The Scottish Emergency Care Summary--an evaluation of a national shared record system aiming to improve patient care: technology report.
In Scotland, out-of-hours calls are all triaged by the National Health Service emergency service (NHS24) but the clinicians receiving calls have no direct access to patient records. To improve the safety of patient care in unscheduled consultations when the usual primary care record is not available. The Emergency Care Summary (ECS) is a record system offering controlled access to medication and adverse reactions details for nearly every person registered with a general practice in Scotland. It holds a secure central copy of these parts of the general practitioner (GP) practice record and is updated automatically twice daily. It is accessible under specified unplanned clinical circumstances by clinicians working in out-of-hours organisations, NHS24 and accident and emergency departments if they have consent from the patient and a current legitimate relationship for that patient's care. We describe the design of the security model, management of data quality, deployment, costs and clinical benefits of the ECS over four years nationwide in Scotland, to inform the debate on the safe and effective sharing of health data in other nations. Forms were emailed to 300 NHS24 clinicians and 81% of the 113 respondents said that the ECS was helpful or very helpful and felt that it changed their clinical management in 20% of cases. The ECS is acceptable to patients and helpful for clinicians and is used routinely for unscheduled care when normal medical records are unavailable. Benefits include more efficient assessment and reduced drug interaction, adverse reaction and duplicate prescribing.


Monitoring of central retinal artery and vein with color Doppler ultrasound during heart surgery as an alternative to transcranial Doppler ultrasonography: a case report.
Cardiac surgery can have severe neurologic complications. The noninvasive monitoring of intracranial circulation during heart surgery is usually performed with transcranial Doppler ultrasonography. We present the case of a 66-year-old man who underwent elective cardiac surgery for aortic valve replacement and coronary artery bypass graft, in whom monitoring was performed by simultaneously assessing blood flow velocity in the central retinal artery and vein.


Integration of a microfluidic chip with a size-based cell bandpass filter for reliable isolation of single cells.
We report a simple, efficient microfluidic array system for reliable isolation of cells. A microfluidic array chip, integrated with a size-based cell bandpass filter, provides the unprecedented capability of organizing single cells from a population containing a wide distribution of sizes.


Patulin immunotoxicology: effect on phagocyte activation and the cellular and humoral immune system of mice and rabbits.
Patulin is a mycotoxin frequently found in rotten apples or molded corn. We have investigated the effect of sublethal doses of patulin on the immune system in mice and rabbits. A significant suppression of the chemiluminescence response of peritoneal leucocytes was observed in both species. Mouse spleen lymphocytes showed a decrease in absolute number, most pronounced for the B-cell population whereas the Ts population showed a relative increase after patulin treatment. The mitogenic response to PHA, Con A and, in particular, PWM was also depressed by patulin. This was paralleled by decreasing serum immunoglobulin levels in the mice and rabbits. The immunosuppressive effect of patulin is reversible and is probably due to interaction with cellular free SH groups since the action of patulin can be circumvented, at least partially, by the prior administration of cystein. Under natural circumstances, patulin may constitute a health risk for animals.


Source apportionment and risk assessment of soil heavy metals around a key drinking water source area in northern China: multivariate statistical analysis approach.
With the intensive urbanization and industrialization in recent years, lots of products containing heavy metals (HMs) have brought in severe environment problems. Yuqiao Reservoir (YQR) is an important drinking water source area in Tianjin of China, and the soil environmental quality of YQR is vital for human health. The goal of this study was to identify the priority control pollutants and hotspots of HMs contamination of YQR catchment. Thus, an integrated field investigation was conducted to analyze the major elements such as As, Cd, Cr, Cu, Hg, Ni, Pb and Zn in soils around YQR. Geoaccumulation index (Igeo), enrichment factor (EF) and potential ecological risk index (PERI) were employed to assess the contamination status of HMs. The average contents of these elements were given as follows: As 7.97 mg/kg, Cd 0.31 mg/kg, Cr 86.1 mg/kg, Cu 24.7 mg/kg, Hg 0.044 mg/kg, Ni 30.7 mg/kg, Pb 27.3 mg/kg and Zn 76.7 mg/kg. According to geoaccumulation index (Igeo) and enrichment factor (EF) values, Cd, Cr, Pb and As showed a prominent enrichment. The result of multivariate statistics showed that Cd, Cr, Cu, As, Ni, Pb and Zn concentrations were mainly affected by human activities, whereas Hg was mainly from natural release. The anthropogenic activities were the major sources with a contribution of 91.46%, while natural origins only contributed 8.54%. And agricultural fertilization, mining and traffic activities are the most probable sources of these heavy metals in the soil. The PERI values indicated that 65.7% of total HMs were at low risk, 22.5% in moderate risk and 11.8% in considerable risk. To ensure soil environmental quality and human health, cadmium should be listed as a priority control pollutant. Spatial maps of HMs and their integrated PERI provided clear hotspots that indicated lower risk in the region close to YQR but higher risk in the region far from YQR.


Micro-regional planning: evidence-based community buy-in for health development in five of Mexico's poorest rural districts.
Community participation was a core tenet of Primary Health Care as articulated in the 1970s. How this could be generated and maintained was less clear. This historical article describes development of protocols for evidence-based community mobilisation in five local administrative units (municipios) in the Mexican state of Guerrero between 1992 and 1995. A sample of five to eight sentinel sites represented each of the most impoverished municipalities of the poorest five of the state's seven regions. A 1992 baseline survey of diarrhoea and its actionable determinants provided the substrate for discussion with local planners and communities. Municipal planners used different strategies to promote participation. In one municipality, new health committees took control of water quality. In another, municipal authorities hired health promoters; a song promoted oral rehydration, and house-to-house interpersonal discussions promoted chlorination. In the poorest and most mountainous municipality, radio casera (home-made radio) soap operas used local "stars". In the largest and most disparate municipality, a child-to-family scheme relied on primary and secondary school teachers. The research team assessed outcomes at intervals and used the results to reinforce local planning and action. Diarrhoea rates declined in all five municipalities, and there were several positive intermediate outcomes from the communication strategies - changing knowledge, household practices and uptake of services. There was a strong link between specific contents of the communication package and the changing knowledge or practices. Apart from these evidence-based interventions, other factors probably contributed to the decline of childhood diarrhoea. But, by monitoring implementation of planning decisions and the impact this has at community level, micro-regional planning can stimulate and reinforce actions likely to improve the health of communities. The process empowered municipalities to get access to more resources from the state government and international agencies.


Fusion to an albumin-binding domain with a high affinity for albumin extends the circulatory half-life and enhances the in vivo antitumor effects of human TRAIL.
Clinical applications of recombinant human tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL) have been limited by their poor pharmacokinetics. Using endogenous albumin as a carrier is an attractive approach for circulatory half-life extension. Here, we produced ABD-hTRAIL and hTRAIL-ABD by fusing the albumin-binding domain (ABD) from protein G to the N- or C-terminus of hTRAIL. We found that ABD-hTRAIL bound human serum albumin (HSA) with a high affinity (0.4 ± 0.18 nM) and formed nanoparticles with an average diameter (~12 nm) above the threshold (~7 nm) of renal filtration. ABD-hTRAIL also bound mouse serum albumin (MSA); thus, its half-life was 40-50-fold greater than that of hTRAIL (14.1 ± 0.87 h vs 0.32 ± 0.14 h). Tumor uptake of ABD-hTRAIL 8-48 h post-injection was 6-16-fold that of hTRAIL. Consequently, the tumor suppression of ABD-hTRAIL in mice bearing subcutaneous xenografts was 3-4 times greater than that of hTRAIL. Additionally, the time period during which ABD-hTRAIL could kill circulating tumor cells was approximately 8 times longer than that of hTRAIL. These results demonstrate that ABD fused to the N-terminus endows hTRAIL with albumin binding ability; once it enters the vasculature, ABD mediates binding with endogenous albumin, thus prolonging the half-life and enhancing the antitumor effect of hTRAIL. However, hTRAIL-ABD did not show a high affinity for albumin and therefore did not display the prolonged circulatory half-life and enhanced antitumor effects. These results demonstrate that N-terminal, but not C-terminal, ABD-fusion is an efficient technique for enhancing the antitumor effects of hTRAIL by using endogenous albumin as a carrier.


Mosaic mentoring: finding the right mentor for the issue at hand.
Mentoring has a vital role throughout the medical profession. Over the past few years, mentoring has become an area of focus as being an important aspect of radiologists' career starting from the early trainee level. A variety of mentorship strategies have come to the forefront, allowing many avenues for those seeking to engage in mentorship as either a mentee or mentor. Mosaic mentoring is a new approach that emphasizes utilizing a collection of mentorship approaches to maximize outcomes based on individual and/or domain-specific needs. The purpose of our paper is to provide a brief overview of a variety of mentorship models while introducing the concept of mosaic mentoring and exploring how it can benefit radiologists throughout their career.


Converting Ecological Currencies: Energy, Material, and Information Flows.
Understanding how the three currencies of life - energy, material, and information - interact is a key step towards synthesis in ecology and evolution. However, current theory focuses on the role of matter as a resource and energy, and typically ignores how the same matter can have other important effects as a carrier of information or modifier of the environment. Here we present the hypothesis that the dynamic conversion of matter by organisms among its three currencies mediates the structure and function of ecosystems, and that these effects can even supersede the effects of matter as a resource. Humans are changing the information in the environment and this is altering species interactions and flows of matter within and among ecosystems.


Delandistrogene Moxeparvovec Gene Therapy in Ambulatory Patients (Aged ≥4 to <8 Years) with Duchenne Muscular Dystrophy: 1-Year Interim Results from Study SRP-9001-103 (ENDEAVOR).
Delandistrogene moxeparvovec is approved in the USA for the treatment of ambulatory patients (4-5 years) with Duchenne muscular dystrophy. ENDEAVOR (SRP-9001-103; NCT04626674) is a single-arm, open-label study to evaluate delandistrogene moxeparvovec micro-dystrophin expression, safety, and functional outcomes following administration of commercial process delandistrogene moxeparvovec. In cohort 1 of ENDEAVOR (N = 20), eligible ambulatory males, aged ≥4 to <8 years, received a single intravenous infusion of delandistrogene moxeparvovec (1.33 × 1014 vg/kg). The primary endpoint was change from baseline (CFBL) to week 12 in delandistrogene moxeparvovec micro-dystrophin by western blot. Additional endpoints evaluated included: safety; vector genome copies; CFBL to week 12 in muscle fiber-localized micro-dystrophin by immunofluorescence; and functional assessments, including North Star Ambulatory Assessment, with comparison with a propensity score-weighted external natural history control. The 1-year safety profile of commercial process delandistrogene moxeparvovec in ENDEAVOR was consistent with safety data reported in other delandistrogene moxeparvovec trials (NCT03375164 and NCT03769116). Delandistrogene moxeparvovec micro-dystrophin expression was robust, with sarcolemmal localization at week 12; mean (SD) CFBL in western blot, 54.2% (42.6); p < 0.0001. At 1 year, patients demonstrated stabilized or improved North Star Ambulatory Assessment total scores; mean (SD) CFBL, +4.0 (3.5). Treatment versus a propensity score-weighted external natural history control demonstrated a statistically significant difference in least squares mean (standard error) CFBL in North Star Ambulatory Assessment, +3.2 (0.6) points; p < 0.0001. Results confirm efficient transduction of muscle by delandistrogene moxeparvovec. One-year post-treatment, delandistrogene moxeparvovec was well tolerated, and demonstrated stabilized or improved motor function, suggesting a clinical benefit for patients with Duchenne muscular dystrophy. ANN NEUROL 2023;94:955-968.


