Clinical features, myocardial strain and tissue characteristics of heart failure with preserved ejection fraction in patients with obesity: A prospective cohort study.
The pathophysiology and subsequent myocardial dysfunction of heart failure with preserved ejection fraction (HFpEF) with comorbid obesity has not been extensively described. This study aimed to investigate the clinical features and cardiovascular magnetic resonance (CMR) derived myocardial strain and tissue characteristics in patients with HFpEF and comorbid obesity phenotype. In this prospective cohort study, we included consecutive patients admitted to Fuwai hospital in China who underwent CMR. Patients with HFpEF or obesity were diagnosed with demographic data, clinical presentation, laboratory test, and echocardiography or CMR imaging. The key exclusion criteria were cardiomyopathy, primary valvular heart disease, and significant coronary artery disease. Participant data were obtained from the electronic medical records database or inquiry. Comparisons of clinical features and CMR derived structural and functional parameters amongst different groups were made using one-way analysis of variance, or χ2 tests, and post hoc Bonferroni analysis where appropriate. Between January 1, 2019 and July 31, 2021, 280 participants (108 patients with HFpEF and obesity, 50 patients with HFpEF and normal weight, 72 patients with obesity, and 50 healthy controls) were enrolled. Compared with patients with HFpEF and normal weight, patients with HFpEF and obesity were younger males, and had higher plasma volume, uric acid and hemoglobin levels, yet less often atrial fibrillation, and lower NT-proBNP levels, and had higher left ventricular mass index, end-diastole/systole volume index, lower left atrial volume index, and worse myocardial strains (all p ≤ 0.05), but no remarkable difference in late gadolinium enhancement (LGE) presence and extracellular volume fraction (ECV). After adjusting for age, atrial fibrillation, and coronary artery disease, only global longitudinal strain (GLS, p = 0.031) and early-diastolic global longitudinal strain rate (eGLSR, p = 0.043) were considerably worse in patients with HFpEF and obesity versus patients with HFpEF and normal weight. Furthermore, early-diastolic strain rates showed no linear association with ECV in patients with HFpEF and obesity. Moreover, GLS demonstrated the highest diagnostic ability when compared with traditional CMR structural parameters and ECV to diagnose patients with HFpEF and obesity in the setting of obesity. Higher systemic inflammation, and worse GLS and eGLSR may be the distinct features of obesity-related HFpEF phenotype; strains and ECV may represent different mechanisms of HFpEF with obesity, deserving further study. The Construction Research Project of Key Laboratory (Cultivation) of Chinese Academy of Medical Sciences (2019PT310025); National Natural Science Foundation of China (81971588); Capital's Funds for Health Improvement and Research (CFH 2020-2-4034); Youth Key Program of High-level Hospital Clinical Research (2022-GSP-QZ-5).


A qualitative evaluation of capnography use in paediatric sedation: perceptions, practice and barriers.
We explored perceptions about capnography for procedural sedation and barriers to use in a paediatric emergency department. Capnography is a sensitive monitor of ventilation and is increasingly being studied in procedural sedation. While benefits have been found, it has not gained wide acceptance for monitoring of children during sedation. A qualitative exploratory study was performed. Using a grounded theory approach, physicians and nurses from the paediatric emergency department participated in one-on-one interviews about their experiences with and opinions of capnography. An iterative process of data collection and analysis was used to inductively generate theories and themes until theoretical saturation was achieved. Five physicians and 12 nurses were interviewed. Themes included: Experiences: Participants felt that procedural sedation is safe and adverse events are rare. Normal capnography readings reassured providers about the adequacy of ventilation. Knowledge: Despite experience with capnography, knowledge and comfort varied. Most participants requested additional education and training. Diffusion of Use: While participants expressed positive opinions about capnography, use for sedation was infrequent. Many participants felt that capnography use increased in other paediatric populations, such as patients with altered mental status, ingestions or head trauma. Barriers: Identified barriers to use included a lack of comfort with or knowledge about equipment, lack of availability of the monitor and cannulas, lack of inclusion of these supplies on a checklist for procedural sedation preparedness, and lack of a policy for use of capnography during sedation. Capnography use during sedation in the paediatric emergency department is limited despite positive experiences and opinions about this device. Addressing modifiable barriers such as instrument availability, continuing education, and inclusion on a checklist may increase use of capnography during sedation. Despite the perceived benefits, a broad implementation plan is required to introduce capnography successfully to the paediatric emergency department.


Seizure susceptibility in prenatally methamphetamine-exposed adult female rats.
The purpose of the present study was to examine the effect of prenatal methamphetamine (MA) exposure on seizures induced by bicuculline and N-methyl-d-aspartate in adult female rats. The present results show that prenatal MA exposure alters seizures in a model-specific manner and that the seizure susceptibility of adult female rats may be affected by the stage of their estrous cycle.


The Beneficial Impact of Antidepressant Drugs on Prenatal Stress-Evoked Malfunction of the Insulin-Like Growth Factor-1 (IGF-1) Protein Family in the Olfactory Bulbs of Adult Rats.
Insulin-like growth factor-1 (IGF-1) promotes the growth, differentiation, and survival of both neurons and glial cells, and it is believed to exert antidepressant-like activity. Thus, disturbances in the IGF-1 system could be responsible for the course of depression. To date, there have been no papers showing the impact of chronic antidepressant treatment on the IGF-1 network in the olfactory bulb (OB) in an animal model of depression. Prenatal stress was used as model of depression. Twenty-four 3-month-old male offspring of control and stressed mothers were subjected to behavioral testing (forced swim test). The mRNA expression of IGF-1 and IGF-1 receptor (IGF-1R) and the protein level of IGF-1 and its phosphorylation, as well as the concentrations of IGF-binding proteins (IGFBP-2, -4, -3, and -6), were measured in OBs before and after chronic imipramine, fluoxetine, or tianeptine administration. Adult rats exposed prenatally to stressful stimuli displayed not only depression-like behavior but also decreased IGF-1 expression, dysregulation in the IGFBP network, and diminished mRNA expression, as well as IGF-1R phosphorylation, in the OB. The administration of antidepressants normalized most of the changes in the IGF-1 system of the OB evoked by prenatal stress. These results suggested a beneficial effect of chronic antidepressant drug treatment in the alleviation of IGF-1 family malfunction in OBs in an animal model of depression.


Oral health of 65-year olds in Sweden and Norway: a global question and ICF, the latest conceptual model from WHO.
The aims of this study were to identify explanatory factors of satisfaction with oral health among Norwegian and Swedish 65 year olds in terms of items from four different domains of ICF and to compare the strengths of the various ICF domains in explaining satisfaction with oral health. Further it was to assess whether the explanatory factors of ICF domains vary between Norway and Sweden. In 2007, standardized questionnaires were mailed to all the residents in certain counties of Sweden and Norway who were born in 1942. Response rates were 73.1% (n = 6078) in Sweden and 56.0% (n = 4062) in Norway. In total, 33 questions based on four different ICF domains were chosen to explain satisfaction with oral health. Logistic regression showed that four different ICF domains in terms of body function, body structure, activity/participation and environmental factors explained, respectively, 53%, 31%, 12% and 34% of the explanatory variance in the satisfaction with oral health. In the final analysis, only nine items were statistically significant (p < 0.05). This study indicates that ICF as a conceptual model could cover a broad spectrum of factors embedded in OHRQoL measured by a global question in Sweden and Norway. Nine items, representing four ICF domains, were important in the final model for explaining satisfaction with oral health.


Comet assay with the fish cell line rainbow trout gonad-2 for in vitro genotoxicity testing of xenobiotics and surface waters.
The present study examines the potential of the comet assay using the rainbow trout gonad cell line-2 (RTG-2) as an in vitro indicator test for genotoxicity assessment of aquatic contaminants and native surface waters. Initially, the comet assay protocol was adapted to the RTG-2 cell line. An exposure period of 2 h was found to be optimal, because DNA damage decreased when exposure was prolonged. Then, the sensitivity of the comet assay with RTG-2 cells toward six genotoxic reference substances was evaluated. The lowest-observed-effect concentration values for the directly acting genotoxins, 4-nitroquinoline-N-oxide and N-methyl-N'-nitro-N-nitrosoguanidine, were in the low nanomolar range. The RTG-2 test system clearly was less sensitive for the indirectly acting genotoxins benzo[a]pyrene, nitrofurantoin, 2-acetylaminofluorene, and dimethylnitrosamine, despite the presence of xenobiotic metabolic capacities in RTG-2 cells. The two effect endpoints used, tail length (TL) and tail moment (TM), did not differ with respect to sensitivity, but the linearity of the concentration-response curve was better with TM than with TL. The overall reproducibility of the assay results was good. Finally, the applicability of the comet assay with RTG-2 cells for genotoxicity screening of native surface water samples was studied. The assay tolerated the use of nonsterile water samples and was able to detect genotoxic potentials in native water samples; that is, extraction and concentration of the samples were not needed. The results of the present study indicate the suitability of the comet assay with the fish cell line, RTG-2, as in vitro screen for detecting genotoxic potencies of xenobiotics and environmental samples.


Antigen- or mitogen-provoked spleen cells produce factors that stimulate the secretion of macrophages of a neutral proteinase degrading cartilage proteoglycans.
Soluble products released by rabbit spleen cells on stimulation with either mitogen or antigen markedly stimulate the secretion of a proteoglycan-degrading neutral proteinase by rabbit bone-marrow macrophages.


Long-term outcomes of repeated ketamine infusions in patients with unipolar and bipolar depression: A naturalistic follow-up study.
Ketamine was proven to have short-term antidepressant effects. There is a paucity of studies focused on the long-term outcomes of repeated infusions of ketamine. This study aimed to examine the long-term outcomes of repeated ketamine infusions in patients with unipolar and bipolar depression METHODS: One hundred and eight patients with unipolar and bipolar depression completed the repeated treatment phase (administered ketamine three times weekly over a 12-day) and entered a 9-month naturalistic follow-up phase. Assessments were obtained at week 2, month 6, and month 9 after the repeated treatment phase. The Patient Health Questionnaire-9 (PHQ-9) Scale and the Global Assessment of Functioning (GAF) Scale were used to assess depressive symptoms and global functional status, respectively. Seventy-one (65.7%) of patients completed the 9-month follow-up. On month 9, the response and remission rate were 80.3% and 78.9%, respectively. Among 56 patients who achieved response after the repeated treatment phase, 26 (46.4%) of patients sustained response during 9-month follow-up and their GAF score remained over 70. Sixteen patients relapsed during the 9-month follow-up and 14 (85.7%) of the relapse occurred during the first 2-week follow-up. The major limitation of this study is the open-label design. This small sample study suggested that patients with unipolar and bipolar depression who response to repeated treatment with continued oral antidepressant may be a viable treatment option, and their global functional status improved with a follow-up. Relapse of depression tended to occur during the 2 weeks follow-up.


