A tertiary approach to improving equity in health: quantitative analysis of the Māori and Pacific Admission Scheme (MAPAS) process, 2008-2012.
Achieving health equity for indigenous and ethnic minority populations requires the development of an ethnically diverse health workforce. This study explores a tertiary admission programme targeting Māori and Pacific applicants to nursing, pharmacy and health sciences (a precursor to medicine) at the University of Auckland (UoA), Aotearoa New Zealand (NZ). Application of cognitive and non-cognitive selection tools, including a Multiple Mini Interview (MMI), are examined. Indigenous Kaupapa Māori methodology guided analysis of the Māori and Pacific Admission Scheme (MAPAS) for the years 2008-2012. Multiple logistic regression models were used to identify the predicted effect of admission variables on the final MAPAS recommendation of best starting point for success in health professional study i.e. 'CertHSc' (Certificate in Health Sciences, bridging/foundation), 'Bachelor' (degree-level) or 'Not FMHS' (Faculty of Medical and Health Sciences). Regression analyses controlled for interview year, gender and ancestry. Of the 918 MAPAS interviewees: 35% (319) were Māori, 58% (530) Pacific, 7% (68) Māori/Pacific; 71% (653) school leavers; 72% (662) females. The average rank score was 167/320, 40-80 credits below guaranteed FMHS degree offers. Just under half of all interviewees were recommended 'CertHSc' 47% (428), 13% (117) 'Bachelor' and 38% (332) 'Not FMHS' as the best starting point. Strong associations were identified between Bachelor recommendation and exposure to Any 2 Sciences (OR:7.897, CI:3.855-16.175; p < 0.0001), higher rank score (OR:1.043, CI:1.034-1.052; p < 0.0001) and higher scores on MAPAS mathematics test (OR:1.043, CI:1.028-1.059; p < 0.0001). MMI stations had mixed associations, with academic preparation and career aspirations more consistently associated with recommendations. Our findings raise concerns about the ability of the secondary education sector to prepare Māori and Pacific students adequately for health professional study. A comprehensive tertiary admissions process using multiple tools for selection (cognitive and non-cognitive) and the provision of alternative entry pathways are recommended for indigenous and ethnic minority health workforce development. The application of the MMI within an equity and indigenous cultural context can support a holistic assessment of an applicant's potential to succeed within tertiary study. The new MAPAS admissions process may provide an exemplar for other tertiary institutions looking to widen participation via equity-targeted admission processes.


Natural killer cell cytotoxicity and paternal lymphocyte immunization in women with recurrent spontaneous abortions.
Natural killer (NK)-cell cytotoxicity in women undergoing lymphocyte immunization prior to and following treatment was investigated. A cohort of 33 women with a history of two or more recurrent spontaneous abortions was prospectively studied. NK-cell cytotoxicity was determined at effector-to-target ratios of 50:1 and 25:1. Peripheral blood CD56+ NK-cell, CD19+ B-cell, CD19+/5+ B-1-cell, and CD3+ pan T-cell levels were studied by flow cytometry before and after lymphocyte immunization treatment. Maternal antipaternal T- and B-cell antibody levels were measured before and after lymphocyte immunization by flow cytometric analysis. Paternal lymphocyte immunizations were given two times with a 4-week interval. Post-lymphocyte immunization testing was done 4 weeks after the second lymphocyte immunization. The controls were 8 normal healthy women. NK assays were done twice with an interval of 8 weeks. NK-cell activity at effector-to-target ratios of 50:1 (P = 0.005) and 25:1 (P = 0.001) were significantly suppressed after lymphocyte immunization. CD3+ pan T-cell levels after lymphocyte immunization were significantly increased compared with levels before lymphocyte immunization (P = 0.008). CD56+ NK-cell levels were significantly suppressed after lymphocyte immunization (P = 0.016). There was no correlation between changes in NK cytotoxicity and differences in antipaternal lymphocyte antibody levels before or after lymphocyte immunization. Lymphocyte immunization suppresses NK-cell cytotoxicity and CD56+ NK-cell levels and increases the peripheral blood CD3+ T-cell population in women with recurrent spontaneous abortions.


A structurally conserved human and Tetrahymena telomerase catalytic core.
Telomerase is a ribonucleoprotein complex that counteracts the shortening of chromosome ends due to incomplete replication. Telomerase contains a catalytic core of telomerase reverse transcriptase (TERT) and telomerase RNA (TER). However, what defines TERT and separates it from other reverse transcriptases remains a subject of debate. A recent cryoelectron microscopy map of Tetrahymena telomerase revealed the structure of a previously uncharacterized TERT domain (TRAP) with unanticipated interactions with the telomerase essential N-terminal (TEN) domain and roles in telomerase activity. Both TEN and TRAP are absent in the putative Tribolium TERT that has been used as a model for telomerase for over a decade. To investigate the conservation of TRAP and TEN across species, we performed multiple sequence alignments and statistical coupling analysis on all identified TERTs and find that TEN and TRAP have coevolved as telomerase-specific domains. Integrating the data from bioinformatic analysis and the structure of Tetrahymena telomerase, we built a pseudoatomic model of human telomerase catalytic core that accounts for almost all of the cryoelectron microscopy density in a published map, including TRAP in previously unassigned density as well as telomerase RNA domains essential for activity. This more complete model of the human telomerase catalytic core illustrates how domains of TER and TERT, including the TEN-TRAP complex, can interact in a conserved manner to regulate telomere synthesis.


A profile analysis of problematic smartphone usage among college students during coronavirus disease 2019: Relations with the impact of news reports.
The coronavirus disease 2019 (COVID-19) outbreak was the first pandemic to occur in a fully globalized society. The aims of the study were to explore the state of problematic smartphone use (PSU) and its risk factors during this incident. A total of 77,211 college students were surveyed online during the COVID-19 pandemic. Conducting latent profile analysis (LPA), we found the most support for a three-class model of subgroups: over-use group (17.3% of the sample), moderate-use group (54.8% of the sample), mild-use group (27.9% of the sample). The results of multinomial logistic regression show that college students who experienced an extreme negative impact from news reports were more likely to be included in the over-use group than in the mild-use group. These results providing insights that may help foster and develop appropriate and effective solutions to prevent PSU among college students during crises, such as reducing the coverage of negative news report. The online version contains supplementary material available at 10.1007/s12144-022-03896-0.


[Nucleic acid concentration and ribonuclease activity in muscles during their activity].
The content of RNA, activity of RNase and content of amino acids in skeletal muscles were studied as affected by muscular activity. The RNA level is shown to increase in the muscles of trained and untrained animals. The RNase activity lowers in animals of both groups. The load causes quantitative changes in amino acidic composition of the muscles; the content of cystine, cysteine, asparaginic acid, lysin and leucine decreases.


Synthetic peptides derived from the Schistosoma mansoni secretory protein Sm16 induce contrasting responses in hepatic stellate cells.
Sm16 is a 16 KDa protein released by Schistosoma mansoni that modulates inflammatory responses in host cells. Sm16 is expressed by several life cycle stages of S. mansoni, including the egg stage. Schistosome eggs are known to provoke chronic schistosomiasis pathology, which involves the development of liver fibrosis. Hepatic stellate cells (HSCs), which are responsible for this fibrosis, are susceptible to immunomodulation by S. mansoni whole egg secretions. To define the effects of Sm16 exposure on HSCs, two synthetic peptide derivatives of Sm16, coined "KS-84″ and "KS-66″, were tested against LX-2 cells, an immortalised human HSC line, and RNA sequencing was used to assess the transcriptional changes induced by each peptide. In total, 78 and 798 genes were found to be significantly differentially expressed by KS-84 and KS-66 treatment, respectively. In silico pathway analysis of these genes revealed that KS-84 reduced LX-2 cell activation and fibrotic potential, whereas KS-66 increased both processes. Reduced transforming growth factor-β1 (TGF-β1) signalling was identified as a potential mechanism of KS-84-induced inhibition of LX-2 activation. Taken together, these findings indicate a potential role for Sm16 in combatting fibrotic liver disease.


Potential applications of passive sampling for monitoring non-polar industrial pollutants in the aqueous environment in support of REACH.
Possible roles of passive sampling within the context of the European REACH legislation are discussed. Passive samplers can provide information on environmental concentrations, fate and behaviour of substances of concern. They can potentially replace biota in the assessment of bioavailability, having advantages including lower cost and variability, and greater repeatability and acceptability on ethical grounds. Where remedial actions (e.g., product withdrawal, replacement or redesign) may be required, wrong decisions are potentially very costly. Against this background it may be possible to develop strategies based on passive sampling that will protect the environment from potential damage whilst minimising operational costs.


The role of chloroplast-membrane-protein synthesis in the circadian clock. Purification and partial characterization of a polypeptide which is suggested to be involved in the clock.
A polypeptide (polypeptide P39), which is presumed to involved in the photosynthetic circadian rhythm in the green alga Acetabularia, was purified from the EDTA-insoluble chloroplast membrane fraction by means of preparative dodecylsulfate gel electrophoresis and then partially characterized. The purity of the isolated polypeptide P39 was confirmed by a further electrophoresis on an analytical dodecylsulfate gel and further elucidated by amino-terminal analysis which shows that glycine is the only amino-terminal amino acid of the purified polypeptide material. The molecular weight of the polypeptide P39 was found to be about 39,000 on analytical gel electrophoresis and the value was further supported by those obtained from amino acid composition and peptide mapping. The amino acid composition of polypeptide P39 showed that the proportion of intermediate amino acid groups is high while the proportion of hydrophilic amino acid groups is well balanced by that of hydrophobic amino acid groups, a property characteristic of membrane proteins.


Comparative investigations with trypaflavin in metaphase-II oocytes and in dominant lethal assay.
Pregnant C3H mice were orally treated with 50 mg Trypaflavin/kg on day 7, 11, 14, or 15 post conception. The embryos were thus treated in utero with the test compound. At the age of 10 weeks, the dominant lethal assay was performed with F1 females. Dominant lethal mutations were induced only in those mice treated in utero on day 7 of the prenatal stage. Female C3H mice were chronically treated with Trypaflavin (50 X 2 mg/kg/day; dissolved in drinking water). These mice were caged with untreated males. The percentage of preimplantation egg loss and the yield of dead implants per female was increased. Female NMRI mice were chronically treated with Trypaflavin (50 X 2 mg/kg/day by stomach tube). In metaphases II of unfertilized oocytes, the yield of all observed aberration types (aneuploidies, gaps, satellite associations, breaks and fragments, deletions, and interchanges) was increased weakly.