Analysis of steroids by capillary supercritical fluid chromatography with phosphorus-selective detection.
Steroids were derivatized with dimethylthiophosphinic chloride to produce steroidal thiophosphinic esters. A catalyst, 4-dimethylaminopyridine, was used to promote quantitative and reproducible thiophosphinic ester formation at low reaction temperatures. The derivatives were analyzed by capillary supercritical fluid chromatography (SFC) with phosphorus thermionic detection. The phosphorus thermionic detector exhibited linearity over 3-4 orders of magnitude. A sensitivity of 120 fg P/s was obtained for the dithiophosphinic ester of pregnanediol at a signal-to-noise ratio of 3. The efficiency of capillary SFC and the excellent sensitivity of the phosphorus thermionic detector were demonstrated by the analysis of steroids isolated from both human urine and plasma.


[Indoor air guide values for benzyl alcohol].
The German Working Group on Indoor Air Guidelines of the Federal Environment Agency and the States' Health Authorities is issuing indoor air guide values to protect public health. For health evaluation of benzyl alcohol in indoor air valid inhalation studies are missing. Following subchronic oral exposure to 800 mg benzyl alcohol/kg body weight and day neurotoxicity was observed in rats. Accounting for data gaps by a factor of 2 and extrapolating to continuous exposure by applying a factor of 2 the lowest adverse effect level for chronic exposure (LAELchron) is assessed as 200 mg benzyl alcohol/kg b. w. and day. By applying an interspecies factor of 10, an intraspecies factor of 10, a path-to-path-extrapolation and a modifying factor of 2 referring to the special physiology of children (higher breathing rate compared to adults) a health hazard guide value (RW II) of 4 mg benzyl alcohol/m3 indoor air and a health precaution guide value (RW I) of 0.4 mg benzyl alcohol/m3 are derived.


Melatonin promotes parthenogenetic development of vitrified-warmed mouse MII oocytes, potentially by reducing oxidative stress through SIRT1.
Previous studies have demonstrated that melatonin could ameliorate oxidative stress during the cryopreservation of mouse MII oocytes and their in vitro culture after parthenogenetic activation. However, the underlying molecular mechanism remained poorly understood. This study was conducted to investigate whether melatonin could modulate the oxidative stress in the parthenogenetic 2-cell embryos derived from vitrified-warmed oocytes through SIRT1. The results showed that the reactive oxygen species levels increased, the glutathione levels and SIRT1 expression decreased significantly in parthenogenetic 2-cell embryos derived from cryopreserved oocyte, and the parthenogenetic blastocyst formation rates significantly decreased when compared to those derived from control oocytes. These unfavorable phenomena were prevented by the addition of either 10-9 mol/L melatonin or 10-6 mol/L SRT-1720 (SIRT1 agonist), and it was restored by the supplementation of 10-9 mol/L melatonin in combination with 2 × 10-5 mol/L EX527 (SIRT1 inhibitor). Therefore, the findings from the present study concluded that melatonin may reduce oxidative stress via regulating SIRT1, and potentially promote the parthenogenetic development of vitrified-warmed mouse MII oocytes.


The role of individual variability on the predictive performance of machine learning applied to large bio-logging datasets.
Animal-borne tagging (bio-logging) generates large and complex datasets. In particular, accelerometer tags, which provide information on behaviour and energy expenditure of wild animals, produce high-resolution multi-dimensional data, and can be challenging to analyse. We tested the performance of commonly used artificial intelligence tools on datasets of increasing volume and dimensionality. By collecting bio-logging data across several sampling seasons, datasets are inherently characterized by inter-individual variability. Such information should be considered when predicting behaviour. We integrated both unsupervised and supervised machine learning approaches to predict behaviours in two penguin species. The classified behaviours obtained from the unsupervised approach Expectation Maximisation were used to train the supervised approach Random Forest. We assessed agreement between the approaches, the performance of Random Forest on unknown data and the implications for the calculation of energy expenditure. Consideration of behavioural variability resulted in high agreement (> 80%) in behavioural classifications and minimal differences in energy expenditure estimates. However, some outliers with < 70% of agreement, highlighted how behaviours characterized by signal similarity are confused. We advise the broad bio-logging community, approaching these large datasets, to be cautious when upscaling predictions, as this might lead to less accurate estimates of behaviour and energy expenditure.


The relationship between ambulatory arterial stiffness index and left ventricular diastolic dysfunction in HFpEF: a prospective observational study.
The relationship between ambulatory arterial stiffness index (AASI) and left ventricular diastolic dysfunction (LVDD) in patients with heart failure with preserved ejection fraction (HFpEF) is unknown. We aimed to investigate the association between the AASI and LVDD in HFpEF. We prospective enrolled consecutive patients with HFpEF in Chongqing, China. Twenty-four-hour ambulatory blood pressure monitoring (24 h-ABPM) and echocardiography were performed in each patient. AASI was obtained through individual 24 h-ABPM. The relationship between AASI and LVDD was analyzed. A total of 107 patients with HFpEF were included. The mean age was 68.45 ± 14.02 years and 63 (59%) were women. The patients were divided into two groups according to the upper normal border of AASI (0.55). AASI > 0.55 group were more likely to be older, to have higher mean systolic blood pressure and worsen left ventricular diastolic function than AASI group ≤ 0.55. AASI was closely positive related to the diastolic function parameters, including mean E/e' (r = 0.307, P = 0.001), septal E/e' (r = 0.290, P = 0.002), lateral E/e' (r = 0.276, P = 0.004) and E (r = 0.274, P = 0.004). After adjusting for conventional risk factors, AASI was still an independent risk factors of mean E/e' > 10 in patients with HFpEF (OR: 2.929, 95%CI: 1.214-7.064, P = 0.017), and the association between AASI and mean E/e' > 14 was reduced (OR: 2.457, 95%CI: 1.030-5.860, P = 0.043). AASI had a partial predictive value for mean E/e' > 10 (AUC = 0.691, P = 0.002), while the predictive value for mean E/e' > 14 was attenuated (AUC = 0.624, P = 0.034). AASI was positive related to E/e' in HFpEF and might be an independent risk factor for the increase of mean E/e'.


Effect of abdominal visceral fat on mortality risk in patients with severe acute pancreatitis.
Obesity is a well-known risk factor for the development and severity of acute pancreatitis (AP), but the relationship between the abdominal visceral fat area (VFA) and mortality is unclear. We evaluated the effect of the VFA on mortality in severe AP (SAP). This retrospective, single-center cohort study examined 119 consecutive patients with SAP from April 2009 to March 2019. The VFA at the umbilical level was assessed using computed tomography. The primary endpoint was to evaluate whether visceral obesity affects mortality in SAP. The median age was 63 years, and 66% of participants were male. Nine patients (7.5%) died during their hospital stay. The median body mass index (BMI) was 22.2 kg/m2, and six obese patients had a BMI of over 30 kg/m2 (5%). The median waist circumference and VFA were 85.5 cm and 112 cm2, respectively. Sixty-eight (57.1%) patients had a VFA over 100 cm2. The prognostic factor score based on the Japanese guidelines for AP management (cutoff value [COV], 4; area under the curve [AUC] = 0.869) and age [COV, 72; AUC = 0.780]) showed moderate accuracy for predicting mortality, followed by the VFA (COV, 167 cm2; AUC = 0.679). Univariate logistic analysis, but not multivariate analysis, showed that an increased VFA was associated with a significantly higher odds ratio (OR) for predicting mortality (OR: 4.38, P = 0.0406). The survival times of SAP patients with and without an increased VFA of 167 cm2 were not significantly different. Visceral obesity did not have a significant impact on predicting mortality in patients with SAP.


Activation of phospholipase D in normodense human eosinophils.
Normodense human eosinophils have been labeled in 1-0-alkyl-phosphatidylcholine (alkyl-PC) with 32P by incubating isolated cells with alkyl-[32P]lysoPC. Stimulation of these 32P-labeled cells with C5a, A23187 or PMA in the presence of 0.5% ethanol resulted in time- and dose-dependent formation of alkyl-[32P]phosphatidic acid (alkyl-[32P]PA) and alkyl-[32P]phosphatidylethanol (alkyl-[32P]PEt). Because cellular ATP does not contain 32P, alkyl-[32P]PA must have been formed by the hydrolytic action of phospholipase D (PLD) and not by the combined actions of phospholipase C and DG kinase. Regardless of the stimulating agent, alkyl-[32P]PEt formation paralleled that of alkyl-[32P]PA, suggesting that alkyl-PEt was the result of a PLD-catalyzed transphosphatidylation reaction between alkyl-PC and ethanol. These data provide the first definitive proof of receptor- and nonreceptor-mediated activation of PLD in normodense eosinophils derived from human blood.


Disease tolerance as a defense strategy.
The immune system protects from infections primarily by detecting and eliminating the invading pathogens; however, the host organism can also protect itself from infectious diseases by reducing the negative impact of infections on host fitness. This ability to tolerate a pathogen's presence is a distinct host defense strategy, which has been largely overlooked in animal and human studies. Introduction of the notion of "disease tolerance" into the conceptual tool kit of immunology will expand our understanding of infectious diseases and host pathogen interactions. Analysis of disease tolerance mechanisms should provide new approaches for the treatment of infections and other diseases.


