Production and recovery of polyunsaturated fatty acids-added lipids from fermented canola.
Canola flake was investigated as a potential substrate for fungal conversion to produce polyunsaturated fatty acids (PUFAs)-added oil in a 7l fermenter. The results showed that yields of total oil were reduced 9-22% compared to initial oil in the canola flake, but as high as 445mg/l arachidonic acid (ARA, C20:4n6) and 67mg/l eicosapentaenoic acid (EPA, C20:5n3) were produced. The percentages of ARA and EPA of total fatty acids in this fermented oil were 15.5% and 2.3%, respectively. Supercritical CO2 extraction was then investigated for the lipid recovery from fermented canola flake, and extraction kinetics were modeled. The feasibility was demonstrated for production of PUFAs in a laboratory-scale fermentor using canola flake as a single nutrient, and for lipid extraction using supercritical CO2.


Apples and Oranges: Developmental Discontinuities in Spoken-Language Processing?
Much research focuses on speech processing in infancy, sometimes generating the impression that speech-sound categories do not develop further. Yet other studies suggest substantial plasticity throughout mid-childhood. Differences between infant versus child and adult experimental methods currently obscure how language processing changes across childhood, calling for approaches that span development.


Identification and analysis of oil candidate genes reveals the molecular basis of cottonseed oil accumulation in Gossypium hirsutum L.
Based on the integration of QTL-mapping and regulatory network analyses, five high-confidence stable QTL regions, six candidate genes and two microRNAs that potentially affect the cottonseed oil content were discovered. Cottonseed oil is increasingly becoming a promising target for edible oil with its high content of unsaturated fatty acids. In this study, a recombinant inbred line (RIL) cotton population was constructed to detect quantitative trait loci (QTLs) for the cottonseed oil content. A total of 39 QTLs were detected across eight different environments, of which five QTLs were stable. Forty-three candidate genes potentially involved in carbon metabolism, fatty acid synthesis and triacylglycerol biosynthesis processes were further obtained in the stable QTL regions. Transcriptome analysis showed that nineteen of these candidate genes expressed during the developing cottonseed ovules and may affect the cottonseed oil content. Besides, transcription factor (TF) and microRNA (miRNA) co-regulatory network analyses based on the nineteen candidate genes suggested that six genes, two core miRNAs (ghr-miR2949b and ghr-miR2949c), and one TF GhHSL1 were considered to be closely associated with the cottonseed oil content. Moreover, four vital genes were validated by quantitative real-time PCR (qRT-PCR). These results provide insights into the oil accumulation mechanism in developing cottonseed ovules through the construction of a detailed oil accumulation model.


Characterization of a novel hatching enzyme purified from starfish Asterina pectinifera.
Hatching enzyme is a protease which can degrade the membrane of egg. In this study, a hatching enzyme was purified from starfish (Asterina pectinifera) with 6.34 fold of purification rate, 5.04 % of yield, and 73.87 U/mg of specific activity. The molecular weight of starfish hatching enzyme was 86 kDa, which was reduced to 62 kDa after removal of N-linked oligosaccharides. The optimal pH and temperature of the hatching enzyme activity were pH 7.0 and 40 °C, respectively, while those of stability were pH 8 and 20 °C. The kinetic parameters, Vmax , Km , K cat and Kcat/Km values were 0.197 U/ml, 0.289 mg/ml, 112.57 s-1, and 389.52 ml/mg s, respectively. Zn2+ increased the enzyme activity by 167.28 %, while EDTA, TPCK, TGCK, leupeptin, PMSF, and TLCK decreased. In addition, Ca2+, Mg2+, and Cu2+ did not affect the enzyme activity. The starfish hatching enzyme activity pretreated with EDTA was recovered by Zn2+. Therefore, the starfish hatching enzyme was classified as a serine-zinc protease.


Intensity modulated photocurrent spectroscopy to investigate hidden kinetics at hybrid perovskite-electrolyte interface.
The numerous assorted accounts of the fundamental questions of ion migration in hybrid perovskites are making the picture further intricate. The review of photo-induced ion migration using small perturbation frequency domain techniques other than impedance spectroscopy is more crucial now. Herein, we probe into this by investigating perovskite-electrolyte (Pe-E) and polymer-aqueous electrolyte (Po-aqE) interface using intensity modulated photocurrent spectroscopy (IMPS) in addition to photoelectrochemical impedance spectroscopy (PEIS). We reported that the electronic-ionic interaction in hybrid perovskites including the low-frequency ion/charge transfer and recombination kinetics at the interface leads to the spiral feature in IMPS Nyquist plot of perovskite-based devices. This spiral trajectory for the perovskite-electrolyte interface depicts three distinct ion kinetics going on at the different time scales which can be more easily unveiled by IMPS rather than PEIS. Hence, IMPS is a promising alternative to PEIS. We used Peter's method of interpretation of IMPS plot in photoelectrochemistry to estimate charge transfer efficiency [Formula: see text] from the Rate Constant Model. The [Formula: see text] at low-frequency for Pe-E interface exceeds unity due to ion migration induced modified potential across the perovskite active layer. Hence, ion migration and mixed electronic-ionic conductivity of hybrid perovskites are responsible for the extraordinary properties of this material.


Visualization of the hybrid state of tRNA binding promoted by spontaneous ratcheting of the ribosome.
A crucial step in translation is the translocation of tRNAs through the ribosome. In the transition from one canonical site to the other, the tRNAs acquire intermediate configurations, so-called hybrid states. At this stage, the small subunit is rotated with respect to the large subunit, and the anticodon stem loops reside in the A and P sites of the small subunit, while the acceptor ends interact with the P and E sites of the large subunit. In this work, by means of cryo-EM and particle classification procedures, we visualize the hybrid state of both A/P and P/E tRNAs in an authentic factor-free ribosome complex during translocation. In addition, we show how the repositioning of the tRNAs goes hand in hand with the change in the interplay between S13, L1 stalk, L5, H68, H69, and H38 that is caused by the ratcheting of the small subunit.


A novel in vitro sperm head decondensation protocol for rapid flow cytometric measurement of deoxyribonucleic acid content.
To set up a novel protocol of sperm head in vitro decondensation that obviates the problematic effect of the variable degree of sperm chromatin packaging on DNA staining needed for flow cytometric analysis. Development of a new cytofluorimetric assay. University laboratory. Semen specimens were obtained from normospermic healthy volunteers at the Department of Life and Environmental Sciences, Università Politecnica delle Marche. Setup of the novel in vitro sperm head decondensation protocol; sperm were then stained and analyzed by flow cytometry to measure DNA content. Mean fluorescent channel, DNA content, percentage diploid sperm. Native nondecondensed fluorochrome-labeled sperm show significant under-staining, resulting in an underestimated C-value (approximately 1.4 pg). This protocol ensures stoichiometric staining of sperm DNA, which becomes fully reachable by fluorescent probes and makes the diploid (7.12 pg) over haploid (3.56 pg) sperm frequency quantification easier. This study establishes a simple method for in vitro sperm head decondensation, which allows accurate detection of the real sperm DNA content.


Phytochemical consumption and the risk of teratozoospermia: findings from a hospital-based case-control study in China.
Are dietary phytochemicals associated with the risk of teratozoospermia? Dietary intake of carotene, including total carotene, α-carotene, β-carotene as well as retinol equivalent, and lutein + zeaxanthin, were inversely correlated with the risk of teratozoospermia. Phytochemicals are natural plant derived bioactive compounds, which have been reported to be potentially associated with male reproductive health. To date, no study has investigated the association between phytochemical intake and the risk of teratozoospermia. This hospital-based case-control study, which included 146 newly diagnosed teratozoospermia cases and 581 controls with normozoospermia from infertile couples, was conducted in a hospital-based infertility clinic in China, from June 2020 to December 2020. Dietary information was collected using a validated semi-quantitative 110-item food frequency questionnaire. Unconditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between phytochemical (i.e. phytosterol, carotene, flavonoid, isoflavone, anthocyanidin, lutein + zeaxanthin, and resveratrol) intake and the risk of teratozoospermia. We observed a decreased risk of teratozoospermia for the highest compared with the lowest tertile consumption of total carotene (OR = 0.40, 95% CI = 0.21-0.77), α-carotene (OR = 0.53, 95% CI = 0.30-0.93), β-carotene (OR = 0.47, 95% CI = 0.25-0.88), retinol equivalent (OR = 0.47, 95% CI = 0.24-0.90), and lutein + zeaxanthin (OR = 0.35, 95% CI = 0.19-0.66), with all of the associations showing evident linear trends (all P trend <0.05). In addition, significant dose-response associations were observed between campestanol and α-carotene consumption and the risk of teratozoospermia. Moreover, there was a significant multiplicative interaction between BMI and lutein + zeaxanthin intake (P interaction <0.05). The cases and controls were not a random sample of the entire target population, which could lead to admission rate bias. Nevertheless, the controls were enrolled from the same infertility clinic, which could reduce the bias caused by selection and increase the comparability. Furthermore, our study only included a Chinese population, therefore caution is required regarding generalization of our findings to other populations. Dietary phytochemicals, namely carotene, lutein, and zeaxanthin, might exert a positive effect on teratozoospermia. These phytochemicals are common in the daily diet and dietary supplements, and thus may provide a preventive intervention for teratozoospermia. This study was funded by Natural Science Foundation of Liaoning Province (No. 2022-MS-219 to X.B.W.), Outstanding Scientific Fund of Shengjing Hospital (No. M1150 to Q.J.W.), Clinical Research Cultivation Project of Shengjing Hospital (No. M0071 to B.C.P.), and JieBangGuaShuai Project of Liaoning Province (No. 2021JH1/1040050 to Y.H.Z.). All authors declared that there was no conflict of interest. N/A.


Effects of Tai Chi and cognitive behavioral therapy for insomnia on improving sleep in older adults: Study protocol for a non-inferiority trial.
Insomnia is a prevailing health problem among older adults. Tai Chi, a popular mind-body exercise practiced by older people in various oriental communities, has been shown to improve sleep. However, Tai Chi has not been directly compared to cognitive behavioral therapy for insomnia (CBT-I), which is the first-line non-pharmacological treatment for insomnia in older adults. This study aims to examine whether Tai Chi is non-inferior to CBT-I as a treatment for insomnia in older adults. This is a single-center, assessor-blinded, non-inferiority randomized controlled trial comparing Tai Chi and CBT-I in 180 older adults aged ≥50 years with chronic insomnia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Participants will be randomly assigned to either the Tai Chi or CBT-I group. Interventions will last for 3 months with a 12-month follow-up. The primary outcome is self-perceived insomnia severity measured by Insomnia Severity Index (ISI) at 3 months and at 15 months. The secondary outcomes include the remission rate of chronic insomnia, insomnia treatment response, subjective sleep quantity and quality, 7-day actigraphy, 7-day sleep diary, sleep medication, health-related quality of life, mental health, body balance and lower extremity function, adverse events, habitual physical activity, and dietary intake. Measurements will be conducted at baseline, 3 months, and 15 months by outcome assessors who are blinded to the group allocation. This will be the first non-inferiority randomized controlled trial to compare the efficacy and long-term outcomes of Tai Chi versus CBT-I for treating insomnia in older adults. This study will be of clinical importance as it supports the use of Tai Chi as an alternative non-pharmacological approach for insomnia treatment and sustainable management.


