Biochemical effects of methyl chloride in relation to its tumorigenicity.
The biochemical effects of methyl chloride were investigated in tissues of F-344 rats and B6C3F1 mice (both sexes). Activities of GST were 2-3 times higher in livers of male B6C3F1 mice, compared with those of female mice, and with rats of both sexes. In kidneys GST activities of (male) mice were about 7 times lower than those found in livers. The activity of FDH was higher in livers of mice (both sexes) than in those of rats. No obvious sex difference was found in livers of rats and mice with respect to FDH. In kidneys, however, (minor) differences in FDH activities occurred between male and female B6C3F1 mice (4.7 vs. 3.1 nmol/min per mg). Sex differences of FDH activity in kidneys were not observed in F-344 rats. The microsomal transformation (by cytochrome P-450) of methyl chloride and S-methyl-L-cysteine to formaldehyde in tissues of B6C3F1 mice occurred preferentially in the liver. More formaldehyde was produced in liver microsomes of male, compared to those of female mice. Kidney microsomes metabolized methyl chloride to formaldehyde much less than liver microsomes. After a single exposure of mice of both sexes to 1000 ppm methyl chloride no elevation in formaldehyde concentrations was observed in livers and kidneys ex vivo. The determination of DNA lesions, using the alkaline elution technique, revealed no DNA-protein crosslinks in kidneys of male B6C3F1 mice after exposure to methyl chloride (1000 ppm, 6 h day-1, 4 days) and gave only minor evidence of single-strand breaks. Lipid peroxidation (production of TBA reactive material), induced by single exposure to methyl chloride (1000 ppm, 6 h), was very pronounced in livers of male and female mice. Smaller increases in peroxidation were observed in the kidneys of exposed mice. The theory that renal tumors observed in male mice after chronic exposure of the test animals to high (1000 ppm) concentrations of methyl chloride, are evoked by intermediates and in situ produced formaldehyde is proven unlikely by our results.


Trends and psychosocial correlates of same day polysubstance use among people who inject drugs in Australia, 2012-2022.
Polysubstance use is associated with negative health and social outcomes among people who inject drugs. We aimed to describe trends in polysubstance use and identify psychosocial correlates and associated drug use risk behaviours. We defined polysubstance use as intentional same day use of more than one of three drug classes: opioids, other non-opioid depressants (hereafter 'depressants'), and stimulants. We used 10 years (2012-2022, excluding 2020) of data from annual surveys in Australian capital cities with people who inject drugs (N=5657) to construct five mutually exclusive polysubstance use profiles: opioid-depressant, opioid-stimulant, stimulant-depressant, opioid-stimulant-depressant, and single drug class use. We examined time trends using the Mann Kendall test and identified correlates using multinomial logistic regression. Same day polysubstance use was relatively common among this sample (43.6%). Opioid-depressant use was the most frequent polysubstance use profile, but this decreased over the study period (32.6% to 13.3%, p<0.001). This aligned with observed decreases in use of pharmaceutical opioids (p<0.001), opioid agonist treatment (p=0.007), and benzodiazepines (p=0.001). There was no evidence for any trend in the other polysubstance use profiles, although single drug class use increased (51.9% to 64.7%, p=0.031). The different polysubstance use profiles were variously associated with psychosocial factors, including unstable housing and very high psychological distress, and other drug use risk behaviours, including non-fatal overdose, receptive and/or distributive needle sharing, and reusing one's own needles. Same day polysubstance use has remained relatively common among this sample over time, although the typology has changed. Collectively, our findings point to diverse drug use patterns among people who inject drugs and reiterate the need for a range of harm reduction, treatment, and support options.


Presence in invertebrate genomes of sequences characterized by the repetition of the triplet CCPurine.
In Drosophila melanogaster (Dm), polypeptidic domains have been found in different morphogenetic genes. Two types of them are characterized by the repetition of nucleotidic triplets: the M repeat (CAX) and the paired repeat (CAXCCX). In this paper we described a third type of repeat isolated from the genome of a Polychaete annelid: Owenia fusiformis. This repeat is characterized by the repetition of the triplet CCPurine. Phylogenetic studies showed the presence of this repeat in all the invertebrate genomes tested (eight copies in Dm genome) while we failed to detect it in vertebrate genomes.


Mass-producible superhydrophobic surfaces.
Mass-producible superhydrophobic surfaces with remarkably identical appearance and efficiency through a mold fabrication and hot embossing process are reported.


Students' and lecturers' perspectives on the implementation of online learning in medical education due to COVID-19 in Germany: a cross-sectional pilot study.
During the coronavirus disease 2019 (COVID-19) crisis, many things changed in universities around the world. In-person learning was not possible. Instead, courses were offered in digital form. The sudden change posed enormous challenges to universities, students, and teachers. The aim of this study was to investigate the disadvantages as well as the advantages and opportunities of digital learning. This study investigated the evaluation of an elective module by medical students and teachers in the traditional in-person and virtual teaching forms during the COVID-19 pandemic. Using the elective module "Sports Medicine," which includes both lectures and practical units, the opinions of the medical students about conventional teaching compared to digital instruction were evaluated. In the winter semester of 2019/2020, all classes were taught face-to-face but had to be switched to virtual teaching in the summer semester of 2020 on an ad hoc basis due to the pandemic. The students were asked to answer questions on general conditions, participant behavior, instructor evaluation, skill acquisition, topic selection, and overall evaluation after both forms of teaching. Likewise, the lecturers of both courses were queried in semiqualitative interviews about the same topics. Descriptive data analysis was performed to process the data. The students perceived digital teaching to be superior in most subareas compared to in-person teaching in terms of framework, instructor evaluation, skill acquisition, topic selection, and overall rating. Medical students seemed to feel better with digital teaching in most areas of evaluation. The lecturers found the new form of teaching rather unsettling and criticized the lack of verbal and especially nonverbal communication as well as the short preparation time for the new challenge. The instructors were uncomfortable with some aspects of the virtual teaching format. In the wake of the COVID-19 pandemic, medical schools should rapidly digitize their teaching offerings and support faculty members in their computer-based competence with continuing education opportunities and time resources.


Impact of bariatric surgery on fetal growth restriction: experience of a perinatal and bariatric surgery center.
Bariatric surgery is known to improve some pregnancy outcomes, but there is concern that it may increase the risk of small for gestational age. To assess the impact of bariatric surgery on pregnancy outcomes and specifically of the type of bariatric surgery on the risk of fetal growth restriction. A single-center retrospective case-control study. The study group comprised all deliveries in women who had undergone bariatric surgery. To investigate the effects of weight loss on pregnancy outcomes, we compared the study group with a control group matched for presurgery body mass index. Secondly, to assess the specific impact of the type of surgery on the incidence of fetal growth restriction in utero, we distinguished subgroups with restrictive and malabsorptive bariatric surgery, and compared outcomes for each of these subgroups with a second control group, matched for prepregnancy body mass index. Among 139 patients operated, 58 had a malabsorptive procedure (gastric bypass) and 81 a purely restrictive procedure (72 a gastric banding and 9 a sleeve gastrectomy). Compared with controls matched for presurgery body mass index, the study group had a decreased rate of gestational diabetes (12% vs 23%, P = .02) and large for gestational age >90th percentile (11% vs 22%, P = .01) but an increased rate of small for gestational age <10th percentile. The incidence of small for gestational age was higher after gastric bypass (29%) than it was after restrictive surgery (9%) or in controls matched for prepregnancy body mass index (6%) (P < .01 between bypass and controls). In multivariable analysis, after adjustment for other risk factors, gastric bypass remained strongly associated with small for gestational age (adjusted odds ratio, 7.16; 95% confidence interval, 2.74-18.72). Malabsorptive bariatric surgery was associated with an increased risk of fetal growth restriction.


Glutamine relieves the hypermetabolic response and reduces organ damage in severe burn patients: A multicenter, randomized controlled clinical trial.
Severe burns can cause a hypermetabolic response and organ damage. Glutamine is a conditionally essential amino acid with various pharmacological effects. In this study, whether glutamine could alleviate the hypermetabolic response and maintain organ function after burn injury was analyzed. A multicenter, randomized, single-blind, parallel controlled trial was conducted to evaluate the efficacy of glutamine in decreasing hypermetabolism after burn injury. Physiological and biochemical indexes, such as vital signs, metabolic hormones, metabolic rate, and organ damage, were recorded on the 7th and 14th days after treatment. In total, 55 adult burn patients with a total burn surface area (TBSA) of 30-70% were included in this study and randomly divided into the burn control (B, 28 patients) and burn+glutamine (B+G, 27 patients) groups. Except for the glutamine administration, the groups did not differ in the other treatments and nutrition supplements. The levels of diamine oxidase (DAO), lactulose/mannitol (L/M), β2-microglobulin, lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBD) and cardiac troponin l (cTnl) in the B+G group were significantly lower than those in the B group (p < 0.05 or 0.01). The levels of resting energy expenditure (REE), serum catecholamines, glucagon, lactate and Homeostasis model assessment (HOMA) in the B+G group were significantly lower than those in the B group (p < 0.05 or 0.01). No significant difference was found in the length of hospitalization or the mortality rate between the two groups (p > 0.05). Glutamine moderately alleviates the hypermetabolic response and reduces organ damage after severe burns. Therefore, the early application of glutamine, which is effective and safe, should be used as an active intervention as early as possible.


Identification of the main active antidepressant constituents in a traditional Turkish medicinal plant, Centaurea kurdica Reichardt.
In Turkish folk medicine, infusions and decoctions prepared from the flowers, fruits and aerial parts of Centaurea kurdica Reichardt (Asteraceae) are used as sedative and antidepressant-like effects of various sedative plants have been identified in many studies. The present study was designed to evaluate the antidepressant activity of this plant. n-Hexane, ethyl acetate (EtOAc), and methanol (MeOH) extracts were prepared from the branches with leaves and also flowers of the plant. Antidepressant potentials of these extracts were researched by using the forced swimming test, tail suspension test, and antagonism of tetrabenazine-induced ptosis, hypothermia, and suppression of locomotor activity. After determination of high antidepressant potentials of MeOH extract prepared from flowers and n-hexane extract prepared from branches with leaves, isolation studies were carried out on these two extracts and the main active components were determined as β-amyrin, mixture of β-sitosterol and stigmasterol and costunolide for the branches with leaves and quercitrin, isoquercetin and naringenin-7-O-glucopyranoside for the flowers. As a result of the mechanistic and toxicity studies planned on this plant, it is thought that C. kurdica may be a glimmer of hope for depressed patients.


