Chat GPT as a Neuro-Score Calculator: Analysis of a Large Language Model's Performance on Various Neurological Exam Grading Scales.
ChatGPT is a large language model artificial intelligence chatbot that has been applied to different aspects of the medical field. Our study aims to assess the quality of chatGPT to evaluate patients based on their exams for different scores including Glasgow Coma Scale (GCS), intracranial hemorrhage score (ICH), and Hunt & Hess (H&H) classification. We created batches of patient test cases with detailed neurological exams, totaling 20 cases and created variants of increasing complex phrasing of the test cases. Using ChatGPT, we assessed repeatability and quantified the errors, including the average error rate (AER) and magnitude of errors (AME). We repeated this process for the H&H and the ICH score using base cases. Specific prompts were created for each calculator. The GCS calculator on 10 base test cases had an AER/AME of 10%/0.150. The accuracy of ChatGPT decreased with increasing complexity; for example, in a variation where crucial information was missing, the AER was 45% for 20 cases. For H&H, AER/AME was 13%/0.13 and for ICH, AER/AME was 27.5%/0.325. Using a simple prompt resulted in a significantly higher error rate of 70%. ChatGPT demonstrates ability in this proof-of-concept experiment in evaluating neuroexams using established assessment scales including GCS, ICH, and H&H. However, it has limitations in accuracy and may "hallucinate" with complex or vague descriptions. Nonetheless, ChatGPT, has promising potential in medicine.


Effect of Sinai san decoction on the development of non-alcoholic steatohepatitis in rats.
To explore the effect of Sinai san decoction on the development of non-alcoholic steatohepatitis induced by CCL4 combined with a fat-rich diet in rats. Twenty-seven Sprague-Dawley rats were divided into three groups randomly: control group (n = 9), model group (n = 9) and treatment group (n = 9). The rats of model group and treatment group were given small dosage of CCL4 combined with a fat-rich diet, and those of control group were given normal diet. After four weeks of fat-rich diet feeding, the rats of treatment group were given Sinai san decoction. The serum levels of aminotransferase and lipid were measured, and the pathology of livers was observed by HE staining after the rats were sacrificed at eight weeks. The rats' livers presented the pathology of steatosis and inflammation with higher serum levels of ALT and AST in the model group. In the treatment group the serum ALT and AST levels decreased significantly and were close to the control group. The hepatic inflammation scores also decreased markedly, but were still higher than those of control group. And the degree of hepatocyte steatosis was similar to that of model group. Sinai san decoction may ameliorate the hepatic inflammation of rats with steatohepatitis induced by small dosage of CCL4 combined with a fat-rich diet, but does not prevent the development of hepatocyte steatosis.


Atrial natriuretic factor: an overview.
Heart atrial muscle cells in mammals are differentiated for a contractile as well as a secretory function. Through the latter, the heart plays an endocrine role; it synthesizes, stores, and releases a group of peptides collectively referred to as atrial natriuretic factor (ANF). ANF has natriuretic and hypotensive properties as well as an inhibitory effect on aldosterone and renin secretion. Thus ANF intervenes in the short- and long-term regulation of water and electrolyte balance and blood pressure. It is expected that further research in this new field will provide fresh insights into the pathophysiology of several important clinical entities and in the development of new pharmaceutical products.


Irisin levels are lower in young amenorrheic athletes compared with eumenorrheic athletes and non-athletes and are associated with bone density and strength estimates.
Irisin and FGF21 are novel hormones implicated in the "browning" of white fat, thermogenesis, and energy homeostasis. However, there are no data regarding these hormones in amenorrheic athletes (AA) (a chronic energy deficit state) compared with eumenorrheic athletes (EA) and non-athletes. We hypothesized that irisin and FGF21 would be low in AA, an adaptive response to low energy stores. Furthermore, because (i) brown fat has positive effects on bone, and (ii) irisin and FGF21 may directly impact bone, we hypothesized that bone density, structure and strength would be positively associated with these hormones in athletes and non-athletes. To test our hypotheses, we studied 85 females, 14-21 years [38 AA, 24 EA and 23 non-athletes (NA)]. Fasting serum irisin and FGF21 were measured. Body composition and bone density were assessed using dual energy X-ray absorptiometry, bone microarchitecture using high resolution peripheral quantitative CT, strength estimates using finite element analysis, resting energy expenditure (REE) using indirect calorimetry and time spent exercising/week by history. Subjects did not differ for pubertal stage. Fat mass was lowest in AA. AA had lower irisin and FGF21 than EA and NA, even after controlling for fat and lean mass. Across subjects, irisin was positively associated with REE and bone density Z-scores, volumetric bone mineral density (total and trabecular), stiffness and failure load. FGF21 was negatively associated with hours/week of exercise and cortical porosity, and positively with fat mass and cortical volumetric bone density. Associations of irisin (but not FGF21) with bone parameters persisted after controlling for potential confounders. In conclusion, irisin and FGF21 are low in AA, and irisin (but not FGF21) is independently associated with bone density and strength in athletes.


Nomenclature of immunoglobulin A and other proteins of the mucosal immune system. IUIS/WHO subcommittee on IgA nomenclature.
The predominant immunoglobulin found in exocrine secretions of humans and most other mammals is secretory IgA, a polymeric form of IgA containing an additional glycoprotein chain designated "secretory component". In this article recommended abbreviations are proposed for the following forms of human IgA and other proteins of related interest: secretory IgA, secretory IgM, secretory component, polymeric immunoglobulin receptor, polymeric IgA, monomeric IgA, IgA subclass 1, IgA subclass 2, A2 allotype marker 1, and A2 allotype marker 2.


Flankophile: a bioinformatic pipeline for prokaryotic genomic synteny analysis.
The Flankophile pipeline enables the analysis and visualization of flanking regions of prokaryotic sequences of interest on large data sets in one step and in a consistent manner. A specific tool for flanking region analysis with automated visualization has not been developed before, and Flankophile will make flanking region analysis easier and accessible to more people. Flankophile will be especially useful in the field of genomic epidemiology of acquired antimicrobial resistance genes. Here, information from flanking region sequences can be instrumental in rejecting or supporting the possibility of a recent common source of the same resistance gene found in different samples.


Prenatal Stress Alters the Development of Socioemotional Behavior and Amygdala Neuron Excitability in Rats.
Prenatal stress (PS) is a risk factor for neurodevelopmental disorders with diverse ages of onset and socioemotional symptoms. Some PS-linked disorders involve characteristic social deficits, such as autism spectrum disorders and schizophrenia, but PS also promotes anxiety disorders. We propose the diversity of symptoms following PS arises from perturbations to early brain development. To this end, we characterized the effects of PS on the developmental trajectory of physiology of the amygdala, a late-developing center for socioemotional control. We found that PS dampened socioemotional behavior and reduced amygdala neuron excitability in offspring during infancy (at postnatal days (P)10, 14, 17 and 21), preadolescence (day 28), and adulthood (day 60). PS offspring in infancy produced fewer isolation-induced vocalizations and in adulthood exhibited less anxiety-like behavior and deficits in social interaction. PS neurons had a more hyperpolarized resting membrane potential from infancy to adulthood and produced fewer action potentials. Moreover, adult amygdala neurons from PS animals expressed larger action potential afterhyperpolarizations and H-current relative to controls, further limiting excitability. Our results suggest that PS can suppress socioemotional behavior throughout development and produce age-specific alterations to amygdala physiology.


Variant histology in nodular lymphocyte predominant Hodgkin lymphoma in an adult population: disease investigations and characteristics from a retrospective cohort.
A subset of variant histological patterns of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) has been associated with advanced disease stage and increased recurrence risk. Histopathology reports on core needle (CNB) and/or surgical excision biopsies (SEB) for 33 adult patients with NLPHL were examined for variant histology prevalence and association with disease stage and clinical outcome. Variant histological pattern was present in 13/33 patients (39%). Obtained tissue was inadequate for diagnosis in 1/23 (4.3%) cases of CNB. Variant histology was associated with stage IV disease at presentation (p<0.001). While SEB should be the procedure of choice in workup of patients for a diagnosis of NLPHL, CNB is an alternate option when SEB is contraindicated or difficult to undertake. Diagnostic reports should specifically note presence of variant histological patterns. Although late-stage disease was associated with progression or recurrence, overall prognosis is excellent for patients with NLPHL.


Evaluation of HIV/AIDS patients' knowledge on antiretroviral drugs.
Lack of information on antiretroviral drugs or the misunderstanding of available information can facilitate incorrect use of such drugs. This can result in non-adherence to the prescribed regimen, leading to a great possibility of a therapeutic failure. The aim of this study was to know which information HIV/AIDS patients, who receive their medicines at the pharmacy of a reference hospital in the northeast Brazil, have on the drugs they use, the source of this information and whether there is a need for additional information. A total of 195 HIV/AIDS patients, who were using either zidovudina + lamivudina 300+150 mg (AZT+3TC), efavirenz 600 mg (EFZ) or lopinavir/ritonavir 133.33/33 mg (LPV/r), were interviewed. The mean age was 41 years (SD = 9.55) and 70.8% were males. Of the total, 55.4% didn't know the effect of the drug in the organism; 35.9% were unaware of the necessity of taking antiretroviral drugs for the rest of their lives; only 14.4% knew how to proceed when a dosage was missed; 22.1% said they could die and the same number of individuals believed in aggravation of the disease in case of treatment interruption. The majority, 68.2%, considered it very necessary to receive drug information. The results show that there is an apparent lack of general information among users of antiretroviral drugs, and at the same time a need for it. It is necessary that all professionals involved in the health care of the patients agree that an efficient supply of information on prescribed drugs is an ethical component of the treatment that favors and fosters its adherence.


Emerging Pathogen Threats in Transfusion Medicine: Improving Safety and Confidence with Pathogen Reduction Technologies.
Emerging infectious disease threats are becoming more frequent due to various social, political, and geographical pressures, including increased human-animal contact, global trade, transportation, and changing climate conditions. Since blood products for transfusion are derived from donated blood from the general population, emerging agents spread by blood contact or the transfusion of blood products are also a potential risk. Blood transfusions are essential in treating patients with anemia, blood loss, and other medical conditions. However, these lifesaving procedures can contribute to infectious disease transmission, particularly to vulnerable populations. New methods have been implemented on a global basis for the prevention of transfusion transmissions via plasma, platelets, and whole blood products. Implementing proactive pathogen reduction methods may reduce the likelihood of disease transmission via blood transfusions, even for newly emerging agents whose transmissibility and susceptibility are still being evaluated as they emerge. In this review, we consider the Mirasol PRT system for blood safety, which is based on a photochemical method involving riboflavin and UV light. We provide examples of how emerging threats, such as Ebola, SARS-CoV-2, hepatitis E, mpox and other agents, have been evaluated in real time regarding effectiveness of this method in reducing the likelihood of disease transmission via transfusions.