Pharmacokinetics of intravenously administered levofloxacin in men and women.
To characterize and compare the pharmacokinetics of levofloxacin in men and women after systemic administration. Prospective, open-label, parallel group pharmacokinetic study. University research center. Eleven healthy men and nine healthy women stratified by body mass index. Subjects received levofloxacin as a single 500-mg intravenous dose. Serum and urine were collected over 36 hours. Levofloxacin concentrations were determined by high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic analysis was performed with ADAPT II software (University of Southern California, Los Angeles, CA). Median (range) body mass index was 23.2 kg/m2 (19.9-28.3 kg/m2) for men and 23.6 kg/m2 (16.0-32.4 kg/m2) for women (p = 0.67). A two-compartment model best fit the pharmacokinetic data: median (range) R2 was 0.996 (0.990-0.999). Women had a 24% greater exposure to levofloxacin, with a significantly smaller steady-state volume of distribution (p < 0.01) and a slower clearance (p < 0.01). Differences exist in the disposition of levofloxacin between healthy men and women after systemic administration. Fixed intravenous doses of levofloxacin will lead to greater drug exposure in women. Thus, women may have more of an increased risk of fluoroquinolone toxicity than men, and men may need higher doses to achieve similar drug efficacy than women. Levofloxacin dosage adjustments based on sex should be considered on an individual basis.


RRx-001 and the "Right stuff": Protection and treatment in outer space.
From antibiotics to aspirin to antimalarials and to anticancer agents, about half of the world's best-selling drugs are derived from nature. However, accelerating climatic disruption, habitat destruction, pollution, and biodiversity loss all negatively impact the potential of natural sources to continue to serve as repositories of novel pharmaceuticals. On that basis, the final frontier for drug development is perhaps not the rainforests, coral reefs, and other natural habitats but rather the aerospace industry with its virtually unlimited and inexhaustible man-made 'library' of potentially bioactive compounds. The first aerospace-sourced therapeutic to reach the clinic is RRx-001, an inhibitor of the NOD-like receptor - Nucleotide-binding oligomerization domain with Leucine rich Repeat and Pyrin domain (NLRP3) inflammasome in a Phase 3 trial for the treatment of small cell lung cancer (SCLC) and in a soon-to-start Phase 3 trial for protection against chemoradiotherapy-induced severe oral mucositis in first line head and neck cancer. As manned missions to the Moon, Mars, and asteroids as well as space tourism beckon, it is perhaps fitting that a compound like RRx-001, which is derived from 1,3,3-Trinitroazetidine (TNAZ), an explosive propellant for rockets, is a potential "all purpose" option to mitigate the major biomedical effects of space radiation exposures including cancer development and other tissue degenerations both within mission and after mission. This article highlights the promise of RRx-001 to attenuate the acute and late effects of radiation exposure on astronauts including the development of cancer.


Differences in the rheological properties and mixing compatibility with heparinoid cream of brand name and generic steroidal ointments: The effects of their surfactants.
Most steroidal ointments contain propylene glycol (PG) and surfactants, which improve the solubility of corticosteroids in white petrolatum. Surfactants aid the uniform dispersal of PG within white petrolatum. Since the surfactants used in generic ointments are usually different from those used in brand name ointments, we investigated the effects of surfactants on the rheological properties of three brand name ointments and six equivalent generic ointments. We detected marked differences in hardness, adhesiveness, and spreadability among the ointments. Further examinations of model ointments consisting of white petrolatum, PG, and surfactants revealed that the abovementioned properties, especially hardness and adhesiveness, were markedly affected by the surfactants. Since steroidal ointments are often admixed with moisturizing creams prior to use, we investigated the mixing compatibility of the ointments with heparinoid cream and how this was affected by their surfactants. We found that the ointments containing glyceryl monostearate demonstrated good mixing compatibility, whereas those containing non-ionic surfactants with polyoxyethylene chains exhibited phase separation. These results were also consistent with the findings for the model ointments, which indicates that the mixing compatibility of steroidal ointments with heparinoid cream is determined by the emulsifying capacity of the surfactants in their oily bases.


Spontaneous healing of Kaposi's angiosarcoma of the penis.
We report a case of Kaposi's angiosarcoma of the penis. Few cases have been reported of the initial and exclusive involvement of Kaposi's angiosarcoma of the glans penis and prepuce. Our case is unique because of the number of lesions and the spontaneous remission.


Human exposure to metals: levels in autopsy tissues of individuals living near a hazardous waste incinerator.
The concentrations of a number of metals were determined in the brain, bone, kidney, liver, and lung of 20 autopsied subjects who had lived, at least 10 years, in the neighborhood of a hazardous waste incinerator (HWI) in Tarragona (Catalonia, Spain). Results were compared with those obtained in 1998 (baseline survey) and previous surveys (2003 and 2007). Arsenic, Be, Ni, Tl, and V showed concentrations below the corresponding detection limits in all tissues. Cadmium showed the highest levels in the kidney, with a mean value of 21.15 μg/g. However, Cd was found below the detection limit in the brain and bone. Chromium showed similar concentrations in the kidney, brain, and lung (range of mean values, 0.57-0.66 μg/g) and higher in the bone (1.38 μg/g). In turn, Hg was below the detection limit in all tissues with the exception of the kidney, where the mean concentration was 0.15 μg/g (range, <0.05-0.58 μg/g). On the other hand, Mn could be detected in all tissues showing the highest levels in the liver and kidney (1.45 and 1.09 μg/g, respectively). Moreover, Pb showed the highest concentrations in bone (mean, 1.39 μg/g; range, <0.025-4.88 μg/g). Finally, Sn could be detected only in some tissue samples, reaching the highest values in the bone (0.17 μg/g). The current metal levels in human tissues from individuals living near the HWI of Tarragona are comparable and of a similar magnitude to previously reported results corresponding to general populations, as well as those of our previous surveys.


Awareness and knowledge regarding of cervical cancer, Pap smear screening and human papillomavirus infection in Gabonese women.
Cervical cancer is the commonest cancer and the leading cause of cancer mortality in women in Gabon. The age-standardized incidence of cervical cancer is 19.9 per 100 000 women and the mortality rate is 8.4 per 100 000. Various international studies have identified the lack of awareness and knowledge about cervical cancer as barriers to use preventive methods. This article assesses the awareness and knowledge about cervical cancer, Pap smear testing and its use and HPV among women living in Libreville, Gabon. This study was conducted in October 2014 in Libreville. A total of 452 women aged 16 years and above were recruited from different town locations. Logistic regression analysis was used to identify the effect of demographic characteristics on the level of knowledge about cervical cancer, Pap smear testing and HPV. Odds ratio and 95% confidence intervals were used to identify the strength of association. Associations were considered statistically significant at p < 0.05. Of all the women interviewed, 91.6% (414/452) had heard about cervical cancer and only 27.9% (126/452) had heard of Pap smear test. Of these 126 women, only 65.1% (82/126) had done cervical cancer screening and 68.3% (56/82) on the suggestion of a doctor. The most common reason for not undergoing Pap smear testing was neglect (50%, 22/44) followed by lack of financial resources (13.6%, 6/44), fear of discovering a serious disease (13.6%, 6/44) and deeming it unimportant (13.6%, 6/44). Only 8% (40/452) of the participants had heard about HPV and their knowledge of HPV was fair. There is a very poor level of knowledge about cervical cancer among Gabonese women. This study demonstrates a very low level of knowledge about cervical cancer, Pap smear testing and HPV in a sample of Gabonese women. There is a critical need for Gabonese women to be informed about cervical cancer and the Pap smear test to improve the use of this preventive method. The implication of health staff and Gabonese media should be included as a centerpiece in the effort to inform the population in order to reduce the burden of cervical cancer in Gabon and save women lives.


Inhibition of protein synthesis in reovirus-infected HeLa cells with elevated levels of interferon-induced protein kinase activity.
Protein synthesis was inhibited in one line of interferon-treated HeLa cells (line 2) upon infection with reovirus, but not in different HeLa cells (line 1) treated in the same way. The inhibition resulted in polysome runoff, suggesting that it was due to an impairment of peptide chain initiation. Interferon induces the synthesis of a protein kinase, which is activated in cell-free systems by double-stranded RNA and phosphorylates the alpha subunit of eukaryotic initiation factor 2, thus inhibiting the initiation of protein synthesis. Therefore, we measured the level of this protein kinase in extracts prepared from the two HeLa cell lines. Cells of line 2 showed about 3-4 times more protein kinase activity than cells of line 1. The inhibition of protein synthesis upon infection with reovirus was correlated with an increased phosphorylation of the alpha subunit of eukaryotic initiation factor 2 in interferon-treated cells labeled with 32P. The kinase was presumably activated in intact cells by viral double-stranded RNA, but this activation resulted in inhibition of protein synthesis only in cells with elevated levels of the kinase.


Pharmacotherapy considerations with finerenone in the treatment of chronic kidney disease associated with type 2 diabetes.
This review provides an overview of the management of chronic kidney disease (CKD) associated with type 2 diabetes (T2D), how the novel treatment class of nonsteroidal mineralocorticoid receptor antagonists (MRAs) fits within the treatment landscape, and how pharmacists can contribute to the multidisciplinary care of patients with CKD associated with T2D. Optimizing pharmacotherapy for patients with CKD associated with T2D is critical to prevent or slow progression to end-stage kidney disease and reduce the incidence of cardiovascular events. However, many patients with CKD receive suboptimal treatment, in part because of the high complexity of care required, a lack of disease recognition among providers and patients, and a failure to utilize new kidney-protective therapies. Finerenone is the first nonsteroidal, selective MRA to be approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of adult patients with CKD associated with T2D. Clinical trials have demonstrated that finerenone significantly reduces the risk of cardiorenal disease progression vs placebo and has a reduced risk of hyperkalemia compared to traditional steroidal MRAs. Initiation of finerenone should follow evaluation of baseline estimated glomerular filtration rate and serum potassium levels. Consideration of potential drug-drug interactions, follow-up monitoring of potassium levels, and coordination of changes in pharmacotherapy across the patient care team are also important. Finerenone is a valuable addition to the treatment landscape for CKD associated with T2D. Through their expertise in -medication -management, transitions of care, and patient education, clinical pharmacists are well positioned to ensure patients receive safe and effective -treatment.