Adversarial symmetric GANs: Bridging adversarial samples and adversarial networks.
Generative adversarial networks have achieved remarkable performance on various tasks but suffer from training instability. Despite many training strategies proposed to improve training stability, this issue remains as a challenge. In this paper, we investigate the training instability from the perspective of adversarial samples and reveal that adversarial training on fake samples is implemented in vanilla GANs, but adversarial training on real samples has long been overlooked. Consequently, the discriminator is extremely vulnerable to adversarial perturbation and the gradient given by the discriminator contains non-informative adversarial noises, which hinders the generator from catching the pattern of real samples. Here, we develop adversarial symmetric GANs (AS-GANs) that incorporate adversarial training of the discriminator on real samples into vanilla GANs, making adversarial training symmetrical. The discriminator is therefore more robust and provides more informative gradient with less adversarial noise, thereby stabilizing training and accelerating convergence. The effectiveness of the AS-GANs is verified on image generation on CIFAR-10, CIFAR-100, CelebA, and LSUN with varied network architectures. Not only the training is more stabilized, but the FID scores of generated samples are consistently improved by a large margin compared to the baseline. Theoretical analysis is also conducted to explain why AS-GAN can improve training. The bridging of adversarial samples and adversarial networks provides a new approach to further develop adversarial networks.


Going Farther by Going Together: Collaboration as a Tool in Advocacy.
With greater understanding of the impact of social determinants on child health, advocacy has become essential to promoting children's health, particularly at the population level. Successful advocacy requires coalition building. Steps on how to create a productive coalition, including the selection of partner organizations, understanding how these groups enhance your activities, and strict definition of assigned roles is reviewed. Examples of successful coalitions are reviewed. A list of potential partners, who focus on various aspects of child health, is provided.


Noise Exposure Criteria for Harbor Porpoises.
Despite a major research effort, no generally accepted exposure limits are available for harbor porpoises. Recent studies of the temporary threshold shift (TTS) in porpoises indicate that the sound exposure levels (SELs) required to induce low levels of TTS depend on stimulus frequency and roughly parallel the shape of the audiogram. A number of studies on behavioral avoidance reactions (negative phonotaxis) to pingers, seal scarers, and pile driving show a similar dependence on stimulus frequency. Both TTS and behavioral data suggest that weighting sound pressure levels with a filter function resembling the inverted audiogram would be appropriate.


Interstellar extinction by graphite, iron and silicate grains.
Recent data on the interstellar extinction curve and on the diffuse galactic light may be accounted for by a mixture of graphite, iron and silicate grains.


Potential Therapeutic Effects of Mg/HCOOH Metal Organic Framework on Relieving Osteoarthritis.
This study was designed to explore the potential therapeutic effects of Mg-based metal organic frameworks (MOFs) in osteoarthritis (OA) and to broaden the application field of MOFs. Mg/HCOOH-MOF was introduced and characterized by using SEM, XRD, TGA, and FTIR. ICP-MS results proved that Mg/HCOOH-MOF is stable in various physiological media and can maintain the release of Mg2+ ions for a long time. In vitro experiments were carried out to evaluate its potential application in attenuating OA. Mg/HCOOH-MOF was successfully synthesized, and results of MTT assays showed that it is biocompatible and can promote cell proliferation. qPCR results suggested that it can significantly regulate the expression of OCN, Axin2, iNOS and IL-1β, which indicated its activity in anti-inflammation and bone protection. We believe that Mg/HCOOH-MOF could benefit OA therapy.


Enhancing Effects of Immobilized Chondroitin Sulfate on Odontogenic Differentiation of Dental Pulp Stem Cells and Reparative Dentin Formation.
Chondroitin sulfate (CS) is a major proteoglycan involved in the mineralization of the organic matrix of dentin. In this study, the roles of CS immobilized in cross-linked collagen I (Col I) hydrogels on odontogenic differentiation of dental pulp stem cells (DPSCs) and reparative dentin formation were investigated. Different concentrations of CS were incorporated into the genipin-cross-linked Col I hydrogels (CS-0.05, CS-0.1, and CS-0.2, respectively). The influences of CS on the proliferation and odontogenic differentiation of DPSCs were investigated. Finally, the effect of the functionalized hydrogel on the formation of reparative dentin was analyzed in a rat pulp capping model in vivo. CS improved the proliferation of DPSCs seeded on the hydrogels (P < .05). CS also enhanced the mineralization activities and increased the expression levels of the odontogenic-related proteins of DPSCs on days 7 and 14 (P < .05). In vivo, CS-0.1 hydrogel induced reparative dentin formation with higher quality compared with mineral trioxide aggregate. CS immobilized in Col I hydrogels could induce odontogenic differentiation of DPSCs in vitro and promote homogeneous mineralized barrier formation in vivo. CS-Col I hydrogel has the potential for reparative dentin formation of high quality in direct pulp capping.


Prognostic factors for recurrence and survival in primary vulvar squamous cell cancer.
To evaluate survival estimates and clinico-pathological variables in women with primary vulvar squamous cancer. Retrospective observational study. Setting. University hospital in Turkey. Patients treated for primary vulvar squamous cancer. Retrospective evaluation of demographic, pathologic and follow-up data of 91 patients obtained from hospital records and private gynecologic oncology files. Recurrence rate and survival estimates. The mean age at the time of diagnosis was 62 years. Of the women, 62% had early stage disease (stages I-II), while 39% had advanced stages (stages III-IV) at diagnosis. The overall recurrence rate was 13%. Recurrence rates were significantly higher in the presence of local wide-deep excision as an initial treatment, larger initial tumor size, positive lymph node involvement, advanced stage, presence of ulcerative lesions and adjuvant radiotherapy. The overall and 5-year survival estimates were 92 and 83%, respectively. Lymph node invasion, stage, having ulcerative lesion, receiving adjuvant therapy, tumor diameter larger than 10 mm and having local excision as primary surgery may increase the risk of recurrent disease.


Reduction of radiation dose estimates in cardiac 64-slice CT angiography in patients after coronary artery bypass graft surgery.
The objectives of this prospective investigation in patients after bypass graft surgery were (1) to estimate radiation dose for routine bypass graft computed tomography (CT) angiography, (2) to study the impact of anatomically adapted and ECG-controlled tube current modulation on radiation dose estimates, and (3) effects on qualitative and quantitative image quality parameters. Radiation dose was estimated for 194 consecutive patients undergoing 64-slice CT angiography (Somatom Sensation 64 Cardiac, Siemens Medical Solutions). The impact of anatomically adapted tube current modulation was studied in 2 consecutive patients groups. Furthermore, the impact of ECG-controlled tube current modulation, applied as indicated, was evaluated in both groups. Mean radiation dose estimate for a 64-slice CT bypass graft study was 18.9 +/- 6.0 mSv (CTDIvol 42.3 +/- 12.9 mGy). The application of anatomically adapted tube current modulation had no effect on dose parameters (CTDIvol 43.3 +/- 13.2 vs. 40.1 +/- 12.1 mGy for those with versus those without anatomically adapted tube current modulation, P = 0.1). Additional implementation of ECG-controlled tube current modulation resulted in reduced dose parameters (CTDIvol of 32.9 +/- 2.6 vs. 58.9 +/- 3.9 mGy and radiation dose estimates: 14.7 +/- 1.9 mSv vs. 26.5 +/- 2.1 mSv for those with versus those without ECG pulsing, both P < 0.01). There was no deterioration in image quality with use of tube current modulation algorithms. The radiation burden associated with 64-slice bypass graft CT angiographies is substantial. Anatomically adapted tube current modulation does not reduce radiation dose parameters, whereas ECG-controlled tube current modulation was associated with a 45% reduction in dose estimates. Application of both tube current modulation algorithms did not result in reduced image quality.


Age-related changes in adipose tissue metabolomics and inflammation, cardiolipin metabolism, and ferroptosis markers in female aged rat model.
Aging adipose tissue exhibits elevated inflammation and oxidative stress that are major sources of age-related metabolic dysfunction. However, the exact metabolic changes associated with inflammation and oxidative stress are unclear. To address this topic, we assessed variation in metabolic phenotypes of adipose tissue from 18 months adult sedentary (ASED), 26 months old sedentary (OSED), and 8 months young sedentary (YSED). The results of metabolomic analysis showed that ASED and OSED group had higher palmitic acid, elaidic acid, 1-heptadecanol, and α-tocopherol levels than YSED, but lower sarcosine levels. Furthermore, stearic acid was specifically elevated in ASED compared with YSED. Cholesterol was upregulated specifically in the OSED group compared with YSED, whereas linoleic acid was downregulated. In addition, ASED and OSED had more inflammatory cytokines, lower antioxidant capacity, and higher expression of ferroptosis-related genes than YSED. Moreover, mitochondrial dysfunction associated with abnormal cardiolipin synthesis was more pronounced in the OSED group. In conclusion, both ASED and OSED can affect the FA metabolism and increase oxidative stress in adipose tissue, leading to inflammation. In particular, linoleic acid content specifically decreases in OSED, which associated with abnormal cardiolipin synthesis and mitochondrial dysfunction in adipose tissue.


Reversible inactivation of cytochrome P450 by alkaline earth metal ions: auxiliary metal ion induced conformation change and formation of inactive P420 species in CYP101.
The effects of the divalent alkaline-earth metal ions (Ca2+ and Mg2+) on the substrate binding affinity, spin-state transition at the heme active site, conformational properties as well as the stability of the active form of cytochrome P450cam (CYP 101) have been investigated using various spectroscopic and kinetic methods. The divalent cations were found to have two types of effects on the enzyme. At the initial stage the alkaline-earth metal ion facilitated enhanced binding of the substrate and formation of the high-spin form of the heme active center of the enzyme compared to that in absence of any metal ion. However, analogous to many other mono-valent metal ions, the alkaline-earth metal ions were also less efficient than K+ in promoting the substrate binding and spin-transition properties of the enzyme. The auxiliary metal ions were shown to cause small but distinct change in the circular dichroism spectra of the substrate-free enzyme in the visible region, indicating that the tertiary structure around the heme was perturbed on binding of the auxiliary metal ion to the enzyme. The effect of the auxiliary metal ion was found to be more prominent in the WT enzyme compared to the Y96F mutant of P450cam suggesting that the Tyr 96 residue plays an important role in mediating the effects of the auxiliary metal ions to the active site of the enzyme. At the second stage of interaction, the alkaline-earth metal ions were found to slowly convert the enzyme into an inactive P420 form, which could be reversibly re-activated by addition of KCl. The results have been discussed in the light of understanding the mechanism of inactivation of certain mammalian P450 enzymes by these alkaline-earth metal ions.


