Ezetimibe decreases serum oxidized cholesterol without impairing bile acid synthesis in Japanese hypercholesterolemic patients.
Cholesterol and diet-derived oxidized cholesterol are absorbed in the small intestine and eliminated by bile acids. We determined whether ezetimibe, a selective cholesterol absorption inhibitor, changes serum oxidized cholesterol levels. We measured levels of plant sterols, cholesterol precursors, and oxysterols by gas chromatography-mass spectrometry in 47 hypercholesterolemics and 32 controls. Twenty-four hypercholesterolemics received 10 mg ezetimibe/day for 4 weeks. Plant sterols were 30-42% higher in hypercholesterolemics than in controls and positively correlated with low-density lipoprotein-cholesterol (LDL-C). Ezetimibe decreased plant sterols by 21-53%, but did not change bile acid synthesis markers. 7β-hydroxycholesterol, a marker for non-enzymatic oxidation of cholesterol, was 66% higher in hypercholesterolemics than controls. Ezetimibe decreased 7β-hydroxycholesterol levels by 15% regardless of LDL-C reduction. Ezetimibe decreases serum oxidized cholesterol generated by non-enzymatic reactions without impairing bile acid synthesis. Ezetimibe may maintain cholesterol excretion into bile and alleviate the diet-derived oxidative burden.


Liquid-Liquid Extraction of Furfural from Water by Hydrophobic Deep Eutectic Solvents: Improvement of Density Function Theory Modeling with Experimental Validations.
This study outlines the methodology to model hydrophobic deep eutectic solvent (HDES) interactions to obtain computational results that accurately represent experimental results of furfural removal from water. Computational prediction with high accuracy of HDES behavior could elucidate hydrogen bond interaction in HDES. COSMOtherm modeling and experimental evaluation demonstrated that both decanoic and dodecanoic acid-based HDES can remove furfural from water even at very low concentrations of 0.1 mol %. The modeling methodology considered salts as independent cations, which were paired with the hydrogen bond donor (HBD) species. These resulted in computational predictions of liquid-liquid equilibrium (LLE) between tetra n-alkyl ammonium bromide salt-based HDES with >95% accuracy of experimental results. The COSMOtherm modeling methodology strengthens the understanding of HDES by considering intermolecular forces that affect electron density (σ) of the HDES components to determine the LLE of the HDES-aqueous system. This results in a deep eutectic phase that has a positive sigma potential (potentials, μ(σ), up to 0.1 kcal/mol Å2) at charge densities associated with hydrogen bonding (±0.0084 e/Å2). Though n-alkyl ammonium salts ranging from tetramethyl- to tetraoctylammonium bromide were considered in the computational model, only pentyl- and longer alkyl chains displayed hydrophobic behavior with less than 1% salt loss to the aqueous phase. However, there was still significant water uptake in the eutectic phase (final phase composition containing greater than 60 mol and 12% by mass) for the hydrophobic DES.


[Reconstructive surgery of aortic arch interruption in adults].
To evaluate surgical results in adults with aortic arch interruption. Seven patients with aortic arch interruption were operated. Two of them (28.6%) underwent aortic arch repair using allograft, 4 (57.21%) - distal arch and proximal descending aortic replacement, 1 (14.3%) - supra-coronary ascending aortic, aortic arch and proximal descending aortic replacement. All operations were performed under moderate hypothermia (25 °С), circulatory arrest with unilateral cerabral perfusion 8-10 ml/kg/min via innominate artery and pressure 69.6±14.7 mm Hg in arterial. Cardiopulmonary bypass (CPB) time was 242±36.1 min, aortic cross-clamping - 110.7±40.4 min, circulatory arrest - 58.6±17.9 min. There were no cases of renal insufficiency, vascular lesion of brain and spinal cord, cardiac events. Resternotomy for bleeding was performed in 1 (14.3%) case. Sufficient descending aortic lumen was achieved in 100% according to CT postoperatively. Peak descending aortic pressure gradient after repair with allograft was 29±1.4 mm Hg, after aortic replaement - 10±4.2 mm Hg. Postoperative and in-hospital 30-day mortality was absent. Reconstructive surgery for aortic arch interruption in adults is effective approach with good clinical and hemodynamic results.


MiR-429 increases the metastatic capability of HCC via regulating classic Wnt pathway rather than epithelial-mesenchymal transition.
Epigenetic modification of miR-429 can manipulate liver T-ICs via targeting the RBBP4/E2F1/Oct4 axis, which might be crucial for hepatocarcinogenesis. However, whether miR-429 plays a role in regulating metastasis of hepatocellular carcinoma is still unclear. Using quantitative methylation analysis and real-time PCR, we have identified the hypomethylated status and upregulation of miR-429 in portal vein metastasis samples in comparison with their matched primary tumor. The ectopic expression of miR-429 dramatically induced the expression of MMP2/7/9 and enhanced HCC migration and invasion in vitro and in vivo in an EMT-independent manner. Both bioinformatics and functional studies elucidated the direct regulation of miR-429 on the 3'UTR of the PTEN gene, which leads to the activation of PI3K/AKT signaling and the nuclear translocation of β-catenin, eventually. Conversely, the knockdown of miR-429 efficiently recovered the expression of PTEN and attenuated PI3K/AKT/β-catenin-mediated cell metastasis. Clinically, the higher expression of miR-429 and nucleus relocation of β-catenin were identified as the adverse prognosis factors for recurrence-free survival (RFS) and overall survival (OS). In summary, our results here defined miR-429 as a key inducer for HCC pathogenesis and metastasis with potential utility for tumor intervention.


The Financial Impact on Reimbursement of Moderately Hypofractionated Postoperative Radiation Therapy for Breast Cancer: An International Consortium Report.
Moderately hypofractionated breast irradiation has been evaluated in several prospective studies, resulting in wide acceptance of shorter treatment protocols for postoperative breast irradiation. Reimbursement for radiation therapy varies between private and public systems and between countries, impacting variably financial considerations in the use of hypofractionation. The aim of this study was to evaluate the financial impact of moderately hypofractionated breast irradiation by reimbursement system in different countries. The study was designed by an international group of radiation oncologists. A web-questionnaire was distributed to representatives from each country. The participants were asked to involve the financial consultant at their institution. Data from 13 countries from all populated continents were collected (Europe: Denmark, France, Italy, the Netherlands, Spain, UK; North America: Canada, USA; South America: Brazil; Africa: South Africa; Oceania: Australia; Asia: Israel, Taiwan). Clinicians and/or departments in most of the countries surveyed (77%) receive remuneration based on the number of fractions delivered to the patient. The financial loss per patient estimated resulting from applying moderately hypofractionated breast irradiation instead of conventional fractionation ranged from 5-10% to 30-40%, depending on the healthcare provider. Although a generalised adoption of moderately hypofractionated breast irradiation would allow for a considerable reduction in social and economic burden, the financial loss for the healthcare providers induced by fee-for-service remuneration may be a factor in the slow uptake of these regimens. Therefore, fee-for-service reimbursement may not be preferable for radiation oncology. We propose that an alternative system of remuneration, such as bundled payments based on stage and diagnosis, may provide more value for all stakeholders.


Description of longitudinal tumor evolution in a case of multiply relapsed clear cell sarcoma of the kidney.
Clear cell sarcoma of the kidney (CCSK) is the second most common pediatric renal tumor. A 2-year-old boy was diagnosed with CCSK, which relapsed four times until he yielded to the disease at the age of 7 years. To characterize the longitudinal genetic alterations occurring in the present case, we performed targeted-capture sequencing by pediatric solid tumors panel (381 genes) for longitudinally sampled tumors, including autopsy samples of metastasis. Internal tandem duplication of BCOR (BCOR-ITD) was the only truncal mutation, confirming the previously reported role of BCOR-ITD in CCSK. Acquisition of additional mutations along tumor relapses and detection of metastasis-specific mutations were reminiscent of the tumor progression and therapeutic resistance of this case, leading to clonal selection and a dismal fate.


Evaluation of prostatitis in autopsied prostates--is chronic inflammation more associated with benign prostatic hyperplasia or cancer?
Chronic inflammation is associated with prostate cancer and benign prostatic hyperplasia. However, the prevalence of chronic inflammation in malignant and benign glands has not been compared. We evaluated the association of inflammation, benign prostatic hyperplasia and cancer in autopsied prostates. We prospectively analyzed 167 autopsied prostates. Pathological analysis identified each focus of cancer, benign prostatic hyperplasia nodules and areas of acute or chronic inflammation. Any cancer focus or benign prostatic hyperplasia nodule involved directly with inflammation was recorded. The association of the prevalence of prostate cancer, benign prostatic hyperplasia and inflammation was statistically assessed. Inflammation was present in 113 (67.6%) of 167 cases. Chronic inflammation was identified in 88 (53%), acute inflammation in 6 (4%), and chronic inflammation and acute inflammation in 19 (11%) glands. In the majority of cases inflammation was present in the transitional zone. A total of 93 glands (56%) were involved with benign prostatic hyperplasia and 49 (29%) with cancer. Of the glands harboring benign prostatic hyperplasia 75% were also involved with chronic inflammation compared to only 50% of those without benign prostatic hyperplasia (p <0.01). Comparatively the glands with or without any evidence of cancer were similarly involved with chronic inflammation (55% vs 58%, p >0.1). Of the 27 glands involved with cancer and benign prostatic hyperplasia, chronic inflammation was more associated with benign prostatic hyperplasia than cancer (p = 0.006). Acute inflammation was not significantly associated with either benign prostatic hyperplasia or cancer. Chronic inflammation was a common finding in autopsied prostates. It appeared to be directly associated with the presence of benign prostatic hyperplasia but not with cancer.


Right ventricular failure in patients with left ventricular assist devices.
Right ventricular (RV) failure that develops following LVAD placement is an important and challenging complication that occurs in approximately 15-25% of LVAD patients. Thus, a thorough evaluation that identifies pre-operative clinical predictors of RV failure is crucial to aid in the appropriate treatment and prognostication. Following LVAD implant, three major physiologic changes invariably occur that will influence RV function: an increase in RV preload, a decrease in RV afterload, and an alteration in RV contractility. Management strategies exist to minimize the likelihood and severity of RV failure post-LVAD. Further studies are needed that also focus on intermediate and late post-LVAD RV failure.


