MAGIC SHIMMING: gradient shimming with magic angle sample spinning.
A simple method to automatically shim NMR samples spinning at the magic angle is introduced based on the gradient shimming approach. The field inhomogeneity along the spinning axis is measured and automatically corrected. The combination of a normal magic angle spinning (MAS) probe, a conventional homospoil gradient, and a set of properly chosen standard room-temperature shims are used to perform the gradient shimming of samples spinning at the magic angle. The resulting (13)C NMR adamantane linewidth is less than 1 Hz (0.0078 ppm at 11.7 T).


Ion currents through pores. The roles of diffusion and external access steps in determining the currents through narrow pores.
External access steps, which may include restricted aqueous diffusion, are introduced into a kinetic model for ion transport through narrow pores. The conductance-concentration relation and the concentration dependence of the biionic permeability are calculated using two alternative assumptions: (a) access to the mouth of the pore is allowed only when no ion is within the lumen or at either mouth; (b) ions remain at the mouth only very transiently. With either assumption the concentration dependence of the fluxes is the same as in previous treatments in which all steps in access were lumped into a single process. Also as before, the biionic permeability ratio is independent of concentration so long as the lumen is never doubly occupied. For narrow pores, such as those formed by gramicidin A, the slowest external portion of the access process must occur close to the pore's mouth, and thus the region an ion must occupy to gain access is small. As a consequence, the probability of finding an ion within this region is also small. On this basis, it is argued that the second assumption is appropriate for these pores. The kinetic equations that result are identical to those used by Urban, B., S.B. Hladky, and D.A. Haydon (1980, Biochim. Biophys. Acta. 602:331-354).


[Lightmicroscopical and histochemical studies on the chorionic plate of the mature human placenta (author's transl)].
The chorionic plate of the normal mature human placenta was studied by light-microscopy and enzyme-histochemistry. Thereby the following findings were obtained in the various layers: The enzyme content of the amniotic epithelium refers to a secretory activity. The question with regard to a resorbant activity remains unclarified. The cells of the amnion mesoderm chiefly show the enzymes of the intermediary metabolism. The intermediate layer consists of mesothelium cells which furthermore have also phagocytotic activity. The chorionic plate mesoderm consists of several layers with connective tissue cells of diverse stage of differentiation. In the early embryonic phase they differentiate amnionward from the primary cytotrophoblast layer and still get cellular supply from residual primary cytotrophoblastic cells up to the date of birth. The enzymes of the primary cytotrophoblast cells refer accordingly with a strong activity of G6PDH to proliferation and differentiation. One part of the X-cells embedded in the Langhans fibrinoid stria descends from this primary cytotrophoblast layer; but in part they differentiate also from the Langhans cells of the placental villi surrounded by the fibrinoid stria. According to their different descent, these cells show a varying content of enzymes. The bordering of the chorionic plate to the intervillous space is represented by a rudimentary, syncytotrophoblast layer.


Channelling and formation of 'active' formaldehyde in dimethylglycine oxidase.
Here we report crystal structures of dimethylglycine oxidase (DMGO) from the bacterium Arthrobacter globiformis, a bifunctional enzyme that catalyzes the oxidation of N,N-dimethyl glycine and the formation of 5,10-methylene tetrahydrofolate. The N-terminal region binds FAD covalently and oxidizes dimethylglycine to a labile iminium intermediate. The C-terminal region binds tetrahydrofolate, comprises three domains arranged in a ring-like structure and is related to the T-protein of the glycine cleavage system. The complex with folinic acid indicates that this enzyme selectively activates the N10 amino group for initial attack on the substrate. Dead-end reactions with oxidized folate are avoided by the strict stereochemical constraints imposed by the folate-binding funnel. The active sites in DMGO are approximately 40 A apart, connected by a large irregular internal cavity. The tetrahydrofolate-binding funnel serves as a transient entry-exit port, and access to the internal cavity is controlled kinetically by tetrahydrofolate binding. The internal cavity enables sequestration of the reactive iminium intermediate prior to reaction with tetrahydrofolate and avoids formation of toxic formaldehyde. This mode of channelling in DMGO is distinct from other channelling mechanisms.


Non-Isothermal Free-Surface Viscous Flow of Polymer Melts in Pipe Extrusion Using an Open-Source Interface Tracking Finite Volume Method.
Polymer extrudate swelling is a rheological phenomenon that occurs after polymer melt flow emerges at the die exit of extrusion equipment due to molecular stress relaxations and flow redistributions. Specifically, with the growing demand for large scale and high productivity, polymer pipes have recently been produced by extrusion. This study reports the development of a new incompressible non-isothermal finite volume method, based on the Arbitrary Lagrangian-Eulerian (ALE) formulation, to compute the viscous flow of polymer melts obeying the Herschel-Bulkley constitutive equation. The Papanastasiou-regularized version of the constitutive equation is employed. The influence of the temperature on the rheological behavior of the material is controlled by the Williams-Landel-Ferry (WLF) function. The new method is validated by comparing the extrudate swell ratio obtained for Bingham and Herschel-Bulkley flows (shear-thinning and shear-thickening) with reference data found in the scientific literature. Additionally, the essential flow characteristics including yield-stress, inertia and non-isothermal effects were investigated.


Peak alpha frequency: an electroencephalographic measure of cognitive preparedness.
Electroencephalographic (EEG) peak alpha frequency (PAF) (measured in Hz) has been correlated to cognitive performance between healthy and clinical individuals, and among healthy individuals. PAF also varies within individuals across developmental stages, among different cognitive tasks, and among physiological states induced by administration of various substances. The present study suggests that, among other things, PAF reflects a trait or state of cognitive preparedness. Experiment 1 involved 19-channel EEG recordings from 10 individuals with traumatic brain injury (TBI) and 12 healthy matched controls, before, during, and after tasks of visual and auditory attention. Experiment 2 involved EEG recordings from 19 healthy young adults before and after a working memory task (WAIS-R Digit Span), repeated on 2 different days to measure within-individual differences. Experiment 1 showed significantly lower PAF in individuals with TBI, mostly during post-task rest. Experiment 2 showed PAF during pre-task baseline to be significantly correlated with Digit Span performance of the same day but not with Digit Span performance of another day. Moreover, PAF was significantly increased after Digit Span for those participants whose PAF was lower than the sample median before the task, but not for those who had it higher. Finally, both PAF and Digit Span performance were increased during the second day. PAF was shown to detect both trait and state differences in cognitive preparedness, as well as to be affected by cognitive tasks. Traits are better reflected during post-task rest, whereas states are better reflected during initial resting baseline recordings.


Primary effusion anaplastic large cell lymphoma with indolent clinical course and IRF4/DUSP22 rearrangement: a case report expanding the spectrum of effusion-based lymphoma.
Effusion-based lymphomas arising from pleural cavities are mostly B cell lymphomas. Non-B cell origins are very rare. These non-B cell lymphomas are usually disseminated and aggressive, and their underlying genetic changes are indeterminate. Here, we reported the first case of primary effusion anaplastic large cell lymphoma (ALCL) with exclusive involvement of a single body cavity, indolent initial presentation, and IRF4/DUSP22 rearrangement. This 73-year-old man had been in his usual health until he presented with exertional dyspnea for 1 month. Physical examination and whole-body imaging indicated isolated left pleural effusion without lymphadenopathies or tumors. Thoracentesis revealed anaplastic large lymphoid cells that were CD30 + , CD3 - , CD8 + , TIA1 + , CD138 - , Epstein-Barr virus-encoded small RNA - , human herpesvirus 8 - , and ALK - . Fluorescence in situ hybridization exhibited IRF4/DUSP22 rearrangement. A primary effusion ALK-negative ALCL was diagnosed. There was no evident progression without chemotherapeutics until 4 months after the diagnosis. Our findings expanded the spectrum of effusion-based lymphoma. Recognition of this disease could prevent misdiagnosis and guide treatment strategies for patients.


Transuterine transport of small- and medium-sized molecules deposited in the uterus in gilts.
Radiolabelled compounds were mixed with seminal plasma and placed in the uterine lumen of anaesthetized gilts which were killed 5 min (N = 1) and 1 h (N = 2) later. After 1 h the distribution patterns of the 2 compounds placed in different horns were similar, indicating transuterine transport. Transuterine transport had begun by 5 min after deposition of seminal plasma. In all 3 gilts, the labelled substances had moved to the anterior segments of the oviduct.


Implementation of ISBT 128, a quality system, a standardized bar code labeling of blood products worldwide, electronic transfusion pathway: four years of experience in Norway.
In today's world of multinational disaster relief programs, blood collected and processed in one country may be used in another. A great deal of important information is carried by a blood product label. Given the concerns about safety and traceability, it is important to use globally unique blood product coding and labeling system. In 1994 the International Society of Blood Transfusion (ISBT) gave a group, ICCBBA (formerly called International Council for Commonality in Blood Banking Automation), the responsibility for implementing a new, safe international system for coding and labeling blood products. This new system is based on 128 bar code symbology and is called ISBT 128. This study describes how ISBT 128 was implemented in blood banks in Norway. As soon as a couple of the most central blood banks implemented the system and started to use it in 2001, they found that it was much easier to handle than their old systems. There were two different software systems being used that were ISBT 128-compliant. The facilities started to export and import blood products to each other. The "foreign" blood products were easily scanned into "own" inventory. They were reluctant to order blood products from blood banks not using ISBT 128. Because of the success in the Department of Immunology and Transfusion Medicine at the University Hospital of Akershus and some other blood banks in Norway, the Norwegian Health Authorities advised all the blood banks to implement ISBT 128. The use of ISBT 128 has been a success from the very beginning.


Evolutionary analysis of prokaryotic heat-shock transcription regulatory protein σ³².
Heat-stress to any living cell is known to trigger a universal defense response, called heat-shock response, with rapid induction of tens of different heat-shock proteins. Bacterial heat-shock genes are transcribed by the σ(32)-bound RNA polymerase instead of the normal σ(70)-bound RNA polymerase. In this study, the diversity in sequence, variation in secondary structure and function amongst the different functional regions of the proteobacterial σ(32) family of proteins, and their phylogenetic relationships have been analyzed. Bacterial σ(32) proteins can be subdivided into different functional regions which are referred to as regions 2, 3, and 4. There is a great deal of sequence conservation among the functional regions of proteobacterial σ(32) family of proteins though some mutations are also present in these regions. Region 2 is the most conserved one, while region 4 has comparatively more variable sequences. In the present work, we tried to explore the effects of mutations in these regions. Our study suggests that the sequence diversities due to natural mutations in the different regions of proteobacterial σ(32) family lead to different functions. So far, this study is the first bioinformatic approach towards the understanding of the mechanistic details of σ(32) family of proteins using the protein sequence information only. This study therefore may help in elucidating the hitherto unknown molecular mechanism of the functionalities of σ(32)family of proteins.


