Low-dose granisetron for postoperative nausea and vomiting prophylaxis.
To evaluate the use of low-dose granisetron in postoperative nausea and vomiting prophylaxis. Clinical trials available through PubMed and OVID (1966-July 2003), as well as information supplied by the drug manufacturer, were accessed. Safety concerns associated with droperidol and limited availability of other agents have created a need to restructure prophylaxis guidelines for postoperative nausea and vomiting. It has recently been proposed that granisetron may be effective at a dose that is one-tenth of the Food and Drug Administration-approved dose. Conflicting evidence for this regimen is evaluated. Based on the scarcity of supporting data, this regimen is not recommended for prophylaxis in patients at risk for postoperative nausea and vomiting.


Screening for cervical cancer in French Guiana: screening rates from 2006 to 2011.
In French Guiana, the age-standardized incidence rate of cervical cancer is four times higher than in France and the mortality rate 5.5 times higher. A survival study revealed that stage at diagnosis was the main factor influencing the prognosis, showing that early detection is crucial to increase cervical cancer survival. The present study aimed at evaluating the cervical cancer screening rate between 2006 and 2011 by age and for a 3-year period in French Guiana. All pap smears realised in French Guiana were analysed in two laboratories allowing exhaustive review of screening data. The screening rate was estimated at about 54% from 2006 to 2011, with a statistical difference between coastal and rural area (56.3% versus 18.7%). Although the methodological difference did not allow comparisons with metropolitan France, these results could be used to evaluate the impact of organised cervical cancer screening by the French Guiana Association for Organized Screening of Cancers which has been implemented in French Guiana since 2012.


A New Strain Energy Function Representing the Passive Behavior of the Myocardium.
Classical models for the passive myocardium, such as the Fung and Holzapfel-Ogden models, are known to have high degeneracy as well as numerous mechanical and mathematical limitations, preventing their utility in microstructural experiments and precision medicine. Hence, the upper triangular (QR) decomposition and orthogonal strain attributes were leveraged to develop a new model using published biaxial data on slabs of left myocardium, resulting in a separable strain energy function. This new model, the Criscione-Hussein model, was compared with both the Fung and Holzapfel-Ogden models by quantifying the uncertainty, computational efficiency, and material parameter fidelity for all three models. As a result, the Criscione-Hussein model was found to significantly reduce the uncertainty and computational time (p < 0.05) and enhance the fidelity of the material parameters. Hence, the Criscione-Hussein model enhances the predictability for the passive behavior of the myocardium and may serve a role in creating more accurate computational models that provide better visualizations for the mechanical behavior of the heart and enable the experimental connection between the model and the myocardial microstructure.


Medroxyprogesterone Acetate Prevention of Cervical Cancer through Progesterone Receptor in a Human Papillomavirus Transgenic Mouse Model.
Cervical dysplastic lesions called cervical intraepithelial neoplasias (CINs) need be treated to prevent cervical cancer. Currently available surgical procedures are effective, but the development of noninvasive treatment is warranted. In human papillomavirus transgenic mice engineered to express human papillomavirus type 16 E6 and E7, short-term treatment with 17β-estradiol induces CINs that progress to cervical cancer if the treatment is continued. In the present study, this mouse model was used to determine whether medroxyprogesterone acetate (MPA), a progestin drug, is chemopreventive. Human papillomavirus transgenic mice bearing CIN lesions were treated with MPA plus 17β-estradiol. Unlike control mice treated with 17β-estradiol alone, cervical cancer was absent in the MPA-treated mice. This observation suggests that MPA prevented CIN from progressing to invasive cancer. MPA was associated with inhibited cell proliferation and the promotion of apoptosis in CIN lesions. Confirming the role of the progesterone receptor, the preventive effect of MPA was absent in human papillomavirus transgenic mice in which the expression of progesterone receptor was genetically ablated. These results suggest that MPA is efficient in treating progesterone receptor-positive CIN lesions. These findings provide the basis for a biomarker-driven clinical trial of the secondary prevention of cervical cancer.


Immunohistochemical and morphometric analysis of calcitonin distribution in anuran ultimobranchial glands.
The presence and distribution of immunoreactive calcitonin (iCT) in the anuran (Rana pipiens) ultimobranchial gland was examined with a specific antiserum to salmon calcitonin. Improved resolution of the distribution of iCT within individual cells allowed recognition of a iCT-negative [iCT(-)] early maturing cell, the primary iCT-positive [iCT-(+)] secretory cell with accumulation of iCT within the basal and apical cytoplasm, an iCT(-) cell that lacks a basal accumulation of secretory material, and a iCT(-) cell that borders the central lumen. A morphometric analysis was made of the entire glandular basal secretory surface area and a calculation was made of the relative area that contained iCT(+) secretory material (expressed as a basal index (BI)). For frogs kept in fresh water, the total basal area of a single gland was 0.335 mm2, with a BI of 0.72 and a total iCT(+) secretory surface of 0.241 mm2. A second group of frogs kept in a high calcium medium for 12 days had a BI of 0.74 with no significant increase in parenchyma volume or total basal area and therefore no increase in the total iCT(+) secretory area. A third group was kept in a high calcium medium for 12 days and given a single oral dose of vitamin D3 (500 IU/g body wt). The BI of this group remained unchanged at 0.75; however, there was a significant glandular hypertrophy concomitant with an increase in secretory surface area to 0.462 mm2. This resulted in a 43% increase in the iCT(+) secretory area to 0.345 mm2. A model is proposed to explain the increase in iCT in the gland in response to a vitamin D and high calcium challenge.


Significance of the initiation time of urate-lowering therapy in gout patients: A retrospective research.
To evaluate the efficacy and safety of the initiation time of urate-lowering treatments (ULT) in gout patients. We retrospectively reviewed patients who were diagnosed with gout and were treated with ULT for at least 3 years. They were divided into two groups: group 1: 123 patients initiating ULT during an acute attack of gout; group 2: 457 patients prescribed ULT after an acute attack. Both demographic and clinical characteristics associated with gout were analyzed. Comparing patients in group 1 versus group 2: the former exhibited a shorter duration of gout (6.3±2.1 vs. 8.9±3.3 years). At the baseline, there was no significant difference in mean serum urate (SU; 7.8±1.4mg/dL vs. 7.9±1.9mg/dL, respectively). SU target levels (<6.0mg/dL) were achieved by 66.7 and 65.6% of the patients, respectively. The duration from initiation of ULT until the SU target was attained was lower in group 1 than in group 2. During the first 12 weeks, patients on ULT in group 1 had higher attack rates than those in group 2. The incidence of chronic kidney disease increased in percentage in group 1 was lower than in group 2. Our survey revealed that in patients experiencing acute gout, initiation of ULT decreased the time required to reach the target SU and the incidence of CKD, but the attack rate was greater in the first 12 weeks.


Mechanical Isolation of Highly Stable Antimonene under Ambient Conditions.
Antimonene fabricated by mechanical exfoliation is highly stable under atmospheric conditions over periods of months and even when immersed in water. Density functional theory confirms the experiments and predicts an electronic gap of ≈1 eV. These results highlight the use of antimonene for optoelectronics applications.


Operative closure of isolated defects of the ventricular septum: planned delay.
Selection of patients and the timing of operation for closure of ventricular septal defect (VSD) can be difficult because the risk of operation must be balanced against the hemodynamic abnormality and the age and size of the infant. In the past 6 years we have individualized our approach to the timing and necessity of operation in the patient with an isolated VSD. During this period, 133 patients with VSD were evaluated, and 71 underwent operative closure of the VSD. Of the 133 patients, 90 were 2 years old or younger, and 40 of them required operation because of congestive failure and growth retardation. Of the 45 infants who did not undergo operation, 17 have small intracardiac shunts with normal pulmonary vascular resistance while the other 28 infants remain compensated and are growing despite moderate left-to-right shunts. A persistent, large intracardiac shunt was the indication for operation in 31 of the 48 older patients; the other 17 older patients remain well. Although 3 severely growth-retarded infants (2 to 4 kg) died soon after operation, all infants weighing 4 kg or more survive. No child has died during preoperative observation, and irreversible pulmonary vascular changes have not occurred. Most infants with VSD and large intracardiac shunts do require early VSD closure, but the risk of operation remains high in the tiny neonate with profound failure. With appropriate hemodynamic and clinical criteria, operation for selected infants can be delayed so that the risk of operation can be minimized.


Plant Growth-Promoting Microorganisms for Environmental Sustainability.
Agrochemicals used to meet the needs of a rapidly growing human population can deteriorate the quality of ecosystems and are not affordable to farmers in low-resource environments. Here, we propose the use of plant growth-promoting microorganisms (PGPMs) as a tool for sustainable food production without compromising ecosystems services.


Features and algorithms: facilitating investigation of secreted effectors in Gram-negative bacteria.
Gram-negative bacteria deliver effector proteins through type III, IV, or VI secretion systems (T3SSs, T4SSs, and T6SSs) into host cells, causing infections and diseases. In general, effector proteins for each of these distinct secretion systems lack homology and are difficult to identify. Sequence analysis has disclosed many common features, helping us to understand the evolution, function, and secretion mechanisms of the effectors. In combination with various algorithms, the known common features have facilitated accurate prediction of new effectors. Ensemblers or integrated pipelines achieve a better prediction of performance, which combines multiple computational models or modules with multidimensional features. Natural language processing (NLP) models also show the merits, which could enable discovery of novel features and, in turn, facilitate more precise effector prediction, extending our knowledge about each secretion mechanism.


Design, synthesis, and QSAR studies of novel lysine derives as amino-peptidase N/CD13 inhibitors.
A series of novel l-lysine derivatives were designed, synthesized, and assayed for their inhibitory activities on amino-peptidase N (APN)/CD13 and matrix metalloproteinase-2 (MMP-2). The preliminary biological test showed that most of the compounds displayed a high inhibitory activity against MMP-2 and a low activity against APN except compound B6 which exhibited good potency (IC(50)=13.2microM) similar with APN inhibitor Bestatin (IC(50)=15.5microM), and could be used as lead compound in the future.


