Acylated derivatives of streptokinase-plasminogen activator complex as thrombolytic agents in a dog model of aged venous thrombosis.
A procedure is described for the establishment of experimental clots, aged in vivo for 72 hr, in the jugular vein of beagle dogs. Two acylated derivatives of streptokinase-human (lys) plasminogen activator complex with greatly differing deacylation rates under physiological conditions were compared as thrombolytic agents in the model. These were BRL 26921 (deacylation half-life, 40 min) and BRL 33575 (deacylation half-life c. 17 hr). The pharmacokinetic clearance rate of BRL 33575 from the circulation was studied and gave a clearance half-life of about 7 hr. BRL 33575 was found to be the superior agent in lysing 72 hr aged clots, being effective at a single bolus dose of 420 micrograms/kg or in three equal divided doses of 140 micrograms/kg given at 12 hr intervals. The single dose regime gave moderate systemic plasminogen activation, and the effect was significantly reduced with the divided dose regime. Infusion of freshly formed streptokinase-human plasminogen activator complex at 420 micrograms/kg over 15 hr gave little thrombolysis despite marked systemic plasminogen activation.


The submucosa of the human colon.
Full-thickness specimens of colon were obtained at operation or autopsy from 20 patients. The submucosa was isolated from the mucosa and muscularis externa, with confirmation by light microscopy. Submucosal specimens were then fixed and prepared for scanning and transmission electron microscopy, with preservation of their orientation. The submucosa was found to consist of a series of layers of collagen fibres, each layer 0.5-2.0 microns thick. The fibres within each layer were co-directionally orientated. The autopsy specimens were comparable in appearance with the operative ones. The mean diameter of the collagen fibrils was 69 +/- 13 nm, and the mean fibril count per unit area was 159 +/- 58/microns2.


National survey on changes in visitation, communication and end-of-life care policies in intensive care units through the different COVID-19 pandemic's waves (COVIFAUCI study).
The pandemic derived from the SARS-CoV-2 infection led to changes in care for both relatives and intensive care patients during the different waves of incidence of the virus. The line of humanization followed by the majority of the hospitals was seriously affected by the restrictions applied. As an objective, we propose to know the modifications suffered during the different waves of the SARS-CoV-2 pandemic in Spain regarding the policy of visits to patients in the ICU, monitoring at the end of life, and the use of new technologies. of communication between family members, patients and professionals. Multicenter cross-sectional descriptive study through a survey of Spanish ICUs from February to April 2022. Statistical analysis methods were performed on the results as appropriate. The study was endorsed by the Spanish Society of Intensive Nursing and Coronary Units. 29% of the units contacted responded. The daily visiting minutes of relatives dropped drastically from 135 (87.5-255) to 45 (25-60) in the 21.2% of units that allowed their access, improving slightly with the passing of the waves. In the case of bereavement, the permissiveness was greater, increasing the use of new technologies for patient-family communication in the case of 96.5% of the units. The family of patients admitted to the ICU during the different waves of the COVID-19 pandemic have suffered restrictions on visits and a change from face-to-face to virtual communication techniques. Access times were reduced to minimum levels during the first wave, recovering with the advance of the pandemic but never reaching initial levels. Despite the implemented solutions and virtual communication, efforts should be directed towards improving the protocols for the humanization of healthcare that allow caring for families and patients whatever the healthcare context.


Characterization of an acidic pectin methylesterase from Paenibacillus xylanexedens and its application in fruit processing.
A pectinase-producing bacterial isolate, identified as Paenibacillus xylanexedens SZ 29, was screened by using the soil dilution plate with citrus pectin and congo red. A pectin methylesterase gene (Pxpme) was cloned and expressed in Escherichia coli. The gene coded for a protein with 334 amino acids and a calculated molecular mass of 36.76 kDa. PxPME showed the highest identity of 32.4% with the characterized carbohydrate esterase family 8 pectin methylesterase from Daucus carota. The recombined PxPME showed a specific activity with 39.38 U/mg against citrus pectin with >65% methylesterification. The optimal pH and temperature for PxPME activity were 5.0 and 45 °C. Its Km and Vmax value were determined to be 1.43 mg/mL and 71.5 μmol/mg·min, respectively. Moreover, PxPME could increase the firmness of pineapple cubes by 114% when combined with CaCl2. The acidic and mesophilic properties make PxPME a potential candidate for application in the fruit processing.


Effector mechanism in rejection of allografts expressing an isolated minor histocompatibility disparity. Importance of cytotoxic T lymphocytes in the rejection of H-43a allografts by H-43b mice.
To explore effector mechanisms in allograft rejection, we transplanted skin grafts (SG) across a single minor histocompatibility locus (H-43) using mouse strains carrying the H-43b allele as SG recipients and those carrying the H-43a allele as SG donors. Recipients' spleen cells (SC) were assayed at various intervals for 200 days for anti-H-43a cytotoxic T lymphocyte (CTL) responsiveness, as well as delayed-type hypersensitivity (DTH) responsiveness. When H-43a SG from C3H.SW mice were transplanted to H-43b CWB mice, two thirds of the recipients rejected the SG, and recipients' SC showed marked self-H-2Kb-restricted anti-H-43a CTL responsiveness until the end of the observation period. In contrast,H-43aSG transplanted to H-43b (B10.BRxCWB)F1 (BWF1) mice survived in almost all of the BWF1 recipients. The anti-H-43a CTL responsiveness of the recipients' SC was evident until day 40 but thereafter started to wane and eventually disappeared. Notably, BWF1 mice whose self-H-2Kb-restricted anti-H-43a CTL precursors had been primed by prior injection with H-43a SC rejected H-2Kb-bearing H-43a CSW SG but not H-2k, H-43a C3H/HeN SG. In contrast, an anti-H-43a DTH response was not induced in any of the CWB and BWF1 recipients, including CWB recipients who rejected the H-43a SG. Since it has been well documented that anti-H-43a CTL are restricted solely by self-H-2Kb, the results in this study indicate that self-H-2Kb-restricted anti-H-43a CTL are responsible for rejection of H-43a allografts by H-43b recipient mice.


Outcomes after surgical resection of pulmonary carcinoid tumors.
Pulmonary carcinoid tumors make up approximately one percent of all pulmonary tumors, and controversy exists regarding management and prognosis. We undertook a retrospective analysis of all patients who underwent surgical resection of pulmonary carcinoid tumors at our institution. From 1992 through 2014, 121 patients who underwent surgical resection of pulmonary carcinoid tumors were retrospectively reviewed. Patient demographics, pathologic data and long-term outcomes were recorded. There were 96 patients with typical carcinoid tumors and 25 patients with atypical carcinoid tumors. All patients received complete resection of their tumors, with 90 % (109/121) of patients undergoing anatomic resection. There were no peri-operative mortalities. Eighty-one percent (98/121) of patients were female. Mean age was 60.7 years. Five and ten year survival rates were 96 % and 88 % respectively for typical carcinoid tumors, as compared to 87 % and 69 % respectively for atypical carcinoid tumors. Tumor size was not associated with survival (p = 0.98). Nodal metastases were evident in 8 % (8/96) of typical carcinoid tumors and 28 % (7/25) percent of atypical carcinoid tumors. Among typical carcinoid cases, the presence of nodal metastases were not associated with overall survival (p = 0.55). Among atypical carcinoid cases, the presence of nodal metastases also was not associated with survival (p = 0.53). No patients received neoadjuvant or adjuvant chemoradiation treatment. Excellent long-term outcomes can be achieved following surgical resection of pulmonary carcinoid tumors. The presence of nodal metastases was not associated with overall survival. Tumor size was not associated with either recurrence rates or survival.


Child sexual abuse survivors: Differential complex multimodal treatment outcomes for pre-COVID and COVID era cohorts.
Child sexual abuse (CSA) is a form of early-life trauma that affects youth worldwide. In the midst of the current COVID-19 pandemic, it is imperative to investigate the potential impact of added stress on already vulnerable populations. The aim of this study was to evaluate the effectiveness of a multimodal treatment program on mental health outcomes for youth CSA survivors aged 8-17. Secondary to this, we explored the potential impact of the COVID-19 on treatment outcomes. Participants of this study were children and youth aged 8-17 who were engaged in a complex multimodal treatment program specifically designed for youth CSA survivors. Participants were asked to complete self-report surveys at baseline and at the end of two subsequent treatment rounds. Surveys consisted of measures pertaining to: (1) PTSD, (2) depression, (3) anxiety, (4) quality of life, and (5) self-esteem. Median scores improved for all groups at all timepoints for all five domains. For the pre-Covid participants, the largest improvements in the child program were reported in depression (36.6 %, p = 0.05); in the adolescent program anxiety showed the largest improvement (-35.7 %, p = 0.006). Improvements were generally maintained or increased at the end of round two. In almost every domain, the improvements of the pre-COVID group were greater than those of the COVID-I group. A complex multimodal treatment program specifically designed for youth CSA survivors has the capacity to improve a number of relevant determinants of mental health and well-being. The COVID-19 pandemic may have retraumatized participants, resulting in treatment resistance.


Effects of muscle fatigue on exercise-induced hamstring muscle damage: a three-armed randomized controlled trial.
Hamstring injuries in soccer reportedly increase towards the end of the matches' halves as well as with increased match frequency in combination with short rest periods, possibly due to acute or residual fatigue. Therefore, this study aimed to investigate the effects of acute and residual muscle fatigue on exercise-induced hamstring muscle damage. A three-armed randomized-controlled trial, including 24 resistance-trained males, was performed allocating subjects to either a training group with acute muscle fatigue + eccentric exercise (AF/ECC); residual muscle fatigue + eccentric exercise (RF/ECC) or a control group with only eccentric exercise (ECC). Muscle stiffness, thickness, contractility, peak torque, range of motion, pain perception, and creatine kinase were assessed as muscle damage markers pre, post, 1 h post, and on the consecutive three days. Significant group × time interactions were revealed for muscle thickness (p = 0.02) and muscle contractility parameters radial displacement (Dm) and contraction velocity (Vc) (both p = 0.01), with larger changes in the ECC group (partial η2 = 0.4). Peak torque dropped by an average of 22% in all groups; stiffness only changed in the RF/ECC group (p = 0.04). Muscle work during the damage protocol was lower for AF/ECC than for ECC and RF/ECC (p = 0.005). Hamstring muscle damage was comparable between the three groups. However, the AF/ECC group resulted in the same amount of muscle damage while accumulating significantly less muscle work during the protocol of the damage exercise. This study was preregistered in the international trial registration platform (WHO; registration number: DRKS00025243).