Multiplexed Digital Detection of B-Cell Acute Lymphoblastic Leukemia Fusion Transcripts Using the NanoString nCounter System.
Chromosomal rearrangements resulting in fusion transcripts have been reported in precursor B-cell acute lymphoblastic leukemia (B-ALL). The identification of fusion events is crucial in the diagnosis of B-ALL. In this study, we used NanoString nCounter technology to design, validate, and evaluate a multiplex panel for the detection of B-ALL fusion transcripts. Fifty-one B-ALL fusion transcripts reported in children in the literature were included in the design of the NanoString panel. Twenty-six fusion transcripts were validated using 64 positive-control samples and 74 negative-control samples with 100% sensitivity and 99% specificity in comparison to RT-PCR. Our results support a potential role of NanoString's technology as a robust and cost-effective technique that could be used in the detection of fusion transcripts and implemented into the diagnostic algorithm of B-ALL.


Proteomic investigation and understanding on IgY purification and product development.
An increasing demand for the development of immunoglobin Y (IgY) illustrates the necessity of the component analysis in the process of conduction and quality control. This study investigated the proteomic changes in crude IgY extracts and purified IgY products obtained by sequential polyethylene glycol precipitation (PEG) of egg yolks followed by human mycoplasma protein-based affinity chromatography compared with intact egg yolks. After confirming the extraction efficiency and purity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, liquid chromatography tandem-mass spectrometry (LC-MS/MS) was performed with samples including fresh yolk, IgY extracted product and purified product. A total of 348 proteins were identified, with 36 proteins deleted and 209 newly detected proteins in the purified product compared to the intact egg yolk. The significantly decreased proteins mainly included phosvitin, albumin, and apolipoprotein B whereas the significantly increased proteins were mainly IgY-related proteins. GO analysis showed that the purified IgY product had ATPase activity and purine ribonucleoside triphosphate binding activity, and was mainly involved in purine and nucleic acid metabolism. This study will inevitably fasten the commercial application of IgY antibodies and is of greater significance for promotion, development and approval for new antibody derived drug products.


Withania somnifera: an Indian ginseng.
Withania somnifera, popularly known as Ashwagandha is widely considered as the Indian ginseng. In Ayurveda, it is classified as a rasayana (rejuvenation) and expected to promote physical and mental health, rejuvenate the body in debilitated conditions and increase longevity. Having wide range of activity, it is used to treat almost all disorders that affect the human health. The present review discusses the pharmacological basis of the use of W. somnifera in various central nervous system (CNS) disorders, particularly its indication in epilepsy, stress and neurodegenerative diseases such as Parkinson's and Alzheimer's disorders, tardive dyskinesia, cerebral ischemia, and even in the management of drug addiction.


Antibacterial immunity and its modeling in experimental tumor tetanus and wound tetanus of the mouse.
The experimental and theoretical analysis of the tumor-tetanus phenomenon has provided us with new insights into the pathogenesis of tetanus infection. Our theoretical model of clostridial propagation in the proliferating tissue is based upon the principle of mitosis-controlled rod division (hit and cloning model). It has lent itself to the description of early growth stages of the clostridial rod population in our experiments of tumor tetanus and of wound tetanus of the mouse. However, the later course of the tetanus lethality curves under antitoxin protection, about a week following injection of the tumor cell-spore or CaCl2-spore suspensions, reveals a pronounced delay in clostridial propagation. Based on our model we can explain this process by a humoral immune reaction directed against the clostridial rods taking into account the variability of elimination of the heterologous tetanus antitoxin applied. The experimental results are in good agreement with those obtained by computer simulation. The theoretical knowledge resulting from these studies can be used for the interpretation of the serodiagnostic tumor test with apathogenic clostridia as well as for the quantitative assessment of the malignancy of neoplastic growth.


Increasing the efficiency and precision of prime editing with guide RNA pairs.
The recently reported prime editor (PE) can produce all types of base substitution, insertion and deletion, greatly expanding the scope of genome editing. However, improving the editing efficiency and precision of PE represents a major challenge. Here, we report an approach termed the homologous 3' extension mediated prime editor (HOPE). HOPE uses paired prime editing guide RNAs (pegRNAs) encoding the same edits in both sense and antisense DNA strands to achieve high editing efficiency in human embryonic kidney 293T cells as well as mismatch repair-deficient human colorectal carcinoma 116 cells. In addition, we found that HOPE shows greatly improved product purity compared to the original PE3 system. We envision that this enhanced tool could broaden both fundamental research and therapeutic applications of prime editing.


Serological cross-reaction and cross-protection in guinea pigs infected with Rickettsia rickettsii and Rickettsia montana.
Antisera produced in guinea pigs inoculated with Rickettsia rickettsii or Rickettsia montana were cross-reactive but sufficiently specific to identify the primary infecting agent. Guinea pigs immunized with R. montana were protected from fatal infection with R. rickettsii, although a few (25%) developed mild fever of short duration.


Malunion of a femoral fracture mimicking osteomyelitis in three phase bone imaging.
A case of greatly increased blood flow in the region of a fracture with malunion of the left femur, both in the flow and immediate blood pool studies during three phase bone imaging, is presented. The sluggish left femoral artery flow resulted from the greatly increased regional perfusion and is similar to the findings in acute osteomyelitis. The sluggish left femoral artery flow and greatly increased regional perfusion of the site is probably best explained as a regional "neurovascular flush" resulting from the pain caused by the malunion of the fracture and/or hyperemia in the area of the malunion responding to inflammation.


Nutritional and pharmacological potentials of orphan legumes: Subfamily faboideae.
Legumes are a major food crop in many developing nations. However, orphan or underutilized legumes are domesticated legumes that have valuable properties but are less significant than main legumes due to use and supply restrictions. Compared to other major legumes, they are better suited to harsh soil and climate conditions, and their great tolerance to abiotic environmental circumstances like drought can help to lessen the strains brought on by climate change. Despite this, their economic significance in international markets is relatively minimal. This article is aimed at carrying out a comprehensive review of the nutritional and pharmacological benefits of orphan legumes from eight genera in the sub-family Faboidea, namely Psophocarpus Neck. ex DC., Tylosema (Schweinf.) Torre Hillc., Vigna Savi., Vicia L., Baphia Afzel. ex G. Lodd., Mucuna Adans, Indigofera L. and Macrotyloma (Wight & Arn.) Verdc, and the phytoconstituents that have been isolated and characterized from these plants. A literature search was conducted using PubMed, Google Scholar, and Science Direct for articles that have previously reported the relevance of underutilized legumes. The International Union for Conservation of Nature (IUCN) red list of threatened species was also conducted for the status of the species. References were scrutinized and citation searches were performed on the study. The review showed that many underutilized legumes have a lot of untapped potential in terms of their nutritional and pharmacological activities. The phytoconstituents from plants in the subfamily Faboideae could serve as lead compounds for drug discovery for the treatment of a variety of disorders, indicating the need to explore these plant species.


Racial differences in distribution of fatty acids in prostate cancer and benign prostatic tissues.
It remains controversial whether and which fatty acids are different between prostate cancer (PCa) and benign prostatic tissues (BPT) in association with occurrence, progression and racial disparity between African American (AA) and Caucasian American (CA) populations. Total fatty acids (TFA) and free fatty acid (FFA) were determined on fresh frozen prostatic tissues including 26 PCa and 21 BPT from AA and CA patients by Gas chromatography with flame ionization detection (GC-FID) and Electrospray Ionization Mass Spectrometry (ESI-MS), respectively. In all studied population, TFA in 8 out of 16 individual species, in total and in groups of saturated total fatty acid (STFA), mono-unsaturated total fatty acid (MUTFA), poly-unsaturated total fatty acid (PUTFA) and n-6 TFA were significantly higher in PCa than in BPT; FFA in 4 out of 10 individual species, in total and in groups of MUFFA, PUFFA, n-6 FFA and n-3 FFA were significantly higher in PCa than in BPT. The concentrations of most fatty acid parameters correlated with Gleason's grade and clinical stage of PCa. As compared with CA men, AA men had higher concentrations of TFA, especially TFA with chains of 14-18 carbons than in BPT, and lower concentrations of TFA in PCa. Increasing in prostatic fatty acids in the form of TFA and FFA correlated to occurrence, progression and racial disparity of PCa.


Replacing the Rhamnose-Xylose Moiety of QS-21 with Simpler Terminal Disaccharide Units Attenuates Adjuvant Activity in Truncated Saponin Variants.
Adjuvants are key immunostimulatory components in vaccine formulations, which improve the immune response to the co-administered antigen. The saponin natural product QS-21 is one of the most promising immunoadjuvants in the development of vaccines against cancer and infectious diseases but suffers from limitations that have hampered its widespread human use. Previous structure-activity relationship studies have identified simplified saponin variants with truncated carbohydrate chains, but have not focused on the influence of the linear oligosaccharide domain of QS-21 in adjuvant activity. Herein, an expeditious 15-step synthesis of new linear trisaccharide variants of simplified QS-21-derived adjuvants is reported, in which the complex terminal xylose-rhamnose moiety has been replaced with commercially available, simpler lactose and cellobiose disaccharides in a β-anomeric configuration. In vivo immunological evaluation of the synthetic saponins showed attenuated antibody responses, highlighting the negative impact of such carbohydrate modifications on adjuvant activity, which could be associated with higher saponin conformational flexibility.


Congenital leptin and leptin receptor deficiencies in nine new families: identification of six novel variants and review of literature.
Early childhood obesity is a real public health problem worldwide. Identifying the etiologies, especially treatable and preventable causes, can direct health professionals toward proper management. Measurement of serum leptin levels is helpful in the diagnosis of congenital leptin and leptin receptor deficiencies which are considered important rare causes of early childhood obesity. The main aim of this study was to investigate the frequency of LEP, LEPR, and MC4R gene variants among a cohort of Egyptian patients with severe early onset obesity. The current cross-sectional study included 30 children who developed obesity during the first year of life with BMI > 2SD (for age and sex). The studied patients were subjected to full medical history taking, anthropometric measurements, serum leptin and insulin assays, and genetic testing of LEP, LEPR and MC4R. Disease causing variants in LEP and LEPR were identified in 10/30 patients with a detection rate of 30%. Eight different homozygous variants (two pathogenic, three likely pathogenic, and three variants of uncertain significant) were identified in the two genes, including six previously unreported LEPR variants. Of them, a new frameshift variant in LEPR gene (c.1045delT, p.S349Lfs*22) was recurrent in two unrelated families and seems to have a founder effect in our population. In conclusion, we reported ten new patients with leptin and leptin receptor deficiencies and identified six novel LEPR variants expanding the mutational spectrum of this rare disorder. Furthermore, the diagnosis of these patients helped us in genetic counseling and patients' managements specially with the availability of drugs for LEP and LEPR deficiencies.


