Phosphatase activity against neurofilament proteins from bovine spinal cord: effect of aluminium and neuropsychoactive drugs.
Protein phosphatase activity associated with neurofilament (NF) rich (Triton X-100 insoluble) fraction was extracted and partially characterised by using known inhibitors of protein phosphatases such as vanadate and fluoride. Protein phosphatase activity was demonstrated with reference to the dephosphorylation of endogenous substrate, NF protein and exogenous protein substrates, casein and phosvitin. Phosphoamino acids and beta-glycerophosphate were found to be poor substrates. Further, new observations have been made regarding the in vitro inhibitory effect of aluminium and the differential effects of some of the neuropsychoactive drugs. The findings could possibly lead to studies explaining the biochemical basis of aluminium induced neurotoxicity as well as the side effects associated with the long term medication of neuropsychoactive drugs.


Early-Life Exposure to Ambient Air Pollution from Multiple Sources and Asthma Incidence in Children: A Nationwide Birth Cohort Study from Denmark.
Ambient air pollution exposure has been associated with childhood asthma, but previous studies have primarily focused on prevalence of asthma and asthma-related outcomes and urban traffic-related exposures. We examined nationwide associations between pre- and postnatal exposure to ambient air pollution components and asthma incidence in children age 0-19 y. Asthma incidence was identified from hospital admission, emergency room, and outpatient contacts among all live-born singletons born in Denmark between 1998 and 2016. We linked registry data with monthly mean concentrations of particulate matter (PM) with aerodynamic diameter ≤2.5μm (PM2.5) and PM with aerodynamic diameter ≤10μm (PM10), nitrogen dioxide (NO2), nitrogen oxides, elemental carbon, and organic carbon (OC), sulfur dioxide, ozone, sulfate, nitrate, ammonium, secondary organic aerosols, and sea salt. Associations were estimated with Cox proportional hazard models using fixed prenatal exposure means and time-varying postnatal exposures. Of the 1,060,154 children included, 6.1% had asthma during the mean follow-up period of 8.8 y. The risk of asthma increased with increasing prenatal exposure to all pollutants except for O3 and sea salt. We also observed increased risk after restriction to asthma after age 4 y, after additional adjustment for area-specific socioeconomic status, and for postnatal exposure to most pollutants. The hazard ratio (HR) associated with an interquartile range increase of 2.4 and 8.7 μg/m3 in prenatal exposure was 1.06 [95% confidence interval (CI): 1.04, 1.08] for PM2.5 and 1.04 (95% CI: 1.02, 1.05) for NO2, respectively. This association with PM2.5 was stable after adjustment for NO2, whereas it attenuated for NO2 to 1.01 (95% CI: 0.99, 1.03) after adjustment for PM2.5. For a 0.5-μg/m3 increase in prenatal OC exposure, for which biomass is an important source, the HR was 1.08 (95% CI: 1.06, 1.10), irrespective of adjustment for PM2.5. These findings suggest that early-life exposure to ambient air pollution from multiple sources contributes to asthma development. https://doi.org/10.1289/EHP11539.


Mothers' Perceptions of the Cardboard Box as a Potential Sleep Space.
Due to increasing popularity, our hospital began considering distributing cardboard boxes combined with safe sleep education to new mothers. As a first step in studying the impact of this intervention on bedsharing in our community, we sought to understand mothers' perceptions of the cardboard box. We recruited primarily low-income, English- or Spanish-speaking mothers of infants aged 2 to 16 weeks during routine primary care visits. Participants responding to a cross-sectional survey about infant sleep practices were invited to participate in in-depth interviews about the cardboard box. We used a grounded theory approach and the constant comparative method until saturation was reached. Of 120 participants in the survey, 50 (42%) participated in the qualitative study. Participants were mothers of infants aged ≤4 weeks (46%), 4 to 8 weeks (32%), and 16 weeks (22%). Of 50 participants, 52% said they would use the cardboard box for their infant to sleep in, if provided, compared with 42% who said they would not and 6% were unsure. Three themes emerged from the data: (1) safety of the cardboard box; (2) appearance, and (3) variation in planned use. Some participants planned to place the cardboard box in their bed. Participants in our study were divided about whether they would use the cardboard box for their infant to sleep in. If distributed, hospital staff should advise families to not place the cardboard box in their bed. Next steps include determining bedsharing frequency among parents who choose to use the cardboard box for their infant.


Immunoreactive prostacyclin and thromboxane metabolites in normal pregnancy and the puerperium.
Prostacyclin and thromboxane have been implicated in the pathophysiology of several disorders of pregnancy, but there is little information on concentrations of these prostaglandins in normal pregnancy. The aim of our study was to determine the range of values throughout normal pregnancy and the puerperium and to compare this with concentrations in normal non-pregnant women. Measurement was by radioimmunoassay of prostacyclin and thromboxane metabolites. We observed a significant difference in prostacyclin metabolites in the first trimester, (mean 19.9, SEM 0.96 pg/ml) compared with the normal non-pregnant group (mean 15.9, SEM 0.68 pg/ml). There were no significant differences between values in the normal non-pregnant group and those in the second and third trimester or postnatally. The increase in prostacyclin in the first trimester may be associated with placentation and physiological vasodilation, and insensitivity to angiotensin II seen in early pregnancy. We noted a significant reduction in thromboxane metabolites in the second (mean 133, SEM 14.9 pg/ml) and third (mean 123, SEM 10.7 pg/ml) trimesters and the puerperium (mean 119, SEM 6.3 pg/ml) compared with the values in the normal non-pregnant group (mean 142, SEM 4.9 pg/ml). This may be due to increased platelet stability or decreased thromboxane synthesis.


The hidden side of infective endocarditis: Diagnostic and management of 500 consecutive cases in noncardiac surgery centers (2009-2018).
We aimed to describe infective endocarditis cases from noncardiac surgery centers, as current knowledge on infective endocarditis is derived mostly from cardiac surgery hospitals. An observational retrospective study (2009-2018) was conducted in 9 noncardiac surgery hospitals in Central Catalonia. All adult patients diagnosed with definitive infective endocarditis were included. Transferred and nontransferred cohorts were compared, and a logistic regression model was used to ascertain the prognostic factors. Overall, 502 infective endocarditis episodes were included: 183 (36.5%) were transferred to the cardiac surgery center, whereas 319 were not, with (18.7%) and without (45%) surgical indications. Cardiac surgery was performed in 83% of transferred patients. In-hospital (14% vs 23%) and 1-year (20% vs 35%) mortality rates were significantly lower in transferred patients (P < .001). Among the patients not undergoing cardiac surgery despite an indication, 55 (54%) died within 1 year. The multivariate analysis identified the following independent predictive factors for in-hospital mortality: Staphylococcus aureus infective endocarditis (odds ratio: 1.93 [1.08, 3.47]), heart failure (odds ratio: 3.87 [2.28, 6.57]), central nervous system embolism (odds ratio: 2.95 [1.41, 5.14]), and Charlson score (odds ratio: 1.19 [1.09, 1.30]), whereas community acquisition (odds ratio: 0.52 [0.29, 0.93]), cardiac surgery (odds ratio: 0.42 [0.20, 0.87]), but not transfer (odds ratio: 1.23 [0.84, 3.95]) were identified as protective factors. One-year mortality was associated with S. aureus infective endocarditis (odds ratio: 1.82 [1.04, 3.18]), heart failure (odds ratio: 3.74 [2.27, 6.16]), and Charlson score (odds ratio: 1.23 [1.13, 1.33]), whereas cardiac surgery (odds ratio: 0.41 [0.21, 0.79]) was identified as a protective factor. Patients not transferred to a referral cardiac surgery center have a worse prognosis compared to those ultimately transferred, as cardiac surgery is associated with lower mortality rates.


Hepatopulmonary syndrome: what are we learning from interventional radiology, liver transplantation, and other disorders?
Interventional radiology (pulmonary angiography, coil embolotherapy, and TIPS) in patients with HPS seems to provide both diagnostic data and therapeutic results of clinical importance. The case report by Riegler et al. is instructive and emphasizes the need for further prospective study to analyze the successes and failures in terms of measurable clinical variable in a procedure such as TIPS. The resolution of hypoxemia following liver transplantation and careful patient selection offers hope to patients with severe, debilitating oxygenation abnormalities caused by HPS.


The role of endorectal coil MRI in patient selection and treatment planning for prostate seed implants.
To assess the role of endorectal coil magnetic resonance imaging (MRI) staging for patients undergoing seed implantation (SI) with or without external beam radiotherapy (EBRT). Between October 1994 and December 1998, 390 patients underwent prostate SI (98% Pd-103, 2% I-125). Seventy-six percent of patients had a prostate serum antigen (PSA) < 10, 17% had PSA of 10-20, and 7% of patients had PSA of > 20. Ten percent of patients had a Gleason score (GS) of 4-5, 54% had GS 6, 29% had GS 7, and 7% had GS >/= 8. Monotherapy was employed in 46% of patients, and the remaining 54% received combined EBRT and SI. Three hundred twenty-seven were staged by high-resolution phased array pelvic coil, or in most cases, an endorectal coil MRI. The MRI findings were used to guide stage-appropriate treatment recommendations, and to assist in the preplanning and optimization of seed distributions. The criteria utilized to determine MRI-based stage were founded on the reported literature from the University of Pennsylvania. All MRI studies were reviewed by C.A., D.B., or W.H., who were unaware of clinical stage at the time of their review. The biopsy report was available to them as the only clinical correlate. Of the 327 patients staged by MRI, 70% were upstaged from the digital rectal examination-based clinical stage; 26% of T(1), T(2) patients were upstaged to T(3). Perineural invasion and the percentage of positive cores predicted for T(3) MRI stage (p < 0.0001 for both variables). MRI findings changed the overall treatment recommendation in 60/327 (18%) patients. The majority of these patients were advised to receive combined therapy instead of monotherapy after the MRI documented more extensive disease. The seed distribution was modified in 183/327 (56%) patients, mostly related to preplanned extracapsular coverage of bulky or extraprostatic disease seen on MRI. With a mean follow-up of 38 months (range 3-72), PSA freedom from progression (FFP) was 94% at 5 years. Cox regression analysis showed that only the percentage of positive cores (p = 0.001) and failure to have MRI staging (p = 0.0008) predicted for failure. Pretreatment PSA level, Gleason score, perineural invasion, and external beam radiotherapy did not significantly predict for PSA failure. We compared our MRI T(3) intermediate-risk group patients treated by combined therapy with a previous study of T(3) intermediate-risk group treated by radical prostatectomy (RP) at the University of Pennsylvania. Our 36-month PSA FFP was 94% compared with 21% for the previous study's RP patients. MRI is a valuable staging procedure for prostate cancer patients treated by SI. PSA FFP results appear to be improved by MRI staging. MRI T(3) disease can be treated more effectively by SI + EBRT than by RP.