Pre-treatment of adult rats with high doses of erythropoietin induces caspase-9 but prevents light-induced retinal injury.
Erythropoietin (Epo) had been shown to have a neuroprotective effect independent from its erythropoietic properties. In this study, we tested whether Epo could protect the retina from damage induced by a long period of moderate light insult and how it protected. First, rats were injected intraperitoneally (i.p.) by human recombinant Epo at 5000 or 30,000U/kg to assess Epo concentration in plasma and retina. Second, rats were untreated or injected i.p. with Epo at 30,000U/kg, 1 or 4h before being placed in constant light (24h; 2200lux). Electroretinograms (ERG) were recorded before treatment, 1day and 15days (D15) after light exposure. After the last ERG, eyes were taken for histology. In parallel, we tested Epo protection against oxidative stressors on isolated retinas and its effect on caspase-9 activity. Epo injected at 30,000U/kg body weight, 4h before exposure to the damaging light, protected retinal function and structure against light damage and induced an increase in caspase-9 activity and expression. Epo had no direct or indirect protective effect against free radicals-induced death on isolated retinas. Epo protected the retina from a long period of moderate light exposure through a mechanism independent from a free radical scavenging property or an antioxidant facilitating activity. The activation of caspase-9, 4h after Epo injection, corresponding to the start of light exposure, suggests that caspase-9 plays a role in neuroprotection.


The role of men's forgiveness in marital satisfaction and coping strategies of infertile iranian women.
Infertility and its related problems create tensions in infertile women, which may lead to reduced marital satisfaction and the use of ineffective coping strategies. Considering the important role of forgiveness, marital satisfaction and effective coping strategies in the quality of life of infertile couples, and taking into account the growing number of Iranian infertile couples, this study was conducted to determine the relationship between men's forgiveness, marital satisfaction, and coping strategies of infertile Iranian women. This cross-sectional study included 200 Iranian infertile couples. The research environment was the most equipped infertility center in the west of Iran. Sampling was continuous. Data collection tools used included a self-generated demographic and fertility questionnaire, the Family Forgiveness Scale (FFS), the Index of Marital Satisfaction (IMS), and the Ways of Coping Questionnaire-revised (WOCQ-R). Husbands' forgiveness had a significant direct relationship with the marital satisfaction of infertile women (r = -0.27, p < 0.001). However, there was no significant correlation between Husbands' forgiveness, emotion-focused, and problem-focused coping of infertile women. Among the subscales of forgiveness, only the subscale of recognition had inversely correlated with the emotional coping of infertile women. The results showed that the higher the forgiveness of husbands, the higher the marital satisfaction of infertile women. Also, with the increase of husbands' forgiveness in the recognition subscale, the use of emotion-focused coping decreased in infertile women. Based on the results with empowering the husbands of infertile women with forgiveness skills, it is possible to take a step towards marital satisfaction and thus improve the quality of life of infertile women.


Early detection of parenting stress in mothers of preterm infants during their first-year home.
Maternal stress following the birth of an infant is well acknowledged. It is particularly so when infants are born prematurely as their mothers cannot fully take on their parenting role until their infant(s) is discharged from neonatal intensive care units (NICUs). In this exploratory study, we examined whether these mothers' parenting stress would lessen during their first-year reunification with their infant(s) as they settle into motherhood at home. Two groups of mothers with infants born between 24- and 33-week gestational age were recruited. A group of 25 mothers were monitored at their infants' 1-month corrected age (CA) and a second group of 24 mothers were monitored at their infants' 12-month CA. Subjects completed the long form Parental Stress Index (PSI) ranking how stressful they perceive the individual subscales in the Child and Parent Domains of the self-reported questionnaire (PSI-3; Abidin; PAR Inc). The PSI theorizes that the stress mothers perceive is a resultant of their respective characteristics, interactions with their infant(s), family, and environment. Statistical analyses include descriptive statistics, χ2 square analysis, and independent t-test. There was no significant difference in the levels of perceived stress in the PSI subscales between the two groups of mothers at 1- and 12-month CA. Scores for the majority of respondents fell within the 15th to 80th percentile (% ile) distribution of Abidin's normative population, with some mothers falling below the 15th % ile. The data collected suggest that: 1. the perceived stress experienced by mothers during their first-year reunited with their preterm infants is within the normal range observed in Abidin's normative population. 2. As the PSI is a self-reported survey, care providers need to be aware that some mothers may downplay their stress responses. 3. With the ability to monitor individual participants, the PSI can be readily offered to mothers at their infants' first year routine clinical visits to assist in the early identification of parenting issues that may threaten the development of a healthy mother-infant dyad. Early appropriate guidance and social support would help "at-risk" mothers develop more constructive parenting routines.


[Induced tolerance to cardiac allografts with intrathymic injection of donor spleen cells].
To study the methods and mechanisms of immune tolerance in cardiac transplantation. Male DA rat hearts were transplanted to male Lewis rats using Ono's model and randomly divided into four groups: untreated (group I), intrathymic injection of 2.5 x 10(7) DA splenocytes to Lewis rat (group II), intraperitoneal injection of 1 ml rabbit anti-rat lymphocyte serum (ALS) to Lewis recipient (group III), intrathymic injection of 2.5 x 10(7) DA splenocytes combined with intraperitoneal injection of 1 ml rabbit anti-rat lymphocyte serum (ALS) to Lewis recipient (group IV). 21 days later heart transplantation was performed. Mean survival time (MST), histological changes and mixed lymphocyte reaction (MLR) were measured after operation. In the group of intrathymic injection of spleen cells combined with ALS treatment, the survival time of heart allografts [MST: (81.8 +/- 7.6)d] was significantly longer than in the groups I [MST: (7.3 +/- 1.0) d], group II [MST:(7.8+/- 1.0)d], and group III [MST(8.2 +/- 1.2) d, P < 0.01]. Only a few inflammatory cells infiltrated in cardiac allografts in group IV. MLR of group IV were significantly decreased compared with those of the normal control (P < 0.01). The role of thymus as a special site for induction and maintenance of specific immunological unresponsiveness to organ allografts was confirmed. T cell clonal deletion may play an important role in this immune tolerance.


Involvement of calcium channels in depolarization-evoked release of adenosine from spinal cord synaptosomes.
The potential involvement of L- and N-type voltage-sensitive calcium (Ca2+) channels and a voltage-independent receptor-operated Ca2+ channel in the release of adenosine from dorsal spinal cord synaptosomes induced by depolarization with K+ and capsaicin was examined. Bay K 8644 (10 nM) augmented release of adenosine in the presence of a partial depolarization with K+ (addition of 6 mM) but not capsaicin (1 and 10 microM). This augmentation was dose dependent from 1 to 10 nM and was followed by inhibition of release from 30 to 100 nM. Nifedipine and nitrendipine inhibited the augmenting effect of Bay K 8644 in a dose-dependent manner, but neither antagonist had any effect on release of adenosine produced by K+ (24 mM) or capsaicin (1 and 10 microM). omega-Conotoxin inhibited K(+)-evoked release of adenosine in a dose-dependent manner but had no effect on capsaicin-evoked release. Ruthenium red blocked capsaicin-induced release of adenosine but had no effect on K(+)-evoked release. Although L-type voltage-sensitive Ca2+ channels can modulate release of adenosine when synaptosomes are partially depolarized with K+, N-type voltage-sensitive Ca2+ channels are primarily involved in K(+)-evoked release of adenosine. Capsaicin-evoked release of adenosine does not involve either L- or N-type Ca2+ channels, but is dependent on a mechanism that is sensitive to ruthenium red.


Design and Development of a Clot Burst Pressure Device to Investigate Resuscitation Strategies.
A reduction in clot strength is a hallmark feature of trauma-induced coagulopathy. A better understanding of clot integrity can optimize resuscitation strategies. We designed a device to gauge clot strength by pressurizing fluids over a formed clot and measuring the pressure needed to dislodge the clot. We hypothesized that this device could distinguish between clots formed in hypocoagulable and hypercoagulable states by observing differences in the clot burst pressure. Whole blood from healthy volunteers was collected into sodium citrate tubes and was treated with heparin or fibrinogen to generate clots in a hypocoagulable or hypercoagulable state, respectively. Small bore holes were drilled into polystyrene plates, and recalcified blood was pipetted into the holes. Plates were incubated at 37°C for 30 min to form clots. A pressure cap with an inlet for fluid from a syringe pump and an outlet leading to a measurement column was secured in the wells with a watertight seal. Clot burst pressure was normalized to individual baseline values to account for inherent differences in clot strength. The 1.0 g/L and 2.0 g/L fibrinogen groups were 1.65 ± 0.07 (P = 0.0078) and 2.26 ± 0.16 (P = 0.0078) times as strong as baseline, respectively. The 0.10, 0.15, or 0.20 USP units/mL groups were 0.388 ± 0.07 (P = 0.125), 0.31 ± 0.07 (P = 0.125), 0.21 ± 0.07 (P = 0.125) times as strong as baseline, respectively. Data were analyzed using Wilcoxon matched pairs signed rank testing. This device tests clot strength using burst pressure, an easily interpreted clinical parameter not measured in existing devices. Future work can test blood from trauma patients to better understand trauma pathophysiology.


Can bilharziasis of the seminal vesicles be a cause of obstructive infertility?
In patients with bilharzial seminal vesiculitis, it has been proved by the fructose test, seminal vesiculography, and casting that the vesicular and ampullary canals as well as the ejaculatory ducts are patient. Thus bilharziasis plays no role in the production of obstructive infertility in males.


Effects of dietary trace mineral levels on physiological responses, reproductive performance, litter performance, blood profiles, and milk composition in gestating sows.
This study was conducted to evaluate the effects of optimal trace mineral levels on the physiological responses, reproductive performance, litter performance, blood profiles and milk composition in gestating sows. A total of 59 multiparous sows (Yorkshire×Landrace) with similar body weight (BW), backfat thickness (BF), and parity were assigned to one of four treatments with 14 or 15 sows per treatment using a completely randomized design. The treatments were 100% (M1), 300% (M3), 600% (M6), and 900% (M9) of the National Research Council (NRC) Nutrient Requirements of Swine. During lactation period, all the sows were fed the same commercial lactation diet. No significant differences were observed in the BW, BF, reproductive performance, milk composition, or growth performance of the piglets. On day 70 of gestation, the serum zinc concentration showed a quadratic response to M6 treatment (quadratic, p<0.05). Moreover, as the dietary mineral levels increased, the zinc concentration increased linearly at 110 days of gestation (linear, p<0.05). Furthermore, copper and iron concentrations in the serum of sows at 24 h postpartum decreased linearly when high levels of dietary minerals were provided (linear, p<0.05). In the serum of piglets, serum zinc concentrations decreased linearly (linear, p<0.05), and iron concentration showed a quadratic response (quadratic, p<0.05) with an increase in trace mineral premix levels in gestation diets. The current trace mineral requirements of NRC (2012) are suitable for gestating sows, and the addition of dietary mineral levels in the gestating diet did not show any improvements during the gestation and lactation periods.