The P140K mutant of human O(6)-methylguanine-DNA-methyltransferase (MGMT) confers resistance in vitro and in vivo to temozolomide in combination with the novel MGMT inactivator O(6)-(4-bromothenyl)guanine.
The O(6)-methylguanine-DNA-methyltransferase (MGMT) inactivator O(6)-benzylguanine (O(6)-beG) is currently under clinical investigation as a potential tumour-sensitising agent. In clinical trials its use has been associated with increased myelotoxicity and a reduced maximum tolerated dose (MTD) for BCNU. Thus the concept of myeloprotection by gene therapy with an O(6)-beG-insensitive mutant of MGMT is soon to be tested. Recently, an alternative inactivator has been described (O(6)-(4-bromothenyl)guanine, PaTrin-2), which shows potential advantages over O(6)-beG in terms of higher activity against wild-type MGMT and oral formulation. The use of PaTrin-2 has also been associated with increased myelotoxicity in clinical trials and thus PaTrin-2 may also be a candidate for use in conjunction with mutant MGMT gene transfer in genetic chemoprotective strategies. However, its activity against mutant MGMTs has not been reported. We show here that the P(140)K mutant of MGMT is highly resistant to inactivation by PaTrin-2. Furthermore, we show that a human haemopoietic cell line (K562) transduced with a retroviral vector encoding MGMT(P140K) is highly resistant to the cytotoxic effects of PaTrin-2 in combination with the methylating agent temozolomide, and that cells expressing MGMT(P140K) can be effectively enriched in vitro following challenge with this drug combination. Finally, we show that animals reconstituted with bone marrow expressing MGMT(P140K) exhibit haemopoietic resistance to PaTrin-2/temozolomide, which results in in vivo selection of gene-modified cells. All of these effects were comparable to those also achieved using O(6)-beG/temozolomide. Thus our data show that MGMT(P140K) is a suitable candidate for chemoprotective gene therapy where PaTrin-2 is being used in conjunction with temozolomide.


Pharmacokinetics, bioavailability and opioid effects of liquid versus tablet buprenorphine.
Two tablet formulations of buprenorphine (a buprenorphine mono-product, Subutex, and a buprenorphine/naloxone combination product, Suboxone) are available for use in the treatment of opioid addiction; however, the bulk of the clinical studies supporting its approval by the US Food and Drug Administration (FDA) were conducted with a sublingual liquid preparation. To assist the clinician in interpreting the relevant literature in establishing dosing parameters for prescription of tablet buprenorphine, this study was designed to compare the steady state: (1) pharmacokinetics and bioavailability, and (2) physiological, subjective and objective opiate effects of two 8 mg buprenorphine tablets (16 mg) to those of 1 ml (8 mg/ml) buprenorphine solution based upon early reports suggesting that the bioavailability of the tablet was approximately 50% of that of the liquid. Randomized, open-label, two-way crossover study. Inpatient hospitalization for 21 days. Twenty-four male and females in general good health and meeting DSM-IV criteria for opiate dependence. Subjects received one of the two buprenorphine formulations in the first 10-day period, and the other for the second 10-day period with no washout. Pharmacokinetic analyses, opiate effects and adverse events. Drug steady state was reached by Day 7 of each 10-day period, area under the curve for 16 mg (two 8 mg) tablets was higher than the solution. The only non-kinetic statistically significant difference observed between the formulations was in changes in total opioid agonist score. The serum concentration achieved by 16 mg of tablet buprenorphine is higher than that of the 8 mg solution, although differences between physiologic, subjective and objective opioid effects were not noted. The relative bioavailability of tablet versus solution is estimated to be 0.71; thus, with respect to dosing parameters for the tablet, clinicians should consider using less than 16 mg to achieve bioequivalence to the 8 mg solution.


Modelling the transportation of marine plastics over the ocean surface by Cellular Automata.
This article describes a novel Cellular Automata (CA) model to predict the transportation of buoyant marine plastics. The proposed CA model provides a simpler and more affordable approach to a field where the computationally intensive Lagrangian particle-tracking models dominate. The transportation of marine plastics was investigated using well-defined, probabilistic rules governing the advection and diffusion processes. The CA model was applied to evaluate the impact of two input scenarios, namely a "population" and a "river" scenario. Of the sub-tropical gyres, a high percentage of buoyant plastics were found in the Indian gyre (population: 5.0 %; river: 5.5 %) and North Pacific gyre (population: 5.5 %; river: 7 %). These findings show good agreement with previously published results from particle-tracking models. The CA model could be a useful rapid-scenario assessment tool for the estimation marine plastic pollution prior to more in-depth studies on effective mitigation measures to, for example, reduce plastics waste.


Is genistein neuroprotective in traumatic brain injury?
The concerns about negative consequences of estrogen therapy have led to introduce other strategies to obtain estrogen's benefits in the brain. The present study tests the hypothesis that a major isoflavone of soy; genistein with estrogen-like activity can be neuroprotective in traumatic brain injury (TBI). The male Wistar rats were randomly divided to four groups: sham, TBI, vehicle and genistein. The TBI was induced by Marmarou method. The brain edema and the disruption of blood-brain-barrier (BBB) were evaluated 48 h post-TBI. Genistein (15 mg/kg) or dimethyl sulfoxide (DMSO) was injected i.p., twice after TBI. The intracranial pressure (ICP), the motor performance, and the beam-walk task (WB) were determined before trauma, on trauma day (D0), and first (D1) and second (D2) days post-TBI. Genistein inhibited a development of brain edema and a BBB permeability in TBI animals. An increase of ICP and a defect in motor and WB performance were showed following TBI, in all times evaluated. An increase of ICP induced by TBI was suppressed by genistein on D1 and D2 times. Genistein improved a motor disorder induced by TBI, on D1 and D2 times. Also an increase of traversal time in WB task was suppressed by genistein in TBI animals, on D1 and D2 times. The results of this study demonstrated that genistein can be neuroprotective in TBI. Genistein inhibited the disruption of BBB, the brain edema and the increase of ICP, and the disturbance of neurobehavioral performance in TBI.


High school quality is associated with cognition 58 years later.
We leveraged a unique school-based longitudinal cohort-the Project Talent Aging Study-to examine whether attending higher quality schools is associated with cognitive performance among older adults in the United States (mean age = 74.8). Participants (n = 2,289) completed telephone neurocognitive testing. Six indicators of high school quality, reported by principals at the time of schooling, were predictors of respondents' cognitive function 58 years later. To account for school-clustering, multilevel linear and logistic models were applied. We found that attending schools with a higher number of teachers with graduate training was the clearest predictor of later-life cognition, and school quality mattered especially for language abilities. Importantly, Black respondents (n = 239; 10.5 percentage) were disproportionately exposed to low quality high schools. Therefore, increased investment in schools, especially those that serve Black children, could be a powerful strategy to improve later life cognitive health among older adults in the United States.


Altered redox status in the blood of psoriatic patients: involvement of NADPH oxidase and role of anti-TNF-α therapy.
Psoriasis is a chronic hyperproliferative inflammatory skin disease, characterized by a generalized redox imbalance. Anti-tumor necrosis factor (TNF)-α therapy is widely used for the treatment of this disease, but its effect on blood redox status hasn't been explored. To investigate the effects of anti-TNF-α therapy on blood redox status in psoriatic patients. Twenty-nine psoriatic patients (PSO) were divided into two groups: one remained untreated (NRT) and to another the anti-TNF-α therapy was prescribed (TR). The levels of main oxidative stress markers and total antioxidant capacity (TAC) in plasma, levels of total reactive oxygen species (ROS) production, lipoperoxidation, TAC, glutathione content, and activity of NADPH oxidase in white blood cells (WBC) were evaluated in PSO, in NTR and TR after 6 months of the study. Plasma levels of malondialdehyde (MDA) and protein carbonyl content (PCO), ROS production, lipoperoxidation, and glutathione content in WBC were increased, while TAC in both plasma and WBC was decreased in PSO with respect to controls. In the plasma of TR, levels of MDA and PCO were significantly lower with respect to PSO and NTR. The activity of NADPH oxidase was significantly increased in WBC of PSO and NTR but not in TR versus controls. Our results represent novel data about the redox status of WBC in psoriatic patients. A significant redox-balancing effect of anti-TNF-α therapy, probably associated with the normalization of NADPH oxidase activity in WBC, was demonstrated.


Dense (aged) circulating red cells contain normal concentrations of adenosine triphosphate (ATP).
The densest 0.1%--1% of circulating red cells were separated from fresh blood, and the ATP content of a representative sample of such cells was determined. The dense ("old") cells had decreased amounts of ATP relative to unfractionated cells. However, the dense cells were also smaller, and the concentration of ATP in these cells was the same as in controls. Therefore, it seems unlikely that loss of cellular ATP is a causative factor in removal of senescent red cells from the circulation.


Determining design and scale-up parameters for degradation of atrazine with suspended Pseudomonas sp. ADP in aqueous bioreactors.
This work investigated the kinetic parameters of atrazine mineralization by suspended cells of Pseudomonas sp. ADP in both shake flasks and spherical stirred tank batch reactors (SSTR). The degradation of atrazine and growth of Pseudomonas sp. ADP were studied. Experiments were performed at different temperatures and stirring speeds in both reactors at varying initial concentrations of atrazine. Cell growth and atrazine concentration were monitored over time, and a Monod model with one limiting substrate was used to characterize the kinetic behavior. Temperature, stirring speed, and reactor type were all found to significantly affect the regressed Monod parameters. At 27 degrees C and 200 rpm, for the shaker flask experiments, mu max and Ks were determined to be 0.14 (+/-0.01) h-1 and 1.88 (+/-1.80) mg/L, respectively. At 37 degrees C, mu max and Ks increased to 0.25 (+/-0.05) h-1 and 9.59 (+/-6.55) mg/L, respectively. As expected, stirrer speed was also found to significantly alter the kinetic parameters. At 27 degrees C and 125 rpm, mu max and Ks were 0.04 (+/-0.002) h-1 and 3.72 (+/-1.05) mg/L, respectively, whereas at 37 degrees C and 125 rpm, mu max and Ks were 0.07 (+/-0.008) h-1 and 1.65 (+/-2.06) mg/L. In the SSTR the kinetic parameters mu max and Ks at room temperature were determined to be 0.12 (+/-0.009) h-1 and 2.18 (+/-0.47) mg/L, respectively. Although the mu max values for both types of reactors were similar, the shaker flask experiments resulted in considerable error. Error analysis on calculated values of Ks were found to impact estimates in atrazine concentration by as much as two orders of magnitude, depending on the reactor design, illustrating the importance of these factors in reactor scale-up.