[Study on Aconitum diterpenoid alkaloids from flowers of Aconitum kusnezoffi and its decoction by ESI-MS].
To study the change of chemical compound after decocting the flowers of Aconitum kusnzoffii Reichb (FAK) by analyzing the alkaloids in FAK and the decoction of FAK qualitatively. The alkaloid extracts of FAK and alkaloid mixtures in the decoction of FAK were directly analyzed by electrospray ionization trap tandem mass spectrometry via by pump. Three novel aconitum alkaloids were found in FAK. In addition, it is found that both diester diterpenoid alkaloids and triester diterpenoid alkaloids were hydrolyzed in the decoction of FAK. The hydrolysis products of the diester-alkaloids are benzoylaconines and aconines; the hydrolysis products of the triester-alkaloids are 3-acetyl-aconines. ESI-MS" method is suitable for the analysis of Aconitum alkaloids in the decoction of FAK as well as other Aconitum plants, which offers the advantages of convenience, speed, sensitivity and specificity.


Hybrid Conferences in the Post-COVID-19 Era: Time Yet for a Paradigm Shift for Medical Associations.
Since the first COVID-19 lockdown in India was declared, all scientific conferences and related activities have been conducted in online formats (1). The ACS(I) [Association of Cutaneous Surgeons (India)] conducted its Annual National Conference called ACSICON-2021 for over 1150 delegates in mid-2021 in a hybrid mode. ACS(I) was one of the first organizations to embrace the hybrid conferencing strategy in the post-COVID-19 era in India. However, while meeting feedback and testimonials are typically gathered, there is very little public data documenting conference attendees' viewpoints. The goal of this research study was to look at the viewpoints of medical conference attendees (such as physicians and medical professionals) on hybrid conferencing as a future trend, the danger of infectivity and transmissibility of COVID-19 during and after the event, the effectiveness of stringent safety protocols and vaccination in preventing the disease and thereby assess the feasibility of hybrid conference as the most convenient mode of learning interaction in the current COVID-19 era and also Post COVID-19 era. The physical attendees were surveyed post-ACSICON 2021 conference online, using a mixed-methods technique. Attendees were given a 16-point questionnaire using Google Forms that covered subjects including the COVID-19 preventive procedure, immunization status, infection rates during and after the conference, and overall satisfaction with the hybrid conference. A total of 231 people were sent the survey questionnaire. Only 0.4% (n = 1) of the participants reported being infected by COVID-19 virus after the conference. 86% (n = 198) of the respondents also felt that all the necessary precautions were taken during the ACSICON 2021conference. Most of the respondents (82%, n = 189) rated the hybrid conference interaction to be more satisfying than an online conference. An overwhelming majority of the respondents (92%, n = 209) found hybrid conferences to be a safer option than regular conference. The COVID-19 pandemic's scope has forced a paradigm change in medical practice and research (1). ACSICON 2021 is an example of how, with careful organization, strict implementation of meticulous preventive procedures, and strict adherence to the COVID-19 protocol, medical conferences may be held without danger of infection and its transmission. Given the pace with which vaccinations are being administered, a new reality in which technology and live networking intersect via hybrid conferences will result in a more engaging and adaptable medical conference experience. In the long run, this can bring about a significant shift in the conduct of scientific meetings to best suit delegates' needs and conveniences.


Using psycho-behavioral phenotyping for overweight and obesity: Confirmation of the 6 factor questionnaire.
Questionnaires that assess dietary habits, eating behaviors, and relevant psychosocial constructs are routinely used in obesity research and clinical practice. The 6 factor questionnaire (6FQ) was previously developed as an assessment tool for psycho-behavioral phenotyping. The primary purpose of this study was to confirm and validate the original findings in a large diverse adult population. A total of 5399 self-selected participants (mean age of 48 ± 13 years and body mass index of 32 ± 8 kg/m2) completed the 6FQ online. The association between self-reported demographic data and 6FQ responses was assessed using linear regression models. Mean factor score and odds ratio analyses consistently demonstrated a statistically significant relationship between factors and body weight even after adjusting for age, sex, and race/ethnicity. Although the study was correlational in design, the results demonstrate that the 6FQ, an instrument that represents multidimensional unhealthful lifestyle patterns associated with diet, physical activity, cognition, and self-perception worsen with increasing body weight. Psycho-behavioral phenotyping may be a useful approach when assessing and treating patients with obesity.


Cell cycle-dependent changes in Golgi stacks, vacuoles, clathrin-coated vesicles and multivesicular bodies in meristematic cells of Arabidopsis thaliana: a quantitative and spatial analysis.
Cytokinesis in plants involves both the formation of a new wall and the partitioning of organelles between the daughter cells. To characterize the cellular changes that accompany the latter process, we have quantitatively analyzed the cell cycle-dependent changes in cell architecture of shoot apical meristem cells of Arabidopsis thaliana. For this analysis, the cells were preserved by high-pressure freezing and freeze-substitution techniques, and their Golgi stacks, multivesicular bodies, vacuoles and clathrin-coated vesicles (CCVs) characterized by means of serial thin section reconstructions, stereology and electron tomography techniques. Interphase cells possess approximately 35 Golgi stacks, and this number doubles during G2 immediately prior to mitosis. At the onset of cytokinesis, the stacks concentrate around the periphery of the growing cell plate, but do not orient towards the cell plate. Interphase cells contain approximately 18 multivesicular bodies, most of which are located close to a Golgi stack. During late cytokinesis, the appearance of a second group of cell plate-associated multivesicular bodies coincides with the onset of CCV formation at the cell plate. During this period a 4x increase in CCVs is paralleled by a doubling in number and a 4x increase in multivesicular bodies volume. The vacuole system also undergoes major changes in organization, size, and volume, with the most notable change seen during early telophase cytokinesis. In particular, the vacuoles form sausage-like tubular compartments with a 50% reduced surface area and an 80% reduced volume compared to prometaphase cells. We postulate that this transient reduction in vacuole volume during early telophase provides a means for increasing the volume of the cytosol to accommodate the forming phragmoplast microtubule array and associated cell plate-forming structures.


Novel therapeutic strategies for treatment of visceral leishmaniasis.
Leishmaniasis reveals itself in two forms, cutaneous and visceral, but the later exerts serious complications and may lead to death, if untreated. The availability of limited number of antileishmanial chemotherapeutic agents, the high cost of treatment, growing incidences of resistance to first line drugs as well as severe toxicities associated with the drugs complicate the treatment of visceral leishmaniasis. To overcome these problems, critical investigation of new therapeutic strategies with potential antileishmanial activity and good tolerability are essential. In this review we explore the different facets of novel therapeutic strategies for treatment of visceral leishmaniasis with a purpose to summarize all the possible treatment tactics, which will help scientists working in this arena to implement their research in a systematic manner.


Isolated gastric involvement of recurrent Hodgkin lymphoma: a case report and review of the literature.
Although the gastrointestinal tract is one of the most common sites for extranodal lymphoma, gastrointestinal lymphoma is a rare disease that is almost exclusively non-Hodgkin lymphoma. We present a rare condition of Hodgkin lymphoma relapse after 12 years as isolated gastric involvement caused massive gastrointestinal bleeding in a 34-year-old Iranian woman. According to the result of the upper endoscopy, laparotomy was performed, and a large mass in the upper part of the fundus, alongside the esophagogastric junction, was seen, so gastrectomy was performed. All symptoms and paraclinical findings for gastrointestinal Hodgkin lymphoma are nonspecific. Therefore, the preoperative diagnosis is challenging. It seems that surgery is a suitable diagnostic and therapeutic method in this field.


Cutaneous anthrax in Eastern Turkey: a review of 85 cases.
Anthrax is a zoonotic disease diminishing worldwide. Although a very rare disease in developed countries, anthrax is still endemic in developing countries. To evaluate the clinical history and features, treatment and outcome of our patients with anthrax and emphasize the importance of the disease in our region. In this study, the records of all patients diagnosed with cutaneous anthrax admitted to Yüzüncü Yil University Medical Faculty between March 2002 and March 2007, were reviewed, and data on age, gender, occupation, clinical symptoms and findings, location and type of lesions, clinical history, laboratory findings, treatment and outcome were recorded. There were 85 patients [46 (54.1%) male, 39 (45.9%) female; mean age 30.6 years, range 6-72]. All the patients had a history of contact with infected animals or animal products. The infectious agent was found using direct examination of Gram-stained smears from 17 patients (20%), and Bacillus anthracis was isolated from vesicle fluid cultures from 11 patients (12.9%). Diagnosis was based on clinical findings in the remaining 57 patients (67.1%). All patients, except for two with respiratory tract obstruction, made a full recovery. Anthrax continues to be an endemic disease in Turkey, and should be considered in patients with a relevant contact history having a painless ulcer and vesicular skin lesions surrounded by a zone of oedema. Gram staining and simple culture methods are useful aids to diagnosis, but diagnosis may have to be based on clinical grounds in the majority of patients.


Emotional organization of autobiographical memory.
The emotional organization of autobiographical memory was examined by determining whether emotional cues would influence autobiographical retrieval in younger and older adults. Unfamiliar musical cues that represented orthogonal combinations of positive and negative valence and high and low arousal were used. Whereas cue valence influenced the valence of the retrieved memories, cue arousal did not affect arousal ratings. However, high-arousal cues were associated with reduced response latencies. A significant bias to report positive memories was observed, especially for the older adults, but neither the distribution of memories across the life span nor response latencies varied across memories differing in valence or arousal. These data indicate that emotional information can serve as effective cues for autobiographical memories and that autobiographical memories are organized in terms of emotional valence but not emotional arousal. Thus, current theories of autobiographical memory must be expanded to include emotional valence as a primary dimension of organization.