Novel fabrication of the recyclable MoS2/Bi2WO6 heterostructure and its effective photocatalytic degradation of tetracycline under visible light irradiation.
Developing cost-effective and highly effective visible-light-driven photocatalysts for decomposition of organic contaminants has been deliberated as an important and viable strategy for environmental remediation. Herein, MoS2/Bi2WO6 heterostructure photocatalysts were fabricated with excellent visible light absorption performance and efficient electron/hole (e-/h+) separation efficacy. As-prepared all photocatalysts were systematically characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), high resolution TEM, X-ray photoelectron spectroscopy (XPS). Although photocatalytic experiments were examined by UV-vis diffuse reflectance spectroscopy (UV-vis DRS), photoluminescence spectroscopy (PL), and transient photocurrent (I-t). Among all the photocatalysts, that synthesized by using the components 10 mg of Bi2WO6 with 100 mg of MoS2 (denoted as MSBW-10), displayed high photocatalytic performance (96.31%) for tetracycline (TC) under visible light irradiation within 90 min. The kinetic rate constant of the MSBW-10 heterostructure was 5.51 and 6.71 times higher than those of MoS2 and Bi2WO6, respectively. Further, radical trapping experiments revealed that ˙OH radicals and holes were the predominant reactive species involved in the photocatalytic course. The recycle tests revealed the stability of the photocatalyst, which exhibited 91.85% TC removal efficacy without obvious decay even after the fourth cycle. Furthermore, the type-II MoS2/Bi2WO6 heterostructure photocatalyst exhibited a slighter band gap with energy band alignments and enhanced visible-light absorption, separation of charge carriers, and good oxidation/reduction capacities. These deeper insights and synergetic effects can afford a new approach for flourishing novel heterostructure photocatalysts.


Mid-range atmospheric dispersion modelling. Intercomparison of simple models in EMRAS-2 project.
An intercomparison of atmospheric dispersion models has been carried out for a hypothetical accident occurring in a nuclear power plant in the center of Spain. The accident consisted of a steam generator tube rupture, and two radionuclides have been considered for the exercise: 137-Cs and 131-I. Meteorological conditions and radionuclide release rates were supplied. Models provided deposition maps, timeintegrated concentrations in air and arrival times of the plumes to specific locations. The effect of the meteorological conditions used in the modelling was clear, with different behavior of the plume with neutral stability vs. stable conditions. The predicted arrival times of the plume at specific locations showed much less variability than deposition and air concentrations. This variability in part reflects the uncertainties inherent in atmospheric dispersion modelling and in the selection of parameter values, such as deposition velocities or diffusivities.


Resting-state cerebral blood flow in amygdala is modulated by sex and serotonin transporter genotype.
Serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with modulation of resting-state amygdala level, which was considered to underlie a risk for mood and anxiety disorders. The findings however have been inconsistent which could be related to interactions of the genotype with other factors e.g. sex or personality characteristics. Therefore, the aim of the present study was to explore the modulation of the amygdala perfusion in the resting-state by sex and 5-HTTLPR/rs25531 genotype, controlled for personality dimensions assessed by Temperament and Character Inventory (Cloninger et al., 1994). The resting-state cerebral blood flow (rCBF) was examined using an arterial spin labelling technique. All participants were genotyped for the 5-HTTLPR/rs25531 genotype (L/L-L/S-S/S genotypes and LA-LG variants). The study group comprised 81 right-handed Caucasian healthy volunteers (42 females) aged 19-55 years. We measured rCBF in the amygdala and in the whole-brain grey matter. The data of blood-oxygen-level-dependent (BOLD) response in amygdala to fearful dynamic faces in the same sample were also analysed. There was a significant main effect of sex in both the left and right amygdalae, with higher rCBF in males. Main effect of 5-HTTLPR/rs25531 genotype which was significant in the right amygdala only, was accounted for by higher rCBF in S/S vs. L/L homozygotes. An interaction between sex and 5-HTTLPR/rs25531 genotype was observed in rCBF in the right amygdala. This was accounted for by higher values of rCBF in the right amygdala in males' S allele carriers compared with females. In females, there was a significant negative correlation between the rCBF and BOLD response in the right amygdala, and more so in S carriers. In males, there was no significant correlation between rCBF and BOLD response in the right amygdala. The novelty of our results lies in the demonstration of gene by sex interaction with resting blood flow in the amygdala that elucidates sex-related differences in emotional reactivity.


Peripheral non-small cell lung cancers 2.0 cm or less in diameter: proposed criteria for limited pulmonary resection based upon clinicopathological presentation.
Clinical features of peripheral non-small cell lung cancer 2.0 cm or less were retrospectively analyzed. Nodal status and prognosis in relation to tumor diameter and histologic type were investigated in 171 consecutive patients with peripheral clinical T1N0M0 non-small cell lung carcinomas 2 cm or less in diameter and who had undergone surgical resection between 1976 and 1997. Of the 171 patients, 136 had adenocarcinoma, 27 had squamous cell carcinoma, four had large cell carcinoma, three had carcinoid and one had adeno-squamous carcinoma. There was no statistically significant difference in the incidence of stage I cases between adenocarcinoma and squamous cell carcinoma. Lymph node involvement was recognized in 30 (17.5%) patients: ten (5.8%) at N1 nodes and 20 (11.7%) at N2 nodes. Lymph node metastasis was significantly more common in tumors 1.5-2.0 cm in diameter (22%) than in those 1.5 cm or less in diameter (14.0%, P = 0.0490). There was no lymph node metastasis in tumors 1.0 cm or less in diameter. The 5-year survival rates cases with or without lymph node involvement were 63.3 and 75.3%, respectively, showing significant difference (P = 0.0338). The result of the present study suggested that systematic mediastinal and hilar lymph node dissection is necessary even for cases with tumor diameter less than 2 cm. However, if the tumor is within 1.0 cm in diameter, mediastinal lymph node dissection might be dispensable; therefore, these cases are good candidates for video-assisted lobectomy.


The leukotriene B4-leukotriene B4 receptor axis promotes cisplatin-induced acute kidney injury by modulating neutrophil recruitment.
Cisplatin is an effective chemotherapeutic agent and widely used in treatment of various solid organ malignancies, including head and neck, ovarian, and testicular cancers. However, the induction of acute kidney injury (AKI) is one of its main side effects. Leukotriene B4 receptor 1 (BLT1) mediates the majority of physiological effects of leukotriene B4 (LTB4), a potent lipid chemoattractant generated at inflammation sites, but the role of the LTB4-BLT1 axis in cisplatin-induced AKI remains unknown. Here we found upregulated LTB4 synthesis and BLT1 expression in the kidney after cisplatin administration. Cisplatin was found to directly upregulate gene expression of leukotriene A4 hydrolase and stimulate LTB4 production in renal tubular epithelial cells. Reduced kidney structural/functional damage, inflammation, and apoptosis were observed in BLT1-/- mice, as well as in wild-type mice treated with the LTA4H inhibitor SC-57461A and the BLT1 antagonist U-75302. Neutrophils were likely the target of this pathway, as BLT1 absence induced a significant decrease in infiltrating neutrophils in the kidney. Adoptive transfer of neutrophils from wild-type mice restored kidney injury in BLT1-/- mice following cisplatin challenge. Thus, the LTB4-BLT1 axis contributes to cisplatin-induced AKI by mediating kidney recruitment of neutrophils, which induce inflammation and apoptosis in the kidney. Hence, the LTB4-BLT1 axis could be a potential therapeutic target in cisplatin-induced AKI.


Note on transmitted complexity for quantum dynamical systems.
Transmitted complexity (mutual entropy) is one of the important measures for quantum information theory developed recently in several ways. We will review the fundamental concepts of the Kossakowski, Ohya and Watanabe entropy and define a transmitted complexity for quantum dynamical systems.This article is part of the themed issue 'Second quantum revolution: foundational questions'.


The effect of auto-vaccination therapy on the phenotypic variation of one clonal type of Staphylococcus aureus isolated from cows with mastitis.
The aim of this study was to demonstrate the effect of auto-vaccine therapy on selected properties of Staphylococcus aureus strains, isolated from milk of cows with subclinical mastitis. The experiment was based on auto-vaccines which were prepared from S. aureus strains isolated from 16 cows. S. aureus strains isolated from cows on the 7th, 21st and 35th day following auto-vaccination, were analyzed phenotypically and genotypically. The isolated strains represented 17 biotypes all belonging to one clonal type. Increases of new biotypes of S. aureus were detected on the 35th day of therapy. Among 48 re-isolated strains, 18.75% (9/48) revealed single and 12.50% (6/48) multiple phenotypical changes. The present study demonstrated that during auto-vaccine therapy, S. aureus strains can change phenotypically, pointing out the necessity for using precise diagnostic methods, that would make possible a better assessment of the used therapy.


Antigenic, sequence, and crystal variation in influenza B neuraminidase.
The neuraminidase (NA) genes of influenza B viruses B/Maryland/59, B/Hong Kong/8/73, B/Singapore/222/79, B/Oregon/5/80, B/USSR/100/83, B/Victoria/3/85, B/Leningrad/179/86, B/Memphis/6/86, and B/Memphis/3/89 have been sequenced. The deduced amino acid sequences show high variability in the stalk domain of the NA, but a surprising degree of sequence conservation in the head region which carries all the antigenic and enzyme activity. The variable region coding for the neuraminidase stalk also translates into a variable section in the overlapping NB polypeptide, which is coded from a second reading frame that overlaps the first 100 amino acids of NA. The influenza B NAs are antigenically distinguishable with monoclonal antibodies in neuraminidase-inhibition tests, even when there is only one amino acid sequence difference. However, seven of nine escape mutants selected with monoclonal antibodies were distinguished only by the antibody used for selection. When NA heads of influenza B viruses are crystallized, there are remarkable differences in crystal morphology between neuraminidases which have very few sequence changes.


Use of functional tests before angiography in patients with normal coronary arteries.
Functional tests provide diagnostic and prognostic information in patients with suspected coronary disease and are recommended in investigating and guiding management of these patients. There is little data on their utilization, especially in patients with low to intermediate pre-test probability of disease. From 6053 consecutive patients who underwent 6830 coronary angiograms for suspected coronary disease, 758 patients were subsequently found to have normal coronary arteries. Clinical data, functional tests performed prior to angiography and referring physicians were analyzed. The 758 patients had mean pre-test probability of disease of 42+/-30%. Only 483 patients had undergone functional tests before angiography. There were no differences in gender, age, and pre-test probability between patients who underwent functional tests and those who did not. Three hundred thirteen patients underwent angiography as inpatients while 445 were day-only patients. Inpatients were less likely to have undergone functional tests prior to angiography. Inpatient status was the only independent predictor of not undergoing functional tests (OR 5.9, p<0.001). Functional tests revealed inducible ischaemia in only 241 of the 483 patients. Patients referred by cardiologists were more likely to have undergone functional tests compared with those referred by other physicians. Procedural cardiologists and non-procedural cardiologists had similar rate of use of functional tests. In our patients with normal coronary arteries, utilization of functional tests was low, particularly for inpatients. A significant proportion proceeded to angiography despite negative functional tests. Referrer characteristics and inpatient status, rather than pre-test probability, appeared to have greater impact on utilization of functional tests.


