Salmonella Typhimurium-based inactivated vaccine containing a wide spectrum of bacterial antigens which mimics protein expression changes during different stages of an infection process.
Salmonella infections are still considered a persistent problem in veterinary medicine. Vaccination is one of the tools for decreasing the burden of many pathogens on animals. However, the efficiency of available commercial or experimental vaccines against non-typhoid Salmonella strains is not yet sufficient. We followed the path of an inactivated vaccine that is safe and well accepted, but whose presented antigen spectrum is limited. We improved this issue by using diverse cultivation conditions mimicking bacterial protein expression during the natural infection process. The cultivation process was set up to simulate the host environment to enhance the expression of SPI-1 (Salmonella pathogenicity island) proteins, SPI-2 proteins, siderophore-related proteins, and flagellar proteins. Three different cultivation media were used and subsequent cultures were mixed together, inactivated, and used for the immunization of post-weaned piglets. A mixture of recombinant Salmonella proteins was also used as a recombinant vaccine for comparison. The clinical symptoms during the subsequent experimental infection, antibody response, and organ bacterial loads were examined. One day after the infection, we observed an increased rectal temperature in the group of unvaccinated animals and the animals vaccinated with the recombinant vaccine. The increase in the temperature of the pigs vaccinated with the inactivated Salmonella mixture was significantly lower. In the same group, we also found lower bacterial loads in the ileum content and the colon wall. The IgG response to several Salmonella antigens was enhanced in this group, but it did not reach the titers of the group vaccinated with the recombinant vaccine. To summarize, the pigs vaccinated with an inactivated mixture of Salmonella cultures mimicking protein expression changes during the natural infection exhibited less serious clinical symptoms and lower bacterial load in the body after the experimental infection compared to the unvaccinated pigs and the pigs vaccinated with a mixture of recombinant Salmonella proteins.


An overview of the effect of pyrolysis process parameters on biochar stability.
Biochar produced from biomass pyrolysis is becoming a powerful tool for carbon sequestration and greenhouse gas (GHG) emission reduction. Biochar C recalcitrance or biochar stability is the decisive property determining its carbon sequestration potential. The effect of pyrolysis process parameters on biochar stability is becoming a frontier of biochar study. This review discussed comprehensively how and why biomass compositions and physicochemical properties and biomass processing conditions such as pyrolysis temperature and reaction residence time affect the stability of biochar. The review found that relative high temperature (400-700 °C), long reaction residence time, slow heating rate, high pressure, the presence of some minerals and biomass feedstock of high-lignin content with large particle size are preferable to biochar stability. However, challenges exist to mediate the trade-offs between biochar stability and other potential wins. Strategies were then proposed to promote the utilization of biochar as a climate change mitigation tool.


Upconversion fluorescence immunoassay for imidaclothiz by magnetic nanoparticle separation.
A sensitive fluorescence immunoassay for the detection of imidaclothiz was established by using magnetic nanoparticles (MNPs) as concentration elements and upconversion nanoparticles (UCNPs) as signal labels. The NaYF4/Yb,Er UCNPs and MNPs were conjugated with imidaclothiz monoclonal antibody and imidaclothiz antigen, respectively. Imidaclothiz could compete with the antigen-conjugated MNPs for binding to the antibody-conjugated UCNPs and resulted in a decreased fluorescence signal when the MNPs were separated by an external magnet. Under the optimal conditions, the concentration of imidaclothiz producing 50% inhibition of the signal (IC50), limit of detection (LOD, IC10), and the linear assay range (IC10-IC90) were 14.59, 0.74, and 0.74-289.30 ng mL-1, respectively. The immunoassay exhibited no obvious cross-reactivity with analogues of imidaclothiz except for imidacloprid, with 89.2% cross-reactivity. The average recoveries measured in paddy water, pear, soil, peach, rice, tomato, wheat, and pakchoi were 75.7-105.2%, and the relative standard deviations (RSDs) were less than 11.2%. In addition, the results of the immunoassay correlated well with that of high-performance liquid chromatography (HPLC) for authentic samples. Graphical abstract Development of an upconversion fluorescence immunoassay for the detection of imidaclothiz by using antibody-modified upconversion nanoparticles (UCNPs) as the detection probe and antigen-modified magnetic nanoparticles (MNPs) as the capture probe.


[Hemangioblastoma of the cerebellum, bulbo-spinal cord syringomyelia and bilateral pheochromocytoma].
A probable diagnosis of an incomplete form of von Hippel Lindau disease was made in a case of combined cerebellar hemangioblastoma, pontobulbar cavitation and bilateral pheochromocytoma. A survey of the literature review found only 3 similar cases among 64 patients reported as having combined lesions. A wide variety of lesions are in fact encountered.


Non-targeted screening approaches for contaminants and adulterants in food using liquid chromatography hyphenated to high resolution mass spectrometry.
The majority of analytical methods for food safety monitor the presence of a specific compound or defined set of compounds. Non-targeted screening methods are complementary to these approaches by detecting and identifying unexpected compounds present in food matrices that may be harmful to public health. However, the development and implementation of generalized non-targeted screening workflows are particularly challenging, especially for food matrices due to inherent sample complexity and diversity and a large analyte concentration range. One approach that can be implemented is liquid chromatography coupled to high-resolution mass spectrometry, which serves to reduce this complexity and is capable of generating molecular formulae for compounds of interest. Current capabilities, strategies, and challenges will be reviewed for sample preparation, mass spectrometry, chromatography, and data processing workflows. Considerations to increase the accuracy and speed of identifying unknown molecular species will also be addressed, including suggestions for achieving sufficient data quality for non-targeted screening applications.


Pantoea conspicua promoted sunflower growth and engulfed rhizospheric arsenate by secreting exopolysaccharide.
A rhizobacterium, Pantoea conspicua, was examined against sunflower seedlings' growth under arsenate stress. Sunflower upon exposure to arsenate resulted in compromised growth that might be due to the accumulation of higher concentrations of arsenate and reactive oxygen species (ROS) in seedlings' tissues. The deposited arsenate led to oxidative damage and electrolyte leakage, making the sunflower seedlings vulnerable to compromise its growth and development. However, inoculation of sunflower seedlings with P. conspicua alleviated arsenate stress in host by initiating a multilayered defence mechanism. In fact, P. conspicua filtered out 75.1% of the arsenate from growth medium that were available to the plant roots in the absence of the said strain. To accomplish such activity, P. conspicua secreted exopolysaccharides as well as altered lignification in host roots. The arsenate (24.9%) that made its way to plant tissues was countered by helping the host seedlings to produce higher levels of indole acetic acid, non enzymatic antioxidants (phenolics and flavonoids) and antioxidant enzymes (catalase, ascorbte peroxidase, peroxidase, superoxide dismutase). As a result, ROS accumulation and electrolyte leakage were brought back to normal levels as observed in control seedlings. Hence, the rhizobacterium associated host seedlings achieved higher net assimilation (127.7%) and relative growth rate (113.5%) under 100 ppm of arsenate stress. The work concluded that P. conspicua alleviated arsenate stress in the host plants by imposing physical barrier as well as improving host seedlings' physiology and biochemistry.


Immunohistochemical detection of CD30 remains negative in nodular lymphocyte-predominant Hodgkin's disease using enhanced antigen retrieval.
The aims of this study were to confirm that CD30 is reproducibly negative in cases of nodular lymphocyte-predominant Hodgkin's disease (nLPHD), and its relationship to further antibody targets for the distinction of L&H cells from classical Hodgkin's and Reed-Sternberg cells. We examined 16 cases of nLPHD from two centres in the UK to characterize immunohistochemically L&H cells for CD30, EMA, J-chain and Oct2, using different methods of antigen retrieval, antigen amplification and antigen detection systems. Two cases could not be stained with J-chain and Oct2. All cases were negative for CD30 following manual and automated staining. Only one case became positive for EMA after manual staining using tyramide amplification. J-chain and Oct2 were negative in all cases following manual staining. J-chain showed a positive result of variable degree in all but one case using automated Dako ChemMate amplification system staining. Oct2 demonstrated a positive, albeit variable, staining pattern in all cases following automated staining. CD30 remains negative in L&H cells of nLPHD using enhanced antigen retrieval and can therefore reliably be used to distinguish nLPHD from classical Hodgkin's disease. The value of EMA in the diagnosis of nLPHD remains uncertain, as it does not reproducibly mark L&H cells, even after the use of enhanced antigen retrieval. J-chain and Oct2 appear to be useful markers in the diagnosis of nLPHD using enhanced immunostaining and should therefore be included in lymphoma panels. Automated enhanced staining, using standardized protocols, precoated slides and the full system of prepared reagents, further diminishes the occurrence of errors associated with manual staining, and thereby improves confidence and reliability in diagnosing nLPHD.


Rh(II)-catalyzed intramolecular C-H insertion of diazo substrates in water: scope and limitations.
Preferential Rh(II) carbenoid intramolecular C-H versus O-H insertion derived from alpha-diazo-acetamides can be achieved in water by using an appropriate combination of the catalyst and amide groups, which creates a larger hydrophobic environment around the reactive carbenoid center.


Effect of radical lymphadenectomy in colorectal cancer with para-aortic lymph node metastasis: a systematic review and meta-analysis.
Colorectal cancer (CRC) with para-aortic lymph node metastasis (PALNM) is an intractable clinical situation, and the role of radical lymphadenectomy in the treatment of CRC with PALNM is still controversial. The aim of the current system review and meta-analysis is to evaluate the clinical efficacy and safety of radical lymphadenectomy in CRC patients with PALAN. We performed a systematic search of PubMed, Embase, Cochrane Library and other online databases up to 31 October 2021. The clinical data including overall survival and postoperative complications were screened and analyzed after data extraction. Odds ratios (ORs) were applied to analyze these dichotomous outcomes with a fixed effects model. A total of 7 available retrospective clinical studies involving 327 patients were finally included. CRC patients with PALNM who underwent radical lymphadenectomy showed significantly overall survival (OR: 6.80, 95% CI: 3.46-13.38, P < 0.01; I2 = 0%) when compared to those who did not receive radical lymphadenectomy. Moreover, in terms of postoperative complications (OR: 0.71, 95% CI: 0.35-1.44, P = 0.48; I2 = 0%), there was no statistical difference between radical lymphadenectomy treatment and control groups. The radical lymphadenectomy treatment has showed the expected clinical efficacy in prolonging overall survival time of CRC patients with PALAN. Moreover, the preemptive radical lymphadenectomy could not cause additional postoperative complications.


p53 regulates mesenchymal stem cell-mediated tumor suppression in a tumor microenvironment through immune modulation.
p53 is one of the most studied genes in cancer biology, and mutations in this gene may be predictive for the development of many types of cancer in humans and in animals. However, whether p53 mutations in non-tumor stromal cells can affect tumor development has received very little attention. In this study, we show that B16F0 melanoma cells form much larger tumors in p53-deficient mice than in wild-type mice, indicating a potential role of p53 deficiency in non-tumor cells of the microenvironment. As mesenchymal stem cells (MSCs) are attracted to tumors and form a major component of the tumor microenvironment, we examined the potential role of p53 status in MSCs in tumor development. We found that larger tumors resulted when B16F0 melanoma cells were co-injected with bone marrow MSCs derived from p53-deficient mice rather than MSCs from wild-type mice. Interestingly, this tumor-promoting effect by p53-deficient MSCs was not observed in non-obese diabetic/severe combined immunodeficiency mice, indicating the immune response has a critical role. Indeed, in the presence of inflammatory cytokines, p53-deficient MSCs expressed more inducible nitric oxide synthase (iNOS) and exhibited greater immunosuppressive capacity. Importantly, tumor promotion by p53-deficient MSCs was abolished by administration of S-methylisothiourea, an iNOS inhibitor. Therefore, our data demonstrate that p53 status in tumor stromal cells has a key role in tumor development by modulating immune responses.