Social-olfactory experience and initiation of copulation in the virgin male rat.
Two experiments examined the role of olfactory sensation for initiation of normal copulatory behavior of mature male rats. Experiment 1 compared copulatory performance of peripherally anosmic social isolates with that of intact isolate controls. The results revealed significantly lower mounting, intromission, and ejaculation frequencies of the anosmic group and suggested that nonolfactory cues attain significance via an associative-learning process. Experiment 2 compared three social isolate groups of mature males with varying sexual experience prior to anosmia. Four 1-hr tests were conducted at 5-day intervals. The results indicated comparable copulatory performance of the experienced groups and absence of copulation by the majority of the nonexperienced group. With a 12-day continuous exposure to intact females, all noncopulators eventually impregnated. The results are discussed with reference to the requirement of social experience for initiation of normal sexual performance in the male rat.


Conducting Psychological Intervention Research in the Information Age: Reconsidering the "State of the Field".
Enthusiasm for technology in mental health has evolved as a function of its promise to increase the reach and impact of services, particularly for traditionally at-risk and underserved groups. Preliminary findings suggest that technology-enhanced interventions indeed hold promise for increasing engagement in and outcomes of evidence-based treatment approaches. The time- and resourceintensive nature of traditional randomized control trials, however, may be even more of a challenge for further advancement in this area, given the rapid innovation of consumer driven new product development. Accordingly, this review aims to summarize how a broader range of scientific designs and analyses may be necessary in order to further advance and optimize the reach and impact of technology-enhanced psychological practice. Examples of various approaches are provided and recommendations are provided for future work in this area.


Stimulation of cells derived from nifedipine-induced gingival overgrowth with Porphyromonas gingivalis, lipopolysaccharide, and interleukin-1beta.
The purpose of this study was to clarify the main contributory factor of nifedipine-induced gingival overgrowth either by Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) or interleukin-1beta (IL-1beta). Human gingival fibroblasts from healthy tissues and nifedipine-induced gingival overgrowth tissues were stimulated with nifedipine, IL-1beta, Escherichia coli lipopolysaccharide (Ec-LPS), and Pg-LPS, and the gene expressions were analyzed by RT-PCR. Analysis of the data showed no strong evidence of a synergistic effect of nifedipine and Pg-LPS on IL-6, connective tissue growth factor (CTGF), and type 1 collagen gene expression of either healthy cells or nifedipine-induced gingival overgrowth cells. Among the three stimulants--IL-1beta, Pg-LPS, and Ec-LPS--androgen receptor and IL-6 gene expressions in both the healthy and nifedipine-induced gingival overgrowth groups were strongly up-regulated by the presence of IL-1beta only. Furthermore, the responses to IL-1beta in the nifedipine-induced gingival overgrowth group were stronger than those of the healthy group. It can be concluded that IL-1beta is an important mediator responsible for the higher IL-6 and androgen receptor expression of nifedipine-induced gingival overgrowth cells.


A universal algorithm for fast and automated charge state deconvolution of electrospray mass-to-charge ratio spectra.
This article describes a new algorithm for charge state determination and deconvolution of electrospray ionization (ESI) mass-to-charge ratio spectra. The algorithm (ZSCORE) is based on a charge scoring scheme that incorporates all above-threshold members of a family of charge states or isotopic components, and deconvolves both low- and high-resolution mass-to-charge ratio spectra, with or without a peak list (stick plot). A scoring weight factor, log (I/I0), in which I is the signal magnitude at a calculated mass-to-charge ratio, and I0 is the signal threshold near that mass-to-charge ratio, was used in most cases. For high-resolution mass-to-charge ratio spectra in which all isotopic peaks are resolved, the algorithm can deconvolve overlapped isotopic multiplets of the same or different charge state. Compared to other deconvolution techniques, the algorithm is robust, rapid, and fully automated (i.e., no user input during the deconvolution process). It eliminates artifact peaks without introducing peak distortions. Its performance is demonstrated for experimental ESI Fourier transform ion cyclotron resonance mass-to-charge ratio spectra (both low and high resolution). Charge state deconvolution to yield a "zero-charge" mass spectrum should prove particularly useful for interpreting spectra of complex mixtures, identifying contaminants, noncovalent adducts, fragments (N-terminal, C-terminal, internal), and chemical modifications of electrosprayed biomacromolecules.


Access to the encephalic ventricles in the Friesian cow: a new surgical approach.
The surgical procedure described in this communication consists in the catheterisation of the ventricular recess within the olfactory bulb. It lies 28 +/- 5 mm under the frontal skin, in a retro-orbital position, and 15 +/- 2 mm from the median plane. Its access is easy in experimental conditions.


Cavidine Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via NF-κB Signaling Pathway in vivo and in vitro.
Acute lung injury (ALI) is characterized by widespread inflammation in the lungs and alveolar-capillary destruction, causing high morbidity and mortality. Cavidine, isolated from Corydalis impatiens, have been exhibited to have potent anti-inflammatory effects in previous studies. The purpose of this study was to evaluate the protective effect of cavidine on lipopolysaccharide (LPS)-induced ALI and to enunciate the underlying in vivo and in vitro mechanisms. Mice were intraperitoneally administrated with cavidine (1, 3, or 10 mg/kg) at 1 and 12 h, prior to the induction of ALI by intranasal administration of LPS (30 mg/kg). Blood samples, lung tissues, and bronchoalveolar lavage fluid (BALF) were harvested after LPS challenge. Furthermore, we used LPS-induced lung epithelial cells A549 to examine the mechanism of cavidine to lung injury. The results showed that pretreatment with cavidine significantly decreased lung wet-to-dry weight (W/D) ratio, reduced pro-inflammatory cytokine levels including TNF-α and IL-6 in BALF and serum from LPS-stimulated mice, and attenuated lung histopathological changes. In addition, western blot results showed that cavidine inhibited the phosphorylation of nuclear factor-kappaB (NF-κB) p65 and IκBα induced by LPS. In conclusion, our results demonstrate that cavidine protects against LPS-induced acute lung injury in mice via inhibiting of pro-inflammatory cytokine TNF-α and IL-6 production and NF-κB signaling pathway activation. Taken together, cavidine may be useful for the prevention and treatment of pulmonary inflammatory diseases, such as ALI.


'Sabbath' electric plate burn: a ritual hazard.
This report describes the burns caused by an electric hot plate which is used by orthodox Jews for keeping food and liquids warm during the Sabbath (Saturday). An illustrative case is presented and the preventable aspects of this particular burn are discussed.


Delayed gametogenesis of Mya arenaria in the Saguenay fjord (Canada): a consequence of endocrine disruptors?
The Saguenay fjord located in Canada on the north coast of the Saint-Lawrence Estuary, is well known for its multiple contaminations following a linear distribution upstream to downstream. Mya arenaria is well established in the fjord and potentially exposed to persistent sediment contamination as an endobenthic bivalve. From May to October 1997, clams energy storage and utilization in the gonad was shown to be closely linked with reproduction. Wherever the sampling site location in the fjord, a seasonal pattern is evident for lipid and glycogen levels in the gonad, this, reflecting the vitellogenic process. Nevertheless, in comparison with energy status and gametogenesis of clams collected on the north coast of the Saint-Lawrence Estuary, clams located in the fjord have to face limited nutritive conditions resulting in a single and shorter reproductive period. Although environmental factors could explain differences in physiological condition and reproductive status observed between clams from the fjord and the estuary, our results can discriminate clams from the upper part of the fjord, according to a delayed gametogenesis, concomitant with significant higher gonad glycogen concentrations observed in June 1996 and 1997. A persistent dysfunction of a vitellogenic process is suspected to be due to the exposure to anti-estrogenic contaminants.


The Effect of Visual Hindsight Bias on Radiologist Perception.
To measure the effect of visual hindsight bias on radiologists' perception during chest radiograph pulmonary nodule detection. This was a prospective multi-observer study to assess the effect of hindsight bias on radiologists' perception. Sixteen radiologists were asked to interpret 15 postero-anterior chest images containing a solitary lung nodule each consisting of 25 incremental levels of blur. Participants were requested initially to detect the nodule by reducing the blur of the images (foresight). They were then asked to increase the blur until the identified nodule was undetectable (hindsight). Participants then repeated the experiment, after being informed of the potential effects of hindsight bias and asked to counteract these effects. Participants were divided into two groups (experienced and less experienced) and the nodules were given different conspicuity ratings to determine the effect of expertise and task difficulty. Eye tracking technology was also utilised to capture visual search. Wilcoxon analysis demonstrated significant differences between foresight and hindsight values of the radiologists (p = 0.02). However, after being informed of hindsight bias, these differences were no longer significant (p = 0.97). Friedman analysis also determined overall significance in the hindsight ratios between nodule conspicuities for both phases (phase 1: p = 0.02; phase 2: p = 0.02). There was no significance difference between the experienced and less experienced groups. This study demonstrated that radiologists exhibit hindsight bias but appeared to be able to compensate for this phenomenon once its effects were considered. Also, visual hindsight bias appears to be affected by task difficulty with a greater effect occurring with less conspicuous nodules.


Hypotaurine disproportionation reaction: identification of products.
Hypotaurine, concentrated under reduced pressure in HCl solution, partially (30-40%) degrades into taurine (about 30%), 2-aminoethyl-2-aminoethanethiolsulfonate (about 10%) and ethanolamine. The degradation products were identified using LC/APCI-MS, NMR, amino acid analysis and various chromatographies. The identities were confirmed by comparing the HPLS, MS and NMR characteristics of authentic compounds. One of the degradation processes during concentration of HCl solution of hypotaurine is therefore a disproportionation reaction which can interfere with the experimental results, when studying hypotaurine in biological systems.


Arsenic exposure increased expression of HOTAIR and LincRNA-p21 in vivo and vitro.
Arsenic is an environmental contaminant, its multiple effects on human tend to increase the rate of disease, cancer and other health problems. Some of long non-coding RNAs (lncRNAs) can be induced in major cellular processes such as necrosis, proliferation, and mutation. While the toxicity of arsenic is well established, the association between arsenic exposure and long non-coding RNAs has not been studied enough. This study investigated the association between arsenic and the expression of HOTAIR and LincRNA-p21 in vivo and vitro. In epidemiological studies, the expression of HOTAIR and LincRNA-p21 was increased after long-term arsenic exposure. HOTAIR and LincRNA-p21 expression were positively linked to monomethylarsenic acid (MMA), dimethylarsenic acid (DMA), inorganic arsenic (iAs), total arsenic (tAs), and MMA% and negatively linked to secondary methylation index (SMI). In A549 cells, arsenic exposure resulted in enhanced HOTAIR and LincRNA-p21 expression dose-dependently. The expression of HOTAIR was considerably high in the presence of NaAsO2 and MMA but showed no difference in DMA compared with control group. And LincRNA-p21 expression was increased in the presence of NaAsO2, MMA, and DMA. The expression of HOTAIR and LincRNA-p21 induced by iAs was much higher than that induced by MMA and DMA. Compared with the control group, treatment of A549 cells with NaAsO2/S-adenosylmethionine (SAM) and NaAsO2/glutathione (GSH) combination increased HOTAIR and LincRNA-p21 expression. The expression of LincRNA-p21 in combination of NaAsO2/GSH was significantly decreased compared with NaAsO2 alone. Besides, in the presence of arsenic, both of HOTAIR and LincRNA-p21 were upregulated significantly when P53 was knocked down. We revealed that inorganic arsenic, its methylated metabolites, and arsenic metabolism efficiency affect the expression of HOTAIR and LincRNA-p21.