Therapeutic actions of insulin-like growth factor I on APP/PS2 mice with severe brain amyloidosis.
Transgenic mice expressing mutant forms of both amyloid-beta (Abeta) precursor protein (APP) and presenilin (PS) 2 develop severe brain amyloidosis and cognitive deficits, two pathological hallmarks of Alzheimer's disease (AD). One-year-old APP/PS2 mice with high brain levels of Abeta and abundant Abeta plaques show disturbances in spatial learning and memory. Treatment of these deteriorated mice with a systemic slow-release formulation of insulin-like growth factor I (IGF-I) significantly ameliorated AD-like disturbances. Thus, IGF-I enhanced cognitive performance, decreased brain Abeta load, increased the levels of synaptic proteins, and reduced astrogliosis associated to Abeta plaques. The beneficial effects of IGF-I were associated to a significant increase in brain Abeta complexed to protein carriers such as albumin, apolipoprotein J or transthyretin. Since levels of APP were not modified after IGF-I therapy, and in vitro data showed that IGF-I increases the transport of Abeta/carrier protein complexes through the choroid plexus barrier, it seems that IGF-I favors elimination of Abeta from the brain, supporting a therapeutic use of this growth factor in AD.


Lessons learned from eight teams: The value of pilot and feasibility studies in self-management science.
Designing and conducting effective intervention research is an important domain of nursing science. Nurse scientists have long recognized people with chronic conditions need effective self-management strategies across the lifespan, so they have led the way in establishing theoretical and practical grounds for the science of self-management. Guidance from pilot and feasibility research for self-management interventions is scarce. Documented exemplars of successes and failures in pilot and feasibility study designs are scant in the literature. The purpose of this paper is to illustrate methodological approaches using pilot and feasibility examples. To maximize collective lessons learned in self-management science study design, features of our pilot and feasibility research strategies that yielded both desirable and undesirable outcomes are described, analyzed, and paired with alternative solutions. A National Institute of Nursing Research P30 grant center, awarded grants to 8 pilot investigators to pilot self-management interventions. A wide variety of chronic conditions were addressed, including heart failure, chronic kidney disease, multiple sclerosis, diabetes, and HIV. The investigators provided their experiences of study implementation. Common themes across the studies were identified. There were four lessons learned from these studies: 1) maximize resources and develop enough evidence for subsequent studies; 2) embed patient-centered feasibility within implementation testing with new patient populations; 3) develop a flexible participant recruitment plan to allow for adjustments when unexpected barriers arise; and 4) define study-specific data collection procedures to demonstrate feasibility. Researchers conducting preliminary small-scale self-management intervention research must balance resources to develop and implement interventions to meet pilot and feasibility objectives.


AZD8233 antisense oligonucleotide targeting PCSK9 does not prolong QT interval.
AZD8233 is a proprotein convertase subtilisin/kexin type 9 (PCSK9) antisense oligonucleotide under development for treatment of hypercholesterolaemia. A prespecified concentration-QT analysis was performed based on data from a single ascending dose study that was prospectively designed to act as a TQT study substitute. Subcutaneous single doses ranging from 4 to 120 mg were evaluated in 73 adult healthy male subjects. Time-matched 12-lead digital ECG and plasma concentrations (n = 15) were measured at baseline and up to 48 hours after dose in each subject. The analysis was performed using a linear mixed effect model, where change from baseline QTc (ΔQTc) was a dependent variable and time-matched AZD8233 concentration was an independent variable. The high clinical exposure scenario was defined as 1.7-fold the expected Cmax following an assumed therapeutic dose of 60 mg, which corresponds to AZD8233 plasma concentration of 1.39 μg/mL. Estimated placebo-corrected and baseline-adjusted QTcF interval (ΔΔQTcF) at this concentration was -2.2 ms (90% CI: -4.11, -0.28). Furthermore, the upper 90% ΔΔQTcF confidence interval was estimated to be below 10 ms at all observed concentrations. As the effect on ΔΔQTcF is below the threshold for regulatory concern (10 ms), it can be concluded that AZD8233 does not induce QTcF prolongation at the high clinical exposure scenario.


Dementia in medical wards.
Patients aged 65 years and over admitted to one Department of Medicine in a University Hospital were evaluated for the frequency and types of dementia, and for the greater workload caused by the demented patients to the hospital. The frequency of moderate and severe dementia among consecutively admitted medical inpatients (N = 282) of all age groups was 12.1%. In the age-group 65-69 years it was 5.7%, and among the patients aged 80 and over 20.7%. Of all the patients at the wards in a one-day sample (N = 85), 40% were moderately or severely demented. Patients with vascular dementia constituted 69.4%, those with primary degenerative dementia 16.1%, and those with dementia due to specific causes 14.5% of all demented patients. The demented patients needed more daily nursing care and their mean hospitalization time was longer than that of the non-demented patients.


The dendritic translocation of translin protein in the form of BC1 RNA protein particles in developing rat hippocampal neurons in primary culture.
Neural BC1 RNA is distributed in neuronal dendrites as ribonucleoprotein particles (RNP). Our previous studies indicated the presence of Translin in BC1 RNPs, which is a translational repressor and links a subset of mRNAs to microtubules. In this study, we confirmed that Translin associates with BC1 RNP and we used immunocytochemical methods to examine the subcellular distribution of Translin in developing hippocampal cells in primary cultures. Translin was detected in both the nuclei and cytoplasm of neurons, whereas in glial cells it was localized in the nuclei. Consistent with the reported developmental time course of BC1 RNA expression and dendritic delivery the translocation of Translin to the neuronal dendrites appeared to correlate with neuronal development and differentiation events such as the onset of synaptogenesis in culture. These observations suggest that BC1 RNP or Translin itself may be relevant to the dendritic translation of mRNAs in response to transsynaptic activity.


Spiroindole-containing compounds bearing phosphonate group of potential Mpro-SARS-CoV-2 inhibitory properties.
Microwave-assisted reaction of 3,5-bis((E)-ylidene)-1-phosphonate-4-piperidones 3a‒g with azomethine ylide (produced through interaction of isatins 4 and sarcosine 5) cycloaddition afforded the corresponding (dispiro[indoline-3,2'-pyrrolidine-3',3″-piperidin]-1″-yl)phosphonates 6a‒l in excellent yields (80-95%). Structure of the synthesized agents was evidenced by single crystal X-ray studies of 6d, 6i and 6l. Some of the synthesized agents revealed promising anti-SARS-CoV-2 properties in the viral infected Vero-E6 cell technique with noticeable selectivity indices. Compounds 6g and 6b are the most promising agents synthesized (R = 4-BrC6H4, Ph; R' = H, Cl, respectively) with considerable selectivity index values. Mpro-SARS-CoV-2 inhibitory properties supported the anti-SARS-CoV-2 observations of the potent analogs synthesized. Molecular docking studies (PDB ID: 7C8U) are consistent with the Mpro inhibitory properties. The presumed mode of action was supported by both experimentally investigated Mpro-SARS-CoV-2 inhibitory properties and explained by docking observations.


A review of clinical and molecular prognostic factors in osteosarcoma.
Traditional prognostic determinants in osteosarcoma have included demographics (age, sex), tumour size, site, stage, and the response to chemotherapy. Many of these are determined using varying techniques and units of measurement, which can make comparison between studies difficult. The absence of survival difference between limb sparing surgery and amputation has been repeatedly demonstrated in primary disease, and even in the setting of pathological fracture. On the other hand, there is still some controversy over the existence of increased local recurrence for limb-sparing surgery, and the implications of this. Commonly used prognostic determinants such as metastases, and response to chemotherapy enable a high degree of prognostic accuracy but usually at a late stage in the course of disease. Leading on from this, there is a need to uncover molecular pathways with specific influence over osteosarcoma progression to facilitate earlier treatment changes. Some important pathways are already being defined, for example the association of CXCR4 with metastases on presentation, the likelihood of doxorubicin resistance with positive P-glycoprotein, and the reduced survival prediction of over expressed survivin. It is anticipated that the future of osteosarcoma treatment will involve treatment tailored to the molecular profile of tumours at diagnosis, adjuvant therapy directed towards dysfunctional molecular pathways rather than the use of cytotoxics, and a more standardised approach to the measurement of clinical prognostic factors.


Surface markers of primate B and T lymphoid cell lines identified by antibodies to human and simian lymphocyte antigens.
Simian B and T lymphoid cell lines were shown to maintain surface markers found on mature lymphocytes in vivo. The T lymphoid cell lines expressed Ia-like antigens on their surfaces, further suggesting that they represent mature, activated T cells. These Ia antigens show a structural similarity to Ia on human cells although some diversity exists. The Ia antigen expressed on T lymphoid cell lines was shown to be very similar to those on B lymphoid cell lines. Owl monkey and marmoset T lymphoid cell lines were also shown to express a VH immunoglobulin-related determinant, a marker which is thought to be associated with T cell antigen receptor. Owl monkey and marmoset T cell lines express a surface antigen which identifies the sheep erythrocyte receptor on human T cells and some of these lines express an antigen found on human helper T cells. It is noteworthy that substantial conservation of surface components has occurred within primate evolution such that monoclonal antibodies to human Ia, OKT-11a and Leu 3a markers can be used to type lymphocytes of lower primates.


On the Conflicting Estimations of Pigment Site Energies in Photosynthetic Complexes: A Case Study of the CP47 Complex.
We focus on problems with elucidation of site energies [Formula: see text] for photosynthetic complexes (PSCs) in order to raise some genuine concern regarding the conflicting estimations propagating in the literature. As an example, we provide a stern assessment of the site energies extracted from fits to optical spectra of the widely studied CP47 antenna complex of photosystem II from spinach, though many general comments apply to other PSCs as well. Correct values of [Formula: see text] for chlorophyll (Chl) a in CP47 are essential for understanding its excitonic structure, population dynamics, and excitation energy pathway(s). To demonstrate this, we present a case study where simultaneous fits of multiple spectra (absorption, emission, circular dichroism, and nonresonant hole-burned spectra) show that several sets of parameters can fit the spectra very well. Importantly, we show that variable emission maxima (690-695 nm) and sample-dependent bleaching in nonresonant hole-burning spectra reported in literature could be explained, assuming that many previously studied CP47 samples were a mixture of intact and destabilized proteins. It appears that the destabilized subpopulation of CP47 complexes could feature a weakened hydrogen bond between the 13(1)-keto group of Chl29 and the PsbH protein subunit, though other possibilities cannot be entirely excluded, as discussed in this work. Possible implications of our findings are briefly discussed.


Normal induction but accelerated decay of LTP in APP + PS1 transgenic mice.
Mice carrying mutated human APPswe and PS1 (A246E) transgenes (A/P mice) show age-dependent memory impairment in hippocampus-dependent tasks. Moreover, the mice show normal learning in the water maze within a day but impairment across days. We recorded LTP in a slice preparation (CA1) and in chronically implanted animals (dentate gyrus, or DG) at 17-18 months of age. The genotypes did not differ in the basal synaptic transmission. Also, LTP induction and its maintenance over 60 min did not differ between A/P and control mice. However, the fEPSP enhancement in vivo decayed to 77% of its maximum in 24 h in A/P mice while remaining at 96% in control mice. The time course of the LTP decay in the A/P mice corresponds to their behavioral impairment and indicates that Abeta accumulation in the dentate gyrus may interfere with the signal transduction pathways responsible for memory consolidation.


