Preclinical evaluation of antimalarial activity of CPF-1 formulation as an alternative choice for the treatment of malaria.
Kheaw Hom remedy is a traditional Thai medicine used to treat fever. Some plants used in the Kheaw Hom remedy show promising in vitro antimalarial activity. This study prepared novel formulations of plants from the Kheaw Hom remedy and evaluated their antimalarial and toxicological activities. Seven new formulations were prepared by combining at least three herbs of six selected plants from the Kheaw Hom remedy, namely Mammea siamensis Kosterm., Mesua ferrea L., Dracaena loureiroi Gagnep., Pogostemon cablin (Blanco) Benth., Kaempferia galanga L, and Eupatorium stoechadosmum Hance. In vitro antimalarial activities of each formulation's aqueous and ethanolic extracts were evaluated using the parasite lactate dehydrogenase (pLDH) assay. Cytotoxicity in Vero and HepG2 cells was assessed using the MTT assay. An extract with good antimalarial potency and selectivity index (SI) was selected for in vivo antimalarial activity using Peter's 4-day suppressive test and acute oral toxicity test in mice. In addition, bioactive compounds were identified using Gas chromatography-mass spectrometry (GC-MS) analysis. Among the seven new formulations, ethanolic extracts of CPF-1 (Formulation 1) showed the highest activity with an IC50 value of 1.32 ± 0.66 µg/ml, followed by ethanolic extracts of Formulation 4 and Formulation 6 with an IC50 value of 1.52 ± 0.28 µg/ml and 2.48 ± 0.34 µg/ml, respectively. The highest SI values were obtained for the ethanolic extract of CPF-1 that was selected to confirm its in vivo antimalarial activity and toxicity. The results demonstrated a significant dose-dependent reduction in parasitemia. Maximum suppressive effect of the extract (72.01%) was observed at the highest dose administered (600 mg/kg). No significant toxicity was observed after the administration of 2000 mg/kg. Using GC-MS analysis, the most abundant compound in the ethanolic extract of CPF-1 was ethyl p-methoxycinnamate (14.32%), followed by 2-propenoic acid, 3-phenyl-, ethyl ester, (E)- (2.50%), and pentadecane (1.85%). The ethanolic extract of CPF-1 showed promising in vitro and in vivo antimalarial efficacy, with no toxic effects at a dose of 2000 mg/kg, suggesting that the ethanolic extract of CPF-1 may serves as a new herbal formulation for the treatment of malaria. Additional research is required for safety and clinical pharmacology studies.


Physician-diagnosed respiratory conditions and mental health symptoms 7-9 years following the World Trade Center disaster.
This study examines the prevalence of physician-diagnosed respiratory conditions and mental health symptoms in firefighters and emergency medical service workers up to 9 years after rescue/recovery efforts at the World Trade Center (WTC). We analyzed Fire Department of New York (FDNY) physician and self-reported diagnoses by WTC exposure and quintiles of pulmonary function (FEV1% predicted). We used screening instruments to assess probable post-traumatic stress disorder (PTSD) and probable depression. FDNY physicians most commonly diagnosed asthma (8.8%) and sinusitis (9.7%). The highest prevalence of physician-diagnosed obstructive airway disease (OAD) was in the lowest FEV1% predicted quintile. Participants who arrived earliest on 9/11 were more likely to have physician-diagnosed asthma (OR = 1.4). Seven percent had probable PTSD. 19.4% had probable depression. Self-reported and physician-diagnosed respiratory conditions remain common, especially among those who arrived earliest at the WTC site. OAD was associated with the lowest pulmonary function. Since respiratory and mental health conditions remain prevalent, ongoing monitoring and treatment is important.


Knowledge of CT exposure parameters among Norwegian student radiographers.
Improvements in the competency levels of student radiographers in computed tomography examinations (CT) are important due to the increasing number of these examinations being undertaken in imaging departments. The present study assesses the knowledge of student radiographers regarding CT exposure parameters. The level of knowledge related to CT exposure parameters was evaluated using a twenty-one-item questionnaire that was distributed to final-year student radiographers. The questionnaire consisted of questions around CT exposure parameters and either allowed respondents to answer "true," or "false" or choose a response from a range of responses where only one answer was correct. Correct answers were given one mark, while no mark was given for an incorrect answer. The score out of possible 21 was converted to a percentage, with a higher percentage signifying greater knowledge. Seventy-two students completed and returned the questionnaire, resulting in a 71% response rate. The mean score was 53%. Only 33% of students correctly identified that kilovoltage peak (kVp) should be increased when patients have metallic implants, and milliampere seconds (mAs) should be increased as body part thickness increases. No one answered all the questions correctly. There was no significant knowledge difference between students who had CT facilities on campus and those that did not. Overall, student radiographers' knowledge of CT exposure parameters was reported to be satisfactory.


The relative importance of patients' decisional control preferences and experiences.
Patients' role in treatment decision-making can influence psychosocial and health-related outcomes (i.e. satisfaction, felt respect, adherence). We examined decisional control in a surgical context, identifying correlates of patients' preferences and experiences. 380 patients and 7 surgeons were surveyed during initial surgical consultation visits in a low-income outpatient clinic. Patients reported preferences for (pre-consultation) and experiences of (post-consultation) decisional control, demographics, satisfaction with care, and adherence to treatment recommendations. Surgeons rated patients' health status. Preferences for and experiences of decisional control were unrelated, suggesting significant preference-experience misalignment. However, this misalignment did not appear to be consequential for patient outcomes. Rather, more decisional control, regardless of patients' preferences, predicted greater satisfaction with care and greater self-reported adherence as assessed at a post-surgical appointment. Decisional control predicts better outcomes for patients, regardless of their preferences for control over treatment decisions. These findings suggest that interventions should aim to increase patients' degree of decisional control when feasible and appropriate.


The PRISMA Symposium 1: outcome tool use. Disharmony in European outcomes research for palliative and advanced disease care: too many tools in practice.
As the European population ages and the number of cancer deaths annually increases, there is an urgent requirement to provide high-quality, effective care. The measurement of outcomes in advanced disease is complex, and to conduct comparative research and meta-analyses, appropriate tool selection is essential. This study aimed to identify the outcome tools currently in use in end-of-life care (both clinically and for research) across Europe and investigate the preferred features of outcome tools from the perspective of those who select and apply them. A pan-European Internet-based survey of tool users was conducted in research and clinical populations. Respondents were asked to identify the tools they are using and describe ideal features of the measures. The study was conducted in accordance with guidance for best practice in web-based research. Of the 311 participants who completed a survey, 99 tools in clinical care and audit, and 94 in research, were cited by less than 10 participants. Further data revealed that respondents require the number of potential tools to be rationalized and that brief tools are favored. The selection of valid and appropriate tools for palliative care populations requires expert guidance and support to ensure that clinicians and researchers are collecting data that have validity and potential for comparison within and between populations and countries.


Dynamic matrix composition in engineered cartilage with stochastic supplementation of growth factors.
Dynamic extracellular matrix (ECM) synthesis is explored in a hypothesized engineered cartilage construct. Growth (alpha) and decay (beta) rate parameters are developed from a previous engineered cartilage model. The presented mathematical model was constructed from the parameterized experimental data using a deterministic and stochastic examination of ECM synthesis based on a negative feedback control mechanism. A growth factor supplementation is incorporated in a probabilistic mathematical approach. The growth factor component modified an initial deterministic model through a Gaussian white noise fluctuation. As the primary constituents of ECM, the mathematical tool is intended to characterize the probable steady state distribution of glycosaminoglycan (GAG) and collagen molecules as well as mean mass accumulation at homeostasis. Computer simulation of the models is applied to reported data from four similar chondrocyte-polymer construct culture systems. The range in rate ratios reflect the differing nature of GAG and collagen synthesis (alphaGAG/betaGAG = 4.2 to 148.6; alphacollagen/betacollagen = 8.1 to 2590.4). This technique reduced the influencing synthesis factors to a few key descriptive parameters. Additional anabolic and catabolic factors may further be built into the models.


MTA resorption and periradicular healing in an open-apex incisor: A case report.
This case report describes the periradicular healing and resorption of an unintentional extrusion of mineral trioxide aggregate (MTA) in an open-apex central incisor. A 22-year old female with a symptomatic open-apex right maxillary central incisor associated with a periradicular lesion was referred for evaluation and treatment. After chemomechanical debridement, the apical third of the root canal was filled with MTA to create an apical plug. Postoperative radiographs showed the extrusion of MTA into the periradicular lesion. The tooth was then restored with a post and crown. At the 2-year follow-up, the tooth was asymptomatic and radiographs revealed complete healing of the periradicular area. At the 7-year follow-up, complete resorption of the extruded MTA was evident. The results of this case study indicate that complete resorption of extruded MTA is possible in the long term; however, the extrusion of MTA in open-apex tooth should still be avoided.


Laboratory evaluation of verbutin as a synergist of acaricides against larvae of Rhipicephalus (Boophilus) microplus (Acari: Ixodidae).
Synergistic effects of verbutin, a member of aryl alkynyl derivatives, to three commonly used acaricides were evaluated with the modified Food and Agricultural Organization Larval Packet Test (FAO-LPT) against both susceptible and resistant strains of the southern cattle tick, Rhipicephalus (Boophilus) microplus (Canestrini) (Acari: Ixodidae). These tick strains demonstrated various levels of resistance to coumaphos (2.5-8.2x), permethrin (57.9-711.7x), and amitraz (3.5-177.5x). Verbutin alone was more toxic to tick larvae than piperonyl butoxide (PBO), a conventional pesticide synergist. With synergism ratios (SRs) ranging from 1.5 to 6.0, verbutin was more potent than PBO (SR = 0.9-1.6) in synergizing coumaphos toxicity to resistant tick larvae. Similarly, verbutin (SR = 1.8-15) was also found to be more potent than PBO (SR = 0.9-2.5) in synergizing amitraz in resistant tick strains. Both verbutin and PBO significantly increased permethrin toxicity to larvae of all tick strains tested, and there was no significant difference between the two synergists. SRs ranged from 2.1 to 4.4 and from 2.1 to 3.6 for PBO and verbutin, respectively.


Salvia divinorum: An overview of the usage, misuse, and addiction processes.
Salvia divinorum, a sage plant with leaves that can produce a psychoactive high, has been used for hundreds of years for its psycho-mimetic effects in religious rituals in South America. Salvia has now become popular mainly with adolescents and young adults for the short-lived relatively pleasant experiences many consider a "legal high" and its ready availability through Internet purchases. The main (psycho)active compound in salvia is Salvinorin A, a potent κ-opioid agonist and although the short and long-term effects have not been examined in sufficient detail, it is widely believed to have low addictive potential and low toxicity. Recent findings, however, seem to suggest that Salvinorin A can precipitate psychiatric symptoms and negatively affect cognition. Its ready availability and increasingly widespread use requires clinicians to have knowledge and awareness of its effects.


