Is the level of institutionalisation found in psychiatric housing services associated with the severity of illness and the functional impairment of the patients? A patient record analysis.
In this cross-sectional study, we investigated whether clinical, social, financial, and care variables were associated with different accommodation settings for individuals suffering from severe and persistent mental disorders. Electronic record data of 250 patients who fulfilled the criteria for persistent and severe mental illness were used. Multiple linear regression models were applied to analyse associations between the types and the costs of housing services and the patients' severity of illness, their functional impairment, and their socio-demographic characteristics. We identified 50 patients living at home without need for additional housing support who were receiving outpatient treatment, 41 patients living in the community with outpatient housing support, 23 patients living with foster families for adults, 45 patients living in group homes with 12-h staff cover, 10 patients living in group homes with 24-h staff, and 81 patients living in psychiatric nursing homes. While this housing differed largely in the level of institutionalisation and also in the costs of accommodation, these differences were not related to a patient's severity of disease or in their functional impairment. In particular, patients living in nursing homes had a slightly higher level of functioning compared to those living in the community without welfare housing services. Only where patients were subject to guardianship was there a significant association with an increased level of institutionalisation. Our study suggests that the level of institutionalisation and the associated costs of welfare housing services do not accurately reflect the severity of illness or the level of functional impairment of the patients there are designed to support. The limitations of the study design and the data do not allow for conclusions about causal relationships or generalisation of the findings to other regions. Therefore, further prospective studies are needed to assess the adequacy of the setting assignment of patients with persistent severe mental illness into different types of housing settings with appropriate (also welfare) services.


Ruthenium-Catalyzed Synthesis of Aryl and Alkenyl Halides from Fluorosulfonates.
Aryl and alkenyl halides are widely used as key intermediates in organic synthesis, particularly for the formation of organometallic reagents or as radical precursors. They are also found in pharmaceutical and agrochemical ingredients. In this work, the synthesis of aryl and alkenyl halides from the corresponding fluorosulfonates using commercially available ruthenium catalysts is reported. Notably, this is the first conversion of phenols to aryl halides that is efficient with chloride, bromide, and iodide. Fluorosulfonates are readily prepared using sulfuryl fluoride (SO2 F2 ) and less expensive substitutes for triflates. Although aryl fluorosulfonates and their reactions are well known, this is the first report of an efficient coupling of alkenyl fluorosulfonates. To finish, it was demonstrated, by means of representative examples, that the reaction is possible in a one-pot process, starting directly from phenol or aldehyde.


COVID-19 vaccination is associated with reduced non-COVID in-hospital mortality.
We retrieved data on a cohort of medical patients at a regional Israeli hospital. The dependent variable was non-COVID-19 hospital mortality; the independent variables were vaccination status, age, and laboratory data. Serum sodium, age, serum creatinine, and COVID-19 vaccination status were the main independent variables associated with non-COVID-19 mortality. The odds ratio for in-hospital deaths of non-vaccinated patients was 2.01 (1.65-2.44) (unadjusted) and 1.61 (1.29-2.03) after adjustment for the independent variables. This "healthy adherer effect" may confound observational assessments of the clinical efficacy of COVID-19 vaccines.


Two learning tasks provide evidence for disrupted behavioural flexibility in an animal model of schizophrenia-like behaviour induced by acute MK-801: a dose-response study.
Schizophrenia is a chronic and devastating illness. Exact causes of the disease remain elusive; however, neurodevelopmental changes in the brain glutamate system are recognized to play an important role. Several animal models of the disease are induced by a systemic blockade of N-methyl-d-aspartate (NMDA) receptors. This study examined the animal model of schizophrenia-like behaviours induced by acute treatment with MK-801, a non-competitive NMDA-receptor antagonist. Behavioural flexibility is an ability to adapt to the changes in environment, and schizophrenia is often accompanied by its decrease. The study tested the effect of MK-801 on behavioural flexibility in an active place avoidance task and the Morris water maze (MWM). Flexibility was tested under reversal conditions, i.e., after changing the location of the target. Each spatial task addressed different functions; continuous coordinate-frame segregation was present in the active place avoidance and precise place representation in the MWM. Results showed that reversal was altered in both tasks by MK-801 at doses of 0.10-0.15 mgkg(-1). Some impairment was observed in the active place avoidance task at 0.08 mgkg(-1). Swimming towards a visible platform was impaired only by the highest dose (0.15 mgkg(-1)). The results demonstrate that a significant impairment of behavioural flexibility accompanies this acute animal model of schizophrenia-like behaviours, and that active place avoidance had higher sensitivity for such deficits than the MWM. This suggests the usefulness of the reversal paradigm in both tasks for examining novel drugs with antipsychotic and procognitive actions.


Failure of naloxone to reverse peripheral transcutaneous electro-analgesia in patients suffering from acute trauma.
Transcutaneous electrical stimulation of the intercostal nerves innervating the site of fractured ribs in 6 patients produced subjective and clinical evidence of decrease in the pain experienced by the patients. This analgesia was not significantly modified by naloxone, a pure narcotic antagonist. The possible role of endogenous morphine-like substances in peripheral electro-analgesia in man is discussed.


Reactions of phosphonate analogs of pyridoxal phosphate with apo-aspartate aminotransferase.
We have investigated reactions of the 5-phosphonoethyl and 5-phosphonoethenyl analogs of pyridoxal 5'-phosphate in the coenzyme site of cytosolic aspartate aminotransferase. Acid dissociation constants and equilibrium constants for hydration and for tautomerization have been evaluated for these compounds. In confirmation of previous results, both compounds are partially active. They bind to apoenzyme well and undergo conversion in the presence of glutamate to amine forms which show induced circular dichroism comparable to that of native enzyme. A normal "external" Schiff base is evidently formed with 2-methylaspartate, but the amounts of quinonoid intermediate formed with erythro-3-hydroxyaspartate are less than those formed with pyridoxal phosphate. The pKa of the imine group of the enzyme reconstituted with the phosphonoethyl analog is more than two units lower than that in the native enzyme. Binding of the dicarboxylates glutarate, 2-oxoglutarate, and succinate shifts the pKa upward. The absorption spectra of the resulting complexes indicate the existence of at least three low pH species. A shift of 2.3 to 2.9 ppm to a lower frequency was observed for the 31P NMR signal upon binding of these dicarboxylates or of 2-methylaspartate. Enzyme containing the analogs crystallizes. Polarized absorption spectra suggest that the coenzyme has an orientation similar to that of pyridoxal phosphate in the native enzyme.


Adsorption to the Surface of Hemozoin Crystals: Structure-Based Design and Synthesis of Amino-Phenoxazine β-Hematin Inhibitors.
In silico adsorption of eight antimalarials that inhibit β-hematin (synthetic hemozoin) formation identified a primary binding site on the (001) face, which accommodates inhibitors via formation of predominantly π-π interactions. A good correlation (r2 =0.64, P=0.017) between adsorption energies and the logarithm of β-hematin inhibitory activity was found for this face. Of 53 monocyclic, bicyclic and tricyclic scaffolds, the latter yielded the most favorable adsorption energies. Five new amino-phenoxazine compounds were pursued as β-hematin inhibitors based on adsorption behaviour. The 2-substituted phenoxazines show good to moderate β-hematin inhibitory activity (<100 μM) and Plasmodium falciparum blood stage activity against the 3D7 strain. N1 ,N1 -diethyl-N4 -(10H-phenoxazin-2-yl)pentane-1,4-diamine (P2a) is the most promising hit with IC50 values of 4.7±0.6 and 0.64±0.05 μM, respectively. Adsorption energies are predictive of β-hematin inhibitory activity, and thus the in silico approach is a beneficial tool for structure-based development of new non-quinoline inhibitors.


[Influence of UV irradiation on microbiological degradation of petroleum products].
Changes in the rates of microbiological degradation of kerosene, diesel fuel, and fuel oil under the effect of UV irradiation were estimated by testing the respiratory activity of microbial communities. The strongest inhibitory effect was observed upon simultaneous UV irradiation of both natural water and petroleum products. Concentrations of CO2 in the microbial communities (microcosms) decreased from 6.7 to 3.6 vol. % upon oxidation of kerosene, from 5.9 to 0.8 vol. % upon oxidation of diesel fuel, and from 5.7 to 0.05 vol. % upon oxidation of fuel oil.


Estimating duration of central venous catheter at time of insertion: Clinician judgment and clinical predictors.
The aim of this study was to investigate whether clinicians can estimate the length of time a central venous catheter (CVC) will remain in place and to identify variables that may predict CVC duration. We conducted a prospective study of patients admitted to the intensive care unit over a 1-year period. Clinicians estimated the anticipated CVC duration at time of insertion. We collected demographics, medical history, type of intensive care unit, anatomical site of CVC placement, vital signs, laboratory values, Sequential Organ Failure Assessment score, mechanical ventilation, and use of vasopressors. Pearson correlation coefficient was used to assess the correlation between estimated and actual CVC time. We performed multivariable logistic regression to identify predictors of long duration (>5 days). We enrolled 200 patients; median age was 65 years (quartiles 52, 75); 91 (46%) were female; and mortality was 24%. Correlation between estimated and actual CVC time was low (r=0.26; r2=0.07; P<.001). Mechanical ventilation (odds ratio, 2.20; 95% confidence interval, 1.22-3.97; P=.009) at time of insertion and a medical history of cancer (odds ratio, 0.35; 95% confidence interval, 0.16-0.75; P=.007) were significantly associated with long duration. Our results suggest a low correlation between clinician prediction and actual CVC duration. We did not find any strong predictors of long CVC duration identifiable at the time of insertion.


Effects of nitrogen stress on uptake and translocation of organophosphate esters by watermifoil (Myriophyllum aquaticum L.) in an aquatic ecosystem.
Although organophosphate esters (OPEs) and nitrogen (N) are normally present in aquatic environments, the effects of the plant uptake, accumulation, and translocation of OPEs in different levels of N remain ambiguous. To better understand these processes, watermifoil (Myriophyllum aquaticum L.) as tested plant was chosen to investigate the effects of different N levels on the uptake and translocation of OPEs by plants in matched water-sediment-plant samples. After two months, we found the root-water concentration factors, root-sediment concentration factors, and translocation factors (TFs) were significantly changed with the levels of N (p < 0.05), implying that the presence of N could alter uptake, accumulation, and translocation of OPEs in M. aquaticum, particularly the process of root absorption. Low concentrations of N could remarkably promote the uptake of OPEs by M. aquaticum. However, when the concentrations of N in water were higher than 200 mg/L, the plants' growth and OPE accumulation by M. aquaticum were obviously inhibited with the elevated N contents. Moreover, the enrichment and environmental transport of OPEs in M. aquaticum seemed to be closely associated with physicochemical parameters; the octanol-water partition coefficient had significant relationships with measured organic carbon-normalized sediment-water partition coefficients and TFs in the present study. Additionally, the substituents and structures of OPEs could also affect the accumulation and translocation of OPEs in M. aquaticum, including the chlorination degree and alkyl chain length. This study could improve our understanding of uptake and translocation of OPEs in aquatic plants under different levels of N.