Immunizations: An Evolving Paradigm for Oral Health Care Providers.
Oral health care professionals are at risk for the transmission of bacterial and viral microorganisms. Providers need to be knowledgeable about the exposure/transmission of life-threatening infections and options for prevention. This article is designed to increase the oral health care provider's awareness of the latest assessment of vaccine-preventable diseases that pose a high risk in the dental health care setting. Specific dosing strategies are suggested for the prevention of infections based on available evidence and epidemiologic changes. This information will provide a clear understanding for prevention of vaccine-preventable diseases that pose a public health consequence.


Imprecise vowel articulation as a potential early marker of Parkinson's disease: effect of speaking task.
The purpose of this study was to analyze vowel articulation across various speaking tasks in a group of 20 early Parkinson's disease (PD) individuals prior to pharmacotherapy. Vowels were extracted from sustained phonation, sentence repetition, reading passage, and monologue. Acoustic analysis was based upon measures of the first (F1) and second (F2) formant of the vowels /a/, /i/, and /u/, vowel space area (VSA), F2i/F2u and vowel articulation index (VAI). Parkinsonian speakers manifested abnormalities in vowel articulation across F2u, VSA, F2i/F2u, and VAI in all speaking tasks except sustained phonation, compared to 15 age-matched healthy control participants. Findings suggest that sustained phonation is an inappropriate task to investigate vowel articulation in early PD. In contrast, monologue was the most sensitive in differentiating between controls and PD patients, with classification accuracy up to 80%. Measurements of vowel articulation were able to capture even minor abnormalities in speech of PD patients with no perceptible dysarthria. In conclusion, impaired vowel articulation may be considered as a possible early marker of PD. A certain type of speaking task can exert significant influence on vowel articulation. Specifically, complex tasks such as monologue are more likely to elicit articulatory deficits in parkinsonian speech, compared to other speaking tasks.


Effects of Lipid Tethering in Extremophile-Inspired Membranes on H(+)/OH(-) Flux at Room Temperature.
This work explores the proton/hydroxide permeability (PH+/OH-) of membranes that were made of synthetic extremophile-inspired phospholipids with systematically varied structural elements. A fluorescence-based permeability assay was optimized to determine the effects on the PH+/OH- through liposome membranes with variations in the following lipid attributes: transmembrane tethering, tether length, and the presence of isoprenoid methyl groups on one or both lipid tails. All permeability assays were performed in the presence of a low concentration of valinomycin (10 nM) to prevent buildup of a membrane potential without artificially increasing the measured PH+/OH-. Surprisingly, the presence of a transmembrane tether did not impact PH+/OH- at room temperature. Among tethered lipid monolayers, PH+/OH- increased with increasing tether length if the number of carbons in the untethered acyl tail was constant. Untethered lipids with two isoprenoid methyl tails led to lower PH+/OH- values than lipids with only one or no isoprenoid tails. Molecular dynamics simulations revealed a strong positive correlation between the probability of observing water molecules in the hydrophobic core of these lipid membranes and their proton permeability. We propose that water penetration as revealed by molecular dynamics may provide a general strategy for predicting proton permeability through various lipid membranes without the need for experimentation.


An Mhc class I allele associated to the expression of T-dependent immune response in the house sparrow.
The major histocompatibility complex (Mhc) encodes for highly variable molecules, responsible for foreign antigen recognition and subsequent activation of immune responses in hosts. Mhc polymorphism should hence be related to pathogen resistance and immune activity, with individuals that carry either a higher diversity of Mhc alleles or one specific Mhc allele exhibiting a stronger immune response to a given antigen. Links between Mhc alleles and immune activity have never been explored in natural populations of vertebrates. To fill this gap, we challenged house sparrows (Passer domesticus) with two T-dependent antigens (phytohemagglutinin and sheep red blood cells) and examined both primary and secondary immune responses in relation to their Mhc class I genotypes. The total number of Mhc alleles had no influence on either primary or secondary response to the two antigens. One particular Mhc allele, however, was associated with an increased response to both antigens. Our results point toward a contribution of the Mhc, or of other genes in linkage disequilibrium with the Mhc, in the regulation of immune responses in a wild animal species.


A novel T-cell receptor mimic defines dendritic cells that present an immunodominant West Nile virus epitope in mice.
We used a newly generated T-cell receptor mimic monoclonal antibody (TCRm MAb) that recognizes a known nonself immunodominant peptide epitope from West Nile virus (WNV) NS4B protein to investigate epitope presentation after virus infection in C57BL/6 mice. Previous studies suggested that peptides of different length, either SSVWNATTAI (10-mer) or SSVWNATTA (9-mer) in complex with class I MHC antigen H-2D(b) , were immunodominant after WNV infection. Our data establish that both peptides are presented on the cell surface after WNV infection and that CD8(+) T cells can detect 10- and 9-mer length variants similarly. This result varies from the idea that a given T-cell receptor (TCR) prefers a single peptide length bound to its cognate class I MHC. In separate WNV infection studies with the TCRm MAb, we show that in vivo the 10-mer was presented on the surface of uninfected and infected CD8α(+) CD11c(+) dendritic cells, which suggests the use of direct and cross-presentation pathways. In contrast, CD11b(+) CD11c(-) cells bound the TCRm MAb only when they were infected. Our study demonstrates that TCR recognition of peptides is not limited to certain peptide lengths and that TCRm MAbs can be used to dissect the cell-type specific mechanisms of antigen presentation in vivo.


Deconstructing Dietary Restriction: A Case for Systems Approaches in Aging.
Dietary restriction is a robust and conserved intervention to slow aging and extend lifespan. In this issue of Cell Metabolism, Hou et al. (2016) use a systems biology approach in C. elegans to uncover key molecular nodes underlying the transcriptomic response to dietary restriction and predict novel regulators of lifespan.


Blockade of IL-6 signaling alleviates atherosclerosis in Tet2-deficient clonal hematopoiesis.
Clonal hematopoiesis (CH) increases the risk of atherosclerotic cardiovascular disease possibly due to increased plaque inflammation. Human studies suggest that limitation of interleukin-6 (IL-6) signaling could be beneficial in people with large CH clones, particularly in TET2 CH. Here we show that IL-6 receptor antibody treatment reverses the atherosclerosis promoted by Tet2 CH, with reduction of monocytosis, lesional macrophage burden and macrophage colony-stimulating factor 1 receptor (CSF1R) expression. IL-6 induces expression of Csf1r in Tet2-deficient macrophages through enhanced STAT3 binding to its promoter. In mouse and human Tet2-deficient macrophages, IL-6 increases CSF1R expression and enhances macrophage survival. Treatment with the CSF1R inhibitor PLX3397 reversed accelerated atherosclerosis in Tet2 CH mice. Our study demonstrates the causality of IL-6 signaling in Tet2 CH accelerated atherosclerosis, identifies IL-6-induced CSF1R expression as a critical mechanism and supports blockade of IL-6 signaling as a potential therapy for CH-driven cardiovascular disease.


Navigating adolescence: an epidemiological follow-up of adaptive functioning in girls with childhood ADHD symptoms and conduct disorder.
The current study investigated the experience of girls growing up with cognitive and social disorders. Eight adolescent girls participated in interviews that were transcribed and analyzed using Interpretative Phenomenological Analysis. Four of the girls had a history of ADHD symptoms and conduct disorder problems (ADHD/CP), four did not. Three master themes emerged within the domain of "Coping Behaviors": seeking social support, bravado, and avoidance. Three master themes emerged within the domain of "Barriers to Adaptive Functioning": lack of support and guidance, poor negotiation of interpersonal conflict, and victimization. Although all participants experienced developmental barriers, the girls with ADHD/CP coped with these barriers in a less effective way. The study raises an important developmental concern, the seemingly ineffective coping strategies of ADHD/CP adolescents.


Statins and C-reactive protein: in silico evidence on direct interaction.
Statins are known to lower CRP, and this reduction has been suggested to contribute to the established efficacy of these drugs in reducing cardiovascular events and outcomes. However, the exact mechanism underlying the CRP-lowering effect of statins remains elusive. In order to test the possibility of direct interaction, we performed an in silico study by testing the orientation of the respective ligands (statins) and phosphorylcholine (the standard ligand of CRP) in the CRP active site using Molecular Operating Environment (MOE) software. Docking experiments showed that all statins could directly interact with CRP. Among statins, rosuvastatin had the strongest interaction with CRP (pKi = 16.14), followed by fluvastatin (pKi = 15.58), pitavastatin (pKi = 15.26), atorvastatin (pKi = 14.68), pravastatin (pKi = 13.95), simvastatin (pKi = 7.98) and lovastatin (pKi = 7.10). According to the above-mentioned results, rosuvastatin, fluvastatin, pitavastatin and atorvastatin were found to have stronger binding to CRP compared with the standard ligand phosphocholine (pKi = 14.55). This finding suggests a new mechanism of interaction between statins and CRP that could be independent of the putative cholesterol-lowering activity of statins.


Trace metal variability in coastal waters of San Jorge Bay, Antofagasta, Chile: An environmental evaluation and statistical approach to propose local background levels.
Between 2008 and 2011, twelve metals from 384 coastal waters samples from San Jorge Bay (Antofagasta, northern Chile) were collected and analyzed. The goal was to evaluate the quality of the bay's water bodies according to the current Chilean Quality Guideline and to establish background levels for these metals. The result suggests that the coastal waters of San Jorge Bay are of very good quality suitable for recreational activities involving human body contact. The natural background thresholds established for this bay were significantly lower than primary and secondary water quality guidelines. The distribution of Cu, Zn and Pb, along the bay's coastline provides evidence of the effects of industrial activity. Both situations suggest that the threshold indicated in the environmental guidelines of the Chilean legislation may be overestimated and do not represent pollution-free environments.