Automated extraction of precise protein expression patterns in lymphoma by text mining abstracts of immunohistochemical studies.
In general, surgical pathology reviews report protein expression by tumors in a semi-quantitative manner, that is, -, -/+, +/-, +. At the same time, the experimental pathology literature provides multiple examples of precise expression levels determined by immunohistochemical (IHC) tissue examination of populations of tumors. Natural language processing (NLP) techniques enable the automated extraction of such information through text mining. We propose establishing a database linking quantitative protein expression levels with specific tumor classifications through NLP. Our method takes advantage of typical forms of representing experimental findings in terms of percentages of protein expression manifest by the tumor population under study. Characteristically, percentages are represented straightforwardly with the % symbol or as the number of positive findings of the total population. Such text is readily recognized using regular expressions and templates permitting extraction of sentences containing these forms for further analysis using grammatical structures and rule-based algorithms. Our pilot study is limited to the extraction of such information related to lymphomas. We achieved a satisfactory level of retrieval as reflected in scores of 69.91% precision and 57.25% recall with an F-score of 62.95%. In addition, we demonstrate the utility of a web-based curation tool for confirming and correcting our findings. The experimental pathology literature represents a rich source of pathobiological information, which has been relatively underutilized. There has been a combinatorial explosion of knowledge within the pathology domain as represented by increasing numbers of immunophenotypes and disease subclassifications. NLP techniques support practical text mining techniques for extracting this knowledge and organizing it in forms appropriate for pathology decision support systems.


Incidence and risk factors for postoperative venous thromboembolism in patients with ovarian cancer: Systematic review and meta-analysis.
Venous Thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with ovarian malignancy. There is no meta-analysis available on this topic so far. The aim of our study was to quantitatively synthesize the data from studies with respect to the incidence and risk factors for postoperative VTE among cases with epithelial ovarian cancer (EOC). PubMed, Web of Science, and Embase were searched for papers containing the key words "venous thromboembolism", "postoperative", "postoperation", "ovarian neoplasm", "ovary neoplasm", "ovarian cancer", "ovary cancer", and "cancer of ovary". Studies selection, data extraction, quality assessment of eligible studies were performed independently by our different reviewers. Meta-analyses were conducted to determine postoperative VTE incidence and risk factors in women with EOC. Sensitivity analysis were used to verify the robustness of the results of meta-analyses if necessary. In total, 19 studies were included in this meta-analysis. The pooled incidence for postoperative symptomatic VTE was 3% (95% CI, 0.03-0.04) and for postoperative symptomatic as well as asymptomatic VTE was 8% (95% CI, 0.07-0.09). The presence of history of VTE (OR, 2.37), advanced-stages (OR, 2.35), high complexity of surgery (OR, 2.20), clear cell carcinoma of ovary (OR, 2.53) and residual disease>1 cm (OR, 2.57) significantly increase the likelihood of having postoperative VTE. Other risk factors for postoperative VTE in EOC patients were BMI>30 (OR, 1.58), per 10-years increase in age (OR, 1.22), ASA score>2 (OR, 1.45), ascites (OR, 2.07), the diameter of residual disease is between 0 cm to 1 cm (OR, 2.06) and smoking history (OR, 1.54). This study revealed that VTE, especially subclinical VTE, is a prevalent complication in postoperative patients with EOC. History of VTE, advanced FIGO stages, high complexity of surgery, obesity, older age, ascites, higher ASA score, smoking history and suboptimal debulking are associated with this increased incidence of postoperative VTE among patients with EOC. PROSPERO registration number: CRD42020209662.


Effect of age on the frequency of active Campylobacter pylori infection diagnosed by the [13C]urea breath test in normal subjects and patients with peptic ulcer disease.
We studied the frequency of active Campylobacter pylori infection in persons from North America (n = 53) or the People's Republic of China (n = 15) who had no gastrointestinal symptoms or a history of ulcer disease and in patients with active or recently active duodenal or gastric ulcers diagnosed by endoscopy (n = 105). C. pylori infection was significantly (P less than .001) more frequent in patients with peptic ulcers (88%) than in the normal group (45%). An age-related increase in the frequency of C. pylori infection in subjects with no gastrointestinal symptoms paralleled the known age-related increase in prevalence of gastritis. The frequency of C. pylori infection in patients with duodenal ulcers was greater than 80%, irrespective of age. C. pylori infection was more common in the Chinese group (age, 20-39 y) than in the North American group of the same age (60% vs. 24%). Association of C. pylori with specific diseases should not be inferred without knowing the prevalence of C. pylori infection in reference populations of the same age and ethnic background.


Antagonistic Interactions between Arsenic, Lead, and Cadmium in the Mouse Gastrointestinal Tract and Their Influences on Metal Relative Bioavailability in Contaminated Soils.
Soils are often co-contaminated with As, Pb, and Cd. To what extent ingested metal(loid)s interact with each other in the gastrointestinal tract and influence their RBA (relative bioavailability) is largely unknown. Three soils predominantly contaminated with As (MS, mining/smelting impacted), Pb (WR, wire rope production impacted), and Cd (EP, enamel pottery production impacted) were administered to mice individually or in binary and tertiary combinations with sodium arsenate, Cd chloride, and/or Pb acetate. In binary combinations, ∼10-fold higher Pb addition decreased As-RBA in MS (26.0 ± 6.28% to 17.1 ± 1.08%), while ∼10-fold higher As addition decreased Pb-RBA in WR (61.3 ± 2.41% to 28.8 ± 5.45%). This was possibly due to the formation of insoluble Pb arsenate in mouse intestinal tract, as indicated by the formation of precipitates when As and Pb co-occurred in water or simulated human gastrointestinal fluids. Due to competition for shared absorption transporters, ∼10- and 100-fold higher Pb addition decreased Cd-RBA in EP (95.8 ± 12.9% to 67.8 ± 12.8% and 62.8 ± 8.24%). Tertiary combinations showed that interactions between two metal(loid)s were affected by the presence of the third metal(loid). Our study suggests that As oxyanion could interact with Pb or Cd ions in the mouse gastrointestinal tract, and the interactions vary depending on concentration and solution characteristics.


Multicenter analysis of risk factors for anastomotic leakage after laparoscopic rectal cancer excision: the Korean laparoscopic colorectal surgery study group.
To assess the risk factors for clinical anastomotic leakage (AL) in patients undergoing laparoscopic surgery for rectal cancer. Little data are available about risk factors for AL after laparoscopic rectal cancer resection. This was a retrospective analysis of 1609 patients with rectal cancer who had undergone laparoscopic surgery for rectal cancer with sphincter preservation. Clinical data related to AL were collected from 11 institutions. Univariate and multivariate analyses were performed to determine the risk factors for AL. AL was noted in 101 (6.3%) of the patients. The leakage rate ranged from 2.0% to 10.3% for each hospital (P = 0.04). In patients without protective stomas (n = 1187), male sex [hazard ratio (HR), 3.468], advanced tumor stage (HR, 2.520), lower tumor level (HR, 2.418), preoperative chemoradiation (HR, 6.284), perioperative transfusion (HR, 10.705), and multiple firings of the linear stapler (HR, 6.181) were significantly associated with AL. Our theoretical model suggested that the HR for patients with 2 risk factors was significantly higher than that the HR for patients with no or only 1 risk factor. Male sex, low anastomosis, preoperative chemoradiation, advanced tumor stage, perioperative bleeding, and multiple firings of the linear stapler increased the risk of AL after laparoscopic surgery for rectal cancer. A diverting stoma might be mandatory in patients with 2 or more of the risk factors identified in this analysis.


Pharmacological study of BRS, a new bicarbonated Ringer's solution, in haemorrhagic shock dogs.
Sodium bicarbonate is the most physiological alkalinizing agent. The effect of a new bicarbonated Ringer's solution (BRS) containing Mg2+, on metabolic acidosis and serum magnesium abnormality were evaluated and compared with those of acetated Ringer's (ARS), lactated Ringer's (LRS) and Ringer's (RS) solutions in an experimental haemorrhagic shock model with dogs. Animals were randomly divided into six groups (n = 6 in each group), a sham-operated group, an operated group without infusion, and 4 operated groups with infusion (BRS, ARS, LRS and RS groups). Each RS was intravenously administered at 60 mL kg(-1) h(-1) for 1.5 h. Arterial blood gases, plasma electrolytes and cardiovascular parameters were analysed. BRS significantly improved blood base excess values, which were decreased by blood-letting, faster and more markedly than did LRS and RS (BRS--6.3 +/- 0.5 mEq L(-1); LRS--9.2 +/- 1.1 mEq L(-1); RS--12.4 +/- 1.0 mEq L(-1) at the end of infusion). The alkalinizing effect of BRS tended to be better than that of ARS but not significantly so. The serum Mg2+ concentration was well-maintained by BRS as compared to other RS (BRS 1.5 +/- 0.0 mgdL(-1); ARS 1.2 +/- 0.0mgdL(-1); LRS 1.1 +/- 0.0mgdL(-1); RS 1.3 +/- 0.1 mgdL(-1), at the end of infusion). These results suggest that BRS is a suitable perioperative solution for metabolic acidosis and serum electrolyte balance among RS tested.


Expressed protein ligation for protein semisynthesis and engineering.
Over the past decade, a significant methodological development in peptide ligation strategies has been elaborated that now permits the assembly of peptides and proteins. Native chemical ligation (NCL) has been introduced to join synthetic unprotected peptides by using the chemoselective reaction between a C-terminal thioester and an N-terminal cysteine residue to result in a native peptide bond. Although this method has been applied to obtain peptides, small proteins, or protein domains (up to approx 150 residues), larger proteins could not been easily received because of the limited size of the ligated fragments. Intein technologies benefit from the opportunity to participate in the production of polypeptides with the reactive groups necessary for NCL aside from the rapid isolation of highly pure recombinant proteins. Expressed protein ligation extends the scope of NCL by overcoming the size limitation of target proteins accessible to synthesis. The intein splicing and EPL have been already proven to be useful for protein semisynthesis and for various investigations, including the studies of protein-protein interactions, segmental isotopic labeling for protein structure determination, synthesis of cytotoxic proteins, protein cyclization, and site-specific incorporation of noncanonical amino acids and biophysical probes into a protein sequence.


