in water without any mechanical action. In summary, the properties evaluated were affected by the extraction of the typical oxyhydroxylated iron forms that fill cracks in the granite and by the formation of new cracks due to the mechanical action. Moreover, colour changes and the chemical contamination (C-rich deposits with Na, S, Cl, Ca and Mg) hindered the effectiveness of the cleaning procedure.


Purine activity of RNase T1RV is further improved by substitution of Trp59 by tyrosine.
Ribonuclease T1 is an enzyme that cleaves single-stranded RNA with high specificity after guanylyl residues. Although this enzyme is a very good characterized protein with respect to structure and enzymatic function, we were only recently successful in generating RNase T1-RV, a variant where the specificity was changed from guanine to purine. As this change of substrate specificity was made at the cost of activity, the aim was now to further improve the overall activity of the enzyme. Therefore, we have substituted the tryptophan in position 59 by tyrosine. This substitution led to an increase of enzymatic activity in comparison to variant RV to 425%. As the extent of this enhancement is unique so far we have crystallized and analyzed the structure of this variant in order to get more insights into the reasons for this. Here, we present the crystal structure of this so-called RNase T1-R2 at 2.1A resolution. The structure was determined by molecular replacement using the coordinates of the RV variant (PDB entry: 1Q9E). The data were refined to an R-factor of 18.7% and R(free) of 24%, respectively. The asymmetric unit contains three molecules and the crystal packing is very similar to that of variant RV.


Staging of esophageal cancer by EUS: staging accuracy revisited.
EUS plays an important role in the preoperative staging of esophageal cancer. Recent data have called into question the staging accuracy of EUS, particularly in patients with early disease. Our goals were to assess our institution's EUS staging accuracy by experienced endosonographers in a contemporary cohort of patients encompassing a wide range of disease stages and to assess staging accuracy after dilation of malignant strictures. Retrospective data review. Single tertiary care center. A total of 42 patients with esophageal cancer undergoing preoperative EUS staging without neoadjuvant chemoradiotherapy between December 1999 and December 2004 were evaluated. EUS T and N stage sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. EUS accurately predicted T stage in 76% of cases and N stage in 89% of cases. Staging accuracy for T3 versus T1 and T2 disease and for N0 versus N1 disease was not significantly different. In 11 cases, malignant strictures required dilation, with 6 tumors being passable post dilation. Post dilation, T staging accuracy was 80% in impassable tumors and 100% in passable tumors, and N staging accuracy was 100% in the passable tumors. Relatively small number of patients. EUS accurately predicts T and N stage in patients with a range of disease stages. EUS provides good staging accuracy after dilation of malignant strictures regardless of whether full tumor traversal post dilation is possible.


[Primary localization of the pathologic process in amyotrophic lateral sclerosis].
The clinico-electromyographical study was conducted in 120 patients with motor disturbances in amyotrophical lateral sclerosis. Comparing the clinical and electromyographical data in different variants of this disease the authors make a conclusion on the simultaneous damage of peripheral and central mononeurons from the very onset of the disease. Along with this the latter is damaged not only primarily, but secondarily as a result of trans-synaptic degerneration due to pathology of the segmental-nucleus motor cells.


Nanomicellar-curcumin exerts its therapeutic effects via affecting angiogenesis, apoptosis, and T cells in a mouse model of melanoma lung metastasis.
Curcumin is a natural phytochemical polyphenol with significant anti-cancer effects and negligible side effects. In this study, the therapeutic capacity of nanomicellar-curcumin for treating lung metastasis was evaluated in an immunocompetent mouse model of metastatic melanoma. Two doses of nanomicellar-curcumin (i.e. 10 and 20 μM) were used to induce cytotoxicity in 3 melanoma cell lines. A total of 60 mice were allocated to 20 mice in each of three groups (10 for survival and 10 for assays). Groups were no treatment control, PBS control, nanomicellar-curcumin 20 mg/kg IP 4 times a week, for three weeks). Immunohistochemistry, TUNEL assay, and Western blots were used on lung samples. Nanomicellar-curcumin inhibited the in vitro growth of B16 F10 melanoma cells at 20 μM over 72 h. In vivo, 20 mg/kg nanomicellar-curcumin injected IP, delayed tumor cell growth and significantly extended mouse survival rate. Tumor infiltration of regulatory T cells and angiogenesis were reduced, while IFN-γ and CXCL10 were increased. Nanomicellar-curcumin can inhibit lung metastasis and growing melanoma via activation of apoptosis, activated T cells and inhibition of angiogenesis, tumor growth and regulatory T cells.


The presence of neutrophils in human cutaneous ultraviolet-B inflammation.
We report the first observation of neutrophils in the dermal inflammatory infiltrate in human skin soon after moderate ultraviolet-B (UVB) irradiation. Thus human UVB-induced cutaneous inflammation, in this as in other respects, appears to resemble other human acute inflammatory responses to injury.


Alteration of cellular ribonucleases associated with murine oncogenic virus infection.
The ribonuclease activity of peripheral lymphocytes from Balb/c mice was studied at various intervals subsequent to infection of mice by oncornavirus. Lymphocytes from mice infected with Friend leukemia virus possessed elevation of RNase activity within 8 days subsequent to infection. Balb/c mice infected with Moloney sarcoma virus demonstrated an analogous elevation of RNase activity with 7-9 days postinfection. Diminishment of cellular RNase activity occurred in the Friend leukemia model concomitant to the occurrence of significant numbers of erythroblasts in the peripheral blood, while ribonuclease activity in lymphocytes from mice infected with Molney sarcoma virus returned to normal 1-2 weeks subsequent to host rejection of tumor. It is concluded that elevation of RNase activity within the lymphocyte represents an early event in oncogenic viral infection within these two tumor models. The possible meaning of elevation of RNase activity is a target (the lymphocyte) not predestined to undergo neoplastic transformation is discussed.


The prevalence and contributing risk factors of coronavirus disease 2019 infection in patients with metabolic syndrome.
Components of metabolic syndrome (MetS) was reported to contribute to severe and worse outcomes of coronavirus disease 2019 (COVID-19). Hereby, we evaluated the association of MetS and its components with susceptibility to COVID-19. Here, 1000 subjects with MetS were recruited that were diagnosed via the International Diabetes Federation (IDF) criterion. Real-time PCR was exerted to detect SARS-CoV-2 in the nasopharyngeal swabs. Among the MetS patients, 206 (20.6%) cases were detected to have COVID-19. Smoking (OR = 5.04, 95%CI = 3.53-7.21, P < 0.0001) and CVD (OR = 1.62, 95%CI = 1.09-2.40, P = 0.015) were associated with increased chance of COVID-19 infection in the MetS patients. BMI was significantly higher (P = 0.0001) in MetS cases with COVID-19 than those without COVID-19. Obesity was associated with increased susceptibility to COVID-19 in MetS patients (OR = 2.00, 95%CI = 1.47-2.74, P < 0.0001). Total cholesterol, TG, LDL were significantly higher in the MetS cases with COVID-19 than those without COVID-19. Dyslipidemia was associated with increased chance of COVID-19 (OR = 1.50, 95%CI = 1.10-2.05, P = 0.0104). FBS level was significantly higher in the MetS cases with COVID-19. T2DM was associated with increased risk of COVID-19 in MetS patients (OR = 1.43, 95%CI = 1.01-2.00, P = 0.0384). Hypertension was associated with increased chance of COVID-19 in the MetS patients (OR = 1.44, 95%CI = 1.05-1.98, P = 0.0234). MetS and its components, like obesity, diabetes, dyslipidemia, cardiovascular complications were associated with increased chance of COVID-19 infection development and probably with aggravated symptoms in such patients.


Methodologic Quality and Statistical Reporting of Physical Therapy Randomized Controlled Trials Relevant to Musculoskeletal Conditions.
To investigate the methodologic quality and statistical reporting of reports of trials indexed on the Physiotherapy Evidence Database (PEDro) classified in the musculoskeletal subdiscipline, and to analyze the characteristics of the trials that can predict trial report quality. Cross-sectional study based on a collection of randomized controlled trials. We randomly selected 19% of trials coded as musculoskeletal from PEDro. Methodologic quality was assessed using the PEDro scale. We assessed aspects of the trial using 9 items from the Consolidated Standards of Reporting Trials (CONSORT) statement. We performed multivariate linear regression analysis models to predict the total PEDro score. Not applicable. Not applicable. Not applicable. Not applicable. A total of 1404 articles were included in the analysis. The mean total PEDro scale score was 5.27±1.63 points, which reflects low methodologic quality. There was a slight improvement in the quality of articles over time. The characteristics that predicted the total PEDro scale score were endorsement of the CONSORT statement, sample size calculation, lower number of primary outcomes, evaluation of electrotherapy as intervention, if the trial reported the research design in the title, reporting of participant flow diagram, years since publication (most recent trials), and trials published in English. The quality of the trials in musculoskeletal physical therapy is suboptimal. The use of reporting checklists (eg, CONSORT statement) should be mandatory in all journals. Journal reviewers and journal editors should also use the CONSORT statement during the review process.