Protein kinase C activity is necessary for estrogen-induced Erk phosphorylation in neocortical explants.
Our laboratory showed previously that estrogen activates ERK in neocortical cultures. To further elucidate the precise signaling sequelae that lead to estrogen-induced ERK activity, we evaluated the involvement of protein kinase C (PKC). We found that neocortical explants expressed primarily PKC gamma and PKC epsilon. Consistent with the involvement of PKC in mediating estrogen-induced ERK phosphorylation, we found that estrogen treatment induced translocation of these PKC isoforms to the plasma membrane. Importantly, inhibition of these isoforms abolished the ability of estrogen to phosphorylate ERK. While direct activation of PKC mimicked the effect of estrogen on ERK, both in pattern of activation and resulting intraneuronal distribution of ERK, PKC-induced ERK phosphorylation required the activity of MEK but not B-Raf. Collectively, these data suggest a critical role for PKC in mediating estrogen induction of ERK activation in the developing brain via a MEK-dependent but B-Raf-independent pathway.


The contribution of magnetic susceptibility effects to transmembrane chemical shift differences in the 31P NMR spectra of oxygenated erythrocyte suspensions.
Triethyl phosphate, dimethyl methylphosphonate, and the hypophosphite ion all contain the phosphoryl functional group. When added to an oxygenated erythrocyte suspension, the former compound gives rise to a single 31P NMR resonance, whereas the latter compounds give rise to separate intra- and extracellular 31P NMR resonances. On the basis of experiments with intact oxygenated cell suspensions (in which the hematocrit was varied) and with oxygenated cell lysates (in which the lysate concentration was varied), it was concluded that the chemical shifts of the intra- and extracellular populations of triethyl phosphate differ as a consequence of the diamagnetic susceptibility of intracellular oxyhemoglobin but that this difference is averaged by the rapid exchange of the compound across the cell membrane. The difference in the magnetic susceptibility of the intra- and extracellular compartments contributes to the observed separation of the intra- and extracellular resonances of dimethyl methylphosphonate and hypophosphite. The magnitude of this contribution is, however, substantially less than that calculated using a simple two-compartment model and varies with the hematocrit of the suspension. Furthermore, it is insufficient to fully account for the transmembrane chemical shift differences observed for dimethyl methylphosphonate and hypophosphite. An additional effect is operating to move the intracellular resonances of these compounds to a lower chemical shift. The effect is mediated by an intracellular component, and the magnitude of the resultant chemical shift variations depends upon the chemical structure of the phosphoryl compound involved.


An estimate of pollen carryover by ants in a natural population of Scleranthus perennis L. (Caryophyllaceae).
Pollen carryover by ants was estimated in a natural population of Scleranthus perennis L. (Caryophyllaceae) using fluorescent dye as a pollen analogue.A highly significant exponential decrease in deposition of dye grains in a sequence of flowers visited by the main flowr visitor, Formica (S.) rufibarbis F., was observed with most grains being deposited in the first few flowers visited. At most 12 flowers were visited in a sequence.The mean between-flower transfer distance was estimated to be 6.2 cm, within-plant pollen transfers being recorded as zero. When all within-plant movements were excluded the mean was 22.5 cm. The distribution of transport distances differed from what I observed for honey-bees which occasionally foraged on dense stands of S. perennis. Calculations made on the deposition of dye grains transferred by ants showed that 7% of the dye grains deposited in the first flower visited after the dye source may reach a flower situated c. 30 cm from the dye source.


High-frequency linear transducer improves detection of an intrauterine pregnancy in first-trimester ultrasonography.
The objective was to determine if the need for transvaginal ultrasonographic examination can be decreased by the addition of the transabdominal high-frequency, 12-4-MHz linear transducer after a failed examination with the 6-2-mHz curvilinear transducer when evaluating for an intrauterine pregnancy (IUP). This is a prospective pilot study of women in their first trimester of pregnancy presenting to the emergency department with abdominal pain and/or vaginal bleeding. If no IUP was identified using the curvilinear transducer via the transabdominal approach, they were subsequently scanned using the linear transducer. Patients without evidence of an IUP transabdominally were scanned via the transvaginal approach. Eighty-one patients were evaluated; no IUP was visualized in 27 using the standard curvilinear transducer approach, and these then had an ultrasonography performed with the linear transducer. Of these, 9 patients (33.3%; 0.95 confidence interval [CO], 15.5%-51.1%) were found to have an IUP with the linear transducer. For the 18 patients who received a transvaginal scan, 15 patients (83.3%; 0.95 CI, 66.1%-100%) had no IUP identified with the transvaginal transducer, and 3 (16.7%; 0.95 CI, 0%-33.9%) had an IUP identified. The transabdominal use of a high-frequency linear transducer in the evaluation of patients in the first trimester after failed curvilinear transducer results in a clinically significant reduction in the need for transvaginal ultrasonography to confirm the presence of an IUP.


[Infliximab-induced hepatitis during treatment of vulvar Crohn's disease].
We report a case of acute cytolytic hepatitis induced by infliximab in a patient with severe vulvar Crohn's disease. A 29-year-old Congolese woman presented with severe vulvar Crohn's disease active for 7 years. In view of resistance to standard medication (corticosteroids and metronidazole), treatment with infliximab 5mg/kg per injection was initiated. The patient developed acute cytolytic hepatitis 10 days after the first injection and the disease was asymptomatic. The various investigations confirmed the direct cytotoxicity of infliximab. A favourable outcome was gradually achieved after increasing the dosage of corticosteroids. At the same time, an improvement in the vulvar lesions was noted after this sole injection. Infliximab-induced is rare, with only 20 reported cases. The physiopathological mechanism is unknown and a number of aetiologies have been suggested. This new case raises the issue of the need for routine liver function testing during infliximab therapy given the asymptomatic nature of this effect.


A case of necrotizing fasciitis due to Streptococcus pneumoniae.
We report a patient suffering from necrotizing fasciitis. The principal pathogen was Streptococcus pneumoniae. As far as we are aware, this is the first reported case of necrotizing fasciitis (NF) attributable to this organism. We discuss the pathogenesis of NF, and review the literature relating to this disorder.


Anatomy of the anterior interosseous innervation of the pronator quadratus: evaluation of structures at risk in the single dorsal incision wrist denervation technique.
Patients with chronic wrist pain often are treated with wrist denervation, which typically involves transecting both the anterior interosseous nerve (AIN) and the posterior interosseous nerve. A single dorsal incision approach is an improvement over the more traditional multiple-incision technique. The purpose of our study was to describe the branches of the AIN to the pronator quadratus and evaluate the risk of denervation with the single dorsal incision technique. Twelve fresh-frozen cadaver forearms were dissected. The branches of the AIN to the pronator quadratus were identified and the individual branch points were measured from the articular edge of the distal radius. Wrist denervation was then performed on each specimen through the single dorsal incision (as suggested by Berger). There were an average of 3 branches from the AIN to the pronator quadratus. All forearms had at least 1 branch to the pronator quadratus more proximal to the distal end of the dorsal skin incision; however, in only 2 of the forearms was the most proximal branch more than 2 cm proximal to the distal end of the dorsal skin incision. Wrist denervation through the recommended single dorsal incision poses a serious risk for completely denervating the pronator quadratus. Therefore the resection of the AIN must be performed close to the distal margin of the pronator quadratus.


Regulation of glucose and lipid metabolism by the pancreatic and extra-pancreatic actions of taurine.
The beneficial actions of L-taurine (Tau) against glucose intolerance, obesity, type 2 diabetes (T2D), and non-alcoholic fat liver disease (NAFLD) have been linked to its antioxidant and anti-inflammatory effects, which ameliorate tissue insulin sensitivity. Importantly, there are several lines of evidence that indicate a direct action of Tau on the endocrine pancreas to regulate the secretion and paracrine actions of insulin, glucagon, and somatostatin. Furthermore, Tau can also ameliorate glucose metabolism through the enhancement of insulin signaling. However, some of the benefits of Tau upon intermediary metabolism may manifest via considerable antagonism of the action of insulin. Therefore, this review discusses the mechanisms of action by which Tau may regulate endocrine pancreatic morphofunction, and glucose and lipid homeostasis.


[Mosaic trisomy 9. Report of a new case and delimitation of the clinical syndrome].
Clinical features of a girl with mosaic 9-trisomy (46,XX/47,XX, + 9) are described. Trisomy was identified by means of G bands. Unusual spine, ribs and CNS abnormalities were observed. A comparison with 14 previous by described cases is made.


Technology-Based Obesity Prevention Interventions Among Hispanic Adolescents in the United States: Scoping Review.
Given that today's adolescents are digital front-runners, technology-based obesity prevention strategies are age-appropriate for this population. The use of remote and wireless technologies may be suitable for extending the reach and engagement of obesity prevention efforts among high-risk Hispanic youths, as this subgroup is disproportionately affected by barriers that limit participation in traditional, in-person interventions. The purpose of this scoping review was to examine the intervention and sample characteristics of technology-based obesity prevention interventions among Hispanic adolescents. We also examined feasibility criteria to assess the acceptability and appropriateness of technology-based strategies among Hispanic youths. A comprehensive search of Embase and PubMed identified 7 studies that met the inclusion criteria. Data were extracted by 2 independent reviewers. Of the 7 included studies, half (n=4, 57%) used a randomized control trial design, with equal implementation in school (n=3, 43%) and clinic (n=4, 57%) settings. Studies commonly targeted improvements in diet (n=4, 57%) and physical activity (n=7, 100%), with only 1 (14%) study focused on sedentary behaviors. Just 2 (29%) studies reported the use of behavioral theories or models. Studies focused primarily on youths in early (n=5, 71%) or middle (n=6, 86%) adolescence, and there was limited information reported on socioeconomic status. Only 3 (43%) study conducted formative work, and few (n=3, 43%) reported on acceptability. Only 1 (14%) study reported that materials were available in Spanish and English, and only 1 (14%) study used culturally tailored content. Additionally, 3 (43%) studies used strategies that considered social determinants of health. To increase our understanding of the feasibility and effectiveness of technology-based obesity prevention strategies among Hispanic adolescents, there is a need for more feasibility studies that are theoretically grounded and comprehensively report on feasibility-related outcomes. Future studies should also leverage technology to simultaneously address multiple health behaviors beyond diet and physical activity. The result of this review can be used to guide the development of future technology-based obesity prevention strategies among Hispanic adolescents. CliniclaTrials.gov NCT04953442; https://clinicaltrials.gov/ct2/show/NCT04953442.