Robotic Kinematic measures of the arm in chronic Stroke: part 1 - Motor Recovery patterns from tDCS preceding intensive training.
Effectiveness of robotic therapy and transcranial direct current stimulation is conventionally assessed with clinical measures. Robotic metrics may be more objective and sensitive for measuring the efficacy of interventions on stroke survivor's motor recovery. This study investigated if robotic metrics detect a difference in outcomes, not seen in clinical measures, in a study of transcranial direct current stimulation (tDCS) preceding robotic therapy. Impact of impairment severity on intervention response was also analyzed to explore optimization of outcomes by targeting patient sub-groups. This 2020 study analyzed data from a double-blind, sham-controlled, randomized multi-center trial conducted from 2012 to 2016, including a six-month follow-up. 82 volunteers with single chronic ischemic stroke and right hemiparesis received anodal tDCS or sham stimulation, prior to robotic therapy. Robotic therapy involved 1024 repetitions, alternating shoulder-elbow and wrist robots, for a total of 36 sessions. Shoulder-elbow and wrist kinematic and kinetic metrics were collected at admission, discharge, and follow-up. No difference was detected between the tDCS or sham stimulation groups in the analysis of robotic shoulder-elbow or wrist metrics. Significant improvements in all metrics were found for the combined group analysis. Novel wrist data showed smoothness significantly improved (P < ·001) while submovement number trended down, overlap increased, and interpeak interval decreased. Post-hoc analysis showed only patients with severe impairment demonstrated a significant difference in kinematics, greater for patients receiving sham stimulation. Robotic data confirmed results of clinical measures, showing intensive robotic therapy is beneficial, but no additional gain from tDCS. Patients with severe impairment did not benefit from the combined intervention. Wrist submovement characteristics showed a delayed pattern of motor recovery compared to the shoulder-elbow, relevant to intensive intervention-related recovery of upper extremity function in chronic stroke. http://www.clinicaltrials.gov . Actual study start date September 2012. First registered on 15 November 2012. Retrospectively registered. Unique identifiers: NCT01726673 and NCT03562663 .


[Aplastic anemia and myelodysplasia: a not-always-easy distinction].
The differential diagnosis between Myelodysplasia and Aplastic anaemia may be sometimes difficult, because clinical and morphological features may appear similar. Two cases, a Myelodysplastic syndrome with hypocellular and an Aplastic anaemia with hypercellular BM aspirates, are described in this report. Reciprocal connections between these two pathological entities, some biological aspects and the value of BM biopsy are also discussed.


Selective attention in dairy cattle.
In a replication of Reynolds (1961), two cows learned to discriminate between compound stimuli in a forced choice procedure where pushing through a one-way gate marked with a red cross (S+) gave access to food. Pushing through a one-way gate marked with a yellow triangle (S-) gave no access to food. To investigate whether shape or colour was controlling behaviour, probe tests varied either the shape or the colour of the stimuli (e.g., a red vs. a yellow cross, and a red cross vs. a red triangle). Results suggested control by colour rather than shape, as the gate marked with the red stimulus was chosen more than the gate marked with the yellow stimulus regardless of stimulus shape, and when two shapes of the same colour (either red or yellow) were presented, cows chose both equally. Further probe tests with painted red, white, and yellow stimuli showed that the cows had learned to avoid yellow rather than to approach red, suggesting discriminative behaviour was controlled by the colour of the negative stimulus and not by either aspect of the positive stimulus. It is not clear why the negative stimulus was more salient, but it may reflect a tendency for cows to learn to avoid farm handling practices which involve mainly negative stimuli.


[Transperitoneal resorption in acute and chronic peritonitis (author's transl)].
Two forms of peritonitis have been examined on 60 rats (Wistar) in three groups. Group 1 = acute peritonitis, group 2 = chronic peritonitis and group 3 = control. All animals have had an injection of an aminoglycosid antibiotic and a proteinase inhibitor into the peritoneal cavity. One intended to measure the influence of the proteinase inhibitor for different kinds of inflammation of the function of resorption of the peritoneum. Serum concentration of the antibiotic after 30, 60, and 90 min was measured. In clinical dosage the resorption of protein-bonded aminoglycosid antibiotics was decreased. The healthy control animals didn't show any effects. Connections concerning molecule size of protein-bonded substances and proteolytic ferments are in discussion. The practical relevance of these results could be found in an retarding effect of the resorption of protein-bonded toxines.


Williamsia soli sp. nov., an actinobacterium isolated from soil at a thermal power plant in Yantai, China.
Strain C17T, a novel strain belonging to the phylum Actinobacteria, was isolated from a thermal power plant in Yantai, Shandong Province, China. Cells of strain C17T were Gram stain positive, aerobic, pink, non-motile and round with neat edges, showing optimum growth at 28 °C. Phylogenetically, strain C17T was a member of the class Actinobacteria, order Mycobacteriales, family Gordoniaceae. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that the related strains were Williamsia faeni JCM 17784 T and Williamsia limnetica KCTC 19981 T with pairwise sequence similarity of 98.5% for both strains. According to the draft genome sequence, the DNA G + C content was 64.7%. The average amino acid identity (AAI), average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between genome sequences of strain C17T and the closest type strain W. faeni JCM 17784 T were 77.5, 77.9, and 20.7%, respectively. Predominant fatty acids were C16:0 (31.7%) and C18:1ω9c (26.8%). The major menaquinone was MK-9. The diagnostic phospholipids were phosphatidylethanolamine (PE), diphosphatidylglycerol (DPG), and phosphatidylinositol (PI). Therefore, the combined phenotypic, chemotaxonomic and phylogenetic data indicated that strain C17T was considered to represent a novel species of the genus Williamsia. Williamsia soli sp. nov. was proposed for strain C17T (= KCTC 49567 T = MCCC 1K04355T).


Biobanking for research: a survey of patient population attitudes and understanding.
Population-based biobanks are a critical resource for genetic research. It is important to know what potential participants understand about the risks and benefits of providing samples in order to ensure adequate informed consent. Kaiser Permanente Colorado (KPCO) is currently planning a biobank where adult members would be asked to contribute an additional tube of blood during a routine blood draw. Adult KPCO members in clinic waiting rooms were asked to read an informational brochure and informed consent form. Respondents then completed a survey to evaluate their understanding of the materials, willingness to provide a blood sample to a biobank, and facilitators and barriers to participation. Two hundred three members participated in the survey, of whom 69 % indicated willingness to contribute to a biobank. Nearly all understood that they would not be paid for any products resulting from the use of their blood and would not receive results from their samples (91 and 84 %, respectively). Seventy-four percent would donate a sample because, "it is important to contribute to research," and over half the participants (56 %) said they had no concerns about contributing to a biobank. Of those with concerns, 35 % said information security was a reason. In multivariate models, older age and trust in KPCO were significant predictors of willingness to participate (p = 0.03 and p < 0.0001, respectively). Data from this survey indicate an overall willingness to participate in a biobank, provide possible barriers to participation, and identify ways to improve informational materials to ensure adequate informed consent.


On-line sensitivity to local and long-distance syntactic dependencies in Broca's aphasia.
Seven agrammatic Broca's aphasics and ten normal control subjects performed a word-monitoring task to determine the degree to which violations of syntax would affect word-monitoring performance. Both local and long-distance dependencies were explored, as well as the effects of additional interceding words. Results indicated that normal subjects' word-monitoring latencies were significantly slower to target words in ungrammatical contexts for both local and long-distance dependencies. Aphasic subjects showed a significant sensitivity to ungrammaticality in the local dependency condition; for the long-distance dependencies, however, no reaction time difference emerged between grammatical and ungrammatical stimuli. Results are discussed in relation to current theories of the nature of agrammatic deficits.


Control of blood volume following hypovolemic challenge in vertebrates: Transcapillary versus lymphatic mechanisms.
Anurans have an exceptional capacity for maintaining vascular volume compared with other groups of vertebrates. They can mobilize interstitial fluids via lymphatic return at rates that are ten-fold higher than mammals. This extraordinary capacity is the result of coordination of specialized skeletal muscles and pulmonary ventilation that vary volume and pressure of subcutaneous lymph sacs, thus moving lymph to dorsally located lymph hearts that return lymph to the vascular space. Variation in the capacity to mobilize lymph within anurans varies with the degree of terrestriality, development of skeletal muscles, lung volume and lung compliance, and lymph heart pressure development. This ability enable anurans, which have the highest rates of evaporative water loss among terrestrial vertebrates, to withstand levels of dehydration far exceeding that of other vertebrates, and to successfully occupy virtually all terrestrial environments during their evolution. Maintenance of vascular fluid volume for all vertebrates can be achieved primarily by moving fluid from the interstitial space to the vascular space by transcapillary uptake and mobilization of interstitial (lymphatic) fluid. Transcapillary fluid uptake at the capillary level has been analyzed historically by Krogh and others from a Starling perspective and involves a balance of hydrostatic and oncotic forces. A complete evaluation of blood volume homeostasis also incorporates pressures and compliances of the vascular and interstitial spaces, but has been applied to only a few species. In this review we outline the current understanding of how anurans and other vertebrates maintain blood volume during hypovolemic challenges such as dehydration and hemorrhage which is crucial for maintaining cardiac output.


Inhibition of barnacle (Amphibalanus amphitrite) cyprid settlement by means of localized, pulsed electric fields.
The increasing needs for environmental friendly antifouling coatings have led to investigation of new alternatives for replacing copper and TBT-based paints. In this study, results are presented from larval settlement assays of the barnacle Amphibalanus (= Balanus) amphitrite on planar, interdigitated electrodes (IDE), having 8 or 25 mum of inter-electrode spacing, upon the application of pulsed electric fields (PEF). Using pulses of 100 ms in duration, 200 Hz in frequency and 10 V in pulse amplitude, barnacle settlement below 5% was observed, while similar IDE surfaces without pulse application had an average of 40% settlement. The spacing between the electrodes did not affect cyprid settlement. Assays with lower PEF amplitudes did not show significant settlement inhibition. On the basis of the settlement assays, the calculated minimum energy requirement to inhibit barnacle settlement is 2.8 W h m(-2).


