Influences of calcium deficiency and cerium on growth of spinach plants.
The main aim of the study was to determine the role of cerium in the amelioration of calcium-deficiency effects in spinach plants. Spinach plants were cultivated in Hoagland's solution. They were subjected to calcium-deficiency and to cerium chloride administered in the calcium-present Hoagland's media and calcium-deficient Hoagland's media. Within 3 weeks, young leaves developed distinct calcium-deficient symptoms, and plant growth significantly inhibited to calcium deprivation as would be expected; cerium-treated groups grown in the same conditions did not develop calcium-deficient symptoms; fresh weight, dry weight and chlorophyll content of spinach plants were increased by 35.9, 45 and 64.05% compared to those of plants cultivated in calcium-deficient media. In addition, calcium deprivation in spinach plants caused the reduction of photosynthetic rate, oxygen evolution rate and ribulose-1,5-bisphosphate carboxylase/oxygenase activity. The reduction of activities of nitrate reductase, glutamate dehydrogenase, glutamate synthase and glutamic-pyruvic transaminase was observed under calcium-deficient media. However, cerium treatment under calcium-deficient media could significantly improve photosynthesis and nitrogen metabolism of spinach plants. This is viewed as evidence that cerium added to calcium-deficient media in the spinach plants could substitute for calcium and improve spinach growth.


Neurosis of acquired helplessness and role of hypoxia in the formation of this disorder in rats.
Acquisition of instrumental defense response with pain reinforcement uncertainty (25% reinforcement) induced the development of acquired helplessness in 50% rats. Acquired helplessness is characterized by the absence of responses to conditioned (light) and unconditioned stimuli (pain), minor response of plasma corticosterone to learning, gas markers of circulatory cerebral hypoxia (Delta A/V pO2 carotid artery/jugular vein), low sensitivity to severe hypobaric conditions, and high resistance of Purkinje cells in the cerebellum. Piracetam improved learning and prevented the development of acquired helplessness. Local changes in cerebral blood flow and energy deficit in neurons responsible for emotional stress during acquired helplessness impair adaptive capacity, but reduce energy consumption and protect neuronal structures.


Hyperoxia and Acute Kidney Injury: A Tale of Oxygen and the Kidney.
Although oxygen supplementation is beneficial to support life in the clinic, excessive oxygen therapy also has been linked to damage to organs such as the lung or the eye. However, there is a lack of understanding of whether high oxygen therapy directly affects the kidney, leading to acute kidney injury, and what molecular mechanisms may be involved in this process. In this review, we revise our current understanding of the mechanisms by which hyperoxia leads to organ damage and highlight possible areas of investigation for the scientific community interested in novel mechanisms of kidney disease. Overall, we found a significant need for both animal and clinical studies evaluating the role of hyperoxia in inducing kidney damage. Thus, we urge the research community to further investigate oxygen therapy and its impact on kidney health with the goal of optimizing oxygen therapy guidelines and improving patient care.


Determination of four immunosuppressive drugs in whole blood using MEPS and LC-MS/MS allowing automated sample work-up and analysis.
In treatment with immunosuppressive drugs, monitoring of blood drug concentration is needed. The aim of this work was to explore micro extraction by packed sorbent (MEPS) as a possible on-line sample preparation method in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for quantification of cyclosporine, everolimus, sirolimus and tacrolimus in whole blood. An automated on-line MEPS system connected with a LC-MS/MS instrument was set up. A C₈ sorbent was used for the MEPS extraction. Subsequent analysis was performed with a gradient LC system. The adduct ions [M+NH₄]⁺ of the analytes were monitored in SRM mode for quantification. Ascomycin and cyclosporine D were used as internal standards. The chromatographic run time 2.5 min and the quantification ranges were 3-1500 ng/mL (r² ≥ 0.999, n=6) for cyclosporine and 0.5-50 ng/mL for everolimus, sirolimus and tacrolimus (r² ≥ 0.998, 0.994 and 0.993, respectively, n=6). Precision and accuracy were documented at three levels. Accuracy results were between 102% and 109% with precision between 2% and 13% and carry over <0.02%. Matrix effects were characterized and found to be below 20%. The quantifications obtained were in agreement with a reference LC-MS/MS method based on protein precipitation, and results obtained from external proficiency test samples compared with the mean of all other LC-mass spectrometry methods showed good agreement. This method provides an accurate, precise and automated procedure that can be applied for therapeutic drug monitoring of immunosuppressive drugs in clinical laboratories equipped with LC-MS/MS.


Prenatal dexamethasone exposure caused fetal rats liver dysplasia by inhibiting autophagy-mediated cell proliferation.
As a synthetic glucocorticoid, dexamethasone has been widely used in the clinical treatment of premature birth and related pregnant diseases, but its clinical use is still controversial due to developmental toxicity. This study aimed to confirm the proliferation inhibitory effect of pregnant dexamethasone exposure (PDE) on fetal liver development and elucidate its molecular mechanism. In vitro studies, we found that dexamethasone inhibited hepatocyte proliferation through autophagy activated by glucocorticoid receptor (GR)-forkhead protein O1 (FOXO1) pathway. Subsequently, in vivo, we confirmed in a PDE rat model that male fetal liver proliferation was inhibited, and the expression of the GR-FOXO1 pathway and autophagy were increased. Taken together, PDE induces autophagy by activating the GR-FOXO1 pathway, which leads to fetal liver proliferation inhibition and dysplasia in offspring rats. This study confirmed that dexamethasone activates cell autophagy in utero through the GR-FOXO1 pathway, thereby inhibiting hepatocyte proliferation and liver development, which provides theoretical basis for understanding the developmental toxicity of dexamethasone and guiding the rational clinical use.


Dacomitinib-induced diarrhoea is associated with altered gastrointestinal permeability and disruption in ileal histology in rats.
Dacomitinib-an irreversible pan-ErbB tyrosine kinase inhibitor (TKI)-causes diarrhoea in 75% of patients. Dacomitinib-induced diarrhoea has not previously been investigated and the mechanisms remain poorly understood. The present study aimed to develop an in-vitro and in-vivo model of dacomitinib-induced diarrhoea to investigate underlying mechanisms. T84 cells were treated with 1-4 μM dacomitinib and resistance and viability were measured using transepithelial electrical resistance (TEER) and XTT assays. Rats were treated with 7.5 mg/kg dacomitinib daily via oral gavage for 7 or 21 days (n = 6/group). Weights, and diarrhoea incidence were recorded daily. Rats were administered FITC-dextran 2 hr before cull, and serum levels of FITC-dextran were measured and serum biochemistry analysis was conducted. Detailed histopathological analysis was conducted throughout the gastrointestinal tract. Gastrointestinal expression of ErbB1, ErbB2 and ErbB4 was analysed using RT-PCR. The ileum and the colon were analysed using multiplex for expression of various cytokines. T84 cells treated with dacomitinib showed no alteration in TEER or cell viability. Rats treated with dacomitinib developed severe diarrhoea, and had significantly lower weight gain. Further, dacomitinib treatment led to severe histopathological injury localised to the ileum. This damage coincided with increased levels of MCP1 in the ileum, and preferential expression of ErbB1 in this region compared to all other regions. This study showed dacomitinib induces severe ileal damage accompanied by increased MCP1 expression, and gastrointestinal permeability in rats. The histological changes were most pronounced in the ileum, which was also the region with the highest relative expression of ErbB1.


Effects of feeding deoxynivalenol (DON)-contaminated wheat to laying hens and roosters of different genetic background on the reproductive performance and health of the newly hatched chicks.
A total of 216 23-week-old laying hens from two different genetic backgrounds (half of the birds were Lohmann brown [LB] and [LSL] hens, respectively) and 24 adult roosters were assigned to a feeding trial to study the effect of increasing concentrations of deoxynivalenol (DON) in the diet (0, 5, 10 mg/kg) on the reproductive performance of hens and roosters, and the health of the newly hatched chicks. Hatchability was adversely affected by the presence of DON in LB hens' diet, while the hatchability of the LSL chicks was significantly higher than LB chicks. An interaction effect between DON in the hens' diet and the breed was noticed on fertility, as the fertility was decreased in the eggs of LB hens receiving 10 mg/kg DON in their diet and increased in the eggs of LSL hens fed 10 mg/kg DON. Moreover, spleen relative weight was significantly decreased in the chicks hatched from eggs of hens fed contaminated diets, while gizzard relative weight was significantly decreased in LB chicks with 10 mg/kg DON in their diet compared with the control group. On the other hand, the chicks' haematology and organ histopathology were not affected by the dietary treatment. Additionally, the presence of DON in the roosters' diet had no effect on fertility (the percentage of fertile eggs of all laid eggs). Consequently, the current results indicate a negative impact of DON in LB hens' diet on fertility and hatchability, indicating that the breed of the hens seems to be an additional factor influencing the effect of DON on reproductive performance of the laying hens.


Effects of Concentrate Levels in Prepartum Diet on Milk Performance, Energy Balance and Rumen Fermentation of Transition Montbéliarde-Holstein Crossbred Cows.
This study was conducted to investigate the effect of three rates of prepartum dietary concentrate feeding on the milk performance, energy balance, and rumen fermentation of Montbéliarde−Holstein crossbred cows. Eighteen transition Montbéliarde−Holstein crossbred cows with similar days of gestation (258 ± 12 day) and body weights (622 ± 44 kg) were selected and randomly divided into three groups. In the prepartum period, the addition of concentrates accounted for 0.3% (low concentrate, LC), 0.6% (medium concentrate, MC), and 0.9% (high concentrate, HC) of the cow's body weight. The forage was corn stover, which was fed to the cows ad libitum with free access to water. Postpartum, all of the cows were fed a common lactation total mixed ration. The experimental period lasted from 21 days prepartum to 28 days postpartum. The energy balance (EB), net energy intake (NEI), and dry matter intake (DMI) of the HC group were greater than those of the other groups (p < 0.05). Likewise, the non-esterified fatty acids (NEFA), β-hydroxybutyric acid (BHBA), and total bilirubin (TBIL) in the blood of the LC group had significantly higher concentrations than they did in the other groups (p < 0.05). Moreover, the increase in the level of dietary concentrate had no significant effect on the rumen fermentation parameters (p > 0.05), and the total intestinal digestibility of dry matter (DM), crude protein (CP), and ether extract (EE) in the HC group was significantly higher (p < 0.05) than it was in the other groups during the prepartum period. In conclusion, the administration of the MC diet in the prepartum period had no negative effect on the performance and rumen fermentation of postpartum dairy cows and can satisfy the energy needs of prepartum dairy cows. Therefore, under our experimental conditions, the 0.6% prenatal concentrate feeding amount was the most appropriate for Montbéliarde−Holstein crossbred cows.


