Age-related oxidative stress compromises endosomal proteostasis.
A hallmark of aging is an imbalance between production and clearance of reactive oxygen species and increased levels of oxidatively damaged biomolecules. Herein, we demonstrate that splenic and nodal antigen-presenting cells purified from aging mice accumulate oxidatively modified proteins with side-chain carbonylation, advanced glycation end products, and lipid peroxidation. Furthermore, we show that the endosomal accumulation of oxidatively modified proteins interferes with the efficient processing of exogenous antigens and degradation of macroautophagy-delivered proteins. In support of a causative role for oxidized products in the inefficient immune response, a decrease in oxidative stress improved the adaptive immune response to immunizing antigens. These findings underscore a previously unrecognized negative effect of age-dependent changes in cellular proteostasis on the immune response.


Interface-induced hysteretic volume phase transition of microgels: simulation and experiment.
Thermo-responsive microgel particles can exhibit a drastic volume shrinkage upon increasing the solvent temperature. Recently we found that the spreading of poly(N-isopropylacrylamide) (PNiPAm) microgels at a liquid interface under the influence of surface tension hinders the temperature-induced volume phase transition. In addition, we observed a hysteresis behavior upon temperature cycling, i.e. a different evolution in microgel size and shape depending on whether the microgel was initially adsorbed to the interface in expanded or collapsed state. Here, we model the volume phase transition of such microgels at an air/water interface by monomer-resolved Brownian dynamics simulations and compare the observed behavior with experiments. We reproduce the experimentally observed hysteresis in the microgel dimensions upon temperature variation. Our simulations did not observe any hysteresis for microgels dispersed in the bulk liquid, suggesting that it results from the distinct interfacial morphology of the microgel adsorbed at the liquid interface. An initially collapsed microgel brought to the interface and subjected to subsequent swelling and collapsing (resp. cooling and heating) will end up in a larger size than it had in the original collapsed state. Further temperature cycling, however, only shows a much reduced hysteresis, in agreement with our experimental observations. We attribute the hysteretic behavior to a kinetically trapped initial collapsed configuration, which relaxes upon expanding in the swollen state. We find a similar behavior for linear PNiPAm chains adsorbed to an interface. Our combined experimental - simulation investigation provides new insights into the volume phase transition of PNiPAm materials adsorbed to liquid interfaces.


Rehabilitation to Improve the Function and Quality of Life of Soft Tissue and Bony Sarcoma Patients.
Sarcomas are bone and soft tissue tumors that can have significant effects on patient function and quality of life. Like most malignancies, treatment includes a combination of chemotherapy, radiation, and surgical resection, all of which also carry risks and long-term effects. A multidisciplinary rehabilitation plan can help minimize symptoms and sequelae which negatively affect the patient function and quality of life, including pain, chemotherapy-induced peripheral neuropathy, radiation fibrosis, activity restrictions following surgical excision, amputation, bowel and bladder dysfunction, and lymphedema. Patients should be evaluated by a rehabilitation specialist at any point during their diagnosis, treatment, and survivorship phase to determine appropriate interventions to minimize the impact of sarcomas and their treatment on patient function and quality of life.


Effects of 8-week in-season upper and lower limb heavy resistance training on the peak power, throwing velocity, and sprint performance of elite male handball players.
The aims of this study were to test the potential of in-season heavy upper and lower limb strength training to enhance peak power output (Wpeak), vertical jump, and handball related field performance in elite male handball players who were apparently already well trained, and to assess any adverse effects on sprint velocity. Twenty-four competitors were divided randomly between a heavy resistance (HR) group (age 20 ± 0.7 years) and a control group (C; age 20 ± 0.1 years). Resistance training sessions were performed twice a week for 8 weeks. Performance was assessed before and after conditioning. Peak power (W(peak)) was determined by cycle ergometer; vertical squat jump (SJ) and countermovement jump (CMJ); video analyses assessed velocities during the first step (V(1S)), the first 5 m (V(5m)), and between 25 and 30 m (V(peak)) of a 30-m sprint. Upper limb bench press and pull-over exercises and lower limb back half squats were performed to 1-repetition maximum (1RM). Upper limb, leg, and thigh muscle volumes and mean thigh cross-sectional area (CSA) were assessed by anthropometry. W(peak) (W) for both limbs (p < 0.001), vertical jump height (p < 0.01 for both SJ and CMJ), 1RM (p < 0.001 for both upper and lower limbs) and sprint velocities (p < 0.01 for V(1S) and V(5m); p < 0.001 for V(peak)) improved in the HR group. Upper body, leg, and thigh muscle volumes and thigh CSA also increased significantly after strength training. We conclude that in-season biweekly heavy back half-squat, pull-over, and bench-press exercises can be commended to elite male handball players as improving many measures of handball-related performance without adverse effects upon speed of movement.


Pyk2 regulates H+-ATPase-mediated proton secretion in the outer medullary collecting duct via an ERK1/2 signaling pathway.
Acid-secreting intercalated cells respond to changes in systemic pH through regulation of apical H(+) transporters. Little is known about the mechanism by which these cells sense changes in extracellular pH (pH(o)). Pyk2 is a nonreceptor tyrosine kinase activated by autophosphorylation at Tyr402 by cell-specific stimuli, including decreased pH, and is involved in the regulation of MAPK signaling pathways and transporter activity. We examined whether the Pyk2 and MAPK signaling pathway mediates the response of transport proteins to decreased pH in outer medullary collecting duct cells. Immunoblot analysis of phosphorylated Pyk2 (Tyr402), ERK1/2 (Thr202/Tyr204), and p38 (Thr180/Tyr182) was used to assay protein activation. To examine specificity of kinase activation and its effects, we used Pyk2 small interfering RNA to knockdown Pyk2 expression levels, the Src kinase inhibitor 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP 1) to inhibit Pyk2 phosphorylation, and the MEK inhibitor U0126 to inhibit ERK1/2 phosphorylation. The pH-sensitive fluorescent probe 2'-7'-bis(carboxyethyl)-5(6)-carboxyfluorescein-acetoxymethyl ester (BCECF-AM) was used to assay H(+) transporter activity. The activity of H(+) transporters was measured as the rate of intracellular pH (pH(i)) recovery after an NH(4)Cl prepulse. We show that Pyk2 is endogenously expressed and activated by acid pH in mouse-derived outer medullary collecting duct (mOMCD1) cells. Incubation of mOMCD1 cells in acid media [extracellular pH (pH(o)) 6.7] increased the phosphorylation of Pyk2, ERK1/2, and p38. Reduction in pH(i) induced by an NH(4)Cl prepulse also increased the phosphorylation of Pyk2, ERK1/2, and p38. Consistent with our previous studies, we found that mOMCD1 cells exhibit H(+)-ATPase and H(+),K(+)-ATPase activity. Pyk2 inhibition by Pyk2 siRNA and PP 1 prevented Pyk2 phosphorylation as well as H(+)-ATPase-mediated recovery in mOMCD1 cells. In addition, ERK1/2 inhibition by U0126 prevented acid-induced ERK1/2 phosphorylation and H(+)-ATPase-mediated pH(i) recovery but not phosphorylation of p38. We conclude that Pyk2 and ERK1/2 are required for increasing H(+)-ATPase, but not H(+),K(+)-ATPase, activity at decreased pH(i) in mOMCD1 cells.


Race and Ethnicity Reporting and Representation in Obstetrics and Gynecology Clinical Trials and Publications From 2007-2020.
Clinical trials guide evidence-based obstetrics and gynecology (OB-GYN) but often enroll nonrepresentative participants. To characterize race and ethnicity reporting and representation in US OB-GYN clinical trials and their subsequent publications and to analyze the association of subspecialty and funding with diverse representation. Cross-sectional analysis of all OB-GYN studies registered on ClinicalTrials.gov (2007-2020) and publications from PubMed and Google Scholar (2007-2021). Analyses included logistic regression controlling for year, subspecialty, phase, funding, and site number. Data from 332 417 studies were downloaded. Studies with a noninterventional design, with a registration date before October 1, 2007, without relevance to OB-GYN, with no reported results, and with no US-based study site were excluded. OB-GYN subspecialty and funder. Reporting of race and ethnicity data and racial and ethnic representation (the proportion of enrollees of American Indian or Alaskan Native, Asian, Black, Latinx, or White identity and odds of representation above US Census estimates by race and ethnicity). Among trials with ClinicalTrials.gov results (1287 trials with 591 196 participants) and publications (1147 trials with 821 111 participants), 662 (50.9%) and 856 (74.6%) reported race and ethnicity data, respectively. Among publications, gynecology studies were significantly less likely to report race and ethnicity than obstetrics (adjusted odds ratio [aOR], 0.54; 95% CI, 0.38-0.75). Reproductive endocrinology and infertility trials had the lowest odds of reporting race and ethnicity (aOR, 0.14; 95% CI, 0.07-0.27; reference category, obstetrics). Obstetrics and family planning demonstrated the most diverse clinical trial cohorts. Compared with obstetric trials, gynecologic oncology had the lowest odds of Black representation (ClinicalTrials.gov: aOR, 0.04; 95% CI, 0.02-0.09; publications: aOR, 0.06; 95% CI, 0.03-0.11) and Latinx representation (ClinicalTrials.gov: aOR, 0.05; 95% CI, 0.02-0.14; publications: aOR, 0.23; 95% CI, 0.10-0.48), followed by urogynecology and reproductive endocrinology and infertility. Urogynecology (ClinicalTrials.gov: aOR, 0.15; 95% CI, 0.05-0.39; publications: aOR, 0.24; 95% CI, 0.09-0.58) had the lowest odds of Asian representation. Race and ethnicity reporting and representation in OB-GYN trials are suboptimal. Obstetrics and family planning trials demonstrate improved representation is achievable. Nonetheless, all subspecialties should strive for more equitably representative research.


