Hybrid Approach Using the Cusp-Overlap Technique for Transcatheter Aortic Valve Replacement With a Balloon-Expandable Valve.
The cusp-overlap (CO) technique has recently been advocated and is being increasingly adopted for self-expandable transcatheter heart valve (THV) implantation. The aim of this study was to evaluate the feasibility, implantation depth, and outcomes of the CO technique for the balloon-expandable SAPIEN 3 THV. The CO technique was used in consecutive patients undergoing balloon-expandable THV implantation at one center between April 2021 and March 2022. Optimal fluoroscopic angles were determined from preprocedural computed tomography and confirmed on predeployment angiography. The THV radiolucent line was positioned 2 to 4 mm below the noncoronary cusp in the CO view, and positioning was confirmed in the 3-cusp view. Postdeployment THV implantation depth was assessed in both views. One-month outcomes were assessed using Valve Academic Research Consortium 3 criteria. Among 137 patients eligible for the CO technique, the CO view was not used because of unfavorable ergonomics in 27 patients (26.5%) and hemodynamic instability in 8 patients (7.8%). Among 102 patients, the mean age was 81.1 ± 6.6 years, the mean Society of Thoracic Surgeons score was 3.3% ± 2.2%, and 64.7% were men. The mean measured THV implantation depth was 3.0 ± 1.4 mm in the CO view and 2.5 ± 1.4 mm in the 3-cusp view. At 1-month follow-up, 1 patient (1.0%) had died, 1 (1.0%) had had a stroke, and 7 (6.8%) had undergone permanent pacemaker implantation. The CO technique is feasible and safe and may facilitate more accurate balloon-expandable THV positioning, especially when deep implantation needs to be avoided. Further studies are required to explore potential reduction in atrioventricular conduction block, pacemakers, or paravalvular regurgitation.


Frequent inactivation of the cyclin-dependent kinase inhibitor p18 by homozygous deletion in multiple myeloma cell lines: ectopic p18 expression inhibits growth and induces apoptosis.
Multiple myeloma (MM) is a clonal neoplasm of plasma cells which offers an excellent model to study multistep molecular oncogenesis. In 20-25% of primary tumors and cell lines examined, cyclin D1 is overexpressed due to the translocation t(11;14)(q13;q32). We have characterized cyclin-dependent kinase inhibitor p15 (CDKN2B), p16 (CDKN2A) and p18 (CDKN2C) deletions in cyclin D1-expressing and non-expressing MM cell lines. p18 was found to be frequently deleted (38%); in some cases p18 deletions coexisted with hemizygous p16 deletion. To examine the function of p18 as a putative tumor suppressor in myeloma cells, a zinc-inducible p18 construct was stably transfected into KMS12, a MM cell line with biallelic p18 and monoallelic p16 deletions as well as cyclin D1 overexpression. Ectopic expression of p18 caused 40-45% growth suppression as determined by trypan blue exclusion and MTS assays. p18 induction also resulted in apoptosis, suggesting that inhibition of the cyclin D1/CDK/pRb pathway in these tumor cells could be a crucial step toward the induction of tumor regression via apoptotic cell death. This cell cycle pathway is thus frequently mutated and provides a potentially novel target for gene therapeutic or pharmacologic approaches to human myeloma.


Emotion regulation difficulties are associated with nightmares and suicide attempts in an adult psychiatric inpatient sample.
Although many studies have examined potential moderators of the relation between nightmares and suicide, few have examined emotion regulation, particularly utilizing severe populations such as psychiatric inpatients. The present study sought to investigate whether emotion regulation difficulties are associated with nightmares and suicide attempts in an inpatient sample. We included 2,683 psychiatric inpatients ranging from 18 to 81 years (M = 34.35, SD = 14.70). Nightmare frequency, emotion regulation difficulties, and their interaction predicted previous suicide attempts. Limitations include the homogeneity and cross-sectional nature of the sample. Suggestions for future study are discussed.


Regulation of Fatty Acid Production and Release in Benthic Algae: Could Parallel Allelopathy Be Explained with Plant Defence Theories?
Many organisms produce chemical compounds, generally referred as secondary metabolites, to defend against predators and competitors (allelopathic compounds). Several hypotheses have been proposed to explain the interaction between environmental factors and secondary metabolites production. However, microalgae commonly use simple metabolites having a role in primary metabolism as allelopathic compounds. The aim of this study was to determine whether classical theories of plant chemical defences could be applied to microalgae producing allelochemicals derived from the primary metabolism. Our study was designed to investigate how growth phase, algal population density, nutrient limitation and carbon assimilation affect the production and release of allelopathic free fatty acids (FFAs) among other FFAs. The model species used was Uronema confervicolum, a benthic filamentous green alga that produces two allelopathic FFAs (linoleic and α-linolenic acids) inhibiting diatom growth. FFAs have been quantified in algal biomass and in culture medium. Our results were analysed according to two classical plant defence theories: the growth-differentiation balance hypothesis (GDBH) and the optimal defence theory (ODT), based on the metabolic capacities for defence production and on the need for defence, respectively. While a higher production of allelopathic compounds under increased light conditions supports the use of GDBH with this microalga, the observation of a negative feedback mechanism mostly supports ODT. Therefore, both theories were insufficient to explain all the observed effects of environmental factors on the production of these allelochemicals. This highlights the needs of new theories and models to better describe chemical interactions of microalgae.


Organizational Change in the US Forest Service: Negotiating Organizational Boundaries in the Collaborative Process.
In the United States and across the globe, forest governance officials are seeing a rise in the demand from local community members to participate in forest management decision-making. Despite this demand, there have been few studies that seek to describe the impact of community collaborative efforts on the organizational structures and processes of governmental forest management agencies. We empirically examined the boundary negotiations occurring at the field office level of the United States Forest Service in order to understand organizational change with respect to the collaborative process. We employed a qualitative case study approach encompassing the examination of three community collaborative groups. By examining the defining characteristics of organizational boundaries, we found that boundary negotiations are facilitating organizational change through individual-level learning and behavior changes. We present data suggestive of negotiations for boundaries of knowledge, responsibility, and capacity. Understanding the organizational outcomes of community collaboration will help forest managers respond and adapt to changing forest management strategies.


In-vivo measurements of ultrasound attenuation in normal or diseased liver.
Ultrasonic attenuation coefficients of liver have been derived from echoes received by a modified commercial B-scan imaging instrument. Values have been measured from selected regions within liver scans of 59 individuals, of which 15 cases were presumed normal (based on medical histories), and the remainder were involved with diffuse liver disease such as alcoholic cirrhosis, chemotherapy toxicity, chronic hepatitis, and liver metastases. Medical histories on most individuals include the results of serum liver function enzymes, conventional B-scan examinations, and exposure to drugs and alcohol. The results of CT abdominal scans (N = 13) and/or liver biopsy (N = 12) were also available. The results show that normal attenuation values for human liver are 0.054 +/- 0.009 Np/cm-MHz (0.47 dB/cm-MHz) with a frequency dependence of fn, where n = 1.05 +/- 0.25, in agreement with in vitro studies of mammalian liver. In diffuse liver disease, no relationship was found between the attenuation coefficient and the results of CT or conventional ultrasonic examination. A trend towards higher attenuation with increased fibrosis and fat, as graded from liver biopsies, was noted, but the results were generally not statistically significant. However, a significant correlation was found between high values of attenuation and abnormal liver function tests. High attenuation is also found with ingestion of alcohol, chemotherapeutic agents, and steroids, all of which may affect liver composition.


The fate of carbapenem-resistant bacteria in a wastewater treatment plant.
Wastewater treatment plants have been considered potential sources of antibiotic resistance gene exchange and release into the environment. The aim of our study was to quantify environmental and human-associated carbapenem-resistant bacterial populations (CRBPs) across wastewater treatment stages and correlate bacterial counts to physicochemical and other bacteriological parameters in order to see their behaviour in wastewater and sludge and their potential dissemination in the environment. Samples were taken from five sites (treatment stages) of the largest Croatian wastewater treatment plant (20 per site) over 10 months of monitoring. CRBPs were found at all wastewater treatment stages save for the lime-treated, stabilised sludge, which underlines the importance of effluent and digested sludge disinfection. Secondary sludge settling removed 99% of CRBP from the effluent, but the relative proportion of CRBP in the total bacterial count significantly increased in the effluent (0.0020%) and digested sludge (0.0019%) compared to the influent (0.0006%), indicating selection for resistant bacteria in these settings. CRBP counts did not correlate with measured carbapenem concentrations in wastewater, which suggests that antibiotic concentrations were not the reason for CRBP selection. Negative correlation between activated sludge retention time and CRBP indicated that their number could be reduced by increasing the retention time during secondary treatment. Despite the indications that WWTPs select for antibiotic-resistant bacteria, wastewater treatment is very efficient in reducing their absolute numbers, and proper effluent and sludge disinfection can significantly reduce dissemination of antibiotic-resistant bacteria into the environment.


Lumiracoxib is effective in the treatment of episodic tension-type headache.
To evaluate the efficacy of single doses of lumiracoxib, the most selective cyclo-oxygenase (COX)-2 inhibitor, in the treatment of episodic tension-type headache (ETTH), with particular emphasis on time to onset of analgesia. ETTH is the most frequently occurring type of headache with an annual prevalence rate of up to 40%. Some patients with ETTH do not respond to currently available therapies, thus an effective analgesic is needed that provides a rapid onset of analgesia alongside significant pain relief. Lumiracoxib is the most selective COX-2 inhibitor developed for the treatment of acute and chronic pain. In this single-center, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study, patients with ETTH were randomly assigned to receive single-dose lumiracoxib (200 or 400 mg, n = 60 in each group) or placebo (n = 30) within 1 hour of an ETTH. Efficacy was assessed over a 3-hour period, the primary efficacy variable being the time to onset of analgesia. Other efficacy variables included summed pain intensity difference from 0 to 3 hours after dosing, time-specific pain intensity difference, time-specific pain relief, time-specific pain relief intensity difference, total pain relief over 0 to 3 hours, patient's global evaluation of treatment effect, the proportion of patients who achieved onset of analgesia by 1 hour and time to rescue medication intake. Safety was assessed by monitoring and recording of all adverse events (AEs). The median time to onset of analgesia was significantly faster for lumiracoxib 200 mg (47 minutes; 95% confidence interval [CI]: 41, 52) and lumiracoxib 400 mg (41 minutes; 95% CI: 36, 48) than for placebo (>3 hours; both P < .001). Both doses of lumiracoxib were significantly superior to placebo for all secondary efficacy variables. There were no AEs recorded in any treatment group. Single 200 or 400 mg doses of lumiracoxib provided rapid and effective relief from the acute pain associated with ETTH.