A study of histamine release from human basophils and lung mast cells by products of lymphocyte stimulation.
It has been previously reported by Thueson and his co-workers [1] that lymphokine-containing supernatant of cultured human peripheral blood lymphocytes stimulated with Concanavalin-A (Con-A) is capable of releasing histamine from human basophils. Here we confirm such findings, show that such release is additive to that due to immunological stimuli (Anti-IgE and antigen) and describe its characteristics and effect in lung tissue. The lymphokine was found to induce a small histamine release from chopped or enzyme-dispersed human lung tissue. As was the case with basophils, the release from lung tissue by this factor, though small, was also found to be additive to that induced by anti-IgE when both agents were added simultaneously. Histamine release from leucocytes by neat supernatant ranged from 9 to 35% and up to 55% when concentrated four-fold. The release resembled that of IgE-mediated reactions in many respects including temperature and calcium dependence, time course and susceptibility to metabolic inhibitors - thus suggesting a non-cytotoxic mechanism. These results show that histamine release by this lymphokine(s) possesses most of the features of an active secretory process. They also suggest that the histamine-releasing factor (HRF) in lymphokine-containing supernatants might be involved in the modulation of type I allergy in humans, apart from its involvement in delayed-type hypersensitivity.


Renovation in hospitals: Training construction crews to work in health care facilities.
Health care facilities require frequent renovations to maintain or enhance their service, and to meet the dynamic demands of their patients. Construction activities in active health care facilities are a significant contributor to various challenges that range from infection to death. It is therefore essential to minimize the adverse impacts of construction activities on health care units as well as their adjacent sites. A questionnaire was developed to study current training modules to prepare construction crews to work in health care environments. The survey was disseminated among professionals of the top 15 health care contractors. A total of 129 individuals participated, and their responses were analyzed using descriptive and categorical statistics. This study investigates current training practices regarding (1) the level of training, (2) the frequency of training, and (3) the impact that the sensitivity of the project has on the training. To effectively prepare construction crews, special training must be provided to them. There are uncertainties about the sufficiency and impact of the existing training. Existing trainings are tailored for upper management positions, and the amount/frequency of training for construction crews are substantially low. Findings of this study contribute to characterizing the activities and conditions pertaining to training of construction crews.


Noncompliance with the world health organization-multidrug therapy among leprosy patients in Cebu, Philippines: its causes and implications on the leprosy control program.
The success of current World Health Organization (WHO) key strategy for leprosy elimination (ie, multidrug therapy [MDT] regimen) depends largely on the efficiency of health care delivery services and patient compliance. A high rate of noncompliance with this regimen has serious implications for the leprosy control program because it can set the stage for the emergence of drug resistance, eventually resulting in treatment failure and failure of the program. A community-based descriptive study using pretested interviews conducted in 12 leprosy endemic areas in Cebu, Philippines, showed that the noncompliance rate with the WHO-MDT regimen among 233 study subjects was 30%. The causes of noncompliance are drug-related, health care provider-triggered, or patient-inducted, or some combination of these. Recommendations on strategic interventions to obviate the cause for noncompliance are presented.


Moral distress and ethical climate in pediatric oncology care impact healthcare professionals' intentions to leave.
To assess perceptions of ethical climate, experiences of moral distress, and intentions to leave among healthcare professionals in Nordic pediatric oncology care. A cross-sectional survey with registered nurses, physicians, and nursing assistants at 20 Nordic pediatric cancer centers. Data were collected by using translated versions of the Swedish Hospital Ethical Climate Survey-Shortened and the Swedish Moral Distress Scale-Revised. Descriptive analyses and non-parametric tests were used to describe, summarize, and compare data. According to 543 healthcare professionals (response rate 58%), the ethical climate in Nordic pediatric oncology care was positive. Inadequate staffing levels, poor continuity and lack of time were the most common causes of moral distress. Registered nurses experienced significantly higher levels of moral distress compared to physicians and nursing assistants. About 6% of the respondents considered leaving due to moral distress. Typically, they assessed the ethical climate as less positive and reported higher levels of moral distress than those who had no intention to leave. Organizational actions that ensure safe staffing levels and improve the continuity of care are needed to prevent moral distress and high staff turnover.


Structure-based design of peptidomimetic ligands of the Grb2-SH2 domain.
We have designed and synthesized a (3-aminomethyl-phenyl)-urea scaffold to mimic the X+1-Asn part of the minimal phosphopeptide sequence, Ac-pTyr-X+1-Asn-NH2, recognized by the Grb2-SH2 domain. The resulting compounds show the same degree of affinity as their peptide counterparts for the Grb2-SH2 domain. This is the first example reported to date of ligands of the Grb2-SH2 domain with substantially reduced peptidic character.


Effect of Age on Tooth Shade, Skin Color and Skin-Tooth Color Interrelationship in Saudi Arabian Subpopulation.
Dental restoration or prosthesis in harmony with adjacent natural teeth color is indispensable part for the successful esthetic outcome. The studies indicate is existence of correlation between teeth and skin color. Teeth and skin color are changed over the aging process. The aim of the study was to explore the role of age on the tooth and skin color parameters, and to investigate the effect of ageing on teeth-skin color correlation. Total of 225 Saudi Arabian ethnic subjects was divided into three groups of 75 each. The groups were divided according to participant's age. The participant's age for Group I, Group II, and Group III was 18-29 years, 30-50 years, and above 50 years, respectively. The tooth color was identified by spectrophotometer in CIE Lab parameters. The skin color was registered with skin surface photography. The data were statistically analyzed with one-way ANOVA and correlation tests with SPSS 18 software. The Group I had the highest 'L' value of 80.26, Group III recorded the least value of 76.66. The Group III had highest yellow value 'b' at 22.72, while Group I had 19.19. The skin 'L' value was highest in the young population; the elder population had the increased red value 'a' in comparison to younger subjects. The 'L' tooth color parameter had a strong positive linear correlation with skin color in young and adult subjects. While Group III teeth showed the strong positive correlation with 'b' parameter at malar region. The elder subjects had darker and yellow teeth in comparison with younger subjects. The reddening of the skin was observed as age-related skin color change. The age had a strong influence on the teeth-skin color correlation.


Capacitación-acción participativa: una experiencia de 24 años en las comunidades rurales de Oaxaca, México.
Resumen: En este artículo presentamos el proyecto de capacitación llevado a cabo en comunidades de la sierra y costa de Oaxaca, México, desde 1991, por el Centro de Capacitación Integral para Promotores Comunitarios (CECIPROC). La decisión de hacer este trabajo en Oaxaca responde a que ese estado ocupa uno de los primeros lugares de marginación y de desnutrición en menores de 5 años. El objetivo es describir un modelo de capacitación y compartir parte de las experiencias derivadas, tanto del modelo como del trabajo realizado en las distintas áreas (nutrición y alimentación, salud comunitaria, ecología y etnobotánica, y educación y organización), por promotores mujeres y hombres en sus comunidades. La experiencia obtenida en 24 años muestra la factibilidad técnica y social del proyecto en el ámbito de la salud, el reconocimiento social del proyecto del CECIPROC como un organismo civil que ha aportado alternativas como solución a la problemática de salud, el hacer suyo el proyecto por algunos promotores y los diferentes obstáculos a los que se ha enfrentado. Enfatizamos el hecho de que la situación socioeconómica y política prevaleciente en el estado de Oaxaca es una limitante para el buen desarrollo de los programas colectivos de salud, e insistimos en la necesidad de compartir nuestras experiencias para que puedan ser utilizadas en la planificación y ejecución de otros proyectos.


Altered splicing leads to reduced activation of CPEB3 in high-grade gliomas.
Cytoplasmic polyadenylation element binding proteins (CPEBs) are auxiliary translational factors that associate with consensus sequences present in 3'UTRs of mRNAs, thereby activating or repressing their translation. Knowing that CPEBs are players in cell cycle regulation and cellular senescence prompted us to investigate their contribution to the molecular pathology of gliomas-most frequent of intracranial tumors found in humans. To this end, we performed methylation analyses in the promoter regions of CPEB1-4 and identified the CPEB1 gene to be hypermethylated in tumor samples. Decreased expression of CPEB1 protein in gliomas correlated with the rising grade of tumor malignancy. Abundant expression of CPEBs2-4 was observed in several glioma specimens. Interestingly, expression of CPEB3 positively correlated with tumor progression and malignancy but negatively correlated with protein phosphorylation in the alternatively spliced region. Our data suggest that loss of CPEB3 activity in high-grade gliomas is caused by expression of alternatively spliced variants lacking the B-region that overlaps with the kinase recognition site. We conclude that deregulation of CPEB proteins may be a frequent phenomenon in gliomas and occurs on the level of transcription involving epigenetic mechanism as well as on the level of mRNA splicing, which generates isoforms with compromised biological properties.


Performance of the Automated Neuropsychological Assessment Metrics (ANAM) in detecting cognitive impairment in heart failure patients.
Evaluate capacity of the Automated Neuropsychological Assessment Metrics (ANAM) to detect cognitive impairment (CI) in heart failure (HF) patients. CI is a key prognostic marker in HF. Though the most widely used cognitive screen in HF, the Mini-Mental State Examination (MMSE) is insufficiently sensitive. The ANAM has demonstrated sensitivity to cognitive domains affected by HF, but has not been assessed in this population. Investigators administered the ANAM and MMSE to 57 HF patients, compared against a composite model of cognitive function. ANAM efficiency (p < .05) and accuracy scores (p < .001) successfully differentiated CI and non-CI. ANAM efficiency and accuracy scores classified 97.7% and 93.0% of non-CI patients, and 14.3% and 21.4% with CI, respectively. The ANAM is more effective than the MMSE for detecting CI, but further research is needed to develop a more optimal cognitive screen for routine use in HF patients.


Benign childhood epilepsy with centrotemporal spikes: a study of 50 Chinese children.
In order to collect local data for children with Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS), we conducted a retrospective study of 50 Chinese children (32 males and 18 females) with BECTS diagnosed in two regional hospitals in Hong Kong from 1995 to 1998. Their peak age of onset was 7 years (range 3-13 years) and a male predominance was observed. Seven patients (14%) had a past history of febrile convulsions and five cases (10%) had a family history of epilepsy. The presentation was protean, but most of them had infrequent, short, nocturnal generalised seizures. The EEG spike foci were most frequently found in mid-temporal regions, followed by centrotemporal regions. Fourteen percent of children did not require anti-epileptic drug treatment. For those who were treated, they were easily controlled on a low dose of carbamazepine (median dosage of 12.75 mg/kg per day) or sodium valproate (median dosage of 20 mg/kg per day). Our study suggested a generally good prognosis for BECTS. No risk factors of frequent seizure recurrence could be identified.