Factors associated with early improvement after intravenous thrombolytic treatment in acute ischemic stroke.
: The aim of this study was to determine the factors associated with early neurological improvement (ENI) in patients who experienced acute ischemic stroke and were treated with intravenous recombinant tissue plasminogen activator (IV rt-PA), and determine the relationship with the outcome at the first control. : This study included 377 patients who were treated with IV rt-PA in Izmir Dokuz Eylül University Hospital between January 2010 and October 2018. ENI was defined as a 4 or more improvement in the National Institutes of Health Stroke Scale (NIHSS) score in the first hour, the twenty-fourth hour and the seventh day when compared to the pretreatment phase. The modified Rankin Scale (mRS) 0-1 score was defined as 'very good outcome'. : The basal NIHSS (p=0.003, p=0.003, p=0.022) was high in the first hour, twenty-fourth hour, and seventh day ENI groups. Blood urea nitrogen (BUN) level was low in the first- and twenty-fourth-hour ENI groups (p=0.007, p=0.020). Furthermore, admission glucose was low at the twenty-fourth hour and on the seventh day ENI groups (p=0.005, p=0.048). A high infarct volume was observed on magnetic resonance imaging (MRI) at the twenty-fourth hour and on the seventh day non-ENI groups (p= <0.001, p= <0.001). : Management of factors associated with ENI and determination of treatment strategies accordingly are important for obtaining a better clinical outcome. It can help quickly select patients, who, even though they will not respond to rt-PA, may be appropriate candidates for bridging therapy.


Risk assessment of metals from consuming vegetables, fruits and rice grown on soils irrigated with waters of the Ebro River in Catalonia, Spain.
The concentrations of arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), manganese (Mn), nickel (Ni), and lead (Pb) were determined in samples of various edible vegetables (artichoke, cauliflower, lettuce, tomato), fruits (apple, mandarin, orange, pear) and rice grown in soils irrigated with water from the Ebro River in Tarragona Province (Catalonia, Spain). Although all food items were randomly acquired in various localities of the area, the local origin was always verified. Arsenic was only detected in rice (all samples) and apple (one sample), while Cd and Hg could not be detected in any of the samples. In general terms, metal concentrations were quite similar or lower than the levels recently reported in the literature. The health risks caused by metal exposure from consuming these agricultural products were assessed for the Catalan population living in the zone under evaluation. For all elements, when the lower bound values were considered, the Hazard Quotient (HQ) was <1, while using the Upper bound values, only for As (children and male seniors) HQ was >1. The intake of the analyzed elements through consumption of the nine selected food items does not mean additional health risks for the consumers of the area.


Estimation of spatial distrubition of groundwater level and risky areas of seawater intrusion on the coastal region in Çarşamba Plain, Turkey, using different interpolation methods.
Groundwater level plays a significant role in coastal plains. Heavy pumping and excessive use of near-coast groundwater can increase the intrusion of seawater into the aquifers. In the present study, groundwater levels were measured at 59 groundwater wells at different times during pre- and post-irrigation seasons (April and September of the year 2012) in Çarşamba Plain, Turkey. To select the best method, two deterministic interpolation methods (inverse distance weighing (IDW) with the weights of 1, 2, and 3 and radial basis function (RBF) with spline with tension (SPT) and completely regularized spline (CRS)) and two stochastic methods (ordinary kriging (OK) with spherical, exponential, and Gaussian variograms) and cokriging (COK)) were compared and then the best interpolation method was used to evaluate the spatial distribution of groundwater levels in different seasons and seasonal changes. A total of nine different techniques were tested. Also, risky areas of seawater intrusion in coastal area were determined using the best methods for two periods. The performance of these interpolation methods is evaluated by using a validation test method. Statistical indices of correlation (R (2)), mean absolute error (MAE), and root-mean-square error (RMSE) were used to select and validate the best methods. Comparisons between predicted and observed values indicated RBF as the optimal method for groundwater level estimation in April and September. When the best method RBF and the worst method IDW were compared, significant differences were observed in the spatial distribution of groundwater. Results of the study also revealed that excessive groundwater withdrawals during the post-irrigation season dropped the groundwater levels up to 2.0 m in some sections. With regard to seawater intrusion, 9,103 ha of land area was determined to be highly risky and risky.


Reach training selectively alters dendritic branching in subpopulations of layer II-III pyramids in rat motor-somatosensory forelimb cortex.
We have previously reported that training rats to reach for bits of cookies resulted in an increase in dendritic length and branching complexity in the apical branches of layer V pyramidal cells within the motor-sensory forelimb cortex. In this paper, we describe the effects of reach training upon the basilar branches of two subpopulations of pyramidal cells in layers II and III. The two subpopulations of pyramids are distinguishable by morphological characteristics and location within layers II and III. The basilar dendrites of one subtype, the forked apical pyramid, are selectively altered in size and complexity during reach training; whereas the other subtype, the single shaft apical cells, do not measurably change during training. Based upon these findings, we postulate that these cells may have different roles in governing the reaching behavior.


Differential regulation of JAK/STAT-signaling in patients with ulcerative colitis and Crohn's disease.
In 2018, the pan-Janus kinase (JAK) inhibitor tofacitinib was launched for the treatment of ulcerative colitis (UC). Although tofacitinib has proven efficacious in patients with active UC, it failed in patients with Crohn's disease (CD). This finding strongly hints at a different contribution of JAK signaling in both entities. Here, we review the current knowledge on the interplay between the JAK/signal transducer and activator of transcription (STAT) pathway and inflammatory bowel diseases (IBD). In particular, we provide a detailed overview of the differences and similarities of JAK/STAT-signaling in UC and CD, highlight the impact of the JAK/STAT pathway in experimental colitis models and summarize the published evidence on JAK/STAT-signaling in immune cells of IBD as well as the genetic association between the JAK/STAT pathway and IBD. Finally, we describe novel treatment strategies targeting JAK/STAT inhibition in UC and CD and comment on the limitations and challenges of the new drug class.


Aza-BOIMPYs: A Tetrazole Auxochrome for Highly Red-Emissive Dipyrromethene-Based Fluorophores.
A structural derivative of the recently designed BOIMPY motif is introduced; this derivative engages a meso tetrazole moiety and a dipyrromethene scaffold in a twofold BF2 -coordination scheme. A one-pot synthesis allows the isolation of unusual dipyrro-perazafulvene precursors and subsequent access to nonfluorescent mono-BF2 and fluorescent bis-BF2 species. The novel fluorophore, denoted Aza-BOIMPY, is highly emissive (ΦF up to 0.82), structurally compact, and provides useful inherent polarity. Absorption and emission events focus at roughly 600 nm with exceptionally small Stokes shifts (209 cm-1 ) and high attenuation coefficients (up to 120 000 m-1 cm-1 ). X-ray crystallographic and computational investigations provide insights into geometrical and electronic properties of the novel dye type.


Quality of Life Improvement: A Novel Framework and Approach to Well-Being.
Physician burnout is a complex problem that requires creative solutions. Despite increasing awareness of the importance of systems approaches to address physician well-being, few tools exist for organizations to bridge the gap between well-being theory and practice. As demonstrated during the COVID-19 pandemic, new threats to well-being can arise at any time, necessitating an iterative approach. Here we outline the quality of life improvement (QOLI) approach, a novel framework and approach that incorporates principles of human-centered design (HCD), quality improvement (QI), and implementation science (IS) to address clinician well-being. Additionally, we share our experience using this approach in a large academic anesthesiology department.


External non-invasive cardiac pacing: a comparative hemodynamic study of two techniques with conventional endocardial pacing.
Out-of-hospital therapy for cardiac arrest due to bradyarrhythmias or asystole is pharmacologic and the outcome is uniformly dismal. Optimal therapy for the latter disturbances may be artificial cardiac pacing, but conventional invasive pacing techniques are not employed or are of limited value in the out-of-hospital and emergency department setting. This investigation compared the hemodynamic effects of two techniques of non-invasive external pacing: 1) transcutaneous transthoracic pacing (TTP) and 2) tongue-to-epigastrium pacing (TEP), with conventional transvenous right ventricular endocardial pacing (RVEP) in a closed-chest, chronic heart block canine model. All techniques significantly increased (p less than .001) cardiac output (CO). However, CO and mean arterial pressure (MAP) measured during external pacing with either non-invasive technique were significantly greater than that during RVEP (p less than .001). TEP produced vigorous skeletal muscle stimulation and, in the canine model, it produced contraction resulting in impaired ventilation, hypoxemia, and a decrease in systemic vascular resistance. TTP in this model resulted in improved MAP and CO when compared with control and RVEP values and did not affect arterial or mixed venous blood gas values. Thus, this study demonstrates that noninvasive TTP is comparable to RVEP in its hemodynamic effects. TTP may offer definitive non-invasive therapy for a subset of victims of out-of-hospital cardiac arrest.


Concurrent and cross-season protection of inactivated influenza vaccine against A(H1N1)pdm09 illness among young children: 2012-2013 case-control evaluation of influenza vaccine effectiveness.
In 2012-2013, we examined 1729 laboratory-confirmed A(H1N1)pdm09 influenza cases matched 1:1 with healthy controls and estimated influenza vaccine effectiveness (VE) for trivalent inactivated influenza vaccine (IIV3) to be 67% (95% confidence interval=58-74%) for ages 8 months to 6 years old. Among children aged 8-35 months old, VE for fully vaccinated children (73%, 60-81%) was significantly higher than VE for partially vaccinated children (55%, 33-70%). Significant cross-season protection from prior IIV3 was noted, including VE of 31% (8-48%) from IIV3 received in 2010-2011 against influenza illness in 2012--2013 without subsequent boosting doses.


Perceptions of people living with dementia regarding patient-centred aspects of their care and caregiver support.
This study examined the perceptions of a sample of Australian people living with dementia regarding the person-centred care and support they received from health professionals and family. Community-dwelling people living with dementia were invited to complete a cross-sectional survey. Seventy-one people participated in the study. More than 90% agreed that health professionals explain who they are, why they are seeing them and listen to what they have to say; 63% agreed that health professionals ask how they would like to be involved in decisions about treatment; 78% agreed health professionals mainly speak to them rather than anyone accompanying them; 76% reported their family 'support you to do tasks by yourself', and 36% indicated that family caregivers 'get frustrated with you'. Results suggest that people living with dementia have a positive perception of the care and support they receive. Improvements may be needed in how health professionals speak directly to the person living with dementia when exploring how they would like to be involved in treatment decisions. Family caregivers may benefit from education and support on how they can manage frustrations and assist the person they support to maintain their independence.