Dispersion of Antibiotic Resistance Genes (ARGs) from stored swine manure biogas digestate to the atmosphere.
Biogas digestate is a reservoir of antibiotic resistance genes (ARGs) and could pose a high health risk to both human and animals if the host microorganisms of ARGs become aerosolized. The purpose of this study was to investigate the diversity and relative abundance characteristics of aerosol-loaded ARGs from biogas digestate during storage, and to explore whether the change of ARGs in biogas digestate directly affect the dispersion of aerosol-loaded ARGs. This study reported for the first time that 28 of 42 ARG subtypes detected in the biogas digestate could be dispersed to the atmosphere via aerosol dispersion in a lab-scale dynamic emission vessels experiment. The relative abundance or diversity of ARGs in aerosols were different from that in biogas digestate, and no significant correlation were observed between the relative abundance of ARGs in biogas digestate and aerosols. The dominant ARGs were tetracycline resistance genes in biogas digestate and β-lactam resistance genes in aerosols. The process of biogas digestate storage reduced the total relative abundance of targeted ARGs in biogas digestate, decreased by 0.35 copies/16S rRNA after 30 days of storage, but increased the abundance of some ARG subtypes, including tetM, tetX, tetQ, tetS, ermF and sul2. High-concerned ARGs, including NDM-1, mcr-1 and vancomycin resistance genes (including vanA, vanB, vanRA and vanSA), were found in biogas digestate, and NDM-1 and vanB were also detected in aerosols. These results indicated a potential risk of ARGs dispersion during biogas digestate storage. Further research on the dispersion of ARGs from biogas digestate is required to elucidate the emission mechanism and develop mitigation measures.


Parthenogenesis without costs in a grasshopper with hybrid origins.
The rarity of parthenogenetic species is typically attributed to the reduced genetic variability that accompanies the absence of sex, yet natural parthenogens can be surprisingly successful. Ecological success is often proposed to derive from hybridization through enhanced genetic diversity from repetitive origins or enhanced phenotypic breadth from heterosis. Here, we tested and rejected both hypotheses in a classic parthenogen, the diploid grasshopper Warramaba virgo. Genetic data revealed a single hybrid mating origin at least 0.25 million years ago, and comparative analyses of 14 physiological and life history traits showed no evidence for altered fitness relative to its sexual progenitors. Our findings imply that the rarity of parthenogenesis is due to constraints on origin rather than to rapid extinction.


Extension to the orbit from paraorbital disease. The sinuses.
Disease of the sinuses frequently involves the orbit. Infection, mucocele, and tumor of the sinuses originally may present with orbital findings. Imaging attempts to evaluate the interface between sinus and orbit. Imaging findings reflect the integrity of the sinus mucosa, the thin bony wall, and the more resistant fibrous periorbita. Both CT and MR imaging play a role in this evaluation.


Some effects of chemotherapeutic drugs. III. Short- and long-term effects of cis-platinum on various hematopoietic compartments and on the kidney of the mouse.
cis-Platinum is a relatively new active anticancer drug. In the study described in this paper, its toxicity was tested in the hematopoietic and renal systems of mice after six injections of 3 mg per kg body weight at 10-day intervals. Acute hematopoietic toxicity was studied by determining the survival of pluripotent (CFU-S) and granulo-macrophagic unipotent (GM-CFC) stem cells. The number of nucleated cells in the bone marrow and in the spleen and the number of granulocytes in the blood were determined. Renal toxicity was studied by histological examination of kidneys from treated mice compared with control animals. The number of stem cells in the bone marrow and in the spleen decreased during the treatment. One year after treatment, the autorepopulating ability of CFU-S was still diminished in spite of normal numbers of these cells. No renal damage could be demonstrated by light microscopy when the protocol described was used.


Development and validation of the Overall Personality Assessment Scale (OPERAS).
The aim of the present research was to develop a short measure for the five-factor model personality traits, which allows scores free of social desirability and acquiescence effects to be obtained. Scales were created using recently developed methods to control response bias effects in a sample of 3,838 participants from a wide age range. The scales were answered in person or on-line. Exploratory and confirmatory factor analysis showed the expected five factor structure. Furthermore, the scales showed good psychometric properties in that they had good reliability, temporal stability and convergence with the widely used Big-Five measures. The test developed in the paper presents acceptable psychometric properties, and it is suitable for individuals up from 13 years old. Because the method used to control response bias means that scales' scoring is based upon factorial scores instead of raw scores, we have also developed an internet public application that can be used to obtain these scores.


Short-term neonatal outcomes in vaginal breech delivery: Results of a retrospective single-centre study.
Vaginal breech delivery (VBD) has been widely discouraged over the last two decades due to associated neonatal risks. However, many gynaecologists are still challenging this approach, at least in selected settings. To study short-term neonatal outcomes in singleton pregnancies undergoing VBD. Retrospective cohort study conducted on singleton pregnancies who delivered in breech presentation between 2012 and 2019. Neonatal complications in terms of mortality, umbilical artery (UA) pH, 5-min Apgar score, and postnatal admission to neonatal intensive care unit (NICU) were evaluated. Overall, 804 breech deliveries were considered. Of these, 53.86 % had VBD, 26.62 % had emergency caesarean sections (CS) and 19.53 % had elective CS. No perinatal deaths were reported. After multivariate adjustment, VBD was associated with higher incidence of UA pH < 7.10 compared with both elective and emergency CS. No significant associations were found between VBD and UA pH < 7.00 or 5-min Apgar score < 3 or < 7. No significant differences in NICU hospitalization were observed for different modes of delivery. Gestational age was inversely correlated with UA pH < 7.00, 5-min Apgar score < 3 and < 7, and NICU hospitalization. VBD in an experienced setting does not increase the risk of negative short-term perinatal outcomes significantly. Gestational age was the most important risk factor for low UA pH or 5-min Apgar score and NICU hospitalization, independent of mode of delivery.


Template copy number and the sensitivity of quantitative PCR for Plasmodium falciparum in asymptomatic individuals.
The identification of asymptomatic individuals with Plasmodium falciparum infection is difficult because they do not seek medical treatment and often have too few asexual parasites detectable using microscopy or rapid diagnostic tests (≤ 200 parasites per μl). Quantitative PCR (qPCR) may provide greater sensitivity and permits estimation of the initial template DNA concentration. This study examined the hypothesis that qPCR assays using templates with higher copy numbers may be more sensitive for P. falciparum than assays based on templates with lower copy numbers. To test this hypothesis, ten qPCR assays for DNA sequences with template copy numbers from 1 to 160 were compared using parasite DNA standards (n = 2) and smear-positive filter paper blots from asymptomatic smear-positive subjects (n = 96). Based on the testing of P. falciparum parasite DNA standards and filter paper blots, cycle threshold values decreased as the concentrations of template DNA and template copy numbers increased (p < 0.001). Likewise, the analytical and clinical sensitivities of qPCR assays for P. falciparum DNA (based on DNA standards and filter paper blots, respectively) increased with template copy number. Despite the gains in clinical sensitivity from increased template copy numbers, qPCR assays failed to detect more than half of the filter paper blots with low parasite densities (≤ 200 asexual parasites per μl). These results confirm the hypothesis that the sensitivity of qPCR for P. falciparum in the blood of individuals with asymptomatic infection increases with template copy number. However, because even the most sensitive qPCR assays (with template copy numbers from 32 to 160) detected fewer than 50% of infections with ≤ 200 asexual parasites per μl, the sensitivity of qPCR must be increased further to identify all smear-positive, asymptomatic individuals in order to interrupt transmission.


Two Genealogies of Human Values: Nietzsche Versus Edward O. Wilson on the Consilience of Philosophy, Science and Technology.
In the twenty-first century, Stephen Hawking proclaimed the death of philosophy. Only science can address philosophy's perennial questions about human values. The essay first examines Nietzsche's nineteenth century view to the contrary that philosophy alone can create values. A critique of Nietzsche's contention that philosophy rather than science is competent to judge values follows. The essay then analyzes Edward O. Wilson's claim that his scientific research provides empirically-based answers to philosophy's questions about human values. Wilson's bold new hypothesis about the 'social conquest of the earth' challenges Nietzsche's vision of philosophy's mission. Confronting both Nietzsche and Wilson, the essay then considers three theoretical proposals for a consilience of philosophy, science, engineering and technology. The conclusion presents a working African model of consilience that addresses the existential problem of poverty in the Global South.


Combined effects of polystyrene microplastics and cadmium on oxidative stress, apoptosis, and GH/IGF axis in zebrafish early life stages.
The toxicological interactions of microplastics (MPs) and heavy metals have been paid much attention in aquatic organism. The mechanisms are not fully clear, particularly in fish early life stages. To the end, zebrafish embryos were exposed to 500 μg/L MPs, 5 μg/L cadmium (Cd), and their combination for 30 days. Body weight, adsorption characteristics of Cd onto MPs, Cd accumulation, oxidative stress, apoptosis, and growth hormone/insulin-like growth factor-I (GH/IGF) axis were examined. Exposure to MPs and Cd alone reduced body weight, which was aggravated by co-exposure. An increase in reactive oxygen species (ROS) levels was observed in larvae exposed to Cd or MPs + Cd, suggesting an induction of oxidative stress. Lipid peroxidation levels were not affected by exposure to MPs and Cd alone but dramatically enhanced by co-exposure, which may be explained by the reduction of total antioxidant capacity (TAOC) and activity levels of Mn-superoxide dismutase (Mn-SOD) and catalase (CAT) after co-exposure. Increased apoptotic cells were observed in the vertebral body of larvae exposed to Cd, the esophagus of larvae exposed to MPs, and both organs of larvae exposed to MPs + Cd, which was further confirmed by changes in the activities of Caspase-3, Caspase-8 and Caspase-9. PCR array on the transcription of genes related to growth, oxidative stress and apoptosis was examined, showing that the combined exposure resulted in greater magnitude of changes than MPs and Cd alone. The results indicate that MPs can enhance the negative effects of Cd on growth, oxidative damage and apoptosis in early life stages of zebrafish. However, the adsorption of Cd onto MPs was not observed and the combined exposure did not increase the Cd content in larvae compared to the single Cd exposure, implying that vector role of MPs in Cd uptake is negligible.