Safety and efficacy of oral fexofenadine in children with seasonal allergic rhinitis--a pooled analysis of three studies.
Allergic rhinitis is one of the most common clinical conditions in children; however, data regarding the safety of antihistamines in children with seasonal allergic rhinitis are limiting. To evaluate the safety and efficacy of fexofenadine in children with seasonal allergic rhinitis, data were pooled from three, double-blind, randomized, placebo-controlled, parallel-group, 2-week trials in children (6-11 year) with seasonal allergic rhinitis. All studies assessed fexofenadine HCl 30 mg b.i.d.; two studies included fexofenadine HCl at 15 and 60 mg b.i.d. Patients (and investigators) reported any adverse events during the trial. Physical examinations, including measurements of vital signs and laboratory tests, were performed. Efficacy assessments (total symptom score and individual symptom scores) were evaluated. Exposure to fexofenadine HCl 30 mg b.i.d. and to any fexofenadine dose exceeded 10,000 and 17,000 patient days, respectively. Incidences of adverse events, and discontinuations because of adverse events, were low and similar across treatment groups. In the placebo group, 24.4% of subjects reported adverse events compared with 24.1% for fexofenadine HCl 30 mg b.i.d., and 28.4% for all fexofenadine-treated groups. The most common adverse event overall was headache (4.3% placebo; 5.8% fexofenadine HCl 30 mg b.i.d.; and 7.2% any fexofenadine doses). Treatment-related adverse events were similar across treatment groups with no sedative effects. Fexofenadine HCl 30 mg b.i.d. was significantly superior to placebo in reducing the total symptom score and all individual seasonal allergic rhinitis symptoms, including nasal congestion (p < 0.05). Fexofenadine, at doses of up to 60 mg b.i.d., is safe and non-sedating, and fexofenadine HCl 30 mg b.i.d. effectively reduces all seasonal allergic rhinitis symptoms in children aged 6-11 years.


Protection of Spanish Ibex (Capra pyrenaica) against Bluetongue virus serotypes 1 and 8 in a subclinical experimental infection.
Many wild ruminants such as Spanish ibex (Capra pyrenaica) are susceptible to Bluetongue virus (BTV) infection, which causes disease mainly in domestic sheep and cattle. Outbreaks involving either BTV serotypes 1 (BTV-1) and 8 (BTV-8) are currently challenging Europe. Inclusion of wildlife vaccination among BTV control measures should be considered in certain species. In the present study, four out of fifteen seronegative Spanish ibexes were immunized with a single dose of inactivated vaccine against BTV-1, four against BTV-8 and seven ibexes were non vaccinated controls. Seven ibexes (four vaccinated and three controls) were inoculated with each BTV serotype. Antibody and IFN-gamma responses were evaluated until 28 days after inoculation (dpi). The vaccinated ibexes showed significant (P<0.05) neutralizing antibody levels after vaccination compared to non vaccinated ibexes. The non vaccinated ibexes remained seronegative until challenge and showed neutralizing antibodies from 7 dpi. BTV RNA was detected in the blood of non vaccinated ibexes from 2 to the end of the study (28 dpi) and in target tissue samples obtained at necropsy (8 and 28 dpi). BTV-1 was successfully isolated on cell culture from blood and target tissues of non vaccinated ibexes. Clinical signs were unapparent and no gross lesions were found at necropsy. Our results show for the first time that Spanish ibex is susceptible and asymptomatic to BTV infection and also that a single dose of vaccine prevents viraemia against BTV-1 and BTV-8 replication.


Glucocorticoid-resistant B-lymphoblast cell line derived from the Bolivian squirrel monkey (Saimiri boliviensis boliviensis).
The goal of the study reported here was to develop a continuous cell line from the squirrel monkey that expresses the species-specific phenotype of impaired sensitivity to glucocorticoids. Thirty milliliters of blood from a male Bolivian squirrel monkey (Saimiri boliviensis boliviensis) was fractionated, and the buffy coat was obtained and incubated in the presence of B95-8 cell-conditioned medium, an abundant source of Epstein-Barr virus (EBV), and 2 micrograms of cyclosporin A/ml. Cell growth was detected within 8 weeks, after which the cells were cloned by use of the limiting dilution method. One clone (4D8) was characterized in detail. The chromosomal count and G-banding pattern confirmed that the cells were of Bolivian squirrel monkey origin. The B-cell origin of these cells was indicated by electron microscopic analysis and was confirmed by expression of CD20. The cells stained strongly for LMP1, a marker of latent EBV infection, and occasionally for the lytic infection marker ZEBRA (BZLF1). The responsiveness of clone 4D8 cells to glucocorticoids was determined by comparing the effects of dexamethasone on cell growth and the induction of a glucocorticoid-inducible mRNA in 4D8 cells with the effects on a human EBV-transformed B-lymphoblast cell line (HL). Dexamethasone inhibited the growth of HL cells, with IC50 of approximately 9 nM, but had no effect on the growth of 4D8 cells. The induction of FK506-binding protein FKBP51 mRNA by dexamethasone was also significantly blunted in 4D8 cells. Thus, we have developed and characterized a squirrel monkey lymphoblastic cell line derived by transformation of B-lymphocytes with EBV; the cell line has diminished growth and transcriptional responses to glucocorticoids.


Decreased content of leaf ferredoxin changes electron distribution and limits photosynthesis in transgenic potato plants.
A complete ferredoxin (Fd) cDNA clone was isolated from potato (Solanum tuberosum L. cv Desiree) leaves. By molecular and immunoblot analysis, the gene was identified as the leaf-specific Fd isoform I. Transgenic potato plants were constructed by introducing the homologous potato fed 1 cDNA clone as an antisense construct under the control of the constitutive cauliflower mosaic virus 35S promoter. Stable antisense lines with Fd contents between 40% and 80% of the wild-type level were selected by northern- and western-blot analysis. In short-term experiments, the distribution of electrons toward their stromal acceptors was altered in the mutant plants. Cyclic electron transport, as determined by the quantum yields of photosystems I and II, was enhanced. The CO2 assimilation rate was decreased, but depending on the remaining Fd content, some lines showed photoinhibition. The leaf protein content remained largely constant, but the antisense plants had a lower total chlorophyll content per unit leaf area and an increased chlorophyll a/b ratio. In the antisense plants, the redox state of the quinone acceptor A in photosystem II (QA) was more reduced than that of the wild-type plants under all experimental conditions. Because the plants with lower Fd amounts reacted as if they were grown under a higher light intensity, the possibility that the altered chloroplast redox state affects light acclimation is discussed.


[From gene to disease; from polycystines to polycystic kidney disease].
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease that results in multiple cysts in the kidneys and other organs and leads to endstage renal failure relatively late in life. The disease results from mutations in one of two independently segregating genes that under normal conditions produce polycystines. Polycystines are membrane proteins that form a complex involved in signal transduction in epithelial cells. Genetic heterogeneity explains in part the various ADPKD phenotypes.


Why do dogs (Canis familiaris) select the empty container in an observational learning task?
Many argue that dogs show unique susceptibility to human communicative signals that make them suitable for being engaged in complex co-operation with humans. It has also been revealed that socially provided information is particularly effective in influencing the behaviour of dogs even when the human's action demonstration conveys inefficient or mistaken solution of task. It is unclear, however, how the communicative nature of the demonstration context and the presence of the human demonstrator affect the dogs' object-choice behaviour in observational learning situations. In order to unfold the effects of these factors, 76 adult pet dogs could observe a communicative or a non-communicative demonstration in which the human retrieved a tennis ball from under an opaque container while manipulating another distant and obviously empty (transparent) one. Subjects were then allowed to choose either in the presence of the demonstrator or after she left the room. Results showed a significant main effect of the demonstration context (presence or absence of the human's communicative signals), and we also found some evidence for the response-modifying effect of the presence of the human demonstrator during the dogs' choice. That is, dogs predominantly chose the baited container, but if the demonstration context was communicative and the human was present during the dogs' choice, subjects' tendency to select the baited container has been reduced. In agreement with the studies showing sensitivity to human's communicative signals in dogs, these findings point to a special form of social influence in observational learning situations when it comes to learning about causally opaque and less efficient (compared to what comes natural to the dog) action demonstrations.


Improving the In Vitro Bioaccessibility of β-Carotene Using Pectin Added Nanoemulsions.
The intestinal absorption of lipophilic compounds such as β-carotene has been reported to increase when they are incorporated in emulsion-based delivery systems. Moreover, the reduction of emulsions particle size and the addition of biopolymers in the systems seems to play an important role in the emulsion properties but also in their behavior under gastrointestinal conditions and the absorption of the encapsulated compound in the intestine. Hence, the present study aimed to evaluate the effect of pectin addition (0%, 1%, and 2%) on the physicochemical stability of oil-in-water nanoemulsions containing β-carotene during 35 days at 4 °C, the oil digestibility and the compound bioaccessibility. The results showed that nanoemulsions presented greater stability and lower β-carotene degradation over time in comparison with coarse emulsion, which was further reduced with the addition of pectin. Moreover, nanoemulsions presented a faster digestibility irrespective of the pectin concentration used and a higher β-carotene bioaccessibility as the pectin concentration increased, being the maximum of ≈36% in nanoemulsion with 2% of pectin. These results highlight the potential of adding pectin to β-carotene nanoemulsions to enhance their functionality by efficiently preventing the compound degradation and increasing the in vitro bioaccessibility.


[Organization of medical support U.S. Armed Forces].
The article describes the structure of the medical service of the U.S. Army, presented by seven corps,principles of planning of capabilities of medical services and their management, personnel policy of the Medical Service, that focuses on the staffing of the medical service of the officers of the possibilities. Organization of medical care during the combat theater provided by 4 echelons is represented. The first echelon "battlefield-Battalion", the second--"brigade combat team", the third is the rear of the theater of operations, the fourth--stationary hospitals outside the theater of operations. The basic direction of reducing the medical costs of all the troops: military personnel, their families, civilian employees of the Ministry of Defence, members of their families, veterans of military service and their families.


