Colposcopy, colpocytology and the vaginal ecosystem. Oncological, bacteriological and hormonal evaluation in a series of 400 women.
The Authors retrospectively considered colpocytological and colposcopic findings in a series of 400 women, aged 16 to 83 years, presenting for the first time at the Oncological Gynaecology Unit of the Institute of Gynaecology and Obstetrics of Padua University between 1991 and 1992. In addition to oncological evaluation, the bacteriological profile and hormone status of cytological samples were formulated in all cases. The most common oncological finding was a cell morphology within normal limits (67%), followed by reactive and reparative changes (19%) and low-grade squamous intraepithelial lesions (SIL, 12%). Histological findings correlated well with the cytological diagnosis, though low-grade SIL was over-estimated. As for the bacteriological profile, a mixed flora was most frequent (56.7%) followed, especially in fertile age, by Döderlein's bacillus (20%) and vaginosis (15.5%). Colposcopy most frequently revealed ectopia and/or a normal transformation zone (50.7%) and dystrophic mucosa (21%). An abnormal transformation zone was more common among women with a moderate-to-abundant flora. Fifteen male partners were also checked: cellular changes typical of human papilloma virus infection were found in 40% and colposcopic findings compatible with said virus were observed in 26.6% of cases. These results confirm that colpocytology provides a complete and simultaneous evaluation not only of cell morphology, but also of the bacterial population and hormones in the vaginal ecosystem. It is therefore the method of choice in screening for cervical and vaginal neoplasms and an effective means for simultaneously evaluating vaginal flora and hormone status.


Tracheal laceration following double-lumen intubation during Ivor Lewis esophagogastrectomy.
A case of a 48-year-old man with an iatrogenic membranous tracheal wall rupture after double-lumen intubation during Ivor Lewis esophagogastrectomy is presented. Tracheal injury was successfully managed surgically with the use of a bovine pericardial patch and reinforcement with the gastric conduit which was moved toward the posterior wall of the membranous trachea sealing the wall laceration.


Participating in communities of practice.
Hospital librarians understand they need to move outside the four walls of the physical library and provide information support for clinicians in various settings. Librarians round with patient care teams as clinical librarians. They sit on quality improvement and patient safety committees in order to provide information to those groups. Many are members of their organization's Institutional Review Board. Some of these activities are done for a specific purpose and are short-lived. Other activities become institutionalized as the value of the librarian's contribution is recognized. This article will describe examples in which hospital librarians are part of multidisciplinary teams created to improve patient care in their hospital.


Glymphatic clearance controls state-dependent changes in brain lactate concentration.
Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep-wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport.


Exploring the existence of a stayer population with mover-stayer counting process models: application to joint damage in psoriatic arthritis.
Many psoriatic arthritis patients do not progress to permanent joint damage in any of the 28 hand joints, even under prolonged follow-up. This has led several researchers to fit models that estimate the proportion of stayers (those who do not have the propensity to experience the event of interest) and to characterize the rate of developing damaged joints in the movers (those who have the propensity to experience the event of interest). However, when fitted to the same data, the paper demonstrates that the choice of model for the movers can lead to widely varying conclusions on a stayer population, thus implying that, if interest lies in a stayer population, a single analysis should not generally be adopted. The aim of the paper is to provide greater understanding regarding estimation of a stayer population by comparing the inferences, performance and features of multiple fitted models to real and simulated data sets. The models for the movers are based on Poisson processes with patient level random effects and/or dynamic covariates, which are used to induce within-patient correlation, and observation level random effects are used to account for time varying unobserved heterogeneity. The gamma, inverse Gaussian and compound Poisson distributions are considered for the random effects.


Accurate ab initio potentials at low cost via correlation scaling and extrapolation: application to CO(A 1Pi).
A recently proposed scheme that enables high quality molecular potentials to be obtained from small basis set calculations via scaling and extrapolation of the electron correlation to the complete basis set limit plus extrapolation to the complete basis set limit of the complete-active-space self-consistent field energy has been applied to the A 1Pi electronic state of CO. Based on standard multireference configuration interaction raw energies calculated with correlation-consistent basis sets of the aug-cc-pVXZ and aug-cc-pCVXZ types for the scaling and extrapolation procedures, a barrier separating the equilibrium region from the dissociation asymptote of 594+/-46 cm(-1) has been predicted at an internuclear distance of 2.25+/-0.01 A in reasonable agreement with some previous theoretical work and a recent direct least-squares fit to available spectroscopic data, while being 38% smaller than an early experimental upper limit of 950+/-150 cm(-1). Good agreement with experiment is also obtained for the minimum well depth and location at equilibrium: 25,532+/-165 cm(-1) at 1.2346+/-0.0015 A (theoretical) versus 25,597 cm(-1) at 1.2346+/-0.0006 A (experimental). The method can be extended to other wave function models, providing a general strategy for accurate potentials of larger dimensionality at costs that can be drastically smaller than traditional ones.


Impaired Balance in Patients with Fibromyalgia Syndrome: Predictors of the Impact of This Disorder and Balance Confidence.
Patients with fibromyalgia syndrome (FMS) have a nonspecific postural balance disorder and a greater prevalence of falls. to clarify which aspects of maintaining balance are associated with the impact of the disorder and with balance confidence. A total of 182 persons with FMS agreed to participate in this study. After re-evaluation, 57 fully met inclusion criteria: age 40-70 years and moderate-severe impact of the illness according to the Fibromyalgia Impact Questionnaire (FIQ). All participants underwent a posture control analysis with a stabilometric platform, an evaluation of the perception of verticality and an exploration of the vestibular system via functional tests. Additionally, they self-completed questionnaires about balance confidence, central sensitization, pain catastrophizing, kinesiophobia, dizziness and days with episodes of instability. The FIQ was associated with central sensitization and dizziness, which explained 56% of its variance (AdjR2 = 0.566), while days with instability, kinesiophobia and dizziness also explained more than half of the variance of the balance confidence scale (AdjR2 = 0.527). A high percentage of positive responses was found for functional tests (>50%) and a high dispersion in the stabilometric parameters. the detection of factors susceptible to intervention, such as disability due to dizziness, takes on special relevance in patients with FMS.


Cancer in a dyadic context: older couples' negotiation of ambiguity and search for meaning at the end of life.
Ambiguity in the dying experience can be a major source of stress for older couples who must often balance the provision of care with respect for autonomy, aggressive treatment with quality-of-life, and individual with dyadic understandings and preferences. This study explores patterns of relationship, support, and communication in married or partnered couples where one partner is diagnosed with advanced and terminal cancer. Thirty-five older spousal/partner dyads participated in focused, semistructured interviews about relational aspects of their illness experiences. Faced with often uncertain and ambiguous circumstances, cancer patients and their partner caregivers describe the individual and dyadic processes that they have engaged in as they approach the end of life. Implications are highlighted for future research and practice with older adult couples at the end of life.


An β-1,4-xylanase with exo-enzyme activity produced by Paenibacillus xylanilyticus KJ-03 and its cloning and characterization.
Paenibacillus xylanilyticus KJ-03 was isolated from soil samples obtained from a field with Amorphophallus konjac plants. A gene encoding xylanase was isolated from KJ-03 and cloned using a fosmid library. The xynA gene encodes xylanase; it consists of 1,035 bp and encodes 345 amino acids. The amino acid sequence deduced from the P. xylanilyticus KJ-03 xylanase showed 81% and 69% identities with those deduced from the P. polymyxa E681 and Paenibacillus sp. HPL-001 xylanases, respectively. The xynA gene comprises a single domain, consisting of a catalytic domain of the glycosyl hydrolase (GH) 10 family. The xynA gene was expressed in Escherichia coli BL21 (trxB), and the recombinant xylanase was purified by Niaffinity chromatography. The purified xylanase showed optimum activity with birchwood xylan as a substrate at 40°C and pH 7.4. Treatment with Mg(2+) and Li(+) showed a slight decrease in XynA activity; however, treatment with 5 mM Cu(2+) completely inhibited its activity. The results of the thin layer chromatography analysis indicated that the major hydrolysis product was xylobiose and small amounts of xylose and xylotriose. XynA showed increased activity with oat spelt xylan and birchwood xylan, but showed only slight activity with locust bean gum.


A comparison of the cluster-span threshold and the union of shortest paths as objective thresholds of EEG functional connectivity networks from Beta activity in Alzheimer's disease.
The Cluster-Span Threshold (CST) is a recently introduced unbiased threshold for functional connectivity networks. This binarisation technique offers a natural trade-off of sparsity and density of information by balancing the ratio of closed to open triples in the network topology. Here we present findings comparing it with the Union of Shortest Paths (USP), another recently proposed objective method. We analyse standard network metrics of binarised networks for sensitivity to clinical Alzheimer's disease in the Beta band of Electroencephalogram activity. We find that the CST outperforms the USP, as well as subjective thresholds based on fixing the network density, as a sensitive threshold for distinguishing differences in the functional connectivity between Alzheimer's disease patients and control. This study provides the first evidence of the usefulness of the CST for clinical research purposes.


A high-resolution copy-number variation resource for clinical and population genetics.
Chromosomal microarray analysis to assess copy-number variation has become a first-tier genetic diagnostic test for individuals with unexplained neurodevelopmental disorders or multiple congenital anomalies. More than 100 cytogenetic laboratories worldwide use the new ultra-high resolution Affymetrix CytoScan-HD array to genotype hundreds of thousands of samples per year. Our aim was to develop a copy-number variation resource from a new population sample that would enable more accurate interpretation of clinical genetics data on this microarray platform and others. Genotyping of 1,000 adult volunteers who are broadly representative of the Ontario population (as obtained from the Ontario Population Genomics Platform) was performed with the CytoScan-HD microarray system, which has 2.7 million probes. Four independent algorithms were applied to detect copy-number variations. Reproducibility and validation metrics were quantified using sample replicates and quantitative-polymerase chain reaction, respectively. DNA from 873 individuals passed quality control and we identified 71,178 copy-number variations (81 copy-number variations/individual); 9.8% (6,984) of these copy-number variations were previously unreported. After applying three layers of filtering criteria, from our highest confidence copy-number variation data set we obtained >95% reproducibility and >90% validation rates (73% of these copy-number variations overlapped at least one gene). The genotype data and annotated copy-number variations for this largely Caucasian population will represent a valuable public resource enabling clinical genetics research and diagnostics.