Biotin provisioning by horizontally transferred genes from bacteria confers animal fitness benefits.
Insect symbionts are widespread in nature and lateral gene transfer is prevalent in insect symbiosis. However, the function of horizontally transferred genes (HTGs) in insect symbiosis remains speculative, including the mechanism that enables insects to feed on plant phloem deficient in B vitamins. Previously, we found there is redundancy in biotin synthesis pathways from both whitefly Bemisia tabaci and symbiotic Hamiltonella due to the presence of whitefly HTGs. Here, we demonstrate that elimination of Hamiltonella decreased biotin levels but elevated the expression of horizontally transferred biotin genes in whiteflies. HTGs proteins exhibit specific expression patterns in specialized insect cells called bacteriocytes housing symbionts. Complementation with whitefly HTGs rescued E. coli biotin gene knockout mutants. Furthermore, silencing whitefly HTGs in Hamiltonella-infected whiteflies reduced biotin levels and hindered adult survival and fecundity, which was partially rescued by biotin supplementation. Each of horizontally transferred biotin genes are conserved in various laboratory cultures and species of whiteflies with geographically diverse distributions, which shares an evolutionary origin. We provide the first experimental evidence that biotin synthesized through acquired HTGs is important in whiteflies and may be as well in other animals. Our findings suggest that B vitamin provisioning in animal-microbe symbiosis frequently evolved from bacterial symbionts to animal hosts through horizontal gene transfer events. This study will also shed light on how the animal genomes evolve through functional transfer of genes with bacterial origin in the wider contexts of microbial ecology.


The Chernobyl accident and mental wellbeing--a population study.
We studied the long-term effects of the 1986 Chernobyl nuclear power plant accident on mental wellbeing 7 years after the event. Mental wellbeing was assessed using a 12-item General Health Questionnaire (GHQ). The study group comprised 325 persons (aged 15-54 years) who had continued to live in the high-fallout area in Bryansk, Russian Federation, classified as a strict control zone with respect to the level of fallout and subsequent radiation protection countermeasures. The control group comprised 278 persons living in a noncontaminated area. The mental wellbeing of women in the study group was poorer than in controls (age-adjusted means). Based on the GHQ score, a minor mental disorder was detected in 48% of the women in the study group and 34% of the female controls. The corresponding figures for men were 26% and 28%, respectively. Those living with a partner coped better mentally than the others. The level of education was not associated with the GHQ score. Poor financial situation and self-rated poor health were associated with a high GHQ score. Fifty-nine per cent of the study group and 14% of the control group wanted to move away from the area of residence, but it was not associated with GHQ score. In a logistic regression analysis, independent factors explaining the GHQ score in the study group were uncertainty about the future in the men and, in addition, poor financial situation and insufficient social support in the women. According the results, the Chernobyl nuclear power plant accident impaired the long-term mental wellbeing of women living in the contaminated area.


Spontaneous and carcinogen-induced tumorigenesis in p53-deficient mice.
Using gene targeting techniques, mice that have been generated with two germ-line p53 null alleles (homozygotes) develop normally but are highly susceptible to early onset spontaneous tumours. Here, we show that mice with a single null p53 allele (heterozygotes) produced in the same way are also susceptible to spontaneous tumours, but with a delayed onset compared to homozygotes. The most frequent tumour type in homozygotes was malignant lymphoma; in heterozygotes, osteosarcomas and soft tissue sarcomas predominated. Heterozygous mice treated with a liver carcinogen, dimethylnitrosamine, showed a decreased survival time in comparison to treated wild type mice, suggesting that the p53-deficient mice may be useful for some in vivo carcinogenesis assays.


Evaluation of the therapeutic efficacy of 213Bi-labelled DOTA-conjugated alpha-melanocyte stimulating hormone peptide analogues in melanocortin-1 receptor positive preclinical melanoma model.
Melanocortin-1 receptor (MC1-R) targeting alpha-melanocyte stimulating hormone-analogue (α-MSH) biomolecules labelled with α-emitting radiometal seem to be valuable in the targeted radionuclide therapy of MC1-R positive melanoma malignum (MM). Herein is reported the anti-tumor in vivo therapeutic evaluation of MC1-R-affine [213Bi]Bi-DOTA-NAPamide and HOLDamide treatment in MC1-R positive B16-F10 melanoma tumor-bearing C57BL/6J mice. On the 6th, 8th and 10th days post tumor cell inoculation; the treated groups of mice were intravenously injected with approximately 5 MBq of both amide derivatives. Beyond body weight and tumor volume assessment, [68Ga]Ga-DOTA-HOLDamide and NAPamide-based PET/MRI scans, and ex vivo biodistribution studies were executed 30,- and 90 min postinjection. In the PET/MRI imaging studies the B16-F10 tumors were clearly visualized with both 68Ga-labelled tracers, however, significantly lower tumor-to-muscle (T/M) ratios were observed by using [68Ga]Ga-DOTA-HOLDamide. After alpha-radiotherapy treatment the tumor size of the control group was larger relative to both treated cohorts, while the smallest tumor volumes were observed in the NAPamide-treated subclass on the 10th day. Relatively higher [213Bi]Bi-DOTA-NAPamide accumulation in the B16-F10 tumors (%ID/g: 2.71 ± 0.15) with discrete background activity led to excellent T/M ratios, particularly 90 min postinjection. Overall, the therapeutic application of receptor selective [213Bi]Bi-DOTA-NAPamide seems to be feasible in MC1-R positive MM management.


Dissemination of carbapenemase-producing Enterobacterales through wastewater and gulls at a wastewater treatment plant in Sweden.
Here we report the detection of carbapenemase-producing Enterobacterales (CPE) isolated from Swedish wastewater and gull faeces. CPE have not been detected in samples from animals in Sweden preceding this report. Sampling of wastewater treatment plant (WWTP) inlet and outlet, sedimentation basins, surface seawater from key aquatic bird habitats and freshly deposited gull faeces was done on six separate occasions during May to September 2021. Following broth enrichment, selective screening of putative CPE was performed on mSuperCarba™ (CHROMagar). Species identification was done with MALDI-TOF. Antimicrobial susceptibility testing was performed according to EUCAST. In total, seventeen CPE were verified by genome sequencing carrying blaGES-5, blaIMI-3, blaOXA-181 or blaOXA-244. The blaGES-5 was carried on IncP plasmids in four different species; Escherichia coli ST10 isolated from WWTP outlet, Raoultella ornithinolytica isolated from WWTP inlet, outlet and sedimentation basins as well as gull faeces collected at the WWTP and Klebsiella spp. isolates from WWTP inlet and outlet. The genetic environment surrounding blaGES-5 was similar in two Citrobacter freundii causing human infections. The blaIMI-3 was carried on IncFII(Yp) plasmids in four Enterobacter ludwigii, isolated from WWTP outlet and gull faeces collected at a recreational city park 2 km from the WWTP. The blaOXA-181 was located on a COLKP3 plasmid found in an E. coli, while blaOXA-244 was chromosomally located in an E. coli ST10, both isolated from WWTP inlet. Phylogenetic analysis of R. ornithinolytica and E. ludwigii isolates indicate that the gulls carried strains related to those identified in the WWTP samples. The results thus add to the increasing evidence of WWTPs as anthropogenic reservoirs for mobile genetic elements with antibiotic-resistance functionality. Such environments could profoundly impact the dissemination and spread of such genetic elements via for example aquatic birds, thereby warranting further study and surveillance.


Cognitive improvement despite minimal arachnoid cyst decompression.
There are relatively few reports that evaluate the cognitive functions of patients with arachnoid cysts. Presumably, these 'silent cysts' are regarded as incidental findings with no functional significance. Although postoperative clinical improvement is well documented in patients with significant reduction in cystic volume, the current report describes a patient who underwent cystoperitoneal shunting due to mass effect, with minimal postoperative decompression. Neuropsychological testing indicated significant cognitive improvement in verbal learning, memory, visual-perceptual abilities, constructional skills, conceptual shifting, and psychomotor speed after shunt placement, despite marginal evidence of decompression. These findings suggest that (1) significant cognitive changes can occur in these patients, despite minimal postoperative regression of the lesion, (2) cognitive measures may provide an alternative, functional index of outcome efficacy, and (3) reliance on traditional outcome measures (i.e. anatomical decompression or resolution of clinical symptoms) may underestimate the efficacy of surgical intervention for these patients.


Immunocytochemical localization of dopamine in the prefrontal cortex of the rat at the light and electron microscopical level.
In the present study the dopaminergic innervation of the prefrontal cortex was studied by means of a recently developed anti-dopamine serum. This method can demonstrate endogenous dopamine in a specific way, and offers the opportunity to study the distribution of dopaminergic fibres in the cortex in detail in counterstained sections. Furthermore, dopaminergic nerve endings can be visualized at the electron microscopic level. Light microscopic observations demonstrated that the highest density of dopaminergic fibres in the frontal cortex is found in the prefrontal cortex and the infralimbic cortex. Within the prefrontal cortex, a good correlation is found between regional differences in distribution of dopaminergic fibres and the cytoarchitectonic parcellation of this part of the cortex. Outside the prefrontal cortex dopaminergic fibres were observed in adjacent frontal areas, the cortex surrounding the entire rhinal sulcus and the retrosplenial cortex. Electron microscopic observations demonstrated dopaminergic terminals through all cortical layers. The majority of dopaminergic terminals in the prefrontal cortex from synaptic contacts with dendritic processes. The synaptic profiles were usually symmetric and were characterized by the presence of many clear vesicles and an occasional dense-core vesicle.


Risk factors and reasons for treatment abandonment among children with lymphoma in Malawi.
Lymphoma is the commonest pediatric cancer in sub-Saharan Africa (SSA). Frequent treatment abandonment contributes to suboptimal outcomes. We examined risk factors and reasons for treatment abandonment for this population in Malawi. We conducted a mixed methods study among children < 18 years old with newly diagnosed lymphoma, prospectively enrolled during 2013-2016. All children received standardized diagnosis and treatment, and were followed for up to 2 years. Treatment abandonment was defined as failure to attend prescribed chemotherapy within 4 weeks, or post-treatment visit within 3 months. Child, guardian, and household characteristics associated with treatment abandonment were assessed. Semi-structured interviews were conducted with primary caregivers of children experiencing treatment abandonment. Of 121 children with newly diagnosed lymphoma, 72 (60%) had complete information regarding child, guardian, and household characteristics. Of these, 56 (78%) had Burkitt's and 16 (22%) Hodgkin's lymphoma. Forty-nine (68%) were male, median age was 10.6 years (interquartile range [IQR] 7.9-13.0), and 26 (36%) experienced treatment abandonment. Lack of guardian education and travel time ≥ 4 h to clinic were independently associated with treatment abandonment, with adjusted hazard ratio (aHR) 3.8 [95% confidence interval (CI) 1.5-8.9, p = 0.005] and aHR 2.9 (95% CI 1.2-6.9, p = 0.019), respectively. Commonest reasons for treatment abandonment endorsed by 15 guardians were community influence, suboptimal clinic environment, logistical challenges, transport costs, treatment toxicities, loss of hope, alternative healers, and beliefs about cure. These findings highlight families at risk for treatment abandonment, underlying reasons, and opportunities to improve retention in care for pediatric cancer patients in SSA.