Deep Simulation of Facial Appearance Changes Following Craniomaxillofacial Bony Movements in Orthognathic Surgical Planning.
Facial appearance changes with the movements of bony segments in orthognathic surgery of patients with craniomaxillofacial (CMF) deformities. Conventional bio-mechanical methods, such as finite element modeling (FEM), for simulating such changes, are labor intensive and computationally expensive, preventing them from being used in clinical settings. To overcome these limitations, we propose a deep learning framework to predict post-operative facial changes. Specifically, FC-Net, a facial appearance change simulation network, is developed to predict the point displacement vectors associated with a facial point cloud. FC-Net learns the point displacements of a pre-operative facial point cloud from the bony movement vectors between pre-operative and simulated post-operative bony models. FC-Net is a weakly-supervised point displacement network trained using paired data with strict point-to-point correspondence. To preserve the topology of the facial model during point transform, we employ a local-point-transform loss to constrain the local movements of points. Experimental results on real patient data reveal that the proposed framework can predict post-operative facial appearance changes remarkably faster than a state-of-the-art FEM method with comparable prediction accuracy.


EUS-guided portal injection chemotherapy for treatment of hepatic metastases: feasibility in the acute porcine model.
Direct injection of chemotherapy into the portal vein for treatment of liver metastases may increase hepatic tissue levels while decreasing systemic levels and toxicities. We aimed to evaluate EUS-guided portal injection chemotherapy (EPIC) by using drug-eluting microbeads or nanoparticles and compare it with systemic injection. We conducted a comparative feasibility trial in the acute porcine model (24 anesthetized pigs). Pigs were treated with irinotecan, doxorubicin, or albumin-bound paclitaxel nanoparticles (n = 8/group). Within each group, pigs were treated with EPIC or a systemic intravenous injection of drug and saline solution into the portal vein (n = 4/treatment). Irinotecan or doxorubicin were loaded onto microbeads for EPIC treatment only. We examined drug levels in tissue (1 hour) and plasma (15 minutes). EUS-guided access and injection was successful in all animals. EPIC with irinotecan-loaded microbeads showed nearly double the hepatic concentration compared with systemic injection (6242 vs 3692 ng/g) and almost half the systemic levels. EPIC with doxorubicin-loaded microbeads showed a 5-fold increase in hepatic levels (35,450 vs 6930 ng/g) and a 30-fold decrease in cardiac levels (153 vs 4805 ng/g) compared with systemic administration (P < .05 for both). EPIC with albumin-bound paclitaxel nanoparticles increased hepatic concentrations by 60% and decreased systemic levels by 24% to 32%. EPIC holds promise as a new treatment for hepatic metastases.


Hormones, ovulatory cycle phase and pathogen disgust: A longitudinal investigation of the Compensatory Prophylaxis Hypothesis.
Multiple studies have argued that disgust, especially pathogen disgust and contamination sensitivity, change across women's ovulatory cycle, with higher levels in the luteal phase due to an increase in progesterone levels. According to the Compensatory Prophylaxis Hypothesis (CPH), women have a higher disgust sensitivity to pathogen cues when in the luteal phase (or when progesterone levels are higher), because progesterone is associated with suppressed immune responses. Evidence for this hypothesis is rather mixed and uncertain, as the largest study conducted so far reported no compelling evidence for an association between progesterone levels and pathogen disgust. Further, ovulatory cycle research has been criticized for methodological shortcomings, such as invalid cycle phase estimates, no direct hormone assessments, small sample sizes or between-subjects studies. To address these issues and to contribute to the literature, we employed a large, within-subjects design (N = 257 with four sessions each), assessments of salivary hormone levels and cycle phase estimates based on luteinizing hormone tests. A variety of multilevel models suggest no compelling evidence that self-reported pathogen disgust or contamination sensitivity is upregulated in the luteal phase or tracks changes in women's hormone levels. We further found no compelling evidence for between-subjects associations of pathogen disgust or contamination sensitivity and hormone levels. Results remain robust across different analytical decisions (e.g. in a subsample of women reporting feeling sick). We discuss explanations for our results, limitations of the current study and provide directions for future research.


Case series and technical report of nasal floor approach for mesiodens.
This case series aims to introduce the nasal floor approach for extracting inverted mesiodens. Through a retrospective chart review between January 2022 and February 2023, we included the mesiodens patients using nasal floor approach, and analysis the location of mesiodens from the anterior nasal spine (ANS), total operation time, and complications. Each mesiodens was located 10 to 12 mm from the ANS and was covered with a cortical layer of the nasal floor. All mesiodens were successfully extracted without exposing the adjacent incisors or nasopalatine nerve within 30 minutes from draping to postoperative dressing. The nasal floor approach is an efficient extraction method that reduces bone removal and prevents anatomical damage while removing the mesiodens just below the nasal floor bone.


Pregnancy and diabetes: the maternal response.
Pregnancy places remarkable stresses on maternal carbohydrate metabolism and pancreatic insulin reserves. The normal mammal responds to pregnancy by increasing pancreatic islet size and insulin secretion. Pregnancy also causes alterations in concentrations of metabolic fuels in maternal circulation. These changes are partly attributed to gestational increases of estrogen, progesterone and human chorionic somatomammotropin, and are thought to provide a proper metabolic and hormonal incubation medium for the fetus. Conversely, the compromised pancreas of the diabetic is unable to meet the additional demands of pregnancy, and carbohydrate metabolism deteriorates. The character of these metabolic changes depends on the time of gestation and the type of diabetes mellitus.


A large intrathoracic goiter with tracheal stenosis: Complete resection using a robot-assisted thoracoscopic approach.
Growing intrathoracic goiters may compress surrounding organs and deteriorate the cardiopulmonary function. Treating such cases requires carefully considering how to maintain oxygenation and resect the tumor with minimal invasiveness without complications. We herein report a surgically resected case of a large intrathoracic goiter-compressed trachea extending from the right lower pole of the thyroid gland to the carina. We secured the airway by intubation preparing for extracorporeal membrane oxygenation and successfully performed surgical complete resection using a robot-assisted thoracoscopic and cervical approach. Intrathoracic goiter is a tumor with abundant neovascularity, and the right vagus nerve is displaced in the thoracic cavity, but a robot-assisted thoracoscopic approach using CO2 insufflation improved visualization at the narrow apex area of the thoracic cavity. Robot-assisted thoracoscopic surgery is a useful surgical procedure enabling safe and minimally invasive surgery without recurrent laryngeal nerve palsy or tracheal injury for intrathoracic giant goiters extending into the thoracic cavity.


Inwardly rectifying potassium channel Kir4.1 is localized at the calyx endings of vestibular afferents.
Inwardly rectifying potassium (Kir) channel Kir4.1 (also called Kcnj10) is expressed in various cells such as satellite glial cells. It is suggested that these cells would absorb excess accumulated K(+) from intercellular space which is surrounded by these cell membranes expressing Kir4.1. In the vestibular system, loss of Kir4.1 results in selective degeneration of type I hair cells despite normal development of type II hair cells. The mechanisms underlying this developmental disorder have been unclear, because it was thought that Kir4.1 is only expressed in glial cells throughout the entire nervous system. Here, we show that Kir4.1 is expressed not only in glial cells but also in neurons of the mouse vestibular system. In the vestibular ganglion, Kir4.1 mRNA is transcribed in both satellite cells and neuronal somata, whereas Kir4.1 protein is expressed only in satellite cells. On the other hand, in the vestibular sensory epithelia, Kir4.1 protein is localized at the calyx endings of vestibular afferents, which surround type I hair cells. Kir4.1 protein expression in the vestibular sensory epithelia is detected beginning after birth, and its localization gradually adopts a calyceal shape until type I hair cells are mature. Kir4.1 localized at the calyx endings may play a role in the K(+)-buffering action of vestibular afferents surrounding type I hair cells.


iACT-CEL: A Feasibility Trial of a Face-to-Face and Internet-Based Acceptance and Commitment Therapy Intervention for Chronic Pain in Singapore.
Psychological interventions are increasingly utilising online or mobile phone based platforms to deliver treatment, including that for people with chronic pain. The aims of this study were to develop an adapted form of Acceptance and Commitment Therapy (ACT) for chronic pain in Singapore and to test the feasibility of elements of this treatment delivered via the internet and email. Methods. Thirty-three participants recruited from a tertiary pain management clinic and via the clinic website participated in this program over a period of five weeks with a 3-month follow-up. Treatment outcomes were assessed at three assessment time points. Results. 90.9% of participants completed the program, with 81.8% reporting high treatment satisfaction. Significant changes in depression, t = 3.08, p = 0.002 (baseline to posttreatment), t = 3.28, p = 0.001 (baseline to follow-up), and pain intensity, t = 2.15, p = 0.03 (baseline to follow-up) were found. Mainly small effect sizes (d = 0.09-0.39) with a moderate effect size (d = 0.51) for depression were found at posttreatment. Clinically meaningful improvement in at least one outcome was demonstrated in 75.8% of participants. Conclusions. An adaptation of ACT for people with chronic pain in Singapore appears promising. Optimal treatment design and more effective ways to target outcomes and processes measured here are required.


Effect of di-isopropanolnitrosamine in European hamsters.
The carcinogenic effects of di-isopropanolnitrosamine (DIPN) were tested in hibernating and non-hibernating European hamsters. The results obtained were compared with those produced by the same substance in Syrian golden hamsters and Sprague-Dawley rats. In European hamsters, tumours were produced in the nasal cavity, trachea, lung, liver and pancreas. The main target organs were the anterior part of the nasal cavity and liver. Only cholangiomas and cholangiocarcinomas were found in the liver. Early changes in the intrahepatic bile ducts and duct epithelium of the pancreas were seen 4 weeks after treatment was started. Fourteen out of 144 treated hamsters developed pancreatic-duct tumours, 2 of which were malignant. The tumorigenic response in the target organs was lower in hibernating than in non-hibernating animals.