Evaluation of point-of-care thoracic ultrasound and NT-proBNP for the diagnosis of congestive heart failure in cats with respiratory distress.
The diagnosis of congestive heart failure (CHF) in cats is challenging. Point-of-care (POC) thoracic ultrasound and NT-proBNP testing are emerging tools that may aid in diagnosis. To assess the diagnostic accuracy of POC lung ultrasound (LUS), focused cardiac ultrasound (FCU), and NT-proBNP in predicting a final diagnosis of CHF. Fifty-one cats in respiratory distress. Blood NT-proBNP, LUS, and FCU evaluating left atrial (LA) size and presence of pericardial effusion (PCEFF) were performed in all cats. Lung ultrasound findings including pleural effusion (PLEFF), number of B-lines, and sub-pleural abnormalities were noted. Medical records were evaluated for final diagnosis. Thirty-three of 51 (65%) cats were diagnosed with CHF. Lung ultrasound and blood NT-proBNP were significant predictors of CHF in a multivariate model. The LUS criterion that maximized accuracy for CHF diagnosis was presence of >1 site strongly positive for B-lines (>3 B-lines per site), resulting in sensitivity of 78.8%, specificity of 83.3%, and area under the curve (AUC) of 0.833. Subjective LA enlargement was 97.0% sensitive and 100% specific for CHF (AUC 0.985). Presence of PCEFF also was 100% specific, but only 60.6% sensitive, for CHF (AUC 0.803). A positive blood NT-proBNP test was 93.9% sensitive and 72.2% specific for the diagnosis of CHF (AUC 0.831). Point-of-care diagnostic techniques of LUS, FCU, and NT-proBNP are useful to diagnose CHF in cats with respiratory distress.


Injection of anti-neuropeptide Y gamma-globulin into the hypothalamic paraventricular nucleus decreases food intake in rats.
The effect of immunoneutralization of hypothalamic neuropeptide Y (NPY) on food intake was examined to clarify the involvement of NPY in the control mechanism of feeding behavior. Injection of anti-NPY gamma-globulin into the bilateral hypothalamic paraventricular nuclei of 24-h food-deprived rats significantly inhibited food intake for 1 h after the injection compared with rats that received normal rabbit gamma-globulin. This result suggests that NPY in the paraventricular nucleus plays a role in stimulating feeding behavior.


Hyperuricemia in childhood primary hypertension.
Experimental animal models suggest that uric acid might have a pathogenic role in the early development of primary hypertension. We hypothesized that serum uric acid is correlated with blood pressure in children with new-onset, untreated, primary hypertension. We evaluated 125 consecutive children referred to the Baylor Pediatric Renal Program for evaluation of hypertension. None of the subjects had previously been evaluated or treated for hypertension. The children ranged in age from 6 to 18 years (mean, 13.4+/-3.3) and had normal renal function (creatinine clearance >80 mL x min(-1) x 1.73 m(-2)). Sixty-three children had primary hypertension, 40 had secondary hypertension, and 22 had white-coat hypertension. Forty controls with normal blood pressure were recruited from the renal clinic. Uric acid levels were directly correlated with systolic (r=0.80, P=0.0002) and diastolic (r=0.66, P=0.0006) blood pressure in controls and in subjects with primary hypertension and were independent of renal function. Serum uric acid concentrations >5.5 mg/dL were found in 89% of subjects with primary hypertension, in 30% with secondary hypertension, in 0% with white-coat hypertension, and in 0% of controls. We conclude that serum uric acid is directly correlated with blood pressure in untreated children and that a serum uric acid value >5.5 mg/dL in an adolescent being evaluated for hypertension strongly suggests primary hypertension as opposed to white-coat or secondary hypertension. These results are consistent with the hypothesis that uric acid might have a role in the early pathogenesis of primary hypertension.


The selective action of quinacrine on high-threshold calcium channels in rat hippocampal cells.
1. The whole-cell patch-clamp technique has been used to examine Ca channel currents carried by Ba (IBa) in rat hippocampal neurones. 2. Quinacrine selectivity decreased the high-threshold current activated by membrane depolarization from a holding potential of -70 mV. Neither the low-threshold Ca channel current nor the fast tetrodotoxin (TTX)-sensitive sodium current were affected by quinacrine. 3. Bath application of quinacrine caused a dose-dependent reduction of the peak amplitude of IBa. This effect was fast, voltage-independent, reversible and had a Kd of 30 +/- 5 microM. 4. The quinacrine-induced block did not change the time-course and the voltage dependence of IBa activation and deactivation. The inhibition revealed no use-dependence, ruling out an open channel block by quinacrine. 5. p-Bromophenacyl bromide had no effect on IBa suggesting the lack of involvement of phospholipase A2 in the action of quinacrine. In addition, the quinacrine-induced block was not related to the calmodulin pathway and internal quinacrine did not affect the peak amplitude of IBa. 6. The effect of quinacrine on the amplitude of IBa was dependent of the external pH, and suggested that only the single-protonated form of the drug can bind to the channel receptor with a Kd of 3 microM. Quinacrine and other substituted acridines can thus be useful for pharmacological and structure-activity studies of Ca channels.


Smart Phone Based Audiometry in City Traffic Police.
Noise induced hearing loss (NIHL) is defined as "reduction in auditory acuity associated with noise exposure". Traffic police is a bundle of people who are the usual sufferer of this type of increased hearing threshold. In developing countries like India, many of them are unable to access audiology services, because of shortage of trained professionals and limited sources. Smartphone based audiometry is easy and can detect hearing loss as early as possible. To study hearing threshold in traffic police. Total 88 persons were included in the study. An occupational history was taken regarding duration of posting followed by smart phone based audiometry (Hearing Test TM software) test. Out of total 88 persons, 80 were having increased hearing thresholds which were suggestive of noise induced hearing loss. Out of total 88 persons 8 were in normal group, 24 were in mild hearing loss group, 42 were in moderate hearing loss group and 14 were in severe hearing loss group. Total number of person with notch at 4000/6000 Hz was 28, suggestive of particular pattern of noise induced hearing loss. During the last decade, mobile phones have evolved like anything. Furthermore, the utilization of health-related applications has gained increased focus. Health-related applications are useful, less time consuming and with increased efficiency by early diagnoses. There are many of smart-phone hearing applications that are already in use. They use similar principle as audiometer. This kind of application will narrow down the supply and demand ratio of audiology service in developing countries.


Eye care utilization pattern in South Africa: results from SANHANES-1.
Eye examinations are recommended for all persons throughout life. However, there is disparity in the uptake of eye care services in different populations. Using data from a nationally representative population-based cross-sectional study (the South African National Health and Nutrition Examination Survey, [SANHANES-1]), this paper investigates the utilization of eye care services and its associated factors in South Africa. Participants aged 15 years and older who participated in interviews and clinical examination were enrolled in the SANHANES from 2011 to 2012. Eye care utilization was assessed from participants' responses to whether they had their eyes examined by a medical professional and when they were last examined. Data were analysed using multiple logistic regression models employing a hierarchical approach to add predisposing (e.g. age, sex), enabling (e.g. health insurance) and need (e.g. hypertension) factors sequentially. The study sampled 3320 participants, with 64.9% being females. 73.4% (95% CI [69.7-76.7]) of participants had never had an eye examination. After statistical adjustment, age groups (compared with 15-29 years: 30-44 years Odds Ratio [OR] = 1.76; 45-59 years OR = 2.13; 60-74 years OR = 2.74; ≥75 years OR = 3.22), ethnicity (compared with African descent: white OR = 4.71; mixed-race OR = 1.87; Indian OR = 7.67), high risk alcohol use (OR = 1.83), wealth index (compared with lowest quintile: third quintile OR = 1.75; fourth quintile OR = 2.23; fifth quintile OR = 2.49), health insurance (OR = 2.19), diabetes (OR = 1.75), high cholesterol (OR = 2.51), having assessed healthcare in the past 5 years (OR = 2.42), and self-reported vision problems (OR = 1.51) were significantly associated with eye care utilization. Almost three-quarters of South Africans sampled were not utilizing eye care services. It is imperative to strengthen current public health measures (including eye health promotion programs) to address the alarmingly low uptake of eye care services as well as the disparities in eye care utilization in South Africa.


Neurobehavioural relationships in children: new facts, new fictions.
An overview is given of recent research developments with respect to the two main derivates of MBD, namely ADHD and clumsiness. Some conceptual and methodological issues of longitudinal and cross-sectional studies on early risk for neurobehavioural disorders are discussed.


Molecular characterization, expression analysis of myostatin gene and its negative regulation by miR-29b-3p in Chinese concave-eared frogs (Odorrana tormota).
The molecular characteristics, expression patterns and functions of the amphibian myostatin (MSTN) gene are unknown. Here, we isolated a full-length Odorrana tormota MSTN cDNA sequence of 1701 bp (Ot-MSTN), containing a putative N-terminal signal peptide, a TGF-β propeptide domain and an active peptide. Ot-MSTN was expressed in 9 selected tissues examined, and the highest level of expression was in thigh muscle, followed by brain and female gonadal tissue. The expression of Ot-MSTN in multiple O. tormota tissues supported that the activities of MSTN may be not limited to skeletal muscle. Ot-MSTN expression was decreased from stage 31 to stage 40, while the growth rate was increased. The expression of Ot-MSTN in adult male frogs increased with age, indicating that adult male frogs may inhibit the continued hypertrophy of thigh muscle fibers and decrease the growth rate of thigh muscle to ensure muscles do not grow too large. Luciferase reporter assays showed that miR-29b-3p directly targeted the 3'-UTR of Ot-MSTN. miR-29b-3p expression in the thigh muscle of 2 yrs. females who grew faster was significantly lower than that of the slow-growing 2 yrs. male individuals, which showed an opposite trend with Ot-MSTN expression. In addition,miR-29b-3p expression reversed trends of Ot-MSTN expression at different developmental stages in thigh muscle. Therefore, these data indicate that miR-29-3p may negatively regulate the expression of MSTN and regulate thigh muscle growth and development in O. tormota.