Comparison of Single and Multiple Turnovers of SecYEG in Escherichia coli.
Precursor proteins are translocated across the cytoplasmic membrane in Escherichia coli by the general secretory, or Sec, pathway. The main components of the pathway are the integral membrane heterotrimeric SecYEG complex and the peripheral membrane ATPase, SecA. In this study, we have applied an in vitro assay using inverted cytoplasmic membrane vesicles to investigate the complex cycle that leads to translocation. We compared the apparent rate constants for nine precursors under two experimental conditions, single turnover and multiple turnovers. For each precursor, the rate constant for a single turnover was higher than for multiple turnovers, indicating that a different step limits the rate under the two conditions. We conclude that the rate-limiting step for a single turnover is an early step in the initial phase of transit through the channel, whereas the rate of multiple turnovers is limited by the resetting of the translocon. The presence of the chaperone SecB during multiple turnovers increased the maximal amplitude translocated for the three precursor species tested, pGBP, pPhoA, and proOmpA, and also increased the apparent rate constants for both pGBP and pPhoA. The rate constant for proOmpA was decreased by the presence of SecB.IMPORTANCE Vastly different experimental techniques and conditions have been used to study export in E. coli We demonstrated that altering experimental conditions can change the step that is observed during study. Investigators should consider specific experimental conditions when comparing data from different laboratories, as well as when comparing data from different experiments within a laboratory. We have shown that each precursor species has inherent properties that determine the translocation rate; thus generalizations from studies of a single species must be made with caution. A summary of advantages and disadvantages in use of nine precursors is presented.


[Indentification of institutional factors affecting the well-being of sedentary and nomadic populations living in the Waza-Logone flood plain along the border between Cameroon and Chad].
This article describes an ongoing research project designed to compile a database to promote pastoral development in the lowlands along the Logone and Chari Rivers in Cameroon. A number of sedentary and nomadic populations depend on these flood plains south of Lake Chad for their livelihood. However the natural resources of the area undergo sharp seasonal variations and sometimes become the property of sedentary groups. As a result nomadic communities experience difficulty not only in gaining access to grazing lands and water but also to quality health care (hospital centers, effective medication). The purpose of this study was to define institutional requirements necessary to ensure access to health care resources for both nomadic and sedentary groups. The main problem for the nomadic population is that, unlike the now defunct pre-colonial structures, today's institutions are not compatible with the subsistence strategies of rural populations. These findings suggest that new institutional frameworks for natural resource management could indirectly improve the health status of nomadic pastoralist.


BCMA-targeted bortezomib nanotherapy improves therapeutic efficacy, overcomes resistance, and modulates the immune microenvironment in multiple myeloma.
Bortezomib (BTZ) is a standard-of-care treatment in multiple myeloma (MM); however, adverse side effects and development of resistance limit its long term benefit. To improve target specificity, therapeutic efficacy, and overcome resistance, we designed nanoparticles that encapsulate BTZ and are surface-functionalized with BCMA antibodies (BCMA-BTZ-NPs). We confirmed efficient cellular internalization of the BCMA-BTZ-NPs only in BCMA-expressing MM cells, but not in BCMA-knockout (KO) cells. In addition, BCMA-BTZ-NPs showed target-specific cytotoxicity against MM cell lines and primary tumor cells from MM patients. The BCMA-BTZ-NPs entered the cell through receptor-mediated uptake, which escapes a mechanism of BTZ resistance based on upregulating P-glycoprotein. Furthermore, BCMA-BTZ-NPs induced cell death more efficiently than non-targeted nanoparticles or free BTZ, triggering potent mitochondrial depolarization followed by apoptosis. In BTZ-resistant cells, BCMA-BTZ-NPs inhibited proteasome activity more effectively than free BTZ or non-targeted nanoparticles. Additionally, BCMA-BTZ-NPs enhanced immunogenic cell death and activated the autophagic pathway more than free BTZ. Finally, we found that BCMA-BTZ-NPs selectively accumulated at the tumor site in a murine xenograft model, enhanced tumor reduction, and prolonged host survival. These results suggest BCMA-BTZ-NPs provide a promising therapeutic strategy for enhancing the efficacy of BTZ and establish a framework for their evaluation in a clinical setting.


Posttranscription regulation of prostate cancer growth.
Advances in the understanding of the molecular mechanisms implicated in prostate cancer progression have allowed identification of many potential therapeutic gene targets that are involved in apoptosis, growth factors, cell signaling, and the androgen receptor. A critical factor responsible for the malignant progression of prostate cancer is the abnormal expression and function of specific proteins. From the transcription of mRNA to the translation of proteins and their function, several steps can be exploited as "drugable" targets. In this article we will review some of the key molecular targets and posttranscriptional strategies that are currently being tested both preclinically and clinically as targeted therapeutic approach for prostate cancer. Most of the targets mentioned in this review involve the prostate cancer signal transduction cascade, and their functions include prosurvival, antiapoptosis, and proangiogenesis. We will focus in particular on the emerging role of the "chromatin modifiers," histone deacetylase inhibitors, not only in transcriptional gene regulation but also in posttranscriptional protein modifications as a tool for therapeutic intervention in prostate cancer.


Angiotensin-converting enzyme insertion/deletion polymorphism and systemic lupus erythematosus: a metaanalysis.
To explore whether insertion (I) and deletion (D) polymorphisms within intron 16 of the angiotensin-converting enzyme (ACE) gene confer susceptibility to systemic lupus erythematosus (SLE) and lupus nephritis (LN). We surveyed studies of ACE I/D polymorphism and SLE using Medline and manual searches. We conducted a metaanalysis of the DD genotype (recessive effect), DD and DI genotype (dominant effect), and D allele of the ACE overall and in each ethnic population. We performed a metaanalysis of ACE I/D polymorphism in SLE and LN. Thirteen comparison studies were included in our metaanalysis consisting of 1411 patients with SLE and 1551 controls. We found no association of ACE I/D polymorphism with SLE in the total sample and by ethnic groups. There was a trend for association of the DD genotype (OR 1.212, 95% CI 0.966-1.520, p = 0.097) and the D allele with SLE in Caucasian patients (OR 1.157, 95% CI 0.991-1.349, p = 0.064); however, this was not statistically significant. The metaanalysis also showed no association of the ACE I/D polymorphisms with LN. This metaanalysis of 2962 subjects showed there is a lack of association of the ACE I/D polymorphism with SLE and LN.


Responses of schools of nursing to physically, mentally, and substance-impaired students.
Responses of schools of nursing to physically, mentally, and substance-impaired applicants and matriculating students were assessed in a 12% simple random sample (n = 132) of the 383 baccalaureate and 715 associate degree nursing schools and programs accredited by the National League for Nursing. A self-administered questionnaire concerning experiences, policies, procedures, and factors influencing decision-making was sent to the 132 deans and directors of the nursing schools and programs. Criteria for defining impairments, resources for developing criteria, methods of identifying impairments, actions taken, and individuals involved in the decision were also assessed. While the schools used external resources to guide decision-making, the majority of the responsibility was with the school of nursing faculty and administration. Schools offered a range of options for impaired individuals continuing in the program while under treatment; nevertheless, seeking treatment was a frequent requirement for continuation in the program.


Phase 2B trial of aminopterin in multiagent therapy for children with newly diagnosed acute lymphoblastic leukemia.
Aminopterin offers advantages over the related antifolate, methotrexate, including greater potency, complete bioavailability, and more consistent accumulation and metabolism by patients' blasts. This current trial was done to document the toxicity of the aminopterin within a multiagent therapeutic regimen for children with newly diagnosed ALL. Patients at high risk of relapse were non-randomly assigned to therapy including oral aminopterin 4 mg/m(2), in two doses 12 h apart, in place of methotrexate 100 mg/m(2) in four divided doses. Thirty-two patients, 22 with pre-B ALL and ten with T-lineage ALL, have been treated with aminopterin, with median follow up of 40 months. Hematologic, mucosal and hepatic toxicity has been tolerable and reversible. There have been no toxic deaths among patients in remission. During weekly AMT therapy, higher mean neutrophil counts were observed among patients who were wild type for polymorphisms in methylene tetrahydrofolate reductase and methionine synthase reductase. Aminopterin can be safely incorporated in multiagent therapy for patients with ALL, in place of systemic methotrexate, without causing excessive toxicity. These results support a larger trial comparing the efficacy and toxicity of aminopterin and methotrexate in therapy for patients with ALL.


Diffuse myocardial fibrosis: mechanisms, diagnosis and therapeutic approaches.
Diffuse myocardial fibrosis resulting from the excessive deposition of collagen fibres through the entire myocardium is encountered in a number of chronic cardiac diseases. This lesion results from alterations in the regulation of fibrillary collagen turnover by fibroblasts, facilitating the excessive deposition of type I and type III collagen fibres within the myocardial interstitium and around intramyocardial vessels. The available evidence suggests that, beyond the extent of fibrous deposits, collagen composition and the physicochemical properties of the fibres are also relevant in the detrimental effects of diffuse myocardial fibrosis on cardiac function and clinical outcomes in patients with heart failure. In this regard, findings from the past 20 years suggest that various clinicopathological phenotypes of diffuse myocardial fibrosis exist in patients with heart failure. In this Review, we summarize the current knowledge on the mechanisms and detrimental consequences of diffuse myocardial fibrosis in heart failure. Furthermore, we discuss the validity and usefulness of available imaging techniques and circulating biomarkers to assess the clinicopathological variation in this lesion and to track its clinical evolution. Finally, we highlight the currently available and potential future therapeutic strategies aimed at personalizing the prevention and reversal of diffuse myocardial fibrosis in patients with heart failure.


Detection of cytotoxic activity of lectin on human colon adenocarcinoma (Sw480) and epithelial cervical carcinoma (C33-A).
Lectins comprise a heterogeneous class of proteins that recognize the carbohydrate moieties of glycoconjugates with high specificity. Numerous studies have shown that lectins are capable of recognizing specific carbohydrate moieties displayed by malignant cells or tissues. The present work was performed to investigate the effects of tepary bean (Phaseolus acutifolius) lectins on proliferation, colony formation, and alteration of DNA synthesis of human malignant cells. Tepary bean lectin showed dose dependent effects on the inhibition of viability as well as on colony formation in two human malignant cells lines (C33-A, Sw480); By contrast, tepary bean lectin only showed significant effects on DNA synthesis on Sw480 cells. Our results provide evidence of the anti- proliferative and cytotoxic effects of the tepary bean lectins on C33-A and Sw480 cells lines.