Circularly polarized printed dual port MIMO antenna with polarization diversity optimized by machine learning approach for 5G NR n77/n78 frequency band applications.
In this communication, a planar dual port multiple input multiple output antenna of size 1.2λ0 × 0.6λ0 × 0.008λ0 with LHCP/RHCP features is reported for the fifth-generation new radio n77/n78 sub-6 GHz wireless applications band. The single unit of the proposed design consists of a modified L-shape rectangular radiator with Z-shape slot loaded DGS. The defected ground structure is optimized through machine learning algorithms to achieve the maximum ARBW (output) by Right Shifting (RS) and left shifting (LS) the DGS and obtaining input features. The performance metric for ANN with ADAM optimizer was found to be optimal with MSE and R2 of 0.99 and 0.82, respectively. ANNs can leverage gradient information to guide the optimization process. This enables faster convergence towards optimal solutions compared to popular GAs and PSO, which are often gradient-free optimization methods. The MIMO configuration is achieved by creating a mirror image of the single unit about the x-axis. The salient features of the proposed design are (a) Impedance bandwidth (IBW) of 3.0-4.2 GHz covering the n77/n78 band, (b) 3-dB axial ratio bandwidth (ARBW) of the 2.6-3.9 GHz (c) Port-1 is generating RHCP while Port-2 is generating LHCP, results in polarization diversity. Different diversity performance parameters (ECC < 0.005, DG ~ 9.99 dB, and MEG < 3 dB) are in the optimum range confirming the proposed configuration as a suitable design for a MIMO radiator.


Prenatal diagnosis of adrenal neuroblastoma: a case report with a brief review of the literature.
A case of adrenal cystic neuroblastoma detected at 37 weeks of gestation is reported. Postnatal ultrasonographic examination showed slightly increased in size demonstrating marked septations within the cyst. After the tumor was resected, histopathological examinations confirmed the diagnosis. The patient is developing normally at 1 year of age.


Use of sulfate reducing cell suspension bioreactors for the treatment of SO2 rich flue gases.
This paper describes a novel bioscrubber concept for biological flue gas desulfurization, based on the recycling of a cell suspension of sulfite/sulfate reducing bacteria between a scrubber and a sulfite/sulfate reducing hydrogen fed bioreactor. Hydrogen metabolism in sulfite/sulfate reducing cell suspensions was investigated using batch activity tests and by operating a completely stirred tank reactor (CSTR). The maximum specific hydrogenotrophic sulfite/sulfate reduction rate increased with 10% and 300%, respectively, by crushing granular inoculum sludge and by cultivation of this sludge as cell suspension in a CSTR. Operation of a sulfite fed CSTR (hydraulic retention time 4 days; pH 7.0; sulfite loading rate 0.5-1.5 g SO3(2-) l(-1) d(-1)) with hydrogen as electron donor showed that high (up to 1.6 g l(-1)) H2S concentrations can be obtained within 10 days of operation. H2S inhibition, however, limited the sulfite reducing capacity of the CSTR. Methane production by the cell suspension disappeared within 20 days reactor operation. The outcompetition of methanogens in excess of H2 can be attributed to CO2 limitation and/or to sulfite or sulfide toxicity. The use of cell suspensions opens perspectives for monolith or packed bed reactor configurations, which have a much lower pressure drop compared to air lift reactors, to supply H2 to sulfite/sulfate reducing bioreactors.


Statistical modeling and optimization of dexamethasone adsorption from aqueous solution by Fe3O4@NH2-MIL88B nanorods: Isotherm, Kinetics, and Thermodynamic.
The presence of pharmaceutical compounds in the environment poses a significant threat to human and aquatic animal health. Dexamethasone (DEX), a synthetic steroid hormone with endocrine-disrupting effects, is one such compound that needs to be effectively removed before discharging into the environment. This research presents a novel approach utilizing magnetically recyclable Fe3O4@NH2-MIL88B NRs as an efficient adsorbent for the treatment of DEX from aqueous solutions. The synthesized adsorbent was characterized by X-ray diffraction (XRD), scanning microscopy (SEM), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), diffuse reflectance spectra (DRS), and Fourier transform infrared spectroscopy (FTIR). Response surface methodology based on central composite design (RSM-CCD) was employed to optimize DEX removal efficiency by determining the optimal conditions, including pH, adsorbent dose, time, and DEX concentration. Under the optimized conditions (pH: 5.53, adsorbent dose: 0.185 g/L, time: 16.068 min, and DEX concentration: 33.491 mg/L), Fe3O4@NH2-MIL88B NRs revealed remarkable DEX adsorption efficiency of 91 ± 1.34% and adsorption capacity of 180.01 mg/g. The Langmuir isotherm and pseudo-second-order kinetic model were found to fit well with the experimental data, indicating a monolayer and chemical adsorption process. Thermodynamic analysis revealed that the adsorption process was spontaneous and endothermic. The study also investigated the inhibitory effect of background ions on DEX removal by Fe3O4@NH2-MIL88B NRs. Magnesium exhibited superior competitive ability with dexamethasone to occupy the active sites of the adsorbent compared to other background ions. The reuse of the adsorbent over ten consecutive cycles resulted in a 39.46% decrease in removal efficiency. The Fe3O4@NH2-MIL88B NRs are surrounded by abundant amounts of functional groups and π-electrons bands that can play a key role in the adsorption and separation of DEX from aqueous environments. The promising results obtained under real conditions highlight the potential of Fe3O4@NH2-MIL88B NRs as a practical and efficient adsorbent for the removal of DEX and other similar corticosteroids from aqueous solutions.


Restoration of lung liquid volume following its acute alteration in fetal sheep.
1. The experiments were aimed at determining the means by which lung liquid volume is controlled in fetal sheep. Six unanaesthetized chronically catheterized fetuses between 121 and 144 days of gestation were used in experiments in which lung liquid volume was acutely reduced or increased. 2. The effects on lung liquid volume, secretion and flow in the trachea were continuously monitored until the original volume was restored. Tracheal pressure, breathing activity, electrocortical activity and laryngeal adductor muscle activity were also monitored. 3. Following a mean reduction in lung liquid volume of 54.1% (40.0 +/- 4.3 ml) there was a reduction in tracheal pressure of 1.91 +/- 0.26 mmHg. There was no change in the rate of lung liquid secretion and there was a near cessation in its rate of efflux from the trachea. Influx of liquid from the upper airway was rarely seen. 4. 5 h after its reduction, lung liquid volume had returned to control values. Tracheal pressure and the rate of liquid flow in the trachea returned to control values over 7-8 h. 5. In the hour following the reduction in lung liquid volume the incidence and amplitude of fetal inspiratory muscle electromyogram (e.m.g.) activity were reduced by 19% and 28% respectively. There was no change in laryngeal adductor muscle activity or in the duration of fetal sleep states. 6. When lung liquid volume was increased by 25.4 +/- 3.1 ml tracheal pressure increased by 2.01 +/- 0.17 mmHg. Although there was no change in the rate of liquid secretion there was a rapid efflux of liquid from the trachea principally during epochs of fetal breathing activity thus returning lung liquid volume to its control value. 7. Following the increase in lung liquid volume there were no changes in the incidence or amplitude of fetal inspiratory muscle activity, the activity of laryngeal adductor muscles or in the duration of sleep states. 8. It is concluded that following its alteration in fetal sheep lung liquid volume is restored by passive means. There was no evidence of volume-receptive neural reflexes being activated in defence of lung liquid volume.


Microbiome assembly predictably shapes diversity across a range of disturbance frequencies in experimental microcosms.
Diversity is often implied to have a positive effect on the functional stability of ecological communities. However, its relationship with stochastic and deterministic assembly mechanisms remains largely unknown, particularly under fluctuating disturbances. Here, we subjected complex bacterial communities in microcosms to different frequencies of alteration in substrate feeding scheme, tracking temporal dynamics in their assembly, structure and function. Activated sludge bioreactors were subjected to six different frequencies of double organic loading, either never (undisturbed), every 8, 6, 4, or 2 days (intermediately disturbed), or every day (press disturbed), and operated in daily cycles for 42 days. Null modeling revealed a stronger role of stochastic assembly at intermediate disturbance frequencies, with a peak in stochasticity that preceded the occurrence of a peak in α-diversity. Communities at extreme ends of the disturbance range had the lowest α-diversity and highest within-treatment similarity in terms of β-diversity, with stronger deterministic assembly. Increased carbon removal and microbial aggregate settleability (general functions) correlated with stronger deterministic processes. In contrast, higher stochasticity correlated with higher nitrogen removal (a specialized function) only during initial successional stages at intermediate disturbance frequencies. We show that changes in assembly processes predictably precede changes in diversity under a gradient of disturbance frequencies, advancing our understanding of the mechanisms behind disturbance-diversity-function relationships.


Immunocytochemical localization of luteinizing hormone-releasing hormone in neurons in the medial basal hypothalamus of the female rat.
Luteinizing hormone-releasing hormone (LHRH)-neurons were localized with a LHRH antiserum (WP-1) in the medial basal hypothalamus (MBH) of the female rat using the sagittal hypothalamic slice preparation in combination with the peroxidase-antiperoxidase immunocytochemical technique of Sternberger (1979). Numerous darkly-stained perikarya were visualized in the cell-poor zone, lateral arcuate nucleus and the median eminence. The processes of these neurons contributed to the intensely-stained fiber bundle above the tuberoinfundibular sulcus. The fibers in this tract run in a rostrocaudal plane in the lateral external zone of the median eminence. Also, numerous fibers course into the internal zone of the median eminence, perpendicular to the rostrocaudal plane. Several LHRH-immunoreactive perikarya also were identified in the periventricular area caudal to the optic chiasm (retrochiasmatic area). The LHRH neurons were small (10 micron) bipolar neurons with fibers (dendrites) exiting from either pole which showed very little branching. It appears that the sagittal slice in combination with the appropriate fixation procedure and LHRH antiserum enabled us to demonstrate the presence of LHRH-immunoreactive perikarya in the MBH of the female rat.