Extracardiac rerouting of the persistent left superior vena cava in the left isomerism heart.
The left isomerism heart is common to have various forms of the systemic and pulmonary venous connections, for which numerous reparative methods have been proposed. This report describes a successful extracardiac rerouting of the persistent left superior vena cava of a 6-year-old girl patient having the isomerism heart, bilateral superior vena cava, partial anomalous pulmonary venous connection, and partial form of the atrioventricular septal defect. Intraatrial rerouting of the left superior vena cava was found unfeasible, since this procedure had a potential hazard to obstruct the systemic and/or pulmonary venous drainage. The patient recovered uneventfully and is leading a normal life 6 years after the surgery.


Non-neurogenic discoordinated voiding in children. The long-term effect of bladder retraining.
Sixteen children with dysfunctional voiding without demonstrable neurological deviation were studied 6 months and five years after completed bladder retraining. The initial good effect on voiding symptoms and urinary tract infections/bacteriuria was confirmed. Moreover, the effect seems to last for several years. Bladder retraining can thus be considered a safe, cheap and relatively effective treatment in many children with symptoms of bladder dysfunction and/or recurrent urinary tract infections.


Taxonomic review of the genus Hydria Hbner, 1822 (Lepidoptera, Geometridae, Larentiinae) in the Middle East, with description of three new species and one new subspecies.
The species of the genus Hydria in the Middle East are revised. The revision is based on morphological examination and genetic data (DNA-barcode). Additionally, information on the habitat preference, pre-imaginal stages and biology of the species are given as much as available. Three species (H. gernoti sp. n., H. schachti sp. n., H. loebeli sp. n.) and one subspecies (Hydria cervinalis taurica ssp. n.) are described as new to science. The taxonomic status of Hydria hyrcana (Staudinger, 1871) as bona species could be confirmed. The East African species, Hydria relicta (Herbulot. 1953) comb. n., is transferred from genus Rheumaptera to Hydria. Wing pattern and genitalia structures of all discussed species are illustrated.


[Neutrophils in the tumor microenvironment-foes or friends?]
Neutrophils are the most abundant white blood cells in the human circulation and are usually associated with inflammation and with fighting infections. In recent years, the role of these cells during cancer progression has been a matter of increasing interest. Tumor-associated neutrophils (TANs) accumulate in cancer patients and represent an important negative prognostic marker in a broad variety of neoplasms. Accordingly, TANs represent a highly attractive therapeutic target. TAN may exhibit tumor-promoting or -inhibiting functions. Pro-tumor neutrophils support tumor angiogenesis and growth and promote metastatic dissemination of tumors via establishment of the premetastatic niche. Studies in animal models have already shown that the depletion of TANs or the inhibition of their migration bears therapeutic potential. Multiple pathways and mediators that induce pro-tumoral functions in neutrophils have been identified. In this review, we provide an up-to-date overview of the pro- and anti-tumor properties of neutrophils as well as the environmental cues that regulate these distinct functions. We also report on our own work that comprehensively investigated the role of neutrophils in head and neck cancer.


Minnelide reduces tumor burden in preclinical models of osteosarcoma.
Osteosarcoma is the most common bone cancer in children and adolescents with a 5-year survival rate of about 70%. In this study, we have evaluated the preclinical therapeutic efficacy of the novel synthetic drug, Minnelide, a prodrug of triptolide on osteosarcoma. Triptolide was effective in significantly inducing apoptosis in all osteosarcoma cell lines tested but had no significant effect on the human osteoblast cells. Notably, Minnelide treatment significantly reduced tumor burden and lung metastasis in the orthotopic and lung colonization models. Triptolide/Minnelide effectively downregulated the levels of pro-survival proteins such as heat shock proteins, cMYC, survivin and targets the NF-κB pathway.


Evaluation of a commercial interferon-γ release assay for the detection of SARS-CoV-2 T-cell response after vaccination.
Evidence regarding the role of cellular immunity in protecting against COVID-19 is emerging. To better assess immune status, simple and robust assays measuring specific T-cell responses associated with humoral responses are needed. We aimed to evaluate the Quan-T-Cell SARS-CoV-2 test for measuring cellular immune responses in vaccinated healthy and immunosuppressed subjects. T-cell responses were assessed in healthy vaccinated and unvaccinated and unexposed healthcare workers to determine the sensitivity and specificity of the EUROIMMUN SARS-CoV-2 Quan-T-Cell IGRA test performed on vaccinated kidney transplant recipients (KTRs). The EUROIMMUN SARS-CoV-2 Quan-T-Cell IGRA test showed good sensitivity (87.2%) and specificity (92.3%) at the calculated 147 mIU/mL cutoff, with an 88.33% accuracy. In KTRs, specific cellular immunity was lower than the antibody response; however, those with a positive IGRA result produced as much IFN-γ as healthy individuals. The EUROIMMUN SARS-CoV-2 Quan-T-Cell IGRA test showed good sensitivity and specificity for the detection of specific T-cell responses against the SARS-CoV-2 spike protein. These results present an additional tool for better management of COVID-19, especially in vulnerable populations.


Advanced Nursing Practice in Austria under consideration of outcome measurement.
Internationally, Advanced Practice Nurses (APN) are associated with improvements when measuring results in health care. Advanced Nursing Practice (ANP) refers to an extended nursing care with the aim of meeting the changing conditions in health care systems by providing evidence-based practice. APN outcomes are the endpoints of nursing interventions based on clinical experience, scientific knowledge, and practical skills. Due to the challenges in health care systems, Advanced Practice Nurses have become well established internationally in various fields. In Austria, the first nurses are currently trained in Advanced Nursing Practice on a master's level according to the International Council of Nurses core curriculum (ICN). However, national implementation and evaluation strategies are still missing. The aim of this short report is (i) to show the current situation of APNs in Austria, and (ii) to underline the importance of measuring APN outcomes in implementing this role for future developments in health care. A literature search was conducted in CINAHL (Cumulative Index to Nursing and Allied Health), PubMed, and the Cochrane Library in the period 09/2019 to 01/2020. With the help of APNs and coordinated, holistic, patient-centered care, a higher quality of care for different patient groups is clearly evident. The cost-effectiveness and the positive experience of both patients and nursing staff have been demonstrated in international studies. In particular, the guidance and educational skills of APNs have been shown to improve health outcomes in vulnerable population groups. With regard to the implementation of APNs in the health care system, more focus is needed on the measurement of outcomes in nursing research. Outcome research has been shown to help identify the unique effect of APNs in patient care and to highlight the health-related improvements through Advanced Nursing Practice for health policy and further developments in the health care system.


Neuroprotection by Epigenetic Modulation in a Transgenic Model of Multiple System Atrophy.
Similar to Parkinson disease, multiple system atrophy (MSA) presents neuropathologically with nigral neuronal loss; however, the hallmark intracellular α-synuclein (αSyn) accumulation in MSA affects typically oligodendrocytes to form glial cytoplasmic inclusions. The underlying pathogenic mechanisms remain unclear. As MSA is predominantly sporadic, epigenetic mechanisms may play a role. We tested the effects of the pan-histone deacetylase inhibitor (HDACi) sodium phenylbutyrate in aged mice overexpressing αSyn under the control of the proteolipid protein promoter (PLP-αSyn) designed to model MSA and characterized by αSyn accumulation in oligodendrocytes and nigral neurodegeneration. HDACi improved motor behavior and survival of nigral neurons in PLP-αSyn mice. Furthermore, HDACi reduced the density of oligodendroglial αSyn aggregates, which correlated with the survival of nigral neurons in PLP-αSyn mice. For the first time, we suggest a role of HDACi in the pathogenesis of MSA-like neurodegeneration and support the future development of selective HDACi for MSA therapy.


Age and clear eyes are associated with an increased risk of cutaneous squamous cell carcinomas in vemurafenib-treated melanoma patients.
Cutaneous squamous cell carcinoma (cSCC) is a frequent side-effect of vemurafenib treatment. The main aim of this study was to identify the clinical risk factors associated with the development of cSCC in melanoma patients treated with vemurafenib. We carried out a retrospective study, including 63 consecutive melanoma patients treated with vemurafenib for BRAF-mutant metastatic melanoma in an oncodermatological department. Clinical and follow-up data were collected and analysed, and a comparison of the subgroups who did and did not develop cSCC was performed. A total of 42.9% of patients (n=27) treated with vemurafenib developed one or more cSCC. Patients with cSCC were significantly older (P=0.01). Clear eyes were also associated with a higher risk of developing cSCC (odds ratio=3.50; 95% confidence interval: 1.08-12.43). Three patients developed cSCC more than 1 year after the initiation of treatment (12, 16 and 18 months, respectively). Clinicians should be vigilant in older patients undergoing vemurafenib therapy as well as patients with clear eyes as they seem to be at increased risk of developing cSCC, even late after the initiation of treatment.


Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy.
Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO2-x ) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase (HAase) and glutathione (GSH) can readily destroy hyaluronic acid (HA) and disulfide bond and releases the Cas9/sgRNA from TiO2-x to target the stress alleviating regulators, i.e., nuclear factor E2-related factor 2 (NRF2) and heat shock protein 90α (HSP90α), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO2-x demonstrates a higher anticancer effect both in vitro and in vivo. This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.


Targeting miRNAs by polyphenols: Novel therapeutic strategy for aging.
Regarding the importance of genetic and epigenetic factors in regulation of aging process, different expression pattern of non-coding RNAs in aging could be investigated. Accordingly, micro RNAs (miRNAs) with a wide range of physiological functions as well as a significant footprint in many diseases have been demonstrated to be down or upregulated during the aging process. Therefore, age-associated microRNAs and their targets have potentially detected the accelerated aging and predicted the risks for age-related diseases. Polyphenols as important antioxidants in human dietary observed in fruits and some beverages have beneficial effects on longevity and aging. Considering miRNAs as an interesting mediator in modulating polyphenols' biological effects, targeting miRNAs which is using polyphenols could be a novel strategy for aging.