Ethyl acetate extract of the Mauritian sponge Jaspis sp. induces cell arrest in human promyelocytic leukemia cells.
Marine sponges are considered as a gold mine of new natural products possessing numerous biological activities. We examined the cytotoxic properties of the ethyl acetate extract (JDE) of the previously unrecorded sponge, Jaspis sp. collected from Mauritius Waters. JDE displayed an interesting IC50 of 0.057±0.04μg/mL on HL-60 cells evaluated by MTS assay. Mitochondrial membrane potential change, microscopic analysis and DNA fragmentation assays also confirmed JDE induced apoptosis on HL-60 cells. Annexin V staining demonstrated that JDE induced apoptosis at different concentrations. Treatment with 100ng/mL of JDE led to an accumulation of cells in G2/M phase after 24 h, causing a significant increase of cells (24h: 5.84%; 48h: 13.41%) in sub-G1 phase suggesting that JDE can induce cell cycle arrest in G2/M phase.


sTREM2 mediates the associations of minimal depressive symptoms with amyloid pathology in prodromal Alzheimer's disease: The CABLE study.
The effects of microglial activation on the associations between depression and Alzheimer's disease (AD) are still unclear. TREM2 gene plays a pivotal role in microglial activation, has been identified as a risk factor for AD. In this work, we aimed to assess the interrelationships of soluble TREM2 (sTREM2) level in cerebrospinal fluid (CSF), minimal depressive symptoms (MDSs), and CSF amyloid markers. The linear regression analyses were conducted on 796 cognitively unimpaired participants from the CABLE (Chinese Alzheimer's Biomarker and LifestylE) study. Causal mediation analyses with 10,000 bootstrapped iterations were used to test the mediation effects. In addition, similar statistical analyses were performed in subgroups stratified by sex, age, and APOE ε4 carrier status. In total subjects, MDSs were associated with lower CSF sTREM2 levels (p < 0.0001), lower CSF amyloid markers (p < 0.0001), and poorer cognitive performance (MMSE, p = 0.0014). The influence of MDSs on CSF amyloid markers was partially mediated by CSF sTREM2 (proportion from 2.91 to 32.58%, p < 0.0001). And we found that the sTREM2-amyloid pathway partially mediated the effects of MDSs on cognition. Of note, exploratory subgroup analyses showed that the above influences of CSF sTREM2 were pronounced in the APOE ε4 (-) group. These results suggest that early depression is associated with amyloid pathology, which might be partly mediated by microglial activation, especially in the absence of APOE ε4.


Surgical strategy for acquired tracheomalacia due to innominate artery compression of the trachea.
We reviewed six cases demonstrating acquired tracheomalacia due to innominate artery compression of the trachea and investigated the benefit and effectiveness of a technique for correcting tracheomalacia. All the patients developed scoliosis and the innominate artery run over the trachea. Four cases had permanent neurologic impairment, whereas two patients developed acquired neurologic impairment. The surgical strategy for acquired tracheomalacia due to innominate artery compression of the trachea involved superior mediastinal exposure, external reinforcement with autologous cartilage graft, anterior sling of the innominate artery with a muscle sling, and tracheopexy. Our surgical procedure has been effective in maintaining the patency of the tracheal lumen in all cases but one. This patient suffered from straight back syndrome and developed recurrence of tracheomalacia owing to mucosal infolding secondary to the deformed spine in a supine position. The authors believe our surgical procedure is effective to relieve the symptoms of tracheomalacia, but it is important to select surgical interventions in accordance with the specific patient's condition.


Fecal microbiota transplantation for Parkinson's disease using levodopa - carbidopa intestinal gel percutaneous endoscopic gastro-jejeunal tube.
We report a patient with a 5-year diagnosis of akinetic-rigid Parkinson's disease under treatment with Levodopa-Carbidopa Intestinal Gel therapy through a PEG-J tube due to motor complications, in which, in the context of a clinical study, we successfully and safely administered fecal microbiota transplant through a PEG-J.


Protein secretion in cockroach salivary glands requires an increase in intracellular cAMP and Ca2+ concentrations.
The salivary glands in the cockroach Periplaneta americana secrete protein-containing saliva when stimulated by serotonin (5-HT) and protein-free saliva upon dopamine stimulation. In order to obtain information concerning the signalling pathways involved in 5-HT-induced protein secretion, we have determined the protein content of saliva secreted after experimental manipulations that potentially elevate intracellular Ca2+ and cyclic nucleotide concentrations in isolated glands. We have found that 5-HT stimulates the rate of protein secretion in a dose-dependent manner (threshold: 3 x 10(-8)M; EC50 1.5 x 10(-6)M). The maximal rate of 5-HT-induced protein secretion was 2.2 +/- 0.2 microg/min. Increasing intracellular Ca2+ or cAMP by bath application of ionomycin (5 microM), db cAMP (10mM), forskolin (100 microM) or IBMX (100 microM), respectively, stimulated protein secretion at significantly lower rates, whereas db cGMP (1mM) did not activate protein secretion. The high rates and the kinetics of 5-HT-induced protein secretion could only be mimicked by either applying forskolin together with IBMX (with or without ionomycin) or by applying IBMX together with ionomycin. Our measurements suggest that 5-HT-induced protein secretion is mediated by an elevation of [cAMP]i and that Ca2+ may function as a co-agonist and augment the rate of protein secretion.


Validation of a Questionnaire on Sexual and Reproductive Health Among Immigrant Vocational Education Students in Portugal from São Tomé and Príncipe.
Sexual and reproductive health interventions' effectiveness should be evaluated using a valid instrument. This study aimed to validate a questionnaire on sexual and reproductive health in adolescents and young adults from São Tomé and Príncipe who voluntarily enrolled in a vocational school in Portugal to complete their 12th school year and obtain a professional card.A questionnaire consisting of perception and knowledge sections was adapted from previous questionnaires. We followed the steps of psychometric analysis. Firstly, we assessed face validity and content validity. We used factorial analysis to validate the perceptions section (which included Likert-type questions). For the knowledge section (which consisted of multiple-choice questions), we used the key check, discrimination index, and difficulty index. We evaluated internal consistency through Cronbach's alpha for the perceptions section and the Kuder-Richardson score for the knowledge section.Out of 105 invited students, a total of ninety students were enrolled in this study, of whom 88 completed most of the questions. The exploratory analysis showed that most students agreed with the right to refuse intercourse. However, while approximately 23% disagreed that consensual sex among adult women or men is always wrong, around the same proportion agreed. A considerable number of students recognized condoms and pills as effective methods of contraception. However, most students were unfamiliar with other methods. Most knowledge questions showed acceptable difficulty levels, and the discrimination index varied among questions. The knowledge questions demonstrated good consistency levels. This study enabled us to develop an appropriate instrument for evaluating the effectiveness of public health interventions and identifying specific knowledge gaps in migrant populations from low-income countries. This will help prioritise topics to be addressed in sexual health education sessions.


Variation of Orthokeratology Lens Treatment Zone (VOLTZ) Study: A 2-year randomised clinical trial.
To compare axial elongation (AE) and treatment zone (TZ) characteristics in children wearing 6 mm or 5 mm back optic zone diameter (BOZD) orthokeratology (ortho-k) lenses over 2 years. Forty-five (6 to <11 years of age) myopic (-4.00 to -0.75 D) children of Chinese ethnicity were randomly assigned to use the two different lens designs (23 and 22 wore the 6 and 5 mm lenses, respectively). Data collection was performed at baseline and every 6-months after commencing lens wear. After 24 months, subjects wearing lenses with a 5 mm BOZD achieved smaller TZ diameter (horizontal: 2.69 ± 0.28 vs. 3.84 ± 0.39 mm; vertical: 2.65 ± 0.22 vs. 3.42 ± 0.34 mm, p < 0.001) and less AE (0.15 ± 0.21 vs. 0.35 ± 0.23, p = 0.005) compared to those using the 6 mm design, with no difference in choroidal thickness (ChT) changes (p = 0.93). A significant increase in ChT, using pooled data analysis, was noted at the 6-month (11.8 ± 19.77 μm, p < 0.001) and 12-month (12.0 ± 23.7 μm, p = 0.004) visits, compared to baseline, indicating a transient change in ChT. Significant associations were noted, using linear mixed models, between AE and the TZ diameters (p < 0.003) after adjusting for baseline data. A very weak association was found between ChT changes and AE, with the effect size close to zero. Smaller BOZD ortho-k lenses resulted in a smaller TZ diameter, which was associated with less AE after 2 years of treatment. The changes in ChT played a very weak role, suggesting that other factors may contribute more to the reduced AE in subjects wearing lenses having a smaller BOZD.


Cytotoxic granzyme C-expressing ILC1s contribute to antitumor immunity and neonatal autoimmunity.
Innate lymphocytes are integral components of the cellular immune system that can coordinate host defense against a multitude of challenges and trigger immunopathology when dysregulated. Natural killer (NK) cells and innate lymphoid cells (ILCs) are innate immune effectors postulated to functionally mirror conventional cytotoxic T lymphocytes and helper T cells, respectively. Here, we showed that the cytolytic molecule granzyme C was expressed in cells with the phenotype of type 1 ILCs (ILC1s) in mouse liver and salivary gland. Cell fate-mapping and transfer studies revealed that granzyme C-expressing innate lymphocytes could be derived from ILC progenitors and did not interconvert with NK cells, ILC2s, or ILC3s. Granzyme C defined a maturation state of ILC1s. These granzyme C-expressing ILC1s required the transcription factors T-bet and, to a lesser extent, Eomes and support from transforming growth factor-β (TGF-β) signaling for their maintenance in the salivary gland. In a transgenic mouse breast cancer model, depleting ILC1s caused accelerated tumor growth. ILC1s gained granzyme C expression following interleukin-15 (IL-15) stimulation, which enabled perforin-mediated cytotoxicity. Constitutive activation of STAT5, a transcription factor regulated by IL-15, in granzyme C-expressing ILC1s triggered lethal perforin-dependent autoimmunity in neonatal mice. Thus, granzyme C marks a cytotoxic effector state of ILC1s, broadening their function beyond "helper-like" lymphocytes.


Presence of corticotropin-releasing factor-like immunoreactivity in human tumors.
Corticotropin-releasing factor (CRF)-like immunoreactivity was measured by radioimmunoassay in human organs and tumors associated with and without ectopic adrenocorticotropic hormone (ACTH) syndrome. It was found to be distributed widely in the stomach, pancreas, adrenal gland, and various tumors (e.g., medullary thyroid carcinoma, small cell carcinoma of the lung, pheochromocytoma, and adenocarcinoma of the gastrointestinal tract and pancreas) in a concentration less than one tenth of that of the hypothalamus. Dilution curves of CRF-like immunoreactivity in tissue extracts paralleled that of synthetic rat (human) CRF. Sephadex G-50 gel filtration showed that a major CRF-like immunoreactivity in tissue extracts coeluted with synthetic rat (human) CRF. Results suggest that a material(s) closely related immunologically to CRF is present widely in normal and tumor tissues outside of the central nervous system.