From bench to bedside: 3D reconstruction and printing as a valuable tool for the chest wall surgeon.
The development of computer-aided design/manufacturing and digital image technology shows promise to revolutionize several medical and surgical fields. In this context, we propose a different approach for minimally invasive repair of pectus excavatum (MIRPE) including preoperative planning, ambulatory template fitting, and implant customization. We prospectively collected data on 130 consecutive patients who underwent a novel process of implant customization for MIRPE between November 2015 and September 2019 at our institution. This process consisted of: 1) preoperative planning using 3D computed tomography scan reconstruction and 3D printing of the implant template, 2) an ambulatory fitting session with the template, and 3) manufacture of a custom made, prebent, metallic implant based on the 3D printed templates. We described the process in detail and analyzed the "implant-deformity" match, need for rebending, modification of the curvature or shape of the pectus implant intraoperatively, and accuracy of the number of bars planned preoperatively. Preoperative planning including 3D reconstruction and printing resulted in a 92.3% optimal "implant-deformity" anatomic match. Minimal rebending without flipping of the implants was required in 5.4% of the patients. In two cases (1.5%), the implants were too short, and they tended to sink into the intercostal space, and in one case (0.8%), the patient's chest was extremely asymmetric, and the implant had to be removed and rebent intraoperatively. The number of implants planned preoperatively was precise in 100%. In this study, we demonstrated that minimally invasive repair of pectus excavatum assisted by preoperative planning, ambulatory template fitting, and implant customization enables an excellent anatomic match, leading to minimal rebending, and avoiding implant flipping or removal after retrosternal passage as well as accuracy in the number of bars programmed preoperatively. Prospective registry. III.


Inhibition of a novel sperm gelatinase in prawn sperm by the male reproduction-related Kazal-type peptidase inhibitor.
Previously, we have identified and characterized a male reproduction-related kazal-type peptidase inhibitor (MRPINK) gene from the prawn, Macrobrachium rosenbergii. In the present study, MRPINK was discovered to have an inhibitory effect on the gelatinolytic activity of M. rosenbergii sperm and immunofluorescence analysis revealed it bound specifically onto the base of sperm. The proteolytic activity of sperm extracts to vitelline coat components was also detected to be interfered by MRPINK. Furthermore, a novel gelatinase on sperm was found to be specifically inhibited by MRPINK and was named M. rosenbergii sperm gelatinase (MSG). MSG was then isolated and purified by reversed-phase high performance liquid chromatography combining with gelatinolytic assay. By amino-terminal amino acid sequence analysis and molecular cloning, the primary structure of MSG was determined. The data presented in this study provided evidence that MRPINK has an inhibitory effect on the gelatinolytic activity as well as proteolytic activity of prawn sperm and specifically blocks the activity of MSG.


[Results on reduction of subcutaneous adipose tissue using a novel body contouring system based on microwave technology].
Over the past decade, the body shaping market has seen steady growth. In order to improve procedures to reduce localized fat deposits, a novel method specifically targeting subcutaneous adipose tissue was developed. The objective of this study is to demonstrate that a novel microwave device with a frequency of 2.45 GHz achieves visible results with greater safety and consistency in reducing adipose tissue. In all, 19 healthy patients (10 women and 9 men; age 24-55 years, average age 39 years) and visible abdominal fat received three microwave treatment sessions (each 4 weeks apart) using the new Onda Plus Body Shaping System (DEKA, Italy). The device uses a handpiece that generates microwaves with a frequency of 2.45 GHz and integrated cooling for optimal patient comfort during treatment. An appropriate treatment protocol was established and applied for approximately 10 min in each treatment area. Before the start of treatment, informed consent and photo release forms were signed by all patients. Before each treatment session, the following were collected: body weight, height, waist circumference, and photographs of the area to be treated. All areas to be treated were premarked with a white skin marker pen while standing. Obese patients and those in whom fat deposits were distributed over the entire body or whose skin was in a state of irreversible flaccidity were excluded. A blood test was performed for each patient, both before the start of treatment (T0) and at the end of the entire treatment protocol (T3). All patients met the inclusion/exclusion criteria of the study and signed an informed consent form. The 19 healthy adults were divided into three groups according to the size of the abdominal fold (pinch): group 1 comprised 4 patients with a pinch greater than 4.5 cm, group 2 had 10 patients with a pinch of 2.5-4.5 cm, and group 3 had 5 patients with a pinch less than 2.5 cm. At the 3‑month follow-up, the clinically measurable reduction in abdominal circumference was 3.80 ± 1.21 cm in all patients. The microwave-based body contouring system was shown to be safe and effective to reduce abdominal circumference. No severe pain or noticeable discomfort was reported during any of the treatment sessions.


Constraints affecting partial prey consumption by a crab spider, Diaea sp. indet. (Araneae: Thomisidae).
The influence of feeding constraints on the feeding behaviour of Diaea sp. indet., was investigated. Diaea is a crab spider which ambushes its prey and practises extraintestinal digestion. A laboratory study was carried out using fruit flies, Drosophila immigrans, as prey. Diaea feeds from two sites on the prey - initially the head, followed by the posterior abdomen, with most of the prey's contents being extracted from the head. If additional prey are available, Diaea will, instead of switching to the posterior abdomen, catch a new prey item. The efficiency with which Diaea can extract food is influenced by changes which occur in the prey as a consequence of it being killed and fed on. Evaporative fluid loss from prey is an important constraint on food uptake because in influences the viscosity of the prey's contents. Regardless of whether a new prey item arrives, Diaea discards the prey item on which it is feeding before all of the available food has been extracted from it. The fluid content of the prey is not only part of the food the spider extracts, it is also a resource enabling efficient transfer of food from prey to predator. The value of the prey's fluid content as a resource decreases as a function of feeding time and as a consequence of the spider feeding on the prey.


Electronmicroscopic observation on chronic cardiopathy in spontaneous diabetic biobreeding rats.
The ultrastructural changes of chronic cardiopathy in diabetic biobreeding rats were observed electronmicroscopically. The thickness of the myocardial capillary basement membrane (CBM) and volume fraction of myofilaments in the myocardium were quantitatively measured with a video interactive display system III (VIDS-III). The effect of metabolic control on chronic diabetic cardiopathy was also investigated.


Efficacy of intense pulsed light combined with topical erythromycin solution 2% versus topical erythromycin solution 2% alone in the treatment of persistent facial erythematous acne macules.
There is always a necessity for newer acne treatments. Intense pulsed light (IPL) technology has been used for this purpose but there are limited studies in this field. As macular and erythematous remnants of acne inflammatory lesions are very common, resistant, and long lasting, we decided to evaluate the efficacy of IPL (as a tool for diminishing erythematous reactions in the tissues) for the treatment of residual erythematous macules following facial acne. Thirty-five patients were registered in the study. Patient recruitment occurred between January 2010 and June 2011, and the study was completed in October 2011. Every patient received three IPL sessions, with a 2 week interval, on the right side of his/her face. Also, we recommended the patients to apply topical erythromycin solution 2% twice daily on their entire face from start to end of the study (i.e. until 3 months after the third IPL session). An independent physician counted the number of erythematous macules before every IPL session and 1 and 3 months after the last session. Thirty-three patients completed the study and were enrolled in analysis. Results of the study show that IPL therapy decreases the number of erythematous macules along the time. IPL can accelerate the improvement rate of persistent erythematous macules remained after inflammatory acne subsides. More studies are needed to explain the exact role of it.


Topological aspects of geometrical signatures of phase transitions.
Certain geometric properties of submanifolds of configuration space are numerically investigated for classical phi(4) models in one and two dimensions. Peculiar behaviors of the computed geometric quantities are found only in the two-dimensional case, when a phase transition is present. The observed phenomenology strongly supports, though in an indirect way, a recently proposed topological conjecture about a topology change of the configuration space submanifolds as counterpart to a phase transition.


Developmental expression of mRNAs from a rat C-erbA genomic locus.
The thyroid hormone receptor alpha gene is alternatively spliced to give the alpha receptor and a variant which does not bind thyroid hormones. An additional alpha-like receptor (Rev-erbA alpha) is transcribed on the opposite strand and overlaps the unique variant sequence. The alpha receptor in rat brain reaches peak levels 5-15 days after birth. The variant remains high from 2 days before birth to old age. The Rev-erbA alpha mRNA increases beginning 5 days after birth, maximizing in adulthood. Thyroid hormone decreases and hypothyroidism increases the level of these 3 messages. We conclude that the levels of these messages are similarly controlled by thyroid hormone but have different ontogenetic controls. No functional results can be seen in vivo from potential anti sense pairing of Rev-erbA alpha with the variant.


Tolerance of nitrosurea-based multiagent chemotherapy regime for low-grade pediatric gliomas.
The aim of this study was to compare tolerance of a nitrosurea-based regime with 'standard' therapy of vincristine (VCR) and carboplatin for low-grade gliomas. Ten children with low-grade gliomas received second line therapy consisting of thioguanine, procarbazine, CCNU and vincristine (TPCV). Two groups were identified, i.e. patients who had either experienced significant toxicity with carboplatin (reaction group) or had re-growth of their tumor (re-growth group) following first line therapy. Patients were evaluated for toxicity. Data was available on nine patients. Patients in the reaction group completed a mean of 3 cycles of TPCV (range 2-4). One patient stopped after 2 cycles of TPCV due to tumor progression and died 3 months later and one remained on therapy at the time of analysis. Patients in the re-growth group received a mean of 5.5 cycles of TPCV (range 4-8). Treatment was discontinued in one patient after 4 cycles due to hematological toxicity, one experienced tumor progression after 4 cycles and one stopped after 6 cycles because of neurological toxicity. There was no difference in the incidence of grade 3/4 neutropenia or thrombocytopenia, transfusion requirements or delays in chemotherapy between TPCV and VCR/carboplatin in either group. There were no serious infections or toxic deaths. Seven of nine patients had stable disease at a mean of 13 months of follow up. TPCV therapy is a well-tolerated regime with comparable bone marrow toxicity to VCR/carboplatin. Significant disease stabilization was observed with TPCV and hence this regime may be used as second line therapy.