Lagrangian coherent structure assisted path planning for transoceanic autonomous underwater vehicle missions.
Transoceanic Gliders are Autonomous Underwater Vehicles (AUVs) for which there is a developing and expanding range of applications in open-seas research, technology and underwater clean transport. Mature glider autonomy, operating depth (0-1000 meters) and low energy consumption without a CO2 footprint enable evolutionary access across ocean basins. Pursuant to the first successful transatlantic glider crossing in December 2009, the Challenger Mission has opened the door to long-term, long-distance routine transoceanic AUV missions. These vehicles, which glide through the water column between 0 and 1000 meters depth, are highly sensitive to the ocean current field. Consequently, it is essential to exploit the complex space-time structure of the ocean current field in order to plan a path that optimizes scientific payoff and navigation efficiency. This letter demonstrates the capability of dynamical system theory for achieving this goal by realizing the real-time navigation strategy for the transoceanic AUV named Silbo, which is a Slocum deep-glider (0-1000 m), that crossed the North Atlantic from April 2016 to March 2017. Path planning in real time based on this approach has facilitated an impressive speed up of the AUV to unprecedented velocities resulting in major battery savings on the mission, offering the potential for routine transoceanic long duration missions.


Granzymes drive a rapid listeriolysin O-induced T cell apoptosis.
The Listeria monocytogenes protein listeriolysin O (LLO) is a pore-forming protein essential for virulence. Although the major role for LLO is to allow L. monocytogenes entry into the cytosol, it also induces apoptosis of activated lymphocytes, an obligatory cellular response that modulates the infection. Induction of apoptosis by LLO proceeds through a fast, caspase-dependent pathway and a slow, caspase-independent pathway. Polyclonal T cell lines were generated from either normal mice or mice deficient in granzyme and perforin proteins, and then treated with apoptogenic doses of LLO. In this study we show that apoptosis of lymphocytes induced by LLO was characterized by activation of caspases as quickly as 30 min that was dependent on the expression of granzymes. In the absence of granzymes, all parameters of apoptosis such as caspase activation, phosphatidylserine exposure, mitochondrial depolarization, and DNA fragmentation were dramatically reduced in magnitude. Removal of perforin inhibited the apoptotic effect of LLO on cells by approximately 50%. Neutralization of intracellular acidification using chloroquine inhibited the rapid apoptotic death. In agreement with these findings granzyme-deficient mice harbored lower bacterial titers and decrease splenic pathology compared with normal mice following L. monocytogenes infection. Thus, LLO exploits apoptotic enzymes of the adaptive immune response to eliminate immune cells and increase its virulence.


Cell adhesion pattern created by OSTE polymers.
Engineering surfaces with functional polymers is a crucial issue in the field of micro/nanofabrication and cell-material interface studies. For many applications of surface patterning, it does not need cells to attach on the whole surface. Herein, we introduce a novel polymer fabrication protocol of off-stoichiometry thiol-ene (OSTE) polymers to create heterogeneity on the surface by utilizing 3D printing and soft-lithography. By choosing two OSTE polymers with different functional groups, we create a pattern where only parts of the surface can facilitate cell adhesion. We also study the hydrophilic property of OSTE polymers by mixing poly(ethylene glycol) (PEG) directly with pre-polymers and plasma treatments afterwards. Moreover, we investigate the effect of functional groups' excess ratio and hydrophilic property on the cell adhesion ability of OSTE polymers. The results show that the cell adhesion ability of OSTE materials can be tuned within a wide range by the coupling effect of functional groups' excess ratio and hydrophilic property. Meanwhile, by mixing PEG with pre-polymers and undergoing oxygen plasma treatment afterward can significantly improve the hydrophilic property of OSTE polymers.


Characterizing durations of heroin abstinence in the California Civil Addict Program: results from a 33-year observational cohort study.
In accordance with the chronic disease model of opioid dependence, cessation is often observed as a longitudinal process rather than a discrete endpoint. We aimed to characterize and identify predictors of periods of heroin abstinence in the natural history of recovery from opioid dependence. Data were collected on participants from California who were enrolled in the Civil Addict Program from 1962 onward by use of a natural history interview. Multivariate regression using proportional hazards frailty models was applied to identify independent predictors and correlates of repeated abstinence episode durations. Among 471 heroin-dependent males, 387 (82.2%) reported 932 abstinence episodes, 60.3% of which lasted at least 1 year. Multivariate analysis revealed several important findings. First, demographic factors such as age and ethnicity did not explain variation in durations of abstinence episodes. However, employment and lower drug use severity predicted longer episodes. Second, abstinence durations were longer following sustained treatment versus incarceration. Third, individuals with multiple abstinence episodes remained abstinent for longer durations in successive episodes. Finally, abstinence episodes initiated >10 and ≤20 years after first use lasted longer than others. Public policy facilitating engagement of opioid-dependent individuals in maintenance-oriented drug treatment and employment is recommended to achieve and sustain opioid abstinence.


[Colonoscopic diagnosis].
Between 1974 and 1992, we perform 3,054 colonoscopies for diagnosis in 2,770 patients, both of sexes, between the ages of 1 and 101 yr, most of them over the fifth decade of life. In 300 procedures the bowel cleansing was made with the standard method of liquid diet and enemas, and in the other 2,754 with the oral administration of saline solution 9% with optimal results. We get the sedation of patients with the intravenous administration of diazepam 10mg, or pethidine 50 mg, or midazolam 2.5 to 5 mg, and in children with ketamine and the anesthesiologist assistance. In 95% of the procedures we can see the cecum and the ileum; the diagnosis was abnormal in 52.78% of cases, normal in 45.20%, and insufficient in 02.02% specially for a bad cleansing of the bowel. In the abnormal group, the most frequent diseases we diagnose were: polyps, cancer, diverticular disease, and specific inflammatory disease of the bowel like TBC, radiation proctosigmoiditis, amebiasis, and non-specific bowel disease: "colitis", ulcerative proctocolitis, erosive colitis, and Crohn's disease. Colonoscopy is a very important method for diagnosis of colon diseases, alone or complementary of double contrast X-ray of the colon.


[IUD-deformation and unusual complications of intrauterine contraception].
Deformations of intrauterine contraceptive devices in the uterine cavity and their consequences are reported. In a period of 16 years we observed two partial perforations and two tuboovarian abscesses with this method of contraception in 3753 women. The value of IUD as a contraceptive of the second range is not degraded by these rare complications.


Biochemical determinants of the IGFBP-3-hyaluronan interaction.
IGFBP-3, the most abundant IGFBP and the main carrier of insulin-like growth factor I (IGF-I) in the circulation, can bind IGF-1 with high affinity, which attenuates IGF/IGF-IR interactions, thereby resulting in antiproliferative effects. The C-terminal domain of insulin-like growth factor-binding protein-3 (IGFBP-3) is known to contain an 18-basic amino acid motif capable of interacting with either humanin (HN) or hyaluronan (HA). We previously showed that the 18-amino acid IGFBP-3 peptide is capable of binding either HA or HN with comparable affinities to the full-length IGFBP-3 protein and that IGFBP-3 can compete with the HA receptor, CD44, for binding HA. Blocking the interaction between HA and CD44 reduced viability of A549 human lung cancer cells. In this study, we set out to better characterize IGFBP-3-HA interactions. We show that both stereochemistry and amino acid identity are important determinants of the interaction between the IGFBP-3 peptide and HA and for the peptide's ability to exert its cytotoxic effects. Binding of IGFBP-3 to either HA or HN was unaffected by glycosylation or reduction of IGFBP-3, suggesting that the basic 18-amino acid residue sequence of IGFBP-3 remains accessible for interaction with either HN or HA upon glycosylation or reduction of the full-length protein. Removing N-linked oligosaccharides from CD44 increased its ability to compete with IGFBP-3 for binding HA, while reduction of CD44 rendered the protein relatively ineffective at blocking IGFBP-3-HA interactions. We conclude that both deglycosylation and disulfide bond formation are important for CD44 to compete with IGFBP-3 for binding HA.


A public health framework for developing local preventive services guidelines.
In this article, we describe the San Francisco Department of Public Health's (SFDPH's) framework for developing evidence-based screening and vaccination recommendations. We first reviewed our local data using surveillance and syndemic data. We then compiled and compared existing federal, state, and local recommendations. Then we identified differences as compared with our local evidence; where more evidence was required to make a recommendation, we culled from additional data sources and conducted additional analyses. Lastly, we developed our guidelines by confirming existing recommendations or making new recommendations based on this process. In the end, we successfully developed evidence-based clinical screening and prevention guidelines that have been adopted by the SFDPH Health Commission. We encourage the use of this framework in other public health settings at the local level.


Rearing environment affects spatial learning in juvenile Chinook salmon Oncorhynchus tshawytscha.
We tested the prediction that a complex physical rearing environment would enhance short-term spatial memory as assessed by learning ability in a spatial navigation task in juvenile Chinook salmon Oncorhynchus tshawytscha. We reared fish in two low-density treatments, where fish were either in bare fiberglass tanks (bare) or in tanks with physical structure (complex). We also tested conventionally reared high-density hatchery fish to compare with these other experimental treatments. Our reason for including this third hatchery treatment is that the two low-density treatments, aside from the manipulation of structure, followed a rearing programme that is designed to produce fish with more wild-like characteristics. We tested individually marked fish for seven consecutive days and recorded movement and time to exit a testing maze. Stimulus conspecific fish outside the exit of the maze provided positive reinforcement for test fish. Fish from the bare treatment were less likely to exit the start box compared with fish in the complex and hatchery treatments. However, fish in the hatchery treatment were significantly more likely to exit the maze on their own compared with both the bare and complex treatments. Hatchery fish effectively learned the task as shown by a decrease in the number of mistakes over time, but the number of mistakes was significantly greater on the first day of trials. Increasing habitat complexity with structure may not necessarily promote spatial learning ability, but differences between hatchery and experimental treatments in rearing density and motivation to be near conspecifics likely led to observed behavioural differences.