Protein digestion and phosphopeptide enrichment on a glass microchip.
This work describes an integrated glass microdevice for proteomics, which directly couples proteolysis with affinity selection. Initial results with standard phosphopeptide fragments from beta-casein in peptide mixtures showed selective capture of the phosphorylated fragments using immobilized metal affinity chromatography (IMAC) beads packed into a microchannel. Complete selectivity was seen with angiotensin, with capture of only the phosphorylated form. On-chip proteolysis, using immobilized trypsin beads packed into a separate channel, was directly coupled to the phosphopeptide capture and the integrated devices evaluated using beta-casein. Captured and eluted fragments were analyzed using both capillary electrophoresis (CE) and capillary liquid chromatography/mass spectrometry (cLC/MS). The results show selective capture of only phosphopeptide fragments, but incomplete digestion of the protein was apparent from multiple peaks in the CE separations. The MS analysis indicated a capture bias on the IMAC column for the tetraphosphorylated peptide fragment over the monophosphorylated fragment. Application to digestion and capture of a serum fraction showed capture of material; however, non-specific binding was evident. Additional work will be required to fully optimize this system, but this work represents a novel sample preparation method, incorporating protein digestion on-line with affinity capture for proteomic applications.


CMY-2, CMY-8b, and DHA-1 plasmid-mediated AmpC β-lactamases among clinical isolates of Escherichia coli and Klebsiella pneumoniae from a university hospital, Thailand.
Between February 2005 and January 2006 in Srinagarind Hospital, Thailand, 44 from 1730 isolates (2.5%) of Escherichia coli and 8 from 982 isolates (0.8%) of Klebsiella pneumoniae were found to produce plasmid-mediated AmpC β-lactamases (pAmpCs) as detected by a cefoxitin-Hodge test followed by a multiplex polymerase chain reaction (PCR) technique. Fifteen of the 52 pAmpC-producing isolates also produced extended-spectrum β-lactamases. The ampC genes found in both organisms were bla(CMY-2) (46 isolates), bla(CMY-8b) (4 isolates), and bla(DHA-1) (2 isolates). These genes were present on plasmids. Twenty-five of the 46 CMY-2-producing isolates could transfer cefoxitin resistance to E. coli UB1637 by conjugation. More than 90% of the pAmpC-producing isolates were resistant to cefoxitin, but 80% to 90% of them were susceptible or intermediately susceptible to ceftazidime or cefotaxime. Enterobacterial repetitive intergenic consensus PCR analysis revealed that most isolates were of different strains, indicating the ease of transmission of these resistance determinants. This is the first report of CMY-2, CMY-8b, and DHA-1 β-lactamases in Thai isolates.


[Diploid hybrids between allotetraploid wild potato species Solanum acaule Bitt., S. stoloniferum Schltdl. and dihaploids of S. tuberosum L].
The possibility to obtain diploid hybrids by pollination of allotetraploid wild potato species Solanum acaule and S. stoloniferum plants with fertile pollen of S. tuberosum dihaploids was demonstrated for the first time. Dihaploid hybrids have arisen with comparatively high frequency (from 12.5 to 33.3%). They were characterized by high regularity of meiosis and high fertility. They easily crossed with S. tuberosum dihaploids, forming viable progeny. This seems prospective for effective introgression of valuable genetic gene pool of wild allotetraploid potato species in breeding material of S. tuberosum on the diploid level.


Education Based on Theory of Planned Behavior over Sexual Function of Menopausal Women in Iran.
More than half of the sexual problems in menopausal women are due to insufficient knowledge or false beliefs about sexual function. Theory of planned behavior (TPB) is one of the important theories that explain the main process of adopting healthy behaviors. This study investigates the effect of education based on TPB over sexual function of menopausal women in Sabzevar, Iran. In this quasi-experimental study, the data were collected through a survey. This study included 180 Iranian menopausal women from five health center of Sabzevar city in Iran from 2016 to 2017. Using a questionnaire, demographic, anthropometric, and TPB by SPSS version 22 software were measured and analyzed. After educational intervention, the average rates of knowledge, attitude, perceived behavioral control, and intention to sexual function in education group were increased meaningfully (sig <0.05); these changes were not meaningful in control group. Furthermore, there was no statistically meaningful difference in subjective norms between two groups after intervention. According to the findings, it is proposed that TPB be used to improve sexual function in Iranian menopausal women.


Mycotoxin formation in moist 2-row and 6-row barley during granary storage.
Eleven-kilogram parcels of 2-row and 6-row barley initially at 18% moisture content were implanted in dry bulk oats in a farm granary in Manitoba for 60 weeks between August 1983 and October 1984. Temperature, moisture content, O2 and CO2 levels, fat acidity values, seed germination, microfloral incidence and abundance and the presence of major mycotoxins (aflatoxins, sterigmatocystin, ochratoxin A, citrinin, penicillinic acid, patulin) were monitored. Ochratoxin A reached maximum levels of 0.97 ppm by week 24 in the 6-row barley, and 0.05 ppm by week 28 in the 2-row; no other mycotoxins were detected. The effect of cultivar type was significant (P less than 0.01) with greater effects in the 6-row barley for the following parameters: fat acidity value, germination, incidence of Alternaria alternata, Penicillium spp. and Helminthosporium sativum, total fungal propagule count and ochratoxin A levels. The effect of time was significant (P less than 0.05) for all variables except oxygen, carbon dioxide, Aspergillus versicolor, and total fungal propagule count. The interaction between cultivar and time was significant (P less than 0.01) for Alternaria and Helminthosporium only.


A comparative review of 1,004 orthopaedic trauma patients before and during the COVID-19 pandemic.
COVID-19 necessitated abrupt changes in trauma service delivery. We compare the demographics and outcomes of patients treated during lockdown to a matched period from 2019. Findings have important implications for service development. A split-site service was introduced, with a COVID-19 free site treating the majority of trauma patients. Polytrauma, spinal, and paediatric trauma patients, plus COVID-19 confirmed or suspicious cases, were managed at another site. Prospective data on all trauma patients undergoing surgery at either site between 16 March 2020 and 31 May 2020 was collated and compared with retrospective review of the same period in 2019. Patient demographics, injury, surgical details, length of stay (LOS), COVID-19 status, and outcome were compared. There were 1,004 urgent orthopaedic trauma patients (604 in 2019; 400 in 2020). Significant reductions in time to theatre and LOS stay were observed. COVID-19 positive status was confirmed in 4.5% (n = 18). The COVID-19 mortality rate was 1.8% (n = 7). Day-case surgery comprised 47.8% (n = 191), none testing positive for COVID-19 or developing clinically significant COVID-19 symptoms requiring readmission, at a minimum of 17 days follow-up. The novel split-site service, segregating suspected or confirmed COVID-19 cases, minimized onward transmission and demonstrated improved outcomes regarding time to surgery and LOS, despite altered working patterns and additional constraints. Day-surgery pathways appear safe regarding COVID-19 transmission. Lessons learned require dissemination and should be sustained in preparation for a potential second wave or, the return of a "normal" non-COVID workload.Cite this article: Bone Joint Open 2020;1-9:568-575.


Influence of lead on stabilization/solidification by ordinary Portland cement and magnesium phosphate cement.
Inorganic binder-based stabilization/solidification (S/S) of Pb-contaminated soil is a commonly used remediation approach. This paper investigates the influences of soluble Pb species on the hydration process of two types of inorganic binders: ordinary Portland cement (OPC) and magnesium potassium phosphate cement (MKPC). The environmental leachability, compressive strength, and setting time of the cement products are assessed as the primary performance indicators. The mechanisms of Pb involved in the hydration process are analyzed through X-ray diffraction (XRD), hydration heat evolution, and thermogravimetric analyses. Results show that the presence of Pb imposes adverse impact on the compressive strength (decreased by 30.4%) and the final setting time (prolonged by 334.7%) of OPC, but it exerts much less influence on those of MKPC. The reduced strength and delayed setting are attributed to the retarded hydration reaction rate of OPC during the induction period. These results suggest that the OPC-based S/S of soluble Pb mainly depends on physical encapsulation by calcium-silicate-hydrate (CSH) gels. In contrast, in case of MKPC-based S/S process, chemical stabilization with residual phosphate (pyromorphite and lead phosphate precipitation) and physical fixation of cementitious struvite-K are the major mechanisms. Therefore, MKPC is a more efficient and chemically stable inorganic binder for the Pb S/S process.


Effect of docosahexaenoic acid supplementation on the macular function of patients with Best vitelliform macular dystrophy: randomized clinical trial.
Best disease is a slowly progressive macular dystrophy that typically has an onset in early childhood. Multiple lines of evidence suggest that dietary docosahexaenoic acid (DHA) protects against the development of macular degeneration. Our trial tested the effect of an oral supplement of DHA on visual function in patients with Best disease. Double-masked, randomized, placebo-controlled, crossover clinical trial. Eight patients with Best disease. Patients were given either an oral supplement of DHA (20 mg/kg daily) or placebo. Primary outcome measures were the multifocal electroretinogram (mfERG) and electro-oculogram (EOG). Plasma DHA was tracked along with visual acuity (Early Treatment Diabetic Retinopathy Study chart), VF-14 scores, and Humphrey visual fields. All 8 patients had increased plasma DHA levels (2-3 fold) during periods of DHA supplementation compared with periods without supplementation. Differences in visual acuity, VF-14 scores, and EOG Arden ratios during periods with and without DHA supplementation were all statistically insignificant. A positive correlation was found between the plasma concentration of DHA and mfERG amplitudes, but amplitude changes during the treatment periods were not significant. A carryover effect of DHA supplementation was a confounding error. Our pilot trial of DHA supplementation in 8 patients with Best disease did not demonstrate an improvement in macular function. An expanded trial would be needed to examine the full effects of DHA supplementation on visual function in Best disease.


The synthesis and properties of T25 blycoprotein in Thy-1-negative mutant lymphoma cells.
The synthesis and properties of T25 glycoprotein which bears the serological specificity Thy-1 have been studied in mutants of cultured mouse lymphoma cells that do not express Thy-1 on their surface. Five complementation classes of mutant cells were previously characterized by somatic genetic analysis. Synthesis of abnormal T25 glycoproteins was detected in four classes of mutants. Each of these aberrant products was degraded move rapidly than T25 glycoprotein of wild-type cells. Defects in the oligosaccharide units of T25 glycoprotein were demonstrated in three classes of mutants. In one of these mutant classes, evidence for a general defect in glycosylation of cell surface glycoproteins was obtained. These data indicate that normal glycosylation of T25 glycoprotein is probably essential for the molecule to be incorporated into the plasma membrane and expressed on the cell surface.