Molecular characterization of the carbon dioxide receptor in the oriental latrine fly, Chrysomya megacephala (Diptera: Calliphoridae).
The blowfly Chrysomya megacephala (Fabricius) (Diptera: Calliphoridae) cannot only act as a mechanical vector of various pathogens, but also infest man and animals causing human health problems and economic losses in the livestock and fish industries. As in other insects, olfaction of this species plays an important role in host location and is presumably mediated via transmembrane receptor signaling pathways. Here, we isolate and characterize CmegGr1 and CmegGr2, two new members of the chemosensory receptor gene family from C. megacephala. The open reading frames of CmegGr1 and CmegGr2 cDNA clones encode 453 and 486 amino acid residues, respectively. These two deduced proteins display high amino acid conservation with previously identified carbon dioxide (CO₂) receptors, such as Drosophila melanogaster Gr21a/Gr63a and Anopheles gambiae s.s. Gr22/Gr24. Further sequence analysis showed that both proteins are consistent with their corresponding orthologs in the membrane topology prediction with some ambiguities in the location of N terminus and the number of transmembrane domains. The transcripts of CmegGr1 and CmegGr2 were detected in the major chemosensory organs including the antennae and proboscises with maxillary palps attached. These results suggest that CmegGr1 and CmegGr2 are likely to be the primary receptors for CO₂ detection in C. megacephala. Knowledge of the molecular identity of the blowfly olfactory CO₂ receptors may aid in the development of novel control strategies designed to take advantage of this unique and critical olfactory pathway.


Large exciton binding energy, superior mechanical flexibility, and ultra-low lattice thermal conductivity in BiI3monolayer.
The exciton binding energy, mechanical properties, and lattice thermal conductivity of monolayer BiI3are investigated on the basis of first principle calculation. The excitation energy of monolayer BiI3is predicted to be 1.02 eV, which is larger than that of bulk BiI3(0.224 eV). This condition is due to the reduced dielectric screening in systems. The monolayer can withstand biaxial tensile strain up to 30% with ideal tensile strength of 2.60 GPa. Compared with graphene and MoS2, BiI3possesses superior flexibility and ductility due to its large Poisson's ratio and smaller Young's modulus by two orders of magnitude. The predicted lattice thermal conductivitykLof monolayer BiI3is 0.247 W m-1 K-1at room temperature, which is lower than most reported values for other 2D materials. Such ultralowkLresults from the scattering between acoustic and optical phonon modes, heavy atomic mass, and relatively weak chemical bond.


Anterior Segment OCTA of Melanocytic Lesions of the Conjunctiva and Iris.
To study the feasibility and diagnostic value of vascular imaging using optical coherence tomography (OCT)-angiography (OCTA) of melanocytic lesions of the conjunctiva and iris. Cross-sectional study. Twenty-five patients with an untreated conjunctival lesion (5 melanoma, 13 nevus, 7 primary acquired melanosis [PAM]) and 52 patients with an untreated iris lesion (10 melanoma, 42 nevus) were included. Patients were imaged using a commercially available OCTA device, with the addition of an anterior segment lens and manual focussing. Tumor vessel presence, vascular patterns and vascular density were assessed. Good OCTA images were obtained in 18 of 25 conjunctival lesions and 42 of 52 iris lesions. Failure was caused by lack of patient cooperation, an unfavorable location, or mydriasis. In all imaged conjunctival lesions and 77% of iris lesions, vascular structures were detected. Conjunctival melanoma and nevi demonstrated the same intralesional tortuous patterns, whereas vasculature in eyes with PAM was similar to normal conjunctiva. Both iris melanoma and nevi demonstrated tortuous patterns, distinct from the radially oriented normal iris vasculature. Optical coherence tomography angiography (OCTA) allows for noninvasive imaging of the vasculature in melanocytic lesions of the conjunctiva and iris. Good image quality depends highly on patient cooperation and lesion characteristics. Differentiation of benign and malignant lesions was not possible. New software is called for to improve image acquisition and analysis.


2-(4-Bromo-phen-yl)-2-oxoethyl naphthalene-1-carboxyl-ate.
In the title compound, C19H13BrO3, an ester of 1-naphthoic acid with an aromatic alcohol, the least-squares planes defined by the C atoms of the respective aromatic systems enclose an angle of 77.20 (5)°. In the crystal, C-H⋯O contacts connect the mol-ecules into undulating sheets parallel (100).


Moral Arguments in the Debate over Nanotechnologies: Are We Talking Past Each Other?
How are we to understand the fact that the philosophical debate over nanotechnologies has been reduced to a clash of seemingly preprogrammed arguments and counterarguments that paralyzes all rational discussion of the ultimate ethical question of social acceptability in matters of nanotechnological development? With this issue as its starting point, the study reported on here, intended to further comprehension of the issues rather than provide a cause-and-effect explanation, seeks to achieve a rational grasp of what is being said through the appeals made to this or that principle in the range of arguments put forward in publications on the subject. We present the results of the study's analyses in two parts. In the first, we lay out the seven categories of argument that emerged from an analysis of the literature: the arguments based on nature, dignity, the good life, utility, equity, autonomy, and rights. In the second part, we present the background moral stances that support each category of argument. Identifying the different categories of argument and the moral stance that underlies each category will enable a better grasp of the reasons for the multiplicity of the arguments that figure in discussions of the acceptability of nanotechnologies and will ultimately contribute to overcoming the tendency towards talking past each other that all too often disfigures the exchange. Clarifying the implications of the moral arguments deployed in the debate over nanotechnologies may make it possible to reduce the confusion observable in these exchanges and contribute to a better grasp of the reasons for their current unproductiveness.


Meta-analysis of protein intake on the effect of Crohn's disease and ulcerative colitis.
published studies have assessed the effect of protein intake on Crohn's disease (CD) and ulcerative colitis (UC). However, the results were inconsistent. To provide a more precise estimation, a meta-analysis was performed to evaluate the association of protein intake in Crohn's disease and ulcerative colitis. the PubMed, Chinese National Knowledge Infrastructure databases (CNKI), and Wanfang databases were searched to identify relevant studies. The summarized results of the relative risk (RR) with the corresponding 95 % confidence intervals (CI) were calculated using a random effects model. the final analysis included a total of nine articles. Nine studies reported on protein intake for the risk of UC and five studies reported on protein intake for the risk of CD. Overall, based on current studies, no significant association was found between protein intake and the risk of UC (RR = 1.13, 95 % CI = 0.82-1.55) or CD (RR = 1.18, 95 % CI = 0.51-2.74). A significant change was not found in the stratified analysis by study design and geographic location. in conclusion, the present meta-analysis suggested that dietary protein intake did not show a significant effect on the risk of UC or CD.


[Effect of cavinton and sulfocamphocain on systemic and cerebral hemodynamics in patients with early forms of cerebrovascular diseases].
In a study involving 33 patients with initial manifestations of inadequate cerebral blood supply and in 22 patients with transient disorders of the cerebral circulation in the presence of atherosclerosis (n = 45) and atherosclerosis with arterial hypertension (n = 8) the authors studied the effect of intravenous administration of cavinton in combination with sulfocamphocain on the clinical manifestations and on the systemic (using the method of Evans' dilution) and cerebral (using Doppler ultrasonography) hemodynamics. It has been demonstrated that both a single intravenous administration of cavinton in conjunction with sulfocamphocain and a course of treatment with these drugs reduce the volume of the circulating blood, lower the stroke and cardiac indices, increase the linear velocity of blood flow along the carotid and vertebral arteries, and decrease neurological symptomatology. The authors discuss the questions related to indications for the administration of cavinton in combination with sulfocamphocain to patients with inadequate cerebral blood supply and transient disorders of the cerebral circulation.


Interaction of dibucaine.HCl local anesthetics with bacteriorhodopsin in purple membrane: a spectroscopic study.
Several spectroscopic techniques (absorption, emission, transient absorption and differential scanning calorimetry--DSC) were used to investigate the deprotonation of dibucaine.HCl in a hydrophobic environment, and the interaction sites and mechanisms of the local anesthetic dibucaine.HCl on bacteriorhodopsin (bR) in purple membrane. The important results are summarized as follows: (1) the visible absorption features of native (lambda max = 568 nm) and deionized (lambda max = 608 nm) bR are sensitive to the amount of dibucaine.HCl added; (2) the emission spectrum of dibucaine.HCl embedded in the retinal-free mutant bR is similar to that of dibucaine free base in Triton X-100 micellar solutions; (3) the phosphorescence emission of dibucaine at 77 K is completely quenched by bR and the fluorescence quenching rate for the incorporated dibucaine.HCl in bR was determined as kq = 4.09 x 10(13) M-1 s-1; (4) the incorporation of dibucaine.HCl in bR inhibits the slow component rate of formation of M412 and decreases the amount of M412 formation in the photochemical cycle of bR; and (5) the thermal stability of native bR was measured by DSC in the presence and absence of dibucaine and yielded an endothermic transition at 95.9 +/- 1.0 degrees C with 13.6 J/g (3.25 +/- 0.12 cal/g) of enthalpy changes. All observations suggest that the action site of the local anesthetic, dibucaine.HCl, is near or at the chromophore, i.e. the retinal Schiff base of bR. The anesthetic action on bR purple membrane is probably via a specific site binding, but not a conformational mechanism.


Kinetic modeling of Moorella thermoacetica growth on single and dual-substrate systems.
Acetic acid is an important chemical raw material that can be produced directly from sugars in lignocellulosic biomass. Development of kinetic models that capture the bioconversion dynamics of multiple sugar systems will be critical to optimization and process control in future lignocellulosic biorefinery processes. In this work, a kinetic model was developed for the single- and dual-substrate conversion of xylose and glucose to acetic acid using the acetogen Moorella thermoacetica. Batch fermentations were performed experimentally at 20 g L(-1) total sugar concentration using synthetic glucose, xylose, and a mixture of glucose and xylose at a 1:1 ratio. The product yield, calculated as total product formed divided by total sugars consumed, was 79.2, 69.9, and 69.7 % for conversion of glucose, xylose, and a mixture of glucose and xylose (1:1 ratio), respectively. During dual-substrate fermentation, M. thermoacetica demonstrated diauxic growth where xylose (the preferred substrate) was almost entirely consumed before consumption of glucose began. Kinetic parameters were similar for the single-substrate fermentations, and a strong linear correlation was determined between the maximum specific growth rate μ max and substrate inhibition constant, K s . Parameters estimated for the dual-substrate system demonstrated changes in the specific growth rate of both xylose and glucose consumption. In particular, the maximum growth rate related to glucose tripled compared to the single-substrate system. Kinetic growth is affected when multiple substrates are present in a fermentation system, and models should be developed to reflect these features.