Mental health services in Nigerian prisons: Lessons from a four-year review and the literature.
Forensic and correctional mental health services may constitute an important "safety net" for the mentally ill and can ensure a degree of public protection. The increasing prison populations and shift towards humane care of the mentally ill that encompasses promotion of human rights, community re-integration, utilitarian safety and operation of internationally comparable mental health legislations underscore the need to appraise correctional psychiatry services, especially in resource-restricted settings. We present findings from a review of the literature and from mental health services provided to 179 inmates in two Nigerian urban prisons. The mental health services spanned four years and allowed a focus on important issues deserving urgent attention. The mean age of participants was 33.10 years (SD = 9.91) and majority (86.6%) were males. The common clinical diagnoses among participants were schizophrenia (49.3%) and mood disorders (29.6%), while approximately half (46.5%) used psychoactive substances. About one-fifth was evaluated as having high risk for violence-dangerousness based solely on clinical evaluation. The majority (88.4%) presented with a first episode of mental illness, and 14% had a prior correctional history. Gender, marital status and hallucinatory experiences were associated with a high risk of dangerousness (p < 0.05), while gender, use of psychoactive substances, previous history of mental disorders and depot medication indexed participants more likely to have a previous forensic history (p < 0.05). Considering the current findings, we advocate for inclusion of validated tools in risk assessments, multipronged intervention strategy to address the unmet needs of prisoners and improved attention to forensic and correctional mental health in relevant policy-law, service-planning, research and training.


Fracture and adhesion of soft materials: a review.
Soft materials are materials with a low shear modulus relative to their bulk modulus and where elastic restoring forces are mainly of entropic origin. A sparse population of strong bonds connects molecules together and prevents macroscopic flow. In this review we discuss the current state of the art on how these soft materials break and detach from solid surfaces. We focus on how stresses and strains are localized near the fracture plane and how elastic energy can flow from the bulk of the material to the crack tip. Adhesion of pressure-sensitive-adhesives, fracture of gels and rubbers are specifically addressed and the key concepts are pointed out. We define the important length scales in the problem and in particular the elasto-adhesive length Γ/E where Γ is the fracture energy and E is the elastic modulus, and how the ratio between sample size and Γ/E controls the fracture mechanisms. Theoretical concepts bridging solid mechanics and polymer physics are rationalized and illustrated by micromechanical experiments and mechanisms of fracture are described in detail. Open questions and emerging concepts are discussed at the end of the review.


Loss-of-function mutations in a glutathione S-transferase suppress the prune-Killer of prune lethal interaction.
The prune gene of Drosophila melanogaster is predicted to encode a phosphodiesterase. Null alleles of prune are viable but cause an eye-color phenotype. The abnormal wing discs gene encodes a nucleoside diphosphate kinase. Killer of prune is a missense mutation in the abnormal wing discs gene. Although it has no phenotype by itself even when homozygous, Killer of prune when heterozygous causes lethality in the absence of prune gene function. A screen for suppressors of transgenic Killer of prune led to the recovery of three mutations, all of which are in the same gene. As heterozygotes these mutations are dominant suppressors of the prune-Killer of prune lethal interaction; as homozygotes these mutations cause early larval lethality and the absence of imaginal discs. These alleles are loss-of-function mutations in CG10065, a gene that is predicted to encode a protein with several zinc finger domains and glutathione S-transferase activity.


Detection of Lotmaria passim in honeybees from Emilia Romagna (Italy) based on a culture method.
Lotmaria passim is considered an emerging field of study in honeybee pathology, since it can threaten the health of the colony leading to a higher mortality rate. However, there is a lack of knowledge regarding the diffusion of this trypanosomatid in Italy. In this study, we highlight the presence of L. passim in the province of Bologna through its culture isolation from honeybee guts and microscopic observation.


[Hypoglycemia caused by insulinoma in diabetes mellitus].
An hyperglycaemic metabolic state disappeared and spontaneous hypoglycaemia occurred in a 58-year-old woman with non-insulin-dependent obese type II diabetes. Abnormal absence of the hunger response with provoked hypoglycaemia, increased serum insulin concentrations and reduced blood glucose/insulin ratio led to the diagnosis of pathological hyperinsulinism, which was found to be due to an insulinoma of the tail of the pancreas. After its excision the patient's carbohydrate metabolism returned to a mild type II diabetic state and there were no further hypoglycaemic attacks.


Ethnic and gender differences in Southwestern students' sources of information about health.
Students from several rural, Southwestern schools rated family, television, teachers and doctors as the most important of 11 sources of information about various health topics. However, doctors were only the fifth-ranked source of information about sex and reproduction and the seventh-ranked source of information about drugs, with friends being the fourth- and third-ranked sources of information about these two more personal and sensitive topics. American Indians reported even stronger reliance on doctors than did Hispanic and Anglo students, and rated clinic nurses as much more important sources of health information than did the other two ethnic groups. Females showed greater reliance on social sources and less on electronic media than did male students, and high school students relied more on print media and less on television, nurses and family than did younger children. Students felt more knowledgeable about smoking, alcohol and exercise than about diet, the heart-blood system and cancer; however, American Indians felt less informed about smoking and alcohol than did Anglos or Hispanics. These findings (especially when compared to previous results) suggest that effective health education programs must be tailored to particular populations and based on specific knowledge of their attitudes, behavior and environment.


Cigarette smoke extract acts directly on CD4 T cells to enhance Th1 polarization and reduce memory potential.
Although cigarette smoke is known to alter immune responses, whether and how CD4 T cells are affected is not well-described. We aimed to characterize how exposure to cigarette smoke extract impacts CD4 T cell effector generation in vitro under Th1-polarizing conditions. Our results demonstrate that cigarette smoke directly acts on CD4 T cells to impair effector expansion by decreasing division and increasing apoptosis. Furthermore, cigarette smoke enhances Th1-associated cytokine production and increases expression of the transcription factor T-bet, the master regulator of Th1 differentiation. Finally, we show that exposure to cigarette smoke extract during priming impairs the ability of effectors to form memory cells. Our findings thus demonstrate that cigarette smoke simultaneously enhances effector functions but promotes terminal differentiation of CD4 T cell effectors. This study may be relevant to understanding how smoking can both aggravate autoimmune symptoms and reduce vaccine efficacy.


Impurity analysis of retinoic acid samples.
The structure of an impurity contained in samples of all trans-retinoic acid was established by means of NMR and MS spectra, and confirmed by X-ray diffraction analysis. The chemical structure of the impurity 2 was found to be strictly correlated to the synthetic procedure employed for the preparation of the retinoic acid samples. Single crystal analysis allowed us to characterise the molecular conformation and the crystal structure of 2.


Thermodynamic limits of countercurrent reactor systems, with examples in membrane reactors and the ceria redox cycle.
Countercurrent reactors can be utilized in chemical reaction systems which involve either a reaction between flows of different phases, or reactions between flows separated by a selective permeable membrane. This idea is quite similar in nature to a countercurrent heat exchanger, where the inlet of one participating flow is exposed to the outlet of the opposite flow. A countercurrent configuration can therefore improve the reaction conversion extent and transport properties. Here we formulate a straightforward approach in terms of an exchange coordinate, in order to determine an upper bound of species exchange in such systems, subject to the second law of thermodynamics and conservation of mass. The methodology is independent of the specifics of reactor design and can be generally applied to determine the maximum thermodynamic benefit of using a countercurrent reactor. We then demonstrate the analysis for a number of thermochemical fuel production routes; membrane thermolysis of carbon dioxide, dry methane reforming across a membrane, reverse water gas shift across a membrane, and the thermochemical ceria cycle.


Angiogenic response of rat hippocampal vasculature to focused ultrasound-mediated increases in blood-brain barrier permeability.
Focused ultrasound (FUS) and circulating microbubbles can induce a targeted and transient increase in blood-brain barrier permeability. While preclinical research has demonstrated the utility of FUS for efficacious drug deliver to the brain, there remain gaps in our knowledge regarding the long-term response of brain vasculature to this intervention. Previous work has demonstrated transcriptional changes in hippocampal microvessels following sonication that are indicative of the initiation of angiogenic processes. Moreover, blood vessel growth has been reported in skeletal muscle following application of FUS and microbubbles. The current study demonstrates that blood vessel density in the rat hippocampus is modestly elevated at 7 and 14 d post-FUS compared to the contralateral hemisphere (7 d: 10.9 ± 6.0%, p = 0.02; 14 d: 12.1 ± 3.2%, p < 0.01), but returns to baseline by 21 d (5.9 ± 2.6%, p = 0.12). Concurrently, relative newborn endothelial cell density and frequency of small blood vessel segments were both elevated in the sonicated hippocampus. While further work is required to determine the mechanisms driving these changes, the findings presented here may have relevance to the optimal frequency of repeated treatments.


Renoprotective effects of febuxostat in hyperuricemic patients with chronic kidney disease: a parallel-group, randomized, controlled trial.
Hyperuricemia is associated with the onset of chronic kidney disease (CKD) and renal disease progression. Febuxostat, a novel, non-purine, selective xanthine oxidase inhibitor, has been reported to have a stronger effect on hyperuricemia than conventional therapy with allopurinol. However, few data are available regarding the clinical effect of febuxostat in patients with CKD. A prospective, randomized, open-label, parallel-group trial was conducted in hyperuricemic patients with stage 3 CKD. Patients were randomly assigned to treatment with febuxostat (n = 21) or to continue conventional therapy (n = 19). Treatment was continued for 12 weeks. The efficacy of febuxostat was determined by monitoring serum uric acid (UA) levels, blood pressures, renal function, and urinary protein levels. In addition, urinary liver-type fatty acid-binding protein (L-FABP), urinary albumin, urinary beta 2 microglobulin (β2MG), and serum high sensitivity C-reactive protein were measured before and 12 weeks after febuxostat was added to the treatment. Febuxostat resulted in a significantly greater reduction in serum UA (-2.2 mg/dL) than conventional therapy (-0.3 mg/dL, P < 0.001). Serum creatinine and estimated glomerular filtration rate changed little during the study period in each group. However, treatment with febuxostat for 12 weeks reduced the urinary levels of L-FABP, albumin, and β2MG, whereas the levels of these markers did not change in the control group. Febuxostat reduced serum UA levels more effectively than conventional therapy and might have a renoprotective effect in hyperuricemic patients with CKD. Further studies should clarify whether febuxostat prevents the progression of renal disease and improves the prognosis of CKD.


