The patient's perspective of the adverse effects of glucocorticoid use: A systematic review of quantitative and qualitative studies. From an OMERACT working group.
Glucocorticoids (GCs) remain widely used. However, the impact of GCs from the perspective of the patient, rather than of the clinician, remains relatively unexplored. Additionally, no general patient reported outcome measure has been developed to assess the effects of GCs across rheumatological conditions. The aim of this literature review was to identify the adverse effects of systemic GC use that are of importance to patients. OVID EMBASE, OVID MEDLINE, PsycINFO and CINAHL was searched relating to three concepts: GCs, the patient perspective and adverse effects. A meta-synthesis of the qualitative data was performed separately by two independent researchers before qualitative metasummary was utilized to quantitatively aggregate the findings (combining quantitative and qualitative results), including the derivation of frequency and intensity effect sizes to identify those outcomes most prominently featured across all reviewed articles. The initial search retrieved 1,356 articles, of which 25 (18 quantitative, 7 qualitative) were deemed suitable for quality assessment and data extraction. Four major themes emerged amongst the 71 discrete outcomes: physical symptoms (44), psychological symptoms (18), effect on participation (6) and contextual factors (3). Patients with a broad range of inflammatory diseases and demographic features describe key cross-cutting themes in relation to GCs and their impact on health-related quality of life. This work will inform the development of a core domain set for clinical trials involving GCs and a patient reported outcome to measure impact of GCs from the patient's perspective.


Is CT scan still necessary for staging in Hodgkin and non-Hodgkin lymphoma patients in the PET/CT era?
The clinical impact of fused PET/CT data on staging and patient management of Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) was assessed. A total of 103 consecutive patients with newly diagnosed NHL (n = 68) and HD (n = 35) were assessed retrospectively. Three comparisons were carried out in an attempt to assess the added value of each modality. For NHL patients, there were significant differences between staging by CT versus PET/CT (P = 0.0001). Disease was upstaged by PET/CT in 31% (mostly in stages I and II) and downstaged in only 1% of patients. In 25% of the patients, the treatment approach was changed according to CT versus PET/CT findings. For HD patients, disease was upstaged by PET/CT in 32% and downstaged by PET/CT in 15% (P = NS). As for NHL, upstaging by PET/CT versus CT was evident mostly for stages I and II. The treatment strategy was altered as determined by CT versus PET/CT in 45% of the patients. The addition of PET/CT to CT changed the management decisions in approximately a quarter of NHL and a third of HD patients, mostly in early disease stages. Thus, PET/CT performed as the initial staging procedure may well obviate the need for additional diagnostic CT in the majority of patients.


Time- and dose-related effects of a gonadotropin-releasing hormone agonist and dopamine antagonist on reproduction in the Northern leopard frog (Lithobates pipiens).
Gonadotropin-releasing hormone (GnRH) stimulates luteinizing hormone release to control ovulation and spermiation in vertebrates. Dopamine (DA) has a clear inhibitory role in the control of reproduction in numerous teleosts, and emerging evidence suggests that similar mechanisms may exist in amphibians. The interactions between GnRH and DA on spawning success and pituitary gene expression in the Northern leopard frog (Lithobates pipiens) were therefore investigated. Frogs were injected during the natural breeding season with a GnRH agonist [GnRH-A; (Des-Gly10, D-Ala6, Pro-NHEt9)-LHRH; 0.1μg/g and 0.4μg/g] alone and in combination with the dopamine receptor D2 antagonist metoclopramide (MET; 5μg/g and 10μg/g). Injected animals were allowed to breed in outdoor mesocosms. Time to amplexus and oviposition were assessed, and egg mass release, incidences of amplexus, egg mass weight, total egg numbers and fertilization rates were measured. To examine gene expression, female pituitaries were sampled at 12, 24 and 36h following injection of GnRH-A (0.4μg/g) alone and in combination with MET (10μg/g). The mRNA levels of the genes lhb, fshb, gpha, drd2 and gnrhr1 were measured using quantitative real-time PCR. Data were analyzed by a two-way ANOVA. Both GnRH-A doses increased amplexus, oviposition and fertilization alone. Co-injection of MET with GnRH-A did not further enhance spawning success. Injection of GnRH-A alone time-dependently increased expression of lhb, fshb, gpha and gnrhr1. The major effect of MET alone was to decrease expression of drd2. Importantly, the stimulatory effects of GnRH-A on lhb, gpha and gnrhr1 were potentiated by the co-injection of MET at 36h. At this time, expression of fshb was increased only in animals injected with both GnRH-A and MET. Spawning success was primarily driven by the actions of GnRH-A. The hypothesized inhibitory action of DA was supported by pituitary gene expression analysis. The results from this study provide a fundamental framework for future time- and dose-response investigations to improve current spawning methods in amphibians.


Effectiveness of Exergaming Training in Reducing Risk and Incidence of Falls in Frail Older Adults With a History of Falls.
To use Nintendo's Wii Fit balance board to determine the effectiveness of exergaming training in reducing risk and incidence of falls in older adults with a history of falls. Randomized controlled trial. Nursing home for older adults. Adults aged 65 years and older (N=60). Participants who lived in a nursing home had 6 weeks of balance training with either Wii Fit equipment or conventional exercise. Physiological Profile Assessment scores and incidence of falls were observed with subsequent intention-to-treat statistical analyses. Physiological Profile Assessment scores and incidence of falls improved significantly in both groups after the intervention (all P<.01), but participants in the Wii Fit training group showed a significantly greater improvement in both outcome measures (P=.004 and P<.001, respectively). In institutionalized older adults with a history of falls, Wii Fit balance training was more effective than conventional balance training in reducing the risk and incidence of falls.


Will older persons and their clinicians use a shared decision-making instrument?
To examine experiences of older persons and their clinicians with shared decision making (SDM) and their willingness to use an SDM instrument. Qualitative focus group study. Four focus groups of 41 older persons and 2 focus groups of 11 clinicians, purposively sampled to encompass a range of sociodemographic and clinical characteristics. APPROACH AND MAIN RESULTS: Audiotaped responses were transcribed, coded independently, and analyzed by 3 reviewers using the constant comparative method. Patient participants described using informal facilitators of shared decision making and supported use of an SDM instrument to keep "the doctor and patient on the same page." They envisioned the instrument as "part of the medical record" that could be "referenced at home." Clinician participants described the instrument as a "motivational and educational tool" that could "customize care for individual patients." Some clinician and patient participants expressed reluctance given time constraints and unfamiliarity with the process of setting participatory clinical goals. Participants indicated that they would use a shared decision-making instrument in their clinical encounters and attributed multiple functions to the instrument, especially as a tool to facilitate agreement with treatment goals and plans.


BDNF and pro-BDNF in serum and exosomes in major depression: Evolution after antidepressant treatment.
The study of clinically related biological indicators in Major Depression (MD) is important. The Brain Derived Neurotrophic Factor (BDNF) appears to play an important role in MD, through its neurotrophic effect, and its levels are significantly decreased. The variation in the serum levels of its precursor proBDNF, which has opposite effects, is not known. Their distribution between serum and exosomes and their evolution during antidepressant treatment is also not known, and may be important in modulating their effects. The aim of this study is to evaluate whether serum and exosome mBDNF and proBDNF levels are altered in patients with MD during antidepressant treatment compared to controls, and their association with clinical improvement and clinical variables. 42 MD subjects and 40 controls were included. Questionnaires to assess the severity of depression and cognitive impairment and blood samples were collected during the three visits at D0 (inclusion) and 3 and 7 weeks after the start of antidepressant treatment. Assays for mBDNF and proBDNF levels were performed in serum and exosomes by ELISA. MD subjects had decreased serum and exosomal BDNF levels and increased proBDNF levels at D0 compared to controls. BDNF and pro-BDNF vary in an inverse manner in both serum and exosomes during antidepressant treatment. No relationship of BDNF and proBDNF levels to clinical improvement and depression scales was found. We demonstrated an evolution of those molecules either in serum or in exosomes after MD treatment. These transport vesicles could have a role in the regulation of BDNF.


Effects of suckling on serum prolactin levels and catecholamine concentrations and turnover in discrete brain regions.
The effects of suckling on serum prolactin levels and catecholamine concentrations and turnover were examined in several discrete brain regions. Turnover rates were assessed by using the synthesis inhibitor alpha-methyltyrosine (alpha-MT) in combination with microdissection techniques for the removal of individual brain regions and sensitive radioenzymatic assays for norepinephrine (NE) and dopaime (DA). Prolactin secretion was induced by mothers experiencing 6 h of pup removal with subsequent pup replacement. Suckling or the administration of alpha-MT to mothers resulted in a marked increase in circulating titers of prolactin. A decrease in steady-state NE concentrations in the anterior hypothalamus and a decrease in steady-state DA concentrations in the ventromedial nucleus were noted in suckled mothers. The comparison of relative rates of NE depletion after alpha-MT treatment revealed a suckling-induced increase in turnover in the ventromedial nucleus and a suckling-induced decrease in turnover in the anterior hypothalamus. Neither suckling nor alpha-MT treatment produced any changes in NE or DA turnover rates in the arcuate nucleus or median eminence. These findings demonstrate that suckling-induced activation of prolactin results in changes in noradrenergic processes in the ventromedial and anterior hypothalamic nuclei. This suggests an involvement of noradrenergic systems in suckling-induced prolactin release.


Health-related quality of life is inversely correlated with C-reactive protein and age in Mycobacterium avium complex lung disease: a cross-sectional analysis of 235 patients.
Mycobacterium avium complex (MAC) lung diseases generally cause chronic disease in immunocompetent hosts. Although a few studies have examined health-related quality of life (HRQL) in patients with MAC lung disease, there have been no large studies. This study aimed to evaluate HRQL and its correlation with clinical outcomes in MAC lung disease. A cross-sectional study was conducted at Keio University Hospital to investigate the factors associated with HRQL in pulmonary nontuberculous mycobacterial diseases. MAC lung diseases were diagnosed according to the 2007 ATS/IDSA guidelines for nontuberculous mycobacterial diseases. The 36-item short form health survey (SF-36) was administered to assess clinical outcomes. Clinical variables included treatment status, latest haematological data, and bacterial smear and culture results. The SF-36 scores for the 235 patients (median age, 69 years; 45 men and 190 women) with MAC lung disease, except for the bodily pain and mental health subscale scores, were significantly lower than the Japanese population norms. In the multivariable analyses, current treatment for MAC and a positive sputum smear or culture within the past year were significantly associated with lower SF-36 scores. C-reactive protein (CRP) and age showed stronger inverse correlations with SF-36 scores. HRQL, especially the physical component, was impaired in patients with MAC lung diseases; this appears to be related with current treatment status, positive sputum smear or culture within the previous year, and particularly CRP and age. Further studies including qualitative assessments are needed to investigate the efficacy of CRP as a marker for progression or treatment response in MAC lung disease. Clinical trial registered with UMIN ( UMIN000007964 ).