Procalcitonin-guided antibiotic therapy for suspected and confirmed sepsis of patients in a surgical trauma ICU: a prospective, two period cross-over, interventional study.
Biomarkers like procalcitonin (PCT) are an important antimicrobial stewardship tool for critically ill patients. There is little evidence regarding the use of PCT-guided antibiotic algorithms in developing countries. Evidence is also lacking for PCT-based antibiotic algorithms in surgical trauma patients admitted to the intensive care unit (ICU). A prospective, two period cross-over study was conducted in a surgical trauma intensive care unit in South Africa. In the first period, 40 patients were recruited into the control group and antibiotics were discontinued as per standard of care. In the second period, 40 patients were recruited into the procalcitonin group and antibiotics were discontinued if the PCT decreased by ≥ 80% from the peak PCT level, or to an absolute value of less than 0.5 μg/L. Antibiotic duration of treatment was the primary outcome. Patients were followed up for 28 days from the first sepsis event. For the first sepsis event the PCT group had a mean antibiotic duration of 9.3 days while the control group had a mean duration of 10.9 days (p = 0.10). Patients in the intervention group had higher mean (SD) antibiotic free days alive of 7.7 (6.57) days compared to the control group mean (SD) of 3.8 (5.22) days, (p = 0.004). In-hospital mortality rate was lower in the intervention group (15%) compared to the control group (30%) and was statistically significant (p = 0.045). There was no significant difference in duration of antibiotic treatment between the two groups. However, the PCT group had more antibiotic free days alive and lower in-hospital mortality compared to the control group.


Reinterpretation of fluorescence of terbium ion-DNA complexes.
Terbium (Tb3+) fluorescence was used to investigate local non-denaturation perturbations of double-helical DNA structure induced in this nucleic acid by various physical and chemical agents. It has been shown that the interaction of Tb3+ with DNA into which single-strand or double-strand breaks have been introduced by DNase I or by low doses of ionizing radiation does not influence the fluorescence of the lanthanide cation. On the other hand, interaction of terbium with DNA modified by the antitumour drug cis-diamminedichloroplatinum(II) at low levels of binding and by low doses of ultraviolet radiation (wavelength 254 nm) has been shown to result in substantial enhancement of the fluorescence of this cation. It has been proposed that the terbium fluorescent probe can also be exploited successfully for the purpose of analysing the guanine bases present in distorted double-stranded regions of DNA, in which only the vertical stacking of the base-pairs is altered.


Heparin prevents M-current over-recovery but not M-current suppression in bullfrog sympathetic ganglion neurones.
The excitatory actions of G-protein-coupled agonists on amphibian sympathetic ganglion cells involve suppression of a voltage and time dependent, non-inactivating K(+)-current called the M-current. Suppression of this current by muscarine or peptides is followed by a phase of 'over-recovery' during which the M-current exceeds its original level. Whilst it has been suggested that release of intracellular Ca2+ following the agonist-induced liberation of inositol 1,4,5-trisphosphate is involved in the suppression phase of the response, another hypothesis suggests that the agonist-induced elevation of intracellular Ca2+ may account for M-current 'over-recovery'. The present study supports the latter hypothesis because intracellular application of the inositol 1,4,5-trisphosphate antagonist, heparin (150 microM), had little or no effect on muscarine-induced M-current suppression whilst the 'over-recovery' phase of the response was markedly attenuated.


Retroviral transduction of T lymphocytes for suicide gene therapy in allogeneic stem cell transplantation.
Transplantation of suicide gene modified allogeneic T lymphocytes is an approach to prevent T cell mediated GVHD while preserving the 'graft-versus-leukemia' (GVL) effect of an allograft. A prerequisite for such a therapy is the efficient transduction of T cells with suitable vectors. Since existing techniques allow only insufficient transduction of T cells, the development of more efficient gene transfer protocols into these cells is of great importance. We present here a protocol for the highly efficient transduction of human primary T cells at high densities (1 x 10(6) cells/ml) by retroviral infection. The presented protocol allowed us to obtain transduction rates of more than 70% of CD3+ cells after two cycles of infection. It is based on the use of FBS-free media for both the production of retrovirus-containing supernatant, as well as the cultivation of the primary T cells. Since the protocol presented here works just as efficiently under large scale conditions, it may easily be adapted to clinical needs and 'good manufacturing practice' (GMP) standards.


Sublethal effect of naphthalene on lipid peroxidation and antioxidant status in the edible marine crab Scylla serrata.
The effect of naphthalene on lipid peroxidation and antioxidants status was studied in hepatopancreas, haemolymph and ovary of the Scylla serrata with reference to the active vitellogenic stage. There was an overall increase in lipid peroxidation activity in the tested samples. In contrast, the enzymatic (catalase, glutathione peroxidase, superoxide dismutase) and non-enzymatic antioxidants (vitamins C, E and glutathione) showed decreased activities for hepatopancreas, haemolymph and ovary.


Characterization and expression profile of AmphiCD63 encoding a novel member of TM4SF proteins from amphioxus Branchiostoma belcheri tsingtauense.
The study on CD antigen genes remains lacking in the cephalochordate amphioxus to date. In this report, the cDNA encoding CD63 was identified for the first time from the gut cDNA library of amphioxus Branchiostoma belcheri tsingtauense. Primary structural examination showed that the protein encoded by the cDNA contained four potential transmembrane domains characteristic of transmembrane 4 superfamily (TM4SF) proteins and a conserved CCG motif in the putative major extracellular loop. BLAST search revealed that the cDNA is closely associated with other known CD63 antigen genes, and it was thus designated AmphiCD63. Phylogenetic analysis indicated that AmphiCD63 is extremely close to vertebrate CD63, CD151 and CD53, suggesting they may have been evolved from a common ancestral gene. RT-PCR analysis exhibited that AmphiCD63 mRNA was abundant in muscle, ovary, foregut including hepatic caecum and hindgut, while it was present at considerably lower levels in notochord and gill and absent in testis.


The biologic actions of solar radiation on skin with a note on sunscreens.
Adverse effects of excessive cutaneous exposure to solar radiation are hazards of considerable importance. As public health measures, new attitudes about sunbathing and new practices to counteract those adverse effects, especially for high-risk individuals, appear warranted.


[Development in mosquitoes of 3 filaria of the South American lizards of the genus Oswaldofilaria].
The development of O. petersi, O. belemensis and O. spinosa is similar to that of O. bacillaris: the larvae are in the adipose tissue of various mosquitoes; the infective stages are characterized by the longitudinal salient ridges of the cuticule, the long tail ended by two lappets, the well-developed glandular oesophagus; the female genital anlage lies in the anterior half part of the body, but is not very far from the median line. This character opposes these species to the other viviparous Filariae and stresses the originality of the Oswaldofilariinar.


The adhesion molecule PECAM-1 enhances the TGF-β-mediated inhibition of T cell function.
Transforming growth factor-β (TGF-β) is an immunosuppressive cytokine that inhibits the proinflammatory functions of T cells, and it is a major factor in abrogating T cell activity against tumors. Canonical TGF-β signaling results in the activation of Smad proteins, which are transcription factors that regulate target gene expression. We found that the cell surface molecule platelet endothelial cell adhesion molecule-1 (PECAM-1) facilitated noncanonical (Smad-independent) TGF-β signaling in T cells. Subcutaneously injected tumor cells that are dependent on TGF-β-mediated suppression of immunity for growth grew more slowly in PECAM-1(-/-) mice than in their wild-type counterparts. T cells isolated from PECAM-1(-/-) mice demonstrated relative insensitivity to the TGF-β-dependent inhibition of interferon-γ (IFN-γ) production, granzyme B synthesis, and cellular proliferation. Similarly, human T cells lacking PECAM-1 demonstrated decreased sensitivity to TGF-β in a manner that was partially restored by reexpression of PECAM-1. Co-incubation of T cells with TGF-β and a T cell-activating antibody resulted in PECAM-1 phosphorylation on an immunoreceptor tyrosine-based inhibitory motif (ITIM) and the recruitment of the inhibitory Src homology 2 (SH2) domain-containing tyrosine phosphatase-2 (SHP-2). Such conditions also induced the colocalization of PECAM-1 with the TGF-β receptor complex as identified by coimmunoprecipitation, confocal microscopy, and proximity ligation assays. These studies indicate a role for PECAM-1 in enhancing the inhibitory functions of TGF-β in T cells and suggest that therapeutic targeting of the PECAM-1-TGF-β inhibitory axis represents a means to overcome TGF-β-dependent immunosuppression within the tumor microenvironment.


Comparison of Effectiveness of Azilsartan Medoxomil and Olmesartan in Blacks Versus Whites With Systemic Hypertension.
Two post hoc analyses in self-identified black and white patients with hypertension evaluated the angiotensin II receptor blocker azilsartan medoxomil (AZL-M) and the fixed-dose combination of AZL-M with chlorthalidone (AZL-M/CLD) versus the ARB olmesartan (OLM) and the OLM fixed-dose combination with hydrochlorothiazide (OLM/HCTZ). One analysis pooled 1,610 patients from two 6-week randomized controlled trials to compare once daily AZL-M 40 mg, AZL-M 80 mg, OLM 40 mg, and placebo. The second analysis included 1,020 patients from a 12-week randomized controlled trial to compare once daily AZL-M/CLD 40/25 mg, AZL-M/CLD 80/25 mg, and OLM/HCTZ 40/25 mg. Efficacy end points were 24-hour mean ambulatory and clinic systolic and diastolic blood pressure (SPB/DBP) and the percentage of patients achieving clinic SBP/DBP targets. Treatment with AZL-M 80 mg lowered mean clinic SBP by 12.5 mm Hg (p <0.01 vs OLM), treatment with AZL-M/CLD 40 mg/25 mg lowered mean ambulatory SBP by 31.0 mm Hg and mean clinic SBP by 39.3 mm Hg (both p <0.05 vs OLM/HCTZ), and treatment with AZL-M/CLD 80 mg/25 mg lowered mean ambulatory SBP by 34.4 mm Hg (p <0.01 vs OLM/HCTZ) and mean clinic SBP by 39.2 mm Hg (p <0.05 vs OLM/HCTZ). Target BP goals were achieved more frequently with AZL-M versus OLM and with AZL-M/CLD versus OLM/HCTZ. In conclusion, in both black and white patients, BP was lowered more effectively with AZL-M versus OLM and with AZL-M/CLD versus OLM/HCTZ. The AZL-M/CLD 40 mg/25 mg combination resulted in a statistically significant reduction in BP in both black and white patients.


A candidate vaccine for human visceral leishmaniasis based on a specific T cell epitope-containing chimeric protein protects mice against Leishmania infantum infection.
Leishmaniases are neglected diseases caused by infection with Leishmania parasites and there are currently no prophylactic vaccines. In this study, we designed in silico a synthetic recombinant vaccine against visceral leishmaniasis (VL) called ChimeraT, which contains specific T-cell epitopes from Leishmania Prohibitin, Eukaryotic Initiation Factor 5a and the hypothetical LiHyp1 and LiHyp2 proteins. Subcutaneous delivery of ChimeraT plus saponin stimulated a Th1 cell-mediated immune response and protected mice against L. infantum infection, significantly reducing the parasite load in distinct organs. ChimeraT/saponin vaccine stimulated significantly higher levels of IFN-γ, IL-12, and GM-CSF cytokines by both murine CD4+ and CD8+ T cells, with correspondingly low levels of IL-4 and IL-10. Induced antibodies were predominantly IgG2a isotype and homologous antigen-stimulated spleen cells produced significant nitrite as a proxy for nitric oxide. ChimeraT also induced lymphoproliferative responses in peripheral blood mononuclear cells from VL patients after treatment and healthy subjects, as well as higher IFN-γ and lower IL-10 secretion into cell supernatants. Thus, ChimeraT associated with a Th1 adjuvant could be considered as a potential vaccine candidate to protect against human disease.


