Gastroprotective effect of topiramate on indomethacin-induced peptic ulcer in rats: Biochemical and histological analyses.
Topiramate is an anticonvulsant drug effective against a wide range of seizures and epilepsies. The present study was conducted to investigate the possible protective effect of topiramate on indomethacin-induced gastric mucosal damage in rats. The animals were randomly distributed into four experimental groups with 10 animals in each group. Group 1 was the control group received vehicle only (DMSO at 1:4 (w/v)), group 2 was the model group received indomethacin (50 mg/kg; i.p.), and groups 3 and 4 received topiramate (100 mg/kg; i.p.) and ranitidine (100 mg/kg; i.p.), respectively, 1 h before indomethacin (50 mg/kg; i.p.). The efficacy of topiramate was compared with ranitidine. Animals were euthanized 4 h after indomethacin administration, and gastric tissues were collected for macroscopical, histopathological, and biochemical analyses. The mucosal lesions in the gastric corpus were evaluated by pathological examinations. The results revealed that the administration of indomethacin caused evident gastric mucosal damage with morphological and histological manifestation, whereas topiramate pretreatment extensively ameliorated the gastric injuries. Topiramate pretreatment also reduced the contents of tissue malonaldehyde, enhanced ferric reducing antioxidant power value and glutathione levels, and increased the activity of superoxide dismutase, catalase, and glutathione peroxidase in gastric mucosa compared to the model group. Our results indicate that topiramate might possess a protective role against indomethacin-induced gastric ulcers by inhibition of oxidative stress in gastric tissue.


Mesenchymal stem cell therapy in decompensated liver cirrhosis: a long-term follow-up analysis of the randomized controlled clinical trial.
Mesenchymal stem cell (MSC) infusion was reported to improve liver function in patients with decompensated liver cirrhosis (DLC); however, whether the medication can improve outcome of these patients is poorly understood. This prospective, open-labeled, randomized controlled study enrolled 219 patients with HBV-related DLC who were divided into control group (n = 111) and umbilical cord-derived MSC (UC-MSC)-treated group (n = 108), then all of them received a follow-up check from October 2010 to October 2017. The treated patients received three times of UC-MSC infusions at 4-week intervals plus conventional treatment that was only used for control group. The overall survival rate and HCC-free survival rate were calculated as primary endpoints and the liver function and adverse events associated with the medication were also evaluated. During the follow-up check period from 13 to 75th months, there was a significantly higher overall survival rate in the treated group than the control group, while the difference of the hepatocellular carcinoma event-free survival rate between the treated and control groups was not observed during the 75-month follow-up. UC-MSC treatment markedly improved liver function, as indicated by the levels of serum albumin, prothrombin activity, cholinesterase, and total bilirubin during 48 weeks of follow-up. No significant side effects or treatment-related complications were observed in the UC-MSC group. Therapy of UC-MSC is not only well tolerated, but also significantly improves long-term survival rate, as well as the liver function in patients with HBV-related DLC. UC-MSC medication, therefore, might present a novel therapeutic approach for the disease.


Aging and brain rejuvenation as systemic events.
The effects of aging were traditionally thought to be immutable, particularly evident in the loss of plasticity and cognitive abilities occurring in the aged central nervous system (CNS). However, it is becoming increasingly apparent that extrinsic systemic manipulations such as exercise, caloric restriction, and changing blood composition by heterochronic parabiosis or young plasma administration can partially counteract this age-related loss of plasticity in the aged brain. In this review, we discuss the process of aging and rejuvenation as systemic events. We summarize genetic studies that demonstrate a surprising level of malleability in organismal lifespan, and highlight the potential for systemic manipulations to functionally reverse the effects of aging in the CNS. Based on mounting evidence, we propose that rejuvenating effects of systemic manipulations are mediated, in part, by blood-borne 'pro-youthful' factors. Thus, systemic manipulations promoting a younger blood composition provide effective strategies to rejuvenate the aged brain. As a consequence, we can now consider reactivating latent plasticity dormant in the aged CNS as a means to rejuvenate regenerative, synaptic, and cognitive functions late in life, with potential implications even for extending lifespan. We review evidence of brain rejuvenation focusing on several systemic manipulations - exercise, caloric restriction, heterochronic parabiosis, and young plasma administration - and their ability to restore regenerative capacity, synaptic plasticity, and cognitive function in the brain.


Studies on sorption kinetics and sorption isotherm for pervaporative separation of benzene from model pyrolysis gasoline using insitu nano silver/polyvinyl alcohol membrane.
Pyrolysis gasoline (Py gas) is used as an octane enhancer of gasoline as it is rich in aromatics. However, removal of carcinogenic benzene from Py gas before blending with gasoline is important to meet the fuel specifications. The main focus of this present study is to determine the sorption kinetics and sorption isotherm of a fabricated insitu nano silver/polyvinyl alcohol (insitu nano Ag/PVA) membrane for pervaporative separation of benzene from model Py gas [mixture of benzene (aromatic) and 1-octene (aliphatic)]. The thickness, surface morphological structure (Atomic Force Microscopy) and degree of swelling of the fabricated membrane were determined. The highest pervaporation separation index achieved for the selected system was 14.259 kg/m2/h at 303 K, with 30 volume% benzene in model Py gas using a downstream pressure of 1 mm of Hg. The sorption kinetics of benzene in insitu nano Ag/PVA membrane obeyed the Elovich model while the Temkin isotherm model fitted the experimental data of the chosen system most accurately.


Carpal Tunnel Syndrome with Wrist Trigger Caused by Hypertrophied Lumbrical Muscle and Tenosynovitis.
We present a case of carpal tunnel syndrome involving wrist trigger caused by a hypertrophied lumbrical muscle with flexor synovitis. The case was a 40-year-old male heavy manual worker complaining of numbness and pain in the median nerve area. On active flexion of the fingers, snapping was observed at the carpal area, and forceful full grip was impossible. Tinel's sign was positive and an electromyographic study revealed conduction disturbance of the median nerve at the carpal tunnel. Magnetic resonance imaging revealed edematous lumbrical muscle with synovial proliferation around the flexor tendons. Open carpal tunnel release was performed under local anesthesia. Synovial proliferation of the flexor tendons was found and when flexing the index and middle fingers, the lumbrical muscle was drawn into the carpal tunnel with a triggering phenomenon. After releasing the carpal tunnel, the triggering phenomenon and painful numbness improved.


Symptomatic axillary hematoma after ultrasound-guided infraclavicular block in a patient with undiagnosed upper extremity mycotic aneurysms.
We present a case of axillary hematoma complicating an ultrasound-guided infraclavicular block in a patient with undiagnosed mycotic aneurysms of the peripheral arteries. Mycotic aneurysm is a rare medical condition with well-identified risk factors. When performing regional anesthesia in patients with these risk factors, clinicians should have a high degree of suspicion about the possible existence of vascular anomalies. A preprocedure Doppler study of the block area and real-time guidance of the needle using ultrasound may be useful.


Pulmonary atelectasis during paediatric anaesthesia: CT scan evaluation and effect of positive endexpiratory pressure (PEEP).
The case series consisted of ten children, ranged in age from one to three years (median 1.8 yrs), and in body weight from 10.2 to 13.5 kg (median 11.7 kg), in ASA class 1 or 2, all without lung disease. Having undergone general anaesthesia for cranial or abdominal CT scans, the patients were studied for pulmonary morphology. The first pulmonary CT scan was taken five min after induction of general inhalational anaesthesia; preoxygenation was avoided and an intraoperative FiO2</=0.4 was used. Densities in dependent regions of both lungs were observed in all children. After ventilation with PEEP of 5 cmH2O, all the observed densities disappeared without impairment of heart rate, blood pressure, haemoglobin saturation and endtidal CO2 (PECO2). We conclude that the appearance in children of atelectasis cannot be explained by a reabsorption of O2 mechanism and by denitrogenation. However, a PEEP of 5 cmH2O is able both to recruit all the available alveolar units, and to induce the disappearance of atelectasis in dependent lung regions.


The development of iron-free partially stabilized cement for use as dental root-end filling material.
To determine the effect of increasing the proportion of zinc on partially stabilized cement (PSC) produced using a one-step sol gel process. A one-step sol-gel process of Portland cement-based PSC with Zn was synthesized by replacing iron nitrate. The crystalline phases of the PSC-Zn powder were analysed by using X-ray diffraction (XRD). The experimental groups [i.e., MTA, PSC-Fe (control), PSC with 1% Zn, PSC with 3% Zn, and PSC with 5% Zn] were immersed in simulated body fluid for 3 h, 1 and 3 days to evaluate the hydration product formation. The microstructure and surface morphology were analysed using scanning electron microscopy (SEM). Initial and final setting times of the materials were determined using an ASTM Vicat needle testing machine. To evaluate the cytotoxicity of PSC-Zn system, primary osteoblasts cell lines were used. The addition of increased weight percentages of Zn, resulted in a more unstable phase which favoured the formation of a monoclinic structure of C3 S with an increased hydration reaction of PSC and reduced setting time. The cytotoxicity testing of PSC with Zn revealed that the material was not toxic. The newly synthesized PSC-Zn material had short setting time and was biocompatible.


Regulation of alpha-melanocyte-stimulating hormone secretion from the pars intermedia of domestic cats.
To identify factors regulating secretion of alpha-melanocyte-stimulating hormone (alpha-MSH) from the pars intermedia (PI) of the pituitary gland of cats. 28 healthy adult cats. Indwelling catheters were placed in 1 jugular vein of each of 7 to 10 cats, depending on treatment group. Sixteen hours later, 3 blood samples were collected for determination of baseline plasma hormone concentrations, and saline solution or a test substance (haloperidol, corticotropin-releasing hormone, bromocriptine, isoproterenol, insulin, or dexamethasone) was administered via the catheter. Subsequent blood samples were collected at regular intervals for up to 240 minutes after injection. Concentrations of ACTH, cortisol, and alpha-MSH were measured in plasma by use of specific radioimmunoassays. Cats were rested for at least 3 weeks between experiments. Administration of haloperidol and isoproterenol resulted in increased, and bromocriptine and insulin in decreased, circulating concentrations of alpha-MSH from baseline. ACTH and plasma cortisol concentrations increased after administration of all test substances except dexamethasone. Dexamethasone injection resulted in decreased plasma concentrations of ACTH and cortisol. Secretion of alpha-MSH from the PI of cats appears to be inhibited by dopaminergic activity and stimulated by beta-adrenergic influences. Activation of secretion of alpha-MSH from the PI can be dissociated from activation of secretion of other pro-opiomelanocortin-derived peptides, such as ACTH, arising from the pars distalis. Regulation of secretory activity of the PI of cats resembles that of rats.