Family-Professional Collaboration on Modified Ride-on Car Intervention for Young Children: Two Case Reports.
The study aimed to describe the implementation of a collaborative ride-on car (ROC) intervention by applying a practice model of family-professional collaboration. The model involves specific strategies for collaboration, "visualizing a preferred future" and "scaling questions." The participants were two young children with mobility limitations and their mothers. The 12-week of ROC intervention involved training sessions with a therapist and home sessions. The outcomes included the Canadian Occupational Performance Measure (COPM) and Goal Attainment Scaling (GAS). The collaborative strategies facilitated parent engagement in goal setting, planning, and evaluation. After the intervention, the mothers' ratings of their children's performance and parent satisfaction on the COPM increased by 6 and 3 points, respectively, and the level of goal attainment exceeded expectations (+1 on GAS) in both families. Prior to the ROC intervention, both families were hesitant to use powered mobility. However, the experience of participating in the ROC intervention process broadened parents' perspectives on self-directed mobility and led them to explore options for their children to move independently. The collaborative ROC intervention can be used as an intervention for early mobility and a bridging step for families reluctant to use a powered wheelchair.


Pattern of neutral and phospholipids in the semen of normospermic, oligospermic and azoospermic men.
Total lipid concentration was elevated in the seminal plasma of oligo- and azoospermic men. The total cholesterol content was comparatively more in the seminal plasma of azoospermic men than in that of normo- and oligospermic men. In general, infertility was associated with increased seminal concentrations for most of the neutral lipid classes. However, total phospholipids and most of the phospholipid classes were diminished in the seminal plasma of oligo- and azoospermic men and in the spermatozoa of oligospermic men. We suggest that there is a positive correlation between seminal phospholipids and fertility and a negative correlation between seminal neutral lipids and fertility.


Orbitozygomatic approach for excisions of orbital tumors with 1 piece of craniotomy bone flap: 2 case reports.
Orbital tumors are classified as primary and secondary. For primary entities, there are variable pathologies with benign and malignant natures. Many of the orbital tumors should be excised through neurosurgical approaches. We reported 2 cases of orbital tumors, which were clearly disclosed by magnetic resonance imaging. Case 1 was a 70-year-old woman and case 2 was a 57-year-old woman. Both cases were presented with progressive unilateral proptosis. The pathologies were intraorbital cavernous hemangioma and lacrimal mixed adenoma, respectively. With the scalp incision all posterior to the hairline, frontotemporal orbitozygomatic approach with 1 piece of craniotomy bone flap was performed after freeing all the remaining periorbita and other soft tissue attachments. This approach assures maximum exposure for successful en bloc excisions of these tumors with minimal bone loss, so the cosmetic results are satisfactory. Even though most orbital tumors are diagnosed by ophthalmologists, most of them should be operated on by neurosurgeons because neurosurgical approaches offer wide and safe surgical windows.


Characteristics of polymerase chain reaction-positive syphilis cases in Manitoba, Canada, 2017 to 2020: Demographic analysis, specimen types, and Treponema pallidum gene targets.
A resurgence of syphilis infections has been described in a number of countries including Canada in the last decade. This study identified polymerase chain reaction (PCR) positive syphilis cases based on detection of Treponema pallidum genes (polA, tpp47, and bmp) in 3,350 clinical specimens obtained from patients in the province of Manitoba, Canada between 2017 and 2020. Patient demographics were obtained from specimen requisition forms. PCR identified 740 syphilis cases: 718 were adolescents and adults, while 22 were congenital syphilis cases. For non-congenital syphilis investigation, the clinical specimens with the highest yield of positive PCR results were genital (632), oral (73), and anal (55), while for congenital syphilis, they were nasal or nasopharyngeal secretions (20), followed by blood (5) and umbilical cord (4). Female syphilis cases appeared younger (61.7% between 14 and 29 years), while male syphilis cases appeared older (58.4% between 30 and 65 years). Although, overall more syphilis cases (62.7%) occurred in the urban cities; the proportion of urban cases showed a significant decline from 87.0% in 2017 to 55.6% in 2020, while in rural regions it increased from 13.0% in 2017 to 44.4% in 2020. Most (98.8%) PCR- positive specimens were found to contain all three T. pallidum genes and 99.8% also displayed the macrolide resistance genotype. This study identified the clinical specimen types and T. pallidum genes most suitable for PCR diagnosis of syphilis. Changing demographics of cases were noted over time.


[The treatment of sub-glottic stenosis by continuous dilatation. Long term results (author's transl)].
From 1973 to 1977, 15 patients with laryngeal stenosis were treated by a method of continuous dilatation in the ENT department of the "Enfants Malades" Hospital. The results were viewed with regard to the importance of the complications, the chance of decanulation, the carrying time of the canula, adaptation to effort, functional respiratory tests, the value of language, intellectual and psychic repercussions, and repercussions on the social life. In this series the method of dilatation seems remarkably reliable.


Nucleoside triphosphatase from the hen's egg white and vitelline membrane: purification, properties and relation to similar enzymes from the oviduct.
Hen's egg white and vitelline membrane nucleoside triphosphatases were purified resulting in active soluble subunits with MR 260,000 +/- 10,000. PH optima are divalent cation dependent and situated at pH 6.2 and 8.0 with ATP and at pH 6.15 with ADP as substrate. Ca2+ and Mg2+ are activators. Km and Ki values for Pi and PPi were determined. The enzymes are specific neither for ATP nor for ADP alone. No separation between nucleoside triphosphatase and nucleoside diphosphatase could be achieved. Differences found in their action can be due to differences in organization and properties of the (intermediary) enzyme-substrate complexes. A close relationship exists with homologous enzymes found in oviductal secretory cells and in oviductal secretions.


Effects of hydrochlorothiazide, amiloride, and lisinopril on the metabolic response to adrenaline infusions in normal subjects.
Twelve healthy male volunteers were given adrenaline infusions, 0.05 microgram/kg body weight/min over 120 minutes in order to achieve serum adrenaline concentrations comparable with those seen in acute myocardial infarction. The infusions were given on four occasions, at intervals of at least 4 weeks. Before the infusions the subjects were given, in random order, 14 days of pretreatment with placebo, hydrochlorothiazide 50 mg once daily, amiloride 10 mg once daily, or lisinopril 20 mg once daily. The adrenaline infusion induced a drop in serum potassium of the same magnitude in all four groups, with the lowest absolute value after hydrochlorothiazide because of the lowest pre-adrenaline level. The infusion-induced decreases in serum calcium and magnesium were of the same magnitude in all groups, with the absolute calcium being least low in the hydrochlorothiazide group because of the highest preinfusion value. Preinfusion serum urate was highest after hydrochlorothiazide and fell during the adrenaline infusion in all groups, although not significantly. Blood glucose increased during the adrenaline infusion in all groups, but significantly more after hydrochlorothiazide and amiloride than after lisinopril. Heart rate increased during the adrenaline infusion in all groups but least after lisinopril. QTc preinfusion was longer after hydrochlorothiazide than after amiloride and placebo, but the infusion-induced prolongation of QTc was of the same magnitude in all pretreatment groups. Since our results were obtained in short-term experiments in normal subjects, their clinical relevance is questionable, but they support the view that ACE inhibitors may have certain metabolic advantages over diuretics.


Moyamoya disease as a cause of subarachnoid haemorrhage. A case report.
A woman with a subarachnoid haemorrhage secondary to an aneurysm associated with moyamoya disease is reported. Moyamoya disease is a rare but well-described disease of the intracranial carotid artery, characterised by an unusual vascular network at the base of the brain.


Effect of glucose administration on hamster liver S9-mediated mutagenesis, metabolism and DNA-binding of benzo[a]pyrene and aflatoxin B1.
Hamster liver S9 prepared from control animals and animals given 30% glucose in drinking water 48 h before killing was used in studies of benzo[a]pyrene (BaP) and aflatoxin (AFB1)-induced mutagenesis, metabolism of BaP and AFB1, and metabolite binding to calf thymus DNA. BAP-induced mutagenesis in Salmonella typhimurium TA100 was reduced 38.5% while AFB1-induced mutagenesis was increased 36% by S9 from glucose-treated hamsters. The reduction of [3H]BaP metabolite binding to calf thymus DNA in incubations with S9 from glucose-treated hamsters correlated with a decrease in unknown BP metabolite-deoxyribonucleoside adducts isolated by high performance liquid chromatography (HPLC). Differences in the 7R and 7S-diol epoxide-1 and 2 deoxyguanosine adducts of BaP between control and glucose-treated S9 were not observed. HPLC analysis of AFB1-DNA adducts showed a 25% increase in [3H]AFB1-N7-guanine in incubations of glucose-treated S9 with [3H]AFB1 and calf thymus DNA. HPLC analysis of the organosoluble fraction of incubations with [3H]BaP and [3H]AFB1 indicated a significant effect by glucose-treated S9 on metabolism. The effect of glucose on metabolism was further reflected in the reduction of both BaP and AFB1 metabolite conjugation with glucuronide and glutathione as determined by separation on an alumina column. These results indicate that the oral administration of 30% glucose in drinking water alters hamster liver S9-mediated mutagenesis and binding of BaP and AFB1 metabolites to DNA through an effect on the metabolism of these two carcinogens.


MetalPredator: a web server to predict iron-sulfur cluster binding proteomes.
The prediction of the iron-sulfur proteome is highly desirable for biomedical and biological research but a freely available tool to predict iron-sulfur proteins has not been developed yet. We developed a web server to predict iron-sulfur proteins from protein sequence(s). This tool, called MetalPredator, is able to process complete proteomes rapidly with high recall and precision. The web server is freely available at: http://metalweb.cerm.unifi.it/tools/metalpredator/ firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Expression and characterization of novel ovine orthologs of bovine placental prolactin-related proteins.
The prolactin-related proteins (PRPs) are non-classical placental-specific members of the prolactin/growth hormone family. Among ruminants, they are expressed in the cotyledonary villi of cattle and goat. We investigated placental PRP in sheep in order to gain a comprehensive understanding of the function and evolution of these molecules. We also examined the sequence properties, expression and lactogenic activation of the cloned genes. We cloned two novel ovine PRPs, named oPRP1 and oPRP2. oPRP2 had a typical PRP sequence similar to bovine PRP1 (bPRP1). oPRP1 had a short sequence identical with bovine or caprine type PRP but the reading frame was shifted. Both oPRPs were expressed in trophoblast giant binucleate cells (BNC) as in cattle and goat. oPRP1 expression declined from the early to the middle stage of gestation. In contrast, oPRP2 expression remained constant throughout the gestation period. oPRP2 was translated to form a mature protein in a mammalian cell expression system. Western blotting showed a molecular mass of 35 kDa for the FLAG-tag fusion oPRP2 protein. This recombinant protein and bPRP1 were bioassayed using Nb2 lymphoma cells; it was confirmed that neither ruminant PRP had lactogenic activity because the Nb2 lymphoma cells did not proliferate. We have identified two novel PRPs, oPRP1 and oPRP2, in ovine placenta. Both these ovine PRPs were localized and quantitatively expressed in BNC. Absence of lactogenic activity was confirmed for the oPRP2 molecule. It is anticipated that novel and known ruminant PRPs have common functions, except for lactogenic activity.