Understanding the Nature of Temperature Stability in Potassium Sodium Niobate Based Ceramics from Structure Evolution under External Field.
Preferable temperature stability of ferroelectric and strain properties can be achieved in potassium sodium niobate (KNN)-based ceramics compared to that of other lead-free piezoelectric material systems, giving it greater potential for use in electronic devices once the temperature reliability issue related to the piezoelectric constant (d33) can be further resolved. Through exploration of the nature of the temperature stability from the evolution of a crystal structure under external fields, it has been determined that the electric field has no effect on the temperature stability of d33, resulting in almost the same trend of changes in d33 with temperature under both in situ and ex situ measurements, which is totally unlike the close relationship between the electric field and the strain temperature stability. With analysis of multiple factors including intrinsic phase coexistence, electric-field-induced domain texturing, lattice distortion, and thermally induced domain detexturing, the intrinsic contribution of phase evolution plays a dominant role in the temperature stability of d33 because of the mutual counteraction of domain texturing, lattice distortion, and thermal domain detexturing. Our research provides a systematic approach to understanding the nature of the d33 temperature stability in KNN-based ceramics and proposes some favorable suggestions on the future design of materials with good temperature reliability.


Antidepressants and menstruation disorders in women: a cross-sectional study in three centers.
The relationship between menstruation disorders and antidepressant drugs usage in women remains unclear. In this study, we aimed to investigate the incidence rate of antidepressant-related menstruation disorders and to examine whether or not antidepressant use is associated with menstrual disorders in women. The study sample was gathered from three centers and four hospitals. A total of 1432 women who met the criteria of inclusion were included in the study. The sample was divided into two groups: the antidepressant group (n=793) and the control group (n=639). The menstruation disorders were established with reports from the study participants on the basis of related gynecological descriptions. The prevalence of menstrual disorders was significantly higher in the antidepressant group (24.6%) than the control group (12.2%). The incidence of antidepressant-induced menstruation disorder was 14.5%. The antidepressants most associated with menstrual disorders were paroxetine, venlafaxine, sertraline and their combination with mirtazapine. Overall, the incidence rate was similar in women receiving selective serotonin reuptake inhibitors and serotonin noradrenaline reuptake inhibitors. The results of the present study suggest that menstruation disorders are frequently observed in women taking antidepressants and that it appears to be associated with antidepressant use at least in some women.


Detection and quantification of microtubule detachment from centrosomes and spindle poles.
Microtubule detachment from microtubule organizing centers is an important cellular process required for normal cell proliferation. When cells enter mitosis, microtubule turnover increases along with a concurrent increase in microtubule detachment. MCAK, a kinesin-related protein whose abundance is highest during the early stages of mitosis, has been shown to regulate microtubule detachment. Abnormal increases or decreases in the frequency of detachment interfere with spindle function and inhibit cell division. It has been shown that drugs able to promote microtubule assembly (e.g., paclitaxel, epothilones) prevent cell division by suppressing microtubule detachment from centrosomes. Conversely, cytotoxic concentrations of microtubule destabilizing drugs (e.g., vinblastine, nocodazole), tubulin mutations that cause paclitaxel resistance, and specific β-tubulin isotypes increase the frequency of microtubule detachment. In this chapter, we describe a method to calculate the frequency of microtubule detachment by transfecting cells with EGFP-MAP4 and directly observing detachment by live cell imaging.


Efficacy and safety profile of intravitreal dexamethasone implant versus antivascular endothelial growth factor treatment in diabetic macular edema: a systematic review and meta-analysis.
To better understand the efficacy of intravitreal dexamethasone implant (Ozurdex) versus antivascular endothelial growth factor (anti-VEGF) treatment in patients with diabetic macular edema (DME). A systematic review and meta-analysis. The study included randomized control trials (RCTs) and non-randomized control trials (Non-RCTs) before December 2021 that compare the efficacy of Ozurdex-related therapyand anti-VEGF therapy. We searched PubMed, Cochrane Library, and EMBASE. The quality of the included studies was assessed carefully. 30 studies were included. Regarding BCVA change, the overall result revealed no significant differences between Ozurdex and anti-VEGF therapies in patients with nonresistant DME, but Ozurdex group had significantly more VA improvement than anti-VEGF therapies in patients with resistant DME (MD 0.12, 95% CI 0.02-0.21). In terms of central retinal thickness (CRT) decrease, there was a significant difference between Ozurdex therapy and anti-VEGF therapy in patients with nonresistant DME (MD 48.10, 95% CI 19.06-77.13) and resistant DME (MD 65.37, 95% CI 3.62-127.13). Overall, Ozurdex therapy resulted in significantly greater VA improvement and CRT decrease than anti-VEGF therapy in resistant DME patients. Ozurdex therapy was not inferior to anti-VEGF therapy in patients with nonresistant DME.


Phylogenetic description of immobilized methanogenic community using real-time PCR in a fixed-bed anaerobic digester.
After immobilization of anaerobes on polyurethane foam in a thermophilic, fixed-bed, anaerobic digester supplied with acetate, the results of real-time PCR analysis indicated that the major immobilized methanogenic archaea were Methanosarcina spp., and that the major free-living methanogenic archaea were Methanosarcina and Methanobacterium spp. 16S rRNA gene densities of Methanosarcina spp. and Methanobacterium spp. immobilized on the polyurethane foam were 7.6x10(9) and 2.6x10(8) copies/cm3, respectively. Immobilized methanogenic archaea could be concentrated 1000 times relative to those in the original anaerobically digested sludge from a completely mixed thermophilic digester supplied with cattle waste. On the other hand, immobilized bacteria could be concentrated only 10 times. The cell densities of the immobilized methanogenic archaea and bacteria were higher than those of the free-living methanogenic archaea and bacteria in the reactor. The results of clone analysis indicate that the major methanogenic archaea of the original thermophilic sludge are members of the order Methanomicrobiales, and that the major methanogenic archaea immobilized on the polyurethane foam are Methanosarcina spp., and those of the liquid phase are Methanobacterium spp. The results of the real time PCR analysis approximately agree with those of the clone analysis. These results indicate that real-time PCR analysis is useful for quantitatively describing methanogenic communities.


[Prevention of mental disorders after the loss of a sibling in childhood].
Reaction to the loss of somebody close is determined, not only by cultural, historical, social and family factors, but above all by the stage of individual development that has been reached. Children behave differently from adults following "object loss". Their ego and object relations are developing rapidly. The classical phenomena of mourning are usually manifested only after adolescence. When their psychological balance has been upset by bereavement children try to restore it through reparative and adaptive measures. If they are not given adequate support from the parents and paediatrician, or psychotherapeutic help when this is called for, then the loss of a significant person frequently disturbs children's further development. There is an important field for preventive psychohygienic measures open in relation to fatal illness in childhood.


Treatment of loss of tooth substance using dentine-bonded crowns: report of a case.
This article discusses the treatment of a bulimic patient with severe tooth substance loss. The patient was provided with dentine-bonded crowns in view of the need for only minimal tooth preparation, their potential for good aesthetics and good patient acceptance. The crowns have performed satisfactorily in clinical service for 4 years.


Is it worth carrying out determination of N-butane in postmortem samples? A case report and a comprehensive review of the literature.
The aim of this article is to illustrate the importance of N-butane determination in postmortem samples through a case report and to propose actions and precautions to be taken into consideration when butane is suspected to be involved in cases of death. The case concerns a 15-year-old boy found dead after sniffing a cigarette lighter refill. Toxicological investigation revealed the presence of butane in the heart and femoral blood (1280 and 1170 μg/L, respectively), in the gastric contents (326 μg/L), and in the liver (1010 μg/kg) and lung tissues (210 μg/kg). Propane was present only in the blood samples at concentrations tenfolds lower.Butane can be involved in three kinds of fatalities: deliberate inhalations including volatile substance abuse (VSA), involuntary exposure, and homicides. A fatal outcome of butane inhalation can be caused by asphyxia and/or cardiac arrhythmia. In the context where butane exposure is evidenced by non-toxicological investigations, the usefulness of the determination of butane in postmortem samples is often questionable. However, it is admitted that butane-related deaths are generally underreported. Several difficulties including sample handling and storage, substantial variation in tissue concentrations, and lack of a lethal threshold make the interpretation of butane results challenging. In our opinion, systematic toxicological methods should be developed in order to analyze butane, at least when it concerns a typical VSA victim, even when butane is not actually suspected to be the cause of death.


[EASYSCAN: French pilot study for securing drug administration by barcode reading].
Medication errors are common at the time of administration. To prevent them, technologies allowing consistency check by bar code technology at bedside have been developed. Our study focuses on the evaluation of a BarCode Medication Administration (BCMA) called EASYSCAN with Electronic Medication Administration Record (e-MAR) to verify both patient's identity and medication to be administrated. A prospective observational study was conducted during seven weeks in a French medicine ward. The performance of the system was evaluated by the success rate of BCMA and by the average time for administration with and without EASYSCAN. A satisfaction questionnaire about BCMA was proposed to nurses. We observed 182 administrations including 87 (48%) with EASYSCAN. The verification of the patient's identity was successful in 77% of administrations and 65% of the drugs were scanned successfully. The main causes of check failures were the lack of datamatrix on the drug (81%), error messages (14%) and the lack of system functionality (5%). The average time for administration per patient was significantly increased: 4.68min/patient with versus 2.87min/patient without EASYSCAN. The study shows the EASYSCAN's performance in its first version. Material and software evolutions and an increase of nurses'pratices will be necessary to continue the experimentation of this system still unpublished in France.


Prevalence of other diabetes-associated complications and comorbidities and its impact on health care charges among patients with diabetic neuropathy.
Diabetic neuropathy (DN) is a common complication associated with diabetes. This study assesses the prevalence of other diabetes-related complications or comorbidities among DN patients and its marginal contribution to health care charges. Using administrative claims database, we studied commercially insured patients below 65 years old with at least one claim of DN anytime from July 2004 through June 2005 (Year 1). Using propensity scoring, a 10:1 ratio of demographically matched controls with diabetes but no DN was constructed. Both DN patients and controls had 12 months of continuous enrollment in Year 1 and Year 2 (July 2005-June 2006). We compared the Year 1 prevalence of other diabetes-associated complications or comorbidities between DN patients and diabetic controls. Controlling for comorbidities, we used multivariate regressions to examine the incremental impact of DN or any other diabetes-related complication or comorbidity on Year 2 health care charges. A higher percentage of DN patients had at least one other diabetes-related complication or comorbidity than diabetic controls. Individuals with DN had a higher prevalence of each individual other diabetes-related complication or comorbidity. Controlling for comorbidities, the presence of any other diabetes-related complication or comorbidity was statistically associated with higher outpatient pharmacy and total charges for both DN patients and controls. Total and outpatient pharmacy charges were also significantly higher for DN patients than for controls, among those with or without any other diabetes-related complications or comorbidities. DN can occur in the absence of other diabetes-related complications or comorbidities. The presence of DN and any other diabetes-related complications or comorbidities significantly increases health care charges.