A phase II study of imatinib in patients with advanced anaplastic thyroid cancer.
Currently, there is no standard treatment for metastatic anaplastic thyroid cancer (ATC). DNA microarray analysis has shown platelet-dervived growth factor receptor (PDGFR) overexpression in ATC relative to well-differentiated thyroid cancer. In p53-mutated/deficient ATC cell lines, cABL is overexpressed, and selective inhibition of cABL results in a cytostatic effect. Imatinib inhibits tyrosine kinase activity of Bcr-ABL and PDGF. We hypothesize that patients with ATC that over-expresses PDGF receptors or cABL will respond to imatinib. Patients with histologically confirmed ATC who had measurable disease and whose disease expressed PDGF receptors by immunohistochemistry were eligible for study. Imatinib was administered at 400 mg orally twice daily without drug holiday. Response to treatment was assessed every 8 weeks. Patients with complete response, partial responses, or stable disease were treated until disease progression. The study was terminated early due to poor accrual. From February 2004 to May 2007, 11 patients were enrolled and were started on imatinib. At baseline, 4/11 had locoregional disease, 5/11 had distant metastases, and 2/11 had both. Nine of 11 had prior chemoradiation, and 7/11 had thyroidectomy. Eight of 11 were evaluable for response; 4 were excluded for lack of follow-up with radiologic evaluation. The overall response rates at 8 weeks were complete response 0/8, partial response 2/8, and stable disease 4/8. The median time to follow-up was 26 months (ranges 23-30 months). The rate of 6-month progression-free survival was 36% (95% confidence interval, 9%-65%). The rate of 6-month overall survival was 45% (95% confidence interval, 16%-70%). The most common grade 3 toxicity was edema in 25%; other grade 3 toxicities included fatigue and hyponatremia (12.5% each). There were no grade 4 toxicities or treatment related deaths. Imatinib appears to have activity in advanced ATC and is well tolerated. Due to difficulty of accruing patients with a rare malignancy at a single institution, further investigation of imatinib in ATC may be warranted in a multi-institutional setting.


[Hemopurification in the management of ARDS complicating multiple organ failure].
In the field of critical care medicine, it has been claimed that ARDS often develops as a part of multiple organ failure (MOF). Since multi-modality therapy is necessary in the management of MOF, it is also mandatory even in the management of ARDS. Among the various therapeutic approaches for patients with MOF, hemopurification is one of the most effective therapeutic tools. Various hemopurification methods such as hemodialysis, peritoneal dialysis, hemoadsorption, hemofiltration and plasma exchange have been applied in the management of MOR. However, our recent experiences suggest that continuous hemofiltration (CHF) and/or continuous hemodiafiltration (CHDF) are safest, most easily performed and effective hemopurification in the management of ARDS/MOF. The efficacy of hemopurification in the management of ARDS is summarized as follows. 1) Removal of humoral mediators and causative substances of ARDS following insults such as sepsis and trauma. 2) Treatment of pulmonary interstitial permeability edema which has been claimed to be one of the most important pathological conditions in ARDS. 3) Removal of excess water given as carrier in IVH solution and accumulating in the body. 4) Immunomodulation which has also been considered to be necessary in the treatment or prevention of ARDS.


[Being a doctor: the influence of gender on the career choices and prospects].
Gender studies of a profession focus on the work distribution between men and women. Sociologists started to study the medical profession in the 80s only. Since it was male-dominated female doctors had no choice but adjusting their behavior to that of men. Nowadays, the majority of the young people interested in becoming a doctor are women. It is mandatory to gain insight into the demographic specificities of the medical population working in a large university hospital (according to sex, age, as well as to the level within the medical hierarchy). It is also important to analyze the key elements that differentiate male and female in their relationship to work and promotion. Finally, it is urgently necessary to change our organizations as well as our practices in order to be able to take into account these major changes of the medical demography.


Antibodies raised against chlamydial lipopolysaccharide antigens reveal convergence in germline gene usage and differential epitope recognition.
The structures of antigen-binding fragments from two related monoclonal antibodies have been determined to high resolution in the presence of several carbohydrate antigens raised against chlamydial lipopolysaccharide. With the exception of CDR H3, antibodies S54-10 and S73-2 are both derived from the same set of germline gene segments as the previously reported structures S25-2 and S45-18. Despite this similarity, the antibodies differ in specificity and the mechanism by which they recognize their cognate antigen. S54-10 uses an unrelated CDR H3 to recognize its antigen in a fashion analogous to S45-18; however, S73-2 recognizes the same antigen as S45-18 and S54-10 in a wholly unrelated manner. Together, these antibody-antigen structures provide snapshots into how the immune system uses the same set of inherited germline gene segments to generate multiple possible specificities that allow for differential recognition of epitopes and how unrelated CDR H3 sequences can result in convergent binding of clinically relevant bacterial antigens.


High-Q silk fibroin whispering gallery microresonator.
We have experimentally demonstrated an on-chip all-silk fibroin whispering gallery mode microresonator by using a simple molding and solution-casting technique. The quality factors of the fabricated silk protein microresonators are on the order of 105. A high-sensitivity thermal sensor was realized in this silk fibroin microtoroid with a sensitivity of -1.17 nm/K, that is 8 times higher than previous WGM resonator-based thermal sensors. This opens the way to fabricate biodegradable and biocompatible protein based microresonators on a flexible chip for biophotonics applications.


Evolution of multidrug-resistant Staphylococcus aureus infections in horses and colonized personnel in an equine clinic between 2005 and 2010.
A total of 70 Staphylococcus aureus isolates from postoperative infections in hospitalized horses were isolated between January 2005 and January 2011. Among them, 12 isolates were methicillin-susceptible S. aureus (MSSA), 18 were borderline-oxacillin-resistant S. aureus (BORSA), and 40 were methicillin-resistant S. aureus (MRSA). During the same period, the equine clinic personnel were screened for nasal carriage of BORSA and MRSA. Genotyping revealed that BORSA ST1(MLST)-t2863(spa) isolates were responsible for most equine infections and were the main isolates found in colonized members of the personnel between 2005 and 2007, and that in 2007, MRSA ST398-t011-IVa(SCCmec) emerged in infection sites and personnel, replacing BORSA. Besides decreased susceptibility to oxacillin, all MRSA and BORSA of these two major clonal lineages displayed resistance to gentamicin and kanamycin conferred by the aac(6')-Ie-aph(2')-Ia gene and to trimethoprim conferred by dfr(K) in MRSA and dfr(A) in BORSA. All MRSA had additional resistance to tetracycline conferred by tet(M), whereas BORSA generally also display resistance to streptomycin conferred by str. The number of hospital-acquired MRSA infections in horses could be limited after the introduction of basic hygiene measures and personnel decolonization. Two MRSA carriers could not be decolonized using mupirocin, and a year after decolonization, additional members were recolonized with MRSA. Hygiene measures should, therefore, be maintained to limit the transmission of S. aureus between personnel and horses.


On the ligand-free palladium cluster catalysed Suzuki-Miyaura reaction.
C-C cross coupling reactions have been widely used for developing synthesis protocols for pharmaceuticals and agricultural products in the past few decades. Of all the reported C-C cross coupling reactions, the Suzuki-Miyaura reaction is preferred because of its mild reaction conditions, the commercial availability of associated reagents and the ease of removal of boron containing by-products. Recently, Corma and co-workers [Leyva-Perez et al., Angew. Chem., 2013, 125, 11768] reported water-stabilized three- and four-atom Pd clusters as highly active catalytic species for C-C coupling reactions. The present work focuses on developing detailed mechanistic insights into the Suzuki-Miyaura reaction with Pd3 and Pd4 clusters utilizing density functional theory calculations. The role of the base in the reaction was analysed in this study, which was found to lower the activation barriers of transmetalation over both Pd3 and Pd4. Free energy landscapes for Suzuki-Miyaura coupling of bromobenzene and phenylboronic acid over Pd3 and Pd4 clusters were developed. The highest free energy barriers of 34.7 and 30.4 kcal mol-1 were observed for the oxidative addition over Pd3 and Pd4, respectively, indicating the oxidative addition as the rate limiting step. Detailed energetics conclusively proved the active nature of small-atom Pd clusters for catalyzing the Suzuki-Miyaura reaction.


Anaphylaxis induced by ingestion of a pollen compound.
We report on the case of a 32-year-old atopic patient who showed a severe anaphylactic reaction due to the ingestion of a pollen compound prepared in an herbalist's. A few minutes after ingestion, generalized pruritus, difuse erythema, facial edema, cough, hoarseness and dysphonia appeared, and the emergency administration of subcutaneous epinephrine and intravenous methylprednisolone was necessary. Skin tests with a battery of inhalants and food allergens were performed. The patient only showed sensitization to Artemisia vulgaris, Taraxacum officinalis and Salix alba. Specific IgE levels were evaluated by FEIA-CAP giving a seric level of CAP class 3 to Artemisia vulgaris and class 2 to Taraxacum officinalis and Salix alba. Samples of the pollen compound were shown in the microscopical analysis to be 93% pollens and 6% fungi. In the qualitative study Taraxacum officinalis (15%), Artemisia vulgaris (5%) and Salix alba (15%) were the main elements identified. In summary, this case study describes a food-induced systemic reaction due to a pollen compound in an atopic patient with a history of allergic rhinitis. Pollinic patients must be informed on the risks that the consumption of these compounds might cause.


New additivity schemes for hydrocarbon energies.
[structure: see text] A new isodesmic additivity scheme based on the energetic relationships among the simplest hydrocarbon molecules reproduces the experimental heats of formation for a broad range of unstrained hydrocarbons with remarkable accuracy. The stabilizations of radicals, double, and triple CC bonds by alkyl substituents (hyperconjugation), as well as the stabilization by 1,3-alkyl group interactions at the same carbon (branching), support conventional interpretations. Statistical data fitting can also be achieved by using only four adjustable parameters.