A predictive multiscale model of in-stent restenosis in femoral arteries: linking haemodynamics and gene expression with an agent-based model of cellular dynamics.
In-stent restenosis (ISR) is a maladaptive inflammatory-driven response of femoral arteries to percutaneous transluminal angioplasty and stent deployment, leading to lumen re-narrowing as consequence of excessive cellular proliferative and synthetic activities. A thorough understanding of the underlying mechanobiological factors contributing to ISR is still lacking. Computational multiscale models integrating both continuous- and agent-based approaches have been identified as promising tools to capture key aspects of the complex network of events encompassing molecular, cellular and tissue response to the intervention. In this regard, this work presents a multiscale framework integrating the effects of local haemodynamics and monocyte gene expression data on cellular dynamics to simulate ISR mechanobiological processes in a patient-specific model of stented superficial femoral artery. The framework is based on the coupling of computational fluid dynamics simulations (haemodynamics module) with an agent-based model (ABM) of cellular activities (tissue remodelling module). Sensitivity analysis and surrogate modelling combined with genetic algorithm optimization were adopted to explore the model behaviour and calibrate the ABM parameters. The proposed framework successfully described the patient lumen area reduction from baseline to one-month follow-up, demonstrating the potential capabilities of this approach in predicting the short-term arterial response to the endovascular procedure.


Vaccine-induced escape mutant of hepatitis B virus.
In southern Italy, 44 contacts of hepatitis B virus carriers, including infants of carrier mothers, became HBsAg positive despite passive and active immunisation according to standard protocols. In 32 of these vaccinees infection was confirmed by the presence of additional markers of viral replication. In 1 infant, serious disease occurred. The virus from this patient is an escape mutant with a different sequence from that of the isolate from the mother. A point mutation from guanosine to adenosine at nucleotide position 587 resulted in an aminoacid substitution from glycine to arginine in the highly antigenic a determinant of HBsAg. This mutation is stable: it is present in an isolate from the child 5 years later. In some of these patients, including this child, the a determinant, to which a large part of the vaccine-induced immunity is directed, has been partly lost. Binding to HBsAg of a monoclonal antibody, previously mapped to the region of the mutation, was reduced in the child relative to that of the mother.


Mig-6 controls EGFR trafficking and suppresses gliomagenesis.
Glioblastoma multiforme (GBM) is the most common and lethal primary brain cancer that is driven by aberrant signaling of growth factor receptors, particularly the epidermal growth factor receptor (EGFR). EGFR signaling is tightly regulated by receptor endocytosis and lysosome-mediated degradation, although the molecular mechanisms governing such regulation, particularly in the context of cancer, remain poorly delineated. Here, high-resolution genomic profiles of GBM identified a highly recurrent focal 1p36 deletion encompassing the putative tumor suppressor gene, Mig-6. We show that Mig-6 quells the malignant potential of GBM cells and dampens EGFR signaling by driving EGFR into late endosomes and lysosome-mediated degradation upon ligand stimulation. Mechanistically, this effect is mediated by the binding of Mig-6 to a SNARE protein STX8, a protein known to be required for late endosome trafficking. Thus, Mig-6 functions to ensure recruitment of internalized receptor to late endosomes and subsequently the lysosomal degradation compartment through its ability to specifically link EGFR and STX8 during ligand-stimulated EGFR trafficking. In GBM, the highly frequent loss of Mig-6 would therefore serve to sustain aberrant EGFR-mediated oncogenic signaling. Together, these data uncover a unique tumor suppression mechanism involving the regulation of receptor trafficking.


Analysis of failures and complications of neodymium: YAG laser photocoagulation in gastrointestinal tract tumors. A retrospective survey of 18 years' experience.
Eight years of experience with endoscopic Nd:YAG laser photocoagulation were analyzed in retrospect in an attempt to identify factors relating to both failures and complications of laser therapy, and to delineate its limits and pitfalls in benign and malignant tumors. Three hundred and seventy-eight patients were studied, including 42 with gastroesophageal cancer, 180 with colorectal adenoma and 156 with colorectal malignancy. Patients with gastroesophageal cancer (n = 42) were referred mainly for obstruction in esophageal cancer and for bleeding in gastric cancer, with successful palliation in 86 and 81%. Hemorrhage was the only complication seen, twice during and twice after treatment. Pain, heat and smoke-induced complaints and sometimes temporary increased dysphagia were mentioned. Two white-surfaced tumors did not react at all. Patients with colorectal adenoma (n = 150) were divided into groups according to the size of the lesion. Definitive, histologically documented eradication of adenomatous tissue was achieved in 43% of the extensive, in 69% of the intermediate, and in 97% of the small adenomas. Major complications, mainly stenosis and hemorrhage, occurred in 6.4%, 7.6% and none of the lesions, respectively, and minor complications were seen in 57.4, 30.8 and 13.8%, respectively. Stenosis appeared to be related only to prior electrocoagulation and to excessive delivery of energy. Post-treatment hemorrhage occurred at about day 7. In familial polyposis (n = 30) surveillance of the rectal stump was successful in 84%, with major and minor complications in 4% and 12%. In colorectal cancers (n = 156) treated for palliation of bleeding and obstruction, success was obtained in 91%. major complications (13%) consisted mainly of stenosis and perforation.(ABSTRACT TRUNCATED AT 250 WORDS)


Growth of Single-Walled Carbon Nanotubes from Solid Carbon Nanoparticle Seeds via Cap Formation Engineering with a Two-Step Growth Process and Water Vapor Supply.
Solid carbon nanoparticles are promising growth seeds to prepare single-walled carbon nanotubes (SWCNTs) at high temperatures, at which the SWCNT crystallinity should be improved significantly but conventional metal catalyst nanoparticles are unstable and suffer from aggregation. The noncatalytic nature of solid carbon nanoparticles, however, makes SWCNT growth inefficient, resulting in a limited growth yield. In this study, we develop a two-step chemical vapor deposition process to efficiently synthesize high-crystallinity SWCNTs at high temperatures from solid carbon nanoparticles obtained from nanodiamond. Based on thermodynamic considerations, the growth conditions are separately adjusted to supply different growth driving forces which are suitable for the formation of the initial cap structures and for the stationary elongation of SWCNTs. This process, called cap formation engineering, improves the nucleation density of the cap structures. We examined the changes in crystallinity, amorphous carbon deposition, diameter, and yield of SWCNTs with respect to the synthesis conditions. By controlling the initial growth conditions, high-quality SWCNTs are grown with improved yield. With the addition of water vapor as the etchant, deposition of amorphous carbon at high temperatures was further prevented. The results provide a pathway for precise growth control of SWCNTs from unconventional solid growth seeds.


Availability, affordability and stock-outs of commodities for the treatment of snakebite in Kenya.
Annually, about 2.7 million snakebite envenomings occur globally. Alongside antivenom, patients usually require additional care to treat envenoming symptoms and antivenom side effects. Efforts are underway to improve snakebite care, but evidence from the ground to inform this is scarce. This study, therefore, investigated the availability, affordability, and stock-outs of antivenom and commodities for supportive snakebite care in health facilities across Kenya. This study used an adaptation of the standardised World Health Organization (WHO)/Health Action International methodology. Data on commodity availability, prices and stock-outs were collected in July-August 2020 from public (n = 85), private (n = 36), and private not-for-profit (n = 12) facilities in Kenya. Stock-outs were measured retrospectively for a twelve-month period, enabling a comparison of a pre-COVID-19 period to stock-outs during COVID-19. Affordability was calculated using the wage of a lowest-paid government worker (LPGW) and the impoverishment approach. Accessibility was assessed combining the WHO availability target (≥80%) and LPGW affordability (<1 day's wage) measures. Overall availability of snakebite commodities was low (43.0%). Antivenom was available at 44.7% of public- and 19.4% of private facilities. Stock-outs of any snakebite commodity were common in the public- (18.6%) and private (11.7%) sectors, and had worsened during COVID-19 (10.6% versus 17.0% public sector, 8.4% versus 11.7% private sector). Affordability was not an issue in the public sector, while in the private sector the median cost of one vial of antivenom was 14.4 days' wage for an LPGW. Five commodities in the public sector and two in the private sector were deemed accessible. Access to snakebite care is problematic in Kenya and seemed to have worsened during COVID-19. To improve access, efforts should focus on ensuring availability at both lower- and higher-level facilities, and improving the supply chain to reduce stock-outs. Including antivenom into Universal Health Coverage benefits packages would further facilitate accessibility.


Molecular Mapping to Discover Reliable Salinity-Resilient QTLs from the Novel Landrace Akundi in Two Bi-Parental Populations Using SNP-Based Genome-Wide Analysis in Rice.
Achieving high-yield potential is always the ultimate objective of any breeding program. However, various abiotic stresses such as salinity, drought, cold, flood, and heat hampered rice productivity tremendously. Salinity is one of the most important abiotic stresses that adversely affect rice grain yield. The present investigation was undertaken to dissect new genetic loci, which are responsible for salt tolerance at the early seedling stage in rice. A bi-parental mapping population (F2:3) was developed from the cross between BRRI dhan28/Akundi, where BRRI dhan28 (BR28) is a salt-sensitive irrigated (boro) rice mega variety and Akundi is a highly salinity-tolerant Bangladeshi origin indica rice landrace that is utilized as a donor parent. We report reliable and stable QTLs for salt tolerance from a common donor (Akundi) irrespective of two different genetic backgrounds (BRRI dhan49/Akundi and BRRI dhan28/Akundi). A robust 1k-Rice Custom Amplicon (1k-RiCA) SNP marker genotyping platform was used for genome-wide analysis of this bi-parental population. After eliminating markers with high segregation distortion, 886 polymorphic SNPs built a genetic linkage map covering 1526.5 cM of whole rice genome with an average SNP density of 1.72 cM for the 12 genetic linkage groups. A total of 12 QTLs for nine different salt tolerance-related traits were identified using QGene and inclusive composite interval mapping of additive and dominant QTL (ICIM-ADD) under salt stress on seven different chromosomes. All of these 12 new QTLs were found to be unique, as no other map from the previous study has reported these QTLs in the similar chromosomal location and found them different from extensively studied Saltol, SKC1, OsSalT, and salT locus. Twenty-eight significant digenic/epistatic interactions were identified between chromosomal regions linked to or unlinked to QTLs. Akundi acts like a new alternate donor source of salt tolerance except for other usually known donors such as Nona Bokra, Pokkali, Capsule, and Hasawi used in salt tolerance genetic analysis and breeding programs worldwide, including Bangladesh. Integration of the seven novel, reliable, stable, and background independent salinity-resilient QTLs (qSES1, qSL1, qRL1, qSUR1, qSL8, qK8, qK1) reported in this investigation will expedite the cultivar development that is highly tolerant to salt stress.