[The combined therapy of local administration of OK-432 and radiation in carcinoma of the trachea].
A newly developed treatment method of local administration of OK-432 bronchoscopically combined with irradiation was applied to a patient with carcinoma of the Trachea complaining dyspnea and dysphagia. The tumor showed extra-wall growth. Dyspnea was improved in a week and the tumor disappeared after the treatment. A patient became to take food orally and could discharge in well condition.


Continuous remote vital sign/environment monitoring for returning soldier adjustment assessment.
A three-stage study to develop and test an unobtrusive room sensor unit and subject data management system to discover correlation between sensor-based time-series measurements of sleep quality and clinical assessments of combat veterans suffering from Post-traumatic Stress Disorder (PTSD) and mild Traumatic Brain Injury (TBI), is described. Experiments and results for testing sensitivity and robustness of the sensor unit and data management protocol are provided. The current sensitivity of remote vital sign monitoring system is below 20% and 10% for respiration and heart rates, respectively.


Localization of sialic acid moieties in the endothelial lining of Schlemm's canal in normal and glaucomatous eyes.
The distribution of sialic acid moieties in the trabecular wall of Schlemm's canal in normal human and monkey eyes, as well as in limited tissue samples from patients with primary open-angle glaucoma (POAG), was investigated by using polycationic ferritin (PCF) at varying pH and colloidal iron at pH 1.8. At pH 1.8-1.9, both PCF and colloidal iron labeled the luminal surface of the endothelial cells of Schlemm's canal in normotensive monkey and human eyes, whereas binding was sparse and random on the basal surface. At a pH of 3.3 and higher, PCF showed increased binding that was confirmed exclusively to the luminal surface of the cells. In trabeculectomy tissue samples from eyes with POAG, PCF at pH 1.9 showed a greater density of labeling on both the basal and luminal cell surfaces, as well as in the subendothelial region, than was observed in normotensive eyes. Given the fact that sialic acid is a moiety which stabilizes cell membranes, we suggest that in normal eyes the absence of sialated molecules on the basal cell surface leaves 'receptor' sites for the initiation of the macrovacuolation process which allows the bulk outflow of aqueous humor across the endothelial barrier of Schlemm's canal. Our preliminary observations in glaucomatous eyes indicate a loss of such receptor sites, which may account for the depletion of macrovacuolar configurations in cases of advanced POAG. Our discussion relates these findings to the pathogenesis of POAG and to the possible role for a defective transmembrane interaction of the surface glycoproteins (fibronectin and laminin) with the cytoskeleton of the endothelial cells lining Schlemm's canal and the cells in the pericanalicular tissue.


A thorough screening based on QTLs controlling zinc and copper accumulation in the grain of different wheat genotypes.
Excess trace metals may cause damage to human health due to the consumption of food grain grown in contaminated soils. This study was designed to understand the genetic mechanisms of copper (Cu) and zinc (Zn) accumulation in wheat grain under stressed environments. The differences of Cu/Zn contents in the grain among 246 wheat varieties were analyzed, and the wheat varieties with low or high accumulation of Cu and Zn in the safe range were also screened out. The accumulation of Cu and Zn in grains of "Chushanbao" was lowest, which could be used as a novel germplasm for wheat breeding under heavy metal stress. We found that Cu contents of wheat grain were significantly and positively correlated with Zn. The quantitative trait loci (QTLs) for grain Cu content (GCuC) and grain Zn content (GZnC) were detected by genome-wide association study (GWAS). Twenty-three loci affecting GCuC were identified on chromosomes 1A, 1D, 2A, 2B, 2D, 3A, 3B, 3D, 4A, 4B 4D, 5A, 6D, 7A, and 7B, explaining 2.6-5.8% of the phenotypic variation. Sixteen loci associated with the GZnC on 11 different chromosomes 1B, 2B, 2D, 3A, 3D, 4A, 4B, 5A, 5D, 6B, and 7D were detected, which could explain 2.7~6.6% of phenotypic variance. We also determined five associated loci on chromosomes 2B, 2D, 3A, 4B, and 5A were in pleiotropic regions affecting both GCuC and GZnC. This study would help in better understanding the molecular basis of Cu/Zn accumulation in wheat grain, and the associated markers may be useful for marker-assisted selection (MAS) breeding program.


Prevalence of Babesia canis, Borrelia afzelii, and Anaplasma phagocytophilum infection in hard ticks removed from dogs in Warsaw (central Poland).
The purposes of this study were to specify the occurrence and prevalence of Babesia canis, Borrelia burgdorferi sensu lato, and Anaplasma phagocytophilum in ticks removed from dogs in Warsaw, and to determine the Borrelia species occurring in Ixodes ricinus ticks. Among 590 collected ticks, 209 were identified as I. ricinus, and 381 as Dermacentor reticulatus. DNA of B. canis was detected in 11% of D. reticulatus ticks. We found that 6.2% of I. ricinus ticks harbored B. burgdorferi s.l. specific DNA and 2.9% harbored A. phagocytophilum DNA. In these samples sequencing of the detected Borrelia amplicon confirmed infection with Borrelia afzelii genospecies. New sequences were submitted to the GenBank database (accession no. EU152128, EU152127, EU152126). This work is the first detection of B. afzelii and A. phagocytophilum in ticks from Warsaw, and the first survey for the prevalence of B. canis, B. afzelii, and A. phagocytophilum in ticks in central Poland.


Nick-directed repair of palindromic loop mismatches in human cell extracts.
Palindromic sequences present in DNA may form secondary structures that block DNA replication and transcription causing adverse effects on genome stability. It has been suggested that hairpin structures containing mispaired bases could stimulate the repair systems in human cells. In this study, processing of variable length of palindromic loops in the presence or absence of single-base mismatches was investigated in human cell extracts. Our results showed that hairpin structures were efficiently processed through a nick-directed mechanism. In a similar sequence context, mismatch-containing hairpins have higher repair efficiencies. We also found that shorter hairpins are generally better repaired. A strand break located either 3' or 5' to the loop is sufficient to activate hairpin repair on the nicked strand. The reaction requires Mg(2+), the four dNTPs and hydrolysis of ATP for efficient repair on both palindromic loop insertions and deletions. Correction of each of these heteroduplexes was abolished by aphidicolin but was relatively insensitive to the presence of ddTTP, suggesting involvement of polymerase(s) alpha and/or delta. These findings are most consistent with the nick-directed loop repair pathway being responsible for processing hairpin heterologies in human cells.


The midwife-woman relationship in a South Wales community: Experiences of midwives and migrant Pakistani women in early pregnancy.
In 2015, 27.5% of births in England and Wales were to mothers born outside of the UK. Compared to their White British peers, minority ethnic and migrant women are at a significantly higher risk of maternal and perinatal mortality, along with lower maternity care satisfaction. Existing literature highlights the importance of midwife-woman relationships in care satisfaction and pregnancy outcomes; however, little research has explored midwife-woman relationships for migrant and minority ethnic women in the UK. A focused ethnography was conducted in South Wales, UK, including semi-structured interviews with 9 migrant Pakistani participants and 11 practising midwives, fieldwork in the local migrant Pakistani community and local maternity services, observations of antenatal appointments, and reviews of relevant media. Thematic data analysis was undertaken concurrently with data collection. The midwife-woman relationship was important for participants' experiences of care. Numerous social and ecological factors influenced this relationship, including family relationships, culture and religion, differing health-care systems, authoritative knowledge and communication of information. Marked differences were seen between midwives and women in the perceived importance of these factors. Findings provide new theoretical insights into the complex factors contributing to the health-care expectations of pregnant migrant Pakistani women in the UK. These findings may be used to create meaningful dialogue between women and midwives, encourage women's involvement in decisions about their health care and facilitate future midwifery education and research. Conclusions are relevant to a broad international audience, as achieving better outcomes for migrant and ethnic minority communities is of global concern.


Benthic habitat condition of the continental shelf surrounding oil and gas platforms in the Santa Barbara Channel, Southern California.
The continental shelf of southern California is an important location for the extraction of petroleum and natural gas. Many platforms in the region have been operating for more than four decades and are being targeted for decommissioning. Information on the condition of surrounding habitats to the platforms will be important for regulators. The condition of sediments near (250 m-2 km) four active oil/gas platforms was evaluated with measures of macrobenthic infauna, toxicity, and chemical composition using standardized assessment indices and compared to that of equivalent locations across the region without platforms. Assessment scores indicated that the sediments surrounding the oil platforms were in a relatively good state, with reference-condition infauna, minimal levels of chemical exposure, and five instances (25% of samples) of low-level toxicity. Samples from around the oil platforms were in overall similar condition to the region, with slightly better condition infauna, nearly identical chemistry, and slightly worse toxicity.


Drug packaging. A key factor to be taken into account when choosing a treatment.
A drug's packaging contributes to its harm-benefit balance. Highlighting the key practical information and identifying potential sources of error or mix-ups is part and parcel of the correct use of medicines. Select labelling that clearly and prominently displays the important information, including the international nonproprietary name (INN).