Mechanism of activation of adenylate cyclase by Vibrio cholerae enterotoxin.
The kinetics and properties of the activation of adenylate cyclase by cholera enterotoxin have been examined primarily in toad erythrocytes, but also in avian erythrocytes, rat fat cells and cultured melanoma cells. When cholera toxin is incubated with intact cells it stimulates adenylate cyclase activity, as measured in the subsequently isolated plasma membranes, according to a triphasic time course. This consists of a true lag period of about 30 min, followed by a stage of exponentially increasing adenylate cyclase activity which continues for 110 to 130 min, and finally a period of slow activation which may extend as long as 30 hr in cultured melanoma cells. The progressive activation of adenylate cyclase activity by cholera toxin is interrupted by cell lysis; continued incubation of the isolated membranes under nearly identical conditions does not lead to further activation of the enzyme. The delay in the action of the toxin is not grossly dependent of the number of toxin-receptor (GM1 ganglioside) complexes, and is still seen upon adding a second dose of toxin to partially stimulated cells. Direct measurements indicate negligible intracellular levels of biologically active radioiodinated toxin in either a soluble or a nuclear-bound form. The effects are not prevented by Actinomycin D (20 mug/ml), uromycin (30 mug/ml), cycloheximide (30 mug/ml), sodium fluoride (10 mM) or sodium azide (1 mM); KCN, however, almost completely prevents the action of cholera toxin. The action of the toxin is temperature dependent, occurring at very slow or negligible rates below certain critical temperatures, the values of which depend on the specific animal species. Thetransition for toad erythrocytes occurs at 15 to 17 degrees C, while rat adipocytes and turkey erythrocytes demonstrate a discontinuity at 26 to 30 degrees C. The temperature effects are evident during the lag period as well as during the exponential phase of activation. The rate of decay of the stimulated adenylate cyclase activity of cultured melanoma cells indicates a half-time of about 36 hr. The rate of exponentially increasing activity and extent of enzyme activation are related to the number of bound toxin molecules according to a Langmuir adsorption isotherm and are half-maximal when about 2000 molecules of toxin are bound per cell. It is proposed that initially cholera toxin binds ineffectively, but that it is converted to an active form during the lag phase. This process may involve lateral motion of toxin-GM1 ganglioside complex within the plane of the membrane. The kinetics of adenylate cyclase activation are consistent with the possibility that during the exponential phase a bimolecular association is proceeding between the active form of the cholera toxin and some other membrane component. The possibility is considered that the cholera toxin molecule may bind directly to adenylate cyclase. These considerations may prove useful in understanding the possible interactions of active hormone-receptor complexes with adenylate cyclase in cell membranes.


Effects of Prenatal Exposure to Bisphenol A Substitutes, Bisphenol S and Bisphenol F, on Offspring's Health: Evidence from Epidemiological and Experimental Studies.
Pregnancy and lactation are critical periods for human well-being and are sensitive windows for pollutant exposure. Bisphenol A (BPA) is well demonstrated as a toxicant and has been replaced in the plastic industry with other bisphenol analogs that share similarities in structure and characteristics, most commonly Bisphenol S (BPS) and Bisphenol F (BPF). Maternal exposure to BPS or BPF can result in their accumulation in the fetal compartment, leading to chronic exposure and potentially limiting normal fetal growth and development. This review summarizes considerable findings of epidemiological or experimental studies reporting associations between BPS or BPF and impaired fetal growth and development. Briefly, the available findings indicate that exposure to the two bisphenol analogs during pregnancy and lactation can result in multiple disturbances in the offspring, including fetal growth restrictions, neurological dysfunctions, and metabolic disorders with the potential to persist throughout childhood. The occurrence of premature births may also be attributed to exposure to the two bisphenols. The possible mechanisms of actions by which the two bisphenols can induce such effects can be attributed to a complex of interactions between the physiological mechanisms, including impaired placental functioning and development, dysregulation of gene expression, altered hormonal balance, and disturbances in immune responses as well as induced inflammations and oxidative stress. In conclusion, the available evidence suggests that BPS and BPF have a toxic potential in a compartment level to BPA. Future research is needed to provide more intensive information; long-term studies and epidemiological research, including a wide scale of populations with different settings, are recommended. Public awareness regarding the safety of BPA-free products should also be enhanced, with particular emphasis on educating individuals responsible for the well-being of children.


Serial Morphological Changes of Side-Branch Ostium after Paclitaxel-Coated Balloon Treatment of De Novo Coronary Lesions of Main Vessels.
The effects on the side-branch (SB) ostium, following paclitaxel-coated balloon (PCB) treatment of de novo coronary lesions of main vessels have not been previously investigated. This study was aimed at evaluating the serial morphological changes of the SB ostium after PCB treatment of de novo coronary lesions of main vessels using optical coherence tomography (OCT). This prospective, single-center observational study enrolled patients with de novo lesions, which were traversed by at least one SB (≥1.5 mm) and were treated with PCB. The SB ostium was evaluated with serial angiographic and OCT assessments pre- and post-procedure, and at 9-months follow-up. Sixteen main vessel lesions were successfully treated with PCB, and 26 SBs were included for analysis. Mean SB ostial lumen area increased at 9-months follow-up (0.92±0.68 mm² pre-procedure, 1.03±0.77 mm² post-procedure and 1.42±1.18 mm² at 9-months). The SB ostial lumen area gain was 0.02±0.24 mm² between pre- and post-procedure, 0.37±0.64 mm² between post-procedure and 9-months, and 0.60±0.93 mm² between pre-procedure and 9-months. The ostial lumen area increased by 3.9% [interquartile range (IQR) of -33.3 to 10.4%] between pre- and post-procedure, 52.1% (IQR of -0.7 to 77.3%) between post-procedure and 9-months and 76.1% (IQR of 18.2 to 86.6%) between pre-procedure and 9-months. PCB treatment of de novo coronary lesions of main vessels resulted in an increase in the SB ostial lumen area at 9-months.


A Prediction Rule to Stratify Mortality Risk of Patients with Pulmonary Tuberculosis.
Tuberculosis imposes high human and economic tolls, including in Europe. This study was conducted to develop a severity assessment tool for stratifying mortality risk in pulmonary tuberculosis (PTB) patients. A derivation cohort of 681 PTB cases was retrospectively reviewed to generate a model based on multiple logistic regression analysis of prognostic variables with 6-month mortality as the outcome measure. A clinical scoring system was developed and tested against a validation cohort of 103 patients. Five risk features were selected for the prediction model: hypoxemic respiratory failure (OR 4.7, 95% CI 2.8-7.9), age ≥50 years (OR 2.9, 95% CI 1.7-4.8), bilateral lung involvement (OR 2.5, 95% CI 1.4-4.4), ≥1 significant comorbidity-HIV infection, diabetes mellitus, liver failure or cirrhosis, congestive heart failure and chronic respiratory disease-(OR 2.3, 95% CI 1.3-3.8), and hemoglobin <12 g/dL (OR 1.8, 95% CI 1.1-3.1). A tuberculosis risk assessment tool (TReAT) was developed, stratifying patients with low (score ≤2), moderate (score 3-5) and high (score ≥6) mortality risk. The mortality associated with each group was 2.9%, 22.9% and 53.9%, respectively. The model performed equally well in the validation cohort. We provide a new, easy-to-use clinical scoring system to identify PTB patients with high-mortality risk in settings with good healthcare access, helping clinicians to decide which patients are in need of closer medical care during treatment.


High-power OPCPA generating 1.7 cycle pulses at 2.5 µm.
We present a high-power mid-infrared (mid-IR) optical parametric chirped-pulse amplifier (OPCPA) generating 14.4 fs pulses centered at 2.5 µm with an average power of 12.6 W and a repetition rate of 100 kHz. The short pulses are obtained without nonlinear pulse compression. This is in contrast to most few-cycle systems operating in the mid-IR. In our case, the ultrashort pulse duration is enabled by a careful design of the gain profile of each amplification stage as well as a precise control of the signal dispersion throughout the system. A pulse shaper is used in the seed beam to adjust the spectral phase at the output of the OPCPA system. This approach allows for a clean temporal profile leading to a high peak power of 6.3 GW.


Detecting Introgression Between Members of the Fusarium fujikuroi and F. oxysporum Species Complexes by Comparative Mitogenomics.
The Fusarium fujikuroi species complex (FFSC) and F. oxysporum species complex (FOSC) are two related groups of plant pathogens causing a wide diversity of diseases in agricultural crops world wide. The aims of this study are (1) to clarify the phylogeny of the FFSC, (2) to identify potential deviation from tree-like evolution, (3) to explore the value of using mitogenomes for these kinds of analyses, and (4) to better understand mitogenome evolution. In total, we have sequenced 24 species from the FFSC and a representative set of recently analyzed FOSC strains was chosen, while F. redolens was used as outgroup for the two species complexes. A species tree was constructed based on the concatenated alignment of seven nuclear genes and the mitogenome, which was contrasted to individual gene trees to identify potential conflicts. These comparisons indicated conflicts especially within the previously described African clade of the FFSC. Furthermore, the analysis of the mitogenomes revealed the presence of a variant of the large variable (LV) region in FFSC which was previously only reported for FOSC. The distribution of this variant and the results of sequence comparisons indicate horizontal genetic transfer between members of the two species complexes, most probably through introgression. In addition, a duplication of atp9 was found inside an intron of cob, which suggests that even highly conserved mitochondrial genes can have paralogs. Paralogization in turn may lead to inaccurate single gene phylogenies. In conclusion, mitochondrial genomes provide a robust basis for phylogeny. Comparative phylogenetic analysis indicated that gene flow among and between members of FFSC and FOSC has played an important role in the evolutionary history of these two groups. Since mitogenomes show greater levels of conservation and synteny than nuclear regions, they are more likely to be compatible for recombination than nuclear regions. Therefore, mitogenomes can be used as indicators to detect interspecies gene flow.


The monstrous metallic in medicine and horror cinema.
`This paper considers the monstrous nature of medical tools and devices through the lens of horror cinema and the art of Damien Hirst. In it I argue for a shift from the monster and the monstrous as organic to the threat of the monster as an inorganic object in tools such as the scalpel and syringe. However, the metaphorical significance of the monster is sustained in these tools where human technological creations continue the discourse of the monster as a product of human creativity.