The reporting of needlestick injuries sustained in theatre by surgeons: are we under-reporting?
Surgeons frequently sustain needlestick injuries when operating. The aim of this study was to evaluate the incidence and reporting rate of needlestick injuries at one institution. A questionnaire was distributed anonymously to 69 surgeons of all grades and specialties in a district general hospital in the UK. The questionnaire was returned by 42 surgeons (60.9%). There were 840 needlestick injuries over two years, of which 126 caused bleeding. Senior surgeons who spent more hours operating per week had a higher rate of needlestick injuries compared with junior surgeons (29.1 vs 6.59 injuries per surgeon over two years). Of the total number of injuries, 19 (2.26%) were reported to Occupational Health according to the surgeons questioned, but only six reported incidents were found in the Occupational Health records. Junior surgeons were significantly more likely to report needlestick injuries than senior surgeons (9.82% vs 1.10% of injuries reported, P=0.0000045). The main reasons for failure to report needlestick injuries were due to the lack of time and excessive paperwork. Seventy-three percent of surgeons did not routinely use double gloves when operating, mainly because of decreased hand sensation. The rate of needlestick injury reporting by surgeons at this institution is extremely low. Previous studies have shown a higher reporting rate suggesting that, despite awareness of blood-borne infections, surgeons are still not following recommended protocols.


Coping self-efficacy buffers psychological and physiological disturbances in HIV-infected men following a natural disaster.
The importance of coping self-efficacy (CSE) appraisals on psychological and physiological functioning for HIV seropositive patients facing a severe environmental stressor was tested comparing 37 HIV-infected gay men and 42 healthy male control participants following Hurricane Andrew. Results suggested that greater levels of CSE were related to lower emotional distress and posttraumatic stress disorder (PTSD) symptoms in both groups. In addition, greater CSE was associated with lower norepinephrine to cortisol ratios in the HIV group but not in the healthy control group. Results are discussed in relation to the coping process for HIV-infected individuals specifically and chronically ill populations in general who face severe environmental stressors.


Combined anterior cruciate ligament reconstruction and lateral extra-articular tenodesis does not result in an increased rate of osteoarthritis: a systematic review and best evidence synthesis.
The role of lateral extra-articular tenodesis (LEAT) as an augment to primary anterior cruciate ligament reconstruction (ACLR) remains controversial. However, concerns exist regarding the risk of development of osteoarthritis due to over constraint of the knee. To systematically review the literature to analyse the long-term incidence of osteoarthritis in patients who had an LEAT performed in isolation or in combination with intra-articular ACLR for the treatment of ACL deficiency. Two reviewers independently searched five databases for randomized controlled trials (RCTs), non-randomized comparative, and retrospective cohort studies (CS) with long-term radiological follow-up of patients with ACL deficiency treated with ACLR combined with LEAT or LEAT in isolation. Risk of bias was performed using a modified Downs & Black's checklist. The primary outcome was the development of osteoarthritis. The studies were divided into those with moderate/severe osteoarthritis at between 5 to 10 years and >10-year follow-up. The rate of meniscal pathology at the time of the index surgery was recorded. A best evidence synthesis was performed. Eight studies reported on 421 patients in which an LEAT procedure was carried out. There were two high-quality RCTs and six low-quality CS. The follow-up was between 5- and 10-years in 5 studies and >10-years in 3. The presence of moderate/severe osteoarthritis was not detected in three studies and was found in 4/44 (9%) and 13/70 (18.6%) patients in the other two. At 11 year follow-up, one study demonstrated no osteoarthritis, while the other two studies reported rates of 54/100 (54%) and 17/24 (71%) respectively at >24 years. In the latter two cases, the rate of meniscal pathology was >50%. A best evidence synthesis revealed that there was insufficient evidence that the addition of a LEAT to an ACLR resulted in an increased rate of osteoarthritis. The best available evidence would suggest that the addition of a LEAT to ACLR does not result in an increase rate of osteoarthritis of the knee. In knees that have undergone a combined ACLR and LEAT, the incidence of osteoarthritis was low up to 11 years but increased thereafter. The presence of meniscal injury at the index surgery was reported to be greater predictor of the development of osteoarthritis. IV.


Tobacco use cessation interventions for lesbian, gay, bisexual, transgender and queer youth and young adults: A scoping review.
Smoking prevalence among LGBTQ + youth and young adults is alarmingly high compared to their non-LGBTQ + peers. The purpose of the scoping review was to assess the current state of smoking prevention and cessation intervention research for LGBTQ + youth and young adults, identify and describe these interventions and their effectiveness, and identify gaps in both practice and research. A search for published literature was conducted in PubMed, Scopus, CINAHL, PsychInfo, and LGBT Life, as well as an in-depth search of the grey literature. All English articles published or written between January 2000 and February 2016 were extracted. The search identified 24 records, of which 21 were included; 11 from peer reviewed sources and 10 from the grey literature. Of these 21, only one study targeted young adults and only one study had smoking prevention as an objective. Records were extracted into evidence tables using a modified PICO framework and a narrative synthesis was conducted. The evidence to date is drawn from methodologically weak studies; however, group cessation counselling demonstrates high quit rates and community-based programs have been implemented, although very little evidence of outcomes exist. Better-controlled research studies are needed and limited evidence exists to guide implementation of interventions for LGBTQ + youth and young adults. This scoping review identified a large research gap in the area of prevention and cessation interventions for LGBTQ youth and young adults. There is a need for effective, community-informed, and engaged interventions specific to LGBTQ + youth and young adults for the prevention and cessation of tobacco.


[Significance and limitations of f/tPSA in differential diagnosis of prostate cancer with tPSA levels between 4 and 10 ng/ml].
To study significance and limitations of the ratio of free to total prostate specific antigen (f/t PSA) in differential diagnosis between prostate cancer and benign prostatehyperplasia (BPH) with total PSA (tPSA) levels between 4 and 10 ng/ml. We analysed retrospectively 180 prostate cancer and BPH patients who were diagnosed and treated in our hospital from October 1998 to October 2002 and had serum tPSA levels between 4 and 10 ng/ml. Of the 180 patients, 36 (20%) were histologically confirmed as prostate cancer and 144 (80%) BPH. The tPSA and free PSA (fPSA) in serum were measured by micropartical enzyme immunoassay. Prostate volume was measured by transabdominal ultrasonography. We chose Student's t-test for comparison between prostate cancer and BPH groups. The correlation between prostate volume and f/t PSA was analyzed using Pearson's correlation coefficient. The mean values of tPSA and f/t PSA were 6.75 ng/ml and 0.17 in patients with prostate cancer, 6.48 ng/ml and 0.25 in patients with BPH. The mean value of tPSA wasn't significantly different between patients with prostate cancer and BPH (P > 0.05). However, the mean value of f/t PSA of patients with prostate cancer was significantly lower than that of patients with BPH (P < 0.01). Furthermore, there were significant and positive correlation between prostate volume and f/t PSA in both groups with prostate cancer and BPH (prostate cancer group's correlation coefficient (r = 0.50, P < 0.01); BPH group (r = 0.24, P < 0.01). There was significant difference in f/t PSA between prostate cancer and BPH patients with prostate volumes more than 40 cm(3) (P < 0.05), but not between these two groups with prostate volumes more than 40 cm(3) (P > 0.05). The f/t PSA is significant in differential diagnosis between prostate cancer and BPH with tPSA levels between 4 and 10 ng/ml. But prostate volume has an effect on f/tPSA. The f/tPSA has diagnostic value of differentiation only when the prostate volume is less than 40 cm(3).


Inactivation of beta-lactamases by sulbactam and enhanced clinical activity due to target-site binding of the combination of sulbactam and ampicillin.
In addition to the beta-lactamase-inactivation activity of sulbactam, a stronger bactericidal activity has been confirmed with sulbactam/ampicillin than with either antibiotic alone. To clarify this latter mechanism, binding affinities of the combination drug were compared with those of ampicillin and sulbactam alone against the PBPs of E. coli, S. aureus, P. vulgaris and H. influenzae. Ampicillin showed the highest binding activity to the PBP fraction essential for septum formation such as PBP3 of E. coli, whereas sulbactam manifested the strongest affinity for the PBP fraction necessary for cell elongation such as PBP1a of E. coli. Sulbactam/ampicillin bound strongly to both PBP fractions. Light microscopy and scanning electronmicroscopy of these bacteria grown in the presence of the antibiotics revealed that more rapid formation of bulge or spheroplast forms of the cells are seen in the presence of small amounts of sulbactam/ampicillin compared to larger amounts of each drug alone. It is concluded that sulbactam/ampicillin, by synergistic inhibition of PBP fractions essential for bacterial cell division, can manifest a stronger bactericidal effect on Gram-positive and Gram-negative bacteria than each drug alone, not only in beta-lactamase-producing strains but also in ampicillin-sensitive strains.