Melatonin content of the pineal, parietal eye and blood plasma of the lizard, Trachydosaurus rugosus: effect of constant and fluctuating temperature.
Lizards acclimated to a light cycle accompanied by a thermocycle of 30 degrees C/15 degrees C had a more robust rhythm in pineal and plasma melatonin levels than those acclimated to constant 30 degrees C. At constant 15 degrees C, the melatonin rhythm was abolished entirely. A similar thermosensitivity in melatonin content was found in the parietal eye, indicating that this photoreceptive structure may also be capable of synthesising methoxyindoles.


A Glb1-2A-mCherry reporter monitors systemic aging and predicts lifespan in middle-aged mice.
The progressive decline of physiological function and the increased risk of age-related diseases challenge healthy aging. Multiple anti-aging manipulations, such as senolytics, have proven beneficial for health; however, the biomarkers that label in vivo senescence at systemic levels are lacking, thus hindering anti-aging applications. In this study, we generate a Glb1+/m‒Glb1-2A-mCherry (GAC) reporter allele at the Glb1 gene locus, which encodes lysosomal β-galactosidase-an enzyme elevated in tissues of old mice. A linear correlation between GAC signal and chronological age is established in a cohort of middle-aged (9 to 13 months) Glb1+/m mice. The high GAC signal is closely associated with cardiac hypertrophy and a shortened lifespan. Moreover, the GAC signal is exponentially increased in pathological senescence induced by bleomycin in the lung. Senolytic dasatinib and quercetin (D + Q) reduce GAC signal in bleomycin treated mice. Thus, the Glb1-2A-mCherry reporter mice monitors systemic aging and function decline, predicts lifespan, and may facilitate the understanding of aging mechanisms and help in the development of anti-aging interventions.


Retreatment with aromatase inhibitor therapy in the management of granulosa cell tumor.
•Over 90% of granulosa cell tumors have a FOXL2 mutation that contributes to aromatase upregulation.•Chemotherapy has demonstrated limited efficacy in the treatment of granulosa cell tumors.•A patient with recurrent granulosa cell tumor responded briefly to anastrazole treatment.•Retreatment with another aromatase inhibitor letrozole led to a durable response of 24 months.


Identification of viral microRNAs.
Given the important function of microRNAs (miRNAs) in the control of gene expression, it is not surprising to find that some viruses encode their own miRNAs. Although the function of the overwhelming majority of these miRNAs remains unknown, at least some of them are expected to play crucial roles in the viral life cycle, and hence there is great interest in identifying novel viral miRNAs. The majority of currently known viral (and host) miRNAs have been identified by cloning of small RNAs, but, due to their small size, viral genomes are especially amenable to alternative methods based on the computational prediction of miRNA candidates. Here, we provide a detailed protocol on how to use computational prediction methods in conjunction with high-throughput microarray analysis to detect miRNAs in viral genomes.


Reduction in neutrophil cell surface expression of tumor necrosis factor receptors but not Fas after transmigration: implications for the regulation of neutrophil apoptosis.
To test the hypothesis that loss of polymorphonuclear neutrophil tumor necrosis factor alpha (TNF-alpha) receptors during transmigration renders the exudate neutrophil refractory to TNF-alpha-mediated stimulation of apoptosis; and to investigate the surface expression of Fas on both circulating and exudate neutrophils. A prospective cohort study. Surgical laboratory of a tertiary care hospital. Twenty-one healthy human volunteers. All subjects had circulating neutrophils and exudate neutrophils collected by venipuncture and skin window methods, respectively. Circulating and exudate neutrophils were incubated in culture medium (1.0x10(6) neutrophils per milliliter) alone or with TNF-alpha (100 ng/mL). Apoptosis was evaluated by flow cytometry (annexin V-fluorescein isothiocyanate and propidium iodide). Tumor necrosis factor alpha-phycoerythrin and anti-human Fas-fluorescein isothiocyanate were used to evaluate neutrophil TNF-alpha receptors and surface expression of Fas. Exudate neutrophils had a significant delay in apoptosis rates when compared with circulating neutrophils. The percentage of neutrophils expressing TNF-alpha receptors was significantly diminished after exudation (80%+/-15% vs 33%+/-9%; P<.001), as was the median channel number of TNF-alpha phycoerythrin fluorescence (8.1+/-1.6 vs 5.2+/-0.5; P=.001). However, the expression of Fas was unchanged after transmigration (percentage positive for Fas: 98.7%+/-0.7% vs 92.8%+/-3.4%, P=.89; Fas antibody-fluorescein isothiocyanate median channel fluorescence: 12.2+/-1.1 vs 13.1+/-1.2; P=.80). Exposure of exudate neutrophils to TNF-alpha failed to increase their rate of apoptosis. Exudate polymorphonuclear neutrophils are confirmed to have delayed apoptosis. Loss of TNF-alpha receptors during transmigration is necessary for neutrophil survival in the extravascular inflammatory milieu.


An experimental model for measuring middle ear antimicrobial drug penetration in otitis media.
Bacteria are an important cause of acute otitis media and successful treatment depends on achieving inhibitory or bacteriacidal antimicrobial drug concentrations in the middle ear. To evaluate further otitis media treatment success and failure, we developed a chinchilla model to study antimicrobial drug penetration through the middle ear mucosa. Using quantitative histomorphometry, we measured the middle ear space in 10 chinchillas and found a mean +/- SD volume of 2.09 +/- 0.08 ml and a mean +/- SD surface area of 14.41 +/- 1.48 cm2. To measure the apparent rate constant (Kc) of antibiotic elimination from the middle ear, through the middle ear mucosa, an antibiotic solution was inoculated into the middle ear cavity, and samples were aspirated between 1 and 8 hr later. In normal ears, the mean Kc +/- SD for amoxicillin was 0.118 +/- 0.013 hr-1, that for a trimethoprim 0.461 +/- 0.090 hr-1, and that for sulfamethoxazole 0.265 +/- 0.062 hr-1. In ears inoculated with type 7F Streptococcus pneumoniae to induce acute otitis media, the Kc +/- SD increased for all three drugs (P less than 0.05): amoxicilin to 0.286 +/- 0.089 hr-1, trimethoprim to 0.662 +/- 0.118 hr-1, and sulfamethoxazole to 0.411 +/- 0.056 hr-1. These values demonstrate that amoxicillin had the lowest apparent penetration rate constant of the three antibiotics but the greatest increase from normal to infected mucosa (142%). Trimethoprim had the highest apparent penetration rate constant of the three antibiotics but the smallest increase from normal to infected mucosa (44%), while the sulfamethoxazone apparent penetration rate constant increased from normal to infected mucosa by 55%.(ABSTRACT TRUNCATED AT 250 WORDS)


A reaction network scheme for hidden Markov model parameter learning.
With a view towards artificial cells, molecular communication systems, molecular multiagent systems and federated learning, we propose a novel reaction network scheme (termed the Baum-Welch (BW) reaction network) that learns parameters for hidden Markov models (HMMs). All variables including inputs and outputs are encoded by separate species. Each reaction in the scheme changes only one molecule of one species to one molecule of another. The reverse change is also accessible but via a different set of enzymes, in a design reminiscent of futile cycles in biochemical pathways. We show that every positive fixed point of the BW algorithm for HMMs is a fixed point of the reaction network scheme, and vice versa. Furthermore, we prove that the 'expectation' step and the 'maximization' step of the reaction network separately converge exponentially fast and compute the same values as the E-step and the M-step of the BW algorithm. We simulate example sequences, and show that our reaction network learns the same parameters for the HMM as the BW algorithm, and that the log-likelihood increases continuously along the trajectory of the reaction network.


Bacterial mutagenicity of aceanthrylene: a novel cyclopenta-fused polycyclic aromatic hydrocarbon of low molecular weight.
Aceanthrylene, a non-alternant cyclopenta-fused hydrocarbon, was shown to be weakly mutagenic without S9 and strongly mutagenic with S9 in the Ames Salmonella plate incorporation assay. The compound was most active in strain TA100 (35 revertants/nmole in the presence of 0.3 mg of S9 protein), and less active in strains TA98, TA1537 and TA1538 (20, 10 and 3.1 rev/nmole respectively, + S9). Strain TA1535 was unresponsive, suggesting that this compound induces frameshift mutations rather than base-pair substitutions. The mutagenic potency of aceanthrylene is consistent with predictions of its activity based on the relatively large delocalization energy (delta E deloc/beta = 0.931) of the carbonium ion which would result from oxirane ring opening of the 1,2-epoxide, a potential active metabolite.


No correlation between minimal electrical charge at the tip of the stimulating catheter and the efficacy of the peripheral nerve block catheter for brachial plexus block: a prospective blinded cohort study.
Stimulating catheters offer the possibility of delivering an electrical charge via the tip of the catheter. This may be advantageous as it allows verifying if the catheter tip is in close proximity to the target nerve, thereby increasing catheter performance. This prospective blinded cohort study was designed to investigate whether there is a correlation between the minimal electrical charge at the tip of the stimulating catheter, and the efficacy of the peripheral nerve block (PNB) catheter as determined by 24 h postoperative morphine consumption. Forty adult patients with ASA physical health classification I-III scheduled for upper extremity surgery under combined continuous interscalene block and general anesthesia were studied. Six patients were excluded from analysis.After inserting a stimulating catheter as if it were a non-stimulating catheter for 2-5 cm through the needle, the minimal electrical charge necessary to obtain an appropriate motor response was determined. A loading dose of 20 mL ropivacaine 0.75% ropivacaine was then administered, and postoperative analgesia was provided by a continuous infusion of ropivacaine 0.2% 8 mL.h-1 via the brachial plexus catheter, and an intravenous morphine patient-controlled analgesia (PCA) device.Main outcome measures include the minimal electrical charge (MEC) at the tip of the stimulating catheter necessary to elicit an appropriate motor response, and the efficacy of the PNB catheter as determined by 24 h postoperative PCA morphine consumption. Mean (SD) [range] MEC at the tip of the stimulating catheter was 589 (1414) [30 - 5000] nC. Mean (SD) [range] 24 h morphine consumption was 8.9 (9.9) [0-29] mg. The correlation between the MEC and 24 h postoperative morphine consumption was Spearman's Rho rs = -0.26, 95% CI -0.56 to 0.09. We conclude that there is no proportional relation between MEC at the tip of the blindly inserted stimulating catheter and 24 h postoperative morphine consumption. Trialregister.nl identifier: NTR2328.