Phylogeny and biogeography of the Asian trogons (Aves: Trogoniformes) inferred from nuclear and mitochondrial DNA sequences.
We present the first species-level molecular phylogenetic hypothesis for the Asian trogons, using DNA sequences of multiple mitochondrial and nuclear loci, and Bayesian and maximum likelihood tree reconstruction methods. The two genera of Asian trogons, Harpactes and Apalharpactes, are distantly related to each other. Within the widespread Southeast Asian genus Harpactes, we recovered three species groups: (1) H. oreskios; (2) H. orrhophaeus and H. duvaucelii; and (3) a clade of the seven large-bodied species. Short internal branch lengths link species in the large-bodied group, suggesting rapid diversification. Apalharpactes, which is currently restricted to the montane forests of Sumatra and Java, appears to be a relictual lineage distantly related to all other trogons. Bayesian and maximum likelihood analyses indicate Apalharpactes is sister to the African genus Apaloderma, although this result was not strongly supported. Overall, the extant Asian trogon species appear to have diversified prior to the Pleistocene, based on large pair-wise mitochondrial divergences between taxa.


IL-10-producing regulatory B10 cells ameliorate collagen-induced arthritis via suppressing Th17 cell generation.
IL-10-producing CD1d(hi)CD5(+) B cells, also known as B10 cells, have been shown to possess a regulatory function in the inhibition of immune responses, but whether and how B10 cells suppress the development of autoimmune arthritis remain largely unclear. In this study, we detected significantly decreased numbers of IL-10-producing B cells, but increased IL-17-producing CD4(+) T (Th17) cells in both spleen and draining lymph nodes of mice during the acute stage of collagen-induced arthritis (CIA) when compared with adjuvant-treated control mice. On adoptive transfer of in vitro expanded B10 cells, collagen-immunized mice showed a marked delay of arthritis onset with reduced severity of both clinical symptoms and joint damage, accompanied by a substantial reduction in the number of Th17 cells. To determine whether B10 cells directly inhibit the generation of Th17 cells in culture, naive CD4(+) T cells labeled with carboxyfluorescein succinimidyl ester (CFSE) were co-cultured with B10 cells. These B10 cells suppressed Th17 cell differentiation via the reduction of STAT3 phosphorylation and retinoid-related orphan receptor γt (RORγt) expression. Moreover, Th17 cells showed significantly decreased proliferation when co-cultured with B10 cells. Although adoptive transfer of Th17 cells triggered the development of collagen-induced arthritis in IL-17(-/-)DBA/1J mice, co-transfer of B10 cells with Th17 cells profoundly delayed the onset of arthritis. Thus, our findings suggest a novel regulatory role of B10 cells in arthritic progression via the suppression of Th17 cell generation.


Redox Activity of IrIII Complexes with Multidentate Ligands Based on Dipyrido-Annulated N-Heterocyclic Carbenes: Access to High Valent and High Spin State with Carbon Donors.
Synthetic strategies to access high-valent iridium complexes usually require use of π donating ligands bearing electronegative atoms (e. g. amide or oxide) or σ donating electropositive atoms (e. g. boryl or hydride). Besides the η5 -(methyl)cyclopentadienyl derivatives, high-valent η1 carbon-ligated iridium complexes are challenging to synthesize. To meet this challenge, this work reports the oxidation behavior of an all-carbon-ligated anionic bis(CCC-pincer) IrIII complex. Being both σ and π donating, the diaryl dipyrido-annulated N-heterocyclic carbene (dpa-NHC) IrIII complex allowed a stepwise 4e- oxidation sequence. The first 2e- oxidation led to an oxidative coupling of two adjacent aryl groups, resulting in formation of a cationic chiral IrIII complex bearing a CCCC-tetradentate ligand. A further 2e- oxidation allowed isolation of a high-valent tricationic complex with a triplet ground state. These results close a synthetic gap for carbon-ligated iridium complexes and demonstrate the electronic tuning potential of organic π ligands for unusual electronic properties.


Crosstalk between glucocorticoids and mitogen-activated protein kinase signalling pathways.
Synthetic glucocorticoids are potent modulators of the immune system, and are clinically invaluable in the treatment of a wide variety of conditions. However, their use can be limited by harmful side effects, and their mechanisms of action remain poorly understood and controversial. It has recently been reported that glucocorticoids induce the expression of two genes that participate in cross-talk with the mitogen-activated protein kinase signalling pathways. It is possible that both therapeutic and harmful effects of glucocorticoids may be mediated by these genes.


Injectable, thermo-reversible and complex coacervate combination gels for protein drug delivery.
Injectable and thermo-reversible physical combination gels were formed in aqueous solution by preparing complex coacervate with two oppositely charged biomacromolecules that composed of negatively charged chondroitin 6-sulfate and positively charged high molecular weight gelatin type A and co-formulating with a negative, thermo-sensitive polysaccharide, methylcellulose containing a salting-out salt, ammonium sulfate. The combination of complex coacervation and a thermo-reversible gel demonstrated synergistic effects on the complex coacervate formation the release rates of model proteins and in situ gel depot formation. Gels indicated sustained release patterns of the protein over 25 days with minimal initial bursts. Optimized novel in situ gel depot systems containing dual advantages of complex coacervation and temperature responsiveness demonstrated a potential for efficient protein drug delivery in terms of high protein loading, sustained protein release, ease of administration, an aqueous environment without toxic organic solvents, and a simple fabrication method.


A prospective survey of patients with presumed accidental ear injury presenting to a paediatric accident and emergency department.
To assess the characteristics of assumed accidental ear injury in children. A prospective survey of 111 children presenting with accidental external or internal ear injuries to a paediatric accident and emergency department. The majority of patients were male (73%). Right and left sided injuries were equally common (51% right, non-bilateral). Presentation with accidental ear injury was very rare in children under the age of 1 year (n=1). Most patients were self referred (98%), and presented within six hours of injury (84%). The mechanism of injury was variable, but cotton bud induced injury was common (7%). The most common injuries were lacerations of the pinna, in 63 patients (56%). Fourteen per cent had blood in the external canal. Only three patients required admission. Lacerations are the commonest form of accidental ear injury. Ear injuries that are bilateral and in children less than 1 year of age are rare and may suggest non-accidental injury. Cotton bud induced injury is common and preventable.


Apparent inhibition of glycoprotein synthesis by S.cerevisiae mating pheromones.
Saccharomyces cerevisiae mating pheromones a and alpha factor strongly inhibit the incorporation of radiolabelled glucosamine into N-glycosylated proteins of corresponding haploid cells. This observation was erroneously interpreted as an inhibition of glycoprotein synthesis. It has turned out that alpha factor causes a 4-5-fold dilution of incorporated [14C]glucosamine with non-radioactive endogenous precursor. In the case of the [14C]chitin synthesized, which does not show inhibition by alpha factor, the lowering of the specific activity of the precursor is exactly compensated for by an increased rate of chitin synthesis caused by alpha factor.


Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells.
Fibulin-1 is an extracellular matrix protein induced by estradiol in estrogen receptor (ER) positive ovarian cancer cell lines. Alternative splicing of fibulin-1 mRNA results in four different variants named A, B, C and D that may have distinct biological functions. We studied the relative expression of fibulin-1 mRNA variants and their estrogen regulation in human ovarian cancer cells. In ovarian tissues and cancer cell lines, fibulin-1C and -1D are the predominant forms, whereas fibulin-1A and -1B are weakly expressed. We developed a competitive PCR assay based on coamplification of fibulin-1C and -1D to study the relative expression of these fibulin-1 variants in human ovarian samples. In ovarian cancer cell lines and ovarian cancer samples, there was a marked increase in the fibulin-1C:1D and fibulin-1C:HPRT mRNA ratios as compared to normal ovaries. In the BG1 estrogen receptor positive ovarian cancer cell line, fibulin-1C mRNA was induced by estradiol in a dose- and time-dependent manner. Since others and we have previously shown an increased expression of ERalpha as compared to ERbeta in ovarian cancer cells, we investigated whether ERalpha or ERbeta is involved in this induction. For this aim, MDA-MB-231 breast cancer cell line, which expresses both low basal levels of ERs and fibulin-1, was infected with recombinant ERalpha or ERbeta encoding adenovirus and treated with estradiol. Fibulin-1C was induced by estradiol in ERalpha- but not ERbeta-infected cells, suggesting that fibulin-1C induction is mediated through ERalpha. In ovarian tumors, a trend towards a correlation between fibulin-1C and ERalpha expression levels was noted. In conclusion, this study showed an increased fibulin-1C:-1D mRNA ratio in ovarian cancer cells as compared to normal ovaries. This finding suggests that the C variant may be involved in ovarian carcinogenesis. Fibulin-1C overexpression may thus be a clue for the understanding of a putative role of estrogens in ERalpha promoted ovarian tumor progression.


Identification of neoblast- and regeneration-specific miRNAs in the planarian Schmidtea mediterranea.
In recent years, the planarian Schmidtea mediterranea has emerged as a tractable model system to study stem cell biology and regeneration. MicroRNAs are small RNA species that control gene expression by modulating translational repression and mRNA stability and have been implicated in the regulation of various cellular processes. Though recent studies have identified several miRNAs in S. mediterranea, their expression in neoblast subpopulations and during regeneration has not been examined. Here, we identify several miRNAs whose expression is enriched in different neoblast subpopulations and in regenerating tissue at different time points in S. mediterranea. Some of these miRNAs were enriched within 3 h post-amputation and may, therefore, play a role in wound healing and/or neoblast migration. Our results also revealed miRNAs, such as sme-miR-2d-3p and the sme-miR-124 family, whose expression is enriched in the cephalic ganglia, are also expressed in the brain primordium during CNS regeneration. These results provide new insight into the potential biological functions of miRNAs in neoblasts and regeneration in planarians.


2q34-qter duplication and 4q34.2-qter deletion in a patient with developmental delay.
The 2q3 duplication and 4q3 deletion syndromes are two conditions with variable phenotypes including Pierre-Robin sequence (PRS), limb anomalies, congenital heart defects (CHD), developmental delays and intellectual disabilities. We describe a patient born to a mother with a balanced t(2; 4) translocation who combines both a 2q34-qter duplication and a 4q34.2-qter deletion through inheritance of the derivative chromosome 4 (der(4)). He showed developmental delay, growth retardation, hearing problems, minor facial and non-facial anomalies, such as bilateral fifth finger shortness and clinodactyly, but no PRS or CHD. The comparison of his features with those of 46 and 65 published cases of 2q3 duplication and 4q3 deletion, respectively, allows us to further restrict the size of the proposed critical intervals for PRS and CHD on chromosome 4.