Limited list: limited effects?
During the first month after the limited National Health Service drug list came into effect 17 cooperative general practitioners recorded the actions taken when a now prohibited drug would formerly have been prescribed. An average of 6% of direct surgery contacts with patients and 8% of indirect contacts with patients were affected by the new regulations, but in 2% and 4% of cases respectively the patient received the same pharmacological substance under a different (generic or approved) name. Where a real change in pharmacological constitution or formulation had been required four fifths of these substitutes were considered by the doctors to result in less effective treatment. In 1% of contacts no drug was issued or recommended where one would formerly have been given.


Meaning Reflectivity in Later Life: The Relationship Between Reflecting on Meaning in Life, Presence and Search for Meaning, and Depressive Symptoms in Older Adults Over the Age of 75.
Background: Over the last decades, there is growing attention for the importance of meaning in life for older adults. However, there is virtually no insight into the mental processes that contribute to this experience. Some scholars recently called for an investigation of meaning reflectivity, or the process of reflecting on issues specifically related to meaning in life. In this study, we explored to what extent older adults talk and think about issues of meaning in life, and how this meaning reflectivity is related to the search for and presence of meaning in life, and to depressive symptoms. Method: In this cross-sectional observational study, 282 community-residing older adults (75 or older) in Belgium filled in paper questionnaires on meaning in life (presence and search), depressive symptoms, and meaning reflectivity (categorical item). ANOVA analyses were used to explore differences in meaning in life and depressive symptoms across the meaning reflectivity categories. Regression and negative binomial models investigated the association between meaning reflectivity and presence, search and depressive symptoms. Finally, an exploratory structural equation model examined whether presence of meaning statistically mediated the relationship between meaning reflectivity and depressive symptoms. Results: The majority of participants (42.4%) indicated that they had thought about meaning in life before, 23.2% indicated that they had talked about it before, 18% indicated that they hadn't thought about it before but found it interesting, and 16.4% indicated that they were indifferent/unconcerned about meaning in life. The latter group reported lower levels of presence of meaning and search for meaning and higher levels of depressive symptoms. Belonging to this category was also associated with lower presence and search in regression analyses, but not with depressive symptoms above the effect of presence of meaning. Exploratory mediation analyses suggested that presence of meaning may be a mediator between meaning reflectivity and depressive symptoms. Conclusion: Meaning reflectivity is an important process to consider in the context of the experience of meaning in life for older adults. Those older adults who are indifferent about issues of meaning in life might be more vulnerable to experience a lack of meaning and depressive symptoms.


Pharmacokinetics and Bioavailability of Inhaled Esketamine in Healthy Volunteers.
Esketamine is traditionally administered via intravenous or intramuscular routes. In this study we developed a pharmacokinetic model of inhalation of nebulized esketamine with special emphasis on pulmonary absorption and bioavailability. Three increasing doses of inhaled esketamine (dose escalation from 25 to 100 mg) were applied followed by a single intravenous dose (20 mg) in 19 healthy volunteers using a nebulizer system and arterial concentrations of esketamine and esnorketamine were obtained. A multicompartmental pharmacokinetic model was developed using population nonlinear mixed-effects analyses. The pharmacokinetic model consisted of three esketamine, two esnorketamine disposition and three metabolism compartments. The inhalation data were best described by adding two absorption pathways, an immediate and a slower pathway, with rate constant 0.05 ± 0.01 min (median ± SE of the estimate). The amount of esketamine inhaled was reduced due to dose-independent and dose-dependent reduced bioavailability. The former was 70% ± 5%, and the latter was described by a sigmoid EMAX model characterized by the plasma concentration at which absorption was impaired by 50% (406 ± 46 ng/ml). Over the concentration range tested, up to 50% of inhaled esketamine is lost due to the reduced dose-independent and dose-dependent bioavailability. We successfully modeled the inhalation of nebulized esketamine in healthy volunteers. Nebulized esketamine is inhaled with a substantial reduction in bioavailability. Although the reduction in dose-independent bioavailability is best explained by retention of drug and particle exhalation, the reduction in dose-dependent bioavailability is probably due to sedation-related loss of drug into the air.


Secondary electron fluence perturbation by high-Z interfaces in clinical proton beams: a Monte Carlo study.
Fluence perturbation of secondary electrons from clinical proton beams (50-250 MeV) by thin high-Z planar interfaces was studied with Monte Carlo simulations. Starting from monoenergetic proton pencil beams, proton depth doses and proton fluence spectra were calculated, both in homogeneous water and near thin high-Z interfaces by using the proton transport Monte Carlo code PTRAN. This code was modified extensively to enable modelling of proton transport in non-homogeneous geometries. From the proton fluence spectra in water and in the interface materials, electron generation spectra were calculated analytically and were then used as input for an electron transport calculation with the Monte Carlo code EGS4/PRESTAII to obtain electron doses and electron fluence spectra. The interface materials used in the study were graphite, Al, Ti, Cu, Sn and Au. We found significant electron fluence perturbations on both sides of the planar interfaces, resulting in an electron dose increase upstream and a decrease downstream from the interfaces, with the magnitude of the effect depending strongly on the atomic number of the interface. For the most extreme case studied, 250 MeV protons and a gold interface, we obtained an electron dose increase of 41% upstream of the interface and a decrease of 15% downstream with both perturbations having a spatial extent of about 700 microm. The total dose perturbation due to this effect amounts to a 5% increase upstream and a 2% decrease downstream. A detailed analysis of dose and fluence perturbation is presented for a wide range of materials and proton energies.


Elevated peripheral levels of receptor-interacting protein kinase 1 (RIPK1) and IL-8 as biomarkers of human amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a devastating fatal neurodegenerative disease with no cure. Receptor-interacting protein kinase 1 (RIPK1) has been proposed to mediate pathogenesis of ALS. Primidone has been identified as an old drug that can also inhibit RIPK1 kinase. We conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1G93A mice and ALS patients. SOD1G93A mice treated with primidone showed significant delay of symptomatic onset and improved motor performance. One-hundred-sixty-two ALS participants dosed daily with primidone (62.5 mg) completed 24-week follow-up. A significant reduction was showed in serum levels of RIPK1 and IL-8, which were significantly higher in ALS patients than that of healthy controls (P < 0.0001). Serum RIPK1 levels were correlated positively with the severity of bulbar symptoms (P < 0.05). Our study suggests that serum levels of RIPK1 and IL-8 in peripheral can be used as clinical biomarkers for the activation of RIPK1 in central nervous system in human ALS patients. Repurposing primidone may provide a promising therapeutic strategy for ALS. The effect of primidone for the treatment of other inflammatory diseases may also be considered, since the activation of RIPK1 has been implicated in mediating a variety of inflammatory diseases including COVID-19-associated cytokine release syndrome (CRS). (ChiCTR2200060149).


The Relationship between Transcranial Doppler Ultrasonography and Visual Field Test Results in Glaucoma and Glaucoma Suspect Patients.
To evaluate the relationships between parameters of transcranial ultrasonography and results of visual field tests in patients with open angle glaucoma or suspected of having glaucoma. This retrospective study was based on data from medical records of patients who visited the Department of Ophthalmology in Kangbuk Samsung Hospital from January 1, 2016, to October 17, 2019, and underwent transcranial Doppler ultrasonography as part of a routine health examination. Ophthalmic data were visual acuity, intraocular pressure, optical coherence tomography, and Humphrey visual field test results. Retinal nerve fiber layer defect was confirmed by a glaucoma specialist. Patients' ophthalmic data, such as average ganglion cell layer thickness, visual field index, pattern standard deviation, and mean deviation, were divided into quartiles. Each ophthalmic artery parameter from transcranial Doppler ultrasonography was compared between quartiles. A total of 162 patients were reviewed. There was no difference in Doppler ophthalmic artery (OA) parameters between patients with or without retinal nerve fiber layer defect. None of the quartile groups of average ganglion cell layer thickness showed significant difference in any OA parameters. Patients in the low-visual field index quartile showed significant low peak systolic velocities of OAs when adjusted for age, sex, and presence of diabetes mellitus or hypertension (p = 0.016). A higher pattern standard deviation showed lower peak systolic velocity (p = 0.046). There was no significant tendency between any other OA parameter and mean deviation value. Our study suggests that hemodynamic parameters of ophthalmic arteries might be associated with visual field status of patients. Further large-population studies are needed in order to better understand the relationship between visual function and ocular blood flow.


Interface Engineering and Boron Modification of Pd-B/Pd Hetero-Metallene Synergistically Accelerate Oxygen Reduction Catalysis.
2D metallene possess high surface area and excellent electron transport capability, thus enabling efficient application in oxygen reduction reaction (ORR). However, the interface regulation and electronic structure optimization of metallene are still great challenges. Herein, Pd-B/Pd hetero-metallene is constructed by interface engineering and B modification strategies for efficient electrocatalytic ORR. The 2D configuration of Pd-B/Pd hetero-metallene exposes a large number of surface atoms and unsaturated defect sites, thus providing abundant catalytic active sites and exhibiting high electron mobility. More importantly, interface engineering and B modification synergistically optimizing the electronic configuration of the metallene system. This work not only provides an effective strategy for the rational regulation of the electronic configuration of metallene, but also offers a reference for the construction of efficient ORR catalysts.


Effect of Extended Pelvic Lymph Node Dissection on Oncologic Outcomes in Patients with D'Amico Intermediate and High Risk Prostate Cancer Treated with Radical Prostatectomy: A Multi-Institutional Study.
Pelvic lymph node dissection represents the gold standard of lymph node staging in patients with prostate cancer. We sought to assess the effect of extended pelvic lymph node dissection on oncologic outcomes in patients with characteristics of D'Amico intermediate or high risk prostate cancer treated with radical prostatectomy. In a multi-institutional database of 4 centers we identified 9,742 patients who underwent radical prostatectomy from 2000 to 2017 with or without pelvic lymph node dissection. Only patients with a greater than 5% probability of lymph node invasion according to the Briganti nomogram were included in study. We performed 2:1 propensity score matching to account for potential differences between the 2 cohorts. Cox regression models were used to test the effect of pelvic lymph node dissection on biochemical recurrence, metastasis and cancer specific mortality. Overall 707 patients (7.3%) did not undergo pelvic lymph node dissection, of whom 520 and 187 harbored D'Amico intermediate and high risk characteristics, respectively. A median of 14 lymph nodes (IQR 8-21) were removed in the pelvic lymph node dissection cohort and 1,714 of these cases (19.0%) harbored lymph node metastasis. After propensity score matching the biochemical recurrence-free, metastasis-free and cancer specific mortality-free survival rates were 60.4% vs 65.6% (p=0.07), 87.0% vs 90.0% (p=0.06) and 95.2% vs 96.4% (p=0.2) for pelvic lymph node dissection vs no pelvic lymph node dissection 120 months after radical prostatectomy. Multivariable Cox regression models adjusted for postoperative and preoperative tumor characteristics revealed that pelvic lymph node dissection performed at radical prostatectomy was no independent predictor of biochemical recurrence, metastasis or cancer specific mortality (all p ≥0.1). There was no significant difference in oncologic outcomes in patients with D'Amico high or intermediate risk prostate cancer in whom pelvic lymph node dissection was or was not performed at radical prostatectomy. The therapeutic value of pelvic lymph node dissection remains unclear.