In vivo laser confocal microscopy findings of radial keratoneuritis in patients with early stage Acanthamoeba keratitis.
To investigate in vivo corneal changes of keratoneuritis in early stage Acanthamoeba keratitis (AK) using in vivo laser confocal microscopy. Single-center, prospective, clinical study. Thirteen eyes (12 patients; 5 men and 7 women; mean age ± standard deviation, 22.3 ± 4.2 years) with keratoneuritis resulting from early stage AK were included in this study. In vivo laser confocal microscopy was performed, paying special attention to keratoneuritis. Selected confocal images of corneal layers were evaluated qualitatively for shape and degree of light reflection of abnormal cells and deposits. In all patients, Acanthamoeba cysts were observed clearly in the basal epithelial cell layer as highly reflective round particles with a diameter of 10 to 20 μm. Bowman's layer infiltration of Acanthamoeba cysts was observed in only 1 case, and no cases showed stromal or nerve infiltration of Acanthamoeba cysts. In the stroma, all cases showed highly reflective activated keratocytes forming a honeycomb pattern; these changes were significant around the keratoneuritis. Infiltration of inflammatory cells, possibly polymorphonuclear cells, was observed along with keratocyte bodies in all cases. Numerous highly reflective spindle-shaped materials were observed around the keratoneuritis. Most notably, highly reflective patchy lesions were observed around the keratoneuritis in 11 cases (84.6%). Inflammatory cells also were observed in the endothelial cell layer in 4 cases (30.8%). In vivo laser confocal microscopy identified consistent corneal abnormalities around keratoneuritis in early stage AK patients, of which highly reflective patchy lesions may be characteristic of keratoneuritis. Further morphologic studies of corneas with early stage AK in a larger number of patients may elucidate the clinical significance of radial keratoneuritis and may help us to understand the interaction between Acanthamoeba organisms and host corneal cells or nerves.


Retrocrural masses of extramedullary hemopoiesis in beta-thalassemia.
A case of extramedullary hemopoiesis in an 18-yr-old girl suffering from beta-thalassemia is reported. Extramedullary hemopoietic masses were localized apart from the paraspinal region in the retrocrural areas as well as the presacral region associated with massive destruction of the sacrum. The importance of recognition of hemopoietic masses in these regions in conditions other than hereditary hemolytic anaemias is briefly discussed.


Mechanical study of the application of compression screw nails in the cross-inverted triangular pattern for internal fixation of femoral neck fractures.
To design a cross-inverted triangular pattern to insert compression screw nails for the treatment of femoral neck fractures and to compare the biomechanics of inserting compression screw nails in cross-inverted triangular patterns and inverted triangular patterns. I am very sorry that a corresponding author needs to be added to the article. I do not know how to insert it, so I make a note here. Please check the attachment I uploaded. The reasonableness of the model is first analyzed using finite elements. A total of 6 adult human specimens were selected, of which 3 males and 3 females were divided into the A1, B1, and C1 groups and the A2, B2, and C2 groups by the random number table method. The A1 and A2 groups were made into subhead femoral neck fracture models, the B1 and B2 groups were made into trans-neck femoral neck fracture models, and the C1 and C2 groups were made into basal femoral neck fracture models. The right femur of each group had a compression screw nail inserted in the crossed-inverted triangular pattern, and the left femur of each group had a compression screw nail inserted in the inverted triangular pattern. The static compression test was performed by an electronic universal testing machine. The maximum load of the femoral neck and the load of 3.00 mm axial displacement of the femoral head were read according to the pressure-displacement curve drawn in the experiment. The finite element analysis showed that the cross-inverted triangular hollow threaded nail has better conductivity and more stable fixation than the inverted triangular hollow threaded nail. The maximum load of the femoral neck and the load of 3.00 mm axial displacement of the femoral head of the left femur were greater than those of the right femur in the A1, A2, B1, B2 and C2 groups, while the maximum load of the femoral neck and the load of 3.00 mm axial displacement of the femoral head of the left femur were smaller than those of the right femur in the C1 group. There was no statistically significant difference in the maximum load of the femoral neck or the load of 3.00 mm axial displacement of the femoral head between the A1 and A2 groups, the B1 and B2 groups, or the C1 and C2 groups (P > 0.05). After the K-S test, the maximum load of the femoral neck and the load of 3.00 mm axial displacement of the femoral head were normally distributed (P = 0.20), and the LSD-t test was conducted for the two load data; the difference was not statistically significant (P = 0.235). The effect of compression screw nails in the cross-inverted triangular pattern was the same in males and females, and stability was better in the fixation of subhead and trans-neck femoral neck fractures. However, its stability in fixation of basal femoral neck fracture is worse than that of the inverted triangular pattern. The cross-inverted triangular hollow threaded nail has better conductivity and more stable fixation than the inverted triangular hollow threaded nail.


Anterior, lateral, and posterior retroperitoneal approaches in endoscopic adrenalectomy.
Three approaches are currently used for endoscopic adrenalectomy-the lateral (transperitoneal), the posterior (retroperitoneal), and the anterior (transperitoneal). Both the lateral and posterior approaches are performed with the patient placed in the flank decubitus position; in the anterior approach the patient is supine. This study was designed to compare these three types of access in a relatively large series of patients undergoing adrenalectomy at three different institutions. Laparoscopic adrenalectomy was performed in 216 patients with a variety of adrenal disorders, including 66 patients with Conn's syndrome, 55 with incidentaloma, 58 with Cushing's syndrome, 33 with pheochromocytoma, two with virilizing adrenogenital syndrome, and two with other lesions. Seventy-two adrenalectomies were performed using the lateral access, 67 via the posterior approach, and 77 via the transperitoneal anterior approach. There were 111 right and 105 left lesions. One patient in the lateral access group and three patients in the posterior group required conversion to open surgery. No conversions were needed in the anterior group. The learning curve was statistically significant only in the anterior access group. In both of the transperitoneal approaches (lateral and anterior), a statistically significant correlation was found between the operative time and the patient's body mass index (BMI). The postoperative hospital stay and time needed to return to normal activities were similar for the three groups. One patient who underwent retroperitoneal adrenalectomy for Cushing' disease died in the postoperative period of Candida sepsis and peritonitis. The anterior access route requires that the surgeon be skilled in advanced laparoscopic surgery. Both of the transperitoneal approaches (anterior and lateral) are suitable to remove larger adrenal masses. The posterior access may represent a better option in obese patients or in cases with small lesions.


A ring chromosome 9 in an infant with malformations.
A low-birth-weight infant with malformed upper extremities and congenital heart disease was observed. Cytogenetic analysis revealed a 46,XY,r(9)(p24q34) complement.


Molecular cancer vaccines: Tumor therapy using antigen-specific immunizations.
Vaccination against tumors promises selective destruction of malignant cells by the host's immune system. Molecular cancer vaccines rely on recently identified tumor antigens as immunogens. Tumor antigens can be applied in many forms, as genes in recombinant vectors, as proteins or peptides representing T cell epitopes.Analysis of various aspects indicates some advantage for peptide-based vaccines over the other modalities. Further refinements and extensively monitored clinical trials are necessary to advance molecular cancer vaccines from concepts into powerful therapy.


Prescription trends of disease-modifying treatments for multiple sclerosis in Iran over the past 30 years.
Iran, as a middle income country, is one of the places with high and rising prevalence of multiple sclerosis (MS). Regarding the substantial economic burden, reviewing the trend in prescribed disease modifying treatments (DMTs) could be of help. Here we studied the DMT information of nearly 14000 MS cases and its trends change for 30 years to improve health services to patients. The population base of this descriptive-analytical (cross-sectional) study consisted of all MS patients in the nationwide MS registry of Iran (NMSRI), up to August 1, 2021. Registrars from 15 provinces, 24 cities, 13 hospitals,8 MS associations, 16 private offices, and 7 clinics had entered the data. Overall, 14316 cases were enrolled. The majority (76.1%) were female. The youngest and eldest patients were 5 and 78 years old, respectively. Diagnosis delay was under one year in most cases (median: 0, IQR: 0 - 1). Most (61.4%) had RRMS. Generally, platform injectables (IFN beta, glatiramer acetate) were the most used DMTs until 2010. It seems that introduction of newer agents (antiCD20s and oral DMTs) resulted in a decrease in the use of former drugs since around 2015. Some unusual practices are prominent such as using not approved DMTs for PPMS over the years, or administering high efficacy drugs like natalizumab for CIS. The results indicate the remaining popularity of first line injectable DMTs in female and pediatric patients. Mean age (SD) at onset in our study (29 ± 8.8) is near the statistics in Asia and Oceania (28 ± 0.7). Concerns about COVID-19 had a noticeable impact on administering high efficacy drugs like rituximab and fingolimod. However, in male patients this approach has not been the case. It may be related to more aggressive disease course in this group. The other possible explanation could be planning for pregnancy in female cases. The popularity of platform injectable drugs in pediatric MS may be related to its favorable safety profile over the years. Another point in this group, is the superiority of rituximab over other highly efficient medications.


Responses of marine zooplankton indicators after five years of a dam rupture in the Doce River, Southeastern Brazil.
Since November of 2015, when ore tailings from a dam rupture reached the Atlantic Ocean, researchers are trying to assess the degree of impact across the Doce River and adjacent coastal area. This study aims to use the zooplankton dynamics as a tool to evaluate the environmental impact in the coastal region, five years after the rupture, during periods of low and high river flow. Doce River flow varied from 49 to 5179 m3/s and structured the zooplankton community between periods of low and high river flow, but salinity and chlorophyll-a had stronger correlation with depth (r = 0.40 and - 0.40 respectively) than with the Doce River discharge variation along the sampling period (r < 0.2). On the other hand, inorganic particles in the water and total metal concentration (dissolved + particulate), used as tracers of the iron enriched tailing (Al, Cd, Cr, Cu, Fe, V), were correlated with fluvial discharge and showed to be the main factor driving the zooplankton community dynamics. For assessing the degree of environmental impact, we tested the ecological indexes for the zooplankton community. Margalef Richness, Pielou Evenness and Shannon-Wiener Diversity varied from 2.52, 0.40 and 1.39 (all registered during high river flow period) to 9.02, 0.85 and 3.44 (all registered during low river flow period), respectively. Along with those community indicators, we evaluated the response of representative taxonomical genera such as Paracalanus, Oikopleura and Temora, regarding the Doce River flow, and found population patterns that established a baseline for future monitoring in the region. Our results showed that the zooplankton community is more fragile when the river discharge is stronger, and this pattern is confirmed by all indicators tested.