Different mutation profiles and clinical characteristics among Hispanic patients with non-small cell lung cancer could explain the "Hispanic paradox".
Sixteen percent of US population is Hispanic, mostly Mexican. Recently, two independent American reports demonstrated a higher overall survival (OS) in Hispanic populations compared with non-Hispanic-white populations (NHW) with non-small-cell lung cancer (NSCLC), even when most Hispanic patients are diagnosed at advanced disease stages and have lower income status. We analyzed the clinical, pathological, and molecular characteristics as well as outcomes in a cohort of NSCLC Hispanic patients from the National Cancer Institute of Mexico that could explain this "Hispanic Paradox". A cohort of 1260 consecutive NSCLC patients treated at the National Cancer Institute of Mexico from 2007 to 2014 was analyzed. Their clinical-pathological characteristics, the presence of EGFR and KRAS mutations and the prognosis were evaluated. Patients presented with disease stages II, IIIa, IIIb and IV at rates of 0.6, 4.8, 18.4 and 76.3%, respectively. NSCLC was associated with smoking in only 56.5% of the patients (76.7% of male vs. 33.0% of female patients). Wood smoke exposure (WSE) was associated with 37.2% of the cases (27.3% in men vs. 48.8% in women). The frequency of EGFR mutations was 27.0% (18.5% in males vs. 36.9% in females, p<0.001) and the frequency for KRAS mutations was 10.5% (10.3% men vs. 10.1% in women p=0.939). The median OS for all patients was 23.0 [95% CI 19.4-26.2], whereas for patients at stage IV, it was 18.5 months [95% CI 15.2-21.8]. The independent factors associated with the OS were the ECOG, disease stage, EGFR and KRAS mutation status. The high frequency of EGFR mutations and low frequency of KRAS mutations in Hispanic populations and different prevalence in lung cancer-related-developing risk factors compared with Caucasian populations, such as the lower frequency of smoking exposure and higher WSE, particularly in women, might explain the prognosis differences between foreign-born-Hispanics, US-born-Hispanics and NHWs.


Anti-inflammatory effect of prunetin via the suppression of NF-κB pathway.
Prunetin is an O-methylated isoflavone, which is found in Prunus yedoensis. To date no report has been published on anti-inflammatory activities of prunetin. In the present study, the anti-inflammatory effect of prunetin on LPS-stimulated RAW 264.7 macrophage and LPS-induced septic shock model were investigated. Inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) expressions were determined by western blot and or realtime-PCR (RT-PCR). To elucidate its underlying mechanism, nuclear factor-kappa B (NF-κb) activation and its downstream pathways were investigated by NF-κB transcription factor assay, reporter gene expression, and western blot. In vivo anti-inflammatory effects of prunetin were evaluated in LPS-induced endotoxemia. Promoter assay revealed that prunetin inhibits LPS-induced nitric oxide and prostaglandin E2 production through the suppression of iNOS and COX-2 at the transcriptional level. In addition, prunetin inhibits NF-κB-dependent inflammatory responses by modulating IκB kinase (IKK)-inhibitor κBα (IκBα)-NF-κB signaling. Consistent with these results, prunetin significantly reduced serum levels of inflammatory cytokines and mortality in mice challenged with lipopolysaccharide. These findings offer a potential mechanism for the anti-inflammatory activity of prunetin.


Hippocratic, religious, and secular ethics: the points of conflict.
The origins of professional ethical codes and oaths are explored. Their legitimacy and usefulness within the profession are questioned and an alternative ethical source is suggested. This source relies on a commonly shared, naturally knowable set of principles known as common morality.


AF150(S): a new functionally selective M1 agonist improves cognitive performance in rats.
This study was aimed at evaluating the ability of a new functionally selective partial M1 agonist, AF150(S), to reverse cognitive impairments in rats. A memory deficits-induced animal model was used that involved AF64A (3 nmol/2 microliters/side) bilaterally injected ICV. AF150(S) was administered PO. The pharmacodynamic profile of the compound was established and its general toxicity was evaluated. Animals were tested on three behavioral tasks: step-through passive avoidance, Morris water maze reference memory paradigm, and radial arm maze working memory paradigm. The sign-free dose of AF150(S) was > 40 mg/kg whereas the LD50 was > 500 mg/kg. In comparison, the effective dose in reversing performance impairments on the various tasks was much lower (0.5-5 mg/kg). The data suggest that AF150(S) possesses potential cognitive enhancement abilities, probably due to a specific increase of cholinergic function.


Generation of reactive oxygen species is not involved in idarubicin-induced apoptosis in human leukaemic cells.
The anthracycline antibiotic idarubicin (IDA) induces double-stranded DNA breaks, the generation of reactive oxygen species (ROS) and apoptosis in human leukaemic cells. It is unclear whether the generation of ROS is associated with the apoptotic process. Using the T-lymphoblastic leukaemic CEM cell line, we found that IDA-induced DNA breaks were correlated with final cell death. The reduction in mitochondrial membrane potential (Deltapsim) and the generation of ROS occurred simultaneously with IDA-induced activation of caspase-9 and caspase-3. Inhibition of caspases by a pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-fmk) completely blocked IDA-induced reduction of Deltapsim, apoptosis and final cell death. Interestingly, ROS generation was significantly enhanced by Z-VAD-fmk. ROS generation was neither caspase dependent nor part of the apoptotic process. IDA-mediated reduction in Deltapsim is caspase dependent and is not a consequence of the generation of ROS. These results indicate that IDA-induced generation of ROS and apoptosis are separate events. Inhibition of caspases facilitates IDA-mediated generation of ROS.


Wirelessly interfacing sensor-equipped implants and MR scanners for improved safety and imaging.
To investigate a novel reduced RF heating method for imaging in the presence of active implanted medical devices (AIMDs) which employs a sensor-equipped implant that provides wireless feedback. The implant, consisting of a generator case and a lead, measures RF-induced E $$ E $$ -fields at the implant tip using a simple sensor in the generator case and transmits these values wirelessly to the MR scanner. Based on the sensor signal alone, parallel transmission (pTx) excitation vectors were calculated to suppress tip heating and maintain image quality. A sensor-based imaging metric was introduced to assess the image quality. The methodology was studied at 7T in testbed experiments, and at a 3T scanner in an ASTM phantom containing AIMDs instrumented with six realistic deep brain stimulation (DBS) lead configurations adapted from patients. The implant successfully measured RF-induced E $$ E $$ -fields (Pearson correlation coefficient squared [R2 ] = 0.93) and temperature rises (R2 = 0.95) at the implant tip. The implant acquired the relevant data needed to calculate the pTx excitation vectors and transmitted them wirelessly to the MR scanner within a single shot RF sequence (<60 ms). Temperature rises for six realistic DBS lead configurations were reduced to 0.03-0.14 K for heating suppression modes compared to 0.52-3.33 K for the worst-case heating, while imaging quality remained comparable (five of six lead imaging scores were ≥0.80/1.00) to conventional circular polarization (CP) images. Implants with sensors that can communicate with an MR scanner can substantially improve safety for patients in a fast and automated manner, easing the current burden for MR personnel.


Recurrent genital herpes treatments and their impact on quality of life.
Herpes genitalis is one of the most common viral sexually transmitted diseases in the world, with an estimated seroprevalence in the US of greater than 20%. Two viruses of the same family cause herpes genitalis: herpes simplex virus 1 and 2. After the resolution of primary infection, the virus persists in the nerve roots of the sacral plexus, often causing recurrent (though generally less severe) outbreaks. These outbreaks, as well as the infectious potential to the patient's sexual partners, results in significant psychological stress on the patient, and has a tremendous negative impact on QOL. Current treatment modalities may result in a reduction in the number of outbreaks and viral shedding, but no cure exists. Although studies have clearly demonstrated the negative impact of recurrent genital herpes on QOL, an assessment scale specific to herpes was not developed until recently. Earlier studies indicated that patients did not perceive a significant benefit from episodic treatment with antivirals, but studies using the Recurrent Genital Herpes Quality of Life Questionnaire (RGHQoL) have now demonstrated that suppressive antiviral therapy improves quality of life in patients with frequent recurrences of genital herpes. However, not all patients with recurrent genital herpes need suppressive therapy, and proposed factors to consider include frequency of recurrence, physical and psychological distress caused by recurrences, and the potential for transmission to the patient's sexual partner. Newer therapeutic modalities, including the topical immune response modifier resiquimod and herpes vaccines, may eventually be shown to further decrease the psychological morbidity of recurrent genital herpes.


[Method of treating femur head dislocation fractures].
The fracture and dislocation of the head of the femur is still an uncommon accident, however, involving many complications. To avoid secondary damage a closed reduction should be obtained as soon as possible and with great care. Osteosynthesis of the femur head fragments is desireable for congruency of the joint surfaces and to prevent post traumatic arthrosis. Only this treatment allows for functional physical therapy. Type 3 fractures in patients over 65 and also multiple fractures of the femur head should be treated with a prosthesis implant. In young people primary reconstruction of the joint should be attempted in every case.


Pediocin-like antimicrobial peptides (class IIa bacteriocins) and their immunity proteins: biosynthesis, structure, and mode of action.
Pediocin-like antimicrobial peptides (AMPs) form a group of lactic acid bacteria produced, cationic membrane-permeabilizing peptides with 37 to 48 residues. Upon exposure to membrane-mimicking entities, their hydrophilic, cationic, and highly conserved N-terminal region forms a three-stranded antiparallel beta-sheet supported by a conserved disulfide bridge. This N-terminal beta-sheet region is followed by a central amphiphilic alpha-helix and this in most (if not all) of these peptides is followed by a rather extended C-terminal tail that folds back onto the central alpha-helix, thereby creating a hairpin-like structure in the C-terminal half. There is a flexible hinge between the beta-sheet N-terminal region and the hairpin C-terminal region and one thus obtains two domains that may move relative to each other. The cationic N-terminal beta-sheet domain mediates binding of the pediocin-like AMPs to the target-cell surface through electrostatic interactions, while the more hydrophobic and amphiphilic C-terminal hairpin domain penetrates into the hydrophobic part of the target-cell membrane, thereby mediating leakage through the membrane. The hinge provides the structural flexibility that enables the C-terminal hairpin domain to dip into the hydrophobic part of the membrane. Despite extensive sequence similarities, these AMPs differ markedly in their target-cell specificity, and results obtained with hybrid AMPs indicate that the membrane-penetrating hairpin-like C-terminal domain is the major specificity determinant. Bacteria that produce pediocin-like AMPs also produce a 11-kDa cognate immunity protein that protects the producer. The immunity proteins are well-structured, 4-helix bundle cytosolic proteins. They show a high degree of specificity in that they largely recognize and confer immunity only to their cognate AMP and in some cases to a few AMPs that are closely related to their cognate AMP. The C-terminal half of the immunity proteins contains a domain that is involved in specific recognition of the C-terminal membrane-penetrating specificity-determining hairpin domain of the cognate AMP.


