Rapid Deployment of Inpatient Telemedicine In Response to COVID-19 Across Three Health Systems.
To reduce pathogen exposure, conserve personal protective equipment, and facilitate health care personnel work participation in the setting of the COVID-19 pandemic, three affiliated institutions rapidly and independently deployed inpatient telemedicine programs during March 2020. We describe key features and early learnings of these programs in the hospital setting. Relevant clinical and operational leadership from an academic medical center, pediatric teaching hospital, and safety net county health system met to share learnings shortly after deploying inpatient telemedicine. A summative analysis of their learnings was re-circulated for approval. All three institutions faced pressure to urgently standup new telemedicine systems while still maintaining secure information exchange. Differences across patient demographics and technological capabilities led to variation in solution design, though key technical considerations were similar. Rapid deployment in each system relied on readily available consumer-grade technology, given the existing familiarity to patients and clinicians and minimal infrastructure investment. Preliminary data from the academic medical center over one month suggested positive adoption with 631 inpatient video calls lasting an average (standard deviation) of 16.5 minutes (19.6) based on inclusion criteria. The threat of an imminent surge of COVID-19 patients drove three institutions to rapidly develop inpatient telemedicine solutions. Concurrently, federal and state regulators temporarily relaxed restrictions that would have previously limited these efforts. Strategic direction from executive leadership, leveraging off-the-shelf hardware, vendor engagement, and clinical workflow integration facilitated rapid deployment. The rapid deployment of inpatient telemedicine is feasible across diverse settings as a response to the COVID-19 pandemic.


"I thought I was going to die": Experiences of COVID-19 patients managed at home in Uganda.
In Uganda, approximately 170,000 confirmed COVID-19 cases and 3,630 deaths have been reported as of January 2023. At the start of the second COVID-19 wave, the Ugandan health system was overwhelmed with a sudden increase in the number of COVID-19 patients who needed care, and the Ministry of Health resorted to home-based isolation and care for patients with mild to moderate disease. Before its rollout, the COVID-19 home-based care strategy had neither been piloted nor tested in Uganda. To explore the experiences of COVID-19 patients managed at home in Uganda. This was a qualitative study that was conducted to explore the lived experiences of COVID-19 patients managed at home. The study was carried out among patients who presented to three hospitals that were designated for treating COVID-19 patients in Uganda. COVID-19 patients diagnosed at these hospitals and managed at home were followed up and contacted for in-depth telephone interviews. The data were analysed using thematic content analysis with the aid of NVIVO 12.0.0 (QRS International, Cambridge, MA). Participants experienced feelings of fear and anxiety: fear of death, fear of losing jobs, fear of infecting loved ones and fear of adverse events such as loss of libido. Participants also reported feelings of loneliness, hopelessness and depression on top of the debilitating and sometimes worsening symptoms. In addition to conventional medicines, participants took various kinds of home remedies and herbal concoctions to alleviate their symptoms. Furthermore, COVID-19 care resulted in a high economic burden, which persisted after the COVID-19 illness. Stigma was a major theme reported by participants. Participants recommended that COVID-19 care should include counselling before testing and during and after the illness to combat the fear and stigma associated with the diagnosis. Another recommendation was that health workers should carry out home visits to patients undergoing home-based care and that COVID-19 treatment should be free of charge. COVID-19 home-based care was associated with fear, anxiety, loneliness, depression, economic loss and stigma. Policymakers should consider various home-based follow-up strategies and strengthen counselling of COVID-19 patients at all stages of care.


Associations of the Mediterranean-DASH Intervention for Neurodegenerative Delay diet with brain structural markers and their changes.
The associations of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with brain structural changes are unclear. Among 26,466 UK Biobank participants, a 15-point MIND score was calculated from 24-hour diet recalls from 2009 to 2012. We assessed its associations with 17 magnetic-resonance-derived brain volumetric markers and their longitudinal changes and explored whether genetic factors modify the associations. Higher MIND adherence was associated with larger volumes of thalamus, putamen, pallidum, hippocampus, and accumbens (beta per 3-unit increment ranging from 0.024 to 0.033) and lower white matter hyperintensities (P-trends < 0.05), regardless of genetic predispositions of Alzheimer's disease. MIND score was not associated with their longitudinal changes (P > 0.05) over a median of 2.2 years among participants with repeated imaging assessments (N = 2963), but was associated with slower atrophy in putamen (beta: 0.026, P-trend = 0.044) and pallidum (beta: 0.030, P-trend = 0.033) among APOE ε4 non-carriers (N = 654). The MIND diet showed beneficial associations with certain brain imaging markers, and its associations with long-term brain structural changes warrants future investigation. Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet was significantly associated with higher volumes and larger gray matter volumes in certain brain regions in UK adults, and the associations were not modified by genetic factors. No significant associations were observed between MIND diet and longitudinal changes in the investigated brain structural markers over a median of 2.2 years. Higher MIND score was significantly associated with slower atrophy in the putamen and pallidum among APOE ε4 non-carriers.


A highly sensitive living probe derived from nanoparticle-remodeled neutrophils for precision tumor imaging diagnosis.
Timely and precise diagnosis of malignant tumors is of great value to patients' treatment and prognosis. Although nanotechnology-based molecular imaging represents a major advancement in the field of tumor imaging diagnosis, it is restricted by the rapid blood clearance of nanoparticles and the diverse physiological barriers in vivo; hence, its further application is greatly hindered. Cell carriers, ascribed to their natural biological properties, are thus gaining increasing attention for addressing such issues. Here, taking full advantage of the inflammation-homing capability of neutrophils, we constructed a highly sensitive cell probe in which reduced bovine-serum albumin (BSA) nanoparticles, loaded with imaging agents (gadolinium (Gd) and BODIPY), were covalently fixed onto the cellular surface by 5-thio-2-nitrobenzoate (TNB)-mediated fast and efficient disulfide-thiol exchange. Impressively, the remodeling process exerted a negligible effect on the neutrophils' biological profiles with regard to cell viability, morphology, and cell-surface protein markers. Compared with nanoparticle-based imaging agents in a lung-cancer xenograft model, the living neutrophil probe demonstrated faster targeting and stronger accumulation in the tumor site, as revealed by fluorescence and magnetic-resonance (MR) imaging. These results indicate the great potential of neutrophil-based living probe for precision tumor-diagnosis applications.


TIMI risk index and the benefit of enoxaparin in patients with ST-elevation myocardial infarction.
The purpose of the study was to evaluate the cause of death, risk of nonfatal complications, and relative outcomes with an enoxaparin versus unfractionated heparin strategy in ST-elevation myocardial infarction stratified using the Thrombolysis in Myocardial Infarction (TIMI) Risk Index (TRI). We evaluated 30-day outcomes in 19,941 patients with ST-elevation myocardial infarction treated with fibrinolysis and unfractionated heparin or enoxaparin. Patients were categorized on the basis of prespecified ranges of the TRI [heart rate x (age/10)2/systolic blood pressure]. There was a strongly graded increase in 30-day mortality with increasing TRI (1.2%-20.7%, P<.0001). The proportion of deaths due to mechanical causes (congestive heart failure, shock, and myocardial rupture) increased progressively with the TRI. There also was a significant positively graded association between the TRI and nonfatal heart failure or shock (0.4%-4.4%, P<.0001). In contrast, death resulting from recurrent ischemic events predominated in the lowest TRI group. The relative reduction in death/myocardial infarction with the enoxaparin strategy appeared inversely graded with the TRI. There was a 38% reduction in the lowest risk group (relative risk 0.62, 95% confidence interval 0.45-0.86) and a decrease in the relative benefit of enoxaparin with increasing risk index. The TRI was a strong predictor of all-cause mortality in a broad population, with a positive association with the risk of death due to mechanical complications and an inverse association with deaths due to recurrent ischemia. The enoxaparin strategy was superior to unfractionated heparin in a majority of patients with ST-elevation myocardial infarction, except for the group at the highest risk for severe mechanical complications, in whom the 2 anticoagulant strategies showed similar results.


Gene expression and chromosomal location for susceptibility to Sjögren's syndrome.
Primary Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease affecting mainly the exocrine glands. Its physio-pathology is poorly understood and most of the knowledge has been related to the inflammatory component. The aim of this work was to evaluate gene expression profiling in fractions enriched in epithelial cells from labial salivary glands (LSGs) of patients with primary SS and identify chromosomal regions harboring susceptibility genes expressed in epithelial cells. A combined approach of gene expression and genome-wide association study was used. Enriched epithelial cell fractions were obtained from LSGs of patients and controls. Amplified total RNA was labeled and hybridized to 10K cDNA microarrays. Results were normalized and subjected to statistical and functional analysis. A genome-wide microsatellite screen at 10 cM resolution (393 markers) was performed. In salivary gland-epithelial cells from patients 528 genes were expressed differentially in comparison to controls. Pathways not previously linked to disease were found to be altered. Twenty-eight and 15 genes associated with apoptosis were up-regulated and down regulated, respectively. Interferon-related genes, most of which participated in interferon signaling, were also found to be up-regulated. From the genome-wide screen, 6 markers showed evidence of highly significant association with the disease. Of these, five loci harbor genes differentially expressed in patients LSG-epithelial cells. Our results show that in enriched gland-epithelial cells of pSS, both pro-apoptotic/anti-apoptotic and interferon signaling inhibition/stimulation balances may occur. Genes found over-expressed in epithelial cells are candidates for disease susceptibility.


Moral habitus: An approach to understanding embedded disrespectful practices.
The moral habitus shows how morally oriented clinical interactions through everyday social evaluations generate and sustain disrespectful attitudes and behaviours that disregard patients and family members. These attitudes and behaviours often result from the habitual nature of interaction styles and embodied bodily dispositions within particular hospital settings. By utilising the data of a qualitative study in two hospitals in the south Indian city of Chennai, I illustrate the role of moral habitus in understanding these disrespectful attitudes and behaviours. I show how the stereotyping and embodied bodily dispositions by healthcare professionals raise moral and ethical questions, such as those related to ethical value of respect for persons. I conclude that studying the moral habitus of hospital settings is significant for proposing ways to respect patients and family members of patients in practice and uphold ethical values, and to have meaningful healthcare interactions. Furthermore, the concept of moral habitus offers theoretical grounds for understanding these attitudes and behaviours in hospital settings, while engaging in ethics and patient-centred care debates, to bridge the gap between theory and practice of respect.