Ultrastructure of the swim bladder of the goldfish, Carassius auratus.
The swim bladder of the cyprinid Carassius auratus (goldfish) is a two-chambered organ connected to the esophagus by a pneumatic duct. The anterior chamber is lined by a single type of squamous epithelial cell. Two types of epithelial cells are present in the posterior chamber. Flattened cells with differences in the electron density of the cytoplasm line most of the chamber. Darker cells generally contain large amounts of glycogen. Cuboidal epithelial cells also occur in the posterior chamber. A glandular layer external to the muscularis in the posterior chamber is composed of large cells containing little glycogen, an extensive Golgi apparatus, and numerous mitochondria with single large granules. Capillaries and nerves are present in large numbers in this layer. Blood vessels form micro-retia mirabilia in the submuscular layer external to the glandular layer. Vessels are of two distinct types with wide lumina and flattened endothelium characterizing the venous vessels. Arterial vessels and have smaller lumina, thick endothelial cells with prominent pinocytotic vesicles, and surrounding pericytes. Collagen is present in three forms in this swim bladder - large tactoids in the tunica externa of the anterior chamber, smaller tactoids in the lamina propria of the posterior chamber, and small fibrils in all other areas.


A baseline study of benthic community associated with Amphioxus Sand in subtropical Hong Kong.
An annual investigation on the seasonal changes of benthic community structure associated with Amphioxus Sand was conducted at two sites in the eastern waters of subtropical Hong Kong, where three species of amphioxus, Branchiostoma belcheri, B. japonicum and B. malayanum coexist. A total of 84 species and 4169 individuals were recorded at Tai Long Wan, whereas a total of 87 species and 3915 individuals were recorded at Pak Lap Wan. Benthic polychaetes were dominant, including high abundance of Onuphis eremita and Prionospio malmgreni. Results of cluster analysis showed significant community structures between the two areas because of difference in sediment granulometry. However, temporal changes within these Amphioxus Sand communities were minimal. In general, the Amphioxus Sand communities in Hong Kong showed higher species richness of Polychaeta as compared with similar studies elsewhere, possibly implying an increased level of organic pollution in Hong Kong waters.


The role of cortisol in immunosuppression in subarachnoid haemorrhage.
We sought to determine the extent to which cortisol suppressed innate and T cell-mediated cytokine production and whether it could be involved in reducing peripheral cytokine production following subarachnoid haemorrhage (SAH). Whole blood from healthy controls, patients with SAH and healthy volunteers was stimulated with lipopolysaccharide (LPS), to stimulate innate immunity, or phytohaemagglutinin (PHA), to stimulate T cell-mediated immunity. Varying concentrations of cortisol were included, with or without the cortisol antagonist RU486. Concentration of interleukin-6 (IL-6), IL-1β and tumour necrosis factor-alpha) TNFα were determined as a measure of innate immunity. IL-6, IL-17 (interferon gamma) IFNƔ and IL-17 were determined as an indicator of T cell-mediated immunity. Suppression of innate responses to LPS was apparent in whole blood from SAH patients, relative to healthy controls, and TNFα production was inversely correlated with plasma cortisol concentration. Cytokine production in whole blood from healthy volunteers was inhibited by cortisol concentrations from 0.33 µM, or 1 µM and above, and these responses were effectively reversed by the cortisol antagonist RU-486. In SAH patients, RU-486 reversed suppression of innate TNF-α and IL-6 responses, but not IL-1ß or T cell-mediated responses. These data suggest that cortisol may play a role in reducing innate, but not T cell-mediated immune responses in patients with injuries such as SAH and that cortisol antagonists could be effective in boosting early innate responses.


[Investigation on health workforce in county anti-schistosomiasis institutions of Jiangxi Province, 2010].
To understand and assess changes of health workforce in county anti-schistosomiasis institutions of Jiangxi Province, so as to provide the evidence for improving the health workforce construction. The status of health workforce of county anti-schistosomiasis institutions was surveyed with self-designed questionnaire, and the results were compared with the baseline survey results in 2007. The total number of employees was 1 384 in 2010 with the decrease of 71 persons compared with that in 2007. The average number of people per institution was 40.71, with the decrease of 0.86 per institution, compared with that of 2007. Compared with 2007, the employees with bachelor degree increased by 6.17%, those with college degree increased by 6.8%, and the attending rate of training and further study also increased. The health workforce has improved in county anti-schistosomiasis institutions of Jiangxi Province. The professional workers should be trained continually to improve their diathesis.


Genome sequence of Streptomyces pluripotens MUSC 135(T) exhibiting antibacterial and antioxidant activity.
Isolated from intertidal soil, Streptomyces pluripotens MUSC 135(T) produces a broad-spectrum bacteriocin against the pathogens methicillin-resistant Staphylococcus aureus (MRSA) ATCC BAA-44(T), Salmonella typhi ATCC 19430(T) and Aeromonas hydrophila ATCC 7966(T). Along with antibacterial activity, fermentation studies on strain MUSC 135(T) revealed production of antioxidant(s). The high quality draft genome of MUSC 135(T) comprises 7,480,269 bp with G+C content of 70.00%. Through bioinformatics analysis, 72 gene clusters identified in the genome were associated with the production of secondary metabolites, which may shed light on the identity of these bioactive compounds.


Multimorbidity and catastrophic health expenditure: Evidence from the China Health and Retirement Longitudinal Study.
Population aging accompanied by multimorbidity imposes a great burden on households and the healthcare system. This study aimed to determine the incidence and determinants of catastrophic health expenditure (CHE) in the households of old people with multimorbidity in China. Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2018, with 3,511 old people (≥60 years) with multimorbidity responding to the survey on behalf of their households. CHE was identified using two thresholds: ≥10% of out-of-pocket (OOP) health spending in total household expenditure (THE) and ≥40% of OOP health spending in household capacity to pay (CTP) measured by non-food household expenditure. Logistic regression models were established to identify the individual and household characteristics associated with CHE incidence. The median values of THE, OOP health spending, and CTP reached 19,900, 1,500, and 10,520 Yuan, respectively. The CHE incidence reached 31.5% using the ≥40% CTP threshold and 45.6% using the ≥10% THE threshold. It increased by the number of chronic conditions reported by the respondents (aOR = 1.293-1.855, p < 0.05) and decreased with increasing household economic status (aOR = 1.622-4.595 relative the highest quartile, p < 0.001). Hospital admissions over the past year (aOR = 6.707, 95% CI: 5.186 to 8.674) and outpatient visits over the past month (aOR = 4.891, 95% CI: 3.822 to 6.259) of the respondents were the strongest predictors of CHE incidence. The respondents who were male (aOR = 1.266, 95% CI: 1.054 to 1.521), married (OR = 1.502, 95% CI: 1.211 to 1.862), older than 70 years (aOR = 1.288-1.458 relative to 60-69 years, p < 0.05), completed primary (aOR = 1.328 relative to illiterate, 95% CI: 1.079 to 1.635) or secondary school education (aOR = 1.305 relative to illiterate, 95% CI: 1.002 to 1.701), lived in a small (≤2 members) household (aOR = 2.207, 95% CI: 1.825 to 2.669), and resided in the northeast region (aOR = 1.935 relative to eastern, 95% CI: 1.396 to 2.682) were more likely to incur CHE. Multimorbidity is a significant risk of CHE. Household CHE incidence increases with the number of reported chronic conditions. Socioeconomic and regional disparities in CHE incidence persist in China.


Sulfur-based autotrophic denitrification from the micro-polluted water.
Eutrophication caused by high concentrations of nutrients is a huge problem for many natural lakes and reservoirs. Removing the nitrogen contamination from the low C/N water body has become an urgent need. Autotrophic denitrification with the sulfur compound as electron donor was investigated in the biofilter reactors. Through the lab-scale experiment, it was found that different sulfur compounds and different carriers caused very different treatment performances. Thiosulfate was selected to be the best electron donor and ceramsite was chosen as the suitable carrier due to the good denitrification efficiency, low cost and the good resistibility against the high hydraulic loads. Later the optimum running parameters of the process were determined. Then the pilot-scale experiment was carried out with the real micro-polluted water from the West Lake, China. The results indicated that the autotrophic denitrification with thiosulfate as electron donor was feasible and applicable for the micro-polluted lake water.


Endophotocoagulation.
A system was developed for transvitreal application of photocoagulation using a fiberoptic probe attached to a portable xenon arc coagulator (endophotocoagulation, EPC). The system is activated by a footswitch, and the probe tip is positioned near the retina after performing a pars plana vitrectomy. This technique can be used to treat posterior retinal breaks, stop retinal bleeding, coagulate retinal neovascularization, apply scatter retinal photocoagulation in certain diabetic eyes, treat some of the ciliary processes in eyes with neovascular glaucoma, and enlarge the pupil in eyes with iris neovascularization and miosis. Endophotocoagulation was used in 169 eyes for one or more of these indications and found to be safe and reliable.


A randomized, phase I, 3-way crossover study to examine the effects of food on the pharmacokinetics of single doses of 400 mg posaconazole oral suspension in healthy male Taiwanese subjects.
The pharmacokinetic parameters of a single 400-mg oral dose of posaconazole suspension, administered under fasting and fed conditions, were compared in healthy male Taiwanese volunteers. After an overnight fast, 16 subjects received a single oral dose of posaconazole suspension (400 mg) under fasting conditions or immediately after a normal-fat (700-800 calories, 30% fat) or high-fat breakfast meal (800-1000 calories, 50% fat). The treatments were administered as per the 3 × 6 Williams square design, with a 1-week washout phase between treatments. Blood samples were drawn at predetermined time points (0, 1, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours). All plasma concentrations of posaconazole were measured by high-performance liquid chromatography. The observed maximum plasma concentration (C max), area under the plasma concentration-time curve (AUC 0-t and AUC 0-∞), time to reach C max (t max), and plasma half-life (t 1/2) were assessed. Fourteen subjects completed the study; 2 subjects withdrew because of adverse events. Thirteen subjects were included in the pharmacokinetic analysis. Sixteen subjects were included in the safety analysis. The mean posaconazole C max, AUC 0-t, and AUC 0-∞ values were significantly lower under fasting conditions than after a normal- or a high-fat meal. The mean C max values under fasting, normal-fat, and high-fat conditions were 279.00 ± 123.32 ng/mL, 662.46 ± 251.02 ng/mL, and 608.38 ± 183.22 ng/mL, respectively (P < 0.0001); the mean AUC 0-t values under each condition were 6828.56 ± 3349.12 ng · mL(-1) · h(-1), 20,629.84 ± 8346.45 ng · mL(-1) · h(-1), and 20,741.09 ± 7681.02 ng · mL(-1) · h(-1), respectively (P < 0.0001); and the mean AUC 0-∞ values under each condition were 7304.72 ± 3444.54 ng · mL(-1) · h(-1), 21,326.65 ± 8495.01 ng · mL(-1) · h(-1), and 21,626.08 ± 8193.31 ng · mL · h(-1), respectively (P < 0.0001). The mean t max value was significantly shorter at 3.15 hours under fasting conditions than at 4.88 hours after normal- or high-fat meals (P = 0.0176). The mean t 1/2 values were 22.0, 20.8, and 22.0 hours, respectively. The posaconazole AUC increased by approximately 3-fold, C max by 2.2-fold, and t max by 1.5-fold when healthy Taiwanese subjects were administered the drug with food compared with under fasting conditions. These parameters were similar when the drug was administered with either a normal- or high-fat meal.