Selection of aptamers against KMP-11 using colloidal gold during the SELEX process.
SELEX procedure is a methodology in which single stranded oligonucleotides are selected from a wide variety of sequences based on their interaction with a target molecule. We have designed a novel SELEX methodology using colloidal gold to select high affinity single stranded DNA aptamers against Leishmania infantum KMP-11. Kinetoplastid membrane protein-11 (KMP-11) is a major component of the cell membrane of kinetoplastid parasites. Although its function is not known, the fact that KMP-11 is a cytoskeleton-associated protein suggests that it may be involved in mobility or in some other aspects of the flagellar structure. We have isolated a single stranded DNA aptamer population that binds specifically to L. infantum KMP-11. This population has been characterized in a series of in vitro experiments suggesting that it may be used as a powerful tool to further investigate the role of KMP-11 during Leishmania development and/or as a diagnostic tool in Leishmania infection.


The recycling of a secretory granule membrane protein.
We have used N-hydroxysuccinimido-d-biotin as a reagent for labeling proteins exposed at the surface of cultured bovine adrenal chromaffin cells during Ba2+-stimulated secretion. A specific secretory granule membrane constituent, dopamine-beta-hydroxylase (DBH), has been investigated using immunoprecipitation followed by electrophoresis. Within 30 min of stimulation, exposed DBH had been cleared from the cell surface. Nevertheless, quantitation of labeled DBH using [125I] streptavidin suggested that it remained undegraded over a period of 24 h, a time during which secretory granule stores of catecholamines were being replenished. Subcellular fractionation of the cultured cells suggested that, after 3 or 4 h, the biotinylated DBH, which was still membrane-bound, was located in particulate material that also contained cytochrome b561, another major secretory granule membrane component.


Impact of sex and serum lipids interaction on working memory: A large-scale brain networks study.
Previous studies have demonstrated that both serum lipid levels and sex are crucial factors associated with individual cognition. However, the impact of sex and serum lipid interaction effects on the brain and cognition remains largely unknown. This study aimed to explore the underlying neural mechanisms among sex, serum lipids, and cognition using large-scale brain networks. Resting-state functional MRI data were collected from 157 young healthy adults. Independent component analysis was used to examine large-scale inter- and intra-network functional connectivity (FCs). Peripheral venous blood samples were collected to measure serum lipid levels. The three-back task was employed to assess cognition (i.e., working memory). General linear model, correlation, and mediation analyses were conducted to examine the interaction effects of sex and serum lipids on large-scale brain networks and their relationship with working memory. We found that inter-network connectivity with the executive control network at its core was more susceptible to sex and triglyceride interaction effects. The intra-network connectivity in the dorsal attention networks (DANs), lateral visual networks, and anterior default mode networks was influenced by the interaction effects of sex and total cholesterol (TC)/low-density lipoprotein cholesterol. Specifically, correlations between serum lipids and affected brain networks were found to be sex-specific. In addition, higher intra-network FC in the right inferior parietal (R-IPL) of the DAN correlated with a longer three-back reaction time in females. More importantly, the relationship between serum TC levels and three-back reaction time was mediated by intra-network connectivity in the R-IPL of the DAN. Our findings describe the impact of sex and serum lipid interaction effects on large-scale brain networks, as well as on cognitive function. Our data suggest that sex-specific usage of serum lipids or brain networks would be beneficial for monitoring and therapy in dyslipidemia-related cognition decline.


The sites of thyroid hormone formation in rabbit thyroglobulin.
Rabbit thyroglobulin (Tg) was labeled in vivo with 125I and purified by gel filtration. Separation by high performance liquid chromatography (HPLC) of tryptic digests of S-cyanoethylated Tg yielded four major iodothyronine-containing peaks, designated A, B, C, and D. These were further purified on HPLC and sequenced for identification of amino acid residues and for location of the iodothyronine by 125I counting. The published primary structure for bovine Tg, derived from cDNA sequencing of the Tg gene (Mercken, L., Simons, M.J., Swillens, S., Massaer, M., and Vassart, G. (1985) Nature 316, 647-651), permitted tentative location of the rabbit hormonogenic peptides within the Tg polypeptide chain. Site A, corresponding to bovine residue 5, contained 44% of Tgs [125I]T4 (thyroxine) and 25% of its [125I]T3 (triiodothyronine); its specific activity of iodine was higher than that for other sites, indicating priority of iodination. Site B, containing 24% of Tgs [125I]T4 and 18% of its [125I]T3, corresponded to bovine residue 2555. Site C, at the third residue from the C terminus (bovine residue 2748), was the major T3 site, accounting for over 50% of Tgs [125I]T3. The amino acid sequence around this site shows less homology among different animal species than do those flanking the other hormonogenic sites. Site D accounted for 17% of Tgs [125I]T4 and corresponded to bovine Tyr-1291, in the midportion of Tgs polypeptide chain. The three major T4-forming sites had the sequence Asp-Tyr (sites B and D) or Glu-Tyr (site A), while the sequence Ser-Tyr-Ser appeared to favor T3 synthesis (site C), suggesting an important influence of primary structure on hormonogenesis. We conclude that site A is the major T4-forming site and site C the major T3-forming one, but others are available and offer the opportunity for flexibility in meeting different demands for hormone formation.


Acoustic overstimulation alters the morphology of the tectorial membrane.
After a permanent threshold shift was induced by exposing guinea pigs to a 1 kHz pure tone at 105 dB(A) for 72 h, light microscopic observations of freshly dissected and stained tectorial membranes showed an increased waviness and clumping of the fibers of the middle zone. Hensen's stripe was not seen as a continuous dense structure running through the middle zone but was at times discontinuous and curved. As measured from cross-sections of the cochlea, the thickness of the tectorial membrane was decreased after acoustic overstimulation. The stereocilia of the inner and outer hair cells lie directly under the middle zone. Visual detection levels of threshold of tectorial membrane movement was determined by stimulating the marginal zone of the tectorial membrane of isolated cochlear coils by an oscillating water jet. After acoustic overstimulation the tectorial membrane became more complaint. The tectorial membrane abnormalities were restricted to the regions of the cochlea that demonstrated a 40-50 dB hearing loss.


Peptides mimicking Vibrio cholerae O139 capsular polysaccharide elicit protective antibody response.
Vibrio cholerae is the etiological agent of cholera. V. cholerae serogroup O1 had been, until 1992, the only serogroup responsible for large epidemics and pandemics of cholera. In 1992, a new serotype of V. cholerae emerged in South-East Asia that caused a massive outbreak of cholera in India and neighboring countries. The new serotype was named V. cholerae O139. The main differences between V. cholerae O139 and O1 are that the former possesses a capsular polysaccharide and different lipopolysaccharide. Capsular polysaccharides are, in general, T-independent antigens giving rise to poor immune responses lacking immunological memory. In order to overcome this, monoclonal antibodies against the capsular polysaccharide of V. cholerae O139 were used to screen different phage-displayed random peptide libraries. Eight different phage clones were selected and characterized using enzyme immunoassay with the monoclonal antibodies, and then tested for specificity by competition with V. cholerae O139 capsular polysaccharide. Selected peptides were sequenced, synthesized and conjugated to bovine serum albumin (BSA) and keyhole limpet hemocyanin (KLH). The conjugated peptides were used to immunize mice. It is evident that the anti-peptide mouse antibodies bind to the V. cholerae O139 capsular polysaccharide. In addition, the anti-peptide antibodies are protective in a suckling mouse model. The protective efficacy is both specific and dose-dependent. A PCT (PCT/IT2003/000489) with the publication number WO 2004/056851 has been filed for the sequences of the eight peptides.


Dexmedetomidine Versus Propofol for Patients With Sepsis Requiring Mechanical Ventilation: A Systematic Review and Meta-Analysis.
Purpose: This meta-analysis was performed to access the influence of dexmedetomidine versus propofol for adult patients with sepsis undergoing mechanical ventilation. Materials and Methods: NCBI PUBMED, Cochrane Library, Embase, China National Knowledge Internet (CNKI), and China Biological Medicine (CBM) were searched. Revman 5.3 and Stata software (version 12.0, Stata Corp LP, College Station, TX, United States) were used for meta-analysis. Results: Fifteen studies were included, and the data from the included studies were incorporated into the meta-analysis. Also, the result shows that compared with propofol, dexmedetomidine does not reduce 28-day mortality [risk ratios (RR) =0.97, 95% confidence interval (CI) =0.83-1.13, p = 0.70]. However, our analysis found that dexmedetomidine could reduce intensive care unit (ICU) stays {standard mean difference (SMD): -0.15; 95% CI: [-0.30-(-0.01)], p = 0.03}, duration of mechanical ventilation {SMD: -0.22; 95% CI: [-0.44-(-0.01)], p = 0.043}, sequential organ failure assessment (SOFA) {SMD: -0.41; 95% CI: [-0.73-(-0.09)], p = 0.013}, levels of interleukin-6 (IL-6) at 24 h (SMD: -2.53; 95% CI: -5.30-0.24, p = 0.074), and levels of CK-MB at 72 h {SMD: -0.45; 95% CI: [-0.83-(-0.08)], p = 0.017}. Conclusions: This meta-analysis (MA) suggests that in terms of 28-day mortality, sepsis patients with the treatment of dexmedetomidine did not differ from those who received propofol. In addition, more high-quality trials are needed to confirm these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42021249780.


Rett syndrome from a family perspective: The Swedish Rett Center survey.
The aim of this study was to make a description of the early development in individuals with the diagnosis Rett syndrome using parents' information. Information received from 125 cases of Rett syndrome in Sweden in 1997 provided us with families' description of early development in gross motor function, fine motor function and communication/social interplay. Best abilities before regression were presented, 62% lost their best abilities, 22% kept them and 5% kept them with deterioration. Seventy-three percent learnt to walk, 20% stopped walking and 2% retrained walking. Concerning feeding, 69% learnt to feed themselves, 57% lost this ability, 7% retrained the ability and 5% learnt to feed after regression. Sixty-four percent were one year or younger when there was a deviation in development. Sixty answers reported the girl was late in developing functions while 35 reported sudden loss of reached abilities. Seventy-four percent developed a scoliosis and 83% reported other deformities; of these, deformities in feet were the most common. Postural control was poor since all but 15 girls/women learnt in different directions when sitting. Transitional movements were difficult to perform. In 80% of cases, the families were those who suspected early that something was wrong in the child's development. Because of this it is essential that medical staff is aware of the different ways RS develops in order to give families early appropriate support and a plan for intervention. Since there is not only loss of function in this group but also kept abilities, retrained abilities and abilities achieved after regression, more research has to be focused on management and treatment to help persons with Rett syndrome keep and develop abilities according to their individual resources.