Safety of conventional immunosuppressive therapies for patients with dermatological conditions and coronavirus disease 2019: A review of current evidence.
The effect of coronavirus disease 2019 (COVID-19) on patients receiving conventional immunosuppressive (IS) therapy has yet to be fully determined; however, research on using IS therapy for treating COVID-19 in acutely ill patients is increasing. While some believe that IS therapy may be protective, others argue that these agents may make patients more susceptible to COVID-19 infection and morbidity and advocate for a more cautious, individualized approach to determining continuation, reduction, or discontinuation of therapy. In this review, we aim to provide an overview of COVID-19 risk in dermatological patients who are receiving conventional IS therapies, including mycophenolate mofetil, methotrexate, cyclosporine, azathioprine, apremilast, JAK inhibitors, and systemic steroids. Additionally, we provide recommendations for management of these medications for dermatological patients during the COVID-19 pandemic. Treatment of dermatological disease during the COVID-19 pandemic should involve shared decision-making between the patient and provider, with consideration of each patient's comorbidities and the severity of the patient's dermatological disease.


Lipoprotein-X levels in extrahepatic versus intrahepatic cholestasis.
Lipoprotein-X (LP-X) is an abnormal lipoprotein characteristic of cholestasis. To assess recent claims that its serum concentration helps differentiate extrahepatic from intrahepatic cholestasis, we studied 42 consecutive LP-X-positive patients. The mean serum LP-X level was higher in 18 patients with extrahepatic obstruction than in 24 with intrahepatic cholestatis, 321 +/- 89 versus 130 +/- 31 SEM mg per dl (P less than 0.05). However, values overlapped in 38 of the 42 cases, and in the other 4 the diagnosis of extrahepatic obstruction was obvious anyway from clinical examination. LP-X concentration gave little more information than did free cholesterol of phospholipid levels, which it closely paralleled (r = 0.89 and 0.81, respectively, P less than 0.01). There was no correlation with standard liver function tests or with activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. Contrary to recent claims, these findings suggest that serum LP-X quantitation has little or no clinical value in distinguishing extrahepatic from intrahepatic cholestasis.


Letermovir for the compassionate therapeutic use of cytomegalovirus infection.
Data on the efficacy, dosing and safety of letermovir for the compassionate therapeutic use of CMV infections are limited. Clinical and virological efficacy of letermovir was assessed in a retrospective single-centre study of patients who received letermovir for the compassionate therapeutic use of CMV infections. Letermovir initiation yielded prompt treatment response in 7 out of 9 patients (77.7%). Letermovir may be an effective and well tolerated option in the compassionate treatment of CMV infections, although recurrence of CMV and emergence of resistance may be issues.


Phenolics profiling by HPLC-DAD-ESI-MSn aided by principal component analysis to classify Rabbiteye and Highbush blueberries.
Although blueberries are widely studied, little information exists on their composition and content of flavonol glycosides. Most studies identify only a few flavonols in blueberries due to separation and identification issues. In the present study, we identified 44 flavonols and chlorogenic acid in 30 samples of Highbush and Rabbiteye blueberry, using HPLC-DAD-ESI-MSn. Highbush group fruits presented mainly quercetin-3-galactoside in their composition, while Rabbiteye group fruits exhibited higher levels of quercetin-3-rhamnoside and quercetin-3-glucuronide. Among the identified flavonols, 8 acylates (acetyl and hydroxymethylglutaroyl) were found, of which quercetin-3-O-[4″-(3-hydroxy-3-methylglutaroyl)]-α-rhamnoside was found for the first time in blueberries. This compound is exclusive to the cultivars Florida and Powderblue, where it is present in high quantities. Glucuronides of syringetin and laricitrin, and rhamnosyl-galactosides of myricetin, quercetin and isorhamnetin were also found for the first time in blueberries. The Principal Component Analysis showed that blueberry groups can be distinguished based on their phenolic compound profile.


Motivating change.
Effective health behaviour change consultations demand a high level of skill and well-practised strategies used in a patient-centred way of working.


The micropolitics of implementation; a qualitative study exploring the impact of power, authority, and influence when implementing change in healthcare teams.
Healthcare organisations are complex social entities, comprising of multiple stakeholders with differing priorities, roles, and expectations about how care should be delivered. To reach agreement among these diverse interest groups and achieve safe, cost-effective patient care, healthcare staff must navigate the micropolitical context of the health service. Micropolitics in this study refers to the use of power, authority, and influence to affect team goals, vision, and decision-making processes. Although these concepts are influential when cultivating change, there is a dearth of literature examining the mechanisms through which micropolitics influences implementation processes among teams. This paper addresses this gap by exploring the role of power, authority, and influence when implementing a collective leadership intervention in two multidisciplinary healthcare teams. The multiple case study design adopted employed a triangulation of qualitative research methods. Over thirty hours of observations (Case A = 16, Case B = 15) and twenty-five interviews (Case A = 13, Case B = 12) were completed. An in-depth thematic analysis of the data using an inductive coding approach was completed to understand the mechanisms through which contextual factors influenced implementation success. A context coding framework was also employed throughout implementation to succinctly collate the data into a visual display and to provide a high-level overview of implementation effect (i.e. the positive, neutral, or negative impact of contextual determinants on implementation). The findings emphasised that implementing change in healthcare teams is an inherently political process influenced by prevailing power structures. Two key themes were generated which revealed the dynamic role of these concepts throughout implementation: 1) Exerting hierarchical influence for implementation; and 2) Traditional power structures constraining implementation. Gaining support across multiple levels of leadership was influential to implementation success as the influence exercised by these individuals persuaded follower engagement. However, the historical dynamics of each team determined how this influence was exerted and perceived, which negatively impacted some participants' experiences of the implementation process. To date, micropolitics has received scant attention in implementation science literature. This study introduces the micropolitical concepts of power, authority and influence as essential contextual determinants and outlines the mechanisms through which these concepts influence implementation processes.


Rapid determination of baicalin and total baicalein content in Scutellariae radix by ATR-IR and NIR spectroscopy.
In this study methods for the quantification of baicalin and total baicalein in Scutellariae radix with near infrared (NIR) spectroscopy and attenuated-total-reflectance mid-infrared (ATR-IR) spectroscopy in hyphenation with multivariate analysis were developed and compared. The reference analysis was performed by high performance liquid chromatography coupled to diode array detection (HPLC-DAD). Different pretreatments like standard normal variate (SNV), multiplicative scatter correction (MSC), first and second derivative Savitzky-Golay were applied on the spectra to optimize the calibrations. A principal component analysis was performed with both spectroscopic methods to distinguish wild and cultivated samples. Quality parameters obtained for test-set calibration models of ATR-IR spectroscopy (baicalin: standard error of prediction (SEP)=1.31, ratio performance to deviation (RPD)=2.91 and R(2)=0.88; total baicalein: SEP=1.02, RPD=3.24 and R(2)=0.89) and NIR spectroscopy (baicalin: SEP=1.50, RPD=2.54 and R(2)=0.88; total baicalein: SEP=1.19, RPD=2.76 and R(2)=0.84) demonstrate that both spectroscopic techniques in combination with multivariate analysis are successful tools for the quantification of baicalin and total baicalein in Scutellariae radix, but it was found that ATR-IR spectroscopy provides higher accuracy in the given application. Furthermore it was proved that wild and cultivated samples can be distinguished by ATR-IR.


The power of Kawaii: viewing cute images promotes a careful behavior and narrows attentional focus.
Kawaii (a Japanese word meaning "cute") things are popular because they produce positive feelings. However, their effect on behavior remains unclear. In this study, three experiments were conducted to examine the effects of viewing cute images on subsequent task performance. In the first experiment, university students performed a fine motor dexterity task before and after viewing images of baby or adult animals. Performance indexed by the number of successful trials increased after viewing cute images (puppies and kittens; M ± SE=43.9 ± 10.3% improvement) more than after viewing images that were less cute (dogs and cats; 11.9 ± 5.5% improvement). In the second experiment, this finding was replicated by using a non-motor visual search task. Performance improved more after viewing cute images (15.7 ± 2.2% improvement) than after viewing less cute images (1.4 ± 2.1% improvement). Viewing images of pleasant foods was ineffective in improving performance (1.2 ± 2.1%). In the third experiment, participants performed a global-local letter task after viewing images of baby animals, adult animals, and neutral objects. In general, global features were processed faster than local features. However, this global precedence effect was reduced after viewing cute images. Results show that participants performed tasks requiring focused attention more carefully after viewing cute images. This is interpreted as the result of a narrowed attentional focus induced by the cuteness-triggered positive emotion that is associated with approach motivation and the tendency toward systematic processing. For future applications, cute objects may be used as an emotion elicitor to induce careful behavioral tendencies in specific situations, such as driving and office work.


Membranous overexpression of S100A10 is associated with a high-grade cellular status of breast carcinoma.
S100A10 promotes tumor invasion in various cancers. Although genetic studies on S100A10 in breast carcinoma (BC) have been used for molecular biological classification, immunohistochemical studies are lacking. We aimed to identify the correlation between S100A10 expression in BC and various pathological parameters, including morphological features to determine histological grade (HG). Immunostained serial paraffin-embedded tissue sections from 176 cases of resected BC or normal mammary ducts (controls) were assessed for the membrane expression of S100A10. Of the 176 cases, 125 conventional infiltrating ductal carcinomas were chosen, comprising 67 (53.6%) S100A10-positive tumors, whereas normal mammary ducts were S100A10-negative. S100A10 immunoreactivity in ductal carcinoma in situ (n = 51) was similar to that of invasive carcinoma. The distinct membrane-immunopositivity was correlated with high HG, severe nuclear pleomorphism, frequent mitotic counts, high Ki-67 labeling index, HER2/neu overexpression, and low estrogen receptor status (P < 0.05), but not with tubular formation, pT categories, node metastasis, vessel permeation, and pStage. Membrane overexpression of S100A10 in BC correlates with the high-grade morphological and molecular status of the carcinoma cell rather than stromal invasion and architectural deviation. Evidence points to the use of S100A10 as a biomarker representing a high-grade cellular status of BC.