Abnormality of c-kit oncoprotein in certain patients with chronic myelogenous leukemia--potential clinical significance.
Chronic myelogenous leukemia (CML) is characterized by the Philadelphia (Ph) chromosome and bcr/abl gene rearrangement which occurs in pluripotent hematopoietic progenitor cells expressing the c-kit receptor tyrosine kinase (KIT). To elucidate the biological properties of KIT in CML leukemogenesis, we performed analysis of alterations of the c-kit gene and functional analysis of altered KIT proteins. Gene alterations in the c-kit juxtamembrane domain of 80 CML cases were analyzed by reverse transcriptase and polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP). One case had an abnormality at codon 564 (AAT --> AAG, Asn --> Lys), and six cases had the same base abnormality at codon 541 (ATG --> CTG, Met --> Leu) in the juxtamembrane domain. Because the change from Met to Leu at codon 541 was a conservative one which was also observed in the normal population and normal tissues of CML patients, it probably represents a polymorphic variation. Although samples of hair roots and leukemic cells from the chronic phase of one CML patient showed no abnormality, an abnormality at codon 541 (ATG --> CTG, Met --> Leu) was found only at blastic crisis (BC) of this case. In the case with the abnormality at codon 564, the mutation was detected only in a sample of leukemic cells collected at BC. To examine the biological consequence and biological significance of these abnormalities, murine KIT(L540) and KIT(K563) expression vectors were introduced into interleukin-3 (IL-3)-dependent murine Ba/F3 cells to study their state of tyrosine phosphorylation and their growth rate. Ba/F3 cells expressing KIT(WT), KIT(L540) and KIT(K563) showed dose-dependent tyrosine phosphorylation after treatment with increasing concentrations of recombinant mouse stem cell factor (rmSCF). The cells expressing KIT(L540) and KIT(K563) were found to have greater tyrosine phosphorylation than cells expressing KIT(WT) at 0.1 and 1.0 ng/ml of rmSCF. The Ba/F3 cells expressing KIT(K563) proliferated in response to 0.1 and 1.0 ng/ml of rmSCF as well as IL-3. The Ba/F3 cells expressing KIT(L540)showed a relatively higher proliferative response to 0.1 ng/ml of rmSCF than the response of cells expressing KIT(WT). These mutations and in vitro functional analyses raise the possibility that the KIT abnormalities influence the white blood cell counts (P < 0.05) and survival (P < 0.04) of CML patients.


Biodegradable Mg-Cu alloys with enhanced osteogenesis, angiogenesis, and long-lasting antibacterial effects.
A series of biodegradable Mg-Cu alloys is designed to induce osteogenesis, stimulate angiogenesis, and provide long-lasting antibacterial performance at the same time. The Mg-Cu alloys with precipitated Mg2Cu intermetallic phases exhibit accelerated degradation in the physiological environment due to galvanic corrosion and the alkaline environment combined with Cu release endows the Mg-Cu alloys with prolonged antibacterial effects. In addition to no cytotoxicity towards HUVECs and MC3T3-E1 cells, the Mg-Cu alloys, particularly Mg-0.03Cu, enhance the cell viability, alkaline phosphatase activity, matrix mineralization, collagen secretion, osteogenesis-related gene and protein expressions of MC3T3-E1 cells, cell proliferation, migration, endothelial tubule forming, angiogenesis-related gene, and protein expressions of HUVECs compared to pure Mg. The favorable osteogenesis and angiogenesis are believed to arise from the release of bioactive Mg and Cu ions into the biological environment and the biodegradable Mg-Cu alloys with osteogenesis, angiogenesis, and long-term antibacterial ability are very promising in orthopedic applications.


Reduction of twenty-four-hour gastric acidity with combination drug therapy in patients with duodenal ulcer.
Four "extra-effort" drug regimens were tested to determine which most nearly eliminated 24-hr gastric acidity in 8 patients with duodenal ulcer. The regimens included two 300 mg cimetidine tablets with meals and at bedtime; one 300 mg cimetidine tablet plus an anticholinergic drug with meals and at bedtime; 300 mg cimetidine with meals and at bedtime plus liquid antacid 1 and 3 hr after meals and at bedtime; and 300 mg cimetidine, an anticholinergic drug, and antacid, taken simultaneously as each meal was finished and at bedtime. No regimen completely eliminated gastric acidity. However, compared to standard cimetidine therapy (300 mg four times daily) which led to a median 24-hr pH of 2.6, each "extra-effort" regimen except cimetidine plus an anticholinergic was significantly better in reducing gastric acidity. During the daytime hours, cimetidine with meals plus antacid 1 and 3 hr after meals was most effective (median pH 5.0). However, the more convenient regimen of cimetidine, an anticholinergic drug, and antacid was almost as effective (median pH 4.3). None of the "extra-effort" regimens was significantly more effective than standard cimetidine therapy during the hours of sleep.


Systematic review: sphincter of Oddi dysfunction--non-invasive diagnostic methods and long-term outcome after endoscopic sphincterotomy.
Sphincter of Oddi dysfunction is a benign, functional gastrointestinal disorder for which invasive endoscopic therapy with potential complications is often recommended. To review the available evidence regarding the diagnostic accuracy of non-invasive methods that have been used to establish the diagnosis and to estimate the long-term outcome after endoscopic sphincterotomy. A systematic review of English language articles and abstracts containing relevant terms was performed. Non-invasive diagnostic methods are limited by their low sensitivity and specificity, especially in patients with Type III sphincter of Oddi dysfunction. Secretin-stimulated magnetic resonance cholangiopancreatography appears to be useful in excluding other potential causes of symptoms, and morphine-provocated hepatobiliary scintigraphy also warrants further study. Approximately 85%, 69% and 37%, of patients with biliary Types I, II and III sphincter of Oddi dysfunction, respectively, experience sustained benefit after endoscopic sphincterotomy. In pancreatic sphincter of Oddi dysfunction, approximately 75% of patients report symptomatic improvement after pancreatic sphincterotomy, but the studies have been non-controlled and heterogeneous. Patients with suspected sphincter of Oddi dysfunction, particularly those with biliary Type III, should be carefully evaluated before considering sphincter of Oddi manometry and endoscopic sphincterotomy. Further controlled trials are needed to justify the invasive management of patients with biliary Type III and pancreatic sphincter of Oddi dysfunction.


COVID-19 as a catalyst for vaccine manufacturing: A South African experience.
COVID-19 highlighted inequitable vaccine distribution and the urgent need for vaccine manufacturing capacity on the African continent. This resulted in a burst of scientific engagement and international funding to augment capacity on the continent. However, short-term investment needs to be reinforced by a robust, strategic long-term plan to ensure sustainability.


Fish bone migration after pancreaticoduodenectomy: Incidence and treatment options.
Migration of a fish bone to the bile duct or pancreatic duct is a possible complication after pancreaticoduodenectomy (PD). The aim of this study was to clarify the incidence and indications for intervention in such cases. We reviewed the cases with fish bone migration after PD detected on computed tomography (CT) scan between October 2000 and October 2020 were reviewed and the incidence of fish bone migration, presence of symptoms and signs, therapeutic modalities and patient outcomes were analyzed. Among the 1475 PD procedures performed at our institution during the study period, 14 cases of fish bone migration were noted on CT, the incidence of which was 0.95% (14/1475). The time duration from surgery to the detection of fish bone ranged from 88 to 5902 days (median 917 d). Ten patients remained asymptomatic without therapeutic intervention for up to 2919 days (median 509 d). Four patients were treated by endoscopy, either at the patient's request (n = 1) or because of their symptoms (n = 3), and removal was successful in three cases but failed in one case in which the fish bone migrated to the right intrahepatic bile duct. No surgical treatment was required in any case. The incidence of fish bone migration on CT after PD was about 1%. Some cases resolved spontaneously, and most of the asymptomatic cases required no intervention. For symptomatic cases, endoscopic treatment should be considered first. It is important to confirm the location of the fish bone by CT and determine whether it can be removed.


Evaluation of inorganic phosphate solubilizing efficiency and multiple plant growth promoting properties of endophytic bacteria isolated from root nodules Erythrina brucei.
In soils, phosphorous (P) mostly exists in fixed/insoluble form and unavailable for plants use in soil solution, hence it is in scarcity. P is fixed in the form of aluminium, iron and manganese phosphates in acidic soils and calcium phosphate in alkaline soils. Phosphate solubilizing bacteria, the ecological engineers play a pivotal role in the mobilization of fixed forms of P by using different mechanisms. The objectives of this study were to evaluate inorganic phosphate solubilizing efficiency and other multiple plant growth promoting traits of Erythrina brucei root nodule endophytic bacteria and to investigate effects of the selected endophytic bacteria on the growth of wheat plant under phosphorous deficient sand culture at greenhouse conditions. Among a total of 304 passenger endophytic bacteria, 119 (39%) exhibited tricalcium phosphate (TCP) solubilization; however, none of them were formed clear halos on solid medium supplemented with aluminum phosphate (Al-P) or iron phosphate (Fe-P). Among 119 isolates, 40% exhibited IAA production. The selected nine potential isolates also exhibited potentials of IAA, HCN, NH3 and/or hydrolytic enzymes production. All the selected isolates were potential solubilizers of the three inorganic phosphates (Al-P, Fe-P and TCP) included in liquid medium. The highest values of solubilized TCP were recorded by isolates AU4 and RG6 (A. soli), 108.96 mg L-1 and 107.48 mg L-1, respectively at sampling day3 and 120.36 mg L-1 and 112.82 mg L-1, respectively at day 6. The highest values of solubilized Al-P and Fe-P were recorded by isolate RG6, 102.14 mg L-1 and 96.07 mg L-1, respectively at sampling days 3 and 6, respectively. The highest IAA, 313.61 µg mL-1 was recorded by isolate DM17 (Bacillus thuringiensis). Inoculation of wheat with AU4, RG6 and RG5 (Acinetobacter soli) increased shoot length by 11, 17.4 and 14.6%, respectively compared to the negative control. Similarly, 76.9, 69.2 and 53.8% increment in shoot dry weight is recorded by inoculation with RG6, AU4 and RG5, respectively. These nine potential endophytic isolates are identified to Gluconobacter cerinus (4), Acinetobacter soli (3), Achromobacter xylosoxidans (1) and Bacillus thuringiensis (1). AU4, RG6 and RG5 can be potential bio-inoculants candidates as low cost agricultural inputs in acidic and/or alkaline soils for sustainable crop production.