Studies in the biodegradation of 5 PAHs (phenanthrene, pyrene, fluoranthene, chrysene und benzo(a)pyrene) in the presence of rooted poplar cuttings.
Cuttings of Populus nigra L. cv. Loenen were cultivated in sand treated with one of the following PAHs: phenanthrene (Phen), fluoranthene (Flt), pyrene (Pyr), chrysene (Chr) and benzo[a]pyrene (BaP). The PAHs were applied at varying levels of concentration to each test series. After 6 weeks the concentration and the distribution of the PAHs in the substrate of the various sets of tests were compared with the concentration in the substrate of the control. Additionally the substrate and the plant roots were tested for evidence of degradation products of PAHs. The results revealed that the levels of concentration of Phen and Pyr detected in the substrate surrounding the roots was in some cases significantly lower than in the corresponding section of substrate in the unplanted set (= control). This phenomenon did not occur for Flt and BaP and in the case of Chr only in those substrates, which had been treated with the highest levels of concentration. As the presence of lesser amounts of Phen and Pyr in the plant pots cannot only be attributed to their accumulation and metabolism in the roots, it is fair to assume that the chemical transformation of these three PAHs took place outside the roots. The set of tests treated with Phen revealed the presence of 2- or 3-hydroxy-Phen (main components), a hydroxy-methoxy-Phen, 9,10-Phenanthrenequinone and one unidentified compound in metabolite form. Altogether eleven metabolites of Pyr were identified in the root extracts, which can be divided into three groups: 1-Hydroxy-Pyr and derivatives, dihydroxy-Pyr and derivatives and ring fission products (4-Hydroxy-Pyr and a derivative of the 4-Phen-carbonic acid). However, the metabolite mass detected for Phen and Pyr represents only an insignificant percentage in comparison with the lesser amounts of PAHs observed in the planted set of tests. This indicates that the three PAHs were reduced to lower molecular compounds, which are methodically impossible to record, and subsequently translocated to other parts of the plant and integrated into the biomass. Although no lesser amount for Flt and BaP was found in the plant pots, 1-Hydroxy-Flt, an unidentified compound of Flt and 1-Methoxy-BaP were detected. These are presumably end products which were enhanced in the roots. It was not possible to identify any transformation products of Chr. It can be assumed that the majority of metabolites were not synthesised in the roots but are a result of microbial degradation in the rhizosphere. The test plants improved the conditions for the biotransformation of Phen and Pyr significantly and accumulated Flt, Pyr, Chr and BaP in their roots. It can therefore be concluded that the use of plants in the bioremediation of contaminated soils is a promising option.


Temperature and nucleotide dependence of calcium release by myo-inositol 1,4,5-trisphosphate in cultured vascular smooth muscle cells.
Inositol 1,4,5-trisphosphate (IP3) rapidly increased 45Ca2+ efflux from a nonmitochondrial organelle in cultured vascular smooth muscle cells that were permeabilized with saponin. A nucleotide, preferably ATP, was essential for IP3-evoked 45Ca2+ release. Two nonhydrolyzable ATP analogues satisfied the nucleotide requirement for IP3-evoked 45Ca2+ release. IP3 strongly stimulated 45Ca2+ efflux at low temperatures (1 to 15 degrees C). Decreasing the temperature from 37 to 4 degrees C inhibited the rate of IP3-stimulated efflux by only about 33%. The failure of such low temperatures to strongly inhibit IP3-induced 45Ca2+ efflux suggests that IP3 activated a Ca2+ channel, rather than a carrier, by a ligand-binding, rather than a metabolic, reaction.


The myofibroblast markers α-SM actin and β-actin are differentially expressed in 2 and 3-D culture models of fibrotic and normal skin.
To characterize the differences between fibrotic myofibroblasts and normal fibroblasts, we studied two differentiation markers: α-smooth muscle (SM) actin, a specific marker of myofibroblast differentiation, and β-actin, which is overexpressed in the fibrotic tissue. Experiments were performed on fibroblasts isolated from normal pig skin and on subcutaneous myofibroblasts isolated from pig radiation-induced fibrosis. Three culture models were used: cells in monolayers, equivalent dermis, consisting of fibroblasts embedded into a matrix composed of type I collagen, and in vitro reconstituted skin, in which the matrix and containing life fibroblasts were overlaid with keratinocytes. Samples were studied using immunofluorescence and western-blotting. In monolayers cultures, both fibrosis and normal cells expressed α-SM actin. Furthermore, similar amounts of β-actin protein were found. In these conditions, the resulting alterations in the phenotypes of cells made comparison of cultured fibrotic and normal cells irrelevant. Under the two 3-D culture models, normal fibroblasts no longer expressed α-SM actin. They expressed β-actin at the basal level. Moreover, the fibrotic myofibroblasts in both 3-D models retained their differentiation features, expressing α-SM actin and overexpressing β-actin. We found that this normalization was mainly related to the genomic programmation acquired by the cells in the tissue. Cellular motility and microenvironment were also involved, whereas cellular proliferation was not a major factor. Consequently, both three-dimensional models allowed the study of radiation-induced fibrosis in vitro, provided good extrapolations to in vivo conditions and avoided certain of culture artefacts.


Biosensor for on-line measurement of bovine progesterone during milking.
Reproductive management is a major financial concern of the dairy industry, with missed estrus detection a main cause of lost income. A biosensor was developed for on-line measurement of progesterone in bovine milk and detection of estrus. The biosensor used an enzyme immunoassay format for molecular recognition, which was developed to run in approximately eight minutes. The sensor was designed to operate on-line in a dairy parlor using microinjection pumps and valves for fluid transport, fiber optics and photodiodes for light measurement, and a control computer for sequencing. Calibration showed a dynamic response between 0.1 and 5 ng/ml progesterone in milk. The reusability of the test well was evaluated. Thiocyanate (0.5 M, pH 5.1) quickly regenerated the antibody surface while maintaining antibody activity for 15-20 cycles, but noise from the residual enzyme limited reusability.


Characterisation of tumour blood flow using a 'tissue-isolated' preparation.
Tumour blood flow was characterised in a 'tissue-isolated' rat tumour model, in which the vascular supply is derived from a single artery and vein. Tumours were perfused in situ and blood flow was calculated from simultaneous measurement of (1) venous outflow from the tumour and (2) uptake into the tumour of radiolabelled iodo-antipyrine (IAP). Comparison of results from the two measurements enabled assessment of the amount of blood 'shunted' through the tumours with minimal exchange between blood and tissue. Kinetics of IAP uptake were also used to determine the apparent volume of distribution (VDapp) for the tracer and the equilibrium tissue-blood partition coefficient (lambda). lambda was also measured by in vitro techniques and checks were made for binding and metabolism of IAP using high-pressure liquid chromatography. VDapp and lambda were used to calculate the perfused fraction (alpha) of the tumours. Tumour blood flow, as measured by IAP (TBFIAP), was 94.8 +/- 4.4% of the blood flow as measured by venous outflow, indicating only a small amount of non-exchanging flow. This level of shunting is lower than some previous estimates in which the percentage tumour entrapment of microspheres was used. The unperfused fraction ranged from 0 to 20% of the tumour volume in the majority of tumours. This could be due to tumour necrosis and/or acutely ischaemic tumour regions. For practical purposes, measurement of the total venous outflow of tumours is a reasonable measure of exchangeable tumour blood flow in this system and allows for on-line measurements. Tracer methods can be used to obtain additional information on the distribution of blood flow within tumours.


Combination chemotherapy following adrenal suppression in androgen- independent prostate cancer.
Recent trials with modern chemotherapy have demonstrated activity in androgen-independent prostate cancer, but all focused on patients with progression following androgen suppression or antiandrogen withdrawal. Limited data are available on the activity of chemotherapy in androgen-independent, hormone-refractory (progressing following adrenal suppression) prostate cancer. We evaluated the activity of estramustine combined with vinblastine in this subset of androgen-independent prostate cancer. From January 1995 until April 1999, 19 patients with hormone-refractory prostate cancer received estramustine 140 mg p.o., three times daily along with weekly vinblastine 5 mg/m(2). A decrease in prostate-specific antigen of 50% or more was noted in 12 patients (63.1%, 95% CI 38.3-83.7%). The median decrease in prostate-specific antigen was 71.2% (range 50.5-85.2%). None of the 7 patients with measurable soft-tissue disease showed an objective response. The median survival from onset of chemotherapy was 6 (range 1.4-27.7) months and from initiation of adrenal suppression 16.9 (range 3.8-40. 5) months. The combination of estramustine and vinblastine is capable of inducing activity in androgen-independent prostate cancer progressing after adrenal suppression. In our small sample, the survival rate was low, and we obtained no response in soft-tissue sites. Future prospective trials are needed to determine the benefit of sequential versus simultaneous incorporation of adrenal suppression with chemotherapy in the management of androgen-independent prostate cancer.


Double-stranded RNA stimulates chemokine expression in microglia through vacuolar pH-dependent activation of intracellular signaling pathways.
During neurotropic virus infection, microglia act as a source of chemokines, thereby regulating the recruitment of peripheral leukocytes and the multicellular immune response within the CNS. Herein, we present a comprehensive study on the chemokine production by microglia in response to double-stranded RNA (dsRNA), a conserved molecular pattern of virus infection. Transcriptional analyses of chemokine genes revealed that dsRNA strongly induces the expression of CXC chemokine ligand 10 (CXCL10) and CC chemokine ligand 5 (CCL5) in microglia. We also observed that the dsRNA stimulation triggered the activation of signaling pathways mediated by nuclear factor kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPK), including extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK). The microglial CXCL10 response to dsRNA was induced via NF-kappaB, p38, and JNK pathways, whereas the dsRNA-induced CCL5 production was dependent on JNK, but not on the other signal-transducing molecules tested. In addition, the acidic environment of intracellular vesicles was required for the activation of cellular signaling in response to dsRNA. Taken together, these results suggest that the recognition of dsRNA structure selectively induces the CXCL10 and CCL5 responses in microglia through vacuolar pH-dependent activation of NF-kappaB and MAPK signaling pathways.