Visualization of c-Ki-ras-2 oncogene sequences in human pancreas, a chemically induced transplantable carcinoma, and carcinomas of pancreas by in situ hybridization.
c-Ki-ras-2 sequences were visualized in paraffin-embedded sections from normal fetal and adult human pancreases, a chemically induced transplantable human pancreas carcinoma (PT-1) and three carcinomas of pancreas by in situ hybridization technique. A biotinylated 1-kilobase-pair (kb) EcoRI fragment of pHiHi3 DNA was used as probe and the oncogene was visualized as one or two large grains of reaction products produced by streptavidin-peroxidase complex and diaminobenzidine tetrachloride in more than 9% of normal pancreas nuclei. Its amplification in the chemically induced cell line was detected as one or more large grains in 72% of the nuclei and numerous cytoplasmic grains. The detection of oncogene in normal pancreases and its amplification in PT-1 cells was validated by Southern analysis of EcoRI digests of genomic DNA extracted from normal pancreases and PT-1 cell line. The oncogene was also demonstrated to be equally amplified in two adenocarcinomas and one undifferentiated carcinoma of human pancreas by in situ hybridization.


Accuracy of serum IgE concentrations and papule diameter in the diagnosis of cow's milk allergy.
To compare serum concentrations of specific IgE and mean papule diameters induced in the immediate skin reactivity test with cow's milk and its fractions with results of the oral challenge test, and to establish cutoff points capable of predicting clinical reactivity to cow's milk in patients treated at a referral service. One hundred and twenty-two children (median of 17 months) with a history of immediate reactions to cow's milk and presence of specific IgE for cow's milk and/or its fractions (positive skin and/or IgE serum tests) were submitted to open oral challenge test with cow's milk. The oral challenge test was positive in 59.8% of the children, 49% of whom were males. Serum levels of specific IgE, as well as mean cow's milk papule diameters, were significantly higher in allergic patients (medians: 3.39kUA/L vs. 1.16kUA/L, 2.5mm vs. 0mm). The optimal cutoff points (Youden's index) of serum IgE specific for cow's milk and its fractions capable of predicting cow's milk reactivity (positive oral challenge test) were: 5.17kUA/L for cow's milk, 0.95kUA/L for α-lactalbumin, 0.82kUA/L for β-lactoglobulin, and 0.72kUA/L for casein, whereas for papule diameters the cutoff points were 3.5mm for cow's milk and 6.5mm, 9.0mm, and 3.0mm for the α-lactalbumin, β-lactoglobulin, and casein fractions, respectively. The cutoff points capable of predicting clinical reactivity to cow's milk were: 5.17kUA/L for serum-specific IgE and 3.5mm for papule diameter measurement, values considered discriminatory for the diagnosis of cow's milk allergy.


Use of soft sensors to monitor a pharmaceuticals freeze-drying process in vials.
This paper presents a soft sensor that can be effectively used for in-line monitoring of the primary drying step of a pharmaceuticals freeze-drying process in vials. Process modeling and product temperature measurements are used to estimate the residual amount of ice in the vial and the heat transfer coefficient from the shelf to the product in the vial. The resistance of the dried cake to vapor flow is determined through the heat balance equation at the interface of sublimation. Mathematical simulation and experimental tests have been carried out to validate the estimations provided by the soft sensor. Accurate estimations of the dynamics of the product until the end of primary drying are obtained, as well as of the heat and mass transfer coefficients, even in the case of a highly non-uniform batch. The reduction in the number of variables directly estimated by the soft sensor allows increasing the robustness of the tool with respect to other sensors presented in the literature. The proposed soft sensor is thus effective for process monitoring and it allows using model-based tools for cycle development in lab-scale units, where thermocouples are usually available, and for process monitoring in industrial-scale freeze-dryers, in case wireless sensors are used.


A Comprehensive Grading System for a Magnetic Sentinel Lymph Node Biopsy Procedure in Head and Neck Cancer Patients.
A magnetic sentinel lymph node biopsy ((SLN)B) procedure has recently been shown feasible in oral cancer patients. However, a grading system is absent for proper identification and classification, and thus for clinical reporting. Based on data from eight complete magnetic SLNB procedures, we propose a provisional grading system. This grading system includes: (1) a qualitative five-point grading scale for MRI evaluation to describe iron uptake by LNs; (2) an ex vivo count of resected SLN with a magnetic probe to quantify iron amount; and (3) a qualitative five-point grading scale for histopathologic examination of excised magnetic SLNs. Most SLNs with iron uptake were identified and detected in level II. In this level, most variance in grading was seen for MRI and histopathology; MRI and medullar sinus were especially highly graded, and cortical sinus was mainly low graded. On average 82 ± 58 µg iron accumulated in harvested SLNs, and there were no significant differences in injected tracer dose (22.4 mg or 11.2 mg iron). In conclusion, a first step was taken in defining a comprehensive grading system to gain more insight into the lymphatic draining system during a magnetic SLNB procedure.


Serum α-linolenic and other ω-3 fatty acids, and risk of disabling dementia: Community-based nested case-control study.
It has been hypothesized that ω-3 polyunsaturated fatty acids have anti-atherosclerotic and neuronal protective functions and may benefit prevention of dementia, but the epidemiological evidence, especially for α-linolenic acid, is quite limited. The aim of this study was to examine whether serum ω-3 polyunsaturated fatty acids are associated with risk of dementia. We performed an intracohort case-control study nested in a community-based cohort, the Circulatory Risk in Communities Study, involving 7586 Japanese individuals aged 40-74 years at the baseline period of 1984-1994. Omega-3 polyunsaturated fatty acid constituents (α-linolenic, eicosapentaenoic, and docosahexaenoic acids) in serum total lipid were measured in 315 cases of incident disabling dementia in the above-mentioned cohort between 1999 and 2004, and in 630 controls whose age, sex, area, and baseline year were matched with the cases. As we had postulated, serum α-linolenic acid was inversely associated with risk of disabling dementia: the multivariate odds ratios (95% confidence intervals) were 0.57 (0.39-0.85), 0.51 (0.34-0.76), and 0.61 (0.41-0.90) for persons with the second, third, and highest quartiles of serum α-linolenic acid, respectively, as compared with the lowest quartile (P for trend = 0.01). Associations of other ω-3 fatty acids with disabling dementia were not statistically significant. Serum α-linolenic acid was inversely associated with risk of disabling dementia. Although the causality needs to be confirmed by randomized control trials, we identified serum α-linolenic acid as a biomarker that predicts future dementia.


Quantitative analysis of nonadiabatic effects in dense H3S and PH3 superconductors.
The comparison study of high pressure superconducting state of recently synthesized H3S and PH3 compounds are conducted within the framework of the strong-coupling theory. By generalization of the standard Eliashberg equations to include the lowest-order vertex correction, we have investigated the influence of the nonadiabatic effects on the Coulomb pseudopotential, electron effective mass, energy gap function and on the 2Δ(0)/TC ratio. We found that, for a fixed value of critical temperature (178 K for H3S and 81 K for PH3), the nonadiabatic corrections reduce the Coulomb pseudopotential for H3S from 0.204 to 0.185 and for PH3 from 0.088 to 0.083, however, the electron effective mass and ratio 2Δ(0)/TC remain unaffected. Independently of the assumed method of analysis, the thermodynamic parameters of superconducting H3S and PH3 strongly deviate from the prediction of BCS theory due to the strong-coupling and retardation effects.


Absence of mutations in the Wilms' tumor gene wt1 in de novo non-small cell lung cancers.
We recently demonstrated that the WT1 gene was overexpressed in the majority of de novo lung cancers regardless of cancer subtypes. Here, we examined WT1 genomic DNA in 38 cases of de novo non-small cell lung cancers (NSCLC) for mutations using direct sequencing. The sequencing analysis showed no mutations of WT1 genomic DNA in any of 38 de novo non-small cell lung cancers examined. These results indicated that the non-mutated, wild-type WT1 gene played an important role in de novo NSCLC.


Implementation and expansion of an electronic medical record for HIV care and treatment in Haiti: an assessment of system use and the impact of large-scale disruptions.
System use is a key criterion of success in an electronic medical record (EMR) implementation, and there is little research on long-term use of systems following implementation. The aim of the paper was to describe the development, implementation and use of iSanté, Haiti's national HIV care and treatment EMR. To build a picture of the history of iSanté, we interviewed 11 staff involved with the development and implementation of the EMR, and reviewed organization records. Data entry and report use were ascertained by querying the central patient database. By the end of 2010 there were 67 sites with iSanté installed, and the scope of the system had been expanded to include primary care and obstetrics and gynecology. New functionality includes data forms specific to subpopulations, the ability to transfer patient records among clinics, and integration with an electronic laboratory system. We observed fluctuations in use over time, with substantial reductions in the number of active sites during times of large-scale disruptions in Haiti. A surge in report use following the January 2010 earthquake suggests that clinics found the EMR to be a valuable source of data during the recovery phase. There is real potential for EMRs in developing countries to improve clinical practice and make data available for efficient reporting, quality improvement and other population health uses. An approach of continuous system improvement, combined with regular assessments of use, is necessary for achieving an effective, national implementation of a standardized EMR. We have achieved successes in terms of rolling out new functionality and expanding to new sites, but more work remains to be done to improve perceptions of data quality and increase use of population data for accurate and timely reporting.


Absence of Exceptional Points in Square Waveguide Arrays with Apparently Balanced Gain and Loss.
The concept of parity-time (PT) symmetry in the field of optics has been intensively explored. This study shows the absence of exceptional points in a three-dimensional system composed of a square waveguide array with diagonally-balanced gain/loss distribution. More specifically, we show that an array of four coupled waveguides supports eight fundamental propagation supermodes, four of which are singlet, and the other two pairs are double degenerated. It is found that the singlet states follow the routine PT phase transition; however, the double-degenerated modes never coalesce as the gain/loss-to-coupling strength level varies, showing no actual PT symmetry-derived behavior. This is evident in the phase rigidity which does not approach zero. The absence of exceptional points is ascribed to the coupling of non-symmetric supermodes formed in the diagonal waveguide pairs. Our results suggest comprehensive interplay between the mode pattern symmetry, the lattice symmetry, and the PT-symmetry, which should be carefully considered in PT-phenomena design in waveguide arrays.


Use of stapling instruments in surgery for aneurysms of the aorta.
Since their inception, surgical stapling devices have been used almost exclusively in pulmonary and gastrointestinal procedures. We present our experience with surgical staplers in operations for aneurysms of the aorta. Three illustrative case reports are presented that demonstrate the applicability of surgical stapling devices in excluding aortic aneurysms. Seven patients have undergone operation using this technique, all with excellent technical results. We believe that surgical stapling devices represent a safe, easy, and rapid means of excluding aneurysms of the aorta.