LDLR and ApoB are major genetic causes of autosomal dominant hypercholesterolemia in a Taiwanese population.
Autosomal dominant hypercholesterolemia (ADH) is an autosomal dominant inherited disease characterized by an increase in low-density lipoprotein cholesterol levels and premature coronary heart disease, which can be caused by mutations in genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9). There is scant information with regard to the role played by each gene in the Taiwanese ADH population, especially the newly discovered PCSK9 gene. We used coupling heteroduplex analysis based on a denaturing high performance liquid chromatography system and DNA sequencing to screen for the LDLR gene, APOB gene and PCSK9 gene in 87 ADH cases recruited from 30 unrelated Taiwanese families. We did not find any mutation-causing variant of the PCSK9 gene in our cases and thus excluded PCSK9 as the major culprit mutation in these families. On the other hand, we identified six previously reported LDLR gene mutations (C107Y, D69N, R385W, W462X, G170X, V408M), two novel LDLR gene mutations (FsG631 and splice junction mutation of intron 10), and one known mutation (R3500W) and one novel missense mutation (T3540M) in the APOB gene that were present in 55 members from 18 ADH families (60%). R3500W, rather than R3500Q, could be the principle mutation responsible for familial defective apolipoprotein B in Taiwanese. The results of our study reveal a characteristic mutation pattern of ADH in Taiwan, mainly in the LDLR and APOB genes. However, PCSK9 gene mutation may not be a major cause of ADH in our study population.


Dissimilar perceptual response between trained women and men in resistance training to concentric failure: A quasi-experimental study.
This study compared sex-related affective responses during resistance training performed to concentric failure. The study was a non-randomized trial (quasi-experimental study). Well-trained young participants were allocated into two groups according to sex (Women, n = 7, 21.1 ± 6.0 years, 57.6 ± 5.0 kg; and Men, n = 7, 28.3 ± 5.7 years, 88.3 ± 11.4 kg). Participants visited the laboratory three times: 1) 12-repetition maximum; 2-3) resistance training to concentric failure sessions. Perceptual measures were assessed before, during, and immediately after the resistance training sessions. The following were assessed: a) rating of perceived exertion for effort (RPE-E) and discomfort (RPE-D), b) feeling scale, c) physical activity affect scale (PAAS), d) felt arousal scale, and e) physical activity enjoyment scale (PACES). High levels of RPE-E and RPE-D were reported without between-groups differences (p > 0.218). Women reported a reduction in the feeling scale (p = 0.001) whereas men did not (p > 0.680). Larger effect sizes were observed for women compared to men in the felt arousal scale and PAAS (negative affect and fatigue). Feeling scale and felt arousal scale data plotted in a circumplex model of affect indicated a transition to high-activation and unpleasant-affect only for the women. There was good reliability between results from sessions 1 and 2. Training to concentric failure resulted in negative changes in affective perceptual responses only for women. This type of training should be used with caution since it may change the affect perception and reduce training adherence in women. Further studies are needed using larger sample sizes, different resistance-training exercises, and diverse training methods.


Influence of ABCB1 genetic polymorphisms on cyclosporine intracellular concentration in transplant recipients.
The expression on lymphocytes of P-glycoprotein, an efflux transporter encoded by the ABCB1 gene, might influence cyclosporine intracellular concentration. ABCB1 genotypes, cyclosporine intracellular and blood concentrations were determined in 64 stable renal, liver or lung transplant recipients. Cyclosporine intracellular concentration correlated moderately with blood concentration (r=0.30, P<0.00005). The ABCB1 1199A carriers presented a 1.8-fold decreased cyclosporine intracellular concentration (P=0.04), whereas the 3435T carriers presented a 1.7-fold increase (P=0.02) as well as a 1.2-fold increased blood concentration (P=0.04). In contrast, ABCB1 61A>G, 1236C>T and 2677G>T polymorphisms did not influence cyclosporine intracellular and blood concentrations. This is the first report demonstrating that ABCB1 polymorphisms influence cyclosporine intracellular concentration. Interestingly, its influence on intracellular concentration is significantly higher than on blood concentration (P<0.002). This may therefore modulate cyclosporine immunosuppressive activity.


An in vivo study of benzene metabolite DNA adduct formation in liver of male New Zealand rabbits.
Rabbits were treated with benzene (586 mg/kg/b.i.d./4 days) after which DNA was isolated from liver and analyzed for adduct formation using the [32P] post-labeling method of Randerath and coworkers (Randerath et al. 1981; Reddy et al. 1984, 1986, 1987). Liver 500 g and 9000 g fractions were analyzed for adducts. There appeared to be several adducts in both the 500 g and 9000 g fractions observed on radioautographs of cellulose-TLC plates. Several adducts were also observed when the 9000 g fraction was studied using HPLC.


In vitro mature embryo culture protocol of einkorn (Triticum monococcum ssp. monococcum) and bread (Triticum aestivum L.) wheat under boron stress.
Mature embryos of einkorn (Triticum monococcum ssp. monococcum) and bread (Triticum aestivum L.) wheat were used for callus induction on media containing four different doses (0, 1, 2 and 4 mg L-1) of 2,4-D and dicamba supplemented with five different boron concentrations (0, 6.2, 12.4, 24.8, and 37.2 mg L-1). The obtained callus was transferred to culture media with three (0, 0.5, and 2 mg L-1) different BAP doses with five boron concentrations for further regeneration. The maximum callus weight in einkorn wheat was in culture media with 1 mg L-1 dicamba and 6.2 mg L-1 (3.71 ± 0.13 g). Bread wheat had the maximum callus weight on culture media with 4 mg L-1 dicamba and 12.4 mg L-1 (3.46 ± 0.40 g). The highest plantlet numbers were in only 2 mg L-1 BAP (2.92 ± 0.88) for einkorn wheat and 0.5 mg L-1 BAP supplemented with 6.2 mg L-1 boron (3.71 ± 1.12) for bread wheat. This indirect regeneration protocol using mature embryos of einkorn and bread wheat under boron stresses expected to be useful for future wheat breeding studies.


Genomic data visualization on the Web.
Many types of genomic data can be represented in matrix format, with rows corresponding to genes and columns corresponding to gene features. The heat map is a popular technique for visualizing such data, plotting the data on a two-dimensional grid and using a color scale to represent the magnitude of each matrix entry. Prism is a Web-based software tool for generating annotated heat map visualizations of genome-wide data quickly. The tool provides a selection of genome-specific annotation catalogs as well as a catalog upload capability. The heat maps generated are clickable, allowing the user to drill down to examine specific matrix entries, and gene annotations are linked to relevant genomic databases. http://noble.gs.washington.edu/prism


The cardiorenal link in advanced cirrhosis.
A considerable number of patients with advanced cirrhosis develop a hepatorenal syndrome. The pathogenesis involves liver dysfunction, splanchnic vasodilatation, and activation of vasoconstrictive systems. There are now several observations that indicate a relation between the renal failure and impaired cardiac function in patients with advanced cirrhosis. Cirrhotic cardiomyopathy has been described as a condition with impaired contractile responsiveness to stress and altered diastolic relaxation. We propose a cardiorenal interaction in patients with advanced cirrhosis and renal dysfunction that refers to a condition where cardiac dysfunction in cirrhosis is a major determinant of kidney function and survival. Thus, the relation between cardiac dysfunction and renal insufficiency should be target for future studies and development of new treatments should focus on ameliorating the cardiac dysfunction.


Environmental risk assessments and spatial variations of polycyclic aromatic hydrocarbons in surface sediments in Yangtze River Estuary, China.
In this study, based on sampling data from 30 sites in August 2010, the environmental risks associated with 16 priority PAHs were estimated in surface sediments from the Yangtze River Estuary (YRE). The results indicated that the toxic equivalent quantities of the benzo[a]pyrene (TEQBap) from 30 sites were in the range of 1.93-75.88ngg(-1), and the low-molecular-weight PAHs were the dominated species with higher potential toxicity. The results of the Incremental Lifetime Cancer Risk (ILCR) model indicated that the ILCR values of dermal contact were higher than 10(-6) in the northeast region, suggesting that there were significant potential carcinogenic health risks for fishermen exposure to sedimentary PAHs via dermal contact in these areas. RQ values of PAHs indicated the various distributions of ecological risk levels in the study area. These variations might be caused by the natural and anthropogenic inputs and currents in the YRE.


[A rare case of the meningoencephalitis form of the Loeffler syndrome].
The article describes a case of benign meningoencephalitis attended by marked eosinophilia. The disease was evaluated as a meningoencephalitic form of Loeffler's syndrome. Drug-induced allergy is considered as a possible cause of the disease.


Antidiabetic drugs, glycemic control and risk of benign prostatic hyperplasia.
Diabetes has been associated with an increased risk of benign prostatic hyperplasia (BPH). However, the role of antidiabetic drugs as a BPH risk factor is unclear. The objective of our study was to examine the risk of BPH by antidiabetic drug use and glycemic control in a large population-based cohort of Finnish men. A total of 74,754 men in the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) free of BPH at baseline in 1996-1999 were linked to the national medication reimbursement database for information on physician-prescribed antidiabetic drug purchases. Information on recorded BPH procedures and diagnoses was obtained from the National Care Register for Health Care, and for a subgroup of 17,739 men, information on blood glucose levels (BGLs) from the Fimlab Laboratories database. Cox regression with antidiabetic drug use and BGL as time-dependent variables was used to analyze the risks for starting BPH medication, recorded BPH diagnosis, and undergoing BPH surgery. The analysis was adjusted for age, use of statins, antihypertensive medication, and nonsteroidal anti-inflammatory drugs. Of the subjects, 14,012 men (18.7%) used antidiabetic medication. Of the subgroup with fasting blood glucose data available, 7487 (42.2%) had diabetic level. The risks for BPH diagnosis (HR: 1.08, 95% CI: 1.03-1.13) and surgery (HR: 1.16, 95% CI: 1.09-1.24) were slightly elevated among antidiabetic drug users compared to nonusers. The association was strongest for insulin use. Similarly, risk of BPH surgery was increased in men with diabetic blood glucose compared to normoglycemic men. The risk association was attenuated by use of antidiabetic drugs. Diabetic BGL and antidiabetic medication use, especially insulin, are associated with an elevated risk of BPH surgery compared to nondiabetic men. These findings support the roles of insulin use and untreated hyperglycemia as possible BPH risk factors.