Genetic moderation of interpersonal psychotherapy efficacy for low-income mothers with major depressive disorder: implications for differential susceptibility.
Genetic moderation of interpersonal psychotherapy (IPT) efficacy for economically disadvantaged women with major depressive disorder was examined. Specifically, we investigated whether genotypic variation in corticotropin releasing hormone receptor 1 (CRHR1) and the linked polymorphic region of the serotonin transporter gene (5-HTTLPR) moderated effects of IPT on depressive symptoms over time. We also tested genotype moderation of IPT mechanisms on social adjustment and perceived stress. Non-treatment-seeking urban women at or below the poverty level with infants were recruited from the community (N = 126; M age = 25.33 years, SD = 4.99; 54.0% African American, 22.2% Caucasian, and 23.8% Hispanic/biracial) and randomized to individual IPT or Enhanced Community Standard groups. The results revealed that changes in depressive symptoms over time depended on both intervention group and genotypes (5-HTTLPR and CRHR1). Moreover, multiple-group path analysis indicated that IPT improved depressive symptoms, increased social adjustment, and decreased perceived stress at posttreatment among women with the 0 copies of the CRHR1 TAT haplotype only. Finally, improved social adjustment at postintervention significantly mediated the effect of IPT on reduced depressive symptoms at 8 months postintervention for women with 0 copies of the TAT haplotype only. Post hoc analyses of 5-HTTLPR were indicative of differential susceptibility, albeit among African American women only.


A lower Instability Severity Index score threshold may better predict recurrent anterior shoulder instability after arthroscopic Bankart repair: a systematic review.
The Instability Severity Index (ISI) score was developed to evaluate a patient's risk of recurrent shoulder instability following arthroscopic Bankart repair. While patients with an ISI score of >6 were originally recommended to undergo an open procedure (ie, Latarjet) to minimise the risk of recurrence, recent literature has called into question the utility of the ISI score. The purpose of this systematic review was to evaluate the efficacy of the ISI score as a tool to predict postoperative recurrence among patients undergoing arthroscopic Bankart procedures. Articles were included if study participants underwent arthroscopic Bankart repair for anterior shoulder instability and reported postoperative recurrence by ISI score at a minimum of 2 years of follow-up. Methodological study quality was assessed using the Methodological Index for Non-Randomized Studies criteria. Pearson's χ2 test was used to compare recurrence rates among patients above and below an ISI score of 4. Sensitivity, specificity, mean ISI scores and predictive value of individual factors of the ISI score were qualitatively reviewed. Four studies concluded the ISI score was effective in predicting postoperative recurrence following arthroscopic Bankart repair; however, these studies found threshold values lower than the previously proposed score of >6 may be more predictive of recurrent instability. A pooled analysis of these studies found patients with an ISI score <4 to experience significantly lower recurrence rates when compared with patients with a score ≥4 (6.3% vs 26.0%, p<0.0001). The mean ISI score among patients who experienced recurrent instability was also significantly higher than those who did not. The ISI score as constructed by Balg and Boileau may have clinical utility to help predict recurrent anterior shoulder instability following arthroscopic Bankart repair. However, this review found the threshold values published in their seminal article to be insufficient predictors of recurrent instability. Instead, a lower score threshold may provide as a better predictor of failure. The paucity of level I and II investigations limits the strength of these conclusions, suggesting a need for further large, prospective studies evaluating the predictive ability of the ISI score. IV.


Hemogram changes in lactating dairy cows given human recombinant granulocyte colony stimulating factor (r-MethuG-CSF).
As a prelude to mammary gland challenge experiments, this investigation was implemented to assess the hematologic changes in lactating dairy cattle induced by two dosage regimes of human recombinant colony stimulating factor (Hr-GCSF). This study documents the capability of the human recombinant colony stimulating factor to produce hematologic changes in both a time and dose dependent manner when administered to the adult lactating bovine. A screening dose of 1 microgram/kg of Hr-GCSF administered to three study subjects produced a three- to four-fold increase in peripheral blood mature neutrophil counts (P less than 0.043) by day 12 of the trial. The priming dose treatment group of four lactating cows (3 micrograms/kg of Hr-GCSF) exhibited a three- to five-fold increase in peripheral blood mature neutrophil counts (P less than 0.05) and two- to three-fold increases in white blood cell counts by day 5 of the trial. Hematologic examinations of the control group (n = 4; no Hr-GCSF administration) did not detect significant changes in their neutrophil counts over baseline values. The milk somatic cell counts did not statistically shift over baseline values in any of the control or Hr-GCSF treatment groups. When attempting to alter the course of infectious disease processes, potential applications of colony stimulating factors provide interesting speculations about new therapeutic modalities.


Long-term response to fractionated radiotherapy of presumed optic nerve sheath meningioma.
BACKGROUND/AIMS To review the long-term results of treatment of optic nerve sheath meningiomas (ONSMs) with conformal radiotherapy. METHODS Eleven patients with presumed ONSM were treated with fractionated conformal radiotherapy using 45-54 Gy in 25-30 fractions and followed for more than 5 years. Affected eye visual acuity in logMAR notation, colour vision, threshold perimetry, mean deviation (dB) and imaging were studied before and after treatment. ANALYSIS Included adverse effects of treatment and the frequency of affected eye maintained or improved vision. RESULTS There were nine women and two men with a mean age of 45.3. Vision or field loss was the most common presentation. All had abnormal MR imaging. The follow-up period after radiotherapy was 61-156 months (mean 89.6). Visual acuity was unchanged or improved in 10 patients (91%). The average difference between pretreatment and final logMAR visual acuity was 0.08, while the average difference in visual-field mean deviation was -4.63 dB. The radiographic appearance of the tumours was stable in size in nine patients and decreased in two. No major side effects from radiation were seen. CONCLUSIONS Vision, MRI and complication outcomes are favourable for using fractionated conformal radiotherapy for ONSM.


Clinical experiences of fetal ovarian cyst: diagnosis and consequence.
Ovarian cysts are the most frequent, prenatally diagnosed intra-abdominal cysts. Fetal ovarian cyst often presents complication such as torsion and seems to be an indication for surgical intervention. In this study, we reviewed pre- and post-natal medical records and ultrasonography of 17 fetuses that were diagnosed with ovarian cysts. In a total of 17 cases, postnatal surgery was performed in 7 infants. Of these cases, four cases of ovarian cyst torsion were confirmed. In the remaining 10 fetuses, one case regressed completely during pregnancy, and the other nine cases including two complex cysts resolve spontaneously after birth. Postnatal symptomatic cysts or cysts with a diameter greater than 5 cm that do not regress or enlarge should be treated, but uncomplicated asymptomatic cysts less than 5 cm in diameter should only be observed and reassessed by serial ultrasonography. If they regress spontaneously, no surgical intervention is necessary independent of their sonographic findings.


Altered binding of the NF-GMa transcription factor is involved in the upregulated production of TNF-alpha by macrophages of mammary tumor bearing mice.
Macrophages from D1-DMBA-3 mammary tumor bearing mice have profound alterations in various functions, i.e. diminished antigen presentation, decreased cytolytic activity and depressed synthesis of IL-12. In contrast, these cells display a significant enhancement in the levels of TNF-alpha, which may be involved in the cachexia observed in animals bearing large mammary tumors. The molecular mechanisms involved in the upregulation of TNF-alpha in macrophages from tumor bearers were investigated. The levels of TNF-alpha RNA were increased in macrophages from tumor bearers, but, this was not due to an increase in the RNA half-life. An analysis of the binding of transcription factors relevant to the TNF-alpha gene regulatory region by electrophoretic mobility shift assays (EMSA) revealed no differences in the binding of any NF-kB complex component between macrophages from normal and tumor bearing mice. Likewise, there were no changes in the binding patterns of SP-1 and NF-Y. In contrast, the binding of the transcription factor, NF-GMa, was altered in macrophages from tumor bearers. Our results and those reported in other models of disease suggest that the excessive production of cytokines in pathological conditions, could be the result of alterations of the production and/or binding of transcription factors.


The half-bridge component Kar1 promotes centrosome separation and duplication during budding yeast meiosis.
The budding yeast centrosome, often called the spindle pole body (SPB), nucleates microtubules for chromosome segregation during cell division. An appendage, called the half bridge, attaches to one side of the SPB and regulates SPB duplication and separation. Like DNA, the SPB is duplicated only once per cell cycle. During meiosis, however, after one round of DNA replication, two rounds of SPB duplication and separation are coupled with homologue segregation in meiosis I and sister-chromatid segregation in meiosis II. How SPB duplication and separation are regulated during meiosis remains to be elucidated, and whether regulation in meiosis differs from that in mitosis is unclear. Here we show that overproduction of the half-bridge component Kar1 leads to premature SPB separation during meiosis. Furthermore, excessive Kar1 induces SPB overduplication to form supernumerary SPBs, leading to chromosome missegregation and erroneous ascospore formation. Kar1--mediated SPB duplication bypasses the requirement of dephosphorylation of Sfi1, another half-bridge component previously identified as a licensing factor. Our results therefore reveal an unexpected role of Kar1 in licensing meiotic SPB duplication and suggest a unique mechanism of SPB regulation during budding yeast meiosis.


KSHV SOX mediated host shutoff: the molecular mechanism underlying mRNA transcript processing.
Onset of the lytic phase in the KSHV life cycle is accompanied by the rapid, global degradation of host (and viral) mRNA transcripts in a process termed host shutoff. Key to this destruction is the virally encoded alkaline exonuclease SOX. While SOX has been shown to possess an intrinsic RNase activity and a potential consensus sequence for endonucleolytic cleavage identified, the structures of the RNA substrates targeted remained unclear. Based on an analysis of three reported target transcripts, we were able to identify common structures and confirm that these are indeed degraded by SOX in vitro as well as predict the presence of such elements in the KSHV pre-microRNA transcript K12-2. From these studies, we were able to determine the crystal structure of SOX productively bound to a 31 nucleotide K12-2 fragment. This complex not only reveals the structural determinants required for RNA recognition and degradation but, together with biochemical and biophysical studies, reveals distinct roles for residues implicated in host shutoff. Our results further confirm that SOX and the host exoribonuclease Xrn1 act in concert to elicit the rapid degradation of mRNA substrates observed in vivo, and that the activities of the two ribonucleases are co-ordinated.