Metabolic defects in lean nondiabetic offspring of NIDDM parents: a cross-sectional study.
First-degree relatives of NIDDM patients have an approximately 40% lifetime risk of developing diabetes, and insulin resistance is the best predictor. However, insulin resistance is altered by many other factors, including age, diet, exercise, and medications. To investigate the metabolic and endocrine alterations associated with insulin resistance when all the above confounding factors are excluded, we examined the first phase of insulin secretion and insulin sensitivity in 49 white normoglycemic (4.99 +/- 0.51 vs. 4.95 +/- 0.41 mmol/l) nonexercising lean (BMI, 24 +/- 3 vs. 23 +/- 2 kg/m2; 105 +/- 3 vs. 104 +/- 3% of ideal body weight) offspring of NIDDM patients. These subjects were compared with 29 matched healthy control subjects by means of an intravenous glucose bolus (0.3 g/kg body wt), immediately followed by a euglycemic-hyperinsulinemic (approximately 420 pmol/l) clamp, along with lipid and amino acid profiles. The offspring showed fasting hyperinsulinemia (40.6 +/- 15.8 vs. 30.9 +/- 13.6 pmol/l; P = 0.005) and higher free fatty acid (FFA) levels (582 +/- 189 vs. 470 +/- 140 micromol; P = 0.007), whereas triglycerides, total cholesterol, and HDL and LDL cholesterol levels were comparable with those of control subjects. Alanine (320 +/- 70 vs. 361 +/- 73 micromol/l; P = 0.017), serine (P = 0.05), and glutamine and glycine (P = 0.02) were lower in the offspring than in the control subjects, whereas branched-chain amino acids (343 +/- 54 vs. 357 +/- 54 micromol/l; P = 0.28) were not different. Insulin sensitivity was lower (4.86 +/- 1.65 vs. 6.17 +/ 1.56 mg x kg(-1) x min(-1); P = 0.001), and an inverse correlation with fasting FFAs in the offspring (adjusted R2 = 0.21, P = 0.0005), but not in control subjects (adjusted R2 = 0.03, P = 0.368), was found. Because insulin sensitivity in the offspring appeared to be a mixture of three distributions, they were subdivided into three subgroups: very low, low, and normal insulin sensitivity (20, 47, and 33%, respectively). The same alterations in amino acid and FFA metabolism were observed in the very low and low subgroups but not in the normal subgroup. The first phase of insulin secretion appeared to compensate significantly for insulin resistance in the low subgroup versus the normal subgroup and controls, but was inappropriately low in the subgroup with very low insulin sensitivity considering its degree of insulin resistance. In conclusion, lean insulin-resistant offspring of NIDDM parents showed 1) trimodal distribution of insulin sensitivity, 2) high fasting plasma FFA concentrations, 3) an inverse correlation between insulin sensitivity and FFA concentration, 4) low plasma gluconeogenic amino acid concentrations, and 5) defective insulin secretion when related to insulin sensitivity in the subgroup of very resistant offspring. These results suggest that, in this white population, insulin sensitivity may be determined by a single major gene and that alterations in FFA metabolism may play a role in the pathogenesis of NIDDM.


Simulation and theory of self-assembly and network formation in reversibly cross-linked equilibrium polymers.
A simulation model of hard spheres capable of reversible assembly into chains, which then may reversibly cross-link into networks, has been studied through grand canonical Monte Carlo simulation. Effects of varying intra- and interchain bond strengths, chain flexibilities, and restrictions on cross-linking angle were investigated. Observations including chain-length distributions and phase separation could be captured in most cases using a simple model theory. The coupling of chain growth to cross-linking was shown to be highly sensitive to the treatment of cross-linking by chain ends. In some systems, ladderlike domains of several cross-links joining two chains were common, resulting from cooperativity in the cross-linking. Extended to account for this phenomenon, the model theory predicts that such cooperativity will suppress phase separation in weakly polymerizing chains and at high cross-link concentration. In the present model, cross-linking stabilizes the isotropic phase with respect to the nematic phase, causing a shift in the isotropic-nematic transition to higher monomer concentration than in simple equilibrium polymers.


Double Rosensweig instability in a ferrofluid sandwich structure.
We consider a horizontal ferrofluid layer sandwiched between two layers of immiscible nonmagnetic fluids. In a sufficiently strong vertical magnetic field the flat interfaces between magnetic and nonmagnetic fluids become unstable to the formation of peaks. We theoretically investigate the interplay between these two instabilities for different combinations of the parameters of the fluids and analyze the evolving interfacial patterns. We also estimate the critical magnetic field strength at which thin layers disintegrate into an ordered array of individual drops.


[Health inequalities: self-reported complaints and their predictors in pupils from Belgium].
This paper identifies socioeconomic and sociodemographic predictors of respiratory/allergic health problems and subjective complaints in adolescents in Belgium. A cross-sectional analysis of the 1998 cross-national study "Health Behaviour of School aged Children" (HBSC) in French-speaking Belgium was undertaken. The survey was based on a self-completed questionnaire concerning various aspects of physical, emotional and social health. The five health problems (asthma, any other respiratory difficulty, allergy, poor subjective health, overweight and depressed feeling) were considered present when a positive reply was given to close-end questions stating if the pupils suffered, or have suffered from these problems during the last six months. We analysed a representative sample of 12,012 pupils aged 11 to 19 years in fifth and sixth grades of primary school, and in all six grades of secondary school. socioeconomics gradients were found for subjective ill health, depressed state and overweight (p<0.01). Depressed state and overweight were linearly associated with a family economic score. Respiratory difficulties and allergies were observed mainly in pupils in technical training. Pupils with a lower economic score have a higher prevalence of subjective complaints. It remains important to define determinants of subjective ill health and moreover, to act upon these results by increasing accessibility to health services when necessary, by adapting some others to young people and by tailoring interventions to objective and self-perceived needs.


Skeletal muscle involvement in human immunodeficiency virus infection: a report of four cases.
Human immunodeficiency virus (HIV) may affect any part of the neuraxis and may affect skeletal muscle in many ways, ranging from myofiber atrophy in the wasting syndrome to inflammatory muscle disease and a host of opportunistic infections involving muscle. We report here a case series of 4 zidovudine-naοve patients with proven HIV infection with myopathy. One was a case of HIV wasting syndrome, and the three others were diagnosed as HIV polymyositis. Muscle biopsy proved invaluable in the characterization of these cases.


Nesfatin-1-like peptide is a novel metabolic factor that suppresses feeding, and regulates whole-body energy homeostasis in male Wistar rats.
Nucleobindin-1 has high sequence similarity to nucleobindin-2, which encodes the anorectic and metabolic peptide, nesfatin-1. We previously reported a nesfatin-1-like peptide (NLP), anorectic in fish and insulinotropic in mice islet beta-like cells. The main objective of this research was to determine whether NLP is a metabolic regulator in male Wistar rats. A single intraperitoneal (IP) injection of NLP (100 μg/kg BW) decreased food intake and increased ambulatory movement, without causing any change in total activity or energy expenditure when compared to saline-treated rats. Continuous subcutaneous infusion of NLP (100 μg/kg BW) using osmotic mini-pumps for 7 days caused a reduction in food intake on days 3 and 4. Similarly, water intake was also reduced for two days (days 3 and 4) with the effect being observed during the dark phase. This was accompanied by an increased RER and energy expenditure. However, decreased whole-body fat oxidation, and total activity were observed during the long-term treatment (7 days). Body weight gain was not significantly different between control and NLP infused rats. The expression of mRNAs encoding adiponectin, resistin, ghrelin, cholecystokinin and uncoupling protein 1 (UCP1) were significantly upregulated, while leptin and peptide YY mRNA expression was downregulated in NLP-treated rats. These findings indicate that administration of NLP at 100 μg/kg BW reduces food intake and modulates whole body energy balance. In summary, NLP is a novel metabolic peptide in rats.


Characterization of the in vitro adherence behavior of ultrasound responsive double-shelled microspheres targeted to cellular adhesion molecules.
We have developed novel adhesion molecule-targeted double-shelled microspheres which encapsulate nitrogen. We report in vitro targeting studies utilizing these microspheres conjugated to target-specific antibodies directed towards ICAM-1 and VCAM-1. In static adherence experiments, the adherence patterns of microspheres conjugated to three different monoclonal antibodies (two targeted to ICAM-1 and one to VCAM-1) to their target surfaces were very different. Maximum microsphere adherence at the lowest target and/or ligand densities was observed with the VCAM-1 system. Differences in target-specific adherence were also observed between anti-ICAM-1 and anti-VCAM-1 microsphere conjugates in flow adherence studies. Equilibrium binding studies of the target proteins in solution to the microsphere-bound ligands showed that the affinity constants of two microsphere-bound monoclonal antibodies for their target proteins are similar. Thus, ligand-target affinity is not the only determinant of microsphere adherence to the target surface in our systems. Shear stress was found to have an effect on the mean diameter of adhered microspheres; a decrease in the mean diameter with increasing shear was observed. The magnitude of this effect was dependent on both microsphere-bound ligand and target surface densities, with a more pronounced change at lower densities. Adhered microspheres were readily detectable using ultrasound at the lowest tested surface density of 40 mm(-2).


Interactions between amplitude modulation and frequency modulation processing: Effects of age and hearing loss.
Frequency modulation (FM) and amplitude modulation (AM) detection thresholds were measured for a 500-Hz carrier frequency and a 5-Hz modulation rate. For AM detection, FM at the same rate as the AM was superimposed with varying FM depth. For FM detection, AM at the same rate was superimposed with varying AM depth. The target stimuli always contained both amplitude and frequency modulations, while the standard stimuli only contained the interfering modulation. Young and older normal-hearing listeners, as well as older listeners with mild-to-moderate sensorineural hearing loss were tested. For all groups, AM and FM detection thresholds were degraded in the presence of the interfering modulation. AM detection with and without interfering FM was hardly affected by either age or hearing loss. While aging had an overall detrimental effect on FM detection with and without interfering AM, there was a trend that hearing loss further impaired FM detection in the presence of AM. Several models using optimal combination of temporal-envelope cues at the outputs of off-frequency filters were tested. The interfering effects could only be predicted for hearing-impaired listeners. This indirectly supports the idea that, in addition to envelope cues resulting from FM-to-AM conversion, normal-hearing listeners use temporal fine-structure cues for FM detection.