Effect of cytochalasin B on intracellular free calcium concentration in human polymorphonuclear leukocytes after repeated stimulation with n-formyl-methionyl-leucyl-phenylalanine.
Cytochalasin B can influence various functions of human polymorphonuclear leukocytes, including chemotaxis, lysosomal enzyme release, and reactive oxygen species generation. In this study we investigated the effect of cytochalasin B on the increase in intracellular free calcium concentration after three consecutive additions of 10(-7) M N-formyl-methionyl-leucyl-phenylalanine. The interval between stimulations was 5 min. Intracellular free calcium concentration was monitored using the fluorescent calcium indicator FURA-2AM. Cytochalasin B (3.3 micrograms/ml) added 60 s before the cell stimulation enhanced all three polymorphonuclear leukocyte calcium responses by increasing the N-formyl-methionyl-leucyl-phenylalanine-induced calcium influx from the extracellular space. Cytochalasin B increased the peak intracellular free calcium concentration and elevated the plateau phase level, but had no influence on its shape. In addition, pretreatment with cytochalasin B of polymorphonuclear leukocytes suspended in low calcium medium restored their capacity to respond to a third stimulation with N-formyl-methionyl-leucyl-phenylalanine. Finally, in resting cells cytochalasin B caused a moderate increase in intracellular free calcium concentration which was independent of extracellular calcium.


Hypercholesterolaemic effect of fish oil in insulin-dependent diabetic patients.
The effect of the daily administration of Max EPA fish oil (equivalent to 2.7 g per day of eicosapentaenoic acid) on serum lipid levels was examined in insulin-dependent male diabetic patients with cholesterol levels of less than 6.5 mmol/L. After three weeks of fish-oil supplementation there was a significant rise in total cholesterol levels, which was due largely to increases in low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)- cholesterol levels. The increase in HDL-cholesterol levels was accounted for by its HDL2 subclass. There was a decrease in serum triglyceride levels, but this was also observed in a control group of diabetic patients who did not receive fish oil and is probably explained by weight loss in this group. Similar changes in lipid levels were found in a subgroup of diabetic patients with retinopathy. The possible detrimental effect of the increase in total cholesterol and LDL-cholesterol levels after Max EPA fish oil at this dose may be offset by the selective rise in the protective HDL2 subclass.


Grindr Killed the Gay Bar, and Other Attempts to Blame Social Technologies for Urban Development: A Democratic Approach to Popular Technologies and Queer Sociality.
This article complicates the popular contention that "Grindr is killing the gay bar" by using qualitative interviews with Grindr users and a diverse literature on urban development. To better understand the factors that have gone into the changing face of the gayborhood and the closing of gay bars, this article encourages stakeholders to focus on a democratic approach to these technologies and considers Grindr and similar apps along with many other factors that affect urban development.


[Geriatry].
n 2015, several studies about hypertension and TAVI emphasize the importance of individualizing treatment goals in very old or vulnerable patients. The anti-pneumococcal conjugate vaccine has demonstrated its effectiveness in community-acquired pneumonia and the arsenal against shingles is extended by a subunit vaccine. A clinical trial confirms the ineffectiveness of testosterone supplementation in arteriosclerotic disease but not its safety. Regarding dementia, a rigorous study shows that a multimodal approach can reduce the risk of cognitive decline. The value of imaging technologies using Tau protein radiotracers is confirmed for monitoring the evolution of Alzheimer's disease and the latest studies about anti-amyloid vaccines finally demonstrate encouraging results.


Bombesin analogues for gastrin-releasing peptide receptor imaging.
The present study describes the design and development of a series of new bombesin (BBN) antagonist peptide ligands of the form [(64)Cu-(NO2A-X-D-Phe(6)-BBN(6-13)NHEt)], where Cu-64=a positron emitting radiometal; NO2A=1,4,7-triazacyclononane-1,4-diacetic acid; X=6-amino hexanoic acid, 8-amino octanoic acid or 9-Aminononanoic acid; and BBN(6-13)NHEt=Gln-Trp-Ala-Val-Gly-His-Leu-NHEt, an antagonist analogue of bombesin peptide for specific targeting of the gastrin-releasing peptide receptor (GRPR). [NO2A-X-D-Phe(6)-BBN(6-13)NHEt] conjugates were manually conjugated with NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid), and the resulting conjugates were labeled with (64)Cu to yield [(64)Cu-(NO2A-X-D-Phe(6)-BBN(6-13)NHEt)]. The metallated and nonmetallated conjugates were purified via reversed-phase high-performance liquid chromatography and characterized by electrospray ionization-mass spectrometry. Competitive displacement binding assays displayed nanomolar binding affinities toward human GRPR for all of the newly formed peptide analogues. Biodistribution studies showed very high uptake and retention of tumor-associated radioactivity in PC-3 (a prostate tumor model known to express the GRPR) tumor-bearing rodent models. The radiolabeled conjugates also exhibited rapid urinary excretion and very high tumor to background ratios. Micro-positron emission tomography (PET) molecular imaging investigations showed clear visualization of tumors in female PC-3 tumor-bearing mice 15 h postinjection. The biodistribution and molecular imaging study suggests that these conjugates can be considered as potential PET tracer candidates for the diagnosis of GRPR-positive tumors in human patients.


Evidence that spinal cord thyrotropin-releasing hormone is independent of the paraventricular nucleus.
To determine whether neuronal perikarya containing thyrotropin-releasing hormone (TRH) in the paraventricular nucleus project to the spinal cord, this region of the hypothalamus was ablated by a midline electrolytic lesion and the spinal cord assayed for its content of TRH. In contrast to the marked diminution of TRH in the median eminence, there was no significant change in the TRH content in the spinal cord. These results indicate the absence of significant afferent input of TRH-containing perikarya in the paraventricular nucleus to the spinal cord.


MEK kinase 1 is essential for Bcr-Abl-induced STAT3 and self-renewal activity in embryonic stem cells.
BCR-ABL oncogene, the molecular hallmark of chronic myelogenous leukemia, arises in a primitive hematopoietic stem cell that has the capacity for both differentiation and self-renewal. Its product, Bcr-Abl protein, has been shown to activate signal transducers and activators of transcription 3 (STAT3) and to promote self-renewal in embryonic stem (ES) cells, even in the absence of leukemia inhibitory factor (LIF). MEK kinase 1 (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase involved in Bcr-Abl signal transduction. To investigate the role of MEKK1 in Bcr-Abl-induced transformation of stem cells, p210 Bcr-Abl was stably transfected into wild-type (WT(p210)) and MEKK1-/- (MEKK1-/-(p210)) ES cells. Bcr-Abl enhanced MEKK1 expression in ES transfectants, as it does in other Bcr-Abl-transformed cells. In the absence of LIF, WT(p210) cells showed constitutive STAT3 activation and formed rounded, compact colonies having strong alkaline phosphatase activity, a characteristic phenotype of undifferentiated ES cells. MEKK1-/-(p210) cells, by contrast, showed less STAT3 activity than WT(p210) cells and formed large, flattened colonies having weak alkaline phosphatase activity, a phenotype of differentiated ES cells. These results indicate that MEKK1 plays a key role in Bcr-Abl-induced STAT3 activation and in ES cells' capacity for LIF-independent self-renewal, and may thus be involved in Bcr-Abl-mediated leukemogenesis in stem cells.


Myoadenylate deaminase deficiency: a new disease of muscle.
Five cases of a new disease presented with muscular weakness or cramping after exercise; three of the cases also had an elevated serum creatine phosphokinase. Muscle biopsies were histologically normal but lacked adenylate deaminase by stain and solution assay, while the erythrocyte isozyme was normal. A clinical diagnostic test has been developed, and the human enzyme was separated by acrylamide-gel electrophoresis.


Corrigendum: American Foulbrood in the Czech Republic: ERIC II Genotype of Paenibacillus Larvae Is Prevalent.
[This corrects the article DOI: 10.3389/fvets.2021.698976.].


Ricardo Miledi and the calcium hypothesis of neurotransmitter release.
Ricardo Miledi has made significant contributions to our basic understanding of how synapses work. Here I discuss aspects of Miledi's research that helped to establish the requirement of presynaptic calcium for neurotransmitter release, from his earliest scientific studies to his classic experiments in the squid giant synapse.


Why women may live longer than men do? A telomere-length regulated and diet-based entropic assessment.
Empirical analyses of the data available around the word concluded that women have longer life span now, when compared to the men. Available literature unfortunately could not offer full answers to this observation. The "entropic age" concept suggests that ageing related changes in the body, such as loss of molecular functions and overwhelming of the maintenance systems, may be explained in terms of entropy generation. Telomere-length regulated entropic assessment based on metabolic activity with four different diets carried out. Estimates of the life expectancy of the women on all of these diets is longer than those of the men. Faster shortening of the telomere lengths in men was the major reason of the shorter life expectancy. The highest and the lowest life expectancy for women were estimated with Mediterranean and the vegetarian diets, respectively; men were estimated to have the longest life span with the vegetarian diet and the shortest life span with the ketogenic diet. A higher rate of metabolism causes higher entropy generation and hints correlations that can be helpful in future ageing research. Faster shortening of the telomere lengths in men was the major reason of the estimation of the shorter life span for men.


Enumeration of acetate-consuming bacteria by microautoradiography under oxygen and nitrate respiring conditions in activated sludge.
Microautoradiography was used to enumerate bacteria able to take up radiolabelled acetate in activated sludge using oxygen or nitrate as electron acceptors. In each of three wastewater treatment plants (WWTP) with nitrification and denitrification (N-removal), the number of bacteria consuming acetate under aerobic and anoxic conditions was identical in contrast to the acetate removal rates. The rates were clearly lower under anoxic conditions suggesting that the specific activity of the cells and not the number of active cells was reduced under anoxic conditions. The fraction of bacteria able to consume acetate varied in three WWTPs between 47% and 93% of the total number of bacteria as determined by DAPI. In a WWTP without N-removal only 20% of the bacteria were able to consume acetate under aerobic conditions and very few of these were able to do it under anoxic conditions. The cell specific acetate removal rates in all WWTPs were found to be 3.0-13.2 x 10(-15) mol cell(-1) h(-1) under aerobic conditions and between 1.9 and 9.1 x 10(-15) mol cell(-1) h(-1) under anoxic conditions.


Tutors´ and Students' Agreement on Social and Cognitive Congruence in a Sonography Peer-assisted-learning Scenario.
Peer-assisted learning has become an integral part within medical education and has been proven to be effective in teaching medical skills. Cognitive and social congruence are important factors that explain the effectiveness of peer-assisted learning. However, although theory suggests this, there is no study to date that demonstrates that students and tutors agree upon the level of cognitive and social congruence. Thus, we compared tutors' and students' perception of cognitive and social congruence and their agreement on the causes of congruence. 36 students and 9 tutors from 9 courses were asked to answer questionnaires for their perception of cognitive and social congruence in a peer-assisted learning sonography scenario. Students and tutors experienced cognitive congruence (t = 0.8277, df = 8, p = .4318, 95% CI = [-0.232; 0.491]) and social congruence (t = 0.962, df = 8, p = .364, 95% CI = [-0.145; 0.354]) similarly. In contrast, students and tutors disagreed on causes of cognitive congruence (agreement = 53.90%) and social congruence (agreement = 58.49%). Tutors rated their empathy and interest toward students as the main cause. Students rated the helpfulness, effectiveness, and approachableness of the tutor as the main cause. Our study filled the gap in previous research on cognitive and social congruence. Consistent with theoretical considerations, it was shown that students and tutors do indeed experience cognitive and social congruence similarly. Nevertheless, differences also emerged that may carry more or less weight depending on the research question. Future studies should therefore carefully examine whether the assessment of cognitive and social congruence of students and tutors is necessary.