Lipid environment induces ER stress, TXNIP expression and inflammation in immune cells of individuals with type 2 diabetes.
Obesity and type 2 diabetes are concomitant with low-grade inflammation affecting insulin sensitivity and insulin secretion. Recently, the thioredoxin interacting protein (TXNIP) has been implicated in the activation process of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we aim to determine whether the expression of TXNIP is altered in the circulating immune cells of individuals with type 2 vs type 1 diabetes and whether this can be related to specific causes and consequences of inflammation. The expression of TXNIP, inflammatory markers, markers of the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress and enzymes involved in sphingolipid metabolism was quantified by quantitative reverse transcription real-time PCR (qRT-PCR) in peripheral blood mononuclear cells (PBMCs) of 13 non-diabetic individuals, 23 individuals with type 1 diabetes and 81 with type 2 diabetes. A lipidomic analysis on the plasma of 13 non-diabetic individuals, 35 individuals with type 1 diabetes and 94 with type 2 diabetes was performed. The effects of ER stress or of specific lipids on TXNIP and inflammatory marker expression were analysed in human monocyte-derived macrophages (HMDMs) and THP-1 cells. The expression of TXNIP and inflammatory and UPR markers was increased in the PBMCs of individuals with type 2 diabetes when compared with non-diabetic individuals or individuals with type 1 diabetes. TXNIP expression was significantly correlated with plasma fasting glucose, plasma triacylglycerol concentrations and specific UPR markers. Induction of ER stress in THP-1 cells or cultured HMDMs led to increased expression of UPR markers, TXNIP, NLRP3 and IL-1β. Conversely, a chemical chaperone reduced the expression of UPR markers and TXNIP in PBMCs of individuals with type 2 diabetes. The lipidomic plasma analysis revealed an increased concentration of saturated dihydroceramide and sphingomyelin in individuals with type 2 diabetes when compared with non-diabetic individuals and individuals with type 1 diabetes. In addition, the expression of specific enzymes of sphingolipid metabolism, dihydroceramide desaturase 1 and sphingomyelin synthase 1, was increased in the PBMCs of individuals with type 2 diabetes. Palmitate or C2 ceramide induced ER stress in macrophages as well as increased expression of TXNIP, NLRP3 and IL-1β. In individuals with type 2 diabetes, circulating immune cells display an inflammatory phenotype that can be linked to ER stress and TXNIP expression. Immune cell ER stress can in turn be linked to the specific exogenous and endogenous lipid environment found in type 2 diabetes.


Covid-19 vaccine approvals and stock market returns: The case of Chinese stocks.
This paper investigates the Chinese stock market reactions to the announcements of Covid-19 vaccine approvals. These announcements generally impacted stock prices, but the impacts appeared to be heterogeneous across sectors. Particularly, firms in the manufacturing, wholesale, retail, and information technology sectors were persistently benefited. We also find that firms with poorer performance, smaller sizes, and greater ages reacted more positively compared to others.


On the phosphorylation of low molecular mass HMG (high mobility group) proteins in Ehrlich ascites cells.
This paper shows that the low molecular mass HMG proteins 14 and 17 do not seem to be phosphorylated in Ehrlich ascites cells whereas two other small HMG proteins designated HMG I and Y are. Amino acid analysis and peptide mapping of all four proteins demonstrated that HMG I and Y were not phosphorylated modifications of HMG 14 or 17.


The effect of cinnamon extract on isolated rat uterine strips.
Cinnamon is a spice used by some populations as a traditional remedy to control blood pressure and thus hypertension. Cinnamon extract decreases contractility in some smooth muscles, but its effect on uterine smooth muscle is unknown. The aim of this study was to determine the physiological and pharmacological effects of cinnamon extract (CE) on the contractions of isolated rat uterine strips and to investigate its possible mechanism of action. Isolated longitudinal uterine strips were dissected from non-pregnant rats, mounted vertically in an organ bath chamber, and exposed to different concentrations of CE (10-20mg/mL). The effect of CE was investigated in the presence of each of the following solutions: 60mM KCl, 5nM oxytocin, and 1μM Bay K8644. CE significantly decreased the force of uterine contraction in a concentration-dependent manner and significantly attenuated the uterine contractions elicited by KCl and oxytocin. In addition, CE significantly decreased the contractile force elicited when L-type Ca(2+) channels were activated by Bay K8644. CE's major mechanism may be inhibition of L-type Ca(2+) channels, which limits calcium influx. These data demonstrate that CE can be a potent tocolytic that can decrease uterine activity regardless of how the force was produced, even when the uterus was stimulated by agonists. As a result, cinnamon may be used to alleviate menstrual pain associated with dysmenorrhoea or prevent unwanted uterine activity in early pregnancy.


DNAJA3/Tid1 Is Required for Mitochondrial DNA Maintenance and Regulates Migration and Invasion of Human Gastric Cancer Cells.
Gastric cancer is a common health issue. Deregulated cellular energetics is regarded as a cancer hallmark and mitochondrial dysfunction might contribute to cancer progression. Tid1, a mitochondrial co-chaperone, may play a role as a tumor suppressor in various cancers, but the role of Tid1 in gastric cancers remains under investigated. The clinical TCGA online database and immunohistochemical staining for Tid1 expression in tumor samples of gastric cancer patients were analyzed. Tid1 knockdown by siRNA was applied to investigate the role of Tid1 in gastric cancer cells. Low Tid1 protein-expressing gastric cancer patients had a poorer prognosis and higher lymph node invasion than high Tid1-expressing patients. Knockdown of Tid1 did not increase cell proliferation, colony/tumor sphere formation, or chemotherapy resistance in gastric cancer cells. However, Tid1 knockdown increased cell migration and invasion. Moreover, Tid1 knockdown reduced the mtDNA copy number of gastric cancer cells. In addition, the Tid1-galectin-7-MMP-9 axis might be associated with Tid1 knockdown-induced cell migration and invasion of gastric cancer cells. Tid1 is required for mtDNA maintenance and regulates migration and invasion of gastric cancer cells. Tid1 deletion may be a poor prognostic factor in gastric cancers and could be further investigated for development of gastric cancer treatments.


Genetic adaptations to grazing and mowing in the unpalatable grass Cenchrus incertus.
To identify morphological and life history adaptations to grazing, mowing, and cultivation, seeds of the grass Cenchrus incertus were collected from two populations in each of three types of sites: cemeteries (mown occasionally), pastures (grazed continuously), and orchards (plowed twice a year). Seeds from each population were germinated and grown in a common greenhouse.Plants originating from the two cemetery populations had, on average, the most leaves and the most tillers per plant at each census, and they were on average the shortest in stature. Cemetery plants had on average the greatest number of panicles and of burs per plant, but the fewest burs per panicle. The occasionally-mown but ungrazed cemetery populations in this study were therefore more similar to grazed populations described in other studies; the pasture and orchard populations in this study were more similar to ungrazed populations described in other studies. We suggest that this may be due to the low acceptability of Cenchrus incertus, which makes its defoliation relatively infrequent in unmown sites.Some of the traits that distinguished the cemetery populations from the orchard and pasture populations, such as shorter stature, are probably direct adaptations to defoliation. Others may be secondary effects of these, or the result of allocation trade-offs.


Social media photos of substance use and their relationship to attitudes and behaviors among ethnic and racial minority emerging adult men living in low-income areas.
Emerging adult minority males have inequitable negative consequences from substance abuse. They are also frequent users of social media, logging into popular sites up to 25 times per week on average, so there may be opportunities to use these technologies for better understanding and preventing substance use behaviors. Through mobile phone monitoring, this study examined how social media sites are used to post substance use-related images and how posting such images is related to behaviors and attitudes. It also explored how self-presentation of masculinity norms, such as coolness and toughness, was related to posting of substance use-related photos. Instagram and/or Twitter posts of 65 minority males aged 18-25 living in low-income areas were monitored for three months using phone tracking software. Over 2200 posted images were content analyzed to determine if they were related to alcohol or marijuana and if they displayed masculinity norms. Behavioral interviewing was also used to examine alcohol and marijuana attitudes, use, and problematic use. Analyses utilized t-tests and multiple and logistic regression. Many participants posted at least one substance use-related photo and a strong majority were exposed to such images through their network. Individuals who posted substance use-related images had more "followers." Posting substance-use related photos was related to marijuana use attitudes, behaviors, and problem behaviors, as well as depictions of toughness in photos. Social media monitoring has potential for use in identifying individuals at-risk for substance abuse and those who may be perpetuating unhealthy substance use norms.


Streptococcal infection in a regional burns centre and a plastic surgery unit.
An outbreak of infection due to group A streptococci of M-type 49 involved first a regional burns centre followed by spread to the intensive care ward of the plastic surgery unit in an associated hospital. Eleven patients and two staff were involved: two of the infected patients developed septicaemia. Serological tests demonstrated marked antibody response to DNAase B(ADB) and there were lesser reactions to other extracellular streptococcal products. Screening of patients and staff identified the likely source of the epidemic which was rapidly controlled by penicillin prophylaxis and other measures.


Cost-benefit analysis comparing trough, two-level AUC and Bayesian AUC dosing for vancomycin.
Area under the time-concentration curve (AUC) -guided dosing provides better estimates of exposure than vancomycin trough concentrations. Though clinical benefits have been reported, the costs of AUC-guided dosing are uncertain. The objective of this study was to quantify the costs of single-sample Bayesian or two-sample AUC strategies versus trough-guided dosing. A cost-benefit analysis from the institutional perspective was conducted using a decision tree to model the probabilities and costs of acute kidney injury (AKI) associated with vancomycin administered over 48 hours up to 21+ days. Costs included vancomycin concentrations, Bayesian software and AKI hospitalization costs, and probabilities were obtained from primary literature. Robustness was assessed via both one-way and probabilistic sensitivity analyses. In the base-case model, two-sample AUC versus trough dosing saved an average of US$ 846 per patient encounter, and single-sample Bayesian AUC versus trough dosing saved an average of US$ 2065 per patient encounter. This translates into annual cost-savings of US$ 846 810 and US$ 2 065 720 for two-sample and single-sample Bayesian methods versus trough dosing, respectively, assuming 1000 vancomycin-treated patients per year. Assuming a budget of US$ 100 000 per year for Bayesian software, an institution would need to treat ≥41 patients with vancomycin for at least 48 hours to break even. There are significant institutional cost benefits using two-sample AUC or single-sample Bayesian methods over trough dosing, even after accounting for the annual costs of Bayesian programs. The potential to decrease rates of AKI, improve clinical outcomes and reduce costs to the institution strongly warrants consideration of improved dosing methods for vancomycin.