Chronic multisite brain recordings from a totally implantable bidirectional neural interface: experience in 5 patients with Parkinson's disease.
OBJECTIVE Dysfunction of distributed neural networks underlies many brain disorders. The development of neuromodulation therapies depends on a better understanding of these networks. Invasive human brain recordings have a favorable temporal and spatial resolution for the analysis of network phenomena but have generally been limited to acute intraoperative recording or short-term recording through temporarily externalized leads. Here, the authors describe their initial experience with an investigational, first-generation, totally implantable, bidirectional neural interface that allows both continuous therapeutic stimulation and recording of field potentials at multiple sites in a neural network. METHODS Under a physician-sponsored US Food and Drug Administration investigational device exemption, 5 patients with Parkinson's disease were implanted with the Activa PC+S system (Medtronic Inc.). The device was attached to a quadripolar lead placed in the subdural space over motor cortex, for electrocorticography potential recordings, and to a quadripolar lead in the subthalamic nucleus (STN), for both therapeutic stimulation and recording of local field potentials. Recordings from the brain of each patient were performed at multiple time points over a 1-year period. RESULTS There were no serious surgical complications or interruptions in deep brain stimulation therapy. Signals in both the cortex and the STN were relatively stable over time, despite a gradual increase in electrode impedance. Canonical movement-related changes in specific frequency bands in the motor cortex were identified in most but not all recordings. CONCLUSIONS The acquisition of chronic multisite field potentials in humans is feasible. The device performance characteristics described here may inform the design of the next generation of totally implantable neural interfaces. This research tool provides a platform for translating discoveries in brain network dynamics to improved neurostimulation paradigms. Clinical trial registration no.: NCT01934296 (clinicaltrials.gov).


Kibale forest wild coffee: challenges to market-based conservation in Africa.
Declining rural security and pressures to reduce public-sector expenditures in the late 1990s spurred efforts to develop alternative funding models for Uganda's Kibale National Park (KNP). The Wild Coffee Project, established in 1999 with support from the U.S. Agency for International Development, the World Bank, and the Ford Foundation, sought to develop a market for wild coffee that had been harvested traditionally from areas within today's KNP. The Kibale Forest Foundation, a U.S.-based nonprofit organization, was created to legalize harvests, obtain third-party wild and organic certification, and coordinate management between KNP, the coffee industry, and local communities. Although the project was successful in legalizing, harvesting, and processing the world's first certified wild and organic coffee, efforts to gain entry into the international marketplace failed. Chief among the lessons learned from this project is that for many wild-grown products, the value of "the story"--in both human and conservation terms--is likely to far exceed actual product values. This value differential should be captured through high-value niche markets to avoid low commodity pricing and subsequent pressures to improve financial returns through over harvesting. In addition, local producers should hold significant assets in whatever brands are developed, creating a shared-equity approach that serves social responsibility goals, fosters project sustainability, and ensures a steady stream of positive stories for use in marketing to build brand value. Shared equity--in this case ownership interest in the intellectual property embodied in the brand--provides a second incentive beyond transactional profits that can only be realized if resource conservation is maintained.


Ventricular hypertrophy--physiological mechanisms.
Adult cardiac myocytes are incapable of mitosis. Dead cells are replaced by connective tissue so that after myocardial infarction (MI), function can only be restored by compensatory hypertrophy of the surviving myocardium. In physiological hypertrophy in response to exercise, high altitude, or mild hypertension, additional myoplasm expands cell diameter in an orderly fashion; Z-lines are in register and the normal ratio of volume densities of contractile elements, mitochondria, and capillaries is conserved. In hypertrophy induced by aortic or pulmonary artery banding or by experimental or congenital hypertension, the borderline between physiological and pathological hypertrophy may be crossed, causing disorganization of fibers and an unfavourable contractile element to capillary ratio. There was, therefore, a need for a graded model of hypertrophy, which involves simulating an altitude of 6,000 m at sea level by supplying rabbits with appropriate nitrogen/oxygen mixtures. In this environment, 50% right ventricular hypertrophy can be achieved without alteration of left ventricular weight or hematocrit. Longer exposures produced 100% right ventricular hypertrophy, with only moderate increases in hematocrit and left ventricular weight. It is well known that adrenergic stimulation causes cardiac hypertrophy, and it has been suggested that release of a trophic factor from sympathetic nerves, either noradrenaline or a protein, might be a necessary stimulus for growth. If so, long-term treatment of post-MI patients with beta-adrenergic blocking agents could inhibit a desirable compensatory hypertrophy of the surviving myocardium. In the above model it has been found, however, that neither beta-blockade nor chemical sympathectomy with guanethidine or 6-hydroxydopamine had any effect on the hypertrophy, nor did treatment with verapamil or nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)


Melanocytic nevi of palms and soles: a histological study according to the plane of section.
Melanocytic nevi of palms and soles (MNPS) cause diagnostic problems to dermatopathologists because they share histologic features with malignant melanoma (MM). Early MNPS frequently display a striate appearance, suggesting that, in this subset of nevi, both melanocytes and melanin might have a particular distribution in relation to dermatoglyphics. To verify this hypothesis, we undertook a histological study on 78 junctional MNPS sampled along a plane either perpendicular or parallel to dermatoglyphics. Histologic examination revealed symmetry in 56% of the lesions, circumscription in 60%, intraepidermal scatter of melanocytes in 79%, and melanin columns in 61%. Interestingly, comparison between histologic features of nevi sampled perpendicularly and those of nevi cut parallely to dematoglyphics showed that features of benignity, namely symmetry, circumscription and melanin columns, were significantly more frequent in lesions dissected along a perpendicular plane. Moreover, in 70% of perpendicular samples, intraepidermal scatter of melanocytes and melanin columns were strictly concentrated in furrows. Therefore, to avoid diagnostic pitfalls in the differentiation between junctional MNPS and MM, we strongly suggest to dissect MNPS along a plane perpendicular to skin markings. We hypothesize that mechanical stress can be responsible for concentration of intraepidermal scatter of melanocytes and melanin columns in skin furrows.


Sleep measures and cardiovascular disease in type 2 diabetes mellitus.
The objective of this study was to assess whether poor sleep is independently associated with cardiovascular disease in people with type 2 diabetes mellitus (T2DM). A cross-sectional study was performed in subjects with T2DM aged between 40 and 80 years. Sleep assessment was achieved by actigraphy and Pittsburgh Sleep Quality Index (PSQI) score. The study population comprised 108 subjects with T2DM. The mean age was 64.9 years, the median diabetes duration was 6 years and 73.1% were men. No association was shown between sleep parameters as assessed by actigraphy and T2DM-associated micro- and macrovascular complications. However, sleep quality as assessed by PSQI was significantly associated with macrovascular disease in univariate analysis. Multivariate logistic regression analysis showed red blood cell distribution width (RDW) (odds ratio (OR) 1.79, p=0.018) and good sleep quality (OR 0.35, p=0.017) to be independently associated. Binary logistic regression analysis revealed that body mass index (BMI) (OR 1.11, p=0.024), RDW (OR 1.95, p=0.007) and Center for Epidemiologic Studies Depression score (OR 1.06, p=0.012] were independently associated with abnormal carotid intima-media thickness (CIMT). Poor sleep quality and higher RDW levels are associated with macrovascular disease in a T2DM population. Increased BMI as well as depression also appear to have an independent role in subclinical atherosclerosis, as assessed by CIMT.


The recovery of semen from bathwater using the Evidence Recovery System (ERS).
Sexual offences are under-reported and ascertaining accurate offence numbers is difficult. Any methods which could increase the ability to obtain biological evidence or reduce the additional distress associated with reporting a sexual offence may result in an increase in reporting this crime type. The Evidence Recovery System (ERS) is designed to collect trace evidence, including hairs, fibres and biological evidence, from bath or shower water in a non-invasive manner. Initially, samples of semen were placed in baths filled with water, and washing was simulated using a range of body wash products. The water was then drained through the ERS before its filters were subjected to acid phosphatase testing and haematoxylin and eosin staining of spermatozoa. Recovered spermatozoa were then graded accordingly. Following this, the experiment was repeated with the addition of dirt/dust particulates during the washing stage, to simulate recovery of biological evidence in a more realistic environment. The results showed that spermatozoa considered 'easy to find' could regularly be obtained from bathwater using the ERS. It appeared that this recovery was not affected by the presence of different body wash products. When dust/dirt particles were added, the number of spermatozoa recovered increased at two of the evidence collection stages. The difference in recovery was considered to be statistically significant. This study provides evidence to suggest the feasibility of use of the ERS as a method to collect semen evidence from individuals subjected to sexual offences. The recovery of spermatozoa does not appear to be affected by the presence of a body wash, but does appear to be improved when skin cells, hair and other debris are transferred into the water, as would be likely during a bath/shower. Further to this, the possibility of obtaining spermatozoa from the home bath or shower of a victim following a post-offence bathing experience is implied.