Electrical stimulation and biofeedback for the treatment of fecal incontinence: a systematic review.
This systematic review determines the best known form of biofeedback (BF) and/or electrical stimulation (ES) for the treatment of fecal incontinence in adults and rates the quality of evidence using the Grades of Recommendation, Assessment, Development, and Evaluation. Attention is given to type, strength, and application mode of the current for ES and to safety. Methods followed the Cochrane Handbook. Randomized controlled trials were included. Studies were searched in The Cochrane Library, MEDLINE, and EMBASE (registration number (PROSPERO): CRD42011001334). BF and/or ES were studied in 13 randomized parallel-group trials. In 12 trials, at least one therapy group received BF alone and/or in combination with ES, while ES alone was evaluated in seven trials. Three (four) trials were rated as of high (moderate) quality. Average current strength was reported in three of seven studies investigating ES; only two studies reached the therapeutic window. No trial showed superiority of control, or of BF alone or of ES alone when compared with BF + ES. Superiority of BF + ES over any monotherapy was demonstrated in several trials. Amplitude-modulated medium-frequency (AM-MF) stimulation, also termed pre-modulated interferential stimulation, combined with BF was superior to both low-frequency ES and BF alone, and 50 % of the patients were continent after 6 months of treatment. Effects increased with treatment duration. Safety reporting was bad, and there are safety issues with some forms of low-frequency ES. There is sufficient evidence for the efficacy of BF plus ES combined in treating fecal incontinence. AM-MF plus BF seems to be the most effective and safe treatment. • The higher the quality of the randomized trial the more likely was a significant difference between treatment groups. • Two times more patients became continent when biofeedback was used instead of a control, such as pelvic floor exercises. • Two times more patients became continent when biofeedback plus electrical stimulation was used instead of biofeedback only. • Low-frequency electrical stimulation can have adverse device effects, and this is in contrast to amplitude-modulated medium-frequency electrical stimulation. • There is high quality evidence that amplitude-modulated medium-frequency electrical stimulation plus electromyography biofeedback is the best second-line treatment for fecal incontinence.


Ethical acceptability, health policy and foods biotechnology based foods: is there a third way between the precaution principle and an overly enthusiastic dissemination of GMO?
The demand for consumer safety with regard to the food-processing industry is becoming, legitimately, more and more urgent. If ingested drugs can carry deleterious effects that exceed the beneficial effect that the research was initially undertaken for, then the same can only be the case for foods that stem from the same new biotechnologies, zero risk being non existent. There are two conflicting viewpoints about the possible risks linked to genetically modified organisms: a posteriori protection (based on vigilance once the product is on the market) and an a priori protection (at present usually supported by the precaution principle). We suggest a third way, which ensures consumer safety, but doesn't hinder scientific progress. Just as there are regulations for the protection of human subjects in biomedical research and regulations for the use of drugs after they are marketed, so should such regulations be introduced in the domains of food production that use biotechnologies. We therefore suggest that the scientific community and the food-processing industry develop evaluation protocols for new foods like the ones that exist for drugs. We thus offer thirteen regulations, based on the Helsinki declaration, in order to establish these protocols. These proposals, applied to food-processing research, would enable the industry to return confidence to consumers and thus avoid the random blocking of scientific progress, which is a source of health for the greater population.


Novel Approaches to Treatment of Advanced Melanoma: A Review on Targeted Therapy and Immunotherapy.
The incidence of malignant melanoma is increasing. The majority of patients are diagnosed in early stages when the disease is highly curable. However, the more advanced or metastatic cases have always been a challenge for clinicians. The poor prognosis for patients with melanoma is now changing as numerous of promising approaches have appeared recently. The discovery of aberrations of pathways responsible for intracellular signal transduction allowed us to introduce agents specifically targeting the mutated cascades. Numerous clinical studies have been conducted to improve effectiveness of melanoma treatment. From 2011 until now, the U.S. FDA has approved seven novel agents, such as BRAF-inhibitors (vemurafenib 2011, dabrafenib 2013), MEK-inhibitors (trametinib 2013), anti-PD1 antibodies (nivolumab 2014, pembrolizumab 2014), anti-CTLA-4 antibody (ipilimumab 2011), or peginterferon-alfa-2b (2011) intended to be used in most advanced cases of melanoma. Nevertheless, clinicians continue working on new possible methods of treatment as resistance to the novel drugs is a commonly observed problem. This paper is based on latest data published until the end of January 2015.


A DNA microarray for identification of selected Korean birds based on mitochondrial cytochrome c oxidase I gene sequences.
DNA barcoding with the gene encoding cytochrome c oxidase I (COI) in the mitochondrial genome has been proposed as a standard marker to identify and discover animal species. Some migratory wild birds are suspected of transmitting avian influenza and pose a threat to aircraft safety because of bird strikes. We have previously reported the COI gene sequences of 92 Korean bird species. In the present study, we developed a DNA microarray to identify 17 selected bird species on the basis of nucleotide diversity. We designed and synthesized 19 specific oligonucleotide probes; these probes were arrayed on a silylated glass slide. The length of the probes was 19-24 bps. The COI sequences amplified from the tissues of the selected birds were labeled with a fluorescent probe for microarray hybridization, and unique hybridization patterns were detected for each selected species. These patterns may be considered diagnostic patterns for species identification. This microarray system will provide a sensitive and a high-throughput method for identification of Korean birds.


Elevated fasting glucose levels within normal range are associated with an increased risk of metabolic syndrome in older women.
The prevalence of cardiovascular disease (CVD) and metabolic syndrome (MetS) increases with increasing fasting plasma glucose (FPG) levels in an elderly population with pre-diabetes or diabetes. However, it remains unknown whether the relationship between elevated FPG and increased risks of MetS exists in older women with normoglycemia (FPG<100mg/dL). Therefore, the present study was conducted to fill the lack of information in that area. We included 6505 apparently healthy women, aged 65years and older, with normoglycemia who participated in routine health checkups at health screening centers in Taiwan. Components of MetS (FPG, waist circumference (WC), high-density lipoprotein cholesterol (HDL-C), triglycerides, and systolic/diastolic blood pressure), body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), total cholesterol, and percentage body fat (PBF) were examined in all subjects. Subjects were sub-grouped by FPG levels (<90mg/dL, 91-95mg/dL and >95mg/dL for group 1, group 2 and group 3, respectively). Subjects in group 2 and group 3 were 1.22-fold (P=0.017) and 1.25-fold (P=0.007) more likely to have MetS compared with those in group 1. Age, WC, BMI, PBF, systolic and diastolic blood pressure, total cholesterol, triglycerides, and HDL-C were significantly correlated with FPG, whereas HDL-C was negatively correlated with FPG. In a multivariate stepwise regression analysis, PBF, LDL-C, triglycerides, and age were significantly and independently associated with FPG. Among older women, the risk of MetS was significantly associated with elevated FPG even for subjects with normal FPG. Lifestyle interventions for reducing PBF and controlling dyslipidemia could help reduce the risk of MetS in this population.


In vitro proton spectroscopy of normal and abnormal prostate.
Previous biochemical and 13C NMR spectroscopic data have suggested that the metabolism of citrate, a secretory product of normal prostate, may be interrupted in prostate cancer. In the present study in vitro 1H NMR spectroscopy was used to see if cell strains derived from prostate cancers could be reliably distinguished from those of normal prostate epithelium. High-resolution one-dimensional and two-dimensional J-resolved 1H NMR spectra as well as gas chromatography coupled with mass spectroscopy were used to study extracts of highly defined cell strains from normal peripheral zone, normal central zone, adenocarcinoma, and benign prostatic hyperplasia. Resonances assigned to citric acid and related metabolites were identified. Cell strains derived from prostate cancers tended to have smaller amounts of citrate than those from normal prostate epithelium. However, the differences were small and not statistically significant. The lack of statistically significant differences may reflect the variability present in both normal and abnormal cell strains and thus underscore the well-known difficulty in differentiating normal and cancerous tissues.


IDH1 Inhibition Reawakens the Immune Response against Cholangiocarcinoma.
Isocitrate dehydrogenase 1 mutations (mIDH1) are common in cholangiocarcinoma, but their exact mechanisms in cholangiocarcinoma initiation and maintenance are unclear. In this issue of Cancer Discovery, Wu and colleagues identify immune suppression via TET2 inactivation as the primary means by which mIDH1 maintains cholangiocarcinoma survival, leading to an efficacious new combination of mIDH1 inhibitors and immune checkpoint blockade targeting regulatory T cells. See related article by Wu et al., p. 812 (9).


[Electron paramagnetic resonance spectra with g=2.03 of the animal liver tissue treated with butylhydroxytoluene and diethylnitrosamine].
ESR spectra g=2.03 intensities of rat liver tissues were studied under the action of cancer agent either diethylnitrosamine (DEN) with butylhydroxytoluene (BHT) injected before DEN or without BHT at 77 K. Combined influence of DEN and BHT upon the intensity change of ESR spectra with g=2.03 at animal disease is explained by modified action of DEN metabolism.


Bioaccumulation of arsenic(V) from wastewater by live and dead Spirogyra sp.
Contaminated water with arsenic causes a negative impact on socioeconomic status in the concerned area. Existing methods are not much adequate, efficient, and appropriate. Bioremediation of heavy metals with microalgae seems to be a promising and holistic approach to counter the pre-existing associated with heavy metal toxicity. A pure culture of live and dead Spirogyra sp. was tested for its ability to adsorb arsenic(V) and modeling of experimental data was used to interpret the mechanism of bioaccumulation. Langmuir and Freundlich isotherm models were used to explain the sorption of arsenic. The maximum sorption capacity of live Spirogyra sp. was 315 mg/g and dead Spirogyra sp. was 207 mg/g. Mechanism of bioaccumulation for As(V) ions by live and dead Spirogyra sp. were studied using several advanced techniques including Fourier-transform infrared, fluorescence microscopy, and scanning electron microscope. The study summarizes, bioaccumulation of AsO4 -3 by live and dead cells of Spirogyra sp. seems to be promising. The pseudo-second-order rate equation described better the kinetics of As(V) adsorption with good correlation coefficients. The results suggested that live Spirogyra sp. was more suitable to remove As(V) as compared to dead Spirogyra sp.