Systematic review with meta-analysis: The effect of vitamin E supplementation in adult patients with non-alcoholic fatty liver disease.
Νon-alcoholic fatty liver disease (NAFLD) is estimated to be the most common cause of end-stage liver disease in the next years. Vitamin E has shown beneficial effects as a possible "scavenger" of oxidative stress products, which play a major role in pathogenesis of the disease. The purpose of the present meta-analysis is to investigate the effects of vitamin E supplementation in biochemical and histological parameters in adult patients with NAFLD. Literature search was performed in major electronic databases (MEDLINE, CENTRAL, and Embase) up to June 2020 for randomized clinical trials, which examined vitamin E versus placebo treatment in adults with NAFLD. Changes in liver enzymes were considered as primary outcomes while changes in histological, biochemical, and metabolic parameters as secondary. Quality of evidence was assessed through risk of bias according to the Cochrane risk of bias tool. Eight studies were included in qualitative analysis and seven in quantitative analysis. Vitamin E reduced the values of liver enzymes compared with placebo (-7.37 IU/L, 95% confidence interval: -10.11 to -4.64 for alanine aminotransferase, and -5.71 IU/L, 95% confidence interval: -9.49 to -1.93 for aspartate aminotransferase). Additionally, vitamin E improved statistically significantly liver pathology in every individual histological parameter as well as low-density lipoprotein cholesterol, fasting blood glucose, and serum leptin values. Vitamin E can improve biochemical and histological characteristics of NAFLD patients, especially of non-alcoholic steatohepatitis patients. The results indicate that vitamin E could be a promising choice and be considered as a treatment option in patients with NAFLD.


Optimal dose of amoxicillin in treatment of otitis media caused by a penicillin-resistant pneumococcus strain in the gerbil model.
Amoxicillin at doses of 0.2 to 5 mg/kg of body weight was administered for the treatment of pneumococcal otitis media in a gerbil model. Doses greater than or equal to 2.5 mg/kg, which resulted in concentrations in middle ear fluid of > or = 1.4 microg/ml and concentrations in serum higher than the MIC (1 microg/ml) for > or = 14% of the dosing interval, were both clinically and bacteriologically effective.


Delineation of suitable sites for groundwater recharge based on groundwater potential with RS, GIS, and AHP approach for Mand catchment of Mahanadi Basin.
Groundwater management requires a systematic approach since it is crucial to the long-term viability of livelihoods and regional economies all over the world. There is insufficient groundwater management and difficulties in storage plans as a result of increased population, fast urbanisation, and climate change, as well as unpredictability in rainfall frequency and intensity. Groundwater exploration using remote sensing (RS) data and geographic information system (GIS) has become a breakthrough in groundwater research, assisting in the assessment, monitoring, and conservation of groundwater resources. The study region is the Mand catchment of the Mahanadi basin, covering 5332.07 km2 and is located between 21°42'15.525″N and 23°4'19.746″N latitude and 82°50'54.503″E and 83°36'1.295″E longitude in Chhattisgarh, India. The research comprises the generation of thematic maps, delineation of groundwater potential zones and the recommendation of structures for efficiently and successfully recharging groundwater utilising RS and GIS. Groundwater Potential Zones (GPZs) were identified with nine thematic layers using RS, GIS, and the Multi-Criteria Decision Analysis (MCDA) method. Satty's Analytic Hierarchy Process (AHP) was used to rank the nine parameters that were chosen. The generated GPZs map indicated regions with very low, low to medium, medium to high, and very high groundwater potential encompassing 962.44 km2, 2019.92 km2, 969.19 km2, and 1380.42 km2 of the study region, respectively. The GPZs map was found to be very accurate when compared with the groundwater fluctuation map, and it is used to manage groundwater resources in the Mand catchment. The runoff of the study area can be accommodated by the computing subsurface storage capacity, which will raise groundwater levels in the low and low to medium GPZs. According to the study results, various groundwater recharge structures such as farm ponds, check dams and percolation tanks were suggested in appropriate locations of the Mand catchment to boost groundwater conditions and meet the shortage of water resources in agriculture and domestic use. This study demonstrates that the integration of GIS can provide an efficient and effective platform for convergent analysis of various data sets for groundwater management and planning.


Preparation and Phase Change Performance of Graphene Oxide and Silica Composite Na2SO4·10H2O Phase Change Materials (PCMs) as Thermal Energy Storage Materials.
In this study, a novel nucleating agent composed of graphene oxide (GO) and silicon dioxide (SiO2) (GO-SiO2) is developed. GO is used as a skeleton material through which SiO2 nanomaterials are absorbed and subsequently incorporated into Na2SO4·10H2O phase change materials (PCMs). Furthermore, this study examines the phase change performance of the composite Na2SO4·10H2O materials. Fourier-transform infrared (FTIR) spectra confirmed the physical combination of GO with a SiO2 nanoparticles. Scanning electron microscope (SEM) results showed that the GO-SiO2 composite exhibited a layered structure and excellent dispersibility. The GO-SiO2 composite Na2SO4·10H2O PCMs displayed a low level of supercooling, i.e., about 1.2 °C with the addition of GO-SiO2 at 2.45 wt%. This was because the synergistic relation of the GO and the high dispersion SiO2, imparted more nucleation sites for Na2SO4·10H2O. Additionally, the prepared PCMs achieved high phase change latent heat and thermal conductivity, even under these conditions. The results show that the GO-SiO2 in the Na2SO4·10H2O exhibited advantageous application prospects for the improvement of the thermal performance of hydrate salts.


Omalizumab's efficacy and safety against chronic spontaneous urticaria.
I have read the article titled, "Efficacy and safety of omalizumab against chronic spontaneous urticaria: Real-world study from China", by Wang et al with great interest. Nevertheless, there are a couple of questions raised in my mind. And clarification of some aspects of the study will help the reader benefit and have a better understanding of the study.


Heat Stress Increases In Vitro Hindgut Fermentation of Distinct Substrates in Iberian Pigs.
Heat stress reduces the feed intake and growth of pigs. We hypothesized that heat stress affects the intestinal fermentation capacity of pigs. Sixteen Iberian pigs (44 ± 1.0 kg) were randomly assigned to one of two treatments (eight pigs/treatment) for 4 weeks-heat stress (HS; 30 °C) ad libitum or thermoneutral (TN; 20 °C) pair feeding. Frozen rectum contents were used as inocula for 24 h in vitro incubations in which a mixture of starches, citrus pectin, inulin from chicory, and cellulose were the substrates. Cellulose was poorly degraded, whereas pectin and the mixture of starches were the most fermentable substrates according to total short-chain fatty acid (SCFA) production. The mixture of starches and inulin produced the greatest amount of gas. For all substrates, heat stress enhanced gas production (8%, p = 0.001), total SCFA production (16%, p = 0.001), and the production of acetate and propionate (12% and 42%, respectively; p = 0.001). The increased isoacid production (33%, p = 0.001) and ammonia concentration (12%, p = 0.001) may indicate protein fermentation under heat stress. In conclusion, the in vitro intestinal fermentation capacity of pigs under heat stress was increased compared to thermoneutral conditions, which may indicate an adaptive response to heat stress.


Urinary polyamines and N-acetylated polyamines in four patients with Alzheimer's disease as their N-ethoxycarbonyl-N-pentafluoropropionyl derivatives by gas chromatography-mass spectrometry in selected ion monitoring mode.
Simultaneous determination of putrescine, cadaverine, spermidine, spermine, N1-acetylputrescine, N1-acetylcadaverine, N1-acetylspermidine, N8-acetylspermidine and N1-acetylspermine in aqueous samples was achieved as their N-ethoxycarbonyl-N-pentafluoropropionyl derivatives by gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring (SIM) mode. The overall GC-SIM-MS method was linear (r> or =0.9987), repetitive (% relative standard deviation=1.3-6.4), and accurate (% relative error=-2.1-8.6). As compared to normal subjects, the levels of putrescine, N1-acetylspermine and spermine were significantly elevated while the levels of N1-acetylputrescine, N1-acetylcadaverine and N1-acetylspermidine were markedly reduced in all four Alzheimer's disease (AD) patients. When star symbol plotting was applied to the normalized levels of nine polyamines relative to the corresponding normal mean values, each star pattern of the AD patients was deformed, thus being readily distinguishable from the nonagon shape of the normal group average.


Solubilization of Morocco phosphorite by Aspergillus niger.
Phosphorus containing fertilizers have an important role in agriculture. Conventionally phosphate fertilizers are obtained by rock phosphate (RP) dissolution using mineral acids. Biotechnological methods can be a promising alternative in RP processing. The influence of Aspergillus niger strain, the composition of a nutritive medium, Morocco phosphorite (MP) concentration in the liquid medium, the time of bioconversion and the preliminary mechanical activation (PMA) of MP on the phosphorite microbial solubilization has been presented. The phosphorus concentration (as P2O5), citric acid production, glucose concentration and pH in the cultural medium were monitored. The phosphate concentration was expressed as water soluble - alpha1 (in the native cultural liquid), citrate soluble - alpha2 (after treating the biomass and remaining mineral mass with citric acid) and biomass available phosphorus - alpha3. Phosphate dissolution was not strongly correlated both with the citric acid production and the incubation period. When the fungi were grown without water soluble phosphorus compounds the MP solubilization had higher values. A maximum of 94.80% total P2O5 extraction was achieved. The PMA activity does not facilitate MP dissolution during the bioconversion.


Retrovirus-mediated siRNA targeting TRPM7 gene induces apoptosis in RBL-2H3 cells.
Calcium signaling is important for both normal physiologic processes and pathology of various diseases. Transient receptor potential melastatin 7 (TRPM7) gene has been reported to be a potential candidate for calcium influx. The present study aimed to investigate the possible role of TRPM7 channels in apoptosis in rat basophilic leukemia mast cell line (RBL-2H3), which is widely used in mast cell-associated studies. A recombinant retrovirus vector siRNA targeting rat TRPM7 gene was constructed and identified. Cellular survival was assessed by MTT. Cell apoptosis was evaluated by flow cytometry and TUNEL-FITC/Hoechst 33258 staining. The transfection efficiency by retrovirus vector was about 60%-70%. Transfection with TRPM7 siRNA significantly reduced TRPM7 expression both at mRNA and protein levels. Suppression of TRPM7 expression by siRNA led to significantly decreased cellular survival rates and increased apoptosis rates in RBL-2H3 cells. This study indicates that TRPM7 is involved in the apoptosis process in RBL-2H3 cells.