Minimally invasive off-pump valve-in-a-valve implantation: the atrial transcatheter approach for re-operative mitral valve replacement.
This study was designed to evaluate the feasibility and haemodynamic performance of transcatheter valve-in-a-valve (VinV) implantation for failed mitral xenografts using a minimally invasive, transatrial, off-pump approach. Nine adult sheep (71.1 +/- 3.4 kg) underwent mitral valve replacement with a 25 mm bioprosthesis using standard conventional techniques. After weaning from cardiopulmonary bypass, a transcatheter 23 mm pericardial prosthesis mounted on a balloon-inflatable steel stent was deployed within the conventional xenograft. The VinV implantation (10.1 +/- 0.9 min) was performed off-pump using an antegrade transatrial approach under fluoroscopic guidance successfully in all nine sheep. Mean transvalvular gradient was 4.6 +/- 1.0 mmHg, and five of nine sheep had no paravalvular leak with two sheep each having mild and moderate one. All transcatheter prostheses were confirmed in good position on post-mortem analysis. In an in vitro model, the minimum force required to dislodge the valve was 22.5 +/- 3.0 N, which was well above the normal estimated forces generated by the left ventricle (LV). When this model was attached to a LV assist device, the VinV withstood pressure loops of 300 mmHg, without dislocation or embolization. Transatrial, transcatheter mitral VinV implantation is feasible off pump. This is a truly minimally invasive concept to treat patients with failed xenografts using a right lateral minithoracotomy.


Sexually transmitted infections and associated risk factors among sexual minority women in China.
There is a potential for transmission of sexually transmitted infections (STIs) within sexual minority women (SMW) in China. However, research specifically focused on STIs among SMW in China is severely limited. This study aims to evaluate the prevalence of STIs and identify associated risk factors among SMW in Beijing, China. This study comprised a baseline assessment followed by a follow-up evaluation. Consistent questionnaire interviews and STI tests were administered during both stages. Participants were recruited online in Beijing between 2020 and 2021 and factors associated with STIs were analyzed using logistic and Cox regression models. The baseline included 219 SMW, and 58.9% (129/219) of these individuals participated in the follow-up. During the baseline assessment, 4.1% (9/219) tested positive for chlamydia infection, while 5.0% (11/219) were HSV-2 seropositive. At the follow-up, the incidence of HSV-2 was 3.7 cases per 100 person-years. Notably, engaging in sexual activity with men and having an increased number of sexual partners were both identified as factors associated with a higher risk of STIs. The findings suggest that SMW in Beijing may face a significant risk of contracting STIs. As a preventive measure, there should be a concerted effort to promote STI testing within the SMW community.


Best practice for bio-waste collection as a prerequisite for high-quality compost.
Due to its high content of humic substances, compost from bio-waste improves the structure and fertility of soils serving also as a sink for CO2. But compost is also contaminated with numerous compounds, for example, plastics, glass particles, etc., mostly due to incorrect sorting by the waste producer, that is, households. The contamination even increases when covering areas of a high population density as is also evident from experience in Germany with a steadily increasing proportion of bio-waste. Only compost with high quality and minimum contamination is an acceptable fertilizer. A structured interview of experts investigated which measures or combinations of measures are best suitable to reduce the rate of misplaced materials in the organic waste. Only responsible persons were interviewed whose municipalities extensively collect separately bio-waste since years and have a low rate of unwanted materials. The questions focus on the identification of the misplacements according to their kind and quantity, the respective collection system, the regional statutes and their enforcement as well as the kind and extent of public awareness measures. The respective necessary measures are being discussed. This systemic approach can be transferred to other regions that intend to collect large quantities of bio-waste separately.


Homozygote inositol transporter knockout mice show a lithium-like phenotype.
Lithium inhibits inositol monophosphatase and also reduces inositol transporter function. To determine if one or more of these mechanisms might underlie the behavioral effects of lithium, we studied inositol transporter knockout mice. We previously reported that heterozygous knockout mice with reduction of 15-37% in brain inositol had no abnormalities of pilocarpine sensitivity or antidepressant-like behavior in the Porsolt forced swim test. We now report on studies of homozygous inositol transporter knockout mice. Homozygote knockout mice were rescued by 2% inositol supplementation to the drinking water of the dam mice through pregnancy and lactation. Genotyping was carried out by polymerase chain reaction followed by agarose electrophoresis. Brain free myo-inositol levels were determined gas-chromatographically. Motor activity and coordination were assessed by the rotarod test. Behavior of the mice was studied in lithium-pilocarpine seizure models for lithium action and in the Porsolt forced swim test model for depression. In homozygote knockout mice, free inositol levels were reduced by 55% in the frontal cortex and by 60% in the hippocampus. There were no differences in weight or motor coordination by the rotarod test. They behaved similarly to lithium-treated animals in the model of pilocarpine seizures and in the Porsolt forced swimming test model of depression. Reduction of brain inositol more than 15-37% may be required to elicit lithium-like neurobehavioral effects.


Direct superior approach versus posterolateral approach in total hip arthroplasty: a randomized controlled trial on early outcomes on gait, risk of fall, clinical and self-reported measurements.
Background and purpose - Several surgical approaches are used in primary total hip arthroplasty (THA). In this randomized controlled trial we compared gait, risk of fall, self-reported and clinical measurements between subjects after direct superior approach (DSA) versus posterolateral approach (PL) for THA.Patients and methods - Participants with DSA (n = 22; age 74 [SD 8.9]) and PL (n = 23; age 72 [7.7]) underwent gait analysis, risk of fall assessment and Timed Up and Go Test (TUG) before (PRE), 1 month (T1) and 3 months after (T3) surgery. Data on bleeding and surgical time was collected.Results - DSA resulted in longer surgical times (90 [14] vs. 77 [20] min) but lower blood loss (149 [66] vs. 225 [125] mL) than PL. DSA had lower risk of fall at T3 compared with T1 and higher TUG scores at T3 compared with T1 and PRE. PL improved balance at T3 compared with T1 and PRE. Spatiotemporal gait parameters improved over time for both DSA and PL with no inter-group differences, whereas DSA, regarding hip rotation range of motion, showed lower values at T3 and T1 compared with PRE and, furthermore, this group had lower values at T1 and T3 compared with PL. All foregoing comparisons are statistically signficant (p < 0.05)Interpretation - DSA showed longer surgical time and lower blood loss compared with PL and early improvements in TUG, spatiotemporal, and kinematic gait parameters, highlighting rapid muscle strength recovery.


CTG repeat instability in a human embryonic stem cell line carrying the myotonic dystrophy type 1 mutation.
Human embryonic stem cells (hESC) are considered to be an indefinite source of self-renewing cells that can differentiate into all types of cells of the human body and could be used in regenerative medicine, drug discovery and as a model for studying early developmental biology. hESC carrying disease-causing mutations hold promise as a tool to investigate mechanisms involved in the pathogenesis of the disease. In this report, we describe the behaviour of an expanded CTG repeat in the 3' untranslated region of the DMPK gene in VUB03_DM1, a hESC line carrying the myotonic dystrophy type 1 (DM1) mutation compared with the normal CTG repeat in two hESC lines VUB01 and VUB04_CF. Expanded CTG repeats were detected by small amount PCR, small pool PCR and Southern blot analysis in consecutive passages of VUB03_DM1. An important instability of the CTG repeat was detected during prolonged in vitro culture, showing stepwise increases of the repeat number in consecutive passages as well as a higher range of variability. This variability was present in cells of different colonies of the same passage and even within single colonies. The high repeat instability is in contrast to the previously observed stability of the repeat in preimplantation embryos and in fetuses during the first trimester of pregnancy. This in vitro culture of affected hESC represents a valuable model for studying the biology of repeat instability.


[SECONDARY PREVENTION IN PATIENTS WITH ACUTE CORONARY SYNDROME HOSPITALIZED IN INTERNAL MEDICINE DEPARTMENTS].
Secondary prevention treatment with aspirin/ clopidogrel, beta blockers, inhibitors of the rennin-angiotensin-aldosterone converting system and statins reduces the morbidity and mortality of patients after acute coronary syndrome (ACS). However, clinical experience suggests that prescription rates in patients hospitalized in internal medicine departments may be low. To determine the rate of administration of secondary prevention in ACS patients hospitalized in internal medicine departments; identify predictors for full regimen use and evaluate reasons for non-prescription of the medications. Retrospective review of the files of 399 patients with ACS hospitalized in the 5 departments of internal medicine in a university affiliated medical center in 2010. Data were collected on demographic and clinical parameters, findings on current admission, medications at admission and at discharge, and reasons for nonprescription of secondary preventive medications. Overall, 62% of patients were discharged with full secondary preventive treatment. In the remainder, the reason for not prescribing the medications was usually not specified. Factors associated with prescription of the "full regimen" were patient receipt of full secondary prevention treatment prior to admission, hypertension, history of myocardial infarction and revascularization, non-ST elevation myocardial infarction as the reason for the current admission, and performance of percutaneous coronary intervention during the current hospitalization. Atrial fibrillation was a negative predictor. The prescription of full secondary prevention treatment in ACS patients hospitalized in internal medicine departments is suboptimal. Further efforts are needed to implement comprehensive guideline-based management.


The critical airway in adults: The facts.
An algorithm on the indications and timing for a surgical airway in emergency as such cannot be drawn due to the multiplicity of variables and the inapplicability in the context of life-threatening critical emergency, where human brain elaborates decisions better in cluster rather than in binary fashion. In particular, in emergency or urgent scenarios, there is no clear or established consensus as to specifically who should receive a tracheostomy as a life-saving procedure; and more importantly, when. The two classical indications for emergency tracheostomy (laryngeal injury and failure to secure airway with endotracheal intubation or cricothyroidotomy) are too generic and encompass a broad spectrum of possibilities. In literature, specific indications for emergency tracheostomy are scattered and are biased, partially comprehensive, not clearly described or not homogeneously gathered. The review highlights the indications and timing for an emergency surgical airway and gives recommendations on which surgical airway method to use in critical airway.