Warm storage of whole blood for 72 hours.
In field emergency medicine, fresh whole-blood units are stored at room temperature up to 24 hours or occasionally longer. Few data exist on the integrity and in vitro functional properties of whole blood stored warm beyond 24 hours. Ten citrate phosphate dextrose solution whole-blood units were collected and divided into two equal volumes. One-half of each unit was stored at 19 degrees C and the other half was stored at 25 degrees C, encompassing the accepted range for room temperature storage. At 6, 24, 48, and 72 hours, aliquots were collected from each unit and whole blood analyzed for cell counts, gases, and clotting function with thromboelastography, red cells for intracellular analytes, platelet (PLT)-rich plasma for aggregometry, and the supernatant for hemoglobin, potassium, glucose, lactate, and plasma clotting studies. Whole-blood units stored at room temperature maintained cellular counts and coagulation activity for up to 72 hours. Units stored at 19 degrees C demonstrated greater RBC adenosine triphosphate and 2,3-diphosphoglycerate (DPG) content and stronger responses in PLT aggregation studies when compared with 25 degrees C storage. No significant hemolysis was observed, and no bacterial growth was detected. Storage of whole blood at room temperature for 72 hours leads to marked reductions in pH and DPG, but the observed reduction in PLT function and plasma coagulation factor activity was surprisingly modest compared to literature values. These findings should prompt additional investigation, given their potential importance for whole blood processing and field-expedient transfusion.


Dicrocoelium ova can block the induction phase of experimental autoimmune encephalomyelitis.
This study aimed at investigating the impact of Dicrocoelium ova on experimental autoimmune encephalomyelitis (EAE) treatment in C57BL6 mice. Twenty-eight C57BL/6 mice were assigned into four groups as PBS, prophylaxis (P), treatment1 (T1) and treatment2 (T2). Prior to induction of EAE in prophylaxis group and on days 7 and 18 in T1 and T2 groups, respectively, Dicrocoelium eggs were injected intraperitoneally to each mouse. The clinical score, weight changes and incidence time of EAE were recorded. IFN-γ and IL-4 expression is quantified on spleen cells. Also, histopathological study by (H&E) and Toluidine-Blue (TB), and Luxol Fast Blue (LFB) were performed. The data were analysed using SPSS version 21. Mean disease scores were significantly lower in P and T1 groups than the PBS group (P = .01). IFN-γ was lower in P and T1 groups than the PBS group. The highest level of IL-4 was observed in T1 group. The total number of neuroglia cells of corpus callosum was similar in all groups, but the density increased in T1 group compared to the PBS group (P = .03). Dicrocoelium eggs have a great potential to stimulate immunomodulation towards treatment of EAE during the initial phase.


Preparation of adult spinal cord motor neuron cultures under serum-free conditions.
Spinal cord motor neuron cultures are an important tool for the study of mechanisms involved in motor neuron survival, degeneration and regeneration, volatile anesthetic-induced immobility, motor neuron disorders such as amyotrophic lateral sclerosis or spinal muscular atrophy as well as in spinal cord injury. Embryonic spinal cord motor neurons derived from rats have been successfully cultured; unfortunately, the culture of adult motor neurons has been problematic due to their short-term survival. Recently, by using a cocktail of target-derived factors, neurotrophins (brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor) and a permeable cyclic adenosine monophosphate analog, we have established a reproducible protocol for long-term cultures of healthy and functional adult motor neurons (Exp Neurol 220:303-315, 2009). Here, we now describe in detail the steps that we used for the optimization of the process of isolation and maintenance of adult rat ventral horn motor neurons in vitro.


Work of breathing and lung volume during forward leaning supported by the upper limbs.
This study compared work of breathing (WOB) and the pressure time product (PTP) to verify whether WOB and PTP decrease in the forward-leaning posture compared with erect sitting. Seven healthy adults (two females and five males) adopted three sitting postures: upright, and two forward-leaning postures of 15° and 30°. The WOB was obtained using the modified Campbell diagram, and PTP was calculated as the time integral of the area between esophageal and chest wall pressure. End-expiratory lung volume and transpulmonary pressure were significantly increased in the 15° and 30° forward-leaning postures compared with erect sitting (p ≦ 0.05). End-inspiratory lung volume was significantly increased in the 30° forward-leaning posture compared to erect sitting (p ≦ 0.05). PTP and inspiratory resistive WOB were significantly lower in the 15° and 30° forward-leaning postures compared to erect sitting (p ≦ 0.05). Forward leaning increases lung volume, which may dilate the airways, decrease resistant WOB, and reduce respiratory muscle activity.


Major abdominal surgery in octogenarians: should high age affect surgical decision-making?
Over the last decades longevity has increased significantly, with more octogenarians undergoing surgery. Here, we assess surgical outcomes after major abdominal surgery in octogenarians. Observational cohort of 874 patients undergoing major abdominal elective surgery between January 2009 and March 2014. Seventy-six octogenarians were propensity matched to 76 younger patients, corrected for sex, body mass index, American Society of Anesthesiologists classification, comorbidity, indication, and type of surgery. Minor complications were more prevalent in octogenarians (P = .01) and consisted mainly of respiratory complications; progressing to respiratory insufficiency requiring intubation in 28.6%. Preoperative weight loss (odds ratio 3 [1.1 to 8.3]) and upper gastrointestinal surgery (odds ratio 11 [2 to 60]) were associated with minor complications. Octogenarians are at increased risk of minor complications after major abdominal surgery. Major complication rates were similar, indicating the importance of preoperative assessment and standardized surgical techniques. Taking into account preoperative morbidities and type of surgery and techniques. Implementation of quality control algorithms may further improve outcomes in octogenarians.


Gender, status, and psychiatric labels.
We examine a key modified labeling theory proposition-that a psychiatric label increases vulnerability to competence-based criticism and rejection-within task- and collectively oriented dyads comprised of same-sex individuals with equivalent education. Drawing on empirical work that approximates these conditions, we expect the proposition to hold only among men. We also expect education, operationalized with college class standing, to moderate the effects of gender by reducing men's and increasing women's criticism and rejection. But, we also expect the effect of education to weaken when men work with a psychiatric patient. As predicted, men reject suggestions from teammates with a psychiatric history more frequently than they reject suggestions from other teammates, while women's resistance to influence is unaffected by their teammate's psychiatric status. Men also rate psychiatric patient teammates as less powerful but no lower in status than other teammates, while women's teammate assessments are unaffected by their teammate's psychiatric status. Also as predicted, education reduces men's resistance to influence when their teammate has no psychiatric history. Education also increases men's ratings of their teammate's power, as predicted, but has no effect on women's resistance to influence or teammate ratings. We discuss the implications of these findings for the modified labeling theory of mental illness and status characteristics theory.


Case study methodology in tissue viability. Part 1: Methodological considerations.
Case studies are often presented in relation to tissue viability problems. Within hierarchies of evidence, case studies are sometimes seen to be on a par with expert opinion. This paper examines the case study as a research method and seeks to determine its value in tissue viability research. The term 'case study' denotes a general strategy for research where several methods of data collection are used to provide an in-depth analysis of an individual, group or institution. Three types of case study are used in research: intrinsic, instrumental and collective. All case studies utilize data triangulation within their design, that is, the use of a variety of sources of data within a study. It is one of the major strengths of the case study method. Data sources include documentary data sources, observation and interviews. As in any research, validity and reliability are important in case study methodology; in particular, construct validity, internal validity and external validity. Case studies are potentially vulnerable to observer error and observer bias. Examples are given of potential case studies in tissue viability and their strengths and weaknesses. If undertaken prospectively, with clearly defined multiple sources of data collection and a documented chain of evidence, case studies can add breadth to our knowledge and experience of caring for patients with tissue viability problems.


Clinical cardiovascular phenotypes and the pattern of future events in patients with type 2 diabetes.
Updated guidelines on diabetes recommend targeting sodium-glucose cotransporter-2 inhibitors (SGLT2i) at patients at risk of heart failure (HF) and glucagon-like peptide-1 receptor agonists (GLP1-RA) at those at greater risk of atherothrombotic events. We estimated the risk of different cardiovascular events in patients with type 2 diabetes (T2D) and newly established cardiovascular disease. Patients with T2D and newly established cardiovascular disease from 1998 to 2016 were identified using Danish healthcare registers and divided into one of four phenotype groups: (1) HF, (2) ischemic heart disease (IHD), (3) transient ischemic stroke (TIA)/ischemic stroke, and (4) peripheral artery disease (PAD). The absolute 5-year risk of the first HF- or atherothrombotic event occurring after inclusion was calculated, along with the risk of death. The main outcome was the first event of either HF or an atherothrombotic event (IHD, TIA/ischemic stroke or PAD) in patients with T2D and new-onset cardiovascular disease. Of the 37,850 patients included, 40% were female and the median age was 70 years. Patients with HF were at higher 5-year risk of a subsequent HF event (17.9%; 95% confidence interval (CI) 17.1-18.8%) than an atherothrombotic event (15.8%; 15.0-16.6%). Patients with IHD were at higher risk of a subsequent atherothrombotic event (24.6%; 23.9-25.3%) than developing HF, although the risk of HF was still substantial (10.6%; 10.2-11.1%). Conversely, patients with PAD were at low risk of developing HF (4.4%; 3.8-5.1%) but at high risk of developing an atherothrombotic event (15.9%; 14.9-17.1%). Patients with TIA/ischemic stroke had the lowest risk of HF (3.2%; 2.9-3.6%) and the highest risk of an atherothrombotic event (20.6%; 19.8-21.4). In T2D, a patient's cardiovascular phenotype can help predict the pattern of future cardiovascular events.


The investigation of functional brain lateralization by transcranial Doppler sonography.
Functional transcranial Doppler sonography (fTCD) adds to the techniques of functional imaging. fTCD measures cerebral perfusion changes related to neural activation in a way comparable to functional magnetic resonance tomography. fTCD contends itself with comparison of averaged, event-related blood flow velocity changes within the territories of two cerebral arteries, for example the left versus the right middle cerebral artery. It can thus serve to evaluate the functional lateralization of higher cognitive functions like hemispheric language dominance (HLD). We present typical applications of fTCD by summarizing studies employing the technique. Then, the physical and physiological underpinnings of fTCD are reviewed. After a brief description of a prototype paradigm for assessing HLD, a detailed outline of the fTCD data analysis is presented. Caveats for fTCD, like other functional imaging techniques, are that the validity of results depends on adequate control of the task parameters, particularly cooperation and reference conditions. We complete the review with examinations of the reliability and validity of the fTCD technique. We conclude that fTCD can be employed to substitute the invasive amobarbital procedure to determine language lateralization in individual patients before undergoing brain surgery. Because of its easy applicability, robustness and mobility, fTCD can also be used to examine many subjects (including children) to obtain representative data on the variability of lateralization of higher cognitive functions, or to scan for atypical patterns of lateralization.