Impact of elexacaftor/tezacaftor/ivacaftor on lung function, nutritional status, pulmonary exacerbation frequency and sweat chloride in people with cystic fibrosis: real-world evidence from the German CF Registry.
Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) improves multiple clinical outcomes in people with cystic fibrosis (pwCF) with at least one F508del allele. This study evaluated the real-world impact of ETI on lung function, nutritional status, pulmonary exacerbation frequency, and sweat chloride concentrations in a large group of pwCF. This observational cohort study used data from the German CF Registry for pwCF who received ETI therapy and were followed up for a period of 12 months. The study included 2645 pwCF from 67 centres in Germany (mean age 28.0 ± 11.5 years). Over the first year after ETI was initiated, percent predicted forced expiratory volume in 1 s (ppFEV1) increased by 11.3% (95% confidence interval [CI] 10.8-11.8, p < 0.0001), body mass index (BMI) z-score increased by 0.3 (95% CI 0.3-0.4, p < 0.0001) in individuals aged 12 to <18 years and BMI in adults increased by 1.4 kg/m2 (95% CI 1.3-1.4, p < 0.0001), pulmonary exacerbations decreased by 75.9% (p < 0.0001) and mean sweat chloride concentration decreased by 50.9 mmol/L (95% CI -52.6, -49.3, p < 0.0001). Improvements in ppFEV1 over the first year of therapy were greater in pwCF who had not previously received cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (12.6% [95% CI 11.9-13.4] vs. 9.7% [95% CI 9.0-10.5] in those with prior CFTR modulator treatment. These real-world data are consistent with the findings of randomised clinical trials, and support the use of ETI as a highly effective treatment option for pwCF who have at least one F508del allele. None.


Effects of 1,25-Dihydroxy vitamin D3 on TNF-α induced inflammation in human chondrocytes and SW1353 cells: a possible role for toll-like receptors.
The purpose of this study is to evaluate anti-inflammatory and chondro-protective effects of 1,25(OH)2D3 in human chondrocytes and SW1353 cells via investigating expressions of MMPs, TIMPs, VDR, and intracellular signalling pathway mediators such as TLR-2 and -4. The HC and SW1353 cells were treated with 1,25(OH)2D3 at 10, 100, and 1000 nM concentrations in the absence/presence of TNF-α (20 ng/mL) for 48 h. The mRNA expressions of MMP-1, -2, -3, -9, and -13, TIMP-1 and -2, VDR, TLR-2 and -4 in HC and SW1353 cells were detected by qPCR after treatments. The cytotoxicity and cell proliferation analyses were assessed by LDH and WST-1 assay, respectively. Protein levels of MMPs, TIMPs, and VDR were analysed by immunocytochemistry and ELISA methods. TNF-α markedly increased cytotoxicity for 24, 48, 72 h (p < 0.05) and vitamin D treatment was shown to diminish the cytotoxic effect of TNF-α. Cell proliferations increased by Vitamin D in a dose-dependent manner. mRNA expressions of MMP-1, -2, -3, -9, and -13, TLR-2 and -4 genes decreased with 1,25(OH)2D3 treatment (p < 0.05). VDR, TIMP-1 and -2 levels elevated after TNF-α exposure compared with the control group in HC cells (p < 0.05). Protein expression levels were determined using Western blotting, ELISA and immunocytochemistry. 1,25(OH)2D3 via binding to VDR, reversed the effects of TNF-α by inhibiting TLR-2 and 4. Decreased levels of VDR, TIMP-1 and -2 after TNF-α treatment were elevated by 1,25(OH)2D3 proportional with increasing 1,25(OH)2D3 doses. 1,25(OH)2D3 and TNF-α co-treatment decreased MMP-1, -2, -3, -9, and -13 levels were after TNF-α exposure.


The Beneficial Effect of the Blockade of Stim-Activated TRPC-ORAI Channels on Vascular Remodeling and Pulmonary Hypertension Induced by Intermittent Hypoxia Is Independent of Oxidative Stress.
Obstructive sleep apnea (OSA), a sleep breathing disorder featured by chronic intermittent hypoxia (CIH), is associated with pulmonary hypertension (PH). Rats exposed to CIH develop systemic and lung oxidative stress, pulmonary vascular remodeling, and PH and overexpress Stim-activated TRPC-ORAI channels (STOC) in the lung. Previously, we demonstrated that 2-aminoethyl-diphenylborinate (2-APB)-treatment, a STOC-blocker, prevents PH and the overexpression of STOC induced by CIH. However, 2-APB did not prevent systemic and pulmonary oxidative stress. Accordingly, we hypothesize that the contribution of STOC in the development of PH induced by CIH is independent of oxidative stress. We measured the correlation between right ventricular systolic pressure (RVSP) and lung malondialdehyde (MDA) with the gene expression of STOC and morphological parameters in the lung from control, CIH-treated, and 2-APB-treated rats. We found correlations between RVSP and increased medial layer and STOC pulmonary levels. 2-APB-treated rats showed a correlation between RVSP and the medial layer thickness, α-actin-ir, and STOC, whereas RVSP did not correlate with MDA levels in CIH and 2-APB-treated rats. CIH rats showed correlations between lung MDA levels and the gene expression of TRPC1 and TRPC4. These results suggest that STOC channels play a key role in developing CIH-induced PH that is independent from lung oxidative stress.


Primary mesenteric gastrointestinal stromal tumour with concomitant mesenteric tuberculosis: Careful histopathology is essential.
Gastro-inestinal stromal tumours (GISTs) comprise 1-2% of all gastrointestinal (GI) tumours. The mesentery, retroperitoneum and omentum are common sites of extra-gastrointestinal stromal tumours (E-GISTs). Isolated involvement of the mesentery by tuberculosis (TB) without any evidence of pulmonary disease is quite unusual. Here we report a case of an E-GIST arising from the small bowel mesentery in a 60-year old female where an incidental concurrent mesenteric tuberculosis was diagnosed following surgical resection.


Lymphatic mapping could not be impaired in the presence of breast carcinoma and coexisting small lymphocytic lymphoma.
Female, 66 FINAL DIAGNOSIS: Infiltrating ductal carcinoma • small lymphocytic lymphoma - - Clinical Procedure: Sentinel Lymph Node Biopsy • lumpectomy • axillary lymph node dissection Specialty: Breast cancer surgery. Rare presentation of two concomitant malingancies. Lymphatic mapping of axillary breast cancer metastases in the presence of concomitant lymphoproliferative disease is still a controversial topic. Previous reports have postulated that tumor collision in the lymph nodes could lead to false-negative results of sentinel lymph node biopsy, leading to erroneous staging. We present the case of a 66-year-old woman with infiltrating ductal breast carcinoma and small lymphocytic lymphoma in whom we performed a lumpectomy and sentinel lymph node biopsy with Technetium-99 and 1% methylene blue, followed by axillary lymph node dissection regardless of the intraoperative status, which was negative. Final pathology confirmed the absence of lymph node metastases. Previously published cases reported correct assessment of SLNB in patients with concomitant small lymphocytic lymphoma and breast carcinoma. We postulate a possible pathological explanation for this: lymphoid cell clusters with pseudofollicles or proliferative centers of small lymphocytic lymphoma are localized outside the nodal sinuses of the lymph node, maintaining its capability of draining, and thus, the feasibility of SLNB in these patients, as in the presented case.


Pathological Features of Brain Metastases.
Metastases are the most common intracranial tumors in adults. Lung cancer, melanoma, renal cell carcinoma, and breast cancer are the most common primary tumors that metastasize to the brain. Improved detection of small metastases by MRI, and improved systemic therapy for primary tumors, resulted in increased incidence of brain metastasis. Advances in neuroanesthesia and neurosurgery have significantly improved the safety of surgical resection of brain metastases. Surgical approach and active management have become applicable for many patients. Subsequently, brain metastases diagnosis no longer equals palliative treatment. Moreover, the demand for diagnosing brain masses has increased with its associated challenges.


A case of splenic artery aneurysm and rupture in a patient on a vascular endothelial growth factor inhibitor for renal cell carcinoma.
Pazopanib is a vascular endothelial growth factor inhibitor that is used in the treatment of metastatic renal cell carcinoma. Post market reports demonstrate an increasing awareness of the association of arterial aneurysms and dissections with vascular endothelial growth factor inhibitor use, although, few reports exist for pazopanib. Here we report a 69-year-old patient with minimal cardiovascular risk factors who developed a rupture of a splenic arterial aneurysm after more than 5 years of effective treatment with pazopanib for metastatic renal cell carcinoma. This case report outlines the necessity to monitor patients while on pazopanib, even when there are minimal risk factors and long periods of tolerance.


More Than "Spending Time with the Body": The Role of a Family's Grief in Determinations of Brain Death.
In many ways, grief is thought to be outside the realm of bioethics and clinical ethics, and grieving patients or family members may be passed off to grief counselors or therapists. Yet grief can play a particularly poignant role in the ethical encounter, especially in cases of brain death, where the line between life and death has been blurred. Although brain death is legally and medically recognized as death in the United States and elsewhere, the concept has been contentious since its inception in 1968. Yet in most cases, families are not allowed to reject the determination of brain death. Apart from religious exemptions, families have no recourse to reject this controversial determination of death. This paper explores the role of grief in brain death determinations and argues that bioethics has failed to address the complexity of grief in determinations of brain death. Grief ought to have epistemological weight in brain death determinations because of the contested nature of the diagnosis and the unique ways in which grief informs the situation. Thus, I argue that, in some rare cases, reasonable accommodation policies should be expanded to allow for refusals of brain death determinations based on the emotional and moral force of grief. By drawing on ethnographic accounts of grief in other cultures, I problematize the current procedural and linear understandings of grief in brain death determinations, and I conclude by offering a new way in which to understand the case of Jahi McMath.


Differentiation of allergic and irritant reactions by transepidermal water loss.
12 patients with known allergy to nickel were patch tested with nickel sulphate, nickel chloride, and sodium lauryl sulphate 1, 2, 5 and 10%. 2 parallel series were performed, i.e., one with 24-h and one with 48-h application time. Reactions were followed by measurement of transepidermal water loss (TEWL). Allergic reactions showed a normal TEWL after 24-h application, and after 48 h, only strong reactions resulted in increased TEWL. In contrast, irritant reactions showed increased TEWL in both series, irrespective of the strength of the reaction. The deficient water barrier of allergic reactions is secondary, probably resulting from the underlying inflammatory process. Consequently, if TEWL measurements are used for the purpose of differentiating allergic and irritant skin reactions, a short application period, i.e., in this study 24 h, is preferable, with recordings performed shortly after removal of test chambers.