Effect of plasma activated water on the postharvest quality of button mushrooms, Agaricus bisporus.
Non-thermal plasma is a new approach to improving microbiological safety while maintaining the sensory attributes of the treated foods. Recent research has reported that plasma activated water (PAW) can also efficiently inactivate a wide variety of microorganisms. This study invested the effects of plasma-activated water soaking on the postharvest preservation of button mushrooms (Agaricus bisporus) over seven days of storage at 20°C. Plasma activated water reduced the microbial counts by 1.5 log and 0.5 log for bacteria and fungi during storage, respectively. Furthermore, the corresponding physicochemical and biological properties were assessed between plasma activated water soaking groups and control groups. The results for firmness, respiration rate and relative electrical conductivity suggested that plasma activated water soaking can delay mushroom softening. Meanwhile, no significant change was observed in the color, pH, or antioxidant properties of A. bisporus treated with plasma activated water. Thus, plasma activated water soaking is a promising method for postharvest fresh-keeping of A. bisporus.


Parathyroid hormone increases thiol proteinase activity by activation of protein kinase C in cultured kidney tubule cells (OK).
Chronic exposure (24 h) to parathyroid hormone (PTH) increases the intracellular proteolytic activity in cultured opossum kidney cells 2-fold at physiological PTH concentrations (10(-12) mol/l). This increase can be blocked by E-64, an inhibitor of thiol proteinases. The phorbol ester TPA mimicks the effect of PTH, whereas the calcium ionophore A23187 reduces the intracellular proteinase activity. Forskolin and dibutyrylic cAMP do not elevate proteinase activity. The protein kinase C inhibitor staurosporine is equally effective in blocking the TPA- and PTH-induced proteinase activity increase. These data indicate that PTH increases the intracellular thiol proteinase activity by an activation of protein kinase C and not by the cAMP dependent way.


Significance of rehabilitative management during the critical period for motor recovery in intracerebral hemorrhage: a case report.
The majority of motor recovery following stroke is known to occur within 3-6 months after onset; this period is therefore regarded as critical for motor recovery in stroke patients. We report here a case of a patient with intracerebral haemorrhage who showed changes in the affected motor function and in the damaged corticospinal tract (CST) at the primary motor cortex (M1) during rehabilitative management. A 51-year-old woman underwent decompressive craniectomy and removal of haematoma due to a rupture of an arteriovenous malformation. Brain magnetic resonance imaging revealed a leukomalactic lesion at the fronto-parietal cortex centred on the precentral knob. Diffusion tensor imaging data were acquired 4 times (5, 8, 11 and 18 weeks after onset) and she started rehabilitation for right hemiplegia at 5 weeks after onset. We found close relationships between changes in the CST branch from M1 on diffusion tensor tractography, the state of motor weakness, and the rehabilitative management: the CST branch from M1 was observed concurrently with motor recovery and the process of rehabilitation. This case report indicates the importance of active and comprehensive rehabilitative management during the critical period for motor recovery in stroke patients.


Influence of Anodizing Parameters on Surface Morphology and Surface-Free Energy of Al₂O₃ Layers Produced on EN AW-5251 Alloy.
The paper presents the influence of the surface anodizing parameters of the aluminum alloy EN AW-5251 on the physicochemical properties of the oxide layers produced on it. Micrographs of the surface of the oxide layers were taken using a scanning electron microscope (SEM). The chemical composition of cross-sections from the oxide layers was studied using energy dispersive spectroscopy (EDS). The phase structure of the Al₂O₃ layers was determined by the pattern method using X-ray diffractometry (XRD). The nanomorphology of the oxide layers were analyzed based on microscopic photographs using the ImageJ 1.50i program. The energetic state of the layers was based on the surface-free energy (SFE), calculated from measurements of contact angles using the Owens-Wendt method. The highest surface-free energy value (49.12 mJ/m²) was recorded for the sample produced at 293 K, 3 A/dm², in 60 min. The lowest surface-free energy value (31.36 mJ/m²) was recorded for the sample produced at 283 K, 1 A/dm², in 20 min (the only hydrophobic layer). The highest average value nanopore area (2358.7 nm²) was recorded for the sample produced at 303 K, 4 A/dm², in 45 min. The lowest average value nanopore area (183 nm²) was recorded for the sample produced at 313 K, 1 A/dm², in 20 min.


Isolation and sequence of a cDNA clone for rabbit fast skeletal muscle troponin C. Homology with calmodulin and parvalbumin.
The binding of Ca2+ to troponin C (TnC) regulates skeletal muscle contraction. We have isolated a full-length cDNA clone for fast skeletal muscle TnC from a neonatal rabbit skeletal muscle library and determined its nucleic acid sequence. The amino acid sequence deduced from this clone matches the previously reported amino acid sequence (Collins, J. H., Greaser, M. L., Potter, J. D., and Horn, M. J. (1977) J. Biol. Chem. 252, 6356-6362) except at the amino terminus. According to the nucleotide sequence, the first 2 residues of TnC are threonine-aspartic acid, which is the reverse of the order reported previously. The isolation of the adult form of TnC from a neonatal library suggests that there may be no developmental isoforms of fast TnC. The protein coding region of the fast TnC clone has 67% homology with the reported nucleotide sequence for chicken slow TnC (Putkey, J. A., Carroll, S. L., and Means, A. R. (1987) Mol. Cell. Biol. 7, 549-1553). The homologies between the nucleotide sequences of TnC, calmodulin, and parvalbumin provide evidence that all three proteins were derived from a common precursor molecule which had four Ca2+-binding sites.


Dissipation of penconazole formulation in horticultural crops by ultrahigh performance liquid chromatography-high resolution mass spectrometry: From the active substance to metabolites.
The present study describes the dissipation and metabolism of penconazole in horticultural products by a method based on ultra-high performance liquid chromatography-quadrupole-orbitrap (UHPLC-Q-Orbitrap). Targeted and suspected analysis were carried out. Two independent trials were performed under laboratory conditions (on courgette samples), and under greenhouse conditions (on tomatoes) during 43 and 55 days, respectively. In both studies, a pesticide formulation (TOPAS® EW) containing penconazole was used. The results showed that penconazole was relatively short-lived (<30 days) in horticultural products. The proposed method allowed for the tentative identification and semi-quantification of nine metabolites. In addition, the potential toxicity of these metabolites was evaluated, observing that some of them are even more toxic than penconazole, as triazole lactic acid. This research may provide a starting point for understanding the dissipation process of penconazole, the formation pathways of its main metabolites, their concentrations and toxicity to ensure food safety and the environmental protection.


Dexamethasone intravitreal implant in diabetic macular oedema refractory to anti-vascular endothelial growth factors: the AUSSIEDEX study.
To evaluate effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX) monotherapy in the AUSSIEDEX study non-responder subgroup, defined by diabetic macular oedema (DME) refractory to anti-vascular endothelial growth factor (anti-VEGF) agents. This prospective, open-label, observational, real-world study included pseudophakic and phakic (scheduled for cataract surgery) eyes that did not achieve a ≥5-letter best corrected visual acuity (BCVA) gain and/or clinically significant central subfield retinal thickness (CRT) improvement after 3-6 anti-VEGF injections for DME (N=143 eyes), regardless of baseline BCVA and CRT. After an initial DEX injection (baseline visit), reinjection was permitted at ≥16-week intervals. changes in mean BCVA and CRT from baseline to week 52. Safety assessments included adverse events. Of 143 eyes, 53 (37.1%) and 89 (62.2%) switched to DEX after 3-6 (early) and >6 (late) anti-VEGF injections, respectively; 1 (0.7%) had missing information. With 2.3 injections (mean) over 52 weeks, the change in mean BCVA from a baseline of 57.8 letters was not significant at week 52. Mean CRT improved significantly from a baseline of 417.8 μm at week 52 (mean change -60.9 μm; p<0.001). Outcomes were similar in eyes switched to DEX early and late. No unexpected adverse events were reported; no filtration surgeries were required. To date, AUSSIEDEX is the largest prospective, real-world study of DEX monotherapy for treatment-naïve or anti-VEGF-refractory DME. Following early or late switch from anti-VEGF agents, DEX significantly improved anatomic outcomes at 52 weeks without new safety concerns, supporting use in anti-VEGF-refractory DME. NCT02731911.


Dabrafenib Versus Dabrafenib + Trametinib in BRAF-Mutated Radioactive Iodine Refractory Differentiated Thyroid Cancer: Results of a Randomized, Phase 2, Open-Label Multicenter Trial.
Background: Oncogenic BRAF mutations are commonly found in advanced differentiated thyroid cancer (DTC), and reports have shown efficacy of BRAF inhibitors in these tumors. We investigated the difference in response between dabrafenib monotherapy and dabrafenib + trametinib therapy in patients with BRAF-mutated radioactive iodine refractory DTC. Methods: In this open-label randomized phase 2 multicenter trial, patients aged ≥18 years with BRAF-mutated radioactive iodine refractory DTC with progressive disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 within 13 months before enrollment were eligible. Patients were randomly assigned to receive dabrafenib alone or dabrafenib + trametinib. The primary endpoint was objective response rate by modified RECIST (minor response of -20% to -29%, partial and complete response) within the first 24 weeks of therapy. Trial Registration Number: NCT01723202. Results: A total of 53 patients were enrolled. The objective response rate (modified RECIST) was 42% (11/26 [95% confidence interval {CI} 23-63%]) with dabrafenib versus 48% (13/27 [CI 29-68%]) with dabrafenib + trametinib (p = 0.67). Objective response rate (RECIST 1.1) was 35% (9/26 [CI 17-56%]) with dabrafenib and 30% (8/27 [CI 14-51%]) with dabrafenib + trametinib. Most common treatment-related adverse events included skin and subcutaneous tissue disorders (17/26, 65%), fever (13/26, 50%), hyperglycemia (12/26, 46%) with dabrafenib alone and fever (16/27, 59%), nausea, chills, fatigue (14/27, 52% each) with dabrafenib + trametinib. There were no treatment-related deaths. Conclusions: Combination dabrafenib + trametinib was not superior in efficacy compared to dabrafenib monotherapy in patients with BRAF-mutated radioiodine refractory progressive DTC.