Incorporation of zinc sulfide nanoparticles, Acinetobacter pittii and Bacillus velezensis to improve tomato plant growth, biochemical attributes and resistance against Rhizoctoniasolani.
Green nanobiotechnology and beneficial bacterial strains as biofertilizers are crucial in agriculture to achieve food security. Both these strategies have been individually studied in improving plant resistance against phytopathogens along with enhancing plant productivity. Therefore, objective of this study was to explore the eco-friendly and cost-effective approach of utilizing plant growth promoting and disease suppressing bacterial strains and nanoparticles, individually as well as in combination, as bio-stimulants to improve plant growth, antioxidant defense system, nutrition and yield of tomato. A pot experiment was conducted to investigate the zinc sulfide nanoparticles (ZnS NPs) synthesized by using Jacaranda mimosifolia flower extracts (JFE), Acinetobacter pittii and Bacillus velezensis either individually or in combinations to check their potential against Rhizoctonia solani in tomato to suppress root rot infection and improve growth and yield. Among all the combinations the JFE-ZnS NPs + B. velezensis compared to untreated infected plants showed minimum disease incidence and maximum significant protection (66%) against R. solani instigated root rot that was followed by JFE-ZnS NPs + A. pittii and individual application of JFE-ZnS NPs by 58%. The same treatment showed maximum significant increase in plant fresh and dry biomass. B. velezensis significantly increased the photosynthetic pigments when applied individually. However, JFE-ZnS NPs alone and in mixed treatments with B. velezensis efficiently improved total soluble protein, sugar and phenolic contents. The same interactive application of JFE-ZnS NPs + B. velezensis improved the tomato plant nutrition (silicon (Si), magnesium (Mg), calcium (Ca) and potassium (K)) and redox quenching status by improving the activity of antioxidant defense enzymes. Overall, the interactive use of JFE-ZnS NPs with A. pittii and B. velezensis very appropriately prepared the host plant to fight against the negative effects of root rot pathogen in tomato. Advancements in interactively investigating the nanoparticles with beneficial plant growth promoting bacterial strains importantly can contribute in resolving the challenges of food security. According to our information, this is a pioneer report for implying JFE-ZnS NPs in synergism with A. pittii and B. velezensis to hinder the root rot in tomatoes.


Acute and subacute toxicity of 7.5% hypertonic saline-6% dextran-70 (HSD) in dogs. 2. Biochemical and behavioral responses.
7.5% Hypertonic saline-6% Dextran-70 (HSD) is currently being evaluated in our laboratory as a resuscitation solution for the treatment of hypovolemia at a dose of 4 ml kg-1 body weight. A few reports of dextran toxicity, particularly of the kidney, have been cited in the literature, so the present study evaluated the acute and subacute toxicity of HSD administered i.v. to beagle dogs. In the acute toxicity studies animals were infused with a single dose of HSD, or its components of hypertonic saline (HS) or Dextran-70 (D-70), at the maximum tolerated dose (MTD: 20 ml kg-1). Controls received Ringers lactate (RL). In the HSD-infused dogs, transient but significant increases in serum alanine (ala) aminotransferase (AT), aspartate (asp) AT and alkaline phosphatase (AP) were observed for the first 72 h. In most cases this increase was also observed in the HS group. In the subacute studies, dogs were infused daily with the MTD of the above test solutions. Serum ala AT activity was 2-3-fold higher in the HSD than the RL group for the first 3 days. Again, a similar effect was observed in the HS group. Slight, transient increases in asp AT and AP activity were also observed in the HSD group. Higher lactate dehydrogenase (LDH) activity was only observed at Day 14 in dogs infused with the MTD of HSD or HS. In both studies, no adverse effects on blood urea nitrogen (BUN) or serum creatinine were observed and other transient changes in serum parameters were attributable to hemodilution induced by HSD.(ABSTRACT TRUNCATED AT 250 WORDS)


The initial slope of human tumor cell survival curves: its modification by the oxic cell sensitizer beta-arabinofuranosyladenine.
The initial slope of the survival curve, which is a characteristic of each tumor cell line, varies with the histological group of the tumor. It is one of the factors on which clinical radioresponsiveness depends. The DNA dependant DNA polymerase inhibitor beta-ara A acts as an oxic cell sensitizer. This study was carried out on human tumor cell lines to look for a correlation between the degree of radiosensitization induced by beta-ara A and the radiosensitivity of a given cell line. Six human tumor cell lines with different radiosensitivities were used (the survival rate at 2 Gy and D ranged from 20 to 73% and from 1.2 to 3.2 Gy, respectively). beta-ara A had a major toxic effect on all cell lines but this varied greatly from one cell line to another and was concentration dependant; this toxic effect was taken into account when calculating the surviving fractions. For all cell lines, beta-ara A acted as an oxic radiosensitizer and the radiosensitization was concentration dependant. Analysis of the survival curves of the 6 cell lines using the linear quadratic model showed that concentrations of beta-ara A between 200 and 1000 microM induced an increase in the linear component while the quadratic component underwent no systematic change. The sensitizing enhancement ratio (SER) measured from the Ds ratios, varied greatly from one line to another. For example, at a concentration of 500 microM, the extreme values of Ds ratios were 1.5 and 2.6. The radiosensitization is greater, the higher the radiosensitivity of the cell line studied during exponential growth. The results do not favor the use of beta-ara A in the treatment of intrinsically radioresistant human tumors.


Determination of the chlorofluorocarbon substitute 1,1,1,2-tetrafluoroethane (HFA-134a) in human and animal blood using gas chromatography with headspace analysis.
A gas chromatographic procedure with headspace analysis and flame-ionization detection is described for the determination of the chlorofluorocarbon substitute 1,1,1,2-tetrafluoroethane (HFA-134a). A 0.5-2 ml sample of heparinized whole blood from a laboratory animal or human is added directly into a presealed headspace vial from which an equivalent volume of air has been removed. The internal standard 1,1,2,2-tetrafluoroethane is added and the sample frozen until analysis. Chromatographic separation is achieved using a PoraPlot Q porous-layer capillary column. The analytical range is 5.8-3298 ng/ml when 2-ml human blood samples are used. The concentration range of the calibration curve can be easily adapted to accommodate the concentrations expected in either pharmacokinetic or toxicokinetic studies. Automation of the assay permits the maximum number of samples to be processed in a day.


Graphene oxide-based biosensor for sensitive fluorescence detection of DNA based on exonuclease III-aided signal amplification.
Based on the super fluorescence quenching efficiency of graphene oxide and exonuclease III aided signal amplification, we develop a facile, sensitive, rapid and cost-effective method for DNA detection. In the presence of target DNA, the target-probe hybridization forms a double-stranded structure and exonuclease III catalyzes the stepwise removal of mononucleotides from the blunt 3' termini of probe, resulting in the recycling of the target DNA and signal amplification. Therefore, our proposed sensor exhibits a high sensitivity towards target DNA with a detection limit of 20 pM, which was even lower than previously reported GO-based DNA sensors without enzymatic amplification, and provides a universal sensing platform for sensitive detection of DNA.


Emerging issues in acute ischemic stroke.
In this update we review studies on a wide range of topics, from diagnostic aspects of acute stroke to the clinical implications of the complex interaction between the brain and the immune system. Recent randomized trials and observational studies have reinforced the effectiveness of intravenous thrombolysis with t-PA in patients that qualify for this treatment, including patients presenting with mild symptoms or on subtherapeutic oral anticoagulation. Despite all the negative studies on the endovascular treatment of acute stroke, the utility of newer mechanical thrombectomy devices in patients with stroke and large vessel occlusion is being assessed in ongoing clinical trials. In addition to the various revascularization therapies that have a limited time window, treatments aimed at protecting the neurovascular unit may be used in more patients if their efficacy is confirmed in humans, and experimental studies suggest that the modulation of specific aspects of the immune system may increase the likelihood of successful recovery after cerebral ischemia.


Mycosis fungoides associated with intestinal mucosa-associated lymphoid tissue lymphoma.
Coexistence of cutaneous T-cell lymphoma (CTCL) and a B-cell malignancy is rare. We report a case of mycosis fungoides (MF) associated with intestinal mucosa-associated lymphoid tissue (MALT) lymphoma, which is a low-grade B-cell lymphoma of marginal cell origin. To the best of our knowledge, there have been only two cases of coexistent CTCL and MALT lymphoma, and this is the first case with typical MF and intestinal MALT lymphoma. The coexistence in our case might be coincidental, but genetic predisposition and the immunoregulatory capacity of neoplastic T lymphocytes may be factors contributing to this association.


Characterization of an acid-tolerant β-1,4-glucosidase from Fusarium oxysporum and its potential as an animal feed additive.
An extracellular β-glucosidase (BGL) from Fusarium oxysporum was purified to homogeneity by a single chromatography step on a gel filtration column. The optimum activity of BGL on cellobiose was observed at pH 5.0 and 60 °C. Under the same conditions, the K(m) and V(max) values for p-nitrophenyl β-D-glucopyranoside and cellobiose were 2.53 mM, 268 U mg protein(-1) and 20.3 mM, 193 U mg protein(-1), respectively. The F. oxysporum BGL enzyme was highly stable at acidic pH (t 1/2 = 470 min at pH 3). A commercial BGL Novo188 (Novozymes) and F. oxysporum BGL were compared in their ability to supplement Celluclast 1.5 L (Novozymes). In comparison with the commercial Novo188 (267 mg g substrate(-1)), F. oxysporum BGL supplementation released more reducing sugars (330 mg g substrate(-1)) from cellulose under simulated gastric conditions. These properties make F. oxysporum BGL a good candidate as a new commercial BGL to improve the nutrient bioavailability of animal feed.


[Transport of the substance through thin membranes with narrow pores after the preceding stage of surface diffusion].
A model of the substance transport through thin membranes is discussed. Existence of a step of the surface diffusion of permeable particles is assumed preceding its entrance into membrane channel. An expression is given for the stationary flow, which has earlier been obtained for other transport models. It is shown that the permeant affinity to the membrane surface is the main condition for the validity of the scheme in question.