Unravelling the relationship between protein sequence and low-complexity regions entropies: Interactome implications.
Low-complexity regions are sub-sequences of biased composition in a protein sequence. The influence of these regions over protein evolution, specific functions and highly interactive capacities is well known. Although protein sequence entropy has been largely studied, its relationship with low-complexity regions and the subsequent effects on protein function remains unclear. In this work we propose a theoretical and empirical model integrating the sequence entropy with local complexity parameters. Our results indicate that the protein sequence entropy is related with the protein length, the entropies inside and outside the low-complexity regions as well as their number and average size. We found a small but significant increment in the sequence entropy of hubs proteins. In agreement with our theoretical model, this increment is highly dependent of the balance between the increment of protein length and average size of the low-complexity regions. Finally, our models and proteins analysis provide evidence supporting that modifications in the average size is more relevant in hubs proteins than changes in the number of low-complexity regions.


Bacteria encapsulated electrospun nanofibrous webs for remediation of methylene blue dye in water.
In this study, preparation and application of novel biocomposite materials that were produced by encapsulation of bacterial cells within electrospun nanofibrous webs are described. A commercial strain of Pseudomonas aeruginosa which has methylene blue (MB) dye remediation capability was selected for encapsulation, and polyvinyl alcohol (PVA) and polyethylene oxide (PEO) were selected as the polymer matrices for the electrospinning of bacteria encapsulated nanofibrous webs. Encapsulation of bacterial cells was monitored by scanning electron microscopy (SEM) and fluorescence microscopy, and the viability of encapsulated bacteria was checked by live/dead staining and viable cell counting assay. Both bacteria/PVA and bacteria/PEO webs have shown a great potential for remediation of MB, yet bacteria/PEO web has shown higher removal performances than bacteria/PVA web, which was probably due to the differences in the initial viable bacterial cells for those two samples. The bacteria encapsulated electrospun nanofibrous webs were stored at 4°C for three months and they were found as potentially storable for keeping encapsulated bacterial cells alive. Overall, the results suggest that electrospun nanofibrous webs are suitable platforms for preservation of living bacterial cells and they can be used directly as a starting inoculum for bioremediation of water systems.


Don't ask, don't tell: patterns of HIV disclosure among HIV positive men who have sex with men with recent STI practising high risk behaviour in Los Angeles and Seattle.
A high incidence of HIV continues among men who have sex with men (MSM) in industrialised nations and research indicates many MSM do not disclose their HIV status to sex partners. Themes as to why MSM attending sexually transmitted infection (STI) clinics in Los Angeles and Seattle do and do not disclose their HIV status are identified. 55 HIV positive MSM (24 in Seattle, 31 in Los Angeles) reporting recent STI or unprotected anal intercourse with a serostatus negative or unknown partner from STI clinics underwent in-depth interviews about their disclosure practices that were tape recorded, transcribed verbatim, coded, and content analysed. HIV disclosure themes fell into a continuum from unlikely to likely. Themes for "unlikely to disclose" were HIV is "nobody's business," being in denial, having a low viral load, fear of rejection, "it's just sex," using drugs, and sex in public places. Themes for "possible disclosure" were type of sex practised and partners asking/disclosing first. Themes for "likely to disclose" were feelings for partner, feeling responsible for partner's health, and fearing arrest. Many reported non-verbal disclosure methods. Some thought partners should ask for HIV status; many assumed if not asked then their partner must be positive. HIV positive MSM's decision to disclose their HIV status to sex partners is complex, and is influenced by a sense of responsibility to partners, acceptance of being HIV positive, the perceived transmission risk, and the context and meaning of sex. Efforts to promote disclosure will need to address these complex issues.


Impact of microbial/plant interactions on the transformation of polycyclic aromatic hydrocarbons in rhizosphere of Festuca arundinacea.
The promotion of polycyclic aromatic hydrocarbon (PAH) degradation was demonstrated in the rhizosphere of Festuca arundinacea with Pseudomonas fluorescens. P. fluorescens 5RL more significantly interacted with salicylate and dextrose in the agar containing tall fescue than agar without plant roots. Although the presence of tall fescue did not promote catabolic enzyme induction in the absence of salicylate, an increase in dioxygenase activity relative to no plant controls implies that this plant may enhance the degradation of PAHs or facilitate the genotypes that are capable of transforming PAH in the rhizosphere.


Efficacy and tolerance of zopiclone in insomniac geriatric patients.
Zopiclone is a cyclopyrrolone derivative which exerts, in animal and man, an hypnotic activity comparable to that of flurazepam. In healthy adult insomniacs it was well tolerated upon repeated administration for 28 days. In a double-blind, placebo-controlled, crossover study, three dose levels of zopiclone (5, 7.5, and 10 mg) were compared to 15 mg of flurazepam in 30 geriatric insomniacs. The 7.5- and 10-mg doses demonstrated hypnotic potency comparable to that of flurazepam, and the active treatments were superior to placebo. For most sleep indices, 7.5 mg was the optimal therapeutic dose. Few side effects were reported. These were not clinically significant. Zopiclone is efficacious and well tolerated in the treatment of geriatric patients suffering from insomnia. A dosage range of 7.5-10 mg is recommended.


Incidence and risk of high-grade stomatitis with mTOR inhibitors in cancer patients.
Inhibitors of the mammalian target of rapamycin (mTOR) pathway including everolimus and temsirolimus have been used extensively in cancer patients. Their use is associated with stomatitis, an adverse event resulting in morbidity and treatment interruptions or discontinuation. This study was conducted to determine the overall incidence and risk of stomatitis in cancer patients treated with the mTOR inhibitors by a meta-analysis of randomized controlled clinical trials (RCTs). Databases from PubMed and abstracts presented at the American Society of Clinical Oncology annual meetings up to October 2013 were searched for relevant studies. Eligible studies included RCTs using everolimus and temsirolimus at approved doses in cancer patients. Summary incidences, relative risks (RR), and 95% confidence intervals (CI) were calculated using a random- or fixed-effects model depending on the heterogeneity of the included trials. A total of 11 RCTs with 4,752 patients (mTORs: 2,725, controls: 2,027) with a variety of solid tumors were included in the analysis. The incidences of all-grade (grade 1-4) and high-grade stomatitis (grade 3-4) were 33.5% (95% CI: 21.9-47.6%) and 4.1% (95% CI: 2.6-6.3%), respectively. The incidence of high-grade stomatitis significantly varied with tumor types (p=.004), and mTOR inhibitors (temsirolimus vs. everolimus, p<.001). In comparison with controls, mTOR inhibitors significantly increased the risk for developing all-grade stomatitis (RR: 4.04, 95% CI: 3.13-5.22, p<.001) and high-grade stomatitis (RR: 8.84, 95% CI: 4.07-19.22, p<.001). The mTOR inhibitors everolimus and temsirolimus significantly increased the risk of high-grade stomatitis in cancer patients. Efforts towards the prevention, treatment, and identification of individuals at risk may allow for improved quality of life and consistent dosing.


Influence of setup errors on spinal cord dose and treatment plan quality for cervical spine tumours: a phantom study for photon IMRT and heavy charged particle radiotherapy.
Tumours partly surrounding the cervical spine may be treated by conformal radiotherapy (RT) using intensity-modulated RT (IMRT) with photons or heavy charged particle RT. For both, a high setup accuracy is required to spare the radiosensitive spinal cord, if a high dose is to be delivered. A phantom study was performed to determine the variation of the dose to the spinal cord surface by predefined setup errors. The measured doses were compared to those calculated by the treatment planning programme. The influence of systematic setup errors on characteristic parameters of the treatment plan quality was quantified. The largest variation of the mean and maximum doses to the spinal cord due to setup errors was significantly larger for carbon ions than for IMRT (mean: 11.9% versus 3.9%, max: 29.2% versus 10.8% of the prescribed dose). For the comparison of measured and calculated doses, mean deviations of 3% (IMRT) and 6% (carbon ions) of the prescribed dose were obtained. These deviations have to be considered, when the spinal cord dose is assessed from the treatment plan and they may also influence the dose prescription. Carbon ions yield better values for coverage (99.9% versus 93.1%) and conformality (110% versus 126%) of the PTV as compared to IMRT, while the spinal cord is better spared. Dose distributions produced with carbon ions, however, are more sensitive to setup errors, which have to be considered during treatment.


Prediction of radiotherapy effect by diffusion-weighted imaging in esophageal carcinoma xenograft model.
This study was to evaluate the value of diffusion-weighted imaging (DWI) in predicting the efficacy of radiotherapy for esophageal cancer from xenograft model level. Thirty-two tumor-bearing mice from the Eca-109 cell line nude mice models were established. The experimental group (n = 16) received a single dose of 15 Gy (6MV X-ray), whereas the control group (n = 16) did not receive any treatment. The tumor volume and apparent diffusion coefficient (ADC) were obtained. The cell density, tissue necrosis ratio, and CD31 expression were determined at matched time points. The tumor volume was smaller in the experimental group than in the control group (P < 0.05) on the 7th day after radiotherapy (1.580 ± 0.965 cm3 vs. 2.671 ± 0.915 cm3). The ADC values were higher in the experimental group than in the control group on the 3rd day (P < 0.05) (998.15 ± 163.76 ×10- 6 mm2/s vs. 833.32 ± 142.15 ×10- 6 mm2/s). On the 3rd day after radiotherapy, the differences in cell density and necrosis ratio between the two groups were statistically significant; the tumor cell density was lower in the experimental group (25.56 ± 1.40%) than in the control group (33.48 ± 4.18%) (P < 0.05), and the proportion of tissue necrosis was higher in the experimental group (32.19 ± 1.21%) than in the control group (29.16 ± 2.16%) (P < 0.05). The negative and weak positive rate of CD31 expression in the experimental group was higher than the control group, whereas the generally positive and strong positive rate of CD31 expression was significantly lower than the control group in the early stage (P < 0.05). ADC values may change at the early stage before the morphological changes of tumors. Changes in cell density and necrosis ratio of transplanted tumors correspond to the changes in ADC values. DWI can be used for the early prediction of esophageal cancer radiotherapy efficacy.