Comparative study of the topical effectiveness of the Andiroba oil (Carapa guianensis) and DEET 50% as repellent for Aedes sp.
DEET (N,N-diethyl-3-methylbenzamide) is nowadays the most effective mosquito repellent available, however, its use can present some topical and systemic side effects. Some botanical compositions, as Andiroba (Carapa guianensis), have been proved repellent properties at low cost and toxicity. An experimental study was driven involving four volunteers submitting their forearms covered with Andiroba oil at 100%, DEET 50%, refined soy oil, Andiroba oil 15% and in the absence of products, directly to healthy females of Aedes sp. The times of first and third bites were checked. The results showed that the median of the first bite without any product was 17.5s and the third bite, 40.0s. In the soy oil, the bites happened in 60.0s and 101.5s, in the presence of Andiroba oil 100%, in 56.0s and 142.5s and in Andiroba oil 15%, in 63.0s and 97.5s. The volunteers using DEET 50% had not received bites after 3600s in most of the experiments (p < 0.001 Wilcoxon). Pure Andiroba oil compared to the soy oil, forearm without product and Andiroba oil 15%, showed discreet superiority (p < 0.001 Wilcoxon). Our conclusion is that this study demonstrated that the pure Andiroba oil presents discreet repellent effect against bite of Aedes sp., being significantly inferior to DEET 50%.


The metabolic and bone density effects of continuous combined 17-beta estradiol and noresthisterone acetate treatments in Thai postmenopausal women: a double-blind placebo-controlled trial.
To compare the changes of lipid parameters, liver function tests, fasting plasma glucose and bone density in Thai postmenopausal women who received this combined hormonal treatment and placebo. Double-blinded, randomized controlled trial study. Sixty postmenopausal women attending the menopause clinic at Chulalongkorn Hospital from July, 1996 to December, 1996, were enrolled in the study. The patients were randomized to receive the placebo or drug (17 beta-estradiol 2 mg and norethisterone acetate 1 mg) continuously. Patient characteristics, physical examination, liver function tests, fasting plasma glucose, lipid parameters (fasting total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein (HDL) and triglyceride level) and bone densitometry were performed before beginning the study. The lipid parameters were repeated at 3, 6 and 12 months. Fasting plasma glucose, liver function tests and bone densitometry were repeated at 12 months. In the drug group, there were significant changes in the cholesterol at 3, 6 and 12 months when compared to the baseline. There were significant differences at 3, 6 and 12 months when compared between groups. The HDL values were not significantly different within groups. The LDL values at 3, 6, 12 months were significantly lower than the baseline in the drug group when compared within groups and at 6, 12 months in the placebo group. The triglyceride values were not significantly different between groups and within groups. There was no significant change between groups and within groups of fasting plasma glucose, total bilirubin, direct bilirubin, AST, ALT, albumin and globulin. The alkaline phosphatase values were significantly decreased at 12 months in the drug group. The bone density of total BMD and T-score at the spine of the drug group increased significantly at 12 months. The per cent change per year was +5.1. In contrast, the values in the placebo group decreased significantly, the per cent change per year was -0.9. The same pattern was also found in the bone density of the total hip. But when focused to the femoral neck, we found no significant change in both groups. This continuous combined treatment resulted in beneficial changes of bone density and lipid profiles. The therapy prevented bone loss and the changes in serum lipoprotein were concordant with a lipid profile associated with a decreased risk of coronary heart disease in Thai postmenopausal women.


Acyclic directed graphs for automatic image analysis of lung parenchymal geometry.
We have developed a simple method for encoding pulmonary alveolar geometry suitable for morphometric analysis and modeling. The approach involves the use of 8-bit video microscopic images of lung which are thresholded to produce binary images. Each alveolar wall was thinned to its midline to produce a skeletonized image. We present an algorithm for converting such an image to an acyclic directed graph. Such a representation is quite suitable for mathematical treatment, lending itself to problems involving simulation or modeling. We present as an example application, the measurement of dihedral angles in rat lung using conventional histological sections.


CD59 expression and complement susceptibility of human neuronal cell line (NTera2).
The present study analysed the susceptibility of neuronal cells to human complement. A human neuronal precursor cell line (NTera2) which can be induced to differentiate into post-mitotic neuronal cells was employed. Using immunocytochemistry, NTera2 neurones, but not their precursors (stem cells), were shown to activate complement in the absence of antibody and to lack CD59, an inhibitor of the terminal stages of the complement cascade. Following exposure to human serum, neurones but not stem cells were lysed by complement, as demonstrated by a cell viability assay and consistent rise in intracellular calcium. This response was abrogated when cells were treated with complement-depleted serum by heat inactivation or cobra venom factor. Protection from lysis was observed following incorporation of CD59 with its glycolipid anchor in the neuronal cell membrane.


A system for classifying disease comorbidity status from medical discharge summaries using automated hotspot and negated concept detection.
OBJECTIVE Free-text clinical reports serve as an important part of patient care management and clinical documentation of patient disease and treatment status. Free-text notes are commonplace in medical practice, but remain an under-used source of information for clinical and epidemiological research, as well as personalized medicine. The authors explore the challenges associated with automatically extracting information from clinical reports using their submission to the Integrating Informatics with Biology and the Bedside (i2b2) 2008 Natural Language Processing Obesity Challenge Task. DESIGN A text mining system for classifying patient comorbidity status, based on the information contained in clinical reports. The approach of the authors incorporates a variety of automated techniques, including hot-spot filtering, negated concept identification, zero-vector filtering, weighting by inverse class-frequency, and error-correcting of output codes with linear support vector machines. MEASUREMENTS Performance was evaluated in terms of the macroaveraged F1 measure. RESULTS The automated system performed well against manual expert rule-based systems, finishing fifth in the Challenge's intuitive task, and 13(th) in the textual task. CONCLUSIONS The system demonstrates that effective comorbidity status classification by an automated system is possible.


Use of letrozole versus clomiphene citrate combined with gonadotropins in intrauterine insemination cycles: a pilot study.
To compare the clinical outcomes between letrozole and clomiphene citrate (CC) in gonadotropin-combined intrauterine insemination (IUI) cycles. Prospective pilot study. One university hospital and two private infertility clinics. Ninety-three infertile couples eligible for superovulation and IUI. A letrozole dose of 2.5 mg/day (n = 66) or a CC dose of 100 mg/day (n = 27) was given on day 3-7 of the menstrual cycle, combined with human menopausal gonadotropin (hMG) at a dose 150 IU every other day starting on day 5. The number of mature follicles, serum estradiol (E2) and progesterone (P) levels, endometrial thicknesses on the day of human chorionic gonadotropin (hCG), and clinical pregnancy rates. The patients' clinical characteristics were comparable between the two groups. The number of mature follicles (3.2 +/- 1.7 vs. 5.6 +/- 2.4) and serum E2 levels on the day of hCG (231.0 +/- 179.8 vs. 1,371.7 +/- 750.5 pg/mL) were significantly lower in the letrozole group. No significant differences were found in endometrial thickness measured on the day of hCG or clinical pregnancy rates (18.2% vs. 25.9%). The rate of patients with serum P levels > 1.0 ng/mL on the day of hCG was significantly lower in the letrozole group (4.5% vs. 25.9%). Letrozole produced a comparable pregnancy rate vs. CC in gonadotropin-combined IUI cycles. Our results should be confirmed in larger populations with proper randomization.


Atomic Diffusion of Indium through Threading Dislocations in InGaN Quantum Wells.
The compositional and structural investigations of threading dislocations (TDs) in InGaN/GaN multiple quantum wells were carried out using correlative transmission electron microscopy (TEM) and atom probe tomography (APT). The correlative TEM/APT analysis on the same TD reveals that the indium atoms are diffused along the TD and its concentration decreases with distance from the InGaN layer. On the basis of the results, we directly observed that the indium atoms originating from the InGaN layer diffuse toward the epitaxial GaN surface through the TD, and it is considered to have occurred via the pipe diffusion mechanism induced by strain energy relaxation.


Tacrolimus: focusing on atopic dermatitis.
Tacrolimus ointment is an effective treatment for atopic dermatitis. As a calcineurin inhibitor, it works through the FK-binding protein, inhibiting calcineurin and preventing dephosphorylation of nuclear factor of activated T cells (NFAT). Systemic absorption from the drug is minimal, allowing a favorable safety profile. In head-to-head clinical trials with pimecrolimus, tacrolimus proved to be a more effective treatment. Tacrolimus ointment has also been compared to standard topical cortico-steroid treatments and is equally effective if not superior to several topical steroids. Overall, tacrolimus ointment is a safe and effective treatment for atopic dermatitis and can be used as an adjunctive treatment to standard management with topical corticosteroids.


A case of idiopathic extracranial carotid artery pseudoaneurysm with a rare clinical course and pathological features.
Extracranial carotid artery aneurysms (ECAAs) are rare, with the etiology mainly classified as degeneration or dissection. Pseudoaneurysms in the region are even rarer and are seen following trauma, iatrogenic injury, or infection. We report a case of extracranial carotid artery pseudoaneurysm (pseudo-ECAA) with a rare clinical course and pathological features. A 58-year-old man presented with swelling and purpura on the left side of his neck after sneezing. Radiological examinations suggested a ruptured left common carotid artery aneurysm. The operative findings were consistent with a pseudoaneurysm. Pathological examination revealed disarrangement and degeneration of smooth muscle fibers in the media, in addition to scattered foci of mucoid accumulation and irregular-shaped cavitation in the medial extracellular matrix, raising the possibility of an intrinsic dysfunction of the vascular wall in the pathological process of pseudoaneurysm formation.


The Clinical Placement Consortium: where education and practice meet.
The process of planning the clinical rotations for nursing students can be challenging for both academia and the clinical service setting. This article will discuss a collaborative model that is used by one nursing community. Advantages and challenges will be presented from both views as well as lessons learned. The Clinical Placement Consortium (CPC) has served as a method to work toward a common goal of quality clinical experiences for all students.


Efficacy of Probiotics as Adjunctive Therapy to Nonsurgical Treatment of Peri-Implant Mucositis: A Systematic Review and Meta-Analysis.
Background: Peri-implant mucositis (PiM) is an inflammation of the soft tissues surrounding the dental implant and is the precursor of the destructive inflammatory peri-implantitis. PiM is usually reversible, but difficult to eradicate. Mechanical debridement (MD) is the conventional procedure to treat PiM although not enough to reach a complete resolution. Recently, probiotics have been considered in the treatment of peri-implant disease. Therefore, the aim of this systematic review and meta-analysis was to investigate the efficacy of the probiotic therapy combined with MD compared with MD alone or MD + placebo in patients with PiM. Methods: A search using electronic databases (MEDLINE, Science Direct databases, and Cochrane Central Register of Controlled Trials) and a manual search were performed up to November 2019 by two reviewers independently of each other. Eligible randomized controlled trials (RCTs) comparing MD + probiotic vs. MD were included. The quality assessment for all the selected RCTs was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. Probing depth reduction was selected as the primary outcome. Weighted mean difference (WMD) and 95% confidence interval (CI) were calculated for continuous outcomes, and odds ratio (OR) and 95% CI were calculated for dichotomous outcomes, using random effect models. This review was registered on the PROSPERO database (CRD42020213625). Results: Five eligible publications were included in this systematic review and four in the meta-analysis. As regards the implant, the WMD in the probing depth reduction between the test and control group was -0.12 mm [95% CI (-0.38, 0.14), p = 0.38], meaning that the adjunctive probiotic therapy was not improving PiM compared with MD alone or MD + placebo. The meta-analysis also showed no statistically significant results in the secondary outcomes (reduction of full mouth plaque index and full mouth bleeding on probing, absence of bleeding on probing at implant level, and changes in microorganism load and species). Conclusion: The findings of this systematic review and meta-analysis suggested that the additional use of probiotics did not improve the efficacy of MD in PiM treatment regarding clinical and microbial outcomes, at least in a short-term.