Peptides as protein binding site mimetics.
The rational/structure-based design and/or combinatorial development of molecules capable of structurally and functionally mimicking the binding sites of proteins represents a promising strategy for the exploration and understanding of protein structure and function. The ultimate goal of using such molecules is the modulation of protein function through controlled interference with the underlying binding events. In addition to their basic significance, such proteinmimetics are also useful tools for a range of biomedical applications, in particular the inhibition of disease-associated protein-ligand interactions. Owing to their chemical and structural relation to proteins, as well as the relative simplicity of their chemical or recombinant synthesis, peptides have emerged as adequate molecules for the mimicry of protein binding sites, as well as the inhibition of protein-protein interactions.


Impacts of dust events on chemical characterization and associated source contributions of atmospheric particulate matter in northern China.
Sand and dust have significant impacts on air quality, climate, and human health. To investigate the influences of dust storms on chemical characterization and source contributions of fine particulate matter (PM2.5) in areas with different distances from dust source regions, PM2.5 and associated chemical composition were measured in two industrial cities with one near sand sources (i.e., Wuhai) and the other far from sand sources (i.e., Jinan) in northern China in March 2021. Results showed that PM mass concentrations significantly increased and exceeded the Chinese National Ambient Air Quality standard during the dust events, with absolute concentrations and fractional contributions of PM2.5-bound crustal and trace elements increased while secondary inorganic ions decreased at both sites. Crustal materials dominated the increased PM2.5 mass from non-dust period to dust period in both cities. These were further evidenced by PM2.5 source apportionment results from positive matrix factorization model. During the dust events, dust sources contributed up to 88% of PM2.5 mass in Wuhai and ∼38% of PM2.5 mass in Jinan, a city about thousands of kilometers away from the sand source. Besides, the measurement data indicated that dust from northwest China may also bring along with high abundance of organic matter and vanadium. Secondary and traffic sources were two of the most important source contributors to PM2.5 in both cities during the non-dust periods. However, the near sand source city was more susceptible to the aggravating effects of dust and minerals, with much higher contributions by crustal materials (∼47%, from the aspect of chemical components) and dust-related sources (∼26%, from the aspect of sources) to PM2.5 mass even during non-dust periods. This study highlighted the urgent need for more action and effective control of sand sources to reduce the impact on air quality in downstream regions.


Land tenure system and harvesting time's influence on the marketing behaviour of cashew farmers in the Bono Region of Ghana.
This study investigated the land tenure system, harvesting time and marketing behaviour of cashew farmers in Ghana. Primary data was compiled from 120 cashew farmers, and the multinomial probit was used to assess the determinants of cashew marketing outlets. Types of land ownership (tenure system) for cashew production in Ghana were leasehold, stool, family, state and customary lands. The sales of cashew nuts to buying companies and/or exporters is positively influenced by the land tenure system, good road network, weekly harvest, contract agreements and grading of cashew nuts. Conversely, the experience of farmers coupled with less than one week of harvesting influences the choice of brokers' outlet. The result implies that, cashew cultivation on stool land, likewise harvesting time increases the probability of selling to buying companies and exporters who offered higher margins compared with brokers. Consequently, generic land reform for the whole country to enhance agribusinesses may be important but unnecessary. It is also suggested that the customary land arrangement provided the opportunity to sell to a profitable marketing outlet, it is suggested that Government and NGOs should rather be interested in strengthening the current customary land regime and consultatively recommend for review where necessary in the study areas.


Focal left atrial tachycardias not associated with prior catheter ablation for atrial fibrillation: clinical and electrophysiological characteristics.
The clinical features and electrophysiological characteristics of patients with focal left atrial tachycardias (LATs) are not well characterized. This study reports the experience of a single center in catheter mapping and radiofrequency ablation of focal LAT not associated with prior atrial fibrillation (AF) ablation, including in cardiac sarcoidosis and transplant patients. Patients with focal LAT without a history of AF ablation were included in this retrospective analysis. A total of 24 focal LATs were documented in 20 patients. Two patients were subsequently diagnosed with cardiac sarcoidosis. Two patients were status post a thoracic transplant. The mean initial cycle length of the focal LATs was 347.4 ± 96.2 ms (range 190-510 ms). Patients with a pulmonary vein (PV) ostium focus (n = 6) demonstrated a shorter cycle length than patients with other LA foci (259.2 ± 56.4 ms vs 371.9 ± 91.1 ms, P = 0.02), as well as a trend for a history of AF (67% vs 21%, P = NS). Catheter ablation was immediately successful for 19 of 22 focal LATs. Focal LATs not associated with prior AF ablation can originate in a variety of LA locations and clinical settings. Focal LAT arising in the PV ostia is associated with a history of AF and demonstrates a faster tachycardia rate. We also report focal LAT in cardiac sarcoidosis patients and in the donor heart of an orthotopic heart transplant recipient. Radiofrequency ablation is a successful treatment for focal LAT not associated with prior ablation, including those refractory to medical therapy.


A histomorphometric determination of iliac bone remodeling in patients with recurrent renal stone formation and idiopathic hypercalciuria.
33 normocalcemic patients (22 males and 11 females) aged 20-68 years with recurrent renal stone formation and idiopathic hypercalciuria were compared to 33 approximately sex- and age-matched normal controls. Quantitative histomorphometric analysis of iliac crest biopsies were performed after intravital tetracycline double labeling in the patients and in 30 sex- and age-matched normal controls. No difference was found between patients and controls in albumin adjusted serum calcium levels. Serum phosphorus was significantly reduced (p less than 0.01) in the patient group whereas the urinary phosphorus/creatinine ratio was increased (p less than 0.01). The serum calcium phosphate product (S-CaxS-P) was significantly reduced in the patients (p less than 0.05). As expected, the urinary calcium/creatinine ratio was higher in the patient group than in the controls (p less than 0.001). Serum parathyroid hormone was normal. The histomorphometric analysis revealed signs of a moderate mineralization defect (reduced adjusted appositional rate (p less than 0.05), prolonged mineralization lag time (p less than 0.05) and prolonged formation (p less than 0.05)), and an increased extension of eroded surfaces (P less than 0.05) in the patients. The amount of trabecular bone and the balance between the thickness of bone resorbed and later formed per remodeling cycle and all other histomorphometric parameters were found normal in the patients. The combined histomorphometric and biochemical data are best explained by a primary renal phosphate leak leading to hypophosphataemia and a slight mineralization defect. The hypercalciuria may be explained by an enhanced renal production of 1.25-dihydroxyvitamin D secondary to the reduced serum levels of phosphorus. No signs of secondary or primary hyperparathyroidism were observed.


Evidence for the presence of a trypsin inhibitor within rabbit and mouse tumour cells.
Post-granule supernatant fractions obtained from induced tumour cells in rabbits and from Ehrlich ascites tumour cells in mice have been shown to contain a protease inhibitor, inhibiting trypsin (EC 188.8.131.52) and neutral proteases located in the cytoplasm of the cells. This inhibition was found to be irreversible over the time period studied, independent of the time of enzyme incubation and independent of the extent of trypsin digestion within an insoluble substrate (within the limits of linear enzyme kinetics).


Pressure study on thermal transitions of oleic acid polymorphs by high-pressure differential thermal analysis.
Transition temperatures for oleic acid polymorphs (alpha, beta and gamma) and the melt were measured under various pressures up to 200 MPa by means of high-pressure differential thermal analysis. The pressure dependences of the transition temperatures were analyzed by applying the Clapeyron equation, and the volume changes associated with the phase transitions were estimated as follows; delta V gamma-alpha = 5.9 cm3/mol, delta V alpha-melt = 29.2 cm3/mol and delta V beta-melt = 41.1 cm3/mol. The volume changes for the gamma-alpha and alpha-melt transitions were discussed in relation to the crystal structures of the alpha and gamma modifications. The experiments showed that the beta modification, whose structural data are lacking, is the most dense. This correlates with the fact that the beta form is thermodynamically most stable among the three modifications of oleic acid.


[Allogeneic hepatic cell suspension in the treatment of liver insufficiency].
A study was made of a possibility of using isolated hepatocytes for the treatment of diseases of the liver in animals. The optimal dose of the cell suspension in intravascular, intraperitoneal, intrapleural and subcutaneous administration was determined; a reaction of the experimental animals to this biological substrate was studied. The efficacy of the isolated hepatocytes in the treatment of hepatic insufficiency is demonstrated; also a comparative assessment of the mentioned methods of the cell suspension administration is given.


BoviPure® density-gradient centrifugation procedure enhances the quality of fresh and cryopreserved dog epididymal spermatozoa.
BoviPure® is a salt solution containing colloidal silica particles coated with silane used to select sperm (e.g., ruminants) by density-gradient centrifugation (DGC). This research assessed the suitability of the BoviPure-DGC and swim-up methods for selecting dog epididymal sperm in fresh, chilled and frozen-thawed samples on post-treatment sperm quality. Sperm samples (n = 60 epididymides) were recovered by retrograde flushing from thirty orchiectomized adult dogs. Thereafter, 20 sperm pools, containing sperm aliquots of three randomly selected animals, were used for chilling (at 5 ºC for 24 h) and freezing (in liquid nitrogen vapors). Sperm selection by BoviPure-DCG and swim-up was performed in both individual and pooled samples, including non-selected samples as controls. Overall, after BoviPure-DGC selection a higher sperm retrieval rate was obtained than the swim-up selection in both individual (P < 0.05) and pooled (P < 0.01) samples. BoviPure-DGC improved (P < 0.05) the total (TM) and progressive (PSM) sperm motilities, curvilinear (VCL) and straight-line (VSL) velocities, linearity (LIN), wobble (WOB), beat-cross frequency (BCF), and integrity of plasmatic (IPM) and acrosomal (IAM) membranes of individual samples in comparison with non-selected samples. In pooled samples, however, the BoviPure-DGC improved (P < 0.05) the PSM, VCL, WOB, and IPM of chilled and frozen-thawed samples. The swim-up method improved (P < 0.05) only some kinematic variables of the individual (VCL, WOB and BCF) and cryopreserved pooled samples (VCL and ALH) in comparison with non-selected samples. In conclusion, BoviPure-DGC was more effective for recovering and selecting both fresh and cryopreserved dog epididymal sperm than the swim-up procedure improving the kinematic variables, and membranes intactness.


Intravesical instillation of Formalin for hemorrhagic cystitis secondary to radiation for gynecologic malignancies.
Our experience with the use of Formalin instillation in interactable gross hematuria secondary to radiation cystitis in patients with gynecological malignancies is reported. This study indicates coagulative effect of low concentration of Formalin with minimal side effects as a method to control hemorrhage.