The Duration of Hardware Retention After Radiologic Union of Surgically Treated Femoral Neck Fractures in Children May Predict the Aggravation or Occurrence of Avascular Necrosis of the Femoral Head or Neck After Hardware Removal.
The incidence of aggravation or occurrence of avascular necrosis (AVN) following hardware removal in surgically treated pediatric femoral neck fractures who achieved radiologic consolidation is unknown. This study aimed to investigate the risk factors for this complication. Seventy-one pediatric (mean age: 9.8±3.9 y) were retrospectively analyzed. Risk factors (age, sex, laterality, severity of initial displacement, type of fracture, time from trauma to reduction, reduction and fixation method, quality of reduction, time required to achieve radiologic union, duration of hardware retention, presence of AVN before hardware removal and follow-up time) were recorded. The severity of AVN was assessed based on radiographs with Ratliff's classification. Following hardware removal, the aggravation/occurrence of AVN was detected in 11 hips (15.5%). Among the 5 hips (7%) with aggravation of AVN, 1 (1.4%) with type II AVN and 3 (4.2%) with type III AVN exhibited aggravation of type I AVN, while the remaining hip (1.4%; type I) showed enlargement of the involved AVN area. Six hips (8.5%) developed AVN following hardware removal: 2 (2.8%) were classified as type I and 4 (5.6%) as type III. Receiver operating characteristic curve analysis indicated that hardware retention >7 months after union is associated with a decreased rate of aggravation or occurrence of AVN of the femoral neck or head following hardware removal. The incidence of aggravation or occurrence of AVN following hardware removal in surgically treated pediatric femoral neck fractures is 15.5%; hardware retention >7 months after radiologic union may reduce the risk of aggravation or occurrence of AVN of the femoral neck or head postimplant removal. Level III.


Assessment of the depth of anaesthesia during inhalational and intravenous induction of general anaesthesia.
Tracheal intubation is one of the strongest stimuli during general anaesthesia and may result in an insufficient depth of anaesthesia. The aim of the study was to compare the clinical evaluation of the depth of anaesthesia with an evaluation using entropy during inhalational and intravenous induction of general anaesthesia. This study involved 60 patients undergoing elective surgery under general anaesthesia. Patients were divided into two groups, group E (etomidate induction) and group S (sevoflurane induction). The systolic arterial pressure (SAP), heart rate (HR), response entropy (RE), and state entropy (SE) were determined at the following seven measurement points: before anaesthesia induction, at the loss of consciousness (LOC) point, before tracheal intubation, immediately after intubation, and 2 min., 4 min. and 6 min. after tracheal intubation. An increase in HR and/or SAP of more than 20% and/or the occurrence of lacrimation and/or perspiration in response to tracheal intubation was considered a marker of inadequate anaesthesia in the clinical evaluation. The depth of anaesthesia was considered insufficient according to entropy monitoring if the RE and SE were above 60. In clinical evaluation, insufficient anaesthesia in response to tracheal intubation was observed in all the patients in group E and in more than half of the patients in group S. At the same time, the majority of patients in both groups had entropy values that did not exceed the recommended value as an appropriate level of anaesthesia. We found a discrepancy in the evaluation of the depth of anaesthesia based on clinical criteria compared with evaluations based on entropy values during both intravenous and inhalational induction of general anaesthesia.


Retrolaminar Migration of Intraocular Silicone Oil.
Migration of intravitreal silicone to the retrolaminar optic nerve was detected pathologically in 1983, symptomatic migration to the subarachnoid space of the optic nerve was reported in 1994, and asymptomatic intraventricular silicone was first seen radiographically in 1999. Since then, little advance has been made in understanding this phenomenon despite numerous case reports. Although some authors have restricted their attention to cases of intraventricular silicone, we believe that these represent part of a clinical spectrum and that all cases with retrolaminar silicone should be considered. The pathophysiology of silicone migration may have significant implications for the management of patients after vitrectomy. Two patients were evaluated by the authors. An internet-based literature review was conducted, beginning with the key search terms "intraventricular, intracranial, subarachnoid, or optic nerve silicone," and "complications of vitrectomy or intravitreal silicone." Further searches cascaded from the initial search results. An additional 24 cases of retrolaminar migration of silicone oil were found and summarized. The relevant anatomy and pathophysiology were reviewed, with attention to additional information from enucleation studies, as well as to gaps in the current understanding of this process. Retrolaminar migration of silicone oil may be more common than previously thought, especially in at-risk patient groups, and may be associated with visual and neurologic symptoms. Some impressions regarding the cause and significance of this syndrome seem incorrect. Although this process is likely linked to postoperative elevations of intraocular pressure, the exact mechanisms of silicone entry into the subarachnoid space remain undefined. A number of anatomic factors may influence the movement of silicone from the orbit and in the various compartments of the subarachnoid space and ventricular system, resulting in variability of clinical presentations and radiologic findings. Implications for clinical decision making and directions for further research are discussed. Greater awareness on the part of treating physicians, systematic study of at-risk populations, and advances in imaging technology will allow further insight into this phenomenon.


Structure-activity analysis of the interaction of curacin A, the potent colchicine site antimitotic agent, with tubulin and effects of analogs on the growth of MCF-7 breast cancer cells.
Originally purified as a major lipid component of a strain of the cyanobacterium Lyngbya majuscula isolated in Curaçao, curacin A is a potent inhibitor of cell growth and mitosis, binding rapidly and tightly at the colchicine site of tubulin. Because its molecular structure differs so greatly from that of colchicine and other colchicine site inhibitors, we prepared a series of curacin A analogs to determine the important structural features of the molecule. These modifications include reduction and E-to-Z transitions of the olefinic bonds in the 14-carbon side chain of the molecule; disruption of and configurational changes in the cyclopropyl moiety; disruption, oxidation, and configurational reversal in the thiazoline moiety; configurational reversal and substituent modifications at C13; and demethylation at C10. Inhibitory effects on tubulin assembly, the binding of colchicine to tubulin, and the growth of MCF-7 human breast carcinoma cells were examined. The most important portions of curacin A required for its interaction with tubulin seem to be the thiazoline ring and the side chain at least through C4, the portion of the side chain including the C9-C10 olefinic bond, and the C10 methyl group. Only two modifications totally eliminated the tubulin-drug interaction. The inactive compounds were a segment containing most of the side chain, including its two substituents, and analogs in which the methyl group at the C13 oxygen atom was replaced by a benzoate residue. Antiproliferative activity comparable with that observed with curacin A was only reproduced in compounds that were potent inhibitors of the binding of colchicine to tubulin. Molecular modeling and quantitative structure-activity relationship studies demonstrated that most active analogs overlapped extensively with curacin A but failed to provide an explanation for the apparent structural analogy between curacin A and colchicine.


Expression and secretion of ficolin beta by porcine neutrophils.
Ficolins are collagenous lectins that bind N-acetylglucosamine (GlcNAc) as well as some bacterial surfaces, and may have opsonic and complement-activating functions. Ficolin alpha in porcine plasma binds Actinobacillus pleuropneumoniae serotype 5 (APP) in a GlcNAc-dependent manner. In the present study, we discovered that porcine neutrophils, but not platelets or mononuclear cells, contained a different ficolin that migrated as a 39-kDa band on SDS-PAGE and resembled a minor component of plasma ficolins that binds APP. However, neutrophil ficolins (pI range 6.4-7.4) were readily distinguished from plasma ficolin alpha (pI 5.2-5.8) by 2D PAGE. Neutrophil ficolin was consistent with ficolin beta by pI and peptide mass fingerprinting with matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Porcine neutrophils expressed ficolin beta, but not ficolin alpha, as determined by RT-PCR. Ficolin beta was present in the membrane and cytoplasmic fractions of nonactivated neutrophils, but the majority of ficolin beta was secreted upon activation with PMA. Ficolin alpha readily bound to intact APP, but ficolin beta did not under the same conditions. These studies demonstrate that neutrophils express ficolin beta and secrete it when activated; however, ficolin beta may have different binding functions than ficolin alpha.


Increased melanomacrophage centres in the liver of reproductively dysfunctional female greater amberjack Seriola dumerili (Risso, 1810).
The greater amberjack Seriola dumerili is a new aquaculture fish that may display reproductive dysfunctions. During extensive follicular atresia, which is a common reproductive dysfunction in females during vitellogenesis, part of the reabsorbed yolk returns to the liver to be metabolized and recycled. Melanomacrophage centres (MMCs) are aggregates of macrophage-like cells that play a role in the destruction, detoxification and recycling of endogenous and exogenous materials, and have been associated with systemic stress. Wild and captive-reared greater amberjack were sampled in the Mediterranean Sea during two different phases of the reproductive cycle. The liver of reproductively dysfunctional captive-reared females sampled during the spawning season showed a high density of both MMCs and apoptotic cells. A weak liver anti-cytochrome P450 monooxygenase 1A immunoreactivity was observed, suggesting that the examined fish were not exposed to environmental pollutants. We propose that the observed increase in MMCs and apoptosis in captive-reared fish was related to the hepatic overload associated to the metabolism of yolk proteins reabsorbed during extensive follicular atresia. Since follicular atresia is a frequent physiological and pathological event in teleosts, we suggest that the reproductive state should be always assessed when MMCs are used as markers of exposure to stress or pollutants.


Conjugative Delivery of CRISPR-Cas9 for the Selective Depletion of Antibiotic-Resistant Enterococci.
The innovation of new therapies to combat multidrug-resistant (MDR) bacteria is being outpaced by the continued rise of MDR bacterial infections. Of particular concern are hospital-acquired infections (HAIs) that are recalcitrant to antibiotic therapies. The Gram-positive intestinal pathobiont Enterococcus faecalis is associated with HAIs, and some strains are MDR. Therefore, novel strategies to control E. faecalis populations are needed. We previously characterized an E. faecalis type II CRISPR-Cas system and demonstrated its utility in the sequence-specific removal of antibiotic resistance determinants. Here, we present work describing the adaption of this CRISPR-Cas system into a constitutively expressed module encoded on a pheromone-responsive conjugative plasmid that efficiently transfers to E. faecalis for the selective removal of antibiotic resistance genes. Using in vitro competition assays, we show that these CRISPR-Cas-encoding delivery plasmids, or CRISPR-Cas antimicrobials, can reduce the occurrence of antibiotic resistance in enterococcal populations in a sequence-specific manner. Furthermore, we demonstrate that deployment of CRISPR-Cas antimicrobials in the murine intestine reduces the occurrence of antibiotic-resistant E. faecalis by several orders of magnitude. Finally, we show that E. faecalis donor strains harboring CRISPR-Cas antimicrobials are immune to uptake of antibiotic resistance determinants in vivo Our results demonstrate that conjugative delivery of CRISPR-Cas antimicrobials may be adaptable for future deployment from probiotic bacteria for exact targeting of defined MDR bacteria or for precision engineering of polymicrobial communities in the mammalian intestine.