[New contributions of the usefulness of electromyography of cavernous bodies in the diagnosis of erectile dysfunction].
To test the concordance between clinical and neurophysiologic data of the various types of erectile dysfunction, and to describe a diagnostic algorithm based on corpus cavernosum electromyography (cc-EMG). 32 patients with a mean age of 50.6 years (typical deviation 13.2 years) referred with the diagnosis of erectile dysfunction underwent medical history, neuroandrologic physical exam, neurophysiologic studies (bulbocavernous muscle electromyography, S2-S4 latency period, threshold and latency of pudendal nerve somatosensory potentials, as well as genital sympathetic evoked potentials-SSR-), and corpus cavernosum electromyography(cc-EMG) both in basal conditions and after administration of 20 micrograms of E-1 prostaglandin (PGE-1). 1--A significative relationship was shown between clinical data of arterial or corpus cavernosum intrinsic origin erectile dysfunction and patients with vascular or structural lesion on cc-EMG data. 2--A significative relationship was shown between patients without previous pathologic history and patients with normal or anxiety cc-EMG. 3--No significative relationship was shown between patients with neurologic lesion and patients with autonomic lesion on cc-EMG. 4--No significative relationship was found between patients with peripheric neurologic lesion and patients with inferior autonomic lesion on cc-EMG. 5--A significative relationship was shown between patients with suprasacral neurologic lesion and patients with superior autonomical lesion on cc-EMG. Isolated application of pudendal nerve neurophysiologic techniques for the diagnosis of erectile dysfunction is not enough. Autonomic innervation studies should be included, with a cc-EMG dichotomic qualitative interpretation.


Why does human culture increase exponentially?
Historical records show that culture can increase exponentially in time, e.g., in number of poems, musical works, scientific discoveries. We model how human capacities for creativity and cultural transmission may make such an increase possible, suggesting that: (1) creativity played a major role at the origin of human culture and for its accumulation throughout history, because cultural transmission cannot, on its own, generate exponentially increasing amounts of culture; (2) exponential increase in amount of culture can only occur if creativity is positively influenced by culture. The evolution of cultural transmission is often considered the main genetic bottleneck for the origin of culture, because natural selection cannot favor cultural transmission without any culture to transmit. Our models suggest that an increase in individual creativity may have been the first step toward human culture, because in a population of creative individuals there may be enough non-genetic information to favor the evolution of cultural transmission.


Intragastric quinine administration decreases hedonic eating in healthy women through peptide-mediated gut-brain signaling mechanisms.
Objectives: Intragastric bitter tastants may decrease appetite and food intake. We aimed to investigate the gut-brain signaling and brain mechanisms underlying these effects.Methods: Brain responses to intragastric quinine-hydrochloride (QHCl, 10 µmol/kg) or placebo infusion were recorded using functional magnetic resonance imaging in 15 healthy women. Appetite-related sensations, plasma levels of gastrointestinal hormones and hedonic food intake (ad libitum drink test) were assessed.Results: Lower octanoylated ghrelin (P<0.04), total ghrelin (P<0.01), and motilin (P<0.01) plasma levels were found after QHCl administration, along with lower prospective food consumption ratings (P<0.02) and hedonic food intake (P<0.05). QHCl increased neural activity in the hypothalamus and hedonic (anterior insula, putamen, caudate, pallidum, amygdala, anterior cingulate cortex, orbitofrontal cortex, midbrain) regions, but decreased activity in the homeostatic medulla (all pFWE-corrected<0.05). Differential brain responses to QHCl versus placebo covaried with subjective and hormonal responses and predicted differences in hedonic food intake.Discussion: Intragastric QHCl decreases prospective and actual food intake in healthy women by interfering with homeostatic and hedonic brain circuits in a ghrelin- and motilin-mediated fashion. These findings suggest a potential of bitter tastants to reduce appetite and food intake, through the gut-brain axis.


[A case of multifocal fibrosis].
We report a case of multifocal fibrosis extending retroperitoneally (Ormond's syndrome) with urinary tract obstruction and bilateral ureterohydronephrosis that resulted in chronic renal insufficiency. The development of mediastinal and pericardial fibrosis was accompanied by clinical symptoms of exudative and constrictive pericarditis. Fibrosis of cardiac conducting system was associated with compromised sinus node and intraventricular blockade. Paraaortic, paraorbital, and periportal extension of fibrosis was documented. Diagnosis was made based on clinical observations and results of MSCT. Duration of the disease was 20 years. Immunosuppressive therapy failed to improve the patient's condition because of irreversible structural and functional changes in the organs.


Hybrid Alginate-Brushite Beads Easily Catalyze the Knoevenagel Condensation On-Water.
An innovative hybrid organic-inorganic material composed of alginate-brushite xerogel beads was successfully applied for the catalysis of the Knoevenagel condensation. The catalyst was derived from phosphated alginate xerogel microspheres formed from the ionotropic gelling effect of phosphated alginate. To this end, alginate was phosphated by the addition of diammonium hydrogen phosphate in a 1% w/w alginate gel. The phosphated alginate was subsequently precipitated by chelation of Ca2+ cations, generating a phosphated alginate hydrogel microsphere, which was washed and dried, forming hybrid organic-inorganic xerogel beads as a crystalline phosphate-rich mineral fraction covered by alginate. X-ray diffraction analysis revealed that the crystalline inorganic matrix of the material was composed predominantly of brushite. SEM analysis revealed plate-like, ribbon-like, or needle-like morphologies in the hybrid alginate-brushite beads. The hybrid material was tested as a catalyst for Knoevenagel condensation, which was performed ″on-water″ under mild conditions with aromatic aldehydes and activated methylene compounds, giving high yields (up to 97%). The reaction rate and product yield increased together with the reaction temperature for all reagents. The recyclable solid catalyst was effective for three runs, revealing the potential of the innovative hybrid catalyst as an eco-friendly heterogeneous catalyst.


Relationships between infection with Plasmodium falciparum during pregnancy, measures of placental malaria, and adverse birth outcomes.
Malaria in pregnancy has been associated with maternal morbidity, placental malaria, and adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of malaria during pregnancy, measures of placental malaria, and birth outcomes. This is a nested observational study of data from a randomized controlled trial of intermittent preventive therapy during pregnancy among 282 participants with assessment of placental malaria and delivery outcomes. HIV-uninfected pregnant women were enrolled at 12-20 weeks of gestation. Symptomatic malaria during pregnancy was measured using passive surveillance and monthly detection of asymptomatic parasitaemia using loop-mediated isothermal amplification (LAMP). Placental malaria was defined as either the presence of parasites in placental blood by microscopy, detection of parasites in placental blood by LAMP, or histopathologic evidence of parasites or pigment. Adverse birth outcomes assessed included low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA) infants. The 282 women were divided into three groups representing increasing malaria burden during pregnancy. Fifty-two (18.4%) had no episodes of symptomatic malaria or asymptomatic parasitaemia during the pregnancy, 157 (55.7%) had low malaria burden (0-1 episodes of symptomatic malaria and < 50% of samples LAMP+), and 73 (25.9%) had high malaria burden during pregnancy (≥ 2 episodes of symptomatic malaria or ≥ 50% of samples LAMP+). Women with high malaria burden had increased risks of placental malaria by blood microscopy and LAMP [aRR 14.2 (1.80-111.6) and 4.06 (1.73-9.51), respectively], compared to the other two groups combined. Compared with women with no malaria exposure during pregnancy, the risk of placental malaria by histopathology was higher among low and high burden groups [aRR = 3.27 (1.32-8.12) and aRR = 7.07 (2.84-17.6), respectively]. Detection of placental parasites by any method was significantly associated with PTB [aRR 5.64 (1.46-21.8)], and with a trend towards increased risk for LBW and SGA irrespective of the level of malaria burden during pregnancy. Higher malaria burden during pregnancy was associated with placental malaria and together with the detection of parasites in the placenta were associated with increased risk for adverse birth outcomes. Trial Registration Current Controlled Trials Identifier NCT02163447.


Shallow-water waveguide acoustic analysis in a fluctuating environment.
The Acoustic Laboratory for Marine Applications (ALMA) is a deployable and autonomous acoustic system, designed by DGA Naval Systems, to address problems in underwater acoustics, such as sound propagation in fluctuating environments. In this article, data from the ALMA-2016 at-sea campaign are used to analyze the ocean fluctuation's influence on sound propagation in a shallow-water waveguide. The experiment took place on the continental shelf of the island of Corsica in November 2016. A source and a receiver array were 9.3 km apart in a nearly constant water depth of 100 m. The source emitted a variety of signals from which the chirp (1-13 kHz) is used to extract the waveguide eigenrays. To do so, a time-domain beamforming is performed on the match-filtered received signals with an automatic detection of local maxima in the time of arrival/direction of arrival (TOA/DOA) domain. A 2 min acquisition period of more than 13 h duration shows significant fluctuations in eigenray TOAs/DOAs. Qualitative comparisons with synthetic signals obtained from simulations in two and three dimensions permit reproduction of the observed eigenray fluctuations without including range dependence of the sound-speed profile.


Hydrodynamic facilitation of gregarious settlement of a reef-building tube worm.
Experiments testing the effects of hydrodynamic processes and chemical cues on substrate selection were conducted with larvae of the marine tube worm Phragmatopoma lapidosa californica. In flume experiments, larvae were presented an array of sand treatments, including two substrates previously shown to induce metamorphosis in this species, under fast and slow flow regimes. Larvae preferentially metamorphosed on the inductive substrates in both flows. Delivery to the array was higher in fast flow because larvae tumbled along the bottom, whereas in slow flow, larvae were observed swimming in the water column. Thus, in addition to chemical cues, behavioral responses to flow conditions may play an important role in larval recruitment to the benthos.