The structural basis of the talin-KANK1 interaction that coordinates the actin and microtubule cytoskeletons at focal adhesions.
Adhesion between cells and the extracellular matrix is mediated by heterodimeric (αβ) integrin receptors that are intracellularly linked to the contractile actomyosin machinery. One of the proteins that control this link is talin, which organizes cytosolic signalling proteins into discrete complexes on β-integrin tails referred to as focal adhesions (FAs). The adapter protein KANK1 binds to talin in the region of FAs known as the adhesion belt. Here, we adapted a non-covalent crystallographic chaperone to resolve the talin-KANK1 complex. This structure revealed that the talin binding KN region of KANK1 contains a novel motif where a β-hairpin stabilizes the α-helical region, explaining both its specific interaction with talin R7 and high affinity. Single point mutants in KANK1 identified from the structure abolished the interaction and enabled us to examine KANK1 enrichment in the adhesion belt. Strikingly, in cells expressing a constitutively active form of vinculin that keeps the FA structure intact even in the presence of myosin inhibitors, KANK1 localizes throughout the entire FA structure even when actomyosin tension is released. We propose a model whereby actomyosin forces on talin eliminate KANK1 from talin binding in the centre of FAs while retaining it at the adhesion periphery.


Vitreal and intraretinal responses to contrast reversing patterns in the pigeon eye.
The pattern electroretinogram (PERG) has been recorded vitreally and intraretinally in the pigeon eye. The amplitude of the PERG increases monotonically as pattern contrast is increased, with saturation at high levels. The PERG of the central yellow field has band-pass spatial tuning, with a high frequency cut-off at 8 c/deg. Time-to-peak is shortest at low spatial frequencies. Both PERG and local b-wave are small and positive-going close to the retinal surface, and large and negative-going in the inner nuclear layer. The PERG and b-wave show qualitatively similar depth profiles.


Risk factors for depression in adults: NR3C1 DNA methylation and lifestyle association.
The aim of this study was to verify determinant factors for depression and analyze the relationship between possible changes in HPA axis and depression, in this case NR3C1 DNA methylation and serum cortisol levels. 349 adult volunteers were recruited to evaluate depression, socio-demographic, economic and lifestyle factors, serum cortisol levels and NR3C1 DNA methylation by pyrosequencing. Depression determinant factors were investigated using a Poisson regression model with robust variance (p < 0.05). Poisson regression with robust variance adjusted by gender, tobacco use, self-perceived stress, leisure activity, suicidal ideation, low cortisol levels and NR3C1 DNA methylation was performed and predicted risk factors for depression. Furthermore, depressive volunteers showed a significant increase in NR3C1 DNA methylation when compared to healthy volunteers. This findings provide a basis for understanding the role of HPA axis in depression, especially its regulation by NR3C1 DNA methylation. Furthermore, it emphasizes the stressful lifestyle risk factors (female, tobacco uso, self perceived stress, leisure activities absence and suicidal ideation) that can contribute to future research and the search for public health policies to improve quality of live, mental and general health.


The distribution of substance P in the primate basal ganglia: an immunohistochemical study of baboon and human brain.
Using immunohistochemical methods we have studied the distribution of substance P fibers, terminals and perikarya throughout the basal ganglia of baboons and at selected levels of the human brain. Immunoreactivity in the substantia nigra pars reticulata, internal segment of the globus pallidus and ventral pallidum was dense and of a characteristic, "woolly-fiber" morphology. The caudate nucleus and putamen contained sharply circumscribed patches of dense immunoreactivity superimposed on a moderately stained background. The external division of the globus pallidus displayed very little immunoreactivity. Two morphological types of immunoreactive cell bodies were present in the caudate nucleus, putamen and nucleus accumbens, and were clustered within the dense patches. The distribution of immunoreactive perikarya within the striatum differed from that reported for rats, as immunoreactive neurons were distributed evenly throughout the rostrocaudal extent rather than being concentrated in the rostral portions.


Effect of difference in occlusal contact area of mandibular free-end edentulous area implants on periodontal mechanosensitive threshold of adjacent premolars.
Implant treatment is believed to cause minimal invasion of remaining teeth. However, few studies have examined teeth adjacent to an implant region. Therefore, this study investigated the effect of occlusal contact size of implants on the periodontal mechanosensitive threshold of adjacent premolars. A cross-sectional study design was adopted. The Department of Oral Implantology, Osaka Dental University, was the setting where patients underwent implant treatment in the mandibular free-end edentulous area. The study population comprised of 87 patients (109 teeth) who underwent follow-up observation for at least 3 years following implant superstructure placement. As variables, age, sex, duration following superstructure placement, presence or absence of dental pulp, occlusal contact area, and periodontal mechanosensitive threshold were considered. The occlusal contact area was measured using Blue Silicone(®)and Bite Eye BE-I(®). Periodontal mechanosensitive threshold were measured using von Frey hair. As quantitative variables for periodontal mechanosensitive threshold, we divided subjects into two groups: normal (≤5 g) and high (≥5.1 g). For statistical analysis, we compared the two groups for the sensation thresholds using the Chi square test for categorical data and the Mann-Whitney U test for continuous volume data. For variables in which a significant difference was noted, we calculated the odds ratio (95 % confidence interval) and the effective dose. There were 93 teeth in the normal group and 16 teeth in the high group based on periodontal mechanosensitive threshold. Comparison of the two groups indicated no significant differences associated with age, sex, duration following superstructure placement, or presence or absence of dental pulp. A significant difference was noted with regard to occlusal contact area, with several high group subjects belonging to the small contact group (odds ratio: 4.75 [1.42-15.87]; effective dose: 0.29). The results of this study suggest an association between implant occlusal contact area and the periodontal mechanosensitive threshold of adjacent premolars. Smaller occlusal contact application resulted in an increased threshold. It appears that prosthodontic treatment should aim not only to improve occlusal function but also to maintain oromandibular function with regard to the preservation of remaining teeth.


Clinical impact and quality of randomized controlled trials involving interventions evaluating artificial intelligence prediction tools: a systematic review.
The evidence of the impact of traditional statistical (TS) and artificial intelligence (AI) tool interventions in clinical practice was limited. This study aimed to investigate the clinical impact and quality of randomized controlled trials (RCTs) involving interventions evaluating TS, machine learning (ML), and deep learning (DL) prediction tools. A systematic review on PubMed was conducted to identify RCTs involving TS/ML/DL tool interventions in the past decade. A total of 65 RCTs from 26,082 records were included. A majority of them had model development studies and generally good performance was achieved. The function of TS and ML tools in the RCTs mainly included assistive treatment decisions, assistive diagnosis, and risk stratification, but DL trials were only conducted for assistive diagnosis. Nearly two-fifths of the trial interventions showed no clinical benefit compared to standard care. Though DL and ML interventions achieved higher rates of positive results than TS in the RCTs, in trials with low risk of bias (17/65) the advantage of DL to TS was reduced while the advantage of ML to TS disappeared. The current applications of DL were not yet fully spread performed in medicine. It is predictable that DL will integrate more complex clinical problems than ML and TS tools in the future. Therefore, rigorous studies are required before the clinical application of these tools.


Correlation of clinical, radiographic, and arthroscopic findings in internal derangements of the TMJ.
Arthroscopic, clinical, and imaging observations were compared in 80 temporomandibular joints with suspected internal derangements. Rating scales were developed for assessment of the key arthroscopic findings of "roofing," vascularity, redundancy, articular surface condition, adhesions, and disc function. Clinical and imaging findings were correlated with the rated arthroscopic findings. The degree of roofing was found to have a significant relationship to disc quality and function. Arthroscopy completed the diagnostic picture in these cases and provided detailed information on the joints that was not elicited from clinical findings or imaging studies.


Role of endothelial cell metabolism in vessel sprouting.
Endothelial cells (ECs) are quiescent for years but can plastically switch to angiogenesis. Vascular sprouting relies on the coordinated activity of migrating tip cells at the forefront and proliferating stalk cells that elongate the sprout. Past studies have identified genetic signals that control vascular branching. Prominent are VEGF, activating tip cells, and Notch, which stimulates stalk cells. After the branch is formed and perfused, ECs become quiescent phalanx cells. Now, emerging evidence has accumulated indicating that ECs not only adapt their metabolism when switching from quiescence to sprouting but also that metabolism regulates vascular sprouting in parallel to the control by genetic signals.


The causes of hyperreflective dots in optical coherence tomography excluding diabetic macular edema and retinal venous occlusion§.
To investigate the causes of hyperreflective dots (HRDs) in spectral domain optical coherence tomography (OCT) excluding diabetic macular edema (DME) and RVO (retinal vein occlusion). The medical records of 56 patients with HRDs documented by OCT were reviewed retrospectively. The patients with DME and RVO were excluded from the study in order to prevent misdiagnosing hard exudates or HRDs. The causes, unilaterality or bilaterality of HRD and demographic properties of the patients with HRD were evaluated. Sixty four eyes of 56 patients having HRDs were included in this study. Of the patients with HRD, 17 (30.36%) were women and 39 (69.64%) were men. The ages of patients were between 13 to 84 years (median 60.18 years). The causes of HRD were as follows: papilledema in 4 eyes (6.25%), active neovascular age related macular degeneration (AMD) in 33 eyes (51.56%), familial dominant drusen in 2 eyes (3.13%), central serous chorioretinopathy in 19 eyes (29.69%) and commotio retina in 2 eyes (3.13%), choroidal folds in one eye (1.56%), branch retinal artery occlusion in one eye (1.56%), central retinal artery occlusion in one patient (1.56%) and Best vitelliform macular dystrophy in one eye (1.56%). The most common cause of HRD was AMD. The causes of HRDs in both eyes were AMD and papilledema. The most common causes of HRDs excluding DME and RVO seem as active exudative AMD. The presence of HRDs in retinal diseases might affect the decisions and the results of the treatment and the prognosis of diseases.


[Thadeo, a listening service for caregivers].
Caregivers, like all working people, can encounter difficulties in the course of their professional activities. These difficulties, compounded by the particularities of caregiving practice, can lead to situations of isolation, overwork, exhaustion, disagreement and even ethical dilemmas in complex situations. Thadeo's free listening service offers support to caregivers who need it.


A prospective trial of primary inguinal hernia repair by surgical trainees.
The main hypotheses were that the Lichtenstein inguinal hernia repair has a lower recurrence rate and similar incidence of chronic groin pain compared to sutured repairs when performed by surgical trainees. In a U.S. Veterans Administration Hospital, 150 primary hernia repairs were randomized to a Lichtenstein, McVay, or Shouldice repair. The Shouldice repair included a routine relaxing incision. First- and second-year residents, under the supervision of an experienced general surgeon, performed the procedure. Long-term follow-up was obtained in 81% of patients. Hernia recurrence rate was Lichtenstein 8%, McVay 10%, Shouldice 5% ( P>0.1) at 6-9 years follow-up. More patients had chronic groin pain following Lichtenstein repair (38%) than after Shouldice repair (7%) ( P<0.05). More information is needed on long-term groin pain following anterior mesh repair. The Shouldice inguinal hernia repair may have a role in open primary herniorrhaphy to decrease the risk of chronic groin pain.