Heparin inhibits spontaneous thrombolysis and the thrombolytic effect of both streptokinase and tissue-type plasminogen activator. An in vitro study of the dislodgement of platelet-rich thrombi formed from native blood.
Two in vitro models of coronary thrombolysis in man, i.e. dislodgement of thrombi formed from non-anticoagulated human blood, either by (i) shear-stress or (ii) interaction of platelets with type I collagen fibre, were studied. Heparinization (1 U/ml) of blood prior to thrombus formation by (i) strongly inhibited spontaneous dislodgement (P less than 0.0001). Heparin (1 U/ml), when added with streptokinase (SK) or tissue-type plasminogen activator (rt-PA) prior to thrombus formation, considerably delayed thrombolysis. Furthermore, thrombolysis occurred much earlier when thrombi were perfused with SK or rt-PA in native than in heparinized blood. Heparin inhibited binding of 125I-rt-PA (17%, P less than 0.02) and plasminogen (88%, P less than 0.0005) to platelets activated by ADP in citrated platelet-rich plasma. We conclude that heparin interferes with the fibrinolytic system at the surface of activated platelets. Our findings suggest that heparin administration prior to thrombolytic therapy for acute myocardial infarction should be questioned.


Persistent replication of SARS-CoV-2 in a severely immunocompromised patient treated with several courses of remdesivir.
Microbiological response of SARS-CoV-2 to remdesivir in immunocompromised patients has not been evaluated. We present the case of a severely immunocompromised patient with persistent replication of SARS-CoV-2, who required different courses of remdesivir. Short courses of remdesivir might be insufficient in immunocompromised patients due to prolonged viral clearance.


Integrated strategy of derivatization and separation for sensitive analysis of salvianolic acids using capillary electrophoresis with laser-induced fluorescence detection.
Salvianolic acids (SAs) are a class of natural active substances that have been widely used in clinical treatment and food adjuvant therapy. In this work, we found that SAs could form the ternary complex with borax and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), thereby sensitizing their weak intrinsic fluorescence to maximized 92-fold for salvianolic acid B (SAB). The formation of ternary complex was dynamic and could complete once mixed, and the fluorescence intensity remained stable within 3 h. On this basis, an integrated strategy of derivatization and separation was proposed for the sensitive analysis of SAs using capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection. After the systematic investigation, a solution consisting of 20 mM borax and 20 mM HP-β-CD (pH 8.5) was selected as the running buffer. By the direct injection of SAs, the dynamic derivatization was realized in the capillary, and the baseline separation was achieved within 6 min, with the detection limits of 1.2-21.2 nM for four SAs (S/N=3). Then, the developed CE-LIF method was successfully applied to the quantitative analysis of SAs in four traditional ginsengs, including Salvia miltiorrhiza, Codonopsis pilosula, Panax quinquefolius and Panax ginseng with the recoveries ranging from 95.2% to 110.7%. Except for four target SAs, a large number of unknown electrophoretic peaks had also been observed in four ginsengs, and then were utilized for the identification of ginseng species via principal component analysis. Furthermore, a hypoxia/reoxygenation model was constructed using Rat cardiomyocyte H9c2 cells, and subsequently, the developed method was applied to continuously monitor the consumption of SAB in cell culture medium after its intervention.


An improved air break receiver unit. A design suited to high-vacuum scavenging systems.
The advantages of active anti-pollution systems are discussed, in particular those depending on a high vacuum and narrow-bore pipework. The design requirements of a receiver for such a system are set out and the detailed design of such a receiver described. The performance of the unit is assessed with special regard to efficiency and safety.


Uptake effects of toxic heavy metals from growth soils into jujube and persimmon of China.
Compared with other agricultural plants, information about uptake effects of toxic heavy metals from growth soils into persimmon and jujube are scarce. In this study, the single and comprehensive uptake effects of five toxic heavy metals (Pb, As, Cd, Cr, and Hg) between the two fruits and their growth soils were investigated. The results showed that the average concentrations of heavy metals in the two fruits were found to be 30 (Pb), 6.6 (As), 2.3 (Cd), 38 (Cr), and 0.33 (Hg) μg/kg, respectively. The average concentrations of heavy metals in their growth soils were 26.31 (Pb), 9.63 (As), 0.12 (Cd), 57.6 (Cr), and 0.049 (Hg) mg/kg, respectively. An uptake effect was observed for the two fruits. The values of Nemerow pollution index (NPI) in the two fruits and their growth soils were 0.10 and 0.55, respectively. The average bioconcentration factor (BCF) values of Pb, As, Cd, Cr, and Hg in the two fruits were 0.0012, 0.00075, 0.021, 0.00077, and 0.012, respectively. Based on the residue levels of toxic heavy metals in the growth soils and soil parameters, the prediction models for NPI and BCF were established, with the adjusted regression coefficients of 0.65 (NPI) and 0.81 (BCF). The contribution rates of different soil parameters to NPI were 21.7% (OC), 16.1% (Pb), 17.1% (Cr), 19.8% (Cd), and 25.4% (As), respectively. The contribution rates of different soil parameters to BCF were 10.2% (OC), 9.4% (Cr), and 80.4% (Cd), respectively.


Longitudinal development of obesity in the post-Fontan population.
An elevated body mass index (BMI) in childhood is a significant risk factor for cardiovascular disease, and it may pose an additional risk to children and adults with palliated univentricular congenital heart disease. However, little is known about longitudinal development of obesity in this population. The objective of this study is to determine the prevalence of overweight (OW) and obese (OB) habitus at the time of Fontan palliative surgery, to track changes in BMI after surgery, and ultimately to determine whether factors such as gender, ethnicity, preoperative heart defect and ventricular dominance are associated with later development of OW or OB. A retrospective chart review of 84 patients undergoing Fontan palliation was performed. Demographic data including gender, ethnicity, preoperative heart defect and ventricular dominance were recorded. Height, weight and BMI were obtained at the time of Fontan and on a yearly basis post surgery. At the time of Fontan palliation, 10.7% of patients were OB or OW. During the five years following palliation, the percentage of OB or OW patients trended upward, from 20.3% the year following surgery to 30% at 5 years post Fontan. Repeated measures generalized estimating equation showed a significant association between Hispanic ethnicity and increased BMI Z-scores for the 5 years after Fontan palliation (P<0.001); there was no association between BMI Z-scores and patient sex, lesion or ventricular dominance. During the first 5 years after Fontan palliation, there is a trend toward increasing percentages of OB and OW patients. In addition, there is a significant association between Hispanic ethnicity and being OW or OB before and after surgery. Further study is needed to determine whether OW/OB status is associated with worse health outcomes in this patient population.


[Doctrinal bases of health activities].
During his administration as Minister of Health, doctor Guillermo Soberón led one of the most important structural changes in health of this century in Mexico. All along the process, an ideological and doctrinal corpus was created. In this paper the main streams of this corpus are presented.


Purification and molecular characterization of a novel mannose-specific lectin from Dioclea reflexa hook seeds with inflammatory activity.
A novel lectin present in Dioclea reflexa seeds (DrfL) was discovered and described in this study. DrfL was purified in a single step by affinity chromatography in a Sephadex G-50 column. The lectin strongly agglutinated rabbit erythrocytes and was inhibited by α-methyl-D-mannoside, D-mannose, and D-glucose. The hemagglutinating activity of DrfL is optimum at pH 5.0-7.0, stable up to 50 °C, and dependent on divalent cations. Similar to other lectins of the subtribe Diocleinae, the analysis by mass spectrometry indicated that DrfL has three chains (α, β, and γ) with masses of 25,562, 12,874, and 12,706 Da, respectively, with no disulfide bonds or glycosylation. DrfL showed inflammatory activity in the paw edema model and exhibited low cytotoxicity against Artemia sp.


Hemorrhagic stroke in setting of severe COVID-19 infection requiring Extracorporeal Membrane Oxygenation (ECMO).
To highlight the increased risk of hemorrhagic stroke secondary to postulated COVID-19 mediated vasculopathy with concomitant ECMO related bleeding complications. COVID-19 has shown to be a systemic illness, not localized to the respiratory tract and lung parenchyma. Stroke is a common neurological complication. In particular, critically ill patients on ECMO are likely at higher risk of developing hemorrhagic stroke. 38-year-old man presented with fever, cough, and shortness of breath. Due to severe respiratory failure, he required ECMO support. Subsequently, he was found to have left temporal intraparenchymal hemorrhage. Overall, his clinical course improved, and he was discharged with minimal neurological deficits. Although intracranial hemorrhage is a known complication of ECMO, patients with COVID-19 infection may be at a higher risk of cerebrovascular complications due to vasculopathy.


Endoscopic and Surgical Management of Gastroesophageal Reflux Disease.
Approximately, 10% to 15% of patients in the United States experience gastroesophageal reflux symptoms on a weekly basis, negatively affecting the quality of life and increasing the risk of reflux-related complications. For patients with symptoms recalcitrant to proton pump inhibitor (PPI) therapy or those who cannot take PPIs, surgical fundoplication is the gold standard. The preoperative workup is complex but vital for operative planning and ensuring good postoperative outcomes. Most patients are highly satisfied after fundoplication, though transient dysphagia, gas bloating, and resumption of PPI use are common postoperatively. Multiple newer technologies offer safe alternatives to fundoplication with similar outcomes.