A novel aryl-guanidinium derivative, VP79s, targets the signal transducer and activator of transcription 3 signaling pathway, downregulates myeloid cell leukaemia-1 and exhibits preclinical activity against multiple myeloma.
We have recently described a novel guanidinium-based compound, VP79s, which induces cytotoxicity in various cancer cell lines. Here, we aim to investigate the activity of VP79s and associated mechanisms of action in multiple myeloma (MM) cells in vitro and ex vivo. The effects of VP79s on cell viability and induction of apoptosis was examined in a panel of drug-sensitive and drug-resistant MM cell lines, as well as ex vivo patient samples and normal donor lymphocytes and platelets. Cell signaling pathways associated with the biological effects of VP79s were analysed by immunoblotting and flow cytometry. Gene expression changes were assessed by quantitative real-time PCR analysis. VP79s was found to rapidly inhibit both constitutively active and IL-6-induced STAT3 signaling with concurrent downregulation of the IL-6 receptors, CD130 and CD126. VP79s induced a rapid and dose-dependent downregulation of anti-apoptotic Bcl-2 family member, myeloid cell leukaemia-1 (MCL-1). VP79s enhanced bortezomib induced cell death and was also found to overcome bone marrow stromal cell induced drug resistance. VP79s exhibited activity in ex vivo patient samples at concentrations which had no effect on peripheral blood mononuclear cells, lymphocytes and platelets isolated from healthy donors. As VP79s resulted in rapid inhibition of the key IL-6/STAT3 signaling pathway and downregulation of MCL-1 expression with subsequent selective anti-myeloma activity, VP79s may be a potential therapeutic agent with a novel mechanism of action in MM cells.


The absolute standardization of 32P and 204Tl at LNMRI.
32P and 204Tl solutions were standardized within the frame of the international key comparisons organized by bureau international des poids et mesures, in 2002. The activity concentration of 32P was measured by counting solid sources in a 4pibeta proportional gas flow counter and by liquid scintillation counting. The self-absorption in solid sources for 4pibeta counting and the presence of 33P as an impurity were evaluated. The combined standard uncertainty for 32P was 0.59% in the 4pibeta counting and 0.38% in the liquid scintillation counting. Liquid scintillation counting was used to measure the activity concentration of 204Tl with combined standard uncertainty of 0.35%.


Effects of dietary tributyrin and physterol ester supplementation on growth performance, intestinal morphology, microbiota and metabolites in weaned piglets.
This study was conducted to investigate the effects of dietary tributyrin (TB) and physterol ester (PSE) supplementation on the growth performance and intestinal health of weaned piglets. Ninety-six piglets were randomly allocated to one of four groups, including a control group (basal diet), TB group (basal diet + 1500 g t-1 TB), PSE group (basal diet + 300 g t-1 PSE) and TB + PSE group (basal diet + 1500 g t-1 TB + 300 g t-1 PSE). All groups had eight replicates with three piglets per replicate. The experiment lasted for 28 days. The results showed that dietary TB supplementation increased (p < 0.05) average daily feed intake and average daily gain, as well as the acetate and butyrate concentration in ileum, and dietary PSE supplementation decreased (p < 0.05) the ratio of feed to gain (F/G) on days 1-14 of the trial. Dietary TB or PSE alone supplementation improved the ratio of villus height to crypt depth (VH/CD) and the expression level of Occludin in ileum. The linear discriminant analysis effect size analysis identified eight biomarkers in the control group, 18 in the TB + PSE group, two in the PSE group in ileum respectively. Correlation analysis showed that the relative abundances of Enterococcus, and Streptococcus were positively correlated (p < 0.05) with propionate concentration, while the relative abundance of Clostridium_sensu_stricto_1 was negatively correlated (p < 0.05) with acetate concentration in ileum. These findings suggest that dietary TB or PSE alone supplementation could alter the growth performance, intestinal morphology, microbiota community and metabolites of weaned piglets. Weaning stress is a major cause of slow growth and increased diarrhoea in piglets. This study demonstrated that dietary TB and PSE presented a beneficial role in growth performance and gut health via regulating intestinal morphology, microbiota composition and metabolites.


Mass spectrometry characterization of Commiphora leptophloeos leaf extract and preclinical evaluation of toxicity and anti-inflammatory potential effect.
Commiphora leptophloeos (Mart.) J.B. Gillett (Burseraceae) is a medicinal plant native from the brazilian northeast caatinga biome, known popularly as "imburana" or "imburana-de-cambão". The leaves of C. leptophloeos are widely used in folk medicine in the treatment of various inflammatory disorders. However, there is no scientific evidence to justify their popular use. This approach aimed to characterize the phytochemical profile of hydroethanolic leaf extract, as well as evaluate the anti-inflammatory and antioxidant potential activity and to investigate the acute toxicity with pre-clinical in vitro and in vivo methodologies. The phytochemical profile was characterized by UPLC-MS and FIA-ESI-IT-MS/MS. The in vitro anti-inflammatory potential the hydroethanolic extract of C. leptophloeos (1, 10, 100 and 200 μg/mL) was investigated by lipopolysaccharide (LPS) induced nitric oxide assay, in order to analyze the potential decrease of nitric oxide (NO) production. For carrageenan-induced paw edema and zymosan-induced air pouch models, the extract (100, 200 and 400 mg/kg) was administrated by intragastric gavage (i.g.) route and used for evaluating the anti-inflammatory effect in vivo. Related to the first animal model, the antiedematogenic activity and myeloperoxidase (MPO) levels could be investigated. In addition, the zymosan-induced air pouch model allowed the analyses of leukocytes migration, total MPO, malondialdehyde (MDA) and cytokines (TNF-α and IL-10) levels. The toxicity in vitro of the extract (1, 10, 100 and 200 μg/mL) was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and acute toxicity in vivo was tested using the extract at 2000 mg/kg by i. g. route. The phytochemical analyses of C. leptophloeos leaf extract pointed the presence of six glycosylated flavonoids, identified as orientin, isoorientin, vitexin and isovitexin, quercetrin and isoquercitrin. A decrease of NO in vitro was noticed by the use of the extract in the LPS-induced nitric oxide assay and an expressive reduction of the paw-edema followed by a decrease of myeloperoxidase activity at doses of 200 and 400 mg/kg. The zymosan-induced air pouch model indicated that the extract, in all doses, significantly reduced the leukocytes migration, total protein concentration, MPO and MDA levels. The levels of cytokines were verified by the administration of extract in this model, revealing a lower of TNF-α level and an increase of the IL-10 production. In the toxicity study, the MTT assay evidenced no cytotoxicity of the tested concentrations and acute toxicity in vivo test did not result in any sign of toxicity and mortality or significant changes on the biochemical parameters. Based on these results, is possible suggest that the anti-inflammatory activity revealed in this approach can be related to the modulating the level of cytokine, decrease of TNF-α, increase of IL-10 in vivo and also the inhibition of the production of nitric oxide RAW 264.7 activated by LPS. These results demonstrate the potential anti-inflammatory effect C. leptophloeos leaf extrat in inflammatory in vivo models, supporting its use in folk medicine for treatment of inflammatory diseases. Finally, glycosylated flavonoids can be responsible, at least in part, for this effect.


CT radiomics prediction of CXCL9 expression and survival in ovarian cancer.
C-X-C motif chemokine ligand 9 (CXCL9), which is involved in the pathological processes of various human cancers, has become a hot topic in recent years. We developed a radiomic model to identify CXCL9 status in ovarian cancer (OC) and evaluated its prognostic significance. We analyzed enhanced CT scans, transcriptome sequencing data, and corresponding clinical characteristics of CXCL9 in OC using the TCIA and TCGA databases. We used the repeat least absolute shrinkage (LASSO) and recursive feature elimination(RFE) methods to determine radiomic features after extraction and normalization. We constructed a radiomic model for CXCL9 prediction based on logistic regression and internal tenfold cross-validation. Finally, a 60-month overall survival (OS) nomogram was established to analyze survival data based on Cox regression. CXCL9 mRNA levels and several other genes involving in T-cell infiltration were significantly relevant to OS in OC patients. The radiomic score (rad_score) of our radiomic model was calculated based on the five features for CXCL9 prediction. The areas under receiver operating characteristic (ROC) curves (AUC-ROC) for the training cohort was 0.781, while that for the validation cohort was 0.743. Patients with a high rad_score had better overall survival (P < 0.001). In addition, calibration curves and decision curve analysis (DCA) showed good consistency between the prediction and actual observations, demonstrating the clinical utility of our model. In patients with OC, the radiomics signature(RS) of CT scans can distinguish the level of CXCL9 expression and predict prognosis, potentially fulfilling the ultimate purpose of precision medicine.


Quality of Life and Associated Factors among Mothers with Gestational Diabetes Mellitus by using a Specific GDMQ-36 Questionnaire: A Cross-Sectional Study.
Gestational Diabetes Mellitus (GDM) has physical, social, mental, and psychological consequences that can affect mothers' Quality of Life (QOL). This study was conducted with the aim to evaluate the QOL of mothers with GDM and its associated factors using a specific questionnaire. This cross-sectional study was conducted on 200 mothers with GDM who were referred to clinics affiliated with Shahid Beheshti University and Qom University of Medical Sciences, Iran, in 2019-2020. The specific QOL questionnaire for women with GDM (GDMQ-36) and the demographic questionnaire were completed for participants. Independent variables were entered into the multiple linear regression model and were analyzed. The total Mean(SD) score of the QOL of mothers with GDM who participated in the study was 46.83 (11.66) based on percentage. The highest and lowest QOL Mean (SD) scores were obtained on the support 76.50 (14.50) and concerns about a high-risk pregnancy 31.40 (19.80), subscales, respectively. The total QOL score decreased by 7.14 and 5 points on average in mothers treated with medication regimens and mothers who had a pre-high school education, respectively. The support subscale score increased by 5 points in mothers who had a previous history of GDM. The present study showed that the QOL of women with GDM had been severely affected by concerns about a high-risk pregnancy. Some individual and social factors can be associated with the QOL of mothers with GDM and its subscales.


The existence of weak solutions to the continuous coagulation equation with multiple fragmentation is shown for a class of unbounded coagulation and fragmentation kernels, the fragmentation kernel having possibly a singularity at the origin. This result extends previous ones where either boundedness of the coagulation kernel or no singularity at the origin for the fragmentation kernel was assumed.


