Sinomenine Attenuated Capsaicin-Induced Increase in Cough Sensitivity in Guinea Pigs by Inhibiting SOX5/TRPV1 Axis and Inflammatory Response.
Chronic cough is a common complaint which affects a large number of patients worldwide. Increased cough sensitivity is a very important cause of chronic persistent cough. However, there are limited clinical diagnosis and treatment for increased cough sensitivity. Transient receptor potential vanilloid-1 (TRPVl) is a member of the transient receptor potential (TRP) family of channels which is very closely associated with respiratory diseases. However, the mechanism through which TRPV1 that influences downstream events is still poorly understood. Capsaicin induced increase in cough sensitivity by upregulating the protein level of TRPV1, leading to the secretions of Substance P and neurokinin A which stimulated neurogenic inflammation. However, sinomenine, a component of traditional Chinese medicine, significantly attenuated the capsaicin-induced cough by inhibiting the expression of TRPV1 in guinea pigs. In addition, capsaicin increased the expression of SOX5 which mediated the transcriptional upregulation of TRPV1. However, pretreatment with sinomenine reduced the expression of SOX5. These results indicate that capsaicin induced increase in cough sensitivity by activating neurogenic inflammation, while sinomenine attenuated the increase in cough sensitivity by inhibiting the expressions of SOX5 and TRPV1 in guinea pigs. This finding may provide a novel target for the treatment of aggravated cough sensitivity.


Prognostic DNA methylation marker in serum of cancer patients.
Changes in the status of DNA methylation are among the most common molecular alterations in human neoplasia. Recent demonstrations of tumor-derived methylated DNA in the blood stream of cancer patients allow the use of these epigenetic markers for risk assessment in cancer patients. We were interested in evaluating the prognostic value of several methylated genes in the serum of cancer patients. Using MethyLight, a high-throughput DNA methylation assay, we analyzed 215 serum samples from patients with cervical (n = 93) or breast cancer (n = 122) for DNA methylation changes. In cervical cancer, hypermethylation of three genes (MYOD1, CDH1, and CDH13) in pretreatment sera was statistically significantly associated with a poorer disease outcome. Additionally, for the first time we used a so-called gene evaluation set to identify the most important DNA methylation changes in the serum of breast cancer patients from a long list of candidate genes. In the gene evaluation set, we detected five genes (ESR1, APC, HSD17B4, HIC1, and RASSF1A) using our criteria for further analysis. Finally, two of the evaluated genes (APC and RASSF1A) proved to be independent prognostic parameters in breast cancer patients. In summary, we detected several prognostic DNA methylation markers in the serum of cervical and breast cancer patients. This finding indicates great potential for the use of these epigenetic markers in clinical, routine risk assessment in patients with various malignancies.


Assessing effector T cells in type 1 diabetes.
The role of T cells specific for islet autoantigens is proven in pathogenesis of type 1 diabetes. Recently, there has been rapid expansion in the number of T-cell subsets identified, this has coincided with an increase in the repertoire of reported islet antigens mainly through the discovery of novel epitopes. A discussion of how these marry together is now warranted and timely. In this review, we will discuss the autoreactivity against neo-epitopes. We then explore the growing array of T-cell subsets for both CD4 T cells, including follicular and peripheral T helper cells, and CD8 T cells, discussing evolution from naïve to exhausted phenotypes. Finally, we detail how subsets correlate with disease stage and loss of β-cell function and are impacted by immunotherapy. The expanding list of T-cell subsets may be potentially encouraging in terms of elucidating disease mechanisms and have a role as biomarkers for disease progression. Furthermore, T-cell subsets can be used in stratifying patients for clinical trials and for monitoring immunotherapy outcomes. However, the definition of subsets needs to be refined in order to ensure that there is a uniform approach in designating T-cell subset attributes that is globally applied.


A simplified minimally invasive approach to mitral valve surgery - optimal access under direct vision.
With increasing enthusiasm in minimally invasive surgery, several approaches and access are being performed with great precision. In this report, we illustrate and describe a minimal invasive approach to mitral valve surgery with optimal access under direct vision, the indications and patient selection, the surgical techniques, its advantages over the other approaches, and its simplicity and reproducibility.