Prophylactic antibiotics for suction curettage in incomplete abortion.
The purpose of this study was to investigate the efficacy of 200 mg of prophylactic doxycycline in preventing pelvic infection after curettage for spontaneous (incomplete) abortion. A randomized, prospective, double-blinded study was carried out involving 300 women with an incomplete abortion who were given either placebo or 200 mg of doxycycline orally 30-60 min prior to curettage. A hematocrit, WBC count, pregnancy test, syphilis serology, Neisseria gonorrhoeae culture, and Micro Trak (monoclonal antibody test, Syba, San Jose, CA) for Chlamydia trachomatis were performed. The patients were scheduled for follow-up 2 weeks later. Antibiotic administration for any reason as well as the postoperative infection rate in these women was assessed. Eleven women were excluded from analysis, leaving 289 evaluable. N. gonorrhoeae was isolated from 6 (2%) women and C. trachomatis from 8 (3%) women, and the syphilis serology was serofast in 4 (1%) women. Endometritis complicated the procedure in 4 women who received placebo and in 1 woman who received doxycycline (P = 0.22). Prophylactic doxycycline is not effective in preventing pelvic infection after curettage for spontaneous (incomplete) abortion.


Class I alloantigen is sufficient for cytolytic T lymphocyte binding and transmembrane signaling.
Based largely on antibody blocking studies, a number of surface "accessory" molecules on effector cytolytic T lymphocytes (CTL) have been implicated as having a role in mediating CTL binding and lysis of target cells, possibly via binding to ligands on the target cell surface. Despite this, cloned allogeneic CTL were able to specifically bind cell-size, artificial membranes (pseudocytes) bearing only class I alloantigen. This binding triggered CTL degranulation, as measured by serine esterase release. Thus, class I alloantigen alone is both a necessary and sufficient ligand for specific binding and effective transmembrane signaling to occur.


An eleven-year cohort of bloodstream infections in 552 febrile neutropenic patients: resistance profiles of Gram-negative bacteria as a predictor of mortality.
Antimicrobial stewardship is of major importance in patients with febrile neutropenia (FN). In this study, we aimed to investigate the trends in resistance and the relationship with mortality rates in patients with FN. The single-center surveillance data of inpatients with FN and diagnosed as microbiologically confirmed bloodstream infections (BSIs) between 2006 and 2016 were reviewed retrospectively. A total of 950 episodes in 552 patients with BSIs were analyzed. Of whom, 55.9% were male, the median age was 43 years, and 35.6% had acute myeloid leukemia. In total, 1016 microorganisms were isolated from blood cultures. Gram-negatives accounted for 42.4% (n = 403) of the episodes. Among Gram-negatives, Enterobacteriaceae accounted for 346 (86%) (E. coli, n = 197; 34% extended-spectrum β-lactamases (ESBL) producers, and Klebsiella spp., n = 120; 48.3% ESBL producers). Also, 24 (20.0%) of Klebsiella spp. had carbapenemase activity. There were 6 (5.0%) colistin-resistant Klebsiella spp. Thirteen (26.5%) of Pseudomonas spp. and 17 (60.7%) of Acinetobacter spp. had carbapenemase activity. There were 2 (5.6%) colistin-resistant Acinetobacter spp. The 30-day mortality rates were 12.0%, 21.5%, 34.6%, and 29.0% in BSIs due to Gram-positive, Gram-negative bacterial, fungal, and polymicrobial etiology respectively (p = 0.001). BSIs with ESBL-producing (p = 0.001) isolates, carbapenem (p < 0.001), and colistin-resistant isolates (p < 0.001) were associated with increased mortality risk. The tremendous rise in resistance rates among Gram-negatives is dreadfully related to increasing mortality and leads to sharp shifts toward extreme restrictions of unnecessary antibiotic uses. Antimicrobial stewardship in patients with FN requires vigilance and tailoring of treatment upon local surveillance data.


Macromolecular relationships of liver nuclei and amino acid composition of total histones during bovine ontogeny.
The weight of the liver and the macromolecular composition of the liver and its nuclei during bovine ontogeny were compared. The findings suggest that bovine liver growth proceeds in three phases. The macromolecular composition of the liver nuclei was found to remain fairly constant throughout bovine ontogeny.


Oncogene jun encodes a sequence-specific trans-activator similar to AP-1.
Proto-oncogenes encode proteins with three main sites of action: the cell-surface membrane, the cytoplasm and the nucleus. Although the exact biochemical function of most proto-oncogene products is not understood, several of them are known to be involved in signal transduction. A role in gene regulation through DNA binding has been suggested for a recently isolated member of the group of oncogenes acting at the nucleus, v-jun. The C-terminus of the putative v-jun-encoded protein is similar in sequence to the C-terminus of the yeast transcriptional activator GCN4 (refs 8, 9), which forms its minimal DNA-binding domain. GCN4 binds to specific sites whose consensus sequence is highly similar to the recognition sequence of the mammalian transcriptional activator AP-1 (refs 12, 13). Like GCN4, AP-1 binds to promoter elements of specific genes and activates their transcription. Because of the similarity between the recognition sites for GCN4 and AP-1, we examined the possibility that AP-1 could be the product of the c-jun proto-oncogene. The experimental results reported here indicate that the JUN oncoprotein is a sequence-specific transcriptional activator similar to AP-1.


Ling classification applied in the preoperative safety and effectiveness assessment of POEM.
At present, peroral endoscopic myotomy (POEM) has been considered as the recommended treatment for achalasia, as it causes trauma to a smaller area and has fewer short-term serious complications than other treatments. However, due to the different morphology of esophagus, not all the patients with achalasia are eligible to receive POEM surgery. And the purpose of our study was to apply Ling classification, which proser Linghu put forward in 2011, in the preoperative assessment of POEM, expecting to reduce the occurrence rate of complications during or post-POEM. The clinical data of 341 achalasia patients were collected and classified, according to the endoscopic pictures related to the middle and the lower parts of the esophagus. The correlation between Ling classification and LESP or Eckardt score was analyzed for the efficiency estimation, and the correlation of Ling classification and incidence of complications was counted for the safety evaluation. Ling classification was correlated with the LESP of 95 patients and Eckardt score of 131 patients. Compared to preoperative data, post-POEM LESP and Eckardt score both decreased significantly in all types of Ling classification (p < 0.05), while no significant difference in the decrease degree of either LESP or Eckardt score was found among different types of Ling classification (p > 0.05). This means Ling classification may not directly affect the postoperative efficacy of POEM. By analyzing the correlation between Ling classification and intraoperative complications, we found that the differences of total complications, gas-related complication and mucosal injury were all significant among all types of Ling classification (p < 0.05). Ling classification can be applied in the preoperative assessment of the safety and efficacy of POEM, and it might provide a guideline for how to reduce the complications during POEM surgery.


Who's more vulnerable? A generational investigation of COVID-19 perceptions' effect on Organisational citizenship Behaviours in the MENA region: job insecurity, burnout and job satisfaction as mediators.
This paper is an empirical investigation that examines a path model linking COVID-19 perceptions to organisational citizenship behaviour (OCBs) via three mediators: job insecurity, burnout, and job satisfaction. The research examines the path model invariance spanning Generations X, Y, and Z. Three countries in the Middle East and North Africa (MENA) were the focus of the study. The data was collected from a sample of employees in service companies (n = 578). We used a Partial Least Square Structural Equation Modelling (PLS-SEM) to analyse the data. Our findings reveal that COVID-19 perceptions positively predict job insecurity, which positively impacts burnout levels. Burnout negatively predicts job satisfaction. The findings established that job satisfaction positively predicts OCBs. The mediation analysis determined that job insecurity, burnout and job satisfaction convey the indirect effects of COVID-19 perceptions onto OCBs. Finally, our hypothesised model is non-equivalent across Generations X, Y and Z. In that regard, our multi-group analysis revealed that the indirect effects of COVID-19 perceptions on OCBs were only valid amongst younger generations, i.e., Generation Y and Generation Z. Specifically, younger generations are substantially more vulnerable to the indirect effects of COVID-19 perceptions on their engagement in OCBs than Generation X whose job satisfaction blocks the effects of COVID-19 perceptions on OCBs. The present study extends our knowledge of workplace generational differences in responding to the perceptions of crises or pandemics. It offers evidence that suggests that burnout, job attitudes and organisational outcomes change differently across generations in pandemic times.


Adaptation of body protein metabolism in adult and aging man.
Aging causes a selective loss in lean body mass, muscle being most extensively eroded. This presentation is an analysis of the consequences of this age-related loss for protein and amino acid metabolism. The use of stable isotopes allows us to measure the dynamics of protein metabolism in the intact human subject, while the output of 3-methylhistidine permits estimates of muscle turnover to be made which show a smaller reduction in body protein turnover per kg body weight in elderly subjects. This is due to the reduced contribution by muscle protein turnover, which decreases from 30 per cent of total body protein turnover in the young adult to 20 per cent in the elderly, and can be entirely accounted for by the reduced mass of muscle, the rate of turnover per unit muscle weight being unchanged. The consequences of the changing proportions of major tissues with age has been examined for its impact on amino acid metabolism. The interaction of various organs in order to ensure metabolism of different amino acids is described. After a meal containing abundant protein, the liver selectively degraded the excess of most essential amino acids, while allowing the three branched-chain essential amino acids to pass through, so that in consequence they account for more than 50 per cent of the amino acid outflow from the splanchnic area. During this period of absorption muscle takes up amino acids, over 70 per cent being the branched-chain amino acids where they are catabolised, the nitrogen becoming available for formation of non-essential amino acids for muscle protein synthesis. The release of large amounts of glutamine from muscle is dependent on branched-chain amino acid degradation, whereas the release of large amounts of alanine is regulated by availability of pyruvate from glucose. The study of amino acid metabolism in elderly compared with young adults and its relationship to the declining mass of muscle with age is still in its initial stages. Metabolism of glycine at different levels of protein intake fails to demonstrate any significant effects of aging on metabolism of this amino acid. On the other hand, the flux of leucine shows a significant reduction in fasting elderly female subjects. This observation should be followed up by studying leucine kinetics following a meal of meat, in order to determine whether the reduced mass of muscle in the elderly will restrict the capacity to metabolise branched-chain amino acids. It has been concluded that the extensive age-related change in muscle mass should be explored for its impact on the nutritional requirements for branched-chain amino acids, their metabolism in health and disease, and their therapeutic uses at different ages.


Evacetrapib.
Considerable attention focuses on the ability to develop therapeutic agents that elevate levels of high-density lipoprotein cholesterol (HDL-C). Cholesteryl ester transfer protein (CETP) inhibitors have been developed on the basis of their ability to raise HDL-C to a greater extent than lipid-modifying therapies currently used in clinical practice. Initial enthusiasm for CETP inhibition decreased as a result of adverse clinical outcomes observed with the agent torcetrapib. Elucidating off-target toxicities of torcetrapib has provided hope that other CETP inhibitors may still be of potential benefit. Evacetrapib is a novel CETP inhibitor, with favorable effects on plasma lipids and no adverse effects on blood pressure or mineralocorticoid activity in early clinical evaluation. The potential effects on cardiovascular outcomes remain to be determined.