Quality of care measures for the treatment of bipolar disorder.
The staff of the American Psychiatric Association (APA), the American Psychiatric Institute for Research and Education (APIRE), and a national panel of experts in bipolar disorder and practice guideline development have collaborated to generate a set of quality of care indicators for the pharmacologic and psychosocial treatment of bipolar disorder. The indicators were derived from APA's evidence-based Practice Guideline for the Treatment of Patients with Bipolar Disorder, 2002 (1) and the Expert Consensus Guideline Series: Medication Treatment of Bipolar Disorder, 2000 (2) These quality indicators can be used for quality monitoring, benchmarking, and quality improvement efforts across health plans, systems of care, and health care providers to improve quality and outcomes of care for patients with bipolar disorder.


Tuberculosis management in India during COVID-19 crisis.
During the early months of the 2020 COVID-19 crisis, critical services in India for tuberculosis (TB) have been disrupted. India has one of the highest burdens of TB and requires continuity of critical TB care. Here, we highlight important points and approaches that can be used to guide navigation of the combined COVID-19 and TB crisis in India.


Preeclampsia among women with COVID-19 during pregnancy and its impact on maternal and perinatal outcomes: Results from a national multicenter study on COVID in Brazil, the REBRACO initiative.
To evaluate the prevalence of preeclampsia among cases of COVID-19 infection during pregnancy and the association between both conditions, in a multicenter cohort of Brazilian women with respiratory symptoms. Ancillary analysis of the Brazilian Network of COVID-19 in Obstetrics (REBRACO) study. We performed a nested case-control analysis selecting all women with COVID-19 and compared outcomes between women with and without PE. Maternal, gestational, and clinical characteristics and perinatal outcomes. Prevalence ratio (PR) and its 95%CI for each of the predictors and outcomes. A total of 203 women were included: 21 (10.3%) in PE group and 182 (89.7%) in non-PE group. Preeclampsia was not different among women with and without COVID-19 (10.3% vs 13.1%, p-value = 0.41), neither complication such as eclampsia and HELLP syndrome. Chronic hypertension (33.4%) (p < 0.01) and obesity (60.0%) (p = 0.03) were the most frequent comorbidities in PE group, and they were significantly more frequent in this group. Women with PE had more cesarean section (RR 5.54 [1.33 - 23.14]) and their neonates were more frequently admitted to neonatal intensive care unit (PR 2.46[1.06 - 5.69]), most likely due to preterm-birth-related complications. The prevalence of PE among women with COVID-19 infection during pregnancy was around 10%; women with COVID-19 and a history of chronic hypertension or obesity are more likely to have preeclampsia. Cesarean section is increased among women with PE and COVID-19, with increased rates of neonatal admission to intensive care units, mostly due to prematurity.


In vivo effect of endrin on three phosphatases in kidney and liver of the fish Ophiocephalus punctatus.
The effect of endrin (0.030 ppm) on the acid phosphatase, alkaline phosphatase and glucose-6-phosphatase activities in the kidney and liver of a teleost fish, Ophiocephalus (Channa) punctatus has been studied. The period of exposure was twenty days. An increase in the acid phosphatase activity is noted in the two tissues examined here. There is no significant change in the activity of alkaline phosphatase in kidney while in liver the enzyme is inhibited. In the kidney glucose-6-phosphatase showed a slight increase in activity but it is inhibited in liver.


Does education really not matter for health?
In a recent paper, Albarrán et al. (2020) use a well-known quasi-randomization strategy to study the impact of education on health outcomes. Concretely, they use the fact that changes in compulsory education laws--usually extending the age of release from the school system--result in exogenous differences in educational attainment between people who may only be separated by a few months of age. They deploy an Instrumental Variable (IV) strategy to compare the outcomes of people forced to stay longer in school to those of individuals who were allowed to drop out earlier. Their empirical strategy does not find a statistically significant effect of education on health outcomes. The paper is timely, well written, and well executed, and deserves careful attention. However, we hope readers consider four caveats--some already raised by the authors--before concluding from the results that education does not matter for health. To help readers interpret this solid research piece, we call attention to: 1) previous research on the links between education and health; 2) the selection of countries in the paper in the presence of heterogenous treatment effects; 3) biases generated by misclassification and measurement errors; and 4) the interpretation of local average treatment effects (LATE) arising from the policy interventions used as instrumental variables.


Occurrence, fate and potential health risks of antibiotic resistomes in a constructed wetlands-reservoir ecosystem for drinking water source improvement.
The development of effective and feasible engineering technologies to control the transmission of antibiotic resistance genes (ARGs) and pathogenic antibiotic-resistant bacteria (PARB) form drinking water sources is urgently needed for ensuring drinking water safety. In this study, metagenomic analysis was applied to systematically explore the full profiles, removal, and potential health risks of antibiotic resistomes in a large constructed wetlands-reservoir ecosystem (CWs-R) for drinking water source improvement. A total of 343 ARG subtypes belonging to 18 ARG types were identified from water and sediment samples in the CWs-R ecosystem, with an average abundance of 0.339 copies/cell, and bacitracin and multidrug resistance genes were the predominant ARG types in the water and sediment, respectively. The CWs-R ecosystem showed an excellent removal efficiency of ARGs and mobile genetic elements (MGEs) in water, with the total removal rate reaching 64.82 % and 77.09 %, respectively, among which the emergent plant zone and ecological storage unit played major roles. The metagenomic assembly tracked many mobile ARGs and opportunistic pathogens in the CWs-R ecosystem and identified 19 contigs as ARG-carrying pathogens, including Staphylococcus aureus, Salmonella enterica, Escherichia coli, and Klebsiella pneumonia. Overall, the CWs-R ecosystem has an important role in reducing the potential public health risks posed by antibiotic resistomes in drinking water sources but still cannot fully eliminate them. Therefore, we further classified water and sediment samples in the CWs-R ecosystem and identified potential ARGs and PARB indicators based on the metagenomic analysis results by considering the potential for horizontal transfer of ARGs to opportunistic pathogens. Taken together, this work demonstrates the CWs-R ecosystem as an economical and feasible engineering technology to reduce the dissemination of antibiotic resistomes in the drinking water source, provides useful information for monitoring and controlling antibiotic resistance in similar water sources, and ensures biosafety of drinking water.


Orosomucoid 1 promotes colorectal cancer progression and liver metastasis by affecting PI3K/AKT pathway and inducing macrophage M2 polarization.
Approximately 25-30% of those affected by colorectal cancer (CRC), the most prevalent gastrointestinal malignancy, develop metastases. The survival rate of patients with liver metastasis of CRC (CRLM) remains low owing to its unpredictability and a lack of biomarkers that can be applied to distinguish groups at higher risk for CRLM among patients with CRC. Therefore, our study aimed to find biomarkers that can predict the risk of CRLM. Screening of the Gene Expression Omnibus database, supported by an analysis of clinically obtained tissue and serum data using qPCR and ELISA, in an attempt to identify relevant biomarkers, enabled us to determine that orosomucoid 1 (ORM1) was differentially expressed in liver metastases and primary tumors of patients with CRC. Functionally, overexpression of ORM1 promoted the epithelial-mesenchymal transition and the proliferative, migratory, and invasive activities of MC38 cells and activated the PI3K/AKT signaling pathway. Moreover, MC38 cells overexpressing ORM1 enhanced the tumor immune microenvironment by promoting macrophage M2 polarization and elevating interleukin-10 (IL-10) expression. In vivo experiments further confirmed in vitro results, indicating that liver metastases elevated by ORM1 were partially attenuated by the depletion of macrophages or IL-10. Considered together, ORM1 promotes CRC progression and liver metastasis by regulating tumor cell growth and inducing macrophage M2 polarization, which mediates tumor immune tolerance, and thus acts as a potential predictive marker and therapeutic target in CRLM.


Ircinin-1 induces cell cycle arrest and apoptosis in SK-MEL-2 human melanoma cells.
We investigated the effects of ircinin-1, a lipid compound (a C25 sesterterpene tetronic acid) isolated from marine sponges (Sarcotragus sp.), on the modulation of cell cycle and induction of apoptosis in SK-MEL-2 human skin cancer cells (mutant p53). Ircinin-1 treatment on SK-MEL-2 cells resulted in a dose-dependent inhibition of cell growth and induced apoptotic cell death. Flow cytometric analysis revealed that ircinin-1 resulted in G1 arrest in cell cycle progression which was associated with a marked decrease in the protein expression of D-type cyclins and their activating partners Cdk 4 and 6 with concomitant inductions of p21WAF1/CIP1 and p27KIP1. The induction of p21WAF1/CIP1 appears to be transcriptionally upregulated and is p53-independent. In addition, ircinin-1 suppressed the phosphorylation of pRb protein and increased the co-association of pRb or proliferating cell nuclear antigen (PCNA) with p21WAF1/CIP1 in these cells. Ircinin-1 treatment also resulted in induction of apoptosis as determined by morphological changes, DNA fragmentation, alternated ratio of Bax/Bcl-2, cleavages of poly(ADP-ribose) polymerase and PLC-gamma1, and flow cytometric analysis. Ircinin-1 also induced cytochrome c release, cleavage activations of caspase-3 and -9, and upregulation of Fas and Fas-L. Even though the inhibitor of apoptosis protein (IAP) was expressed in ircinin-1-untreated or -treated SK-MEL-2 cells, only the level of cIAP-1, but not XIAP or cIAP-2, was decreased during ircinin-1-induced apoptosis at Western blot and RT-PCR studies. Taken together, these findings suggest that ircinin-1 has strong potential for development as an agent for prevention against skin cancer.


Deciphering environmental factors and defense response of rice genotypes against sheath blight disease.
Sheath blight (ShB) is one of the most serious diseases in rice, leading to severe yield losses globally. In our study, we evaluated a total of 63 rice genotypes for resistance against sheath blight disease by artificial inoculation over two seasons under field conditions and studied the weather parameters associated with disease incidence. Based on two years of testing, 23 genotypes were found moderately resistant, 38 were moderately susceptible, and 2 exhibited a susceptible reaction to sheath blight disease. Among the specific four genotypes (IC283139, IC283041, IC283038, and IC283023) of the moderately resistant group exhibited less disease reaction in comparison with check variety Tetep. Further, the correlation of percent disease index (PDI) with weather parameters revealed negative associations between PDI and maximum temperature, minimum temperature, low rainfall and the positive association with maximum relative humidity (RH) suggest that very low temperature or high precipitation might have a negative impact on pathogen establishment. In addition, the sheath blight-linked SSRs were assessed using distance and model-based approaches, results of both the models revealed that genotypes distinguished the resistant population from the susceptible one. From the output of two years of principal component analysis, two genotypes from each group of moderately resistant, moderately susceptible and susceptible were studied for their biochemical reaction against the sheath blight pathogen. The biochemical study revealed that the accumulation of defense and antioxidant enzymes, namely, polyphenol oxidase, peroxidase, total phenol, phenylalanine ammonia-lyase, catalase, and superoxide dismutase, were higher in moderately resistant genotypes, but was observed to be lower in moderately susceptible and susceptible genotypes. The statistical analysis revealed the enzyme activities (defense and antioxidant) exhibited a strong negative correlation with area under the disease progress curve (AUDPC) and influence of weather parameter RH. This demonstrates that the environment factor RH plays a major role in imparting the resistance mechanism by decreasing the enzymes activities and increasing PDI. This study found that the identified novel resistant genotype (IC283139) with purple stem base demonstrated improved resistance against sheath blight infection through a defense response and the use of antioxidant machinery.