The inflammatory versus constitutive trafficking of mononuclear phagocytes into the alveolar space of mice is associated with drastic changes in their gene expression profiles.
Mononuclear phagocytes enter the lungs both constitutively to maintain alveolar macrophage and dendritic cell homeostasis, as well as during lung inflammation, where the role of these cells is less well defined. We used a transgenic mouse strain (CX3CR1(+/GFP)) that harbors a GFP label in circulating monocytes to identify and sort these cells from the vascular and alveolar compartments under both constitutive and acute lung inflammatory conditions. Using nylon arrays combined with real-time RT-PCR for gene expression profiling, we found that flow-sorted, highly purified mononuclear phagocytes recruited to acutely inflamed mouse lungs showed strongly up-regulated mRNA levels of the neutrophil chemoattractants KC, MIP-2, and IP-10, which contrasted with alveolar mononuclear phagocytes that immigrated in steady state. Similar observations were made for the lysosomal cathepsins B, L, and K being strongly up-regulated in mononuclear phagocytes upon recruitment to inflamed lungs but not during constitutive alveolar immigration. Inflammatory elicited mononuclear phagocytes also demonstrated significantly increased mRNA levels of the cytokine TNF-alpha and the PRR-associated molecules CD14, TLR4, and syndecan-4. Together, inflammatory elicited mononuclear phagocytes exhibit strongly increased neutrophil chemoattractants, lysosomal proteases, and LPS signaling mRNA transcripts, suggesting that these cells may play a major role in acute lung inflammatory processes.


Angiotensin-converting enzyme inhibitors and type 2 diabetic nephropathy: a meta-analysis.
To perform a meta-analysis on studies evaluating the effect of angiotensin-converting enzyme (ACE) inhibitors on diabetic nephropathy in patients with type 2 diabetes mellitus. A computerized literature search was conducted for articles of studies comparing ACE inhibitors with a control in patients with diabetes, in which measurement of albuminuria or proteinuria was an outcome. Each article was abstracted by two of the authors. Data from the articles were presented as geometric or arithmetic means. The data were summarized separately by using standard techniques for meta-analysis. Statistically significant reductions in albuminuria were observed regardless of whether data were described with geometric or arithmetic means. Both were associated with significant heterogeneity. When studies reporting geometric means were stratified and analyzed, the heterogeneity was lost and statistically significant reductions in albuminuria were observed. The same procedure was repeated for studies reporting arithmetic means, but heterogeneity remained. The ACE inhibitors produce statistically significant reductions in albuminuria associated with significant heterogeneity of effect. Stratification reduces the heterogeneity and supports treatment with ACE inhibitors to reduce the progression of nephropathy in patients with type 2 diabetes mellitus.


Intestinal bacterial flora of the household lizard, Gecko gecko.
A total of 114 isolates was recovered from the intestines of 43 househould lizards, Gecko gecko. Among the important ones were Staphylococcus aureus, Salmonella typhimurium, Pseudomonas aeruginosa, Proteus mirabilis and Edwardsiella tarda.


Unraveling the genetic basis of fast l-arabinose consumption on top of recombinant xylose-fermenting Saccharomyces cerevisiae.
One major challenge in the bioconversion of lignocelluloses into ethanol is to develop Saccharomyces cerevisiae strains that can utilize all available sugars in biomass hydrolysates, especially the d-xylose and l-arabinose that cannot be fermented by the S. cerevisiae strain naturally. Here, we integrated an l-arabinose utilization cassette (AUC) into the genome of an efficient d-xylose fermenting industrial diploid S. cerevisiae strain CIBTS0735 to make strain CIBTS1972. After evolving on arabinose, CIBTS1974 with excellent fermentation capacity was obtained. A comparison between genome sequences of strains CIBTS1974 and CIBTS1972 revealed that the copy number of the AUC had increased from 1 to 12. We then constructed the AUC null-mutant CIBTS1975 and gradually rescued the l-arabinose utilization defect by integrating AUC iteratively. On the other hand, the parental strain CIBTS0735 was able to acquire the same performance as CIBTS1974 by the direct introduction of 12 copies of the AUC; the performance was further improved by adding two more copies. Besides, we found that not the two transporters present in the AUC were both needed during l-arabinose utilization, GAL2 was necessary and STP2 was not essential. We have described for the first time that a high copy number of AUC is sufficient for the strain to metabolize l-arabinose efficiently independent of evolution.


Rapid detection of molybdenum ore grade based on visible-infrared spectroscopy and MTSVD-TGJO-ELM.
The rapid determination of ore grade can improve the efficiency of beneficiation. The existing molybdenum ore grade determination methods lag behind the beneficiation work. Therefore, this paper proposes a method based on a combination of Visible-infrared spectroscopy and machine learning to rapidly determine molybdenum ore grade. Firstly, 128 molybdenum ores were collected as spectral test samples to obtain spectral data. Then 13 latent variables were extracted from the 973 spectral features using partial least square. The Durbin-Watson test and the runs test were used to detect the partial residual plots and augmented partial residual plots of LV1 and LV2 to determine the non-linear relationship between spectral signal and molybdenum content. Extreme Learning Machine (ELM) was used instead of linear modeling methods to model the grade of molybdenum ores because of the non-linear behavior of the spectral data. In this paper, the Golden Jackal Optimization of adaptive T-distribution was used to optimize the parameters of the ELM to solve the problem of unreasonable parameters. Aiming at solving ill-posed problems by ELM, this paper decomposes the ELM output matrix by using the improved truncated singular value decomposition. Finally, this paper proposes an extreme learning machine method based on a modified truncated singular value decomposition and a Golden Jackal Optimization of adaptive T-distribution (MTSVD-TGJO-ELM). Compared with other classical machine learning algorithms, MTSVD-TGJO-ELM has the highest accuracy. This provides a new method for rapid detection of ore grade in the mining process and facilitates accurate beneficiation of molybdenum ores to improve ore recovery rate.


Accessory role of autologous T lymphocytes and adherent cells for the in vitro proliferation of T-cell colony-forming cells from patients with T-cell acute lymphoblastic leukemia.
Peripheral blood T colony-forming cells (T-CFC) from patients with T-cell malignancies can proliferate in methylcellulose in the absence of added growth factors or mitogenic stimulation. Mononuclear cells (MNC) from 7 patients with T-cell acute lymphoblastic leukemia were separated into cells forming rosettes with sheep erythrocytes (E+) or not (E-). E- cells were further depleted by complement-mediated cytotoxicity with OKT3 monoclonal antibody (E-OKT3- cells). The study of their spontaneous T-cell colony-forming ability suggested that proliferation of T-CFC in the absence of added growth factors requires cellular cooperation because: (1) No colony growth was observed at low cell concentrations (up to 2 X 10(4) cells/ml) whereas at higher cell densities the number of colonies increased exponentially; (2) The plating efficiency from unfractionated MNC was higher than that from E-OKT3- or E+ cells. Irradiated autologous E+ cells enhanced the plating efficiency from blast-enriched cell fractions (E-OKT3-) when co-cultured either directly in methylcellulose or separately in a two layer assay (agar-methylcellulose), suggesting that their activity could be due to diffusible factors; (3) Adherent-cell depletion of MNC decreased colony formation. Autologous irradiated adherent cells were able to restore the plating efficiency from MNCA- cells when co-cultured directly in methylcellulose but not in separate layers; however, media conditioned by patients' A+ cells could enhance the colony growth from patients' MNCA- cells, indicating that their activity could also be mediated by constitutively released soluble factors.


Identification of two pesticide-tolerant bacteria isolated from Medicago sativa nodule useful for organic soil phytostabilization.
Plant-microbe interactions such as rhizobacteria legumes are interesting in organic farming that has undergone significant expansion in the world. The organic agriculture is as an environment-friendly technique and a sustainable alternative to intensive agricultural system. Three types of soil were chosen, organic (ORG), conventional (CON), and fallow land (NA) to isolate soil bacteria-nodulating Medicago sativa, in order to develop microbial inoculants for use in agricultural sustainable system. Soil analysis revealed significant higher amounts of total nitrogen, organic carbon, total phosphorus, and matter detected in ORG. As for heavy metals, ORG showed high Cu content due to the authorized chemical use in organic farming. A sample of 130 bacteria was isolated from Medicago sativa nodule, genetically characterized by PCR/RFLP of ribosomal 16S RNAs, and a great dominance of Sinorhizobium meliloti (88.4%, 73.8%, and 55.5%) is obtained among NA-, CON-, and ORG-managed soils, respectively. The ORG showed the high bacterial diversity with 13.3% of non-identified strains. The resistance against five pesticides (Prosper, Cuivox, Fungastop, Nimbecidine, and Maneb) revealed a maximum of inhibitory concentration about 10 mg l-1 of Prosper, 12 mg l-1 of Cuivox, 6 ml l-1 of Fungastop, 7.5 ml l-1of Nimbecidine, and 25 ml l-1 of Maneb. The analysis of the symbiotic properties and plant growth-promoting potential revealed two efficient strains significantly increased alfalfa dry weight through producing siderophores, phosphorus, and indole acetic acid (13.6 mg ml-1 and 19.9 mg ml-1 respectively). Hence, we identify two tolerant and efficient strains, Achromobacter spanium and Serratia plymuthica, isolated from Medicago sativa nodule with valuable potential able to phytostabilize pesticide-contaminated soils.


Detection of prostate cancer with magnetic resonance imaging: optimization of T1-weighted, T2-weighted, dynamic-enhanced T1-weighted, diffusion-weighted imaging apparent diffusion coefficient mapping sequences and MR spectroscopy, correlated with biopsy and histopathological findings.
The aim of this study was to optimize and predict the most efficient magnetic resonance imaging (MRI) sequences; T1-weighted (T1W), T2-weighted (T2W), dynamic contrast-enhanced (DCE) T1W, diffusion-weighted imaging (DWI) apparent diffusion coefficient (ADC) mapping sequences and proton MR spectroscopy (H-MRS) for the detection of prostate cancer. After institutional review board approval and informed consent taken from all the patients, 40 patients with prostate cancer were included in this research. Two readers independently evaluated the results of T1W, T2W, DCE T1W, and DWI-ADC mapping sequences and proton H-MRS for the depiction of prostate cancer. Reference standard was the transrectal ultrasonography-guided biopsy and the surgical histopathological results. Statistical analysis was assessed by the Fisher exact t test, Wilcoxon signed rank test, variance analysis test with kappa (κ) values and receiver operating characteristics (ROC) curve for ADC values, choline (Cho)/citrate (Cit) and Cho+creatine (Cre)/Cit ratios for each observer. Based on both readers' results, sensitivity declined to 31% and specificity to 75% for the T1W sequence, sensitivity declined to 43% and specificity to 67% for the DCE T1W sequence, sensitivity declined to 46% and specificity to 68% for the T2W sequence, sensitivity declined to 29% and specificity to 82% for the DWI-ADC mapping; and specificity was 49% for the Cho/Cit and Cho+Cre/Cit ratios, sensitivity was 69% for the Cho/Cit ratio, and sensitivity was 70% for the Cho+Cre/Cit ratio for H-MRS. The T2W sequence and H-MRS presented significant statistical differences for the depiction of prostatic cancer (P < 0.05), the most efficient sequence to detect prostatic cancer was H-MRS: Cho+Cre/Cit and Cho/Cit ratios. Instead of using either sequences alone owing to low sensitivity and specificity rates, combined use of MRI techniques could easily improve the detection and staging of prostate cancer.