Fetal neural tube defects detected by rocket-on-line immunoelectrophoresis of amniotic fluids.
Immunization of rabbits with human fetal brain membranes evoked antisera with reactivity against D-2 protein from brain and cerebrospinal fluid. In amniotic fluids from pregnancies with fetal neural tube defects the presence of D2-protein could be demonstrated by rocket-on-line immunoelectrophoresis. In a prospective study on 72 amniotic fluids with increased alphafetoprotein concentration neural tube defects were correctly predicted in 26 pregnancies. One false-negative and four false-positive pregnancies were encountered. D2-protein determination may thus have a role in antenatal diagnosis of neural tube malformations as a supplement to alphafetoprotein analysis.


Interactions of "de novo" designed peptides with bacterial membranes: Implications in the antimicrobial activity.
Antimicrobial peptides are small molecules that display antimicrobial activity against a wide range of pathogens. In a previous work, by using model membranes we studied P6, a peptide that shows no antimicrobial activity, and P6.2, which exhibits antibacterial activity. In the present work we aimed to unravel the mode of action of these peptides by studying their interaction in vivo with Escherichia coli and Staphylococcus aureus. In this sense, to study the interactions with bacterial cells and their effect on the bacterial surface, zeta potential, spectroscopic, and microscopic methodologies were applied. P6.2 exhibits a higher affinity toward both bacterial envelopes. The ability of both peptides to disrupt afterwards the bacterial membrane was also studied. Both peptides were able to induce bacterial membrane damage, but higher concentrations of P6 were needed to obtain results comparable to those obtained for P6.2. Additionally, P6.2 exhibited faster damage kinetics. Altogether, these data allow postulating, in a physiologic model, that the lower affinity of P6 for bacterial envelope results in a minor final concentration of the peptide in the bacterial membrane unable to trigger the antimicrobial activity. Finally, the fact that the active P6.2 has the same MIC value for the Gram-positive and Gram-negative bacteria tested, but not the same profile in the permeabilization assays, reinforces the question of whether cell wall components act as electrostatic barriers preventing or minimizing membrane-active AMPs lethal action at the membrane level.


Levoketoconazole improves clinical signs and symptoms and patient-reported outcomes in patients with Cushing's syndrome.
The efficacy of levoketoconazole in treating hypercortisolism was demonstrated in an open-label phase 3 study (SONICS) of adults with endogenous Cushing's syndrome (CS) and baseline mean urinary free cortisol (mUFC) ≥ 1.5× ULN. Clinical signs and symptoms and patient-reported outcomes from the SONICS trial were evaluated in the current manuscript. Patients titrated to an individualized therapeutic dose entered a 6-month maintenance phase. Secondary endpoints included investigator-graded clinical signs and symptoms of CS during the maintenance phase, and patient-reported quality of life (CushingQoL questionnaire) and depression symptoms (Beck Depression Inventory II [BDI-II]). Of 94 enrolled patients, 77 entered the maintenance phase following individualized dose titration. Significant mean improvements from baseline were noted at end of maintenance (Month 6) for acne, hirsutism (females only), and peripheral edema. These improvements were observed as early as Day 1 of maintenance for hirsutism (mean baseline score, 7.8; ∆ - 1.9; P < 0.0001), end of Month 1 for acne (mean baseline score, 2.8; ∆ - 1.2; P = 0.0481), and Month 4 for peripheral edema (mean baseline score, 1.0; ∆ - 0.5; P = 0.0052). Significant mean improvements from baseline were observed by Month 3 of maintenance for CushingQoL (mean baseline score, 44.3; ∆ + 6.9; P = 0.0018) and at Month 6 for BDI-II (mean baseline score, 17.1; ∆ - 4.3; P = 0.0043) scores. No significant mean improvement was identified in a composite score of 7 other clinical signs and symptoms. Treatment with levoketoconazole was associated with sustained, meaningful improvements in QoL, depression, and certain clinical signs and symptoms characteristic of CS. ClinialTrials.gov identifier: NCT01838551.


Histone deacetylase inhibitor SAHA induces ERalpha degradation in breast cancer MCF-7 cells by CHIP-mediated ubiquitin pathway and inhibits survival signaling.
Estrogen receptor alpha (ERalpha) plays an important role in the development and progression of breast cancer, and recent studies showed that ERalpha expression is associated with resistance to hormonal therapy. Therefore, a number of studies have explored ways to deplete ERalpha from breast cancer cells as a new therapy especially for hormone-refractory breast cancer. We reported here that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, effectively depletes ERalpha in breast cancer MCF-7 cells. However, the intrinsic mechanisms by which SAHA decreases ERalpha levels are not clear. Our present data demonstrated that both inhibition of ERalpha mRNA level and promotion of ERalpha degradation by the proteasome contribute to SAHA-induced ERalpha depletion, indicating that SAHA may exert its effects through transcriptional and posttranslational mechanisms. Furthermore, the decrease of ERalpha protein level in MCF-7 cells after SAHA treatment is mainly the result of its rapid degradation by the ubiquitin-proteasome pathway rather than transcriptional inhibition. In addition, we showed that inactivation of the heat shock protein-90 (Hsp90) is involved in SAHA-induced ERalpha degradation, and ubiquitin ligase CHIP (C-terminal Hsc70 interacting protein) enhances SAHA-induced ERalpha degradation. SAHA-induced ERalpha depletion is paralleled with reduction of transcriptional activity of ERalpha and SAHA is able to effectively inhibit cell proliferation and induce apoptosis of MCF-7 cells. Taken together, our results revealed a mechanism for SAHA-induced ERalpha degradation and indicated that SAHA is a suitable pharmacological agent for depletion of ERalpha and a potential choice for breast cancer expressing high ERalpha.


Chiral Phosphoric Acid Catalyzed Asymmetric Hydrolysis of Biaryl Oxazepines for the Synthesis of Axially Chiral Biaryl Amino Phenol Derivatives.
The development of catalytic asymmetric reaction with water as the reactant is challenging due to the reactivity- and stereoselectivity-control issues resulted from the low nucleophilicity and the small size of water. We disclose herein a chiral phosphoric acid (CPA) catalyzed atroposelective ring-opening reaction of biaryl oxazepines with water. A series of biaryl oxazepines undergo the CPA catalyzed asymmetric hydrolysis in a highly enantioselective manner. The key for the success of this reaction is the use of a new SPINOL-derived CPA catalyst and the high reactivity of biaryl oxazepine substrates towards water under acidic conditions. Density functional theory calculations suggest that the reaction proceeds via a dynamic kinetic resolution pathway and the CPA catalyzed addition of water to the imine group is both enantio- and rate-determining.


Glucocorticoids inhibit IL-4 and mitogen-induced IL-4R alpha chain expression by different posttranscriptional mechanisms.
A high level of expression of IL-4Ralpha chain on the surface of lymphocytes has been described in certain allergic and inflammatory autoimmune diseases. Progression of these diseases are usually controlled by steroid treatment. One mechanism by which these drugs exert their antiinflammatory and immunosuppressive effects is by widely repressing or enhancing the production of cytokines and their receptors. The effect of glucocorticoids on IL-4Ralpha chain expression has not been previously studied, and this is the aim of the present report. For this purpose, human lymphocytes were induced to express IL-4Ralpha chain by means of protein kinase C (PKC) activation with phorbol myristate acetate (PMA) or by triggering the Janus kinase-Stat pathway with IL-4 in the presence or absence of pharmacologic doses of dexamethasone. IL-4Ralpha cell surface expression was studied by flow cytofluorometry. The levels and stability of mRNA were assessed by Northern blot analysis. The effect of dexamethasone on the IL-4Ralpha rate of transcription was determined by nuclear run-on experiments. Dexamethasone significantly downregulated PMA-induced IL-4Ralpha mRNA and protein levels in total peripheral blood mononuclear cells and in isolated T cells. The mechanism involved a posttranscriptional regulation of IL-4Ralpha expression because dexamethasone decreased the PMA-induced IL-4Ralpha mRNA half-life. However, we found that PMA did not influence the transcription rate of IL-4Ralpha gene, irrespective of the presence or absence of dexamethasone. This immunosuppressor also diminished the IL-4-induced IL-4Ralpha expression on the surface of isolated T and B lymphocytes but, interestingly, without modifying mRNA levels that indicates that dexamethasone downregulated IL-4-dependent IL-4Ralpha expression by acting at a translational or posttranslational level. In fact, we observed that the drug did not affect IL-4-induced IL-4Ralpha gene transcription rate nor did it shorten mRNA half-life. The effect of dexamethasone on the IL-4Ralpha was steroid specific because it was totally reversed by the glucocorticoid receptor antagonist RU486. Our results support that dexamethasone may influence the course of allergic and inflammatory diseases by downregulating the expression of IL-4Ralpha.


Thoracoscopic surgery for pneumothorax in older patients.
Secondary pneumothorax is more common in older pneumothorax patients. Therefore, we set out to investigate the usefulness of thoracoscopic surgery in this group. A total of 59 operations were performed on patients aged > or = 50 years, with the goal of excising only the lesions responsible for air leaks by using the minimum degree of dissection. If the patients were found to have numerous bullae, the lesions responsible were identified by pleurography. The duration of chest tube drainage, hospital stay, and recurrence were assessed. The air leaks stopped and all patients were discharged without drains. Postoperative drainage time was 3.8 +/- 3.0 days. Postoperative hospital stay was 10.8 +/- 9.2 days. Six patients died of other diseases, but there was only one recurrence of pneumothorax. We consider video-assisted thoracic surgery (VATS), with the goal of excising only the lesions responsible for air leaks, to be particularly efficacious in older pneumothorax patients.


Different reactivities of monoclonal antibodies to ganglioside lactones.
Six murine monoclonal antibodies were found to react with ganglioside GD2 lactone as well as purified ganglioside GD2. However, the reactivities of these antibodies to various ganglioside lactones were found to differ from each other. Four antibodies only reacted with GD2 lactones, while the other two cross-reacted with lactones of other gangliosides such as GD1b and GT1b.


Changes in localization of synaptophysin following fluid percussion injury in the rat brain.
Traumatic brain injuries damage neurons and cause progressing dysfunctions of the brain. Synaptophysin (SYP), a major integral transmembrane protein of synaptic vesicles, provides a molecular marker for the synapse and serves as a functional marker of the brain. This study examined magnitude-dependent changes of SYP in the rat brain 2 days following low, moderate or high fluid percussion injuries and investigated time-dependent changes of SYP in the rat brain with moderate fluid percussion injury 2, 15 and 30 days after trauma using immunohistochemistry and Western blotting. SYP immunoreactivity increased in the lateral cortex and in the subcortical white matter, with increasing magnitude of injury and time after trauma. Increased SYP immunoreactivity was accompanied with degeneration of neuronal cell bodies, their processes and terminals as well as glial cell proliferations. Amounts of SYP measured by Western blotting remained unchanged in brains with moderate fluid percussion within 30 days after trauma. These findings indicate that trauma accumulates SYP at injured sites of neurons without changing SYP contents and that increased SYP immunoreactivity in the cerebral cortex following traumatic injury reflects an inhibition of synaptic vesicle transportation and dysfunction of synapses, thus providing a histological substrate for brain dysfunctions.