Leptin attenuates oxidative stress and neuronal apoptosis in hyperglycemic condition.
One of the main pathological mechanisms of neurotoxicity in diabetic situation is oxidative stress promoted by hyperglycemia. It has been shown that leptin has neuroprotective effects and may provide neuronal survival signals. This study was designed to reveal the possible neuroprotective effects of leptin in hyperglycemic conditions. Pheochromocytoma (PC12) cell viability was assessed via the MTT test. Cellular reactive oxygen species (ROS) generation was determined by DCFH-DA analysis. The malondialdehyde (MDA) and glutathione (GSH) levels were measured in high-glucose-treated PC12 cells with and without leptin cotreatment. Western blotting was performed to measure apoptosis markers (Cleaved caspase-3 and Bax/Bcl2 ratio). Elevation of glucose levels (100 mmol/L) consecutively increased intracellular ROS and MDA level, and apoptosis in PC12 cells after 24 h leptin administration (12 and 24 nmol/L) decreased the high-glucose-induced cell toxicity, caspase-3 activation, and Bax/Bcl-2 ratio. Also, cotreatment with leptin (12 and 24 nmol/L) significantly reduced oxidative damage to PC12 cells in high-glucose condition, as reflected by the diminution in MDA and ROS levels and the increase in GSH content. Our finding demonstrates that leptin has protective effects against hyperglycemia-induced neural damage. This could be related to the attenuation of oxidative stress and neural apoptosis.


Conflict side of creativity: Role of supervisory support and team affective tone in facilitating creative idea validation.
We seek to understand whether relationship conflicts of co-workers affect the validation of creative ideas or not. Furthermore, what boundary conditions may help prevent potential drawbacks of relationship conflicts with co-workers to validate their creative ideas? The proposed model was tested by using multisource data collected across two points in time from final year nursing students and medical dispensers of five nursing colleges of south-Punjab, Pakistan. The model was analyzed with Mplus for random coefficient models for direct effects, mediated moderation, and UCINET for central tendency of creative idea validation. It was found that relationship conflicts with co-workers were negatively related to their validation of creative ideas. However, supervisory support and team affective tone independently attenuate the negative effects of relationship conflicts with co-workers and the validation of creative ideas. Positive affective tone emerged as a positive predictor of creative idea validation. Additionally, positive affective tone as affected by supervisory support attenuated the negative relationship between relationship conflicts with co-workers and their validation of creative ideas. Finally, the relationship between relationship conflicts with co-workers and their validation of creative ideas is more positive when both supervisory support and positive affective tone are high, however, low otherwise. This study will help policymakers understand what might be hindering the transfer of creative ideas to influential others (Leaders, Managers, etc.) and what they need to do to enhance the creative pool of their organizations. Although developing an environment that fosters creativity is important for the organizations, developing strategies to manage relationship conflicts related to supervisory support and positive affective tone will help transfer creative ideas to higher offices even when there are dysfunctional conflicts. This research shifts the conventional focus of understanding creativity from the generating side by explaining challenges that creative individuals face in promoting creative ideas with more criticism and offense by coworkers than support. Also, the interplay between the relationship conflicts with co-workers and team affective tone affected by supervisory support for validation of creative ideas enhanced our understanding of the boundary conditions of relationship conflict and creative idea validation.


Single ventricle repair in children with Down's syndrome.
There is a paucity of information regarding appropriate management of children with Down's syndrome and a functional single ventricle. We report the results of bidirectional superior cavopulmonary shunts in six patients with Down's syndrome with a functional single ventricle. Between January 1991 and December 2004, we identified six patients with Down's syndrome among 263 who had undergone bidirectional superior cavopulmonary shunts (BCPSs). There were four males and two females. The age at BCPS ranged from 1 to 12 years (mean 4.3 +/- 3.9 years), and body weight varied between 8.2 and 29.4 kg (mean 13.8 +/- 7.8 kg). All six patients had an unbalanced complete atrioventricular septal defect, with right ventricular hypoplasia present in five and left ventricular hypoplasia in one. There were no operative deaths, but one case required takedown of the BCPS. Except for this case, postoperative courses were generally uneventful. The median duration of follow-up was 46 months (range 12-80 months). Only two of five survivors after BCPS underwent a subsequent Fontan procedure, and one of these patients died of pulmonary hypertension post-operatively. The remaining three patients appeared to have significant risk factors for the Fontan procedure due to severe common atrioventricular valve regurgitation or persistent pulmonary vascular obstructive disease, including one who has completely dropped out from the Fontan track. Down's syndrome is a risk factor in patients with functionally single ventricle due to persistent pulmonary hypertension and airway obstruction. These results show that single ventricle repair in patients with Down's syndrome is accompanied with difficulties, and patient selection for the Fontan procedure should be done carefully.


A longitudinal study on high risk pregnancy and its outcome among antenatal women attending rural primary health centre in Puducherry, South India.
Almost 15% of all pregnant women can develop potentially life-threatening complications. As a result, identification of high-risk pregnancy at earliest stage will be useful in directing appropriate intervention. Hence, the current study was done to determine the prevalence and outcome of high-risk pregnancy among antenatal women in rural Puducherry. A record-based longitudinal study was done during March 2018 among 569 antenatal women who have attended rural health center of tertiary care institute. High-risk pregnancy was classified based on the guidelines from Pradhan Mantri Surakshit Matritva Abhiyan and outcome assessment based on the obstetric and neonatal outcomes. Among 569 antenatal case record reviewed, 315 (55.3%) were in the age group of 20-25 years and majority (463, 81.4%) belonged to below poverty line families; 410 (74.3%) registered their current pregnancy within the first trimester. The prevalence of high-risk pregnancy among study participants was 18.3% (95% confidence interval: 15.3%-21.7%). Majority (81.9%) had term delivery. Regarding obstetric and neonatal outcomes, majority had spontaneous vaginal delivery (73.9%); about 10.4% gave birth to low-birth weight baby, and only 1.7% had stillbirth. Parity, socioeconomic status, and unfavorable outcomes such as low-birth weight, preterm, and postterm delivery were associated with high-risk pregnancy. The current study found that almost one-fifth of the pregnant women in rural area have high-risk pregnancy. Unfavorable obstetric and neonatal outcomes were common among high-risk cases. Hence, early detection of high-risk pregnancy needs to be done at primary health-care level to improve the maternal, obstetric, and neonatal outcomes.


Predictors of neonatal mortality in Ghana: evidence from 2017 Ghana maternal health survey.
Neonatal mortality contributes about 47% of child mortality globally and over 50% of under-5 deaths in Ghana. There is limited population level analysis done in Ghana on predictors of neonatal mortality. The objective of the study was to examine the predictors of neonatal mortality in Ghana. This study utilizes secondary data from the 2017 Ghana Maternal Health Survey (GMHS). The GMHS survey focuses on population and household characteristics, health, nutrition, and lifestyle with particular emphasis on topics that affect the lives of newborns and women, including mortality levels, fertility preferences and family planning methods. A total of 10,624 respondents were included in the study after data cleaning. Descriptive statistical techniques were used to describe important background characteristics of the women and Pearson's Chi-squares (χ2) test used to assess association between the outcome (neonatal death) and independent variables. Multivariate logistic regression analysis was done to estimate odd ratios and potential confounders controlled. Confidence level was held at 95%, and a p < 0.05 was considered statistically significant. Data analysis was done using STATA 15. The prevalence of neonatal mortality was 18 per 1000 live births. ANC attendance, sex of baby, and skin-to-skin contact immediately after birth were predictors of neonatal mortality. Women with at least one ANC visit were less likely to experience neonatal mortality as compared to women with no ANC visit prior to delivery (AOR = 0.11; CI = 0.02-0.56, p = 0.01). Girls were less likely (AOR = 0.68; CI = 0.47-0.98; p = 0.03) to die during the neonatal period as compared to boys. Neonates who were not put skin-to-skin contact immediately after birth were 2.6 times more likely to die within the neonatal period than those who were put skin-to-skin contact immediately after birth (AOR = 2.59; CI = 1.75-3.83, p = 0.00). Neonatal mortality remains a public health concern in Ghana, with an estimated rate of 18 deaths per 1,000 live births. Maternal and neonatal factors such as the sex of the newborn, the number of antenatal care visits, and skin-to-skin contact between the newborn and mother immediately after birth are the predictors of neonatal mortality in Ghana.


Spermatogenesis and chromatin condensation in male germ cells of sea cucumber Holothuria leucospilota (Clark, 1920).
Male germ cells in the testis of Holothuria leucospilota can be divided into 12 stages based on ultrastructure and patterns of chromatin condensation. The spermatogonium (Sg) is a spherical-shaped cell with a diameter of about 6.5-7microm. Its nucleus mostly contains euchromatin and small blocks of heterochromatin scattered throughout the nucleus. The nucleolus is prominent. Primary spermatocytes are divided into six stages, i.e., leptotene (LSc), zygotene (ZSc), pachytene (PSc), diplotene (DSc), diakinesis (DiSc) and metaphase (MSc). The early cells are round while in DiSc and in MSc cells are oval in shape. From LSc to MSc, the sizes of cells range from 3.5 to 4microm. LSc contains large blocks of heterochromatin as a result of increasingly condensed 17nm fibers. In ZSc, the nucleus contains prominent synaptonemal complexes but a nucleolus is absent. In PSc, heterochromatin blocks are tightly packed together by 26nm fibers and appeared as large patches in DSc. Heterochromatin patches were enlarged to form chromosomes in DiSc and MSc and then the chromosome are moved to be aligned along equatorial region. The secondary spermatocyte (SSc) is an oval cell about 4.5-5.5microm. Their nuclei contain large clumps of heterochromatin along the nuclear envelope and in the center nuclear region. Spermatids are divided into two stages, i.e., early spermatid (ESt) and late spermatid (LSt). The nuclei decrease in size by a half and become spherical; thus the chromatin fibers condensed into 20nm and are closely packed together leaving only small spaces in LSt. The spermatozoa (Sz), with chromatin tightly packed in the spherical nucleus with a diameter of 2microm and a small acrosome situated at the anterior of the nucleus. The tail consists of a pair of centrioles lying perpendicular to each other and surrounded by a mitochondrial ring, and an axonemal complex, surrounded by a plasma membrane.