Phytoremediation and phytosensing of chemical contaminant, toluene: identification of the required target genes.
As an industrial chemical produced worldwide in high volumes, toluene is commonly detected in ambient air and water. It can combine with oxygen and form compounds that are harmful to humans. In recent years, phytoremediation has been increasingly applied to repair the environmental damage caused by pollutants. However, insufficient knowledge is available regarding the response of plants to toluene. To detect the potential genes in plants that are related to the sensing mechanism and metabolism of toluene, a microarray analysis has been conducted on Arabidopsis thaliana seedlings grown on toluene-containing media. Following the validation of data and the application of appropriate selection criteria, the results show a coordinated induction and suppression of 202 and 67 toluene-responsive genes, respectively. Within the functional class "metabolism", the genes encoding detoxification proteins represent the most strongly up-regulated group. These include genes encoding cytochrome P450s, glucosyl transferases, and transporters. Subsequently, the toluene-induced genes of Arabidopsis are analyzed in detail.


Prognostic value of positive surgical margins after resection of cholangiocarcinoma. Experience at a high-volume hospital center specializing in hepatopancreatobiliary surgery.
Cholangiocarcinoma accounts for 3% of gastrointestinal tumors and is the second most frequent hepatic neoplasia after hepatocellular carcinoma. The primary aim was to evaluate the median disease-free period and survival in patients with cholangiocarcinoma diagnosis through the comparison of R0 and R1 resection margins. A retrospective analysis was conducted on 36 patients that underwent some type of surgical resection due to cholangiocarcinoma diagnosis, within the time frame of 2000-2017, at a center specializing in hepatopancreatobiliary surgery. Population, preoperative, and oncologic variables were included. The IBM Statistical Package for the Social Sciences for Mac, version 16.0, software (IBM SPSS Inc., Chicago, IL, USA) was employed. Thirty-one patients underwent hepatectomy, the Whipple procedure, or bypass surgery, depending on tumor location. The statistical significance of survival between patients with positive margins and those with negative margins was evaluated through the Mann-Whitney U test, with a P<.05 as the reference value. No statistically significant difference was found. The overall morbidity rate was 58.06% (n=18) and the mortality rate was 12.9% (n=4). No statistically significant difference in relation to the incidence of disease recurrence or general survival resulted from the comparison of microscopically positive surgical margins (R1) and negative surgical margins (R0). There was also no correlation between preoperative CA 19-9 levels and disease prognosis.


Pretreatment of sperm with human follicular fluid for borderline male infertility.
To test the usefulness of human follicular fluid (FF) in treating male infertility, we incubated washed sperm specimens from 31 couples undergoing intrauterine insemination (IUI), for male and/or unexplained infertility, with either FF or Ham's F-10 medium (Gibco, Grand Island, NY), in alternating cycles in a randomized manner. Semen specimens from 28 men were incubated with either medium or FF. Incubations with FF have increased sperm penetration assay (SPA) scores from 24.8 +/- 17.3 to 34.3 +/- 13.6 (P less than 0.01). Incubation with heat-inactivized FF also has increased SPA scores, although to a lesser extent than noninactivized FF. Seventeen pregnancies occurred in the 31 couples treated by IUI (54.8%), 16 of them in FF-treated cycles (51.6%) and one in "control" IUI cycles (3.2%, P less than 0.01). All pregnancies occurred within four treatment cycles. Thus, IUI after sperm wash and preincubation with FF may be suggested for four to six cycles to couples with male factor and/or unexplained infertility who are reluctant to resort to artificial insemination by donor or adoption, before attempting the more costly and complex in vitro fertilization-embryo transfer procedure.


The vascularization of the human flexor pollicis longus tendon.
The vascularization of the human flexor pollicis longus tendon was outlined by the use of microangiographic techniques, applied on freshly amputated arms. At the insertion of the tendon there was regularly a very well developed vinculum brevis, often extending proximally to the middle of the base phalanx of the thumb. Proximally to the metacarpo phalangeal joint there was a mesotenon of various shape, originating from the volar-ulnar (non-friction) side of the synovial tendon sheath. There seemed to exist a non-interrupted intrinsic longitudinal vascular system in the tendon, and the vessels were located in those parts of the tendon which are not subjected to friction.


Are microproerythroblasts in human bone marrow real or artefacts? A cytochemical note.
Early erythroid precursors were studied in human bone marrow smears to provide more information on small proerythroblasts--"microproerythroblasts"--using a silver reaction to demonstrate silver stained nucleolar organizer regions (AgNORs) and light microscopic densitometry of large irregularly shaped nucleoli and cytoplasm stained for RNA. No significant differences were found for the density of such nucleoli and basophilic cytoplasm between characteristic large proerythroblasts with a nuclear diameter larger that 9 microm (K2 and K1 erythroblasts) and small proerythroblasts--"microproerythroblasts" representing a subpopulation of K1/2 erythroblasts (early basophilic erythroblasts), which are characterized by a smaller nuclear diameter. In addition, large irregularly shaped nucleoli of "microproerythroblasts" possessed numerous silver stained particles representing AgNORs similar to those of large proerythroblasts. The number of AgNORs in "microproerythroblasts" was slightly, but significantly, smaller than that in large characteristic proerythroblasts.


[Gas composition and acid-base equilibrium of blood of patients operated on under conditions of epidural anesthesia].
The results of the studies on the gas composition and acid-base equilibrium of the blood in patients operated upon under epidural anesthesia have proved the rise of venous hyperoxia and the drop of the gas utilization percentage both in anesthetized and non-anesthetized regions. At the level of the whole organism, however, no essential changes of oxygen metabolism are noted.


The paradigm shift towards online learning during Covid-19 pandemic: an assessment of the attitudes on the learning practices among University of Zambia pharmacy students.
The nexus between higher education and digital technology has been extensively studied in the past and recently during the COVID-19 pandemic. This study aims to ascertain pharmacy students' attitudes towards using online learning during COVID-19. This cross-sectional study assessed the University of Zambia's (UNZA) pharmacy students' adaptive characteristics, such as attitude, perception, and barriers to online learning during the COVID-19 pandemic. Data from a survey of N = 240 were collected using a self-administered, validated questionnaire along with a standard tool. Findings were statistically analysed using STATA version 15.1. Of the 240 respondents, 150 (62%) had a negative attitude towards online learning. Further, 141 (58.3%) of the respondents find online learning less effective than traditional face-to-face learning. Regardless, 142 (58.6%) of the respondents expressed a desire to modify and adapt online learning. The mean scores for the six domains of attitude (perceived usefulness, intention to adapt, ease of use of online learning, technical assistance, learning stressors, and distant use of online learning) were 2.9, 2.8, 2.5, 2.9, 2.9, and 3.5, respectively. After multivariate logistic regression analysis, no factors in this study were significantly associated with attitude towards online learning. The high cost of the internet, unreliable internet connectivity and lack of institutional support were perceived barriers to effective online learning. Although most of the students in this study had a negative attitude toward online learning, they are willing to adopt it. Online learning could supplement traditional face-to-face learning in pharmacy programs if it can be made more user-friendly, have fewer technological barriers, and be complemented by programs that help improve practical learning abilities.


Synthesis of 13C labelled daidzein and formononetin.
Efficient methods are described for the synthesis of daidzein and formononetin labelled with a single 13C atom at the 4-position, to prepare material for metabolic studies.


Midterm Results of High-Dose-Rate Intraoperative Brachytherapy in the Treatment of Soft Tissue Sarcomas.
According to the literature only sparse data are available on the use of high-dose-rate intraoperative brachytherapy (IOHDR-BT) as a boost to external-beam irradiation (EBRT) in combination with a wide resection in patients with high-grade soft tissue sarcomas (STS). Applying a retrospective study design, we investigated all patients who between 2010 and 2016 underwent marginal resection of a high-grade STS and intraoperative radiotherapy, followed by EBRT. We included only patients with a traceable follow-up time of at least two years. Of 89 patients, 35 met our inclusion criteria and showed an average follow-up of four years. We found an overall 2-year local control rate of 94.3%. The local recurrence rate for R0 resections was 6%, whereas recurrences occurred in 13% of R1 resections and in 100% of R2 resections. One affected patient received only intraoperative radiotherapy. The recurrence rate by tumour entity was 36% for LPS, 11% for myxofibrosarcoma and 17% for undifferentiated pleomorphic sarcoma. The treatment regimen consisting of limb-preserving surgery, IORT and pre- or postoperative radiotherapy consistently shows excellent local control rates.


Antibiotic Treatment in an Animal Model of Inflammatory Lung Disease.
Allergic disease is on the rise and yet the underlying cause and risk factors are not fully understood. While lifesaving in many circumstances, the use of antibiotics and the subsequent disruption of the microbiome are positively correlated with the development of allergies. Here, we describe the use of the antibiotic vancomycin in combination with the papain-induced mouse model of allergic disease that allows for the assessment of microbiome perturbations and the impact on allergy development.


HBV Genome and Life Cycle.
Chronic hepatitis B virus (HBV) infection remains to be a serious threat to public health and is associated with many liver diseases including chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma. Although nucleos(t)ide analogues (NA) and pegylated interferon-α (Peg-IFNα) have been confirmed to be efficient in inhibiting HBV replication, it is difficult to eradicate HBV and achieve the clinical cure of CHB. Therefore, long-term therapy has been recommended to CHB treatment under the current antiviral therapy. In this context, the new antiviral therapy targeting one or multiple critical steps of viral life cycle may be an alternative approach in future. In the last decade, the functional receptor [sodium-taurocholate cotransporting polypeptide (NTCP)] of HBV entry into hepatocytes has been discovered, and the immature nucleocapsids containing the non- or partially reverse-transcribed pregenomic RNA, the nucleocapsids containing double-strand linear DNA (dslDNA), and the empty particles devoid of any HBV nucleic acid have been found to be released into circulation, which have supplemented the life cycle of HBV. The understanding of HBV life cycle may offer a new instruction for searching the potential antiviral targets, and the new viral markers used to monitor the efficacy of antiviral therapy for CHB patients in the future.


ZFAS1 Promotes Cisplatin Resistance via Suppressing miR-421 Expression in Oral Squamous Cell Carcinoma [Retraction].
[This retracts the article DOI: 10.2147/CMAR.S248869.].