Buildup and release from proactive interference - Cognitive and neural mechanisms.
Interference from related memories is generally considered one of the major causes of forgetting in human memory. The most prevalent form of interference may be proactive interference (PI), which refers to the finding that memory of more recently studied information can be impaired by the previous study of other information. PI is a fairly persistent effect, but numerous studies have shown that there can also be release from PI. PI buildup and release have primarily been studied using paired-associate learning, the Brown-Peterson task, or multiple-list learning. The review first introduces the three experimental tasks and, for each task, summarizes critical findings on PI buildup and release, from both behavioral and imaging work. Then, an overview is provided of suggested cognitive mechanisms operating on the encoding and retrieval stages as well as of neural correlates of these mechanisms. The results indicate that, in general, both encoding and retrieval processes contribute to PI buildup and release. Finally, empirical gaps in the current work are emphasized and suggestions for future studies are provided.


Depression and obesity.
The prevalence of depression (10%) and overweight (65%) indicates that there is a probability that they will co-occur, but are they functionally related? This report used the moderator/mediator distinction to approach this question. Moderators, such as severity of depression, severity of obesity, gender, socioeconomic status (SES), gene-by-environment interactions and childhood experiences, specify for whom and under what conditions effects of agents occur. Mediators, such as eating and physical activity, teasing, disordered eating and stress, identify why and how they exert these effects. Major depression among adolescents predicted a greater body mass index (BMI = kg/m(2)) in adult life than for persons who had not been depressed. Among women, obesity is related to major depression, and this relationship increases among those of high SES, while among men, there is an inverse relationship between depression and obesity, and there is no relationship with SES. A genetic susceptibility to both depression and obesity may be expressed by environmental influences. Adverse childhood experiences promote the development of both depression and obesity, and, presumably, their co-occurrence. As most knowledge about the relationship between these two factors results from research devoted to other topics, a systematic exploration of this relationship would help to elucidate causal mechanisms and opportunities for prevention and treatment.


Boron oxynitride nanoclusters on tungsten trioxide as a metal-free cocatalyst for photocatalytic oxygen evolution from water splitting.
Here we show that B(2)O(3-x)N(x) nanoclusters can be formed on the surface of WO(3) particles by a combination of thermal oxidation of tungsten boride (WB) in air and the subsequent nitriding process in gaseous ammonia. The resultant nanoclusters are found to play an apparent role in improving the photocatalytic oxygen evolution of WO(3) by promoting the surface separation of photoexcited charge-carriers.


Teaching basic life support: a prospective randomized study on low-cost training strategies in secondary schools.
Cardiopulmonary resuscitation (CPR) training at school is recommended. Limited school resources prevent implementation. The learning efficacy of low-cost training strategies is unknown. To evaluate the efficacy of different CPR learning strategies using low-cost didactic tools. Children (n=593, 15-16 years) were randomized to four training conditions: (1) manikin+teacher instruction (control group), (2) manikin+video instruction, (3) foam dice+plastic bag+peer training+teacher instruction, and (4) foam dice+plastic bag+peer training+video instruction. After a 50 min training, a 3 min CPR test on a manikin was performed using SkillReporting Software (Laerdal, Norway), and repeated after 6 months. The data of children without previous CPR training were analysed. Analysis of variance and the χ-test assessed differences between groups. Complete data sets were available for 165 pupils. Initially, group 3 scored lower on the mean ventilation volume (P<0.05). The control group scored better than the alternative groups (P<0.05) on the mean compression rate. After 6 months, the differences disappeared. All groups scored equally on ventilation volume (P=0.12), compression depth (P=0.11), compression rate (P=0.10), correct hand position (P=0.46) and number of correct compressions (P=0.76). Ventilation volume was sufficient in 32% of the pupils, 18% had a correct compression depth and 59% had a correct compression rate. Training efficacy with low-cost equipment was not different from training with a manikin. The outcome for all training strategies was suboptimal. The basics of CPR can be taught with alternative equipment if manikins are not available.


Risk of bias assessment in preclinical literature using natural language processing.
We sought to apply natural language processing to the task of automatic risk of bias assessment in preclinical literature, which could speed the process of systematic review, provide information to guide research improvement activity, and support translation from preclinical to clinical research. We use 7840 full-text publications describing animal experiments with yes/no annotations for five risk of bias items. We implement a series of models including baselines (support vector machine, logistic regression, random forest), neural models (convolutional neural network, recurrent neural network with attention, hierarchical neural network) and models using BERT with two strategies (document chunk pooling and sentence extraction). We tune hyperparameters to obtain the highest F1 scores for each risk of bias item on the validation set and compare evaluation results on the test set to our previous regular expression approach. The F1 scores of best models on test set are 82.0% for random allocation, 81.6% for blinded assessment of outcome, 82.6% for conflict of interests, 91.4% for compliance with animal welfare regulations and 46.6% for reporting animals excluded from analysis. Our models significantly outperform regular expressions for four risk of bias items. For random allocation, blinded assessment of outcome, conflict of interests and animal exclusions, neural models achieve good performance; for animal welfare regulations, BERT model with a sentence extraction strategy works better. Convolutional neural networks are the overall best models. The tool is publicly available which may contribute to the future monitoring of risk of bias reporting for research improvement activities.


[Novel anti-osteoporotic drugs on the horizon].
In recent years the great progress in knowledge on bone cell biology has allowed identification of molecular structures that can be targeted with pinpoint precision (druggable targets). Osteoclasts are regulated via the RANK-RANK-ligand (RANKL) signaling pathway and osteoblasts via the Wnt signaling pathway, both of which can be influenced for therapeutic measures. As a result the number of (functional) osteoclasts can be decreased or the genesis of osteoblasts can be increased and bone resorption is inhibited or bone formation is enhanced, respectively. Osteoclasts degrade collagen through cathepsin K and inactivation of this enzyme stabilizes the bone matrix; however, as osteoclasts are still able to maintain a stimulatory cross-talk with osteoblasts, formation of new bone will not be reduced. Parathyroid hormone-related protein plays a role in endochondral ossification and a synthetic analogue of this protein may have potent bone anabolic activity; however, the use of such new and highly efficient therapeutic principles comes with new questions and uncertainties on the sequence of therapies, duration of therapy, long-term side effects, undesired activation of metabolic pathways and effectiveness in comparison to other strategies of fracture prevention.


Effects of garlic (Allium sativum L.) supplementation on cytochrome P450 2D6 and 3A4 activity in healthy volunteers.
Garlic (Allium sativum L.) is a commonly used food and herbal supplement. The objective of this study was to assess in healthy volunteers (N = 14) the influence of a garlic extract on the activity of cytochrome P450 (CYP) 2D6 and 3A4. Probe substrates dextromethorphan (CYP2D6) and alprazolam (CYP3A4) were administered orally at baseline and again after treatment with garlic extract (3 x 600 mg twice daily) for 14 days. Urinary dextromethorphan/dextrorphan ratios and alprazolam plasma concentrations were determined by HPLC at baseline and after garlic extract treatment. The ratio of dextromethorphan to its metabolite was 0.044 +/- 0.48 at baseline and 0.052 +/- 0.095 after garlic supplementation. There were no significant differences between the baseline and garlic phases (P > or =.05). For alprazolam, there were no significant differences in pharmacokinetic parameters at baseline and after garlic extract treatment (all P values > or =.05; maximum concentration in plasma, 27.3 +/- 2.6 ng/mL versus 27.3 +/- 4.8 ng/mL; time to reach maximum concentration in plasma, 1.9 +/- 1.4 h versus 2.4 +/- 1.8 h; area under the time-versus-concentration curve, 537 +/- 94 h. ng. mL(-1) versus 548 +/- 159 h. ng. mL(-1); half-life of elimination, 13.7 +/- 4.4 h versus 14.5 +/- 4.3 h). Our results indicate that garlic extracts are unlikely to alter the disposition of coadministered medications primarily dependent on the CYP2D6 or CYP3A4 pathway of metabolism.


Layer-by-layer assembly induced strong, hydrophobic and anti-bacterial TEMPO oxidized cellulose nanofibrils films for highly efficient UV-shielding and oil-water separation.
Anti-ultraviolet material with cost-effectiveness, environmental friendliness, and multifunction is urgently needed to address the serious problem of ultraviolet radiation. However, traditional anti-ultraviolet products based on plastics are unsustainable and harmful to the environment. Herein, the cellulose films with a sandwich structure using a surface assembly technique were reported. Natural L-phenylalanine was grafted onto cellulose nanofibrils via amidation to enhance their UV-shielding property. To address the hydrophilic nature and limited mechanical strength of cellulose films, we employed octadecyltrichlorosilane and 4ARM-PEG-NH2 for hydrophobic coating and mechanical reinforcement, respectively. In addition to providing complete UV resistance in the wavelength range of 200-320 nm, sample OPT5 exhibited significantly improved tensile stress, Young's modulus, and toughness, measuring 174.09 MPa, 71.11 MPa, and 295.33 MJ/m3, respectively. Furthermore, due to the presence of antibacterial amine groups, the modified film demonstrated a satisfactory inhibitory effect on the growth of Escherichia coli and Bacillus subtilis. Compared to natural cellulose films, the hydrophobically modified material achieved a contact angle of up to 121.1°, which enabled efficient separation of oil-water mixtures with a maximum separation efficiency of 93.87 %. In summary, the proposed TOCNF-based UV-shielding film with multifunctionality holds great potential for replacing petrochemical-derived plastics and serving as an applicable and sustainable membrane material.


[Meta-analysis of laparoscopic versus open total mesorectal excision for middle and low rectal cancer].
To evaluate the efficacy of laparoscopic total mesorectal excision (laparoscopic TME) versus open total mesorectal excision (open TME) in the treatment of middle and low rectal cancer using meta-analysis. From 1991 to 2012, the Chinese and English articles of randomized controlled trails (RTCs) about laparoscopic TME versus open TME in the treatment of middle and low rectal cancer were collected, and a meta-analysis was performed with RevMan 5.1 software. Eight RCTs including 863 patients with middle and low rectal cancer (428 cases in laparoscopic TME group, 435 cases in open TME group) were enrolled in the meta-analysis. Laparoscopic TME was associated with significantly less intraoperative blood loss (P<0.01), earlier to pass first flatus (P<0.01), shorter hospital stay (P<0.05), less postoperative incision infections (P<0.01) and postoperative bleeding (P<0.05) compared to open TME. There were no significant differences between laparoscopic TME and open TME groups in operative time, number of resected lymph nodes, anastomotic leak, ileus and pelvic abscess (all P>0.05). As compared to open TME, laparoscopic TME has similar efficacy in terms of lymph nodes harvest, and it can promote postoperative recovery, and reduce incision infection and postoperative bleeding.