Antibacterial efficacies and time-kill kinetics of indigenous Ghanaian spice extracts against Listeria monocytogenes and some other food-borne pathogenic bacteria.
Increase in food-borne outbreaks has become public health concern worldwide. Exploitation of the antimicrobial properties of dietary spices has become important pharmaceutical tool for controlling food-borne pathogens. This study aimed at evaluating the antibacterial potentials of Ghanaian spices against Listeria monocytogenes and other prevalent food-borne pathogens. In preliminary studies, Listeria was isolated from some food samples. The overall prevalence of Listeria spp. was 23% (13/56). Of the 56 samples examined, 7% showed pathogenic potential for L. monocytogenes. Different solvent extracts of thirteen spices namely Calabash nutmeg, West African black pepper, Aidan, Grains of paradise, Negro pepper, Aniseed, African locust bean, Cinnamon, Black pepper, Clove, Cayenne, Basil, and Rauvolfia were tested for their potentials to inhibit clinical and isolated strains of L. monocytogenes using qualitative and quantitative antimicrobial assay methods. Only clove and negro pepper among the thirteen different solvent extracts showed bacteriostatic and bactericidal activity against L. monocytogenes indicated by minimum inhibitory concentrations ranging from 0.05% to 0.4% and minimum bactericidal concentrations ranging from 0.1% to > 0.4% under experimental conditions. Time-kill study demonstrated listericidal activity of ethanolic clove and negro pepper extracts indicated by absolute mortality of more than 3 log units at 2x MIC and 4x MIC. GC-MS analysis revealed three and eight major chemical components present in clove and negro pepper respectively. Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus cereus, and B. subtilis also showed satisfactory susceptibilities to ethanolic extracts with MIC ranging from 0.025% to > 0.8%. In general, negro pepper showed broad activity eliciting inhibitory effects against all the tested pathogens. The findings suggest that clove and negro pepper may be promising antibacterial candidates for the decontamination and control bacterial pathogens in food and food supply chain.


Rebound activity after fingolimod cessation: A case - control study.
There has been an increase in the number of reports of multiple sclerosis (MS) rebound activity (RA), which is usually defined as a severe disease reactivation after natalizumab or fingolimod withdrawal that exceeds pre-treatment baseline inflammatory activity. The frequency and risk factors that could predict RA remain unknown. Fingolimod is currently the most frequently prescribed disease modifying therapy for MS in Argentina, so that there is a need to determine possible predictors of RA. To identify risk factors for developing RA after fingolimod cessation; to describe RA characteristics, management and evolution. The study was a multicenter, retrospective, case-control study of patients with MS who had discontinued fingolimod and were followed up to nine months after discontinuation. Demographic, clinical and paraclinical data was extracted, including age, gender, MS phenotype, reason for discontinuation, number of relapses during the year prior to suspension, time treated with fingolimod, EDSS before, during and after rebound, MRI findings. 26 cases of RA were matched 1:1 with patients without RA. The median time elapsed to RA was 50 days. 68% showed worsening of the EDSS in the evaluation at 3 months of RA. When compared with the control group, no difference was found in terms of age, gender, phenotype, EDSS at the moment of suspension, reason for discontinuation, number of relapses in the previous year, and time on therapy. In this case-controlled study, no risk factors could be identified to predict RA after fingolimod cessation. Further controlled, prospective, better powered studies are needed to confirm these findings.


Mesenteric cystic lymphangioma: unusual cause of intra-abdominal catastrophe in an adult.
Mesenteric cystic lymphangiomas (MCLs) are rare benign cystic tumours of unknown aetiology, most often seen in paediatric patients. The clinical presentation is diverse, ranging from an incidentally discovered abdominal cyst to symptoms of acute abdomen. A 20-year-old male presented with generalised abdominal pain, nausea and vomiting of several hours duration following heavy lifting. Emergency laparotomy revealed a 15 x 10 x 8-cm pedicled cystic mass of the mid-ileal mesentery, causing a volvulus. The cyst and a 20-cm gangrenous intestinal segment were resected with anastomosis. The postoperative course was uncomplicated. MCLs should be included in the differential diagnosis of cystic intra-abdominal lesions. Even when asymptomatic and discovered incidentally, they must be treated surgically because of the potential to grow, invade vital structures and develop life-threatening complications.


Cannulated versus non-cannulated cancellous screw fixation for femoral neck fractures: a synthetic bone biomechanical study.
To compare the compressive strength of cannulated versus non-cannulated cancellous screws for undisplaced femoral neck fractures in synthetic bones. 18 synthetic proximal femurs simulating an AO B1 valgus impacted femoral neck fracture in osteoporotic bone were used. The fracture angles were between 55º and 63º (Pauwels grade 2). Fixation was made using 6.5-mm non-cannulated screws (n=6), 6.5-mm cannulated screws (n=6), or 7.3-mm cannulated screws (n=6). A custom-built jig was designed to guide the insertion of the screws in an identical triangular configuration. Screws were tightened by a single operator using a torque-measuring screwdriver. The femoral head was subjected to progressive axial loading at 5 mm/min. The load to failure and displacement were recorded. The 3 groups did not differ significantly except that the load to failure was higher in the construct with 6.5-mm non-cannulated screws than that with 6.5-mm cannulated screws (1222 N vs 1008 N, p=0.003). The compressive strength of a synthetic bone hip fracture model fixed with non-cannulated screws was higher than that of cannulated screws of the same diameter.


Gas chromatographic analysis of amino acid enantiomers in Carbetocin peptide hydrolysates after fast derivatization with pentafluoropropyl chloroformate.
A novel sample preparation protocol for gas chromatographic (GC) analysis of amino acid enantiomers in peptides was developed. It comprises traditional acid hydrolysis, a novel treatment of the analytes with a fluoroalkyl chloroformate and GC/FID separation of enantiomers on a chiral capillary column. The major improvements consist in that the derivatization step proceeds in organic-aqueous media within seconds and the amino acid derivatives are volatile enough to suit the temperature range of the chiral Chirasil-Val capillary column. The approach was found beneficial for chiral analysis of pharmaceutically important Carbetocin peptide.


Green synthesis of copper oxide nanoparticles from Murraya koenigii and its corrosion resistivity on Ti-6Al-4V dental alloy.
The present work describes green-mediated copper oxide nanoparticles as a potential corrosion inhibitor for the dental alloy Ti-6Al-4V. The salt of copper was reduced to metal nanoparticles using Murraya koenigii leaves, which helps with the agglomeration and nanocluster formation through a reduction mechanism. The current synthesis is a single-step process and is cost-effective. The synthesized nanoparticle was characterized using UV, FTIR, XRD, Zeta potential and Particle size analyzer, SEM, and EDX. The particles were then electrodeposited on Ti-6Al-4V alloy, and the corrosion resistivity in the dental medium was analyzed using Electrochemical parameters such as Corrosion current, Corrosion potential, and anodic and cathodic intercepts through the Tafel and Nyquist plots. The synthesized nanoparticles showed characteristic absorbance at 359 nm. FTIR peaks confirm the phytochemical constituents present in the Murraya koenigii that accounts for the formation of nanoparticles. The XRD predicts the crystalline nature, which is further studied using SEM and EDX. The Zeta potential and Particle size analyzer confirms the negative-negative interactive nature of the synthesized CuO NPs. The NPs showed explicit corrosion inhibition properties with an overall inhibition efficiency of 58.15% and 25.6%, respectively. The study confirms the advantage of using Copper Oxide nanoparticles as a potential coating agent in dental implant alloys in increasing its corrosion efficiency.


Studies on the activity of the renin-angiotensin-aldosterone system (RAAS) in patients with cirrhosis of the liver.
Plasma renin activity (PRA), plasma renin concentration (PRC), angiotensinogen, angiotensin II (AT II) and plasma aldosterone were determined by radioimmunoassay in 77 patients with cirrhosis of the liver [group I: with ascites, untreated (n=23); group II: patients with ascites during treatment (n=32); group III: after removal of fluids, but under further spironolactone therapy (n=10); group IV: untreated subjects without ascites (n=12)]. With the exception of decreased angiotensinogen values in all groups ranging between 39% (group IV) and 73% (group III) no significant changes of the other parameters of the RAAS were found in untreated patients. A highly significant increase of PRA, PRC, AT II and plasma aldosterone was observed in treated cirrhotics with (group II) or without (group III) ascites. In the total series of patients AT II was closely related to PRA, PRC and aldosterone emphasizing aldosterone secretion. Plasma sodium was inversely correlated to PRA, PRC, AT II and aldosterone, but no relationship was detected between these parameters of the RAAS and plasma potassium. Our results indicate that hyperaldosteronism in cirrhosis appears unlikely to be the major determinant of avid renal sodium retention and ascites formation. An increased activity of the RAAS is most often initiated by therapeutic factors and/or markedly altered electrolyte metabolism. Therefore, basal conditions of the patients to be studied must be well defined to exclude any artificially induced stimulation of the RAAS.


Identification and determination of inorganic anions in real extracts from pre- and post-blast residues by capillary electrophoresis.
Fast, selective, and sensitive analysis of inorganic anions is compulsory for the identification of explosives in post-blast or environmental samples. For the last twenty years, capillary electrophoresis (CE) has become a valuable alternative to ion chromatography (IC) for the analysis of inorganic-based explosives because of its low running costs and its simplicity of use. This article focuses on the development and validation of a CE method for the simultaneous analysis of 10 anions (chloride, nitrite, nitrate, thiosulphate, perchlorate, chlorate, thiocyanate, carbonate, sulphate, and phosphate) which can be found in post-blast residues, plus for the first time azide anion, possibly present in the composition of detonators, and the internal standard (formate) in 20 min total runtime. Intermediate precisions were 2.11% for normalized areas and 0.72% for normalized migration times. Limits of detection close to 0.5 ppm for all anions were obtained with the use of preconcentration techniques, thanks to a fast and simple sample preparation allowing the analysis of a large variety of matrices with the developed generic CE method. The matrix effects were statistically studied for the first time in the explosive field for different matrices, containing interfering anions and cations, sometimes at high levels. In fact, no significant matrix effect occurred (tests with blank matrix extracts of soil, cloth, glass, plastic, paper, cotton, and metal). Finally, analyses of real post-blast residues and real detonator extracts were performed. The CE results were compared with those obtained with the IC method used routinely and showed excellent correlation.