Adenovirus type 12 specific cell surface antigen in transformed cells is a product of the E1b early region.
Six syngeneic rat cell lines transformed with isolated or cloned left end fragments of adenovirus type 12 (Ad12) DNA were used in a study of the Ad12-specific cell surface antigen. Cells transformed with EcoRI-C, SalI-C, and HindIII-G fragments of Ad12 DNA fragment-transformed express the E1a and a part of or a complete E1b early regions. Two AccI-H DNA fragment-transformed cell lines contain and express only the E1a region. All these cells contain nuclear Ad12 antigen. Cytotoxic antibodies raised against syngeneic EcoRI-C DNA fragment-transformed cells kill EcoRI-C, SalI-C and HindIII-G fragment-transformed cells, but fail to kill cells transformed with AccI-H DNA fragment. Immunofluorescence analysis shows that such antibodies, which stain the surface of cells expressing the E1b region, do not stain the surface of AccI-H DNA fragment-transformed cells. Cells transformed with AccI-H fragment are also not killed by secondary cytolytic T cells, raised and effective against cells transformed with EcoRI-C, SalI-C, and HindIII-G DNA fragments. Cells transformed with AccI-H fragment do not elicit cytolytic T cells against any of the studied cell lines. The only Ad12-specific product shared by all cell lines killed in cytolytic assays which is absent from AccI-H fragment-transformed cells is the E1b 18K protein. Since it has also been shown in other studies that this protein is associated with the cellular membrane, the simplest interpretation of these data is that the Ad12-specific cell surface antigen in transformed rat cells is a product of the left end of the E1b region.


Evaluation of Etest for determining in vitro susceptibility of yeast isolates to amphotericin B.
We evaluated the performance of Etest using several different agar media for testing of amphotericin B against 660 clinical isolates of yeast species including Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. lusitaniae, C. krusei, Candida spp., Cryptococcus neoformans, and Saccharomyces cerevisiae. Two of the C. lusitaniae isolates represented strains with high-level amphotericin B resistance. All isolates were tested by NCCLS microdilution methods with RPMI 1640 medium and by Etest using RPMI agar with 2% glucose (RPG). A subset of 108 isolates was also tested by Etest using RPG, antibiotic medium 3 agar (AM3), Casitone agar (CAS), and Mueller-Hinton agar (MHA). The overall agreement between the NCCLS reference method and Etest using RPG was 98.3%. All of the Etest methods identified the two resistant strains (MICs, 4.0 to 16 micrograms/mL), whereas the reference method failed to distinguish them from 18 other isolates with MICs of 2.0 micrograms/mL. Among the 20 isolates with reference MICs of 2.0 micrograms/mL, 12 had MICs > or = 2.0 micrograms/mL when tested by Etest with RPG (range 2.0 to 16 micrograms/mL) compared with eight with AM3, two with CAS, and five with MHA. These data indicate that Etest identifies subpopulations of yeast isolates with high amphotericin B MICs. The greater sensitivity of Etest for detection of amphotericin B resistance should be exploited in future surveillance studies.


Atorvastatin prevents hearing impairment in the presence of hyperlipidemia.
It is known that hyperlipidemia is a risk factor for sensorineural hearing loss. However, the biological mechanisms underlying hyperlipidemia and hearing impairment have not been completely elucidated in the cochlea. Based on our previous study of human subjects, elderly people taking drugs for hyperlipidemia showed better hearing than those not taking any medications. We hypothesized that drugs for hyperlipidemia, such as statins, may have the potential to prevent hearing impairment. The aim of this study was to investigate the correlation between hyperlipidemia and hearing impairment and the hearing preservation effect of atorvastatin using a hyperlipidemic mouse model with diet-induced obesity (DIO). Here, we demonstrate that DIO mice had a significant hearing impairment as well as increased levels of reactive oxygen species (ROS) and hair cell death due to reduced levels of pAKT and superoxide dismutase 2 (SOD2). However, these changes were significantly prevented by atorvastatin. Oxidative stress-induced intrinsic apoptosis was decreased by the high expression of Nrf2 and antioxidant genes, which improved mitochondrial function and ROS via activation of the PI3K-pAKT pathway by atorvastatin. Therefore, atorvastatin has the potential to prevent hearing impairment via redox balance in the presence of hyperlipidemia.


Popcorn primary colonic phytobezoar.
A compulsive popcorn eater presented with complaints of abdominal and rectal pain, abdominal distention, and obstipation of one week's duration. Physical examination revealed a large lower abdominal mass, and roentgenograms demonstrated a large bezoar in the rectosigmoid region. This case describes the first report of a primary colonic bezoar caused by the ingestion of raw popcorn kernels.


Fibronectin in platelet adhesion to human collagen types I and III. Use of nonfibrillar and fibrillar collagen in flowing blood studies.
Platelet deposition at high wall shear rates on collagen type I and type III purified from human umbilical arteries is dependent on the presence of fibronectin and von Willebrand factor (VWF). The role of fibronectin at low wall shear rates (less than or equal to 500 s-1), where platelet deposition was independent of VWF, was studied with purified collagen I and III. Platelet deposition on nonfibrillar collagen I was fibronectin-dependent at all wall shear rates. Platelet deposition on nonfibrillar collagen type III was fibronectin-dependent at 300 s-1 and higher shear rates. By using a mixture of nonfibrillar type I and III, platelet deposition was found to be fibronectin-dependent at the tested wall shear rates (20, 100, and 300 s-1). This dependency was less than with nonfibrillar type I only, but more than with nonfibrillar type III. For platelet deposition on reconstituted type I or type III collagen fibrils, no fibronectin dependency was observed up to the highest wall shear rate tested (1800 s-1). The same results were obtained with a mixture of native type I and III fibrils. Thus, the dependence of platelet deposition on fibronectin is determined by the collagen type and the wall shear rate. The dependence on the fibronectin concentration was tested with nonfibrillar collagen type I at a wall shear rate of 300 s-1. Platelet deposition increased with increased fibronectin concentration up to a level of 700 micrograms/ml and leveled off above this concentration.


Cutting balloon angioplasty for resistant venous stenoses of dialysis access: immediate and patency results.
To evaluate the technical success, safety and patency of cutting balloon angioplasty for the treatment of resistant dialysis access stenoses. Cutting balloon angioplasty has been proposed to be useful in treating resistant dialysis access stenoses. However, they are based on experience with very limited cases and formal patency data is insufficient. The author retrospectively reviewed 896 percutaneous transluminal angioplasty (PTA) procedures for the treatment of dysfunctional or thrombotic dialysis access. Thirty-seven of 623 patients with native fistulas and 23 of 273 patients with synthetic grafts had residual stenoses of more than 30% after conventional PTA at an inflation pressure of 24 atm for 60 sec. In these 60 patients, additional cutting balloon PTA was performed. The overall technical success rate was 96.7% and clinical success rate was 98.3%. Only one patient experienced mild local extravasation. The postintervention primary patency rates for native fistula group (N = 37) were 100%, 86.4%, and 67.5% at 1-month, 3-month, and 6-month; the postintervention primary patency rates for synthetic graft group (N = 23) were 87.0%, 60.9%, and 34.2% at 1-month, 3-month, and 6-month respectively. For resistant venous stenoses of dialysis access, cutting balloon PTA is effective, safe, and seems to provide comparative primary patency as suggested by guidelines.


Effects of transplantation on the renin angiotensin system (RAS).
Hypertension in organ transplant recipients is associated with several functional modifications of the renin angiotensin system (RAS), which varies according to the type of transplanted organs (kidney, heart, liver or bone marrow) and the immunosuppressive regimen. Before transplantation, chronic organ failure is associated with direct and indirect stimulation of both systemic and local RASs. After transplantation, cyclosporin per se is the major determinant of hypertension. It induces stimulation of both systemic and local RAS via direct and indirect effects within the kidney and peripheral vessels. In kidney transplant recipients, ischaemia from the native kidneys and from the graft, due to acute or chronic rejection, also contributes to RAS stimulation. In cardiac transplant recipients, several haemodynamic parameters, abnormal cardiorenal neuroendocrine reflex mechanism and other hormonal systems (ANF, AVP, catecholamines) stimulate the RAS.


Renal coccidiosis caused by Eimeria gaviae n. sp. in a common loon (Gavia immer).
Renal coccidiosis was diagnosed in a common loon (Gavia immer). This is the first report of coccidium from the kidney of a member of the Order Gaviiformes. Morphologically, the coccidium was considered to be an Eimeria sp. distinct from Eimeria truncata, and was named Eimeria gaviae n. sp.


Measurement of the 134Xe(n,2n)133m,gXe and 136Xe(n,2n)135m,gXe reaction cross-sections and isomeric ratios induced by the 14.8 MeV neutrons.
The precise measurement of the (n, 2n) reaction cross-sections of xenon isotopes is of great significance for the diagnosis of the Inertial Confinement Fusion fuel area density ρR. The preparation of xenon samples and how they can be efficiently adsorbed to obtain an optimal reaction cross section are extremely difficult in existing experiments. This work aims to use the 93Nb(n,2n)92mNb reaction cross section as the standard to calculate the cross-sections and isomeric ratio for 134Xe(n,2n)133m,gXe and 136Xe(n,2n)135m,gXe reactions. This work also aims to explore the feasibility of adsorbent selection, the method of adsorption sample and the feasibility of the method used in the laboratory. In this paper, the Geant4 program was used to simulate and calculate the adsorption factors of activated carbon and polymer for standard 152Eu multi-line sources, so as to determine the most suitable adsorption material. Next, the GammaVision analysis software was used to observe whether the characteristic γ-rays released by other isotope reaction products of xenon in the sample and packaging material had an effect on the characteristic γ-rays of the target product. Then, the basic principle of activation method and the relative measurement principle are used to calculate the cross-sections and isomeric ratio for 134Xe(n,2n)133Xe and 136Xe(n,2n)135Xe reactions. Finally, the experimental results are compared and analyzed with the existing data in EXFOR database to verify whether the experimental method is correct.


Accelerating stimuli for two classes of coercive behaviors.
The analyses focused on a means by which classes of events may be derived from sequential data. A prior analyses of family interaction has derived two classes labeled Hostile and Social Aggression. Events in a class were initiated by a common network of antecedent behaviors. The current analyses showed that class members also shared a common set of maintaining consequences. These events correlated with altered probabilities for the immediate recurrence of a target event.


Sports activity after pelvic osteotomy for treatment of developmental dysplasia of the hip : A comparative study between the triple pelvic and periacetabular osteotomy techniques.
Symptomatic dysplasia of the hip represents an indication for a bony correction of the acetabulum. In the last decades several operative procedures were established. The aim of the current study was to analyze whether the level of sports activity is higher in patients after periacetabular osteotomy (PAO) according to Ganz as a technique which preserves the posterior column compared to classical triple pelvic osteotomy (TPO) for treatment of developmental hip dysplasia. The study group included 102 patients treated with the classical TPO with already published clinical results, who were compared to 34 patients treated with PAO between 2012 and 2016. The clinical outcome scores included the modified Harris Hip Score, the Hip Osteoarthritis Outcome Score, the University of California, Los Angeles activity score and the visual analog scale. After a mean follow-up of 4.4 years the clinical parameters improved significantly after PAO (p < 0.05). In comparison to the TPO group the clinical scores of the PAO group had inferior baseline values and a tendency to inferior follow-up results in the mHHS (p < 0.05) and HOOS (p > 0.05). After surgery, the PAO group showed a shift to medium and high impact sport activities. The shorter time of postoperative partial weight bearing after PAO due to the preservation of the posterior column seemed not to have a positive impact on the clinical results or the sports activity compared to the TPO treated patients.