Features of trisomy 18 and 18p- syndromes in an infant with 45,XY,i(18q).
An isochromosome for the long arm of chromosome number 18 - 46,XY,i(18q) - was found in an infant who had features of both trisomy 18 and 18p- syndromes. Findings compatible with trisomy 18 included postmature delivery, prominent occiput, severe congenital heart disease, overlapping fingers, and rocker-bottom feet. Those of 18p- syndrome, which frequently resembles Turner syndrome, were downward obliquity to the palpebral fissures, short, webbed neck, low posterior hairline, and widely-spaced nipples. The infant died of heart failure at 3.5 months of age. Parental karyotypes were normal.


Food production and agricultural systems on the southwestern frontier of the Han Empire: archaeobotanical remains from the 2016 excavation of Hebosuo, Yunnan.
Dian Basin in Yunnan province is an important center for both early agricultural production and centralized state formation. Settled agricultural villages are present in the province since at least the third millennium BC, and by the first millennium BC, the Dian Culture, a highly specialized bronze polity, flourished in the Dian Basin and surrounding area, until it was conquered by the Han in 109 BC. The increased deployment of flotation at recent archaeological excavations in Yunnan allowed the reconstruction of agricultural practices from the Neolithic to the early Bronze Age, documented at Baiyangcun, Haimenkou, and Xueshan among others. However, archaeobotanical evidence relating to the pivotal period right before and after the Han conquest have so far been lacking, with only limited written records about agricultural production in the Shiji by Sima Qian. Here we present for the first time direct archaeobotanical evidence relating to this transitional period as revealed by rich Han period deposits found during the 2016 excavation of Hebosuo, the largest Dian settlement investigated in Yunnan so far, dated by direct AMS on charred cereal grains and artefactual evidence as spanning from between 850 BC-220 AD. Following the Han conquest, the main components of the agricultural system did not undergo radical changes, but the weedy flora indicates a heavier reliance of wet-land rice systems, evidencing a higher level of water management or even irrigation practices, and the consequent intensification of the agricultural production. These findings on shifting agricultural regimes in Yunnan also contribute to current debates about the interplay between intensification, food risk, and ecology in times of political instability. The online version contains supplementary material available at 10.1007/s12520-023-01766-9.


Improving surgical outcomes with data tool.
Risk-adjusted data: Is it more valuable data? Nurse reviewer critical to NSQIP process. Get docs on board with NSQIP by explaining how data are used.


Metal-promoted variants of the Passerini reaction leading to functionalized heterocycles.
[reaction: see text]. The effect of replacing the Brønsted acid in classic Passerini reactions with a mild Lewis acid has been studied. Triggered by metal-promoted silylation, condensations of aliphatic or aromatic carbonyl compounds with appropriately substituted isonitriles capable of neighboring group donation afford alpha-hydroxyamides, substituted oxazoles, and other useful heterocycles.


Molecular epidemiology and clinical characteristics of Clostridioides difficile infection in patients with inflammatory bowel disease from a teaching hospital.
Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is of increasing concern. This study aimed to investigate the molecular epidemiology and antimicrobial susceptibilities of toxigenic C. difficile isolated from IBD patients and to evaluate the risk factors for CDI in IBD population. Loose or watery stools from IBD patients were tested for glutamate dehydrogenase, C. difficile toxins A&B and anaerobic culture. Toxigenic C. difficile isolates were characterized by multi-locus sequence typing, ribotyping and antimicrobial susceptibility testing. The prevalence of CDI in IBD patients was 13.6% (43/317). The dominant sequence types (STs) were ST35 (20.9%), ST2 (18.6%) and ST37 (16.3%). The most common ribotypes (RTs) were RT 017 (18.6%), RT 012 (14.0%), and RT 220 (14.0%), whereas RT 027 and RT 078 were not detected in this study. All the isolates were susceptible to vancomycin and metronidazole. The multidrug resistance rate of C. difficile RT 017 was higher (p < 0.01) than that of other RT strains. Recent hospitalization, use of corticosteroids and proton pump inhibitors were related to increased risk of CDI in IBD patients; of these, recent hospitalization and proton pump inhibitors use were independent risk factors. Patients with IBD have a relatively high incidence rate of CDI. C. difficile RT 017 is most frequently isolated from IBD patients in this region and warrants more attention to its high resistance rate. Clinicians should pay greater attention to CDI testing in IBD patients with diarrhea to ensure early diagnosis and initiation of effective treatment.


Adolescent respiratory symptoms--girls are at risk: the Young-HUNT study, Norway.
The objective was to study sex differences in adolescence regarding prevalence of asthma and current wheeze and to explore the association between respiratory symptoms and hereditary, lifestyle and socioeconomic factors. Young-HUNT included data comprehensive questionnaire on health, disease, lifestyle and social factors from 8817 teenagers 13-19 years conducted in 1995/97 (89% response rate). Questionnaire on respiratory symptoms was based on the International Study of Asthma and Allergy in Childhood (ISAAC). In age groups 13-16 and 17-19 years, current wheeze was reported by 29.0% and 33.5% among girls and 20.4% and 22.1% among boys, whilst the corresponding figures for asthma were 8.5% and 12.2% among girls and 7.1% and 7.0% among boys. Both wheeze and asthma were significantly more prevalent and increased with age in girls compared to boys. Heredity was associated with asthma, but the association was strongest between parents and children of the same sex. Environmental smoking was associated with asthma and wheeze in girls only. Girls reported more asthma and wheeze in association with overweight compared to boys. Girls reported more wheeze and asthma than boys and seemed more susceptible to risk factors such as environmental smoking and overweight than boys. Moreover, girls with mothers having asthma were more likely to be diagnosed as asthmatics themselves.


Metapopulation dynamics on the brink of extinction.
We analyse metapopulation dynamics in terms of an individual-based, stochastic model of a finite metapopulation. We suggest a new approach, using the number of patches in the population as a large parameter. This approach does not require that the number of individuals per patch is large, neither is it necessary to assume a time-scale separation between local population dynamics and migration. Our approach makes it possible to accurately describe the dynamics of metapopulations consisting of many small patches. We focus on metapopulations on the brink of extinction. We estimate the time to extinction and describe the most likely path to extinction. We find that the logarithm of the time to extinction is proportional to the product of two vectors, a vector characterising the distribution of patch population sizes in the quasi-steady state, and a vector-related to Fisher's reproduction vector-that quantifies the sensitivity of the quasi-steady state distribution to demographic fluctuations. We compare our analytical results to stochastic simulations of the model, and discuss the range of validity of the analytical expressions. By identifying fast and slow degrees of freedom in the metapopulation dynamics, we show that the dynamics of large metapopulations close to extinction is approximately described by a deterministic equation originally proposed by Levins (1969). We were able to compute the rates in Levins' equation in terms of the parameters of our stochastic, individual-based model. It turns out, however, that the interpretation of the dynamical variable depends strongly on the intrinsic growth rate and carrying capacity of the patches. Only when the local growth rate and the carrying capacity are large does the slow variable correspond to the number of patches, as envisaged by Levins. Last but not least, we discuss how our findings relate to other, widely used metapopulation models.


Psychological resilience contributes to low emotional distress in cancer patients.
Although a considerable number of cancer patients suffer from emotional distress which may have an impact on their quality of life, it still remains poorly understood which psychosocial factors contribute to individual vulnerabilities to emotional distress of cancer patients. Recently, resilience has been suggested as the capacity to cope with adversities like cancer. In this study, we investigated the relationships between resilience and emotional distress in cancer patients. One hundred fifty-two cancer patients who were consecutively hospitalized for their scheduled treatments at the Seoul St. Mary's Hospital were enrolled and completed the Connor-Davidson Resilience Scale and Hospital Anxiety Depression Scale to measure resilience and emotional distress. The relationships between the levels of psychological resilience and emotional distress were evaluated using univariate and multivariate logistic regression analyses. Psychological resilience levels were negatively associated with emotional distress after controlling for relevant covariates. The highest quartile of resilience level was associated with a 90% (adjusted odds ratio [OR] = 0.10, 95% confidence interval [CI] = 0.03-0.34, P < 0.001) reduction in the risk for emotional distress compared to the lowest quartile. Among metastatic cancer patients, resilience was also found to be a significant protective factor for emotional distress (adjusted OR = 0.14, 95% CI = 0.02-0.79, P = 0.02). The present study suggests that psychological resilience may independently contribute to low emotional distress in cancer patients. The relationship between resilience and emotional distress was also significant in the subgroup of metastatic cancer patients. Psychosocial interventions to enhance resilience might provide useful approaches to overcome cancer-related emotional distress.


Time-Trends of U.S. Occupational Noise Standard Violations by OSHA Region and Industry Type 1972 to 2019.
We examined time-trends in Occupational Noise Standard violations by OSHA region and industry type over 48 years. Along with descriptive analysis of original data, negative binomial regression and Poisson regression were applied to the analysis of 1972 to 2019 and 1972 to 2012 data, respectively. A small annual decrease in violation units over the periods was revealed. The three analyses produced differing timetrends. The manufacturing industry had more violations, and Region 4 had the most violations. Regarding numbers of units, the 10 regions and 2 industries were jointly significant. Some interaction between regions and industry types appeared in both regressions. OSHA should specify how many regions report noise violations each year to ensure accurate identification of noise-related health risks to American workers. Further time-trend studies are needed for specific regions and industry types.