[Analysis of screening tests for Streptococcus agalactiae in pregnant women from the West Pomeranian region].
The aim of the study was to determine the degree of colonization Streptococcus agalactiae (GBS--Group B Streptococcus) in women at 35.-37. weeks of pregnancy and to evaluate drug susceptibility of the isolated strains. We analyzed the results of 1111 tests for GBS colonization performed between 2010-2013 in pregnant women (aged 16-40) from the West Pomeranian region. Swabs were taken from the vagina and the anus of the study subjects at 35.-37. weeks of pregnancy Materials were cultured on Granada Agar and in selective Todd-Hewitt broth, which was next cultured on Granada Agar The degree of GBS colonization was determined by the semi-quantitative method on solid media. The strains were tested for susceptibility to penicillin, erythromycin and clindamycin by disc diffusion method according to the EUCAST standards. Positive cultures for S. agalactiae were found in 22.5% of the pregnant women. The highest (25.4%) and the lowest (15.9%) rates of GBS colonization were observed in the age groups of 31-35 and 16-20 years, respectively Massive GBS colonization was detected in 68.4% of pregnant subjects, with the highest and the lowest rates in the age groups of 31-35 and 16-20 years, (75.3% and 50.0%, respectively). All isolated GBS strains were sensitive to penicillin. Macrolide, lincosamide and streptogramin B resistance (MLSB) was found in 28% of the isolates, resistance only to erythromycin (phenotype M) in 2% of the strains. There were no significant differences in the degree of GBS colonization and drug sensitivity of GBS strains versus the year of our examination. Monitoring for GBS colonization in the last weeks of pregnancy seems to be necessary for effective prevention of S. agalactiae infections.


Dicer partner protein tunes the length of miRNAs using base-mismatch in the pre-miRNA stem.
Dicer partner proteins Drosophila Loquacious-PB (Loqs-PB) and human TRBP tune the length of miRNAs produced by Dicer from a subset of pre-miRNAs and thereby alter their target repertoire, by an unknown mechanism. Here, we developed a novel high-throughput method that we named Dram-seq (Dice randomized pre-miRNA pool and seq) to study length distributions of miRNAs produced from thousands of different pre-miRNA variants. Using Dram-seq, we found that a base-mismatch in the pre-miRNA stem can alter the length of miRNAs compared with a base-pair at the same position in both Drosophila and human, and is important for the miRNA length tuning by Loqs-PB. Loqs-PB directly bound base-mismatched nucleotides in the pre-miRNA stem. We speculate that Loqs-PB tunes miRNA length by changing the conformation of base-mismatched nucleotides in the pre-miRNA stem to that of base-paired ones and thereby altering the distance of the pre-miRNA stem.


Effects of short inter-pregnancy interval on maternal and perinatal outcomes: A cohort study of pregnant women in a low-income country.
Short inter-pregnancy interval (IPI) is a potential risk factor for adverse pregnancy outcomes. Previous reports from sub-Sahara Africa documented increasing incidence of short IPI but evidence is lacking in its effect on pregnancy outcome. The study aimed to determine the effect of short IPI on pregnancy outcome in Nigeria. It was a prospective cohort study of 271 pregnant women receiving antenatal care in a tertiary hospital in Nigeria. For every eligible woman with short IPI (<18 months) recruited; a suitable control with IPI ≥18 months was selected. Statistical analysis was both inferential and descriptive using the statistical package for social sciences version 24 (SPSS Inc. Chicago, Illinois, USA) for windows. A P value of less than 0.05 was considered statistically significant. Incidence of maternal anemia was higher in women with short IPI than control (RR: 2.091; 95% CI: 1.4433.031; P < 0.001). Other maternal and perinatal outcome measures including premature rupture of membranes, preterm labor/delivery, pregnancy induced hypertension, third trimester bleeding, postpartum hemorrhage, and inadequate gestational weight gain did not show any significant association with short IPI (P > 0.05). Short IPI is associated with anemia in pregnancy in Nigeria. Public health campaigns for improvement in uptake of family planning services and breastfeeding may help reduce the incidence of short IPI and anemia in low income countries.


