A novel splice-site mutation of ATP2A2 gene in a Chinese family with Darier disease.
Darier disease (DD; OMIM 124200) is a rare, autosomal dominant hereditary skin disorder characterized by abnormal keratinization and acantholysis. The causes of DD are defects in the ATP2A2 gene, which encodes the sarco/endoplasmic reticulum Ca(2+) ATPase isoform 2 (SERCA2). The aim of this study was to report a novel splice-site mutation and to examine the relative quantity expression of ATP2A2 gene in a Chinese family with DD. Polymerase chain reaction (PCR) was carried out to amplify the exons and flanking intron boundaries of the ATP2A2 gene followed by direct sequencing. A novel splice-site mutation (IVS20-6T>A) was found in the family, which was confirmed by creating a novel HinfI (NEB Inc) recognition site and RT-PCR. Real-time quantitative PCR showed approximately 53 and 52% reduction of ATP2A2 expression of the proband and his father, respectively. The results support the proposition that haploinsufficiency is a common mechanism for the dominant inheritance of DD.


What Is the Role of Transcarotid Artery Revascularization?
Carotid endarterectomy (CEA) is the gold-standard method of carotid revascularization in symptomatic patients with ≥50% and in asymptomatic patients with ≥70% stenosis. Transfemoral carotid artery stenting (TFCAS) has been associated with higher perioperative stroke rates compared to CEA in several studies. On the other hand, transcarotid artery revascularization (TCAR) has outperformed TFCAS in patients who are considered high risk for surgery. There is increasing data that supports TCAR as a safe and efficient technique with outcomes similar to those of CEA, but additional level-one studies are necessary to evaluate the long-term outcomes of TCAR in high- and standard-risk patients.


Can growth hormone increase, after clonidine administration, predict the dose of human menopausal hormone needed for induction of ovulation?
Recent observations claimed that growth hormone (GH) administration increased the sensitivity of the ovary to gonadotropin stimulation. These findings prompted us to assess whether ovarian response to human menopausal gonadotropin (hMG) is correlated to GH reserve. Before hMG administration, 25 patients were tested for GH reserve by administration of clonidine. Of the 25 patients, 8 showed a significant increase in GH (9.2 +/- 4.5 ng/mL) and needed a significantly lower dose of hMG/human chorionic gonadotropin to elicit a good ovarian response than the 17 patients who did not respond to clonidine administration may help to estimate the initial dose range of hMG necessary for induction of ovulation.


Recreating in vitro tripartite mycorrhizal associations through functional bacterial biofilms.
Arbuscular mycorrhizal fungi (AMF) and beneficial bacteria are found naturally associated with most terrestrial plant roots. While it is now well known that bacteria colonize AMF and can form aggregates and biofilms, little is known about how interactions between bacterial communities and AMF take place under both in situ and in vitro conditions. We investigated the impact of inoculation with AMF-associated bacteria (AABs) of AMF by in vitro recreation of the interaction on synthetic growth media in a two-compartment Petri plate system. The inoculated AABs were found to be associated with the mycorrhizal co-culture and were found to migrate along growing AMF hyphae and to be associated with the spore surface. AABs differentially influenced the growth of the AMF and their functional capability demonstrated by analysis of phosphate solubilization, nitrogen fixation, and biofilm formation. We have thus characterized these important interactions adding to a further understanding of the synergistic relationship between the two cross-kingdom microbial partners. KEY POINTS: • An in vitro assay was utilized to recreate functional biofilms with AMF-associated bacteria. • AMF-associated bacteria formed a biofilm and enhanced sporulation of Rhizophagus irregularis. • AMF-bacterial interactions through biofilm formation influence the functional capability of both partners.


Non-Disclosure of HIV-Positive Serostatus: Unmatched Case-Control Study in People Living with HIV in Public Health Facilities of Gedeo Zone, Southern Ethiopia.
Non-disclosure of HIV-positive status (NDHPSS) is the individual's experience of hiding their HIV status from other people or groups. People who fail to reveal their HIV-positive serostatus risk contracting the virus again, not receiving the best possible care, and even dying. To assess predictors of NDHPSS in people living with HIV in public health facilities in Gedeo-Zone, Southern-Ethiopia. In Gedeo-Zone, Southern Ethiopia, a facility-based, unmatched, case-control study was carried out from the first of February to March 30, 2022GC. With a case-to-control ratio of 1:1, a total of 360 respondents (89 cases and 271 controls) were involved. The respondents were chosen using a sequential sampling technique. EpiData-V-3.1 was used to enter the data, and SPSS-V-25 was used to analyse it. To determine the factors that were connected to the result, a binary logistic regression analysis was performed. AOR at the 95% confidence interval and p-values under 0.05 were utilised to explain their statistical significance. The study had 360 participants in total-271 controls and 89 cases-resulting in a response rate of 97.6%. The average age of the participants was 35.6 years (SD: 8.3). After adjusting the possible confounders, sex (AOR = 2.8, 95% CI: 1.04-7.56), residence (AORs = 3.52, 95% CI: 2.83-9.39), WHO clinical stage I (AORs = 4.68, 95% CI: 1.9-22.1), short duration of ART follow-up care (AOR = 4.21, 95% CI: 1.65-10.73), and number of lifetime sexual partners (AOR = 6.9, 95% CI: 1.86-26.3) were significantly associated factors with the outcome. According to this study, living in a rural area and being in WHO clinical stage one, in addition to being a woman and having multiple sexual partners during one's lifetime, were predictors of non-disclosure of an HIV-positive serostatus. As a result, encouraging people with HIV in WHO stage I and those who have had more than one sexual partner in their lifetime to disclose their status and expanding counselling services for rural residents and women have a substantial impact on reducing the HIV load.


Eravacycline infusion-related hypoesthesia: A case report.
Eravacycline (ERV) is often used for drug-resistant gram-negative and nontuberculous mycobacteria (NTM) infections, but infusion site reactions are a potential adverse effect. We report a case of severe hypoesthesia secondary to ERV infusion. A 74-year-old man presented with dyspnea, shortness of breath, and hemoptysis after being treated for community-acquired pneumonia. On the basis of respiratory cultures performed several weeks before the index hospitalization, he was diagnosed with Mycobacterium chelonae pneumonia. On hospital day (HD) 2, the infectious diseases consult team, guided by susceptibilities, initiated a regimen of azithromycin, levofloxacin, and ERV 80 mg (1 mg/kg) intravenously every 12 hours infused over 1 hour in 250 mL of normal saline. Approximately 25 minutes after the ERV infusion began, the patient reported tingling and numbness in his fingers, hands, and mouth, with shooting pain in his head. Symptoms resolved with cessation of the ERV infusion. On HD 3, the same ERV dose and volume was administered with an extended infusion time of 2 hours. The patient experienced the same reaction after 58 minutes, which ceased shortly after the infusion was stopped. Use of ERV was subsequently discontinued. The Naranjo adverse drug reaction probability scale score was 9, indicating a definite reaction. A review of the Food and Drug Administration Adverse Event Reporting System through March 2021 identified 22 ERV-associated events. Among these, 18% appear to be related to ERV infusions. Published results from phase 3 clinical trials did not document any hypoesthesia. It is unknown whether there is a correlation between concentration, dose, or infusion time and associated reactions. This is a unique case of severe hypoesthesia secondary to ERV infusion leading to drug discontinuation. More data are needed to determine effective mitigation strategies.


New regulators of NF-kappaB in inflammation.
Research on the biological function of nuclear factor-kappaB (NF-kappaB), a key mediator of inducible transcription in the immune system, has traditionally focused on its role in the initiation of innate and adaptive immune responses. These studies have largely concentrated on the mechanisms of signalling that lead to NF-kappaB activation and on the positive role of NF-kappaB in both physiological immunity and pathological inflammation. More recently, there has been growing interest in the mechanisms that directly regulate the NF-kappaB transcriptional programmes. As a result, several new NF-kappaB regulatory components have been identified and some of the known components have been assigned new roles. In this Review, we discuss these new insights into the regulation of NF-kappaB.


Evolutionary variation and adaptation in a conserved protein kinase allosteric network: implications for inhibitor design.
The activation of protein kinases involves conformational changes in key functional regions of the kinase domain, a detailed understanding of which is essential for the design of selective protein kinase inhibitors. Through statistical analysis of protein kinase sequences and crystal structures from diverse organisms, we recently proposed that the activation of protein kinases involves a hidden strain switch in the catalytic loop. Specifically, we demonstrated that the backbone torsion-angles of residues in the catalytic loop switch from a "relaxed" to "strained" conformation upon kinase activation and the strained geometry results in a network of hydrogen bonds involving conserved non-catalytic residues in the ATP and substrate binding lobes. Here, we further explore this activation mechanism by analyzing families that lack the canonical hydrogen bonding interactions with the strained backbone. We find that alternative mechanisms have evolved to maintain catalytic loop strain. In PIM kinase, for example, two water molecules account for the lack of a conserved aspartate in the substrate binding by hydrogen bonds to the strained backbone. We discuss the relevance of these findings in the design of family-specific allosteric inhibitors, and in predicting the structural and functional impact of cancer mutations that alter the strain associated hydrogen bonding network. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012).


Urotensin II acts as a modulator of mesopontine cholinergic neurons.
Urotensin II (UII) is a vasomodulatory peptide that was not predicted to elicit CNS activity. However, because we have recently shown that the urotensin II receptor (UII-R) is selectively expressed in rat mesopontine cholinergic (MPCh) neurons, we hypothesize that UII may have a central function. The present study demonstrates that the UII system is able to modulate MPCh neuron activity. Brain slice experiments demonstrate that UII excites MPCh neurons of the mouse laterodorsal tegmentum (LDTg) by activating a slow inward current. Furthermore, microinfusion of UII into the ventral tegmental area produces a sustained increase in dopamine efflux in the nucleus accumbens, as measured by in vivo chronoamperometry. In agreement with UII activation of MPCh neurons, intracerebroventricular injections of UII significantly modulate ambulatory movements in both rats and mice but do not significantly affect startle habituation or prepulse inhibition. The present study establishes that UII is a neuromodulator that may be exploited to target disorders involving MPCh dysfunction.