Mineralocorticoid Antagonism and Diabetic Kidney Disease.
Type 2 diabetes (T2D) is associated with an increased risk of diabetic kidney disease (DKD), cardiovascular disease, and heart failure, in part through activation of the renin-angiotensin-aldosterone system (RAAS). Although recent cardiovascular outcome trials have identified newer therapeutic agents such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1)-receptor agonists that reduce the risk of these complications, patients still exhibit residual cardiorenal morbidity and mortality. Accordingly, the identification of pharmacological agents that attenuate micro- and macrovascular complications related to T2D is a major priority. Our aim was to review evidence for the role of novel mineralocorticoid receptor antagonists (MRAs) that are being developed as adjunctive therapies to reduce the risk of DKD and cardiovascular disease in the setting of T2D. Dual RAAS blockade with angiotensin-converting enzyme (ACE) inhibitor plus angiotensin receptor blockade (ARB) or ARB plus renin inhibition increases serious adverse events such as acute kidney injury and stroke. Due to the potential for these serious side effects, more recent interest has focused on newer, more selective non-steroidal MRAs such as finerenone as cardiorenal protective therapies. Finerenone reduces albuminuria in the setting of DKD in patients with T2D and has a lower risk of hyperkalemia compared to currently available MRAs. Novel MRAs such as finerenone have the potential to reduce the risk of DKD progression in patients with T2D. The impact of finerenone on hard, long-term cardiorenal endpoints is being examined in the FIGARO and FIDELIO trials in patients with DKD.


All-cause and tumor-specific mortality trends in elderly primary central nervous system lymphoma (PCNSL) patients: a surveillance, epidemiology, and end results (SEER) analysis.
Recent primary central nervous system lymphoma (PCNSL) literature indicates that younger patients benefit from improved survival, however, this benefit is not shared by those 70+ years of age. The purpose of this study is to examine mortality trends in PCNSL patients 70+ years of age to better understand why improved prognosis has not yet reached this rapidly growing population subset. 2075 cases (1973-2012, age at diagnosis 70+ years) within the Surveillance, Epidemiology, and End Results (SEER) database were included in Kaplan-Meier and multivariate Cox Regression analyses. Variables include age at diagnosis, decade of diagnosis (1=1973-1982, 2=1983-1992, 3=1993-2002, 4=2003-2012), sex, race and surgery. Before stratification, both univariate and multivariate analyses agreed that patients aged 70-74 years at diagnosis lived the longest, while those 85+ years lived the shortest (median±SD; 6.0±0.5 months vs 2.0±0.2 months, respectively, p<0.0005); women lived longer than men (5.0±0.3 months vs 4.0±0.3 months, respectively, p=0.01); patients who received surgery (6.0±0.5 months) lived longer than those who did not (contraindicated = 1.0±0.5 months, p<0.0005; not performed = 4.0±0.3 months, p<0.0005). Univariate analysis showed decade 4 lived longer than only decade 3 (4.0±0.3 vs 4.0±0.5, respectively, p=0.008), while multivariate analysis showed decade 4 lived longer than both 2 (5.0±0.8 months, p=0.03) and 3 (p<0.0005). Following stratification, decade and sex no longer influenced survival. Race did not influence survival. Minimal clinically meaningful improvements in elderly PCNSL patient all-cause and tumor-specific mortality have been made since 1973, while the best predictors of longevity include younger age and surgery.


Bunyavirales: Scientific Gaps and Prototype Pathogens for a Large and Diverse Group of Zoonotic Viruses.
Research directed at select prototype pathogens is part of the approach put forth by the National Institute of Allergy and Infectious Disease (NIAID) to prepare for future pandemics caused by emerging viruses. We were tasked with identifying suitable prototypes for four virus families of the Bunyavirales order (Phenuiviridae, Peribunyaviridae, Nairoviridae, and Hantaviridae). This is a challenge due to the breadth and diversity of these viral groups. While there are many differences among the Bunyavirales, they generally have complex ecological life cycles, segmented genomes, and cause a range of human clinical outcomes from mild to severe and even death. Here, we delineate potential prototype species that encompass the breadth of clinical outcomes of a given family, have existing reverse genetics tools or animal disease models, and can be amenable to a platform approach to vaccine testing. Suggested prototype pathogens outlined here can serve as a starting point for further discussions.


Comparative Evaluation of the Accuracy of Gingival Thickness Measurement by Clinical Evaluation and Intraoral Ultrasonography.
This study aimed to investigate the accuracy of gingival thickness measurement by two methods of clinical evaluation and intraoral ultrasonography. The gingival thickness was measured in the midbuccal area of the right maxillary lateral incisor and first molar teeth in 30 individuals. For clinical measurement, a #15 K-file with rubber stops was vertically inserted 2 mm apical to the gingival margin and the length of the file in the tissue was measured using a digital caliper. Ultrasonographic measurement was performed using an intraoral probe on the gingival surface in the midbuccal area, at the entry point of the file. Statistical analysis was performed by paired t-test, correlation coefficient, and receiver operating characteristic (ROC) curve (α = 0.05). In the anterior region, the mean gingival thicknesses using ultrasonography (1.517 ± 0.293 mm) and clinical evaluation (1.610 ± 0.272 mm) were not significantly different (p = 0.434). In the posterior region, the mean gingival thicknesses were significantly different between ultrasonography (1.372 ± 0.442 mm) and clinical evaluation (1.626 ± 0.310 mm) (p = 0.006). The area under ROC curve values for ultrasonographic measurements in the anterior and posterior regions were 0.681 and 0.597, respectively. The use of ultrasonography with an intraoral probe has acceptable accuracy for the determination of gingival thickness, especially for the anterior regions.


New Lupanes from Alstonia scholaris Reducing Uric Acid Level.
Twelve lupanes including three new compounds named alstoscholarilups A-C (1: -3: ) were isolated from the leaves of Alstonia scholaris. Their structures were elucidated by spectroscopic analysis and ECD calculation. Structurally, compound 1: with a rare A ring-seco skeleton formed lactone and degraded C-3, while 2: with a 28-nor and 3: with a 29-nor-lupane skeleton supported the phytochemical diversity and novelty of the plant. Pharmacologically, compounds 4, 7: , and 10: reduced the serum uric acid (UA) levels of mice significantly.


Transoral Laser Microsurgery versus Robot-Assisted Surgery for Squamous Cell Carcinoma of the Tongue Base (Oncological and Functional Results)-A Retrospective GETTEC Multicenter Study.
The base of the tongue (BOT) is the second most common site for squamous cell carcinoma (SCC) in the oropharynx. There are currently no clear guidelines for the management of BOT SCC. Our main objective was to compare the oncological outcomes of two minimally invasive approaches, transoral laser microsurgery (TLM) and transoral robot-assisted surgery (TORS). This was a retrospective French GETTEC (Groupe d'Études des Tumeurs de la Tête et du Cou) multicenter study of patients with BOT SCC removed surgically either by TLM or TORS between 2005 and 2021. The study group included 16 patients treated by TLM and 38 by TORS, with median follow-up times of 14.4 and 37.2 months, respectively. The overall survival (OS) rates at 2 and 3 years were 67% in the TLM group and 90% at 2 years and 86% at 3 years in the TORS group (p = 0.42, p = 0.20). There was no significant difference in recurrence-free survival (RFS) between the two techniques after 2 and 3 years. The tumors removed by TORS were significantly larger. Operative times were significantly shorter in the TLM group. There were no differences in feeding resumption; none of the patients in the TLM group required a tracheotomy. Postoperative hemorrhagic complication rates were similar in the two groups (12% for TLM and 13% for TORS). Both TORS and TLM showed encouraging oncological, functional, and safety results in BOT SCC even in recurrence or second primary cancer patients, without a technique being found superior in terms of OS or RFS. Tumors removed by TORS were larger without an increase in postoperative bleeding, extending the possibilities of transoral treatment.


The Bisdioxopiperazine ICRF-193 Attenuates LPS-induced IL-1β Secretion by Macrophages.
Inhibiting pathological secretion of Interleukin-1β has shown beneficial effects in disease models and in the clinic and thus there is interest in finding inhibitors that can reduce its release from macrophages in response to their activation by foreign pathogens. We used an in vitro human macrophage model to investigate whether ICRF-193, a Topoisomerase II inhibitor could modulate IL1B mRNA expression and IL-1β secretion. These macrophage-like cells readily secrete IL-1β in response to Lipopolysaccharide (LPS). Upon exposure to a non-toxic dose of ICRF-193, IL-1β secretion was diminished by ~ 40%; however, level of transcription of IL1B was unaffected. We show that there was no Topoisomerase 2B (TOP2B) binding to several IL1B gene sites, which may explain why ICRF-193 does not alter IL1B mRNA levels. Hence, we show for the first time that ICRF-193 can reduce IL-1β secretion. Its low cost and the development of water-soluble prodrugs of ICRF-193 warrants its further investigation in the modulation of pathological secretion of this cytokine for the treatment of inflammatory disorders. (165 words).


[Multifamily Therapy with Anorectic Children and Adolescents in a Day Care Clinic].
Multifamily Therapy with Anorectic Children and Adolescents in a Day Care Clinic The treatment of children and adolescents suffering from anorexia nervosa represents an enormous challenge for therapists and families as well. After release form inpatient hospital treatment, there frequently is a period of renewed weight loss and a return to anorectic comportment and thought patterns. In view of what may be understood as a relapse, feelings of guilt and shame on the part of both the patients and their parents can be triggered. This often supports dysfunctional relationship dynamics within the affected families. Maintaining anorexia nervosa may be facilitated by being a suitable strategy to solve problems of the family system. Multifamily therapy aims at breaking this cycle and ensuring a stable transition from inpatient to outpatient settings of therapy. It requires an intensive and continuous involvement of the patients' parents in the therapy. Six families participating in a closed group are accompanied over one year by two multifamily therapists during the post inpatient phase. During this period, the parents remain responsible for their children. In the course of a day hospital intervention taking fifteen single days over a year, the parents develop a sense of competence in dealing with the disease. Thereby, the patients get the opportunity to overcome the anorectic isolation and pseudo-autonomy through experiencing their parents as able to understand them and their illness. In this contribution we present first results of a pilot study that suggest effectiveness of this therapy method.