Expression of functionally active cytochrome b5 in Escherichia coli: isolation, purification, and use of the immobilized recombinant heme protein for affinity chromatography of electron-transfer proteins.
Cytochrome b5 is an integral membrane protein which is localized in endoplasmic reticulum membranes. In this paper we present the results on expression in E. coli, purification, and characterization of recombinant rat cytochrome b5. The full-length cDNA for rat liver microsomal cytochrome b5 has been modified using polymerase chain reaction (PCR) to introduce corresponding restriction sites as well as to insert silent mutations in the N-terminal sequence to increase the content of A and T nucleotides that prevents formation of elements of secondary structure of the mRNA transcripts and facilitates high expression. The expression plasmid was constructed by cloning of amplified cDNA to pCWori+ plasmid and used for transformation of E. coli DH5 alpha. The optimization of recombinant cytochrome b5 expression procedure induces expression level up to 3000 nmoles per liter of growth medium; this confers in the cells a deep pink color. The most interesting fact is that cytochrome b5 is expressed in this system in the reduced state. Recombinant cytochrome b5 was purified from solubilized cell membranes by a combination of ion-exchange chromatography and gel filtration. During purification, part of the cytochrome b5 is subjected to limited proteolysis with formation of truncated form. Sequencing of the N-terminal part of the recombinant cytochrome b5 indicates that it coincides with the sequence of rat cytochrome b5. Recombinant cytochrome b5 was found to have physicochemical, catalytic, and immunochemical properties to that of the native protein and was used as an efficient affinity matrix for purification of the various electron-transfer proteins.


Lactose tolerance in lambs with rotavirus diarrhoea.
It has been suggested that lactose malabsorption is an important factor in producing the diarrhoea of acute rotavirus infection. Accordingly, the lactose tolerance of gnotobiotic newborn lambs, infected with lamb rotavirus, has been investigated by clinical studies and tissue enzyme assays. Although lactase activity is low in affected areas of the small intestine, rotavirus infected lambs are not lactose intolerant as assessed by the measurement of reducing substances in the faeces, or by the clinical effects and blood glucose levels after a 5.8 mmol (2 g)/kg lactose load on the second day post-infection. Lactose intolerance could be demonstrated by using extremely high (29.2 mmol (10 g)/kg) doses of lactose, three or four times the normal dietary lactose intake. These experiments suggest that lactose-containing feeds (such as maternal milk) are not necessarily contraindicated in patients or animals with rotavirus diarrhoea.


Analysis of pathogenic factors on the death rate of sepsis patients.
The Surviving Sepsis Campaign (SSC) believed that early identification of septic shock, aggressive fluid resuscitation and maintenance of effective perfusion pressure should be carried out. However, some of the current research focused on a single death factor for sepsis patients, based on a limited sample, and the research results of the relationship between comorbidities and sepsis related death also have some controversies. Therefore, our study used data from a large sample of 9,544 sepsis patients aged 18-85 obtained from the MIMIC-IV database, to explore the risk factors of death in patients with sepsis. We used the general clinical information, organ dysfunction scores, and comorbidities to analyze the independent risk factors for death of these patients. The death group had significantly higher organ dysfunction scores, lower BMI, lower body temperature, faster heart rate and lower urine-output. Among the comorbidities, patients suffering from congestive heart failure and liver disease had a higher mortality rate. This study helps to identify sepsis early, based on a comprehensive evaluation of a patient's basic information, organ dysfunction scores and comorbidities, and this methodology could be used for actual clinical diagnosis in hospitals.


Complementary sample preparation strategies (PVD/BEXP) combining with multifunctional SPM for the characterizations of battery interfacial properties.
The cathode/anode-electrolyte interfaces in lithium/sodium ion batteries act as the "gate" for the ion exchange between the solid electrode and liquid electrolyte. Understanding the interfacial properties of these solid-liquid interfaces is essential for better design high-performance lithium/sodium ion batteries. Here, we provide a novel method for studying solid-liquid interfacial properties of battery materials through combining physical vapor deposition (PVD) and beam-exit cross-sectional polishing (BEXP) followed by controlled environment multifunctional Scanning Probe Microscope (SPM). In this method, commercial battery materials can be either directly grown on the current collector substrates, or polished by obliqued Ar-ion beams to get a nanoscale flat surface which allows the multifunctional SPM to study sample directly in the liquid electrolyte or in protective oxygen/H2O free environment. This approach allows to investigate wide range of interfacial properties, including surface morphology, internal cracks, mechanical properties, electronic/ionic conductivity and surface potential, with nanoscale resolution in-operando during the battery cycles as well as post-mortem.•PVD and novel BEXP methods were introduced to prepare battery powder materials as perfect specimens for nanoscale SPM characterization.•Various physical/chemical properties of battery materials can be probed on the as-prepared specimens under liquid electrolyte using in situ/operando SPM techniques.•Ex situ/post-mortem analyses based on the controlled environment multifunction SPM characterizations can be achieved in the BEXP polished degradation battery electrodes.


Non-invasive investigation of endothelium-dependent dilatation of the brachial artery in women with primary Raynaud's phenomenon.
1. Primary Raynaud's phenomenon is characterized by white fingers and toes with impaired perfusion in response to cold or emotional stress. The aetiology has not been clarified. In previous studies we have demonstrated a season-linked inability in women with primary Raynaud's phenomenon to raise their plasma cGMP levels in response to whole-body cooling, suggesting a dysfunction of the L-arginine-NO-cGMP pathway. To further elucidate the possibility of such a defect in patients with primary Raynaud's phenomenon, we determined flow-mediated dilatation of the brachial artery. 2. Twenty-two premenopausal, non-smoking women with primary Raynaud's phenomenon (mean age 39 +/- 8 years) and 23 healthy controls (mean age 41 +/- 7 years) were studied during two winter weeks. The diameter of the right arm brachial artery was measured by high resolution ultrasonography, at rest and during reactive hyperaemia. The investigation was conducted both with the participants at rest at room temperature and after 40 min of whole-body cooling. 3. Both study groups showed a marked attenuation of flow-mediated dilatation during whole-body cooling, which could partly but not solely be explained by a decreased shear rate. There was, however, no significant difference in flow-mediated diameter (D) increase (% flow-mediated dilatation; delta D/D x 100) between primary Raynaud's phenomenon and controls, either at room temperature (7.8 +/- 0.8 and 9.0 +/- 0.8) or in response to whole-body cooling (3.8 +/- 1.2 and 4.4 +/- 0.7). 4. Thus, whole-body cooling markedly impairs flow-mediated dilatation in women. Flow-mediated dilatation is, however, not decreased in women with primary Raynaud's phenomenon at room temperature or during whole-body cooling, indicating that this particular aspect of endothelial function is not impaired in this setting.


MobiDB: a comprehensive database of intrinsic protein disorder annotations.
Disordered protein regions are key to the function of numerous processes within an organism and to the determination of a protein's biological role. The most common source for protein disorder annotations, DisProt, covers only a fraction of the available sequences. Alternatively, the Protein Data Bank (PDB) has been mined for missing residues in X-ray crystallographic structures. Herein, we provide a centralized source for data on different flavours of disorder in protein structures, MobiDB, building on and expanding the content provided by already existing sources. In addition to the DisProt and PDB X-ray structures, we have added experimental information from NMR structures and five different flavours of two disorder predictors (ESpritz and IUpred). These are combined into a weighted consensus disorder used to classify disordered regions into flexible and constrained disorder. Users are encouraged to submit manual annotations through a submission form. MobiDB features experimental annotations for 17 285 proteins, covering the entire PDB and predictions for the SwissProt database, with 565 200 annotated sequences. Depending on the disorder flavour, 6-20% of the residues are predicted as disordered. The database is freely available at http://mobidb.bio.unipd.it/. email@example.com.


[Quality of life related to oral health among addicts].
In this study, the impact of oral health on the daily functioning of a group of individuals addicted to alcohol and/or drugs that were being treated at a centre for specialized dentistry in Amsterdam was investigated. Every new patient who reported to the clinic received the OHIP-14-questionnaire at home by post with the request that it be filled in and returned. A total of 110 usable questionnaires were returned (response 27.5%). The average OHIP-score (40.6; standard deviation 12.9) can be termed substantial when compared to other patient groups. On the subcategories 'physical pain', 'psychological discomfort' and 'psychological disability; the patients scored highest, and on the subcategory functional limitations' the lowest. The poor oral health of the patient group studied has a substantial impact on daily functioning. These baseline results will be used for measuring the effect of dental health treatment at this centre for specialized dentisty.


Diethyl ether anesthesia induces transient cytosolic [Ca2+] increase, heat shock proteins, and heat stress tolerance of photosystem II in Arabidopsis.
General volatile anesthetic diethyl ether blocks sensation and responsive behavior not only in animals but also in plants. Here, using a combination of RNA-seq and proteomic LC-MS/MS analyses, we investigated the effect of anesthetic diethyl ether on gene expression and downstream consequences in plant Arabidopsis thaliana. Differential expression analyses revealed reprogramming of gene expression under anesthesia: 6,168 genes were upregulated, 6,310 genes were downregulated, while 9,914 genes were not affected in comparison with control plants. On the protein level, out of 5,150 proteins identified, 393 were significantly upregulated and 227 were significantly downregulated. Among the highest significantly downregulated processes in etherized plants were chlorophyll/tetrapyrrole biosynthesis and photosynthesis. However, measurements of chlorophyll a fluorescence did not show inhibition of electron transport through photosystem II. The most significantly upregulated process was the response to heat stress (mainly heat shock proteins, HSPs). Using transgenic A. thaliana expressing APOAEQUORIN, we showed transient increase of cytoplasmic calcium level [Ca2+]cyt in response to diethyl ether application. In addition, cell membrane permeability for ions also increased under anesthesia. The plants pre-treated with diethyl ether, and thus with induced HSPs, had increased tolerance of photosystem II to subsequent heat stress through the process known as cross-tolerance or priming. All these data indicate that diethyl ether anesthesia may partially mimic heat stress in plants through the effect on plasma membrane.