Effect of intradermal needle therapy at combined acupoints on patients' gastrointestinal function following surgery for gastrointestinal tumors.
Postoperative gastrointestinal function recovery is critical for rapid rehabilitation of patients with gastrointestinal tumors. Traditional Chinese medicine offers considerable advantages for gastrointestinal disease treatment. However, no study has reported the clinical efficacy of intradermal needle therapy (INT) at the Yuan-source, Luo-connecting, and He-sea points of the corresponding meridian for gastrointestinal function in patients following surgery for gastrointestinal tumors. To investigate the effect of INT at combined acupoints on patients' gastrointestinal function following surgery for gastrointestinal tumors. This randomized controlled trial was conducted at the Second Affiliated Hospital of Xi'an Jiaotong University on patients with diagnosed gastrointestinal cancer, no distant metastases or organ failure, and hospitalized for elective radical tumor resection, who did not receive preoperative radiotherapy or chemotherapy. Participants were randomly allocated to either the intervention (n = 32) or the control (n = 32) group. Participants in the control group received enhanced recovery care, while those in the intervention group received enhanced recovery care combined with INT at the Yuan-source, Luo-connecting, and He-sea points. After surgery, INT was performed immediately upon the patient's return to the ward, and continued for seven consecutive days. The independent samples t-test, chi-square test, and generalized estimating equations were used for data analysis. The participants' ages ranged from 40 to 80 years (average 63 ± 10.1 years). Most participants underwent surgery for either gastric (43.8%) or colon cancer (39.1%) and had adenocarcinoma (87.5%). Significant differences were noted in time to first postoperative flatus passage (66 ± 27 h vs 103 ± 41 h, P < 0.001), time to first defecation (106 ± 44 h vs 153 ± 50 h, P < 0.001), and time to first oral feeding (73 ± 30 h vs 115 ± 38 h, P < 0.001) between the intervention and control groups. Gastrointestinal symptoms, including abdominal distension, nausea, and fatigue 48 h and 72 h after surgery, were significantly alleviated in the intervention group compared with that observed in the control group (P < 0.05). INT at the Yuan-source, Luo-connecting, and He-sea points can promote recovery of gastrointestinal function and ease gastrointestinal symptoms in patients following surgical resection of gastrointestinal tumors.


Assessment of the informed consent process in the provision of dental care in Mulago hospital, Uganda.
Informed consent is grounded in the principle of autonomy and represents patients' right to participate in clinical decisions regarding their treatment. It is equally an ethical and legal requirement in dental care. The dental practitioner must offer appropriate information about all aspects of the treatment and ensure that a patient understands and makes an informed decision. There is limited literature on informed consent for dental care in Uganda. This study assessed patients' comprehension of the informed consent process and dental practitioners' practices in obtaining informed consent. This was a cross-sectional descriptive study conducted in the Dental Outpatient Department of Mulago Hospital. Two separate questionnaires were employed to collect data from dental patients and dental practitioners, respectively. Data were entered into Epi-data, coded, and imported into STATA 14 for statistical analysis. Overall, the level of patients' comprehension of the informed consent process was 91.1%, with 96.3% who felt the dental practitioners satisfactorily explained to them the treatment received and, 65.1% understood very well the information given to them. About 93.5% of the patients confessed that they were given other options of treatment while 98.5% consented before the dental practitioners started treatment. Most dental practitioners 94.7% followed good clinical practices in obtaining informed consent and 98.7% gave information before initiation of treatment while 85.3% obtained consent from patients before starting any procedures. However, only 5.3% of the dental practitioners obtained written informed consent from patients. There is a need to devise ways of improving patients' understanding of the treatment information given to them to support them make better and informed decisions regarding their care. Dental practitioners need to put more emphasis on the use of written consent in dental care because documentation helps in providing accountability and protects dentists from medical litigation in case the patients were to sue them for any treatment-related complications.


Single cell full-length transcriptome of human subcutaneous adipose tissue reveals unique and heterogeneous cell populations.
White adipose tissue (WAT) is a complex mixture of adipocytes and non-adipogenic cells. Characterizing the cellular composition of WAT is critical for identifying where potential alterations occur that impact metabolism. Most single-cell (sc) RNA-Seq studies focused on the stromal vascular fraction (SVF) which does not contain adipocytes and have used technology that has a 3' or 5' bias. Using full-length sc/single-nuclei (sn) RNA-Seq technology, we interrogated the transcriptional composition of WAT using: snRNA-Seq of whole tissue, snRNA-Seq of isolated adipocytes, and scRNA-Seq of SVF. Whole WAT snRNA-Seq provided coverage of major cell types, identified three distinct adipocyte clusters, and was capable of tracking adipocyte differentiation with pseudotime. Compared to WAT, adipocyte snRNA-Seq was unable to match adipocyte heterogeneity. SVF scRNA-Seq provided greater resolution of non-adipogenic cells. These findings provide critical evidence for the utility of sc full-length transcriptomics in WAT and SVF in humans.


The effects of external beam irradiation on the growth of flat bones in children: modeling a dose-volume effect.
To model the effects of external beam irradiation on the developing flat bones of pediatric patients undergoing radiation therapy (RT) for tumors involving the musculoskeletal system. Patients with image-guided RT plans including areas adjacent to facial or pelvic flat bones underwent retrospective contouring of nontumor involved flat bones ipsilateral and contralateral to the treatment side. Radiation dose-volume information and bone volume data (initial and the most recent follow-up) were analyzed in 15 paired flat bones from 10 patients (ages 1.0-17.0 years). The models to predict bone growth after completion of RT (v(post)) were based on initial bone volume (v(pre)), the patient's age, time to follow-up (t), and the dose-volume parameter (v(Int35+)). We developed a dose effects model as follows: Log (v(post) / v(pre)) = beta(time)t + beta(age group)t + beta(dose)t v(Int35). The dose-volume parameter v(Int35) predicted significantly for alterations in growth in younger patients, but not for older patients. The predictability of the fitted model for relative change in bone growth improved in the younger age group with the addition of the dose-volume term v(Int35) (correlation coefficient of r = 0.5510 to r = 0.6760 with the addition v(Int35)). Our model accurately predicted flat bone growth and is notable for the inclusion of radiation dose-volume information, which is now available in the image-guided RT era. Further refinement of this model in a prospective patient population is underway.


Micro-vibrations at 30 Hz on bone cells cultivated in vitro produce soluble factors for osteoclast inhibition and osteoblast activity.
It has been claimed that micro-pulse vibration can accelerate the rate of tooth movement during orthodontic treatment; however, the underlying cellular mechanism has yet to be elucidated. The purpose of this study was to understand the mechanisms underlying tooth movement acceleration by measuring alterations in a panel of intercellular signalling molecules and markers of osteoblast/osteoclast function following micro-pulse vibration for 20 min at 30 Hz. Primary BALB/c mouse calvarial osteoblasts were cultivatedin vitro and subjected to micro-pulse vibration (0.25 N; 30 Hz) with the AcceleDent® Aura appliance for 20 min and assayed for IL-4, IL-13, IL-17, OPG, soluble RANKL and TGF-β protein by ELISA; for PCNA in osteoblasts and caspase 3/7 in osteoclasts by immunohistochemistry; for IL-4, IL-13, and Il-17 in osteoclasts by ELISA; and for cathepsin K by flow cytometry. After micro-pulse vibration, the murine osteoblast culture supernatant showed increased IL-4, IL-13, IL-17, OPG and TGF-β levels and decreased RANKL levels; PCNA in osteoblasts and caspase 3/7 in osteoclasts were also upregulated. The osteoclast culture supernatant had increased levels of IL-4, IL-13 and IL-17, and cathepsin K was upregulated in the treatment group compared with the control group. Micro-pulse vibration promotes the production of soluble factors that inhibit osteoclasts, promote apoptosis and activate osteoblasts in vitro, which could increase bone mineral density. Further studies should be conducted in order to understand the biological mechanism of how micro-vibration might influence tooth movement during orthodontic treatment.


The emerging potential role of p62 in cancer treatment by regulating metabolism.
p62 is an important multifunctional adaptor protein participating in autophagy and many other activities. Many studies have revealed that p62 is highly expressed in multiple cancers and decreasing its level can effectively lower the proliferation ability of cancer cells. Moreover, much research has highlighted the significant role of the regulation of cancer cell metabolism in helping to treat tumors. Recent reports demonstrate that p62 could regulate cancer cell metabolism through various mechanisms. However, the relationship between p62 and cancer cell metabolism as well as the related mechanisms has not been fully elucidated. In this review, we describe glucose, glutamine, and fatty acid metabolism in tumor cells and some signaling pathways that can regulate cancer metabolism and are mediated by p62.


Admission C-reactive protein, WBC count, glucose, and body temperature in severe odontogenic infections: a retrospective study using severity scores.
The purpose of this study was to determine whether various serum marker levels (C-reactive protein [CRP], white blood cell [WBC] count, glucose) or body temperature at admission are associated with severity of odontogenic infections. This retrospective chart review of patients admitted to the hospital for treatment of severe odontogenic infections (SOIs) over a 5-year period (2016-2020) assigned patients with a severity score (SS) ≥5 to group A and those with an SS <5 to group B. Serum marker levels and temperature at admission were collected, and comparisons between group A and group B were conducted for serum marker levels and body temperature at admission using 2-sample t tests. The mean serum CRP and temperature at admission between the 2 groups was not statistically significant (P > .05). The mean WBC count and serum glucose at admission between the 2 groups was statistically significant (P = .001 and P = .036, respectively). This study demonstrates that serum glucose and WBC at admission are significantly higher in patients with more SOIs. In addition, serum CRP and body temperature at admission are not adequate prognostic indicators of odontogenic infection severity.


Clinical features related to hospital expenses for non-cystic fibrosis bronchiectasis in China.
Bronchiectasis is a common chronic airway disease. We investigated the economic burden and associated factors of bronchiectasis in China. In this multicenter retrospective cohort study, we reviewed medical records of patients admitted to 18 tertiary hospitals during 2010 to 2014 with a bronchiectasis-related diagnosis. A total 5469 patients with bronchiectasis were admitted, accounting for 3.13% ± 1.80% of all discharged patients with any diagnosis during the same period; 13 patients died upon discharge. The median hospitalization cost was RMB 8421.52 (RMB 5849.88-12,294.47). Risk factors associated with hospitalization costs included age at admission (>70 vs. <40 years, odds ratio (OR) = 1.221, 95% confidence interval (CI) = 1.082-1.379; >80 vs. <40 years, OR = 1.251, 95% CI = 1.089-1.438), smoking (≤15 packs/year vs. non-smokers, OR = 1.125, 95% CI = 1.006-1.271; >15 packs/year vs. non-smokers, OR = 1.127, 95% CI = 1.062-1.228), length of hospitalization (OR = 1.05, 95% CI = 1.046-1.054), combination antibiotic treatment (OR = 1.089, 95% CI = 1.033-1.148), cough (OR = 0.851, 95% CI = 0.751-0.965), dyspnea (OR = 0.93, 95% CI = 0.878-0.984), chronic obstructive pulmonary disease (OR = 0.935, 95% CI = 0.878-0.996), respiratory failure (OR = 0.923, 95% CI = 0.862-0.989), cor pulmonale (OR = 0.919, 95% CI = 0.859-0.982), and death (OR = 1.816, 95% CI = 1.113-2.838). Age, smoking status, symptoms, and respiratory comorbidities were associated with hospitalization costs of bronchiectasis.