Osteoid osteoma of the capitate bone.
A case of osteoid osteoma of the capitate bone is presented. The osteoma was accompanied by synovial changes in the neighbouring intercarpal joint, and this characterized the clinical features. Resection of the osteoma afforded relief from symptoms.


Action of agonists and antagonists at muscarinic receptors present on ileum and atria in vitro.
The action of 'selective' agonists and antagonists at muscarinic receptors mediating ileal contractions, and the rate and force of atrial contractions has been assessed. The effect of nicotinic receptor stimulation, catecholamine release and acetylcholinesterase (AChE) action on muscarinic activity has also been assessed. The nicotinic actions of carbachol did not affect its agonist potency nor the antagonist affinity data obtained when this agonist was used in atrial and ileal preparations. Antagonist data indicated that muscarinic receptors mediating the rate and force of atrial contractions did not differ. Differences in agonist potencies at these two muscarinic receptors were attributable to either differences in intrinsic efficacy or susceptibility to the action of acetylcholinesterase. The small differences in agonist potency observed between atrial and ileal muscarinic receptors were considered not sufficient to indicate receptor heterogeneity. The pirenzepine affinity data indicated that all three receptors are of the M2 type. Affinity data using secoverine and 4-diphenyl-acetoxy-N-methyl piperidine methiodide indicated that ileal and atrial muscarinic receptors differ. Data obtained using gallamine, pancuronium and stercuronium cannot be regarded as indicative of receptor affinity since the antagonism is not competitive; it did nonetheless corroborate the conclusion that ileal and atrial muscarinic receptors are different.


Can Clinical Postpartum Muscle Assessment Help Predict the Severity of Postpartum Pelvic Girdle Pain? A Prospective Cohort Study.
The purpose of this study was to evaluate whether the clinical assessment of pelvic floor muscles and the diastasis recti abdominis could predict the severity of pelvic girdle pain during the first year postpartum. Between 2018 and 2020, 504 women were recruited to this prospective longitudinal cohort study. At 2 to 3 months postpartum, their pelvic floor muscles and diastasis recti abdominis were assessed using vaginal palpation, observation, and caliper measurement. The participants completed the Pelvic Girdle Questionnaire (PGQ) at 2 to 3, 6, 9, and 12 months postpartum. Mixed-effect models were used to determine how the results of pelvic floor muscle and diastasis recti abdominis assessments predicted the PGQ score. A sub-analysis for middle to high PGQ scores was conducted. Maximal voluntary pelvic floor muscle contractions ≥3 (Modified Oxford Scale, scored from 0 to 5) predicted a decreased PGQ score (β = -3.13 [95% CI = -5.77 to -0.48]) at 2 to 3 months postpartum, with a higher prediction of a middle to high PGQ score (β = -6.39). Diastasis recti abdominis width did not have any significant correlation with the PGQ score. A sub-analysis showed that a diastasis recti abdominis width ≥35 mm predicted an increased PGQ score (β = 5.38 [95% CI = 1.21 to 9.55]) in women with pelvic girdle pain. The distinction between weak and strong maximal voluntary pelvic floor muscle contractions is an important clinical assessment in women with postpartum pelvic girdle pain. The exact diastasis recti abdominis width, measured in millimeters, showed no clinical relevance. However, a diastasis recti abdominis width ≥35 mm was associated with a higher PGQ score, and further research about this cutoff point in relation to pain is needed. This study highlights the importance of clinical assessment of pelvic floor muscles in patients with postpartum pelvic girdle pain. A better understanding of the role of this muscle group will enable more effective physical therapist treatment of pelvic girdle pain.


The impact of automated blood pressure devices on the efficiency of clinical trials.
By reducing measurement error, automated blood pressure (BP) devices should enhance the precision of BP estimation and thereby decrease sample size requirements in clinical trials of BP-lowering therapy. Enhanced precision would be particularly relevant to clinical trials assessing the efficacy of nonpharmacological therapies. In the present investigation, resting (clinic) BPs by the Dinamap 8100 (a stationary device) and the Accutracker II (an ambulatory device) were as precise as manual BPs given an equal number of observations by each method. However, both the Dinamap and Accutracker devices underestimated resting diastolic BP in comparison to the manual observers. Estimates of average daytime and 24-hour ambulatory BP, based on large numbers of observations over an extended period of time, were extremely precise. These findings suggest that the use of automated devices to measure resting BP may not reduce samples sizes, whereas use of ambulatory BP devices should reduce samples sizes considerably.


[Poliomyelitis].
The epidemiology of poliomyelitis, the poliovaccines and the present state of the WHO campaign for world-wide eradication of the polioviruses until the year 2000 are reviewed. In a second part, the recommendations of the "Ständige Impfkommission (STIKO, immunization task force)" from 1994 for Germany concerning poliovaccination are discussed. In contrast to the industrialized countries, the oral vaccination of infants in protection rates. After changes in vaccination strategy including mass vaccination days, the eradication campaign has succeeded in a considerable number of developing nations. However, because of limited financial resources and organizational difficulties the year 2000 goal for global eradication of polioviruses will hardly be met. The vaccination strategy of the STIKO continues to rely essentially on the trivalent oral poliovirus vaccine. The enhanced-potency inactivated polio vaccine is recommended for immunodeficient and all HIV-positive vaccinees as well as vaccinees with immunodeficient or HIV-positive contacts. Combined use of oral live vaccine and inactivated poliovirus vaccine induces an excellent local and systemic immunity. A combined vaccination strategy should be of particular interest in situations where other strategies fail.


GalNAc moieties in O-linked oligosaccharides of the primordial germ cells of Xenopus embryos.
Glycoconjugates could play a role in cell adhesion and migration mechanisms, including the locomotive movements of the primordial germ cells (PGCs) during the development of the embryo. In the present work, we have studied by lectin histochemistry the presence of N-acetylgalactosamine (GalNAc) in the glycans of the Xenopus PGCs, as a first approach to identifying their glycoconjugates which could be involved in the migration mechanism. The PGCs were negative for three of the GalNAc-binding lectins employed (from soybean, SBA; from lima bean, LBA; and from snail, HPA). However, when sialic acid (NeuAc) was previously removed by acid hydrolysis, SBA and HPA, but not LBA, labeled the PGCs, except if the staining was combined with the beta-elimination procedure. This suggests the presence of GalNAc alpha(1,3)-linked to galactose (Gal) in O-linked oligosaccharides, in a subterminal position to NeuAc. As the PGCs were always negative for LBA, the absence of fucose alpha(1,2)-linked to subterminal Gal is suggested. With the lectin from horse gram (DBA), the PGCs were stained, although beta-elimination turned the cells negative and acid hydrolysis increased the labeling, suggesting that GalNAc(alpha)(1,3)GalNAc was in O-linked glycans in terminal and subterminal to NeuAc position.


Craniopharyngioma: the pendulum of surgical management.
For a long time, craniopharyngiomas have been considered surgically attractive tumours. The fact that they are rare, histologically benign, and located in a challenging (but considered accessible) area made them worthy surgical prizes. As we have saved vision and "cured" many of these tumours, the insidious and devastating effects on quality of life for these children has become evident. The state-of-the-art in the surgical management of craniopharyngioma is now turning to multi-modality treatment strategies (combination surgery and radiotherapy) aiming to limit morbidity. Questions remain-what factors influence our surgical decision making? Do we understand the long-term effects of the radiotherapy now being employed? We review a series of craniopharyngiomas looking for variables that correlated with outcome as perceived in terms of quality of life and we review briefly the history of craniopharyngioma surgery and the relevant literature.


Peptidergic transmission in sympathetic ganglia of the frog.
1. A slow synaptic potential recorded in neurones of sympathetic ganglia of bullfrog, the late slow e.p.s.p., is probably mediated by a peptide resembling luteinizing hormone-releasing hormone (LHRH), because (1). a LHRH-like peptide is contained in preganglionic nerve terminals and is released upon nerve stimulation, (2) application of LHRH to ganglion cells mimics the effects of the natural transmitter for the late slow e.p.s.p., and (3) the pharmacological properties of LHRH and the natural transmitter for the late slow e.p.s.p. are similar. 2. Neurones in frog sympathetic ganglia are also depolarized by substance P. The substance P receptors, unlike the LHRH receptors or the post-synaptic receptors for the late slow e.p.s.p., are not blocked by antagonist of LHRH. No cross-desensitization was found between the substance P-induced response and the LHRH-induced response or the late slow e.p.s.p. 3. Substance P-like immunoreactivity is contained in bundles of axons passing through the ganglia. This distribution is distinct from the distribution of LHRH-like immunoreactivity in preganglionic nerve terminals. Thus, substance P receptors and substance P-containing fibers are distinct from the post-synaptic receptors and preganglionic fibers responsible for the late slow e.p.s.p. 4. Physiological and anatomical evidence is presented which indicates that the peptidergic transmitter for the late slow e.p.s.p. can diffuse for many micrometres before acting on ganglion cells.


Metabolism of androstenedione by placental microsomes in pregnancy hypertension.
The metabolism of [19-3H3]androstenedione by human placental microsomes was studied in vitro by radiometric analysis which distinguishes between 19-hydroxylation and elimination of the C-19 carbon. The ratio of the metabolic products tritiated water/tritiated formic acid is significantly greater for microsomes from patients with pregnancy hypertension when compared with normotensive pregnant women. This indicates that aromatization (2-hydroxylation) is deficient in pregnancy hypertension.


Lifelong learning and productive aging among the baby-boomers in Singapore.
Coined in 1982, the term productive aging is commonly associated with active participation in work, although it has since expanded beyond employment to include other dimensions of work, such as volunteering, caregiving and other activities that "produce(s) good/service for society, whether paid or unpaid" (Caro, Bass and Chen, 1993, p. 6). In this paper focusing on examining lifelong learning as one of the other activities in what comprises productive aging, we seek to explore the connections of lifelong learning to the notions of productive aging from the perspective of baby-boomers in Singapore. Using data from the qualitative study of Lifelong Learning among Older Adults in Singapore, which included 64 interviews with learners and non-learners of the baby-boomer generation (age 50-64), we first explore the grounded meanings of productive aging as articulated through lifelong learning. Next, we examine the benefits of lifelong learning as perceived by the baby-boomers, in particular, focusing on general wellbeing in enhancing productive aging. This is followed with a section examining barriers to lifelong learning to provide insight into deterrence to learning. Through the discussion of older adults' perceptions on lifelong learning and their engagement or lack of engagement especially with formal and non-formal learning, we hope to provoke a further re-thinking of what constitutes being productive in later life. Finally, we argue that beyond just another component to productive aging, lifelong learning should perhaps be further recognized as an enabler contributing to capacity-building of the other components including economic production, family care and volunteer services in enhancing productive aging.