How to Measure Racism in Academic Health Centers.
Institutional racism is a set of practices and policies that disadvantage individuals not part of societies' dominant groups. In academic health centers (AHCs), institutional racism mediates structural racism; it is embedded in institutional policies, clinical practice, health professional training, and biomedical research. Measuring institutional racism in AHCs at the individual, intra-organizational, and extra-organizational levels renders visible how AHCs mediate structural racism by implementing policies that unfairly treat minority groups.


Using IP-videoconferencing systems in a surgery consulting.
In this paper we describe how to use IP-videoconferencing systems in medical surgery consulting. We started to think about how we could use special doctor's services without patients having to travel a long way. The answer to this question is that the information goes from one place to another, not the patient. First we had a pilot project, where we used the 3xISDN transmission rate and now we are using ATM. We have here in Satakunta a local area network between our Satakunta Central Hospital and the Health Care Center in Noormarkku and Kankaanpää, so we have very good environment to do this kind of research. Our network is quite fast, we can use the 10 Mbps bitrate and in this network there are no other activities in this moment, so there are not any interferences. There is a surgery specialist in the hospital and a doctor in the health care center with a patient. The specialist looks at the monitor, where there is a videopicture of the patient from the health care center. Then the specialist makes the treatment plan for the patient.


Glycation Reduces the Stability of ApoAI and Increases HDL Dysfunction in Diet-Controlled Type 2 Diabetes.
Hyperglycemia plays a key role in the pathogenesis of cardiovascular complications of diabetes. Type 2 diabetes mellitus (T2DM) is associated with high-density lipoprotein (HDL) dysfunction and increased degradation of apolipoprotein I (ApoAI). The mechanism(s) of these changes is largely unknown. To study the role of hyperglycemia-induced glycation on ApoAI kinetics and stability in patients with diet-controlled T2DM. 2H2O-metabolic labeling approach was used to study ApoAI turnover in patients with diet-controlled T2DM [n = 9 (5 F); 59.3 ± 8.5 years] and matched healthy controls [n = 8 (4 F); 50.7 ± 11.6 years]. The effect of Amadori glycation on in vivo ApoAI stability and the antioxidant and cholesterol efflux properties of HDL were assessed using a proteomics approach and in vitro assays. Patients with T2DM had increased turnover of ApoAI and impaired cholesterol efflux and antioxidant properties of HDL. Glycated hemoglobin was negatively correlated with the half-life of ApoAI and cholesterol efflux function of HDL. Proteomics analysis identified several nonenzymatic early (Amadori) glycations of ApoAI at lysine sites. The kinetics analysis of glycated and native ApoAI peptides in patients with T2DM revealed that glycation resulted in a threefold shorter ApoAI half-life. The 2H2O method allowed the detection of early in vivo impairments in HDL metabolism and function that were related to hyperglycemia-induced glycation of ApoAI in T2DM.


Anthropometric risk factors for elevated blood pressure in adolescents in Turkey aged 11-17.
To investigate the relationship between anthropometric parameters and elevated blood pressure in adolescents, we measured blood pressure (BP), height, weight, triceps skinfold (TSF) thickness, waist circumference (WC), and mid-upper-arm circumference (MUAC) in 2,860 student volunteers aged 11-17 years in Kayseri, Turkey. Waist-to-height ratio (WHtR), waist-to-arm-span ratio (WASR), body mass index (BMI), arm-fat area (AFA), and fat percentage (FP) were also calculated. Participants were divided into two groups: hypertensive [systolic blood pressure (SBP) or diastolic blood pressure (DBP) ≥ 95th percentiles, n = 246] and normotensives (SBP or DBP < 95th percentiles, n = 2614). Multiple logistic regression models were produced within these groups for the examined risk factors, and cutoff points were investigated for SBP or DBP ≥ 95th percentiles using receiver operating characteristics (ROC) analysis. BMI, WC, WHtR, WASR, MUAC, and BMI had statistically significant cutoffs among boys. Whereas BMI, WHtR, WASR, WC, MUAC, AFA, and TSF were statistically significant for girls younger than 15, only BMI and WC were statistically significant for participants older than 15. The independent risk factors for elevated BP were determined according to BMI and WC. Although several anthropometric measurements were significant in our participants, BMI and WC were significant among all participants irrespective of age and sex.


Advances in metered dose inhaler technology with the development of a chlorofluorocarbon-free drug delivery system.
The impending phaseout of chlorofluorocarbon (CFC)-containing metered dose inhalers (MDIs) has challenged the pharmaceutical industry to rethink and redesign many components of the technology involved in delivering asthma medication to the lungs. Along with the emergence of the first formulation using the nonozone-depleting propellant, hydrofluoroalkane (HFA) 134a to replace CFC propellants, advances in drug delivery technology have improved the performance characteristics of the MDI itself. Although MDIs have remained the mainstay of asthma therapy for 40 years, MDI technology still presents challenges. Some of the shortcomings of existing CFC MDIs affect the reliability of dosing. These challenges have been addressed in the development of the first CFC-free beta-agonist for the treatment of asthma. Airomir CFC-free (salbutamol sulfate; 3M Pharmaceuticals, St. Paul, MN), which is currently available in over 30 countries and was recently approved in the United States (Proventil HFA; Schering-Plough, Madison, NJ), incorporates numerous design and technological improvements which together with the introduction of CFC-free propellants mark the beginning of the next generation of asthma therapy. Although the new generation of CFC-free MDIs incorporates several improvements in dose reproducibility, these changes should be virtually transparent to the patient switching from a CFC MDI to a CFC-free MDI. What may be noticeable is a "softer puff," which is the result of valve and actuator redesign. The taste of the new CFC-free product may also be a little different yet totally acceptable to users.


[Conjunctival microcirculation and hemorheology in patients with venous occlusions of the retina].
Forty-two patients with branch vein or central retinal vein occlusion were enrolled in this randomized placebo-controlled study. We studied the influence of hemodilution therapy with hydroxyethyl-starch (HAES-steril) combined with pentoxifylline (Trental) for 6 months. In the bulbar conjunctiva, capillary red blood cell (RBC) velocities and vessel diameters and rheological parameters of hematocrit, erythrocyte aggregation and plasma viscosity were examined. In the hemodilution group we observed no changes in vessel diameter and a significant increase in RBC velocity after therapy. After 6 weeks the RBC velocity showed 30% higher values but there was no statistically significant difference. After hemodilution therapy hematocrit, erythrocyte aggregation and plasma viscosity were significantly different from those in the control group. After 6 weeks we observed significant differences only in erythrocyte aggregation. This examination verifies the positive influence of hemodilution therapy on microcirculation and hemorheology.


[Endogenous opioid peptides in cattle during pregnancy, birth and the newborn period].
The concentrations of beta-endorphin and met-enkephalin in plasma were investigated in cows in different stages of gestation, during parturition and in the early postpartum period as well as in their newborn calves. Plasma beta-endorphin concentrations were low in the early stages of pregnancy. In the last month of gestation beta-endorphin levels almost as high as during parturition were found. Therefore in cattle the antepartum increase in plasma beta-endorphin concentration is not linked to the onset of labour. Met-enkephalin levels in plasma of calving cows were higher than those in cows in the last month of gestation. For met-enkephalin a relation to the stress of parturition is more likely than for beta-endorphin. In conjunction with a cesarean section the concentrations of beta-endorphin and met-enkephalin in plasma increased during surgery. This increase is likely to be caused by surgery-related stress. Calves showed highest beta-endorphin concentrations immediately after delivery. One hour post natum beta-endorphin levels were markedly decreased and showed only minor changes thereafter. In calves born at term highest met-enkephalin concentrations were found immediately post natum with levels decreasing continuously over the first two days of life. Preterm calves showed lower met-enkephalin concentrations in plasma than those born at term. During the first hour post natum in preterm animals met-enkephalin levels in plasma even increased. A highly significant correlation existed between met-enkephalin levels and the degree of acidosis in calves. An antagonism between endogenous opioids and catecholamines in newborns is suggested.


Isolation, characterization, and expression patterns of a DMC1 homolog from the basidiomycete Pleurotus ostreatus.
Here we describe the isolation of a Pleurotus ostreatus gene PoDMC1. The predicted amino acid sequence of the oyster mushroom gene is 62% identical to the yeast DMC1 and 60% identical to human DMC1. The highest degree of amino acid identity (88%), however, was shown with Coprinus CoLIM15, a DMC1 homolog recently found in Coprinus cinereus. The exact matching of sizes and positions of most introns in both basidiomycete genes underlines the close relationship between these DMC1 orthologs. The RecA homolog DMC1 from yeast and its orthologs from other species have been reported to be meiosis specific and essential for sporulation. Here we show that PoDMC1 is exclusively expressed in the lamellae/basidiospore fraction of fruit bodies and not in somatic cells of fruiting bodies or in vegetative mycelium. Furthermore, the gene is not expressed in the lamellae/basidiospore fraction of a nonsporulating mutant of P. ostreatus. Since one of the major problems in cultivating the oyster mushroom is the abundant sporulation that causes allergic reactions in man, PoDMC1 could be an important target gene in constructing sporeless Pleurotus strains.