Anemia among children living with HIV/AIDS on HAART in Mekelle Hospital, Tigray regional state of northern ethiopia - a cross-sectional study.
Anemia is a common complication of HIV/AIDS in children. There is lack of evidence on anemia prevalence among children living with HIV/AIDS on highly active antiretroviral therapy (HAART) in Tigray regional state, which the current study aimed to generate. An institution-based cross-sectional study was conducted on 241 children living with HIV/AIDS on HAART attending the antiretroviral therapy (ART) clinic of Mekelle hospital from November 2018-January 2019. Socio-demographic data were collected using a structured pretested questionnaire. Participants' hemoglobin level was utilized to determine the prevalence of anemia. WHO cut-off values for Hgb were used to categorise the severity of anemia. Microscopic examination was performed for morphological classification of anemia. Among the participants, 7 % (n = 16) were anemic in this study. Of these, 56 %, 19 %, and 25 % had mild, moderate, and severe anemia, respectively. Morphologically, normocytic-normochromic anemia was found the most common type of anemia in this study. The prevalence of anemia among participants was low in this study. However, a considerable proportion of participants had severe anemia, requiring regular monitoring of anemia status in these patients for better clinical outcomes and quality of life improvements.


Contesting competence--change in the Danish food safety system.
This paper presents the rationalisation and centralisation in the last decade in the Danish food safety system and illustrates some of the frustration it raised among market actors. The article argues that, even if the reforms did not change formal division of responsibilities for securing food safety, the implementation of new principles in the food safety control procedure in the form of HACCP and the publication of results from public food inspection visits (The Danish Smiley System) have altered the roles and responsibilities of market actors and public actors at a practical level. In this way the reform raises new questions about the efficiency of the food safety control system.


Evaluation of the satisfaction level of patients visiting dental emergency services.
Inadequate data is available of patient satisfaction in dental emergency departments in India. This study was undertaken with the aim to evaluate the satisfaction level of patients visiting emergency services of a dental institute in an Indian city. A questionnaire-based cross-sectional exploratory study was designed over a period of 2 months. A total of 51 subjects visiting the dental emergency services after routine working hours participated in this questionnaire-based study and submitted their responses. Pearson's Chi-square test. A statistically significant correlation (P < 0.05) was observed between effectiveness of the treatment given in terms of relief from complaints with the experience at reception, rating the hospital in terms of overall waiting time for any service with ambience (P = 0.031), between effectiveness of the treatment given in terms of control/relief from complaints (P = 0.00), 'rating patient's experience with "on-duty doctor" (response time, behavior, appearance, attitude etc.), rating the hospital in terms of overall waiting time for any service (P = 0.010), experience' with nursing staff (responsive, courteous, polite) and rating the hospital in terms of overall waiting time for any service. Emergency care where patients were satisfied included reception, greeting while entering the department, ambience of the hospital and the Emergency Department, and good experience with the on-duty doctor, nursing staff, and security. Waiting time for treatment at emergency care was less. Recommending this hospital to others was statistically significant with the experience of the patient with the staff.


Parenteral selenium and vitamin E supplementation of weaned beef calves.
The weaning process in beef calves elicits physiological stress responses that can negatively affect performance and health. Supplementation of vitamins and minerals, particularly selenium (Se) and vitamin E, might be warranted. That parenteral administration of Se or vitamin E would correct or prevent deficiencies of these nutrients in postweaned beef calves during a backgrounding period (42 days after weaning). One hundred and forty-four weaned steers (200-250 kg) in 3 trials. One trial was conducted with cattle on a dry lot fed a total mixed ration and 2 trials were conducted on cattle on pasture. Selenium was administered at 0.05 mg/kg BW (SC) and vitamin E was administered at 1500 IU on days 0 and 28 (SC). A treatment effect attributable to Se or vitamin E supplementation on average daily gain was not detected in any trials. Parenteral supplementation with Se on days 0 and 28 resulted in higher serum Se concentrations as compared with controls on day 42. Parenteral supplementation with Se on days 0 and 28 improved Se status from marginal to adequate in 1 trial. Parenteral supplementation with vitamin E did not improve serum vitamin E concentrations in any experiment. Supplementation with vitamin E or Se or a combination of both did not have a significant effect on calf performance during the 42-day backgrounding period.


The height limit of a siphon.
The maximum height of a siphon is generally assumed to be dependent on barometric pressure-about 10 m at sea level. This limit arises because the pressure in a siphon above the upper reservoir level is below the ambient pressure, and when the height of a siphon approaches 10 m, the pressure at the crown of the siphon falls below the vapour pressure of water causing water to boil breaking the column. After breaking, the columns on either side are supported by differential pressure between ambient and the low-pressure region at the top of the siphon. Here we report an experiment of a siphon operating at sea level at a height of 15 m, well above 10 m. Prior degassing of the water prevented cavitation. This experiment provides conclusive evidence that siphons operate through gravity and molecular cohesion.


Diagnostic accuracy, sensitivity, and specificity of CT pulmonary artery to aorta diameter ratio in screening for pulmonary hypertension in end-stage COPD patients.
To determine the diagnostic accuracy of pulmonary artery to aorta ratio in screening for pulmonary hypertension in advanced chronic obstructive pulmonary disease (COPD) patients. A prospective, diagnostic study was conducted in University Hospital Center Zagreb between January 2015 and March 2018. The study enrolled 100 patients who consecutively underwent chest computed tomography (CT), echocardiographic exam, and right heart catheterization. Two independent observers measured pulmonary artery and ascending aorta diameters. The correlation between the ratio and mean pulmonary artery pressure, measured invasively, was assessed. Patients with echocardiographic signs of moderate systolic or diastolic left ventricular dysfunction were excluded (n=44). Sixty-six patients (55.5% men), with a median age of 61, were identified. Median forced expiratory volume during the first second (FEV1) was 34±12, FEV1/forced vital capacity <0.70. Patients with and without pulmonary hypertension had pulmonary artery diameter of 36±7 mm and 27±4.6 mm, respectively (P<0.001). Median pulmonary artery/aorta (PA/A) ratios for patients with and without pulmonary hypertension were 1.05 and 0.81, respectively (P<0.001). PA/A ratio above 0.95 was an independent predictor of pulmonary hypertension with a specificity of 100% and a sensitivity of 74.51% (area under the curve=0.882; standard error=0.041; P<0.001). PA/A ratio as measured on chest CT images can be used as a screening tool instead of echocardiography.


The effects of cAMP, Ca2+, and phorbol esters on ouabain-induced depression of acetylcholine responses in Helix neurons.
1. Using internal perfusion and concentration-clamp procedures applied to Helix neurons, the effects of cAMP, Ca2+, and phorbol esters on ouabain-induced depression of acetylcholine Cl-dependent responses were determined. 2. Intracellular cAMP (10(-4) M) depressed those acetylcholine responses which were blocked by ouabain but had no effect on ouabain-insensitive acetylcholine responses. In the presence of elevated intracellular cAMP, ouabain had no further depressant effect on these acetylcholine responses. Both elevated cAMP and ouabain reduced the acetylcholine response without altering the current-voltage curves. 3. An increase in intracellular Ca2+ concentration depressed the amplitude of current induced by application of acetylcholine in neurons with ouabain-sensitive responses and shifted the dose-response relationship to the right. However, elevated Ca2+ did not reduce the maximal response induced by acetylcholine, nor did it prevent the reduction of that response by ouabain. 4. 12-O-Tetradecanoylphorbol-13-acetate (TPA), a potent stimulator of protein kinase C activity, caused depression of both the ouabain-sensitive and the ouabain-insensitive acetylcholine responses. The inhibitory effect of TPA was markedly enhanced after addition of ATP to the intracellular medium and was greatly reduced by cooling to 5 degrees C. The blocking effect of ouabain, however, reexamined in the presence of TPA. 5. These observations are consistent with the hypothesis that the depression of acetylcholine induced Cl--responses in Helix neurons is a result of an increase in intracellular cAMP concentration but is unrelated to activation of protein kinase C or increases in intracellular Ca2+.


Determination of resin cure using infrared analysis without an internal standard.
The purpose of this study was to develop a methodology whereby the monomer conversion of dental restorative resins which contain no functional group acting as an internal standard can be easily determined using infrared spectroscopy. Calibration solutions of MMA were made from which the quantification of weight percent methacrylate groups (CH2 = C(CH3)C = O) (termed WPMG) could be determined using infrared spectroscopy. The extent of resin cure using the WPMG method consisted of calculating the changes in WPMG pre- and post-cure. The extent of cure of a commercial unfilled bonding resin was calculated using infrared methods utilizing the internal aromatic standard, and also by means of WPMG. WPMG had an identical optical constant for a wide range of monomers: MMA, TEGDMA, EGDMA, HEMA: The extent of monomer conversion using both methods of analysis indicated statistically equivalent results: 75.2 +/- 1.0% using an internal standard, and 76.0 +/- 1.1% using WPMG. The methods developed in this study using infrared spectroscopic methods facilitate the determination of cure of dental resins which do not have functional groups to serve as internal standards.


Rapid and simple purification of human immunodeficiency virus 1 epitope gp41.
In order to develop a reliable and inexpensive serodiagnostic method, part of the transmembrane glycoprotein gene of HIV-1, gp41', (HIV-env 548-646) was cloned into an expression vector, pCT10 with a sequence encoding a hydroxylamine cleavage site and with a part of Lac Z gene (Lac 2": 834 base pairs) as a fusion partner. Overexpression of Lac Z"-gp41' was induced in E. coli and the gp41' fusion protein was purified to homogeneity by centrifugation, hydroxylamine cleavage and an ion-exchange chromatography. Western blot analysis and enzyme-linked immunosorbant assay (ELISA) using the purified gp41 fragment showed high sensitivity and specificity of gp41 as an antigen to detect anti HIV-1 antibodies in testing human sera. These results suggest that this simple and rapid purification method is reliable for obtaining a large quantity of purified gp41'.