Establishment and characterization of cell lines from human endometrial epithelial and mesenchymal cells from patients with endometriosis.
To establish and characterize cell lines derived from human endometrial epithelial cells (ECs) and mesenchymal cells (MCs) from patients with and without endometriosis. In vitro experimental study. University and national cancer center research institute. Two women with endometriosis and two women without endometriosis. Sampling of endometrial ECs and MCs. Establishing immortalized endometrial ECs and MCs with quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunocytochemical analysis, and RNA sequence profiling performed to characterize the immortalized cells and a cell proliferation assay, three-dimensional culture, and assays for hormone responses performed to characterize the features of ECs. The qRT-PCR, immunocytochemical analysis, and Western blot analysis revealed that the ECs and MCs maintained their original features. Moreover, the immortalized cells were found to retain responsiveness to sex steroid hormones. The ECs formed a gland-like structure in three-dimensional culture, indicating the maintenance of normal EC phenotypes. The RNA sequence profiling, principal component analysis, and clustering analysis showed that the gene expression patterns of the immortalized cells were different from those of cancer cells. Several signaling pathways that were statistically significantly enriched in ECs and MCs with endometriosis were revealed. We successfully obtained four paired immortalized endometrial ECs and MCs from patients with and without endometriosis. Using these cells could help identify diagnostic and therapeutic targets for endometriosis. The cell lines established in this study will thus serve as powerful experimental tools in the study of endometriosis.


Efficacy of praziquantel against Schistosoma nasale infection in cattle.
Cattle naturally infected with nasal schistosomiasis were treated with a single oral dose of praziquantel at 20 mg/kg body weight. The drug was highly effective causing a considerable reduction in egg counts, cessation of clinical signs and progressive regression of the nasal granulomatous growths.


Methamphetamine use and utilization of medications for opioid use disorder among rural people who use drugs.
Methamphetamine use is common among persons with opioid use disorder. This study evaluated associations between methamphetamine use and treatment with agonist medications for opioid use disorder (MOUD, specifically buprenorphine, and/or methadone) in U.S. rural communities. The Rural Opioid Initiative (ROI) is a consortium spanning 10 states and 65 rural counties that included persons who reported past 30-day use of opioids and/or injection drug use between 1/2018 and 3/2020. Analyses were restricted to participants who had ever used opioids and had data on past 30-day methamphetamine use. Multivariable models examined the relationship between methamphetamine use and utilization of agonist MOUD. Among 2899 participants, 2179 (75.2%) also reported recent methamphetamine use. Persons with methamphetamine use compared to those without were younger, more likely to have injected drugs, be unhoused, criminal justice involved, and less likely to have health insurance. Adjusted for age, sex, race, and study site, recent methamphetamine use was associated with lower relative odds of past 30-day methadone treatment (aOR=0.66; 95% CI: 0.45-0.99) and fewer methadone treatment days (aIRR=0.76; 0.57-0.99), but not past 30-day buprenorphine receipt (aOR=0.90; 0.67-1.20), buprenorphine treatment days in past 6 months: aIRR=0.88; 0.69-1.12) or perceived inability to access buprenorphine (aOR=1.12; 0.87-1.44) or methadone (aOR=1.06; 0.76-1.48). Methamphetamine use is common among persons who use opioids in rural U.S. areas and negatively associated with current treatment and retention on methadone but not buprenorphine. Future studies should examine reasons for this disparity and reduce barriers to methadone for persons who use opioids and methamphetamine.


Measurement of the knee flexion angle with a Smartphone-application is precise and accurate.
We hypothesized that the measurement of the knee flexion angle measured with a specific Smartphone application was different from the reference measurement with a navigation system designed for total knee arthroplasty (TKA). Ten consecutive patients operated on for navigation assisted TKA were selected. Six navigated and 6 Smartphone measurements of knee flexion angle were obtained for each patient. The paired difference between measurements and their correlation were analyzed. The mean paired difference between navigated and Smartphone measurements was -1.1° ± 6.8° (n.s.). There was a significant correlation between both measurements. The coherence between both measurements was good. The intra-observer and inter-observer reproducibility were good. The Smartphone application used may be considered as precise and accurate. The accuracy may be higher than other conventional measurement techniques.


Regional and strain variation in brain 3':5' cyclic adenosine monophosphate of inbred mice.
Regional variations were found in cAMP levels in flash frozen mouse brains with the pons and cerebellum having higher levels than the cerebrum. There were also strain variations with CBA/J and BALB/cJ having higher levels than C57B1/6J in the pons and cerebellum.


Identification and transcriptional analysis of nitrate assimilation genes in the halophilic archaeon Haloferax mediterranei.
Sequencing a 6,720-bp segment of the extreme halophilic archaeon Haloferax mediterranei genome has revealed the genomic organization of the putative structural genes for nitrate assimilation. We report a gene operon containing nasABC and nasD gene. nasA encodes an assimilatory nitrate reductase, nasB codes for a membrane protein with similarity to the NarK transporter, nasC encodes a protein with similarity to MobA; and nasD codes for an assimilatory ferredoxin-dependent nitrite reductase. Reverse transcription-PCR and primer extension experiments have demonstrated the existence of one polycistronic messenger nasABC and one monocistronic nasD initiated from a different promoter. The gene order and the grouping in two adjacent transcriptional units constitutes a novel organization of nas genes. The promoter regions harbor direct palindromes reminiscent of target sites for binding of a hypotetical regulatory protein(s). Transcription of the nasABC and nasD regions was found to be repressed by the presence of ammonium as nitrogen source.


Antagonistic properties of a natural product-Bicuculline with the gamma-aminobutyric acid receptor: studied through electrostatic potential mapping, electronic and vibrational spectra using ab initio and density functional theory.
(+)-Bicuculline (hereinafter referred to as bicuculline), a phthalide isoquinoline alkaloid is of current interest as an antagonist of gamma-aminobutyric acid (GABA). Its inhibitor properties have been studied through molecular electrostatic potential (MEP) mapping of this molecule and GABA receptor. The hot site on the potential surface of bicuculline, which is also isosteric with GABA receptor, has been used to interpret the inhibitor property. A systematic quantum chemical study of the possible conformations, their relative stabilities, FT-Raman, FT-IR and UV-vis spectroscopic analysis of bicuculline has been reported. The optimized geometries, wavenumber and intensity of the vibrational bands of all the conformers of bicuculline have been calculated using ab initio Hartree-Fock (HF) and density functional theory (DFT) employing B3LYP functional and 6-311G(d,p) basis set. Mulliken atomic charges, HOMO-LUMO gap ΔE, ionization potential, dipole moments and total energy have also been obtained for the optimized geometries of both the molecules. TD-DFT method is used to calculate the electronic absorption parameters in gas phase as well as in solvent environment using integral equation formalism-polarizable continuum model (IEF-PCM) employing 6-31G basis set and the results thus obtained are compared with the UV absorption spectra. The combination of experimental and calculated results provides an insight into the structural and vibrational spectroscopic properties of bicuculline.


Two new species of the bamboo-feeding leafhopper genus Abrus Dai & Zhang (Hemiptera, Cicadellidae, Deltocephalinae) from China.
Two new species of the bamboo-feeding genus Abrus Dai & Zhang, 2002, Abrus xishuiensis sp. n. and Abrus langshanensis sp. n., are described and illustrated from Guizhou and Hunan, South China. A checklist and a key to 13 known species are given.


Social acquisition context matters: Increased neural responses for native but not nonnative taboo words.
This study examined whether the context of acquisition of a word influences its visual recognition and subsequent processing. We utilized taboo words, whose meanings are typically acquired socially, to ensure that differences in processing were based on learned social taboo, rather than proficiency. American English-speaking participants made word/non-word decisions on American taboo (native dialect), British taboo (non-native dialect), positive, neutral, and pseudo- words while EEG was recorded. Taboo words were verified as taboo by both American and British English speakers in an independent norming survey. American taboo words showed a more positive amplitude of the Late Positive Complex (LPC), a neural correlate of emotionality and social processing, compared with British taboo words and all other word categories. Moreover, in an item-wise analysis, LPC amplitudes of American taboo words were positively correlated with their taboo ratings. British taboo words did not show this effect. This indicates that American participants, who had very limited social contact with British English, did not have the same perception of social threat from British taboo words as they had from American taboo words. These results point to the importance of social context of acquisition in establishing social-affective meaning in language.


Effect of Bacillus subtilis C-3102 Spores as a Probiotic Feed Supplement on Growth Performance, Nutrient Digestibility, Diarrhea Score, Intestinal Microbiota, and Excreta Odor Contents in Weanling Piglets.
It has been well-documented that the dietary supplementation of Bacillus subtilis could improve piglet performance. The present study was conducted to investigate the effect of Bacillus subtilis C-3102 spores as a probiotic feed supplement on growth performance, nutrient digestibility, fecal score, intestinal microbiota, and excreta odor contents in weanling piglets. A total of 150 crossed ((Yorkshire × Landrace) × Duroc) weanling piglets (28-days-old), with an average initial body weight of 7.53 ± 1.23 kg, were divided into two treatment groups according to sex and initial body weight (BW) for a 6-week experiment. In each group, fifteen replicate pens consisting of five piglets per pen (three gilts and two barrows) were used in a randomized complete block design. Treatments consisted of (1) CON, a basal diet; (2) BSC, a diet of CON + 300 g Bacillus subtilis (B. subtilis) C-3102 spores per ton of feed. Supplementation with the B. subtilis C-3102 spores in the diet increased the BW, average daily gain (ADG), and gain-to-feed ratio (G:F) throughout the whole trial (p < 0.05). Weanling piglets that were fed B. subtilis C-3102 spores had increased dry matter (DM), crude protein (CP), and energy (E) digestibility compared to the CON group (p < 0.05). Lower diarrhea scores were observed in the B. subtilis C-3102 spores group on Day 7 (p < 0.05). Taken together, our results suggest that dietary supplementation with B. subtilis C-3102 spores could benefit the BW, ADG, and G:F of weanling piglets and improve the apparent total tract digestibility (ATTD) of the DM, CP, and E.


Differential response of normal rat mammary epithelial cells to mammogenic hormones and EGF.
A simple dissociation procedure and the collagen gel culture system have been utilized to determine the effects of mammogenic hormones and epidermal growth factor (EGF) on the proliferation of normal rat mammary epithelial (RME) cells in serum-free culture. Epithelial fragments, isolated from normal virgin F344 rat mammary glands by enzyme digestion followed by Percoll density gradient centrifugation, were embedded within a rat tail collagen matrix. A three- to four-fold increase in cell number was observed when ovine prolactin (PRL) and progesterone (P) were present in the basal medium during 7 days of culture. Mouse EGF stimulated one cell doubling during the same culture period. Isolated mammary organoids produced a 'stellate' type colony when PRL + P were present in the culture medium. These colonies were composed of small, tightly packed cuboidal cells. The addition of EGF to the basal medium produced a diffuse 'basket' type colony which was composed of large, elongate cells. When the complete hormonal and growth factor combination (PRL + P + EGF) was present, a 'mixed' type colony was observed which contained both the large and small epithelial cell types. Immunocytochemical analysis revealed that both the cuboidal and elongate cells present in the two colony types stained with antibodies to keratin indicating that these cells were epithelial in nature. The small cuboidal cells also expressed thioesterase II and alpha-lactalbumin, both specific for secretory mammary epithelial cells. The large, elongate cell type, however, was positive for actin but did not stain for either secretory epithelial specific marker. The results reported here suggest that normal rat mammary tissue may contain two epithelial populations, one which responds to PRL + P and the other which responds to EGF.