Strong opioids for noncancer pain due to musculoskeletal diseases: Not more effective than acetaminophen or NSAIDs.
The classification of morphine as a step III analgesic, based on pharmacological data, creates a strong bias toward a belief in the efficacy of this drug. However, double-blind emergency-room trials showed similar levels of pain relief with intravenous acetaminophen as with intravenous morphine in patients with renal colic, low back pain or acute limb pain. In patients with chronic noncancer low back pain, morphine and other strong opioids in dosages of up to 100mg/day were only slightly more effective than their placebos, no more effective than acetaminophen, and somewhat less effective than nonsteroidal anti-inflammatory drugs (NSAIDs). In patients with osteoarthritis, strong opioids were not more effective than NSAIDs and, in some studies, than placebos. The only randomized controlled trial in patients with sciatica found no difference with the placebo. Chronic use of strong opioids can induce hyperalgesia in some patients. Hyperpathia with increased sensitivity to cold leading the patient to request higher dosages should suggest opioid-induced hyperalgesia. Pain specialists in the US have issued a petition asking that strong opioids be used in dosages no higher than 100mg/day of morphine-equivalent, in an effort to decrease the high rate of mortality due to the misuse and abuse of strong opioids (10,000 deaths/year in the US). Healthcare providers often overestimate the efficacy of step III analgesics, despite pain score decreases of only 0.8 to 1.2 points.


[Effect of micropolarization of focal and extrafocal brain structures on experimental epilepsy].
The influence of micropolarization (MCP, 0.05-0.75 muA) was studied in chronic experiments on rabbits with epileptogenic foci provoked by penicillin (doses of 500 and 1000 U) injection into the motor cortex. A single MCP of extrafocal structure (the corpus calossum, nucleus caudatus) and the site of the focus inhibited the development of seizure reactions. Numerous MCP of the focus facilitated the seizure reactions. These effects may be explained not only by the specific role of the structures studied in the processes of the formation and propagation of the excitation, their initial functional state, but also by the dependence of the activity of these structures on the MCP regimen.


Chronic hyperglycemia and insulin concentrations in fetal lambs.
Insulin concentrations were measured in 20 chronically instrumented fetuses of 10 sheep with alloxan-induced chronic hyperglycemia and 10 control sheep to examine if the hyperglycemia resulted in high fetal insulin concentration. Additionally, in six neonatal lambs of three chronically hyperglycemic ewes and three control sheep, insulin concentrations were measured after intravenous glucose injection. After a 2-month period of significant maternal hyperglycemia, no relationship between concentrations of fetal glucose and insulin could be detected. The mean fetal glucose concentration was 3.5 +/- 0.5 mmol/L in the hyperglycemic group and 0.6 +/- 0.1 mmol/L in the control group. Mean fetal insulin levels were 12.5 +/- 1.4 and 10.7 +/- 1.3 microU/ml, respectively. The neonatal lambs of the hyperglycemic and control ewes showed comparable concentrations of glucose and insulin after infusion of glucose. It is presumed that persistent high glucose levels depress the insulin secreting capacity of the fetal pancreas.


Effect of Liposome-Encapsulated Zoledronic Acid on Microenvironment of Hepatocellular Carcinoma May Depend on the Ratio Between M1 and M2 Polarized Macrophages.
We studied the effect of zoledronic acid encapsulated into liposomes (L-ZOL) on tumorassociated macrophages in the stroma of hepatocellular carcinoma xenograft. Liposomes were prepared from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-snglycero-3-phospho-sn-1-glycerol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] using thin film method and loaded with zoledronic acid. It was shown that L-ZOL promoted apoptosis of RAW264.7 cells, eliminate much more protumoral M2 macrophages than antitumoral M1 macrophages in the tumor xenograft, and did not significantly reduce the size of xenograft in 6 days. Thus, the effect of treatment depends on the ratio between antitumoral M1 and protumoral M2 polarized macrophages in the tumor.


Cultural adaptation and validation of the Systemic Sclerosis Quality of Life questionnaire into Arabic language.
Systemic sclerosis (SSc) is a chronic connective tissue disease affecting all quality of life (QoL) parameters. In addition to clinical assessment, QoL measures should be included in patient assessment. There is no Arabic tool specific for assessing QoL in Arabic SSc patients; therefore, this work was designed to translate the SScQoL questionnaire, culturally adapt and check its reliability and validity. Based on the principle of translation and cross-cultural adaptation in other language, the SScQoL questionnaire was translated into Arabic. Correlation of SScQoL scores for 50 patients with Short Form Health Survey (SF-36) scores has been tested for convergent validity and discriminate validity evaluated by stratifying clinical parameters of patients and disease subtypes. The intraclass correlation coffee (ICC) was used to assess reliability by interviewing patients twice 14 days apart. Correlations were present between SScQoL scores and physical and mental component scores of SF-36 questionnaire. We found strong negative correlation between the physical component of SF-36 and QoL function, QoL emotion, QoL total scores (r = - 0.654**, r = - 0.512**, r = - 0.540**) and moderate negative correlation present between SF-36 mental component and QoL function, QoL emotion, QoL social, and QoL total (r = - 0.314*, r = - 0.486**, r = - 0.357*, r = - 0.433*). Also, significant association (P < 0.05*) between scores of total QoL and visceral involvements (GIT involvement, pericardial effusion, and LVDD) was evident. The Arabic edition of SScQoL has a Cronbach's alpha of 0.78. The translated Arabic version is a valid and reliable tool to assess Egyptian SSc patients' QoL. Key Points • The SScQoL questionnaire items have a convergent validity with physical and mental component scores of SF-36, and discriminant validity with visceral involvement. • The Arabic edition of SScQoL is reliable with a Cronbach's alpha of 0.78.


Risk factors for periappendiceal adhesions in acute appendicitis: a retrospective comparative study.
Acute appendicitis usually requires immediate surgical treatment, but appendectomies were difficult for some patients with severe periappendiceal adhesions. We investigated risk factors of intraoperative adhesions to help surgeons make better treatment plans for appendicitis. We retrospectively analyzed 186 cases diagnosed with acute appendicitis and underwent surgery in Shandong Provincial Hospital affiliated to Shandong First Medical University between January 2018 and December 2019. According to the degree of intraoperative adhesions, they were divided into mild, moderate and severe groups. Then, we analyzed a number of preoperative factors contributed to adhesions, suppuration and perforation during appendectomy in 186 patients. Contrast to the moderate group (MoG) and the mild group (MiG), the severe degree of adhesions group (SG) had a higher intraoperative perforation and suppuration rate, a greater likelihood of conversion to open and more postoperative complications. Multivariable logistic regression analysis showed that recurrent appendicitis and high neutrophil percentage were independently associated with periappendiceal adhesions. The preoperative ultrasonography (US) revealed periappendiceal fluid and high neutrophil percentage were independently associated with appendix suppuration. A high preoperative neutrophil percentage was independently associated with appendix perforation. Recurrent appendicitis and preoperative high neutrophil percentage were risk factors of periappendiceal adhesions; preoperative US revealed periappendiceal fluid and high neutrophil percentage were risk factors of appendix suppuration; and a high preoperative neutrophil percentage was a risk factor of appendix perforation.


Ketamine may be related to reduced ejection fraction in children during the procedural sedation.
Ketamine is a dissociative anesthetic agent with sympathomimetic effects used commonly for procedural sedation in emergency department. The present study aimed to reveal the effect of ketamine on myocardium by measuring ejection fraction (EF). Patients less than 9 years old undergoing procedural sedation with ketamine secondary to minor trauma composed the study population by convenience sampling. Study patients received ketamine at a dose of 1.5 mg/kg. A cardiologist performed the measurements of cardiac contractility pre-ketamine and 10 min after the ketamine administration. A total of 22 patients were enrolled into the study. Patient recruitment has been ceased after the 22nd patient because of the thought that more patients would not provide additional information. The study subjects had a mean age of 3.5 ± 2.2 years and 14 (64%) of them were male. EF reduced in 14 (63.6%) patients (mean: 5.6 ± 3.1; median: 5; interquartile range (IQR): 3.75-7; minimum-maximum (min-max): 1-14). Systolic blood pressures reduced in 10 of 14 patients with decreased EF and increased in 8 of 10 patients without decreased EF. The changes in systolic blood pressure in patients with decreased EF ( n = 14) were as follows: -7.6 ± 10.9; median: -7.5; IQR: -16.5 to 1.75; and min-max: -30 to 9. There were two patients with elevated high-sensitive troponin. Ketamine may reduce EF and systolic blood pressure in children less than 9 years old undergoing procedural sedation.