Are media reports able to cause somatic symptoms attributed to WiFi radiation? An experimental test of the negative expectation hypothesis.
People suffering from idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF) experience numerous non-specific symptoms that they attribute to EMF. The cause of this condition remains vague and evidence shows that psychological rather than bioelectromagnetic mechanisms are at work. We hypothesized a role of media reports in the etiology of IEI-EMF and investigated how somatosensory perception is affected. 65 healthy participants were instructed that EMF exposure can lead to enhanced somatosensory perception. Participants were randomly assigned to watch either a television report on adverse health effects of EMF or a neutral report. During the following experiment, participants rated stimulus intensities of tactile (electric) stimuli while being exposed to a sham WiFi signal in 50% of the trials. Sham WiFi exposure led to increased intensity ratings of tactile stimuli in the WiFi film group, especially in participants with higher levels of somatosensory amplification. Participants of the WiFi group reported more anxiety concerning WiFi exposure than the Control group and tended to perceive themselves as being more sensitive to EMF after the experiment compared to before. Sensational media reports can facilitate enhanced perception of tactile stimuli in healthy participants. People tending to perceive bodily symptoms as intense, disturbing, and noxious seem most vulnerable. Receiving sensational media reports might sensitize people to develop a nocebo effect and thereby contribute to the development of IEI-EMF. By promoting catastrophizing thoughts and increasing symptom-focused attention, perception might more readily be enhanced and misattributed to EMF.


Value of continuous monitoring of mixed venous blood oxygen saturation in the management of critically ill patients.
Continuous SVO2 measurement using a triple-lumen flow-directed pulmonary artery catheter with fiberoptic filaments has been described. The purpose of this study was to identify whether the availability of SVO2 as a continuously monitored signal could have altered patient management decisions made by the medical staff on the basis of clinical and laboratory data and signals currently used in ICUs. Subjects for this study were 15 critically ill patients requiring arterial cannulation and insertion of a pulmonary artery catheter. The central processor of the device was placed in a specially constructed wooden box in such a way as to conceal the digital display of the signal. The folded paper used for a continuous 72-h recording of the signal was also not available to the personnel managing the patient. In detailed and repeated assessments of the patient's status, the medical team managing the patient entered on a special form all clinical and laboratory data as well as medical decisions made. At the end of each study the SVO2 value recorded at each assessment was entered on the form. The investigators then determined whether knowledge of SVO2 would have changed the clinical decision actually made. The SVO2 signal was continuously recorded for a total of 1065 h and 173 individual assessments. The SVO2 signal as measured by the Oximetrix device was compatible with decisions made on the basis of standard measurements used in the ICU in a majority of cases.(ABSTRACT TRUNCATED AT 250 WORDS)


Caries experience of children aged 6-9 years in Jeddah, Saudi Arabia.
This study was conducted to examine the caries experience of children aged 6-9 years in Jeddah, Saudi Arabia. Overall, 1522 children were examined from six primary schools located in different areas of the city. Results showed that the mean dmft and DFT were 4.23 and 1.85, respectively. The mean dmft and DFT values excluding caries-free children, however, were 5.71 and 2.95, respectively. Only 26.1% of the children were caries free. There was a high proportion of untreated dental caries and most of the carious teeth were treated by extraction. The need for effective preventive measures was stressed.


Bristlecone Pine: Science and Esthetics: A 7100-year tree-ring chronology aids scientists; old trees draw visitors to California mountains.
A 7100-year tree-ring chronology has been developed for bristlecone pine, Pinus aristata Engelm., in the White Mountains of east-central California by the addition of data from long-dead specimens to the 4600-year record from living trees. These dendrochronological studies have major applications to climatic interpretations, radiocarbon analysis, and the dating of past events. The great age of these trees and the esthetic appeal of both the trees and their environment are drawing increasing numbers of visitors to the bristlecone pine areas. Concern is expressed for the preservation of this ancient wood.


Competition drives the response of soil microbial diversity to increased grazing by vertebrate herbivores.
Scientists have largely neglected the effects of grazing on soil microbial communities despite their importance as drivers of ecosystem functions and services. We hypothesized that changes in soil properties resulting from grazing regulate the diversity of soil microbes by releasing/suppressing subordinate microbial taxa via competition. To test this, we examined how intensity of vertebrate herbivores influences the diversity and composition of soil bacteria and fungi at 216 soil samples from 54 sites across four microsites. Increasing grazing intensity reduced soil carbon, suppressing the dominant bacterial phylum Actinobacteria (indirectly promoting bacterial diversity) and increasing the dominant fungal phylum Ascomycetes (indirectly reducing fungal diversity). Our data provide novel evidence that grazing modulates the diversity and composition of soil microbes via increases or reductions in competition by dominant taxa. Our results suggest that grazing can potentially alter soil function by altering microbial community composition, providing a clear link between grazing management, carbon availability and ecosystem functions.


Intranasal drugs for analgesia and sedation in children admitted to pediatric emergency department: a narrative review.
Acute pain is one of the most common symptoms in children admitted to the Pediatric Emergency Department (PED) and its management represents a real clinical challenge for pediatricians. Different painful procedures can be very stressful for young children and their perception of pain can be enhanced by emotional factors, such as anxiety, distress, or anger. Adequate procedural sedation reduces anxiety and emotional trauma for the patient, but it reduces also stress for operators and the time for procedures. We have reviewed the literature on this topic and the drugs covered in these papers were: midazolam, fentanyl, ketamine, and dexmedetomidine. There are several routes of administering for these drugs to provide analgesia and anxiolysis to children: oral, parenteral, or intranasal (IN). Intravenous (IV) sedation, since it involves the use of needles, can be stressful; instead, IN route is a non-invasive procedure and generally well tolerated by children and it has become increasingly widespread. Some medications can be administered by a mucosal atomizer device (MAD) or by drops. The benefits of the atomized release include less drug loss in the oropharynx, higher cerebrospinal fluid levels, better patient acceptability, and better sedative effects. IN midazolam has a sedative, anxiolytic and amnesic effect, but without analgesic properties. Fentanyl and ketamine are mainly used for pain control. Dexmedetomidine has anxiolytic and analgesic properties. In conclusion, IN analgo-sedation is a simple, rapid and painless option to treat pain and anxiety in the PED requiring brief training on the administration process and experience in sedation.


[An experimental study on inhibitory effect of Chinese medicine tai-bao on antisperm antibody].
To investigate whether Chinese medicine Tai-bao could inhibit antisperm antibody in experimental mice. The experimental immunoinfertility mice were due to antisperm antibody induced by injection of human sperm membrane antigens. The experimental immuno-infertile mice used in the present study were divided into four groups including Tai-bao high dose group (46.8 g.kg-1.d-1), Tai-bao low dose group (31.2 g.kg-1.d-1), prednisone group and normal saline group. The enzyme linked immune sorbent assay (ELISA) and microcytotoxic assay were used for detection of antisperm antibody. The change of levels of antisperm antibody before and after treatment, pregnant rate, and the number of implantation were investigated in tested mice. The pregnant rates in normal saline group, prednisone group, Tai-bao high dose group and low dose were 38.89%, 47.06%, 70.00% and 75.00% respectively. The rate of pregnancy in Tai-bao low dose group was significantly higher as compared with normal saline group (P < 0.05). The rate of implantation in Tai-bao low dose group was significantly higher than that in prednisone group (P < 0.05). The results of detection of the cytotoxic antibody to sperm showed that cytotoxic percentages in Tai-bao high dose group (63.0 +/- 10.3%) and prednisone group (56.3 +/- 13.7%) were significantly lower (P < 0.05 and P < 0.01) than that in normal saline group (72.84 +/- 5.05%). Chinese medicine Tai-bao possesses regulatory effect on reproductive immune function, inhibitory effect on antisperm cytotoxic antibody, and promoting effect on pregnancy.


Fusibacter bizertensis sp. nov., isolated from a corroded kerosene storage tank.
Strain LTF Kr01(T), a novel mesophilic, anaerobic, halotolerant, rod-shaped bacterium, was isolated from a drain at the bottom of a corroded kerosene storage tank of the Société Tunisienne des Industries de Raffinage (STIR), Bizerte, northern Tunisia. Cells were Gram-positive-staining rods, occurred singly or in pairs, and were motile by one lateral flagellum. Strain LTF Kr01(T) grew at temperatures between 15 and 40 °C (optimum 30 °C), between pH 5.5 and 8.2 (optimum pH 7.2) and at NaCl concentrations between 0 and 50 g l(-1) (optimum 5 g l(-1)). It reduced thiosulfate and elemental sulfur into sulfide, but did not reduce sulfate or sulfite. It utilized a wide range of carbohydrates (cellobiose, d-glucose, d-fructose, d-mannitol, d-ribose, sucrose, d-xylose, maltose, d-galactose, starch and trehalose) and produced acetate, CO2 and H2 as end products from glucose fermentation. The DNA G+C content was 37.4 mol%. The predominant cellular fatty acids were C14:0 and C16:0. Phylogenetic analysis of the 16S rRNA gene sequence suggested that Fusibacter tunisiensis was the closest relative of strain LTF Kr01(T) (gene sequence similarity of 94.6%). Based on phenotypic, phylogenetic and genotypic taxonomic characteristics, strain LTF Kr01(T) is proposed to represent a novel species of the genus Fusibacter, order Clostridiales, for which the name Fusibacter bizertensis sp. nov. is proposed. The type strain is LTF Kr01(T) ( = DSM 28034(T) = JCM 19376(T)).


Two-week normobaric intermittent hypoxia exposures enhance oxyhemoglobin equilibrium and cardiac responses during hypoxemia.
Intermittent hypoxia (IH) is extensively applied to challenge cardiovascular and respiratory function, and to induce physiological acclimatization. The purpose of this study was to test the hypothesis that oxyhemoglobin equilibrium and tachycardiac responses during hypoxemia were enhanced after 14-day IH exposures. Normobaric-poikilocapnic hypoxia was induced with inhalation of 10% O2 for 5-6 min interspersed with 4 min recovery on eight nonsmokers. Heart rate (HR), arterial O2 saturation (SaO 2), and end-tidal O2 (PetO 2) were continuously monitored during cyclic normoxia and hypoxia. These variables were compared during the first and fifth hypoxic bouts between day 1 and day 14. There was a rightward shift in the oxyhemoglobin equilibrium response following 14-day IH exposures, as indicated by the greater PetO 2 (an index of arterial Po2) at 50% of SaO 2 on day 14 compared with day 1 [33.9 ± 1.5 vs. 28.2 ± 1.3 mmHg (P = 0.005) during the first hypoxic bout and 39.4 ± 2.4 vs. 31.4 ± 1.5 mmHg (P = 0.006) during the fifth hypoxic bout] and by the augmented gains of ΔSaO 2/ΔPetO 2 (i.e., deoxygenation) during PetO 2 from 65 to 40 mmHg in the first (1.12 ± 0.08 vs. 0.80 ± 0.02%/mmHg, P = 0.001) and the fifth (1.76 ± 0.31 vs. 1.05 ± 0.06%/mmHg, P = 0.024) hypoxic bouts. Repetitive IH exposures attenuated (P = 0.049) the tachycardiac response to hypoxia while significantly enhancing normoxic R-R interval variability in low-frequency and high-frequency spectra without changes in arterial blood pressure at rest or during hypoxia. We conclude that 14-day IH exposures enhance arterial O2 delivery and improve vagal control of HR during hypoxic hypoxemia.