Bosentan for high-risk outpatients with COVID-19 infection: a randomized, double blind, placebo-controlled trial.
The endothelium is supposedly activated and damaged in COVID-19 because of endothelin-1 over-secretion. This study evaluates the effect of bosentan as an endothelin receptor blocker on the progression of disease in high-risk outpatients with COVID-19 infection. From 15 December 2021 to 15 May 2022, high-risk outpatients were randomly assigned to receive bosentan, 62.5 mg or placebo twice daily from enrollment for 30 days. Both groups received standard medical treatment too. On day 30 of the trial, the patients underwent complete doppler ultrasound of the lower extremities to detect asymptomatic thromboembolic events. The primary outcome in this study was hospitalization or death from any cause within the first 15 days. Secondary outcomes included thromboembolic events, hospital-free days and death from any cause within 30 days after randomization (IRCT.ir, IRCT20211203053263N1). Basal characteristics of the two groups were similar. Primary outcomes occurred in 3 (2.3%) of the 129 patients in the bosentan group versus 15 (11.5%) of the 130 patients in the placebo group [risk difference: -9.2% (95% CI: -15.3 to -3.1), P = 0.006]. Median hospital-free days was significantly higher in the bosentan group (P = 0.004). A total of three deaths occurred and all were in the control group. Bosentan was associated with a nonsignificant reduction in mortality compared with placebo (P = 0.24). Thromboembolic events occurred in one (1%) of 97 patients in the bosentan group versus nine (8.7%) of 104 patients in the placebo group within 30 days after randomization [risk difference: -8.3% (95% CI: -14.4 to -2.2), P = 0.008]. Early administration of bosentan may prevent disease progression and thromboembolic events in high-risk outpatients with COVID-19. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.


Ocurrence of anti-Wr a in blood donors and in selected patient groups, with a note on the incidence of the Wr a antigen.
The occurrence of the Wr a antigen on the red blood cells of 5,000 primarily Caucasian New York State blood donors was shown to be 1:1,000. Anti-Wr a was detected in sera from random blood donors with a frequency of 1:56 and with progressively increasing frequency in postpartum women, patients undergoing open-heart surgery, hemodialysis subjects, and random persons with other alloantibodies. Anti-Wr a was found in one fourth of sera from patients with positive direct antiglobulin tests, including 12 of 23 in whom the positive test was associated with alphamethyldopa treatment.


Analysis of RAS mutation in thyroid nodular hyperplasia and follicular neoplasm in a Korean population.
To investigate the difference in frequency of RAS mutations between nodular hyperplasia (NH), follicular thyroid adenomas (FTAs) and follicular thyroid carcinomas (FTCs) in a Korean population. RAS mutations in 50 NH, 57 FTAs and 39 FTCs between January 2002 and May 2015 were analysed by pyrosequencing. Nine nodules of 50 NHs (18%), 18 nodules of 39 FTCs (46.2%) and 19 nodules of 57 FTAs (33.3%) harboured RAS mutations. Three FTCs and three FTAs showed two point mutations simultaneously. N-RAS codon 61 (n = 6 of 9, 66.7%) and H-RAS codon 61 (n = 3 of 9, 33.3%) were found in NHs. K-RAS codons 12-13, K-RAS codon 61, N-RAS codons 12-13 and H-RAS codons 12-13 were not found in NHs. N-RAS codon 61 (n = 7 of 21, 33.3%), K-RAS codons 12-13 (n = 6 of 21, 28.6%), H-RAS codon 61 (n = 4 of 21, 19.0%), K-RAS codon 61 (n = 3 of 21, 14.3%) and N-RAS codons 12-13 (n = 1 of 21, 4.7%) were found in FTCs, and N-RAS codon 61 (n = 10 of 22, 45.5%), K-RAS codons 12-13 (n = 5 of 22, 22.7%), H-RAS codon 61 (n = 5 of 22, 22.7%), K-RAS codon 61 (n = 1 of 22, 4.5%) and N-RAS codons 12-13 (n = 1 of 22, 4.5%) were observed in FTAs. The frequencies of RAS mutations among our Korean population were 18% in NHs, 46.2% in FTC and 33.3% in FTAs. N-RAS codon 61 was the most frequent mutation in NHs, FTCs and FTAs, and the frequency was not significantly different among the three groups. K-RAS codons 12-13 were the second most commonly involved site in FTCs and FTAs, whereas no mutation was detected at this site in NHs.


Gray whales and the structure of the Bering Sea benthos.
The purpose of this study was to look at the effect of foraging by gray whales on the benthic community. The gray whale, the only mysticete whale which feeds mainly upon benthic organisms, relies on the amphipod crustacean assemblages of the northern Bering Sea and the Chukchi Sea for most of its annual food intake. Foraging whales leave identifiable depressions 0.6 to 3 m long in the bottom sediments in their wake. Patterns in the infaunal community composition appeared to be correlated with the size of the pit and by inference, the age of the pit. Large, deep pits were characterized by species considered early colonists of disturbed areas. Smaller, shallow depressions did not have elevated numbers of early colonists. Abundance of Ampelisca macrocephala, the dominant bottom organism and whale prey item, was depressed in all pits sampled.


Modifiable Parent Factors Associated with Child and Adolescent School Refusal: A Systematic Review.
School refusal is a complex problem that refers to difficulty attending/remaining at school due to emotional distress about attendance. Despite its occurrence being associated with negative outcomes, many are unresponsive to the current treatment options. While parent factors have a key role to play in school refusal, they are not adequately addressed in existing treatments. Further research is needed to consolidate understanding and implement new treatments. Employing the PRISMA method, this review aims to identify modifiable parent factors associated with child and/or adolescent school refusal. Eight studies met inclusion criteria from which nine factors were identified. Factors found to be associated with school refusal included: parent psychopathology, family functioning and maternal overprotection (communication subdomain). Other factors such as maternal overprotection (affection, assistance and travel subdomains) and parental self-efficacy had weak or inconsistent results warranting further investigation. Overall, findings call for action in this field that has sparse and dated literature.


Spatiotemporal frequency tuning of BOLD and gamma band MEG responses compared in primary visual cortex.
In this study, the spatial and temporal frequency tuning characteristics of the MEG gamma (40-60 Hz) rhythm and the BOLD response in primary visual cortex were measured and compared. In an identical MEG/fMRI paradigm, 10 participants viewed reversing square wave gratings at 2 spatial frequencies [0.5 and 3 cycles per degree (cpd)] reversing at 5 temporal frequencies (0, 1 6, 10, 15 Hz). Three-dimensional images of MEG source power were generated with synthetic aperture magnetometry (SAM) and showed a high degree of spatial correspondence with BOLD responses in primary visual cortex with a mean spatial separation of 6.5 mm, but the two modalities showed different tuning characteristics. The gamma rhythm showed a clear increase in induced power for the high spatial frequency stimulus while BOLD showed no difference in activity for the two spatial frequencies used. Both imaging modalities showed a general increase of activity with temporal frequency, however, BOLD plateaued around 6-10 Hz while the MEG generally increased with a dip exhibited at 6 Hz. These results demonstrate that the two modalities may show activation in similar spatial locations but that the functional pattern of these activations may differ in a complex manner, suggesting that they may be tuned to different aspects of neuronal activity.


Glaucomatous optic neuropathy: Mitochondrial dynamics, dysfunction and protection in retinal ganglion cells.
Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by a slow, progressive, and multifactorial degeneration of retinal ganglion cells (RGCs) and their axons, resulting in vision loss. Despite its high prevalence in individuals 60 years of age and older, the causing factors contributing to glaucoma progression are currently not well characterized. Intraocular pressure (IOP) is the only proven treatable risk factor. However, lowering IOP is insufficient for preventing disease progression. One of the significant interests in glaucoma pathogenesis is understanding the structural and functional impairment of mitochondria in RGCs and their axons and synapses. Glaucomatous risk factors such as IOP elevation, aging, genetic variation, neuroinflammation, neurotrophic factor deprivation, and vascular dysregulation, are potential inducers for mitochondrial dysfunction in glaucoma. Because oxidative phosphorylation stress-mediated mitochondrial dysfunction is associated with structural and functional impairment of mitochondria in glaucomatous RGCs, understanding the underlying mechanisms and relationship between structural and functional alterations in mitochondria would be beneficial to developing mitochondria-related neuroprotection in RGCs and their axons and synapses against glaucomatous neurodegeneration. Here, we review the current studies focusing on mitochondrial dynamics-based structural and functional alterations in the mitochondria of glaucomatous RGCs and therapeutic strategies to protect RGCs against glaucomatous neurodegeneration.


Using environmental DNA to better inform decision making around decommissioning alternatives for offshore oil and gas infrastructure.
Artificial reefs are being utilised globally to aid in natural resource management, conservation, restoration or the creation of unique marine habitats. There is discussion around the optimal construction materials and designs for artificial reefs, the influences these have on biological communities, and the resulting ecological and social benefits. This discussion also includes the ecological value of repurposed marine infrastructure, such as decommissioned oil and gas platforms. Platforms often have an operational life spanning multiple decades, over which time they can develop extensive and unique community assemblages. The creation of artificial reefs by repurposing oil and gas platforms can have ecological, economic and sociological merit. However, with >12,000 platforms requiring decommissioning globally, there is the need for holistic assessment of biological communities associated with these platforms to inform the potential outcomes of different decommissioning options. We use environmental DNA metabarcoding (eDNA) of water, bio-foul and sediment samples to census broad eukaryotic diversity at eight platforms in the Gulf of Thailand (GoT) and five nearby soft sediment habitat locations. We sampled three target depths at sites (shallow, mid, deep) and detected 430 taxa at platforms, with higher diversity in shallow (near-surface) samples (313 taxa), compared to mid (30 m collection depth; 261 taxa) and deep (50 m; 273 taxa). Three percent of taxa were shared among all depths at platforms with distinct assembles at each depth. Introduced species are an ongoing risk for platforms, however the eDNA detected no known introduced species. While the eDNA data provide broad taxon coverage and significant assemblage patterns, ongoing sampling innovation, assay design and local reference material still require development to obtain the maximum benefit of the technique. This study highlights the versatility and scalability of eDNA metabarcoding to holistically census marine infrastructure and inform the management and potential conservation of extant communities.