The relationship of agonist muscle single motor unit firing rates and elbow extension limb movement kinematics.
This study explored the relationship between single motor unit (MU) firing rates (FRs) and limb movement velocity during voluntary shortening contractions when accounting for the effects of time course variability between different kinematic comparisons. Single MU trains recorded by intramuscular electromyography in agonist muscles of the anconeus (n = 15 participants) and lateral head of the triceps brachii (n = 6) were measured during each voluntary shortening contraction. Elbow extension movements consisted of a targeted velocity occurring along the sagittal plane at 25, 50, 75 and 100% of maximum velocity. To account for the effect of differences in contraction time course between parameters, each MU potential was time locked throughout the shortening muscle contraction and linked with separated kinematic parameters of the elbow joint. Across targeted movement velocities, instantaneous FRs were significantly correlated with elbow extension rate of torque development (r = 0.45) and torque (r = 0.40), but FRs were not correlated with velocity (r = 0.03, p = n.s.). Instead, FRs had a weak indirect relationship with limb movement velocity and position assessed through multiple correlation of the stepwise kinematic progression. Results show that voluntary descending synaptic inputs correspond to a more direct relationship between agonist muscle FRs and torque during shortening contractions, but not velocity. Instead, FRs were indirectly correlated to preparing the magnitude of imminent movement velocity of the lagging limb through torque.


Dyslipidemia in pediatric renal disease: epidemiology, pathophysiology, and management.
Dyslipidemia increases the risk of cardiovascular events among individuals with renal disease, and there is a growing body of evidence that it hastens the progression of renal disease itself. Children with nephrotic syndrome or renal transplants have easily recognized hyperlipidemia. Among those with chronic renal insufficiency or end-stage renal disease, detection of dyslipidemia requires more careful analysis and knowledge of normal pediatric ranges. Disordered lipoprotein metabolism results from complex interactions among many factors, including the primary disease process, use of medications such as corticosteroids, the presence of malnutrition or obesity, and diet. The systematic treatment of dyslipidemia in children with chronic renal disease is controversial because conclusive data regarding the risks and benefits are lacking. Hepatic 3-methylglutaryl coenzyme A reductase inhibitors (statins), fibrates, plant stanols, bile acid-binding resins, and dietary manipulation are options for individualized treatment. Prospective investigations are required to guide clinical management.


[Phosphocalcic anomalies and bone fragility keys for the general practitioner].
How to recognize secondary causes of bone fragility in relation with an abnormal calcium and phosphate laboratory in general practice ? Through clinical cases presentations we will discuss the calcium and phosphate abnormalities which can be related to bone fragility and for which a-specific approach must be proposed. It can be abnormal results of calcium, phosphate or vitamin D. Some causes are frequent, others are iatrogenic, and others are related to a rare disease sometimes of genetic cause which consequences are more important than expected.


Utilization of Time-driven Activity-based Costing to Determine the True Cost of a Single or 2-level Anterior Cervical Discectomy and Fusion.
This is a prospective case series. To determine the actual cost of performing 1- or 2-level anterior cervical discectomy and fusion (ACDF) using actual patient data and the time-driven activity-based cost methodology. As health care shifts to use value-based reimbursement, it is imperative to determine the true cost of surgical procedures. Time-driven activity-based costing determines the cost of care by determining the actual resources used in each step of the care cycle. In total, 30 patients who underwent a 1- or 2-level ACDF by 3 surgeons at a specialty hospital were prospectively enrolled. To build an accurate process map, a research assistant accompanied the patient to every step in the care cycle including the preoperative visit, the preadmission testing, the surgery, and the postoperative visits for the first 90 days. All resources utilized and the time spent with every member of the care team was recorded. In total, 27 patients were analyzed. Eleven patients underwent a single-level ACDF and 16 underwent a 2-level fusion. The total cost for the episode of care was $29,299±$5048. The overwhelming cost driver was the hospital disposable costs ($13,920±$6325) which includes every item used during the hospital stay. Intraoperative personnel costs including fees for the surgeon, resident/fellow, anesthesia, nursing, surgical technician, neuromonitoring, radiology technician and orderlies, accounted for the second largest cost at $6066±$1540. The total cost excluding hospital overhead and disposables was $9071±$1939. Reimbursement for a bundle of care surrounding a 1- or 2-level ACDF should be no less than $29,299 to cover the true costs of the care for the entire care cycle. However, this cost may not include the true cost of all capital expenditures, and therefore may underestimate the cost.