Visceral Fat Is an Independent Predictor of Cerebral Microbleeds in Neurologically Healthy People.
Obesity has a significant contribution to the risk of intracerebral hemorrhage (ICH). However, little is known about the association between central obesity and the presence of cerebral microbleeds (CMBs), a precursor of ICH. We sought to assess whether visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are associated with the presence of CMB. We conducted a cross-sectional study of 1,737 neurologically healthy people (mean age 55.9 ± 9.1; 790 men), who underwent brain MRI and abdominal CT. Risk factors, anthropometric parameters and clinical information were obtained. CMBs were evaluated through T2*-weighted gradient-recalled echo MRI. The cross-sectional surface areas of the abdominal fat compartments were calculated. Study subjects were stratified into quartiles according to the distribution of VAT/SAT ratio. A total of 75 (4.3%) subjects were found to have CMBs. Subjects with a greater quartile of VAT/SAT ratio were more likely to have higher numbers of CMBs (0 to ≥2; p = 0.001). In multivariable analysis, age and history of hypertension were associated with the presence of CMB (OR 1.09, 95% CI 1.06-1.13, p < 0.001; OR 1.70, 95% CI 1.01-2.84, p = 0.046, respectively). A dose-response relationship was observed between the extent of VAT/SAT quartile and CMB: compared to the lowest VAT/SAT quartile, OR 2.14 (95% CI 0.86-5.35) for second VAT/SAT quartile; OR 2.26 (95% CI 0.86-5.92) for third VAT/SAT quartile; and OR 2.91 (95% CI 1.04-8.12) for the highest VAT/SAT quartile (p for trend 0.03). In our study, higher VAT/SAT ratios were found to be independent predictors of CMBs in neurologically healthy people. This finding strengthens previous data, suggesting that visceral fat distribution is an important contributor to cerebral small vessel disease.


Atipamezole reverses ketamine-dexmedetomidine anesthesia without altering the antinociceptive effects of butorphanol and buprenorphine in female C57BL/6J mice.
Butorphanol and buprenorphine are common analgesics used in laboratory mice. Inadvertent attenuation of the antinociceptive effects of these analgesics via the administration of an anesthetic reversal agent could result in postprocedural pain and distress, with subsequent negative effects on animal welfare, study outcomes, and regulatory compliance. This study was undertaken to determine whether atipamezole reverses ketamine-dexmedetomidine anesthesia and alters the antinociceptive effects of butorphanol and buprenorphine in female C57BL/6J mice. Atipamezole reliably reversed the anesthetic effects of ketamine-dexmedetomidine, and mice were ambulatory 17.4 ± 30.6 min after administration of the α2-adrenoreceptor antagonist. Atipamezole alone had no significant effect on tail-flick latency and did not alter the antinociceptive properties of butorphanol or low-dose (0.05 mg/kg) or high-dose (0.1 mg/kg) buprenorphine in female C57BL/6J mice. After reversal of ketamine-dexmedetomidine anesthesia, tail-flick latency at 30, 60, and 150 min after analgesic treatment differed significantly between mice treated with atipamezole alone and those given atipamezole followed by butorphanol or high-dose buprenorphine. These results suggest that the analgesic effects of butorphanol and buprenorphine are not affected by atipamezole. Buprenorphine (0.1 mg/kg) administered 30 min prior to or at the time of anesthesia resulted in a greater magnitude of antinociception after antagonism of anesthesia than when given at the time of reversal. Given these results, we recommend the use of ketamine-dexmedetomidine anesthesia with buprenorphine administered either preemptively or at the time of anesthetic induction to provide a defined period of surgical anesthesia that is effectively reversed by atipamezole.


Influences of the Unified Service Action Model on the HL7 Reference Information Model.
Modeling information for the electronic medical record (EMR) builds on a century of study on information and its relationship to cost and quality improvement. An initiative to examine the focus of cost and quality improvement and its relationship to information modeling resulted in the development of the Unified Service Action Model of healthcare processes, which focuses on the action as the center of cost accounting, quality accounting and privacy management. The application of this model to the HL7 Reference Information Model produced a simplification of the HL7 model at the cost of increased reliance on vocabulary terms for actions.


Altered energy balance and cytokine gene expression in a murine model of chronic infection with Toxoplasma gondii.
The temporal pattern of changes in energy balance and cytokine mRNA expression in spleen and brain were examined in a mouse model of infection with Toxoplasma gondii. During days 1-7 postinfection, food intake was unaltered, but energy expenditure was significantly increased, and this was associated with elevated tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-5, and interferon (IFN)-gamma. The hypermetabolic state persisted during subsequent anorexia, whose onset coincided with elevated IL-2, and at the end of the acute phase of cachexia, the dual anorexic and hypermetabolic states were associated with the cytokines examined: TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-gamma. In the chronic phase of the infection, the mice showed either partial weight recovery (gainers) or no weight regain (nongainers). The infected gainers, though still hypophagic, were no longer hypermetabolic, and their cytokine mRNA was no longer elevated, except for TNF-alpha and IL-10. In contrast, the infected nongainers continued to show both anoroxia and hypermetabolism, which were associated with elevations in all cytokines examined and particularly those of the TH2 profile (IL-4 and IL-5) and IL-6. Taken together, these studies reveal a distinct pattern of cytokine mRNA expression underlying 1) hypermetabolism vs. anorexia, 2) acute vs. chronic cachexia, and 3) stable weight loss vs. partial weight recovery.


EGFR exon 19 insertions: a new family of sensitizing EGFR mutations in lung adenocarcinoma.
Epidermal growth factor receptor (EGFR) genotyping is now standard in the management of advanced lung adenocarcinoma, as this biomarker predicts marked benefit from treatment with EGFR tyrosine kinase inhibitors (TKI). EGFR exon 19 insertions are a poorly described family of EGFR mutations, and their association with EGFR-TKI sensitivity in lung adenocarcinoma is uncertain. Patients with lung cancers harboring EGFR exon 19 insertions were studied. The predicted effects of the insertions on the structure of the EGFR protein were examined, and EGFR exon 19 insertions were introduced into Ba/F3 cells to assess oncogenicity and in vitro sensitivity to EGFR-TKIs. In patients receiving TKI, response magnitude was assessed with serial computed tomographic (CT) measurement. Twelve tumors harboring EGFR exon 19 insertions were identified; patients were predominately female (92%) and never-smokers (75%). The 11 specimens available for full sequencing all showed an 18-bp insertion that resulted in the substitution of a Pro for Leu at residue 747. The mutant EGFR transformed the Ba/F3 cells, which were then sensitive to EGFR-TKI. Six patients with measurable disease received TKI and five had a response on serial CT. EGFR exon 19 insertions are a newly appreciated family of EGFR-TKI-sensitizing mutations, and patients with tumors harboring these mutations should be treated with EGFR-TKI. While these mutations may be missed through the use of some mutation-specific assays, the addition of PCR product size analysis to multigene assays allows sensitive detection of both exon 19 insertion and deletion mutations.


Economics and the evaluation of health care programmes: generalisability of methods and implications for generalisability of results.
Increasing attention is being given to identifying standardised methods of analysis for the economic evaluation of health care programmes and generating generalisable findings from these methods. In this paper, we show how these approaches fail to reflect the social science foundations of the economics discipline and the economic theory of individual behaviour. Using simple examples, we show that the technical efficiency of a particular programme differs between communities, even though the underlying technology is the same for the communities. Similarly, the subjective considerations represented by the utility function are not generally transferable between settings or between individuals within settings. As a result, the efficiency of an intervention will be influenced by the context in which the intervention is experienced, even in the presence of identical production and utility functions. The lack of generalisability includes the validity of the methods used to analyse the subjective component of the evaluation exercise. The adoption of standardised methods of measurement and analysis, together with the use of findings from the application of these methods in other settings, might ease the administrative burden presented in resource allocation exercises. However, these approaches do not accommodate the intellectual substance of the wide range of problems and circumstances that underlie these exercises.


Detecting methylation quantitative trait loci using a methylation random field method.
DNA methylation may be regulated by genetic variants within a genomic region, referred to as methylation quantitative trait loci (mQTLs). The changes of methylation levels can further lead to alterations of gene expression, and influence the risk of various complex human diseases. Detecting mQTLs may provide insights into the underlying mechanism of how genotypic variations may influence the disease risk. In this article, we propose a methylation random field (MRF) method to detect mQTLs by testing the association between the methylation level of a CpG site and a set of genetic variants within a genomic region. The proposed MRF has two major advantages over existing approaches. First, it uses a beta distribution to characterize the bimodal and interval properties of the methylation trait at a CpG site. Second, it considers multiple common and rare genetic variants within a genomic region to identify mQTLs. Through simulations, we demonstrated that the MRF had improved power over other existing methods in detecting rare variants of relatively large effect, especially when the sample size is small. We further applied our method to a study of congenital heart defects with 83 cardiac tissue samples and identified two mQTL regions, MRPS10 and PSORS1C1, which were colocalized with expression QTL in cardiac tissue. In conclusion, the proposed MRF is a useful tool to identify novel mQTLs, especially for studies with limited sample sizes.


Intrinsic halotolerance of the psychrophilic alpha-amylase from Pseudoalteromonas haloplanktis.
The halotolerance of a cold adapted alpha-amylase from the psychrophilic bacterium Pseudoalteromonas haloplanktis (AHA) was investigated. AHA exhibited hydrolytic activity over a broad range of NaCl concentrations (0.01-4.5 M). AHA showed 28% increased activity in 0.5-2.0 M NaCl compared to that in 0.01 M NaCl. In contrast, the corresponding mesophilic (Bacillus amyloliquefaciens) and thermostable (B. licheniformis) alpha-amylases showed a 39 and 46% decrease in activity respectively. Even at 4.5 M NaCl, 80% of the initial activity was detected for AHA, whereas the mesophilic and thermostable enzymes were inactive. Besides an unaltered fluorescence emission and secondary structure, a 10 degrees C positive shift in the temperature optimum, a stabilization factor of >5 for thermal inactivation and a Delta T(m) of 8.3 degrees C for the secondary structure melting were estimated in 2.7 M NaCl. The higher activation energy, half-life time and T(m) indicated reduced conformational dynamics and increased rigidity in the presence of higher NaCl concentrations. A comparison with the sequences of other halophilic alpha-amylases revealed that AHA also contains higher proportion of small hydrophobic residues and acidic residues resulting in a higher negative surface potential. Thus, with some compromise in cold activity, psychrophilic adaptation has also manifested halotolerance to AHA that is comparable to the halophilic enzymes.