The highest-elevation frog provides insights into mechanisms and evolution of defenses against high UV radiation.
Defense against ultraviolet (UV) radiation exposure is essential for survival, especially in high-elevation species. Although some specific genes involved in UV response have been reported, the full view of UV defense mechanisms remains largely unexplored. Herein, we used integrated approaches to analyze UV responses in the highest-elevation frog, Nanorana parkeri. We show less damage and more efficient antioxidant activity in skin of this frog than those of its lower-elevation relatives after UV exposure. We also reveal genes related to UV defense and a corresponding temporal expression pattern in N. parkeri. Genomic and metabolomic analysis along with large-scale transcriptomic profiling revealed a time-dependent coordinated defense mechanism in N. parkeri. We also identified several microRNAs that play important regulatory roles, especially in decreasing the expression levels of cell cycle genes. Moreover, multiple defense genes (i.e., TYR for melanogenesis) exhibit positive selection with function-enhancing substitutions. Thus, both expression shifts and gene mutations contribute to UV adaptation in N. parkeri. Our work demonstrates a genetic framework for evolution of UV defense in a natural environment.


Retinoid and thyroid hormone receptors: ligand-regulated transcription factors as proto-oncogenes.
The retroviral v-erb A locus is derived from a cellular gene, c-erb A, encoding a thyroid hormone receptor. The v-erb A and c-erb A proteins are, in turn, members of a larger family of structurally and functionally interrelated polypeptides that includes the steroid, retinoic acid, and vitamin D3 receptors. These nuclear hormone receptors act by binding to specific sites on the cell genome and, in response to cognate hormone, modulating the transcription of adjacent 'target' genes. The expression, properties, and mechanisms of action of the thyroid hormone receptors (c-erb A proteins) and the closely related retinoic acid receptors are discussed.


Preventing pain after breast surgery: A systematic review with meta-analyses and trial-sequential analyses.
The aim of this systematic review was to indirectly compare the efficacy of any intervention, administered perioperatively, on acute and persistent pain after breast surgery. We searched for randomized trials comparing analgesic interventions with placebo or no treatment in patients undergoing breast surgery under general anaesthesia. Primary outcome was intensity of acute pain (up to 6 hr postoperatively). Secondary outcomes were cumulative 24-hr morphine consumption, incidence of postoperative nausea and vomiting (PONV), and chronic pain. We used an original three-step approach. First, meta-analyses were performed when data from at least three trials could be combined; secondly, trial sequential analyses were used to separate conclusive from unclear evidence. And thirdly, the quality of evidence was rated with GRADE. Seventy-three trials (5,512 patients) tested loco-regional blocks (paravertebral, pectoralis), local anaesthetic infiltrations, oral gabapentinoids or intravenous administration of glucocorticoids, lidocaine, N-methyl-D-aspartate antagonists or alpha2 agonists. With paravertebral blocks, pectoralis blocks and glucocorticoids, there was conclusive evidence of a clinically relevant reduction in acute pain (visual analogue scale > 1.0 cm). With pectoralis blocks, and gabapentinoids, there was conclusive evidence of a reduction in the cumulative 24-hr morphine consumption (> 30%). With paravertebral blocks and glucocorticoids, there was conclusive evidence of a relative reduction in the incidence of PONV of 70%. For chronic pain, insufficient data were available. Mainly with loco-regional blocks, there is conclusive evidence of a reduction in acute pain intensity, morphine consumption and PONV incidence after breast surgery. For rational decision making, data on chronic pain are needed. This quantitative systematic review compares eight interventions, published across 73 trials, to prevent pain after breast surgery, and grades their degree of efficacy. The most efficient interventions are paravertebral blocks, pectoralis blocks and glucocorticoids, with moderate to low evidence for the blocks. Intravenous lidocaine and alpha2 agonists are efficacious to a lesser extent, but with a higher level of evidence. Data for chronic pain are lacking.


Reduction of myocardial infarct size by SM-197378, a novel Na+/H+ exchange inhibitor, in rabbits.
The effects of SM-197378, 2-[[[amino(imino)methyl]amino]carbonyl]-1-methyl-4-trifluoromethyl-1H-indol-7-yl=hydrogen=sulfate monohydrate, a novel potent Na+/H+exchange inhibitor, on heart injury were studied using a rabbit model involving 30 min of myocardial ischemia and 5 h of reperfusion. Intravenous administration of SM-197378 before ischemia reduced the infarct size by approximately 30-50% in a dose-dependent manner. This anti-necrotic effect was achieved without significant hemodynamic changes. Moreover, administration of SM-197378 before reperfusion also resulted in a significant, approximately 30-40%, reduction in the infarct size. The anti-necrotic effect of pre-ischemic bolus treatment with SM-197378 was compared with that of nicorandil, a K+channel opener with nitrate-like activity, and ischemic preconditioning. With 30 and 60 min of ischemia, the anti-necrotic effects of SM-197378 and ischemic preconditioning were similar and superior to that of nicorandil. With 90 min of ischemia, the anti-necrotic effect of SM-197378 was superior to that of ischemic preconditioning.


Turnour necrosis factor stimulates endothelin-1 gene expression in cultured bovine endothelial cells.
We have studied the effect of human recombinant tumour necrosis factor-alpha (TNF-alpha) on gene expression and production of endothelin-1 in cultured bovine aortic endothelial cells. TNF-alpha (10 and 100 ng ml(-1)) increased in a time dependent manner the preproendothelin-1 mRNA levels in respect to unstimulated endothelial cells. TNF-alpha induced endothelin-1 gene expression was associated with a parallel increase in the release of the corresponding peptide in the culture medium. These findings suggest that the enhanced synthesis and release of endothelin-1 occurring in conditions of increased generation of TNF, may act as a modulatory factor that counteracts the hypotensive effect and the excessive platelet aggregation and adhesion induced by TNF.


Imaging of slow viruses.
The symptoms associated with slow viral or prion diseases of the central nervous system tend to have multiple neurologic symptoms, and different patients may present with different symptoms. This review discusses the most common slow virus infections and their imaging findings.


Begomoviruses infecting weeds in Cuba: increased host range and a novel virus infecting Sida rhombifolia.
As a result of surveys conducted during the last few years to search for wild reservoirs of begomoviruses in Cuba, we detected a novel bipartite begomovirus, sida yellow mottle virus (SiYMoV), infecting Sida rhombifolia plants. The complete genome sequence was obtained, showing that DNA-A was 2622 nucleotides (nt) in length and that it was most closely related (87.6% nucleotide identity) to DNA-A of an isolate of sida golden mosaic virus (SiGMV) that infects snap beans (Phaseolus vulgaris) in Florida. The DNA-B sequence was 2600 nt in length and shared the highest nucleotide identity (75.1%) with corchorus yellow spot virus (CoYSV). Phylogenetic relationship analysis showed that both DNA components of SiYMoV were grouped in the Abutilon clade, along with begomoviruses from Florida and the Caribbean islands. We also present here the complete nucleotide sequence of a novel strain of sida yellow vein virus found infecting Malvastrum coromandelianum and an isolate of euphorbia mosaic virus that was found for the first time infecting Euphorbia heterophylla in Cuba.


Development of vestibulo-ocular response in the kitten.
Vestibulo-ocular response (VOR) has been recorded in kittens aged between 10 and 61 postnatal days. Responses to velocity steps and to sinusoidal oscillations are present on the earliest recordings, though they are limited to a low gain slow compensatory gaze displacement. Vestibular-induced saccades appear only around postnatal day 30, but adult-like responses with a high gain are not displayed before the end of the second month. Optokinetic nystagmus (OKN) appears earlier (around postnatal day 25) and maturates faster.


Cellular immune response parameters that influence IgE sensitization.
In vitro basophil responses have long been used in mechanistic studies to help assess the human allergic diathesis, particularly during therapeutic intervention. Recent evidence points to the use of dendritic cells (DCs) in also being valuable in evaluating therapies aimed at lessening disease through immunomodulation. This review article therefore takes a look at some of the recent advances in old and new assays employing both basophils and DCs, with the added perception that the responses mediated by two cell types are insightful towards understanding immune cell mechanisms underlying allergic disease.


Synthesis of (R)-(-)- and (S)-(+)-4-fluorodeprenyl and (R)-(-)- and (S)-(+)-[N-11C-methyl]-4-fluorodeprenyl and positron emission tomography studies in baboon brain.
(R)-(-)- and (S)-(+)-alpha-methyl-beta-4-(fluorophenyl)-N-methyl-N- propynylethylamine [R)-(-)- and (S)-(+)-4-fluorodeprenyl) were synthesized via the reaction of 4-fluorobenzaldehyde with nitroethane followed by reduction with lithium aluminum hydride to produce racemic 4-fluoroamphetamine, which was resolved by recrystallization with L- or D-N-acetylleucine to yield (R)-(-)-4-fluoroamphetamine or (S)-(+)-4-fluoroamphetamine in greater than 96% enantiomeric excesses and in yields of 42 and 39%, respectively. Alkylation with propargyl bromide gave (R)-(-)- or (S)-(+)-4-fluoronordeprenyl which was reductively methylated (Borch conditions) to produce (R)-(-)- or (S)-(+)-4-fluorodeprenyl. Alkylation of (R)-(-)- or (S)-(+)-4-fluoronordeprenyl with carbon-11 labeled methyl iodide gave (R)-(-)- or (S)-(+)-[N-11C-methyl]-4-fluorodeprenyl in a radiochemical yield of 30-40%. Comparative PET studies of the two labeled enantiomers in baboons showed a significantly lower retention of radioactivity in the striatum for the (S)-(+) enantiomer relative to the (R)-(-) enantiomer.