Is being resolute better than being pragmatic when it comes to breastfeeding? Longitudinal qualitative study investigating experiences of women intending to breastfeed using the Theoretical Domains Framework.
In the UK, initiating then discontinuing breastfeeding before two weeks post-partum is common. The aim of this longitudinal qualitative study was to explore which psychosocial factors may influence discontinuation. A sample of 10 pregnant women intending to breastfeed were recruited. A longitudinal qualitative design was used to capture views prior to and two weeks following birth. Semi-structured interviews were conducted underpinned by the Theoretical Domains Framework to explore a comprehensive list of psychosocial factors. Four women discontinued breastfeeding at the time of the second interview. Pre-partum differences were identified between maintainers and discontinuers; discontinuers appeared to have stronger intentions to breastfeed based on their self-determination, self-confidence and perception of fewer barriers to breastfeeding. Post-partum, discontinuers highlighted how they felt physically unable to carry on; their feeding experiences elicited negative emotions and pain. Negative emotions appeared to be exacerbated by original breastfeeding beliefs and advice given by healthcare professionals. The women in this study who discontinued breastfeeding showed less cognitive flexibility, which appeared to exacerbate post-partum emotional distress, when they encountered difficulties. Women with strong intentions and self-determination might benefit from support in anticipating potential barriers and identifying ways of overcoming them.


Stenotrophomonas rhizophila Ep2.2 inhibits growth of Botrytis cinerea through the emission of volatile organic compounds, restricts leaf infection and primes defense genes.
The bacterium Stenotrophomonas rhizophila is known to be beneficial for plants and has been frequently isolated from the rhizosphere of crops. In the present work, we isolated from the phyllosphere of an ornamental plant an epiphytic strain of S. rhizophila that we named Ep2.2 and investigated its possible application in crop protection. Compared to S. maltophilia LMG 958, a well-known plant beneficial species which behaves as opportunistic human pathogen, S. rhizophila Ep2.2 showed distinctive features, such as different motility, a generally reduced capacity to use carbon sources, a greater sensitivity to fusidic acid and potassium tellurite, and the inability to grow at the human body temperature. S. rhizophila Ep2.2 was able to inhibit in vitro growth of the plant pathogenic fungi Alternaria alternata and Botrytis cinerea through the emission of volatile compounds. Simultaneous PTR-MS and GC-MS analyses revealed the emission, by S. rhizophila Ep2.2, of volatile organic compounds (VOCs) with well-documented antifungal activity, such as furans, sulphur-containing compounds and terpenes. When sprayed on tomato leaves and plants, S. rhizophila Ep2.2 was able to restrict B. cinerea infection and to prime the expression of Pti5, GluA and PR1 plant defense genes.


Experiments and quantitative analysis of frequency division multiplexing confocal fluorescence microscopy with UV excitation.
In this paper, we experimentally demonstrated a two-channel frequency division multiplexing confocal fluorescence microscopy system using a UV laser as the excitation source. In our two-channel frequency division multiplexing confocal fluorescence system, the incoming laser beam was divided into two beams and each beam was modulated with an individual carrier frequency. These two laser beams were then spatially combined with a small angle and focused into two diffraction-limited spots on the targeted cell (rat neural cell) surface to generate fluorescent signal. As a result, the fluorescent signals from two spots of the rat neural cell surface can be demodulated and distinguished during data processing. Furthermore, a quantitative analysis on the cross-talk among different frequencies was provided as well. The experimental results confirm that the two-channel frequency division multiplexing confocal fluorescence technology can not only maintain the high spatial resolution, but also realize the multiple points detection simultaneously with high temporal resolution (within millisecond level range), which benefits the dynamic studies of living biological cells.


[Inhalation corticosteroids for COPD: possible less mortality].
General practitioners find it difficult to accurately distinguish asthma from COPD. However, this differential diagnosis is important, as the treatment of the two entities is different. Asthma is by definition steroid responsive, whereas several long-term trials have demonstrated that in COPD, the lung function is not affected by steroid treatment. Yet it is questionable whether lung function is a good parameter for evaluating treatment effects, as there are indications that steroids affect the quality of life and the number of exacerbations. Moreover, an observational study has shown that inhaled steroids might affect mortality. Observational studies do not normally provide conclusive evidence, due to the possible inclusion of many confounding factors (such as confounding by indication). Nevertheless, this observational study indicates that it might be possible to treat COPD with steroids. A large prospective randomised trial that is currently in progress will need to confirm whether or not this is the case.


Administration errors with a conventional metered dose inhaler versus a novel breath actuated device.
Metered dose inhalers are difficult for patients to use. A device that eliminates coordination and timing of actuation may simplify the use of metered dose inhalers. This trial compared (1) number of errors made and (2) specific errors made between the conventional press and breathe metered dose inhaler (MDI) and the novel breath actuated Autohaler inhalation device in 24 subjects. We studied the use of each device in 12 patients trained and experienced in using an MDI and in 12 volunteers who had never been exposed to any inhalation device. We observed that even experienced patients continue to have difficulty with the coordination and timing of metered dose inhalers. The volunteer group had equal difficulty with both devices but it appeared that it was easier for them to learn how to use the breath actuated device than the MDI.


Investigation into the interaction of recombinant human serum albumin with Re-lipopolysaccharide and lipid A.
The interaction of bacterial endotoxins, deep rough mutant lipopolysaccharide LPS Re and the 'endotoxic principle' lipid A, with recombinant human serum albumin (rHSA) was investigated with a variety of physical techniques and biological assays. With Fourier-transform infrared spectroscopy and differential scanning calorimetry, the influence of albumin on the acyl chain melting behavior of the endotoxins was measured. Also, the effect on the functional groups of the endotoxins, in particular with respect to their orientation, was studied, including competition experiments with polymyxin B. Furthermore, the influence of endotoxin binding to rHSA on the protein's secondary structure was investigated. The results indicate a non-electrostatic binding with no change of the backbone orientation of LPS and only a slight change of the secondary structure of rHSA. Correspondingly, the amount of charge neutralization of the endotoxins due to rHSA measured by the electrophoretic mobility exhibited only a slight reduction of the surface potential. From these measurements and isothermal titration calorimetry, the lipid:protein binding stoichiometry was estimated to [LPS]:[rHSA], 10:1 molar. The determination of the aggregate structure of the endotoxins by X-ray small-angle scattering exhibited a complex change of a cubic into a non-lamellar structure. No influence of rHSA on endotoxin intercalation into phospholipid liposomes induced by lipopolysaccharide-binding protein could be detected by fluorescence resonance energy transfer. Finally, the LPS-induced cytokine production of human mononuclear cells was only slightly increased at high molar rHSA excess, while the coagulation of amebocyte lysate in the Limulus test yielded a complex change due to rHSA binding of LPS.


Dengue Encephalopathy or Dengue Encephalitis? You Decide.
Awareness of neurological sequelae of dengue fever is increasing. However, as this case illustrates, there is a diagnostic conundrum in determining whether certain features are in keeping with dengue encephalopathy or dengue encephalitis. Further consensus is required.


Chemosensitizing indomethacin-conjugated dextran-based micelles for effective delivery of paclitaxel in resistant breast cancer therapy.
Multidrug resistance (MDR) against chemotherapeutic agents has become the major obstacle to successful cancer therapy and multidrug resistance-associated proteins (MRPs) mediated drug efflux is the key factor for MDR. Indomethacin (IND), one of the non-steroidal anti-inflammatory agents, has been demonstrated to increase cytotoxic effects of anti-tumor agents as MRP substrates. In this study, dextran-g-indomethacin (DEX-IND) polymeric micelles were designed to delivery paclitaxel (PTX) for the treatment of MDR tumors. The DEX-IND polymer could effectively encapsulate PTX with high loading content and DEX-IND/PTX micelles present a small size distribution. Compared with free PTX, the release of PTX from DEX-IND/PTX micelles could be prolonged to 48 h. Cellular uptake test showed that the internalization of DEX-IND/PTX micelles by drug-sensitive MCF-7/ADR cells was significantly higher than free PTX benefiting from the inhibitory effect of IND on MRPs. In vitro cytotoxicity test further demonstrated that DEX-IND/PTX micelles could enhance the cytotoxicity of PTX against MCF-7/ADR tumor cells. In vivo pharmacokinetic results showed that DEX-IND/PTX micelles had longer systemic circulation time and slower plasma elimination rate in comparison to PTX. The anti-tumor efficacy test showed that DEX-IND/PTX micelles exhibited greater tumor growth-inhibition effects on MDR tumor-bearing mice, with good correlation between in vitro and in vivo. Overall, the cumulative evidence indicates that DEX-IND/PTX micelles hold significant promise for the treatment of MDR tumors.


Ultra-High-Field Neuroimaging Reveals Fine-Scale Processing for 3D Perception.
Binocular disparity provides critical information about three-dimensional (3D) structures to support perception and action. In the past decade significant progress has been made in uncovering human brain areas engaged in the processing of binocular disparity signals. Yet, the fine-scale brain processing underlying 3D perception remains unknown. Here, we use ultra-high-field (7T) functional imaging at submillimeter resolution to examine fine-scale BOLD fMRI signals involved in 3D perception. In particular, we sought to interrogate the local circuitry involved in disparity processing by sampling fMRI responses at different positions relative to the cortical surface (i.e., across cortical depths corresponding to layers). We tested for representations related to 3D perception by presenting participants (male and female, N = 8) with stimuli that enable stable stereoscopic perception [i.e., correlated random dot stereograms (RDS)] versus those that do not (i.e., anticorrelated RDS). Using multivoxel pattern analysis (MVPA), we demonstrate cortical depth-specific representations in areas V3A and V7 as indicated by stronger pattern responses for correlated than for anticorrelated stimuli in upper rather than deeper layers. Examining informational connectivity, we find higher feedforward layer-to-layer connectivity for correlated than anticorrelated stimuli between V3A and V7. Further, we observe disparity-specific feedback from V3A to V1 and from V7 to V3A. Our findings provide evidence for the role of V3A as a key nexus for disparity processing, which is implicated in feedforward and feedback signals related to the perceptual estimation of 3D structures.SIGNIFICANCE STATEMENT Binocular vision plays a significant role in supporting our interactions with the surrounding environment. The fine-scale neural mechanisms that underlie the brain's skill in extracting 3D structures from binocular signals are poorly understood. Here, we capitalize on recent advances in ultra-high-field functional imaging to interrogate human brain circuits involved in 3D perception at submillimeter resolution. We provide evidence for the role of area V3A as a key nexus for disparity processing, which is implicated in feedforward and feedback signals related to the perceptual estimation of 3D structures from binocular signals. These fine-scale measurements help bridge the gap between animal neurophysiology and human fMRI studies investigating cross-scale circuits, from micro circuits to global brain networks for 3D perception.