Design and evaluation of in vivo bioavailability in beagle dogs of bilayer tablet consisting of immediate release nanosuspension and sustained release layers of rebamipide.
The purpose of this study was to develop a once-daily, bilayer matrix tablet with immediate (IR) and sustained release (SR) layers of poorly water-soluble and absorption site dependent rebamipide (RBM) to substitute three times a day IR tablet. Owing to the pH-dependent poor water solubility of RBM in low pH condition, salt-caged nanosuspensions (NSPs) consisting of RBM and poloxamer 407 (POX 407) or poloxamer 188 (POX 188) were prepared using an acid-base neutralization method to increase the dissolution rate, which was subsequently applied to the immediate-release (IR) layer. Polyethylene oxide (PEO) with different molecular weights (PEO 100,000 and PEO 5,000,000) and hydroxypropyl methylcellulose 4000 (HPMC 4000) were then investigated as SR agents to incorporate into the SR layer with pure RBM via wet granulation method. The dissolution profile of the optimized bilayer tablet having 50% IR and 50% SR layer of 300 mg RBM showed that the IR layer could rapidly disintegrate in pH 1.2 buffer solution within 2 h, reaching 50% of drug release from the tablet, followed by an extended drug release from the SR layer in pH 6.8 buffer over 24 h. An in vivo pharmacokinetic study was carried out in beagle dogs to compare the optimal formulation (300 mg RBM bilayer tablet) and the commercial tablet (Mucosta® 100 mg) as a reference. Unexpectedly, despite enhanced dissolution rate in a controlled manner, a designed bilayer tablet had no dose- and dosage form dependent in vivo bioavailability in beagle dogs as compared with IR 100 mg RBM reference tablet. It was evident that solubility in low pH condition, gastric residence time and absorption site of RBM should be carefully considered for designing specific SR or gastroretentive dosage form to improve therapeutic outcomes.


Effect of age on lipid profiles in pediatric heart transplant recipients.
This study's objectives were to determine if pediatric orthotopic heart transplant (OHT) recipients over all ages develop hyperlipidemia and, secondarily, to identify the effects of immunosuppressive agents and statins on lipid profiles in these patients. Retrospective chart review was performed for pediatric patients transplanted between January 1987 and June 2002. Of the 100 OHTs performed, 50 patients satisfied the inclusion criteria and were grouped by age at OHT as follows: group 1 (n = 16): 0-4 yr; group 2 (n = 10): 5-9 yr; group 3 (n = 15): 10-14 yr; group 4 (n = 9): 15-18 yr. There were 2789 lipid levels recorded, and each patient had an average of 14 post-OHT lipoprotein panels measured. Post-OHT total cholesterol and low-density lipoprotein (LDL) levels were significantly greater than those of the general population for the entire follow-up period in all age groups, except for LDL levels in group 2. Cyclosporin level and prednisone dose were positively associated with total cholesterol and LDL levels (p < 0.03). Statins significantly decreased total cholesterol and LDL levels (p < 0.001). Hyperlipidemia affects OHT patients of all ages. Even the youngest patients may benefit from immunosuppression using an alternative to cyclosporin, such as tacrolimus, and steroid-free regimens, which may improve lipid profiles. Once safety and efficacy data are available, all age groups may benefit from statins.


The poly(A)-binding protein and an mRNA stability protein jointly regulate an endoribonuclease activity.
We previously identified a sequence-specific erythroid cell-enriched endoribonuclease (ErEN) activity involved in the turnover of the stable alpha-globin mRNA. We now demonstrate that ErEN activity is regulated by the poly(A) tail. The unadenylated alpha-globin 3' untranslated region (3'UTR) was an efficient substrate for ErEN cleavage, while the polyadenylated 3'UTR was inefficiently cleaved in an in vitro decay assay. The influence of the poly(A) tail was mediated through the poly(A)-binding protein (PABP) bound to the poly(A) tail, which can inhibit ErEN activity. ErEN cleavage of an adenylated alpha-globin 3'UTR was accentuated upon depletion of PABP from the cytosolic extract, while addition of recombinant PABP reestablished the inhibition of endoribonuclease cleavage. PABP inhibited ErEN activity indirectly through an interaction with the alphaCP mRNA stability protein. Sequestration of alphaCP resulted in an increase of ErEN cleavage activity, regardless of the polyadenylation state of the RNA. Using electrophoretic mobility shift assays, PABP was shown to enhance the binding efficiency of alphaCP to the alpha-globin 3'UTR, which in turn protected the ErEN target sequence. Conversely, the binding of PABP to the poly(A) tail was also augmented by alphaCP, implying that a stable higher-order structural network is involved in stabilization of the alpha-globin mRNA. Upon deadenylation, the interaction of PABP with alphaCP would be disrupted, rendering the alpha-globin 3'UTR more susceptible to endoribonuclease cleavage. The data demonstrated a specific role for PABP in protecting the body of an mRNA in addition to demonstrating PABP's well-characterized effect of stabilizing the poly(A) tail.


Diagnosis and phylogenetic analysis of bovine papillomaviruses in cattle papillomatosis cases by different methods.
Papillomaviruses, known as epitheliotropic, cause proliferation in the skin, mucosa, and different visceral organs. In this study, it was aimed to diagnose bovine papillomavirus (BPV) by using different methods in the lesion taken from twenty cattle with papillomas in different areas of the body and to reveal its molecular characterization. In our study, molecular, immunohistochemistry, and transmission electron microscopy (TEM) methods were used for virus identification. Additionally, sequencing analysis was used to ascertain the phylogenetic relationship between the obtained field strains and other isolates submitted to GenBank. Histopathological analyses of the collected samples were done in addition to diagnostic procedures. Intranuclear virus particles were detected when the papillomas were investigated with TEM. In PCR analyses using degenerate and type-specific primer sets, the presence of BPV nucleic acid was determined in 70% (14/20) and 90% (18/20) of the samples, respectively. No virus could be detected in PCR applications using MY 09/11 degenerate primer sets. Twenty animals of different ages, races, and genders included in the study by random sampling method from different herds were divided into 4 groups according to the body regions where the lesions were located. Sequence analysis was performed on a sample from each group that showed strong positivity in the PCR technique using FAP 59/64 degenerate primer set and type-specific primer set. Sequence analyses were performed using FAP 59/64 degenerate primers of amplicons for phylogenetic research. In these analyses, three of the isolated strains were identified as BPV-1, which is in the Deltapapillomavirus 4 genus, and one as BPV-2. As a result of the study, it was concluded that molecular and phylogenetic studies using type-specific primers are more beneficial in order to fully reveal the etiology of papillomatosis in cattle and it would be correct to determine BPV types before prophylactic (vaccine, etc.) applications.


Web-based language production experiments: Semantic interference assessment is robust for spoken and typed response modalities.
For experimental research on language production, temporal precision and high quality of the recorded audio files are imperative. These requirements are a considerable challenge if language production is to be investigated online. However, online research has huge potential in terms of efficiency, ecological validity and diversity of study populations in psycholinguistic and related research, also beyond the current situation. Here, we supply confirmatory evidence that language production can be investigated online and that reaction time (RT) distributions and error rates are similar in written naming responses (using the keyboard) and typical overt spoken responses. To assess semantic interference effects in both modalities, we performed two pre-registered experiments (n = 30 each) in online settings using the participants' web browsers. A cumulative semantic interference (CSI) paradigm was employed that required naming several exemplars of semantic categories within a seemingly unrelated sequence of objects. RT is expected to increase linearly for each additional exemplar of a category. In Experiment 1, CSI effects in naming times described in lab-based studies were replicated. In Experiment 2, the responses were typed on participants' computer keyboards, and the first correct key press was used for RT analysis. This novel response assessment yielded a qualitatively similar, very robust CSI effect. Besides technical ease of application, collecting typewritten responses and automatic data preprocessing substantially reduce the work load for language production research. Results of both experiments open new perspectives for research on RT effects in language experiments across a wide range of contexts. JavaScript- and R-based implementations for data collection and processing are available for download.


Booster seat use by children aged 4-11 years: evidence of the need to revise current Australasian standards to accommodate overweight children.
To examine the relationship between child weight and vehicle booster seat usage in the context of current Australasian booster seat standards. Questionnaire survey conducted between February and April 2005. A convenience sample of parents with children aged 4-11 years in New South Wales and Victoria completed a questionnaire, reporting on the height and weight of their children and the nature of restraint devices used in the family vehicle. Proportion of children meeting standard-specified weight and height criteria who are not restrained in booster seats; proportion of children who meet the specified height criteria but whose weight exceeds the specified weight. 699 of 3959 questionnaires were returned (response rate, 18%), of which seven lacked essential details. The remaining 692 responses provided information on 1500 children. Of these children, 633 aged 4-11 years fell within the recommended height range for using booster seats, but only 29% were typically restrained in booster seats, the majority (70%) being restrained in normal seatbelts. A key finding was that 37% of the children who met the recommended height criteria exceeded the maximum weight for booster seats stipulated by the current Australasian safety standard. In view of increasing rates of overweight and obesity in children, it is important to reassess current Australasian standards for child restraints in vehicles. A concerted parental education campaign is also needed to raise awareness of which restraint types are appropriate for children of various heights and weights.


Perceived maternal parenting self-efficacy scale: Factor structure and psychometric properties among Portuguese postpartum women.
The aim of this study was to investigate the factor structure and psychometric properties of the Perceived Maternal Parenting Self-Efficacy (PMPS-E) Scale among Portuguese postpartum women. Quantitative cross-sectional study. Data were collected through an online survey placed on social media websites targeting Portuguese adult women in the postpartum period (0-12 months after delivery). The total sample consisted of 893 participants who gave birth after 37 weeks of gestation. After conducting exploratory and confirmatory factor analyses, our results revealed that a correlated three-factor model yielded a significantly better fit to the data than the original four-factor model. High reliability was found for the total scale (α= 0.95) and for the three factors (α from 0.88 to 0.94). The PMPS-E presented significant and moderate to large correlations with other measures related to maternal self-efficacy. Participants who were multiparous, had older infants (>5 months old) and perceived their infant temperament as easy reported higher maternal parenting self-efficacy than those who were primiparous, had younger infants (≤5 months old) and perceived their infant temperament as difficult. The results of this study showed that the European Portuguese version of the PMPS-E is a valid and reliable instrument for assessing maternal parenting self-efficacy among postpartum women. The PMPS-E may be a valuable instrument to detect parenting self-efficacy difficulties among postpartum women and thus contribute to strategies to improve women's overall psychological adjustment to the postpartum period, with a possible impact on the mother-infant relationship.