Vascular complications in Chuvash polycythemia.
Chuvash polycythemia is characterized by a homozygous 598C> T germline mutation in the von Hippel-Lindau gene ( VHL), upregulation of hypoxia-inducible factor-1alpha during normoxia, and resulting augmentation of erythropoietin and several other hypoxia-controlled genes. Although endemic to the Chuvash population of Russia, this mutation occurs worldwide and usually originates from a single ancient event. Matched-cohort and case-control analyses have shown that VHL 598C> T homozygosity is associated with lower peripheral blood pressures, varicose veins, vertebral hemangiomas, lower white blood cell and platelet counts, and elevated serum concentrations of vascular endothelial growth factor and plasminogen activator inhibitor-1. These studies have also shown associations with arterial and venous thrombosis, major bleeding episodes, cerebral vascular events, and premature mortality. Spinocerebellar hemangioblastomas, renal carcinomas, and pheochromocytomas typical of classical VHL tumor predisposition syndrome have not been found, and no increased risk of cancer has been demonstrated. Retrospective analyses among patients with Chuvash polycythemia have not shown benefit for therapy with phlebotomy or aspirin, but these and other modes of therapy should be studied prospectively. Further investigation of the vascular complications of Chuvash polycythemia may increase our fundamental knowledge of thrombophilia, bleeding diatheses, and protection from cancer.


The diagnostic value of compression ultrasonography in patients with suspected recurrent deep vein thrombosis.
Diagnosis of recurrent deep-vein thrombosis (DVT) is difficult because of limitations in distinguishing acute from old thrombi. In the past, an ultrasound method for diagnosis of recurrent ipsilateral DVT was developed, which relies on repeated measurements of the diameters of the common femoral and popliteal veins. To assess the safety of withholding anticoagulation from patients with improved or stable compression vein diameters, 205 consecutive patients presenting with suspected recurrent ipsilateral DVT were evaluated. The vein diameter was measured under compression with the transducer and compared with earlier ultrasound results. Patients with stable or improved ultrasound findings had repeat ultrasound assessments after 2 (+/- 1) and 7 (+/- 1) days. Patients with repeatedly normal ultrasound results were followed-up for six months to determine the incidence of symptomatic recurrent venous thromboembolism. Of the 205 patients, 153 had stable or improved ultrasound findings. Repeat ultrasound assessment became abnormal in 3, and recurrence was confirmed by venography in all. A six months follow-up was done in the remaining 150 patients with repeatedly normal ultrasound tests and showed 2 (1.3%; 95% CI, 0.02 to 4.7%) confirmed non-fatal venous thromboembolic complications. The positive predictive value of a stable or improved ultrasound was 90% (95% CI, 77 to 97%). In conclusion, it is safe to withhold anticoagulant treatment from patients with suspected recurrent ipsilateral DVT in whom compression ultrasonography showed improved or stable vein diameters.


Who gets to talk: Interruptive behaviors in engager and non-engager intake sessions of psychodynamic psychotherapy.
Objectives: Many clients do not return after intake. We speculated that similarities between therapists and clients in terms of interruptive behaviors would predict whether clients returned after intake (engaged).Methods: Trained judges coded therapist and client interruptive behaviors (interruptions, overlaps of speech, and sentence completions) for one engager (client returned for at least 10 sessions) and one non-engager (client did not return after intake) adult clients for each of 25 doctoral student therapists in individual psychodynamic psychotherapy.Results: Although all interruptive behaviors were infrequent, clients were most likely to return after intake (engage) when they interrupted at about the same amount as their therapists, overlapped less than their therapists, and completed sentences more than their therapists.Conclusions: Interruptions, sentence completions, and overlaps of speech are types of interruptive behavior that appear to have different relational consequences.


Diffractive-refractive optics: low-aberration Bragg-case focusing by precise parabolic surfaces.
Based on analytical formulae calculations and ray-tracing simulations a low-aberration focal spot with a high demagnification ratio was predicted for a diffractive-refractive crystal optics device with parabolic surfaces. Two Si(111) crystals with two precise parabolic-shaped grooves have been prepared and arranged in a dispersive position (+,-,-,+) with high asymmetry. Experimental testing of the device at beamline BM05 at the ESRF provided a focal spot size of 38.25 microm at a focal distance of 1.4 m for 7.31 keV. This is the first experiment with a parabolic-shaped groove; all previous experiments were performed with circular grooves which introduced extreme aberration broadening of the focal spot. The calculated and simulated focal size was 10.8 microm at a distance of 1.1 m at 7.31 keV. It is assumed that the difference between the measured and calculated/simulated focal spot size and focal distance is due to insufficient surface quality and to alignment imperfection.


Coherent backscattering in lithium niobate whispering-gallery-mode resonators.
Splitting of high-Q whispering gallery modes into a doublet of counterpropagating modes was observed in a resonator fabricated from LiNbO(3). An energy-transfer rate of 10 MHz was calculated by measuring the frequency detuning of the doublet structure. The splitting rate is also used to calculate the maximum variation in the internal index of refraction over one wavelength, which is of the order of 10(-7). This shows that the mechanical process used to fabricate whispering-gallery-mode resonators from LiNbO(3) is sufficient to achieve material-limited quality factors.


A novel approach for localization of the continuous protein antigenic sites by comprehensive synthetic surface scanning: antibody and T-cell activity to several influenza hemagglutinin synthetic sites.
The determination in this laboratory of the complete antigenic structures of several proteins initially relied on a multi-approach complex chemical strategy and revealed that antigenic sites are surface locations which could be either 'continuous' or 'discontinuous' in architecture. More recently, we introduced a simplified comprehensive synthetic approach for the localization of the continuous antigenic sites of a protein. The approach depends on the synthesis of consecutive overlapping peptides, of uniform size and overlaps, and encompass the entire protein chain, from the beginning to the end. The latter approach is rather costly and labor-intensive, especially when applied to large protein molecules. All these studies showed, however, that protein antigenic sites occupy surface areas on a protein molecule. In order to render the determination of protein antigenic sites more feasible within a reasonable period of time, we considered that only the protein surface needs to be examined. Thus, for a protein of known three-dimensional structure, the protein surface can be readily screened for the continuous antigenic sites by the systematic synthesis and examination of immunochemical activity of all exposed segments of the protein. We have applied this approach here to influenza A virus hemagglutinin. Twelve peptides (11 reported for the first time here, and one reported previously), representing continuous surface segments of the molecule, have so far been synthesized, purified, characterized and their immunochemical activity studied. The peptides were found to bind anti-viral antibodies raised in outbred mice and antibodies in human sera from individuals that had suffered a recent influenza A infection. In one mouse strain (Balb/c; H-2d) so far examined, several of the peptides stimulated an in vitro proliferative response of T cells from virus (X-31)- primed mice. Finally, antisera to the peptides were raised in mice and, as expected, were found to bind to intact virus. In most cases, anti-peptide antibodies, did not bind disrupted virus. These studies indicate that protein 'continuous' antigenic sites can be localized by systematic synthetic scanning of the surface. It is emphasized that the approach is useful only for the localization of 'continuous' sites. The results also reveal that the antigenic structure of influenza virus hemagglutinin is more complex than has hitherto been suspected.


Lawsone derivatives target the Wnt/β-catenin signaling pathway in multidrug-resistant acute lymphoblastic leukemia cells.
Multidrug resistance (MDR) represents a serious problem in cancer treatment. One strategy to overcome this obstacle is to identify agents that are selectively lethal to MDR cells. The aim of this study was to discover novel compounds against MDR leukemia and to determine the molecular mechanisms behind collateral sensitivity. A library of 1162 compounds was tested against parental, drug-sensitive CCRF-CEM cells using the resazurin assay. A total of 302 compounds showed reasonable activity (less than 50% cell viability). Eleven out of 30 lawsone derivatives revealed considerable collateral sensitivity in MDR P-glycoprotein (Pgp)-overexpressing CEM/ADR5000 cells. They reduced β-catenin activity in a Wnt/β-catenin reporter cell line. Their activities significantly correlated with apolar desolvation (R = 0.819). Compound (1) (3-hydroxy-1,4-dioxo-N-phenyl-naphthalene-2-carboxamide) was the most active compound and dose-dependently down-regulated protein expression of β-catenin, c-MYC, Pgp and Frizzled 7. By molecular docking, we predicted that compound (1) bound to the palmitoyl-binding groove of the cysteine-rich domain of Frizzled-7 and Frizzled-8. Compound (1) neither stimulated ATPase activity of Pgp nor reactive oxygen species generation, both of which have been previously described as possible mechanisms of collateral sensitivity. Instead, we found that Wnt/β-catenin signaling was selectively inhibited in CEM/ADR5000 cells, but not in CCRF-CEM cells. In conclusion, we found for the first time that the inhibition of Wnt/β-catenin signaling may represent a novel molecular mechanism of collateral sensitivity in MDR cells. Wnt/β-catenin signaling, therefore, represents a potential therapeutic target for the selective killing of Pgp-mediated MDR.


Ginsenoside Rh2 induces apoptosis and inhibits epithelial-mesenchymal transition in HEC1A and Ishikawa endometrial cancer cells.
Anticancer effect of ginsenoside Rh2 has been found in various cancer cells. However, the anticancer effect of Rh2 in endometrial cancer cells is still unclear. We aimed to determine the anticancer effect of Rh2 and elucidate its mechanism in endometrial cancer cells, using HEC1A and Ishikawa cell lines, in this study. Cell proliferation was assessed by MTT assay, and cell apoptosis was visualized by TdT mediated-dUTP Nick-End Labeling (TUNEL) method. Western blot were performed to detect the expression of apoptosis and epithelial-mesenchymal transition (EMT)-related proteins. Further, cell invasion and migration assays were conducted to estimate cell migration and invasion abilities. Rh2 treatment significantly suppressed cell proliferation in HEC1A and Ishikawa cells, in dose-dependent manner. Levels of cleaved poly adenosine diphosphate-ribose polymerase (PARP) and cleaved caspase-3 increased in the both cell lines with Rh2 compared with control. In Western blotting analysis after Rh2 treatment, the expression of E-cadherin increased, while the expression of EMT-related proteins including vimentin, TGF-β, and Snail markedly decreased in both cell lines. The cell invasion and migration assays results indicated that Rh2 inhibited the cell invasion and migration in HEC1A cells. Our findings suggested that Rh2 exerts the anticancer effect in endometrial cancer cells through the apoptosis induction and EMT inhibition.