Possible factors influencing the duration of hospital stay in patients with psychiatric disorders attempting suicide by jumping.
Patients with psychiatric disorders have a high rate of suicide. The present study investigated factors influencing hospital stays for Japanese patients with psychiatric disorders attempting suicide by jumping. We diagnosed all suicide attempts (n = 113) by jumping based on the International Classification of Diseases 10th Revision (ICD-10) and investigated the mean hospital stays of patients with each diagnosis based on the ICD-10 code. We then analyzed differences in the demographic and clinical characteristics between the diagnostic groups to identify factors influencing the duration of hospital stay. Patients diagnosed with schizophrenia (F2 code) were the most frequent (32.7%) of all diagnoses; therefore, we divided the diagnostic groups into schizophrenia group (n = 37) and other psychiatric diagnoses group (n = 76). The patients with schizophrenia showed a significantly longer hospital stay (125.7 ± 63.9 days) compared with the patients with other psychiatric diagnoses (83.6 ± 63.2) (β ± SE = 42.1 ± 12.7, p = 0.0013), whereas there was no difference in the jump height between the two groups (the average was the 3rd to 4th floor; p > 0.05). The number of injured parts, particularly lower-limb fractures, was significantly higher (p = 0.017) in patients with schizophrenia than in patients with other psychiatric diagnoses. The duration of psychiatric treatment in patients with schizophrenia were significantly longer (z = 3.4, p = 0.001) than in patients with other psychiatric diagnoses. Our findings indicate that the number of injuries and the body parts injured in patients with schizophrenia are associated with a longer duration of hospital stay following a suicide attempt by jumping. The current use of antipsychotics and a longer duration of taking antipsychotics might contribute to the risk of bone fracture via hyperprolactinemia. Further cognitive impairment in patients with schizophrenia might prevent rehabilitation for the management of lower-limb fractures. From these results, we suggest that clinicians should monitor the level of prolactin and cognitive function in patients with schizophrenia in future studies on managing of lower-limb fractures.


[In vitro demonstration of the effect of lindane on isolated synaptosome preparations].
Lindane neurotoxicity is studied in vitro on Rat brain synaptosomes. Calcium uptake of isolated synaptosomes increases in the presence of pesticide; lindane action is observed on both normal and depolarized preparations.


The effect of pyrophosphate analogues on influenza virus RNA polymerase and influenza virus multiplication.
Analogues of pyrophosphate have been tested as inhibitors of influenza virus-RNA polymerase activity in cell-free assays. The most active compound, phosphonoformic acid (PFA), reduced the polymerase activity to 50 per cent at a concentration of 20 muM. The inhibition was dependent on the type of divalent cation present in the assay. PFA at a concentration of 400 muM also inhibited the influenza virus plaque formation by 90 per cent.


Enhancement of antitumor immunotherapy using mitochondria-targeted cancer cell membrane-biomimetic MOF-mediated sonodynamic therapy and checkpoint blockade immunotherapy.
Immunotherapeutic interventions represent a promising approach to treating cancer, with strategies such as immune checkpoint blockade (ICB), immunogenic sonodynamic therapy (SDT), and immune adjuvant T cell delivery having exhibited clinical promise. In this report, we describe the use of cancer cell membrane-coated triphenylphosphonium (TPP) decorated nano-metal-organic framework (nMOF) constructs [Zr-TCPP(TPP)/R837@M] that were used to generate homologous, mitochondria-targeted platforms with a high rate of sonosensitizer loading. This construct was utilized to simultaneously promote tumor antigen presentation via enhancing SDT while synergistically promoting dendritic cell (DC) maturation through the delivery of the Toll-like receptor agonist R837. In vitro, these functionalized nMOFs were readily internalized by homologous tumor cells in which they were efficiently targeted to the mitochondria, promoting DC activation through the induction of immunogenic cell death (ICD) following ultrasound exposure. Moreover, this nanoplatform was able to achieve in vivo synergy with anti-CTLA-4 ICB to reverse immunosuppression tumor microenvironment (TME), thus achieving more robust antitumor efficacy capable of suppressing metastatic disease progression and facilitating the development of durable antitumor memory responses. Together, these results highlight a promising approach to achieving enhanced SDT activity while overcoming an immunosuppressive TME, thereby achieving more robust antitumor immunity.


Effects of oil contamination on plant growth and development: a review.
Oil spills generate several environmental impacts and have become more common with the increase in petroleum extraction, refining, transportation, and trade. In soil, oil contamination increases water and nutrient availability and compaction, directly affecting plant growth and development. Different aspects of phytotoxicity can be observed and will vary according to the characteristics of soil and plants. Oil-contaminated soil also results in negative effects on biomass and changes in leaves and roots. Investigating the effects of oil contamination on plant growth and development can aid in the conservation of plant species and in the development of techniques such as bioremediation and biomonitoring. Thus, this review aims to discuss the main effects of oil contamination on plants, such as environmental stress and morphological, physiological, and anatomical changes, and the strategies developed by plants to survive contamination, as well as to identify plants with phytoremediation potential that can assist in removing oil from the environment.


Na+ and Cl- conductances are controlled by cytosolic Cl- concentration in the intralobular duct cells of mouse mandibular glands.
Our previously published whole-cell patch-clamp studies on the cells of the intralobular (granular) ducts of the mandibular glands of male mice revealed the presence of an amiloride-sensitive Na+ conductance in the plasma membrane. In this study we demonstrate the presence also of a Cl- conductance and we show that the sizes of both conductances vary with the Cl- concentration of the fluid bathing the cytosolic surface of the plasma membrane. As the cytosolic Cl- concentration rises from 5 to 150 mmol/liter, the size of the inward Na+ current declines, the decline being half-maximal when the Cl- concentration is approximately 50 mmol/liter. In contrast, as cytosolic Cl- concentration increases, the inward Cl- current remains at a constant low level until the Cl- concentration exceeds 80 mmol/liter, when it begins to increase. Studies in which Cl- in the pipette solution was replaced by other anions indicate that the Na+ current is suppressed by intracellular Br-, Cl- and NO3- but not by intracellular I-, glutamate or gluconate. Our studies also show that the Cl- conductance allows passage of Cl- and Br- equally well, I- less well, and NO3-, glutamate and gluconate poorly, if at all. The findings with NO3- are of particular interest because they show that suppression of the Na+ current by a high intracellular concentration of a particular anion does not depend on actual passage of that anion through the Cl- conductance. In mouse granular duct cells there is, thus, a reciprocal regulation of Na+ and Cl- conductances by the cytosolic Cl- concentration.(ABSTRACT TRUNCATED AT 250 WORDS)


Directional-path modification strategy enhances PET hydrolase catalysis of plastic degradation.
Poly (ethylene terephthalate) (PET) is a widely used type of general plastic that produces a significant amount of waste due to its non-degradable properties. We propose a novel directional-path modification (DPM) strategy, involving positive charge amino acid introduction and binding groove remodeling, and apply it to Thermobifida fusca cutinase to enhance PET degradation. The highest value of PET degradation (90%) was achieved in variant 4Mz (H184S/Q92G/F209I/I213K), exhibiting values almost 30-fold that of the wild-type. We employed molecular docking, molecular dynamics simulations, and QM/MM MD for the degradation process of PET, accompanied by acylation and deacylation. We found that the distance of nucleophilic attack was reduced from about 4.6 Å in the wild type to 3.8 Å in 4Mz, and the free energy barrier of 4Mz dropped from 14.3 kcal/mol to 7.1 kcal/mol at the acylation which was the rate-limiting step. Subsequently, the high efficiency and universality of the DPM strategy were successfully demonstrated in LCC, Est119, and BhrPETase enhancing the degradation activity of PET. Finally, the highest degradation rate of the pretreated commercial plastic bottles had reached to 73%. The present study provides insight into the molecular binding mechanism of PET into the PET hydrolases structure and proposes a novel DPM strategy that will be useful for the engineering of more efficient enzymes for PET degradation.


[Antiviral activity of Ingavirin on an animal model for experimental disseminated adenovirus infection].
Adenoviruses constitute a clinically important family of human pathogens. Due to their wide tissue tropism, adenoviruses are able to induce different diseases from moderate respiratory disorders to fatal outcomes in patients with immunodeficiencies. The authors present the results of a trial of the antiviral activity of the new drug Ingavirin [2-(imidazole-4-yl-ethanamide) pentandioic-1,5 acid] against human adenovirus type 5 on an animal model. Ingavirin is shown to decrease an adenoviral infectious titer in the liver and lung of neonatal Syrian hamsters (by approximately 1 log10 TCID50 as compared to the control) and to reduce the sizes of liver inflammation foci by 2-fold. Furthermore, it also decreases the count of virus-infected cells detectable by morphological analysis. Hepatocytes from Ingavirin-treated animals appear intact unlike strongly vacuolized cells from the animals given placebo. The findings make it possible to regard Ingavirin as a promising agent of the combination therapy of human adenovirus disease.


How can we predict which morbidly obese patients will adhere to weight-loss programs based on life style changes?
Dropout is a highly prevalent and serious problem in assessing the effectiveness of weight loss studies and a major cause of treatment failure in the management of morbidly obese patients. To determine which tests used for the psychometric evaluation of morbidly obese patients are more predictive of success/dropout in a weight loss program. Sixty patients aged 18-65 attending the Outpatient Obesity Clinic between 2009 and 2011, were recruited for an intensive life style weight loss program. We compared the results obtained in Hamilton Depression scale, Hamilton Anxiety scale, Golombok Rust Inventory of Sexual Satisfaction, Eating Disorders Inventory-2, SF-36 Health Survey and Plutchik's Impulsivity questionnaire between patients who completed the intervention with those obtained in patients who did not complete it. The rate of decline in the patients attending our program was 41.6% in the first year. Our results suggest that the Plutchik Impulsivity questionnaire, could be used as a predictive tool for success/attrition in intensive life style weight loss program. Our results suggest that the Plutchik Impulsivity questionnaire, could be used as a predictive tool for success/attrition in intensive life style weight loss program. The screening of patients prior to inclusion in these programs should help to optimize its efficacy and efficiency.