Conversion and degradation of [125I] labelled angiotensin I in isolated perfused porcine coronary and carotid arteries.
The aims were (1) to quantitate angiotensin I to II conversion on the endothelial surface and at deeper sites in isolated arteries, (2) to assess whether the angiotensin II that is formed at deeper sites is released into the vascular lumen, and (3) to examine whether enzymes other than angiotensin converting enzyme (ACE) are involved in vascular angiotensin I to II conversion. Metabolism of [125I]-angiotensin I was studied in isolated perfused porcine coronary and carotid arteries after luminal administration of the labelled peptide (in the perfusion fluid) and after adventitial administration (in the organ bath). Measurements were made both in the presence and in the absence of captopril. [125I]-angiotensin II was a major metabolite and its formation was virtually completely blocked by captopril, after both luminal and adventitial administration of [125I]-angiotensin I. In coronary arteries (n = 8), the [125I]-angiotensin I to II conversion rate after adventitial administration was about half that after luminal administration. In coronary arteries (n = 6) the conversion rate after adventitial administration was 10-20 times lower than after luminal administration. Degradation of [125I]-angiotensin I into peptides other than [125I]-angiotensin II was also observed, with both luminal and adventitial administration. No [125I]-angiotensin I or II was released into the organ bath after luminal administration of [125I]-angiotensin I, and very little [125I]-angiotensin I and II entered the lumen after adventitial administration of [125I]-angiotensin I. (1) Vascular angiotensin I to II conversion is not limited to the endothelial surface. (2) ACE is the most important, if not the only, enzyme responsible for vascular angiotensin I to II conversion. (3) If angiotensin I and II are formed in the adventitia or media, little of these peptides will enter the vascular lumen.


Pure spinal epidural cavernous hemangioma.
Pure epidural cavernous hemangiomas without bony involvement are rare, representing 4% of all spinal epidural tumors. Most of these are case reports and are easily misdiagnosed. Herein nine patients (male:female, 5:4, average age: 51 years) with symptomatic pure epidural spinal cavernous hemangioma between 2005 and 2011 were treated, and the clinical, radiological, and pathological records, treatment, and prognosis were discussed. All patients experienced a slowing progressive clinical course, except for one with intralesional hemorrhage. Clinical manifestations included back or radiating pain, sensorimotor deficits, and sphincters disturbance. Eight lesions were isointense on T1- and hyperintense on T2-weighted images with homogenously strongly enhancement and one was mixed signal with heterogeneous enhancement because of intratumoral hemorrhage. Hemilaminotomoy or laminotomy was performed and total resection was achieved. All patients experienced a gradual neurological improvement with no recurrence. Spinal epidural cavernous hemangioma is a benign vascular malformation that should be excluded in the diagnosis of epidural lesion. Total surgical resection is recommended and usually results in a good prognosis.


Circulation of multiple Rickettsiales bacteria in ticks from Sichuan province, Southwest China.
During 2021, 403 ticks including Haemaphysalis qinghaiensis, Ixodes ovatus, Ixodes acutitarsus, and Rhipicephalus microplus were collected from three sites (590, 310, and 576 km away from each other) in Sichuan Province, China. A total of nine Rickettsiales species were identified in them, including three Rickettsia spp., five Anaplasma spp., and one Ehrlichia sp. Anaplasma ovis and a novel Rickettsia sp. named "Candidatus Rickettsia liangshanensis" were characterized in I. ovatus ticks from Liangshan, with positive rates of 11.11% and 45.56%, respectively. Anaplasma capra (13.33%) and Anaplasma bovis (15.33%) were detected in H. qinghaiensis ticks from Maerkang. Phylogenetic analysis based on 16S rRNA, gltA, and groEL gene sequences indicated that the A. bovis strains were divided into two groups. Additionally, a novel Ehrlichia species named "Candidatus Ehrlichia maerkangensis" was identified. It is closely related to "Candidatus Ehrlichia zunyiensis" which was previously reported in Berylmys bowersi rats from Zunyi City, Southwest China. In R. microplus from Mianyang, "Candidatus Rickettsia jingxinensis" was detected with a high prevalence (92.99%). Notably, a variant of R. raoultii was identified in I. acutitarsus (33.33%). This may be the first Rickettsiales bacterium reported in I. acutitarsus. Our results reveal the remarkable biodiversity of Rickettsiales in this area. Some of these bacteria are human pathogens, indicating the potential exposure risk to local people.


Altered coordination between frontal delta and parietal alpha networks underlies anhedonia and depressive rumination in major depressive disorder.
A hyperactive default mode network (DMN) has been observed in people with major depressive disorder (MDD), and weak DMN suppression has been linked to depressive symptoms. However, whether dysregulation of the DMN contributes to blunted positive emotional experience in people with MDD is unclear. We recorded 128-channel electroencephalograms (EEGs) from 24 participants with MDD and 31 healthy controls in a resting state (RS) and an emotion-induction state (ES), in which participants engaged with emotionally positive pictures. We combined Granger causality analysis and data-driven decomposition to extract latent brain networks shared among states and groups, and we further evaluated their interactions across individuals. We extracted 2 subnetworks. Subnetwork 1 represented a delta (δ)-band (1~4 Hz) frontal network that was activated more in the ES than the RS (i.e., task-positive). Subnetwork 2 represented an alpha (α)-band (8~13 Hz) parietal network that was suppressed more in the ES than the RS (i.e., task-negative). These subnetworks were anticorrelated in both the healthy control and MDD groups, but with different sensitivities: for participants with MDD to achieve the same level of task-positive (subnetwork 1) activation as healthy controls, more suppression of task-negative (subnetwork 2) activation was necessary. Furthermore, the anticorrelation strength in participants with MDD correlated with the severity of 2 core MDD symptoms: anhedonia and rumination. The sample size was small. Our findings revealed altered coordination between 2 functional networks in MDD and suggest that weak suppression of the task-negative α-band parietal network contributes to blunted positive emotional responses in adults with depression. The subnetworks identified here could be used for diagnosis or targeted for treatment in the future.


Awareness and attitudes towards advance care planning in primary care: role of demographic, socioeconomic and religiosity factors in a cross-sectional Lebanese study.
To assess awareness and attitudes towards engaging in advance care planning (ACP) and their relationship with demographic, socioeconomic and religiosity factors among Lebanese middle-aged to older-aged adults in primary care. A cross-sectional survey study. Tertiary referral hospital in Beirut, Lebanon. A total of 215 middle-aged to older-aged adults. Out of 215 participants, 18.6% of participants knew about ACP; 94% favoured truth-telling; 87.4% favoured healthcare autonomy; 77.2% favoured documenting their own health values and preferences; and 29.3% were willing to undergo life-prolonging interventions. Among participants who were aware of ACP, 67.5% preferred ACP documentation and 85% had negative attitudes towards life-sustaining interventions. Women were more aware about ACP than men. Those who were willing to undergo life-prolonging interventions were found to be men and had higher religiosity scores. Large deficit in ACP awareness was evident despite the high preference for healthcare autonomy. Medical and public health efforts should strive to enhance patients' ACP awareness and engagement in ACP while considering factors relevant to gender, culture and religiosity.


The MYO9B gene is a strong risk factor for developing refractory celiac disease.
Celiac disease (CD) is associated with HLA-DQ2 and HLA-DQ8 and has been linked to genetic variants in the MYO9B gene on chromosome 19. HLA-DQ2 homozygosity is associated with complications of CD such as refractory celiac disease type II (RCD II) and enteropathy-associated T-cell lymphoma (EATL). We investigated whether MYO9B also predisposes to RCD II and EATL. Genotyping of MYO9B and molecular HLA-DQ2 typing were performed on 62 RCD II and EATL patients, 421 uncomplicated CD patients, and 1624 controls. One single nucleotide polymorphism in MYO9B showed a significantly different allele distribution in RCD II and EATL patients compared with controls (P = .00002). The rs7259292 T allele was significantly more frequent in RCD II and EATL patients compared with CD patients (P = .0003; odds ratio [OR], 3.61; 95% confidence interval [CI], 1.78-7.31). The frequency of the haplotype carrying the T allele of this single nucleotide polymorphism was significantly increased in RCD II and EATL patients (11%), compared with controls (2%) and CD patients (3%) (OR, 6.76; 95% CI, 3.40-13.46; P = 2.27E-09 and OR, 4.22; 95% CI, 1.95-9.11; P = .0001, respectively). Both MYO9B rs7259292 and HLA-DQ2 homozygosity increase the risk for RCD II and EATL to a similar extent when compared with uncomplicated CD patients (OR, 4.3; 95% CI, 1.9-9.8 and OR, 5.4; 95% CI, 3.0-9.6, respectively), but there was no evidence for any interaction between these 2 risk factors. We show that both MYO9B and HLA-DQ2 homozygosity might be involved in the prognosis of CD and the chance of developing RCD II and EATL.


Metabolic Activation of Flavin Monooxygenase-mediated Trimethylamine-N-Oxide Formation in Experimental Kidney Disease.
Cardiovascular disease (CVD) remains the leading cause of death in chronic kidney disease (CKD) patients despite treatment of traditional risk factors, suggesting that non-traditional CVD risk factors are involved. Trimethylamine-N-oxide (TMAO) correlates with atherosclerosis burden in CKD patients and may be a non-traditional CVD risk factor. Serum TMAO concentrations are significantly increased in CKD patients, which may be due in part to increased hepatic flavin monooxygenase (FMO)-mediated TMAO formation. The objective of this work was to elucidate the mechanism of increased FMO activity in CKD. In this study, FMO enzyme activity experiments were conducted in vitro with liver microsomes isolated from experimental CKD and control rats. Trimethylamine was used as a probe substrate to assess FMO activity. The FMO activator octylamine and human uremic serum were evaluated. FMO gene and protein expression were also determined. FMO-mediated TMAO formation was increased in CKD versus control. Although gene and protein expression of FMO were not changed, metabolic activation elicited by octylamine and human uremic serum increased FMO-mediated TMAO formation. The findings suggest that metabolic activation of FMO-mediated TMAO formation is a novel mechanism that contributes to increased TMAO formation in CKD and represents a therapeutic target to reduce TMAO exposure and CVD.