Picrotoxin-induced epileptiform activity in hippocampus: role of endogenous versus synaptic factors.
Picrotoxin-(PTX) induced epileptiform activity was studied in guinea pig hippocampal slices maintained in vitro, using intra- and extracellular recording techniques. The observed pattern of spontaneous and evoked epileptiform activity was quite complex. Spontaneous epileptiform events originated in the CA3 region and subsequently spread or propagated to CA1. Activation of CA1 could then reactivate CA3. This reverberation of activity was seen also following stimulation of the mossy fiber afferents from the dentate gyrus to CA3. Stimulation of fibers in the stratum radiatum of the CA1 region could trigger, at short latency, epileptiform activity that either was localized in CA1 or also occurred in CA3, with a late secondary discharge in CA1. This is attributed to a backfiring of the Schaffer collaterals and illustrates the ability of a variety of CA3 inputs to trigger epileptiform activity. Bath-applied PTX, at concentrations of 50-200 microM, had no apparent effect on the resting membrane potential or input resistance of the CA3 cells tested. Depolarizing current pulses elicited characteristic endogenous-burst responses that were not altered by PTX. Synaptic activity evoked by mossy fiber stimulation was altered markedly by PTX. The pattern of observed changes indicated that PTX reduced inhibitory postsynaptic potential (IPSP) amplitudes, resulting in the appearance of repetitive (presumably recurrent) excitatory inputs. Paroxysmal depolarizing shifts ( PDSs ) were generated by the coalescence of these excitatory inputs. Two types of spontaneous bursting were observed after PTX application. The first type was nonepileptiform , all or none in nature, and its frequency was voltage dependent. The second type of spontaneous burst was the PDS. It was epileptiform in character because it was associated with the synchronous discharge of many neurons. It was graded in nature, and its frequency was voltage independent. The graded nature of the PDS was demonstrated by varying the duration and intensity of the orthodromic stimulation. Trains of stimulation could produce PDSs that lasted 500-800 ms. A refractory period was observed following a PDS. By varying the strength of the orthodromic stimulation, it was possible to demonstrate that for the intervals tested this was a relative, not absolute, refractory period. Intracellular recordings in CA3 neurons indicated that each spontaneous PDS was followed by an afterhyperpolarization (AHP).


Polyamines Regulate Strawberry Fruit Ripening by Abscisic Acid, Auxin, and Ethylene.
Polyamines (PAs) participate in many plant growth and developmental processes, including fruit ripening. However, it is not clear whether PAs play a role in the ripening of strawberry (Fragaria ananassa), a model nonclimacteric plant. Here, we found that the content of the PA spermine (Spm) increased more sharply after the onset of fruit coloration than did that of the PAs putrescine (Put) or spermidine (Spd). Spm dominance in ripe fruit resulted from abundant transcripts of a strawberry S-adenosyl-l-Met decarboxylase gene (FaSAMDC), which encodes an enzyme that generates a residue needed for PA biosynthesis. Exogenous Spm and Spd promoted fruit coloration, while exogenous Put and a SAMDC inhibitor inhibited coloration. Based on transcriptome data, up- and down-regulation of FaSAMDC expression promoted and inhibited ripening, respectively, which coincided with changes in several physiological parameters and their corresponding gene transcripts, including firmness, anthocyanin content, sugar content, polyamine content, auxin (indole-3-acetic acid [IAA]) content, abscisic acid (ABA) content, and ethylene emission. Using isothermal titration calorimetry, we found that FaSAMDC also had a high enzymatic activity with a Kd of 1.7 × 10-3 m In conclusion, PAs, especially Spm, regulate strawberry fruit ripening in an ABA-dominated, IAA-participating, and ethylene-coordinated manner, and FaSAMDC plays an important role in ripening.


Direct and indirect hydrogen abstraction in Cl + alkene reactions.
Reactions between Cl atoms and propene can lead to HCl formation either by direct H abstraction or through a chloropropyl addition complex. Barring stabilizing collisions, the chloropropyl radical will either decompose to reactants or form HCl and allyl products. Using velocity-map imaging to measure the quantum state and velocity of the HCl products provides a view into the reaction dynamics, which show signs of both direct and indirect reaction mechanisms. Simulated trajectories of the reaction highlight the role of the direct H-abstraction pathways, and the resultant simulated scattering images show reasonable agreement with measurement. The simulations also show the importance of large excursions of the Cl atom far from equilibrium geometries within the chloropropyl complex, and these large-amplitude motions are the ultimate drivers toward HCl + allyl fragmentation. Gas-phase measurements of larger alkenes, 2-methylpropene and 2,3-dimethylbut-2-ene, show slightly different product distributions but still feature similar reaction dynamics. The current suite of experiments offers ready extensions to liquid-phase bimolecular reactions.


Haemostatic responses and vasopressin release during colonoscopy in man.
1. During major abdominal surgery there are increases in Factor VIII and plasminogen activator activity, associated with elevated plasma concentrations of vasopressin, of a magnitude shown to affect haemostasis. 2. To investigate the mechanisms involved in the haemostatic response to surgery, 12 patients undergoing fibre-optic colonoscopy were studied, of which six had a complete and six had an incomplete examination. 3. Venous blood samples were taken before, during and after the procedure for assay of plasma vasopressin, adrenaline and noradrenaline concentrations, Factor VIII coagulant activity, von Willebrand factor antigen level, euglobulin clot lysis time, tissue-type plasminogen activator activity and tissue-type plasminogen activator inhibition. 4. In the six patients who underwent a complete procedure the median plasma vasopressin concentration rose from 0.6 pg/ml to 153 pg/ml during colonoscopy. Factor VII coagulant activity rose from 0.9 to 2.4 i.u./ml and von Willebrand factor antigen level rose from 139 to 224%. Plasminogen activator activity increased from 20 to 144 units and tissue-type plasminogen activator activity rose from 107 to 1338 m-i.u./ml, whereas tissue-type plasminogen activator inhibition fell from 4.8 to 1.0 i.u./ml. 5. In the six patients in whom a limited procedure was performed, there were no changes in haemostatic function or in plasma vasopressin concentration. Plasma concentrations of adrenaline and noradrenaline did not change in either group. 6. The results indicate that vasopressin regulates the intrinsic coagulation pathway and fibrinolytic system in the absence of adrenaline release.


Topographical control of cells.
We review the literature on the reaction of cells to their surrounding topography. The topography may be that of surrounding cells, intercellular materials or biomaterials. The reactions include cell orientation, rates of movement, and activations of the cells. We concentrate on those papers where quantitative measurements of the reactions have been made and largely ignore those on subjective impressions. A wide range of topographies are considered but special attention is given to results on groove-ridge topographies. The question of whether the cells are reacting to the topography directly or to patterned substratum chemistry formed on the topography is discussed. The review ends with a summary of the types of prosthesis where advantage has been taken of the ability to fabricate topography.


Availability and Quality of Online Information on Sub-Internships in U.S. Orthopaedic Residency Programs.
The purpose of the present study was to assess the availability and quality of online information regarding sub-internships in orthopaedics among U.S. orthopaedic residency programs. Each U.S. orthopaedic surgery residency program web site was assessed for the following 4 criteria: any mention of a sub-internship offered by that program, contact information regarding the sub-internship, a list of learning objectives to be met by the rotating student during the sub-internship, and presence of a web page dedicated solely to the orthopaedic sub-internship. Each web site was given a sub-internship score (SI score) from 0 to 4 based on how many of the above criteria were met. From the 151 analyzed U.S. orthopaedic surgery residency program web sites, 69 (46%) did not have any mention of a sub-internship and thus received a score of 0, 4 (3%) received a score of 1, 18 (12%) received a score of 2, 20 (13%) received a score of 3, and 40 (26%) received a score of 4. The average SI score was 1.05 for the community-based orthopaedic residency programs, compared with 1.98 for the university-based orthopaedic programs (p = 0.003). Subgroup analysis based on SI scores (0 vs. 1 to 4) revealed that the higher-score group (1 to 4) had a higher percentage of university-based programs than the lower-score (0) group (80% vs. 62%; p = 0.003) and was associated with a greater number of residents per program than the lower-score group (mean, 26.4 vs. 21.0; p = 0.04). There was a weak association between the SI score and the number of residents in a given program (R2 = 0.074, p = 0.0004). The availability and quality of online information regarding sub-internships offered at orthopaedic residency programs in the U.S. are variable. Nearly half of the programs did not have any available online information on their web sites regarding orthopaedic surgery sub-internships. Larger and university-based orthopaedic programs have more robust information regarding sub-internships than smaller and community-based programs. There needs to be greater awareness and more uniformly accessible online information regarding orthopaedic surgery sub-internships for senior medical students seeking elective orthopaedic rotations prior to applying for residency training.


Evaluation and differential diagnosis of marked, persistent eosinophilia.
High-grade eosinophilia can be a diagnostic dilemma, as the etiologies are extensive and varied. Hypereosinophilic syndromes (HES) are a group of heterogeneous disorders, many of which remain poorly defined. By definition, HES must be distinguished from other disorders with persistently elevated eosinophilia with a defined cause. Although marked eosinophilia worldwide is most commonly caused by helminth (worm) infections, non-infectious causes must be considered, and include drug reactions, malignancies, and immunologic, inflammatory and allergic diseases.


Cell surface antigens of melanocytes and melanoma.
One major focus of cancer immunology is the question of tumour-specific antigens, the existence of which has yet to be proven. The prime candidates for antigens that can be considered tumour-specific are the class 1 unique antigens that have been serologically defined on human malignant melanomas by antibodies from the tumour-bearing host. In addition to these antigens, intensive immunological, biochemical and genetic analyses of melanoma have permitted a rudimentary classification of other surface antigens expressed by this tumour type. Cell-surface antigens of melanoma can be grouped into three general classes: restricted antigens (i.e. antigens which are expressed by melanomas and astrocytomas) many of which are differentiation markers characterizing cells of neuroectodermal origin; antigens with intermediate distribution (i.e. antigens which are present on some cell tumour types but not on others and which show a limited distribution on normal tissues and cells); and antigens with broad distribution (i.e. antigens expressed by most human cells either malignant or normal). The detailed knowledge of the surface antigens (i.e. differentiation antigens and class 1 unique antigens) of melanoma cells has permitted a rational and coherent approach to assessing the possibility of immunological control of malignant melanoma in the clinic.