Recombinant fowlpox virus vaccines for poultry.
The intensive poultry industries rely heavily upon the use of vaccines for disease control. Viral vector based vaccines offer new avenues for the development of vaccines for effective disease control in poultry. Techniques developed for the construction of recombinant vaccinia viruses have been readily adapted to the construction of recombinant viruses based on fowlpox virus (rFPV). The ability to insert several genes into the large genome of fowlpox may enable the development of multivalent vaccines and vaccines incorporating immune response modifiers such as lymphokines. Newcastle disease, avian influenza, infectious bursal disease and Marek's disease antigens expressed by rFPV have been shown to be effective vaccines in poultry. None appear, however, to provide a substantial improvement in vaccine efficacy. Recombinant FPV will be a valuable adjunct to conventional vaccines currently in widespread use. Whether rFPV or other vector based vaccines can circumvent the problems of vaccination in the presence of high maternally derived antibodies is yet to be resolved. The observation that avipoxvirus recombinants may be suitable for the vaccination of non-avian species provides an added dimension to vaccines based on FPV or other avipoxviruses. Recombinant FPV will find a useful role in poultry disease control when used in conjunction with conventional vaccines.


PTCy, abatacept, and a short course of tacrolimus for GVHD prevention after haploidentical transplantation.
Reducing the incidence of graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (HSCT) is warranted. Posttransplant cyclophosphamide (PTCy) is the main agent used for GVHD prevention in this setting. It remains unknown whether costimulation blockade can be safely combined with PTCy and enhance its efficacy. We performed a phase 1b-2 clinical trial to examine the combination of PTCy, abatacept, and a short course of tacrolimus (CAST) after peripheral blood haploidentical HSCT. The primary end point was the incidence of grades 2-4 acute GVHD by day +120. The study enrolled 46 patients with a median age of 60 years (range, 18-74 years). The cumulative incidences of grades 2-4 and 3 or 4 acute GVHD were 17.4% (95% confidence interval [CI], 9.2-32.9) and 4.4% (95% CI, 1.1-17.1), respectively. With a median follow-up of 15.3 months, the cumulative incidence of 1-year treatment-related mortality was 4.4% (95% CI, 1.1-17.1). The estimated 1-year moderate-to-severe chronic GVHD rate, relapse rate, progression-free survival, overall survival, and GVHD- and relapse-free survival were 15.9% (95% CI, 8-31.7), 11.7% (95% CI, 5-27.2), 84.1% (95% CI, 73.8-95.7), 85.9% (95% CI, 75.9-97.2), and 66.1% (95% CI, 53.4-81.8), respectively. Toxicities were similar to those expected in patients receiving haploidentical HSCT. This clinical trial showed that the CAST regimen is safe and effective in reducing the rate of grades 2-4 acute GVHD after haploidentical peripheral blood HSCT. This trial was registered at www.clinicaltrials.gov as #NCT04503616.


Reactive oxygen species acts as executor in radiation enhancement and autophagy inducing by AgNPs.
Malignant glioma is one of the most common intracranial tumor with a dismal prognosis. The radiosensitizing effect of silver nanoparticles (AgNPs) on glioma both in vitro and in vivo were demonstrated in the previous studies of our group. However, the underlying mechanism is still unclear. In this present study, the use of antioxidants is employed for the regulating of reactive oxygen species (ROS) in U251 cells treated with various agents, and the results shows that ROS played an essential role in the autophagy inducing and radiosensitization effect of AgNPs. Moreover, the inhibition of protective autophagy with 3-MA is another way to increase ROS, resulting in the increasing of cell death and apoptosis. Taken together, understanding the relationship between the elevated ROS and autophagy and the effect of ROS should be useful to the clinical applications of AgNPs. These findings could potentially be exploited for new therapeutic strategies in glioma radiotherapy.


Autism interest intensity in early childhood associates with executive functioning but not reward sensitivity or anxiety symptoms.
Personal interests in autism are a source of joy, pride, and assist with the formation of social relationships. However, highly intense engagement can also interfere with other activities including activities of daily living. Theories have suggested that intense interests relate to executive functioning, reward sensitivity, and anxiety symptoms; but none of these theories have been tested in early childhood. Understanding which behavioral traits relate to intense interests in early childhood could help understand how intense interests may emerge, while also providing clues for how to manage interest intensity and best promote the many benefits of personal interests. We recruited families with autistic and non-autistic children aged 3-6 years. Parents completed questionnaires to assess children's interest diversity and intensity, executive functioning, reward sensitivity, and anxiety symptoms. We found that for autistic and non-autistic children, greater difficulty shifting attention between activities related to more intense interests. In autistic children only, difficulty with inhibitory control of attention also related to more intense interests. However, reward sensitivity and anxiety symptoms did not relate to interest intensity. Based on these observations, assisting young children with developing executive functioning skills could help with mediating the interference of interests in daily life to ultimately promote the many benefits of personal interests.


Inflammatory Cues Direct Skin-Resident Type 1 Innate Lymphoid Cells to Adopt a Psoriasis-Promoting Identity.
Innate lymphoid cells (ILCs) are gatekeepers in barrier organs, where they maintain tissue integrity and contribute to host defense as well as tissue repair. Inappropriate activation of ILCs, however, can lead to immunopathology with detrimental results. In this study, we focused on type 1 ILCs (ILC1s), which under inflammatory conditions constitute a poorly defined population with ambiguous functions. To delineate the properties of ILC1s in skin pathology, we used the well-established mouse model of imiquimod-induced psoriasis. Although ILC1s represented a minority among cutaneous lymphocytes in vehicle-treated controls, they rapidly expanded during early psoriasis and ultimately increased by >20-fold. This rapid increase was verified using two additional psoriasis models. Inflammatory ILC1s from imiquimod-treated skin were defined as CD44+, CXCR6+, and CD11b+ and substantially contributed to TNF-α and GM-CSF production, rendering them a potential candidate to shape the inflammatory infiltrate. In accordance with the psoriasis-specific microenvironment, skin ILC1s upregulated the IL-23 receptor whereas expression of the IL-12Rβ2 subunit was diminished. As a consequence, neutralization of IL-12 only had a minor impact, whereas blocking IL-23 reduced both ILC1 abundance and disease severity. Together, our findings identify skin ILC1s as a likely player in early psoriasis and a prospective target for therapeutic approaches.


Correlation between seminal oxidative stress biomarkers and antioxidants with sperm DNA damage in elite athletes and recreationally active men.
To evaluate the seminal plasma 8-isoprostane, reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase, total antioxidant capacity (TAC), and levels of sperm DNA fragmentation in elite athletes and recreationally active men. Prospective design was used for this study. The study was performed in the Exercise Physiology Laboratory of the Urmia University. Fifty-six elite athletes and 52 recreationally active men (18-28 years) participated in this study. All subjects had a semen sampling at baseline. Total antioxidant capacity and SOD activity were measured by colorimetric assay. Levels of ROS were measured by a chemiluminescence assay. Malondialdehyde levels were measured by thiobarbituric acid reactive substance assay. Catalase activity was measured by monitoring the initial rate of disappearance of hydrogen peroxide. Concentration of free 8-isoprostane was measured by enzyme immunoassay method. Sperm DNA fragmentation was evaluated with the terminal deoxynucleotidyl transferase-mediated fluorescein dUTP nick end-labeling assay. Recreationally active men have significantly higher levels of body fat, seminal SOD, TAC, and catalase and lower levels of V[Combining Dot Above]O2max, seminal ROS, MDA, and 8-isoprostane and subsequently lower rate of sperm DNA fragmentation when compared with elite athletes (P < 0.001). Significantly negative correlation was observed between sperm DNA fragmentation with body fat, seminal SOD, catalase, and TAC levels (P < 0.001). Significantly positive correlation was observed between sperm DNA fragmentation with V[Combining Dot Above]O2max, seminal 8-isoprostane, ROS, and MDA levels (P < 0.001). Spermatozoa from recreationally active men may be less susceptible to oxidative stress-induced DNA damage and hence infertility.


The plasma levels of atrial natriuretic peptide and brain natriuretic peptide in type 2 diabetes treated with sodium-glucose cotransporter-2 inhibitor.
The aim of this study was to determine the levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) after treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitor or dipeptidyl peptidase-4 (DPP4) inhibitor in patients with type-2 diabetes inadequately controlled by insulin, and to determine whether variation in ANP levels can explain favorable cardiovascular outcome. We enrolled 56 patients, aged 18-80years, with type-2 diabetes inadequately controlled by insulin: i.e., HbA1c level 7.5-10.5% despite at least 8weeks' injectable insulin at a stable mean dose of 20-150IU daily, with or without no more than two oral antidiabetic agents. The 56 patients were randomized between 3 treatment groups: SGLT2 inhibitor (n=18), DPP4 inhibitor (n=19) and placebo (n=19). Patients who received SGLT2 inhibitor or DPP4 inhibitor treatment all showed significantly lower HbA1c levels, fasting blood glucose (FBG) levels and systolic blood pressure at 24weeks than controls. SGLT2 inhibitor treatment decreased ANP levels, BNP levels, systolic blood pressure and weight compared with placebo. Compared to those receiving DPP4 inhibitor, patients receiving SGLT2 inhibitor showed lower HbA1c levels (7.01 vs. 7.58%; P=0.03), ANP levels (28.41 vs. 43.03 pg/mL; P=0.00) and weight (66.14 vs. 71.76 kg; P=0.04) at 24weeks after adjusting for baseline values. The SGLT2 inhibitor group showed higher sodium concentrations than the placebo and DPP4 inhibitor groups (145.89 vs. 143.89 and 144.79 mmol/L, respectively; P=0.00 and P=0.04) at 24 weeks. ANP and BNP levels did not significantly correlate with HbA1c and blood glucose levels. These results indicated that SGLT2 inhibitors may be superior to DPP4 inhibitors in reducing risk of cardiovascular disease in diabetic patients. The major study limitation was the small number of patients per group, which should be enlarged in further research.


Self-Assembled Peptide-Labeled Probes for Agglutination-Based Sensing.
The use of polydiacetylene (PDA) vesicles in sensing systems are wide-spread due to the interesting optical properties of this stimuli-responsive material; however, agglutination based sensing with PDA have been relatively underutilized. To demonstrate the means for rapidly generating an agglutination probe based on peptide-displaying polydiacetylene vesicles, we implement here the use of a biotin mimetic peptide functionalized to a diacetylene amphiphile for proof-of-concept detection of a multivalent target, specifically streptavidin. Tuning of the vesicle composition revealed a distinct limit in the surface density of peptide amphiphile that could be displayed for this particular peptide sequence. A wide operational detection range was demonstrated, and the result also revealed an effective agglutination response of the PDA-based probe to streptavidin suggesting possible use of future formulations in profiling other multivalent targets.