Localization of PPAR isotypes in the adult mouse and human brain.
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. PPAR agonists have well-documented anti-inflammatory and neuroprotective roles in the central nervous system. Recent evidence suggests that PPAR agonists are attractive therapeutic agents for treating neurodegenerative diseases as well as addiction. However, the distribution of PPAR mRNA and protein in brain regions associated with these conditions (i.e. prefrontal cortex, nucleus accumbens, amygdala, ventral tegmental area) is not well defined. Moreover, the cell type specificity of PPARs in mouse and human brain tissue has yet to be investigated. We utilized quantitative PCR and double immunofluorescence microscopy to determine that both PPAR mRNA and protein are expressed ubiquitously throughout the adult mouse brain. We found that PPARs have unique cell type specificities that are consistent between species. PPARα was the only isotype to colocalize with all cell types in both adult mouse and adult human brain tissue. Overall, we observed a strong neuronal signature, which raises the possibility that PPAR agonists may be targeting neurons rather than glia to produce neuroprotection. Our results fill critical gaps in PPAR distribution and define novel cell type specificity profiles in the adult mouse and human brain.


The roles of autophagy in vascular smooth muscle cells.
Autophagy, which is an evolutionarily conserved mechanism and links to several cellular pathways, impacts vascular smooth muscle cells (VSMCs) survival and function. Activation of autophagy by intercellular and/or extracellular stimuli has protective effects on VSMCs against cell death, while on the contrary, overloading autophagy has been recognized as a deleterious process by excessive self-digestion. Alterations in autophagy has been documented in VSMC in response to various stimuli, resulting in modulation of VSMC functions, including proliferation, migration, matrix secretion, contraction/relaxation, and differentiation. Each of these changes in VSMC functions plays a critical role in the development of vascular diseases. Importantly, emerging evidence demonstrates that autophagy deficiency in VSMCs would contribute to atherosclerosis and restenosis, shedding novel light on therapeutic target of the vascular disorders. Herein, this review summarizes the recent progress associated with the roles of autophagy in VSMC and offers the perspectives to several challenges and future directions for further studies.


Immunogenetic factors in beryllium sensitization and chronic beryllium disease.
Exposure to beryllium in the workplace can cause beryllium sensitization and chronic beryllium disease. Sensitization to beryllium can be detected in the laboratory using the beryllium lymphocyte proliferation test. It was shown that anti-HLA antibodies could block the beryllium-specific response in the beryllium lymphocyte proliferation test, thereby implicating HLA genes in chronic beryllium disease. A supratypic genetic marker, HLA-DPB1*E69, was found to be strongly associated with immunologic sensitization to beryllium and chronic beryllium disease in beryllium workers. However, there are 40 HLA-DPB1 gene variants that have E69 but that also have other DNA sequence variations. The purpose of the study was to evaluate the evidence for potential differential susceptibility that may be associated with the physical characteristics of HLA protein molecules for which different HLA-DPB1*E69 variants code; that is, do some HLA-DPB1*E69 variants convey higher risk of beryllium sensitization and chronic beryllium disease than others. To do this, two approaches were pursued: first, detailed analysis of the findings from the published literature was performed, and second, computational chemistry was used to seek clues concerning the physical properties of the HLA protein molecules for which these alleles code. Among the 40 HLA-DPB1 gene variants that code for E69, molecular epidemiological studies have suggested a risk hierarchy, where some variants appear to convey low to moderate risk of chronic beryllium disease (e.g., HLA-DPB1*0201, approximately 3-fold increased risk), some convey an intermediate risk (e.g., HLA-DPB1*1901, approximately 5-fold) and others convey high risk (e.g., HLA-DPB1*1701, >10-fold). Molecular modeling has been used to further investigate a potential mechanistic basis for these observations. We found a strong correlation between the hierarchical order of risk of chronic beryllium disease associated with specific alleles and the predicted surface electrostatic potential and charge of the corresponding isotypes. Therefore, when alleles were grouped by the relative negative charge on the molecules for which they code, the data suggest that those alleles associated with the most negatively charged proteins carry the greatest risk of beryllium sensitization and disease.


Discovery of a novel ferroptosis inducer-talaroconvolutin A-killing colorectal cancer cells in vitro and in vivo.
Ferropotsis is among the most important mechanisms of cancer suppression, which could be harnessed for cancer therapy. However, no natural small-molecule compounds with cancer inhibitory activity have been identified to date. In the present study, we reported the discovery of a novel ferroptosis inducer, talaroconvolutin A (TalaA), and the underlying molecular mechanism. We discovered that TalaA killed colorectal cancer cells in dose-dependent and time-dependent manners. Interestingly, TalaA did not induce apoptosis, but strongly triggered ferroptosis. Notably, TalaA was significantly more effective than erastin (a well-known ferroptosis inducer) in suppressing colorectal cancer cells via ferroptosis. We revealed a dual mechanism of TalaA' action against cancer. On the one hand, TalaA considerably increased reactive oxygen species levels to a certain threshold, the exceeding of which induced ferroptosis. On the other hand, this compound downregulated the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) but upregulated arachidonate lipoxygenase 3 (ALOXE3), promoting ferroptosis. Furthermore, in vivo experiments in mice evidenced that TalaA effectively suppressed the growth of xenografted colorectal cancer cells without obvious liver and kidney toxicities. The findings of this study indicated that TalaA could be a new potential powerful drug candidate for colorectal cancer therapy due to its outstanding ability to kill colorectal cancer cells via ferroptosis induction.


Effect of solid-state fungal fermentation on the non-volatiles content and volatiles composition of Coffea canephora (Robusta) coffee beans.
In this study, the effects of fungal fermentation on green canephora coffee beans were evaluated by observing the changes to selected non-volatile parameters before roasting, and subsequently the volatile profile after roasting. Solid-state fermentation (SSF) by Aspergillus spp. and Mucor spp. on green canephora coffee beans was shown to modulate the contents of free sugars, free amino acids and polyphenolic compounds such as caffeoylquinic acids (CQAs). Significant strain-specific differences were observed in the contents of aroma compounds after roasting. A significant increase in pyrazines was observed in the Aspergillus oryzae-fermented samples, while higher levels of furans were detected in the Mucor plumbeus-fermented samples. The present work shows that fungal fermentation of green canephora coffee beans is a potentially promising method for the modulation and improvement of coffee flavour and aroma.


The cellular immunology of myasthenia gravis.
The possible role of the thymus in autosensitization to the acetylcholine receptor (AChR) in myasthenia gravis is briefly discussed, and work on autoantibody synthesis in vitro is reviewed. Whereas blood lymphocytes sometimes make anti-AChR in response to mitogens, spontaneous production is more regularly observed in cells from lymph nodes, bone marrow and, above all, thymus, where it is selectively activated. Cell separation studies imply a dominant contribution by the germinal centre cells and plasma cells there, many of which are autonomous (i.e. no longer require T cell help). The need for germinal centre-directed immunosuppressive regimes is discussed.


Quantitative assessment of cerebellar ataxia, through automated limb functional tests.
Cerebellar damage can often result in disabilities affecting the peripheral regions of the body. These include poor and inaccurate coordination, tremors and irregular movements that often manifest as disorders associated with balance, gait and speech. The severity assessment of Cerebellar ataxia (CA) is determined by expert opinion and is likely to be subjective in nature. This paper investigates automated versions of three commonly used tests: Finger to Nose test (FNT), test for upper limb Dysdiadochokinesia Test (DDK) and Heel to Shin Test (HST), in evaluating disability due to CA. Limb movements associated with these tests are measured using Inertial Measurement Units (IMU) to capture the disability. Kinematic parameters such as acceleration, velocity and angle are considered in both time and frequency domain in three orthogonal axes to obtain relevant disability related information. The collective dominance in the data distributions of the underlying features were observed though the Principal Component Analysis (PCA). The dominant features were combined to substantiate the correlation with the expert clinical assessments through Linear Discriminant Analysis. Here, the Pearson correlation is used to examine the relationship between the objective assessments and the expert clinical scores while the performance was also verified by means of cross validation. The experimental results show that acceleration is a major feature in DDK and HST, whereas rotation is the main feature responsible for classification in FNT. Combining the features enhanced the correlations in each domain. The subject data was classified based on the severity information based on expert clinical scores. For the predominantly translational movement in the upper limb FNT, the rotation captures disability and for the DDK test with predominantly rotational movements, the linear acceleration captures the disability but cannot be extended to the lower limb HST. The orthogonal direction manifestation of ataxia attributed to sensory measurements was determined for each test. Human Research and Ethics Committee, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia (HREC Reference Number: 11/994H/16).


Evidence that store-operated Ca2+ channels are more effective than intracellular messenger-activated non-selective cation channels in refilling rat hepatocyte intracellular Ca2+ stores.
Liver cells possess store-operated Ca2+ channels (SOCs) with a high selectivity for Ca2+ compared with Na+, and several types of intracellular messenger-activated non-selective cation channels with a lower selectivity for Ca2+ (NSCCs). The main role of SOCs is thought to be in refilling depleted endoplasmic reticulum Ca2+ stores [Cell Calcium 7 (1986) 1]. NSCCs may be involved in refilling intracellular stores but are also thought to have other roles in regulating the cytoplasmic-free Ca2+ and Na+ concentrations. The ability of SOCs to refill the endoplasmic reticulum Ca2+ stores in hepatocytes has not previously been compared with that of NSCCs. The aim of the present studies was to compare the ability of SOCs and maitotoxin-activated NSCCs to refill the endoplasmic reticulum in rat hepatocytes. The experiments were performed using fura-2FF and fura-2 to monitor the free Ca2+ concentrations in the endoplasmic reticulum and cytoplasmic space, respectively, a Ca2+ add-back protocol, and 2-aminoethyl diphenylborate (2-APB) to inhibit Ca2+ inflow through SOCs. In cells treated with 2,5-di-t-butylhydroquinone (DBHQ) or vasopressin to deplete the endoplasmic reticulum Ca2+ stores, then washed to remove DBHQ or vasopressin, the addition of Ca2+ caused a substantial increase in the concentration of Ca2+ in the endoplasmic reticulum and cytoplasmic space due to the activation of SOCs. These increases were inhibited 80% by 2-APB, indicating that Ca2+ inflow is predominantly through SOCs. In the presence of 2-APB (to block SOCs), maitotoxin induced a substantial increase in [Ca2+](cyt), but only a modest and slower increase in [Ca2+](er). Under these conditions, Ca2+ inflow is predominantly through maitotoxin-activated NSCCs. It is concluded that SOCs are more effective than maitotoxin-activated NSCCs in refilling the endoplasmic reticulum Ca2+ stores. The previously developed concept of a specific role for SOCs in refilling the endoplasmic reticulum is consistent with the results reported here.