Inhibition of anion transport in human red blood cells by 5,5'-dithiobis(2-nitrobenzoic acid).
The uptake of [32P]phosphate into human red blood cells was inhibited (Ki = 0.6 mM) by the sulfhydryl reagent 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). 2-Nitro-5-thiobenzoic acid (NTB), the reduced form of DTNB, was a less potent inhibitor (Ki = 7 mM). The inhibition of anion transport by DTNB could be reversed by washing DTNB-treated cells with isotonic buffer, or by incubating DTNB-treated cells with 2-mercaptoethanol, which converted DTNB to NTB. DTNB competitively inhibited the binding of 4-[14C]-benzamido-4'-aminostilbene-2,2'-disulfonate, a potent inhibitor of anion transport (Ki = 1-2 microM), to band 3 protein in cells and ghost membranes. These results suggest that the stilbene-disulfonate binding site in band 3 protein can readily accommodate the organic anion DTNB, and that inhibition by DTNB was not due to reaction with an essential sulfhydryl group.


Effect of infusion of vasoactive intestinal peptide (VIP)-antisense oligodeoxynucleotide into the third cerebral ventricle above the hypothalamic suprachiasmatic nucleus on the hyperglycemia caused by intracranial injection of 2-deoxy-D-glucose in rats.
We examined the effect of the infusion of a vasoactive intestinal peptide (VIP) antisense oligodeoxynucleotide into the third cerebral ventricle above the hypothalamic suprachiasmatic nucleus (SCN) using osmotic minipump for 3 days (0.2 nmol/ml per h) on the hyperglycemic response to intracerebroventricular injection of 2-deoxy-D-glucose (2DG) (80 micromol) in rats. After the infusion of the VIP antisense the inhibition of VIP expression in the SCN was observed in association with suppressions of the hyperglycemia, hyperglucagonemia and relative hypoinsulinemia due to the 2DG injection. Furthermore, additional intracranial injection of VIP (4 nmol) restored these responses to the 2DG injection in rats treated with the VIP antisense. These findings suggest that VIP neurons in the SCN are involved in the regulation of glucose metabolism.


Metallic nanoparticle contamination from environmental atmospheric particulate matter in the last slab of the trophic chain: Nanocrystallography, subcellular localization and toxicity effects.
Atmospheric particulate material (PM) from mining and steel industries comprises several metallic contaminants. PM10 samples collected in a Brazilian region with a recognized influence of the steel and iron pelletizing industries were used to investigate metallic nanoparticle incorporation into human fibroblast cells (MRC-5). MRC-5 cells were exposed to 0 (control, ultrapure water), 2.5, 5, 10, 20 and 40 μg PM10 mL-1, for 24 h. Cytotoxic and genotoxic dose-response effects were observed on lysosome and DNA structure, and concentrations high as 20 and 40 μg PM10 mL-1 induced elevated cell death. Ultrastructure analyses showed aluminosilicate, iron, and the emerging metallic contaminants titanium, bismuth, and cerium nanoparticles were incorporated into lung cells, in which the nanocrystallography analysis indicated the bismuth as Bi2O3. All internalized metallic nanoparticles were free and unbound in the cytoplasm and nucleus thereby indicating bioavailability and potential interaction to biological processes and cellular structures. Pearson's correlation analysis showed Fe, Ni, Al, Cr, Pb and Hg as the main cytotoxic elements which are associated with the stainless steel production. The presence of internalized nanoparticles in human lung cells exposed to environmental atmospheric matter highlights the need for a greater effort by regulatory agencies to understand their potential damage and hence the need for future regulation, especially of emerging metallic contaminants.


Regeneration of autotransplanted lymph node fragments.
In normal young minipigs thin slices of autologous mesenteric or superficial inguinal lymph nodes were implanted either in the greater omentum or subcutaneously in the groin region. The regeneration was studied histologically and connections between the afferent lymphatics and the regenerated tissue were checked. In the greater omentum, no regenerated lymph node tissue was found. In the inguinal region, lymphoid tissue with all the typical lymph node compartments was identified following antigenic stimulation in the draining area. Sinuses, germinal centres with a lymphatic corona, and a paracortex with typical high endothelial venules were seen. There was evidence of afferent lymphatics, e.g., macroscopically visible lymphatics, the occurrence of a subcutaneously injected dye, the effect of antigenic stimulation and a normal lymph node structure. Avascular transplants of autologous lymph node fragments regenerate subcutaneously, possibly providing a future technique for treating lymphoedema after radical excision or irradiation of lymph nodes.


Lower esophageal sphincter pressure in Chagas' disease.
It is known that lower esophageal sphincter (LES) pressure in patients with idiopathic achalasia is higher than in normal subjects, but in patients with Chagas' disease, who have esophageal disease with similar clinical, manometric, and radiologic results, studies of LES pressure show contradictory findings. We measured the LES pressure in 118 patients with chronic Chagas' disease, 14 patients with idiopathic achalasia, and 50 control subjects using a perfused catheter and the stationary pull-through (SPT) technique. The patients with Chagas' disease had normal esophageal radiologic examination (group A, N = 50), delay in esophageal clearance without dilatation (group B, N = 41), or delay in esophageal clearance with dilatation (group C, N = 27). The LES pressure of Chagas' disease patients of group A (18.6 +/- 9.1 mm Hg, mean +/- SD), group B (17.8 +/- 9.7 mm Hg), and group C (21.6 +/- 10.1 mm Hg) was lower (P less than 0.001) than the LES pressure of the controls (24.9 +/- 10.2 mm Hg). In patients with idiopathic achalasia, the LES pressure (40.7 +/- 17.8 mm Hg) was higher than in control subjects (P less than 0.01) and Chagas' disease patients (P less than 0.001). We conclude that the LES pressure of patients with Chagas' disease tended to be lower than that of control subjects and achalasia patients.


Magnetic resonance imaging in the assessment of ventricular remodeling and viability.
Cardiovascular MRI has effectively become a reference standard for quantifying ventricular volumes and function and for measuring the myocardial scar burden after myocardial infarction. Imaging of late gadolinium enhancement and microvascular obstruction carries strong prognostic information for identifying patients who would benefit from anti-remodeling therapy. The combination of gadolinium enhancement, perfusion, and cine imaging should make MRI the modality of choice in the assessment of left ventricular dysfunction and remodeling. The use of MRI in clinical trials of heart failure could help reduce sample size requirements because of its accuracy and reproducibility. This review describes the use of MRI in assessing ventricular remodeling and viability and summarizes the few studies that have relied on MRI for image-based markers of ventricular remodeling.


Ionic currents on type-I cells of the rabbit carotid body measured by voltage-clamp experiments and the effect of hypoxia.
Type-I cells (from rabbit embryos) in primary culture were studied in voltage-clamp experiments using the whole cell arrangement of the patch-clamp technique. With a pipette solution containing 130 mM K+ and 3 mM Mg-ATP, large outward currents were obtained positive to a threshold of about -30 mV by clamping cells from -50 mV to different test pulses (-80 to 50 mV). Negative to -30 mV, the slope conductance was low (outward rectification). The outward currents were blocked by external Cs+ (5 mM) and partially blocked by TEA (5 mM) and Co2+ (1 mM). The initial part of the outward currents during depolarizing voltage pulses exhibited a transient Ca2+ inward component partially superimposed to a Ca2+-dependent outward current. Inward currents were further characterized by replacing K+ with Cs+ in the intra- and extracellular solution in order to minimize the outward component and by using 1.8 mM Ca2+, 10.8 mM Ca2+ or 10.8 mM Ba2+ as charge carrier. Slow-inactivating inward currents were recorded at test potentials ranging from -50 to 40 mV (holding potential -80 mV). The maximal amplitude, measured at 10 mV in the U-shaped I-V curve, amounted to 247 +/- 103 pA (n = 3). This inward current was insensitive to 3 microM TTX, but blocked by 1 mM Co2+ and partially reduced by 10 microM D600 and 3 microM PN 200-100. In contrast to outward currents, the inward currents exhibited a 'run-down' within about 10 min. Lowering the pO2 from the control of 150 Torr (air-gassed medium) to 28 Torr had no apparent effect on inward currents, but depressed reversibly outward currents by 28%. In conclusion, it is suggested that type-I cells possess voltage-activated K+ and Ca2+ channels which might be essential for chemoreception in the carotid body.


Network connectivity between benevolent childhood experiences and uncertainty stress among Chinese university students.
The purpose of this study was to explore the association between benevolent childhood experiences (BCEs) and uncertainty stress among Chinese university students by network analysis. A total of 1,830 university students from three Chinese cities were recruited. Respondents' BCEs and uncertainty stress were self-reported using online questionnaire. The structure of the BCEs-uncertainty stress and related centrality indicators were examined for this sample. The overall network model showed that "no ways to suit the important changes in life" was the most influential, followed by "all things are not going well," "feel that there is nothing to do," and "worry about the future." And in this network, the most influential bridge symptom was "having a positive self-concept." The central symptoms of the BCEs-uncertainty stress network should be prioritized as targets in interventions and prevention efforts to reduce uncertainty stress among Chinese university students. Improving university students' positive self-concept is important to alleviate the level of uncertainty stress among Chinese university students.


Microsurgical tubal anastomosis in the rabbit following three types of sterilisation procedure.
The reversibility of Falope ring, Pomeroy and unipolar cautery methods of sterilisation was examined in 30 rabbits. Using microsurgical techniques, an overall pregnancy rate of 56.6% was attained. Reversibility was more readily achieved and resulted in a higher pregnancy rate after Falope ring than Pomeroy or cautery sterilisation. The pregnancy rate after each method of sterilisation seems to correlate with the results obtained for reversal of sterilisation in the human.


Comparative evaluation of conventional and dynamic magnetic resonance imaging of the pituitary gland for the diagnosis of Cushing's disease.
The ability of MRI to detect pituitary ACTH-secreting adenomas in patients with Cushing's disease is limited. Owing to different dynamics of contrast enhancement between adenomas and normal pituitary tissue, it has been suggested that obtaining images within seconds after gadolinium (Gad) injection using dynamic procedures increases the sensitivity of MRI in the detection of pituitary microadenomas. The objective of this study was to compare the ability of conventional magnetic resonance imaging (CMRI) and dynamic MRI (DMRI) to detect ACTH-secreting pituitary adenomas. Twenty-six consecutive patients with ACTH-dependent Cushing's syndrome and 10 normal subjects were investigated. According to the results of inferior petrosal sinus sampling, 21 patients had Cushing's disease and five had ectopic ACTH syndrome. Patients with Cushing's disease were operated regardless of the results of imaging studies. All underwent identical MRI and DMRI procedures using a 1.0 T magnet. Image sampling time during DMRI was 19 sec. Scans were randomly mixed and analysed blind, retrospectively and independently by two experienced radiologists. The clarity of the images was assessed by the analysis of agreement among radiologists. MRI findings were compared to surgical and histopathological findings. Surgical exploration identified three macrodenomas and 14 microadenomas. One microadenoma was found at pathological examination after subtotal hypophysectomy and no tumour was found in three cases. According to the combined opinion of radiologists, the three macroadenomas were identified equally well with CMRI and DMRI. Eight ACTH-secreting microadenomas were detected with CMRI and 11 with DMRI. The three microadenomas detected with DMRI only were visualized within 60 sec following Gad injection. No false positives occurred with CMRI. Three false positives were obtained with DMRI: one in a patient with ectopic ACTH syndrome while a silent microprolactinoma and normal tissue were found at the site of the radiological abnormality in two patients with Cushing's disease. In our study, the sensitivity of DMRI is greater than that of CMRI (0.67 vs. 0.52) but is associated with a loss in specificity (0.80 vs. 1.00). False positives may result from the increased sensitivity of DMRI which detects incidental pituitary lesions, technical artefacts or lowest clarity of images, as suggested by a lower observer agreement of DMRI (Kappa statistic 0.66 vs. 0.83). Overall, the two MR procedures had equivalent diagnostic power (0.72). In our hands, dynamic procedures did not improve the usefulness of MRI in Cushing's syndrome.