Hydrogen adsorption on inorganic benzenes decorated with alkali metal cations: theoretical study.
Hydrogen adsorption on different benzenes, both organic and inorganic, decorated with Li cations (Li+) was systematically studied by using quantum chemistry techniques. Our calculations demonstrate that Li+-decoration enhances the hydrogen storage ability of the complexes. MP2 calculations reveal that one to five hydrogen molecules per Li+ have high adsorption energies (Ead), up to -4.77 kcal mol-1, which is crucial for effective adsorption/desorption performance. The assessed hydrogen capacity of studied complexes is in the range of 10.0-10.6 wt%. SAPT2 calculations confirmed that induction and electrostatic interactions play the major role for H2 adsorption of the investigated systems, whereas London dispersion contributes to Ead moderately only in the cases of large number of hydrogen molecules adsorbed. Independent gradient model (IGM) analysis showed that there exists non-covalent bonding between Li+ and H2. The obtained van't Hoff desorption temperatures substantially exceed the temperature of liquid nitrogen. Ab initio molecular dynamics simulations confirmed the stability of the studied complexes. Our investigations establish the high potential of the studied complexes for usage in systems for hydrogen storage.


Interventions to address mental health issues in healthcare workers during infectious disease outbreaks: A systematic review.
Considering the importance of evidence on interventions to tackle mental health problems in healthcare workers (HCWs) during pandemics, we conducted a systematic review, aiming to identify and summarize the implemented interventions to deal with mental health issues of HCWs during infectious disease outbreaks and report their effectiveness. Web of Science, PubMed, Cochrane, Scopus, CINAHL and PsycInfo electronic databases were searched until October 2nd, 2020. Primary-data articles, describing any implemented interventions and their effectiveness were considered pertinent. Studies were screened according to the inclusion/exclusion criteria and subsequently data extraction was performed. Twenty-four articles, referring to SARS, Ebola, Influenza AH1N1 and COVID-19 were included. Interventions addressing mental health issues in HCWs during pandemics/epidemics were grouped into four categories: 1) informational support (training, guidelines, prevention programs), 2) instrumental support (personal protective equipment, protection protocols); 3) organizational support (manpower allocation, working hours, re-organization of facilities/structures, provision of rest areas); 4) emotional and psychological support (psychoeducation and training, mental health support team, peer-support and counselling, therapy, digital platforms and tele-support). These results might be helpful for researchers, stakeholders, and policymakers to develop evidence-based sustainable interventions and guidelines, aiming to prevent or reduce the immediate and long-term effect of pandemics on mental health status of HCWs.


Multiple statistical analysis techniques corroborate intratumor heterogeneity in imaging mass spectrometry datasets of myxofibrosarcoma.
MALDI mass spectrometry can generate profiles that contain hundreds of biomolecular ions directly from tissue. Spatially-correlated analysis, MALDI imaging MS, can simultaneously reveal how each of these biomolecular ions varies in clinical tissue samples. The use of statistical data analysis tools to identify regions containing correlated mass spectrometry profiles is referred to as imaging MS-based molecular histology because of its ability to annotate tissues solely on the basis of the imaging MS data. Several reports have indicated that imaging MS-based molecular histology may be able to complement established histological and histochemical techniques by distinguishing between pathologies with overlapping/identical morphologies and revealing biomolecular intratumor heterogeneity. A data analysis pipeline that identifies regions of imaging MS datasets with correlated mass spectrometry profiles could lead to the development of novel methods for improved diagnosis (differentiating subgroups within distinct histological groups) and annotating the spatio-chemical makeup of tumors. Here it is demonstrated that highlighting the regions within imaging MS datasets whose mass spectrometry profiles were found to be correlated by five independent multivariate methods provides a consistently accurate summary of the spatio-chemical heterogeneity. The corroboration provided by using multiple multivariate methods, efficiently applied in an automated routine, provides assurance that the identified regions are indeed characterized by distinct mass spectrometry profiles, a crucial requirement for its development as a complementary histological tool. When simultaneously applied to imaging MS datasets from multiple patient samples of intermediate-grade myxofibrosarcoma, a heterogeneous soft tissue sarcoma, nodules with mass spectrometry profiles found to be distinct by five different multivariate methods were detected within morphologically identical regions of all patient tissue samples. To aid the further development of imaging MS based molecular histology as a complementary histological tool the Matlab code of the agreement analysis, instructions and a reduced dataset are included as supporting information.


Delirium-associated disulfiram and ethanol interactions.
Disulfiram, an agent used for the treatment of alcohol dependence, can exacerbate psychiatric syndromes (including psychosis, catatonia, delirium, depression, and mania) after extended use. However, delirium has yet to be reported following the short-term use of disulfiram in the setting of alcohol use. We report a case with a neuropsychiatric presentation and discuss the prevention and the progression of delirium associated with an interaction of disulfiram and ethanol. We report the case of a 51-year-old woman who developed disorganized speech, diminished communication, a decrease in appetite, and thoughts of suicide 10 days after she began taking disulfiram (250 mg/day), to which she added 1 glass of alcoholic beverage for 2 days. Delirium developed in association with an interaction between disulfiram and alcohol. The patient met DSM-IV criteria for major depressive disorder, alcohol dependence, and delirium. Neuropsychiatric manifestations may develop in association with co-administration of disulfiram and alcohol; timely recognition and treatment are recommended.


EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses.
Relapses, exacerbations or attacks of multiple sclerosis are the dominating feature of relapsing-remitting multiple sclerosis (MS), but are also observed in patients with secondary progressive MS. High-dose methylprednisolone is the routine therapy for relapses at present, but other treatments are also in current use. The objective of the task force was to review the literature on treatment of MS relapses to provide evidence-based treatment recommendations. Review was carried out on the literature with classification of evidence according to the EFNS guidelines for scientific task forces. Short-term, high-dose methylprednisolone treatment should be considered for the treatment of relapses of MS (level A recommendation). The optimal glucocorticoid treatment regimen, in terms of clinical efficacy and adverse events, remains to be established. A more intense, interdisciplinary rehabilitation programme should be considered as this probably further improves recovery after treatment with methylprednisolone (level B recommendation). Plasma exchange is probably efficacious in a subgroup of patients with severe relapses not responding to methylprednisolone therapy, and should be considered in this patient subgroup (level B recommendation). There is a need for further randomized, controlled trials in order to establish the optimal treatment regimen for relapses of MS.


Glucose metabolism in the human cerebellum: an analysis of crossed cerebellar diaschisis in children with unilateral cerebral injury.
Using high-resolution positron emission tomography (PET), we have recently described the normal pattern of glucose utilization in 11 anatomical regions of the human cerebellum. In the present study, we evaluated the phenomenon of crossed cerebellar diaschisis in 40 patients (mostly children) with unilateral cerebral injury sustained at various periods of brain development. Diaschisis refers to a functional impairment at a remote site following injury to an anatomically connected area of brain and, presumably due to a loss of afferent input to the remote site. Of the 40 patients, 11 had sustained their cerebral injury prenatally, 7 in the perinatal period (+/- 24 hours of birth), and 22 postnatally (1 day to 15 years). Crossed cerebellar hypometabolism was seen in 22 patients; symmetric cerebellar metabolism was found in 16 subjects. The presence of crossed cerebellar hypometabolism was typically associated (75% of cases) with a postnatal injury, while symmetric cerebellar metabolism was seen only in patients with injury occurring prior to 4 weeks of age (13 of the 16 had prenatal or perinatal insults). A third pattern of cerebellar metabolism, consisting of paradoxical crossed cerebellar hypermetabolism, was seen in two patients; both had sustained their cerebral injury at 4 months of age. These findings suggest the presence of considerable plasticity, which is dependent on age at injury, in the cerebrocerebellar pathway of developing brain.


Metallochain cluster complexes and metallomacrocyclic triangles based on coordination bonds between palladium or platinum and diphosphinoacetylene ligands.
To explore the potential of the coordination chemistry of Pd and Pt halides with phosphinoacetylene ligands for the generation of novel, highly metallated organometallic coordination polymers, investigations on model compounds [MX2(PPh2 C identical to CPh)2] that exhibit trans-configured Pd centers and cis-configured Pt centers have been performed. The molecular structure of the trans-Pd complexes 2 (M = Pd, X = Br) and 5 (M = Pd, X = I) appeared suitable for the generation of linear materials, whereas the cis-Pt complex 6 (M = Pt, X = I) suggested the prospective formation of ring systems. The presence of acetylene moieties allowed for further increase of metal concentration by cluster formation with [Co2(CO)8]. Two novel bimetal cluster complexes 7 and 8 were obtained from 5 and 6, respectively, and these exhibit a bridging iodine ligand as an interesting structural motif leading to heterocyclic systems with M-I-Co-C-P skeletons (M = Pd or Pt). A similar approach with [Fe2(CO)9] led to the formation of several products, including an unusual Pd-Fe cluster-containing compound 10. The extension of the coordination strategy to rigid bis(phosphinoacetylene) ligands gave rise to strained ring systems. Surprisingly, for the cis-configured PtCl2 center, a rarely observed triangular structure 12 was obtained exclusively. The corresponding PtI2 analog, 13a rearranged over time to form a "ring-fused" system 13b with an extended BINAP-like ligand.


[Clinical application of negative-pressure wound therapy in split-thickness skin grafting at hard-to-fix sites].
Objective: To compare the clinical effects of continuous negative-pressure wound therapy (NPWT) and conventional pressure dressing at at hard-to-fix sites after split-thickness skin grafting. Methods: From September 2017 to August 2019, 129 patients who met the inclusion criteria and had spilt-thickness skin grafting at hard-to-fix sites were admitted to the First Affiliated Hospital of Air Force Medical University and included in this retrospective cohort study. The patients were divided into NPWT group (67 patients, 41 males and 26 females, aged (32±6) years) and conventional pressure dressing group (62 patients, 37 males and 25 females, aged (30±5) years) according to whether the hard-to-fix sites were applied with NPWT after spilt-thickness skin grafting. After debridement and spilt-thickness skin grafting at hard-to-fix sites in patients of 2 groups, the wounds of patients in conventional pressure dressing group were applied with conventional pressure bandaging after being filled with dry gauze; for the wounds of patients in NPWT group, the semi-permeable membrane was pasted and sealed for continuous negative pressure suction after filled with dry gauze and placed the drainage foam or drainage tube, with the negative pressure ranging from -16.6 to -9.9 kPa. The bandage was opened during the first dressing change on the 5th day after surgery in NPWT group and on the 7th day after surgery in conventional pressure dressing group. The skin graft surviving area and proportion, the area and proportion of hematoma, the incidence of common complications of skin graft were observed and calculated. The times of postoperative dressing change and the length of hospital stay were counted. Data were statistically analyzed with two independent sample t test, Cochran & Cox approximate t test, chi-square test, and Fisher's exact probability test. Results: (1) At the first dressing change, the skin graft surviving area of patients in NPWT group was (420±94) cm(2), which was significantly larger than (322±97) cm(2) in conventional pressure dressing group (t'=12.33, P<0.01); the skin graft surviving area proportion of patients in NPWT group was (97.0±2.3)%, which was significantly higher than (74.4±4.8)% in conventional pressure dressing group (t'=50.11, P<0.01). (2) At the first dressing change, the skin hematoma area of patients in conventional pressure dressing group was (31.7±10.1) cm(2), which was significantly larger than (3.2±0.7) cm(2) in NPWT group (t'=23.04, P<0.01); the skin hematoma area proportion of patients in conventional pressure dressing group was (7.3±2.3)%, which was significantly higher than (0.7±0.3)% in NPWT group (t'=76.21, P<0.01). (3) At the first dressing change, there was 1 case of skin movement and no case of skin graft edge tear in NPWT group with an incidence of 1.5% (1/67). In the conventional pressure dressing group, there were 4 cases of skin movement and 2 cases of skin graft edge tear with an incidence of 9.7% (6/62), P<0.05. The incidence of complication of skin graft of patients in NPWT group was significantly lower than that in conventional pressure dressing group (P<0.05). (4) The times of postoperative dressing change of patients in NPWT group was significantly less than that in conventional pressure dressing group (t=7.93, P<0.01). The postoperative length of hospital stay in NPWT group was significantly less than that in conventional pressure dressing group (t=11.71, P<0.01). Conclusions: Continuous NPWT can effectively promote wound healing, improve the survival rate of skin graft, reduce the incidence of complications after skin grafting, and shorten the length of hospital stay in split-thickness skin grafting at hard-to-fix sites.