Comparison of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitors in patients undergoing an invasive strategy: a meta-analysis of randomized clinical trials.
This meta-analysis was performed to assess the efficacy and safety of bivalirudin compared with unfractionated heparin or enoxaparin plus glycoprotein (GP) IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention (PCI). Pharmacotherapy for patients undergoing PCI includes bivalirudin, heparin, and GP IIb/IIIa inhibitors. We sought to compare ischemic and bleeding outcomes with bivalirudin versus heparin plus GP IIb/IIIa inhibitors in patients undergoing PCI. A literature search was conducted to identify fully published randomized trials that compared bivalirudin with heparin plus GP IIb/IIIa inhibitors in patients undergoing PCI. A total of 19,772 patients in 5 clinical trials were included in the analysis (9785 patients received bivalirudin and 9987 patients received heparin plus GP IIb/IIIa inhibitors during PCI). Anticoagulation with bivalirudin, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, results in no difference in major adverse cardiovascular events (odds ratio [OR] 1.07, 95% confidence interval [CI] 0.96 to 1.19), death (OR 0.93, 95% CI 0.72 to 1.21), or urgent revascularization (OR 1.06, 95% CI 0.86 to 1.30). There is a trend towards a higher risk of myocardial infarction (OR 1.12, 95% CI 0.99 to 1.28) but a significantly lower risk of TIMI major bleeding with bivalirudin (OR 0.55, 95% CI 0.44 to 0.69). In patients who undergo PCI, anticoagulation with bivalirudin as compared with unfractionated heparin or enoxaparin plus GP IIb/IIIa inhibitors results in similar ischemic adverse events but a reduction in major bleeding.


Competitive protein tyrosine phosphatase 1B (PTP1B) inhibitors, prenylated caged xanthones from Garcinia hanburyi and their inhibitory mechanism.
Protein tyrosine phosphatase 1B (PTP1B) plays important role in diabetes, obesity and cancer. The methanol extract of the gum resin of Garcinia hanburyi (G. hanburyi) showed potent PTP1B inhibition at 10µg/ml. The active compounds were identified as prenylated caged xanthones (1-9) which inhibited PTP1B in dose-dependent manner. Carboxybutenyl group within caged motif (A ring) was found to play a critical role in enzyme inhibition such as 1-6 (IC50s=0.47-4.69µM), whereas compounds having hydroxymethylbutenyl 7 (IC50=70.25µM) and methylbutenyl 8 (IC50>200µM) showed less activity. The most potent inhibitor, gambogic acid 1 (IC50=0.47µM) showed 30-fold more potency than ursolic acid (IC50=15.5µM), a positive control. In kinetic study, all isolated xanthones behaved as competitive inhibitors which were fully demonstrated with Km, Vmax and Kik/Kiv ratio. It was also proved that inhibitor 1 operated under the enzyme isomerization model having k5=0.0751µM-1S-1, k6=0.0249µM-1S-1 and Kiapp=0.499µM. To develop a pharmacophore model, we explored the binding sites of compound 1 and 7 in PTP1B. These modeling results were in agreement with our findings, which revealed that the inhibitory activities are tightly related to caged motif and prenyl group in A ring.


The innervation of the uterus in Salamandra salamandra (L.) (Amphibia, Urodela). A morphological and biochemical study.
The innervation of the uterus in the ovoviviparous urodele Salamandra salamandra was studied. In whole mount preparations of the thin-walled uterus of pregnant females, a dense adrenergic network was demonstrated using a modified glyoxylic acid fluorescence technique. Based on vesicle type and cytochemical reactivity after chromate/dichromate fixation for electron microscopy at least two types of neural process were distinguished and classified as adrenergic and cholinergic. Both types are preferentially situated above or between the smooth muscles of the uterine tissue. Adjacent to the muscles in the walls of arterioles mainly adrenergic fibers are seen. Using high performance liquid chromatography with electrochemical detection in tissue homogenates of uterus a considerable amount of noradrenaline could be identified. The significance of the dense innervation is discussed with respect to the function of the uterus during pregnancy and birth.


Midface volumization with injectable fillers.
The aging midface has long been overlooked in cosmetic surgery. Our understanding of facial aging in terms of 3 dimensions has placed increased importance on volume restoration. Although an "off-label" indication for most fillers in this facial region, volumization of the midface with injectable fillers is usually a safe and straightforward procedure technically. Injectors, nevertheless, need to have an excellent understanding of facial anatomy and the characteristics of the injected products should problems arise.


Effect of ozone on colon anastomoses in rat peritonitis model.
To investigate the effects of medical ozone theraphy on the colon anastomosis of peritonitis model in rats. Eighteen rats were randomly assigned into three equal groups; control, cecal punctuation and colon anastomosis and ozone theraphy. Sepsis was performed with a cecal punctuation in groups 2 and 3. The medical ozone theraphy was administered intraperitonealy for three weeks in group 3 while the other rats received saline injection. At the twenty second day serum were obtained for TNF-α and IL-1β, the colonic burst pressures were measured and colonic tissue samples were obtained for MDA and MPO levels. Histolopatological examination was evaluated with H&E stain, and Ki-67, IL-1β and the VEGF immunostaining densities were also compared. Intraperitoneal ozone administration reversed TNF-α, IL-1β, MDA and MPO levels and the colonic burst pressures. There was also a significant difference at immunostaining densities of histopathological examination. Medical ozone therapy may contribute to tissue healing by affecting the proliferation and the vascularization thus has benefits on colonic anastomosis at peritonitis in rats.


A novel MGST2 non-synonymous mutation in a Chinese pedigree with psoriasis vulgaris.
A balanced translocation was recently identified in a German psoriasis patient. One of the breakpoints was mapped immediately upstream of the microsomal glutathione S-transferase 2 (MGST2) gene, suggesting it as a candidate gene. Here, we report the identification of a novel non-synonymous mutation in MGST2 by a comprehensive sequence analysis of MGST2's coding region in Chinese psoriasis samples. We demonstrate that this mutation co-segregated with the disease phenotype within a Chinese family affected with psoriasis vulgaris and is predicted to have an impact on the normal function of MGST2 protein. However, the mutation was absent in 551 additional cases and 384 healthy Chinese controls. While requiring independent confirmation, our results suggest that this rare mutation could play a causal role in a small subset of psoriasis individuals.


Vagus nerve stimulation: can it be used in adolescents or children with treatment-resistant depression?
Vagus nerve stimulation (VNS) therapy has been approved by the US Food and Drug Administration for treatment-resistant depression in patients 18 years of age and older and for intractable epilepsy. Long-term studies suggest VNS has an antidepressant effect in adults. This paper reviews the available clinical data for VNS therapy. Its potential application for treatment-resistant depression in adolescents and children is also discussed.


Medical treatment for rhinosinusitis associated with adenoidal hypertrophy in children: an evaluation of clinical response and changes on magnetic resonance imaging.
The association between adenoidal hypertrophy and rhinosinusitis with upper airway inflammation is increasingly recognized; however, no study has used magnetic resonance imaging (MRI) to assess the changes in adenoid size after medical treatment of rhinosinusitis. Thirteen children referred to a tertiary allergy clinic with symptoms of rhinosinusitis received medical treatment over a 4-month period. All underwent MRI before and after treatment. The medical treatment regimen comprised a short course of oral antibiotics and oral steroids and a longer course of oral antihistamines and intranasal steroids. The pretreatment MRI demonstrated enlarged adenoids and rhinosinusitis in all 13 children, with evidence of extensive rhinosinusitis in 9 of the 13. The treatment resulted in an improvement in overall symptom score; the most significant improvement was seen in mouth breathing. The posttreatment MRI showed a statistically significant reduction in adenoid size and adenoid/nasopharynx ratio, which was associated with a significant decrease in sinus involvement on MRI. There is a high association between adenoidal hypertrophy and rhinosinusitis in the context of an allergy clinic. Magnetic resonance imaging can document the changes in adenoid size associated with resolution of rhinosinusitis. Further studies are necessary to validate these pilot data and further assess the effects of medical treatment and the role of MRI in adenoidal hypertrophy.


Quantitative neuropathology of a focal nerve injury causing hyperalgesia.
The chronic constriction injury (CCI) model of neuropathy in the rat produces hyperalgesia and allodynia in the sciatic distribution of one hindlimb. We previously described the pathology of the affected nerves at the light microscopic and electron microscopic levels and in this report quantify the morphological changes of the nerves. This analysis gives new insights into the pathophysiology and pain-related mechanisms in this model of human neuropathy. We observed that total fascicular area increased up to fourfold due to an initial massive increase in edema and, later, endoneurial cells. Intact myelinated nerve fibers were reduced from 75% of fascicular area to 29.7% on day 1 and to a minimum of less than 0.5% on day 14 when edema had resolved. The few surviving myelinated fibers were in the small to medium size range. Fiber size histograms revealed an increase in fiber size early on, corresponding to fiber swelling, and the later loss of large as well as small myelinated fibers. Unmyelinated nerve fibers dropped from 19.36/1,000 microns 2 to 6.08/1,000 microns 2 on day 5, and increased from there on. Sprouts were first visible on light micrographs on day 7, occupying 6.8% of fascicular area, while regenerating fibers that were undergoing myelination reached 42.6% of fascicular area by day 42. Macrophage numbers were maximal on day 14 and were still increased on day 42. These data support the hypothesis that the pathogenesis of the extended hyperalgesia following chronic constrictive nerve injury is temporally linked with Wallerian-like degeneration and macrophage activation.(ABSTRACT TRUNCATED AT 250 WORDS)


A new strategy for determination of hydroxylamine and phenol in water and waste water samples using modified nanosensor.
A carbon paste electrode modified with p-chloranil and carbon nanotubes was used for the sensitive and selective voltammetric determination of hydroxylamine (HX) and phenol (PL). The oxidation of HX at the modified electrode was investigated by cyclic voltammetry (CV), chronoamperommetry, and electrochemical impedance spectroscopy. The values of the catalytic rate constant (k), and diffusion coefficient (D) for HX were calculated. Square wave voltammetric peaks current of HX and PL increased linearly with their concentrations at the ranges of 0.1-172.0 and 5.0-512.0 μmol L(-1), respectively. The detection limits for HX and PL were 0.08 and 2.0 μmol L(-1), respectively. The separation of the anodic peak potentials of HX and PL reached to 0.65 V, using square wave voltammetry. The proposed sensor was successfully applied for the determination of HX and PL in water and wastewater samples.


Cytogenetic studies of a diffuse mixed cell lymphoma of T cell origin.
The chromosome finding obtained from a lymph node of a patient with T cell lymphoma is described. Two different abnormal clones were found; one of them had a t(14;18)(q32;q21), along with other structural and numerical abnormalities, including 1p+q-,1p-,2p+q+, der(11),t(11;?)(q13;?),+20,+21,22p+. The other clone contained der(13),t(13;?)(q22;?).