Kidney transplantation from cadaveric donors unsuitable for other centers and older than 60 years of age.
The demand for kidney transplants and the improvement in recipient outcomes over the last years have stimulated surgeons to expand the criteria for usable donor organs, by accepting older patients to expand their donor pool. We herein report our experience with kidney transplants from donors aged older than 60 years, who have been declined by other transplantation centers. Sixty kidney transplantations were performed with grafts procured from donors aged older than 60 years. Forty-five patients received a single kidney graft (SKG) and 15 received a dual kidney graft (DKG). Mean donor age was 62 years for SKG and 64 years for DKG. Double kidney transplantations were performed with the ipsilateral allocation of both grafts. No primary graft nonfunction occurred. Delayed graft function was observed in 22 SKG (48.8%) and in 7 DKG (46.6%). Acute rejection rates were 9% for SKG and 0% for DKG. One-year patient survival rates were 95% and 100% for SKG and DKG, respectively. Mean serum creatinine levels at 1-year posttransplantation were 1.9 mg/dL for SKG and 1.3 mg/dL for DKG. There were no surgical postoperative complications and mortality. Death censored 1-year graft survival rate was 88% for SKG and 94% for DKG. Our experience with marginal donors who have been declined by other transplantation centers has demonstrated that such organs, with accurate selection criteria, could be safely allocated to elderly recipients with no increase in postoperative complications, guaranteeing satisfactory results in the short and medium term, allowing a significant improvement in the number of transplants.


Coexistence of immunoreactive substance P and serotonin in neurones of the gut.
Serotonin (5-HT) and substance P (SP) were visualized by indirect immunofluorescence using two fluorochromes applied sequentially on the same preparation of myenteric plexus from the guinea pig gut. Three groups of labelled neurones were found: (i) neurones with 5-HT-like immunoreactivity only; (ii) neurones with SP-like immunoreactivity only; (iii) neurones with both 5-HT- and SP-like immunoreactivity, which represented approximately one-third of the 5-HT-like immunoreactive neurones.


Targeting GM-CSF in inflammatory diseases.
Granulocyte-macrophage colony stimulating factor (GM-CSF) is a growth factor first identified as an inducer of differentiation and proliferation of granulocytes and macrophages derived from haematopoietic progenitor cells. Later studies have shown that GM-CSF is involved in a wide range of biological processes in both innate and adaptive immunity, with its production being tightly linked to the response to danger signals. Given that the functions of GM-CSF span multiple tissues and biological processes, this cytokine has shown potential as a new and important therapeutic target in several autoimmune and inflammatory disorders - particularly in rheumatoid arthritis. Indeed, GM-CSF was one of the first cytokines detected in human synovial fluid from inflamed joints. Therapies that target GM-CSF or its receptor have been tested in preclinical studies with promising results, further supporting the potential of targeting the GM-CSF pathway. In this Review, we discuss our expanding view of the biology of GM-CSF, outline what has been learnt about GM-CSF from studies of animal models and human diseases, and summarize the results of early phase clinical trials evaluating GM-CSF antagonism in inflammatory disorders.


Training is not enough: child and adolescent psychiatry clinicians' impressions of telepsychiatry during the first COVID-19 related lockdown.
To ensure the continuity of care during the COVID-19 pandemic, clinicians in Child and Adolescent Psychiatry (CAP) were forced to immediately adapt in-person treatment into remote treatment. This study aimed to examine the effects of pre-COVID-19 training in- and use of telepsychiatry on CAP clinicians' impressions of telepsychiatry during the first two weeks of the Dutch COVID-19 related lockdown, providing a first insight into the preparations necessary for the implementation and provision of telepsychiatry during emergency situations. All clinicians employed by five specialized CAP centres across the Netherlands were invited to fill in a questionnaire that was specifically developed to study CAP clinicians' impressions of telepsychiatry during the COVID-19 pandemic. A total of 1065 clinicians gave informed consent and participated in the study. A significant association was found between pre-COVID-19 training and/or use of telepsychiatry and CAP clinicians' impressions of telepsychiatry. By far, the most favourable impressions were reported by participants that were both trained and made use of telepsychiatry before the pandemic. Participants with either training or use separately reported only slightly more favourable impressions than participants without any previous training or use. The expertise required to provide telepsychiatry is not one-and-the-same as the expertise that is honed through face-to-face consultation. The findings of this study strongly suggest that, separately, both training and (clinical) practice fail to sufficiently support CAP clinicians in the implementation and provision of telepsychiatry. It is therefore recommended that training and (clinical) practice are provided in conjunction.


A meta-analysis of the effect of Sjögren's syndrome on adverse pregnancy outcomes.
This study aimed to assess the correlation between Sjögren's Syndrome (SS) and adverse pregnancy outcomes, with the aim of providing a basis for preconception and pregnancy interventions in women with SS. A search of electronic databases in English and Chinese databases from January 2005 to December 2021, was conducted to collect the literature of case-control studies or cohort studies on the association between SS and pregnancy outcome studies. Literature inclusion and data extraction were performed according to established criteria, and the Newcastle-Ottawa scale was used to evaluate the quality of the literature. Stata 15 software was used for meta-analysis. A total of nine papers were included in this study. Meta-analysis results showed that SS was associated with spontaneous abortion (RR = 8.85, 95% CI 3.10‒25.26), preterm birth (RR = 2.27, 95% CI 1.46‒3.52), low birth mass (RR = 1.99, 95% CI 1.34‒2.97), and birth defects (RR = 4.28, 95% CI 3.08‒5.96). SS can increase the incidence of adverse pregnancy outcomes.


Diagnostic and therapeutic implications of genetic heterogeneity in myeloid neoplasms uncovered by comprehensive mutational analysis.
While growing use of comprehensive mutational analysis has led to the discovery of innumerable genetic alterations associated with various myeloid neoplasms, the under-recognized phenomenon of genetic heterogeneity within such neoplasms creates a potential for diagnostic confusion. Here, we describe two cases where expanded mutational testing led to amendment of an initial diagnosis of chronic myelogenous leukemia with subsequent altered treatment of each patient. We demonstrate the power of comprehensive testing in ensuring appropriate classification of genetically heterogeneous neoplasms, and emphasize thoughtful analysis of molecular and genetic data as an essential component of diagnosis and management.


A Garnet-Type Solid-Electrolyte-Based Molten Lithium-Molybdenum-Iron(II) Chloride Battery with Advanced Reaction Mechanism.
Solid-electrolyte-based molten-metal batteries have attracted considerable attention for grid-scale energy storage. Although ZEBRA batteries are considered one of the promising candidates, they still have the potential concern of metal particle growth and ion exchange with the β"-Al2 O3 electrolyte. Herein, a Li6.4 La3 Zr1.4 Ta0.6 O12 solid-electrolyte-based molten lithium-molybdenum-iron(II) chloride battery (denoted as Li-Mo-FeCl2 ) operated at temperature of 250 °C, comprising a mixture of Fe and LiCl cathode materials, a Li anode, a garnet-type Li-ion ceramic electrolyte, and Mo additive, is designed to overcome these obstacles. Different from conventional battery reaction mechanisms, this battery revolutionarily synchronizes the reversible Fe-Mo alloying-dealloying reactions with the delithiation-lithiation processes, meaning that the porous Mo framework derived from Fe-Mo alloy simultaneously suppresses the growth of pure Fe particles. By adopting a Li anode and a Li-ion ceramic electrolyte, the corrosion problem between the cathode and the solid electrolyte is overcome. With similar battery cost ($12 kWh-1 ), the theoretical energy density of Li-Mo-FeCl2 battery surpasses that of a Na-FeCl2 ZEBRA battery over 25%, to 576 Wh kg-1 and 2216 Wh L-1 , respectively. Experimental results further prove this cell has excellent cycling performance (472 mAh gLiCl -1 after 300 cycles, 50 mg active material) and strong tolerance against the overcharge-overdischarge (3-1.6 V) and freezing-thawing (25-250 °C) incidents.


Amphetamine-induced dopamine release and impulsivity in Parkinson's disease.
Impulsive-compulsive behaviours manifest in a substantial proportion of subjects with Parkinson's disease. Reduced ventral striatum dopamine receptor availability, and increased dopamine release is noted in patients with these symptoms. Prior studies of impulsivity suggest that midbrain D2 autoreceptors regulate striatal dopamine release in a feedback inhibitory manner, and in healthy populations, greater impulsivity is linked to poor proficiency of this inhibition. This has not been assessed in a Parkinson's disease population. Here, we applied 18F-fallypride PET studies to assess striatal and extrastriatal D2-like receptor uptake in a placebo-controlled oral dextroamphetamine sequence. We hypothesized that Parkinson's disease patients with impulsive-compulsive behaviours would have greater ventral striatal dopaminergic response to dextroamphetamine, and that an inability to attenuate ventral striatal dopamine release via midbrain D2 autoreceptors would underlie this response. Twenty patients with Parkinson's disease (mean age = 64.1 ± 5.8 years) both with (n = 10) and without (n = 10) impulsive-compulsive behaviours, participated in a single-blind dextroamphetamine challenge (oral; 0.43 mg/kg) in an OFF dopamine state. All completed PET imaging with 18F-fallypride, a high-affinity D2-like receptor ligand, in the placebo and dextroamphetamine state. Both voxelwise and region of interest analyses revealed dextroamphetamine-induced endogenous dopamine release localized to the ventral striatum, and the caudal-medial orbitofrontal cortex. The endogenous dopamine release observed in the ventral striatum correlated positively with patient-reported participation in reward-based behaviours, as quantified by the self-reported Questionnaire for Impulsivity in Parkinson's disease Rating Scale. In participants without impulsive-compulsive behaviours, baseline midbrain D2 receptor availability negatively correlated with ventral striatal dopamine release; however, this relationship was absent in those with impulsive-compulsive behaviours. These findings emphasize that reward-based behaviours in Parkinson's disease are regulated by ventral striatal dopamine release, and suggest that loss of inhibitory feedback from midbrain autoreceptors may underlie the manifestation of impulsive-compulsive behaviours.