Normalization of coagulopathy is associated with improved outcome after isolated traumatic brain injury.
Acute traumatic coagulopathy (ATC) has been reported in the setting of isolated traumatic brain injury (iTBI) and is associated with poor outcomes. We aimed to evaluate the effectiveness of procoagulant agents administered to patients with ATC and iTBI during resuscitation, hypothesizing that timely normalization of coagulopathy may be associated with a decrease in mortality. A retrospective review of the Alfred Hospital trauma registry, Australia, was conducted and patients with iTBI (head Abbreviated Injury Score [AIS] ⩾3 and all other body AIS <3) and coagulopathy (international normalized ratio ⩾1.3) were selected for analysis. Data on procoagulant agents used (fresh frozen plasma, platelets, cryoprecipitate, prothrombin complex concentrates, tranexamic acid, vitamin K) were extracted. Among patients who had achieved normalization of INR or survived beyond 24hours and were not taking oral anticoagulants, the association of normalization of INR and death at hospital discharge was analyzed using multivariable logistic regression analysis. There were 157 patients with ATC of whom 68 (43.3%) received procoagulant products within 24hours of presentation. The median time to delivery of first products was 182.5 (interquartile range [IQR] 115-375) minutes, and following administration of coagulants, time to normalization of INR was 605 (IQR 274-1146) minutes. Normalization of INR was independently associated with significantly lower mortality (adjusted odds ratio 0.10; 95% confidence interval 0.03-0.38). Normalization of INR was associated with improved mortality in patients with ATC in the setting of iTBI. As there was a substantial time lag between delivery of products and eventual normalization of coagulation, specific management of coagulopathy should be implemented as early as possible.


Deep-sequencing transcriptome analysis of field-grown Medicago sativa L. crown buds acclimated to freezing stress.
Medicago sativa L. (alfalfa) 'Zhaodong' is an important forage legume that can safely survive in northern China where winter temperatures reach as low as -30 °C. Survival of alfalfa following freezing stress depends on the amount and revival ability of crown buds. In order to investigate the molecular mechanisms of frost tolerance in alfalfa, we used transcriptome sequencing technology and bioinformatics strategies to analyze crown buds of field-grown alfalfa during winter. We statistically identified a total of 5605 differentially expressed genes (DEGs) involved in freezing stress including 1900 upregulated and 3705 downregulated DEGs. We validated 36 candidate DEGs using qPCR to confirm the accuracy of the RNA-seq data. Unlike other recent studies, this study employed alfalfa plants grown in the natural environment. Our results indicate that not only the CBF orthologs but also membrane proteins, hormone signal transduction pathways, and ubiquitin-mediated proteolysis pathways indicate the presence of a special freezing adaptation mechanism in alfalfa. The antioxidant defense system may rapidly confer freezing tolerance to alfalfa. Importantly, biosynthesis of secondary metabolites and phenylalanine metabolism, which is of potential importance in coordinating freezing tolerance with growth and development, were downregulated in subzero temperatures. The adaptive mechanism for frost tolerance is a complex multigenic process that is not well understood. This systematic analysis provided an in-depth view of stress tolerance mechanisms in alfalfa.


High burden and diversity of carbapenemase-producing Enterobacterales observed in wastewater of a tertiary care hospital in Germany.
Hospitals are one of the main reservoirs of multi-resistant Enterobacterales (MRE). As MRE are resistant to the most frequently used antibiotics, therapy for patients with MRE infections is challenging. It has been previously described that MRE from hospital wastewater can pass into municipal wastewater and even surface water. In this study, we investigated the diversity and epidemiology of MRE in the wastewater of a large tertiary care hospital. Wastewater samples were collected for a four-day period and tested for the presence of Enterobacterales resistant to 3rd gen. cephalosporins. Representative isolates were further characterized by whole genome sequencing. In 120 β-glucuronidase-producing isolates, 68 Escherichia coli and, interestingly, also 52 Citrobacter freundii were identified. In 120 β-glucosidase-producing isolates 45 Serratia marcescens, 34 Klebsiella oxytoca, 32 Enterobacter cloacae and 9 Klebsiella pneumoniae were observed. For all species various MLST sequence types and different clusters of resistance genes were determined, showing a great diversity within the different Enterobacterales, further corroborated by clonal analysis performed by cgMLST. The most prominent clone was wastewater associated E. coli ST635, which accounted for 47.1% of all E. coli isolates. Interestingly, 45.6% of E. coli, 88.5% of C. freundii, 95.6% of S. marcescens, 91.2% of K. oxytoca, 96.9% of E. cloacae and 88.9% of K. pneumoniae isolates carried a carbapenemase gene, indicating a high burden with carbapenemase-producing Enterobacterales. Comparison with clinical isolates from the same hospital displayed few clonal matches. One wastewater isolate of K. pneumoniae was identified to be closely related compared to a clone that had been introduced into the hospital during an outbreak four years earlier. One E. coli isolate was identified as identical to an isolate from a patient, with inpatient stay during the sampling period. The data obtained in this study highlight the problem of antibiotic resistance of Enterobacterales in hospital wastewater. In particular, the clustered occurrence of carbapenemase genes is of great concern and underscores the problem of increasingly scarce antibiotic options against these bacteria.


Acyl-Coenzyme A synthetase and fatty acid oxidation in rat liver peroxisomes.
Rat liver peroxisomes oxidized palmitate in the presence of ATP, CoA and NAD+, and the rate of palmitate oxidation exceeded that of palmitoyl-CoA oxidation. Acyl-CoA synthetase [acid: CoA ligase (AMP-forming); EC 188.8.131.52] was found in peroxisomes. The substrate specificity of the peroxisomal synthetase towards fatty acids with various carbon chain lengths was similar to that of the microsomal enzyme. The peroxisomal synthetase activity toward palmitate (40--100 nmol/min per mg protein) was higher than the rate of palmitate oxidation by the peroxisomal system (0.7--1.7 nmol/min per mg protein). The data show that peroxisomes activate long chain fatty acids and oxidize their acyl-CoA derivatives.


Data mining from process monitoring of typical polluting enterprise.
With the increasing volume of environmental monitoring data, extracting valuable insights from multivariate time series sensor data can facilitate comprehensive information utilization and support informed decision-making in environmental management. However, there is a dearth of comprehensive research on multivariate data analysis for process monitoring in typical polluting enterprises. In this study, an artificial neural network model based on back-propagation algorithm (BP-ANN) was developed to predict the wastewater and exhaust gas emissions using IoT data obtained from process monitoring of a typical polluting enterprise located in Taizhou, Zhejiang Province, China. The results indicate that the model constructed has a high predictive coefficient of determination (R2) with values of 0.8510, 0.9565, 0.9561, 0.9677, and 0.9061 for chemical oxygen demand (COD), potential of hydrogen (pH), electrical conductivity (EC), flue gas emission (FGE), and non-methane hydrocarbon concentration (NMHC) respectively. For the first time, the variable importance measure (VIM)-assisted BP-ANN was employed to investigate the internal and external correlations between wastewater and exhaust gas treatment, thereby enhancing the interpretability of mapping features in the BP-ANN model. The predicted errors for pH and FGE have been demonstrated to fall within the range of - 0.62 ~ 0.30 and - 0.21 ~ 0.15 m3/s, respectively, with average relative errors of 1.05% and 9.60%, which is advantageous in detecting anomalous data and forecasting pollution indicator values. Our approach successfully addresses the challenge of segregating data analysis for wastewater disposal and exhaust gas disposal in the process monitoring of polluting enterprises, while also unearthing potential variables that significantly contribute to the BP-ANN model, thereby facilitating the selection and extraction of characteristic variables.


Memantine attenuated alcohol withdrawal-induced anxiety-like behaviors through down-regulating NR1-CaMKII-ERK signaling pathway.
Alcohol abuse and anxiety disorders often occur concurrently, but their underlying cellular mechanisms remain unclear. N-methyl-D-aspartic acid receptors (NMDARs) have recently received attention from those interested in the neurobiology of anxiety. A chronic alcohol exposure rat model (28 consecutive days of 20% alcohol intake and 6 h of withdrawal) was established. Here, we investigated the NMDAR1 (NR1), Ca2+/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinases (ERK) pathway in the modulation of anxiety-like behaviors in rats exposed to an open field and elevated plus maze (EPM) through systematic injections of memantine (a NMDAR inhibitor). We found that the NR1-CaMKII-ERK signaling pathway was activated after alcohol withdrawal in medial prefrontal cortex (mPFC) and nucleus accumbens shell (NAcSh) but not core (NAcC). Memantine treatment greatly ameliorated anxiety-like behavior in the rats experiencing alcohol withdrawal. Moreover, memantine uniformly suppressed the phosphorylation of NR1-CaMKII-ERK pathway induced by alcohol withdrawal. Our results suggest that activation of the NR1-CaMKII-ERK pathway in the mPFC and NAcSh is an important contributor to the molecular mechanisms underlying alcohol withdrawal-induced anxiety behaviors. NMDAR signaling pathway inhibitors are thus potential therapeutics for treating alcohol abuse.


Diabetes alters vascular mechanotransduction data: Pressure-induced regulation of mTor and associated signaling in the rat inferior vena cava.
Diabetes is a multifaceted disease with various etiologies. The complexity of this pathology creates a myriad of factors that must be considered when addressing surgical outcomes and prognosis. Of vital importance to cardiovascular surgery is the viability of homographic vein grafts. Due to the fact, diabetic patients have a higher rate of vein graph failure, a greater understanding of the effect diabetes has on vascular mechano-transductive response is critical to improving patient prognosis. This article represents data regarding a study published in Cardiovascular Diabetology (Rice et al., 2006) [1] and Open Journal of Endocrine and Metabolic Diseases (Rice et al., 2015) [2] with the purpose of evaluating the effect of pressurization on rat inferior venae cavae (IVC). Here we provide the information about the method and processing of raw data related to our prior publish work and Data in Brief articles (Rice et al., Submitted for publication) [3,4]. The data contained in this article evaluates the contribution of mTor signaling and associated proteins. IVC from lean and obese animals were exposed to a 30 min perfusion of 120 mm Hg pressure and evaluated for changes in expression and phosphorylation of mTor, p70s6k, GSK3β, and 4EBP-1.