Self-Assembly Properties of an Amphiphilic Phosphate Ester Prodrug Designed for the Treatment of COVID-19.
PF-07304814 is a water-soluble phosphate ester prodrug of a small molecule inhibitor for the SARS CoV-2 3CL protease designed for the treatment of COVID-19. The amphiphilicity and self-assembly behavior of the prodrug was investigated computationally and experimentally via multiple orthogonal techniques to better design formulations for intravenous infusion. The self-assembly of PF-07304814 into micellar structures enabled an increase in the solubility of lipophilic impurities by up to 1900x in clinically relevant formulations. The observed solubilization could help extend the drug product shelf-life and in use stability through inhibition of precipitation, without the need for solubilizing excipients. The work presented in this manuscript provides a roadmap for the characterization of prodrug self-assembly and highlights the potential for prodrug modifications to enhance solubility of both active ingredients and impurities and to extend drug product shelf-life.


Previous treatment with morphine and sensitization to the excitatory actions of opiates: dose-effect relationship.
The stimulatory effect of morphine on locomotor activity has been shown to be largely modified in rats that have been formerly dependent on this drug. In the present study, the relationship between the chronic dose of morphine and the degree of sensitization to the excitatory effect of opiates was investigated. To this end, four groups of rats were treated daily for 30 days with 1.25, 5, 20 and 80 mg/kg of morphine (i.p.) and challenged with morphine (1.25 and 2.5 mg/kg) or fentanyl (40 and 80 micrograms/kg) 1-4 months after ceasing the treatment. Drug-induced hypermotility in post-dependent rats appeared to be linearly related to the dose of the preceding chronic treatment after test doses of both morphine and fentanyl. The results are discussed in terms of a persistent dose-related modification of the neuronal mechanism subserving the excitatory component of the action of opiates; such a modification might offer a neurobiological basis for the fact that "relapse tendencies" for opiates persist for a long time after withdrawal.


Flank pain in the third trimester as a clue to diagnose spontaneous adrenal hemorrhage.
Flank pain in pregnancy is a serious complaint and may have several etiologies, such as pyelonephritis or trauma. Spontaneous adrenal hemorrhage is rare in pregnancy, but is life threatening. We report a third-trimester pregnant woman with idiopathic bilateral spontaneous adrenal hemorrhage who presented with acute-onset severe flank pain and developed adrenal insufficiency. Normal blood pressure following hemorrhagic infarction may obscure the underlying adrenal insufficiency.


Controlled surface charging as a depth-profiling probe for mesoscopic layers
Probing the structure of material layers just a few nanometres thick requires analytical techniques with high depth sensitivity. X-ray photoelectron spectroscopy (XPS) provides one such method, but obtaining vertically resolved structural information from the raw data is not straightforward. There are several XPS depth-profiling methods, including ion etching, angle-resolved XPS (ref. 2) and Tougaard's approach, but all suffer various limitations. Here we report a simple, non-destructive XPS depth-profiling method that yields accurate depth information with nanometre resolution. We demonstrate the technique using self-assembled multilayers on gold surfaces; the former contain 'marker' monolayers that have been inserted at predetermined depths. A controllable potential gradient is established vertically through the sample by charging the surface of the dielectric overlayer with an electron flood gun. The local potential is probed by measuring XPS line shifts, which correlate directly with the vertical position of atoms. We term the method 'controlled surface charging' and expect it to be generally applicable to a large variety of mesoscopic heterostructures.


Inequalities in health and health behaviours between couple and lone mothers before and during the financial crisis in Spain (2003-2012).
Lone mothers report worse health and adopt more risky health behaviours than couple mothers, as largely documented in several European countries, but not deeply in Spain. The primary aim of this study was to identify the possible existence of inequalities in health and health behaviours between couple and lone mothers in Spain by occupational social class and employment status. A second aim was to explore whether any inequalities were influenced by the economic crisis beginning in 2008, analysing changes in inequalities between 2003-2004 and 2011-2012. Two waves of the cross-sectional Spanish National Health Survey data were used. Analyses were restricted to mothers aged 16-64 years, with at least one child aged 18 years or younger. The sample consisted of 2982 mothers in 2003-2004 and 3070 in 2011-2012, representing more than 80% of couple mothers. Two health outcomes and two health behaviour measurements were used. Robust Poisson regression was run to estimate inequalities between couple and lone mothers, calculating prevalence ratios adjusted by age and stratified by social class and employment status. We found inequalities in health and health behaviours between couple and lone mothers in Spain amongst the manual social class, with lone mothers reporting a more than 30% higher prevalence of poor self-perceived health and being smoker in both time points of study compared with couple mothers. Furthermore, lone mothers were at 50% higher risk of having at least one selected chronic condition and 86% higher probability of sleeping less than 6 hours/day in 2011-2012 This study could not confirm that inequalities between couple and lone mothers changed in Spain during the study period, although some patterns were noticeable. Inequalities pointed towards an increase amongst mothers in the manual social class with paid employment, while inequalities amongst unemployed mothers (both manual and non-manual social class) pointed towards a decrease.


Treating anxiety in patients with coronary heart disease: a randomized controlled trial.
Anxiety is frequent in patients with coronary heart disease (CHD) and influences the course of the disease, but no randomized controlled trial has investigated the effects of a psychotherapy intervention in CHD patients with elevated anxiety scores. The main aim of this study was to evaluate the effects of a 6-month psychotherapy intervention on anxiety in this group of patients. Fifty-two patients (61 ± 8.0 years, 14 female) with CHD and elevated levels of anxiety completed the study after randomization into a 6-month psychotherapy intervention or a control condition. Medically eligible patients were screened for anxiety with the Hospital Anxiety and Depression Scale (HADS) and were included if they had a score of 8 or higher. Anxiety scores were reevaluated at 6-month follow-up (after the treatment). At 6-month follow-up significant reductions (intervention group: -2.0 ± 2.3; control group: -1.8 ± 2.8; p < 0.01) were found in both groups in the HADS anxiety scale but no significant differences between the groups were observed. Adjustment for baseline differences and disease severity did not change these results. Our study showed that elevated anxiety scores were reduced over time but there was no statistically significant effect of the psychotherapy intervention in anxious patients with CHD. Changes in the design of the intervention and study might be useful to further investigate this topic in the future.


Fibrinolytic treatment of acute prosthetic heart valve thrombosis. 5 cases and a review.
Acute thrombotic obstruction of prosthetic heart valves has usually needed an emergency operation and carries a high mortality. Over the past 16 years, sporadic papers have appeared reporting the successful use of fibrinolytic therapy with a low mortality. We report five consecutive cases treated in this way. The diagnosis of valve thrombosis was made on clinical, echocardiographic and cineradiographic grounds. Treatment consisted of streptokinase (SPK) in a loading dose of 250,000 units in one case and 500,000 units in the remaining four cases, followed by 100,000 units hourly. Rapid improvement in clinical state was seen in all five patients. Four patients recovered completely and have been followed up for a minimum of 3 years. One patient died of a retroperitoneal haemorrhage, a recognised complication of fibrinolytic therapy. A review of the literature is presented. Fibrinolytic therapy is recommended in the acute episode and should result in either a return to normal valve function or sufficient improvement in haemodynamics to allow semielective surgery at considerably lower risk.


Recent evolutionary origin within the primate lineage of two pseudogenes with similarity to members of the transforming growth factor-beta superfamily.
Using a search engine called Motifer, we searched the public database of the human genome for genes matching a consensus pattern of cysteine residues derived from members of the transforming growth factor-beta (TGF-beta) superfamily. We identified two genes (named MDF451 and MDF628) that display sequence similarity to members of the TGF-beta superfamily in the arrangement of six conserved cysteine residues. Phylogenetic analyses revealed that MDF451 and MDF628 constitute a distinct subgroup within the TGF-beta superfamily, distantly related to the GDNF subfamily of ligands. Both genes could be identified in several primate species in addition to human, including chimpanzee, gorilla, guereza, and green and gray monkey, but not in rodents or other non-primate mammals, and appear not to be present in the genomes of mouse, rat or zebrafish. RNAs for MDF451 and MDF628 were expressed at low levels within distinct regions of the human central nervous system, including adult cerebellum, adult spinal cord and fetal brain. Despite expression at the RNA level, both genes presented a transcribed upstream stop codon that would prevent translation of the TGF-beta-like reading frame. The coding potential of alternative reading frames was not immediately apparent. The two genes may represent TGF-beta-like pseudogenes that have recently appeared in evolution in a common ancestor of the primate lineage by duplication from a GDNF/TGF-beta-like ancestral gene.


Age-Related Trends in the Predictive Value of Carotid Intima-Media Thickness for Cardiovascular Death: A Prospective Population-Based Cohort Study.
Background The age-related trends in the predictive ability of carotid intima-media thickness (CIMT) for cardiovascular risk remain unclear. We aimed to identify the age-related trends in the predictive value of CIMT for cardiovascular death. Methods and Results In a prospective cohort of adults aged 35 to 75 years without history of cardiovascular disease who were enrolled between 2014 and 2020, we measured CIMT at baseline and collected the vital status and cause of death. We divided the study population into 4 age groups (35-44, 45-54, 55-64, and 65-75 years). Competing risk models were fitted to estimate the associations between CIMT and cardiovascular death. The added values of CIMT in prediction were assessed by the differences of the Harrell's concordance index and the net reclassification improvement index. We included 369 478 adults and followed them for a median of 4.7 years. A total of 4723 (1.28%) cardiovascular deaths occurred. After adjusting for the traditional risk factors, the hazard ratios for CIMTmean per SD decreased with age, from 1.27 (95% CI, 1.17-1.37) in the 35 to 44 years age group to 1.14 (95% CI, 1.10-1.19) in the 65 to 75 years age group (P for interaction <0.01). Meanwhile, the net reclassification improvement indexes for CIMTmean were attenuated with age, from 22.60% (95% CI, 15.56%-29.64%) in the 35 to 44 years age group to 7.00% (95% CI, -6.82% to 20.83%) in the 65 to 75 years age group. Similar results were found for maximum CIMT in all age groups. Conclusions CIMT may improve cardiovascular risk prediction in the young and middle-aged populations, rather than those aged ≥55 years.