In vivo epiluminescence microscopy of pigmented skin lesions. II. Diagnosis of small pigmented skin lesions and early detection of malignant melanoma.
Pattern analysis by epiluminescence microscopy of pigmented skin lesions was tested in a study of 318 small pigmented skin lesions that were diagnostically equivocal when examined with the naked eye. An improvement of clinical diagnosis was achieved by epiluminescence microscopy for practically all lesions, both benign and malignant, and was equally impressive for melanocytic and nonmelanocytic lesions. Improvement in diagnostic accuracy was as follows: for small nodular melanomas, from 50% to 70%; for superficial spreading melanoma in situ, from 46% to 80%; for invasive superficial spreading melanoma, from 64% to 90%; and for early lentigo maligna and lentigo maligna melanoma, from 67% to 88%. Conversely, the diagnosis of pigmented Spitz nevi improved from 46% to 93% and of pigmented basal cell carcinomas from 60% to 90%, which appears equally important because most of these lesions had clinically been considered to represent melanomas. The use of epiluminescence microscopy also resulted in considerable improvement in the diagnosis of dysplastic nevi, which was particularly helpful in making therapeutic decisions. Epiluminescence microscopy greatly expands the diagnostic armamentarium available for pigmented skin lesions at a clinical level and thus increases the chances of detecting or ruling out melanoma in its earliest stages.


Inorganic substances and their uses in Nikolaos Myrepsos' Dynameron. Recent applications in modern therapy.
Inorganic compounds have been known and used since antiquity. Dynameron is the largest Byzantine medical manuscript divided into 24 sections, in accordance with the letters of the Hellenic alphabet, which contains 2667 recipes. The majority of them contain ingredients of plant origin, followed by animal origin, while fewer inorganic substances are quoted. In the present study, the latter ones are listed. Moreover, the information on the uses of inorganic ingredients in the treatment of many diseases in the late Byzantine era is presented and their evaluation in light of the modern Pharmacology and Toxicology.


Low molecular weight glutenin subunit gene Glu-B3h confers superior dough strength and breadmaking quality in wheat (Triticum aestivum L.).
Low molecular weight glutenin subunit is one of the important quality elements in wheat (Triticum aestivum L.). Although considerable allelic variation has been identified, the functional properties of individual alleles at Glu-3 loci are less studied. In this work, we performed the first comprehensive study on the molecular characteristics and functional properties of the Glu-B3h gene using the wheat cultivar CB037B and its Glu-B3 deletion line CB037C. The results showed that the Glu-B3h deletion had no significant effects on plant morphological or yield traits, but resulted in a clear reduction in protein body number and size and main quality parameters, including inferior mixing property, dough strength, loaf volume, and score. Molecular characterization showed that the Glu-B3h gene consists of 1179 bp, and its encoded B-subunit has a longer repetitive domain and an increased number of α-helices, as well as higher expression, which could contribute to superior flour quality. The SNP-based allele-specific PCR markers designed for the Glu-B3h gene were developed and validated with bread wheat holding various alleles at Glu-B3 locus, which could effectively distinguish the Glu-B3h gene from others at the Glu-B3 locus, and have potential applications for wheat quality improvement through marker-assisted selection.


The Drosophila single-minded gene encodes a nuclear protein with sequence similarity to the per gene product.
Mutations in the single-minded (sim) gene of Drosophila result in the loss of the precursor cells giving rise to the midline cells of the embryonic central nervous system. We have examined the structure of the sim product by sequencing a sim cDNA clone, and have also determined the subcellular localization of the protein and its developmental expression by staining embryos with an antiserum against a sim fusion protein. The results indicate that sim is a nuclear protein specifically expressed along the midline of the neuroepithelium, the same subset of cells that are missing in the mutant. No similarity is observed between sim and any known nuclear protein, but, surprisingly, it is similar to the Drosophila period (per) locus gene product, which controls the periodicity of biological rhythms.


Regulation of the Hippo Pathway Transcription Factor TEAD.
The TEAD transcription factor family is best known for transcriptional output of the Hippo signaling pathway and has been implicated in processes such as development, cell growth and proliferation, tissue homeostasis, and regeneration. Our understanding of the functional importance of TEADs has increased dramatically since its initial discovery three decades ago. The majority of our knowledge of TEADs is in the context of Hippo signaling as nuclear DNA-binding proteins passively activated by Yes-associated protein (YAP) and transcriptional activator with PDZ-binding domain (TAZ), transcription coactivators downstream of the Hippo pathway. However, recent studies suggest that TEAD itself is actively regulated. Here, we highlight evidence demonstrating Hippo-independent regulation of TEADs and the potential impacts these studies may have on new cancer therapeutics.


Management of Arrhythmias Associated with COVID-19.
Cardiac arrhythmias are known complications in patients with COVID-19 infection that may persist even after recovery from infection. A review of the spectrum of cardiac arrhythmias due to COVID-19 infection and current guidelines and assessment or risk and benefit of management considerations is necessary as the population of patients infected and covering from COVID-19 continues to grow. Cardiac arrhythmias such as atrial fibrillation, supraventricular tachycardia, complete heart block, and ventricular tachycardia occur in patients infected, recovering and recovered from COVID-19. Personalized care while balancing risk/benefit of medical or invasive therapy is necessary to improve care of patients with arrhythmias. Providers must provide thorough follow-up care and use necessary precaution while caring for COVID-19 patients.


Reversal of mitochondrial malate dehydrogenase 2 enables anaplerosis via redox rescue in respiration-deficient cells.
Inhibition of the electron transport chain (ETC) prevents the regeneration of mitochondrial NAD+, resulting in cessation of the oxidative tricarboxylic acid (TCA) cycle and a consequent dependence upon reductive carboxylation for aspartate synthesis. NAD+ regeneration alone in the cytosol can rescue the viability of ETC-deficient cells. Yet, how this occurs and whether transfer of oxidative equivalents to the mitochondrion is required remain unknown. Here, we show that inhibition of the ETC drives reversal of the mitochondrial aspartate transaminase (GOT2) as well as malate and succinate dehydrogenases (MDH2 and SDH) to transfer oxidative NAD+ equivalents into the mitochondrion. This supports the NAD+-dependent activity of the mitochondrial glutamate dehydrogenase (GDH) and thereby enables anaplerosis-the entry of glutamine-derived carbon into the TCA cycle and connected biosynthetic pathways. Thus, under impaired ETC function, the cytosolic redox state is communicated into the mitochondrion and acts as a rheostat to support GDH activity and cell viability.


Determination of 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine enantiomers in whole blood.
A method for the determination of the enantiomeric content of 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in microsamples (200 microliters) of whole blood is described. The method involves liquid-liquid extraction of MDA and MDMA from blood and derivatization with the chiral reagent N-trifluoroacetyl-L-prolyl chloride. Separation, identification and quantitation of diastereomeric derivatives is by gas chromatography-mass spectrometry. The analytical range of the assay is from 0.12 ng to 48 ng injected on-column. Details for the synthesis of the enantiomers of MDMA are also provided.


Synthesis of poly(sorbitan methacrylate) hydrogel by free-radical polymerization.
Hydrogels are materials with the ability to swell in water through the retention of significant fractions of water within their structures. Owing to their relatively high degree of biocompatibility, hydrogels have been utilized in a host of biomedical applications. In an attempt to determine the optimum conditions for hydrogel synthesis by the free-radical polymerization of sorbitan methacrylate (SMA), the hydrogel used in this study was well polymerized under the following conditions: 50% (w/v) SMA as monomer, 1% (w/w) alpha, alpha'-azo-bis(isobutyro-nitrile) as thermal initiator, and 1% (w/w) ethylene glycol dimethacrylate as cross-liking agent. Under these conditions, the moisture content of the polymerized SMA hydrogel was higher than in the other conditions. Moreover, the moisture content of the poly(SMA) hydrogel was also found to be higher than that of the poly(methyl methacrylate [MMA]) hydrogel. When the Fourier transform-infrared spectrum of poly(SMA) hydrogel was compared with that of poly(MMA) hydrogel, we noted a band at 1735-1730/cm, which did not appear in the Fourier transform-infrared spectrum of poly(MMA). The surface of the poly(SMA) hydrogel was visualized through scanning electron microscopy, and was uniform and clear in appearance.


Ack1 is a dopamine transporter endocytic brake that rescues a trafficking-dysregulated ADHD coding variant.
The dopamine (DA) transporter (DAT) facilitates high-affinity presynaptic DA reuptake that temporally and spatially constrains DA neurotransmission. Aberrant DAT function is implicated in attention-deficit/hyperactivity disorder and autism spectrum disorder. DAT is a major psychostimulant target, and psychostimulant reward strictly requires binding to DAT. DAT function is acutely modulated by dynamic membrane trafficking at the presynaptic terminal and a PKC-sensitive negative endocytic mechanism, or "endocytic brake," controls DAT plasma membrane stability. However, the molecular basis for the DAT endocytic brake is unknown, and it is unknown whether this braking mechanism is unique to DAT or common to monoamine transporters. Here, we report that the cdc42-activated, nonreceptor tyrosine kinase, Ack1, is a DAT endocytic brake that stabilizes DAT at the plasma membrane and is released in response to PKC activation. Pharmacologic and shRNA-mediated Ack1 silencing enhanced basal DAT internalization and blocked PKC-stimulated DAT internalization, but had no effects on SERT endocytosis. Both cdc42 activation and PKC stimulation converge on Ack1 to control Ack1 activity and DAT endocytic capacity, and Ack1 inactivation is required for stimulated DAT internalization downstream of PKC activation. Moreover, constitutive Ack1 activation is sufficient to rescue the gain-of-function endocytic phenotype exhibited by the ADHD DAT coding variant, R615C. These findings reveal a unique endocytic control switch that is highly specific for DAT. Moreover, the ability to rescue the DAT(R615C) coding variant suggests that manipulating DAT trafficking mechanisms may be a potential therapeutic approach to correct DAT coding variants that exhibit trafficking dysregulation.