Human Reconstituted Nasal Epithelium, a promising in vitro model to assess impacts of environmental complex mixtures.
Considering the impact of respiratory diseases around the world, appropriate experimental tools to help understand the mechanisms involved in such diseases are becoming essential. Our aim was to investigate the cellular and morphological reactivity of a human Reconstituted Nasal Epithelium (hRNE) to evaluate the impact of environmental complex mixture (ECM), with tobacco smoke as a model, after three weeks of repeated exposures. Staining of hRNE showed a multilayered ciliated epithelium, with a regular cilia beats, and a mucus production. When hRNE was exposed to ECM for 5 min once or twice a week, during 3 weeks, significant changes occurred: IL-8 production significantly increased 24h after the first exposure compared with Air-exposure and only during the first week, without any loss of tissue integrity. Immunostaining of F-actin cytoskeleton showed a modification in cellular morphology (number and diameter). Taken together our results indicate that hRNE is well suited to study the cellular and morphological effects of repeated exposures to an environmental complex mixture. Human reconstituted epithelium models are currently the best in vitro representation of human respiratory tract physiology, and also the most robust for performing repeated exposures to atmospheric pollutants.


Screening for partner violence during pregnancy.
An analysis of the international literature on partner violence provides insights for health care providers caring for women. The current literature on partner violence epidemiology, screening, and interventions was reviewed, focusing on pregnancy. Adolescent girls and pregnant women are at highest risk for partner violence and homicide. Health care providers need to offer clinical screening and interventions to prevent consequences of partner violence, including homicide.


Combined test of hypothalamic-pituitary function in growth-retarded children treated with growth hormone. II. Secretion of LH, FSH, TSH, prolactin and ACTH.
A total number of 23 patients treated with human growth hormone were retested by use of a combined pituitary stimulation test. Plasma concentrations of GH, FSH, LH, TSH, T4, T3, prolactin (PRL), ACTH and cortisol were measured before and after stimulation with hypoglycemia, TRH and LHRH. The test was performed in patients with persistent GH deficiency (group A) and patients with transitory GH deficiency (group B). In group A a normal pubertal development was found in three patients, whereas in prepubertal subjects the FSH/LH responses were smaller than those of prepubertal patients in group B. Also plasma ACTH increase was less pronounced in group A patients than in group B. In contrast, the plasma TSH and PRL responses were more sustained in group A than in group B. The secretory pattern of TSH and PRL was comparable in the two groups of patients. Thus, in patients with persistent GH deficiency additional multiple disturbances of the hypothalamic-pituitary function often appeared whereas in most patients with transitory GH deficiency the combined pituitary test was normal at the reinvestigation.


Efficiency of 3D-printed composite resin restorations compared with subtractive materials: Evaluation of fatigue behavior, cost, and time of production.
Three-dimensionally (3D)-printed composite resins have been marketed as materials for definitive restorations. However, limited information is available regarding the stability of the adhesive interface and the efficiency of 3D-printed composite resins. The purpose of this in vitro study was to evaluate the integrity of the marginal adhesive interface before and after thermal and mechanical fatigue of an initial formulation of a 3D-printed composite resin and to evaluate the efficiency of this manufacturing method. Freshly extracted molars were prepared for onlays and adhesively restored with either 3D-printed composite resin (VarseoSmile Crown Plus) (Group 3D), milled composite resin (Tetric CAD) (Group MCOMP), milled PMMA (Telio CAD) (Group PMMA), and milled lithium disilicate (IPS e.max CAD) (Group EM). Marginal analysis was performed under a scanning electron microscope before and after fatigue by thermomechanical cyclic loading, and initial and terminal percentages of continuous margin (%CM) were compared. The time required for the production of each type of restoration was recorded, and the production costs were also compared. Before aging, 3D, MCOMP, and EM presented comparable values of %CM (69.8%, 75.9%, and 63.1%, respectively) that were statistically significantly higher (P<.05) than those of PMMA (45.1%). After aging, 3D and EM had comparable results (44.7% and 43.7%, respectively), which were lower than those of the MCOMP group (68.5%) but higher than those of the PMMA group (20.5%). Regarding time efficiency, 3D printing took less time than MCOMP or PMMA if more than 8 restorations were fabricated. For the production costs, 3D printing was 5.5, 8.7, and 10.2 times less expensive than PMMA, MCOMP, and EM, respectively. The initial equipment cost was also lower for the additive manufacturing method. However, 3D printing did not always considerably reduce waste. In terms of marginal adaptation, the evaluated initial formulation of a 3D-printed composite resin behaved similarly to other well-established definitive restoration materials and better than milled PMMA, both before and after fatigue. Three-dimensionally printed resins present advantages in terms of equipment and consumable costs, even for a single restoration, but also for production time when more than 8 restorations were fabricated.


Electrochemical deposition of sol-gel films for enhanced chromium(VI) determination in aqueous solutions.
A pyridine-functionalized sol-gel film has been formed by electrodeposition at a glassy carbon electrode surface. When this protonated film is exposed to a Cr(VI) solution, the Cr(VI) anions are preconcentrated at the electrode surface. Using square wave voltammetry, the Cr(VI) species are reduced to Cr(III), and a peak current corresponding to this reduction is generated at 0.17V. The peak currents can be correlated with the Cr(VI) concentration. The functionalized sol-gel films demonstrated an enhanced sensitivity for Cr(VI) in aqueous solutions, providing a limit of detection at the low ppb level. Interference studies also displayed the high selectivity of the films for Cr(VI), and the system was able to tolerate a large excess of Cr(III) with no adverse affects. The reported electrodeposition method of film formation uses commercially available reagents and yields films quickly and reproducibly. The growth of these sol-gel films was monitored using an electrochemical quartz crystal microbalance (EQCM), and they were characterized by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). The reported work shows the promise of such an electrode for use in Cr(VI) sensing applications.


Stable and null current hysteresis perovskite solar cells based nitrogen doped graphene oxide nanoribbons hole transport layer.
Perovskite solar cells are becoming one of the leading technologies to reduce our dependency on traditional power sources. However, the frequently used component poly(3,4-ethylenedioxythiophene) polystyrene sulfonate ( PSS) has several shortcomings, such as an easily corroded indium-tin-oxide (ITO) interface at elevated temperatures and induced electrical inhomogeneity. Herein, we propose solution-processed nitrogen-doped graphene oxide nanoribbons (NGONRs) as a hole transport layer (HTL) in perovskite solar cells, replacing the conducting polymer PSS. The conversion efficiency of NGONR-based perovskite solar cells has outperformed a control device constructed using PSS. Moreover, our proposed NGONR-based devices also demonstrate a negligible current hysteresis along with improved stability. This work provides an effective route for substituting PSS as the effective HTL.


Why do some psychiatric patients somatize?
A study was made of a series of 139 outpatients referred by the medical and surgical services of a general hospital for evaluation by the psychiatry unit. In accordance with established criteria, this population was divided into somatizers (56) and non-somatizers (75), and the socio-demographic and clinical characteristics of both groups were comparatively analyzed. The results show that the group of somatizers was younger, had more histrionic personality traits and more stress factors related with alterations in interpersonal relationships or death or disease of relatives. It is emphasized that somatization is poorly known by psychiatrists--whose diagnostic criteria practically omit these aspects--and by other physicians, in spite of its importance and frequency.


Corrigendum: Strontium-doped chromium oxide for RhB reduction and antibacterial activity with evidence of molecular docking analysis.
[This corrects the article DOI: 10.3389/fchem.2023.1167701.].


Heat stress-induced resistance to myocardial infarction in the isolated heart from transgenic [(mREN-2)27] hypertensive rats.
Heat stress (HS) is known to confer protection against ischaemia-reperfusion injury, including mechanical dysfunction and myocardial necrosis. However, the effects of disease states on this HS-induced cytoprotective response are less known. Therefore, we investigated the effects of prior heat stress on the infarct size in the isolated rat heart and on the myocardial heat stress protein (HSP) 72 synthesis, in transgenic [(mREN-2)27] hypertensive (TGH) rats or normotensive (NT) controls. TGH or NT rats were either heat stressed (42 degrees C for 15 min) or sham anaesthetised. After 24 h, their hearts were isolated, perfused using the Langengorff technique, and subjected to a 35-min occlusion of the left coronary artery followed by 120 min of reperfusion. Myocardial HSP72 content was measured 24 h after HS or sham treatment using electrophoresis coupled with Western blot analysis. Infarct-to-risk (I/R) ratio was significantly reduced in HS (15.5 +/- 1.2%) compared to sham (42.2 +/- 2.1%) hearts of NT rats. This reduction in infarct size was maintained in TGH hearts (I/R: 20.0 +/- 1.0 vs. 48.0 +/- 3.8%). Risk zones were similar between all experimental groups. The incidence of ventricular arrhythmias during ischaemia and reperfusion periods was not different between the four experimental groups. Western blot analysis of the myocardial HSP72 content showed a heat stress-induced increase of this protein, in both TGH and NT animals. These results demonstrate that the myocardial protective effect induced by heat stress could extend to a pathological animal model like the transgenic [(mREN-2)27] hypertensive rat and is correlated with a myocardial HSP72 induction.


Lack of relationship between genotype and virulence in Candida species.
The virulence of isolates among different Candida species causing candidemia may play a role in the prognosis of the patients. Furthermore, the potential relationship between genotype and virulence is still unclear and need to be further studied. We aim to assess the relationship between genotype and virulence in Candida species using a Galleria mellonella larvae infection model. One hundred and ninety-four isolates from 68 clusters (Candida albicans, 114/41; Candida parapsilosis, 74/24; Candida tropicalis, 6/3) were compared against the same number of each species singleton genotypes in terms of survival of G. mellonella larvae. The median of survival and the IQR ranges of clusters and singleton were as follows: C. albicans (2 days, IQR 1.5-2 vs. 2 days, IQR 1-2.25), C. parapsilosis (2 days, IQR 1.5-2.6 vs. 2 days, IQR 2-3.3), and C. tropicalis (1 day, IQR 1-3.5 vs. 2 days, IQR 2-3.5; p<0.05). High intra-cluster variability in terms of median of survival was found regardless the species. No relationship between genotype and virulence in Candida was observed with the G. mellonella model.


Fine-needle aspiration diagnosis of metastatic urothelial carcinoma: a review.
Urothelial carcinoma (UC) is the most common malignant neoplasm of the urinary tract. Metastases of UC are most common in the regional lymph nodes, lungs, liver, bone, and adrenal glands. Fine-needle aspiration cytology diagnosis of such metastases can be difficult, particularly in the setting of incomplete clinical history or when multiple primary neoplasms may be present. This review focuses on the cytologic features helpful in differentiating UC from its potential mimics, as well as ancillary studies that may be helpful in the distinction.