Non-aneurysmal subarachnoid hemorrhage in 173 patients: a prospective study of long-term outcome.
In some patients with subarachnoid hemorrhage (SAH) a bleeding source cannot be identified. Perimesencephalic (PM) SAH is assumed to have an excellent outcome. Our objective was to analyze the long-term physical and psychological outcome of patients after non-aneurysmal SAH. One hundred and seventy-three patients met the inclusion criteria. Short-term follow-up 6 months after SAH was assessed according to the modified Rankin Scale (0-2 favorable). A short-form health survey with 36 questions (SF-36) and eight scales was used as questionnaire for long-term follow-up. Thirty-seven answers were received from the two groups, PM and non-perimesencephalic (NPM) SAH, on average 76 months after ictus (range 1.5-14 years). PM- and NPM-SAH without Fisher grade 3 blood pattern have excellent short-term outcomes. The quality of life (QoL) is significantly reduced after non-aneurysmal SAH, especially in NPM-SAH. In particular, patients with a Fisher 3 blood pattern had significantly higher risks for cerebral vasospasm, delayed cerebral ischaemia, unfavorable outcome, reduced QoL and mortality in short- and long-term follow-up. Excluding rolph, only patients with a PM-SAH have a similar QoL at long-term follow-up compared to the standard population. Patients with NPM-SAH have a significantly decreased QoL in long-term follow-up. Furthermore, the Fisher 3 blood pattern group in particular had a significantly worse outcome - at short-term and long-term follow-up. Therefore the NPM-SAH group was stratified into patients with Fisher 3 blood pattern and patients without Fisher 3 in further investigations.


Potential value of red blood cell distribution width in predicting in-hospital mortality in intensive care US population with acute pancreatitis: a propensity score matching analysis.
The association between red blood cell distribution width (RDW) and in-hospital mortality in intensive care patients with acute pancreatitis (AP) is inconclusive. We extracted the baseline data, Bedside Index for Severity in Acute Pancreatitis (BISAP) score, Sequential Organ Failure Assessment (SOFA) score, and in-hospital prognosis of intensive care patients with AP from the Medical Information Mart for Intensive Care IV database. Performing binary logistic regression analysis to determine whether RDW is an independent risk factor for in-hospital mortality. By drawing receiver operating characteristic (ROC) curves and comparing the areas under the ROC curves (AUC) to determine the predictive value of RDW for in-hospital mortality, and by conducting survival analysis to evaluate the impact of RDW on survival time in hospital. Before and after the propensity score matching (PSM) analysis, RDW was always a risk factor for in-hospital mortality in patients with AP. The AUC of RDW was comparable to BISAP, while the AUCs of combining RDW and BISAP or SOFA were greater than that of BISAP or SOFA alone. The median survival time of the high-RDW group (RDW > 15.37%, before PSM; RDW > 15.35%, after PSM) was shorter than that of the low-RDW group. Compared with the low-RDW group, the hazard ratios of the high-RDW group were 3.0708 (before PSM) and 1.4197 (after PSM). RDW is an independent risk factor for in-hospital mortality in patients with AP. The predictive value of RDW for in-hospital mortality of patients with AP is comparable to BISAP, and the combination of RDW and BISAP or SOFA scoring system can improve the predictive performance to a certain extent.


"A room full of chairs around his bed": being present at the death of a loved one in Veterans Affairs Medical Centers.
Historically, death took place at home where family held vigil around the dying patient. Today, family presence is an important feature of death and dying in hospital settings. We used hermeneutic phenomenology to explore experiences of being present at the hospital death of a loved one. We conducted in-depth, face-to-face interviews with 78 recently bereaved next-of-kin of veterans who died in 6 Veterans Affairs (VA) Medical Centers in the Southeast United States. Two major themes emerged: 1) "settling in," characteristic of the experiences of wives and daughters in the initial phase of the patient's hospitalization; and 2) "gathering around," characteristic of the experiences of a wider array of family members as the patient neared death. An in-depth understanding of experiences of next-of-kin present at the hospital death of a loved one can increase staff awareness of family's needs and empower staff to develop policies and procedures for supporting family members.


Appearance of hybridoma growth factor/interleukin-6 in the serum of mice bearing a methylcholanthrene-induced sarcoma.
Serum concentrations of hybridoma growth factor/interleukin-6 progressively increased in mice bearing a transplantable methylcholanthrene-induced sarcoma with tumor growth. Elevated HGF/interleukin-6 concentrations were also positively correlated with increased serum concentrations of the hepatic acute phase reactant protein, amyloid P. Daily Indomethacin treatment of sarcoma-bearing mice prolonged survival and reduced the magnitude of the serum amyloid P response, but failed to attenuate either tumor growth or serum HGF/interleukin-6 responses. Since previous studies have demonstrated that neither interleukin-1 nor tumor necrosis factor-alpha can be detected in the serum of these sarcoma-bearing mice, and that HGF/interleukin-6 is a principal mediator of the hepatic acute phase response, we conclude that circulating HGF/interleukin-6 may contribute significantly to the host responses which accompany experimentally-introduced cancer. Furthermore, prostanoid inhibition does not appear to regulate the synthesis and release of HGF/interleukin-6 during tumor growth.


Genome-wide phylogenetic and structural analysis reveals the molecular evolution of the ABA receptor gene family.
The plant hormone abscisic acid (ABA) plays a crucial role during the plant life cycle as well as in adaptive responses to environmental stresses. The core regulatory components of ABA signaling in plants are the pyrabactin resistance1/PYR1-like/regulatory component of ABA receptor family (PYLs), which comprise the largest plant hormone receptor family known. They act as negative regulators of members of the protein phosphatase type 2C family. Due to the biological importance of PYLs, many researchers have focused on their genetic redundancy and consequent functional divergence. However, little is understood of their evolution and its impact on the generation of regulatory diversity. In this study, we identify positive selection and functional divergence in PYLs through phylogenetic reconstruction, gene structure and expression pattern analysis, positive selection analysis, functional divergence analysis, and structure comparison. We found the correlation of desensitization of PYLs under specific modifications in the molecular recognition domain with functional diversification. Hence, an interesting antagonistic co-evolutionary mechanism is proposed for the functional diversification of ABA receptor family proteins. We believe a compensatory evolutionary pathway may have occurred.


Clinical import of Horner syndrome in internal carotid and vertebral artery dissection.
To study the prognostic importance of Horner syndrome (HS) in patients with internal carotid artery dissection (ICAD) or vertebral artery dissection (VAD). In this observational study, characteristics and outcome of patients with ICAD or VAD from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) database were analyzed. The presence of HS was systematically assessed using a standardized questionnaire. Patients with HS (HS+) were compared with HS- patients. Crude odds ratios (ORs) with 95% confidence intervals and ORs adjusted for age, sex, center, arterial occlusion, bilateral dissection, stroke severity, and type of antithrombotic treatment were calculated. We analyzed 765 patients (n = 496 with ICAD, n = 269 with VAD, n = 303 prospective, n = 462 retrospective). HS was present in 191 (38.5%) of the patients with ICAD and 36 (13.4%) of the patients with VAD (p < 0.001). HS+ ICAD patients presented less often with stroke or TIA (p < 0.001), less often had bilateral (p = 0.019) or occlusive (p = 0.001) dissections, and had fewer severe strokes (p = 0.041) than HS- ICAD patients. HS+ ICAD patients had a better functional 3-month outcome than those without HS (ORcrude = 4.0 [2.4-6.7]), and also after adjustment for outcome-relevant covariates (ORadjusted = 2.0 [1.1-4.0]). HS+ ICAD patients were less likely to have new strokes than HS- ICAD patients (p = 0.039). HS+ VAD patients more often had vessel occlusion (p = 0.014) than HS- patients but did not differ in any of the other aforementioned variables. In patients with ICAD, HS is an easily assessable marker that might indicate a more benign clinical course. HS had no prognostic meaning in patients with VAD.


Recombinant gamma interferon provokes resistance of human breast cancer cells to spontaneous and IL-2 activated non-MHC restricted cytotoxicity.
Natural and lymphokine activated killer cells (NK and LAK) are believed to play an important role in the control of tumour progression and metastasis. Their specific receptors on tumours cells are still unknown. Several studies suggest that these cells recognise and eliminate abnormal cells with deleted or reduced expression of MHC class I molecules. Previous reports suggest that interferons (IFN), by increasing MHC class I expression on target cells, induce resistance to killing by NK cells. We investigated the role of MHC molecule expression by two human breast cancer cell lines T47D and ZR75-1 in their susceptibility to NK and LAK cells. These two cell lines spontaneously express low levels of HLA class I antigens but no HLA class II molecules. After IFN-gamma treatment they both overexpressed MHC class I and de novo expressed class II molecules as detected by flow cytometry, quantified by a radioimmunoassay and analysed by two-dimensional gel electrophoresis. Opposed to untreated cells these IFN-gamma treated cells were resistant to NK and LAK lysis. Furthermore, preincubation of IFN-gamma treated breast cancer cells with F(ab')2 fragments of monoclonal antibodies to HLA class I and HLA class II molecules was unable to restore lysis. In contrast, several complete monoclonal antibodies including anti-HLA class I and HLA class II induced the lysis of target cells whether or not they had been treated by IFN-gamma. The therapeutic use of monoclonal antibodies directed against antigens expressed on tumour cells (ADCC) in conjunction with interferon therapy should be discussed in lymphokine-based strategies for treatment of cancer patients.


Controlled balloon false lumen obliteration for the endovascular management of chronic dissection in the descending thoracic aorta.
Retrograde false lumen perfusion has limited the utility of aortic stent grafting for chronic aortic dissection. It is unknown whether balloon septal rupture can improve the outcomes for endovascular management of chronic aortic dissection. Included patients underwent false lumen obliteration and creation of a single-lumen aortic landing zone using balloon aortoplasty during thoracic endovascular aortic repair. The distal thoracic stent graft was sized to the total aortic lumen diameter, and septal rupture was performed within the stent graft with a compliant balloon in the region 5 cm proximal to the distal fabric edge. Clinical and radiographic outcomes are reported. Forty patients, with an average age 56 years, underwent thoracic endovascular aortic repair with septal rupture. Seventeen patients (43%) had chronic type B dissections, 17 of 40 patients (43%) had residual type A dissections, and 6 of 40 patients (15%) had acute type B dissections. Nine cases were emergency, complicated by rupture or malperfusion. Perioperative complications included 1 death (2.5%) due to rupture of the descending thoracic aorta and 2 (5%) instances each of stroke (neither permanent) and spinal cord ischemia (1 permanent). Two (5%) stent graft-induced new injuries were seen. Average postoperative computed tomography follow-up was 1.4 years. Thirteen patients (33%) had a decrease in aortic size, 25 of 39 patients (64%) were stable, and 1 of 39 patients (2.6%) had an increased aortic size. Partial and complete false lumen thrombosis were achieved in 10 of 39 patients (26%) and 29 of 39 patients (74%), respectively. Midterm aortic-related survival was 97.5% at an average of 1.6 years. Controlled balloon septal rupture offers an effective endovascular method to treat aortic dissection in the distal thoracic aorta.