Determining the Role of Dynamic Hyperinflation in Patients with Severe Chronic Obstructive Pulmonary Disease.
Dynamic hyperinflation due to increased respiratory frequency during exercise is associated with limitations in exercise capacity in patients with moderately severe chronic obstructive pulmonary disease (COPD). The present study assessed whether the manually paced tachypnea (MPT) test, sitting at rest, induces dynamic hyperinflation correlating with exercise capacity in patients with very severe COPD. Dynamic hyperinflation was induced by the MPT test, using a breathing frequency of 40/min for 1 min. Dynamic hyperinflation was defined as a 'change' in inspiratory capacity (IC) before and directly after the MPT test. At baseline, static hyperinflation by body plethysmography was measured, as well as the 6-min walking test and spirometry. We studied 74 patients with severe COPD (age 59 ± 9 years, FEV1 28 ± 10% predicted). All patients tolerated the MPT test well. It induced a significant decrease in IC: -0.65 ± 0.33 liters, p < 0.001, correlating with the 6-min walking distance (rho = -0.246, p = 0.034). Static hyperinflation [IC/total lung capacity (TLC)] at baseline correlated stronger with the 6-min walking distance (r = 0.582, p < 0.001). Multiple regression analysis showed that IC/TLC, but not dynamic hyperinflation, was the only independent predictor of walking distance. In patients with very severe COPD, dynamic hyperinflation measurement by the MPT test is feasible and contributes less importantly to exercise performance than static hyperinflation.


Methane production on thickened, pre-fermented manure.
Over 9 million dairy cows generate an estimated 226 billion kg of wet manure annually in the US. The purpose of this study was to demonstrate the viability of a novel two-stage anaerobic digestion (AD) process for producing methane-rich biogas on pre-fermented dairy manure. In summary, it was observed that AD of thickened pre-fermented manure can generate comparable biogas quantities to AD using raw manure, with enhanced methane content. Despite receiving a lower quality (i.e., partially biodegraded) substrate, biogas stoichiometry and overall process stability in the two-stage system was also comparable to AD receiving raw manure. Finally, the two-stage AD was more enriched with the acetoclastic methanogen Methanosarcinaceae (Msc; compared to AD of raw manure) and biogas production appeared closely linked with the Msc fraction. In fact, the enhanced enrichment of Msc likely contributed to the successful and stable operations.


[Not Available].
The results of a silage trial with DON contaminated ensiled wheat shows a good fermentation quality and a complete reduction of the DON content in the silage. The ensiling of DON contaminated corn meal shows a strong reduction from the DON content of the fermented corn meal. Also reduced the fermentation of whole plant maize the DON content. The present analytic of DON gives no answer about transformation and metabolism. Therefore more research is necessary in analytical methods and toxicity of DON in silage.


A three-step method for modular lymphadenectomy in gastric cancer surgery: The ability to retrieve sufficient lymph nodes and improve survival.
Systematic lymphadenectomy for the resection of sufficient lymph nodes is the most important part of curative resection in gastric cancer surgery. Here, we explore the outcomes of the three-step method for modular lymphadenectomy (TSMML) and determine its safety and efficacy, compared with the conventional method for lymphadenectomy (CML). From 2008 to 2011, 270 patients with gastric cancer were divided into 2 subgroups: the TSMML group and the CML group. Patients in the TSMML group had a significantly higher median number of retrieved lymph nodes (rLNs), lower median metastatic lymph node ratios (MLRs), and superior 5-year relapse-free survival (RFS) than the CML group. Moreover, the use of the TSMML procedure was an independent protective factor for RFS. No significant intergroup differences were found in morbidity or mortality in these two groups. The TSMML procedure is safe and effective and is easy to learn.


Combined laser treatment of actinic sun damage and acne scarring.
Since its approval for use in 2007, many surgeons have been using the laser for subcutaneous use, primarily for lipolysis, facial neck and body contouring, and skin tightening. Techniques have recently evolved to enable use of the subcutaneous laser with concurrent skin resurfacing techniques for improvement of photoaging and acne or facial scarring. The technique shows great promise in patients with facial aging and photodamage who are not deemed candidates for rhytidectomy surgery. With strict patient-selection criteria of mild to moderate facial laxity and mild to moderate photoaging, the procedure can be gratifying for the surgeon and patient alike.


Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial.
To assess the efficacy and safety of favipiravir in adults with mild-to-moderate coronavirus disease 2019 (COVID-19). In this randomized, open-label, parallel-arm, multicenter, phase 3 trial, adults (18-75 years) with RT-PCR confirmed COVID-19 and mild-to-moderate symptoms (including asymptomatic) were randomized 1:1 to oral favipiravir (day 1: 1800 mg BID and days 2-14: 800 mg BID) plus standard supportive care versus supportive care alone. The primary endpoint was time to the cessation of viral shedding; time to clinical cure was also measured. From May 14 to July 3, 2020, 150 patients were randomized to favipiravir (n = 75) or control (n = 75). Median time to the cessation of viral shedding was 5 days (95% CI: 4 days, 7 days) versus 7 days (95% CI: 5 days, 8 days), P = 0.129, and median time to clinical cure was 3 days (95% CI: 3 days, 4 days) versus 5 days (95% CI: 4 days, 6 days), P = 0.030, for favipiravir and control, respectively. Adverse events were observed in 36% of favipiravir and 8% of control patients. One control patient died due to worsening disease. The lack of statistical significance on the primary endpoint was confounded by limitations of the RT-PCR assay. Significant improvement in time to clinical cure suggests favipiravir may be beneficial in mild-to-moderate COVID-19.


Persistence of petroleum hydrocarbon contamination in sediments of the canals in Venice, Italy: 1995 and 1998.
Total hydrocarbon and selected polycyclic aromatic hydrocarbon (PAH) levels were examined in sediments collected from known problematic areas in the canals of Venice, Italy, in 1995 and 1998. Hydrocarbon concentrations were greatest in the interior canals, moderate in the partially enclosed locations and lowest in the open-water sites. Total hydrocarbon and PAH concentrations declined from 1995 to 1998. Ancillary data suggest that this decline may have been in response to the elimination of many industrial activities in the lagoon and to initiating an aggressive canal dredging program. The distributions of individual components were generally similar both years regardless of the total PAH concentration or the location of sample collected. PAH alkyl homolog distributions suggest that atmospheric deposition of petrochemical combustion products is the main source of PAHs to Venice's sediments. In some cases however, the presence of low levels of the two-ring naphthalene homologous series indicate additional low-level inputs of fresh oil.


Mental health and psychological resilience during the COVID-19 pandemic: A cross-cultural comparison of Japan, Malaysia, China, and the U.S.
The current study examined how psychological resilience acted as a buffer against mental health deterioration during the coronavirus disease 2019 (COVID-19) pandemic. We conducted an online survey in four countries (Japan, Malaysia, China, and the U.S.) to examine how psychological resilience functions toward the maintenance of mental health during the COVID-19 pandemic. We collected data from 1583 citizens from four countries via an online survey between October 14 and November 2, 2020. We gathered demographic data and measured mental distress (depression, anxiety, and stress) and fear of COVID-19. Data on sense of control, ego-resilience, grit, self-compassion, and resilience indicators were also collected. Sense of control was negatively associated with mental distress in all four countries. Self-compassion was negatively associated with mental distress in the samples from Japan, China, and the U.S. We also found an interaction effect for sense of control: the lower the sense of control, the stronger the deterioration of mental distress when the fear of COVID-19 was high. This study's cross-sectional design precludes causal inferences. Further, lack of data from people who were actually infected with the virus limits comparisons of people who were and were not infected. Finally, as this study only compared data from four countries, comparisons with more countries are needed. A sense of control and self-compassion may help buffer against mental health deterioration during the COVID-19 pandemic. Sense of control was consistently associated with mental health across cultures.


HLA system in relation to carbohydrate metabolism in lichen planus.
HLA antigens were determined in a group of fifty-two patients with lichen planus. In the group as a whole the frequency of A28 was increased but not significantly so. When the patients were subdivided according to the results of an oral glucose tolerance test, however, a highly significant increase in the frequency of A28 was found among the non-diabetic patients.


Imaging the "Hot Phase" of a Familiar Left-Dominant Arrhythmogenic Cardiomyopathy.
We describe the case of a young man with an initial diagnosis of acute myocarditis that was finally recognized as a familial left-dominant arrhythmogenic cardiomyopathy. The diagnostic process was also based on demonstration, serial cardiac magnetic resonance imaging, and typical patterns of myocardial damage, including features of the disease's inflammatory "hot phase".


Systematic review of program evaluation in baccalaureate nursing programs.
Program evaluation is a common practice in nursing education programs; however, evidence indicates that many schools only focus on program evaluation around the scheduled accreditation period, thus reducing the potential value of the evaluation. This systematic review explores the current program evaluation practices of prelicensure baccalaureate nursing programs. ERIC, CINAHL, and Scopus databases were searched to locate original research articles published in English. Twenty articles met the inclusion criteria. The purposes of the evaluated studies varied from needing to meet external accountability requirements to proposing conceptual frameworks and evaluation tools. However, most studies focused on summative evaluation assessing program products and on providing evidence of program evaluation based on descriptive data. Notably, few studies employed a rigorous method to evaluate and interpret program evaluation findings. Most studies solicited information from multiple stakeholder groups, with students being the most represented. Despite the wide range of data collection tools used in the reviewed studies, reporting of validity and reliability was limited. Student grade point average, graduation rate, NCLEX passing rate, and satisfaction with the learning experience were the most common variables. Further studies are needed to assess the effectiveness of current educational program evaluation practices in nursing education.