Cerebrovascular Pressure Reactivity in Children with TBI.
Investigators from University of Melbourne, Australia, studied Pressure-Reactivity Index (PRx) and optimal Cerebral Perfusion Pressure (CPP) in 36 children aged between 6 months and 16 years treated for traumatic brain injury (TBI) at the Royal Children's Hospital, Melbourne, from 2007 to 2013.


Hemangioma of the rectum: clinical appearance and treatment.
A 53-year-old woman who had severe rectal bleeding was found to have a perirectal hemangioma as a source of the bleeding. Four years prior to this admission, she had undergone, in another hospital, hemorrhoidectomy, which had required resuturing several times in order to stop rebleeding. The diagnosis of hemangioma was established after extensive roentgenographic examination. The patient was treated with low-dose irradiation, divided into five consecutive sessions, to the affected area. The bleeding stopped, and the patient has been free of disease since treatment two years ago. The lumen of the rectum is not narrowed, the mucosa appears normal, and the elasticity of the rectal wall has been preserved.


Prognostic significance of NPM1 mutation-modulated microRNA-mRNA regulation in acute myeloid leukemia.
Distinct microRNA (miRNA) and mRNA signatures were reported in nucleophosmin (NPM1)-mutated acute myeloid leukemia (AML). However, it remains unknown whether the mutation participates in the dynamic interaction between miRNA and mRNA. In this study, we aimed to investigate the role of NPM1 mutation in modulating miRNA-mRNA regulation (MMR). From the sample-paired miRNA/mRNA microarrays of 181 de novo AML patients, we found that MMR was dynamic and could be affected by NPM1 mutation. By a systematic framework, we identified 493 NPM1 mutation-modulated MMR pairs, where the strength of MMR was significantly attenuated in patients carrying NPM1 mutations, compared to those with wild-type NPM1. These miRNAs/mRNAs were associated with pathways implicated in cancer and known functions of NPM1 mutation. Such modulation of MMR was validated in two independent cohorts as well as in cells with different NPM1 mutant burdens. Furthermore, we showed that the regulatory strength of nine MMR pairs could predict patients' outcomes. Combining these pairs, a scoring system was proposed and shown to predict survival in discovery and validation data sets, independent of other known prognostic factors. Our study provides novel biological insights into the role of NPM1 mutation as a modulator of MMR, based on which a novel prognostic marker is proposed in AML.


Safety and efficacy of peripheral nerve blocks to treat refractory headaches after aneurysmal subarachnoid hemorrhage - A pilot observational study.
Headache after aneurysmal subarachnoid hemorrhage (HASH) is common, severe, and often refractory to conventional treatments. Current treatment standards include medications including opioids, until the pain is mitigated. Peripheral nerve blocks (PNBs) may be an effective therapeutic option for HASH. We conducted a small before-and-after study of PNBs to determine safety, feasibility, and efficacy in treatment of HASH. We conducted a pilot before-and-after observational study and collected data for 5 patients in a retrospective control group and 5 patients in a prospective intervention PNB group over a 12-month period. All patients received a standard treatment of medications including acetaminophen, magnesium, gabapentin, dexamethasone and anti-spasmodics or anti-emetics as needed. Patients in the intervention group received bilateral greater occipital, lesser occipital, and supraorbital PNBs in addition to medications. The primary outcome was pain severity, measured by Numeric pain rating scale (NPRS). All patients were followed for 1 week following enrollment. The mean ages in the PNB group and control group were 58.6 and 57.4, respectively. One patient in the control group developed radiographic vasospasm. Three patients in both groups had radiographic hydrocephalus and IVH, requiring external ventricular drain (EVD) placement. The PNB group had an average reduction in mean raw pain score of 2.76 (4.68, 1.92 p = 0.024), and relative pain score by 0.26 (0.48, 0.22 p = 0.026), compared to the control group. The reduction occurred immediately after PNB administration. PNB can be a safe, feasible and effective treatment modality for HASH. Further investigations with a larger sample size are warranted.


Pharmacological and toxicological aspects of carbon nanotubes (CNTs) to vascular system: A review.
Carbon nanotubes (CNTs) are novel carbon based nanomaterials (NMs) that could be used in many areas ranging from electronics to biotechnology. The present review summarized pharmacological and toxicological aspects of CNTs to vascular systems, because the vascular systems are important targets for CNTs during manufacturing process, daily contact and biomedical uses. Functionalized CNTs could be used as novel nanoplateforms to regulate angiogenesis for cancer therapy, as well as nanocarriers to cross blood brain barrier (BBB), one of the major obstacles to prevent the entering of therapeutic substances into brains. However, it has also been shown that inhalational or intravenous contact with CNTs might induce adverse vascular effects, such as progression of atherosclerotic plaque, vasomotor dysfunction, and changes of blood pressure and/or heart rate in laboratory animals, although currently there are only limited reports obtained from CNT-exposed human beings and the results are inconclusive. The mechanisms associated with the vascular toxicity of CNTs remain poorly understood, and it appears that multiple signaling pathways are likely to be involved. The toxicity of CNTs to vascular systems might be reduced by controlling the physicochemical properties of CNTs, particularly lengths, diameters and surface chemistry. At present, the beneficial and adverse effects of CNTs to vascular systems are still largely unknown and require further extensive studies.


Sleep duration and blood pressure: a longitudinal analysis from early to late adolescence.
The aim of this study was to evaluate the association between sleep duration and blood pressure using a cross-sectional and longitudinal approach. As part of a population-based cohort, 1403 adolescents were evaluated at 13 and 17 years old. Sleep duration was estimated by the difference between self-reported usual bedtime and wake-up time. Blood pressure was measured using the auscultatory method. Regression coefficients (β) and respective 95% confidence intervals were computed to evaluate the association between sleep duration and blood pressure, using linear regression models adjusted for practice of sports and body mass index at 17 years old. The mean (standard deviation) sleep duration at 13 years old was 9.0 (0.76) h per day, and on average it decreased by 46 min up to 17 years old. The median (25th-75th) systolic blood pressure at 17 years old was 110.0 (103.5-119.0) mmHg in females and 114.0 (106.0-122.0)mmHg in males (P < 0.001); for diastolic blood pressure the values were 66.0 (60.0-71.0) and 69.0 (62.0-75.0) mmHg, respectively (P < 0.001). In cross-sectional analysis, at 17 years old, after adjustment, a positive association was found between sleep duration and blood pressure, significant only for systolic blood pressure among females [β = 0.730 (0.005; 1.455)]. In girls, no significant association was found between sleep duration at 13 years old and blood pressure at 17 years old, but in males an inverse association was found between sleep duration at 13 years old and blood pressure at 17 years old significant only for systolic blood pressure [β = -1.938 (-3.229; -0.647)]. This study found no association between sleep duration at 13 years old and blood pressure at 17 years old in girls, but among males an inverse association was found.


[Simultaneous determination of aspartame and alitame in jellies and preserved fruits by HPLC].
To establish a determination method for aspartame and alitame in jellies and preserved fruits. Aspartame and alitame in jellies were extracted with 80% methanol at 70 degrees C. Preserved fruits were homogenized with water and then were extracted with 50% methanol. A chromatographic column Zorbax SB-C18 was used; the mobile phase was methanol/water (40 + 60, volume ratio), and a diode array detector was used for the detection at wavelength 200 nm. The limits of quantification of aspartame and alitame were both 8 mg/kg for jellies and both 20 mg/kg for preserved fruits; the calibration curves were linear in the range of tested concentration. The correlation coefficients were better than 0.9996. The average recovery rates were in the range of 98.1% -101.2%, the relative standard deviations were 2.21% - 4.10%. The method is simple, practical, accurate, reliable and successful in the determination of aspartame and alitame in jellies and preserved fruits from various brands on markets.


Cholecystocolonic fistula mimicking acute cholecystitis diagnosed unequivocally by computed tomography.
Cholecystocolonic fistula is an uncommon potential complication of cholecystitis found intraoperatively in 0.06-0.14 % of patients undergoing cholecystectomy and 0.1-0.5 % of autopsy series. Although cholecystocolonic fistula is the second most common cholecystoenteric fistula, second only to cholecystoduodenal fistula, it is diagnosed preoperatively in only 7.9 % of patients. Failure to preoperatively diagnose cholecystocolonic fistula places surgeons in precarious positions, as they may be forced to convert a seemingly routine cholecystectomy to a more sophisticated procedure coupled with adhesiolysis, colonic suturing, or colonic resection. We report a young patient who presented to the emergency department with complaints indicative of acute cholecystitis; however, preoperative ultrasound was suggestive of a cholecystoenteric fistula. Computed tomography and pathology were pathognomonic with clear visualization of the cholecystocolonic fistulous tract.


Detection of Subchondral Bone Microcirculatory Perfusion in Adults with Early Osteonecrosis of the Femoral Head Using Contrast-Enhanced Ultrasound: A Prospective Study.
The aim of this study was to quantitatively assess subchondral bone microcirculation perfusion in adults with early osteonecrosis of the femoral head (ONFH) using contrast-enhanced ultrasound (CEUS) and to evaluate its correlation with the Association Research Circulation Osseous (ARCO) stage. We investigated 97 adult patients with definite ONFH by imaging a total of 155 hips, performing CEUS, storing images of CEUS processes at different ARCO stages and generating CEUS time-intensity curves (TICs) to obtain perfusion parameters. Differences in CEUS parameters at different ARCO stages were analyzed, and correlations were explored. A logistic regression model was constructed by incorporating the meaningful CEUS indicators. The CEUS parameters time to peak (TTP), peak intensity (PI), enhanced intensity (EI), ascending slope (AS), descending slope (DS) and area under the receiver operating characteristic curve (AUC) were significantly different in ARCO stage Ⅰ compared with stage ⅢA, and the same results were obtained in stage Ⅱ compared with stage ⅢA. However, there were no significant differences between stages Ⅰ and Ⅱ. The MTT (mean transit time) assay was not significantly different between the different stages. The receiver operating characteristic curve analysis of TTP, PI, EI, AS, DS and AUC in stages Ⅰ and ⅢA had a certain diagnostic efficacy, similar to the results in stages Ⅱ and ⅢA. The diagnostic performance of DS was less accurate in stages Ⅰ and ⅢA, while the diagnostic performance of TTP was less accurate in stages Ⅱ and ⅢA. ARCO stage was independently and negatively correlated with TTP and DS and independently and positively correlated with PI, EI, AS and AUC. The MTT assay was not correlated with ARCO stage. Logistic regression models containing statistically significant TTP, EI and AUC values were constructed, and all three values were closely related to the ARCO stage. In patients with different ARCO stages of ONFH, CEUS can effectively assess subchondral bone perfusion of the femoral head and is expected to become an effective imaging method for the diagnosis of early ONFH.