Structural mechanism of human oncochannel TRPV6 inhibition by the natural phytoestrogen genistein.
Calcium-selective oncochannel TRPV6 is the major driver of cell proliferation in human cancers. While significant effort has been invested in the development of synthetic TRPV6 inhibitors, natural channel blockers have been largely neglected. Here we report the structure of human TRPV6 in complex with the plant-derived phytoestrogen genistein, extracted from Styphnolobium japonicum, that was shown to inhibit cell invasion and metastasis in cancer clinical trials. Despite the pharmacological value, the molecular mechanism of TRPV6 inhibition by genistein has remained enigmatic. We use cryo-EM combined with electrophysiology, calcium imaging, mutagenesis, and molecular dynamics simulations to show that genistein binds in the intracellular half of the TRPV6 pore and acts as an ion channel blocker and gating modifier. Genistein binding to the open channel causes pore closure and a two-fold symmetrical conformational rearrangement in the S4-S5 and S6-TRP helix regions. The unprecedented mechanism of TRPV6 inhibition by genistein uncovers new possibilities in structure-based drug design.


Enteral administration of alectinib for ALK-positive non-small cell lung cancer in an elderly patient: A case report.
Alectinib is a tyrosine kinase inhibitor (TKI) approved for use as first-line metastatic therapy for patients with anaplastic lymphoma kinase-rearranged non-small cell lung cancer. Certain medical conditions related to the tumor lesions may not allow oral administration of TKIs. We hereby report the case of a 90-year-old patient with anaplasic lymphoma kinase-rearranged lung cancer with severely impaired general condition and swallowing disorders. A thoracic computerized tomography (CT)-scan confirmed the presence of a mediastinal tumor lesion explaining the swallowing disorders secondary to recurrent paralysis. As no oral administration was feasible, alectinib was administered by percutaneous gastrostomy. The patient had few side-effects. He presented a major clinical and radiological response. After 2 months of treatment with alectinib, his mini-mental state examination had increased from 8/30 to 23/30. He had a 60% reduction in targeted pulmonary, bone and node lesions according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). After 6 months of treatment, the patient's performance status had evolved from 3 to 1. This improvement in general condition made it possible to remove the feeding tube. In cases of lung cancer with oncogenic addiction, enteral administration of TKIs should be considered for elderly patients with an impaired general condition.


Development of eye-movement control.
Cognitive control of behavior continues to improve through adolescence in parallel with important brain maturational processes including synaptic pruning and myelination, which allow for efficient neuronal computations and the functional integration of widely distributed circuitries supporting top-down control of behavior. This is also a time when psychiatric disorders, such as schizophrenia and mood disorders, emerge reflecting a particularly vulnerability to impairments in development during adolescence. Oculomotor studies provide a unique neuroscientific approach to make precise associations between cognitive control and brain circuitry during development that can inform us of impaired systems in psychopathology. In this review, we first describe the development of pursuit, fixation, and visually-guided saccadic eye movements, which collectively indicate early maturation of basic sensorimotor processes supporting reflexive, exogenously-driven eye movements. We then describe the literature on the development of the cognitive control of eye movements as reflected in the ability to inhibit a prepotent eye movement in the antisaccade task, as well as making an eye movement guided by on-line spatial information in working memory in the oculomotor delayed response task. Results indicate that the ability to make eye movements in a voluntary fashion driven by endogenous plans shows a protracted development into adolescence. Characterizing the transition through adolescence to adult-level cognitive control of behavior can inform models aimed at understanding the neurodevelopmental basis of psychiatric disorders.


Evaluation of the antioxidant capacity of natural polyphenolic compounds using a macrocyclic Ni-(II) complex-catalysed Briggs-Rauscher reaction.
This paper reports a method for evaluating antioxidant capacity based on the inhibitory effects of a macrocyclic Ni(II) complex-catalysed Briggs-Rauscher reaction. The macrocyclic Ni(II) complex NiL(ClO4)2, in which L is 5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene, is a porphyrin-like compound, the structure of which can be found in certain enzymes. The experiments indicated that three natural compounds could temporarily quench the oscillations for a period of time prior to regeneration of oscillations. The inhibition time was related to the compound type and concentration; thus, procedures for evaluating the antioxidant activities of polyphenolic compounds were successfully established. Three polyphenolic compounds were tested to evaluate their antioxidant activities: protocatechuic acid, rutin hydrate and procyanidin. Of these three naturally occurring compounds, procyanidin was found to be the most efficient antioxidant. We have also discussed the reaction of the antioxidant with the hydroperoxyl radical (HOO) present in the oscillating system.


Impact of rituximab on the T-cell flow cytometric crossmatch.
Rituximab is frequently used in the setting of ABO-incompatible renal transplants, and highly sensitized patients. Its interference with B-cell flow cytometric crossmatch (B-FCXM) is well known. However, its effect on the T-cell flow cytometric crossmatch (T-FCXM) has not been described. We aimed to evaluate the effect of rituximab on the T-FCXM using non-pronase and pronase treated donor lymphocytes and compare results with the single antigen bead (SAB) assay. In this retrospective study, 28 patients on rituximab therapy were evaluated against 30 donors. Using non-pronase treated donor lymphocytes, all 30 FCXMs showed strong B-cell positivity {median (IQR) B-cell ratio: 184.65 (253.17)} which significantly reduced {1.0 (1.18); p < 0.00001} with pronase treatment. 'T-cell tailing' phenomenon was observed in 17/30 FCXMs in the non-pronase group as a 'tail of T-cells', indicating a rare sub-population. However, it disappeared in the pronase-treated group. SAB assay did not show donor-specific antibodies (DSA) in all 17 patients with 'T-cell tailing' phenomenon. Although, rituximab is described to impact only B-FCXM, we have consistently found 'T-cell tailing' in 57% of T-FCXMs, which clears with pronase treatment. The 'T-cell tailing' led to weak positive T-FCMX ratios due to increased MFI in the FL1 channel. However, the absence of DSA in all recipients reinforces the fact that this is a false positive finding and should not be misconstrued as a possible class I DSA. Structural homology of Fc receptors on activated T-cells to CD20 could be a possible explanation of the same and provide insight into a novel mechanism of action of rituximab.


Impact of Functional Magnetic Resonance Imaging on Clinical Outcomes in a Propensity-Matched Low Grade Glioma Cohort.
This study aims to evaluate the impact of preoperative functional magnetic resonance imaging (fMRI) on clinical outcomes in patients with low grade glioma (LGG). In a retrospective propensity-matched cohort study, we compared patients with LGG based on whether they underwent fMRI as part of preoperative assessment. Twelve patients with LGG who underwent preoperative fMRI were selected, and a contemporaneous group of 12 control patients with LGG who did not undergo fMRI were matched to the fMRI group based on age, sex, and 1p/19q status. fMRI group subjects tended to have more aggressive surgeries (67% resection, 33% biopsy) than the control group (33% resection, 67% biopsy). There were no significant differences in outcomes between the 2 groups. Time between clinical assessment and surgery tended to be longer in the fMRI group (6.3 ± 4.2 weeks) than in the control group (2.7 ± 2.2 weeks). Extent of resection was similar between the 2 cohorts. fMRI group subjects had lower preoperative functional status and tended to have a greater postoperative functional status improvement than control group subjects. Mean survival was not significantly different (fMRI group 5-year survival: 88.9%, control group 5-year survival: 61.1%). We evaluated the impact of preoperative fMRI in patients with LGG in this propensity-matched cohort study. This study has not demonstrated any significant difference in outcomes between the fMRI and control groups; however, there were nonsignificant trends for patients who underwent fMRI to undergo more aggressive surgical interventions and have a greater postoperative functional status improvement.


Acyl-CoA thioesterase 12 suppresses YAP-mediated hepatocarcinogenesis by limiting glycerolipid biosynthesis.
Cancer cells use acetate to support the higher demand for energy and lipid biosynthesis during uncontrolled cell proliferation, as well as for acetylation of regulatory proteins. Acyl-CoA thioesterase 12 (Acot12) is the enzyme that hydrolyzes acetyl-CoA to acetate in liver cytosol and is downregulated in hepatocellular carcinoma (HCC). A mechanistic role for Acot12 in hepatocarcinogenesis was assessed in mice in response to treatment with diethylnitrosamine(DEN)/carbon tetrachloride (CCl4) administration or prolonged feeding of a diet that promotes non-alcoholic steatohepatitis (NASH). Relative to controls, Acot12-/- mice exhibited accelerated liver tumor formation that was characterized by the hepatic accumulation of glycerolipids, including lysophosphatidic acid (LPA), and that was associated with reduced Hippo signaling and increased yes-associated protein (YAP)-mediated transcriptional activity. In Acot12-/- mice, restoration of hepatic Acot12 expression inhibited hepatocarcinogenesis and YAP activation, as did knockdown of hepatic YAP expression. Excess LPA produced due to deletion of Acot12 signaled through LPA receptors (LPARs) coupled to Gα12/13 subunits to suppress YAP phosphorylation, thereby promoting its nuclear localization and transcriptional activity. These findings identify a protective role for Acot12 in suppressing hepatocarcinogenesis by limiting biosynthesis of glycerolipids including LPA, which preserves Hippo signaling.


Molecular Pathophysiology of Fragile X-Associated Tremor/Ataxia Syndrome and Perspectives for Drug Development.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited neurodegenerative disorder manifesting in carriers of 55 to 200 CGG repeats in the 5' untranslated region (UTR) of the fragile X mental retardation gene (FMR1). FXTAS is characterized by enhanced FMR1 transcription and the accumulation of CGG repeat-containing FMR1 messenger RNA in nuclear foci, while the FMRP protein expression levels remain normal or moderately low. The neuropathological hallmark in FXTAS is the presence of intranuclear, ubiquitin-positive inclusions that also contain FMR1 transcript. Yet, the complete protein complement of FXTAS inclusions and the molecular events that trigger neuronal death in FXTAS remain unclear. In this review, we present the two most accepted toxicity mechanisms described so far, namely RNA gain-of-function and protein gain-of-function by means of repeat-associated non-AUG translation, and discuss current experimental and computational strategies to better understand FXTAS pathogenesis. Finally, we review the current perspectives for drug development with disease-modifying potential for FXTAS.