Benefits of universal gloving on hospital-acquired infections in acute care pediatric units.
To prevent transmission, some pediatric units require clinicians to wear gloves for all patient contacts during RSV season. We sought to assess whether a mandatory gloving policy reduced the risk of other health care-acquired infections (HAIs). This retrospective cohort study included all patients admitted to pediatric units of a tertiary care center between 2002 and 2010. Poisson regression models were used to measure the association between mandatory gloving and HAI incidence. Autoregressive models were used to adjust for time correlation. During the study period, 686 HAIs occurred during 363 782 patient-days. The risk of any HAI was 25% lower during mandatory gloving periods compared with during nongloving periods (relative risk [RR]: 0.75; 95% confidence interval [CI]: 0.69-0.93; P = .01), after adjusting for long-term trends and seasonal effect. Mandatory gloving was associated with lower risks of bloodstream infections (RR: 0.63; 95% CI: 0.49-0.81; P < .001), central line-associated bloodstream infections (RR: 0.61; 95% CI: 0.44-0.84; P = 0.003), and hospital-acquired pneumonia (RR: 0.20; 95% CI: 0.03-1.25; P= 0.09). The reduction was significant in the PICU (RR: 0.63; 95% CI: 0.42-0.93; P = .02), the NICU (RR: 0.62; 95% CI: 0.39-0.98; P = .04), and the Pediatric Bone Marrow Transplant Unit (RR: 0.52; 95% CI: 0.29-0.91, P = .02). Universal gloving during RSV season was associated with significantly lower rates of bacteremia and central line-associated bloodstream infections, particularly in the ICUs and the Pediatric Bone Marrow Transplant Unit.


Streptococcus thermophilus, an emerging and promising tool for heterologous expression: Advantages and future trends.
Streptococcus thermophilus is the second most used bacterium in dairy industry. It is daily consumed by millions of people through the worldwide consumption of yogurts, cheeses and fermented milks. S. thermophilus presents many features that make it a good candidate for the production of heterologous proteins. First, its ability to be naturally transformable allows obtaining swiftly and easily recombinant strains using various genetic tools available. Second, its Generally Recognised As Safe status and its ability to produce beneficial molecules or to liberate bioactive peptides from milk proteins open up the way for the development of new functional foods to maintain health and well-being of consumers. Finally, its ability to survive the intestinal passage and to be metabolically active in gastrointestinal tract allows considering S. thermophilus as a potential tool for delivering various biological molecules to the gastrointestinal tract. The aim of this review is therefore to take stock of various genetic tools which can be employed in S. thermophilus to produce heterologous proteins and to highlight the advantages and future trends of use of this bacterium as a heterologous expression host.


Alcohol-induced pseudo-Cushing's syndrome mimicking Cushing's disease in a patient with an adrenal mass.
Alcohol-induced pseudo-Cushing's syndrome is a disorder in which patients exhibit clinical and/or biochemical features similar to those in patients with Cushing's syndrome, but these features, related to alcohol abuse, may be transient and resolve during abstinence from alcohol. In most previous reports of alcohol-induced pseudo-Cushing's syndrome, detailed endocrinologic data supporting a diagnosis of Cushing's syndrome have been lacking. This report describes a patient with clinical features of Cushing's syndrome, increased plasma ACTH values, and elevated levels of basal urinary free cortisol and 17-hydroxysteroids that were not suppressed by low-dose dexamethasone but were suppressed by high-dose dexamethasone. Detailed test results were indistinguishable from those in Cushing's disease, which had been the initial diagnosis. When an occult history of alcohol abuse was discovered, the suspicion of alcohol-induced pseudo-Cushing's syndrome was raised. During an extended hospitalization and abstinence from alcohol, abnormal endocrinologic test results gradually became normal. This patient also demonstrated a further complicating feature, a left adrenal mass, which appeared to be a benign, coincidental lesion. Because of the high prevalence of alcohol abuse and the possibility that test results may be identical to those in Cushing's disease, clinicians should be familiar with this disorder to avoid misdiagnosis and inappropriate therapy.


Effect of posture on oxygenation and respiratory muscle strength in convalescent infants.
To determine if differences in respiratory muscle strength could explain any posture related effects on oxygenation in convalescent neonates. Infants were examined in three postures: supine, supine with head up tilt of 45 degrees, and prone. A subsequent study was performed to determine the influence of head position in the supine posture. In each posture/head position, oxygen saturation (SaO2) was determined and respiratory muscle strength assessed by measurement of the maximum inspiratory pressure (PIMAX). Twenty infants, median gestational age 34.5 weeks (range 25-43), and 10 infants, median gestational age 33 weeks (range 30-36), were entered into the first and second study respectively. Oxygenation was higher in the prone and supine with 45 degrees head up tilt postures than in the supine posture (p<0.001), whereas PIMAX was higher in the supine and supine with head up tilt of 45 degrees postures than in the prone posture (p<0.001). Head position did not influence the effect of posture on PIMAX or oxygenation. Superior oxygenation in the prone posture in convalescent infants was not explained by greater respiratory muscle strength, as this was superior in the supine posture.


Polybrominated diphenyl ethers and HBCD in bird eggs of South Africa.
In this paper, the first data on brominated flame retardants (BFRs), in particular polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD) in eggs of bird species from South Africa are described (N=43). Concentrations of PBDEs were detected in all the studied species and in all the geographic areas. Highest concentrations of PBDEs were measured in bird eggs from the Vaal River, which is situated downstream of the most industrialized area in South Africa. Sum-PBDE concentrations were highest in eggs of one African sacred ibis (396 ng g(-1) lipid weight (lw)), possibly due to foraging on dumping sites. Lowest mean level of sum-PBDEs (2.3 ng g(-1) lw) was measured in cattle egrets (N=11) from Barberspan Sanctuary, a Ramsar site. The PBDE congener pattern showed large differences, reflecting different trophic levels, migratory behavior, distance to the source, and, exposure to different PBDE mixtures, among others. HBCD was detected only in four species, and highest levels were measured in one egg of African sacred ibis (71 ng g(-1) lw). In most species, levels of PBDEs were one to several orders of magnitude lower than levels of DDTs and PCBs. PBDEs correlated strongly with DDTs, PCBs and some other organochlorines (OCs), indicating the same source. The widespread occurrence of PBDEs in the South African avian species showed a strong need for further investigations of PBDEs in the Southern African environment.


Children's dental service use reflects their parents' dental service experience and insurance.
Decisions about children's oral health care are made by parents. Parents' dental insurance, dental service use, and perceived affordability all influence their children's oral health care. Using data from the 2016 National Health Interview Survey, the authors constructed a database of 4,396 nationally representative US children and their linked household adults. The authors assessed the relationship between children's and parents' use of dental services, private and public dental insurance, and deferral of oral health care owing to cost. To adjust for factors that may influence outcomes independently, the authors performed multivariate analyses to consider child, parent, and household characteristics. Children have 2 times the risk of lacking a dental visit in a year if the parent has none, 7 times the risk of reportedly lacking dental coverage if the parent has none, and nearly 10 times the risk of having care deferred owing to cost if the parent finds oral health care unaffordable. Affordability risk factors for children include older age and minority race, whereas protective factors include public insurance, parents with higher educational attainment, and female-led households. Increased oral health care use by children was associated with states that provide more extensive adult Medicaid dental benefits. Greater parental dental service use, dental coverage, and ability to afford care benefit their children's use of oral health care. Policies by employers and government that expand quality private and public coverage for adults hold strong promise to improve oral health care for both parents and their children.


Differential response of Daphnia genotypes to oxygen stress: respiration rates, hemoglobin content and low-oxygen tolerance.
Laboratory respiration rate experiments using three electrophoretically identified clones of the fresh water, planktonic cladoceran, Daphnia pulex, from an eutrophic farm pond, indicated that clones acclimated to both low and high oxygen levels, regulated oxygen consumption across a wide range of oxygen concentrations (1.0-9.0 mg· liter-1). A "threshold" oxygen level of 0.5-1.0 mg·liter-1 was reached, where animals succumbed to oxygen stress, regardless of hemoglobin content. No significant clonal differences in respiration rates were found. These data suggest that members of this Daphnia population are able to regulate oxygen metabolism across a wide range of ambient oxygen concentrations, and indicate a well-adapted respiratory system.Low-oxygen tolerance experiments and hemoglobin measurements indicated further that physiological differences indeed exist between clones; one clone produced the lowest amount of hemoglobin and was least tolerant of low oxygen levels. These data imply that spatial and temporal changes in dissolved oxygen concentration may be an important selective force influencing the clonal (genotypic) composition of natural cladoceran populations.


The use of in vitro fertilization to evaluate putative tests of human sperm function.
Results of 106 in vitro fertilization procedures were used to evaluate the usefulness of tests of human sperm function for predicting fertilization rates. Sperm tests included concentration, motility, morphology, vitality (eosin Y exclusion), nuclear immaturity (aniline blue stain), and hypo-osmotic swelling. Only the number of sperm in the insemination medium, percentage normal morphology, and vitality were statistically significant in logistic regression models of fertilization rates. The other tests, such as the hypo-osmotic swelling test, did not give additional information about fertilization rates in this study. It is concluded that logistic regression analysis of factors affecting results of fertilization in vitro provides a powerful tool for evaluating some clinical tests of sperm function.