ChatGPT: The transformative influence of generative AI on science and healthcare.
In an age where technology is evolving at a sometimes incomprehensibly rapid pace, the liver community must adjust and learn to embrace breakthroughs with an open mind in order to benefit from potentially transformative influences on our science and practice. The Journal of Hepatology has responded to novel developments in artificial intelligence (AI) by recruiting experts in the field to serve on the Editorial Board. Publications introducing novel AI technology are no longer uncommon in our journal and are among the most highly debated and possibly practice-changing papers across a broad range of scientific disciplines, united by their focus on liver disease. As AI is rapidly evolving, this expert paper will focus on educating our readership on large language models and their possible impact on our research practice and clinical outlook, outlining both challenges and opportunities in the field. "To improve is to change; to be perfect is to change often." - Winston S. Churchill.


Heterogeneous nuclear ribonucleoprotein G, nitric oxide, and oral carcinogenesis.
Nitric oxide (NO) is a multifunctional regulator, critical to various biochemical processes, including inflammation, vasodilatation, intra- and intercellular signaling, apoptosis, and carcinogenesis. In particular, recent studies have indicated the association between elevated NO production and neoplastic cell transformation, suggesting procarcinogenic effects of NO. To investigate the mechanism by which NO facilitates oral carcinogenesis, we tested the effects of exogenous NO on the expression of hnRNP G, a novel protein demonstrating tumor suppressive effects against oral squamous cell carcinomas. Oral epithelial cells exposed to NO donor demonstrated significant reduction in the level of hnRNP G protein and mRNA expression. Also, exposure to NO donor led to decreased hnRNP G promoter activity in cells, indicating that NO negatively regulates hnRNP G expression at the level of transcription. Since hnRNP G expression is markedly decreased or completely abolished in precancerous and malignant oral lesions in situ, these results suggest the possibility that NO facilitates the progression of the disease by targeting hnRNP G expression. In this article, we review the role of hnRNP G in tumor suppression and maintenance of genetic integrity, with focus on its potential association with NO in the context of oral carcinogenesis.


Effectiveness of sirolimus-eluting stent for treatment of left main coronary artery disease.
The present study reports on the clinical outcome of 31 consecutive patients with left main coronary artery disease treated with a sirolimus-eluting stent. The implantation of this stent was associated with abolition of post-discharge fatal events and percutaneous reintervention.


Structure-activity relationship studies of Longicalcynin A analogues, as anticancer cyclopeptides.
Cancer has emerged as the main cause of the highest rate of mortality in the world. Drugs used in cancer, although, show some beneficial effects on cancerous organs, demonstrate side effects on other normal tissues. On the other hand, anticancer peptides, being effective on target tissues, should be safe and less harmful on healthy organs, since peptides have several advantages, i.e., high activity, specificity, affinity, being less immunogenic and not accumulate in the body. In the present work, analogues of Longicalcynin A, a naturally occurring anticancer cyclopeptide, were synthesized and evaluated their cytotoxicity in order to gain information from structure-activity relationships of the such cyclopeptides which may lead to find novel and safer anticancer peptide compound(s) to be used in clinic. Peptides were prepared by the solid-phase peptide synthesis method using trityl-resin. Peptide cyclization was performed in liquid phase. To study anticancer activity of the peptide analogues of Longicalycinin A, several methods including MTT, flow cytometry analysis and Lysosomal membrane integrity assay were employed using two cell lines HepG2 and HT-29. Fibroblast cells were used to control the safety of the synthesized cyclopeptides on normal cells. Two cyclopeptides 11 and 17 with the sequences of cyclo-(Thr-Val-Pro-Phe-Ala) and cyclo-(Phe-Ser-Pro-Phe-Ala), respectively were cytotoxic against the colon as well as hepatic cancer cells with safety profile against fibroblast cells, probably with the mechanism of apoptosis as lysosomal membrane integrity damaged. These cyclopeptides showed to be more favorable compounds better than Longicalycinin A and good candidates to develop cyclopeptides as anticancer agents.


Steroid hormones and gonadotropins in a case of ovarian endometriosis associated with virilization.
The clinical course, the hormone secretion, the testosterone receptors and the enzymatic activities related to androgen metabolism in a 56-year-old postmenopausal woman with a history of virilization and ovarian endometrioma are reported. Unexpectedly, at the time of examination, no evidence of biochemical hyperandrogenism was obtained. The uncommon association of virilization and ovarian endometrioma simulating a functioning tumor of the ovary is discussed.


Isolation and partial characterization of 2-microns yeast plasmid as a transcriptionally active minichromosome.
Yeast cell extracts from 2-microns-containing strains (cir+) showed higher transcriptional activity than their corresponding isogenic sets (cir0). These extracts were used to purify transcriptionally active 2-microns minichromosomes in a sucrose gradient. Minichromosomes were transcribed in vitro and, employing hybridization techniques, the RNA synthesized was shown to present 2-microns-specific sequences. This model system should permit the direct study of transcriptionally active eucaryotic chromatin.


Enhanced transgene expression in primitive hematopoietic progenitor cells and embryonic stem cells efficiently transduced by optimized retroviral hybrid vectors.
Oncoretroviral vectors have been successfully used in gene therapy trials, yet low transduction rates and loss of transgene expression are still major obstacles for their application. To overcome these problems we modified the widely used Moloney murine leukemia virus-derived retroviral vector pMX by replacing the 3'LTR with the spleen focus-forming virus LTR and inserting the woodchuck hepatitis B virus post-translational regulatory element. To compare requirements crucial for efficient transgene expression, we generated the hybrid retroviral vectors pMOWS and pOWS that harbor the complete murine embryonic stem cell virus (MESV)-leader sequence or a shortened MESV-leader not comprising primer binding site (PBS) and splice donor (SD). Applying these retroviral vectors significantly augmented transgene expression in hematopoietic cell lines and progenitor cells. For transduction of murine embryonic stem (ES) cells the retroviral vector pMOWS that harbors the MESV-PBS and -SD was superior resulting in 65% green fluorescent protein (GFP) expressing ES cells. Surprisingly, in murine and human primitive hematopoietic progenitor cells (HPC), the highest efficiency of up to 66% GFP expressing cells was achieved with pOWS, a retroviral vector that retains the negative regulatory element coinciding with the MoMuLV-PBS. In summary our hybrid retroviral vectors facilitate significantly improved transgene expression in multipotent cells and thus possess great potential for reconstituting genes in primary cells of disease models, as well as for gene therapy.


Side of lesion influences interhemispheric inhibition in subjects with post-stroke hemiparesis.
To examine changes in interhemispheric inhibition (IHI) during homologous muscle activation in healthy subjects and in people with hemiparesis. IHI in the abductor pollicus brevis (APB) muscle was examined using paired transcranial magnetic stimulation. Stimuli were delivered while the target APB was at rest or activated, and while the non-target contralateral APB was at rest or activated. In control subjects, IHI in the resting target APB was enhanced during activation of the contralateral APB, and was greater from the dominant hemisphere to the non-dominant. In stroke subjects, IHI in the non-affected APB was not modulated during voluntary activation of the affected APB, but was influenced by the prior dominance of affected hemisphere. Bilateral muscle activation did not elicit any changes in IHI in either group. IHI is asymmetrical between hemispheres but only when the target muscle is at rest. Subjects with stroke have an impaired ability to modulate IHI during unilateral muscle activation. In people with stroke, the extent and modulation of interhemispheric transfer is influenced by the prior dominance of the affected hemisphere. This may impact on the efficacy of treatment interventions incorporating bilateral activation.


Factors affecting sperm motility. II. Human sperm velocity and percentage of motility as influenced by semen dilution.
Spermatozoal velocity and percentage of motility were analyzed objectively with the multiple exposure photography method before and after specimens from fertile and infertile men were diluted in their own seminal plasma or normal saline. No significant change in percentage of motility was found in samples diluted up to 1:6 in both kinds of diluents. However, a significant relative increase (up to 25% of the original velocity) was found when a specimen was diluted with its own seminal plasma, and an even greater increase (up to 37% of the original velocity) was found when it was diluted with saline. Compared with undiluted specimens, there was no delayed effect on spermatozoal motility when semen was diluted with saline after up to 4 hours' incubation time. Contrary to the findings in animal and human semen described by others, there was no deleterious effect on sperm motility with this kind and rate of dilution and duration of time. The assumption that the increase in sperm velocity caused by dilution is not excitatory but is due only to a decrease of seminal fluid viscosity and a reduced number of spermatozoa which interfere with sperm free movement is discussed. We recommend evaluation of spermatozoal motility in diluted specimens in addition to evaluation of the original specimen in any routine semen analysis in order to determine true spermatozoal motility potential under optimal conditions.


Chile's agricultural research institute plant tissue analysis dataset.
This dataset holds 9,175 entries that report the nitrogen, phosphorus, potassium, calcium, magnesium, zinc, manganese, copper and boron contents of various plant species, with a focus on crops. The dataset accounts data of 94 plant species, and present nutrient concentration of 14 different plant tissues. The data are derived from the Soil and Plant Nutrition Lab of the Chilean Agricultural Research Institute, which provided services to farmers in the Chilean Central Valley between 2006 and 2020. The analytical methods used to generate these data were consistent across all years, ensuring the reliability of the information. Specifically, nitrogen content was determined using the Kjeldahl method, while all other analytes were quantified via colorimetry (phosphorus and boron) or atomic absorption spectrometry following high-temperature oxidation and dilution of the ashes with hydrochloric acid. The dataset has numerous potential applications, including the estimation of crop nutrient extraction rates, the identification of nutrient deficiencies or excesses, and the provision of reference or prior information for researchers studying plant physiology. The dataset includes 21 Chilean endemic species, which might be of particular interest to researchers studying the biodiversity and ecology of Chile's Central Valley.


1-(2-Methyl-phen-yl)-4,4'-bipyridin-1-ium tetra-fluorido-borate.
Crystals of the title compound, C17H15N2 +·BF4 -, were unexpectedly grown from crystallization attempts of [Pt(4,4'-bpy)4](BF4)2 [Smith et al. (2019 ▸). Comments Inorg. Chem. 39, 188-215] using toluene and aceto-nitrile. The tetra-fluoro-borate anion and the central pyridinium ring of the cation are disordered, with atomic site occupancies close to ½. The tolyl group of the cation has a 75.31 (11)° twist relative to the unsubstituted pyridyl group. This rotation allows for a centrosymmetric dimer of cations with weak hydrogen bonding between the pyridyl nitro-gen atom and a methyl H atom on the neighbouring cation.