Threat of soil formation rate to health of karst ecosystem.
Karst ecosystems are important to several billion people, so it is necessary to accurately diagnose and evaluate the health of these ecosystems for socioeconomic development; however, the existing evaluation methods have many limitations, so they cannot accurately evaluate the ecosystem health in karst areas. In particular, they ignore the influence and restriction of the soil formation rate on the ecosystem health. To this end, we established a new index to represent the actual health status of karst ecosystems. The soil formation rate was found to pose a threat to the health of 28 % of the world's karst ecosystems, covering an area of 594 km2. In addition, a dataset of global karst ecosystem health index values with a spatial resolution of about 8 km × 8 km from 2000 to 2014 was created, and the proportion of unhealthy areas was found to be as high as 75.91 %. This study highlights the contribution of the soil formation rate to karst ecosystem health and provides a new method and deeper scientific understanding for further accurate evaluation of karst ecosystem health, which can improve future ecosystem health research and social management.


Quantification of cerebral arterial blood volume and cerebral blood flow using MRI with modulation of tissue and vessel (MOTIVE) signals.
Regional cerebral arterial blood volume (CBVa) and blood flow (CBF) can be quantitatively measured by modulation of tissue and vessel (MOTIVE) signals, enabling separation of tissue signal from blood. Tissue signal is selectively modulated using magnetization transfer (MT) effects. Blood signal is changed either by injection of a contrast agent or by arterial spin labeling (ASL). The measured blood volume represents CBVa because the contribution from venous blood was insignificant in our measurements. Both CBVa and CBF were quantified in isoflurane-anesthetized rats at 9.4T. CBVa obtained using a contrast agent was 1.1 +/- 0.5 and 1.3 +/- 0.6 ml/100 g tissue (N = 10) in the cortex and caudate putamen, respectively. The CBVa values determined from ASL data were 1.0 +/- 0.3 ml/100 g (N = 10) in both the cortex and the caudate putamen. The match between CBVa values determined by both methods validates the MOTIVE approach. In ASL measurements, the overestimation in calculated CBF values increased with MT saturation levels due to the decreasing contribution from tissue signals, which was confirmed by the elimination of blood with a contrast agent. Using the MOTIVE approach, accurate CBF values can also be obtained.


Erratum: Blanco-Elices, C. et al. In Vitro Generation of Novel Functionalized Biomaterials for Use in Oral and Dental Regenerative Medicine Applications. Running Title: Fibrin-Agarose Functionalized Scaffolds. Materials 2020, 13, 1692.
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Effect of high-frequency electromagnetic fields with a wide range of SARs on chromosomal aberrations in murine m5S cells.
To investigate the induction of chromosomal aberrations in mouse m5S cells after exposure to high-frequency electromagnetic fields (HFEMFs) at 2.45 GHz, cells were exposed for 2 h at average specific absorption rates (SARs) of 5, 10, 20, 50 and 100 W/kg with continuous wave-form (CW), or at a mean SAR of 100 W/kg (with a maximum of 900 W/kg) with pulse wave-form (PW). The effects of HFEMF exposure were compared with those in sham-exposed controls and with mitomycin C (MMC) or X-ray treatment as positive controls. We examined all structural, chromatid-type and chromosome-type changes after HFEMF exposures and treatments with MMC and X-rays. No significant differences were observed following exposure to HFEMFs at SARs from 5 to 100 W/kg CW and at a mean SAR of 100 W/kg PW (a maximum SAR of 900 W/kg) compared with sham-exposed controls, whereas treatments with MMC and X-rays increased the frequency of chromatid-type and chromosome-type aberrations. In summary, HFEMF exposures at 2.45 GHz for 2 h with up to 100 W/kg SAR CW and an average 100 W/kg PW (a maximum SAR of 900 W/kg) do not induce chromosomal aberrations in m5S cells. Furthermore, there was no difference between exposures to CW and PW HFEMFs.


Natural essential oils: A promising strategy for treating cardio-cerebrovascular diseases.
Essential oils (EO) are volatile compounds obtained from different parts of natural plants, and have been used in national, traditional and folk medicine to treat various health problems all over the world. Records indicate that in history, herbal medicines rich in EO have been widely used for the treatment of CVDs in many countries, such as China. This review focused on the traditional application and modern pharmacological mechanisms of herbal medicine EO against CVDs in preclinical and clinical trials through multi-targets synergy. Besides, the EO and anti-CVDs drugs were compared, and the broad application of EO was explained from the properties of drugs and aromatic administration routes. Information about EO and CVDs was collected from electronic databases such as Web of Science, ScienceDirect, PubMed, and China National Knowledge Infrastructure (CNKI). The obtained data sets were sequentially arranged for better understanding of EO' potential. The study showed that EO had significant application in CVDs at different countries or regions since ancient times. Aiming at the complex pathological mechanisms of CVDs, including intracellular calcium overload, oxidative stress, inflammation, vascular endothelial cell injury and dysfunction and dyslipidemia, we summarized the roles of EO on CVDs in preclinical and clinical through multi-targets intervention. Besides, EO had the dual properties of drug and excipients. And aromatherapy was one of the complementary therapies to improve CVDs. This paper reviewed the EO on traditional treatment, preclinical mechanism and clinical application of CVDs. As important sources of traditional medicines, EO' remarkable efficacy had been confirmed in comprehensive literature reports, which showed that EO had great medicinal potential.


Trajectory of systolic blood pressure in children and adolescents.
Rapid height and weight changes during childhood contribute markedly to blood-pressure change during children's physical growth. This article evaluates the differences in systolic blood pressure (SBP) growth or changes between four gender-ethnic groups: African American males (AM), Caucasian males (CM), African American females (AF), and Caucasian females (CF). Subjects 6-9 years old at entry (n = 1302) were followed for 12 years. The repeated-measure data of SBP were analyzed using the Gompertz growth model with random coefficients. Mean SBP (mmHg) at age 6 years was lowest in African American girls (82.23 +/- 0.76) and highest in Caucasian boys (102.83 +/- 0.5). And for both ethnic groups, girls had lower levels at which SBP growth stopped. The peak growth ages (years) also differed by group: 9.30 +/- 0.73, 9.91 +/- 0.28, 10.00 +/- 0.82, and 10.60 +/- 0.22 for African American girls, African American boys, Caucasian girls and Caucasian boys, respectively. SBP growth differed among gender-ethnic groups with respect to mean SBP level at age 6, the level at which SBP growth stops and the mean age at which SBP growth rate was at its peak.


Effect of intravenous ascorbic acid infusion on blood loss during laparoscopic myomectomy: a randomized, double-blind, placebo-controlled trial.
Most interventions aimed at reducing bleeding during myomectomy lack sufficient evidence regarding their effectiveness. Recently, it was reported that intraoperative ascorbic acid administration effectively reduced blood loss during abdominal myomectomy. Therefore, this study aimed to investigate whether intravenous ascorbic acid infusion would affect intraoperative blood loss in women undergoing laparoscopic myomectomy. A randomized, double-blind, parallel-group, placebo-controlled trial including 50 women undergoing laparoscopic myomectomy was conducted. Women with ≤4 myomas, ≤9cm in maximum diameter were eligible. The study:control group ratio was 1:1. Starting 30minutes before anesthesia, 2g of ascorbic acid or a placebo were administered for 2hours intraoperatively. Intraoperative blood loss, the primary endpoint, was calculated as the difference between the volume of fluids acquired from suction and that used for irrigation of the abdominal cavity during surgery using constant values. Among the 50 randomized women, 1 and 3 in the study and control groups, respectively, were excluded due to withdrawal of consent, cancelation of surgery, or non-measurement of the primary endpoint. The baseline and operative characteristics were similar between the study and control groups, as was the intraoperative blood loss (193±204mL vs. 159±193mL, P=0.52). In addition, the operating time (95±29min vs. 110±52min; P=0.50) and decrease in hemoglobin level after surgery (1.9±1.31g/dL vs. 1.4±1.4g/dL; P=0.24) were similar between the study and control groups. Intravenous ascorbic acid infusion did not reduce intraoperative blood loss in women undergoing laparoscopic myomectomy. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01715597.


Pulmonary disposition of inhaled NO2-nitrogen in isolated rat lungs.
Nitrogen dioxide (NO2) is a relatively insoluble, reactive gas that, on inhalation, generates a diverse array of pulmonary toxic effects. Its uptake and transformation in isolated lungs have been shown to be proportional to inspired dose and associated with significant accumulations of the nitrite ion. However, not all absorbed NO2 is directly detectable as soluble nitrite. To further characterize its uptake and chemical disposition, we determined the chemical fate of 15NO2-nitrogen in isolated perfused (red cell-free) rat lungs that were exposed to 20 ppm 15NO2 for 60 min. Total excess 15N (relative to unexposed controls) was determined by isotope ratio mass spectrometry and total nitrogen analysis. Excess 15N was detected in whole lungs and in soluble and insoluble fractions but not in the total lipid pool. Perfusate excess 15N and nitrate correlated and accounted for all absorbed NO2 not detectable in tissue fractions. Exogenously instilled [15N]nitrite distributed within lung tissue, bound to insoluble elements, and diffused to the vascular space similar to NO2-nitrogen. Instilled [15N]nitrate did not distribute or bind like NO2-nitrogen or nitrite. Dialysis (1000 molecular weight cutoff) of cytosol, membranes, and perfusate removed excess 15N and nitrite derived from NO2, nitrite, or nitrate sources. We conclude that in isolated lungs, inhaled NO2 (1) undergoes rapid uptake and transformation in sites accessible to the pulmonary circulation; (2) does not form stable addition products with lipids; and (3) forms small-molecular-weight soluble reaction product(s) that behave similarly to nitrite, most likely indicating predominant univalent reduction of NO2 via initial hydrogen abstraction and subsequent HNO2 dissociation.


Inhibition of plasma cholinesterase prevents the dopamine DA-1 receptor mediated renal vasodilation produced by ibopamine.
We have studied the dopamine DA-1 receptor mediated renal vasodilator response of the inotropic pro-drug, ibopamine, the diisobutyrate ester of epinine. In anesthetized dogs pretreated with phenoxybenzamine and propranolol to eliminate alpha- and beta-adrenoceptor mediated responses, respectively, ibopamine and epinine produced dose-dependent renal vasodilation. Treatment of animals with the cholinesterase inhibitor, physostigmine, markedly inhibited the renal vasodilation produced by ibopamine, but had no effect on the renal vasodilator response of epinine. We conclude that hydrolysis of ibopamine by plasma cholinesterase to yield epinine is necessary for the production of the dopamine DA-1 receptor mediated renal vasodilator response to ibopamine.