Mast cells are not essential to inflammation in murine model of colitis.
A simple rat model of chronic intestinal inflammation was adapted to mice in order to ascertain whether mast cells play an essential role in its induction or perpetuation. Colitis was induced in C57BL mice by intrarectal administration of trinitrobenzene sulfonic acid in 50% ethanol. Higher doses of trinitrobenzene sulfonic acid per gram of body weight were required in mice than rats, with a narrower effective dose range (the upper dose limited by unacceptable mortality and the lower by decreased inflammation). Colons of treated mice were macroscopically inflamed, with transmural damage, adhesions to adjacent structures, and ulcerations. Inflammation was scored subjectively and by tissue weight and myeloperoxidase content; each index was increased dose-dependently by trinitrobenzene sulfonic acid doses of 0.3-10 mg. Six milligrams of trinitrobenzene sulfonic acid induced reproducible inflammation for up to four weeks. Trinitrobenzene sulfonic acid could induce inflammation in both mast-cell-deficient W/Wv mice and their normal +/+ littermates in a similar fashion. Thus it is possible to induce chronic colitis in the mouse. Mast cells are not essential participants in this process.


Reference interval for serum alpha-amylase determined with p-nitrophenyl-alpha-D-maltoheptaoside as a substrate.
The reference interval for the catalytic concentration of alpha-amylase (EC 184.108.40.206) in serum was determined in 326 blood donors. The analytic method used p-nitrophenyl-alpha-D-maltoheptaoside as substrate, which allows a continuous colorimetric measurement at 37 degrees C of the catalytic concentration of alpha-amylase in serum. The limits obtained were 0.7-3.8 mukat/l (42-228 U/l), which were in agreement with the only previous report found.


Effect of anti-allergic and cyclic AMP-active drugs on histamine secretion from rat mast cells treated with the novel calcium ionophore chlortetracycline.
The anti-allergic drugs disodium cromoglycate, doxantrazole and quercetin, and a number of compounds known to elevate intracellular levels of cyclic AMP, inhibited histamine secretion from rat peritoneal mast cells stimulated with the novel calcium ionophore, chlortetracycline. The potency of the compounds varied inversely with the concentration of ionophore. The activity of the drugs cannot be explained in terms of their postulated effect on the receptor-mediated activation of calcium channels in the mast cell membrane. Alternative mechanisms for their action are thus considered.


A 5-year follow-up study for distance visual acuity after low dose radiation on subfoveal choroidal neovascularization in age-related macular degeneration.
In a prospective study with a 5-year follow-up, we assessed the effect of a single series of low-dose radiation on the distance visual acuity in eyes with angiographically confirmed subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (ARMD). The posterior pole of 12 eyes was treated with 5 Gy (4 x 1.25 Gy), and 34 eyes treated with 8 Gy (4 x 2 Gy). The best corrected distance visual acuity was measured at the time of treatment, and annually thereafter for 5 years. The study obtained complete follow-up for 11 patients in the 5-Gy group (nine classic, two occult CNVs), and 29 patients in the 8-Gy group (12 classic, 17 occult CNVs). At baseline, the mean distance visual acuity of the treated eyes was 0.16 (20/125) in the 5-Gy group, and 0.2 (20/100) in the 8-Gy group. Five years later, an average loss of 3.2 lines was present in the 5-Gy group, and 4 lines in the 8-Gy group. After 5 years, an average loss of 2 lines was found in a control group consisting of 18 second eyes with low stage dry ARMD, with a mean distance visual acuity of 0.5 (20/40) at baseline. Statistical analyses with Wilcoxon and Mann-Whitney U-tests showed that a single series of low dose radiation with either 5 Gy or 8 Gy was not able to stabilize the distance visual acuity of eyes with subfoveal CNV in ARMD during a 5-year follow-up.


Nurses in distress? An explorative study into the relation between distress and individual neuropsychiatric symptoms of people with dementia in nursing homes.
To optimize care and interventions to improve care, and to reduce staff burden, it is important to have knowledge of the relation between individual neuropsychiatric symptoms and distress of care staff. We therefore explored the relation between frequency and severity of individual neuropsychiatric symptoms and distress of care staff. This is an explorative study with a cross-sectional design. Care staff was interviewed regarding 432 residents of 17 nursing homes for people with dementia. Behavioural problems were assessed using the Nursing Home version of the Neuropsychiatric Inventory (NPI-NH) questionnaire. The distress scale of the NPI-NH was used to determine the distress of care staff. Agitation/aggression had the highest mean distress score and was also the most prevalent symptom. Disinhibition and irritability/lability also had high mean distress scores, whereas euphoria/elation, hallucinations and apathy had the lowest mean distress score. The symptom severity of each symptom strongly predicted the distress score, whereas the frequency of the symptoms was a less important factor. Although some of these findings are in accordance with studies among informal caregivers, there are also notable differences. Apathy caused little distress among care staff. Therefore, care staff might not feel the urgency to explore the causes of this symptom. The findings of this study emphasize the importance of supporting care staff in the management of behavioural problems, especially aggression and apathy.


Hypertension and age-related changes in the heart. Implications for drug therapy.
Heart disease in older individuals can be characterised as the result of 2 processes, hypertension and atherosclerosis, which are the major causes of heart failure in the elderly population. The aging heart undergoes changes at the molecular, cellular and organ levels. These age-related changes may then be modulated by pathological conditions, such as hypertension, and by the reduction of blood pressure. One characteristic of the aged heart is a limited capacity for adaptation, by hypertrophy, to increased mechanical load. This age-related attenuation of the hypertrophic response may be attributed to the diminished induction of proto-oncogenes such as c-fos, c-myc and c-jun. This diminution results from aging of the heart per se and may be modulated by extracardiac factors. With regard to the coronary vasculature, the age at which hypertension develops seems to be an important factor for determining the vascularity of hypertrophied hearts. Late-onset hypertension is not accompanied by coronary angiogenesis, and it decreases dilator reserve in spite of the absence of myocardial hypertrophy. In contrast, mechanical overload in infant hearts is accompanied by angiogenesis and normal dilator reserve. In principle, the normalisation of hypertension results in the regression of myocardial hypertrophy and decreased coronary dilator reserve. In aged hearts, it is not clear how hypertension-induced myocardial hypertrophy or coronary vascular changes regress. Although antihypertensive treatment is clearly associated with an improvement of cardiovascular mortality and morbidity in hypertensive elderly individuals, it remains unclear how treatments ameliorate the hypertension-induced alterations.


Relative sea-level data from the SEAMIS database compared to ICE-5G model predictions of glacial isostatic adjustment.
The SEAMIS database (Mendeley data repository; https://doi.org/10.17632/wp4ctb4667.1) contains 546 relative sea-level indicators from 31 different studies within the broader Southeast Asian region including the Maldives, India and Sri Lanka. Here we compare quality-controlled and site-specific relative sea-level data from 23 studies from the SEAMIS database to a suite of ICE-5G glacial isostatic adjustment models. The relation between robust and, if applicable, tectonically corrected relative sea-level data with the broad predictions of glacial isostatic adjustment models is interpreted and discussed in the article "Holocene sea levels in Southeast Asia, Maldives, India and Sri Lanka: The SEAMIS database" [1] in Quaternary Science Reviews.


Review of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation Clinical Presentation, Treatment, and Outcomes.
The Necrotizing Enterocolitis Surgery Trial (NEST) highlights the importance of distinguishing necrotizing enterocolitis (NEC) from spontaneous intestinal perforation (SIP) when developing surgical treatment plans. Further research is needed to increase the accuracy of this distinction, but even with our current abilities to do this initial laparotomy appears to be optimal for infants with presumed NEC. The preferred initial operation for those with SIP is more equivocal. Rates of NEC are likely decreasing slowly, whereas those with SIP are not. New imaging modalities, especially ultrasound, are becoming more useful but require more detailed investigation. Understanding the mechanisms causing these two conditions remains of paramount importance.


Relationship between parathyroid oxyphil cell proportion and clinical characteristics of patients with chronic kidney disease.
Parathyroid glands consist of chief cells and oxyphil cells. The parathyroid oxyphil cell proportion increased dramatically in patients with chronic kidney disease (CKD). The importance of the oxyphil cell in the treatment of secondary hyperparathyroidism (SHPT) has been enhanced in recent years. The aim of this study was to explore the possible relationship between parathyroid oxyphil cell proportion and clinical features of patients with CKD. From December 2010 to December 2018, 78 consecutive patients with CKD 5 who underwent parathyroidectomy (PTX) were reviewed. None of the patients had used Cinacalcet. Patients were divided into two groups according to their parathyroid oxyphil cell proportion. The mean parathyroid oxyphil cell proportion of all the patients was obtained. Group 1 consisted of 37 patients, the parathyroid oxyphil cell proportion of whom was more than or equal to mean proportion. Group 2 consisted of 41 patients, the parathyroid oxyphil cell proportion of whom was less than mean proportion. The demographic and biochemical data of the two groups were compared. Preoperative parathyroid hormone (PTH) and total weight of removed parathyroid glands in the patients of group 1were less than those in group 2. There was no difference between the two groups in terms of preoperative calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), age and dialysis years. The parathyroid oxyphil cell proportion was associated with preoperative PTH and total weight of removed parathyroid glands in the patients with CKD. Patients with more parathyroid oxyphil proportion had lower preoperative PTH level and smaller total weight of the removed parathyroid glands.