Understanding the COVID-19 pandemic from a gender perspective.
Under the threat of the new coronavirus pandemic, women have been uniquely impacted financially, economically, and socially. However, in terms of disease incidence and lethality, women perform better than men. The main reason is that, in addition to women's own hormonal protection, women's immune systems are superior to those of men. Women also exhibit more protective behavior (e.g., hand-washing) and more closely follow protection guidelines, which greatly reduces the chance of infection. In the future, more studies that adopt a gender perspective are needed to understand the various dilemmas faced by women in infectious diseases and pandemics; only then can women demonstrate better outcomes.


[The application of intraoperative cholangiography in laparoscopic cholecystectomy].
To evaluate the role of intraoperative cholangiography in laparoscopic cholecystectomy (LC). Intraoperative cholangiography was attempted in 1 466 patients, and was successfully completed in 1382 patients. The success rate was 94.27%. Stones in the common bile duct in 92 patients, bile duct injury in 8 patients and abnormal bile duct in one patient were found. Intraoperative cholangiography is an accurate and safe procedure, can provide clear films of biliary tree, and has a high success rate. Its application can reduce the rate of bile duct injury and improve the quality of LC.


Housing modification for malaria control: impact of a "lethal house lure" intervention on malaria infection prevalence in a cluster randomised control trial in Côte d'Ivoire.
In recent years, the downward trajectory of malaria transmission has slowed and, in some places, reversed. New tools are needed to further reduce malaria transmission. One approach that has received recent attention is a novel house-based intervention comprising window screening (S) and general house repairs to make the house more mosquito proof, together with EaveTubes (ET) that provide an innovative way of targeting mosquitoes with insecticides as they search for human hosts at night. The combined approach of Screening + EaveTubes (SET) essentially turns the house into a 'lure and kill' device. This study evaluated the impact of SET on malaria infection prevalence in Côte d'Ivoire and compares the result in the primary outcome, malaria case incidence. Malaria infection prevalence was measured in a cross-sectional survey in 40 villages, as part of a cluster-randomised trial evaluating the impact of SET on malaria case incidence. Infection prevalence, measured by rapid diagnostic test (RDT), was 50.4% and 36.7% in the control arm and intervention arm, respectively, corresponding to an odds ratio of 0.57 (0.45-0.71), p < 0.0001). There was moderate agreement between RDT and microscopy results, with a reduction in odds of infection of 36% recorded when infection was measured by microscopy. Prevalence measured by RDT correlated strongly with incidence at a cluster level. In addition to reducing malaria case incidence, house screening and EaveTubes substantially reduced malaria infection prevalence 18 months after installation. Infection prevalence may be a good metric to use for evaluating malaria interventions in areas of similar transmission levels to this setting. ISRCTN18145556, registered 1 February 2017.


Biochar improves heavy metal passivation during wet anaerobic digestion of pig manure.
Anaerobic digestion (AD) is regarded as an effective treatment to stabilize organic materials and recycle the energy in pig manure. In this study, 0%, 3%, 5%, and 7% biochar (based on dry weight) were added to pig manure to investigate its influence on improving biogas production and reducing heavy metal bioavailability. The potential ecological risk of heavy metals (namely Mn, Zn, Cu, Ni, As, Cd, Pb, and Cr) in digestates was also assessed. Results show that the methane yield was significantly (P < 0.05) increased by 26.7%, 23.0%, and 26.4% following addition of 3%, 5%, and 7% biochar, respectively. Moreover, there was a significant change in the heavy metal speciation in amendment each group. The 5% biochar group showed the highest passivation rate of Ni, As, and Pb, while the highest passivation rate of Cd, Cr, Mn, and Zn was observed with 7% biochar. Although the anaerobic digestion process slightly increased the ecological risk of heavy metals, all tested digestates were still classified as a moderate risk. Results of this study can provide a reference for the treatment of heavy metal pollution in large- and medium-sized anaerobic digesters treating pig manure.


Intrathecal CGRP8-37-induced bilateral increase in hindpaw withdrawal latency in rats with unilateral inflammation.
1. Recent work in our laboratory has demonstrated that intrathecal administration of a selective antagonist of calcitonin gene-related peptide (CGRP), CGRP8-37, increased the hindpaw withdrawal latency (HWL) to thermal stimulation and hindpaw withdrawal threshold (HWT) to pressure in normal rats, and that these effects were more pronounced than in rats with mononeuropathy. 2. The present study was performed to investigate the effects of intrathecal administration of CGRP8-37 on the HWL and HWT in rats with unilateral hindpaw inflammation induced by subcutaneous injection of carrageenin. The effect of naloxone was also studied. 3. Subcutaneous injection of 0.1 ml of carrageenin into the plantar region of the left hindpaw induced a significant increase in the volume of the ipsilateral hindpaw (P < 0.001), and significant bilateral decreases of the HWL to thermal stimulation (ipsilateral: P < 0.001; contralateral: P < 0.01) and HWT to pressure (ipsilateral: P < 0.001; contralateral: P < 0.01). 4. Intrathecal administration of 10 nmol of CGRP8-37, but not of 1 or 5 nmol, induced a significant bilateral increase in the HWL and HWT in rats with experimentally induced inflammation (thermal test: P < 0.001; mechanical test: P < 0.001). 5. The effect of intrathecal administration of 10 nmol CGRP8-37 on HWL and HWT was significantly more pronounced in intact rats than in rats with experimentally induced inflammation (ipsilateral: P < 0.001; contralateral: P < 0.001). 6. The effect of CGRP8-37 on withdrawal responses in the inflamed paw was partly reversed by intrathecal injection of naloxone at a dose of 88 nmol in the thermal (ipsilateral: P < 0.01; contralateral: P = 0.14) and mechanical tests (ipsilateral: P < 0.05; contralateral: P = 0.60). 7. A significant bilateral increase in the concentration of CGRP-like immunoreactivity in the perfusate of both hindpaws was demonstrated 24 h after unilateral injection of carrageenin (ipsilateral: P < 0.001; contralateral: P < 0.05). There was also an increase in the amount of CGRP-like immunoreactivity in the cerebrospinal fluid (P < 0.001), but not in plasma (P = 0.75). 8. The present study demonstrates that acute experimentally-induced unilateral hindpaw inflammation, induces bilateral increases in the amount of CGRP-like immunoreactivity in hindpaw perfusates. Intrathecal administration of CGRP8-37 increased the HWL to thermal stimulation and HWT to pressure bilaterally. 9. The results indicate that CGRP plays a role in the transmission of presumed nociceptive information in the spinal cord of rats with experimentally induced inflammation. Furthermore, our findings suggest that opioids can modulate CGRP-related effects in the spinal cord.


The Differences in Postprandial Serum Concentrations of Peptides That Regulate Satiety/Hunger and Metabolism after Various Meal Intake, in Men with Normal vs. Excessive BMI.
The energy balance regulation may differ in lean and obese people. The purposes of our study were to evaluate the hormonal response to meals with varying macronutrient content, and the differences depending on body weight. The crossover study included 46 men, 21⁻58 years old, normal-weight and overweight/obese. Every subject participated in two meal-challenge-tests with high-carbohydrate (HC), and normo-carbohydrate (NC) or high-fat (HF) meals. Fasting and postprandial blood was collected for a further 240 min, to determine adiponectin, leptin and total ghrelin concentrations. In normal-weight individuals after HC-meal we observed at 60min higher adiponectin concentrations (12,554 ± 1531 vs. 8691 ± 1070 ng/mL, p = 0.01) and significantly (p < 0.05) lower total ghrelin concentrations during the first 120 min, than after HF-meal intake. Fasting and postprandial leptin levels were significantly (p < 0.05) higher in overweigh/obese men. Leptin concentrations in normal-weight men were higher (2.72 ± 0.8 vs. 1.56 ± 0.4 ng/mL, p = 0.01) 180 min after HC-meal than after NC-meal intake. Our results suggest that in normal-body weight men we can expect more beneficial leptin, adiponectin, and total ghrelin response after HC-meal intake, whereas, in overweight/obese men, the HC-meal intake may exacerbate the feeling of hunger, and satiety may be induced more by meals with lower carbohydrate content.


Predictive and construct validity of the Bayley Scales of Infant Development and the Wechsler Preschool and Primary Scale of Intelligence with the Taiwan Birth Cohort Study instrument.
This study aimed to investigate the concurrent validity of the parent-report Taiwan Birth Cohort Study Developmental Instrument (TBCS-DI) with the Bayley Scales of Infant Development-Second Edition (BSID-II) and the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R) at 6, 18, 36, and 60 months. 100 children were recruited at 6 months, 88 children followed-up at 18 months, 71 at 36 months, and 53 at 60 months. Longitudinally, the parent-report TBCS-DI, with the professional psychological assessments of the BSID-II and the WPPSI-R showed predictive validity. Looking at each time point in cross section, at 6 and 18 months the TBCS-DI had good concurrent validity with the BSID-II, and at 36 and 60 months the TBCS-DI was correlated only with the motor and performance domains of the BSID-II and WPPSI-R. With further investigation, the TBCS-DI may be used both in research and in clinical settings.


Association between radiography-based subchondral bone structure and MRI-based cartilage composition in postmenopausal women with mild osteoarthritis.
Our aim was to investigate the relation between radiograph-based subchondral bone structure and cartilage composition assessed with delayed gadolinium enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 relaxation time. Ninety-three postmenopausal women (Kellgren-Lawrence grade 0: n = 13, 1: n = 26, 2: n = 54) were included. Radiograph-based bone structure was assessed using entropy of the Laplacian-based image (ELap) and local binary patterns (ELBP), homogeneity indices of the local angles (HIAngles,mean, HIAngles,Perp, HIAngles,Paral), and horizontal (FDHor) and vertical fractal dimensions (FDVer). Mean dGEMRIC index and T2 relaxation time of tibial cartilage were calculated to estimate cartilage composition. HIAngles,mean (rs = -0.22) and HIAngles,Paral (rs = -0.24) in medial subchondral bone were related (P < 0.05) to dGEMRIC index of the medial tibial cartilage. ELap (rs = -0.23), FDHor,0.34 mm (r = 0.21) and FDVer,0.68 mm (r = 0.24) in medial subchondral bone were related (P < 0.05) to T2 relaxation time values of the medial tibial cartilage. FDHor at different scales in lateral subchondral bone were related (P < 0.01) to dGEMRIC index (r = 0.29-0.41) and T2 values of lateral tibial cartilage (r = -0.28 to -0.36). FDVer at larger scales were related (P < 0.05) to dGEMRIC index (r = 0.24-0.25) and T2 values of lateral tibial cartilage (r = -0.21). HIAngles,Paral (r = -0.25) and FDVer,0.68 mm (rs = 0.22) in the lateral tibial trabecular bone were related (P < 0.05) to dGEMRIC index of the lateral tibial cartilage. Our results support the presumption that several tissues are affected in the early osteoarthritis (OA). Furthermore, they indicate that the detailed analysis of radiographs may serve as a complementary imaging tool for OA studies.