Penile sensitivity in men with premature ejaculation.
Premature ejaculation is the most prevalent form of male sexual dysfunction, but its cause has not been well established. Recent studies have indicated that in men with premature ejaculation, penile sensitivity is increased. To investigate whether penile hypersensitivity is a cause of premature ejaculation, we prospectively evaluated the penile sensitivity of 18 patients with a lifelong history of premature ejaculation from the first coital experience and 15 controls, both in the flaccid and erect state. We used an SMV-5 vibrometer (Suzuki-Matsuoka, Teknologue, Tokyo, Japan), which automatically controls stimulatory strength; its precision and reproducibility are thus higher than analogue-type biothesiometers. At the styloid process of the ulna and medial maleolus of the tibia, there was no significant statistical difference in vibratory threshold between the two groups (P > 0.05). Also we did not find significant statistical differences in sensitivity of the glans penis, dorsum of the penile shaft, or frenulum of the penis between the two groups, in either the flaccid or erect state (P > 0.05). According to our results, penile hypersensitivity, as measured by an SMV-5 vibrometer, does not appear to be a major factor contributing to premature ejaculation.


Antihypertensive mechanism of ketanserin in postoperative hypertension after cardiopulmonary bypass.
The effect of ketanserin (0.15 mg/kg followed by an infusion at 6 mg/hr) was studied in 13 patients who developed hypertension (blood pressure greater than 150/90 mm Hg) after cardiopulmonary bypass (CPB) for coronary artery bypass grafting. Eleven patients responded to ketanserin with a decrease of arterial pressure from 159 +/- 15/83 +/- 10 mm Hg to 131 +/- 9/70 +/- 12 mm Hg (P less than 0.01), which was sustained during the subsequent infusion of ketanserin. Mean plasma ketanserin concentrations were maintained at 187 micrograms/L (range 118-525). No significant changes in plasma levels of 5-hydroxyindoles or in platelet 5-hydroxytryptamine content were observed during or after CPB, or after administration of ketanserin. Plasma epinephrine (398 +/- 124 pg/ml) and norepinephrine (1161 +/- 673 pg/ml) concentrations were markedly increased during the hypertensive period after CPB. Plasma epinephrine concentrations decreased (P less than 0.01) during ketanserin infusion to 213 +/- 101 pg/ml, whereas plasma norepinephrine concentrations did not change. The pressor response to three graded doses of phenylephrine was decreased during CPB (P less than 0.01), and a further decrease (P less than 0.05) occurred during infusion of ketanserin. The hypotensive effect of ketanserin after CPB may be attributable to alpha 1-adrenoceptor blockade rather than to its antiserotoninergic effect. Serotonin does not appear to be involved in the short-term disturbances of arterial pressure during or after CPB.


A retino-pulvinar projection in the cat.
Injections of tritiated amino acids were made in one eye of Siamese and common cats including young kittens. After survival periods of 1--7 days axoplasmically transported label accumulated in a portion of the pulvinar nucleus as well as in the other known sites of termination of the retinofugal pathway. The retino-pulvinar projection is present at birth; it is bilateral and approximately symmetrical in common cats but the ipsilateral component is markedly reduced in Siamese animals. Labeled terminal ramifications of the retinal fibers in the pulvinar take the form of a thin, interrupted sheet oriented dorsoventrally and lying at the extreme lateral edge of the pulvinar nucleus. It appears to be continuous caudally with the medial interlaminar nucleus of the lateral geniculate complex, but the cells about which the grains cluster are clearly different from those of the medial interlaminar nucleus.


Epigenetic and gene expression alterations of FOXP3 in the T cells of EAE mouse model of multiple sclerosis.
Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination and neurodegeneration of the central nervous system. It has been shown that the regulatory T (Treg) cells are responsible for maintaining tolerance to self-antigens and can suppress the autoimmune process in several animal models such as experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Recent basic studies have demonstrated that forkhead box P (FOXP3) and BTB domain and CNC homolog 2 (BACH2) are the master transcription factors of these cells playing a pivotal role in the polarization of naïve T cells into Treg cells. In the current study, the expression of FOXP3 and BACH2 genes and FOXP3 promoter methylation were evaluated in T cells of the EAE-induced mice. The results of this study showed a prominent and significant hypermethylation of the FOXP3 gene promoter in the EAE-induced mice compared to the sham and control groups. The expression of FOXP3 and BACH2 genes was significantly decreased in the EAE group in comparison with the sham and control groups. This study suggests that the epigenetic modification of FOXP3 gene is involved in the pathogenesis of EAE and this could be important in therapy in an appropriate and logical statement.


Idiopathic omental hemorrhage: a case report and review of the literature.
A spontaneous rupture of an omental vessel can cause severe intraabdominal hemorrhage. We present a case of idiopathic omental hemorrhage caused by a vascular malformation. The literature is systematically reviewed. A 65-year-old Iranian man was admitted to the emergency department for 10 days with abdominal pain. His medical history was not significant. Fever, vomiting, nausea, or anorexia were not reported. However, he was suffering from diaphoresis and malaise at the time. He did not smoke or drink alcohol. During physical examination, blood pressure was 82/60 mmHg with a temperature of 36.6 °C; heart rate was 96 beats/minute and respiratory rate was 18 breaths per/minute. An abdominal examination revealed mild tenderness in the periumblical. The focused assessment with sonography in trauma examination yielded positive results. The complete blood count showed 14 × 103/mcL of white blood cells and 185 × 103/mcL of platelets. The hemoglobin value was 6.7 g/L at admission. To stabilize the patient's condition, a unit of packed cell was administered. A double contrast enhancement abdominal computer tomography was performed, which revealed a massive hemoperitoneum. Subsequently, an exploratory laparoscopy was performed to search for the responsible pathology. But it was not successful. The surgical plan was changed to laparotomy. The hemorrhage source was not found during laparotomy. Observation revealed a massive hemoperitoneum originating in the omental vessels. A portion of the omentum located on the greater omentum at the greater curve was removed. Based on the pathological examination of the extracted tissue, vascular malformations were identified. The patient recovered uneventfully and was discharged from the hospital 7 days after surgery. Previous reports assessing idiopathic omental bleeding were systematically reviewed. A total of 14 hits were identified in PubMed and Scopus from 2015 to November 2022 for idiopathic omental bleeding. Presence of positive focused assessment with sonography in trauma, abdominal pain, imaging evidence of fluid accumulation, and a reduction in hemoglobin levels collectively indicate the likelihood of arteriovenous malformation occurrence. The treatment options include surgical intervention and transcatheter arterial embolization. Surgical intervention is recommended for subjects with hemodynamic instability, persistent hypotension and those whose diagnosis is unconfirmed.


Pomegranate Bioactive Constituents Suppress Cell Proliferation and Induce Apoptosis in an Experimental Model of Hepatocellular Carcinoma: Role of Wnt/ β -Catenin Signaling Pathway.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, and chemoprevention represents a viable approach in lowering the mortality of this disease. Pomegranate fruit, an abundant source of anti-inflammatory phytochemicals, is gaining tremendous attention for its wide-spectrum health benefits. We previously reported that a characterized pomegranate emulsion (PE) prevents diethylnitrosamine (DENA)-induced rat hepatocarcinogenesis though inhibition of nuclear factor-kappaB (NF- κ B). Since NF- κ B concurrently induces Wnt/ β -catenin signaling implicated in cell proliferation, cell survival, and apoptosis evasion, we examined antiproliferative, apoptosis-inducing and Wnt/ β -catenin signaling-modulatory mechanisms of PE during DENA rat hepatocarcinogenesis. PE (1 or 10 g/kg) was administered 4 weeks before and 18 weeks following DENA exposure. There was a significant increase in hepatic proliferation (proliferating cell nuclear antigen) and alteration in cell cycle progression (cyclin D1) due to DENA treatment, and PE dose dependently reversed these effects. PE substantially induced apoptosis by upregulating proapoptotic protein Bax and downregulating antiapoptotic protein Bcl-2. PE dose dependently reduced hepatic β -catenin and augmented glycogen synthase kinase-3 β expression. Our study provides evidence that pomegranate phytochemicals exert chemoprevention of hepatic cancer through antiproliferative and proapoptotic mechanisms by modulating Wnt/ β -catenin signaling. PE, thus, targets two interconnected molecular circuits (canonical NF- κ B and Wnt/ β -catenin pathways) to exert chemoprevention of HCC.


The membrane form of variant surface glycoproteins of Trypanosoma brucei.
African trypanosomes are parasitic protozoa which are enveloped by a surface coat consisting of a matrix of identical glycoprotein molecules. Variations in the composition of these variant surface glycoproteins (VSGs) allow the parasite to escape the host's immune system and render effective immunoprophylaxis improbable. However, underlying the surface coat, all variant antigen types contain common membrane components, some of which can activate complement by the alternative pathway, leading to lysis of uncoated trypanosomes. Hence, stimulation of VSG release in vivo should be a potential form of chemotherapy, and we have therefore investigated the mode of attachment of VSG to the plasma membrane. Biochemical characterization of VSGs from several species has been performed on material purified after release from the cell surface following rupture of the trypanosome. We demonstrate here that VSGs of Trypanosoma brucei when bound to the membrane exist in a form which differs both biochemically and immunochemically from VSGs purified in the conventional manner. After rupture of the cell, membrane-form VSG (mfVSG) is enzymatically transformed into the commonly isolated water-soluble released form (sVSG). In conditions in which this modification does not take place, purified VSGs have amphiphilic properties and behave as integral membrane proteins by the criterion of charge-shift electrophoresis. The difference between the two forms lies in the C-terminal domain, which is phosphorylated in both forms. This domain in sVSGs contains an immunogenic oligosaccharide known as the cross-reacting determinant (CRD), attached to the C-terminal amino acid. Recognition of this determinant by anti-CRD antibodies is impaired in the membrane form.


Altered vesicular dopamine storage in Parkinson's disease: a premature demise.
Dopamine is a potentially toxic neurotransmitter that has long been speculated to contribute to the pathogenesis of Parkinson's disease (PD). Recent work has demonstrated the importance of proper storage of dopamine in vesicles to maintain dopamine homeostasis, thus protecting neurons from the detrimental effects of dopamine accumulation and breakdown in the cytosol. These studies suggest that factors which affect dopamine storage might increase the susceptibility of dopamine neurons to further environmental or genetic insults, exacerbating the neuronal degeneration that characterizes PD. This review seeks to revisit the pathogenicity of cytosolic dopamine and further address the critical role of neurotransmitter storage in dopamine-mediated neurotoxicity.