Analysis of the efficacy of a single subumbilical stoma for bilateral cutaneous ureterostomy after radical cystectomy.
Radical cystectomy and urinary diversion are the standard surgical treatments for patients with muscle-invasive or high-risk, or recurrent non-muscle-invasive bladder cancer. Although this approach significantly prolongs patient survival, it can lead to postoperative complications. This study aims to compare the efficacy and complications of bilateral cutaneous ureterostomy with a single subumbilical stoma to those of cutaneous ureterostomy with two stomas and an ileal conduit as a means of urinary diversion after radical cystectomy. The findings of this study will provide valuable information for healthcare providers in selecting the appropriate urinary diversion method for their patients. The clinical data for 108 patients who received bilateral cutaneous ureterostomy with a single subumbilical stoma (ureterostomy with a single stoma group), cutaneous ureterostomy with two stomas (ureterostomy with two stomas group), or an ileal conduit (ileal conduit group) after radical cystectomy were retrospectively analysed. The operative time, pathological stage, survival status, perioperative complication rate, rate of successful first extubation, rehospitalization rate at 6 months after surgery,ostomy-related medical costs,and postoperative quality of life were compared between the three groups of patients. A significant difference in the operative time was found between the three groups (P = 0.001). No significant differences in pathological stage, survival status, perioperative complication rate, rehospitalization rate at 6 months after surgery, or bladder cancer index (BCI) score were identified among the three groups. The difference in the successful first extubation rate between the three groups of patients was significant (P = 0.001). Significant differences in ostomy-related medical costs were observed among the three groups of patients (P = 0.006). A single subumbilical stoma for bilateral cutaneous ureterostomy after radical cystectomy may result in shorter surgery time, increased success rates for initial catheter removal, and lower medical expenses. However, to confirm these findings, further prospective randomized clinical trials are necessary.


Relationship between kinetic and thermodynamic characteristics of oxygen dissociative adsorption on close-packed metal surfaces.
The activation energies and rate constants characterizing dissociative oxygen adsorption on transition and noble metal surfaces are calculated using a previously developed analytical formalism. Three approaches are considered: classical and quantum nonadiabatic approaches as well as a classical adiabatic approach. The results show a nonlinear relationship between the activation energies and the corresponding reaction energies. The effects due to the quantum description of the O-O bond and due to the Condon approximation are discussed. Calculated activation energies are compared with published experimental data.


Cavernous sinus thrombosis caused by zygomycosis after unrelated bone marrow transplantation.
Invasive zygomycosis is a devastating fungal infection occurring as an opportunistic infection after bone marrow transplantation (BMT). Sinusitis can lead to fungal infection in immunosuppressed patients, and cavernous sinus thrombosis, an uncommon condition in immunocompetent patients, typically follows an infection involving the medial third of the face, nose, or paranasal sinuses. Patients undergoing unrelated-donor BMT (UD-BMT) are prone to develop life-threatening infections because of poor recovery of cellular immunity. Despite adequate clinical evaluation and treatment, the prognosis of patients with invasive fungal infections is dismal, especially when intracerebral structures are affected. We describe a case of a patient who underwent an UD-BMT and developed cavernous sinus thrombosis after sinusitis due to zygomycosis. Moreover, he also had disseminated fungal (Zygomycetes and Aspergillus) and viral (cytomegalovirus and adenovirus) infections.


Adult normative data of the Wisconsin Card Sorting Test in Taiwan.
The Wisconsin Card Sorting Test (WCST) is a widely used neuropsychological test for assessing executive functions. However, the lack of culture-specific norms has often limited clinical interpretation of performance on the WCST. The aims of this study were to establish adult norms for the WCST in Taiwan, and to understand the development of performance on the WCST among age groups. A total of 475 participants (233 males, 242 females) aged from 20 to 89 years were divided into 10 age groups. All of the participants completed the WCST, and 6 indices of WCST were calculated, including percent errors (PE), percent perseverative responses (PPR), percent perseverative errors (PPE), percent non-perseverative errors (PNPE), percent conceptual-level responses (PCLR), and categories completed (CC). There were several findings. First, our data showed that there was no evidence of a significant difference between manual card and computerized card presentation versions of WCST on the PE, PPR, PPE, PNPE, PCLR, and CC indices. Second, no education and gender effects on WCST performance were found. Third, although WCST indices were significantly different among age groups, no remarkable differences among the groups after 30 years of age were found. Finally, compared with Heaton's USA norms, WCST performance in Taiwanese was poorer than the USA sample in most age groups. The WCST is not sensitive enough to detect aging-related cognitive changes in the Taiwanese population, and there are different performances on WCST between Taiwanese and USA people. The adult norms for WCST in Taiwan will provide an important reference for future research and clinical practice.


Radiosensitive antioxidant membrane-bound factors in rat liver microsomes: II. The role of cytosol.
In vitro lipid peroxidation initiated by NADPH/ADP/Fe3+ reveals an alteration of rat liver microsomal membrane at day D+4 after whole-body gamma irradiation (8Gy). This alteration is reversed by Trolox-C 100 microM plus GSH 2mM in association with the soluble supernatant from irradiated or control rats. The antioxidant capacity of the soluble supernatant is not inactivated by gamma irradiation. We conclude that the control of in vivo lipid peroxidation is membranous and cytosolic, and that the preservation of this activity is GSH and Vitamin E dependent.


The role of penicillin G potassium in managing Clostridium perfringens in broiler chickens.
The efficacy of penicillin G potassium (Pot-Pen) administered via drinking water to manage necrotic enteritis (NE) was investigated in a Clostridium perfringens (CP) challenge study using 1600 broiler chickens assigned to one of four treatment groups: nonchallenged, nonmedicated; challenged, nonmedicated; challenged, Pot-Pen 0.2 g/L; challenged, Pot-Pen 0.4 g/L. Overall mortality due to NE was significantly reduced among Pot-Pen-treated pens; mortality due to other causes did not differ among the treatment groups. Among all birds, growth performance parameters were significantly improved among Pot-Pen-treated pens. When considering birds randomly sacrificed 4 days post-Pot-Pen initiation, mean NE lesion scores were greatest among the challenged, nonmedicated pens; only one of 80 randomly sacrificed birds treated with Pot-Pen had NE lesions. Among the nonmedicated control pens, body weight (BW) was significantly greater among birds that did not have NE-associated lesions. When sacrificed birds were stratified by NE lesion score, there were no significant differences in BW among the treatment groups. Results of this study suggest that CP-associated subclinical disease can significantly reduce broiler performance. Furthermore, the positive effects of treatment with Pot-Pen appeared to be associated with the prevention and/or treatment of NE-specific lesions.


The effect of beta-blocker therapy on clinical outcome in patients with Marfan's syndrome: a meta-analysis.
To assess the effect of beta-blockade therapy on clinical outcome in patients with Marfan's syndrome. Despite the lack of definitive evidence to support its efficacy, beta-blocker therapy is widely used prophylactically in patients with Marfan's syndrome. A meta-analysis was instituted, which included studies identified by a systematic review of MEDLINE of peer-reviewed publications and by abstracts from annual scientific meeting. Outcome measures of mortality and major morbidity were compared between patients treated and untreated with beta-blockade therapy. Data was combined according to both a fixed-effects and random-effects model. The endpoints included aortic dissection or rupture, cardiovascular surgery, or death. Six studies were included, 5 were non-randomized follow-up studies and 1 was a prospective randomized trial (802 patients). Ninety-six of 433 patients treated with beta-blocker therapy and 74 of 369 untreated patients reached designated endpoints. Utilizing a fixed-effects model, patients treated with beta-blocker therapy were more likely to reach an endpoint (odds ratio=1.50 with 95% CI 1.05-2.16). However, by a random-effects model, the treatment effect failed to reach significance (1.54 with 95% CI 0.99-2.40). On the basis of this meta-analysis, there is no evidence that beta-blockade therapy has clinical benefit in patients with Marfan's syndrome.


Moderate ischemic mitral regurgitation: Is there a case for early intervention?
Ischemic mitral regurgitation (IMR) results from left ventricular remodelling after myocardial infarction and severely affects cardiovascular mortality and morbidity. Ischemic mitral valve regurgitation also represents a negative prognostic factor for long-term survival in patients undergoing surgical myocardial revascularization. While severe mitral regurgitation should always be corrected during a coronary artery bypass operation, the decision making is more difficult in patients with a moderate degree of regurgitation. In this review, we wish to highlight the negative impact of IMR on long-term survival and discuss the available evidence for surgical correction of IMR at the time of coronary revascularization.


Lipomas of the peripheral lung--a case report and review of the literature.
Bronchial lipomas are uncommon benign neoplasms of the lung and the number of these tumours is only 109 cases in the international literature (108 cases reported in English and one in German) up to date. Moreover, most of the tumours occur in the proximal portions of lobar or segmental bronchi: the references in the literature to peripheral lipoma of the lung make up only 6 cases. Peripheral lipomas of the lung are thought to originate from fatty tissue in the wall of peripheral bronchi. We present a further case of peripheral lipoma and analyze the reported 7 cases.


NF1/X represses PDGF A-chain transcription by interacting with Sp1 and antagonizing Sp1 occupancy of the promoter.
The regulatory mechanisms mediating basal and inducible platelet-derived growth factor (PDGF)-A expression have been the focus of intense recent investigation, but repression of PDGF-A expression is largely unexplored. Here we isolated a nuclear factor that interacts with the proximal region of the PDGF-A promoter using bulk binding assays and chromatography techniques. Peptide mass fingerprint and supershift analysis revealed this DNA-binding protein to be NF1/X. NF1/X repressed PDGF-A promoter-dependent transcription and endogenous mRNA expression, which was reversible by oligonucleotide decoys bearing an NF1/X-binding site. Mutation in the DNA-binding domain of NF1/X abolished its repression of PDGF-A promoter. NF1/X antagonized the activity of a known activator of the PDGF-A chain, Sp1, by inhibiting its occupancy of the proximal PDGF-A promoter. NF1/X physically and specifically interacts with Sp1 via its subtype-specific domain and blocks Sp1 induction of the promoter. NF1/X residues 311-416 mediated NF1/X suppression of basal PDGF-A transcription, whereas residues 243-416 were required for NF1/X repression of Sp1-inducible promoter activity. These findings demonstrate that repression of PDGF-A gene transcription is governed by interplay between NF1/X and Sp1.