Complete nucleotide sequence of Oat necrotic mottle virus: a distinct Tritimovirus species (family Potyviridae) most closely related to Wheat streak mosaic virus.
The RNA genome (9346 nucleotides) of Oat necrotic mottle virus (ONMV) was cloned and sequenced. Complete genome comparisons indicated that ONMV, currently classified as a rymovirus, was most closely related ( approximately 73% nucleotide, approximately 79% amino acid identity) to the tritimovirus Wheat streak mosaic virus (WSMV). ONMV encoded a single polyprotein, with proteinase cleavage sites very similar to those of WSMV. Pairwise comparison of ONMV and WSMV cistrons revealed that P3 was most conserved ( approximately 79% nucleotide, approximately 86% amino acid), whereas HC-Pro was most divergent ( approximately 67% nucleotide, approximately 69% amino acid). In contrast, the ONMV sequence was distantly related ( approximately 40% nt, approximately 26% amino acid identity) to that of the rymoviru s Ryegrass mosaic virus, with highest sequence conservation noted within the NIb cistron ( approximately 47% nucleotide, approximately 41% amino acid identity). These results firmly establish that ONMV is not a rymovirus but is instead a distinct species of the genus Tritimovirus.


Perfluorooctylbromide (PFOB) as a vitreous substitute in non-human primates.
We evaluated the toxicity of perfluorooctylbromide in the primate eye as a short-term postoperative vitreous substitute. Four eyes of 4 African green monkeys underwent complete vitrectomy and vitreous replacement with 1.5-2.0 ml of PFOB. One additional animal received BSS as a control vitreous substitute in one eye. Animals were examined twice weekly for clarity and consistency of the vitreous replacement substance. Anterior segment and lenses remained clear in all eyes, although in the immediate postoperative period one eye became inflamed and had a culture-negative vitritis. The other eyes showed a minimal anticipated postoperative vitreous inflammation. Emulsification of the PFOB began within 3 days of injection and progressed up to 3 weeks, precluding fundus examination and fluorescein angiography after 2 weeks. Eyes were enucleated and light microscopy performed at 2 days, 10 days, 33 days, and 45 days. No toxic effects to the retinal cells were detectable by histological examination, but perivasculitis of retinal vessels was noted at 45 days. Indirect examination was normal up to 10 days; thereafter, the fundus view was obscured by the emulsified PFOB. Because of cellular migration into the vitreous cavity and retinal perivasculitis, observed histologically, PFOB seems most suitable for intraoperative rather than postoperative use.


Live Imaging of Xist RNA.
Live imaging gives additional layers of information such as physical dynamics of a molecule of your interest. Aptamer-based green fluorescent protein (GFP) labeling is suitable for visualization of RNA molecules. Here we describe a method to visualize Xist RNA using the Bgl aptamer system.


Eco-physiological studies on desert plants : II. Germination of Zygophyllum coccineum L. seeds under different conditions.
Zygophyllum coccineum seeds were tested for germination under different conditions. They showed ability to germinate under a wide range of temperature from 10 to 35°C. The maximum percentage of germination was 92.5, reached at 25°C in darkness.Germination at alternating temperatures was lower than at 25°C. Seeds failing to germinate at 4 and 40°C showed high rate of germination when transferred to 25°C in dark.Exposure of seeds to light during germination inhibited the rate and percentage of germination at all temperatures. The germination percentage in alternating light was higher than that in continuous light, but both were lower than the percentage in complete darkness. The radicle is longer in dark germinated seedlings than in light germinated ones.The optimal depth of sowing was found to be 1 cm. Such a depth has numerous advantages for the germinating seeds. These advantages include the protection of the seeds against the inhibitory effect of light and against the rapid desiccation of the superficial soil layer.The seeds were able to germinate under high moisture stress in the order of 20 atm. The increase of the moisture stress up to a level of 8 atm did not affect the germination percentage significantly. The presence of salts in the germination medium inhibited germination to an extent more than that due to moisture stress alone. Seeds failing to germinate in salt solutions with osmotic values higher than 12 atm were able to germinate when washed with water.The present investigation shows that the seeds of Z. occineum have the ability to germinate under a wide variety of conditions. This represent an adaptation to the drastic prevailing conditions in the habitat of this plant.


Inhibition of interleukin-1β signalling promotes atherosclerotic lesion remodelling in mice with inflammatory arthritis.
Rheumatoid arthritis (RA), an inflammatory joint disorder, independently increases the risk of cardiovascular disease (CVD). IL-1β contributes to both RA and CVD. We hypothesised that inhibiting IL-1 signalling with the IL-1R antagonist, anakinra, would dampen inflammation and promote resolution of atherosclerosis in arthritic mice. Low-density lipoprotein receptor (Ldlr)-deficient mice were fed a Western-type diet for 14 weeks to develop atherosclerotic plaques. Mice were then switched to a chow diet, promoting lesion regression, and randomised to a control group or into groups where arthritis was induced by passive transfer of K/BxN arthritogenic serum. The arthritic mice were further randomised to vehicle or anakinra. Arthritis impaired atherosclerotic lesion regression when cholesterol was lowered. This was associated with a higher burden of plaque macrophages, likely due to monocytosis, driven by myelopoiesis in the bone marrow and spleen. Interestingly, delayed intervention with anakinra had no effect on arthritis in these mice. However, a significant improvement in atherosclerotic plaque remodelling to a more stable phenotype was observed. This was associated with fewer circulating monocytes, caused by a reduction in splenic extramedullary myelopoiesis. We show that inhibiting IL-1 signalling in arthritic mice with pre-existing atherosclerosis promotes lesion remodelling to a more stable phenotype, that is less likely to rupture and cause ischemic events such as myocardial infarction. This suggests that IL-1R antagonism may suppress CVD complications in patients with RA. Furthermore, inhibiting IL-1β signalling in other patients with inflammatory diseases that also predispose to CVD may also benefit from anti-IL-1 therapy.


The Liverpool duodenum-and spleen-preserving near-total pancreatectomy can provide long-term pain relief in patients with end-stage chronic pancreatitis.
Total pancreatectomy may improve symptoms in patients with severe end-stage chronic pancreatitis. This might be achieved whilst preserving both the duodenum- and spleen-(DPSPTP). Mature clinical outcomes of this approach are presented. Single-centre prospective cohort study performed between September 1996 and May 2016. Demographic, clinical details, pain scores and employment status were prospectively recorded during clinic attendance. Fifty-one patients (33 men, 18 women) with a median (interquartile range) age of 40.8 (35.3-49.4) years, a median weight of 69.8 (61.0-81.5) Kg and a median body mass index of 23.8 (21.5-27.8), underwent intended duodenum-and spleen-preserving near-total pancreatectomy for end-stage chronic pancreatitis. Aetiology was excess alcohol in 25, idiopathic (no mutation) in 15, idiopathic (SPINK-1/CFTR mutations) in two, hereditary (PRSS1 mutation) in seven and one each post-necrotising pancreatitis and obstructive pancreatic duct divisum in 1. The main indication for surgery was severe pain. Findings included parenchymal calcification in 79% and ductal calculi in 24%, a dilated main pancreatic duct in 57% and a dilated main bile duct in 17%, major vascular involvement in 27% and pancreato-peritoneal fistula in 2%. Postoperative complications occurred in 20 patients with two deaths. Median pain scores were 8 (7-8) preoperatively and 3 (0.25-5.75) at 5 years (p = 0.013). Opiate analgesic use was significantly reduced postoperatively (p = 0.048). Following surgery, 22 (63%) of 38 patients of working age re-entered employment compared with 12 (33%) working preoperatively (p = 0.016). Duodenum-and spleen-preserving near-total pancreatectomy provided long-term relief in adult patients with intractable chronic pancreatitis pain, with improved employment prospects.


We Must Do Better: Addressing High Mortality After Release from Incarceration.
People who are incarcerated have high rates of mental illness, substance use disorder, suicide attempts, and chronic medical conditions. Mortality rates are also significantly elevated following release. Additional work needs to be done to understand the risk factors for increased morbidity and mortality of people impacted by incarceration to better inform future interventions and system changes.


Surgical management of CSF otorrhoea (a case report).
Four cases of CSF otorrhoea following surgery are presented. The etiopathology and its surgical management are discussed.


Comparison of growth characteristics and roquefortin C production ofPenicillium roqueforti from blue-veined cheese.
The properties of 21 isolates ofPenicillium roqueforti from just as many commercial blue-veined cheeses, purchased from the Argentinean market (domestic and imported products) were comparatively examined. Isolates were investigated for their ability to grow at different temperatures, pH values and concentration of NaCl, as well as for their proteolytic and lipolytic activities, respectively. The potential of these strains to produce roquefortin in vitro, and the actual levels of roquefortin in 10 of these cheeses were analysed by TLC. All strains showed similar growth properties in aspects of salt concentration and pH-value of the medium, and all grew well at 10 °C. Only four strains showed proteolytic activity on casein agar, while all strains were lipolytic on trybutirin agar. After incubation at 25 °C for 16 days, all strains produced roquefortin in Yeast Extract Sucrose (25.6-426.7 μg/g) and in reconstituted (10%) sterile skim milk (26.9-488 μg/g). Roquefortin at >0.1 μg/g was also found in 9 out of 10 analysed samples of blue-veined cheeses (8 from Argentine, 1 from Spain), with a maximum value 3.6 μg/g. During the ripening process of blueveined cheese, production of roquefortin seems to be unavoidable. Care should be taken to select strains with low toxin production characteristics, to minimize potential health risks. Roquefortin C production byP. roqueforti in vitro was not correlated with roquefortin C levels found in cheese.


The 'tired person' syndrome. Understanding the pathologic factors in these 'problem' patients.
Many "problem" patients seen in primary care settings cannot be easily classified as "masked depressives" or seekers of secondary gain. Rather, they fit into a third category--those with the "tired person" syndrome. The essential feature of this syndrome is the decrease in self-esteem that follows the real or perceived loss of the ability to work productively. The decrease in self-esteem triggers anxiety, which may be so severe as to approach a panic state. The patient then becomes increasingly disabled or has increasing physical symptoms and enters a vicious cycle culminating in debility. Treatment is aimed at the physician's accepting and legitimizing the very real loss that the patient perceives in order to help him or her become comfortably dependent.