Ascitic fluid analysis in the differentiation of spontaneous bacterial peritonitis from gastrointestinal tract perforation into ascitic fluid.
A review of patients with bacterial peritonitis and ascites revealed six patients with gastrointestinal tract perforation into their ascitic fluid and 33 episodes of spontaneous bacterial peritonitis in 32 patients. Signs and symptoms were not helpful in differentiating the two groups; however, ascitic fluid analysis was found to be useful. All patients with perforation peritonitis fulfilled at least two of the following criteria: ascitic fluid total protein greater than 1 gm per dl, glucose less than 50 mg per dl and lactate dehydrogenase greater than 225 mU per ml. In only two episodes of spontaneous bacterial peritonitis were two of the criteria fulfilled.


Co-occurring mental and somatic diagnoses of alcohol dependent patients in relation to long-term aftercare alcohol abstinence and well-being.
There are many evidences of co-morbidity influence on alcohol dependency treatment outcome. We were interested in the question 'Do alcohol dependent patients with different co-occurring mental and medical conditions significantly differ in subjective attributes of well-being and in abstinence rate two years after the end of intensive alcohol dependency treatment'. 222 ex - patients participated in the research 24 months after the end of intensive alcohol dependency treatment, 74% of them males (mean age = 46.17, SD = 8.79) and 26% females (mean age = 46.35, SD = 8.10). No significant differences were found in any dependent variable regarding any independent variable in "presence of any somatic diagnose" (yes/no) and "personality disorders". "Depressive vs. non depressive" differed significantly only in the evaluation of important interpersonal relations, while "anxious vs. non - anxious" and "benzodiazepine dependent vs. nondependent" significantly differed in all self - evaluations, except in evaluation of important interpersonal relations. No significant differences were found between (non)abstinents regarding any of six categories of mental disorder and medical conditions (yes/no) and no significant differences were found in any self - evaluation regarding the participation in different kinds of after-care. A greater number of patients continued to abstain from alcohol if they continued in aftercare 24 months after the end of intensive treatment. Patients with different somatic and mental co-occurring disorders did not differ in abstinence rate. However, membership in after-care 24 months after the end of intensive therapy significantly contributed to the abstinence rate. Abstinence was found to be connected with more positive self-evaluation. Patients with somatic co-occurring diagnoses tended to have more positive self-perceptions than patients with co-occurring mental disorders.


Fluoxetine pharmacokinetics and tissue distribution quantitatively supports a therapeutic role in COVID-19 at a minimum dose of 20 mg per day.
Background. Various in vitro studies have shown fluoxetine inhibits multiple variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen causing the coronavirus disease 2019 (COVID-19) worldwide pandemic and multiple observational clinical studies have shown that patients receiving fluoxetine experienced clinical benefit by lowering the risk of intubation and death. The aim of this study is to conduct population pharmacokinetic dosing simulations to quantify the percentage of patients achieving a trough level for the effective concentration resulting in 50% (EC50) and 90% (EC90) inhibition of SARS-CoV-2 as reported in Calu-3 human lung cells. Methods. Pharmacometric parameter estimates used in this study were obtained from the U.S. FDA website from a new drug application for fluoxetine hydrochloride. A population of 1,000 individuals were simulated at standard fluoxetine antidepressant doses (20 mg/day, 30 mg/day, 40 mg/day, 50 mg/day, and 60 mg/day) to estimate the percentage of the patients achieving a trough plasma level for the EC50 and EC90 SARS-CoV-2 inhibition. All analyses were conducted in R. Results. By day-10 at 20 mg/day, 93.2% and 47% of the population will achieve the trough target plasma EC50 and EC90 concentrations, respectively, which translates to a lung tissue distribution coefficient of 60-times higher EC50 (283.6 ng/ml [0.82 mM]) and EC90 (1390.1 ng/ml [4.02 mM]). Further, by day-10 at an ideal dose of 40 mg/day, 99% and 93% of patients will reach the trough EC50 and EC90 concentrations, respectfully. Lastly, only a dose of 60 mg/day will reach the SARS-CoV-2 EC90 inhibitory concentration in the brain at pharmacokinetic steady-state. Conclusion. Overall, with a minimum treatment period of 10-days and a minimum dose of 20 mg/day, this study corroborates in vitro studies reporting fluoxetine inhibiting SARS-CoV-2 titers and also multiple observational clinical studies showing therapeutic benefit of fluoxetine in COVID-19 patients.


Plasma levels of main granulocyte components during hemodialysis: effects of immunosuppression.
Plasma levels of granulocyte lactoferrin, granulocyte myeloperoxidase and granulocyte elastase in complex with alpha 1-proteinase inhibitor were investigated during hemodialysis in oliguric patients following cadaveric renal transplantation (CRT). The results were compared with those of patients undergoing regular hemodialysis treatment (RDT) using different membrane materials. In RDT patients, plasma lactoferrin levels increased from 61.9 +/- 10.2 to 417.9 +/- 96.7 using dialyzers made of cuprophane. Dialyzers made of polymethyl methacrylate induced an increase of lactoferrin from 166.6 +/- 28.5 to 712.5 +/- 165.9 and dialyzers made of polyacrylonitrile an increase from 122.6 +/- 23.5 to 647.7 +/- 203.6 ng/ml. In CRT patients, in contrast, plasma lactoferrin levels increased from 49.1 +/- 10.9 to 199.6 +/- 45.9 (cuprophane), from 30.1 +/- 6.9 to 252.5 +/- 46.9 (polymethyl methacrylate), and from 43.3 +/- 9.1 to 174.2 +/- 39.3 ng/ml (polyacrylonitrile). On the other hand, the plasma levels of myeloperoxidase and elastase in complex with alpha 1-proteinase inhibitor increased comparably in both groups of patients. Our data suggest that immunosuppression might prevent degranulation of specific granules independently of the used dialyzer membrane material, whereas no effect was observed on two main components of azurophilic granules.


My Sadness - Our Happiness: Writing About Positive, Negative, and Neutral Autobiographical Life Events Reveals Linguistic Markers of Self-Positivity and Individual Well-Being.
Objective: Narratives of autobiographical events contain rich information about an individual's private experience, his/her deepest thoughts, feelings, and emotions. The present study investigates linguistic markers of emotion expression and subjective well-being in adults during one session of positive, negative, and neutral expressive writing. Participants (N = 28 healthy participants, N = 7 adults with depressive symptoms), all native speakers of German were instructed to write expressively about personally relevant autobiographical life events of negative, positive, and neutral content. Methods: Quantitative text analysis was performed to determine the amount of emotional words, first person pronouns (singular vs. plural), and cognitive function words used in positive, negative, and neutral narratives and to examine the potency of these classes of words as linguistic markers of positivity/negativity, self-reference, and cognitive reappraisal. Additionally, the relationship between expressive writing and subjective well-being was explored by assessing changes in self-reported psychosomatic symptoms and in bodily and emotional awareness immediately after positive, negative, and neutral writing. Results: Regarding healthy participants, negative narratives contained significantly more negative emotional words than positive or neutral narratives. However, negative narratives also contained more positive emotional words compared to negative emotional words in positive narratives. Moreover, negative narratives contained more cognitive function words than positive narratives, suggesting that healthy participants tried to reappraise negative experiences while writing about negative personal life events. Positive narratives were characterized by an increased use of positive words and of pronouns of the first person plural ("we"), supporting a positivity bias and an extension of self-reference from first person singular to plural (we-reference) during positive expressive writing. Similarly, writing about neutral events was characterized by a positivity bias. Although based on descriptive analysis only, preferential use of positive words and cognitive function words in negative narratives was absent in participants reporting depressive symptoms. Positive, negative, and neutral expressive writing was accompanied by differential changes in bodily sensations, emotional awareness, and self-reported psychosomatic symptoms in all participants. Discussion: The findings are discussed with respect to previous research, a self-positivity bias, and a universal positivity bias in language use highlighting the relevance of these biases as markers of subjective well-being.


Chemoselective hydroxyl group transformation: an elusive target.
The selective reaction of one functional group in the presence of others is not a trivial task. A noteworthy amount of research has been dedicated to the chemoselective reaction of the hydroxyl moiety. This group is prevalent in many biologically important molecules including natural products and proteins. However, targeting the hydroxyl group is difficult for many reasons including its relatively low nucleophilicity in comparison to other ubiquitous functional groups such as amines and thiols. Additionally, many of the developed chemoselective reactions cannot be used in the presence of water. Despite these complications, chemoselective transformation of the hydroxyl moiety has been utilized in the synthesis of complex natural product derivatives, the reaction of tyrosine residues in proteins, the isolation of natural products and is the mechanism of action of myriad drugs. Here, methods for selective targeting of this group, as well as applications of several devised methods, are described.


Choosing where to put your energy: a qualitative analysis of the role of physical activity in the lives of working adults with arthritis.
Research points to many potential benefits of physical activity (PA) for those with arthritis. However, PA has not typically been examined within the context of other life roles. This study examined the perceptions of PA among individuals managing arthritis in addition to employment and other role demands. Eight focus groups were conducted with 24 women and 16 men (age range 29-72 years) who were currently or recently employed (within 2 years) and had osteoarthritis or inflammatory arthritis. Participants were recruited from community newspaper advertisements, rheumatology clinics, and arthritis groups. Discussions were audiotaped and transcribed. Transcripts were analyzed using qualitative content analysis. All groups discussed the impact of arthritis on a range of PAs. Overall, participants discussed PA as positively influencing their health and well-being. Yet, several overarching themes highlighted the complexity of PA, including 1) PA as a potential cause of arthritis; 2) the reciprocal impact of arthritis on PA and PA on arthritis; 3) physical and psychological benefits and harms of PA, such as difficulty making PA decisions when living in pain or when faced with episodic symptoms; 4) perceived choices about engagement in PA (e.g., role overload); and 5) social support. The relationships among work, health, and other roles were complex. Competing demands, pain, energy, episodic symptoms, support, and decisions to disclose one's illness at work influenced PA. Changes to PA not only affected physical health but also people's self-identity. PA interventions may be improved by taking into account the demands of multiple life roles.