Dual Enhancement of Gold Nanocluster Electrochemiluminescence: Electrocatalytic Excitation and Aggregation-Induced Emission.
Ligand-protected gold nanoclusters (AuNCs) have emerged as a new class of electrochemiluminescence (ECL) luminophores for their interesting catalytic and emission properties, although their quantum yield (ΦECL ) in aqueous medium is low with a poor mechanistic understanding of the ECL process. Now it is shown that drying AuNCs on electrodes enabled both enhanced electrochemical excitation by an electrocatalytic effect, and enhanced emission by aggregation-induced ECL (AIECL) for 6-aza-2-thiothymine (ATT) protected AuNCs with triethylamine (TEA) as a coreactant. The dried ATT-AuNCs/TEA system resulted in highly stable visual ECL with a ΦECL of 78 %, and a similar enhancement was also achieved with methionine-capped AuNCs. The drying enabled dual-enhancement mechanism has solved a challenging mechanistic problem for AuNC ECL probes, and can guide further rational design of ECL emitters.


A paradigmatic shift in the care of male factor infertility: how can the recommendations for basic semen examination in the sixth edition of the WHO manual and the ISO 23162:2021 standard help?
The WHO laboratory manual for the examination and processing of human semen is a worldwide recognized source of information on reliable techniques for semen examination. Since its initial publication, aimed at providing useful data in the evaluation of male contraceptive drugs, the manual has developed to focus mainly on discovering male factors of infertility as a basis for medical assisted reproduction. The principles for basic semen examination remain mainly unchanged in the sixth edition. Some important adjustments have been made to improve efficacy, compliance with basic laboratory science and user-friendly instructions. For human sperm morphology assessment, more rationale and techniques are given for the assessment of defects in all parts of the spermatozoa. More data from men in couples with less than 1 year to initiation of pregnancy have been incorporated into the manual. The general problem, however, has been that these ranges and limits have been misinterpreted as distinct limits between fertility and infertility. This review discusses how the available distribution of data from men in couples achieving pregnancy should be interpreted. Another important aspect is the use of human sperm morphology for better understanding of functions and disorders of the male reproductive organs to increase the focus on men's reproductive health.


A pilot randomized controlled trial comparing THUNDERBEAT to the Maryland LigaSure energy device in laparoscopic left colon surgery.
The THUNDERBEAT is a multi-functional energy device which delivers both ultrasonic and bipolar energy, but there are no randomized trials which can provide more rigorous evaluation of the clinical performance of THUNDERBEAT compared to other energy-based devices in colorectal surgery. The aim of this study was to compare the clinical performance of THUNDERBEAT energy device to Maryland LigaSure in patients undergoing left laparoscopic colectomy. Prospective randomized trial with two groups: Group 1 THUNDERBEAT and Group 2 LigaSure in a single university hospital. 60 Subjects, male and female, of age 18 years and above undergoing left colectomy for cancer or diverticulitis were included. The primary outcome was dissection time to specimen removal (DTSR) measured in minutes from the start of colon mobilization to specimen removal from the abdominal cavity. Versatility (composite of five variables) was measured by a score system from 1 to 5 (1 being worst and 5 the best), and adjusted/weighted by coefficient of importance with distribution of the importance as follow: hemostasis 0.275, sealing 0.275, cutting 0.2, dissection 0.15, and tissue manipulation 0.1. Other variables were: dryness of surgical field, intraoperative and postoperative complications, and mortality. Follow-up time was 30 days. 60 Patients completed surgery, 31 in Group 1 and 29 in Group 2. There was no difference in the DTSR between the groups, 91 min vs. 77 min (p = 0.214). THUNDERBEAT showed significantly higher score in dissecting and tissue manipulation in segment 3 (omental dissection), and in overall versatility score (p = 0.007) as well as versatility score in Segment 2 (retroperitoneal dissection p = 0.040) and Segment 3 (p = 0.040). No other differences were noted between the groups. Both energy devices can be employed effectively and safely in dividing soft tissue and sealing mesenteric blood vessels during laparoscopic left colon surgery, with THUNDERBEAT demonstrating some advantages over LigaSure during omental dissection and tissue manipulation. gov # NCT02628093.


Levodopa/dopamine analogs as inhibitors of DNA synthesis in human melanoma cells.
Compounds possessing the ortho-dihydroxybenzene moiety and structurally related to levodopa and dopamine appear to belong to a new class of biologically active agents that are capable of inhibiting DNA synthesis in a variety of normal and malignant eukaryotic cells. They appear to work in part through their properties as potent reducing agents, and thereby interfere with several redox reactions that are crucial to the synthesis of cellular DNA. Interestingly, the compounds can then be converted to their oxidized or quinone forms, which are powerful electrophiles, and further disrupt cellular metabolism. This latter mechanism appears to account for the relatively increased cytotoxicity observed in melanin-producing cells. In addition to providing potential new agents for the treatment of advanced malignant melanoma, these compounds might prove to be valuable tools in determining the factors that influence rates of DNA synthesis in normal and malignant cells.


4-Aminopyridine causes a voltage-dependent block of the transient outward K+ current in rat melanotrophs.
1. Whole-cell voltage-clamp recordings were made from acutely dissociated melanotrophs obtained from adult rats. 2. In the presence of external Na+ and Ca2+ channel blockers and 20 mM-tetraethylammonium (TEA) depolarizations to -40 mV or more evoked a fast-activating fast-inactivating outward K+ current (IK(f)). Double-pulse experiments showed that steady-state half-inactivation occurred near -37 mV; half-maximal activation of IK(f) occurred at -15 mV. Recovery from inactivation in most cells fitted a single exponential with a time constant of 40-50 ms. 3. When applied either internally or externally, 1-2.5 mM-4-aminopyridine (4-AP) substantially reduced IK(f) but the degree of block was affected by the intensity, duration and frequency of depolarizing commands. 4. Analysis of the steady-state voltage dependence of the block by 4-AP showed that half-maximal blocking occurred at approximately -31 mV. This implied that 4-AP binds to the resting state of the IK(f) channel. 5. Studies of the time dependence for the blocking or unblocking of IK(f) showed that both processes were exponential with mean time constants of 1942 ms (at -70 mV) and 726 ms (at 20 mV), respectively. Recovery from inactivation was apparently unaffected by 4-AP. 6. A four-state sequential model in which 4-AP reversibly binds to the resting state of the channel replicates the frequency dependence of the 4-AP blockade.


Karyotypic variations in human meningioma cell cultures under different in vitro conditions.
Examined were how changes of the culture medium, cultivating procedure and cultivating time will influence numerical representation of different karyotypes in a total of 27 cell cultures of meningiomas with two or more cytogenetically distinguishable cell lines. It could be shown that in medium I (80% Mc Coy 5 A, 20% fetal calf serum) more cell lines with a higher degree of hypodipoidy occurred than in medium II (50% TC 199, 40% bovine amniotic fluid, 10% calf serum). The number of cells with normal karyotype was higher in cultures which were grown from trypsinized biopsy material in stationary flasks when compared to particle cultures in roller tubes. Cells with a normal karyotype also increased after 1--6 subcultures. By demonstration of SV 40 tumor antigen it could be shown in two cultures that these normal mitoses derived from tumoral and not from stromal tissue.


Sex Differences in Heart Failure With Preserved Ejection Fraction Pathophysiology: A Detailed Invasive Hemodynamic and Echocardiographic Analysis.
This study sought to identify sex differences in central and peripheral factors that contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF) by using complementary invasive hemodynamic and echocardiographic approaches. Women are overrepresented among patients with HFpEF, and there are established sex differences in myocardial structure and function. Exercise intolerance is a fundamental feature of HFpEF; however, sex differences in the physiological determinants of exercise capacity in HFpEF are yet to be established. Patients with exertional intolerance with confirmed HFpEF were included in this study. Evaluation of the subjects included resting and exercise hemodynamics, echocardiography, and mixed venous blood gas sampling. A total of 161 subjects included 114 females (71%). Compared to males, females had a higher pulmonary capillary wedge pressure (PCWP) indexed to peak exercise workload (0.8 [0.5 to 1.2] mm Hg/W vs. 0.6 [0.4 to 1] mm Hg/W, respectively; p = 0.001) and lower systemic (1.1 [0.9 to 1.5] ml/mm Hg vs. 1 [0.7 to 1.2] ml/mm Hg, respectively; p = 0.019) and pulmonary (2.9 [2.2 to 4.2] ml/mm Hg vs. 2.4 [1.9 to 3] ml/mm Hg, respectively; p = 0.032) arterial compliance at exercise. Mixed venous blood gas analysis demonstrated a greater rise in lactate indexed to peak workload (0.05 [0.04 to 0.09] mmol/l/W vs. 0.04 [0.03 to 0.06] mmol/l/W, respectively; p = 0.007) in women compared to men. Women had higher mitral inflow velocity to diastolic mitral annular velocity at early filling (E/e') ratios at rest and peak exercise, along with a higher ejection fraction and smaller ventricular dimensions. Women with HFpEF demonstrate poorer diastolic reserve with higher echocardiographic and invasive measurements of left ventricular filling pressures at exercise, accompanied by lower systemic and pulmonary arterial compliance and poorer peripheral oxygen kinetics.


Ventricular arrhythmias in cardiac anaphylaxis.
Arrhythmogenic effects of anaphylaxis and histamine were studied in guinea pigs by measuring changes of transmembrane potentials from isolated papillary muscles. Antigenic challenge of preparations obtained from passively sensitized animals induced ventricular automaticity in 1/3 of the experiments. The arrhythmogenic effects of cardiac anaphylaxis could be reproduced by exogenous histamine. Abnormal automaticity was associated with a stable diastolic membrane potential in most of the ventricular fibres and only occasionally ectopic pacemaker potentials were observed in fibres near the ventricular septum. The effective refractory period, maximum rate of depolarization of the action potential and electrical threshold were not significantly changed in ventricular anaphylaxis but in the presence of histamine the refractory time was shortened. Ventricular arrhythmias induced by histamine were increased at high extracellular Ca2+ concentrations and inhibited by Mn2+ and D 600 but were only moderately antagonized by tetrodotoxin. Pretreatment with reserpine had no effect on the abnormal automaticity. Spontaneous ventricular activity caused by histamine was markedly inhibited by the histamine H2-receptor antagonist burimamide and also by the antiarrhythmic drug, prajmalium bitartrate. The H1-receptor antagonist brompheniramine, hydrocortisone and propranolol had little or no antiarrhythmic effect.