Neutrophil gelatinase-associated lipocalin curve and neutrophil gelatinase-associated lipocalin extended-range assay: a new biomarker approach in the early diagnosis of acute kidney injury and cardio-renal syndrome.
Cardio-Renal syndrome (CRS) is a common and complex clinical condition in which multiple causative factors are involved. The time window between renal insult and development of acute kidney injury (AKI) in acute heart failure (AHF) can be varied in different patients and AKI often is diagnosed too late, only when the effects of the insult become evident with a loss or decline of renal function. For this reason, pharmaceutical interventions for AKI that have been shown to be renoprotective or beneficial when tested in experimental conditions do not display similar results in the clinical setting. In most cases patients with AHF are admitted with clinical signs and symptoms of congestion and fluid overload. Loop diuretics, typically used to induce an enhanced diuresis in these congested patients, often are associated with a subsequent significant decrease in glomerular filtration rate and cause a creatinine increase that is apparent within 72 hours. Early detection of AKI is not possible with the use of serum creatinine and there is a need for a timely diagnostic tool able to address renal damage while it is happening. We need to define the diagnosis of both AHF and AKI in the early phases of CRS type 1 by coupling a kidney damage marker such as neutrophil gelatinase-associated lipocalin (NGAL) with B-type natriuretic peptide (BNP). Indeed, it would be ideal to make available a panel including whole blood or plasma cardiac and renal biomarkers building specific, pathophysiologically based, molecular profiles. Based on current knowledge and consensus, we can use kidney damage biomarkers such as plasma NGAL for an early diagnosis of AKI. However, differences in individual patient values and uncertainties about the ideal cut-off values may currently limit the application of these biomarkers. We propose that NGAL may increase its usefulness in the diagnosis and prevention of CRS if a curve of plasma values rather than a single plasma measurement is determined. To apply the concept of measuring an NGAL curve in AHF patients, however, assay performance in the lower-range values becomes a critical factor. For this reason, we propose the use of the new extended-range plasma NGAL assay that may contribute to remarkably improve the sensitivity of AKI diagnosis in AHF and lead to more effective intervention strategies.


Valvular and systemic arterial hemodynamics in aortic valve stenosis. A model-based approach.
Assessment of the severity of a stenotic aortic valve has been confounded by reports of flow dependence of stenosis severity. We hypothesized that the pressure gradient at the stenotic aortic valve would be dependent on the characteristics of the arterial circulation. Therefore, clinically useful measures of the severity of aortic valve stenosis may have to take this dependence into account. We developed an analog model of the systemic arterial circulation in the presence of a stenotic aortic valve. The model clearly describes the dependence of stenosis severity (described by coefficients A and B) on the resistive and capacitive properties of the arterial system. We used high-fidelity pressure recordings obtained at the time of diagnostic cardiac catheterizations and found that a highly significant relation between the measured mean transvalvular gradient and that predicted by the model was demonstrated both at rest (r2 = .90) and with exercise (r2 = .80). Furthermore, the relative constancy of stenosis coefficients A and B was validated. Transvalvular hemodynamics in patients with aortic valve stenosis are dependent on the properties of the arterial system. The current model describes such behavior, correctly predicts the transvalvular gradient from model parameters, and may be useful in the assessment of stenosis severity under various clinical and physiological conditions.


Studying the visceral physiology of tadpoles through their naturally transparent abdominal walls.
We propose using anuran tadpoles with naturally transparent abdominal skin to study the visceral physiology of amphibian larvae under microgravity. The transparency of the abdominal wall in certain tadpoles enables one to evaluate the basal physiological state and temporal changes in viscera from their movements without any invasive treatment. In order to validate our experimental design, the intestinal motility and heart rate of Rhacophorus tadpoles were examined as indices of physiological responses to stepwise changes in temperature.


Cancer patients with fractures are rarely assessed or treated for osteoporosis: a population-based study.
Among 4238 cancer and 16,418 cancer-free individuals with incident major non-traumatic fractures (hip, clinical vertebral, forearm, humerus), post-fracture osteoporosis care was equally poor for both groups, whether assessed from bone mineral density (BMD) testing, initiation of osteoporosis therapy or either intervention (BMD testing and/or osteoporosis therapy). Most individuals sustaining a fracture do not undergo evaluation and/or treatment for osteoporosis. Cancer survivors are at increased risk for osteoporosis and fracture. Whether cancer survivors experience a similar post-fracture "care gap" is unclear. Using population-based databases, we assessed whether cancer patients are evaluated and/or treated for osteoporosis after a major fracture. From the Manitoba Cancer Registry, we identified cancer cases (first cancer diagnosis between 1987 and 2013) and cancer-free controls with incident major non-traumatic fractures (from provincial physician billing claims and hospitalization databases). The outcomes were performance of BMD testing (from the BMD Registry), initiation of osteoporosis therapy (from drug dispensation database) or either intervention (BMD testing and/or osteoporosis therapy) in the 12 months post-fracture. There were 4238 cancer and 16,418 cancer-free individuals who sustained a fracture after the index date (cancer diagnosis) and were followed for at least 1 year post-fracture. Subsequent BMD testing was performed in 11.0% of cancer cases versus 11.5% non-cancer controls (P = 0.43), osteoporosis treatment in 22.9% cancer cases versus 21.8% non-cancer controls (P = 0.15), and either testing or treatment in 28.9% cancer cases versus 28.4% non-cancer controls (P = 0.53). Predictors of BMD testing and/or initiation of therapy were similar for non-cancer and cancer patients. Post-fracture interventions were consistently used more frequently among women, older patients (age 50 years or older), those who sustained fractures in a later calendar period, and (for treatment) after vertebral fracture. Cancer-specific variables (cancer type, years from cancer diagnosis to fracture, specialty of care provider) showed only weak and inconsistent effects. A large care gap exists among cancer patients who sustain a fracture, similar to the general population, whereby the evaluation or treatment for osteoporosis is seldom conducted. Care maps may need to be developed for cancer populations to improve post-fracture care.


Intermittent dystonia in Hartnup disease.
A 6-month-old girl developed intermittent dystonic posture of the legs and eczematous dermatitis without ataxia. Qualitative and quantitative urine amino acid testing confirmed the diagnosis of Hartnup disease. Cranial computed tomography, electroencephalogram, electromyogram/nerve conduction study, posterior tibial somatosensory evoked potentials, 24-hour electroencephalographic telemetry, and metrizamide myelogram were normal. Spinal fluid hydroxy-indoleacetic acid concentration was less than or equal to 2 S.D. of normal; oral tryptophan loading (70 mg/kg) resulted in a two-fold rise in cerebrospinal fluid 5-hydroxy-indoleacetic acid concentration. Tryptophan administered alone or with nicotinic acid failed to improve the dystonia; however, trihexyphenidyl (1-2 mg/kg/day) dramatically improved it. Hartnup disease should be considered in children with unexplained dystonia.


New class of HIV-1 integrase (IN) inhibitors with a dual mode of action.
tert-Butoxy-(4-phenyl-quinolin-3-yl)-acetic acids (tBPQA) are a new class of HIV-1 integrase (IN) inhibitors that are structurally distinct from IN strand transfer inhibitors but analogous to LEDGINs. LEDGINs are a class of potent antiviral compounds that interacts with the lens epithelium-derived growth factor (LEDGF) binding pocket on IN and were identified through competition binding against LEDGF. LEDGF tethers IN to the host chromatin and enables targeted integration of viral DNA. The prevailing understanding of the antiviral mechanism of LEDGINs is that they inhibit LEDGF binding to IN, which prevents targeted integration of HIV-1. We showed that in addition to the properties already known for LEDGINs, the binding of tBPQAs to the IN dimer interface inhibits IN enzymatic activity in a LEDGF-independent manner. Using the analysis of two long terminal repeat junctions in HIV-infected cells, we showed that the inhibition by tBPQAs occurs at or prior to the viral DNA 3'-processing step. Biochemical studies revealed that this inhibition operates by compound-induced conformational changes in the IN dimer that prevent proper assembly of IN onto viral DNA. For the first time, tBPQAs were demonstrated to be allosteric inhibitors of HIV-1 IN displaying a dual mode of action: inhibition of IN-viral DNA assembly and inhibition of IN-LEDGF interaction.


The intramandibular gland of leaf-cutting ants (Atta sexdens rubropilosa Forel 1908).
The eusociality developed in Hymenoptera and Isoptera is driven by an efficient interaction between exocrine glands and jointed appendages, both in close interaction with the environment. In this context, the mandible of ants plays an important role, since, in addition to being the main jointed appendage, it possess glandular functions. As an example we might name the two glands associated with the mandible: the mandibular and the intramandibular glands. The intramandibular gland is found inside the mandible and consists of a hypertrophied secretory epithelium and secretory cells in the mandible's lumen. The secretion of the secretory epithelium is liberated through intracuticular ducts that open at the base of hairs at the mandible's surface. The secretion of the intramandibular gland (epithelium and secretory cells) reacted positively to tests for the detection of polysaccharides and proteins, thus suggesting that it consists of glycoproteins. The ultrastructure of the secretory epithelium presents variations related to the developmental stage of the individual, showing a large number of ribosomes and microvilli close to the cuticle in young individuals, while in the older specimens it was possible to note the formation of an intracellular reservoir. These variations of secretory epithelium, as also the interaction between the cellular groups inside the mandible, are important information about this gland in leaf-cutting ants.


Assessment of risk factors and molecular biomarkers in children with supernumerary teeth: a single-center study.
Supernumerary teeth are considered one of the commonly observed dental anomalies in children. Several theories have been proposed to explain the presence of supernumerary teeth, including environmental and genetic factors. This study aimed to identify the different risk factors and molecular biomarkers in patients presented with supernumerary teeth. This case-control study included 240 children, 6 to 12-year-old. They were divided into a test group (n = 120 children presented with supernumerary teeth) and a control group (n = 120 children with no supernumerary teeth). Questionnaires were distributed to assess demographics and exposure to several environmental factors. Ten extracted supernumerary teeth from the test group were processed for histopathological analysis. Male gender, dental history of severe oral infection or medical history of chemotherapy treatment, previous history of taking medication or illness during pregnancy, family history of neoplastic disorders, use of electronic devices, and living beside agricultural fields or industrial areas were found to be statistically significant associated with the risk of supernumerary teeth development. Immunohistochemistry panel revealed that supernumerary teeth showed enhanced expression of wingless (Wnt) and sonic hedgehog (SHH) proteins as well as a reduced expression of adenomatous polyposis coli (APC) protein, denoting molecular derangement in a group of pathways classically believed to be involved in its pathogenesis. Males were more frequently affected by supernumerary teeth than females. Several risk factors were notably correlated with the existence of supernumerary teeth. Additionally, molecular biomarkers assessment demonstrated a high expression level of pro-tumorigenic proteins such as Wnt and SHH in patients with supernumerary teeth.