Toxicogenomics profiling of bone marrow from rats treated with topotecan in combination with oxaliplatin: a mechanistic strategy to inform combination toxicity.
Combinations of anticancer agents may have synergistic anti-tumor effects, but enhanced hematological toxicity often limit their clinical use. We examined whether "microarray profiles" could be used to compare early molecular responses following a single dose of agents administered individually with that of the agents administered in a combination. We compared the mRNA responses within bone marrow of Sprague-Dawley rats after a single 30 min treatment with topotecan at 4.7 mg/kg or oxaliplatin at 15 mg/kg alone to that of sequentially administered combination therapy or vehicle control for 1, 6, and 24 h. We also examined the histopathology of the bone marrow following all treatments. Drug-related histopathological lesions were limited to bone marrow hypocellularity for animals dosed with either agent alone or in combination. Lesions had an earlier onset and higher incidence for animals given topotecan alone or in combination with oxaliplatin. Severity increased from mild to moderate when topotecan was administered prior to oxaliplatin compared with administering oxaliplatin first. Notably, six patterns of co-expressed genes were detected at the 1 h time point that indicate regulatory expression of genes that are dependent on the order of the administration. These results suggest alterations in histone biology, chromatin remodeling, DNA repair, bone regeneration, and respiratory and oxidative phosphorylation are among the prominent pathways modulated in bone marrow from animals treated with an oxaliplatin/topotecan combination. These data also demonstrate the potential for early mRNA patterns derived from target organs of toxicity to inform toxicological risk and molecular mechanisms for agents given in combination.


A response to euthanasia initiatives.
The outcome of the physician-assisted suicide and euthanasia debate will profoundly influence physicians' role in society, the kind of society we become, and the way physicians and patients relate to one another. Three forces account for the move to physician-assisted suicide and euthanasia: an abuse of scientific advancement, a new political philosophy, and the erosion of religious consensus. The relationship between patients and physicians has often been understood as a convenant with rights on patients' part and duties on physicians' part. Physicians' duties in this covenantal relationship are to act for patients' good (a positive duty) and to do no harm (a negative duty). Euthanasia and assisted suicide are morally wrong because, as the Judeo-Christian ethic teaches, human beings are creatures of God and have only stewardship, not dominion, over life. But in our pluralistic society, which seems to lack consensus on religion, on communal responsibility, and on common values, one cannot argue against mercy killing and assisted suicide on theological grounds. Our society generally agrees, however, that a discussion of values may take place in the language of moral philosophy, a language that expresses right reason.


Comparing spondylolysis in cricketers and soccer players.
To determine whether the location of spondylolysis in the lumbar spine of athletes differs with biomechanical factors. Single photon emission computerised tomography and reverse gantry computerised tomography were used to investigate 42 cricketers and 28 soccer players with activity related low back pain. Sites of increased scintigraphic uptake in the posterior elements of the lumbar spine and complete or incomplete fracture in the pars interarticularis were compared for these two sports. Thirty seven (90.4%) cricketers and 23 (82.1%) soccer players studied had sites of increased uptake. In cricketers, these sites were on the left of the neural arch of 49 lumbar vertebrae and on the right of 33 vertebrae. In soccer players there was a significantly different proportion, with 17 sites on the left and 28 on the right (difference of 22.0%; 95% confidence interval (CI) 0.04 to 0.38). Lower lumbar levels showed increased scintigraphic uptake more frequently than did higher levels, although the trend was reversed at L3 and L4 in soccer. Forty spondylolyses were identified in the lumbar vertebrae of the cricketers and 35 spondylolyses in the soccer players. These comprised 26 complete and 14 incomplete fractures in the cricketers, and 25 complete and 10 incomplete fractures in the soccer players. Similar numbers of incomplete fractures were found either side of the neural arch in soccer players, but there were more incomplete fractures in the left pars (14) than in the right (2) in cricketers. The proportion of incomplete fractures either side of the neural arch was significantly different between cricket players and soccer players (difference of 37.5%; 95% CI 0.02 to 0.65). Most complete fractures were at L5 (66.7%) and more were found at L3 (15.7%) than L4 (6.9%). However, incomplete fractures were more evenly spread though the lower three lumbar levels with 41.7% at L5, 37.5% at L4, and 20.8% at L3. Fast bowling in cricket is associated with pars interarticularis bone stress response and with development of incomplete stress fractures that occur more frequently on the left than the right. Playing soccer is associated with a more symmetrical distribution of bone stress response, including stress fracturing. Within cricketers, unilateral spondylolyses tend to arise on the contralateral side to the bowling arm.


Developing an artificial intelligence diagnostic tool for paediatric distal radius fractures, a proof of concept study.
In the UK, 1 in 50 children sustain a fractured bone yearly, yet studies have shown that 34% of children sustaining an injury do not have a visible fracture on initial radiographs. Wrist fractures are particularly difficult to identify because the growth plate poses diagnostic challenges when interpreting radiographs. We developed Convolutional Neural Network (CNN) image recognition software to detect fractures in radiographs from children. A consecutive data set of 5,000 radiographs of the distal radius in children aged less than 19 years from 2014 to 2019 was used to train the CNN. In addition, transfer learning from a VGG16 CNN pretrained on non-radiological images was applied to improve generalisation of the network and the classification of radiographs. Hyperparameter tuning techniques were used to compare the model with the radiology reports that accompanied the original images to determine diagnostic test accuracy. The training set consisted of 2,881 radiographs with a fracture and 1,571 without; 548 radiographs were outliers. With additional augmentation, the final data set consisted of 15,498 images. The data set was randomly split into three subsets: training (70%), validation (10%) and test (20%). After training for 20 epochs, the diagnostic test accuracy was 85%. A CNN model is feasible in diagnosing paediatric wrist fractures. We demonstrated that this application could be utilised as a tool for improving diagnostic accuracy. Future work would involve developing automated treatment pathways for diagnosis, reducing unnecessary hospital visits and allowing staff redeployment to other areas.


Hot spots of bleaching in massive Porites coral colonies.
Coral bleaching events have become more frequent and severe due to ocean warming. While the large-scale impacts of bleaching events are well-known, there is growing recognition of the importance of small-scale spatial variation in bleaching and survival probability of individual coral colonies. By quantifying bleaching in 108 massive Porites colonies spread across Lizard Island, Great Barrier Reef, during the 2016 bleaching event, we investigated how hydrodynamic exposure levels and colony size contribute to local variability in bleaching prevalence and extent. Our results revealed that exposed locations were the least impacted by bleaching, while lagoonal areas exhibited the highest prevalence of bleaching and colony-level bleaching extents. Such patterns of bleaching could be due to prolonged exposure to warm water in the lagoon. These findings highlight the importance of considering location-specific factors when assessing coral health and emphasize the vulnerability of corals in lagoonal habitats to rapid and/or prolonged elevated temperatures.


Boosting quantification accuracy of chemical exchange saturation transfer MRI with a spatial-spectral redundancy-based denoising method.
Chemical exchange saturation transfer (CEST) is a versatile technique that enables noninvasive detections of endogenous metabolites present in low concentrations in living tissue. However, CEST imaging suffers from an inherently low signal-to-noise ratio (SNR) due to the decreased water signal caused by the transfer of saturated spins. This limitation challenges the accuracy and reliability of quantification in CEST imaging. In this study, a novel spatial-spectral denoising method, called BOOST (suBspace denoising with nOnlocal lOw-rank constraint and Spectral local-smooThness regularization), was proposed to enhance the SNR of CEST images and boost quantification accuracy. More precisely, our method initially decomposes the noisy CEST images into a low-dimensional subspace by leveraging the global spectral low-rank prior. Subsequently, a spatial nonlocal self-similarity prior is applied to the subspace-based images. Simultaneously, the spectral local-smoothness property of Z-spectra is incorporated by imposing a weighted spectral total variation constraint. The efficiency and robustness of BOOST were validated in various scenarios, including numerical simulations and preclinical and clinical conditions, spanning magnetic field strengths from 3.0 to 11.7 T. The results demonstrated that BOOST outperforms state-of-the-art algorithms in terms of noise elimination. As a cost-effective and widely available post-processing method, BOOST can be easily integrated into existing CEST protocols, consequently promoting accuracy and reliability in detecting subtle CEST effects.


Chronic hepatitis in patients with hemophilia A: histologic studies in patients with intermittently abnormal liver function tests.
Recent studies in multiply transfused patients with hemophilia A and persistent liver function abnormalities have shown a high incidence of chronic active hepatitis. The purpose of the present study was to determine the severity of liver disease in multiply transfused patients with intermittent liver enzyme abnormalities. Fifteen patients with elevated enzymes on two or three out of four determinations at 6-mo intervals were studied. None had signs or symptoms of chronic liver disease. Thirteen had serologic evidence of prior exposure to the hepatitis B virus. Liver biopsy performed on these patients after replacement therapy with factor VIII showed chronic persistent hepatitis or other mild forms of liver disease in 14 of the 15 patients. Patients with chronic persistent hepatitis had significantly higher mean liver enzymes at time of biopsy than patients with milder forms of hepatic inflammation, but there was no relationship between liver histology and hepatitis B serology or the amount of factor VIII used in the 6 mo preceding biopsy. These findings support the continued use of factor VIII concentrates in patients with hemophilia.


Simple acyclic molecules containing a single charge-assisted O-H group can recognize anions in acetonitrile : water mixtures.
Hydroxypyridinium and hydroxyquinolinium compounds containing acidic O-H groups attached to a cationic aromatic scaffold were synthesized, i.e. N-methyl-3-hydroxypyridinium (1+) and N-methyl-8-hydroxyquinolinium (2+). These very simple compounds are capable of binding to chloride very strongly in CD3CN and with moderate strength in 9 : 1 CD3CN : D2O. Comparison with known association constants reveals that 1+ and 2+ bind chloride in CD3CN or CD3CN : D2O with comparable affinities to receptors containing significantly more hydrogen bond donors and/or higher positive charges. Crystal structures of both compounds with coordinating anions were obtained, and feature short O-Hanion hydrogen bonds. A receptor containing two hydroxyquinolinium groups was also prepared. While the low solubility of this compound caused difficulties, we were able to demonstrate chloride binding in a competitive 1 : 1 CD3CN : CD3OD solvent mixture. Addition of sulfate to this compound results in the formation of a crystallographically-characterised solid state anion coordination polymer.


Children of the Sun: a historical look at how pediatric light therapy shaped attitudes and behaviors toward sunbathing.
Today, parents are warned to protect their children from the sun's ultraviolet (UV) rays, the most preventable and leading cause of skin cancer. Yet, during the first half of the 20th century, the medical community widely extolled the health benefits of daily sunbaths for babies and children. What initially had begun as evidence-based medical therapies to prevent pediatric diseases, specifically tuberculosis and rickets, soon took on a life of its own as physicians, public health experts, and the general public embraced sunbathing and tanning as a means to ensure health and wellbeing for children and families. Here, we trace how specific medical therapies entered mainstream pediatric medicine and, converging with societal and cultural forces, shaped attitudes and behaviors towards sunbathing that still exist today. Understanding our complex history with the sun may shed light on the current peak of skin cancer incidence and future disease development. Moreover, it may help improve how we educate parents and children about sun safety by taking into account the current social and cultural context of medical practice and health communication.