How do emergency department physicians rate their orthopaedic on-call coverage?
Throughout the United States, the lack of orthopaedic on-call coverage at many institutions has been described as a "crisis." This study sought to understand how emergency department (ED) physicians perceive their orthopaedic on-call coverage. Specifically, the study looked at availability of orthopaedic coverage, adequacy of coverage, and reasons for patient transfers. After Institutional Review Board approval, written questionnaires were mailed to the ED directors at 39 of the 41 emergency departments in New Hampshire and Vermont. The instrument consisted of 25 items. Survey domains included ED physician demographics, availability and adequacy of orthopaedic coverage, and reasons for patient transfer. All responses were anonymous. A total of 31 questionnaires was returned. Approximately one third (36%) of ED physicians reported they had full-time orthopaedic coverage with 8% reporting they "never" had coverage. Almost two thirds (64%) of respondents felt their daytime orthopaedic coverage was adequate, but this number dropped to 52% for night coverage and 48% for weekend coverage. Over half (55%) of respondents felt their orthopaedist was reluctant to come in to evaluate a patient when the ED physician felt the patient warranted orthopaedic consultation. Approximately half (52%) felt it was often the case that a patient's care could have been improved if they had been evaluated by an orthopaedist. Only 29% of respondents said their orthopaedist always came in when asked to evaluate a patient. The top three reasons ED physicians felt their orthopaedist declined to care for a patient were complexity of the injury, the time of day/night, and if it was a weekend. The findings in this study suggest there is substantial room for improvement in orthopaedic on-call coverage for emergency departments.


The effectiveness of technology-based cognitive behavioral therapy on perinatal depression and anxiety: A systematic review and meta-analysis.
Extensive literature has shown the effectiveness of cognitive behavioral therapy in treating perinatal depression, but little is known about the effectiveness of its technology-based version. The aim of this review was to examine the effectiveness of technology-based cognitive behavioral therapy in reducing depressive and anxiety symptoms in women suffering from or at risk of experiencing perinatal depression. Six electronic databases were searched until February 2023 for articles published in English. Random-effect meta-analyses were conducted. Heterogeneity was assessed using the I2 statistics and Cochran's Q chi-squared test. Sensitivity analyses and subgroup analyses were also performed, and quality appraisals at the study and outcome levels were conducted. A total of 16 randomized controlled trials were included in the review. Results from meta-analyses suggest that technology-based cognitive behavioral therapy has a medium effect in reducing perinatal depressive symptoms and a small effect in reducing perinatal anxiety symptoms. Overall, women suffering from or at risk of perinatal depression may benefit from technology-based cognitive behavioral therapy. Future interventions can be improved by addressing both perinatal depression and anxiety, paying more attention to antenatal women to prevent postnatal mental health issues, and using self-guided mobile applications for accessibility.


Improving the Energy Density and Efficiency of the Linear Polymer PMMA with a Double-Bond Fluoropolymer at Elevated Temperatures.
A variety of applications can be found for high-temperature film capacitors, including energy storage components and pulsed power sources. In this work, in order to increase the energy density (U e), poly(vinylidene fluoride-chlorotrifluoroethylene-double bond) (P-DB) is introduced into poly(methyl methacrylate) (PMMA) to manufacture composite films by a solution casting process. In the case of the pure PMMA film, there is significant improvement in the polarization (P max) and breakdown field (E b) of the composite film. These improvements can effectively increase the U e of the composite film at room temperature and the elevated temperature. The results show that at an elevated temperature of 90 °C and at 350 MV/m, the U e of 40 vol % P-DB reaches 8.7 J/cm3, and the efficiency (η) of 77% is also considerable. Compared with biaxially oriented polypropylene (2.0 J/cm3), the proposed film exhibits 4 times enhancement in the energy storage density, meaning that it can be an energy storage capacitor with huge potential at high temperatures.


Responses of Phragmites australis to copper stress: A combined analysis of plant morphology, physiology and proteomics.
Few relevant research attempts have been made to determine heavy metal resistance mechanisms of rhizomatous perennial plants. Thus, it is pertinent to investigate the physiological and biochemical changes in Phragmites australis under metal-stressed conditions to facilitate the development of strategies to enhance copper (Cu) tolerance. We measured parameters related to plant growth and development, metal translocation and physiological responses of P. australis subjected to Cu stress. In addition, the differentially expressed proteins (DEP) were evaluated using the isobaric tag for relative and absolute quantification (iTRAQ) system. A large amount of copper accumulates in the roots of P.australis, but the growth parameters were not sensitive to Cu. However, the high concentration of Cu reduced the content of chlorophyll a and chlorophyll b, and the expression of important photosynthesis proteins PsbD, PsbO and PsaA were all down-regulated, so photosynthesis was inhibited. In contrast, the content of ascorbic acid and proline both increased with the increase of copper stress. P.australis fixed a large amount of Cu in its roots, limiting the migration of Cu to other parts of the plant. Moreover, Cu stress can affect photosynthesis by inhibiting the activity of PSI, PSII and LHCII. In addition, P.australis synthesizes ascorbic acid through the D-mannose/L-galactose pathway, and synthesizes proline through the ornithine pathway. Ascorbic acid and proline can increase Cu tolerance and protect photosynthesis. These results provide a theoretical basis for understanding the tolerance and repair mechanisms of plants in response to heavy metal pollution.


Spontaneous remission of agnogenic myeloid metaplasia in a splenectomized patient: a case report with erythrokinetic studies.
A 67-year-old woman with agnogenic myeloid metaplasia, who underwent splenectomy 1 year after the diagnosis, experienced spontaneous hematologic remission 6 years after splenectomy. Ten months before her anemia improved, peripheral leukocytes no longer showed a shift to the left and peripheral erythroblasts had disappeared. Sequential erythrokinetic studies revealed ineffective erythropoiesis with mild hemolysis and expansion of marrow activity in the tibia and femur but no erythropoiesis in the sacral or vertebral marrow.


A device that facilitates screwing at an appropriate angle in quadrilateral surface fractures: 105-degree drill attachment.
Within this study, we aimed to investigate the radiological and functional outcomes of acetabular fractures involving quadrilateral surface using 105° drill attachment in the anterior intrapelvic approach. The 35 patients who underwent surgical treatment from January 2016 and January 2020 for acetabular fractures involving quadrilateral surface with anterior intrapelvic approach using 105° drill attachment and a minimum of 12 months of postoperative follow-up were included. Perioperative complications, operation duration, and the quality of reduction were evaluated. Reduction quality was classified as poor, imperfect, and anatomic. Functional evaluation was performed according to the Harris Hip Score (HHS) and Merle d'Aubigne Score. Among 35 patients (median age 36 (21-80)), radiological results of the acetabular fixations were anatomic, imperfect, and poor in 28 (80%), 5 (14.3%), and 2 (5.7%) patients, respectively. Postoperative 1-year functional outcomes with Merle d'Aubigne scores and HHS were median 18 (10-18) and 90 (60-96), respectively. The clinical outcomes of the patients showed concordance with reduction quality. The median operation duration was 180 minutes (range 125-270). Iatrogenic neurovascular damage was not noted in any patients. Reduction and fixation of deep intrapelvic fractures are risky and difficult due to the narrow anatomy and adjacent crucial neurovascular structures. As the 105-degree drill application is safe and easy to intervene in, short surgery duration and satisfactory results with minimum complications can be obtained with a 105 angulated drill in the deep pelvic region.


Comparison of capnovolumetry-derived dead space parameters with pulmonary function test in normal adults using histamine provocation.
This study in healthy adults was conducted to explore the clinical application of capnovolumetric indices as compared to lung function parameters using histamine provocation. Forty healthy subjects received aerosol histamine or salbutamol in an automatic stimulation system with escalating doses of histamine. Dead space volumes of capnovolumetry and lung function parameters were examined with increased concentrations of histamine at a fixed time interval. The doses of histamine were selected from 0.0562 mg-2.2 mg and 0.1 mg salbutamol was inhaled when a maximal dose of histamine was reached. Baseline values in each group were calculated prior to histamine inhalation. Fowler dead space (VDF), Wolff dead space (VDW), threshold dead space (VDT), Bohr dead space (VDB), forced expiratory volume in 1 s (FEV1 ) and peak expiratory flow (PEF) showed a dose-dependent reduction following histamine provocation, but there were no statistical differences in the measurements at baseline and post S6 provocation. The value of dC3/DV at the maximal dose was significantly increased over its baseline value (P < 0.05). VDF, VDT and VDW were significantly increased after bronchodilator use (P < 0.05 or <0.01). The changes in capnovolumetry did not correspond with the results of lung function test. The dC3/DV and airway dead spaces of capnovolumetry in healthy adults are significantly increased compared to lung function parameters before or after bronchodilator use, suggesting that capnovolumetry is feasible in diagnostic evaluation of airway reactivity, especially for persons who are unable to undertake lung function test.


Lysyl oxidase-like 2 promotes esophageal squamous cell carcinoma cell migration independent of catalytic activity.
Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase (LOX) family that contributes to tumor cell metastasis. Our previous data identified two splice variants of LOXL2 (i.e., LOXL2 Δ72 and Δ13) in esophageal squamous cell carcinoma (ESCC) cells that increased cell invasiveness and migration but had lower LOX activities than wild-type LOXL2 (LOXL2 WT). We generated a series of LOXL2 deletion mutants with different deleted biochemical domains and examined the relationship between the cell migration abilities and catalytic activities, as well as subcellular locations, of these deletion mutants compared with LOXL2 WT in ESCC cells to explore the mechanism of LOXL2-driven ESCC cell migration. Our results indicated that the deletion mutants of LOXL2 had impaired deamination enzymatic activity; LOXL2 ΔSRCR4, which lacks the fourth scavenger receptor cysteine-rich (SRCR) domain, had lower enzymatic activity; and LOXL2 Y689F had no catalytic activity compared with LOXL2 WT. However these two mutants stimulated greater cellular migration than LOXL2 WT. Furthermore, the degree of cell migration promoted by LOXL2 ΔLO (in which the LOX-like domain was deleted) was higher than that of LOXL2 WT, and LOXL2 ΔSRCR3, which does not have the third SRCR domain, had lower LOX activity and cellular migration ability than LOXL2 WT. These results suggested that LOXL2 promotes ESCC cell migration independent of catalytic activity.