Anti-analgesic activity of enterostatin (VPDPR) is mediated by corticosterone.
Although enterostatin (VPDPR) inhibited morphine-induced analgesia, it had no affinity for mu-opioid receptors. VPDPR administration was reported to elevate serum corticosterone levels. We found that corticosterone exhibited a similar anti-analgesic effect selective for mu-opioid. Furthermore, the anti-analgesic effect of VPDPR was inhibited by RU486, an antagonist for the glucocorticoid receptor. The anti-analgesic effect of VPDPR was not observed in adrenalectomized mice. These results suggest that the anti-analgesic activity of VPDPR is mediated by corticosterone released from the adrenal cortex.


Preoperative Nutritional Status and Risk for Subsyndromal Delirium in Older Adults Following Joint Replacement Surgery.
Subsyndromal delirium following surgery in older adults is related to increased lengths of hospital stay and increased admissions to long-term care. Impaired nutrition increases risk for delirium, but its relationship to subsyndromal delirium remains unclear. This correlational study examined the relationship between nutritional status and subsyndromal delirium in older adults. Assessments for subsyndromal delirium in 53 adults 65 years or older were completed for three consecutive days following joint replacement surgery. Relationships between nutritional status and subsyndromal delirium were analyzed. Level of significance for all tests was set at p ≤ .05. Participants' scores from the Mini Nutritional Assessment screen were significantly related (p = .05) to subsyndromal delirium severity after accounting for variability posed by age and cognition status. When preoperative risk assessment of older adults indicates nutritional risk, preoperative optimization may improve effectiveness of delirium prevention efforts.


Long-term observation of two cases of locked-in syndrome with recovery. Clinical and CT-scan features.
We report clinical features of two patients suffering from Locked-In Syndrome (LIS) who made a moderate recovery, some years after the onset: a 29-year-old man, with mitral valve stenosis, and a 41-year-old diabetic woman. CT scan findings showing cerebellar and brain stem atrophy, as well as hypodensity areas in the ventral pons, are described.


Central administration of neuromedin U activates neurons in ventrobasal hypothalamus and brainstem.
Neuromedin U (NMU) is a peptide isolated from the porcine spinal cord. Recently, two receptors for NMU have been identified and characterized. A recent study indicated that NMU is an anorectic chemical in the brain. The present study shows that NMU has an action in the brain to inhibit food intake in rats. Intracerebroventricular injection of NMU inhibited dark-phase feeding. Animals injected with NMU showed a strong increase in Fos-immunoreactive nuclei in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus, and in the parabrachial nucleus of the brain stem. Double immunohistochemistry revealed that a high number of oxytocin-immunoreactive neurons in the PVN and SON contained Fos after intracerebroventricular injection of NMU. In addition, a small proportion of vasopressinergic cells within the PVN and SON were found to contain Fos. The effect of NMU on the hypothalamus and brain stem contributes to the inhibitory effects of NMU on feeding behavior.


Color Vision: Glasses Half Full.
A new study finds that individuals with color deficiencies report long-term changes in their color vision after only a few days of wearing glasses that boost color contrasts, potentially because they learn to see or interpret color in new ways.


The use of peer mentors to enhance a smoking cessation intervention for persons with serious mental illnesses.
We evaluated a well-specified peer mentor program that enhanced a professionally led smoking cessation group for persons with serious mental illnesses. Participants were 8 peer mentors, persons with serious mental illnesses who had successfully quit smoking, and 30 program participants, persons with serious mental illnesses enrolled in a 6-month intervention. Peer mentors were trained and then helped to deliver a smoking cessation group and met with program participants individually. We assessed the mentors' skills after training, their fidelity to the model, and the program's feasibility and acceptability. We also measured the smoking outcomes of the program participants including change in exhaled carbon monoxide, a measure of recent smoking, and aspects of the peer mentor-program participant relationship. Peer mentors attained a mean score of 13.6/14 on role play assessments after training and delivered the intervention with fidelity as assessed by adherence and competence ratings (mean scores of 97% and 93%, respectively). The feasibility and acceptability of the intervention was demonstrated in that 28/30 participants met with their peer mentors regularly and only 1 participant and no peer mentor discontinued in the study. Both parties rated the interpersonal alliance highly, mean of 5.9/7. The program participants had a decline in carbon monoxide levels and number of cigarettes smoked per day (repeated measures ANOVA F = 6.04, p = .008; F = 15.87, p < .001, respectively). A total of 22/30 (73%) made a quit attempt but only 3 (10%) achieved sustained abstinence. Our study adds to the growing literature about peer-delivered interventions.


Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence.
Replication defective viral genomes (DVGs) generated during virus replication are the primary triggers of antiviral immunity in many RNA virus infections. However, DVGs can also facilitate viral persistence. Why and how these two opposing functions of DVGs are achieved remain unknown. Here we report that during Sendai and respiratory syncytial virus infections DVGs selectively protect a subpopulation of cells from death, thereby promoting the establishment of persistent infections. We find that during Sendai virus infection this phenotype results from DVGs stimulating a mitochondrial antiviral-signaling (MAVS)-mediated TNF response that drives apoptosis of highly infected cells while extending the survival of cells enriched in DVGs. The pro-survival effect of TNF depends on the activity of the TNFR2/TRAF1 pathway that is regulated by MAVS signaling. These results identify TNF as a pivotal factor in determining cell fate during a viral infection and delineate a MAVS/TNFR2-mediated mechanism that drives the persistence of otherwise acute viruses.Replication defective viral genomes (DVGs) can facilitate persistence of paramyxoviruses, but the underlying mechanisms are unclear. Using FISH, Xu et al. here analyze the cellular response to DVGs on a single cell level and show that a MAVS-mediated TNF response specifically extends survival of cells enriched in DVGs.


Evaluating the performance of different Bayesian count models in modelling childhood vaccine uptake among children aged 12-23 months in Nigeria.
Choosing appropriate models for count health outcomes remains a challenge to public health researchers and the validity of the findings thereof. For count data, the mean-variance relationship and proportion of zeros is a major determinant of model choice. This study aims to compare and identify the best Bayesian count modelling technique for the number of childhood vaccine uptake in Nigeria. We explored the performances of Poisson, negative binomial and their zero-inflated forms in the Bayesian framework using cross-sectional data pooled from the Nigeria Demographic and Health Survey conducted between 2003 and 2018. In multivariable analysis, these Bayesian models were used to identify factors associated with the number of vaccine uptake among children. Model selection was based on the -2 Log-Likelihood (-2 Log LL), Leave-One-Out Cross-Validation Information Criterion (LOOIC) and Watanabe-Akaike/Widely Applicable Information Criterion (WAIC). Exploratory analysis showed the presence of excess zeros and overdispersion with a mean of 4.36 and a variance of 12.86. Observably, there was a significant increase in vaccine uptake over time. Significant factors included the mother's age, level of education, religion, occupation, desire for last-child, place of delivery, exposure to media, birth order of the child, wealth status, number of antenatal care visits, postnatal attendance, healthcare decision maker, community poverty, community illiteracy, community unemployment, rural proportion and number of health facilities per 100,000. The zero-inflated negative binomial model was best fit with -2Log LL of -27171.47, LOOIC of 54464.2, and WAIC of 54588.0. The Bayesian zero-inflated negative binomial model was most appropriate to identify factors associated with the number of childhood vaccines received in Nigeria due to the presence of excess zeros and overdispersion. Improving vaccine uptake by addressing the associated risk factors should be promptly embraced.


Heat stress causes alterations in the cell-wall polymers and anatomy of coffee leaves (Coffea arabica L.).
Coffee plants were subjected to heat stress (37 °C) and compared with control plants (24 °C). Cell wall polysaccharides were extracted using water (W), EDTA (E) and 4M NaOH (H30 and H70). In addition, monolignols were analyzed, and the leaves were observed by microscopy. Plants under heat stress accumulated higher contents of arabinose and galactose in fraction W. Xylose contents were observed to decrease in H30 fractions after the heat stress, whereas galactose and uronic acid increased. H70 fractions from plants exposed to heat stress showed increased xylose contents, whereas the contents of arabinose and glucose decreased. Differences in the molar-mass profiles of polysaccharides were also observed. The primary monolignol contents increased after the heat stress. Structural alterations in palisade cells and ultrastructural damage in chloroplasts were also observed. Our results demonstrate that the chemical profile of coffee cell-wall polymers and structural cell anatomy change under heat stress.


Risk of hepatitis B exacerbation is low after transcatheter arterial chemoembolization therapy for patients with HBV-related hepatocellular carcinoma: report of a prospective study.
Systemic chemotherapy may lead to immune suppression and possible reactivation of hepatitis B virus (HBV), suggesting prophylactic antiviral therapy in cancer patients with HBV. Transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) is not a systemic chemotherapy, but has been partially associated with HBV reactivation. The aim of this study was to evaluate whether TACE aggravates HBV hepatitis in patients with HBV-related HCC. Eighty-nine patients with HBV-related HCC were studied prospectively. Patients treated with TACE were enrolled in the case group (n = 69), and patients in follow-up or awaiting treatment were enrolled in the control group (n = 20). TACE was performed with doxorubicin (20-60 mg) and lipiodol (2-20 mL). Three (4.3%) patients in the TACE group and 2 (10%) patients in the control group showed HBV reactivation (p= 0.334). A twofold or more increase in serum HBV DNA was detected in 21 (30.4%) patients in the TACE group and 4 (20%) patients in the control group (p= 0.361). Exacerbation of viral hepatitis B was found in 4 (5.8%) patients in the TACE group and no patients in the control group, but the difference between the two rates was not statistically significant (p= 0.271). Three of the four reactivated patients showed spontaneous recovery within 1 month, and one showed tumor-progression-related exacerbation. One session of TACE using doxorubicin and lipiodol does not significantly aggravate HBV hepatitis in patients with HBV-related HCC.


Why put all your eggs in one basket? Evolutionary perspectives on the origins of monogenic reproduction.
Sexual reproduction is ubiquitous in eukaryotes, but the mechanisms by which sex is determined are diverse and undergo rapid turnovers in short evolutionary timescales. Usually, an embryo's sex is fated at the moment of fertilisation, but in rare instances it is the maternal genotype that determines the offspring's sex. These systems are often characterised by mothers producing single-sex broods, a phenomenon known as monogeny. Monogenic reproduction is well documented in Hymenoptera (ants, bees and wasps), where it is associated with a eusocial lifestyle. However, it is also known to occur in three families in Diptera (true flies): Sciaridae, Cecidomyiidae and Calliphoridae. Here we review current knowledge of monogenic reproduction in these dipteran clades. We discuss how this strange reproductive strategy might evolve, and we consider the potential contributions of inbreeding, sex ratio distorters, and polygenic control of the sex ratio. Finally, we provide suggestions on future work to elucidate the origins of this unusual reproductive strategy. We propose that studying these systems will contribute to our understanding of the evolution and turnover of sex determination systems.