Effects of berberine on 6-hydroxydopamine-induced neurotoxicity in PC12 cells and a rat model of Parkinson's disease.
Protoberberine isoquinoline alkaloids including berberine inhibit dopamine biosynthesis and aggravate l-DOPA-induced cytotoxicity in PC12 cells. In this study, the effects of berberine on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity in PC12 cells and on unilateral 6-OHDA-lesioned rats were investigated. In PC12 cells, berberine at 10 and 30μM associated with 6-OHDA (10, 20, and 50μM) enhanced cytotoxicity at 48h compared to 6-OHDA alone, indicated by an increase in apoptotic cell death. In addition, treatment with berberine (5 and 30mg/kg, i.p.) for 21 days in 6-OHDA-lesioned rats markedly depleted tyrosine hydroxylase-immunopositive cells in the substantia nigra as compared to berberine-untreated rats. Further, the levels of dopamine and norepinephrine were also significantly decreased by berberine administration (5 and 30mg/kg) in the striatal regions of 6-OHDA-lesioned rats. These results suggested that berberine aggravated 6-OHDA-induced cytotoxicity in PC12 cells, and led to the degeneration of dopaminergic neuronal cells in the substantia nigra of 6-OHDA-lesioned rats. It is, therefore, suggested that the use of long-term l-DOPA therapy with isoquinoline derivatives including berberine may need to be examined for the presence of adverse symptoms.


Seafood consumption patterns, their nutritional benefits and associated sociodemographic and lifestyle factors among First Nations in British Columbia, Canada.
To describe seafood consumption patterns in First Nations (FN) in British Columbia (BC) and examine lifestyle characteristics associated with seafood consumption; to identify the top ten most consumed seafood species and their contributions to EPA and DHA intake; and to estimate dietary exposure to methylmercury, polychlorinated biphenyls and dichlorodiphenyldichloroethylene. Dietary and lifestyle data from the First Nations Food Nutrition and Environment Study, a cross-sectional study of 1103 FN living in twenty-one communities across eight ecozones in BC, Canada, were analysed. Seafood consumption was estimated using a traditional FFQ. Seafood samples were analysed for contaminant contents. Seafood consumption patterns varied significantly across BC ecozones reflecting geographical diversity of seafood species. The top ten most consumed species represented 64 % of total seafood consumption by weight and contributed 69 % to the total EPA+DHA intake. Mean EPA+DHA intake was 660·5 mg/d in males, 404·3 mg/d in females; and 28 % of FN met the Recommended Intake (RI) of 500 mg/d. Salmon was the most preferred species. Seafood consumption was associated with higher fruit and vegetable consumption, lower smoking rate and increased physical activity. Dietary exposure to selected contaminants from seafood was negligible. In FN in BC, seafood continues to be an essential part of the contemporary diet. Seafood contributed significantly to reaching the RI for EPA+DHA and was associated with a healthier lifestyle. Given numerous health benefits, seafood should be promoted in FN. Efforts towards sustainability of fishing should be directed to maintain and improve access to fisheries for FN.


High-throughput screening of corticosteroids and basic drugs in horse urine by liquid chromatography-tandem mass spectrometry.
This paper describes two high-throughput liquid chromatography-tandem mass spectrometry (LC-MS-MS) methods for the screening of two important classes of drugs in equine sports, namely corticosteroids and basic drugs, at low ppb levels in horse urine. The method utilized a high efficiency reversed-phase LC column (3.3 cm L x 2.1 mm i.d. with 3 microm particles) to provide fast turnaround times. The overall turnaround time for the corticosteroid screen was 5 min and that for the basic drug screen was 8 min, inclusive of post-run and equilibration times. Method specificity was assessed by analysing a total of 35 negative post-race horse urine samples. No interference from the matrices at the expected retention times of the targeted masses was observed. Inter-day precision for the screening of 19 corticosteroids and 48 basic drugs were evaluated by replicate analyses (n = 10) of a spiked sample on 4 consecutive days. The results demonstrated that both methods have acceptable precision to be used on a routine basis. The performance of these two methods on real samples was demonstrated by their applications to drug administration and positive post-race urine samples.


Vitamin D status and supplementation impacts on skeletal muscle function: comparisons between young athletes and older adults.
The present narrative review analyzes emerging research implicating vitamin D status and supplementation with skeletal muscle homeostasis and functions in two distinct segments of the adult population: young athletes and older adults. Vitamin D deficiency compromises multiple indices of muscle function in young athletes and older adults. A variety of vitamin D3 (cholecalciferol) supplementation regimens may transition young athletes and older adults from deficient or inadequate to adequate vitamin D status. Vitamin D supplementation, used to treat a vitamin D deficiency, but not necessarily an inadequacy, promotes muscle anabolism in older adults. For both young athletes and older adults, vitamin D supplementation, which transitions them from inadequate to adequate vitamin D status, may not beneficially affect measures of muscle strength and power, or physical performance. Also, when vitamin D status is adequate, vitamin D supplementation to further increase serum 25(OH)D concentrations does not seem to confer additional benefits to muscle strength and power and physical performance. The impacts of vitamin D status and supplementation on skeletal muscle homeostasis and functions seem comparable in young athletes who strive to maximize physical performance and older adults who seek to attenuate muscle mass and physical performance declines.


Down syndrome.
Down syndrome (DS; Trisomy 21) is the most common chromosomal disorder in humans. It has numerous associated neurologic phenotypes including intellectual disability, sleep apnea, seizures, behavioral problems, and dementia. With improved access to medical care, people with DS are living longer than ever before. As more individuals with DS reach old age, the necessity for further life span research is essential and cannot be overstated. There is currently a scarcity of information on common medical conditions encountered as individuals with DS progress into adulthood and old age. Conflicting information and uncertainty about the relative risk of dementia for adults with DS is a source of distress for the DS community that creates a major obstacle to proper evaluation and treatment. In this chapter, we discuss the salient neurologic phenotypes of DS, including Alzheimer's disease (AD), and current understanding of their biologic bases and management.


Esterases of Mus musculus: substrate and inhibition characteristics, new isozymes, and homologies with man.
A wide range of fluorogenic and naphthol esters has been tested as substrates for mouse esterases. New esterases have been identified in liver and kidney extracts with palmityl, oleyl, and elaidyl esters. From substrate, inhibition, and molecular weight studies, three homologies between human and mouse esterases are suggested. A new allele at Es-6 is also described.


Pt3Ni@C Composite Material Designed and Prepared Based on Volcanic Catalytic Curve and Its High-Performance Static Lithium Polysulfide Semiliquid Battery.
There are many challenges for the Static lithium polysulfide semiliquid battery in its commercial application, such as poor stability of the cathode material and further amplification of the lithium polysulfide shuttle effect. Therefore, this manuscript introduced a new type of Pt3Ni@C composite material as cathode working electrode based on the principle of volcanic catalytic curve. Through symmetric battery test, CV, polarization curves and impedance test, it was found that Pt3Ni@C composite material had good catalytic activity of lithium polysulfide to improve electrochemical kinetics. When the catholyte was Li2S8 and the charge-discharge voltage range was 1.8~2.6 V, the capacity maintained at approximately 550 mAh g-1, and the coulombic efficiency maintained at approximately 95% after 100 cycles at a current rate of 0.5 mA cm-2. The Pt3Ni@C composite material is a potential cathode material with the specific capacity and long cycling stability of the static lithium polysulfide semiliquid battery.


Effects of platelet-activating factor, thromboxane A2 and leukotriene D4 on isolated perfused rat liver.
Vasoconstrictive lipid mediators, thromboxane A(2) (TxA(2)), platelet-activating factor (PAF) and leukotriene D(4) (LTD(4)) have been implicated as mediators of liver diseases. There are species differences in the primary site of hepatic vasoconstriction in response to these mediators. We determined the effects of a TxA(2) analogue (U-46619), PAF and LTD(4) on the vascular resistance distribution, weight and oxygen consumption of isolated rat livers portally perfused with blood. The sinusoidal pressure was measured by the double occlusion pressure (P(do)), and was used to determine the pre- (R(pre)) and post-sinusoidal (R(post)) resistances. All these three mediators increased the hepatic total vascular resistance (R(t)). The responsiveness to PAF was 100 times greater than that to U-46619 or LTD(4). Both of PAF and U-46619 predominantly increased R(pre) over R(post). At the comparable increased R(t) levels, U-46619 more preferentially increased R(pre) than PAF. In contrast, LTD(4) increased both the R(pre) and R(post) to similar extent. U-46619 caused liver weight loss, while high concentrations of either LTD(4) or PAF produced liver weight gain, which was caused by substantial post-sinusoidal constriction and increased P(do). PAF and U-46619 decreased hepatic oxygen consumption while LTD(4) induced biphasic change of an initial transient decrease followed by an increase. In conclusion, PAF is the most potent vasoconstrictor of rat hepatic vessels among these three mediators. Both TxA(2) and PAF constrict the pre-sinusoidal veins predominantly. TxA(2) more preferentially constricts the pre-sinusoids than PAF, resulting in liver weight loss. However LTD(4) constricts both the pre- and post-sinusoidal veins similarly. High concentrations of LTD(4) and PAF cause liver weight gain by substantial post-sinusoidal constriction. PAF and TxA(2) decrease hepatic oxygen consumption, whereas LTD(4) causes a biphasic change of it.


Use of high-concentration contrast media in multiple-detector-row CT: principles and rationale.
Contrast-medium-enhanced multiple-detector-row CT (MDCT) is a powerful technique for vascular and hepatic imaging. With increasingly faster acquisition speeds, which have become possible with latest 8- and 16-channel scanner systems, contrast medium delivery is becoming increasingly difficult. This article reviews the pharmacokinetic and physiologic principles of vascular and hepatic enhancement following the intravenous injection of iodinated contrast medium. The effects of user-selectable injection parameters, such as the injection rate, the injection duration, and the contrast medium concentration on arterial and parenchymal enhancement are elucidated. Equipped with this knowledge, rational injection strategies for CT angiographic protocols for scanners with different acquisition speeds are derived. Furthermore, injection and timing protocols, optimized for hepatic MDCT during the early arterial, late arterial, and parenchymal phases, are developed.


CD117 expression in normal, neoplastic, inflammatory, and reactive lesions of the thyroid.
The mutations of c-kit gene, which encodes a transmembrane receptor tyrosine kinase (CD117-KIT) or activation of CD117, lead to the activation of signal transduction cascades regulating cell proliferation, apoptosis, chemotaxis, and adhesion. The aim of this study was to investigate the expression of CD117 in normal, inflammatory, neoplastic, and reactive lesions of the thyroid. Using polyclonal anti-CD117 antibody, we performed immunohistochemical staining on tissue blocks from 230 cases obtained from the archives of the Department of Pathology, Ondokuz Mayis University (Samsun, Turkey), collected between 1990 and 2006. Each slide was evaluated for extent and intensity of staining. Staining extent was expressed as the percentage of stained cells. Staining of <10% of the cells was accepted as negative. Staining intensity was evaluated only in positive cases. By addition of the extent and intensity scores, the combined score was calculated. In our study, the combined CD117 staining scores of neoplastic and inflammatory groups were found to be higher than the reactive and normal groups. Within the neoplastic group, papillary carcinomas differed from follicular adenomas significantly, although papillary carcinomas showed no statistically significant difference compared to follicular carcinomas. Immunohistochemical CD117 positivity was detected in a wide range of neoplastic and inflammatory thyroid diseases. The neoplastic group and, within them, the papillary carcinomas showed a higher ratio of CD117 positivity. Although our results need to be confirmed by other molecular and genetic studies, the high rate of positivity in papillary carcinomas was one of the striking findings, which may result in novel diagnostic and therapeutic approaches.