Faecal chitinase 3-like 1 is a reliable marker as accurate as faecal calprotectin in detecting endoscopic activity in adult patients with inflammatory bowel diseases.
Faecal biomarkers are emerging tools in the assessment of mucosal healing in inflammatory bowel diseases (IBDs). To evaluate the accuracy of faecal chitinase 3-like 1(CHI3L1) compared to calprotectin in detecting endoscopic activity in IBD. Overall, 86 IBD adults underwent colonoscopy consecutively and prospectively, with Crohn's disease Endoscopic Index of Severity (CDEIS) or Mayo endoscopic subscore calculation for ulcerative colitis, and stool collection. Faecal calprotectin was measured using quantitative immunochromatographic testing. Faecal CHI3L1 was quantified by ELISA. CHI3L1 cut-off value was determined using a receiver-operating curve. In 54 Crohn's disease patients, faecal CHI3L1 (ρ = 0.70, P < 0.001) and calprotectin (ρ = 0.74, P < 0.001) levels correlated with CDEIS and were significantly increased in patients with endoscopic ulceration. In patients with ileal Crohn's disease, faecal CHI3L1 seemed to be better correlated with CDEIS than faecal calprotectin (ρ = 0.78 vs. ρ = 0.62, P < 0.001 for both). CHI3L1 > 15 ng/g detected endoscopic ulceration in Crohn's disease with a sensitivity of 100% and a specificity of 63.6%, compared to faecal calprotectin > 250 μg/g showing a sensitivity of 90.5% and a specificity of 59.1%. In 32 ulcerative colitis patients, faecal CHI3L1 and calprotectin levels correlated with Mayo endoscopic subscore (ρ = 0.44 and 0.61, respectively, P < 0.001 for both) and were significantly increased in ulcerative colitis patients with endoscopic activity. In ulcerative colitis patients, faecal CHI3L1 > 15 ng/g predicted endoscopic activity with a sensitivity of 81.8% and a specificity of 80.0%, compared to faecal calprotectin>250 μg/g showing a sensitivity of 86.4% and a specificity of 80.0%. Faecal CHI3L1 is a reliable biomarker in detecting endoscopic activity in IBD.


Cytotoxic and genotoxic effects of the azo-dye p-dimethylaminoazobenzene in mice: a time-course study.
The cytotoxic and genotoxic effects of chronic feeding of the azo-dye p-dimethylaminoazobenzene (p-DAB) during 7, 15, 30, 60, 90 and 120 days have been assessed in mice. The endpoints used for genotoxic analysis were chromosome aberrations (CA), micronuclei (MN) and mitotic index (MI) in bone-marrow cells, and sperm-head abnormality (SHA) in male gonads. The activities of marker enzymes for toxicity, such as glutamate oxalo-acetate transaminase (GOT), glutamate pyruvate transaminase (GPT), acid phosphatase (ACP) and alkaline phosphatase (ALKP) were also assayed periodically, as was lipid peroxidation (LPO). Chronic feeding of p-DAB produced increased numbers of chromosome aberrations, nuclear anomalies and sperm-head abnormalities, as compared with normal untreated controls, generally in a time-dependent manner until 60 days, after which the anomalies persisted, but rather erratically. However, although there was some noticeable modulation in enzyme activities in the corresponding p-DAB-fed mice as well, these were not strictly time-dependent.


Associations of visceral fat area and physical activity levels with the risk of metabolic syndrome in postmenopausal women.
This study was aimed at the evaluation of relationship between visceral fat area (VFA) and physical activity (PA) with the metabolic syndrome (MetS) risk in the physically active postmenopausal women. A total of 85 attendants of the University of the Third Age (U3A) aged 62.8 ± 5.9 years (median time since menopause 11.8 y), participated in this study. VFA was assessed by bioimpedance method using InBody 720 analyzer. PA was assessed using the ActiGraph GT1 M accelerometer. Fasting levels of serum lipids (TG, HDL), serum glucose, waist circumference (WC) and blood pressure were measured to diagnose MetS according to NCEP-ATP III criteria. In 73 out of 85 participants the VFA exceeded the upper normal level of 100 cm2, however, in almost a half of this group (n = 36) with elevated VFA (139.5 ± 26.1 cm2 on average), only 2 out of 5 criteria for MetS diagnosis were met. Participants were physically active, making on average 10,919 ± 3435 steps/day. The risk of MetS occurrence in women with VFA > 100 cm2 was twelve times higher (OR 12.33; CI 95% [1.5; 99.8]) than in the group with VFA < 100 cm2. The participants from the group with the highest PA level (≥12,500 steps/day) were at almost 4 times lower risk for MetS, than their less active counterparts (OR 3.84; CI 95% [1.27;11.64]). Increased level of VFA is a strong risk factor for the MetS in postmenopausal women, however high level of regular PA above the threshold of 12,500 steps/day may substantially reduce it.


Aurora promotes cell division during recovery from TOR-mediated cell cycle arrest by driving spindle pole body recruitment of Polo.
The coordination of cell division and growth in response to changes in nutrient supply is mediated by TOR signalling. In fission yeast, increased nutrient provision transiently delays mitotic onset without affecting growth. The result is an increase in cell size at division. We find that this block to cell division relies upon TOR and MAPK signalling and that mitotic entry during recovery from this block is regulated by the Aurora kinase Ark1. We show that Ark1 phosphorylation of polo kinase Plo1 within the linker region between the kinase domain and polo boxes drives Plo1 onto the spindle poles where it promotes mitosis. Interestingly, the use of Ark1 to phosphorylate Plo1 and promote mitotic entry is dependent on the environment.


Improved lymph node retrieval in Whipple specimens as a result of implementation of a new uncinate margin protocol.
Lymph node status is an important prognostic factor in pancreatic and peri-ampullary adenocarcinoma. We recently changed our protocol for assessment of the uncinate margin of Whipple specimens and noted that lymph nodes were often present in uncinate margin sections. Whipple specimens from 2004 to 2006 were divided into two groups, those that were handled according to the en face protocol, and those handled according to the radial protocol. The numbers of lymph nodes found in uncinate margin sections were assessed, as well as the total number of nodes found in the specimen. Sixteen cases were handled according to the en face protocol, and 20 according to the radial protocol. In the en face group, 2 benign nodes were found in the uncinate margin (0.1 nodes per case), while in the radial group, 36 nodes (1.8 nodes per case) were identified (p=0.0005). Eight cases in the latter group had positive nodes in the uncinate margin sections. In two of these cases the positive lymph node was the only lymph node with metastasis, and in an additional case the involved node was one of two positive lymph nodes. Total lymph node retrieval was 15.5 lymph nodes per case in the en face group, and 20 nodes per case in the radial group (p=0.02). The improved lymph node retrieval may be due to additional nodes found in radial sections of the uncinate margin, or alternatively, due to increased vigilance in specimen handling. In 3 of 20 cases, nodes found in the radial sections influenced staging.


Identification of influencing factors for suicidal ideation and suicide attempts among adolescents: 11-year national data analysis for 788,411 participants.
Suicide is one of the most common causes of death in adolescents. This study identified trends in the prevalence of and factors influencing suicidal ideation and attempts among Korean adolescents. Data were drawn from the third through the thirteenth (2007-2017) annual Korean Youth Risk Behavior Web-based Surveys. Participants included stratified, multistage clustered samples selected from 400 middle schools and 400 high schools annually. Depression, suicidal ideation, and suicide attempts were binary dependent variables (requiring answers of yes or no). A total of 818,684 adolescents were targeted and 788,411 adolescents completed the survey. The prevalence rates of both suicidal ideation and attempts gradually decreased from 23.7% and 5.8%, respectively, in 2007 to 12.1% and 2.6%, respectively, in 2017. Overall, 16.8% of participants had suicidal ideation and 3.9% had suicide attempts during the survey period. During logistic regression analysis, depression was most strongly associated with suicidal ideation (adjusted odds ratio: 5.78 [95% confidence interval: 5.64-5.88]) and suicide attempts (adjusted odds ratio: 5.56, [95% confidence interval: 5.22-5.83]). Despite decreasing trends, the high rate of suicidal behaviors remains a critical public health problem. Depression most strongly predicts suicidal behaviors. Early interventions are essential to treat depression and reduce or prevent suicide.


Psoas abscess twenty-one years after ipsilateral nephrectomy.
We report an unusual case of psoas abscess, which developed twenty-one years after ipsilateral nephrectomy and was caused by infrequent pathogen, Proteus mirabilis. It was diagnosed by computed tomography and was drained percutaneously with a nephrostomy tube guided by ultrasonography.


A comparison of the fracture resistance of premolars without a ferrule with different post systems.
Which type of post improves the performance of endodontically treated mandibular premolars without a ferrule remains unclear. The purpose of this in vitro study was to compare the restoration of endodontically treated mandibular premolars without a ferrule by using different post systems. Thirty extracted mandibular premolars were endodontically treated, and their crowns removed. They were divided into 3 groups with different post systems (n=10): zirconia ceramic posts (ZRPs), fiber posts (FPs), and bundled glass fiber-reinforced composite resin posts (GTPs). After post placement and core fabrication, computer-aided design and computer-aided manufacture (CAD-CAM) lithium disilicate crowns were cemented. The specimens were subjected to thermocycling and mastication simulation before a fracture test in a universal testing machine. The maximum load at which the fracture occurred was recorded, and the fractured specimens were examined by using an optical microscope. The data were analyzed for statistical differences with a 1-way ANOVA and the Tukey honestly significant difference post hoc test (α=.05). No statistically significant difference in fracture strength was found among the groups (P=.970). From the light microscopy examination, catastrophic failure was observed in all specimens, and there was no failure of the ceramic crowns. Based on the findings of this in vitro study, the choice of post material with a low or high modulus of elasticity did not prevent catastrophic failures in endodontically treated teeth without a ferrule.