Common bile duct anteroposterior movement synchronized with inferior vena cava pulsation observed by cine magnetic resonance imaging.
To reveal the phenomenon of common bile duct (CBD) anteroposterior movement caused by inferior vena cava (IVC) pulsation depending on the cardiac cycle using cine magnetic resonance imaging. A breath-hold trans-axial cine segmented true fast imaging with steady-state precession (trueFISP) sequence was prospectively performed on 11 healthy volunteers to observe CBD anteroposterior movement and IVC pulsation during the cardiac cycle. Changes in IVC anterior-posterior diameter and CBD location were compared using Pearson rank correlation analysis. Nine (81.8%) of 11 CBDs moved back and forth in synchronicity with IVC anterior wall motion depending on the cardiac cycle; the mean maximum and minimum IVC diameters were 16.2+/-2.7 and 12.9+/-3.1 mm, respectively. Two (18.2%) of 11 CBDs and IVC walls did not move; the mean unchanged IVC diameter was 5.3+/-2.1 mm. There were significant correlations between the mean change in IVC diameter and distance of CBD anteroposterior movement (2.7+/-2.1 and 1.8+/-1.4 mm, respectively, r=0.911, P<.05). Many CBDs move back and forth in synchronicity with IVC pulsation depending on the cardiac cycle.


Satellite Rod Fixation around Rod-fracture Area in Revision Surgery after Three-column Osteotomy for Severe Kyphoscoliosis.
Three-column osteotomy (3CO) is considered valuable and increasingly utilized in the surgical treatment of severe spine deformity while associated with high implant-related complications and revision risks. This study aims to evaluate the feasibility and clinical outcomes of satellite rod fixation used around the rod-fracture area in revision surgery due to rod fracture after 3CO. Twenty-five patients applying satellite rod fixation in revision surgery from August 2012 to May 2016 were retrospectively reviewed as the SR group. Patients undergoing revision surgery with traditional strategy after 3CO due to rod-fracture were selected as the TR group. Cobb angle, distance between C7 plumb line and center sacral vertical line (C7 PL-CSVL), global kyphosis (GK) and sagittal vertical axis (SVA) were assessed. Patients were required to fulfill the Scoliosis Research Society-22 questionnaire (SRS-22) at pre-revision and the last follow-up. The paired t test was used to analyze the difference among pre-revision, post-revision and last follow-up. There was no statistical difference in terms of age, gender, body mass index (BMI), fusion level at 1st surgery, and follow-up period between SR and TR group (all P > 0.05). The operation time (1.5 ± 0.7 h vs 3.2 ± 0.9 h, P < 0.001) and intraoperative blood loss (178 ± 51 mL vs 324 ± 96 mL, P < 0.001) were significantly higher in the TR group. Patients in both groups obtained obvious deformity correction after revision surgery. For patients in SR group, the coronal Cobb angle significantly improved from 27.9 ± 21.5° at pre-revision to 21.8 ± 16.6° at post-revision (P = 0.034). The C7 PL-CSVL decreased from 22.6 ± 14.3 mm to 21.3 ± 10.9 mm (P = 0.719). Similarly, improvement was attained in post-revision GK (25.8 ± 17.0° vs 20.2 ± 15.1°, P = 0.061). SVA was corrected from 35.6 ± 33.9 mm to 30.8 ± 24.3 mm after revision (P = 0.182). At the last follow-up, no significant correction loss was observed in both coronal and sagittal parameters (all P > 0.05). All patients responded to the SRS-22 questionnaire and all the domains showed improvements in different levels. As compared to the TR group, the SR group had significantly better pain and management satisfaction scores (all P < 0.05). Additionally, there was no reoccurrence of implant failure during follow-up and all patients achieved solid bony fusion in SR group. Satellite rod fixation around rod-fracture area is indicated for patients in the requirement of revision surgeries due to rod fracture after 3CO. Compared with traditional revision strategies, revision surgery with satellite rods, if patients are selected adequately, is a simpler procedure with less intraoperative blood loss and shorter operating time.


Damage clusters after gamma irradiation of a nanoparticulate plasmid DNA peptide condensate.
We have gamma-irradiated plasmid DNA in aqueous solution in the presence of submillimolar concentrations of the ligand tetra-arginine. Depending upon the ionic strength, under these conditions, the plasmid can adopt a highly compacted and aggregated form which attenuates by some two orders of magnitude the yield of damage produced by the indirect effect. The yields of DNA single- and double-strand breaks (SSB and DSB) which result are closely comparable with those produced in living cells. The radical lifetimes, diffusion distances, and track structure are expected to be similarly well reproduced. After irradiation, the aggregation was reversed by adjusting the ionic conditions. The approximate spatial distribution of the resulting DNA damage was then assayed by comparing the increases in the SSB and DSB yields produced by a subsequent incubation with limiting concentrations of the eukaryotic base excision repair enzymes formamidopyrimidine-DNA N-glycosylase (the FPG protein) and endonuclease III. Smaller increases in DSB yields were observed in the plasmid target that was irradiated in the condensed form. By modeling the spatial distribution of DNA damage, this result can be interpreted in terms of a greater extent of damage clustering.


MicroRNA-29 regulates myocardial microvascular endothelial cells proliferation and migration in association with IGF1 in type 2 diabetes.
In our study, we investigated the expression and function of microRNA-29 in myocardial microvascular endothelial cells (MMEVC) in type 2 diabetic Goto-Kakizaki (GK) rats. MiR-29 gene expression was compared, by qRT-PCR between diabetic GK rat MMEVC and non-diabetic Wistar rat MMEVC. MiR-29 was downregulated in GK MMEVC and its effect on angiogenic properties of proliferation and migration was examined. Potential downstream target gene of miR-29, insulin growth factor 1 (IGF1), was assessed by dual-luciferase reporter assay, qRT-PCR and western blot in GK MMEVC. IGF1 was also downregulated by siRNA in miR-29-downregulated GK MMEVC. Its effect on miR-29-associated angiogenic regulation on MMEVC proliferation and migration was further investigated. MiR-29 was substantially upregulated in GK MMEVC than in Wistar MMEVC. Transfection of synthetic miR-29 inhibitor successfully downregulate endogenous miR-29 in GK MMEVC, and subsequently promoted angiogenesis by increasing cell proliferation and migration. IGF1 was confirmed to be downstream target gene of miR-29 in GK MMEVC, with its gene and protein expressions both upregulated in miR-29-downregualted GK MMEVC. Conversely, siRNA-mediated IGF1 downregulation reversed the pro-angiogenic effect of miR-29 downregulation in GK MMEVC, as it decreased cell proliferation and migration. Our study suggests that miR-29 downregulation, through its inverse regulation on downstream target of IGF1 gene, is a pro-angiogenic factor in MMEVC in type 2 diabetic rats.


Home assessment of diurnal intraocular pressure in healthy children using the Icare rebound tonometer.
Although intraocular pressure (IOP) is known to vary with the circadian cycle in nonglaucomatous and glaucomatous eyes of adults, the clinical assessment of IOP often relies on periodic measurements obtained at office visits during daytime hours. Little has been reported on diurnal IOP patterns in healthy children. The purpose of this study was to evaluate diurnal IOP in normal eyes of healthy children with the Icare rebound tonometer and when recorded by a parent at home. This was a prospective study of IOP in normal eyes of healthy children. Children were recruited from a pediatric eye clinic. A parent was instructed on the use of the Icare rebound tonometer by a study physician and demonstrated proficiency its use in the clinic, at which time a masked IOP reading was also made with Goldmann applanation by a different study clinician. Home IOPs were then obtained and recorded 6 times daily at 2- to 3-hours intervals during 2 consecutive days by a parent. A total of 22 normal eyes (of 11 children) were included. We found that children without glaucoma demonstrate mean diurnal IOP fluctuation of 4-6 mm Hg, with similar IOP between right and left eyes, fair repeatability between consecutive days, and a tendency for higher early morning and lower late evening IOP. Healthy children without glaucoma demonstrate some diurnal fluctuation in IOP, comparable with that reported in nonglaucomatous eyes of adults. This information should prove as comparative for assessment of IOP fluctuation in children with known or suspected glaucoma.


Determination of inorganic phosphate in drug formulations and biological fluids using a plant tissue electrode.
A suitable biosensor for the analysis of inorganic phosphate was developed by coupling the enzyme glucose oxidase to a slice of potato (Solanum tuberosum) containing the acid phosphatase, and using an amperometric Clark electrode as an indicating sensor. Phosphate concentration can be determined from its inhibition on the acid phosphatase activity. Measurements were carried out at steady-state conditions and the available concentration range of phosphate, repeatability and accuracy, on phosphate standard solutions, were experimentally determined. Finally the sensor was used in pharmaceutical and biological matrices. The results were compared with those ones obtained by Bartlett's spectrometric method.


Solid and solution NMR studies of the complexation of Ag+ with the trans isomer of captopril: biological activities of this high blood pressure drug along with its Ag+ complex.
Complexation of Ag(+) with captopril, 1-[(2S)-3-mercapto-2-methylpropionyl]-L-proline, has been studied by (1)H and (13)C-NMR spectroscopy. The equilibrium constants for the trans to cis isomers of captopril bound to Ag(+) were measured by (1)H NMR spectroscopy. It is observed that the trans isomer of the drug binds more strongly to Ag(+) between pH 5 and 8, as shown by the broadening of the trans isomer's resonances in (13)C NMR spectra on complexation. A monodentate complexation of the trans captopril with Ag(+) via the thiol site is proposed based on the solid-state NMR and IR data. A superior antimicrobial activity is exhibited by the Cap-Ag(I) complex compared to captopril ligand itself against Heterotrotropic Plate Counts (HPC), Pseudomonas aeruginosa and Fecal streptococcus bacteria.


Comparative study of the therapeutic effect of Doxorubicin and Resveratrol combination on 2D and 3D (spheroids) cell culture models.
The assessment of drug-combinations for pancreatic cancer treatment is usually performed in 2D cell cultures. In this study, the therapeutic effect and the synergistic potential of a particular drug-combination towards 2D and 3D cell cultures of pancreatic cancer were compared for the first time. Thus, the effect of Doxorubicin:Resveratrol (DOX:RES) combinations (at molar ratios ranging from 5:1 to 1:5) in the viability of PANC-1 cells cultured as 2D monolayers and as 3D spheroids was analyzed. The results showed that the cells' viability was more affected when DOX:RES combinations containing higher contents of RES (1:2-1:5 molar ratios) were used. This can be explained by the ability of RES to reduce the P-glycoprotein (P-gp)-mediated efflux of DOX. Further, it was also revealed that the synergic effect of this drug combination was different in 2D and in 3D cell cultures. In fact, despite of the 1:4 and 1:5 DOX:RES ratios being both synergistic for both types of PANC-1 cell cultures, their Combination Indexes (CI) in the monolayers were lower than those attained in spheroids. Overall, the obtained results revealed that the DOX:RES combination is promising for pancreatic cancer treatment and corroborate the emergent need to evaluate drug combinations in 3D cell cultures.