Phosphorylation of eukaryotic initiation factor 2 during physiological stresses which affect protein synthesis.
Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2) is a major mechanism regulating protein synthesis in rabbit reticulocytes. To determine whether phosphorylation of eIF-2 alpha is a likely regulatory mechanism in the Ehrlich cell, we have measured the percent of cellular eIF-2 alpha which is phosphorylated in cells exposed to heat shock, 2-deoxyglucose, or amino acid deprivation, conditions which rapidly decrease the concentration of 40 S initiation complexes and inhibit protein synthesis. eIF-2 alpha and eIf-2 alpha (P) were separated by isoelectric focusing and were detected by immunoblotting with a monoclonal antibody we developed for this purpose. Under the above three inhibitory conditions, phosphorylation of eIF-2 alpha increased rapidly, and this increase correlated in time with the rapid inhibition of protein synthesis. In heat-shocked cells which were returned to 37 degrees C, both phosphorylation and protein synthesis remained unchanged for 10 min and then returned toward control values slowly and in parallel. The close temporal correspondence between changes in protein synthesis and phosphorylation supports an important regulatory role for phosphorylation in protein synthesis. An increase of 25-35 percentage points, to 50-60% phosphorylation from control levels of 20-30% phosphorylation, correlated with an 80-100% inhibition of protein synthesis. This steep curve of inhibition is consistent with a mechanism in which eIF-2 alpha (P) saturates and inhibits the guanine-nucleotide exchange factor.


Relapsing Guillain Barré Syndrome and nephrotic syndrome secondary to focal segmental glomerulosclerosis.
A 49-year-old man developed simultaneously a Guillain Barré Syndrome (GBS) and a nephrotic syndrome (NS). The patient relapsed twice, despite treatment with intravenous immunoglobulins (IVIg) after a full or partial recovery, and became resistant to IVIg. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS). He responded to plasmapheresis and corticosteroids with simultaneous recovery of his GBS and NS, suggesting a common pathogenesis of the two conditions.


Management of prostate cancer patients following radiation therapy after radical surgery referred from urology to radiation oncology departments in Spain.
To define usual clinical management of prostate cancer (PCa) patients following postoperative radiation therapy (RT) (adjuvant or salvage) and its evolution over time in radiation oncology (RO) departments in Spain. An epidemiological, cross-sectional, multicentre study was conducted. 567 PCa patients that had undergone radical prostatectomy (RP) and received postoperative RT between February and December of both 2006 and 2011 participated in the study. In patients from 2006, health-related quality of life (HRQoL) was assessed using the EPIC questionnaire. Investigators completed a specific survey on two clinical cases of adjuvant and salvage RT. 70.6 % of patients received salvage RT versus 29.4 % who received adjuvant RT; no significant differences were found in terms of frequency for each procedure between both the years. Regarding the survey, a positive surgical margin was the main criteria used in adjuvant RT decision making. In terms of salvage RT scenario, 85.7 % of the investigators stated that adjuvant RT should have been offered instead, 81.4 % of the investigators agreed on a PSA score >0.2 ng/mL as the main criteria for identifying biochemical recurrence after RP, and 67.4 % of investigators did not consider any PSA score for ruling out salvage RT treatment. Most patients are referred to RO departments to receive salvage RT. Despite the publication of three IA evidence level randomized clinical trials, the patterns for using adjuvant and salvage RT did not change from 2006 to 2011, although patients' profile did. A consensus regarding postoperative RT indications should be reached in order to correct this controversial situation.


Application of hull, bur and leaf chestnut extracts on the shelf-life of beef patties stored under MAP: Evaluation of their impact on physicochemical properties, lipid oxidation, antioxidant, and antimicrobial potential.
The impact of chestnut extracts (Castanea sativa) from leaf, bur and hull at different concentrations on the shelf-life of beef patties during 18 days of refrigerated storage at (2 ± 1 °C) was studied and compared to control and synthetic antioxidant (BHT) samples. Total phenolics and in vitro antioxidant capacity of extracts were evaluated by using DPPH, FRAP, reducing power and oil accelerated oxidation test (peroxide value, conjugated dienes, p-anisidine and fatty acid profile). The microbial spoilage, colour parameters, lipid oxidation and sensorial properties were used to assess antioxidant activity in beef patties. The highest total phenolic content was found in bur extracts (43.68 ± 2.05 g/100 g lyophilized extract). In addition, bur extracts showed the strongest antioxidant activity in all in vitro assays. None of the evaluated extracts showed antimicrobial activity. The addition of hull extracts at 500 and 1000 ppm resulted in the highest (P < .05) metmyoglobin reduction in the surface of beef patties compared to control and the others batches after 15 days of storage. However, leaf extract at 1000 ppm was the most effective in inhibiting lipid oxidation. Overall, for all extracts evaluated, the increase in the concentration of chestnuts extracts improved the desired effect, hence our findings suggest the possibility of using chestnuts extracts (preferable a mixture from the different parts of the chestnut byproducts) rather than synthetic antioxidants. Finally, sensorial analysis did not show any detrimental effect from a sensory point of view, after the addition of chestnuts extracts, thus indicating a potential to develop chestnut extracts as food ingredients.


Prolonged elevation in hippocampal Aβ and cognitive deficits following repeated endotoxin exposure in the mouse.
Alzheimer's disease (AD) is characterized by neuronal cell death and atrophy in regions of the adult brain, including the hippocampus and cortex, due to formation of amyloid beta (Aβ) plaques and neurofibrillary tangles. The presence of these pathologies can limit normal signaling properties and ultimately lead to learning and memory deficits. Chronic inflammation has been implicated in the onset and progression of these AD-related pathologies. Our study was designed to assess the effects of peripheral inflammation on pathologies associated with AD by using the bacterial endotoxin lipopolysaccharide (LPS). C57BL/6J mice were given intraperitoneal injections of LPS or saline for 1, 3, or 7 consecutive days. Hippocampal tissue from animals receiving LPS contained significantly higher levels of Aβ1-42, a peptide component of AD plaques, than did those from saline control animals. Central and peripheral pro-inflammatory cytokine levels were increased following a single injection of LPS, but retuned to baseline levels before cognitive testing began. We show that one injection of LPS leads to sickness behavior, but 7 consecutive days does not, indicating tolerance to the endotoxin. Cognitive testing was then conducted to determine if whether deficits from increased Aβ1-42 was evident. Results from both Morris water maze and contextual fear conditioning revealed cognitive deficits in LPS-treated mice. In summary, multiple injections of LPS resulted in increased Aβ1-42 in the hippocampus and cognitive deficits in mice.


Study to Evaluate the Pattern of Nodal Distribution in Papillary Thyroid Cancer.
Among the thyroid cancers, papillary thyroid cancer (PTC) is the most common with lymphatic metastasis. It has the propensity to spread to the level II-VI lymph nodes in a predictable manner. We evaluated the pattern of nodal distribution at different levels of neck in papillary thyroid cancer in this Observational Prospective study. Total 41 patients of PTC (Papillary thyroid cancer) were included in the study. 36 out of them were diagnosed as PTC by FNAC and underwent total thyroidectomy and central neck dissection, while 5 patients were histologically confirmed cases of PTC on previous hemithyroidectomy and underwent completion thyroidectomy and central neck dissection .Patients with T3/T4 stage or N1 underwent lateral neck dissection also. Clinicopathological factors such as age, sex, tumor stage, nodal metastasis and extracapsular invasion, were evaluated. Lymph node metastasis was noted in 21 patients (51.2%) and all these patients had central (level VI) lymph node involvement. Among 21 patients, pathological ipsilateral lateral neck metastasis was noted in 6 patients (28.57%) at level II, 10 patients (47.62%) at level III and 8 patients (38.10%) at level IV. Only 5 patients (23.81%) had metastasis at level V. Extracapsular invasion was observed in 10 (24.4%) patients. We concluded that patients with PTC show higher rates of metastasis at central neck (level VI) and are not easily detected on clinical examination or by USG due to low sensitivity but are sensitive and specific for lateral neck nodes in late stages . Thus, ipsilateral selective neck dissection should be considered with total thyroidectomy and central neck dissection in presence of clinically or radiologically evident lateral lymph nodes (preoperatively) and in T3, T4 stage (late stages) tumors.


p-Chlorphenylalanine effect on phenylalanine hydroxylase in hepatoma cells in culture.
We have investigated the p-chlorophenylalanine-dependent loss of phenylalanine hydroxylase activity in cultured hepatoma cells. The similarity of the effect of p-chlorophenylalanine on phenylalanine hydroxylase in the hepatoma cells and that reported from studies in vivo indicates that the loss of phenylalanine hydroxylase activity is due to a direct interaction of the amino acid analogue with the liver. We can find no evidence that the loss of phenylalanine hydroxylase activity is due to: a direct inactivation of the hydroxylase by p-chlorophenylalanine or an inhibitor produced by p-chlorophenylalanine treatment; an effect similar to that of p-fluorophenylalanine; or leakage of enzyme from the cells during p-chlorophenylalanine treatment. The data presented indicate: (a) the p-chlorophenylalanine effect is rather specific for phenylalanine hydroxylase; (b) following p-chlorophenylalanine removal, new protein synthesis is necessary for restoration of the hydroxylase activity; (c) the rate of loss of phenylalanine hydroxylase activity after the addition of p-chlorophenylalanine is much faster than the rate of restoration of the hydroxylase activity after removal of p-chlorophenylalanine; (d) even in the presence of p-chlorophenylalanine, hydrocortisone greatly stimulates the hydroxylase activity; (e) the cell density-dependent increase of phenylalanine hydroxylase activity is blocked by p-chlorophenylalanine. A discussion of the possible mechanisms of p-chlorophenylalanine-dependent loss of phenylalanine hydroxylase is presented. To measure very low leanine-dependent loss of phenylalanine hydroxylase is presented. To measure very low levels of phenylalanine hydroxylase activity, a new procedure, based on isotope dilution, was developed for isolating the tyrosine formed during the enzymatic reaction.


Universal access -- but when? Treating the right patient at the right time: access to electrophysiology services in Canada.
The Canadian Cardiovascular Society Access to Care Working Group has published a series of commentaries on access to cardiovascular care in Canada. The present article reviews the evidence for timely access to electrophysiology services. Using the best available evidence along with expert consensus by the Canadian Heart Rhythm Society, the panel proposed a series of benchmarks for access to the full scope of electrophysiology services, from initial consultation through to operative procedures. The proposed benchmarks are presented herein.