Burns from a stove burst: analysis of 34 cases.
Burns continue to be a major environmental factor responsible for significant morbidity and mortality in developing countries and, in particular, burns due to stove bursts are a major problem. Two types of stoves are available in Pakistan: gas stoves and kerosene stoves. The state is considered of patients burned by stove bursts in general, and also with specific reference to 34 adult patients admitted with stove burns to our hospital in Pakistan. Various treatment options were used, and the patients' treatment and outcome are reported. The continued commercialization of such stoves, and especially of the gas stove, is is a cause of serious and permanent consequences that represent a danger for the population. Proper care should be observed when handling them because, as always, prevention is better than cure.


[Efficacy and side effects of methotrexate in the treatment of ectopic pregnancy].
To study the efficacy and side effects of methotrexate with different protocols in the treatment of ectopic pregnancy (EP). Total of 648 patients who had EP and were treated only with MTX were analysed. Patients were divided into six groups according to protocol: Group 1, 100 mg intravenously (IV); Group 2, 100 mg, IV, followed by citrovorum factor; Group 3, 20 mg, IV every day for five days; Group 4, 20 mg intramusculary (IM) every day for five days; Group 5, 75 mg, IV; Group 6, 75 mg, IM. The rates of repeated MTX injection in group 1 - 6 because of inadequate decrease of hCG were 23.3%, 25.0%, 21.4%, 20.6%, 24.4% and 22.4% respectively. Success rates were 87.4%, 85.4%, 90.5%, 92.6%, 86.3% and 91.4% respectively. Rates of liver dysfunction were 10.3%, 8.3%, 64.3%, 69.1%, 8.7% and 31.0%. Single-dose of 75 mg MTX IV injection may be the best regimen in the treatment of EP because of the same efficacy but the least side effects.


Are active children and young people at increased risk of injuries resulting in hospital admission or accident and emergency department attendance? Analysis of linked cohort and electronic hospital records in Wales and Scotland.
Children and young people (CYP) are encouraged to increase time spent being physically active, especially in moderate and vigorous intensity pursuits. However, there is limited evidence on the prospective association of activity levels with injuries resulting in use of hospital services. We examined the relationship between objectively-measured physical activity (PA) and subsequent injuries resulting in hospital admissions or accident and emergency department (A&E) attendances, using linked electronic hospital records (EHR) from a nationally representative prospective cohort of CYP in Wales and Scotland. We analysed accelerometer-based estimates of moderate to vigorous (MVPA) and vigorous PA (VPA) from 1,585 (777 [46%] boys) seven-year-old Millennium Cohort Study members, living in Wales or Scotland, whose parents consented to linkage of cohort records to EHRs up until their 14th birthday. Negative binomial regression models adjusted by potential individual, household and area-level confounders, were fitted to estimate associations between average daily minutes of MVPA, and VPA (in 10-minute increments), and number of injury-related hospital admissions and/or A&E attendances from age nine to 14 years. CYP spent a median of 59.5 and 18.1 minutes in MVPA and VPA/day respectively, with boys significantly more active than girls; 47.3% of children experienced at least one injury-related admission or A&E attendance during the study period. Rates of injury-related hospital admission and/or A&E attendance were positively associated with MVPA and VPA in boys but not in girls: respective adjusted incidence rate ratios (95% CI) for boys: 1.09 (1.01, 1.17) and 1.16 (1.00, 1.34), and for girls: 0.94 (0.86, 1.03) and 0.85 (0.69, 1.04). Boys but not girls who engage in more intense PA at age seven years are at higher risk of injury-related hospital admission or A&E attendance when aged nine to 14 years than their less active peers. This may reflect gender differences in the type and associated risks of activities undertaken. EHRs can make a useful contribution to injury surveillance and prevention if routinely augmented with information on context and setting of the injuries sustained. Injury prevention initiatives should not discourage engagement in PA and outdoor play given their over-riding health and social benefits.


Current State of the Surgical Treatment of Terminal Neuromas.
Painful terminal neuromas resulting from nerve injury following amputation are common. However, there is currently no universally accepted gold standard of treatment for this condition. A comprehensive literature review is presented on the treatment of terminal neuromas. Four categories of terminal neuroma surgical procedures are assessed: epineurial closure; nerve transposition with implantation; neurorrhaphy, and alternate target reinnervation. Significant patient and case studies are highlighted in each section, focusing on surgical technique and patient outcome metrics. Studies presented consisted of a PubMed search for "terminal neuromas," without year limitation. The current available research supports the use of implantation into muscle for the surgical treatment of terminal neuromas. However, this technique has several fundamental flaws that limit its utility, as it does not address the underlying physiology behind neuroma formation. Regenerative peripheral nerve interfaces and targeted muscle reinnervation are 2 techniques that seem to offer the most promise in preventing and treating terminal neuroma formation. Both techniques are also capable of generating control signals which can be used for both motor and sensory prosthetic control. Such technology has the potential to lead to the future restoration of lost limb function in amputees. Further clinical research employing larger patient groups with high-quality control groups and reproducible outcome measures is needed to determine the most effective and beneficial surgical treatment for terminal neuromas. Primary focus should be placed on investigating techniques that most closely approximate the theoretically ideal neuroma treatment, including targeted muscle reinnervation and regenerative peripheral nerve interfaces.


Nitroxidergic neurons in nuclei of the medulla oblongata in hypertensive and normotensive rats.
Distribution of nitroxidergic neurons and neuronal NO-synthase activity in certain medulla oblongata nuclei were studied in normotensive and hypertensive rats with different types of arterial hypertension. In rats with renovascular hypertension, neuronal NO-synthase activity markedly decreased in most nuclei 2 weeks after surgery, while the number of NO-positive cells did not change significantly; after 4 weeks, the percentage of NO-positive neuron markedly decreased and neuronal NO-synthase activity also slightly decreased. No further decrease in neuronal NO-synthase activity was observed 8 week after intervention, but the percentage of NO-neurons decreased compared to that in normotensive rats. In spontaneously hypertensive rats, changes in most nuclei were directed similarly to those observed in 8-week renovascular hypertension, but motor nuclei demonstrated less differentiated reaction to hypertension. In all cases, changes in the parameters observed in sensory nucleus (n. solitarius) appeared earlier and were more pronounced than in nuclei of the reticular formation related to bulbar vasomotor center.


Migraine--more than a headache: women's experiences of living with migraine.
In this qualitative study the aim was to explore the meaning of living with migraine. In-depth interviews were conducted with ten women about their experience of living with migraine. Halfway through the interview, the women drew a picture of what living with migraine is like, and the interview continued with the conversation being guided by the picture. The interviews were analyzed using a hermeneutic phenomenological method inspired by van Manen. The analysis revealed an essence "Being obliged to endure a life accompanied by an unpredictable and invisible disorder" and three themes "Being besieged by an attack", "Struggling in a life characterized by uncertainty" and "Living with an invisible disorder." Migraine is a debilitating disorder which accompanies life in the sense that it or the threat of its return is always present, and yet invisible to others. The struggle of enduring life with migraine is worsened by the feeling of having an invisible disorder and of being doubted. There is a need to increase the knowledge among healthcare professionals about what it means to live with migraine, something this qualitative study offers.


Musculoskeletal and Neurological Pain Symptoms Among Hospitalized COVID-19 Patients.
As the coronavirus disease 2019 pandemic continues to grow, its clinical manifestations are still emerging and are being widely investigated. However, the pain symptoms, including neurological and musculoskeletal pain symptoms, are still poorly understood. In this cross-sectional study, we investigated the prevalence of musculoskeletal and neurological pain symptoms among hospitalized coronavirus disease 2019 patients. Furthermore, the association of clinical and demographic factors with the prevalence of pain symptoms was also investigated. We included 182 hospitalized coronavirus disease 2019 patients with a mean age of 48.86 ± 13.98 yrs. Pain symptoms were reported by 61.54% patients (n = 112). Most common symptoms reported were generalized myalgia (n = 60, 32.96%), headache (n = 50, 27.47%), and low back pain (n = 41, 22.53%). Interestingly, neuropathic pain was present in 14 participants (7.69%). Logistic regression analysis revealed an association of pain symptoms with coronavirus disease 2019 severity, male sex, higher body mass index, and a history of addiction. Pain symptoms are common manifestation of coronavirus disease 2019. Generalized myalgia, headache, and low back pain are the three most common new-onset pain symptoms in hospitalized coronavirus disease 2019 patients. Further investigation of pain symptoms and their predictive factors are recommended, which may guide healthcare workers and policymakers to plan in this direction. Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. Upon completion of this article, the reader should be able to: (1) Understand common musculoskeletal and neurological pain symptoms among hospitalized COVID-19 patients; (2) Understand the basic etiopathogenesis of COVID-19 associated pain; and (3) Identify factors associated with presence of COVID-19 pain symptoms. Advanced. The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.