Comparative study on glutathione transferases of rat brain and testis under the stress of phenobarbitol and beta-methylcholanthrene.
A comparative study was made on the tissue specific expression of glutathione transferases (GST) in brain and testis after exposure of rat to phenobarbitol (PB) and b-methylcholanthrene (MC). Glutathione transferases, a family of multifunctional proteins are involved in intracellular transport processes and in detoxication of electrophilic xenobiotics by catalyzing reactions such as conjugation, isomerization, reduction and thiolysis. On purification, the yield of GST proteins by affinity chromatography was 39% in testis and 32% in brain. The affinity purified testis GSTs were resolved by chromatofocusing into six anionic and four cationic isozymes, and in brain glutathione transferases were resolved into four anionic and three cationic isozymes, suggesting the presence of multiple isozymes with Yc, Yb, Ybeta and Ydelta in both of them. In testis and brain, these isozymes at identical pI values showed variable functions with a battery of substrates and the cationic isozymes of brain and testis showed identical properties in CHP (cumene hydroperoxide) at pH values of above 7.0. Substrate specificity studies and immunoblot analysis of testis and brain proteins revealed that they play a predominant role in the detoxication of phenobarbitol or beta-methylcholanthrene. Expression of the isozymes in testis and brain on exposure to PB and MC indicated elevated subunit variation. In both testis and brain, Ydelta of pi class was expressed on PB treatment and Yc of alpha class and Ybeta of mu class was expressed in MC treated testis and only Yc was predominantly expressed in MC treated brain. Thus these subunits expression is considered as markers for carcinogenesis and specific to chemical toxicity under phenobarbitol and beta-methylcholanthrene stress.


Surgical anatomy of the posterior liver surface: the retrohepatic lamina as the basis for mobilisation of the right liver.
During right hepatectomies, dissection of the bare area is performed to obtain mobilisation of the liver. Fifty computed tomography scans of the upper abdomen of patients were examined. Specimens of supramesocolic compartment were sampled from 10 un-embalmed cadavers. Macrosections were cut for histotopographic study. In four cadavers, in situ dissection of the posterior liver surface was performed. The hepatophrenic tissue showed a stratigraphic organisation resulting from the juxtaposition of thin layer of dense connective tissue corresponding to the inferior diaphragmatic fascia (mean thickness is 30 ± 4 μm); variable amount of fibroadipose tissue corresponding to retroperitoneal fibroadipose tissue (mean thickness is 34 ± 8 μm); two connective layers with nets of flat cells forming a fusion fascia, the retrohepatic lamina (mean thickness 24 ± 6 μm); and layer of connective tissue corresponding to the hepatic capsule. The juxta-caval portion of the retrohepatic lamina, connecting the right and left sides of the caval groove, forms the inferior vena cava ligament. During dissection, fluid injection developed a preferential plane between the two layers of the retrohepatic lamina, close to the hepatic surface, and no major or minor vessels were ever found along this plane. During right hepatectomy, to reduce the risk of dissemination of tumour cells, the dissection plane should be performed between the two layers of the retrohepatic lamina.


The endocrine control of the onset of thermogenesis at birth.
The experimental studies in the fetal sheep demonstrate that the central hypothalamic mechanisms for responding to a cold stress have differentiated well before birth. There are several major determinants of the initiation of maximal thermogenesis at birth. These are cutaneous cooling, oxygenation and separation from the placenta. Firstly the stimulation of cutaneous cold receptors regulates sympathetic nervous system activity, primarily local noradrenaline release from sympathetic nerve termini to the brown adipocyte adrenoreceptors. Circulating catecholamines, the euthyroid state and other hormones also play a role. Secondly an increase in oxygen delivery to brown adipose tissue through increased oxygen content and increased blood flow is required. Finally, our observations suggest that separation from the placenta is necessary for maximal nonshivering thermogenesis. The effects on thermogenesis of interrupting and reestablishing placental flow are rapid and reversible. Umbilical cord occlusion is the signal for a rapid increase in thermogenesis, while the release of cord occlusion is followed by an equally rapid fall in thermogenesis. This strongly suggests the presence of a placental inhibitor of brown adipose tissue thermogenesis. The problem of the regulation of growth and recruitment of brown adipose tissue in the fetus despite the lack of thermal stress in utero may be resolved by this evidence for an inhibitory factor of thermogenesis produced by the placenta. The withdrawal of the inhibitor at birth by separation from the placenta will allow the rapid initiation of thermogenesis in response to sympathetic nervous system stimulation of the brown adipose tissue.


Metabolic evolution of Corynebacterium glutamicum for increased production of L-ornithine.
L-ornithine is effective in the treatment of liver diseases and helps strengthen the heart. The commercial applications mean that efficient biotechnological production of L-ornithine has become increasingly necessary. Adaptive evolution strategies have been proven a feasible and efficient technique to achieve improved cellular properties without requiring metabolic or regulatory details of the strain. The evolved strains can be further optimised by metabolic engineering. Thus, metabolic evolution strategy was used for engineering Corynebacterium glutamicum to enhance L-ornithine production. A C. glutamicum strain was engineered by using a combination of gene deletions and adaptive evolution with 70 passages of growth-based selection. The metabolically evolved C. glutamicum strain, named ΔAPE6937R42, produced 24.1 g/L of L-ornithine in a 5-L bioreactor. The mechanism used by C. glutamicum ΔAPE6937R42 to produce L-ornithine was investigated by analysing transcriptional levels of select genes and NADPH contents. The upregulation of the transcription levels of genes involved in the upstream pathway of glutamate biosynthesis and the elevated NADPH concentration caused by the upregulation of the transcriptional level of the ppnK gene promoted L-ornithine production in C. glutamicum ΔAPE6937R42. The availability of NADPH plays an important role in L-ornithine production in C. glutamicum. Our results demonstrated that the combination of growth-coupled evolution with analysis of transcript abundances provides a strategy to engineer microbial strains for improving production of target compounds.


A simple and efficient liposome method for transfection of DNA into mammalian cells grown in suspension.
For a highly efficient plasmid transfection into mammalian cells grown in suspension, DNA was entrapped in liposomes prepared by the phosphatidylserine calcium-induced fusion method. Employing this technique, a transfection efficiency of about 2% was achieved, with 22 tk+-transformants obtained from 10(3) of mouse mammary carcinoma FM3Atk- cells transfected with a plasmid carrying the thymidine kinase (tk+) gene of the Herpes simplex virus. As compared with a previous report [Ayusawa et al., J. Biol. Chem. 258 (1983) 48-53], this transfection method was more than four orders of magnitude higher than the calcium phosphate method used for FM3Atk- cells. It was shown that the tk+ gene was integrated into the chromosomal DNA and was expressed in all the tk+-transformant clones tested. The described method could be applied to various types of DNA and cells, including those grown as monolayers.


Detection of Ketones by a Novel Technology: Dipolar Proton Transfer Reaction Mass Spectrometry (DP-PTR-MS).
Proton transfer reaction mass spectrometry (PTR-MS) has played an important role in the field of real-time monitoring of trace volatile organic compounds (VOCs) due to its advantages such as low limit of detection (LOD) and fast time response. Recently, a new technology of proton extraction reaction mass spectrometry (PER-MS) with negative ions OH- as the reagent ions has also been presented, which can be applied to the detection of VOCs and even inorganic compounds. In this work, we combined the functions of PTR-MS and PER-MS in one instrument, thereby developing a novel technology called dipolar proton transfer reaction mass spectrometry (DP-PTR-MS). The selection of PTR-MS mode and PER-MS mode was achieved in DP-PTR-MS using only water vapor in the ion source and switching the polarity. In this experiment, ketones (denoted by M) were selected as analytes. The ketone (molecular weight denoted by m) was ionized as protonated ketone [M + H]+ [mass-to-charge ratio (m/z) m + 1] in PTR-MS mode and deprotonated ketone [M - H]- (m/z m - 1) in PER-MS mode. By comparing the m/z value of the product ions in the two modes, the molecular weight of the ketone can be positively identified as m. Results showed that whether it is a single ketone sample or a mixed sample of eight kinds of ketones, the molecular weights can be detected with DP-PTR-MS. The newly developed DP-PTR-MS not only maintains the original advantages of PTR-MS and PER-MS in sensitive and rapid detection of ketones, but also can estimate molecular weight of ketones. Graphical Abstract .


The effects of lignan-riched extract of Shisandra chinensis on amyloid-β-induced cognitive impairment and neurotoxicity in the cortex and hippocampus of mouse.
The fruits of Schisandra chinensis (Trucz.) Baill. (Schisandraceae) which have been used as a tonic especially for kidney yin deficiency in Chinese traditional medicine are recently receiving attention for its preventive activity on age-related neurodegenerative diseases. A variety of studies demonstrated the cognitive-enhancing effects of Schisandra chinensis through animal tests and also in clinical trials. In this study, we attempted to investigate the effects of the lignan-riched extract of Schisandra chinensis fruits (ESP-806) on neurotoxicity and memory impairment induced by Aβ1-42 injection in mice. The fruits of Schisandra chinensis were extracted with the mixture of n-hexane:ethanol (9:1), which is riched with bioactive dibenzocyclooctadiene lignans, schizandrin, gomisin N, wuweigisu C. After oral treatment of ESP-806 (100 mg/kg body weight) followed by injection of Aβ1-42 (2 μg/mouse, i.c.v.), novel object recognition and passive avoidance tests were evaluated. To verify the cognition enhancing effects of ESP-806, we examined the effects of ESP-806 on the activities of β-secretase and acetylcholinesterase, and the contents of Aβ and the reduced glutathione within the cortex and hippocampus of Aβ-injected mice. Oral treatment of ESP-806 (100 mg/kg body weight) significantly attenuated Aβ1-42-induced memory impairment evaluated by behavioral tests. Furthermore, the treatment of ESP-806 attenuated the elevation of β-secretase activity accompanying the reduced level of Aβ1-42 in the cortex and hippocampus of the brain. ESP-806 also significantly inhibited the acetylcholinesterase activity in the hippocampus and increased the content of the reduced glutathione in the cortex and hippocampus of mouse brain. These data suggested that the extract of Schisandra chinensis fruits riched with dibenzocyclooctadiene lignans may be useful in the prevention and treatment of Alzheimer's disease.


Draft Genome Sequence of Salmonella enterica subsp. enterica Serovar Napoli Strain SN310, Cause of a Multischool Outbreak in Milan, Italy, in 2014.
We report the draft genome sequence of Salmonella enterica subsp. enterica serovar Napoli strain SN310, isolated from a stool sample of an affected pupil during a multischool outbreak in 2014 in Milan, Italy. This represents the first reported draft genome sequence of the emerging serovar Napoli.