Glabrol impurity exacerbates glabridin toxicity in zebrafish embryos by increasing myofibril disorganization.
Glabridin, extracted from Glycyrrhiza glabra L., is widely used for the treatment of hyperpigmentation because of its anti-inflammatory and antioxidant activities and its ability to inhibit melanin synthesis. This led to the strict regulation of its quality and safety. However, traditional quality control methods used for plant extracts cannot reflect the product quality owing to multiple unknown impurities, which necessitates the further analysis of impurities. The study identified the toxic impurities of glabridin and their toxicological mechanism. In total, 10 glabridin samples from different sources were quantified using high-performance liquid chromatography. Sample toxicities were evaluated using zebrafish and cell models. To identify impurities, samples with different toxicity were analyzed by ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry. The toxicity of related impurities was verified in the zebrafish model. Phalloidin stain was used to evaluate subtle changes in myofibril alignment. Although glabridin content in the samples was similar, there were significant differences in toxicity. The results were verified using four different mammalian cell lines. Higher contents of glabrone and glabrol were identified in the sample with the highest toxicity. In the zebrafish model, the addition of glabrol reduced the LC50 of glabridin to 9.224, 6.229, and 5.370 μM at 48, 72, and 96 h post-fertilization, respectively, whereas glabrone did not have any toxic effect. Phalloidin staining indicated that a glabrol impurity exacerbates the myotoxicity of glabridin in zebrafish embryos. Glabrol, but not glabrone, was identified as a key impurity that increased glabridin toxicity. This finding indicates that controlling glabrol content is necessary during glabridin product production.


Immunoneutralization of endogenous glucagon-like peptide-2 reduces adaptive intestinal growth in diabetic rats.
Supraphysiological doses of glucagon-like peptide-2 (GLP-2) have been shown to induce intestinal growth by increasing villus height and crypt depth and by decreasing apoptosis, but a physiological effect of GLP-2 has not yet been demonstrated. Earlier, we found elevated levels of endogenous GLP-2 in untreated streptozotocin diabetic rats associated with marked intestinal growth. In the present study, we investigated the role of endogenous GLP-2 for this adaptive response. We included four groups of six rats: (1) diabetic rats treated with saline, (2) diabetic rats treated with non-specific antibodies, (3) diabetic rats treated with polyclonal GLP-2 antibodies and (4) non-diabetic control rats treated with saline. All animals were treated with once daily intraperitoneal injections for 13 days and killed on day 14. Diabetic rats treated with saline or non-specific antibodies had a significantly (P<0.01) increased area of mucosa (13.00+/-0.64 and 13.37+/-0.60 mm(2), respectively) in the proximal part of the small intestine compared with non-diabetic controls (7.97+/-0.70 mm(2)). In contrast, diabetic rats treated with GLP-2 antibodies had a significantly (P<0.01) smaller increase in area of mucosa in the proximal part of the small intestine (10.84+/-0.44 mm(2)). Antibody treatment had no effect on body weight, blood glucose concentrations and food intake. Thus, blocking of endogenous GLP-2 in a model of adaptive intestinal growth reduces the growth response, providing strong evidence for a physiological growth factor function of GLP-2.


The enhanced antigen-specific production of cytokines induced by pertussis toxin is due to clonal expansion of T cells and not to altered effector functions of long-term memory cells.
Pertussis toxin (PT) has been shown to act as an adjuvant that enhances the production of both Th1 and Th2 cytokines to coinjected protein antigens. It has remained unresolved, however, how PT affects the clonal sizes, long-term effector functions, and Th1/Th2/Th0 differentiation of the T cell responses induced. We have studied the effects of PT on the development of the CD4(+) T cell response to a prototypic antigen, hen eggwhite lysozyme (HEL). HEL injection with incomplete Freund's adjuvant (IFA) resulted in an IFN-gamma(-)/IL-5(+) Th2 recall response. In comparison, co-administration of PT with HEL:IFA enhanced the frequencies of IL-5-producing T cells up to eightfold, and induced the differentiation of high frequencies of IFN-gamma-producing CD4(+) T cells. The results showed that the IFN-gamma and IL-5 produced, originated from clonally expanded Th1 and Th2, but not Th0 cells, and that the effector functions of long-term memory cells were unaffected. Adoptive transfer experiments suggested that PT mediated these effects via activation of APC, not by acting on the T cells directly. The effects of PT on the developing T cell response required the presence of the holotoxin (A- and B-subunit); the individual subunits did not show adjuvant effects. The data suggest that PT enhanced cytokine production by promoting differentiation and vigorous clonal expansion of Th1 and Th2 cells via activation of APC.


Fluorescence nanoparticles from instant coffee accumulated in lysosome and induced lysosome-dependent cell death via necroptosis-like pathway.
Fluorescence nanoparticles (FNs) are a type of nano-dots generated during baking process, and their safety on organism is unclear and little is known to their cytotoxicity. In this study, the FNs from instant coffee were purified and characterized. The FNs with an average size about 2.08 nm emitted bright blue fluorescence with lifetime about 2.74 ns. The element and functional groups were analyzed by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy, respectively. The results indicated that these FNs were internalized in lysosomes and induced apoptosis of normal rat kidney (NRK) and Caco-2 cells. While, the pan-caspase inhibitor, Z-VAD-FMK didn't decrease the rate of apoptosis and cell death of the FNs-treated NRK and Caco-2 cells. These internalized FNs enlarged lysosomes, decreased lysosomal enzyme degradation activity and increased lysosomal pH value. Partial co-localization of receptor-interacting serine-threonine kinase 3 (RIPK3) to lysosomes in FNs-treated cells was observed, and the amount of RIPK1 and RIPK3 increased after treatment with FNs. The results demonstrated that the FNs from instant coffee induced lysosomal membrane permeabilization and initiated necroptosis.


Cryo-EM structures of a LptDE transporter in complex with Pro-macrobodies offer insight into lipopolysaccharide translocation.
Lipopolysaccharides are major constituents of the extracellular leaflet in the bacterial outer membrane and form an effective physical barrier for environmental threats and for antibiotics in Gram-negative bacteria. The last step of LPS insertion via the Lpt pathway is mediated by the LptD/E protein complex. Detailed insights into the architecture of LptDE transporter complexes have been derived from X-ray crystallography. However, no structure of a laterally open LptD transporter, a transient state that occurs during LPS release, is available to date. Here, we report a cryo-EM structure of a partially opened LptDE transporter in complex with rigid chaperones derived from nanobodies, at 3.4 Å resolution. In addition, a subset of particles allows to model a structure of a laterally fully opened LptDE complex. Our work offers insights into the mechanism of LPS insertion, provides a structural framework for the development of antibiotics targeting LptD and describes a highly rigid chaperone scaffold to enable structural biology of challenging protein targets.


Small bowel capillary dilatation in portal hypertension.
A patient with small bowel capillary dilatation and cirrhosis is reported. This patient had persistent, unexplained gastrointestinal bleeding. Small bowel capillary dilatation appears to be unique to patients with portal hypertension. The possible role of small bowel capillary dilatation in causing gastrointestinal bleeding is discussed.


Long-term neuroplasticity of the face primary motor cortex and adjacent somatosensory cortex induced by tooth loss can be reversed following dental implant replacement in rats.
Tooth loss is common, and exploring the neuroplastic capacity of the face primary motor cortex (face-M1) and adjacent primary somatosensory cortex (face-S1) is crucial for understanding how subjects adapt to tooth loss and their prosthetic replacement. The aim was to test if functional reorganization of jaw and tongue motor representations in the rat face-M1 and face-S1 occurs following tooth extraction, and if subsequent dental implant placement can reverse this neuroplasticity. Rats (n = 22) had the right maxillary molar teeth extracted under local and general anesthesia. One month later, seven rats had dental implant placement into healed extraction sites. Naive rats (n = 8) received no surgical treatment. Intracortical microstimulation (ICMS) and recording of evoked jaw and tongue electromyographic responses were used to define jaw and tongue motor representations at 1 month (n = 8) or 2 months (n = 7) postextraction, 1 month postimplant placement, and at 1-2 months in naive rats. There were no significant differences across study groups in the onset latencies of the ICMS-evoked responses (P > 0.05), but in comparison with naive rats, tooth extraction caused a significant (P < 0.05) and sustained (1-2 months) decreased number of ICMS-defined jaw and tongue sites within face-M1 and -S1, and increased thresholds of ICMS-evoked responses in these sites. Furthermore, dental implant placement reversed the extraction-induced changes in face-S1, and in face-M1 the number of jaw sites even increased as compared to naive rats. These novel findings suggest that face-M1 and adjacent face-S1 may play a role in adaptive mechanisms related to tooth loss and their replacement with dental implants.


The effect of acute running and cycling exercise on T cell apoptosis in humans: A systematic review.
This review analyses the influence of acute running and cycling exercise on T lymphocyte apoptosis. We included randomized controlled trials (RCTs) and non-randomized case-control studies (NRCTs) measuring apoptosis by flow cytometry. Cochrane Library, Scopus, PubMed and Ovid were searched for running and cycling intervention studies. Risk of bias was assessed by Cochrane Collaboration's tools. We included five NRCTs and one RCT with a total of 93 participants. The RCT found a higher percentage of apoptotic T helper cells identified by upregulation of Annexin V, caspase-3 and caspase-9 under hypoxic conditions, and only one NRCT reported a higher percentage of highly differentiated apoptotic T cells immediately after exercise. Three hours after exercise, the same NRCT showed an increase in several T cell subsets such as T helper, cytotoxic T, low differentiated and regulatory T cells. The interventions were very heterogeneous by exercise protocol and external conditions. High risk of bias in NRCTs restricts accuracy of the included studies. Imprecision due to the small sample size limits further evidence. In the future, scientists should include apoptotic measures into their research design, plan RCTs, measure apoptosis at different time points post-exercise and increase sample size.


Serum sphingomyelins and ceramides are early predictors of memory impairment.
A blood-based biomarker of Alzheimer's disease (AD) progression could be instrumental in targeting asymptomatic individuals for treatment early in the disease process. Given the direct connection between sphingomyelins (SM), ceramides, and apoptosis, these lipids may be indicators of neurodegeneration and AD progression. Baseline serum SM and ceramides from 100 women enrolled in a longitudinal population-based study were examined as predictors of cognitive impairment. Participants were followed up to six visits over 9 years. Baseline lipids, in tertiles, were examined in relation to cross-sectional and incident impairment (<1.5 S.D. below standard norms) on HVLT-immediate and -delayed memory recall and Trails A and B. SM and ceramides varied in relation to the timing of HVLT-delayed impairment: low levels were associated with cross-sectional impairment; high levels predicted incident impairment in asymptomatic individuals. Lipids were not associated with loss-to-follow-up. Results suggest serum SM and ceramides vary according to the timing of the onset of memory impairment and may be good pre-clinical predictors, or biomarkers, of memory impairment: a deficit observed early in AD pathogenesis.