Flowers help bees cope with uncertainty: signal detection and the function of floral complexity.
Plants often attract pollinators with floral displays composed of visual, olfactory, tactile and gustatory stimuli. Since pollinators' responses to each of these stimuli are usually studied independently, the question of why plants produce multi-component floral displays remains relatively unexplored. Here we used signal detection theory to test the hypothesis that complex displays reduce a pollinator's uncertainty about the floral signal. Specifically, we asked whether one component of the floral display, scent, improved a bee's certainty about the value of another component, color hue. We first trained two groups of bumble bees (Bombus impatiens Cresson) to discriminate between rewarding and unrewarding artificial flowers of slightly different hues in the presence vs absence of scent. In a test phase, we presented these bees with a gradient of floral hues and assessed their ability to identify the hue rewarded during training. We interpreted the extent to which bees' preferences were biased away from the unrewarding hue ('peak shift') as an indicator of uncertainty in color discrimination. Our data show that the presence of an olfactory signal reduces uncertainty regarding color: not only was color learning facilitated on scented flowers but also bees showed a lower amount of peak shift in the presence of scent. We explore potential mechanisms by which scent might reduce uncertainty about color, and discuss the broader significance of our results for our understanding of signal evolution.


Glutamic acid-induced shoot differentiation in tobacco callus tissues and changes in nicotine content and in activities of aminotransferases, ornithine transcarbamylase, and arginase.
Floral bud calluses of Nicotiana tabacum L. var. Anand-2 produced multiple shoots on Murashige and Skoog's (MS) medium supplemented with 2 mg/l indole-3-acetic acid (IAA), 0.4 mg/l kinetin (Kn), and L-glutamic acid (2.5 mM). However cultures of calluses on MS medium containing only the IAA and Kn did not differentiate shoots. Specific activities of phenylalanine aminotransferase, tyrosine aminotransferase, and ornithine aminotransferase were over 7-, 5- and 5-fold higher, respectively, in the glutamic acid-treated calluses than in the nonshoot-forming ones on the day of shoot emergence. Activities of ornithine transcarbamylase and arginase decreased after the onset of the differentiation process. Implications of the enzyme activities in the differentiation process and in nicotine biogenesis are discussed.


Impact of oral anticholinergic on insulin response to oral glucose load in patients with impaired glucose tolerance.
Preliminary data indicates there is a cholinergic basis to insulin secretion. To investigate the impact of oral anticholinergics on insulin secretion in subjects with impaired glucose tolerance (IGT), in comparison with volunteers having normal glucose tolerance (NGT). Material & Methods: This prospective observational study recruited 10 IGT and 10 NGT subjects. An oral glucose tolerance test (OGTT) was conducted twice in the absence and presence of hyoscine butyl-bromide (HBB). The plasma glucose (PG) and insulin levels were serially estimated at 30-min increments for 2 h after the OGTT. Early (ΔI30/ΔPG30) & late (insulin/PGAUC 60-120) phase insulin activity were assessed subsequently. The study constituted of 10 IGT (4M/6F, BMI: 28.80 ± 2.30) and 10 NGT (5M/5F, BMI: 23.00 ± 0.80) subjects. In the NGT group, the pre-HBB mean glucose levels (0-120 min) were comparable with those recorded after HBB intake. However, after HBBB, the mean insulin levels decreased significantly at t = 90 and 120min, confirmed by attenuated late phase insulin activity in IGT (P = 0.023) & NGT (P = 0.006) group. On the other hand, in the IGT group, however, HBB did not impact on the mean PG and insulin levels (0-120 min). Our study findings indicate that insulin secretion is influenced by cholinergic system and that oral anticholinergics may attenuate the late phase insulin activity in varying degrees of glycemic status.


Is bitter actually better? Targeting a soyasaponin acetyltransferase affects soybean seed germination.
This Highlight features a recent study showing that the soybean BAHD-type soyasaponin acetyltransferase GmSSAcT1 is responsible for three or four sequential acetylation steps in type-A soyasaponin biosynthesis and that loss of GmSSAcT1 function strongly inhibits soybean seed germination.