Folding and association of oligomeric enzymes.
The spontaneous structure formation of oligomeric enzymes consists of the consecutive 'folding' and association of the constituent polypeptide chains. Whether catalytic function is an intrinsic property of the folded monomers may be determined using kinetic reconstitution experiments. It is shown that full activity requires association; the correct assembly of subunits depends on their proper folding. The native structure is determined as the kinetically accessible state of lowest free energy.


Depth and phase of respiration modulate cortico-muscular communication.
Recent studies in animals have convincingly demonstrated that respiration cyclically modulates oscillatory neural activity across diverse brain areas. To what extent this generalises to humans in a way that is relevant for behaviour is yet unclear. We used magnetoencephalography (MEG) to assess the potential influence of respiration depth and respiration phase on the human motor system. We obtained simultaneous recordings of brain activity, muscle activity, and respiration while participants performed a steady contraction task. We used corticomuscular coherence as a measure of efficient long-range cortico-peripheral communication. We found coherence within the beta range over sensorimotor cortex to be reduced during voluntary deep compared to involuntary normal breathing. Moreover, beta coherence was found to be cyclically modulated by respiration phase in both conditions. Overall, these results demonstrate how respiratory rhythms influence the synchrony of brain oscillations, conceivably regulating computational efficiency through neural excitability. Intriguing questions remain with regard to the shape of these modulatory processes and how they influence perception, cognition, and behaviour.


Biomarkers Predictive of Long-Term Outcome After Ischemic Stroke: A Meta-Analysis.
The goal of this study was to systematically review the usefulness of serum biomarkers in the setting of ischemic stroke (IS) to predict long-term outcome. A systematic literature review was performed using the PubMed and MEDLINE databases for studies published between 1986 and 2018. All studies assessing long-term functional outcome (defined as ≥30 days) after IS with respect to serum biomarkers were included. Data were extracted and pooled using a meta-analysis of odds ratios. Of the 2928 articles in the original literature search, 183 studies were selected. A total of 127 serum biomarkers were included. Biomarkers were grouped into several categories: inflammatory (n = 32), peptide/enzymatic (n = 30), oxidative/metabolic (n = 28), hormone/steroid based (n = 23), and hematologic/vascular (n = 14). The most commonly studied biomarkers in each category were found to be CRP, S100β, albumin, copeptin, and D-dimer. With the exception of S100β, all were found to be statistically associated with >30-day outcome after ischemic stroke. Serum-based biomarkers have the potential to predict functional outcome in patients with IS. This meta-analysis has identified C-reactive protein, albumin, copeptin, and D-dimer to be significantly associated with long-term outcome after IS. These biomarkers have the potential to serve as a platform for prognosticating stroke outcomes after 30 days. These serum biomarkers, some of which are routinely ordered, can be combined with imaging biomarkers and used in artificial intelligence algorithms to provide refined predictive outcomes after injury. These tools will assist physicians in providing guidance to families regarding long-term independence of patients.


Establishing an international awareness day for paediatric rheumatic diseases: reflections from the inaugural World Young Rheumatic Diseases (WORD) Day 2019.
There is a lack of awareness of paediatric rheumatic diseases (PRDs), among the public, and certain groups of healthcare professionals (HCPs), including general practitioners. To help improve international awareness and understanding of PRDs, World yOung Rheumatic Diseases (WORD) Day was established on 18 March 2019. Its aim was to raise awareness of PRDs and the importance of timely referral plus early diagnosis and access to appropriate treatment and support. A steering committee was established, and an external agency provided digital support. A social media campaign was launched in December 2018 to promote it, and analytics were used to measure its impact. Face-to-face and virtual events took place globally on or around WORD Day 2019, with 34 countries reporting events. Examples included lectures, social gatherings and media appearances. A total of 2585 and 660 individuals followed the official Facebook and Twitter accounts respectively, up until WORD Day. The official #WORDDay2019 hashtag was seen by 533,955 unique accounts on 18 March 2019 alone, with 3.3 million impressions. WORD Day 2019 was the first international campaign focused solely on PRDs. It demonstrated that despite awareness events being often resource-light, they can be implemented across a range of diverse settings. WORD Day has now become an annual global awareness event, facilitated by a growing network of patient, parent and professional community supporters.


Building resilience to body image triggers using brief cognitive training on a mobile application: A randomized controlled trial.
Body image disturbance (BID) is common among women, characterized by persistent and distressing appearance dissatisfaction, and linked with eating disorders. Although effective, cognitive behavioral therapy (CBT) delivered by trained professionals is not easily accessible. This randomized trial evaluated the effects of a CBT-based mobile application designed to increase resilience to body image triggers and reduce BID symptoms. A non-clinical sample of women (N = 90; Mage = 23.52) was randomized to use the mobile application for approximately 4 min of daily exercises for two weeks or to a control condition. Body image was measured at baseline, immediately after two weeks of mobile application use, and at 1-month follow-up. To examine whether using the application was associated with increased resilience to common BID triggers, participants completed an Instagram exposure resilience task upon completion and at 1-month follow-up. Relative to those in the control condition, participants who used the application demonstrated increased resiliency and reduced BID symptoms. Theses effects were medium-to-large and were maintained at 1-month follow-up. These results underscore the potential usefulness of brief, low-intensity, portable interventions in reducing BID symptoms and in increasing resilience to thin-ideal body messages often portrayed on social media.


KlcAHS genes are ubiquitous in clinical, blaKPC-2-positive, Klebsiella pneumoniae isolates.
Carbapenemase-producing Klebsiella pneumoniae has emerged and spread widely throughout the world. The mechanisms involved remain unclear. To provide insight, five plasmids were obtained from carbapenemase-producing K. pneumoniae clinical isolates. The five sequences were acquired, aligned and analyzed. In addition to the blaKPC-2 gene, which encodes beta lactamase, essentially all the plasmids contained a putative anti-restriction protein-encoding gene, KlcAHS. The KlcAHS gene was found in 98.2% of the blaKPC-2-positive, imipenem-resistant K. pneumoniae clinical isolates and in <1% of the blaKPC-2-negative control group. A searched of the GenBank database indicated that KlcAHS was mainly submitted by Chinese investigators beginning in 2010. Seventeen different KlcA amino acid sequences were found in the database using the restricting words: KlcA and Klebsiella pneumoniae. These sequences were used to generate a phylogenetic tree via MEGA6 software, revealing a distant evolutionary relationship between KlcAHS and other KlcAs. The secondary structure of KlcAHS, predicted with PROMALS3D software, exhibited highly conserved α-helices and β-strands. KlcAHS expressed anti-restriction activity in vivo. In summary, KlcAHS genes are ubiquitous in blaKPC-2-positive Klebsiella pneumoniae clinical isolates collected at Huashan Hospital, China. The KlcAHS protein possesses a secondary structure similar to that exhibited by anti-restriction proteins and displays anti-restriction activity. As such, KlcAHS is a probable factor in the accelerated spread of blaKPC-2 and carbapenem-resistance among clinical, K. pneumoniae isolates.


Toward a mechanistic understanding of trophic structure: inferences from simulating stable isotope ratios.
Stable isotope ratios (SIR) are widely used to estimate food-web trophic levels (TLs). We built systems dynamic N-biomass-based models of different levels of complexity, containing explicit descriptions of isotope fractionation and of trophic level. The values of δ15N and TLs, as independent and emergent properties, were used to test the potential for the SIR of nutrients, primary producers, consumers, and detritus to align with food-web TLs. Our analysis shows that there is no universal relationship between TL and δ15N that permits a robust prognostic tool for configuration of food webs even if all system components can be reliably analysed. The predictive capability is confounded by prior dietary preference, intra-guild predation and recycling of biomass through detritus. These matters affect the dynamics of both the TLs and SIR. While SIR data alone have poor explanatory power, they would be valuable for validating the construction and functioning of dynamic models. This requires construction of coupled system dynamic models that describe bulk elemental distribution with an explicit description of isotope discriminations within and amongst functional groups and nutrient pools, as used here. Only adequately configured models would be able to explain both the bulk elemental distributions and the SIR data. Such an approach would provide a powerful test of the whole model, integrating changing abiotic and biotic events across time and space.


Resistance to antiretroviral treatment in Gabon: need for implementation of guidelines on antiretroviral therapy use and HIV-1 drug resistance monitoring in developing countries.
The protease and reverse transcriptase (RT) genes were studied in antiretroviral (ARV)-experienced and drug-naive HIV-1-infected individuals in Libreville, Gabon. We have shown, although on a limited number of samples that in 58% (11/19) of the patients, with a mean of 17.7 months of ARV drug experience, major mutations inevitably inducing resistances to ARV drugs were present. Resistance was mainly observed to the NRTIs (nucleoside analogue RT inhibitors). This high prevalence may reflect inappropriate ARV drug use. In order to avoid the rapid emergence of resistant viruses on a large scale in the developing world, it is important that the infrastructures necessary to monitor ARV treatment are also rapidly implemented in these countries and that clinicans are trained in the appropriate use of ARV drugs. A continuous surveillance of the circulation of ARV drug-resistant viruses must be organized to guide ARV treatment strategies and policies.


Classic Timothy Syndrome Associated With Bilateral Border Digit Syndactyly: A Case Series.
Timothy syndrome (TS) is characterized by congenital long-QT arrhythmia and limb syndactyly. Patients who undergo syndactyly repair with undiagnosed TS may have their abnormal cardiac electrical activity unmasked during surgery. The purpose of this study was to detail the extremity phenotype seen in patients with TS, which may help hand surgeons in their preoperative assessment. This was a retrospective review of all patients with TS seen at our institution from 1998 to 2022. Descriptive statistics regarding their demographics, medical and surgical histories, and syndactyly phenotypes were obtained. Seven patients (5 males and 2 females) with TS were seen at our institution for multidisciplinary evaluation (median age at presentation was 23 months). Six patients had finger syndactyly and 5 had toe syndactyly. One patient did not have any extremity syndactyly and was noted to have a specific TS mutation known to lack musculoskeletal abnormalities. All patients with finger syndactyly had border digit involvement, with 5 out of 6 patients displaying syndactyly of the middle-ring and ring-little finger web spaces. Toe syndactyly was more heterogeneous, with 1 patient lacking any lower extremity syndactyly and others having variable involvement of the second-third, third-fourth, and fourth-little toe web spaces. Complexity ranged from simple to complete. Four patients had intraoperative cardiac events leading to TS diagnoses after surgery. Bilateral border digit hand syndactyly, with or without bilateral toe syndactyly, should raise concerns for TS and prompt further investigation into potential cardiac disease to avoid perioperative cardiac morbidity and mortality. Therapeutic V.