Discrepancy between Self-Reported and Urine-Cotinine Verified Smoking Status among Korean Male Adults: Analysis of Health Check-Up Data from a Single Private Hospital.
Enquiry into smoking status and recommendations for smoking cessation is an essential preventive service. However, there are few studies comparing self-reported (SR) and cotinine-verified (CV) smoking statuses, using medical check-up data. The rates of discrepancy and under-reporting are unknown. We performed a cross-sectional study using health examination data from Healthcare System Gangnam Center, Seoul National University Hospital in 2013. We analyzed SR and CV smoking statuses and discrepancies between the two in relation to sociodemographic variables. We also attempted to ascertain the factors associated with a discrepant smoking status among current smokers. In the sample of 3,477 men, CV smoking rate was 11.1% higher than the SR rate. About 1 in 3 participants either omitted the smoking questionnaire or gave a false reply. The ratio of CV to SR smoking rates was 1.49 (95% confidence interval [CI], 1.38-1.61). After adjusting for confounding factors, older adults (≥60 years) showed an increased adjusted odds ratio (aOR) for discrepancy between SR and CV when compared to those in their twenties and thirties (aOR, 5.43; 95% CI, 2.69-10.96). Educational levels of high school graduation or lower (aOR, 2.33; 95% CI, 1.36-4.01), repeated health check-ups (aOR, 1.45; 95% CI, 1.03-2.06), and low cotinine levels of <500 ng/mL (aOR, 2.03; 95% CI, 1.33-3.09), were also associated with discordance between SR and CV smoking status. Omissions and false responses impede the accurate assessment of smoking status in health check-up participants. In order to improve accuracy, it is suggested that researcher pay attention to participants with greater discrepancy between SR and CV smoking status, and formulate interventions to improve response rates.


Causal factors in primary open angle glaucoma: a phenome-wide Mendelian randomisation study.
Primary open angle glaucoma (POAG) is a chronic, adult-onset optic neuropathy associated with characteristic optic disc and/or visual field changes. With a view to identifying modifiable risk factors for this common neurodegenerative condition, we performed a 'phenome-wide' univariable Mendelian randomisation (MR) study that involved analysing the relationship between 9661 traits and POAG. Utilised analytical approaches included weighted mode based estimation, the weighted median method, the MR Egger method and the inverse variance weighted (IVW) approach. Eleven traits related to POAG risk were identified including: serum levels of the angiopoietin-1 receptor (OR [odds ratio] = 1.11, IVW p = 2.34E-06) and the cadherin 5 protein (OR = 1.06, IVW p = 1.31E-06); intraocular pressure (OR = 2.46-3.79, IVW p = 8.94E-44-3.00E-27); diabetes (OR = 5.17, beta = 1.64, IVW p = 9.68E-04); and waist circumference (OR = 0.79, IVW p = 1.66E-05). Future research focussing on the effects of adiposity, cadherin 5 and angiopoietin-1 receptor on POAG development and progression is expected to provide key insights that might inform the provision of lifestyle modification advice and/or the development of novel therapies.


Biomarkers in diagnosis and therapy of oral squamous cell carcinoma: A review of the literature.
Oral squamous cell carcinoma (OSCC) represents the sixth most common cancer, accounting for 2-4% of all malignancies worldwide. The overall survival rate of less than 60% remains generally poor, with prognosis heavily relying on the TNM staging system. Tumor size as well as the presence and extent of lymph node metastases are widely recognized as the most important predictors. However, the underlying mechanisms that lead to an aggressive phenotype are not yet fully understood. Therefore, possible biomarkers are much in need to predict prognosis, to help individualize therapy approaches, and to overcome possible resistance mechanisms. Despite a multitude of recently published biomarkers for OSCC, there is still an ongoing debate regarding their implementation in the clinical workflow. Thus, a systematic literature search via PubMed was performed to update the current literature with the latest evidence. In total, 128 studies were included and over 100 different biomarkers evaluated with reference to their influence of survival, tumor recurrence, advanced grading and lymph node metastasis. In this review, we highlight the important molecular mechanism underlying possible markers in tissue, blood or saliva samples for OSCC. As a major result, no clinical trials could be obtained to prove clinical importance of the validated predictors for survival, tumor recurrence, lymph node metastasis and therapy resistance. Therefore, further clinical investigations are much needed.


The value of electrical impedance tomography in assessing the effect of body position and positive airway pressures on regional lung ventilation in spontaneously breathing subjects.
Functional electrical impedance tomography (EIT) measures relative impedance changes in lung tissue during tidal breathing and creates images of local ventilation distribution. A novel approach to analyse the effect of body position and positive pressure ventilation on intrapulmonary tidal volume distribution was evaluated in healthy adult subjects. Prospective experimental study in healthy adult subjects in the intensive care unit at university hospital. Ten healthy male adults. Change in body position from supine to prone, left and right lateral during spontaneous breathing and positive pressure support ventilation. EIT measurements and multiple-breath sulphur hexafluoride (SF6) washout were performed. Profiles of average relative impedance change in regional lung areas were calculated. Relative impedance time course analysis and Lissajous figure loop analysis were used to calculate phase angles between dependent or independent lung and total lung (phi). EIT data were compared to SF6 data washout measuring the lung clearance index (LCI). Proposed EIT profiles allowed inter-individual comparison of EIT data and identified areas with reduced regional tidal volume using pressure support ventilation. Phase angle phi of dependent lung in supine position was 11.7+/-1.4 degrees, in prone 5.3+/-0.5 degrees, in right lateral 11.0+/-1.3 degrees and in left lateral position 10.8+/-1.0 degree. LCI increased in supine position from 5.63+/-0.43 to 7.13+/-0.64 in prone position. Measured phi showed inverse relationship to LCI in the four different body positions. EIT profiles and phi of functional EIT are new methods to describe regional ventilation distribution with EIT allowing inter-individual comparison.


Reducing COVID-19 Vaccine Decisional Conflict in Parents of 5-11-Year-Old Children in Australia: A Single Arm Pre-Post Study.
COVID-19 vaccine uptake among 5-11-year-olds is significantly lower than that of the 12+ age group. Some parents may have decided against vaccinating their children for COVID-19; others may be undecided and may be seeking more information to support their decision. We aimed to assess the effect of a decision support tool on parents' level of decisional conflict, vaccine hesitancy, and intention to vaccinate. We conducted a single-arm, cross-sectional online pre-post intervention survey of parents from Victoria, Australia, who had not yet vaccinated their 5-11-year-old child for COVID-19. We measured change in decisional conflict, intention, and hesitancy towards COVID-19 vaccines for children before and after viewing a decision support tool. We used logistic regression to identify characteristics associated with reduced decisional conflict. Between May and September 2022, 108 parents took part in the study. The tool reduced decision conflict in 25% (27/107) of parents, with reduced decisional conflict more likely among parents initially undecided about vaccinating, compared to parents who did not intend to vaccinate their child (OR, 12.58 95% CI 3.21 to 9.30). For most parents, hesitancy (83%, 90/108) and intention (89%, 96/108) remained the same. The decision support tool was modestly effective at reducing decisional conflict, particularly among undecided parents.


[Vaccination strategies for the general practitioner. III. Difficulties encountered in practice: various references].
The vaccinal cover is still too small in the french communities and to increase it, the general practitioner needs a good consensus and few clear reference points. We will expose some of these points in this following article.


Dietary nucleotides modulate mitochondrial function of intestinal mucosa in weanling rats with chronic diarrhea.
Chronic diarrhea during early infancy is characterized by intestinal mucosal injury, and as a consequence, the mitochondrial system of oxidation and reduction and energy production is altered. Since dietary nucleotides have been associated with the process of intestinal mucosal repair in rats with chronic diarrhea, the aim of this study was to examine the effects of dietary nucleotides on the functioning of mucosal mitochondria. Weanling rats were fed with a semipurified synthetic diet (C) or the same diet in which carbohydrates were substituted by lactose (L), resulting in chronic diarrhea. During recovery, rats were fed with the semipurified synthetic diet (LC) or the same diet supplemented with nucleotides (LN). The activities of adenosine triphosphate synthase (ATPase), cytochrome c oxidase, citrate synthase, and malate dehydrogenase were measured in mitochondria from ileum and colon mucosa. These enzymatic activities rose in rats with chronic diarrhea, possibly to compensate for the drastic decline in adenosine triphosphate (ATP) synthesis. Dietary nucleotide supplementation allowed normalizing of the activities of ATPase (C: 0.37 +/- 0.16 microg/min/mg protein; L: 0.68 +/- 0.25 microg/min/mg protein; LC: 0.60 +/- 0.20 microg/min/mg protein; LN: 0.42 +/- 0.22 microg/min/mg protein), citrate synthase (C: 0.12 +/- 0.05 mM/min/mg protein; L: 0.21 +/- 0.07 mM/min/mg protein; LC: 0.21 +/- 0.06 mM/min/mg protein; LN: 0.12 +/- 0.02 mM/min/mg protein), and malate dehydrogenase (C: 0.77 +/- 0.48 mM/min/mg protein; L: 3.08 +/- 0.85 mM/min/mg protein; LC: 2.11 +/- 0.44 mM/min/mg protein; LN: 1.13 +/- 0.51 mM/min/mg protein) in the ileum mitochondria of the diarrheic rats. In colonic mucosa, mitochondrial enzymatic activities were restored after eliminating lactose from the diet. These results suggest that dietary nucleotides promote earlier restoration of the ileal mitochondrial function after chronic diarrhea.