Heartland Virus in Humans and Ticks, Illinois, USA, 2018-2019.
In 2018, Heartland disease virus infected 2 persons in Illinois, USA. In 2019, ticks were collected at potential tick bite exposure locations and tested for Heartland and Bourbon viruses. A Heartland virus-positive pool of adult male Amblyomma americanum ticks was found at 2 locations, 439 km apart, suggesting widespread distribution in Illinois.


Retinal twin cones or retinal double cones in fish: misnomer or different morphological forms?
Scanning retinal electronmicroscopy studies demonstrated the presence of both twin cones (two identical cones adhered together) and double cones (two non-identical cones adhered together) in the retinae of the major forms of fish, which included actinopterygi, elasmobranch, and teleosts. The complexity of these visual cells in the retinae of different groups of fishes was revealed for the first time and reflected on the diversities of functions of the fish retina in general.


Radio-frequency spectroscopy of the active fiber heating under condition of high-power lasing generation.
A novel method for the precise temperature measurement of active fibers in high-power fiber lasers and amplifiers is introduced. This method allows the determination of active fiber longitudinal temperature distribution at different optical pump powers.


Further studies on tryptophan hydroxylase from neoplastic murine mast cells.
Tryptophan hydroxylase (tryptophan, tetrahydropteridine: oxygen oxidoreductase (5-hydroxylating) EC 220.127.116.11) purified from the neoplastic murine mast cells by hydroxylapatite chromatography following ammonium sulfate fractionation showed maximum activity at pH 6.0 in the presence of 2-mercaptoethanol, 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetra-hydropteridine and Fe2+, and pH 7.6 to 8.0 in the absence of addED Fe2+. The Km values were 38.5 muM and 22.2 muM for tryptophan, 298 muM and 204 muM for 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetra-hydropteridine, and 6.45% for oxygen in either presence or absence of added Fe-2+, respectively. From kinetic data the reaction mechanism of tryptophan hydroxylation appears to be of the sequential, rather than the ping-pong, type. Tryptophan hydroxylase from mast cells was considerably inhibited by o-phenanthroline like phenylalanine hydroxylase as well as tyrosine hydroxylase from other sources, and its Ki was between 1.2 muM and 4.53 muM. It was found that the inhibition by o-phenanthroline was competitive with respect to both tryptophan and 2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine, but not molecular oxygen under the assay conditions employed.


Pharmacological characterization of 3,4-methylenedioxyamphetamine (MDA) analogs and two amphetamine-based compounds: N,α-DEPEA and DPIA.
3,4-methylenedioxyamphetamine (MDA) is a psychoactive compound chemically related to the entactogen MDMA. MDA shares some of the entactogenic effects of MDMA but also exerts stimulant effects and psychedelic properties at higher doses. Here, we examined the pharmacological properties of MDA analogs and related amphetamine-based compounds detected in street drug samples or in sport supplements. We examined the key pharmacological mechanisms including monoamine uptake inhibition and release using human embryonic kidney 293 cells stably transfected with the respective human transporters. Additionally, we assessed monoamine transporter and receptor binding and activation properties. MDA, its fluorinated analogs, as well as the α-ethyl containing BDB and the dimeric amphetamine DPIA inhibited NET with the greatest potency and preferentially inhibited 5-HT vs. dopamine uptake. The β‑methoxy MDA analog 3C-BOH and the amphetamine-based N,α-DEPEA inhibited NET and preferentially inhibited dopamine vs. 5-HT uptake. The test drugs mediated efflux of at least one monoamine with the exception of DPIA. Most compounds bound to 5-HT2A and 5-HT2C receptors (Ki ≤ 10 µM) and several substances activated the 5-HT2A and 5-HT2B receptor as partial or full agonists. Furthermore, several compounds interacted with adrenergic receptors and the trace amine-associated receptor 1 (TAAR1) in the micromolar range. The pharmacological profiles of some fluorinated and nonfluorinated MDA analogs resemble the profile of MDMA. In contrast, 3C-BOH and N,α-DEPEA displayed more pronounced dopaminergic activity similar to amphetamine. Pharmacokinetics and pharmacodynamics studies are necessary to better establish the risks and therapeutic potential of the tested drugs.


MRI Radiomic Features: A Potential Biomarker for Progression-Free Survival Prediction of Patients With Locally Advanced Cervical Cancer Undergoing Surgery.
To investigate the prognostic role of radiomic features based on pretreatment MRI in predicting progression-free survival (PFS) of locally advanced cervical cancer (LACC). All 181 women with histologically confirmed LACC were randomly divided into the training cohort (n = 126) and the validation cohort (n = 55). For each patient, we extracted radiomic features from whole tumors on sagittal T2WI and axial DWI. The least absolute shrinkage and selection operator (LASSO) algorithm combined with the Cox survival analysis was applied to select features and construct a radiomic score (Rad-score) model. The cutoff value of the Rad-score was used to divide the patients into high- and low-risk groups by the X-tile. Kaplan-Meier analysis and log-rank test were used to assess the prognostic value of the Rad-score. In addition, we totally developed three models, the clinical model, the Rad-score, and the combined nomogram. The Rad-score demonstrated good performance in stratifying patients into high- and low-risk groups of progression in the training (HR = 3.279, 95% CI: 2.865-3.693, p < 0.0001) and validation cohorts (HR = 2.247, 95% CI: 1.735-2.759, p < 0.0001). Otherwise, the combined nomogram, integrating the Rad-score and patient's age, hemoglobin, white blood cell, and lymph vascular space invasion, demonstrated prominent discrimination, yielding an AUC of 0.879 (95% CI, 0.811-0.947) in the training cohort and 0.820 (95% CI, 0.668-0.971) in the validation cohort. The Delong test verified that the combined nomogram showed better performance in estimating PFS than the clinical model and Rad-score in the training cohort (p = 0.038, p = 0.043). The radiomics nomogram performed well in individualized PFS estimation for the patients with LACC, which might guide individual treatment decisions.


Hypothalamic control of brown adipose tissue in Zucker lean and obese rats. Effect of electrical stimulation of the ventromedial nucleus and other hypothalamic centres.
Electrophysiological stimulation of the hypothalamic ventromedial nucleus (VMN) resulted in an increase in interscapular brown adipose tissue (BAT) temperature in both lean and obese (fa/fa) rats. Graded stimulations resulted in progressively larger temperature increases in both lean and obese (fa/fa) groups. Both intraperitoneal injection of propranolol and surgical denervation (but not sham denervation) abolished the increase in BAT temperature following VMN stimulation, in both lean and obese (fa/fa) groups. Electrical stimulation of the supraoptic region, and certain anterior hypothalamic regions also resulted in increases in BAT temperature of lean and obese (fa/fa) rats, but stimulation of the dorsomedial nucleus and regions of the lateral hypothalamus did not affect BAT temperature. All hypothalamic regions capable of activating BAT gave a similar maximum rise in temperature for a given stimulus in lean and obese (fa/fa) rats. These results suggest that the efferent sympathetic pathway from the VMN and other hypothalamic regions of BAT is normal in the obese (fa/fa) rat.


Facial thermography is a sensitive tool to determine antihistaminic activity: comparison of levocetirizine and fexofenadine.
To assess the antihistaminic activity of levocetirizine and fexofenadine 2 h and 24 h after drug administration using facial thermography and to compare the results with those using well-established parameters of antihistaminic activity in the nose and skin. This was a randomized, double-blind, three-treatment, three-period, single-dose, cross-over study in healthy males taking levocetirizine 5 mg, fexofenadine 120 mg or placebo. The primary endpoint was nasal skin temperature after nasal histamine challenge recorded for 20 min at 2 and 24 h after drug intake. The secondary endpoints were nasal symptoms and a histamine skin prick test. Thirty subjects were randomized. At 2 h after drug intake the inhibition of the nasal temperature increase from baseline was not significantly different between levocetirizine and fexofenadine. At 24 h it was significantly more pronounced after levocetirizine than fexofenadine (difference: least-squares mean: -0.13 degrees C; P < or = 0.024, 95% CI -0.24, -0.02). Both drugs significantly reduced (P < or = 0.001) the mean temperature increase from baseline compared with placebo at 2 and 24 h (least-squares mean increase and (95% CI): levocetirizine, -0.28 degrees C (-0.42, -0.14) and -0.32 degrees C (-0.43, -0.21); fexofenadine -0.35 degrees C (-0.49, -0.21) and -0.19 degrees C (-0.30, -0.08), respectively). Results of nasal symptom score and wheal and flare were consistent with the thermography results. Facial thermography is an objective, non-invasive and sensitive method to study antihistaminic activity at the nose level. Levocetirizine and fexofenadine demonstrate the same activity at 2 h after drug intake, but levocetirizine has a more sustained activity at 24 h.


Clinical and genetic features of a case with juvenile onset sandhoff disease.
Sandhoff disease (SD) is a rare neurological disease with high clinical heterogeneity. SD in juvenile form is much rarer and it is often misdiagnosed in clinics. Therein, it is necessary to provide more cases and review the literature on juvenile onset SD. A 14 years-old boy with eight years of walking difficulties, and was ever misdiagnosed as spinocerebellar ataxia. We found this patient after genetic testing carried rs201580118 and a novel gross deletion in HEXB (g.74012742_74052694del). Through review the literature, we found that was the first gross deletion identified at the 3'end of HEXB, associated with juvenile onset SD from China. This case expanded our knowledge about the genotype and phenotype correlations in SD. Comprehensive genetic testing is important for the diagnosis of unexplained ataxia.


Genome-wide identification and expression analysis of the bHLH gene family in cauliflower (Brassica oleracea L.).
Basic helix-loop-helix (bHLH) transcription factors (TFs) are one of the largest TF families in plant species, and they play important roles in plant growth, development and stress responses. The present study systematically identified members of the cauliflower (Brassica oleracea L.) bHLH gene family based on genomic data. Analysis of bHLH family gene numbers, evolution, collinearity, gene structures and motifs indicated that cauliflower contained 256 bHLH family genes distributed on 10 chromosomes. Most of these genes have been localized in the nucleus, and they were divided into 18 subgroups which have been relatively conserved during evolution. Promoter analysis showed that most cis-acting elements were related to MeJA and ABA. Expression analysis suggested that 14 bHLH genes may be involved in the transformation of cauliflower curd from white to purple. An expression analysis of these 14 genes in FQ136 material was performed using qRT-PCR, and 9 bHLH genes (BobHLH1, 14, 58, 61, 63, 84, 231, 239 and 243) showed significantly increased or decreased expression in cauliflower from white to purple, which suggests that these 9 genes play important roles in the accumulation of anthocyanins in cauliflower. The coexpression network of these 9 genes and anthocyanin synthesis-related key genes was analyzed using weighted gene coexpression network analysis (WGCNA). In conclusion, our observations suggested that the bHLH gene family plays an important role in the accumulation of anthocyanins in cauliflower and provide an important theoretical basis for further research on the functions of the bHLH gene family and the molecular mechanism of cauliflower coloration. The online version contains supplementary material available at 10.1007/s12298-022-01238-9.