Laparoscopic pelvic mesh placement with closure of pelvic floor entrance to prevent small intestine radiation trauma - A retrospective cohort analysis.
In most pelvic malignancies radiation therapy is a main part of the treatment concept. The main dose limiting organ is the small intestine. Different mechanical methods to prevent radiation damage to the small intestine have been described. We herein report a retrospective study of laparoscopic placement of an absorbable vicryl mesh in patients requiring pelvic radiotherapy displacing the bowel out of the radiation field. The study included 6 consecutive patients requiring definitive radiotherapy due to locally advanced prostate cancer. All patients had small intestine within the radiation fields despite the use of non-invasive displacement methods. All patients underwent laparoscopic small bowel displacement from the pelvis and closure of the pelvic floor entrance using vicryl mesh placement. Peri- or postoperative complications were not seen. Postoperative radiotherapy planning CT scans confirmed displacement of the small intestine allowing all patients to receive the planned radiotherapy volume. Laparoscopic mesh placement represents a safe and efficient procedure in patients requiring high-dose pelvic radiation, presenting with unacceptable small intestine volume in the radiation field. As an alternate to native tissue, the vicryl mesh is a safe, effective substitute for small bowel exclusion from external-beam radiation therapy.


Oxidative stress in children late after Kawasaki disease: relationship with carotid atherosclerosis and stiffness.
Persistent arterial dysfunction in patients with a history of Kawasaki disease (KD) and an integral role of oxidative stress in the development of cardiovascular disease are increasingly recognized. We sought to test the hypothesis that oxidative stress is increased in KD patients and related to carotid atherosclerotic changes and stiffness. We compared the serum levels of oxidative stress biomarkers, carotid intima-media thickness (IMT), and carotid stiffness index among KD patients with coronary aneurysms (n = 32), those without coronary complications (n = 19), and controls (n = 32). Compared with controls, patients with coronary aneurysms had significantly higher serum levels of malonaldehyde (2.62 +/- 0.12 microM vs 2.22 +/- 0.07 microM, p = 0.014) and hydroperoxides (26.50 +/- 1.13 microM vs 22.50 +/- 0.62 microM, p = 0.008). A linear trend of the magnitude of oxidative stress in relation to inflammatory damage was observed for malonaldehyde (p = 0.018) and hydroperoxides (p = 0.014) levels. Serum malonaldehyde and hydroperoxide levels correlated positively with carotid IMT (p < 0.001 and p = 0.034, respectively) and stiffness index (p = 0.001 and p = 0.021, respectively). Multiple linear regression analysis identified serum malonaldehyde level as a significant determinant of carotid IMT (beta = 0.31, p = 0.006) and stiffness (beta = 0.27, p = 0.008). Our findings suggest oxidative stress is increased in KD patients with coronary aneurysms and is associated with carotid intima-media thickening and stiffening.


Hydrodynamic cavitation as a novel approach for delignification of wheat straw for paper manufacturing.
The present work deals with application of hydrodynamic cavitation for intensification of delignification of wheat straw as an essential step in the paper manufacturing process. Wheat straw was first treated with potassium hydroxide (KOH) for 48 h and subsequently alkali treated wheat straw was subjected to hydrodynamic cavitation. Hydrodynamic cavitation reactor used in the work is basically a stator and rotor assembly, where the rotor is provided with indentations and cavitational events are expected to occur on the surface of rotor as well as within the indentations. It has been observed that treatment of alkali treated wheat straw in hydrodynamic cavitation reactor for 10-15 min increases the tensile index of the synthesized paper sheets to about 50-55%, which is sufficient for paper board manufacture. The final mechanical properties of the paper can be effectively managed by controlling the processing parameters as well as the cavitational parameters. It has also been established that hydrodynamic cavitation proves to be an effective method over other standard digestion techniques of delignification in terms of electrical energy requirements as well as the required time for processing. Overall, the work is first of its kind application of hydrodynamic cavitation for enhancing the effectiveness of delignification and presents novel results of significant interest to the paper and pulp industry opening an entirely new area of application of cavitational reactors.


Multistage orbital hybridization induced by multisite exchange interactions in high-entropy perovskites for high oxygen evolution reaction.
The oxygen evolution reaction (OER) has garnered considerable attention because of its promising prospects in electrochemical energy conversion applications, but a significant challenge is faced by the insufficient understanding of sluggish OER kinetics. In fact, the intrinsic "acceptance-donation" process of electrons between active sites and reactants is responsible for improving OER activity. Herein, we suggest a multielement hybridization strategy to rematch spin electron occupation and energy splitting in high-entropy perovskites with multiple orbital coordination. In this concept, electronic hopping between t2g and eg orbitals among particular catalytic sites can be obviously enforced due to introducing more favorable energy levels from neighboring metal sites, which can demonstrate multistage orbital hybridization reaction activity. As a result, our proposed multistage-hybridized high-entropy perovskites display an impressive activity of 199.8 mA cm-2 as an overpotential of ∼0.46 V, which is ∼5.3 times that of pristine perovskite. Different from traditional catalyst designs, this study focuses on multistage orbital hybridization and electron exchange interactions through a multisite coordination mechanism to construct a fast reaction pathway. Our findings provide a new strategy for accelerating OER catalytic kinetics.


Neglected elements: What we should cover more of in international business research.
The international business (IB) field is maturing and developing conceptual frameworks, dedicated applications, and precise tools. In the course of this progression, the field has started to break away from its disciplinary roots, establishing parsimonious models using finely tuned but confined approaches. While fruitful in solidifying the sovereignty of the field, this progression comes at the expense of detecting and building on major undercurrents that define the rich IB context. We return here to the foundations of IB research to identify neglected elements and offer suggestions as to why they should and how they can be incorporated to deepen and strengthen the field's reach and impact. We discuss the neglected elements in five clusters, namely audiences and actors (intended readers and key players), locations (research sites), environmental layers (contextual tiers), history (prior paths), and interactions (among players and elements). We highlight how those clusters taken together on their conceptual underpinnings and empirical proxies will support IB research, first by way of producing a virtuous cycle of theory-to-issue research to open the perennial "black box"; and second by enabling eclectic, interdisciplinary research and retrospective investigation using a multifaceted lens.


Maternal reproductive hormone levels after repeated ACTH application to pregnant gilts.
Prenatal stress has been seen as a reason for reproductive failures in pig offspring mostly originated or mediated by changed maternal functions. In pregnant gilts, three experiments (EXP I-III) were conducted to characterize the effects of repeated ACTH on maternal cortisol concentrations (EXP I) and on the secretion of maternal reproductive hormones (LH, progesterone, estrone sulfate; EXP II + III). Exogenous ACTH was given six times every alternate day beginning either on day 49 (EXP I + II) or day 28 (EXP III) of pregnancy. As a result of treatment, elevated cortisol levels were observed for more than 6 h (EXP I). Plasma concentrations of LH were at low basal level (0.1-0.2 ng/ml), but showed a pulsatory release pattern both during first and second trimester of pregnancy. The number of LH pulses/6 h (L.S.M. +/- S.E.) of saline treated controls increased with ongoing pregnancy (1.4 +/- 0.1 versus 2.0 +/- 0.2 in EXP III and EXP II, respectively). After ACTH treatment the number of LH pulses did not differ between the two gestational stages (1.3 +/- 0.2 and 1.4 +/- 0.2 in EXP III and EXP II, respectively). However, differences ( P < 0.05) were obtained comparing the LH pulse number of ACTH and saline treated sows during the second trimester of pregnancy. Moreover, areas under the curve (AUC) of each LH pulse and of all LH values over the baseline were significantly reduced by treatment. The levels of progesterone increased (P < 0.05) for 150-170 min after each ACTH application both in EXP II and EXP III. The concentrations of 17alpha-hydroxy-progesterone revealed likewise a significant elevation after each ACTH injection. Throughout EXP III, estrone sulfate concentrations were found to decrease (from 2.8-16.9 ng/ml on day 28 to 0.02-0.04 ng/ml on day 38) but without differences between ACTH-and saline-treated gilts. Further data of EXP II and EXP III, e.g. number of piglets born alive, confirmed the absence of detrimental treatment effects. Thus, repeated ACTH administration with subsequent release of cortisol is able to influence the release pattern of maternal reproductive hormones. However, these findings demonstrate that stress-related effects are dependent on the stage of pregnancy. The detected changes may affect feto-maternal interactions and, as a result, fetal reproductive development.


Total assignments, including four aromatic residues, and sequence confirmation of the decapeptide tyrocidine A using difference double resonance. Qualitative nuclear overhauser effect criteria for beta turn and antiparallel beta-pleated sheet conformations.
The complete assignments of all the proton magnetic resonance signals from each NH-CalphaH-CbetaH2 moiety in a complex peptide containing several residues of the same type has not yet been achieved without specific or stereospecific isotopic enrichment. We report the sequencing and proton magnetic resonance spectral assignments, including those of 4 aromatic residues, of tyrocidine A, an analog of the decapeptide gramicidin S. Two complementary methods, proton-proton nuclear Overhauser enhancements and scalar decoupling, evaluated by two distinct forms of difference double resonance, were used. All chemical shifts, scalar coupling constants, and [1H:1H] nuclear Overhauser enhancements for the backbone protons are reported. The [1H:1H] nuclear Overhauser enhancements are consistent with tyrocidine A possessing a beta-I turn/beta-II' turn/antiparallel beta-pleated sheet conformation. In addition to the previously proposed nuclear Overhauser enhancement criteria for beta turns and antiparallel beta sheets, another criterion for identifying the antiparallel beta sheet is demonstrated; namely, the nuclear Overhauser enhancement between 2 CalphaH protons of the central resisdues, in this case the Phe7CalphaH and Orn2CalphaH.


[Differentiation of achondroplasia and other similar genetic dwarfism by FGFR3 gene analysis].
To study the gene mutation of Chinese patients with achondroplasia(ACH) and to set up a simple and rapid molecular diagnostic method to differentiate ACH from other similar genetic dwarfism. The specific fragment of fibroblast growth factor receptor 3(FGFR3) transmembrane domain was amplified from dried blood spots of 21 patients with ACH and 6 suspicious patients with ACH by polymerase chain reaction, then mutation was screened and detected by restrictive enzyme analysis, single strand conformation polymorphism(SSCP) and denaturing gradient gel electrophoresis(DGGE). One out of 6 suspicious cases was ACH and 5 were pseudoachondroplasia(PSACH). Twenty-one out of 22 patients with ACH bore a G to A transition at nucleotide 1138 and 1 bore a G to C transversion at this same position. The nucleotide 1138 of FGFR3 gene is also the hotspot of mutation in Chinese patients with ACH. A simple and rapid molecular diagnostic method has been set up to differentiate ACH from other similar genetic dwarfism.