Comparative bioavailability of 875 mg amoxicillin tablets in healthy human volunteers.
To compare the bioavailability of amoxicillin 875 mg tablets (EMS Sigma Pharma used as test formulation) and Amoxil BD 875 mg tablets (GlaxoSmithKline used as reference formulation) in 26 healthy volunteers. 26 healthy volunteers (13 males and 13 females) received each formulation in an open, 2 x 2 crossover, randomized study with seven days of washout period between doses. Plasma samples were obtained over a 12-hour interval after administration. Plasmatic amoxicillin concentrations were obtained by combined reversed-phase liquid chromatography and mass spectrometry with positive ion electrospray ionization using the select ion monitoring method. AUC was calculated by the trapezoidal rule extrapolation method. Cmax and tmax were compiled from the plasmatic concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC0-inf, AUC0-12 h, Cmax and untransformed tmax. The mean values (+/- SD) for AUC0-12 h (microg x h x ml(-1)), AUC0-inf (microg x h x ml(-1)), Cmax (microg x ml(-1)), t1/2 (h) and tmax (h), were, respectively: 55.42 (+/- 16.85), 55.42 (+/- 16.85), 18.59 (+/- 6.3), 1.49 (+/- 1.57) and 2.04 (+/- 0.75) concerning the test formulation, and 51.11 (+/- 18.9), 51.29 (+/- 19.12), 17.83 (+/- 5.86), 1.52 (+/- 1.31) and 2.02 (+/- 0.87) concerning the reference formulation. Confidence intervals (90%) of amoxicillin means of AUC0-12 h and Cmax ratios (test/reference) were: 0.961-1.149 and 0.914-1.142, respectively, agreeing with the bioequivalence criteria established by the Brazilian National Health Surveillance Agency. Both formulations were bioequivalent based on both the rate and extent of absorption.


Schistosoma haematobium: the pathology of experimental infection.
The pathologic changes in experimental animals infected with Schistosoma haematobium are reviewed and compared to the pathology in infected humans. The clinically important lesions in persons infected with S. haematobium are generally confined to the urogenital system. In experimental animals, functionally important lesions of the urogenital system are the exception but do occur in a significant proportion of infected primates. The acute lesions of the urinary tract in primates are similar to those in infected persons. Chronic lesions characterized by the extensive submucosal accumulation of calcified eggs are common in infected humans but uncommon in S. haematobium-infected animals.


Pharmacological modification of hemoglobin F expression in sickle cell anemia: an update on hydroxyurea studies.
The most studied pharmacological intervention in sickle cell anemia aiming at elevating HbF expression is the use of hydroxyurea. At the present time the experience has been that after 1 year of treatment with maximum tolerated doses (MTD) all patients showed increases of percent HbF, with a mean of 15% HbF, without apparent side effects besides the reversible ones observed during the process of attaining the MTD. The question of efficacy is presently being investigated by a multicenter placebo controlled double blind clinical trial that involves more than 20 sites. The goal of the study is to determine if hydroxyurea can decrease the incidence of painful crises by 50%. Results of this study are not expected before the end of 1993.


Transmural fibre orientations based on Laplace-Dirichlet-Rule-Based-Methods and their influence on human heart simulations.
It is well known that the orthotropic tissue structure decisively influences the mechanical and electrical properties of the heart. Numerous approaches to compute the orthotropic tissue structure in computational heart models have been developed in the past decades. In this study, we investigate to what extent different Laplace-Dirichlet-Rule-Based-Methods (LDRBMs) influence the local orthotropic tissue structure and thus the electromechanical behaviour of the subsequent cardiac simulation. In detail, we are utilising three Laplace-Dirichlet-Rule-Based-Methods and compare: (i) the local myofibre orientation; (ii) important global characteristics (ejection fraction, peak pressure, apex shortening, myocardial volume reduction, fractional wall thickening); (iii) local characteristics (active fibre stress, fibre strain). We observe that the orthotropic tissue structures for the three LDRBMs show significant differences in the local myofibre orientation. The global characteristics myocardial volume reduction and peak pressure are rather insensitive to a change in local myofibre orientation, while the ejection fraction is moderately influenced by the different LDRBMs. Moreover, the apical shortening and fractional wall thickening exhibit a sensitive behaviour to a change in the local myofibre orientation. The highest sensitivity can be observed for the local characteristics.


Should We Strive to Make Science Bias-Free? A Philosophical Assessment of the Reproducibility Crisis.
Recently, many scientists have become concerned about an excessive number of failures to reproduce statistically significant effects. The situation has become dire enough that the situation has been named the 'reproducibility crisis'. After reviewing the relevant literature to confirm the observation that scientists do indeed view replication as currently problematic, I explain in philosophical terms why the replication of empirical phenomena, such as statistically significant effects, is important for scientific progress. Following that explanation, I examine various diagnoses of the reproducibility crisis, and argue that for the majority of scientists the crisis is due, at least in part, to a form of publication bias. This conclusion sets the stage for an assessment of the view that evidential relations in science are inherently value-laden, a view championed by Heather Douglas and Kevin Elliott. I argue, in response to Douglas and Elliott, and as motivated by the meta-scientific resistance scientists harbour to a publication bias, that if we advocate the value-ladenness of science the result would be a deepening of the reproducibility crisis.


Genome-wide identification and expression analysis of the bHLH gene family in passion fruit (Passiflora edulis) and its response to abiotic stress.
Passion fruit is a tropical fruit crop with significant agricultural, economic and ornamental values. The growth and development of passion fruit are greatly affected by climatic conditions. In plants, the basic helix-loop-helix (bHLH) gene family plays essential roles in the floral organ and fruit development, as well as stress response. However, the characteristics and functions of the bHLH genes of passion fruit remain unclear. Here, 138 passion fruit bHLH members were identified and classified into 20 subfamilies. The structural analysis illustrated that PebHLH proteins of the specific subfamily are relatively conserved. Collinearity analysis indicated that the expansion of the PebHLH gene family mainly took place by segmental duplication, and the structural diversity of duplicated genes might contribute to their functional diversity. PebHLHs, which potentially regulate different floral organ and fruit development, were further screened out, and many of these genes were differentially expressed under various stress treatments. The co-presence of different cis-regulatory elements involved in developmental regulation, hormone and stress responses in the promoter regions of PebHLHs might be closely related to their diverse regulatory roles. Overall, this study will be helpful for further functional investigation of PebHLHs and provides clues for improvement of the passion fruit breeding.


Avian anticoccidial activity of a novel membrane-interactive peptide selected from phage display libraries.
In the present work, we describe the discovery of PW2, a novel peptide presenting in vitro activity against Eimeria acervulina and E. tenella sporozoites. PW2 was selected from phage display (Ph.D.) peptide libraries by an alternative method of panning using living purified E. acervulina sporozoites as targets. Our results showed that the peptide disrupts the sporozoite pellicle, resembling the effect caused by most natural antimicrobial peptides. PW2 peptide was also effective against fungi and showed low activity against Toxoplasma gondii tachyzoites, but no activity against Trypanosoma cruzi, Crithidia fasciculata epimastigotes, and bacteria. Additionally, the parasiticidal concentrations of PW2 produced a very low lytic effect on mammalian and avian cells. The effectiveness against Eimeria sporozoites and the absence of adverse effects to host cells indicates that PW2 may be used as a model to generate new drugs for the control of avian coccidiosis.


Creating an appropriate adaptation of a healthy lifestyle intervention for people after stroke.
To describe (1) an evidence-based approach to promoting a healthy lifestyle, the Diabetes Prevention Program Group Lifestyle Balance intervention, and (2) our work with input from an Advisory Board of stakeholders to modify the program to meet the unique needs of people post stroke. Community-Based Participatory Research. An Advisory Board of stakeholders was convened to modify the Group Lifestyle Balance intervention to meet the unique needs of people post stroke. The primary adaptations that emerged from the Advisory Board included (1) curriculum emphasis on heart health after stroke, (2) care partner participation, (3) physical activity, dietary, and weight loss modifications specific to people after stroke, and (4) general programmatic recommendations (e.g., wider age range of participants; eligibility based on time since stroke; alternative modes of delivery). Feedback from the diverse group of stakeholders provides the basis for modifying an evidence-based healthy lifestyle intervention to meet the unique needs of people after stroke. Future research efforts should examine the efficacy and effectiveness of the adapted program to prevent weight gain after stroke and reduce the risk of chronic conditions including diabetes, metabolic syndrome, and heart disease.


Inhibitory effects of cholinergic agents on the release of transmitter at the frog neuromuscular junction.
1. The cholinesterase inhibitors neostigmine, edrophonium and eserine (7 x 10(-7) M) reduced m.e.p.p. frequency by some 50% at the frog neuromuscular junction. Neostigmine also produced a small reduction in quantal content. 2. Tetraisopropylpyrophosphoramide, with a high specificity for non-specific cholinesterase, has a similar effect on m.e.p.p. frequency but ambenonium, with a high specificity for acetylcholinesterase, was markedly less effective in this respect. 3. Carbachol (10(-5) M) and the muscarinic agonists muscarine and metacholine (7 x 10(-7) M) also reduced the rate of spontaneous release. 4. The action of neostigmine was antagonized by atropine, but not by D-tubocurarine. Muscarine did not have any further effect when m.e.p.p. frequency was reduced with neostigmine. 5. Experiments with reduced extracellular Ca2+ concentration suggest that the cholinergic agents reduce Ca2+ permeability directly at the presynaptic terminals and that they do not act via a change in PNa or PK. It is suggested that the consequent reduction in Ca2+ entry causes a fall in both evoked release and in intracellular Ca2+ concentration, thereby reducing m.e.p.p. frequency. 6. It is concluded that non-specific cholinesterases present on the presynaptic terminals can act as inhibitory muscarinic cholinergic receptors. This form of presynaptic inhibition at the amphibian neuromuscular junction contrasts with that described in the mammalian preparation in which the sites are blocked by D-tubocurarine and are excitatory.