Identification of the urease operon in Helicobacter pylori and its control by mRNA decay in response to pH.
We investigated the transcription of the urease gene cluster ureABIEFGH in Helicobacter pylori to determine the regulation of gene expression of the highly produced enzyme urease. Northern blot hybridization analysis demonstrated that cells of the wild-type strain grown in an ordinary broth had transcripts of ureAB, ureABI, ureI, ureIE' and ure'FGH, but cells of a ureI-disrupted mutant had only the ureAB transcript. When the wild-type cells were exposed to pH 8 for 30 min, very little mRNA was detected. However, when exposed to pH 6, a large amount of the ureIE" transcript, which was longer than the ureIE' transcript, together with the additional transcripts ureABIEFGH and ure'EFGH were detected. Rifampicin addition experiments demonstrated that urease mRNAs, and the ureIE' transcripts in particular, are more stable at pH 5.5 than at pH 7. In accord with these results, urease activity in the crude cell extract of the pH 5.5 culture was twice as much as that of the pH 7 culture, although the amounts of UreA and UreB detected by immunoblot analysis were similar. The transcription start point of ureI was identified by primer extension using a ureA promoter-deleted mutant, and a consensus sequence of RpoD-RNA polymerase was found in the ureI promoter. The 3' end of the ureIE" mRNA, determined using S1 nuclease mapping, revealed that the transcript is able to cover the majority of the ureE open reading frame (ORF) that might be sufficient for UreE activity. Based on the above results, we conclude that the urease gene cluster of H. pylori consists of two operons, ureAB and ureIEFGH, and that primary transcripts of the latter as well as the read-through transcript, ureABIEFGH, are cleaved to produce several species of mRNA. It has been suggested that the ureIEFGH operon is regulated post-transcriptionally by mRNA decay in response to environmental pH. We are tempted to speculate that the ureE" transcript present in acidic pH may contribute to produce an active product that can proceed the nickel incorporation to the active centre, the final step of urease biosynthesis.


Computational model-based assessment of baroreflex function from response to Valsalva maneuver.
Functional metrics of autonomic control of heart rate, including baroreflex sensitivity, have been shown to be strongly associated with cardiovascular risk. A decrease in baroreflex sensitivity with aging is hypothesized to represent a contributing causal factor in the etiology of primary hypertension. To assess baroreflex function in human subjects, two complementary methods to simulate the response in heart rate elicited by the Valsalva maneuver were developed and applied to data obtained from a cohort of healthy normal volunteers. The first method is based on representing the baroreflex arc as a simple linear filter, transforming changes in arterial pressure to changes in R-R interval. The second method invokes a physiologically based model for arterial mechanics, afferent baroreceptor strain-dependent firing, and control of heart rate via central autonomic response to changes in afferent inputs from aortic and carotid sensors. Analysis based on the linear filter model reveals that the effective response time of the baroreflex arc tends to increase with age in healthy subjects and that the response time/response rate is a predictor of resting systolic pressure. Similar trends were obtained based on the physiologically based model. Analysis of the Valsalva response using the physiologically based model further reveals that different afferent inputs from the carotid sinus and the aortic arch baroreceptors govern different parts of the heart rate response. The observed relationship between baroreflex sensitivity and systolic pressure is surprising because hypertensive subjects were excluded from the study, and there was no observed relationship between arterial pressure and age. NEW & NOTEWORTHY We introduce two methods to assess baroreflex function from data recorded from human subjects performing the Valsalva maneuver. Results demonstrate that the baroreflex response time tends to increase with age in healthy subjects, that response time represents a predictor of resting systolic pressure, and that the Valsalva response reveals different effects mediated by baroreceptors in the carotid sinus compared with those in the aortic arch.


Astragalus saponins modulate cell invasiveness and angiogenesis in human gastric adenocarcinoma cells.
We had reported that Astragalus saponins (AST) exert promising anti-tumorigenic effects by suppressing the growth of HT-29 human colon cancer cells and tumor xenograft. In the present study, we further investigated the anti-angiogenic property of AST in human gastric adenocarcinoma cells (AGS) and attempted to elucidate the underlying mechanism. Viability of AGS cells was measured by using the MTT reduction method. Western blotting was performed to examine the effect of AST on apoptotic- and cell growth-related protein expression. Effect of AST on cell cycle progression was also evaluated using PI staining. A Matrigel invasion assay was then employed to demonstrate the effect of AST on the invasiveness of gastric cancer cells. The expression of invasion-associated proteins (VEGF and MMPs) was also investigated. AST could induce apoptosis in AGS cells by activating caspase 3 with subsequent cleavage of poly(ADP-ribose) polymerase. Besides, cell cycle arrest at the G2/M phase had been observed in AST-treated cells, leading to substantial growth inhibition. The anti-proliferative effect of AST was associated with the regulation of cyclin B1, p21 and c-myc. Results indicate that the number of AGS cells invaded through the Matrigel membrane was significantly reduced upon AST treatment, with concomitant down-regulation of the pro-angiogenic protein vascular endothelial growth factor (VEGF) as well as the metastatic proteins metalloproteinase (MMP)-2 and MMP-9. AST derived from the medicinal plant Astragalus membranaceus could modulate the invasiveness and angiogenesis of AGS cells besides its pro-apoptotic and anti-proliferative activities. These findings also suggest that AST has the potential to be further developed into an effective chemotherapeutic agent in treating advanced and metastatic gastric cancers.


Oxidant stress reduces insulin responsiveness in 3T3-L1 adipocytes.
Increased oxidant stress has been suggested to occur in diabetes and to contribute to the development of late diabetic complications. Whether oxidant stress plays a role in the development or progression of insulin resistance is not known. In this study we hypothesized that exposing 3T3-L1 adipocytes to prolonged micromolar concentrations of H2O2 would reduce their acute metabolic responses to insulin stimulation. 3T3-L1 adipocytes exposed to 25 mU/ml glucose oxidase (GO) for 18 h exhibited a threefold increase in basal 2-deoxyglucose (2-DG) uptake activity. However, net increase in 2-DG uptake activity after acute insulin (100 nM) stimulation was 355 +/- 56 pmol.mg protein-1.min-1 in control vs. 198 +/- 41 pmol.mg protein-1.min-1 in GO-pretreated cells (P < 0.05). Basal lipogenesis activity was significantly enhanced by GO, but acute insulin stimulation resulted in significantly reduced lipogenesis activity (29 +/- 4 vs. 11 +/- 1 nmol glucose/well for control and 50 mU/ml GO, respectively, P = 0.001). Glycogen synthase alpha activity was reduced by GO (78 +/- 1 vs. 43 +/- 2 pmol UDP-glucose.mg protein-1.min-1, P = 0.03), whereas insulin stimulation of glycogen synthase was reduced, exhibiting a right shift in the insulin dose-response curve. These effects of GO were associated with increased GLUT-1 and reduced GLUT-4 protein and mRNA content. In conclusion, our data suggest that oxidant stress alters glucose transporters expression and insulin-stimulated metabolism in 3T3-L1 adipocytes.


[Use of series E prostaglandins in the treatment of essential hypertension].
Fifty-four hypertensive patients with the average BP level of 208 +/- 3.2/125 +/- 2.4 mm Hg were infused 2 doses of PGE. Forty patients received PGE2 in the form of protein (USA) and 14 patients were administered PGE1 in the form of alprostadil (USA). Each patient received on the average 3.5 mg of PGE2 or 0.7 mg of PGE1 during 48 hours. PGE infusion by the devised scheme induced no significant side-effects, was attended by an increase in the diuresis and natriuresis as well as a BP decrease (more pronounced with PGE1) not only in the period of the infusion but also during the 2-3 days following it. The hypotensive effect and BP fall in the orthostatic position were more marked following PGE2 infusion. PGE enhanced the sensitivity of the patients to obsidan, clophelin, hydrochlorothiazide and to a lesser degree to corinfar. Infusion of PGE2 to patients with essential hypertension resistant to hypotensive agents reduced the BP and made it possible to diminish the number of the drugs prescribed and their doses. The hypotensive effect of the drugs administered persisted for up to 5-7 months. It can be expected that repeated infusions of PGE2 every 6 months, will contribute to an alleviation of arterial hypertension, the patient's clinical improvement and the lowering of doses of hypotensive drugs.


Leucine metabolism in thyrotoxicosis: plasma aminogram and 3-methylhistidine excretion before and after treatment.
Previous studies have suggested increased protein catabolism and altered muscle metabolism in hyperthyroid patients. In this experiment we investigated parameters of protein and leucine metabolism before and after treatment of hyperthyroidism. While confined in a metabolic ward, patients' daily caloric intake was based on the resting energy expenditure and an allowance for 16 hours of light physical activity. We found no significant difference in plasma aminogram and urinary 3-methylhistidine excretion (an index of protein catabolism) before and after treatment. On the other hand, hyperthyroidism appeared to increase the rates of oxidation, turnover, and plasma clearance of endogenous leucine. However, only the 60% increase in the rate of leucine oxidation was statistically significant. We conclude that in spite of increased catabolism, basal levels of branched-chain amino acids are well maintained in plasma of hyperthyroid patients consuming a diet that compensates for their hypermetabolic state.


Molecular and morphological supertrees for eutherian (placental) mammals.
A large body of diverse comparative data now exists for a major phylogenetic synthesis of the higher-level relationships among eutherian (placental) mammals. We present such a phylogenetic synthesis using the composite trees or supertrees from the combined and separate analyses of their published molecular and morphological source phylogenies. Our combined and separate supertrees largely support the same suprafamilial taxa and orders, but different interordinal clades. These similarities and differences reinforce the continuing contributions of morphological studies, while highlighting the growing influence of molecular information on the field. As current summaries of past research, our supertrees emphasize opportunities for future work, while providing a step toward the eventual integration of the data and characters themselves.


Thrombin-Based Hemostatic Agent in Primary Total Knee Arthroplasty.
The present meta-analysis pooled the results from randomized controlled trials (RCTs) to identify and assess the efficacy and safety of thrombin-based hemostatic agent in primary total knee arthroplasty (TKA). Potential academic articles were identified from the Cochrane Library, Medline (1966-2015.5), PubMed (1966-2015.5), Embase (1980-2015.5), and ScienceDirect (1966-2015.5). Relevant journals and the recommendations of expert panels were also searched by using Google search engine. RCTs assessing the efficacy and safety of thrombin-based hemostatic agent in primary TKA were included. Pooling of data was analyzed by RevMan 5.1 (The Cochrane Collaboration, Oxford, UK). A total of four RCTs met the inclusion criteria. The meta-analysis revealed significant differences in postoperative hemoglobin decline (p < 0.00001), total blood loss (p < 0.00001), drainage volume (p = 0.01), and allogenic blood transfusion (p = 0.01) between the treatment group and the control group. No significant differences were found regarding incidence of infection (p = 0.45) and deep vein thrombosis (DVT; p = 0.80) between the groups. Meta-analysis indicated that the application of thrombin-based hemostatic agent before wound closure decreased postoperative hemoglobin decline, drainage volume, total blood loss, and transfusion rate and did not increase the risk of infection, DVT, or other complications. Therefore, the reviewers believe that thrombin-based hemostatic agent is effective and safe in primary TKA.