Determination of cis-diol-containing flavonoids in real samples using boronate affinity quantum dots coated with imprinted silica based on controllable oriented surface imprinting approach.
Novel boronate affinity imprinted quantum dots (BA-CdTe@MIPs QDs) were used to develop a selective and sensitive fluorescent nanosensor for determination of cis-diol-containing flavonoids such as quercetin (Qu), baicalein (Bai) and luteolin (Lut) based on controllable oriented surface imprinting approach. The boronate affinity imprinted silica was used as recognition elements. Under the optimum conditions, the imprinting factor (IF) for Qu, Bai and Lut was evaluated to be 9.42, 6.58 and 10.91, respectively. The results indicated that the boronate affinity quantum dots coated with imprinted silica were successfully prepared. The obtained BA-CdTe@MIPs QDs provided high selectivity and high sensitivity for cis-diol-containing flavonoids such as quercetin and luteolin. The BA-CdTe@MIPs QDs exhibited linear decrease in fluorescence intensity with the increase of concentration of quercetin in the 0.05-25 μM concentration range. The detection limit (LOD) is evaluated to be 0.02 μM. The obtained fluorescent nanosensor could be successfully applied to efficient detection of cis-diol-containing flavonoids in onion skin and human urine samples. The recoveries for the spiked onion skin and urine samples were evaluated to be 83.50-104.00% and 86.67-105.00%, respectively. Clearly, this study provides a rapid and efficient fluorescent detection tool for cis-diol-containing flavonoids in real samples.


Determining reference data for overnight oximetry in neonates: A pilot study.
To determine the variability of overnight oximetry parameters in a group of normal, healthy term infants; to enable the calculation of the number of subjects required to produce reliable reference ranges for neonatal overnight oximetry. A convenience sample of normal, healthy term neonates was recruited. Each had overnight oximetry using the Masimo SET Radical oximeter (data downloaded using Profox software). The report included the number of oxygen desaturation events (an absolute decrease in SpO2 of 4 or more), and the duration of oxygen saturations <90%. 21 babies were recruited with data available from 19. 32% were female; 68% born by vaginal delivery; 37% fully breast feeding, 53% bottle and 11% by a combination of both. The mean (SD) GA was 39.2 (0.79) weeks, the mean (SD) BW was 3477 (240) grams. The median (IQR) post-natal age at the time the oximetry recording started was 31 (28-41) hours; four babies were <24 h old. All babies had some desaturation events ranging from 4 to 36 times per hour. On average babies spent 3.0% (SD 2.3) of the time with an SpO2 < 90% (range 0.12-7.94). In a cohort of healthy term neonates, as assessed by overnight oximetry, the mean SpO2 was 97% (SD 1, range 95-99). All neonates had a number of oxygen desaturation events ranging from 4 to 36 per hour. The mean proportion of time spent with oxygen saturations below 90% was around 3%.


Relationship of cytosolic ion fluxes and protein kinase C activation to platelet-derived growth factor induced competence and growth in BALB/c-3T3 cells.
Platelet-derived growth factor (PDGF) and other agents that activate protein kinase C (PKC) rapidly alter cytosolic pH (pHi) and intracellular free calcium ([Ca++]i) in BALB/c-3T3 fibroblasts. To define whether changes in pHi or [Ca++]i are linked to PDGF-stimulated mitogenesis, these parameters were assessed in control and PKC depleted fibroblasts. PDGF addition to BALB/c-3T3 fibroblasts resulted in transient acidification of the cytoplasm followed by prolonged cytosolic alkalinization. Exposure of cells to 12-tetradecanoylphorbol-13-acetate (TPA), a phorbol ester that activates PKC, resulted in cytosolic alkalinization without prior acidification. Overnight incubation with 600 nM TPA decreased the total cell PKC histone phosphorylating activity in BALB/c-3T3 fibroblasts by greater than 90%. In PKC-deficient fibroblasts, TPA, and PDGF-induced alkalinization was abolished. In addition, the transient drop in pHi seen initially in control cells treated with PDGF is sustained to the point where pHi is fully 0.6-0.7 pH units below control cell values for up to 30 minutes. PDGF increased [Ca++]i threefold; this transient rise in [Ca++]i was only minimally affected (less than 15%) by lowering of the extracellular calcium level with ethylene glycol bis(b-aminoethyl ether)0 N,N,N' tetraacetic acid (EGTA) or blocking calcium influx with CoCl2. In contrast, 8-(diethylamine)-octyl-3,4,5-trimethoxybenzoate (TMB-8), an agent thought to inhibit calcium release from intracellular stores, substantially inhibited the rise in [Ca++]i caused by PDGF. TPA and 1-oleoyl-2-acetylglycerol (OAG) increased [Ca++]i but in contrast to PDGF this effect was blocked by pretreatment of cells with EGTA or CoCl2. In PKC-deficient fibroblasts, PDGF still increased [Ca++]i and stimulated DNA synthesis as effectively as in controls. TPA and OAG however, no longer increased [Ca++]i. The continued ability of PDGF to stimulate DNA synthesis in the face of sustained acidification and the absence of PKC activity suggests that cytosolic alkalinization and PKC activation are not essential for PDGF-induced competence in BALB/c-3T3 fibroblasts.


The influence of circadian time and sleep dose on subjective fatigue ratings.
Subjective ratings of fatigue are increasingly being used as part of a suite of tools to assess fatigue-related risk on the road and in the workplace. There is some debate however, as to whether individuals can accurately gauge their own fatigue states, particularly under conditions of sleep restriction. It is also unclear which references are used by individuals to assess fatigue - for example prior sleep, time of day, workload, or previous ratings. The current study used a sophisticated laboratory protocol to examine the independent contributions of sleep, circadian phase and sleep debt to fatigue ratings. Importantly, participants had no knowledge of time of day, how much sleep they were getting, or how long they were awake. Twenty-eight healthy, young males participated in one of two conditions of a 28 h forced desynchrony protocol - severe sleep restriction (4.7h sleep and 23.3h wake) or moderate sleep restriction (7h sleep and 21 h wake). Fatigue ratings were provided prior to and following each sleep period using the Samn-Perelli fatigue scale. Repeated measures ANOVAs were used to analyse the effects of circadian phase, sleep dose and study day. Results demonstrated an effect of circadian phase on both pre-sleep and post-sleep fatigue ratings. The significant effect of study day is interpreted as an effect of circadian time, as opposed to accumulating sleep debt. An effect of sleep dose was only seen in post-sleep fatigue ratings. The findings suggest that post-sleep fatigue ratings may be sensitive to prior sleep and may be useful as an indicator of fatigue-related risk, particularly when triangulated with information about recent total sleep time.


Effects of dapagliflozin on renal function in type 1 diabetes patients in the real world: A retrospective multicenter study of the KAMOGAWA-A cohort.
This study aimed to investigate the effects of dapagliflozin on renal function of type 1 diabetes patients. This retrospective multicenter cohort study enrolled 295 type 1 diabetes patients. The primary outcome was defined as the change in the estimated glomerular filtration rate (eGFR) after 24 months of dapagliflozin treatment. The secondary outcomes were defined as the changes in HbA1c, daily insulin dosage, and urinary albumin-to-creatinine ratio (UACR) after 24 months. Finally, 255 patients were included in the final analysis (dapagliflozin group; 76 patients, non-use group; 179 patients), with a median eGFR of 74.0 mL/min/1.73 m2. A 1:1 propensity score matching was performed, and 142 patients were analyzed in a linear mixed model. The least squares mean change in eGFR in the dapagliflozin group was -3.14 mL/min/1.73 m2 (95% CI: -5.62 to -0.66), a significantly smaller decrease than in the non-use group (-6.94 mL/min/1.73 m2 (95% CI: -9.39 to -4.50)) (p = 0.032). HbA1c level, total insulin dose, and UACR change were significantly lower in the dapagliflozin group than in the non-use group. At 24 months, the decline in eGFR was significantly lower in the dapagliflozin group than in the non-use group without increasing diabetic ketoacidosis and hypoglycemia.


Nitrogen removal from opto-electronic wastewater using the simultaneous partial nitrification, anaerobic ammonium oxidation and denitrification (SNAD) process in sequencing batch reactor.
Simultaneous partial nitrification, anaerobic ammonium oxidation and denitrification (SNAD) system was applied to treat the opto-electronic industrial wastewater in a 2.5L sequencing batch reactor. The characteristics of wastewater were low C/N ratio (≈ 0.2) with 100mg-COD/L and 567 mg NH(4)(+)-N/L. The experiment was carried out over 8 months in six different stages, where nitrogen loading rate was gradually increased from 16 g-N/m(3)d in stage I to 230 g-N/m(3)d in stage VI. The COD and nitrogen removal rates by the SNAD system reached to 28 g COD/m(3)d and 197 g NH(4)(+)-N/m(3)d, respectively in stage VI. These results showed that the SNAD system is suitable to treat wastewater containing high nitrogen pollutants with low COD level. Presence of ammonium oxidizing bacteria and anammox bacteria were confirmed by polymerase chain reaction (PCR). PCR results also indicated that Candidatus Kuenenia stuttgartiensis may be one of the dominant species in the reactor.


Spatially dependent atom-photon entanglement.
The atom-photon entanglement using the Laguerre-Gaussian (LG) beams is studied in the closed-loop three-level V-type quantum systems. We consider two schemes with near-degenerate and non-degenerate upper levels: in the first, the effect of the quantum interference due to the spontaneous emission is taken into account and in the second, a microwave plane wave is applied to the upper levels transition. It is shown that the atom-photon entanglement in both schemes depends on the intensity profile as well as the orbital angular momentum (OAM) of the applied fields so that the various spatially dependent entanglement patterns can be generated by Laguerre-Gaussian beams with different OAMs. However, due to the zero intensity,no entanglement appears in the center of the optical vortex beams. As a result, the entanglement between dressed atom and its spontaneous emissions in different points of the atomic vapor cell can be controlled by the OAM of the applied fields. Moreover, our numerical results show that the number of the local maximum degree of entanglement (DEM) peaks depends on the OAM of the applied fields. The degrees of freedom for OAM play a crucial role in spatially dependent atom-photon entanglement in such a way that it may possess broad applications in high-dimensional quantum information processing and data storage.