Sand fly species of Sanliurfa province in Turkey.
The species composition and seasonal abundance of sand flies (Diptera: Phlebotominae) were studied in the years 2000-2002 in the Sanliurfa region, which is the largest focus of cutaneous leishmaniasis in south-eastern Turkey. Sixteen species were identified among 29 771 specimens collected at 17 different sites by light traps, sticky papers and aspirators. The most common species were Phlebotomus papatasi (Scopoli) (45.4%), P. perfiliewi Parrot (21.9%), and P. sergenti Parrot (19.4%). The other species found were P. major Adler & Theodor (3%), P. neglectus Leger & Pesson (2.2%), P. brevis Theodor & Mesghali (2%), P. alexandri Sinton (1.9%), P. galilaeus Theodor (1.6%), P. halepensis Theodor (0.84%), Sergentomyia adleri Theodor (0.78%), S. dentata Sinton (0.49%), S. minuta Rondani (0.42%), S. theodori Parrot (0.16%), P. kazeruni Theodor & Mesghali (0.001%) and P. mascitti Grassi (0.001%) and one unidentified Phlebotomus species. Among these species P. galilaeus, S. minuta and S. dentata are the first records for this area. All species showed seasonal fluctuations, with the period of highest abundance between May and October.


The janus facet of nanomaterials.
Application of nanoscale materials (NMs) displays a rapidly increasing trend in electronics, optics, chemical catalysis, biotechnology, and medicine due to versatile nature of NMs and easily adjustable physical, physicochemical, and chemical properties. However, the increasing abundance of NMs also poses significant new and emerging health and environmental risks. Despite growing efforts, understanding toxicity of NMs does not seem to cope with the demand, because NMs usually act entirely different from those of conventional small molecule drugs. Currently, large-scale application of available safety assessment protocols, as well as their furthering through case-by-case practice, is advisable. We define a standard work-scheme for nanotoxicity evaluation of NMs, comprising thorough characterization of structural, physical, physicochemical, and chemical traits, followed by measuring biodistribution in live tissue and blood combined with investigation of organ-specific effects especially regarding the function of the brain and the liver. We propose a range of biochemical, cellular, and immunological processes to be explored in order to provide information on the early effects of NMs on some basic physiological functions and chemical defense mechanisms. Together, these contributions give an overview with important implications for the understanding of many aspects of nanotoxicity.


Job satisfaction among dental hygienists.
This paper presents definitions of job satisfaction from organizational theory, and a review of the dental hygiene literature on job satisfaction. Most studies of dental hygienists have used one or two global measures of satisfaction. Very few studies have used dimensional measures of satisfaction; and those that have, have not used identical measures. The studies--which measured satisfaction in a variety of ways and quantified dental hygienists' satisfaction in terms of percent satisfied--established that between 70% and 99% of dental hygienists are satisfied with their jobs.


Tumor necrosis factor-alpha inhibits seizures in mice via p75 receptors.
Brain inflammatory reactions have been described in various neurological disorders, including epilepsy. Although there is clear evidence that cytokines affect neuroglial functions and blood-brain barrier permeability, scarce information is available on the functional consequences of brain inflammation on seizures. We studied the role of tumor necrosis factor-alpha (TNF)-alpha and its p55 and p75 receptors in seizure modulation. We found that intrahippocampal injection of murine recombinant TNF-alpha potently inhibits seizure in mice while human recombinant TNF-alpha, which shows strong specificity for mouse p55 receptors, was ineffective. p75 receptors were detected in mouse hippocampal neurons, whereas p55 receptors were absent. Transgenic mice with a perturbed TNF-alpha system showed profound alterations in seizure susceptibility: astrocytic overexpression of TNF-alpha was associated with reduced seizures, whereas mice lacking TNF-alpha p75 or both p55 and p75, receptors showed prolonged seizures. Mice deficient in p55 receptor only showed reduced seizures; and both p75 and TNF receptor-associated factor 2 protein levels were upregulated in their hippocampi. Our findings show that increased brain levels of TNF-alpha result in significant inhibition of seizures in mice, and this action is mediated by neuronal p75 receptors. This evidence highlights a novel function of TNF-alpha in brain and indicates a new system for anticonvulsive intervention.


Osteopontin modulates microglial activation states and attenuates inflammatory responses after subarachnoid hemorrhage in rats.
Osteopontin (OPN) has demonstrated neuroprotective effects in various stroke models. Its role in neuroinflammation after brain injury remains to be elucidated. This study aims to clarify the effect of OPN on neuroinflammation, particularly on the functional states of microglia after subarachnoid hemorrhage (SAH). 77 rats were randomly divided into the following groups: Sham, SAH 24 h, SAH + rOPN, SAH + Vehicle (PBS), SAH + OPN siRNA, and SAH + Scr siRNA, SAH + rOPN+Fib-14 and SAH + rOPN+DMSO. Modified Garcia and beam balance tests were used to evaluate neurobehavioral outcomes. Semi-quantitative immunofluorescence staining was performed to measure expression of myeloperoxidase (MPO) and microglia activation state markers CD16, CD206 after SAH and recombinant OPN treatment. The quantification of microglia activation and functional markers CD16, CD206, TNF-α and IL-10 were further evaluated using Western-blotting. Nasal administration of rOPN improved neurological dysfunction, attenuated neutrophil infiltration, and decreased expression of phenotypic and functional markers of pro-inflammatory microglia CD16 and TNF-α. It also promoted an anti-inflammatory microglial state, as evidenced by increased expression of CD206 and IL-10. Furthermore, after blocking the phosphorylation of FAK signaling, the effects of rOPN on microglial activation states were partially reversed. The downstream pathways of STAT3 and NF-κB also exhibited consistent changes, suggesting the involvement of the STAT3 and NF-κB pathways in OPN's modulation of microglial activation via integrin-FAK signaling. OPN attenuates inflammatory responses after SAH by promoting an anti-inflammatory microglial state, potentially mediated through the integrin-FAK-STAT3 and NF-κB signaling pathways.


Thermodynamics of stacking interactions in proteins.
Using a database of 6166 experimental structures taken from the Protein Data Bank, we have studied pair interactions between planar residues (Phe, Tyr, His, Arg, Glu and Asp) in proteins, known as pi-pi interactions. On the basis of appropriate coordinates defining the mutual arrangement of two residues, we have calculated 2-D potentials of mean force aimed at determining the stability of the most probable structures for aromatic-aromatic, aromatic-cation and aromatic-anion bound pairs. Our analysis reveals the thermodynamic relevance and the ubiquity of stacked complexes in proteins.


Topical erythritol combined with L-ascorbyl-2-phosphate inhibits staphylococcal growth and alleviates staphylococcal overgrowth in skin lesions of canine superficial pyoderma.
Erythritol (ERT) and L-ascorbyl-2-phosphate (APS) are bacteriostatic, but their effects on staphylococcal skin infections remain unknown. We aimed to determine whether ERT combined with APS inhibits the growth of staphylococci that are commonly isolated from pyoderma skin lesions in dogs. We investigated the individual and combined effects of ERT and APS on the growth of Staphylococcus pseudintermedius, S. schleiferi, and S. aureus using turbidity assays in vitro. Skin lesions from 10 dogs with superficial pyoderma were topically treated with 5% ERT and 0.1% APS for 28 days, and swabbed skin samples were then analyzed using 16S rRNA amplicon sequencing and quantitative real-time PCR (qPCR). Results showed that ERT inhibited S. pseudintermedius growth regardless of harboring the mecA gene, and APS increased the inhibitory effects of ERT against S. pseudintermedius, S. schleiferi, and S. aureus in vitro. Moreover, combined ERT and APS decreased the prevalence of staphylococci on canine skin lesions at the genus level. The combination slightly increased the α-diversity but did not affect the β-diversity of the microbiota. The qPCR results revealed that the combination significantly decreased S. pseudintermedius and S. schleiferi in skin lesions. Topical administration of EPS combined with APS can prevent staphylococcal colonization on the surface of mammalian skin. The results of this study may provide an alternative to systemic antibiotics for treating superficial pyoderma on mammalian skin surfaces.


Gremlin-mediated decrease in bone morphogenetic protein signaling promotes pulmonary fibrosis.
Members of the transforming growth factor (TGF)-beta superfamily, including TGF-betas and bone morphogenetic proteins (BMPs), are essential for the maintenance of tissue homeostasis and regeneration after injury. We have observed that the BMP antagonist, gremlin, is highly up-regulated in idiopathic pulmonary fibrosis (IPF). To investigate the role of gremlin in the regulation of BMP signaling in pulmonary fibrosis. Progressive asbestos-induced fibrosis in the mouse was used as a model of human IPF. TGF-beta and BMP expression and signaling activities were measured from murine and human fibrotic lungs. The mechanism of gremlin induction was analyzed in cultured lung epithelial cells. In addition, the possible therapeutic role of gremlin inhibition was tested by administration of BMP-7 to mice after asbestos exposure. Gremlin mRNA levels were up-regulated in the asbestos-exposed mouse lungs, which is in agreement with the human IPF biopsy data. Down-regulation of BMP signaling was demonstrated by reduced levels of Smad1/5/8 and enhanced Smad2 phosphorylation in asbestos-treated lungs. Accordingly, analyses of cultured human bronchial epithelial cells indicated that asbestos-induced gremlin expression could be prevented by inhibitors of the TGF-beta receptor and also by inhibitors of the mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase pathways. BMP-7 treatment significantly reduced hydroxyproline contents in the asbestos-treated mice. The TGF-beta and BMP signaling balance is important for lung regenerative events and is significantly perturbed in pulmonary fibrosis. Rescue of BMP signaling activity may represent a potential beneficial strategy for treating human pulmonary fibrosis.