Outcome of staged surgical approach to neonates with single left ventricle and moderate size bulboventricular foramen.
Neonates with double-inlet left ventricle or tricuspid atresia with transposed great arteries and a bulboventricular foramen (BVF) area <2 cm(2)/m(2) develop BVF obstruction. This study examined the outcome of neonates with BVF area between 1 and 2 cm(2)/m(2) whose BVF was bypassed after the neonatal period. We reviewed 29 neonates with double-inlet left ventricles (n = 18) or tricuspid atresia (n = 11) and transposed great arteries. The study group consisted of 9 patients with neonatal BVF areas of 1 to 2 cm(2)/m(2) who did not undergo repair of the BVF obstruction as a neonate. The comparison group consisted of 8 "ideal" patients without BVF obstruction. Precavopulmonary shunt data from cardiac catheterization and echocardiogram and outcomes of the cavopulmonary shunt were compared. Study group patients developed a mild BVF gradient (18 +/- 10 mm Hg by cardiac catheterization) by a mean of 7 months. Left ventricular wall thickness, however, remained in the normal range (4.2 +/- 0.3 mm) and was not statistically different from the comparison group (4.1 +/- 0.4 mm). No difference was found in the precavopulmonary mean pulmonary artery pressure (15 +/- 5 vs 15 +/- 6 mm Hg), transpulmonary gradient (8 +/- 4 vs 8 +/- 5 mm Hg), and left ventricular end-diastolic pressure (7 +/- 2 vs 8 +/- 3 mm Hg). One patient in the study group died from respiratory syncytial virus pneumonia while awaiting cavopulmonary shunt. Neither group had mortality from the cavopulmonary shunt. The lengths of hospital stay were comparable (8.3 +/- 3.7 vs 8.9 +/- 6.0 days). Thus, neonates with BVF area between 1 and 2 cm(2)/m(2) develop mild but hemodynamically insignificant BVF gradient by 7 months of age. This group of patients can be managed safely with relief of BVF obstruction later in infancy.


RIG-I-based immunotherapy enhances survival in preclinical AML models and sensitizes AML cells to checkpoint blockade.
Retinoic acid-inducible gene-I (RIG-I) is a cytoplasmic immune receptor sensing viral RNA. It triggers the release of type I interferons (IFN) and proinflammatory cytokines inducing an adaptive cellular immune response. We investigated the therapeutic potential of systemic RIG-I activation by short 5'-triphosphate-modified RNA (ppp-RNA) for the treatment of acute myeloid leukemia (AML) in the syngeneic murine C1498 AML tumor model. ppp-RNA treatment significantly reduced tumor burden, delayed disease onset and led to complete remission including immunological memory formation in a substantial proportion of animals. Therapy-induced tumor rejection was dependent on CD4+ and CD8+ T cells, but not on NK or B cells, and relied on intact IFN and mitochondrial antiviral signaling protein (MAVS) signaling in the host. Interestingly, ppp-RNA treatment induced programmed death ligand 1 (PD-L1) expression on AML cells and established therapeutic sensitivity to anti-PD-1 checkpoint blockade in vivo. In immune-reconstituted humanized mice, ppp-RNA treatment reduced the number of patient-derived xenografted (PDX) AML cells in blood and bone marrow while concomitantly enhancing CD3+ T cell counts in the respective tissues. Due to its ability to establish a state of full remission and immunological memory, our findings show that ppp-RNA treatment is a promising strategy for the immunotherapy of AML.


Concomitant mutagenicity of ethanol and x-ray irradiation in the mouse male germ cells.
The mutagenic effect of ethanol and x-ray irradiation on the male germ cells was investigated in the mouse. The meiotic micronuclei in the testis were recorded and the abnormalities in the epididymal sperm heads were counted. The number of micronuclei in early spermatids did not differ in the ethanol-exposed groups from that of their control groups at the end of 5 week ethanol diets. However, in the mice irradiated with a dose of 0.5 Gy, there was a statistically significant (p less than 0.01) difference in micronucleus induction between the groups of different ethanol exposure levels. No statistically significant differences were found in the numbers of abnormal sperm heads immediately after the diet or 25 days, 5 weeks and 10 weeks after the cessation of the diet. However, sperm abnormality frequencies were elevated at 5 weeks after 4 and 6% (v/v) ethanol diets and at 25 days after the 6% diet. The results suggest that ethanol is co-mutagenic with x-rays in the mouse male germ cells. Ethanol alone showed also a tendency to be mutagenic in the sperm abnormality test. The stage and mechanism of action of ethanol is discussed.


The "Liaison" in Consultation-Liaison Psychiatry: Helping Medical Staff Cope with Pediatric Death.
Pediatric consultation-liaison clinicians are well positioned to provide support, guidance, and systemic recommendations about how to help medical clinicians cope with the stresses of working with dying children. Interventions to support sustainability in this work need to occur at the institutional and team-based levels as well as in individual practice. Shared clinical work around challenging cases provides opportunities to engage with medical clinicians about their difficult experiences and provide reflection and support. Psychiatry services may also be in a role of advocating for institutionally based interventions that can help their medical colleagues.


Ruthenium ammine complexes as electron acceptors for growth stimulation by plasma membrane electron transport.
Ammineruthenium(III) complexes have been found to act as electron acceptors for the transplasmalemma electron transport system of animal cells. The active complexes hexaammineruthenium(III), pyridine pentammineruthenium(III), and chloropentaammineruthenium(III) range in redox potential (E'0) from 305 to -42 mV. These compounds also act as electron acceptors for the NADH dehydrogenase of isolated plasma membranes. Stimulation of HeLa cell growth, in the absence of calf serum, by these compounds provides evidence that growth stimulation by the transplasma membrane electron transport system is not entirely based on reduction and uptake of iron.


Physiological Changes in Chicken Embryos Inoculated with Drugs and Viruses Highlight the Need for More Standardization of this Animal Model.
Several studies have been developed using the Gallus gallus embryo as an experimental model to study the toxicity of drugs and infections. Studies that seek to standardize the evaluated parameters are needed to better understand and identify the viability of CEs as an experimental model. Therefore, we sought to verify whether macroscopic, histopathological, blood count, metabolites and/or enzymes changes and oxidative stress in CE of different ages are specific to the model. To achieve this goal, in ovo assays were performed by injecting a virus (Gammacoronavirus) and two drugs (filgrastim and dexamethasone) that cause known changes in adult animals. Although congestion and inflammatory infiltrate were visible in the case of viral infections, the white blood cell count and inflammation biomarkers did not change. Filgrastim (FG) testing did not increase granulocytes as we expected. On the other hand, CE weight and red blood cell count were lower with dexamethasone (DX), whereas white blood cell count and biomarkers varied depended on the stage of CE development. Our work reinforces the importance of standardization and correct use of the model so that the results of infection, toxicity and pharmacokinetics are reproducible.


Genetic markers in Malaysians: variants of soluble and mitochondrial glutamic oxaloacetic transaminase and salivary and pancreatic amylase, phosphoglucomutase III and saliva esterase polymorphisms.
Malaysians of Malay, Chinese, and Indian ancestries were electrophoretically phenotyped for Amy1 and saliva esterase region 1 (Set-1) from saliva, Amy2 from plasma, soluble and mitochondrial GOT and PGM3 from leukocyte and placenta. Kadazans and Bajaus, the indigenous people of Sabah, East Malaysia were surveyed for Amy2. Three types of variants were observed for Amy1, one type for Amy2. Only Indians were found to be polymorphic for Amy1. Two GOTs 2-1 and three GOTm 2-1 variants were found among 281 Chinese while three GOTm 2-1 variants were found among 311 Malays. Malaysian Malays, Chinese, and Indians were found to be polymorphic for Set-1 and PGM3. The gene frequencies in Malays are Set-1F=0.601 +/- 0.021, Set-1S = 0.399 +/- 0.021; PGM13 = 0.788 +/- 0.020, PGM23 = 0.212 +/- 0.020; in Chinese Set-1F = 0.497 +/- 0.028, Set-1S = 0.503 +/- 0.028; PGM13 = 0.745 +/- 0.24, PGM23 = 0.255 +/- 0.024; in Indians, Set-1F = 0.449 +/- 0.031, Set-1S = 0.551 +/- 0.031; PGM13 = 0.755 +/- 0.029, PGM23 = 0.245 +/- 0.029.


Gustavia gracillima Miers. flowers effects on enzymatic targets underlying metabolic disorders and characterization of its polyphenolic content by HPLC-DAD-ESI/MSn.
Notwithstanding Gustavia gracillima Miers widespread distribution in neotropical regions, its chemical profile and biological properties remain uninvestigated. A methanol extract obtained from the flowers was characterized through HPLC-DAD-ESI/MSn, nine ellagic acid derivatives and twelve kaempferol 3-O-glycosides being identified and quantitated for the first time at the species and genus. Preliminary cytotoxicity screening did not reveal noticeable effects upon gastrointestinal representative cell lines (AGS, Caco-2 and Hep G2), which further prompted us to evaluate the impact in a series of targets involved in metabolic disorders and associated complications. Despite of the moderate inhibition towards 5-lipoxygense activity, G. gracillima methanol extract displayed significant effects on carbohydrates-hydrolysing enzymes. In contrast with the antidiabetic reference drug acarbose, the extract was able to selectively inhibit yeast α-glucosidase activity (IC50 = 4.72 µg/mL), with negligible inhibitory effects upon α-amylase. Kinetic studies pointed to a model of mixed inhibition with a great binding activity, characterized by an inhibitory constant of 2.91 µg/mL. The notable inhibitory activity was also confirmed in α-glucosidase homogenates isolated from human intestinal cells (IC50 = 34.03 µg/mL). Moreover, the extract obtained from the flowers of G. gracillima displayed significant aldose reductase inhibition (IC50 = 61.88 µg/mL), as well as O2- and NO scavenging properties. A moderate inhibitory effect was also recorded against pancreatic lipase (IC50 = 362.17 µg/mL) through a mixed inhibition mode. Recorded data supports the potential incorporation of G. gracillima flowers on antidiabetic herbal formulations and/or supplements, with not only straight action on carbohydrates digestion, but also direct interference with targets involved on subsequent diabetes events, such as triglycerides metabolism, inflammation and radical-mediated stress.