F-prostanoid receptor alters adhesion, morphology and migration of endometrial adenocarcinoma cells.
Cellular adhesion to extracellular matrix is a central phenomenon for the maintenance of tissue integrity and cellular movement. Collectively, these processes are regulated by a fine-tuned balance between the formation and loosening of adhesive contacts, a process involving integrins, and the elevation and diminution of cytoplasmic signalling molecules. We demonstrate that prostaglandin (PG) F(2alpha) stimulation rapidly increases the capacity of Ishikawa cells stably expressing the F-prostanoid receptor (FPS) to adhere to vitronectin. Coincident with this elevation in matrix adhesion, we demonstrate a profound PGF(2alpha)-induced alteration in cytoskeletal remodelling, characterized by polymerization of the actin cytoskeleton and recruitment of focal adhesion kinase at focal adhesions and enhanced cell migration. Moreover, we show that these PGF(2alpha)-induced alterations in adhesion and morphology on vitronectin and migration could be abolished by cultivating FPS cells in the presence of integrin alphavbeta3 antibody or alphavbeta3-directed tetrapeptide arg-gly-asp-ser or inhibition of FP receptor signalling with the FP receptor antagonist, chemical disruptors of the phospholipase C-beta, protein kinase A, c-Src and epidermal growth factor receptor kinase pathways or inhibition of the monomeric G proteins Rho, Rac and CDC42. These results reveal a mechanism by which prostanoids regulate cell movement, which may be relevant to pathologies of the endometrium.


Technetium-99m(V)-DMSA and gallium-67 in the assessment of bone and joint infection.
The aim of our study was to investigate the diagnostic value of scans with 99mTc(V)-dimercaptosuccinic acid (DMSA) to localize bone and joint infection compared with scans using 67Ga. Thirty-six patients referred for investigation of bone and joint infection were studied. In all patients, a bone scan was obtained initially. Subsequently, comparative scans with 99mTc(V)-DMSA and 67Ga were performed 1 wk apart. Microbiological findings, pathologic findings and/or clinical follow-up (until symptoms disappeared) were considered to be proof of the presence of bone and joint infection. Technetium-99m (V)-DMSA showed greater sensitivity and accuracy than 67Ga in the assessment of bone and joint infection, although the difference was not statistically significant. In comparison with a 67Ga scan, a 99mTc(V)-DMSA scan, in combination with a bone scan, is a reliable way to diagnose bone and joint infection. Both tracers were useful in the diagnosis of bone and joint infection.


Ongoing toxin-positive diphtheria outbreaks in a federal asylum centre in Switzerland, analysis July to September 2022.
Two diphtheria outbreaks occurred in a Swiss asylum center from July to October 2022, one is still ongoing. Outbreaks mainly involved minors and included six symptomatic respiratory diphtheria cases requiring antitoxin. Phylogenomic analyses showed evidence of imported and local transmissions of toxigenic strains in respiratory and skin lesion samples. Given the number of cases (n = 20) and the large genetic diversity accumulating in one centre, increased awareness and changes in public health measures are required to prevent and control diphtheria outbreaks.


The stochastic organization of genomes and the doctrine of energy-information evolution based on bio-antenna arrays.
The article is devoted to the possibilities of considering the evolution of biological systems in connection with the unique emergent properties of antenna arrays, that is, systems of mutually matched antennas widely used in technology. Materials are presented in favor of the proposition that the evolution of biosystems can be formally considered as the evolution of systems of bio-antenna arrays and their energy-information wave activity, which participates in biological computation and contributes to the unification of body parts into a coherent whole. The use of digital antenna arrays in technology is based on their tensor-matrix theory. The author discovers a structural analogy of this theory with the tensor-matrix features of genetic coding systems, as well as algebraic modeling of the universal rules for the stochastic DNA organization of the genomes of higher and lower organisms. This analogy is just one of the facts presented in the article in favor of the usefulness of borrowing knowledge from modern antenna technology to consider the evolution of biosystems. The described new approach may exist along with other known approaches in evolutionary biology.


Patient Preparation and Paradigm Design in fMRI.
Functional magnetic resonance imaging (fMRI) is useful for localizing eloquent cortex in the brain prior to neurosurgery. Language and motor paradigms offer a wide range of tasks to test brain regions within the language and motor networks. With the help of fMRI, hemispheric language dominance can be determined. It also is possible to localize specific motor and sensory areas within the motor and sensory gyri. These findings are critical for presurgical planning. The most important factor in presurgical fMRI is patient performance. Patient interview and instruction time are crucial to ensure that patients understand and comply with the fMRI paradigm.


Determination of polyamines by precolumn derivatization with 9-fluorenylmethyl chloroformate and reverse-phase high-performance liquid chromatography.
A high-performance liquid chromatography (HPLC) method for the determination of picomole levels of polyamines (putrescine, spermidine, and spermine) is described. Amino groups in polyamines react with 9-fluorenylmethyl chloroformate (FMOC) to form stable and highly fluorescent derivatives which can be separated and quantitatively estimated by HPLC in about 12 min. The mean relative elution times (n = 14) for putrescine, spermidine and spermine are 4.21 +/- 0.02, 10.09 +/- 0.02 and 11.19 +/- 0.04 min, respectively. The method has been applied to determine polyamine concentration in rat dorsal root ganglia (DRG) without interference with endogenous amino acids. Polyamine content of individual rat DRG has been calculated and the values are as follows: putrescine, 36.8 +/- 2.01, spermidine, 1652 +/- 131.0 and spermine 388.5 +/- 38.4 pmol/DRG. Information on polyamine concentrations in DRG may be useful in understanding the mechanism of action of toxic chemicals on nervous system.


Observations of the delayed-choice quantum eraser using coherent photons.
Quantum superposition is the cornerstone of quantum mechanics, where interference fringes originate in the self-interference of a single photon via indistinguishable photon characteristics. Wheeler's delayed-choice experiments have been extensively studied for the wave-particle duality over the last several decades to understand the complementarity theory of quantum mechanics. The heart of the delayed-choice quantum eraser is in the mutually exclusive quantum feature violating the cause-effect relation. Here, we experimentally demonstrate the quantum eraser using coherent photon pairs by the delayed choice of a polarizer placed out of the interferometer. Coherence solutions of the observed quantum eraser are derived from a typical Mach-Zehnder interferometer, where the violation of the cause-effect relation is due to selective measurements of basis choice.


Loss of PPR protein Ppr2 induces ferroptosis-like cell death in Schizosaccharomyces pombe.
Ferroptosis is a form of iron- and lipid peroxidation-mediated programmed cell death that occurs widely in mammalian cells. However, this phenomenon is rarely reported in unicellular eukaryotes. Here, we address whether ferroptosis occurs in the model unicellular eukaryote Schizosaccharomyces pombe (S. pombe). Deletion of the pentatricopeptide repeat (PPR) gene ppr2 encoding as a general mitochondrial translation factor required for mitochondrial translation disrupts iron homeostasis and induces oxidative stress, resulting in loss of cell viability. The small-molecular ferroptosis inhibitors deferoxamine (DFO) and ferrostatin-1 (Fer-1) partially rescued the ppr2 deletion-induced cell death. The amount of malondialdehyde, a lipid peroxidation marker, in Δppr2 cells was higher than that in wild type. Using C11-BODIPY 581/591, an oxidation-sensitive fluorescent lipid peroxidation probe, we showed that Δppr2 cells have a large amount of lipid peroxidation compared to wild-type cells. Deletion of ferric reductase transmembrane component 1 (frp1) encoding S. pombe ferric reductase, which is required for ferric iron uptake, partially rescued the cell death of Δppr2 cells. Our results suggest that ppr2 deletion causes an imbalance in iron homeostasis and redox, leading to ferroptosis-like cell death in S. pombe.


Whole-Brain Connectome of GABAergic Neurons in the Mouse Zona Incerta.
The zona incerta (ZI) is involved in various functions and may serve as an integrative node of the circuits for global behavioral modulation. However, the long-range connectivity of different sectors in the mouse ZI has not been comprehensively mapped. Here, we obtained whole-brain images of the input and output connections via fluorescence micro-optical sectioning tomography and viral tracing. The principal regions in the input-output circuits of ZI GABAergic neurons were topologically organized. The 3D distribution of cortical inputs showed rostro-caudal correspondence with different ZI sectors, while the projection fibers from ZI sectors were longitudinally organized in the superior colliculus. Clustering results show that the medial and lateral ZI are two different major functional compartments, and they can be further divided into more subdomains based on projection and input connectivity. This study provides a comprehensive anatomical foundation for understanding how the ZI is involved in integrating different information, conveying motivational states, and modulating global behaviors.


Meal-stimulated gastrin release and calcitonin secretion.
In order to study the effects of a physiologic meal on calcitonin (CT) secretion we studied 6 normal male volunteers (aged 28-34 yr). Each subject was given, on two separate days, either a mixed meal or 200 ml of distilled water, in random order. Gastrin (G) was effectively stimulated by the meal (F = 8.82; p less than 0.001) and reached a peak (with an average 100% increase) 30 min after the end of the meal, slowly decreasing thereafter; no increase was seen after water ingestion. On the other hand, CT levels remained stable throughout the observation period on both occasions. Ionized and total calcium did not show significant variations either after the meal or after water ingestion. These findings suggest that G alone, at the concentrations usually reached after a physiologic meal, is unable to stimulate CT secretion, at least in the absence of calcium increases.


Mediastinal emphysema around the left carotid arteries from a toothbrush impalement injury.
This report describes a case of a pediatric patient with a fever after an oral cavity injury caused by a toothbrush. On physical examination, no bleeds or injuries in his mouth were evident, but diagnostic imaging revealed wide mediastinal emphysema including the left carotid arteries. It shows the importance of carefully examining patients not to miss life-threating conditions.


Aurothiomalate inhibits COX-2 expression in chondrocytes and in human cartilage possibly through its effects on COX-2 mRNA stability.
Cyclooxygenase-2 (COX-2) is expressed in rheumatoid and osteoarthritic cartilage and produces pro-inflammatory prostanoids in the joint. In the present study, we investigated the effects of disease modifying anti-rheumatic drugs on COX-2 expression in chondrocytes. Unlike the other tested drugs, aurothiomalate was found to inhibit COX-2 expression in chondrocytes. In the further studies, effects and mechanisms of action of aurothiomalate were investigated in more detail. Aurothiomalate inhibited IL-1beta-induced COX-2 protein expression and PGE(2) production in chondrocytes in a dose-dependent manner. Because aurothiomalate did not alter IL-1beta-induced mRNA levels when measured 0-3 h after addition of IL-1beta, its effects on COX-2 mRNA degradation were tested by Actinomycin D assay. The half-life of COX-2 mRNA was reduced from 3 h to less than 1.5 h in aurothiomalate-treated cells. The 3'-untranslated region (3'-UTR) of COX-2 mRNA contains an ARE element which has been shown to bind mRNA stabilizing factor HuR. Interestingly, aurothiomalate inhibited HuR expression which may explain its destabilizing effect on COX-2 mRNA. Aurothiomalate reduced COX-2 expression and PGE(2) production also in human cartilage at drug concentrations which have been measured in serum and synovial fluid during treatment with aurothiomalate. The results show that aurothiomalate reduces COX-2 expression and PGE(2) production in chondrocyte cultures and in human cartilage. The action is likely mediated by enhanced COX-2 mRNA degradation possibly through a mechanism related to reduced expression of HuR. The results provide a novel mechanism of action for aurothiomalate which may be important in the treatment of arthritis.