Establishment of a 3D Model to Characterize the Radioresponse of Patient-Derived Glioblastoma Cells.
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. Despite modern, multimodal therapeutic options of surgery, chemotherapy, tumor-treating fields (TTF), and radiotherapy, the 5-year survival is below 10%. In order to develop new therapies, better preclinical models are needed that mimic the complexity of a tumor. In this work, we established a novel three-dimensional (3D) model for patient-derived GBM cell lines. To analyze the volume and growth pattern of primary GBM cells in 3D culture, a CoSeedisTM culture system was used, and radiation sensitivity in comparison to conventional 2D colony formation assay (CFA) was analyzed. Both culture systems revealed a dose-dependent reduction in survival, but the high variance in colony size and shape prevented reliable evaluation of the 2D cultures. In contrast, the size of 3D spheroids could be measured accurately. Immunostaining of spheroids grown in the 3D culture system showed an increase in the DNA double-strand-break marker γH2AX one hour after irradiation. After 24 h, a decrease in DNA damage was observed, indicating active repair mechanisms. In summary, this new translational 3D model may better reflect the tumor complexity and be useful for analyzing the growth, radiosensitivity, and DNA repair of patient-derived GBM cells.


Continuous intra-arterial nimodipine for the treatment of cerebral vasospasm.
Two patients with refractory symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) were treated by continuous intra-arterial nimodipine infusion via a catheter placed in the internal carotid artery or vertebral artery for 3 and 12 days, respectively. Recovery of the neurological deficits, normalization of MR perfusion, a decrease in the elevated mean flow velocity measured by transcranial duplex sonography, and angiographic recanalization were observed. Continuous intra-arterial nimodipine might be a treatment option in severe refractory vasospasm following SAH.


Prediction of recurrence in the treatment of Dupuytren's disease: evaluation of a histologic classification.
Histologic staging of Dupuytren's lesions into three types is proposed: a proliferative type with high cellularity and mitosis, a fibrocellular type characterized by the presence of a reticulin network, and a fibrous type with few cells. Sixty-three patients (77 hands) who had selective fasciectomy as a primary procedure and whose histologic specimen was available were clinically reviewed for disease recurrence and extension. Twenty-two hands (29%) were free of disease; twenty-five (32%) were free from recurrence but showed an extension, and thirty (39%) had a recurrence. This histologic classification seems to have a prognostic value because the recurrence rate is higher in type I (70%) and lower in type III (18%). The risk of extension did not correlate with the histologic type.


[Study of the effect of a short-chain vitamin E analog on the structural and functional state of the plasma membrane of cardiomyocytes in vitro].
The results of study of influence of C6-analog of alpha-tocopherol on the structural and functional state of cardiomyocytes plasma membranes (CPM) in vitro are given. Under condition of incubation of CPM of intact animals the level of phospholipids was decreased, the level of fatty acids was increased, intensity of processes of free-radical oxidation (FRO) was significantly increased and activity of Na+, K(+)-ATPase was decreased in control samples of CPM. The analog of vitamin E supplementation at a concentration of 10 mg/ml of the medium significantly prevented the development of these changes. All of these can be evidence of effective membranes protective action of C6-analog of vitamin E on CPM.


Early Diagnostics of Freemartinism in Polish Holstein-Friesian Female Calves.
Freemartinism in females born from heterosexual multiple pregnancies is characterized by the presence of XX/XY cell lines due to the formation of a shared blood system by anastomoses between fetal membranes of co-twins and leads to disturbed development of the reproductive system, including infertility. The aim of this study was to estimate the most precise and effective diagnostic method, especially useful for early identification of freemartinism in young female calves. The cytomolecular evaluation results of 24 Holstein-Friesian heifers from heterosexual twins was verified by molecular techniques: PCR, short tandem repeats (STRs), and relative quantitative PCR. The molecular analyses have been found to be a more efficient testing strategy, with a higher diagnostic success rate than karyotype evaluation. In 21 heifers, leucocyte chimerism determined by the 60, XX/60, XY karyotype was revealed-the proportion of the 60, XY male cell line in individual animals was in the range of 4-66%. In three cases, a normal karyotype 60, XX was identified, which indicates that anastomoses did not occur in 12.5% of studied twins and suggests that these potentially fertile heifers can be qualified for further breeding. The precise and early identification of freemartinism can be the basis for guidelines and selection recommendations concerning the reproductive performance of heifers born from heterosexual multiple pregnancies.


Reciprocal interactions between olfactory receptor axons and olfactory nerve glia cultured from the developing moth Manduca sexta.
In olfactory systems, neuron-glia interactions have been implicated in the growth and guidance of olfactory receptor axons. In the moth Manduca sexta, developing olfactory receptor axons encounter several types of glia as they grow into the brain. Antennal nerve glia are born in the periphery and enwrap bundles of olfactory receptor axons in the antennal nerve. Although their peripheral origin and relationship with axon bundles suggest that they share features with mammalian olfactory ensheathing cells, the developmental roles of antennal nerve glia remain elusive. When cocultured with antennal nerve glial cells, olfactory receptor growth cones readily advance along glial processes without displaying prolonged changes in morphology. In turn, olfactory receptor axons induce antennal nerve glial cells to form multicellular arrays through proliferation and process extension. In contrast to antennal nerve glia, centrally derived glial cells from the axon sorting zone and antennal lobe never form arrays in vitro, and growth-cone glial-cell encounters with these cells halt axon elongation and cause permanent elaborations in growth cone morphology. We propose that antennal nerve glia play roles similar to olfactory ensheathing cells in supporting axon elongation, yet differ in their capacity to influence axon guidance, sorting, and targeting, roles that could be played by central olfactory glia in Manduca.


Changes in diet and supplement use in dogs with cancer.
Many dog owners alter their dog's nutritional regimen after a diagnosis of cancer. There are limited data as to specific changes made and reasons behind these changes. To collect updated and detailed data on changes made by owners to their dog's diet and supplements after a cancer diagnosis. Responses were collected from a survey of dog owners who brought their dogs to the UC Davis Veterinary Medical Teaching Hospital's Oncology Service for the first time after a cancer diagnosis. Dogs with recurrence or presenting for a second type of cancer were excluded. Eligible owners were surveyed between December 2020 and March 2022. The survey contained 62 questions regarding diet, supplement use, and treats, and how these were altered after a cancer diagnosis. Responses were matched to medical record data. One hundred twenty-eight surveys were retained for analysis, including 120 respondents that completed the survey. In response to a cancer diagnosis, 54.8% (95% CI; 45.7%-63.8%) of owners altered diets or supplements or both. The most common informational resource for dog diets was veterinarians (53.9%). Usage of home-prepared foods significantly increased after a cancer diagnosis (P = .03). There was no significant difference in commercial diet usage before or after a diagnosis (P = .25). Joint support products were the most common supplements given both before (37.4%) and after (35.0%) diagnosis. Many dog owners alter their dog's nutritional intake after a cancer diagnosis. These owners should be provided information relating to commonly observed alterations, including home-prepared foods and supplements.


Metabolic changes accompanying the loss of fumarate hydratase and malate-quinone oxidoreductase in the asexual blood stage of Plasmodium falciparum.
In the glucose-rich milieu of red blood cells, asexually replicating malarial parasites mainly rely on glycolysis for ATP production, with limited carbon flux through the mitochondrial tricarboxylic acid (TCA) cycle. By contrast, gametocytes and mosquito-stage parasites exhibit an increased dependence on the TCA cycle and oxidative phosphorylation for more economical energy generation. Prior genetic studies supported these stage-specific metabolic preferences by revealing that six of eight TCA cycle enzymes are completely dispensable during the asexual blood stages of Plasmodium falciparum, with only fumarate hydratase (FH) and malate-quinone oxidoreductase (MQO) being refractory to deletion. Several hypotheses have been put forth to explain the possible essentiality of FH and MQO, including their participation in a malate shuttle between the mitochondrial matrix and the cytosol. However, using newer genetic techniques like CRISPR and dimerizable Cre, we were able to generate deletion strains of FH and MQO in P. falciparum. We employed metabolomic analyses to characterize a double knockout mutant of FH and MQO (ΔFM) and identified changes in purine salvage and urea cycle metabolism that may help to limit fumarate accumulation. Correspondingly, we found that the ΔFM mutant was more sensitive to exogenous fumarate, which is known to cause toxicity by modifying and inactivating proteins and metabolites. Overall, our data indicate that P. falciparum is able to adequately compensate for the loss of FH and MQO, rendering them unsuitable targets for drug development.


Impact of cardio-renal syndrome on adverse outcomes in patients with Fabry disease in a long-term follow-up.
Fabry disease (FD) is a rare X-linked lysosomal storage disease with a deficiency of α-galactosidase A leading to progressive sphingolipid accumulation in different organs, among them heart and kidney. We evaluated the impact of cardio-renal syndrome (CRS) on the incidence of major cardiovascular complications and death in a prospective FD cohort. A total of 104 genetically proven FD patients were annually followed at the University Hospitals Zurich and Bern. The main outcome was a composite of incident renal replacement therapy (RRT), hospitalisation due to decompensated Heart Failure, new onset atrial fibrillation, pacemaker/ICD implantation, stroke/TIA and death. Estimated glomerular filtration rate (eGFR) and left ventricular myocardial mass index (LVMMI) where explored as the primary exposure variables. During the median follow-up of 103 [59-155] months, events occurred in 27 patients. In a Cox regression analysis, both higher LVMMI and lower eGFR were independently associated with a greater risk of developing adverse events after adjustment for multiple confounders (HR 1.67 [1.04-2.73] P=0.03 per SD increase in LVMMI, HR 0.45 [0.25-0.83], P=0.01 per SD decrease in eGFR). In patients with CRS, the risk to develop events was significantly increased if adjusted for demographics and RRT (HR 4.46 [1.07-18.62], P=0.04), approaching significance if additionally adjusted for hypertension (HR 4.05 [0.95-17.29], P=0.06). In Kaplan-Meier-Analysis, the poorest event-free survival was observed among patients with CRS. CRS was associated with a high risk to develop cardiovascular complications and death, emphasizing the importance of its prevention and early recognition. A focus on cardio-reno-protective therapies is crucial.


Nu-Way Snaps and Snap Leads: an Important Connection in the History of Behavior Analysis.
Beginning in the early 1950s, the snap lead became an integral and ubiquitous component of the programming of electromechanical modules used in behavioral experiments. It was composed of a Nu-Way snap connector on either end of a colored electrical wire. Snap leads were used to connect the modules to one another, thereby creating the programs that controlled contingencies, arranged reinforcers, and recorded behavior in laboratory experiments. These snap leads populated operant conditioning laboratories from their inception until the turn of the twenty-first century. They allowed quick and flexible programming because of the ease with which they could be connected, stacked, and removed. Thus, the snap lead was integral to the research activity that constituted the experimental analysis of behavior for more than five decades. This review traces the history of the snap lead from the origins of the snap connector in Birmingham, England, in the late eighteenth century, through the use of snaps connected to wires during the Second World War, to its adoption in operant laboratories, and finally to its demise in the digital age.