Investigating resilience in emergency management: An integrative review of literature.
There is a growing need for resilience in dealing with unexpected events during disasters. The purpose of this review was to summarize and synthesize the literature that examined resilience in the context of emergency management (EM). Four groups of findings were synthesized: definitions, key dimensions, technical tools, and research settings employed in the research. First, definitions of resilience, improvisation, and adaptation were summarized and critically evaluated. Second, four key dimensions of EM resilience were identified: collective sensemaking, team decision making, harmonizing work-as-imagined and work-as-done, and interaction and coordination. Third, this review identified five prevalent technical tools used to enhance resilience in EM: mapmaking, event history logging, mobile communication applications, integrated information management system, and decision support tools. Fourth, two major design features of emergency simulations, incident scenarios and participant roles, are evaluated. For each finding, directions for future research efforts to improve resilience in EM are proposed.


The role of endotoxaemia in the development of renal disorders in experimental obstructive jaundice in rats.
In rats with 2-week obstructive jaundice the sensitivity to endotoxin was studied and the effect of a single dose of endotoxin on histological development in the kidney, liver and spleen was also investigated. We were tested the effect on accumulation and distribution within organs, of fibrinogen labelled with radioactive iodine I 125. We showed an increased sensitivity to endotoxin in obstructive jaundice. The cause of death in most rats was acute circulatory failure during the course of endotoxic shock, without clinical features of disseminated intravascular coagulation. In the isotope study, after endotoxin administration there was a specific dynamic increase of fibrinogen accumulation in the kidneys of rats with obstructive jaundice. We proposed, that the cause of the kidney changes during the course of obstructive jaundice could be the local activation of intrarenal coagulation.


Lessons from an isocyanate tragedy.
This paper highlights the features of prevention of isocyanate-induced occupational asthma from various angles: the employer, the employee, as well as the occupational physician entrusted with the care of such occupationally-exposed group of workers. The difficulties posed by the variability of the presentation, not least because of the relatively long latency, as well as the sensitising nature of the hazard, are discussed.


[Surgical treatment of cancers of the stomach].
Gastric cancer remains a serious health problem 5 years survival remains low and early diagnosis anecdotical in France. Gastrectomy is the only curative treatment and the extent of surgery depends upon the tumor location. The extent of the node dissection is under discussion, Japanese surgeons recommend extensive dissection and publish better results in term of survival than Europeans groups. Two randomized prospectives trials comparing limited and extensive dissection have not shown any difference but an increased morbidity in the group with extensive dissection. Adjuvant treatments radiation or chemotherapy should be given therapeutic trials because they have not been proved as efficient.


Management of glioblastoma: State of the art and future directions.
Glioblastoma is the most common malignant primary brain tumor. Overall, the prognosis for patients with this disease is poor, with a median survival of <2 years. There is a slight predominance in males, and incidence increases with age. The standard approach to therapy in the newly diagnosed setting includes surgery followed by concurrent radiotherapy with temozolomide and further adjuvant temozolomide. Tumor-treating fields, delivering low-intensity alternating electric fields, can also be given concurrently with adjuvant temozolomide. At recurrence, there is no standard of care; however, surgery, radiotherapy, and systemic therapy with chemotherapy or bevacizumab are all potential options, depending on the patient's circumstances. Supportive and palliative care remain important considerations throughout the disease course in the multimodality approach to management. The recently revised classification of glioblastoma based on molecular profiling, notably isocitrate dehydrogenase (IDH) mutation status, is a result of enhanced understanding of the underlying pathogenesis of disease. There is a clear need for better therapeutic options, and there have been substantial efforts exploring immunotherapy and precision oncology approaches. In contrast to other solid tumors, however, biological factors, such as the blood-brain barrier and the unique tumor and immune microenvironment, represent significant challenges in the development of novel therapies. Innovative clinical trial designs with biomarker-enrichment strategies are needed to ultimately improve the outcome of patients with glioblastoma.


Proteinase 3 Is a Phosphatidylserine-binding Protein That Affects the Production and Function of Microvesicles.
Proteinase 3 (PR3), the autoantigen in granulomatosis with polyangiitis, is expressed at the plasma membrane of resting neutrophils, and this membrane expression increases during both activation and apoptosis. Using surface plasmon resonance and protein-lipid overlay assays, this study demonstrates that PR3 is a phosphatidylserine-binding protein and this interaction is dependent on the hydrophobic patch responsible for membrane anchorage. Molecular simulations suggest that PR3 interacts with phosphatidylserine via a small number of amino acids, which engage in long lasting interactions with the lipid heads. As phosphatidylserine is a major component of microvesicles (MVs), this study also examined the consequences of this interaction on MV production and function. PR3-expressing cells produced significantly fewer MVs during both activation and apoptosis, and this reduction was dependent on the ability of PR3 to associate with the membrane as mutating the hydrophobic patch restored MV production. Functionally, activation-evoked MVs from PR3-expressing cells induced a significantly larger respiratory burst in human neutrophils compared with control MVs. Conversely, MVs generated during apoptosis inhibited the basal respiratory burst in human neutrophils, and those generated from PR3-expressing cells hampered this inhibition. Given that membrane expression of PR3 is increased in patients with granulomatosis with polyangiitis, MVs generated from neutrophils expressing membrane PR3 may potentiate oxidative damage of endothelial cells and promote the systemic inflammation observed in this disease.


Upper partial fibulectomy improves knee biomechanics and function and decreases knee pain of osteoarthritis: A pilot and biomechanical study.
To investigate the change in clinical outcomes and biomechanical properties of the knee in response to upper partial fibulectomy. Sixteen patients with medial compartment knee osteoarthritis (KOA) underwent upper partial fibulectomy. Visual analog scale (VAS) pain, the hospital for special surgery knee score (HSS), hip-knee-ankle (HKA) angle (measured in the frontal plane), and flexion/extension range of motion of the knee were assessed before and up to 6 months after surgery. Patients were evaluated for gait parameters and overall peak knee adduction moment (KAM). Patient-specific finite element knee models were developed to investigate changes in load in response to fibulectomy. Both VAS pain and HSS score were significantly improved (P < .001) one day after surgery and steadily improved during the subsequent 6 months. HKA angle improved (P = .006) immediately and remained stable by 3 months after surgery. A significant inverse relationship (R = -0.528, P = .012) between the overall peak KAM (decreased by 19.1%) and the HKA (increased by 1.24° from a more varus to more neutral alignment) angle was observed. The minor load supported by the fibula preoperatively was spread post-operatively over the cortical bone of the tibial shaft. The mean stress in the medial tibial plateau was significantly decreased (P < .001), with a portion of the stress transferred to the posterior-lateral region of the tibial plateau after upper partial fibulectomy. This pilot study provides objective 3D gait and plausible biomechanical evidence for the improvement in clinical symptoms from partial upper fibulectomy.


Molecular characterization of fungal endophthalmitis and keratitis caused by yeasts.
Candida species are the most common causes of sight-threatening fungal ocular infections in temperate regions of the world. Despite their relevance, little is known about the emergence of novel species and the molecular epidemiology of these infections. Here, we molecularly characterized 38 yeast isolates collected from patients diagnosed with endophthalmitis or keratitis at Massachusetts Eye and Ear from 2014 to 2021. Sequencing of the ITS1-5.8S-/ITS2 regions demonstrated that this population of yeasts was dominated by Candida spp. (37 out of 38; 97%), with 58% of the cases caused by C. albicans (n = 22) and the remaining by emerging non-albicans species, predominantly by C. parapsilosis (n = 8) and C. dubliniensis (n = 6). One isolate each was identified as C. tropicalis and Clavispora lusitaniae. Interestingly, all C. dubliniensis were isolated from endophthalmitis and most C. parapsilosis from keratitis. Multilocus sequence typing analysis of C. albicans showed a prevalence of CC-1 isolates that has DST69 as the putative founder, with 64% of them belonging to this clonal complex (CC). Isolates grouped within this cluster were more predominant in endophthalmitis (10 out of 14; 71%). One C. albicans CC-1 isolate was multi-azole resistant. In conclusion, we observed that nearly half of the ocular infections caused by yeasts are associated with C. albicans, with evidence for the emergence of non-albicans species that are differentially enriched in distinct ocular niches. Candida albicans isolates clustered within the predominant CC-1 group were particularly more common in endophthalmitis, demonstrating a potential pattern of ocular disease enrichment within this clade.


Heterozygous and homozygous mutations in PITX3 in a large Lebanese family with posterior polar cataracts and neurodevelopmental abnormalities.
The PITX3 gene, which codes for a homeobox bicoidlike transcription factor is responsible for dominant cataract and anterior segment mesenchymal dysgenesis in humans. In the current study, a family with autosomal dominant posterior polar cataract (PPC) and a PITX3 mutation that cosegregates with the disease was examined. Also studied were two siblings who were homozygous for the PITX3 mutation who had microphthalmia and significant neurologic impairment. A genome-wide screen, linkage analysis in the PITX3 chromosomal region 10q25, haplotype analysis, and sequencing of the PITX3 gene were performed on 28 affected and 14 unaffected member of a three-generation Lebanese family. Genome-wide linkage analysis showed a lod score of 3.56 at theta = 0.00 on chromosome 10 at area q25. Analysis of the haplotypes and phenotypes confined the disease locus to a region on 10q25 between the markers D10S1239 and D10S1268. A candidate gene, PITX3, maps to that region. Sequencing of the PITX3 gene revealed a heterozygous G deletion mutation in 25 of the 42 family members. In addition, two siblings from a consanguineous marriage were found to be homozygous for the deletion. This is the first report of homozygous PITX3 mutations in humans. The phenotype in these individuals highlights the role of PITX3 in ocular and central nervous system (CNS) development.