A broken heart: right ventricular rupture after blunt cardiac injury.
A 68 year old woman who was a restrained driver was brought to the hospital after sustaining severe motor vehicle accident. She underwent CT of the chest demonstrating pulmonary infiltrates, multiple rib fractures, bilateral hemo- and pneumothoraces. Subsequent review of the images noted contrast extravasating from the apical portion of the right ventricle into the pericardial space, demonstrating a confined rupture of right ventricle. Cardiac rupture is a common complication of a rare event and there are few examples in the imaging literature capturing such event.


Recent Advances in the Studies of Molecular Mechanisms Regulating Multidrug Resistance in Cancer Cells.
Here we present new approaches to better understanding multidrug resistance (MDR) development in cancer cells, such as identification of components of a complex process of MDR evolution. Recent advances in the studies of MDR are discussed: 1) chemotherapy agents might be involved in the selection of cancer stem cells resulting in the elevated drug resistance and enhanced tumorigenicity; 2) cell-cell interactions have a great effect on the MDR emergence and evolution; 3) mechanotransduction is an important signaling mechanism in cell-cell interactions; 4) proteins of the ABC transporter family which are often involved in MDR might be transferred between cells via microvesicles (epigenetic MDR regulation); 5) proteins providing cell-to-cell transfer of functional P-glycoprotein (MDR1 protein) via microvesicles have been investigated; 6) P-glycoprotein may serve to regulate apoptosis, as well as transcription and translation of target genes/proteins. Although proving once again that MDR is a complex multi-faceted process, these data open new approaches to overcoming it.


Association of Age, Sex, and Heart Failure Etiology in Continuous Flow Left Ventricular Assist Device Patients.
Advanced heart failure studies demonstrate that ischemic factors increase in prevalence with age and are more prominent in men. Ejection fraction (EF) cannot be preserved in these patients, and ischemic cardiomyopathy develops. Non-ischemic factors are more prominent in female heart failure patients, where the EF is preserved. Although an age-associated increase in the rate of heart failure is acknowledged in both sexes, etiologic classifications by sex-based age groups are still lacking. This study examined the etiology of heart failure according to age and sex in ventricular assist device patients. The patient population included 457 end-stage heart failure patients who received a continuous flow-left ventricular assist device at Ege University Hospital between 2010 and 2017. Age, sex, and cardiomyopathy etiology data were obtained from the hospital database. The Mann-Whitney U test was applied to test the statistical significance among subgroups (95% CI, P < .05 for statistical significance). The prevalence of ischemic cardiomyopathy was significantly lower in male patients aged 18 to 39 years compared to older patients. Conversely, no difference was seen among female patients. The prevalence of dilated cardiomyopathy was higher in male patients who were 18 to 39 years of age compared to older patients, but no difference was present among the female patients. Age and heart failure etiology were demonstrated to be interrelated in men but not in women. The fact that etiologic factors of advanced heart failure in women have a wider range than in men makes the current classification systems insufficient for use in female populations.


Simultaneous IR-Spectroscopic Observation of α-Synuclein, Lipids, and Solvent Reveals an Alternative Membrane-Induced Oligomerization Pathway.
The intrinsically disordered protein α-synuclein (αS), a known pathogenic factor for Parkinson's disease, can adopt defined secondary structures when interacting with membranes or during fibrillation. The αS-lipid interaction and the implications of this process for aggregation and damage to membranes are still poorly understood. Therefore, we established a label-free infrared (IR) spectroscopic approach to allow simultaneous monitoring of αS conformation and membrane integrity. IR showed its unique sensitivity for identifying distinct β-structured aggregates. A comparative study of wild-type αS and the naturally occurring splicing variant αS Δexon3 yielded new insights into the membrane's capability for altering aggregation pathways.


Vocal Tract Discomfort Scale: Validation of the Argentine Version.
The objective of this study was to validate the Vocal Tract Discomfort Scale (VTD) Argentine version. Nonrandomized, cross-sectional prospective study with control group. The VTD Scale was culturally and linguistically adapted to Argentinian Spanish according to the recommended requirements of translation, closely observing the methodology that was suggested (translation, summary, review and back-translation). The scale Argentine version (Escala de disconfort del tracto vocal) was administered to 107 patients with muscle-tension dysphonia (MTD) (23 men and 84 women, mean ages being: 32.30 ± 9.09 years old for MTD type I, and 31.23 ± 8.45 years old for MTD type II) and 30 volunteers with no vocal pathology (9 men and 21 women, mean ages being: 44.3 ± 8.72 years old). All patients completed the Escala de disconfort del tracto vocal before and after Mathieson Laryngeal Manual Therapy. The results of the VTD Scale administered in both patients and vocally healthy subjects were initially compared; the changes arising from pre and post therapy were also compared in the second phase. The internal consistency of the VTD Scale was assessed using Cronbach alpha coefficient. The internal consistency assessed was considered acceptable for both subscales within the VTD Scale. The values obtained for frequency, severity, and total score of the Scale were similar in patients with MTD I and MTD II, marking a difference with those obtained in the control group of healthy volunteers. A lump feeling in the throat was one of the most frequent symptoms in both MTD and vocally healthy groups. The VTD Scale shows an acceptable consistency, so it is a highly reproducible, reliable, and valuable instrument of evaluation to assess Argentinian patients with voice disorders.


Experiencing the possibility of near death on a daily basis: A phenomenological study of patients with chronic heart failure.
Chronic heart failure (CHF) is a syndrome that greatly impacts people's lives. Due to the poor prognosis of CHF, together with the frequent exacerbations of symptoms, death is a topic that is very present in the lives of patients with CHF. To explore thoughts about death experienced by patients with chronic heart failure in their daily lives. A hermeneutic phenomenological study was carried out. Conversational interviews were conducted with 20 outpatients with chronic heart failure. Analysis of the responses was based on the method proposed by van Manen. From the analysis, four main themes emerged: (1) Feeling afraid of the possibility of dying; (2) Acceptance of the possibility of death; (3) Desiring death for relief from suffering; and (4) Striving to continue living to enjoy family. This study presents, as a novel finding, that people with CHF experience the possibility of near death on a daily basis. This experience, which they must encounter on their own, makes them afraid. In addition, some of them, in view of the discomfort they are living, wish to die, with some even considering committing suicide.


TGF-β regulation of the uPA/uPAR axis modulates mesothelial-mesenchymal transition (MesoMT).
Pleural fibrosis (PF) is a chronic and progressive lung disease which affects approximately 30,000 people per year in the United States. Injury and sustained inflammation of the pleural space can result in PF, restricting lung expansion and impairing oxygen exchange. During the progression of pleural injury, normal pleural mesothelial cells (PMCs) undergo a transition, termed mesothelial mesenchymal transition (MesoMT). While multiple components of the fibrinolytic pathway have been investigated in pleural remodeling and PF, the role of the urokinase type plasminogen activator receptor (uPAR) is unknown. We found that uPAR is robustly expressed by pleural mesothelial cells in PF. Downregulation of uPAR by siRNA blocked TGF-β mediated MesoMT. TGF-β was also found to significantly induce uPA expression in PMCs undergoing MesoMT. Like uPAR, uPA downregulation blocked TGF-β mediated MesoMT. Further, uPAR is critical for uPA mediated MesoMT. LRP1 downregulation likewise blunted TGF-β mediated MesoMT. These findings are consistent with in vivo analyses, which showed that uPAR knockout mice were protected from S. pneumoniae-mediated decrements in lung function and restriction. Histological assessments of pleural fibrosis including pleural thickening and α-SMA expression were likewise reduced in uPAR knockout mice compared to WT mice. These studies strongly support the concept that uPAR targeting strategies could be beneficial for the treatment of PF.


Microarray for epigenetic changes: gene expression arrays.
Microarrays can be used to examine changes involving all aspects of the epigenetic interactions. As the relationship between DNA methylation, histone modifications, and gene expression is elucidated, an important aspect to investigate is how the epigenetic status regulates the cell through differential expression of genes. This can provide data from work including experimental drug investigations from cell line models, or more directly patient comparison data.


Controlling for exogenous environmental variables when using data envelopment analysis for regional environmental assessments.
Researchers are increasingly using data envelopment analysis (DEA) to examine the efficiency of environmental policies and resource allocations. An assumption of the basic DEA model is that decisionmakers operate within homogeneous environments. But, this assumption is not valid when environmental performance is influenced by variables beyond managerial control. Understanding the influence of these variables is important to distinguish between characterizing environmental conditions and identifying opportunities to improve environmental performance. While environmental assessments often focus on characterizing conditions, the point of using DEA is to identify opportunities to improve environmental performance and thereby prevent (or rectify) an inefficient allocation of resources. We examine the role of exogenous variables such as climate, hydrology, and topography in producing environmental impacts such as deposition, runoff, invasive species, and forest fragmentation within the United States Mid-Atlantic region. We apply a four-stage procedure to adjust environmental impacts in a DEA model that seeks to minimize environmental impacts while obtaining given levels of socioeconomic outcomes. The approach creates a performance index that bundles multiple indicators while adjusting for variables that are outside management control, offering numerous advantages for environmental assessment.


Fine motor skills and finger gnosia contribute to preschool children's numerical competencies.
Facets of fine motor skills (FMS) and finger gnosia have been reported to predict young children's numerical competencies, possibly by affecting early finger counting experiences. Furthermore, neuronal connections between areas involved in finger motor movement, finger gnosia, and numerical processing have been posited. In this study, FMS and finger gnosia were investigated as predictors for preschool children's performance in numerical tasks. Preschool children (N = 153) completed FMS tasks measuring finger agility and finger dexterity as well as a non-motor finger gnosia task. Furthermore, children completed numerical tasks that involved finger use (i.e., finger counting and finger montring), and tasks that did not (i.e., picture-aided calculation and number line estimation). To control for possible confounding influences of domain general skills, we included measures of reasoning and spatial working memory. We found associations between FMS and both finger counting and calculation, but not finger montring. In contrast, finger gnosia was only associated with finger montring, but not finger counting and calculation. Surprisingly, there were no associations between FMS or finger gnosia with number line estimation. Findings highlight that the relationship between finger gnosia, FMS, and numerical skills is specific to task requirements. Possible implications are discussed.