Ethical and Psychosocial Impact of Female Infertility.
This manuscript reviews research from the past year on the ethical and psychosocial impact of infertility on women and men. We discuss several issues surrounding ovarian stimulation, particularly high-order multiple births, egg banking (especially for research purposes), and diminished ovarian reserve. We also present recent work on distress and counseling, which includes greater attention to subgroups of infertile women. More research on issues confronting men has emerged recently, and we outline these with regard to their relationships with infertile women, or as the infertility patient. Last, we outline some ethical issues posed by newer procedures of fertility preservation and uterine transplant.


Medaka--a model organism from the far East.
Genome sequencing has yielded a plethora of new genes the function of which can be unravelled through comparative genomic approaches. Increasingly, developmental biologists are turning to fish as model genetic systems because they are amenable to studies of gene function. Zebrafish has already secured its place as a model vertebrate and now its Far Eastern cousin--medaka--is emerging as an important model fish, because of recent additions to the genetic toolkit available for this organism. Already, the popularity of medaka among developmental biologists has led to important insights into vertebrate development.


Pulmonary problems.
Prevention of pulmonary complications continues to be a major goal of therapy in the care of patients in the postoperative period. Numerous factors, including anesthesia and surgery-induced diaphragmatic dysfunction, reductions in lung volumes and capacities, and release of mediators that damage the endothelium, set the stage for the development of complications such as atelectasis, pneumonia, and ARDS. Nursing assessment focuses on the early identification and evaluation of respiratory distress and degree of oxygen supply/demand imbalance. Intervention focuses on restoration of appropriate ventilation/perfusion matching and provision of adequate oxygen to meet tissue metabolic demands.


Identification and application of threonine aldolase for synthesis of valuable α-amino, β-hydroxy-building blocks.
Chiral β-hydroxy α-amino acid structural motifs are interesting and common synthons present in multiple APIs and drug candidates. To access these chiral building blocks either multistep chemical syntheses are required or the application of threonine aldolases, which catalyze aldol reactions between an aldehyde and glycine. Bioinformatics tools have been utilized to identify the gene encoding threonine aldolase from Vanrija humicola and subsequent preparation of its recombinant version from E. coli fermentation. We planned to implement this enzyme as a key step to access the synthesis of our target API. Beyond this specific application, the aldolase was purified, characterized and the substrate scope of this enzyme further investigated. A number of enzymatic reactions were scaled-up and the products recovered to assess the diastereoselectivity and scalability of this asymmetric synthetic approach towards β-hydroxy α-amino acid chiral building blocks.


Digestion characteristics of polysaccharides from Gracilaria lemaneiformis and its interaction with the human gut microbiota.
The health effects of polysaccharides have attracted lots of attention, but the exact mechanism remains unclear. This study indicated that polysaccharides from Gracilaria lemaneiformis (GLPs) tolerated the conditions of mouth, stomach, and small intestine, and it reached the colon integrally, where it increased the production of short chain fatty acids, altered the gut microbiota, and especially increased the level of Bacteroides. To explore the underlying mechanism, hundreds of Bacteroides strains were isolated from the human feces and identified by MALDI-TOF/MS. It showed that Bacteroides species profile was different between individuals, revealing an inherent difference in the human gut microbiota. The use of Bacteroides on GLPs was species-dependent, and various small molecular GLPs fragments can be liberated from growth of Bacteroides species. On the other hand, Bacteroides species that unable to grow with GLPs can live in GLPs-derived fragments, forming a GLPs utilization network. It should be noted that small molecular GLPs fragments can be easier to be metabolized by intestinal microbes and have better effect on cellular response. It suggested that the effect of polysaccharides cannot only be attributed to modulation of the gut microbiota, but also associated with the effect of microbial degradation on GLPs own activities.


Blockade of OX40/OX40 ligand to decrease cytokine messenger RNA expression in acute renal allograft rejection in vitro.
The aim of this study was to investigate cytokine messenger RNA (mRNA) expression by peripheral blood mononuclear cells (PBMCs) from renal recipients experiencing acute rejection by blocking OX40-OX40L interactions with recombinant human OX40-Fc fusion protein (rhOX40Fc) in vitro. PBMCs were isolated from 20 recipients experiencing acute rejection episodes (rejection group) and 20 recipients with stable graft function (stable group). Levels of Th1 (interferon [IFN]-γ) and Th2 (interleukin [IL]-4) mRNA expressions by PBMCs were measured using real-time reverse transcriptase-polymerase chain reactions. IFN-γ mRNA expression levels were significantly higher in the rejection than the stable group (P < .05). Levels of IL-4 mRNA expression were not significantly different. Among the rejection group, rhOX40Fc reduced significantly the expression of IFN-γ and IL-4 mRNA by anti-CD3-monoclonal antibody stimulated PBMCs (P < .05, and P < .01, respectively). Blocking of the interaction between OX40 and OX40L in vitro inhibited production of Thl and Th2 type cytokines.


Purification, characterization and immunolocalization of fimbrial protein from Porphyromonas (bacteroides) gingivalis.
Rapid and reproducible method is described here for the purification of the 43 kDa fimbrial protein from P. gingivalis by preferential fractionation in the presence of 1% SDS and 0.2M of a bivalent cation at pH 6.5. Homogeneity of the purified 43 kDa was confirmed by SDS-PAGE and Western blot analysis using monoclonal and polyclonal antibodies raised against this protein. Amino acid composition and the amino acid sequence of the first 30 amino acid residues of the purified fimbriae are consistent with the composition and sequence predicted from the cloned gene of the fimbrial subunit. Circular dichroism spectra shows high levels of beta-sheet structure. The purified 43 kDa polymer shows fimbriae-like morphology under the electron microscope. Ultrastructural localization of the 43 kDa protein by the immunogold technique revealed specific labeling of the fimbriae with a diameter of approximately 3.5 to 5.0 nm. Localization of this protein suggest that the 43 kDa component is a fimbrial subunit.


The effects of sunitinib malate used in targeted therapy on the proliferation of HeLa cells in vitro.
In this study, the antiproliferative and apoptotic effects of sunitinib (SU-11248, Sutent) which is used for targeted therapy was evaluated on HeLa cell line originated from human cervix carcinoma. Three different doses of sutent (D1= 1 μM, D2= 5 μM, D3= 10 μM) were administered to cells for 72 h to determine the optimal dose. Increase in apoptotic index (AI), decrease in mitotic index (MI) of cells and slow down in proliferation rate were achieved at the dose level of 10 μM, especially at 72 h. All these findings were statistically significant (p<0.001). In addition, anaphase bridges and existence of tripolar metaphase cells that were observed at 72 h were possibly attributable to a chromosomal instability arising from shortening of telomere. In this study, sutent effected cell kinetic parameters significantly. These results are consistent with other studies in the literature. In addition, anaphase bridges which were seen in mitosis preparations were interpreted as shortening or degradation of the telomere.


The relationship between transepithelial sodium movement and potential difference in the larva of Camptochironomus tentans (Fabr.) and some observations on the accumulation of other ions.
In fourth instar larvae of Camptochironomus tentans, net sodium uptake from 2 mM-NaCl has an electrogenic component. During net uptake the transepithelial potential (TEP) alters from a value of approximately - 40 mV (sign refers to haemolymph), in depleted animals, to approximately o mV. The TEP in depleted larvae is dependent upon external sodium concentration above about I mM-Na+, becoming increasingly electropositive (haemolymph relative to medium) at high sodium concentrations. This effect is exaggerated in Na2SO4 compared with NaCl. At an external concentration of 2mM-NaCl, chloride is carried by an electroneutral mechanism, probably a closely coupled Cl-/anion exchange. However, it is possible that chloride transport could become somewhat electrogenic at higher concentrations. Lithium competes with sodium for the electrogenic pump. Observed TEPs differ greatly from those required to maintain passively the haemolymph concentrations of sodium and chloride.


Effects of sphingosine and sphingosine analogues on the free radical production by stimulated neutrophils: ESR and chemiluminescence studies.
Sphingolipids inhibit the activation of the neutrophil (PMN) NADPH oxidase by protein kinase C pathway. By electron spin resonance spectroscopy (ESR) and chemiluminescence (CL), we studied the effects of sphingosine (SPN) and ceramide analogues on phorbol 12-myristate 13-acetate (PMA, 5x10(-7) M) stimulated PMN (6x10(6) cells). By ESR with spin trapping (100 mM DMPO: 5,5-dimethyl-1-pyrroline-Noxide), we showed that SPN (5 to 8x10(-6) M), C2-ceramide (N-acetyl SPN) and C6-ceramide (N-hexanoyl SPN) at the final concentration of 2x10(-5) and 2x10(-4) M inhibit the production of free radicals by stimulated PMN. The ESR spectrum of stimulated PMN was that of DMPO-superoxide anion spin adduct. Inhibition by 5x10(-6) M SPN was equivalent to that of 30 U/ml SOD. SPN (5 to 8x10(-6) M) has no effect on in vitro systems generating superoxide anion (xanthine 50 mM/xanthine oxidase 110 mU/ml) or hydroxyl radical (Fenton reaction: 88 mM H2O2, 0.01 mM Fe2+ and 0.01 mM EDTA). SPN and N-acetyl SPN also inhibited the CL of PMA stimulated PMN in a dose dependent manner (from 2x10(-6) to 10(-5) M), but N-hexanoyl SPN was less active (from 2x10(-5) to 2x10(-4) M). These effects were compared with those of known PMN inhibitors, superoxide dismutase, catalase and azide. SPN was a better inhibitor compared with these agents. The complete inhibition by SPN of ESR signal and CL of stimulated PMN confirms that this compound or one of its metabolites act at the level of NADPH-oxidase, the key enzyme responsible for production of oxygen-derived free radicals.