Weaning predictors do not predict extubation failure in simple-to-wean patients.
Predictor indexes are often included in weaning protocols and may help the intensive care unit (ICU) staff to reach expected weaning outcome in patients on mechanical ventilation. The objective of this study is to evaluate the potential of weaning predictors during extubation. This is a prospective clinical study. The study was conducted in 3 medical-surgical ICUs. Five hundred consecutive unselected patients ventilated for more than 48 hours were included. All patients were extubated after 30 minutes of successful spontaneous breathing trial and followed up for 48 hours. The protocol evaluated hemodynamics, ventilation parameters, arterial blood gases, and the weaning indexes frequency to tidal volume ratio; compliance, respiratory rate, oxygenation, and pressure; maximal inspiratory pressure; maximal expiratory pressure; Pao(2)/fraction of inspired oxygen; respiratory frequency; and tidal volume during mechanical ventilation and in the 1st and 30th minute of spontaneous breathing trial. Reintubation rate was 22.8%, and intensive care mortality was higher in the reintubation group (10% vs 31%; P < .0001). The areas under the receiver operating characteristic curve showed that tests did not discriminate which patients could tolerate extubation. Usual weaning indexes are poor predictors for extubation outcome in the overall ICU population.


Treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study.
Herbal medicines are widely used for the treatment of pain, although there is not much information on their effectiveness. This study was designed to evaluate the effectiveness of willow (Salix) bark extract, which is widely used in Europe, for the treatment of low back pain. We enrolled 210 patients with an exacerbation of chronic low back pain who reported current pain of 5 or more (out of 10) on a visual analog scale. They were randomly assigned to receive an oral willow bark extract with either 120 mg (low dose) or 240 mg (high dose) of salicin, or placebo, with tramadol as the sole rescue medication, in a 4-week blinded trial. The principal outcome measure was the proportion of patients who were pain-free without tramadol for at least 5 days during the final week of the study. The treatment and placebo groups were similar at baseline in 114 of 120 clinical features. A total of 191 patients completed the study. The numbers of pain-free patients in the last week of treatment were 27 (39%) of 65 in the group receiving high-dose extract, 15 (21%) of 67 in the group receiving low-dose extract, and 4 (6%) of 59 in the placebo group (P <0.001). The response in the high-dose group was evident after only 1 week of treatment. Significantly more patients in the placebo group required tramadol (P <0.001) during each week of the study. One patient suffered a severe allergic reaction, perhaps to the extract. Willow bark extract may be a useful and safe treatment for low back pain.


'Never mind the quality, feel the width': the nonsense of 'quality', 'excellence', and 'audit' in education, health and research.
The worlds of health care and education have been colonised by 'The Audit Society' and managerialism. Under the benign guise of 'improving quality' and 'ensuring value for money' a darker, more Orwellian purpose operates. Academics had to be transformed into a workforce of 'docile bodies', willing to scrutinise and survey themselves and their 'performance' as outcome deliverers and disciples of the new 'Qualispeak'. This paper critiques the current obsession with audit and performativity, the constant and often pointless 'change' is that held to be so self-evidently 'a good thing' and the linguistic wasteland that so often passes for discussion or policy in the Brave New Worlds of health and education.


Anterolateral Extra-articular Soft Tissue Reconstruction in Anterolateral Rotatory Instability of the Knee.
Anterolateral rotatory instability (ALRI) occurs after injury to the anterior cruciate ligament (ACL) and the anterolateral structures of the knee. We present a technique for anterolateral extra-articular soft-tissue (ALES) reconstruction of the knee that can be used in revision ACL reconstruction cases, cases of persistent ALRI after adequate ACL reconstruction, and cases with severe ALRI after primary ACL rupture. The surgeon performs ALES reconstruction with a strip of iliotibial tract autograft while respecting the anatomic origin and insertion of the anterolateral ligament. The purpose of this reconstruction is to restore the normal anterolateral rotatory stability of the knee in ALES-deficient patients.


Sodium channel expression in optic nerve astrocytes chronically deprived of axonal contact.
Immunocytochemical and electrophysiological methods were used to examine the effect of retinal ablation on the expression of sodium channels within optic nerve astrocytes in situ and in vitro. Enucleation was performed at postnatal day 3 (P3), and electron microscopy of the enucleated optic nerves at P28-P40 revealed complete degeneration of retinal ganglion axons, resulting in optic nerves composed predominantly of astrocytes. In contrast to control (non-enucleated) optic nerve astrocytes, which exhibited distinct sodium channel immunoreactivity following immunostaining with antibody 7493, the astrocytes in enucleated optic nerves did not display sodium channel immunoreactivity in situ. Cultures obtained from enucleated optic nerves consisted principally (greater than 90%) of glial fibrillary acidic protein (GFAP)+/A2B5- ("type-1") astrocytes, as determined by indirect immunofluorescence; GFAP+/A2B5+ ("type-2") astrocytes were not present, nor were GFAP-/A2B5+ (O-2A) progenitor cells. Sodium channel immunoreactivity was not present in GFAP+/A2B5- astrocytes obtained from enucleated optic nerves; in contrast, GFAP+/A2B5- astrocytes from control optic nerves exhibited 7493 immunostaining for the first 4-6 days in culture. Sodium current expression, studied using whole-cell patch-clamp recording, was attenuated in cultured astrocytes derived from enucleated optic nerves. Whereas 39 of 50 type-1 astrocytes cultured from intact optic nerves showed measurable sodium currents at 1-7 days in vitro, sodium currents were present in only 6 of 38 astrocytes cultured from enucleated optic nerves. Mean sodium current densities in astrocytes from the enucleated optic nerves (0.66 +/- 0.3 pA/pF) were significantly smaller than in astrocytes from control optic nerves (7.15 +/- 1.1 pA/pF). The h infinity-curves of sodium currents were similar in A2B5- astrocytes from enucleated and control rat optic nerves. These results suggest that there is neuronal modulation of sodium channel expression in type-1 optic nerve astrocytes, and that, following chronic loss of axonal association in vivo, sodium channel expression is down-regulated in this population of optic nerve astrocytes.


Modified protocol for culturing Drosophila S2 R+ cells and adult plasmatocytes to study actin cytoskeleton dynamics.
Here, we describe a protocol to culture Drosophila S2R+ cells and to extract plasmatocytes from adult flies. The modified seeding approach detailed here, in combination with coating of coverslips with concanvalin A, enables enhanced adhesion and spreading of cells. We describe the steps for confocal microscopy and a detailed quantification pipeline to evaluate changes in cortical actin cytoskeleton dynamics. The protocol can be applied to a variety of genetic or chemical perturbations. For complete details on the use and execution of this protocol, please refer to Nath et al. (2022).


A Rare Case of Submandibular Actinomycosis.
Actinomycosis is caused by actinomyces israelii, a gram positive nonacid fast, anaerobic, commensal bacterium within the oral cavity. Though it is a commensal in oral cavity, it seldom presents as cervicofacial actinomycosis. But there is limited access to literature proving cervicofacial actinomycosis existence so far. We report a case of 35 year old gentleman who presented with painless progressive neck swelling associated with pain while chewing food. On examination, 3.5*2.5 swelling was noted in right submandibular gland area, radiologically a foreign body was detected in the right submandibular gland. Mass was excised in toto and sent for HPE which revealed submandibular gland actinomycosis. Post operatively, patient was managed with long-term broad-spectrum beta lactams and was on regular follow-up. No evidence of recurrence/ fresh complaints noted till date. Although cervicofacial actinomycosis is rare and dangerous with debilitating complications, timely diagnosis and early intervention with broad spectrum antibiotics and surgical excision (if required) shows promising results with complete eradication of disease leaving no residues. The online version contains supplementary material available at 10.1007/s12070-023-03498-7.


Comparison of integrin adhesion molecules expressed by primary brain lymphomas and nodal lymphomas.
The expression of 17 adhesion molecules was immunohistochemically examined in 5 primary cerebral lymphomas (PCL) and in 5 histologically similar nodal lymphomas (NL) to evaluate their possible involvement in selective targeting of lymphoma cells to the brain. PCL and NL tumor cells showed very similar expression patterns: they were consistently positive for alpha 3, alpha 4 and beta 1 integrin chains; negative for alpha 1, alpha 2, alpha 6, beta 3 and beta 4 integrin chains; and heterogeneous for alpha 5, alpha L, alpha M, alpha X, beta 2 and beta 7 integrin chains, as well as for intercellular adhesion molecule-1 (ICAM-1) and the selectin LECAM-1. Loosely infiltrating PCL showed lower levels of the alpha L beta 2 integrin than compact cell clusters. Vessels stained for ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1). We conclude that the adhesion molecules implicated in the extravasation of non-neoplastic leukocytes (alpha 4 beta 1/VCAM-1 and alpha L beta 2/ICAM-1) are also expressed by both PCL and NL. The adhesion molecules examined are apparently not selective mediators of lymphoma cell homing to the brain, but at least alpha L beta 2 integrin might be related to the infiltration pattern of PCL within the brain parenchyma.


Bortezomib-induced peripheral neuropathy: A genome-wide association study on multiple myeloma patients.
The proteasome-inhibitor bortezomib was introduced into the treatment of multiple myeloma more than a decade ago. It is clinically beneficial, but peripheral neuropathy (PNP) is a side effect that may limit its use in some patients. To examine the possible genetic predisposing factors to PNP, we performed a genome-wide association study on 646 bortezomib-treated German multiple myeloma patients. Our aim was to identify genetic risk variants associated with the development of PNP as a serious side effect of the treatment. We identified 4 new promising loci for bortezomib-induced PNP at 4q34.3 (rs6552496), 5q14.1 (rs12521798), 16q23.3 (rs8060632), and 18q21.2 (rs17748074). Even though the results did not reach genome-wide significance level, they support the idea of previous studies, suggesting a genetic basis for neurotoxicity. The identified single nucleotide polymorphisms map to genes or next to genes involved in the development and function of the nervous system (CDH13, DCC, and TENM3). As possible functional clues, 2 of the variants, rs12521798 and rs17748074, affect enhancer histone marks in the brain. The rs12521798 may also impact expression of THBS4, which affects specific signal trasduction pathways in the nervous system. Further research is needed to clarify the mechanism of action of the identified single nucleotide polymorphisms in the development of drug-induced PNP and to functionally validate our in silico predictions.