Meat consumption patterns and preparation, genetic variants of metabolic enzymes, and their association with rectal cancer in men and women.
Meat consumption, particularly of red and processed meat, is one of the most thoroughly studied dietary factors in relation to colon cancer. However, it is not clear whether meat, red meat, heterocyclic amines (HCA), or polycyclic aromatic hydrocarbons (PAH) are associated with the risk for rectal cancer. Rectal cancer cases (n = 952) and controls (n = 1205) from Utah and Northern California were recruited from a population-based case-control study between September 1997 and February 2002. Detailed in-person interviews regarding lifestyle, medical history, and diet were conducted. DNA was extracted from peripheral lymphocytes obtained from whole-blood samples, and glutathione S-transferase (GST)M1 enzyme and N-acetyl transferase (NAT)2 enzyme genotypes were assessed. Although energy and cholesterol intakes were higher among cases than controls, adjustment for confounders accounted for the differences. Increased consumption of well-done red meat [odds ratio (OR) 1.33 95% CI 0.98, 1.79] was associated with an (P = 0.04) increase in risk for rectal cancer among men. The mutagen index, calculated on the bases of reported amount, doneness, and method of cooking meat, was also positively but not significantly (P = 0.24) associated with risk of rectal cancer for men (OR 1.37 95% CI 0.98, 1.92). NAT2-imputed phenotype and GSTM1 did not consistently modify rectal cancer risk associated with meat intake. These data suggest that mutagens such as HCA that form when meat is cooked may be culpable substances in rectal cancer risk, not red meat itself.


Engineered expression of the TLR5 ligand flagellin enhances paramyxovirus activation of human dendritic cell function.
The paramyxovirus simian virus 5 (SV5) is a poor activator of human dendritic cell (DC) maturation pathways in vitro, and infected DC do not upregulate cell surface costimulatory proteins or secretion of immunomodulatory cytokines. We evaluated the hypothesis that activation of SV5-infected DC would be enhanced by engineering SV5 to express a Toll-like-receptor (TLR) ligand. To test this hypothesis, a novel virus was engineered such that the gene encoding an intracellular form of the TLR5 ligand flagellin was expressed from the genome of wild-type (WT) SV5 (SV5-flagellin). Cells infected in vitro with the flagellin-expressing virus released low levels of biologically active flagellin, which was capable of stimulating TLR5 signaling. Infection of human peripheral blood mononuclear cell-derived immature DC with SV5-flagellin resulted in enhanced levels of interleukin-6 (IL-6) and IL-12 compared to infection with DC with the parental virus, WT SV5. In contrast to cytokine induction, the flagellin-expressing virus did not appreciably increase DC surface expression of the costimulatory molecule CD80 or CD86 above the level seen with WT SV5 alone. In mixed-culture assays, DC infected with the flagellin-expressing virus were more effective at activating gamma interferon secretion from both CD8(+) and CD4(+) allogeneic T cells than DC infected with WT SV5. Our results with SV5-directed intracellular expression of flagellin may be applicable to other vectors or pathogenic viruses where overcoming impairment of DC activation could contribute to the development of safer and more effective vaccines.


Integrative "omics"-approach discovers dynamic and regulatory features of bacterial stress responses.
Bacteria constantly face stress conditions and therefore mount specific responses to ensure adaptation and survival. Stress responses were believed to be predominantly regulated at the transcriptional level. In the phototrophic bacterium Rhodobacter sphaeroides the response to singlet oxygen is initiated by alternative sigma factors. Further adaptive mechanisms include post-transcriptional and post-translational events, which have to be considered to gain a deeper understanding of how sophisticated regulation networks operate. To address this issue, we integrated three layers of regulation: (1) total mRNA levels at different time-points revealed dynamics of the transcriptome, (2) mRNAs in polysome fractions reported on translational regulation (translatome), and (3) SILAC-based mass spectrometry was used to quantify protein abundances (proteome). The singlet oxygen stress response exhibited highly dynamic features regarding short-term effects and late adaptation, which could in part be assigned to the sigma factors RpoE and RpoH2 generating distinct expression kinetics of corresponding regulons. The occurrence of polar expression patterns of genes within stress-inducible operons pointed to an alternative of dynamic fine-tuning upon stress. In addition to transcriptional activation, we observed significant induction of genes at the post-transcriptional level (translatome), which identified new putative regulators and assigned genes of quorum sensing to the singlet oxygen stress response. Intriguingly, the SILAC approach explored the stress-dependent decline of photosynthetic proteins, but also identified 19 new open reading frames, which were partly validated by RNA-seq. We propose that comparative approaches as presented here will help to create multi-layered expression maps on the system level ("expressome"). Finally, intense mass spectrometry combined with RNA-seq might be the future tool of choice to re-annotate genomes in various organisms and will help to understand how they adapt to alternating conditions.


Individual, psychosocial, and social correlates of unprotected anal intercourse in a new generation of young men who have sex with men in New York City.
We examined associations of individual, psychosocial, and social factors with unprotected anal intercourse (UAI) among young men who have sex with men in New York City. Using baseline assessment data from 592 young men who have sex with men participating in an ongoing prospective cohort study, we conducted multivariable logistic regression analyses to examine the associations between covariates and likelihood of recently engaging in UAI with same-sex partners. Nineteen percent reported recent UAI with a same-sex partner. In multivariable models, being in a current relationship with another man (adjusted odds ratio [AOR] = 4.87), an arrest history (AOR = 2.01), greater residential instability (AOR = 1.75), and unstable housing or homelessness (AOR = 3.10) was associated with recent UAI. Although high levels of gay community affinity and low internalized homophobia were associated with engaging in UAI in bivariate analyses, these associations did not persist in multivariable analyses. Associations of psychosocial and socially produced conditions with UAI among a new generation of young men who have sex with men warrant that HIV prevention programs and policies address structural factors that predispose sexual risk behaviors.


TMD warning sign: cephalometrics.
The significance of predisposing factors to TMD is quite evident when considering the prevalence of orthodontic relapse and with the occurrence of TMD related symptoms observed in previously treated orthodontic patients. In using the Modified Sassouni Plus Cephalometric Analysis, the clinician now possesses an invaluable tool that is readily available without adding to the examination expense. The invaluable information gained from cephalometric evaluation should not, however, be used to replace other diagnostic TMJ radiographs. If a joint problem is suspected, one should follow the normal protocol for the examination of the temporomandibular joints.


Identification of the vibrational modes in the far-infrared spectra of ruthenium carbonyl clusters and the effect of gold substitution.
High-quality far-IR absorption spectra for a series of ligated atomically precise clusters containing Ru3, Ru4, and AuRu3 metal cores have been observed using synchrotron radiation, the latter two for the first time. The experimental spectra are compared with predicted IR spectra obtained following complete geometric optimization of the full cluster, including all ligands, using DFT. We find strong correlations between the experimental and predicted transitions for the low-frequency, low-intensity metal core vibrations as well as the higher frequency and intensity metal-ligand vibrations. The metal core vibrational bands appear at 150 cm(-1) for Ru3(CO)12, and 153 and 170 cm(-1) for H4Ru4(CO)12, while for the bimetallic Ru3(μ-AuPPh3)(μ-Cl)(CO)10 cluster these are shifted to 177 and 299 cm(-1) as a result of significant restructuring of the metal core and changes in chemical composition. The computationally predicted IR spectra also reveal the expected atomic motions giving rise to the intense peaks of metal-ligand vibrations at ca. 590 cm(-1) for Ru3, 580 cm(-1) for Ru4, and 560 cm(-1) for AuRu3. The obtained correlations allow an unambiguous identification of the key vibrational modes in the experimental far-IR spectra of these clusters for the first time.


Circumferential Fence With the Use of Polyethylene Terephthalate (Dacron) Vascular Graft for All-in-One Hepatic Venous Reconstruction in Right-Lobe Living-Donor Liver Transplantation.
Integration of hepatic vein tributaries with a diameter ≥ 5 mm into the drainage system in right-lobe living-donor liver transplantation (LDLT) is of vital importance for graft function. Recently, the most commonly emphasized hepatic venous reconstruction model is the all-in-one reconstruction model. In the final stage of this model that aims to form a common large opening, allogeneic vascular grafts are almost always used to construct a circumferential fence. To date, no other study has reported the use of polyethylene terephthalate (Dacron) vascular graft as a circumferential fence in LDLT. We aimed to present the 1st 4 cases of circumferential fences created with Dacron vascular graft. Four right-lobe grafts weighing 522-1,040 g were used. A polytetrafluoroethylene vascular graft was used for the integration of segment 5 vein and segment 8 vein into the drainage model, whereas a Dacron graft was used to creating a circumferential fence. The patency of hepatic outflow evaluated with the use of multidetector computerized tomography at postoperative day 7. Venous outflow obstruction was not detected in any cases. This study suggested that owing to its flexible structure the polyethylene terephthalate vascular graft can be an alternative to allogeneic vascular grafts in forming circumferential fence.


[Effect of aminazine, caffeine and the intensity of mental stress on psychophysiological functions and work effectiveness of humans].
The effect of CNS activation and mental load on human organism depends on the operator's working routine and is, to a great extent, connected with broad individual peculiarities of the tested subjects. The CNS activation increase is conducive to a favourable effect of activities under low mental loads and it also intensifies the appearance of erroneous actions under medium and high loads. The CNS activation decrease does not reduce the capacity to detect significant signals but tells on the speed and correctness of decision making. The application of the variance analysis while experimentally studying the combined effect of the CNS activation and mental load gives sufficient information on the effect of the CNS activation, load intensity and duration and the interaction thereof which can attain considerable values.


Evaluating the Validity and Reliability of the Gender Equitable Men's Scale Using a Longitudinal Cohort of Adolescent Girls and Young Women in South Africa.
Inequitable gender norms and beliefs contribute to increased sexual risk behavior, and, among adolescent girls and young women (AGYW), risk of HIV acquisition. We investigated the longitudinal measurement properties of the Gender Equitable Men's Scale (GEMS) when applied to a cohort of AGYW in rural South Africa (2011-2015). We used item response theory [Person-Item maps, Differential Item Functioning (DIF)] and measurement invariance confirmatory factor analysis models to assess the validity and reliability of the GEMS instrument. Item difficulty and endorsement of gender equitable beliefs both shifted over time. DIF analysis identified item bias for over half of the items; influenced by age, pregnancy, sexual debut, and intimate partner violence. Measurement invariance models revealed strong longitudinal invariance properties. GEMS is a reliable longitudinal measurement of gender equitable beliefs, with notable bias for specific items when administered to subgroups. Additional items specific to the adolescent experience are warranted for a more stable assessment of gender equitable beliefs in a population facing shifting norms as they mature.