IME1, a positive regulator gene of meiosis in S. cerevisiae.
IME1 (Inducer of MEiosis) was cloned due to its high copy number effect: it enabled MAT insufficient strains to undergo meiosis. Disruption of IME1 results in a recessive Spo- phenotype. Diploids homozygous for the two mutations ime1-0, rme1-1 are also meiosis deficient. We conclude that IME1 is a positive regulator of meiosis that normally is repressed by RME1. RME1 is repressed by a complex of MATa1 and MAT alpha 2 gene products. IME1 is also regulated by the environment: no transcripts could be detected in glucose growing cells, in contrast to acetate growing cells. Starvation for nitrogen further induced (6- to 8-fold) transcription of IME1, but, as expected, the induction was found only in MATa/MAT alpha or rme1-1/rme1-1 diploids. Furthermore, the IME1 multicopy plasmids promoted sporulation in rich media.


Study on electrooxidation of cefadroxil monohydrate and its determination by differential pulse voltammetry.
In this work electrooxidation of cefadroxil monohydrate was investigated using a glassy carbon electrode depending on pH and supporting electrolyte. It was shown that the direct determination of the substance from capsules and in oral suspension could be made by differential pulse voltammetry (DPV). UV and first derivative UV spectrophotometric methods are also proposed as comparative methods.


Comparative Study of Cortical Bone Trajectory-Pedicle Screw (Cortical Screw) Versus Conventional Pedicle Screw in Single-Level Posterior Lumbar Interbody Fusion: A 2-Year Post Hoc Analysis from Prospectively Randomized Data.
The aim of this study was to report 2-year follow-up outcomes of posterior lumbar interbody fusion (PLIF) with cortical bone trajectory-pedicle screw (CS), in terms of fusion rates, clinical outcomes, surgical outcomes, and complications, and to compare these outcomes with outcomes for PLIF with conventional pedicle screw (PS). We enrolled 79 patients and randomly assigned them to 2 groups (group A with PS, 39 patients; group B with CS, 40 patients), and finally 37 and 35 in group A and B were analyzed in the study. The primary outcome measure was the fusion rate, evaluated by dynamic radiographs and computed tomography scans. Secondary outcome measures included 1) patient satisfaction; 2) clinical outcomes measured with pain intensity using a visual analog scale, the Oswestry Disability Index, and 12-Item Short Form Health Survey; 3) radiologic outcomes; and 4) complications. At 2-year follow-up, the fusion rate was comparable between the PS and CS groups (35 of 37 patients in the PS group; 32 of 35 patients in the CS group; P > 0.99). The patient satisfaction rate at the 1-month follow-up was significantly greater in the CS group than in the PS group (P = 0.03); however, there was no significant difference between the groups at the 1-year and 2-year follow-ups. Clinical outcomes, radiologic outcomes, and related complications revealed no significant differences in both groups within 2 years postoperatively. We suggest that CS in single-level PLIF may be an alternative to PS.


Heparin and penicillamine-hypotaurine-epinephrine (PHE) solution during bovine in vitro fertilization procedures impair the quality of spermatozoa but improve normal oocyte fecundation and early embryonic development.
The presence of heparin and a mixture of penicillamine, hypotaurine, and epinephrine (PHE) solution in the in vitro fertilization (IVF) media seem to be a prerequisite when bovine spermatozoa are capacitated in vitro, in order to stimulate sperm motility and acrosome reaction. The present study was designed to determine the effect of the addition of heparin and PHE during IVF on the quality and penetrability of spermatozoa into bovine oocytes and on subsequent embryo development. Sperm quality, evaluated by the integrity of plasma and acrosomal membranes and mitochondrial function, was diminished (P<0.05) in the presence of heparin and PHE. Oocyte penetration and normal pronuclear formation rates, as well as the percentage of zygotes presenting more than two pronuclei, was higher (P<0.05) in the presence of heparin and PHE. No differences were observed in cleavage rates between treatment and control (P>0.05). However, the developmental rate to the blastocyst stage was increased in the presence of heparin and PHE (P>0.05). The quality of embryos that reached the blastocyst stage was evaluated by counting the inner cell mass (ICM) and trophectoderm (TE) cell numbers and total number of cells; the percentage of ICM and TE cells was unaffected (P>0.05) in the presence of heparin and PHE (P<0.05). In conclusion, this study demonstrated that while the supplementation of IVF media with heparin and PHE solution impairs spermatozoa quality, it plays an important role in sperm capacitation, improving pronuclear formation, and early embryonic development.


Microwave therapy for the treatment of plantar warts.
Plantar warts, or verrucae plantaris, are common lesions causing considerable pain during weightbearing activity. Although current treatment modalities have low success rates, microwave therapy has been introduced as a promising intervention. This study aimed to determine the effectiveness of microwave therapy for the treatment of plantar warts and to determine the clinical factors associated with plantar wart resolution. A retrospective analysis of 150 plantar warts from 45 patients treated with microwave therapy was undertaken. Binomial regression was conducted to explore clinical characteristics (age, gender, immunosuppression, impaired healing, multiple vs single wart, location of lesion, lesion diameter) associated with lesion resolution. Of the total 150 plantar warts treated with microwave therapy, 125 (83.3%) warts resolved and 25 (17%) warts did not resolve. The mean (SD) total treatment sessions for resolved lesions was 2.8 (1.0). Decreasing age (P = 0.046) was the only clinical characteristic associated with resolution. This retrospective study has shown that plantar warts may be resolved with two to three sessions of microwave therapy, which may be more successful in younger populations.


Purpose in life protects against the development of suicidal thoughts and behaviors in U.S. veterans without a history of suicidality: A 10-year, nationally representative, longitudinal study.
To determine the incidence of suicidal ideation and suicide attempts (STBs) in veterans without an endorsed history of STBs and identify baseline predictors of these outcomes over a 10-year period. Population-based prospective cohort study of 2307 US military veterans using five waves of the 2011-2021 National Health and Resilience in Veterans Study. Baseline data were collected in 2011, with follow-up assessments conducted 2-(2013), 4-(2015), 7-(2018), and 10-years (2021) later. In total, 10.1 % (N = 203) of veterans endorsed incident suicidal ideation (SI) over the 10-year period and 3.0 % (N = 55) endorsed an incident suicide attempt (SA). Multivariable regression analyses revealed the following baseline predictors of incident SI: lower annual household income, current posttraumatic stress disorder, current alcohol use disorder (AUD), disability with activities of daily living (i.e., ADLs) or instrumental activities of daily living (i.e., IADLs), lower perceived social support, lower community integration, and lower purpose in life. Current AUD, greater cumulative trauma burden, and lower purpose in life at baseline were predictive of incident SA. Relative importance analyses revealed that lower purpose in life was the strongest predictor of both incident SI and SA. Psychosocial determinants of health, such as purpose in life, may be more reliable predictors of incident suicidal thoughts and behaviors than traditional risk factors (e.g., psychiatric distress; history of SA) in those without a history of STBs. Evidence-based interventions that facilitate purpose in life and feelings of connectedness and belonging should be examined as possible treatments for STBs.


Effects of temperature and pH on reduction of bacteria in a point-of-use drinking water treatment product for emergency relief.
The effects of temperature and pH on the water treatment performance of a point-of-use (POU) coagulant/disinfectant product were evaluated. Cold temperatures (∼5°C) reduced the bactericidal efficiency of the product with regard to Escherichia coli and total coliform log(10) reductions.


Optimized total thoracoscopic and laparoscopic esophagectomy for esophageal cancer.
Total thoracoscopic and laparoscopic esophagectomy (TLE) has attracted attention with the advantage of better operative field and minimal wound for the esophageal cancer. However, various severe complications are also reported during the TLE such as cervical anastomotic leakage, chylothorax, and tracheal injury. The aim of this study was to introduce a new optimized TLE procedure for the esophageal cancer and assess its safety and clinical effects. We retrospectively collected the clinical data of 30 patients with esophageal cancer who underwent optimized TLE procedures between January 2014 and December 2014. The optimized TLE procedures mainly include as follows: (1) 50 ml of sesame oil-milk mixture (1:1) is injected via gastric tube after endotracheal intubation; (2) patients are intubated with a single lumen endotracheal tube; (3) patients were positioned at 150° in the left prone position rather than lateral decubitus position; and (4) duodenal feeding tube was not placed intraoperatively and however triple lumen nasojejunal feeding tube was placed on the second postoperative day under imaging guidance. Operation time, amount of blood loss, number of dissected nodes, length of hospital stays, and complications were recorded. The mean operation time of the optimized TLE group was 202.13 ± 13.74 min. The mean visible blood loss of the optimized TLE group was 300.00 ± 120.12 ml. The postoperative hospital stays in the optimized TLE group were 16.27 ± 4.51 days. The number of dissected nodes in the optimized TLE group was 13.57 ± 2.76. The postoperative complications for the optimized TLE procedure were seen in one case (3.3%). The method of optimized TLE is an effective, reliable, and safe procedure for the treatment of esophageal cancer, which provide favorable outcomes in terms of operation time, blood loss, length of hospital stays, the number the dissected nodes, and reduced incidence of postoperative complications compared to previous literatures. Further studies with a large number of samples are warranted.


The value of mastectomy flap fixation in reducing fluid drainage and seroma formation in breast cancer patients.
Prolonged and excessive drainage of serous fluid and seroma formation constitute the most common complications after mastectomy for breast carcinoma. Seroma formation delays wound healing, increases susceptibility to infection, skin flap necrosis, persistent pain and prolongs convalescence. For this, several techniques have been investigated to improve primary healing and minimize seroma formation. Between June 2009 and July 2010 forty patients with breast carcinoma, scheduled for modified radical mastectomy, were randomly divided into 2 groups, the study group (20) and the control group (20). In the study group; the mastectomy flaps were fixed to the underlying muscles in raws, at various parts of the flap and at the wound edge using fine absorbable sutures. In the control group; the wound was closed in the conventional method at the edges. Closed suction drains were used in both groups. Patients, tumor characteristics and operative related factors were recorded. The amount and color of drained fluid were recorded daily. The drains were removed when the amount become less than 50 cc. The total amount and duration of drained fluid and the formation of seroma were recorded and the results were compared between the two groups. In the flap fixation group, the drain was removed in significantly shorter time compared to the control group (p < 0.001). Also, the total amount of fluid drained was significantly lower in the flap fixation group (p < 0.001). The flap fixation group showed a significantly lower frequency of seroma formation compared to the control group, both clinically (p = 0.028) and ultrasonographically (p = 0.047). The mastectomy flap fixation technique is a valuable procedure that significantly decreases the incidence of seroma formation, and reduces the duration and amount of drained fluid. However, it should be tried on a much wider scale to prove its validity.