The efficacy and safety of the combination of photobiomodulation therapy and pulsed electromagnetic field therapy on androgenetic alopecia.
Photobiomodulation therapy (PBMT) appears to be safe and effective for hair loss. Pulsed electromagnetic field therapy (PEMF) also has a positive biological effect on hair re-growth. We evaluated the efficacy and safety of both PBMT and PEMF for the treatment of androgenetic alopecia (AGA). This study was a 24-week, randomized, double-blind, sham device-controlled trial. We recruited 80 subjects with androgenetic alopecia. The subjects got treatment every week for the 1st 12 weeks, every other week for the next 8 weeks. PBMT entails 15-min therapy, and PEMF was carried out for 10 min. The baseline hair density was 114.57 (±28.75)/cm2 and 113.31 (±30.07)/cm2 in both treatment and control groups. After 24 weeks of treatment, the mean hair density increased to 139.37 (±31.4)/cm2 in the treatment group but only to 119.78 (±31.92)/cm2 in the control group. The difference between two groups was statistically significant (p < 0.05). Based on the global assessment of independent experts, the score was 0.41 (±0.62) in the treatment group and 0.07 (±0.45) in the control group. Only very mild erythema or irritation was reported, and no serious adverse reactions were reported. A combination of PBMT and PEMF is a valid and safe treatment option for AGA.


The adhesion behavior of the retina.
Ocular diseases and treatment related to rhegmatogenous retinal detachment (RRD) are highly correlated with retinal adhesion behavior. Therefore, this paper proposes to study the adhesion behavior of the intact retina. This can provide theoretical guidance for the treatment and research of retinal detachment (RD) related diseases. To systematically analyze this aspect, two experiments were performed on the porcine retina. The pull-off test combined with the modified JKR theory was used to study the adhesion behavior of the vitreoretinal interface, while the peeling test was used to study the adhesion behavior of the chorioretinal interface. In addition, the adhesion phase involved in the pull-off test was simulated and analyzed by building the corresponding finite element method (FEM). The experimental results of adhesion force on the vitreoretinal interface were obtained by pull-off test with five sizes of rigid punch. The experimental value of the pull-off force FPO tends to increase gradually with increasing punch radius in the range of 0.5-4 mm. A comparison of the experimental results with the simulation results shows that they are in a well agreement. And there is no statistical difference between the experimental and theoretical values of the pull-off force FPO. In addition, the values of retinal adhesion work were also obtained by pull-off test. Interestingly, there is a significant scale effect of the retinal work of adhesion. Finally, the peeling test gave a maximum peeling strength TMax of about 13 mN/mm and a stable peeling strength TD of about 11 mN/mm between the retina and the choroid. The pull-off test well shows the process of retinal traction by the diseased vitreous at the beginning of RRD. A comparison of the experimental results with the finite element results verifies the accuracy of the simulation. The peeling test well investigated the adhesion behavior between the retina and the choroid and obtained key biomechanical data (peeling strength, etc.). The combination of the two experiments allows a more systematic study of the whole retina. This research can provide more complete material parameters for finite element modeling of retina-related diseases, and it also can provide the theoretical guidance for individualized design of retinal repair surgery.


Role of contextual cues in determining transfer of oddity rule in children.
60 kindergarten and 60 first grade children were trained on an oddity problem with perceptual (P) or conceptual (C) attribute for a fixed number of trials (30). After mastering the training problem, the subjects were randomly assigned to either an intradimensional (CC or PP group) or an extradimensional (CP or PC group) oddity shift. The transfer performance showed CC greater than PC greater than PP = CP group. These differences were attributed to the pattern hypotheses sampled at the start of transfer. Subjects who had acquired a conceptual oddity rule in the training had a strong tendency to sample hypotheses by the prior rule, but subjects under conditions where a perceptual-oddity rule was relevant tended to make a shift to a cue from new (conceptual oddity) rule. The older children yielded more of such a sampling mode than the younger children did, and the former were easily able to abandon a disconfirmed rule and sample hypotheses from the relevant rule domain.


[Biosafety. Natural contaminants of food mycotoxin].
The present paper review the current knowledge on principal mycotoxins of confirmed or potential relevance in human health with respect to occurrence, toxicology and risk assessment.


Hypoxia-independent activation of HIF-1 by enterobacteriaceae and their siderophores.
Hypoxia inducible factor-1 (HIF-1) is the key transcriptional regulator during adaptation to hypoxia. Recent studies provide evidence for HIF-1 activation during bacterial infections. However, molecular details of how bacteria activate HIF-1 remain unclear. Here, we pursued the role of bacterial siderophores in HIF-1 activation during infection with Enterobacteriaceae. In vivo, HIF-1 activation and HIF-1-dependent gene induction in Peyer's patches were analyzed after orogastric infection with Yersinia enterocolitica. The course of an orogastric Y enterocolitica infection was determined using mice with a deletion of HIF-1alpha in the intestine. In vitro, the mechanism of HIF-1 activation was analyzed in infections with Y enterocolitica, Salmonella enterica subsp enterica, and Enterobacter aerogenes. Infection of mice with Y enterocolitica led to functional activation of HIF-1 in Peyer's patches. Because mice with deletion of HIF-1alpha in the intestinal epithelium showed a significantly higher susceptibility to orogastric Y enterocolitica infections, bacterial HIF-1 activation appears to represent a host defense mechanism. Additional studies with Y enterocolitica, S enterica subsp enterica, or E aerogenes, and, moreover, application of their siderophores (yersiniabactin, salmochelin, aerobactin) caused a robust, dose-dependent HIF-1 response in human epithelia and endothelia, independent of cellular hypoxia. HIF-1 activation occurs most likely because of inhibition of prolylhydroxylase activity and is abolished upon infection with siderophore uptake deficient bacteria. Taken together, this study reveals what we believe to be a previously unrecognized role of bacterial siderophores for hypoxia-independent activation of HIF-1 during infection with human pathogenic bacteria.


In Vitro Study on Spermicidal Action of Hydro-methanol Extract of Tinospora cordifolia (Willd.) Stem in Rat and Human Sperm: a Comparative Analysis.
Human fertility regulation is a major way to control overpopulation. In this perspective, this study emphasized the in vitro effect of hydro-methanol extract of Tinospora cordifolia (TCHME) stem for spermicidal and reproductive hypo-functions using human and rat samples. Control, 0.5-, 1-, and 2-mg TCHME-charged groups were considered to assess the relevant parameters. Levels of spermiological parameters like sperm motility, viability, the integrity of plasma and acrosomal membrane, and nuclear chromatin decondensation were significantly reduced (p < 0.05) in the dose- and duration-dependent TCHME-charged groups compared to the control. The inhibitory concentration 50 (IC50) of TCHME on motile human and rat sperms were 0.8 and 0.4 mg/ml, respectively. Testicular androgenic key enzymes and antioxidant enzymes (human sperm pellet, testes, and epididymis of rat)' activities were significantly diminished (p < 0.05), while antioxidant enzymes' activities were significantly elevated (p < 0.05) in renal and insignificantly (p > 0.05) elevated in hepatic tissues of rat in TCHME-charged groups compared to the control. Significant elevation (p < 0.05) of thiobarbituric acid reactive substances (TBARS)' level in human sperm pellet, testes, and epididymis of rats and significant diminution (p < 0.05) in TBARS levels of liver and kidney were observed in TCHME-charged groups. It focused that TCHME is more potent for stress imposition on reproductive tissues and sperm compared to the other tested tissues. Non-significant alterations (p > 0.05) in glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities in the said organs of rat indicated its non-toxic effect. It highlighted that TCHME possesses spermicidal and reproductive tissue-specific effects which strengthen the possibilities of male contraceptive development from it.


Tissue plasminogen activator for occluded peritoneal dialysis catheter.
Inadequate flow in a peritoneal catheter is a common problem in pediatric patients. We report the effectiveness of the intra-catheter application of tissue plasminogen activator for the resolution of a malfunctioning peritoneal dialysis catheter in a child.


Anti-Toxocara spp. antibodies in an adult healthy population: serosurvey and risk factors in Southeast Brazil.
To evaluate the frequency of anti-Toxocara spp. antibodies in an adult healthy population. The study was performed by interviewing 253 blood donors, from 19 to 65 years of age, in a hematological centre in Presidente Prudente, São Paulo, southeast Brazil. A survey was applied to blood donors in order to evaluate the possible factors associated to the presence of antibodies, including individual (gender and age), socioeconomic (scholarship, familial income and sanitary facilities) and habit information (contact with soil, geophagy, onycophagy and intake of raw/undercooked meat) as well as the presence of dogs or cats in the household. ELISA test was run for detection of the anti-Toxocara spp. IgG antibodies. Bivariate analysis followed by logistic regression was performed to evaluate the potential risk factors associated to seropositivity. The overall prevalence observed in this study was 8.7% (22/253). Contact with soil was the unique risk factor associated with the presence of antibodies (P=0.017 8; OR=3.52; 95% CI=1.244-9.995). The results of this study reinforce the necessity in promoting preventive public health measures, even for healthy adult individual, particularly those related to the deworming of pets to avoid the soil contamination, and hygiene education of the population.


Threatened species could be more vulnerable to climate change in tropical countries.
Climate change is a major threat impacting insects globally, yet the impact on tropical insects is largely unknown. Here, I assessed the climatic vulnerability of Bangladeshi butterflies (242 species). About 42 % of species could experience range contraction, and the impact could be significantly more severe among threatened species. Depending on Socio-Economic Pathways (ssps), the future climatic condition could be unsuitable for 2 (ssp126) - 34 % (ssp585) species. The mean elevation of the suitable habitat could increase by 238 %, and the situation could be more severe for the threatened butterflies. Further, 54 % of the realised niche of butterflies could be altered. Although there might be no significant association between the shift in habitat suitability along the elevational gradient, migratory species could experience a more significant shift than non-migrants. Overall, climate change could have a severe impact on Bangladeshi butterflies. To mitigate insect decline globally and meet the Post 2020 Biodiversity Framework targets, immediate detection of climate change impact on tropical insects and developing effective conservation strategies is essential.