Psychosis risk research versus daily prognosis uncertainties: A qualitative study of French youth psychiatrists' attitudes toward predictive practices.
Over the last twenty years, predicting psychosis has become a priority of both research and policies. Those approaches include the use of the At Risk Mental State category (ARMS) and of standardized predictive tools. In comparison to most developed countries, early interventions programs are only little developed in France. However, cases of young patients presenting unclear symptoms that might be a beginning psychosis or might as well reflect some adolescent unease are commonplace in psychiatry. Yet little is known about the routine practices of youth psychiatrists regarding psychosis risk management. Do they anticipate mental disorders? The Grounded Theory is an agreed-upon qualitative method in social science field that links subjective experiences (individual narratives) to social processes (professional norms and mental health policies). 12 French youth psychiatrists were interviewed about psychosis early management and their daily prognosis practices with teenagers. If all participants were aware of early intervention programs, most of them did not make use of standardized scales. Psychiatrists' reluctance toward a psychosis risk standardized assessment was shaped by three difficulties: first the gap between theoretical knowledge and practice; second their impossibility to make reliable prognoses; and third, the many uncertainties surrounding medical judgment, adolescence and the nature of psychosis. Nevertheless, they provided their young patients with multiple months follow up without disclosing any risk category. Anticipating a psychosis onset remains a highly uncertain task for psychiatrists. In France, psychiatrists' inconspicuous risk management might be supported by the universal costs coverage that is not conditional on a diagnosis disclosure.


The effect of acupuncture on postmenopausal symptoms and reproductive hormones: a sham controlled clinical trial.
Acupuncture is commonly used to treat menopausal symptoms and other gynaecological conditions. In this study, the authors aimed to investigate whether acupuncture has an effect on menopausal symptoms and to explore whether this effect is related to changes in hormone levels. Materials and methods A total of 53 postmenopausal women were alternately assigned into two treatment groups: acupuncture (n=27) and sham acupuncture (n=26). Menopausal symptoms were assessed using the Menopause Rating Scale (MRS). The serum oestradiol, follicular stimulating hormone (FSH) and luteinising hormone (LH) levels were measured at baseline and again after the first and last sessions. The Student t test was used for normally distributed data and the Wilcoxon signed rank test for not normally distributed data. The group differences in MRS scores were assessed using non-parametric Mann-Whitney U test. After treatment, total MRS, and the somatic and psychological subscale scores were significantly lower in the acupuncture group than the sham group (all p=0.001). The severity of hot flushes was found to be significantly decreased after treatment in acupuncture group (p=0.001). In the acupuncture group LH levels were lower and oestradiol levels were significantly higher than sham group (p=0.046 and p=0.045, respectively) after treatment, but there was no difference in FSH levels. Acupuncture was effective in reducing menopausal complaints when compared to sham acupuncture and can be considered as an alternative therapy in the treatment of menopausal symptoms.


Pseudorhodobacter wandonensis sp. nov., isolated from wood falls, and emended description of the genus Pseudorhodobacter.
A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterial strain, designated WT-MW11(T), was isolated from wood falls on the coast of Wando, an island of South Korea, and its taxonomic position was investigated by using a polyphasic approach. Strain WT-MW11(T) grew optimally at pH 7.0-8.0, at 25 °C and in the presence of 2.0-3.0 % (w/v) NaCl. Bacteriochlorophyll a was not produced. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain WT-MW11(T) clustered with Pseudorhodobacter ferrugineus IAM 12616(T) and Pseudorhodobacter aquimaris HDW-19(T), with which it exhibited 16S rRNA gene sequence similarity values of 97.9 and 95.5 %, respectively. Strain WT-MW11(T) contained Q-10 as the predominant ubiquinone and C18 : 1ω7c as the major fatty acid. The polar lipid profile of strain WT-MW11(T) was similar to those of P. ferrugineus JCM 20687(T) and P. aquimaris HDW-19(T). The DNA G+C content of strain WT-MW11(T) was 61.6 mol% and its mean DNA-DNA relatedness value with P. ferrugineus JCM 20687(T) was 12.3 %. The phylogenetic and genetic distinctiveness and differential phenotypic properties revealed that strain WT-MW11(T) was distinguishable from the two recognized species of the genus Pseudorhodobacter. On the basis of the data presented, strain WT-MW11(T) is considered to represent a novel species of the genus Pseudorhodobacter, for which the name Pseudorhodobacter wandonensis sp. nov. is proposed. The type strain is WT-MW11(T) ( = KCTC 23672(T) = CCUG 61506(T)). The description of the genus Pseudorhodobacter is emended.


Infections of Paramecium bursaria with bacteria and yeasts.
Infections of Paramecium bursaria with bacteria and yeasts are reported. Bacteria and yeasts multiply in the algae-free ciliate and are transmitted at various conditions as are symbiotic chlorellae. Like chlorellae, the bacteria and the yeast cells are situated in perisymbiont vacuoles. Both bacteria and yeasts maintain their capability for independent existence and can be grown on standard nutrient agar. Infection experiments show that aposymbiotic P. bursaria can be infected with Chlorella, bacteria and yeast. Chlorella-bearing P. bursaria cannot be infected with bacteria or yeast. Bacteria-bearing paramecia can be infected with Chlorella but not with yeast. Yeast-bearing paramecia can be infected with Chlorella but not with bacteria. Following infections with Chlorella the paramecia lose their bacteria or yeast symbionts. The bacteria found in P. bursaria probably belong to the genus Pseudomonas; the yeast has been identified as Rodutorula rubra.


Meet the Authors: Fardin Aryan, Diego Detrés, and Eliezer Calo.
We talk to co-first authors Fardin Aryan and Diego Detrés along with lead contact Eliezer Calo about their paper "Nucleolus activity-dependent recruitment and biomolecular condensation by pH sensing" (this issue of Molecular Cell), what drew them to a career in science, and overcoming challenges posed by the global pandemic.


Structural and bioinformatic analyses of Azemiops venom serine proteases reveal close phylogeographic relationships to pitvipers from eastern China and the New World.
The semi-fossil and pit-less Azemiops feae is possibly the most primitive crotalid species. Here, we have cloned and sequenced cDNAs encoding four serine proteases (vSPs) from the venom glands of Chinese A. feae. Full amino-acid sequences of the major vSP (designated as AzKNa) and three minor vSPs (designated as AzKNb, AzKNc and Az-PA) were deduced. Using Protein-BLAST search, the ten most-similar vSPs for each Azemiops vSP have been selected for multiple sequence alignment, and all the homologs are crotalid vSPs. The results suggest that the A. feae vSPs are structurally most like those of eastern-Chinese Gloydius, Viridovipera, Protobothrops and North American pitvipers, and quite different from more-specialized vSPs such as Agkistrodon venom Protein-C activators. The vSPs from Chinese A. feae and those from Vietnamese A. feae show significant sequence variations. AzKNa is acidic and contains six potential N-glycosylation sites and its surface-charge distribution differs greatly from that of AzKNb, as revealed by 3D-modeling. AzKNb and AzKNc do not contain N-glycosylation sites although most of their close homologs contain one or two. Az-PA belongs to the plasminogen-activator subtype with a conserved N20-glycosylation site. The evolution of this subtype of vSPs in Azemiops and related pitvipers has been traced by phylogenetic analysis.


Spinal cord compression in Paget's disease.
Three cases of spinal cord compression secondary to Paget's disease of the spine are reported. In two of the cases a relatively short history with pain as a prominent feature suggested initially a diagnosis of extradural malignancy. The usual clinical features of this rare disorder are discussed and the characteristic radiological findings are emphasized.


Torus Tubarius Hypertrophy After Adenoidectomy.
Backgrounds: Adenoidectomy is widely used to cure sleep-disordered breathing symptoms in children, torus tubarius hypertrophy (TTH) after adenoidectomy causing recurred snoring, sleep apnea, nasal obstruction, or mouth breathing was rarely reported, and the causes of TTH are still unclear. Objectives: To report a rare complication TTH after adenoidectomy, and the features of TTH. Material and Methods: A total of 36 pediatric patients with TTH diagnosed by our hospital from January 2017 to 2023 were included in this study. All children were treated conservatively for a month at first, and 13 patients underwent partial resection of TTH. The influencing factors (sex, age, allergic rhinitis [AR], and first operation way) were analyzed. Results: There were 36 patients with TTH: 27 boys and 9 girls. The age of the first operation ranged from 20 to 63 months, and the interval time of TTH after operation ranged from 3 to 55 months. Thirteen patients underwent partial resection of TTH. Thirteen children had definite symptoms and signs of AR. Conclusions and Significance: TTH is a rare complication after adenoidectomy, which is common in male children (75.0%) and in patients who took adenoidectomy before the age of 5 years (94.4%). TTH can occur as early as 3 months after adenoidectomy. AR and the operation way might have relationships with TTH.


NF-kappaB plays a major role in the maturation of human dendritic cells induced by NiSO(4) but not by DNCB.
Dendritic cell (DC) activation is a critical event for the induction of an immune response to haptens. Although signaling pathways such as mitogen-activated protein kinase (MAPK) family members have been reported to play a role in DC activation by haptens, little is known about the implication of the nuclear factor kappa B (NF-kappaB) pathway. In this work, we showed that NiSO(4) induced the expression of HLA-DR, CD83, CD86, and CD40 and the production of interleukin (IL)-8, IL-6, and IL-12p40 in human DCs, whereas DNCB induced mainly the expression of CD83 and CD86 and the production of IL-8. NiSO(4) but not DNCB was able to activate the degradation of IkappaB-alpha leading to the binding of the p65 subunit of NF-kappaB on specific DNA probes. Inhibition of the NF-kappaB pathway using BAY 11-7085 prevents both CD40 and HLA-DR expression and cytokine production induced by NiSO(4). However, BAY 11-7085 only partially inhibited CD86 and CD83 expression induced by NiSO(4). In addition, p38 MAPK and NF-kappaB were independently activated by NiSO(4) since SB203580 did not inhibit NF-kappaB activation by NiSO(4). Interestingly, we also showed that DNCB inhibited the degradation of IkappaB-alpha induced by tumor necrosis factor-alpha leading to alteration of CD40, HLA-DR, and CD83 expression but not of CD86 and CCR7. Extensive modifications of DC phenotype by NiSO(4) in comparison to DNCB are probably the consequence of NF-kappaB activation by NiSO(4) but not by DNCB.