Epidemiology of acute respiratory illness during an influenza outbreak in a nursing home. A prospective study.
We observed an influenza epidemic caused by influenza A/Arizona/82 (H3N2) in a nursing home during 1982 to 1983. A survey indicated that 59% of the residents were immunized before the outbreak. The outbreak was observed to begin in November, peak in February, and disappear in April. A significant level of herd immunity may have accounted for the slow progression through the nursing home. In addition, serologic evidence of concurrent infection with respiratory syncytial virus, parainfluenza virus, and Mycoplasma pneumoniae was present in many residents. Epidemics of influenza in a closed, partially immunized population in a nursing home may proceed at a slower rate than in an open, largely unimmunized community. By monitoring for infection with other respiratory agents, the complex nature of the outbreak in this nursing home became evident.


Pulmonary recruitment maneuver reduces the intensity of post-laparoscopic shoulder pain: a systematic review and meta-analysis.
Post-laparoscopic shoulder pain (PLSP) is a common complication following laparoscopic surgeries. This meta-analysis aimed to investigate whether pulmonary recruitment maneuver (PRM) was beneficial to alleviated shoulder pain after laparoscopic procedures. We reviewed existing literature in the electronic database from the date of inception to January 31, 2022. The relevant RCTs were independently selected by two authors, after which data extraction, assessment of the risk of bias, and comparison of results. This meta-analysis included 14 studies involving 1504 patients, among which 607 patients were offered pulmonary recruitment maneuver (PRM) alone or in combination with intraperitoneal saline instillation (IPSI), while 573 patients were treated with passive abdominal compression. The administration of PRM significantly decreased the post-laparoscopic shoulder pain score at 12 h (MD (95%CI) - 1.12(-1.57, - 0.66), n = 801, P < 0.001, I2 = 88%); 24 h (MD (95%CI) - 1.45(-1.74, - 1.16), n = 1180, P < 0.001, I2 = 78%) and at 48 h (MD (95%CI) - 0.97(-1.57, - 0.36), n = 780, P < 0.001, I2 = 85%). We observed high heterogeneity in the study and analyzed the sensitivity but failed to identify the cause of the heterogeneity, which may have resulted from the different methodologies and clinical factors in the included studies. This systematic review and meta-analysis indicate that PRM can reduce the intensity of PLSP. More studies may be needed to explore the usefulness of PRM in more laparoscopic operations besides gynecological surgeries and determine the optimal pressure of PRM or its appropriate combination with other measures. The results of this meta-analysis should be interpreted with caution owing to the high heterogeneity between the analyzed studies.


Electron microscopic visualization of the N terminus of the myosin heavy chain using a site-directed antibody.
We determined the spatial location of the N terminus of the heavy chain of rabbit skeletal muscle myosin by electron microscopy, using a site-directed antibody raised against its N-terminal eight residues as an electron microscopic probe. By examining rotary-shadowed images of the heavy meromyosin-antibody complex, we measured distances between the head-rod junction and the attachment site of the antibody bound on the head. The average distance was estimated to be about 12 nm. The result indicates that the N terminus of the heavy chain is located at the middle region of the head.


Directed Evolution of Adenoviruses.
The ability to evolve viruses in cell culture in the face of selective pressure is an invaluable method to elucidate the molecular mechanisms of synthetic or natural antivirals, expand tropism, or alter virulence. Recently, mutations to the human adenovirus polymerase that reduce replicative fidelity were described, and we have incorporated one of these mutations into the pol gene of a conditionally replicating human adenovirus serotype 5 (HAdV-5)-based vector (Uil et al., Nucleic Acids Res 39:e30, 2011; Myers et al., J Virol 87:6047-6050, 2013). Here, we describe methods to evolve this virus (HAdV-5.polF421Y) under selective pressure from antivirals to identify their mechanisms of action.


Dual HIV-1 infection associated with rapid disease progression.
Infection with two strains of HIV-1 has implications for understanding HIV transmission and vaccine development; however, frequency and pathogenic consequences of dual infection are unknown. We assessed 64 patients for dual infection with heteroduplex mobility assay, viral sequencing, and phylogenetic methods. HIV disease outcomes were available in 34 patients. Five of these with AIDS endpoints had dual infection with HIV-1: four were cases of coinfection and one was superinfection. In all five, time from seroconversion to clinical AIDS or to CD4+ T-cell count less than 200 cells per microL was very rapid (<3.4 and <3.1 years, respectively). Our findings should prompt larger studies to assess the effect of dual infection at the population level.


Metabolic effects of Troglitazone in patients with diet-controlled type 2 diabetes.
In order to study the mechanisms of action of Troglitazone (TGZ) in vivo in Type 2 diabetes, its effects were studied on glucose metabolism, lipolysis and very low-density lipoprotein (VLDL) apolipoprotein B100 (apoB) kinetics. A placebo-controlled, double-blind study was performed in 24 diet-treated patients randomized to receive TGZ 600 mg day(-1), TGZ 200 mg day(-1) or placebo for 8 weeks. Glucose and glycerol turnover were assessed after an overnight fast, and during sequential low-dose insulin infusions (0.01 U kg(-1) h(-1) followed by 0.015 U kg(-1) h(-1)) using 6,6-2H Glucose and 1,2,3-2H Glycerol. Very low-density lipoprotein apoB secretion was measured using l-13C-leucine, monitoring isotopic enrichment by gas chromatography-mass spectrometry. Treatment effects were analyzed by analysis of covariance, adjusting for baseline. Therapy resulted in a significant group differences in fasting plasma glucose adjusting for baseline (P=0.039). This was most evident at TGZ 600 mg daily [glucose decrease from (mean +/- SD) 9.2 +/- 2.7 to 6.6 +/- 0.9 mmol L(-1)]. HbA1c and insulin levels did not change significantly. Plasma nonesterified fatty acid (NEFA) levels decreased (P=0.045), most evidently at TGZ 200 mg daily, but glycerol was not significantly affected. Although no significant effects were observed on VLDL apoB or triglyceride concentrations, there were treatment differences in the absolute secretion rate of VLDL apoB of borderline (P=0.056) statistical significance, with a decrease observed at TGZ 600 mg daily [geometric mean, SD range, 0.94 (0.41-2.15) to 0.40 (0.14-1.13 mg kg(-1) h(-1))]. Very low-density lipoprotein apoB fractional secretion rate and pool size were unaffected. The VLDL triglyceride: apoB molar ratio differed between treatment groups (P=0.013), being higher in the TGZ 600 mg group [5714 (4128-7741) to 8092 (5669-11552)]. Neither glucose nor glycerol rates of appearance were significantly altered by TGZ and nor did TGZ affect their suppression by insulin. The PPARgamma agonist, troglitazone, decreases fasting glucose and NEFA levels in diet-treated Type 2 diabetes. It may also decrease VLDL particle secretion. These effects would be considered beneficial. The biological importance of the increase in VLDL-triglyceride enrichment warrants further study.


The mutagenic effect of measles virus on cell cultures of different origin.
Differences between strains of measles virus in their mutagenic effect on cells of different animals and man were found. The mutagenic activity of measles virus strains was species-specific. In the process of spontaneous transformation the sensitivity of cells to the mutagen changed.


Octahedral spinel electrocatalysts for alkaline fuel cells.
Designing high-performance nonprecious electrocatalysts to replace Pt for the oxygen reduction reaction (ORR) has been a key challenge for advancing fuel cell technologies. Here, we report a systematic study of 15 different AB2O4/C spinel nanoparticles with well-controlled octahedral morphology. The 3 most active ORR electrocatalysts were MnCo2O4/C, CoMn2O4/C, and CoFe2O4/C. CoMn2O4/C exhibited a half-wave potential of 0.89 V in 1 M KOH, equal to the benchmark activity of Pt/C, which was ascribed to charge transfer between Co and Mn, as evidenced by X-ray absorption spectroscopy. Scanning transmission electron microscopy (STEM) provided atomic-scale, spatially resolved images, and high-energy-resolution electron-loss near-edge structure (ELNES) enabled fingerprinting the local chemical environment around the active sites. The most active MnCo2O4/C was shown to have a unique Co-Mn core-shell structure. ELNES spectra indicate that the Co in the core is predominantly Co2.7+ while in the shell, it is mainly Co2+ Broader Mn ELNES spectra indicate less-ordered nearest oxygen neighbors. Co in the shell occupies mainly tetrahedral sites, which are likely candidates as the active sites for the ORR. Such microscopic-level investigation probes the heterogeneous electronic structure at the single-nanoparticle level, and may provide a more rational basis for the design of electrocatalysts for alkaline fuel cells.


Automated classification of neonatal sleep states using EEG.
To develop a method for automated neonatal sleep state classification based on EEG that can be applied over a wide range of age. We collected 231 EEG recordings from 67 infants between 24 and 45weeks of postmenstrual age. Ten minute epochs of 8 channel polysomnography (N=323) from active and quiet sleep were used as a training dataset. We extracted a set of 57 EEG features from the time, frequency, and spatial domains. A greedy algorithm was used to define a reduced feature set to be used in a support vector machine classifier. Performance tests showed that our algorithm was able to classify quiet and active sleep epochs with 85% accuracy, 83% sensitivity, and 87% specificity. The performance was not substantially lowered by reducing the epoch length or EEG channel number. The classifier output was used to construct a novel trend, the sleep state probability index, that improves the visualisation of brain state fluctuations. A robust EEG-based sleep state classifier was developed. It performs consistently well across a large span of postmenstrual ages. This method enables the visualisation of sleep state in preterm infants which can assist clinical management in the neonatal intensive care unit.