Prediction of learning rate from the hippocampal electroencephalogram.
Samples of spontaneous electroencephalographic (EEG) activity from the dorsal hippocampus of rabbits were recorded immediately before classical conditioning of the nictitating membrane response. Computer analysis revealed a significant predictive relationship between EEG frequency characteristics and the subsequent rate of learning.


Effect of antipsychotics on cortical inhibition using transcranial magnetic stimulation.
Previous studies suggest that antipsychotic medications may alter cortical inhibition (CI). The current study was designed to determine if typical or atypical antipsychotics indeed alter CI in healthy subjects using three CI paradigms as measured with transcranial magnetic stimulation (TMS): short interval intracortical inhibition (SICI), cortical silent period (CSP) and transcallosal inhibition (TCI). CI was measured before, 6 and 24 h after being randomly assigned to receive a single dose of 2 mg haloperidol (n=8), 10 mg olanzapine (n=10) or placebo (n=9). There was no significant effect on any measure of CI at 6 and 24 h after receiving olanzapine, haloperidol or placebo. Moreover, no significant change in the motor threshold was observed across the three medication groups. Therefore, single administration of an antipsychotic has no effect on CI or resting motor threshold. Whether chronic, repeated administration of antipsychotics has effects on CI requires further investigation.


Death, taxes, and trapeziometacarpal arthrosis.
Hand surgeons treat trapeziometacarpal arthrosis as if everyone with the disease presents for treatment despite evidence that suggests that trapeziometacarpal arthrosis is a normal part of human aging for which--it seems safe to assume--most people never seek medical attention. The aims of our study were (1) to confirm the prevalence of radiographic trapeziometacarpal arthrosis in a very large sample and to determine if age and sex are associated with (2) any radiographic evidence of trapeziometacarpal arthrosis; and (3) radiographic evidence of severe trapeziometacarpal arthrosis. A total of 2321 patients 31 years or older with radiographs obtained during treatment of a distal radius fracture at a tertiary care medical center emergency department between 2002 and 2012 were analyzed. Trapeziometacarpal arthrosis was graded using the 3-point scale of Sodha et al. (none, definite, destroyed trapeziometacarpal joint); we used regression analyses to determine the association of age (in 10-year age groups) and sex with the presence of trapeziometacarpal arthrosis. The prevalence of trapeziometacarpal arthrosis steadily increased to 85% between the ages of 71 and 80 years and reached 100% in women (with 50% of them being classified as severe) aged 91 years or older and 93% in men of 81 years or older. Severe arthrosis was more prevalent at earlier ages among women and reached 35% in women and 34% in men who were 81 years or older. Logistic regression identified higher age as the strongest factor associated with trapeziometacarpal arthrosis, but sex was also a factor. Radiographic trapeziometacarpal arthrosis is an expected part of human aging. Given that only three patients in this large cohort had evidence of prior surgery, it seems that most people adapt to trapeziometacarpal arthrosis. Treatments that optimize adaptation in patients who present with trapeziometacarpal arthrosis-related symptoms and disability merit additional study.


Molecular basis for the inhibition of 1,4-dihydropyridine calcium channel drugs binding to their receptors by a nonspecific site interaction mechanism.
The "membrane bilayer" pathway (Rhodes, D. G., J. G. Sarmiento, and L. G. Herbette. 1985. Mol. Pharmacol. 27:612-623.) for 1,4-dihydropyridine calcium channel drug (DHP) binding to receptor sites in cardiac sarcolemmal membranes has been extended to include the interaction of amphiphiles within the lipid bilayer. These studies focused on the ability of the Class III antiarrhythmic agents bretylium and clofilium to nonspecifically inhibit DHP-receptor binding in canine cardiac sarcolemma. Clofilium was found to inhibit nimodipine binding with an inhibition constant of approximately 5 microM, whereas bretylium had no effect on nimodipine binding. Small angle x-ray diffraction was then used to examine the differential ability of these two Class III agents to inhibit DHP-receptor binding. The time-averaged locations of bretylium, clofilium, and nimodipine in bovine cardiac phosphatidylcholine (BCPC) bilayers (supplemented with 13 mol% cholesterol) were determined to a resolution of 9 A. The location of bretylium as dominated by its phenyl ring in BCPC bilayers was found to be at the hydrocarbon core/water interface, similar to that of the dihydropyridine ring of nimodipine. The location of clofilium as dominated by its phenyl ring was found to be below the hydrocarbon/core water interface within the hydrocarbon chain region of the bilayer, similar to that of the phenyl ring of nimodipine. The location of the dihydropyridine ring portion of nimodipine has previously been shown by neutron diffraction to be located at the hydrocarbon core/water interface of native sarcoplasmic reticulum, consistent with the small angle x-ray data from model membranes in this paper. Therefore, we speculate that the nonspecific inhibition arises from the interaction of clofilium's phenyl ring with the site on the calcium channel receptor where the phenyl ring portion of nimodipine must interact. The DHP-receptor binding pathway would then involve both nonspecific (membrane) and specific (protein) binding components, both of which are necessary for receptor binding.


Evolution Law of Helium Bubbles in Hastelloy N Alloy on Post-Irradiation Annealing Conditions.
This work reports on the evolution law of helium bubbles in Hastelloy N alloy on post-irradiation annealing conditions. After helium ion irradiation at room temperature and subsequent annealing at 600 °C (1 h), the transmission electron microscopy (TEM) micrograph indicates the presence of helium bubbles with size of 2 nm in the depth range of 0-300 nm. As for the sample further annealed at 850 °C (5 h), on one hand, a "Denuded Zone" (0-38 nm) with rare helium bubbles forms due to the decreased helium concentration. On the other hand, the "Ripening Zone" (38-108 nm) and "Coalescence Zone" (108-350 nm) with huge differences in size and separation of helium bubbles, caused by different coarsening rates, are observed. The mechanisms of "Ostwald ripening" and "migration and coalescence", experimentally proved in this work, may explain these observations.


Rapid cycle development of a multifactorial intervention achieved sustained reductions in central line-associated bloodstream infections in haematology oncology units at a children's hospital: a time series analysis.
Immunocompromised children are at high risk for central line-associated bloodstream infections (CLABSIs) and its associated morbidity and mortality. Prevention of CLABSIs depends on highly reliable care. Since the summer of 2013, we saw an increase in patient volume and acuity in our centre. Additionally, CLABSIs rates more than tripled during this period. The purpose of this initiative was to rapidly identify and mitigate potential underlying drivers to the increased CLABSI rate. Through small tests of change, we implemented a standard process for daily hygiene; increased awareness of high-risk patients with CLABSI; improved education/assistance for nurses performing high-risk central venous catheter procedures; and developed a system to improve allocation of resources to de-escalate system stress. The CLABSI rate from June 2013 to May 2014 was 2.03 CLABSIs/1000 line days. After implementation of our interventions, we saw a significant decrease in the CLABSI rate to 0.39 CLABSIs/1000 line days (p=0.008). Key processes have become more reliable: 100% of dressing changes are completed with the new two-person standard; daily hygiene adherence has increased from 25% to 70%; 100% of nurses are approached daily by senior nursing for assistance with high-risk procedures; and patients at risk for a CLABSI are identified daily. Stress to a complex system caring for high-risk patients can challenge CLABSI rates. Identifying key processes and executing them reliably can stabilise outcomes during times of system stress.


Evolutionary rates and timescale comparison of Chikungunya viruses inferred from the whole genome/E1 gene with special reference to the 2005-07 outbreak in the Indian subcontinent.
Chikungunya (CHIK) virus reemerged during 2005-07 as an important pathogen causing massive disease outbreaks affecting India and several countries of the Indian Ocean. Knowledge of the evolutionary rates and divergence times of the CHIK virus may help to better understand the disease epidemiology. Considering the limited availability of such information, we estimated the substitution rates and the ancestral times for all the CHIK genotypes and also the time to the most recent common ancestor (tMRCA) of the 2005-07 isolates. Using whole genomes and partial E1 gene datasets, we applied the Bayesian Markov Chain Monte Carlo (MCMC) framework that explicitly accounts for lineage-specific evolutionary rates through the use of 'relaxed' molecular clock models. Under a constant population relaxed clock model, the evolutionary timescale of CHIK viruses in this study was estimated to be in the last 300 years. The progenitor of the 2005-07 viruses was found to have existed around 9 years ago, and to have originated from Central Africa. The presence of a strain in India in 2000 that bears 99% identity with a Ugandan strain of 1982, which correlates with the tMRCA of the Indian and Indian Ocean isolates, confirms our earlier report that the progenitor of the 2005-07 isolates originates from Uganda's neighbourhood. The 'A226V' mutation that existed in the Indian Ocean isolates since late 2005 was found to occur only in the 2007 isolate from India. The study confirms the epidemiological data, specifically with regard to the re-emergence of CHIKV and throws light on the evolutionary dynamics of CHIK viruses.


Outcomes for Patients With Chronic Lymphocytic Leukemia (CLL) Previously Treated With Both a Covalent BTK and BCL2 Inhibitor in the United States: A Real-World Database Study.
This study describes the treatment patterns and outcomes of patients with CLL/SLL in a de-identified real-world oncology electronic health records database. Adult patients with CLL/SLL were eligible if they had received cBTKi therapy, both a cBTKi and a BCL2i, or all 4 drug classes (cBTKi, BCL2i, rituximab, and chemotherapy) at any time during the first 5 lines of therapy. Time-to-event outcomes were evaluated using Kaplan Meier method. No statistical comparisons were conducted; all analyses were descriptive and conducted using SAS Enterprise. A total of 9578 patients were eligible: 52.0% (n = 4983) received at least one cBTKi, 6.1% (n = 581) received both a cBTKi and BCL2i, and 2.3% (n = 218) received all four therapies (cBTKi, BCL2i, rituximab, and chemotherapy). Of those who discontinued these treatments, only 39.5% (n = 1 206/3 577), 59.7% (n = 228/382), and 55.0% (n = 82/149) received subsequent therapy (post-cBTKi, post-cBTKi/post-BCL2i, and post-all 4 therapies, respectively). Median time from treatment discontinuation of these therapies to the discontinuation of subsequent therapy or death was 9.5 months (all patients who discontinued the cBTKi) 5.6 months (those who discontinued both a cBTKi and BCL2i) and 3.9 months (patients who discontinued all four therapies). The median duration of the next treatment among those who received additional therapy was post-cBTKi treatment duration = 4.1 months; post-cBTKi/post-BCL2i treatment duration = 5.5 months; and median duration of the immediate next therapy after discontinuation of all 4 therapies = 5.1 months. The poor outcomes observed across cohorts in this study demonstrate the need for effective treatments that can improve outcomes in patients with CLL/SLL.