A novel cell-based transplantation method using a Rho kinase inhibitor and a specific catheter device for the treatment of salivary gland damage after head and neck radiotherapy.
Radiotherapy (RT) for head and neck cancer results in irreversible damage to salivary glands (SGs) and decreases saliva production, leading to a dry mouth. To date, there are no satisfactory therapies to solve this problem. We recently established a novel culturing method using a Rho kinase inhibitor (RI), Y-27632, that maintained cellular morphology and function for a prolonged period of time. In the present study, we investigated whether cell-based transplantation using our culturing method ameliorated the dysfunction of irradiated SGs. First, rat SG cells were cultured in a medium with RI. Cells were characterized by morphological findings and mRNA expression analysis. We also assessed features of SG cells in three-dimensional (3-D) culture by scanning electron microscopy and immunohistochemistry (IHC). The RI-containing medium led to higher cell proliferation of rat SG cells with preservation of cell morphology and higher alpha-amylase (AMY) expression in both 2-D and 3-D culture systems. To establish the atrophic-SG models, external RT at a dose of 15 Gy was delivered to the head and neck fields of nude rats. The SG cells derived from GFP-rats were cultured in medium with RI, after which they were transplanted into the submandibular glands of atrophic-SG rats using a catheter placed into Wharton's duct. IHC and salivary flow rate (SFR) analyses were measured 12 weeks after the transplantation. Following transplantation, donor cells (GFP-SG cells) were primarily located in the ductal region of the SG, and AMY expression in SGs and the SFR were increased in the SG cell transplantation group compared with the control. Those data indicated that cell-based therapy using RI-treated SG cells could restore salivary hypofunction of irradiated SGs by direct integration of the donor cells in the duct of SGs. We propose that these data support future clinical plans in which SG cells would be excised from the labial minor SGs of the patients with head and neck cancers prior to RT, cultured during RT, and auto-transplanted into SGs using a catheter into the Wharton's duct. We believe that our culturing and transplantation methods can be applied to SG cells, constituting a therapeutic approach for the treatment of patients with dry mouth after not only RT but also aging and Sjögren's syndrome.


Design and synthesis of small molecule-conjugated photoaffinity nanoprobes for a streamlined analysis of binding proteins.
We designed and synthesized a set of photoaffinity nanoprobes, which multivalently display a small molecule ligand and a photoreactive group on gold nanoparticles. Due to the typically hydrophobic nature of these two functional groups, a hydrophilic spacer was additionally introduced to co-functionalize the nanoprobes to maintain their dispersibility in aqueous buffer solutions. Photoaffinity labeling studies using the nanoprobes composed of different ratios of three functional groups showed that including high density of the spacer group attenuates crosslinking efficiency. Comparative analysis of the reactivity among three major photoreactive groups suggested that unlike in the context of conventional photoaffinity probes, arylazide group enables the most selective crosslinking of a model small molecule binding protein.


An unusual site of heterotopic calcification.
Heterotopic calcification may occur following paralysis from spinal cord injury, most commonly affecting the hips. This case demonstrates a bone scan on a T5 paraplegic patient showing an unusual site of heterotopic calcification in the paravertebral musculature in addition to the hip regions. Subsequent CT scanning confirmed the presence of calcification in the erector spinae musculature.


A locking bar modification for splint localisation.
Currently used techniques for the construction of localising bars are generally regarded to constitute a disadvantage of cap splints. A simplified method of localisation is described.


Eco-physiological performance of two invasive weed congeners (Ageratum conyzoides L. and Ageratum houstonianum Mill.) in the Indo-Gangetic plains of India.
Morphological (easily measureable) and physiological (hard to measure) traits of two closely related invasive alien congeners-Ageratum conyzoides L. and Ageratum houstonianum Mill. were studied with a perspective that which species will be potentially be more successful as an invader in the Indo-Gangetic plains of India. Leaf construction cost (LCC) is considered as a quantifiable measure of energy demand for biomass production and is related to energy use efficiency as it include component of both morphological and physiological traits. We hypothesised that a low LCC would give the invaders growth advantage by utilizing energy efficiently. Low LCC of A. houstonianum on mass basis (0.54 g glucose g( -1)) and area basis (20.48 g m( -2)) gives insight into the success of this invasive weed over A. conyzoides. The present study gives evidence that how the morphological traits are linked to physiological traits that could directly affect invasive attributes of the invader, which in turn would be crucial to prioritize species for ecosystem management.


Motion robust GRAPPA for echo-planar imaging.
A readout-segmented method for acquiring robust GRAPPA calibration data for echo-planar imaging (EPI) was proposed and compared with two previous methods, including the gold standard interleaved approach and a single shot method with halved phase encode resolution. The readout-segmented and single shot techniques acquire adjacent phase encode lines in the same shot to obtain the calibration data, rather than interleaving of lines between shots, to decrease sensitivity to motion. Additionally, it uses multiple segments with shortened frequency encode extent to match the phase encode bandwidth to the undersampled data, which decreases sensitivity to B0 inhomogeneity. The three methods were tested using simulations and EPI scans of the brain in healthy volunteers. The interleaved approach exhibited high sensitivity to motion, while residual undersampling artifacts remained in the single shot method due to mismatch of B0 inhomogeneity between the calibration and undersampled data. The readout segmented method exhibited no such errors, having 30% lower ghosting intensity than the single shot method and 90% lower ghosting intensity than the interleaved approach in moving subjects. Artifacts from B0 inhomogeneity and motion during calibration scans for EPI GRAPPA can be mitigated with a readout segmented calibration scan.


Aqueous ethanol organosolv process for the valorization of Brewer's spent grain (BSG).
Brewers spent grain (BSG), the main solid byproduct of brewing, is annually generated by ca 37 million tons worldwide, which due to limited application, mostly ends up in landfills. This study aims to separate BSG's fractions (lignin, cellulose, and hemicellulose) by ethanol organosolv pretreatment. Lignin-rich fractions were recovered using a two-step separation technique. The effects of temperature, retention time, and ethanol concentration on the quantity and quality of fractions were studied. The temperature considerably impacted the quality and quantity of obtained fractions, while other parameter effects greatly depended on the temperature. Substantial hemicellulose removal (90 %) along with lignin removal (56 %) and recovery (57 %) were obtained at 180 °C. The highest lignin purity (95 %) was obtained at the pretreatment conditions of 180 °C, 120 min, and 50 % ethanol concentration. This work provides an alternative route for BSG utilization, mitigating its environmental impact while enhancing the economy of a brewery.


Water-dilutable microemulsions for transepithelial ocular delivery of riboflavin phosphate.
Riboflavin phosphate (RFP) is an essential compound in the treatment of keratoconus - a degenerative, non-inflammatory disease of the cornea. Currently, the quantitative and efficient transport of riboflavin to the cornea is possible after mechanical removal of the epithelium. To avoid surgical intervention, it is therefore important to develop a method for quantitatively transporting riboflavin across the intact epithelium. In the present study, an RFP-loaded microemulsion was prepared, which could potentially function as an ocular drug delivery system crossing the eye epithelium. The specially designed water-dilutable microemulsion was based on a mixture of nonionic surfactants. Propylene glycol and glycerol acted as cosurfactant and cosolvent assisting in the solubilization of the RFP. The glycerol-rich water-free concentrate consisted of direct micelles for which glycerol served as the hydrophilic phase. In formulations with up to 40wt% water, the hydrophilic surfactant headgroups and glycerol strongly bind water molecules (DSC and SD-NMR). Above 60wt% water, globular, O/W nanodroplets, ∼14nm in diameter, are formed (SAXS, cryo-TEM, and SD-NMR). The structure of microemulsions loaded with 0.14-4.25wt% RFP (0.29-8.89mmol per 100g formulation) is not significantly influenced by the presence of the RFP. However, in the microemulsions containing 10-80wt% water, the mobility of RFP in the microemulsion is constrained by strong interactions with the surfactants and cosurfactant, and therefore free transport of the molecule can be achieved only upon higher (>80wt%) water dilutions.


Immune Thrombocytopenia: Characteristics of the Population and Treatment Methods-One-Center Experience.
Immune thrombocytopenia (ITP) is a disease with variable clinical presentation, requiring different treatment lines. The study aimed to characterize a group of ITP patients in terms of clinical picture and disease treatment, as well as to present the current standard of care of ITP in Poland, in the context of local and international guidelines. The study included adult patients diagnosed with ITP, treated at the Department of Haematology of the Jagiellonian University Hospital in Krakow from January 2006 to January 2021. Patient characteristics, clinical manifestation of ITP, and treatment methods were analyzed. A total of 245 ITP patients were included. 57.1% of them were asymptomatic at diagnosis. Most common symptoms were thrombocytopenic purpura (68.2%), followed by epistaxis (34.7%) and gum bleeds (19.2%). Life-threatening bleedings were noted in three cases (1.2%). 23.2% of patients did not require treatment. Prednisone was the most commonly used first-line therapy (75.5% of patients). Treatment with eltrombopag and romiplostim was used in 40.4 and 8.5% of patients requiring second-line therapy, respectively. 14.3% of all patients ultimately underwent splenectomy, including 51.5% of those who needed second-line treatment. The initial response rate was 74.3%; however, post-splenectomy relapses occurred in 22.9% of patients. ITP is a disease of mild clinical course, often asymptomatic. Chronic disease often requires multiple treatment lines and balancing between bleeding risk and treatment toxicity, based on individual risk-benefit assessment. Local access restrictions to thrombopoietin receptor agonists determined the treatment strategy.


Low dihydropyridine receptor density in vasa deferentia of castrated rats.
Radioligand binding studies in crude membrane preparations of vasa deferentia of normal rats, with the 1,4-dihydropyridine (+)-[3H]-PN200-110 (isradipine) showed typical saturation isotherms. The binding exhibited a KD of 259 +/- 60 pM and Bmax of 144 +/- 20 fmol mg-1 protein. The low KD and the stereoselective displacement of (+)-[3H]-PN200-110 binding by (+)- and (-)-PN200-110 and by nifedipine suggests that these tissues contain dihydropyridine receptors probably coupled to voltage-sensitive, L-type calcium channels. In membrane preparations from vasa deferentia from rats castrated 30 days previously the maximum specific binding was 25 +/- 10 fmol mg-1 protein, representing only 11% of total binding; thus, the calculation of reliable KD values was not feasible. These findings suggest that a testicular hormone, possibly testosterone, plays an important role in the regulation of dihydropyridine-sensitive, voltage-dependent calcium channels in the rat vas deferens.