Orthodontic mini-implant stability at different insertion depths : Sensitivity of three stability measurement methods.
The purpose of this work was to evaluate the influence of insertion depth on the stability of orthodontic mini-implants. Sensitivity of three different methods to measure implant stability based on differences in insertion depth were determined. A total of 82 mini-implants (2 × 9 mm) were inserted into pelvic bone of Swabian Hall pigs. Each implant was inserted stepwise to depths of 4, 5, 6, 7, and 8 mm. At each of these depths, three different methods were used to measure implant stability, including maximum insertion torque (MIT), resonance frequency analysis (RFA), and Periotest(®). Differences between the recorded values were statistically analyzed and the methods tested for correlations. Almost linear changes from each insertion depth were measured with the values of RFA [implant stability quotient (ISQ) values range from 1-100], which increased from 6.95 ± 2.85 ISQ at 4 mm to 34.63 ± 5.51 ISQ at 8 mm, and with those of Periotest(®) [periotest values (PTV) range from -8 to 50], which decreased from 13.24 ± 4.03 PTV to -2.89 ± 1.87 PTV. Both methods were found to record highly significant (p < 0.0001) changes for each additional millimeter of insertion depth. The MIT increased significantly (p < 0.0001) from 153.67 ± 69.32 Nmm to 261 ± 103.73 Nmm between 4 and 5 mm of insertion depth but no further significant changes were observed as the implants were driven deeper. The RFA and Periotest(®) values were highly correlated (r = -0.907). Mini-implant stability varies significantly with insertion depth. The RFA and the Periotest(®) yielded a linear relationship between stability and insertion depth. MIT does not appear to be an adequate method to determine implant stability based on insertion depth.


Venlafaxine antagonizes the noradrenaline-promoted colon cancer progression by inhibiting the norepinephrine transporter.
Epidemiological studies have demonstrated that the use of antidepressants is associated with a decreased risk of colorectal cancer (CRC); however, the mechanisms behind this association are yet unknown. Adrenergic system contributes to the stress-related tumor progression, with norepinephrine (NE) mainly secreted from adrenergic nerve fibers. Norepinephrine serotonin reuptake inhibitors are successfully used antidepressants. This study demonstrates that a widely used antidepressant venlafaxine (VEN) antagonizes NE-promoted colon cancer in vivo and in vitro. Bioinformatic analysis suggested that NE transporter (NET, SLC6A2), a target of VEN, was closely associated with the prognosis of clinical patients with CRC. In addition, the knockdown of NET antagonized the effect of NE. The NET-protein phosphatase 2 scaffold subunit alpha/phosphorylated Akt/vascular endothelial growth factor pathway partially mediates the antagonizing effect of VEN on NE's actions in colon cancer cells. These were also confirmed by in vivo experiments. Our findings revealed for the first time that, in addition to its primary function as a transporter, NET also promotes NE-enhanced colon cancer cell proliferation, tumor angiogenesis, and tumor growth. This provides direct experimental and mechanistic evidence for the use of antidepressant VEN in the treatment of CRC and a therapeutic potential for repurposing existing drugs as an anti-cancer approach to improve the prognosis of patients with CRC.


The mechanisms of traumatic rupture of the thoracic aorta.
This paper reviews evidence and ideas on closed accidental rupture of the aorta, and refers to an analysis of 37 subjects in whom traumatic aortic ruptures were found at necropsy. The mechanisms of rupture of the ascending aorta and the proximal and distal parts of the descending aorta are discussed. Aortic rupture is one of the major causes of rapid death after traffic accidents, especially in occupants of motor vehicles. However, about 20 per cent of subjects survive for hours, days or longer after the accident, allowing time for surgical repair in some cases.


Effect of Epac1 on pERK and VEGF Activation in Postoperative Persistent Pain in Rats.
The function of guanine nucleotide exchange protein conversion factor (Epac1) in regenerating nerves, stimulating insulin release, controlling vascular pressure, and controlling other metabolic activities has been recognized; however, few studies have addressed the potential role of Epac1 in controlling chronic postoperative pain. Using a rat model of skin/muscle incision and retraction (SMIR), our study tested the hypothesis that increased Epac1 signaling is a factor in postoperative chronic pain. Rats were randomly divided into normal, sham operation, SMIR, SMIR + Epac1 siRNA (Epac1 inhibitor), and normal + 8-pCPT (Epac1 agonist) groups. The mechanical withdrawal threshold (MWT) was used as an index of pain sensitivity. Epac1 expression in the incision-site muscle, DRG, and spinal cord was assessed using western blotting and immunofluorescence. The effects of Epac1 agonists and Epac1 siRNA on MWT and phosphorylated extracellular signal-regulated kinase (pERK), vascular endothelial growth factor (VEGF), protein release in the spinal cord, and DRG levels were also studied. SMIR increased Epac1 expression in the incision-site muscle, spinal cord, and DRG, and decreased MWT. 8-pCPT induced the development of hypersensitivity and increased pERK and VEGF expression in normal rats, whereas siRNA decreased the expression of pERK and VEGF. This study suggests that activation of the Epac1 signal might induce local postoperative recovery process, which could be an important mechanism by which to control postoperative chronic pain. Our data suggest that therapy targeted at decreasing Epac1 levels provides promise for the prevention and treatment of chronic postoperative pain.


Optimal diet theory: behavior of a starved predatory snail.
The tenets of optimal foraging theory are used to contrast the behavior of the predatory snail Acantina spirata when feeding on the barnacles Balanus glandula and Chthamalus fissus under conditions of satiation and starvation. As predicted in optimal diet models, A. spirata is less selective (ratio of attack frequency on a prey species to number of individuals available) when the higher ranking prey has low abundance. When given a choice, starved snails attack both barnacle species equally, whereas satiated individuals preferentially attack B. glandula, the more profitable prey (ash-free dry weight of barnacles ingested per unit handling time). Under starvation conditions, equal attack frequency does not result in equal prey species consumption because Acanthina spirata is more successful at attacking C. fissus than B. glandula.The assumption of constant prey encounter rates in optimal diet models is not met when A. spirata goes from a state of satiation to starvation. The encounter rate on B. glandula is lowered due to a decrease in attack success. A loss of feeding skills in starved A. spirata is responsible for the greater difficulty snails have in gaining access through the opercular plates of B. glandula.Behavioral changes in A. spirata as snails pass from satiation to hunger translate into an energetic disadvantage during feeding for hungry snails for two reasons. First, higher prey handling times result in a decreased rate of biomass intake. Second, alteration in the relative attack frequency between barnacle species, combined with a decrease in attack success on the more profitable prey leads to more frequent ingestion of the less profitable prey.


Design of actively shielded main magnets: an improved functional method.
An improved functional approach for designing MRI (magnetic resonance imaging) main magnets with active shielding is presented. By nulling one or two external moments as well as a certain series of internal moments of the magnetic field, new designs with improved shielding in combination with or without shorter magnet lengths are obtained. The improved method can be employed to design short and practical superconducting magnets at any given field strength. The resulting designs yield the desired field homogeneity inside the region of interest without using superconducting shim coils. This approach requires only a modest amount of computing power. One of the design steps, a contour plot of the continuous current solutions, can be utilized to study stretch goals for favorable design parameters.


Pulse Pressure Variation Adjusted by Respiratory Changes in Pleural Pressure, Rather Than by Tidal Volume, Reliably Predicts Fluid Responsiveness in Patients With Acute Respiratory Distress Syndrome.
1) To evaluate the ability of pulse pressure variation adjusted by respiratory changes in pleural pressure to predict fluid responsiveness compared with pulse pressure variation alone. 2) To identify factors explaining the poor performance of pulse pressure variation in acute respiratory distress syndrome. Prospective study. Forty-bed university hospital general ICU. Ninety-six mechanically ventilated acute respiratory distress syndrome patients requiring fluid challenge. Fluid challenge, 500 mL saline over 20 minutes. Before fluid challenge, esophageal pressure was measured at the end-inspiratory and end-expiratory occlusions. Change in pleural pressure was calculated as the difference between esophageal pressure measured at end-inspiratory and end-expiratory occlusions. Hemodynamic measurements were obtained before and after the fluid challenge. Patients were ventilated with tidal volume 7.0 ± 0.8 mL/kg predicted body weight. The fluids increased cardiac output by greater than 15% in 52 patients (responders). Adjusting pulse pressure variation for changes in pleural pressure (area under the receiver operating characteristic curve, 0.94 [0.88-0.98]) and the ratio of chest wall elastance to total respiratory system elastance (area under the receiver operating characteristic curve, 0.93 [0.88-0.98]) predicted fluid responsiveness better than pulse pressure variation (area under the receiver operating characteristic curve, 0.78 [0.69-0.86]; all p < 0.01). The gray zone approach identified a range of pulse pressure variation/changes in pleural pressure values (1.94-2.1) in 3.1% of patients for whom fluid responsiveness could not be predicted reliably. On logistic regression analysis, two independent factors affected the correct classification of fluid responsiveness at a 12% pulse pressure variation cutoff: tidal volume (adjusted odds ratio 1.57/50 mL; 95% CI, 1.05-2.34; p = 0.027) and chest wall elastance/respiratory system elastance (adjusted odds ratio, 2.035/0.1 unit; 95% CI, 1.36-3.06; p = 0.001). In patients with chest wall elastance/respiratory system elastance above the median (0.28), pulse pressure variation area under the receiver operating characteristic curve was 0.94 (95% CI, 0.84-0.99) compared with 0.76 (95% CI, 0.61-0.87) otherwise (p = 0.02). In acute respiratory distress syndrome patients, pulse pressure variation adjusted by changes in pleural pressure is a reliable fluid responsiveness predictor despite the low tidal volume (< 8 mL/kg). The poor predictive ability of pulse pressure variation in acute respiratory distress syndrome patients is more related to low chest wall elastance/respiratory system elastance ratios than to a low tidal volume.


Low occurrence of pathogenic Yersinia enterocolitica in pig tonsils at slaughter in Southern Brazil.
Yersinia enterocolitica is a foodborne pathogen and pigs are the main reservoir of it in their tonsils. As Brazil is a large producer and exporter of pork meat and information regarding this pathogen is still quite scarce, this study aimed at evaluating the direct detection of Y. enterocolitica followed by pathogenic Y. enterocolitica (PYE) determination in tonsils of slaughtered pigs. For this purpose, 400 pig tonsils were collected from 15 farms in four federally certified slaughterhouses in Southern Brazil. Initially, samples were screened using conventional PCR targeting of the 16sRNA gene, followed by multiplex PCR (mPCR) in order to detect three virulence genes (ail, yadA, and virF) and quantitative real-time PCR (qPCR) for the detection of the ail gene. One hundred and one (25.2%) of the samples tested positive for the 16sRNA gene. However, a PYE was detected in one out of the 101 Y. enterocolitica positive samples. The three virulence genes were determined by mPCR and confirmed by partial DNA sequencing. Thus, a significant occurrence of Y. enterocolitica was observed in pig tonsils from federally inspected slaughterhouses in Brazil, although the presence of pathogenic strains was quite low.