Nanofibrillated cellulose originated from Rhododendron ponticum to produce scaffolds using 3D printing for biomedical applications.
Rhododendron ponticum is an invasive species that spreads rapidly and is described as one of the biggest threats to peatlands in Ireland. This study offers an innovative approach to utilizing Rhododendron waste. Initially, sawdust was submitted to a bleaching treatment and the nanofibrillated cellulose (NFC) was obtained using two different methods: ultra-fine friction grinding and twin-screw extrusion with the assistance of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) pre-treatment. The samples processed through twin-screw extrusion exhibited the presence of NFC at five intervals, as confirmed by TEM analysis. However, these samples displayed a higher diameter deviation compared to those processed through grinding alone. Notably, after 20 extrusion steps, the NFC diameter became more uniform, reaching approximately 35 nm. Sedimentation tests showed that extrusion produced more homogeneous cellulose size than the grinder method. However, FTIR characterization for the samples showed a unique band related to C-O-C glycosidic linkage. The results showed that grinding breaks these groups resulting in crystallinity values lower than extrusion, 50 % compared 60 %. Therefore, NFC with 20 steps by grinding was blended with polycaprolactone to produce a 3D scaffold using a 3D printer at different ratios of 1-5 % addition. The effect of 1 % of NFC was unique showing significant enhanced mechanical properties compared to pure polycaprolactone (PCL), additionally, the NFC does not exhibit toxicity so these materials show promise for biomedical applications.


Modelling the effect of minor orthopaedic day surgery on patient mood at the early post-operative period: a prospective population-based cohort study.
The effect of minor orthopaedic day surgery (MiODS) on patient's mood. A prospective population-based cohort study of 148 consecutive patients with age above 18 and less than 65, an American Society of Anaesthesiology (ASA) score of 1, and the requirement of general anaesthesia (GA) were included. The Medical Outcomes Study - Short Form 36 (SF-36), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) were used pre- and post-operatively. The mean physical component score of SF-36 before surgery was 45.3 (SD=+/-10.1) and 8 weeks following surgery was 44.9 (SD=+/-11.04) [n=148, p=0.51, 95% CI=(-1.03 to 1.52)]. For the measurement of the changes in mood using BDI, BAI and SF-36, latent construct modelling was employed to increase validity. The covariance between mood pre- and post-operatively (cov=69.44) corresponded to a correlation coefficient, r=0.88 indicating that patients suffering a greater number of mood symptoms before surgery continue to have a greater number of symptoms following surgery. When the latent mood constructs were permitted to have different means the model fitted well with chi(2) (df=1)=0.86 for which p=0.77, thus the null hypothesis that MiODS has no effect on patient mood was rejected. MiODS affects patient mood which deteriorates at 8 weeks post-operatively regardless of the pre-operative patient mood state. More importantly patients suffering a greater number of mood symptoms before MiODS continue to have a greater number of symptoms following surgery.


Low-normal systolic blood pressure and secondary stroke risk.
A recent observational study of >20,000 patients with recent ischemic stroke suggested that systolic blood pressure (SBP) maintained in a low-normal range may be associated with increased risk of recurrent stroke, especially within the first 6 months after the first stroke. Using a distinct cohort, the current study aimed to independently evaluate the relationship between low-normal SBP levels and risk of recurrent stroke through analysis of a trial dataset involving 3680 patients with recent noncardioembolic ischemic stroke aged ≥ 35 years recruited from 56 centers between September 1996 and May 2003 and followed for 2 years. Subjects were categorized based on their mean in-trial SBP value as low-normal (<120 mm Hg), high-normal (120 to <140 mm Hg), or high (>140 mm Hg). The primary outcome was stroke. Multivariate analyses used competing-risks Cox regression models. The rate of recurrent stroke was 9.1% in the low-normal group, 6.7% in the high-normal group, and 10% in the high group. The difference in recurrent stroke rate between the low-normal and high-normal groups was more prominent within the first 6 months (low-normal, 4.5%; high-normal, 2.5%; high, 3.4%) than after 6 months (low-normal, 4.6%; high-normal, 4.2%; high, 6.6%). Over the study period, compared with the high-normal group, the risk of the primary outcome trended higher in the low-normal group (adjusted hazard ratio, 1.47; 95% confidence interval, 0.94-2.29; P = .09) and was higher in the high group (adjusted hazard ratio, 1.39; 95% confidence interval, 1.08-1.79; P = .01). These results support the recently described pattern of increased risk of recurrent stroke in patients with low-normal SBP levels, especially within the first 6 months after first stroke. However, this study likely was not sufficiently powered to detect more than a strong statistical trend underlying this relationship.


Failing Fontan cardiovascular support: Review.
Although all congenital heart defects (CHD) present unique challenges, univentricular CHD are especially challenging given the difficulty of passively perfusing pulmonary blood flow. Three surgical procedures are required within the first years of life, with the final completing a Fontan circulation in which the inferior vena cava is connected to the pulmonary artery and previously connected superior vena cava. This allows passive venous return to the pulmonary circulation then flow into the single ventricle for systemic circulation. Although a Fontan provides successful palliation for two to three decades, many complications can arise as pulmonary resistance must remain low to allow adequate forward flow. Eventually, the failing Fontan circulation requires temporary support as the patient awaits a heart transplant. We reviewed PubMed, Google Scholar, and U. Kentucky library for different techniques evaluated to support a failing Fontan circulation. Multiple technologies have been developed as a bridge to transplant to decrease morbidity. Innovative types of extracorporeal membrane oxygenation, ventricular assist devices, and total artificial hearts have been attempted in laboratory settings as well as in Fontan patients with varying degrees of success. This article emphasizes the strengths and weaknesses of each technology in the context of Fontan physiology. The end game for these patients remains a heart transplant. Without easy access to donors, each of the options discussed is a potential bridge to limit morbidity and mortality until a suitable donor heart becomes available.


Chromatin structure, DNA methylation, and gene expression at sites of viral integration in human fibroblasts. Implications for chromosomal fragility.
We analyzed the structural and functional properties of a chromosomal region in which a recombinant hybrid virus adenovirus 5/SV40 preferentially integrates. Our results demonstrated that the structure of the cellular targets for DNA and RNA viruses is very similar and that the cellular sequence flanking the integrated virus possesses, simultaneously, all the features postulated to be the molecular basis for chromosomal fragility.


Phagocytic killing of microorganisms by radical processes: consequences of the reaction of hydroxyl radicals with chloride yielding chlorine atoms.
Chloride anions and hydrogen peroxide serve as substrates for myeloperoxidase (MPO) in order to produce hypochlorous acid (HOCl) as one of the major killing agents of phagocytic leukocytes. Apart from this role of being a substrate for the MPO-reaction the chloride anion has been considered as unreactive and has not been implicated in radical reactions which contribute to the killing process. From the inherent reactivities of the pertinent radicals (as determined by pulse radiolysis experiments), the great abundance of chloride, and the most probable distribution of reactants within the phagosome, we deduce estimates for the average life-time and free diffusion path-length in this milieu and arrive at a model according to which chloride ions enter into radical chains and influence the killing of ingested bacteria to an extraordinarily high extent. We propose that hydroxyl radicals--despite some controversial arguments in the literature--may still be considered as important contributors to cell killing especially since we show that their reactions are made more effective by producing chlorine radicals in a cyclic process. We furthermore present arguments how the phagocyte may protect itself from harmful actions of HOCl and H2O2 after the superoxide-generating activity of NADPH oxidase is turned off.


Cardiac contractile reserve parameters are related to prognosis in septic shock.
Cardiac reserve could be defined as the spontaneous magnitude from basal to maximal cardiac power under stress conditions. The aim of this study was to evaluate the prognostic value of cardiac reserve parameters in resuscitated septic shock patients. Seventy patients with septic shock were included in a prospective and observational study. Prior to inclusion, patients were resuscitated to reach a mean arterial pressure of 65-75 mmHg with an euvolemic status. General, hemodynamic, and cardiac reserve-related parameters (cardiac index, double product, and cardiac power index) were collected at inclusion and at day 1. Seventy patients were included with 28-day mortality at 38.5%. Ten of the 70 patients died during the first day. In multivariate analysis, independent predictors of death were SAPS II ≥ 58 (OR: 3.36 [1.11-10.17]; P = 0.032), a high double product at inclusion (OR [95% IC]: 1.20 [1.00-1.45] per 10(3) mmHg · min; P = 0.047), and at day 1, a decrease in cardiac index (1.30 [1.08-1.56] per 0.5 L/min/m(2); P = 0.007) or cardiac power index (1.84 [1.18-2.87] per 0.1 W/m(2), P = 0.008). In the first 24 hours, parameters related to cardiac reserve, such as double product and cardiac index evolution, provide crucial and easy to achieve hemodynamic physiological information, which may impact the outcome.


Impact of harmonic scalpel on operative time during video-assisted thyroidectomy.
Minimally invasive video-assisted thyroidectomy (MIVAT) has been practiced in our department since 1998. It has some advantages over conventional surgery in terms of postoperative pain and cosmetic result. The aim of this study was to evaluate the use of the Harmonic scalpel (HS) on the performance of this procedure. Between October 1998 and January 2001, 116 patients underwent MIVAT. The HS was used for the last 26 operations. We compared this group of patients (HS-G) with a control group (C-G) of 26 patients who had undergone MIVAT before the introduction of the HS. The following parameters were considered: age, gender, preoperative diagnosis, size of the lesion, type of operation (lobectomy or total thyroidectomy), operative time, complication rate, and postoperative hospital stay. The two groups were well matched for age, gender, preoperative diagnosis, lesion size, and type of operation. The mean operative time was significantly reduced in the HS-G for both lobectomy (37.3 +/- 8.4 vs 49.4 +/- 18.0 min) and total thyroidectomy (53.8 +/- 16.3 vs 90.6 +/- 22.1 min). No differences were found for postoperative stay. One patient in the C-G experienced a transient recurrent nerve palsy. There were no other complications. This study showed that the utilization of the HS for MIVAT is safe and associated with a shorter operative time. A reduction of the rates for such complications such as hypoparathyroidism and recurrent nerve injuries was not possible to demonstrate in the present study. Much larger series are needed for further evaluation of this instrument.