Affinity chromatography of glucose dehydrogenase.
Porcine liver beta-D-glucose dehydrogenase, a multi-functional protein, has been purified to apparent homogeneity. The enzyme has been separated from the endoplasmic reticulum using Triton X-114 and further purified using NAD to release glucose dehydrogenase from a NADP-linked sepharose column. The purified enzyme is capable of producing both NADH and NADPH in vivo as indicated by kinetic studies.


Frequency of Infection during Fever Episodes among Long-Term Care Residents.
Empirical data regarding the frequency of infection during fever episodes among women in long-term care facilities are lacking. We conducted a case-series analysis of women long-term care residents enrolled in a randomized trial evaluating cranberry capsules to reduce bacteriuria plus pyuria across twenty-one long-term care facilities in CT, USA. Fever episodes identified during adverse event surveillance were assessed using established guidelines for older adults. Among fever episodes, infections were classified using standardized infection surveillance definitions in long-term care residents. We identified 123 fever episodes among 80 women long-term care residents. Median age was 88 years (range, 65-101), and 81% (N=65) had dementia. Among 123 fever episodes, 79 (64%) met criteria for 86 total infections (lower respiratory tract, N=43; pneumonia, N=27; gastroenteritis, N=9; urinary tract, N=7). Data from this study suggest that approximately two-thirds of fever episodes involve infection among women in long-term care facilities. These data may guide provider assessments of fever in older adult women in long-term care facilities.


Insulin-dependent covalent reassociation of isolated alpha beta heterodimeric insulin receptors into an alpha 2 beta 2 heterotetrameric disulfide-linked complex.
The purified human placental alpha 2 beta 2 heterotetrameric insulin receptor complex was reduced and dissociated into functional alpha beta heterodimers by a combination of alkaline pH and dithiothreitol treatment. Insulin treatment of the isolated alpha beta heterodimeric complex was observed to induce the complete reassociation to an alpha 2 beta 2 heterotetrameric state when analyzed by nondenaturing Bio-Gel A-1.5m gel filtration chromatography. Nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis of 125I-insulin affinity cross-linked and 32P-autophosphorylated alpha beta heterodimers demonstrated that the insulin-dependent reassociation to the alpha 2 beta 2 heterotetrameric state occurred both covalently and noncovalently under these conditions. Comparison by reducing and nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the insulin-dependent covalent reassociation to an alpha 2 beta 2 heterotetrameric complex was due to the formation of a disulfide linkage(s) between the alpha beta heterodimers. beta subunit autophosphorylation of the control alpha 2 beta 2 heterotetrameric insulin receptor preparation was maximally stimulated within 5 min of insulin preincubation and occurred exclusively in the Mr = 400,000 alpha 2 beta 2 complex. Similarly, maximal insulin-stimulated beta subunit autophosphorylation of the alpha beta heterodimeric preparation occurred within 5 min of insulin pretreatment in the Mr = 210,000 alpha beta complex. However, 4 h of insulin pretreatment of the alpha beta heterodimer preparation induced the formation (6-fold) of a covalent 32P-labeled alpha 2 beta 2 heterotetrameric complex. Maximal stimulation of substrate phosphorylation for the alpha 2 beta 2 heterotetrameric complex was also observed to occur within 5 min of insulin treatment, whereas maximal insulin-stimulated substrate phosphorylation of the alpha beta heterodimeric complex required greater than 4 h. These data demonstrate that (i) insulin treatment can induce the reassociation of the alpha beta heterodimeric complex into a covalent alpha 2 beta 2 heterotetrameric state, and (ii) insulin-dependent protein kinase activation of the alpha beta heterodimeric insulin receptor correlates with the covalent reassociation into a disulfide-linked alpha 2 beta 2 heterotetrameric complex.


The high affinity interleukin 2 receptor: evidence for three distinct polypeptide chains comprising the high affinity interleukin 2 receptor.
Low and high affinity receptors for interleukin 2 were investigated on interleukin 2 (IL-2) receptor bearing cells by chemical cross-linking of 125I-labelled IL-2 to its receptor, or membrane proteins associated with the IL-2 binding sites. SDS-PAGE analysis of the cross-linked complexes of the murine CTLL 16 cells and human T-blasts, which bear high and low affinity IL-2 receptors, showed three distinct bands. The fastest of those three bands ran in parallel to the single band of 65-70 kDa found on the only low affinity receptor bearing mouse T-lymphoma Eb, which is thought to be one beta-chain (55 kDa IL-2 binding protein) and one IL-2. Both upper bands ran in parallel with those produced by the 2C8 clone of the NK-like cell line YT which lacks the 55 kDa binding protein and bears only a single class of receptors with an intermediate affinity. Internalisation studies using CTLL 16 cells revealed that all three bands disappeared under conditions allowing receptor internalisation. Low and high affinity binding sites of CTLL 16 cells were destroyed by trypsinisation and the IL-2 binding properties of the cells were regenerated in parallel with the reappearance of all bands. These results show in addition to the beta-chain (55 kDa binding protein) and the alpha-chain 75 kDa binding protein, an IL-2 membrane protein complex with an apparent mol. wt of 115 kDa in CTLL 16 cells. They are the first direct indication of a putative gamma-chain of the high affinity IL-2 receptor.


Nonintentional task set activation: evidence from implicit task sequence learning.
Studies have shown that task sets could be configured endogenously (i.e., on the basis of memory) according to an explicit sequence or exogenously according to a task cue. In two experiments, we examined whether an implicitly learned sequence could facilitate task set configuration without participants' intention. These experiments led to opposite conclusions regarding this question, but their methodology made it impossible to distinguish between the interpretations. We altered the task-switching paradigm by embedding a hidden task sequence, while randomizing all other aspects, including perceptual (i.e., task cues) and motor elements. We found that a sequence of tasks, proper, was learned implicitly and that the memory of that sequence endogenously facilitated task decision processes without the participants' explicit knowledge.


The pelvitrainer for training in laparoscopic surgery - A prospective, multicenter, interdisciplinary study: Experimental research.
Minimally invasive surgical procedures have a flat learning curve, especially in the initial period of a surgeon's training. Pelvitrainers enable the prospective surgeon to drill the surgical technique, including camera navigation, instrument manipulation, and the individual steps of the operation, on a model rather than a patient. Integrating the pelvitrainer into standardized surgical training programs is challenging, but would be essential to achieve optimum effects of long duration in surgical education. The pelvitrainer Realsimulator 2.0 (Endodevelop) was evaluated in 16 standardized training courses (at three training centers) of the German Working Group for Gynecological Endoscopy (AGE e.V.) from 2017 to 2020, The training concept was implemented and evaluated in a prospective, multicenter, interdisciplinary, multinational setting. One hundred and eighty of 206 physicians (response rate 87.4%) completed the multi-stage training concept successfully. A significant (p < 0.001) objective improvement (positive learning curve) was observed for all exercises on the pelvitrainer. The trainer's subjective evaluation revealed positive ratings for design (median 82%, IQR 71-91%), camera navigation (87%, IQR 76-95%), and instrument manipulation (median 87%, IQR 77-94%). A follow-up survey performed six months after the course confirmed its sustainable and high benefits in clinical routine (median 82%, IQR 70-97%). The present investigation proved the high educational value of pelvitrainers, which can be enhanced by using a structured training concept. The benefit of training courses for health care justifies their incorporation into a standardized training curriculum. The completion of such training courses should be regarded as a prerequisite for a doctor to qualify as an independent surgeon.


Caveolin-1 in endothelial cells: A potential therapeutic target for atherosclerosis.
Atherosclerosis (AS) is a chronic vascular disease characterized by lipid accumulation and the activation of the inflammatory response; it remains the leading nation-wide cause of death. Early in the progression of AS, stimulation by pro-inflammatory agonists (TNF-α, LPS, and others), oxidized lipoproteins (ox-LDL), and biomechanical stimuli (low shear stress) lead to endothelial cell activation and dysfunction. Consequently, it is crucial to investigate how endothelial cells respond to different stressors and ways to alter endothelial cell activation in AS development, as they are the earliest cells to respond. Caveolin-1 (Cav1) is a 21-24-kDa membrane protein located in caveolae and highly expressed in endothelial cells, which plays a vital role in regulating lipid transport, inflammatory responses, and various cellular signaling pathways and has atherogenic effects. This review summarizes recent studies on the structure and physiological functions of Cav1 and outlines the potential mechanisms it mediates in AS development. Included are the roles of Cav1 in the regulation of endothelial cell autophagy, response to shear stress, modulation of the eNOS/NO axis, and transduction of inflammatory signaling pathways. This review provides a rationale for proposing Cav1 as a novel target for the prevention of AS, as well as new ideas for therapeutic strategies for early AS.


Effects of methylene blue on propofol requirement during anaesthesia induction and surgery.
Delayed emergence from anaesthesia and neurological disturbances have been reported in patients undergoing parathyroidectomy who received methylene blue (MB) pre-operatively. We hypothesised that MB would decrease propofol requirements. The Bispectral index (BIS) and a target-controlled infusion of propofol were used in two groups of 11 matched patients. Patients in one group were pretreated with MB. During induction, clinical sedation scores and BIS values were significantly lower at the predicted effect-site propofol concentration of 2 microg x ml(-1) in the MB compared with the control group. Intra-operatively, although similar BIS values were achieved in the two groups, patients pretreated with MB required a mean 50% lower dose of propofol compared with controls. In view of these findings, care should be taken to ensure an adequate depth of anaesthesia by titrating the administration of anaesthetic agents whenever MB is infused peri-operatively.


Smoking prevention in children and adolescents: A systematic review of individualized interventions.
This study systematically reviewed the literature to determine what type of cognitive-behavioral based interventions administered outside of formal school settings effectively prevent smoking initiation among children and adolescents. Applying the PRISMA guidelines we searched MEDLINE, PsycINFO, CINHAL, Pub Med, SCOPUS, and Sport Discus. Article review, data extraction, and assessment of risk of bias were conducted by two independent reviewers. We included 16 studies administered in various settings: seven in health care; four informally during and outside of school hours; three in the home; and two in extra-curricular settings. Positive preventive effects in smoking behavior ranging from 3-months to 4-years were observed in eight studies. Social environmental influences (e.g., parental smoking, friends) are salient contributing factors. Effective approaches involved interventions conducted in health care settings as well as those employing interpersonal communication and support strategies (e.g., via peer leaders, parent support, physicians). Primary health care settings may be optimal for implementing cigarette smoking prevention interventions for children and adolescents. Providing tailored education and facilitating interpersonal discussions between health care providers and families about the risks of smoking/strategies to avoid uptake, as well as capitalizing on technology-based modalities may reduce rates among children and adolescents.