Diabetic Foot Ulcer Patients' Uncertainty Regarding Their Prognosis: A Q-Methodological Study.
The purpose of this qualitative study was to identify the subjective patient perspectives toward the uncertainty regarding diabetic foot ulcer (DFU) prognosis. Q-methodology, which is a qualitative method for analyzing subjective viewpoints, was used. Forty patients with DFUs who were admitted to the diabetic wound center of a university hospital in Seoul, South Korea. Data were collected on the subjective viewpoint of patients regarding their DFU prognosis uncertainty and analyzed by the software program PQMethod 2.35 using a principal component analysis and varimax rotation. This study revealed 4 factors characterizing patient subjective experience related to DFU prognosis: confusion from a lack of knowledge, concerns about a negative future, overdependence on information, and expectations for a positive outlook about favorable results. The findings of this study suggest various intervention methods for patients with DFU facing uncertainty about their prognosis based on the 4 viewpoints identified. The identification of the factor causing uncertainty and integration of all uncertainty factors are expected to be used as the basis for reducing patients' uncertainty and helping nurses care for patients more effectively.


Towards carbon neutrality: The role of different paths of technological progress in mitigating China's CO2 emissions.
China's carbon neutrality in 2060 is a hot issue discussed by policymakers and scholars. Previous literature shows that technological progress is the key to CO2 emission mitigation, but ignores the role of different paths of technological progress. This paper uses the panel data covering China's 30 provinces from 2008 to 2017 to study the effect of different paths of technological progress on CO2 emissions including domestic innovation, foreign technology import and regional technology transfer. Furthermore, the assimilation effect of technologies from domestic and foreign is investigated, and its impact on CO2 emissions is explored. The empirical evidence indicates that: (1) there is an inverted U-shaped relationship between domestic innovation and China's CO2 emissions. (2) Foreign technology imports cannot decrease CO2 emissions and carbon intensity in high-emission regions. Meanwhile, domestic technology transfer increase CO2 emissions and carbon intensity in high-emission regions. However, foreign technology import of low-emission areas can achieve CO2 emission mitigation. (3) The assimilation of technologies from abroad and domestic can increase CO2 emissions and carbon intensity in high-emission regions. But the absorption effect of technologies from domestic can decrease CO2 emissions and carbon intensity in low-carbon regions. According to the above results, this paper proposes some targeted policy suggestions for the choice of technological progress paths for CO2 emission mitigation in different regions of China.


[Influence of ApoE gene polymorphisms on therapeutic effects of lipid-lowering statins among patients with ischemic cerebral infarction].
To assess the influence of apolipoprotein E (ApoE) gene polymorphisms on the therapeutic effect of lipid-lowering statins in patients with ischemic cerebral infarction. One hundred and six patients with ischemic cerebral infarction who orally took lipid-lowering statins for 3 months were enrolled. Changes in serum triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) before and after the drug administration were analyzed. ApoE gene polymorphisms were detected by real-time fluorescent quantitative PCR, and genotypes of ApoE gene in patients with different effects were compared. The detection rates for E2/E2, E2/E3, E3/E3, E2/E4 and E3/E4 genotypes were 0.94%, 11.32%, 63.21%, 1.89% and 22.64%, respectively. And the detection rates for E2, E3 and E4 alleles were 7.55%, 80.19% and 12.26%, respectively. Biochemical phenotypes included E2 type (13 cases, 12.26%), E3 type (69 cases, 65.09%) and E4 type (24 cases, 22.65%). Before administration, TG and TC of E2 type were the highest (P<0.05), but no significant difference was detected in HDL-C and LDL-C among the three phenotypes (P>0.05).Following the drug administration, TG, TC and LDL-C were decreased, while HDL-C was increased. HDL-C of E2 type was the highest, TC and LDL-C of E4 type were the highest (P<0.05). The E3/E3 ratio in low-efficiency group at admission was lower than that in the high-efficiency group, while the E3/E4 ratio was higher than that in the high-efficiency group (P<0.05). The proportion of E3 allele in low-efficiency group was lower than that in high-efficiency group, while the proportion of E4 allele was higher than that in high-efficiency group (P<0.05). ApoE gene polymorphisms are closely correlated with the therapeutic effect of lipid-lowering statins in patients with ischemic cerebral infarction. The lipid-lowering effects are more significant in patients with E2 and E3 genotypes, but were poor in those with the E4 genotype. Personalized regimens should be applied.


Apollonian dynamics, mitotic spindle and anaphase chromatids.
The so-called 'Apollonian gasket' offers interesting suggestions on how chromatids might be packaged among microtubular bundles of the mitotic spindle. While transiting through the spindle's viscous environment, the helical motions of coiled chromatids engender important interactions via synergistic or antagonistic torques that are instrumental for both shape and function of normal genomes as well as for certain anomalies (aneuploidy, nuclear deformations, etc) often associated to the malignant state.


Nitrile and amide biotransformations for the synthesis of enantiomerically pure 3-arylaziridine-2-carboxamide derivatives and their stereospecific ring-opening reactions.
Catalyzed by Rhodococcus erythropolis AJ270 (whole cell catalyst) under very mild conditions, a number of racemic trans-3-arylaziridine-2-carbonitriles and amides were efficiently transformed into enantiopure 2R,3S-3-arylaziridine-2-carboxamides. While the nitrile hydratase exhibits low selectivity against nitrile substrates, the amidase is highly enantioselective toward 2S,3R-3-arylaziridine-2-carboxamides. Upon the treatment with catalytic hydrogenation, amine, or water in the presence of one equivalent of TFA, the resulting aziridine-2-carboxamides underwent highly efficient and stereospecific ring-opening reactions to produce enantiopure alpha-amino-, alpha,beta-diamino-, and alpha-amino-beta-hydroxy-propanamide derivatives in high yields.


A guide to fragile sites on human chromosomes.
This is a guide to 107 fragile sites, all those considered at the most recent International Workshop on Human Gene Mapping, HGM 9.5, held in 1988. The chromosome band locations of all 107 fragile sites are given, together with their gene symbols, frequency, mode of induction, and status. The majority of these fragile sites are common ones induced to expression by aphidicolin. Fragile sites are nonrandomly distributed within the genome. Chromosome 3 is especially short of known fragile sites. Chromosome 21, the chromosome triplicated in Down syndrome, has no known fragile sites.


Recombinant spike protein vaccines coupled with adjuvants that have different modes of action induce protective immunity against SARS-CoV-2.
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a glycoprotein, expressed on the virion surface, that mediates infection of host cells by directly interacting with host receptors. As such, it is a reasonable target to neutralize the infectivity of the virus. Here we found that a recombinant S protein vaccine adjuvanted with Alhydrogel or the QS-21-like adjuvant Quil-A effectively induced anti-S receptor binding domain (RBD) serum IgG and neutralizing antibody titers in the Syrian hamster model, resulting in significantly low SARS-CoV-2 replication in respiratory organs and reduced body weight loss upon virus challenge. Severe lung inflammation upon virus challenge was also strongly suppressed by vaccination. We also found that the S protein vaccine adjuvanted with Alhydrogel, Quil-A, or an AS03-like adjuvant elicited significantly higher neutralizing antibody titers in mice than did unadjuvanted vaccine. Although the neutralizing antibody titers against the variant viruses B.1.351 and B.1.617.2 declined markedly in mice immunized with wild-type S protein, the binding antibody levels against the variant S proteins were equivalent to those against wild-type S. When splenocytes from the immunized mice were re-stimulated with the S protein in vitro, the induced Th1 or Th2 cytokine levels were not significantly different upon re-stimulation with wild-type S or variant S, suggesting that the T-cell responses against the variants were the same as those against the wild-type virus. Upon Omicron XBB-challenge in hamsters, wild-type S-vaccination with Alhydrogel or AS03 reduced lung virus titers on Day 3, and the Quil-A adjuvanted group showed less body weight loss, although serum neutralizing antibody titers against XBB were barely detected in vitro. Collectively, recombinant vaccines coupled with different adjuvants may be promising modalities to combat new variant viruses by inducing various arms of the immune response.


Antecedents of fatigue, close calls, and crashes among commercial motor-vehicle drivers.
Minimizing driver fatigue among commercial motor-vehicle (CMV) drivers is a major safety issue in the United States. This study examines the effects of potentially fatigue-inducing factors inherent in truck driving work and company safety management in explaining: (a) drivers driving while fatigued, (b) the frequency of close calls due to fatigue, and (c) actual crashes among CMV drivers. Data for this study are derived from a survey of CMV drivers in 116 trucking firms, with all data being driver-reported. The relative roles of fatigue-inducing factors and safety management practices in explaining variation in fatigue, close calls, and crashes are reported, along with the roles of fatigue in affecting close calls and crashes via hierarchical regression. Findings indicated that fatigue-inducing factors inherent in driving work and safety practices accounted for appreciable variation in driving fatigued (R(2) =.42) and close calls (R(2) =.35), but not crash involvement. Driving while fatigued also accounted for incremental increases in the amount of variation in close calls, after consideration of inherent factors and safety practices. Findings indicate that safety practices (e.g., establishment of a strong safety culture, dispatcher scheduling practices, company assistance with fatiguing behaviors such as loading and unloading) have considerable potential to offset fatigue-inducing factors associated with truck driving work.


Development and small-scale validation of a novel pigeon-associated mitochondrial DNA source tracking marker for the detection of fecal contamination in harvested rainwater.
The current study was aimed at designing and validating (on a small-scale) a novel pigeon mitochondrial DNA (mtDNA) microbial source tracking (MST) marker for the detection of pigeon fecal matter in harvested rainwater. The pigeon mtDNA MST marker was designed to target the mtDNA Cytochrome b gene by employing mismatch amplification mutation assay kinetics. The pigeon marker was validated by screening 69 non-pigeon and 9 pigeon fecal samples. The host-sensitivity of the assay was determined as 1.00 while the host-specificity of the assay was 0.96. Harvested rainwater samples (n=60) were screened for the prevalence of the marker with the mtDNA Cytochrome b marker detected in 78% of the samples. Bayes' theorem was applied to calculate the conditional probability of the marker detecting true pigeon contamination and the marker subsequently displayed a 99% probability of detecting true pigeon contamination in the harvested rainwater samples. In addition, the mtDNA Cytochrome b marker displayed high concurrence frequencies versus heterotrophic bacteria (78.3%), E. coli (73.3%), total coliforms (71.1%) and fecal coliforms (66.7%). This study thus validates that targeting mtDNA for the design of source tracking markers may be a valuable tool to detect avian fecal contamination in environmental waters.