ZnO-based nanofungicides: Synthesis, characterization and their effect on the coffee fungi Mycena citricolor and Colletotrichum sp.
In this work we compare the antifungal capacity of zinc oxide nanoparticles (ZnO-NPs) synthesized by a chemical route and a ZnO-based nanobiohybrid obtained by green synthesis in an extract of garlic (Allium sativum). To find out the characteristics of the materials synthesized, X-ray diffraction (XRD), IR spectroscopy and absorption in UV-Vis were used, as well as both scanning (SEM) and transmission (TEM) electron microscopy. The results showed that the samples obtained were of nanometric size (<100 nm), with a predominance of the wurtzite crystal phase of ZnO and little crystallization of the nanobiohybrids. Their antifungal capacity on two pathogenic fungi of coffee, Mycena citricolor (Berk and Curt) and Colletotrichum sp. was also evaluated. Both nanomaterials showed an efficient antifungal capacity, particularly the nanobiohybrids, with ~97% inhibition in growth of M. citricolor, and ~93% for Colletotrichum sp. The microstructural study with high resolution optical (HROM) and ultra-structural microscopy (using TEM) carried out on the fungi treated with the synthesized nanomaterials showed a strong nanofungicidal effect on the vegetative and reproductive structures and fungal cell wall, respectively. The inhibition of the growth of the fungi and micro and ultra-structural affectations were explained considering that the size of the nanomaterials allows them to pass easily through the cell membranes. This indicates that they can be absorbed easily by the fungi tested here, causing cellular dysfunction. Nanofungicide effects are also attributable to the unique properties of nanomaterials, such as the high surface-to-bulk ratio of atoms and their surface physicochemical characteristics that could directly or indirectly produce reactive oxygen species (ROS), which affect the proteins of the cell wall.


Is it prime time for sex and gender considerations in traumatic brain injury? Perspectives of rehabilitation care professionals.
The purpose of this study was to explore rehabilitation clinicians' understanding of how sex and gender facilitate or hinder care provided to patients with traumatic brain injury (TBI). Sixteen clinicians from various specialities, attending to patients with TBI from a large rehabilitation hospital in Ontario, Canada, were recruited using purposive sampling. Data was collected through semi-structured interviews and thematic analysis was used to identify reoccurring themes. Three themes that facilitate or hinder care of TBI patients were identified: (1) knowledge and evidence; (2) gender and other aspects of recovery; and (3) family caregiving. Lack of education about the topic and inconsistent scientific evidence limited clinicians' attention to sex and gender topics. Social, financial, and cultural characteristics of patients were considered to be more relevant than their sex and gender. The gendered nature of caregiving and its burden on caregivers' health were acknowledged. Currently, attention to topics of sex and gender as they may influence patients' recovery is limited. However, clinicians are willing to be educated on these topics to enhance rehabilitation care. Further research on the gendered nature of interactions between patient, clinician, and family caregiver during recovery is warranted.IMPLICATIONS FOR REHABILITATIONSex and gender matter for patients undergoing recovery for their traumatic brain injury; however, clinical attention to this topic is limited.Based on the clinicians' perceptions, resources that address patients' psychosocial vulnerabilities should be prioritized (e.g., unequal access to care, financial status, cultural diversity etc.).Clinicians highlighted that psychosocial vulnerability and patients' life roles, before and after injury, are sex and gender specific.Guidelines about sex and gender influences in traumatic brain injury rehabilitation have the potential to enhance clinical practice.


Histological ulceration as a prognostic factor in cutaneous melanoma: a study of 423 cases in Spain.
Histological ulceration in cutaneous melanoma carries a high risk of metastasis and has a poor prognosis. However, some epidemiological and survival studies of patients with cutaneous melanoma do not consider histological ulceration as one of the main prognostic factors. Epidemiological, clinical, histological and survival characteristics of all patients diagnosed with cutaneous melanoma over a 10-year period (1994- 2003) were retrospectively analysed. Ulcerated melanoma was observed in 77 of 423 patients (18.2%). Ulceration was significantly associated with male sex, deeper tumour thickness, positive sentinel lymph node biopsy and metastasis (p<0.001). Histological ulceration indicates a high relative risk (RR) of death from melanoma (RR 9.41; 95% CI 4.52-19.59) and a significant risk of metastasis (RR 5.72; 95% CI 3.56-9.19) (p<0.001). Histological ulceration is associated with lower overall survival and disease-free survival in patients with cutaneous melanoma. Presence of ulceration must be included in the clinical history of patients with melanoma to ensure a careful diagnostic work-up and follow-up.


Comparative bioavailability of lornoxicam as single doses of quick-release tablet, standard tablet and intramuscular injection: a randomized, open-label, crossover phase I study in healthy volunteers.
Lornoxicam is an NSAID used to obtain short-term relief of acute mild to moderate pain and symptomatic relief of pain and inflammation in rheumatoid arthritis and osteoarthritis. The aim of this study was to compare and evaluate the pharmacokinetic parameters of lornoxicam 8 mg as quick-release (QR) tablet, standard tablet (ST) and intramuscular injection (IM). Eighteen healthy volunteers (9 male, 9 female; average age 26.9 (SD 3.0) years; average body mass index 21.8 (SD 2.3) kg/m2 were randomized to three different treatment groups. Subjects received a single 8-mg dose of each lornoxicam formulation in a three-way crossover design on days 1, 8 and 15. Lornoxicam plasma concentrations were obtained from baseline to 24 hours using high-pressure liquid chromatography. The pharmacokinetic parameters area under the plasma concentration-time curve from zero to infinity (AUCinfinity), maximum plasma concentration (Cmax), time to maximum plasma concentration (tmax), terminal half-life (t1/2)) and mean residence time (MRT) were calculated. Lornoxicam-QR was comparable with lornoxicam-ST and lornoxicam-IM regarding AUCinfinity, t1/2 and MRT. The AUCinfinity ratio (90% CI) was 1.07 (0.94, 1.20) for lornoxicam-QR/lornoxicam-ST and 1.10 (0.97, 1.24) for lornoxicam-QR/lornoxicam-IM. Cmax and tmax did not differ between lornoxicam-QR and lornoxicam-IM (p=0.66 and 0.07, respectively). Both lornoxicam-QR and lornoxicam-IM showed significantly shorter tmax and significantly higher Cmax values than lornoxicam-ST. Lornoxicam-QR and lornoxicam-IM did not differ with respect to AUCinfinity, Cmax and tmax, but both lornoxicam-QR and lornoxicam-IM showed significantly shorter tmax and significantly higher Cmax values than lornoxicam-ST.


Uncommon manifestations of erysipelas.
Erysipelas is a common infection of soft tissues by streptococci or Staphylococcus aureus. Uncommon manifestations of erysipelas include atypical localizations, unusual spreading of lesions, and atypical clinical morphology or course of the disease including the absence of general signs.


Computational design of new enzymes for hydrolysis and synthesis of third-generation cephalosporin antibiotics.
Engineering active sites in inert scaffolds to catalyze chemical transformations with unnatural substrates is still a great challenge for enzyme catalysis. In this research, a p-nitrobenzyl esterase from Bacillus subtilis was identified from the structural database, and a double mutant E115A/E188A was designed to afford catalytic activities toward the hydrolysis of ceftizoxime. A quadruple mutant E115A/E188A/L362S/I270A with enhanced catalytic efficiency was created to catalyze the condensation reaction of ethyl-2-methoxy-amino-2-(2-aminothiazole-4-yl) acetate with 7-amino-3-nor-cephalosporanic acid to produce ceftizoxime in a fully aqueous medium. The catalytic efficiencies of the computationally designed mutants E115A/E188A/L362S/I270A and E115A/Y118 K/E188 V/I270A/L362S can be taken as starting points to further improve their properties towards the practical application in designing more ecology-friendly production of third-generation cephalosporins.


Fluorescence emission spectra of photosystem I, photosystem II and the light-harvesting chlorophyll a/b complex of higher plants.
Fluorescence emission spectra excited at 514 and 633 nm were measured at -196 degrees C on dark-grown bean leaves which had been partially greened by a repetitive series of brief xenon flashes. Excitation at 514 nm resulted in a greater relative enrichment of the 730 nm emission band of Photosystem I than was obtained with 633 nm excitation. The difference spectrum between the 514 nm excited fluorescence and the 633 nm excited fluorescence was taken to be representative of a pure Photosystem I emission spectrum at -196 degrees C. It was estimated from an extrapolation of low temperature emission spectra taken from a series of flashed leaves of different chlorophyll content that the emission from Photosystem II at 730 nm was 12% of the peak emission at 694 nm. Using this estimate, the pure Photosystem I emission spectrum was subtracted from the measured emission spectrum of a flashed leaf to give an emission spectrum representative of pure Photosystem II fluorescence at -196 degrees C. Emission spectra were also measured on flashed leaves which had been illuminated for several hours in continuous light. Appreciable amounts of the light-harvesting chlorophyll a/b protein, which has a low temperature fluorescence emission maximum at 682 nm, accumulate during greening in continuous light. The emission spectra of Photosystem I and Photosystem II were subtracted from the measured emission spectrum of such a leaf to obtain the emission spectrum of the light-harvesting chlorophyll a/b protein at -196 degrees C.


Metabolic modeling of organ-specific doses to carcinogens as illustrated with alpha-radiation emitting radionuclides.
Quantitative estimation of doses of carcinogens delivered to physiologic targets facilities specification of organ-specific dose-response functions. Typically, exposure measurements, such as air or water concentrations of carcinogens, are used as dose surrogates in epidemiologic studies. An illustrative exception to this usual situation is the case of airborne alpha radiation-emitting radionuclides, for which organ-specific doses can be derived. A metabolic modeling approach for estimating doses delivered to the lung, gastrointestinal tract and bone is described for three classes of radionuclides: soluble uranium, insoluble uranium and plutonium. The dose models are defined in terms of biological retention patterns and organ-specific depositions affinities. Application of the metabolic modeling approach is illustrated with a hypothetical example of excess lung cancer risk projection in a cohort of persons exposed to plutonium. Also, a simple example is presented to demonstrate how adherence to the metabolic model structure can avoid gross overestimation of doses in the case of multiple in vivo lung counting measurements taken in close temporal proximity following a large exposure intake.


Filling the Gap in the Metallacrown Family: The 9-MC-3 Chromium Metallacrown.
In this work, we report on a long-sought missing complex in the metallacrown family. We synthesized and characterized the novel chromium metallacrown (MC) complex {CrIII (μ2 -piv)3 [9-MCCr(III)N(shi) -3](morph)3 }⋅MeOH (in which shi3- =salicyl hydroxamate, piv=pivalate, and morph=morpholine). The MC with a 9-MC-3 cavity of kinetically inert chromium(III) ions was synthesized by a solvothermal reaction. Magnetization measurements reveal a high spin ground state.


Histopathological findings in COVID-19-induced cutaneous lesions. Clinicopathological correlation of SARS-CoV-19 dermatologic patterns: review of the literature.
An increasing number of publications have brought attention to COVID-19-associated cutaneous lesions. Histopathological descriptions and clinical correlation of the histopathological findings of COVID-19 skin lesions are lacking. In this manuscript, we reviewed and described the histopathological characteristics of COVID-19 infection cutaneous patterns reported in the literature.