Molecular and cellular mechanisms underlying postoperative paralytic ileus by various immune cell types.
Postoperative ileus (POI) is a well-known complication following gut manipulation or surgical trauma, leading to an impaired gut motility and prolonged postoperative recovery time. Few current therapeutic strategies can prevent POI, and this disorder remains to be a major clinical challenge for patients undergoing surgery. Comprehensive understanding of cellular and molecular mechanisms related to the pathogenesis of POI stimulates the discovery of more promising targets for treatment. POI is closely associated with a series of inflammatory events within the bowel wall, and as key components of inflammatory mechanisms, different types of immune cells, including macrophages, dendritic cells, and T lymphocytes, play significant roles during the development of POI. A variety of immune cells are recruited into the manipulation sites after surgery, contributing to early inflammatory events or impaired gut motility. Our review intends to summarize the specific relationship between different immune cells and POI, mainly focusing on the relevant mechanisms underlying this disorder.


Efficacy of catheter ablation from the noncoronary aortic cusp of verapamil-sensitive atrial tachycardia arising near the atrioventricular node.
The efficacy of catheter ablation from the noncoronary aortic cusp (NCC) of verapamil-sensitive atrial tachycardia arising near the atrioventricular node (AVN-AT) has yet to be fully clarified. We elucidated the determinant of an effective AVN-AT ablation from the NCC. After identifying the earliest atrial activation site (EAAS) during tachycardia, the direction of the slow conduction zone (SCZ) of the reentry circuit was identified by demonstrating manifest entrainment in 26 patients with AVN-AT. Catheter ablation was initially performed from the NCC irrespective of the local activation time. If NCC ablation was ineffective, catheter ablation was performed targeting the SCZ entrance. Then the anatomical relationship between the SCZ and the successful ablation site was elucidated. NCC catheter ablation terminated AVN-AT in 14 patients (NCC group) but not in 12 (non-NCC group). Catheter ablation targeting the SCZ entrance terminated all non-NCC group ATs. The local activation time at the NCC relative to the EAAS did not differ between the NCC and non-NCC groups (10.1 ± 6.5 ms vs 11.2 ± 4.8 ms; P = .6333). The direction of the SCZ was posterior to the EAAS in all NCC group patients; however, it was posterolateral (n = 5) and lateral (n = 7) to the EAAS in the non-NCC group, suggesting that the SCZ existed in the direction of the NCC in the NCC group but was away from the NCC in the non-NCC group. A close proximity between the NCC and the SCZ of the reentry circuit, but not the local activation time at the NCC, determined the efficacy of NCC catheter ablation in AVN-ATs.


Geminivirus C4 proteins inhibit GA signaling via prevention of NbGAI degradation, to promote viral infection and symptom development in N. benthamiana.
The phytohormone gibberellin (GA) is a vital plant signaling molecule that regulates plant growth and defense against abiotic and biotic stresses. To date, the molecular mechanism of the plant responses to viral infection mediated by GA is still undetermined. DELLA is a repressor of GA signaling and is recognized by the F-box protein, a component of the SCFSLY1/GID2 complex. The recognized DELLA is degraded by the ubiquitin-26S proteasome, leading to the activation of GA signaling. Here, we report that ageratum leaf curl Sichuan virus (ALCScV)-infected N. benthamiana plants showed dwarfing symptoms and abnormal flower development. The infection by ALCScV significantly altered the expression of GA pathway-related genes and decreased the content of endogenous GA in N. benthamiana. Furthermore, ALCScV-encoded C4 protein interacts with the DELLA protein NbGAI and interferes with the interaction between NbGAI and NbGID2 to prevent the degradation of NbGAI, leading to inhibition of the GA signaling pathway. Silencing of NbGAI or exogenous GA3 treatment significantly reduces viral accumulation and disease symptoms in N. benthamiana plants. The same results were obtained from experiments with the C4 protein encoded by tobacco curly shoot virus (TbCSV). Therefore, we propose a novel mechanism by which geminivirus C4 proteins control viral infection and disease symptom development by interfering with the GA signaling pathway.


Inhibition of inflammation and infiltration of M2 macrophages in NSCLC through the ATF3/CSF1 axis: Role of miR-27a-3p.
Non-small cell lung cancer (NSCLC) imposes a significant economic burden on patients and society due to its low overall cure and survival rates. Tumour-associated macrophages (TAM) affect tumour development and may be a novel therapeutic target for cancer. We collected NSCLC and tumour-adjacent tissue samples. Compared with the tumour-adjacent tissues, the Activation Transcription Factor 3 (ATF3) and Colony Stimulating Factor 1 (CSF-1) were increased in NSCLC tissues. Levels of ATF3 and CSF-1 were identified in different cell lines (HBE, A549, SPC-A-1, NCI-H1299 and NCI-H1795). Overexpression of ATF3 in A549 cells increased the expression of CD68, CD206 and CSF-1. Moreover, levels of CD206, CD163, IL-10 and TGF-β increased when A549 cells were co-cultured with M0 macrophages under the stimulation of CSF-1. Using the starbase online software prediction and dual-luciferase assays, we identified the targeting between miR-27a-3p and ATF3. Levels of ATF3, CSF-1, CD206, CD163, IL-10 and TGF-β decreased in the miR-27a mimics, and the tumour growth was slowed in the miR-27a mimics compared with the mimics NC group. Overall, the study suggested that miR-27a-3p might inhibit the ATF3/CFS1 axis, regulate the M2 polarization of macrophages and ultimately hinder the progress of NSCLC. This research might provide a new therapeutic strategy for NSCLC.


HybridArc: a novel radiation therapy technique combining optimized dynamic arcs and intensity modulation.
This investigation focuses on possible dosimetric and efficiency advantages of HybridArc-a novel treatment planning approach combining optimized dynamic arcs with intensity-modulated radiation therapy (IMRT) beams. Application of this technique to two disparate sites, complex cranial tumors, and prostate was examined. HybridArc plans were compared with either dynamic conformal arc (DCA) or IMRT plans to determine whether HybridArc offers a synergy through combination of these 2 techniques. Plans were compared with regard to target volume dose conformity, target volume dose homogeneity, sparing of proximal organs at risk, normal tissue sparing, and monitor unit (MU) efficiency. For cranial cases, HybridArc produced significantly improved dose conformity compared with both DCA and IMRT but did not improve sparing of the brainstem or optic chiasm. For prostate cases, conformity was improved compared with DCA but not IMRT. Compared with IMRT, the dose homogeneity in the planning target volume was improved, and the maximum doses received by the bladder and rectum were reduced. Both arc-based techniques distribute peripheral dose over larger volumes of normal tissue compared with IMRT, whereas HybridArc involved slightly greater volumes of normal tissues compared with DCA. Compared with IMRT, cranial cases required 38% more MUs, whereas for prostate cases, MUs were reduced by 7%. For cranial cases, HybridArc improves dose conformity to the target. For prostate cases, dose conformity and homogeneity are improved compared with DCA and IMRT, respectively. Compared with IMRT, whether required MUs increase or decrease with HybridArc was site-dependent.


Egyptian perspectives on potential risk of paracetamol/acetaminophen-induced toxicities: Lessons learnt during COVID-19 pandemic.
Paracetamol/Acetaminophen was widely used as a first-line antipyretic and analgesic for COVID-19 patients without giving any attention to the potential risk of related toxicities. A survey was conducted on 176 Egyptians using an online survey portal to assess their knowledge, and attitude regarding potential risk of paracetamol toxicities and whether COVID-19 pandemic affected their practices regarding safe use of paracetamol. The self-administered questionnaire was developed by the researchers and was validated by expert opinions. A pilot testing of the questionnaire was done. Alpha Cronbach test used to assess the internal consistency reliability of the survey revealed good reliability. Overall percent-score revealed that only 24.4% of participants had good knowledge about paracetamol and its related potential toxicities. 62.5% of participants considered paracetamol safer than other medications of the same indications. 42.6% of participants could advise others to use paracetamol without prescription. According to the participants' responses, physicians were less concerned to give instructions about possibility of overdosage. Our results also revealed that participants' administration of paracetamol without physician prescription was more during COVID-19. Practice of paracetamol administration more than the allowed number of tablets/day was significantly more evident during the pandemic. We concluded that the unsupervised use of paracetamol is an alarming sign that should be addressed as this could lead to a high rate of accidental paracetamol toxicity. A lesson learnt from COVID-19 pandemic is the need to implement behavior change measures to mitigate the risk of accidental paracetamol toxicity.


Effects of fungicides on fitness and Buchnera endosymbiont density in Aphis gossypii.
Several agricultural fungicides are known to affect insect pests directly and these effects may be transgenerational and mediated through impacts on endosymbionts, providing opportunities for pest control. The cotton aphid Aphis gossypii is a polyphagous pest that can cause large crop yield losses. Here, we tested the effects of three fungicides, pyraclostrobin, trifloxystrobin and chlorothalonil, on the fitness and Buchnera endosymbiont of A. gossypii. The formulations of trifloxystrobin and pyraclostrobin, and the active ingredient of pyraclostrobin produced dose-dependent mortality in A. gossypii, whereas there was no dose-dependent mortality for chlorothalonil. The formulations of trifloxystrobin and pyraclostrobin significantly reduced the lifespan and fecundity of A. gossypii, and increased the density of Buchnera in the parental generation but not the (unexposed) F1 . When the active ingredient of pyraclostrobin was tested, the lifespan of the F0 generation was also reduced, but the density of Buchnera was not, indicating that non-insecticidal chemicals in the fungicide formulation may affect the density of the endosymbiont of A. gossypii. There was no transgenerational effect of the active ingredient of pyraclostrobin on the lifespan and Buchnera of (unexposed) F1 . Our results suggest that formulations of two strobilurin fungicides have immediate impacts on the fitness of A. gossypii, and chemicals in the formulation impact the density of the primary Buchnera endosymbiont. Our study highlights the potential effects of non-insecticidal chemicals of fungicides on aphid pests and their primary endosymbionts but direct connections between fitness and Buchnera densities remain unclear. © 2023 Society of Chemical Industry.