[Molecular pathophysiology of sideroblastic anemia].
Sideroblastic anemias (SAs) are heterogeneous congenital and acquired disorders characterized by anemia and the presence of ring sideroblasts in bone marrow. Congenital sideroblastic anemia (CSA) is a rare disease caused by mutations in genes that are involved in heme biosynthesis, iron-sulfur [Fe-S] cluster biosynthesis, and mitochondrial protein synthesis. The most common form of CSA is X-linked sideroblastic anemia; it occurs because of mutations in the erythroid-specific δ-aminolevulinate synthase gene (ALAS2), which is the first enzyme of the heme biosynthesis pathway in erythroid cells. Additionally, SAs can occur after exposure to certain drugs or alcohol and with copper deficiency (secondary SA) ; they are also detected in association with myelodysplastic syndrome (idiopathic SA). Among all types of SAs, idiopathic SA is the most common form. This review encompasses the current understanding of the molecular pathophysiology of SA.


Multiple actions of U-37883A, an ATP-sensitive K+ channel blocker, on membrane currents in pig urethra.
The effects of U-37883A, a vascular ATP-sensitive K(+) channel (K(ATP) channel) blocker, on membrane currents were investigated in pig urethral myocytes by use of patch-clamp techniques (conventional whole-cell recordings, nystatin-perforated patches and cell-attached configuration). Tension measurement was also performed to study the effects of U-37883A on the levcromakalim-induced urethral relaxation and the urethral resting tone in the absence and presence of Bay K 8644. Although cumulative application of U-37883A produced a concentration-dependent inhibitory effect on the levcromakalim-induced urethral relaxation, U-37883A did not abolish the relaxation. In nystatin-perforated patch recording, K(ATP) currents activated by levcromakalim were inhibited by U-37883A in a concentration-dependent manner (K(i), 4.7 microM). Approximately 10% of the K(ATP) currents still remained even in the presence of 300 microM U-37883A. In cell-attached mode, extracellular application of U-37883A (100 microM) irreversibly inhibited the activity of the levcromakalim-induced K(ATP) channels. In whole-cell configuration, U-37883A suppressed the peak amplitude of voltage-dependent Ba(2+) currents in a concentration- and voltage-dependent manner, and at 30 microM, shifted the steady-state inactivation curve of the Ba(2+) currents to the left at -90 mV. These results demonstrate that U-37883A reduces not only the activities of K(ATP) channels but also voltage-dependent Ca(2+) channels. Therefore, it is not appropriate to define U-37883A as solely a vascular K(ATP) channel blocker.


Evaluation of the melatonin and oxidative stress markers level in serum of fertile and infertile women.
Infertility is defined as the inability to achieve the pregnancy within a year of unprotected intercourse. Infertility is a complex issue and different factors such as stress oxidative can be involved in this problem. So, any attempt to neutralize oxidative stress would be helpful in the treatment of infertility. Melatonin is a known scavenger of free radicals. The aim of our study was to evaluate the level of melatonin and its correlation with oxidative biomarkers in fertile and infertile women. The participants including fertile and infertile women were divided into two groups of 30 people. Blood sampling was performed and sera were collected. The level of Malondialdehyde (MDA), total antioxidant capacity (TAC) and melatonin were detected. Data were analyzed using T-test and their correlation was assessed using Spearman test. Serum melatonin from fertile women was higher than infertile women but the difference was not significant (p= 0.46). MDA level in fertile women was significantly lower than infertile women (p<0.001) and the level of TAC in fertile women was significantly higher than infertile women (p<0.001). Spearman test revealed a significant and direct correlation between melatonin and TAC in fertile and infertile women and a significant but reverse correlation between melatonin and MDA in infertile and fertile women. Differences in the level of oxidative stress biomarkers in fertile and infertile individuals have been reported. This study revealed a significant correlation between melatonin and oxidative stress biomarkers, concluding that melatonin level could be involved in infertility.


Periodontal repair for advanced bone loss caused by orthodontic elastic bands: A case report with 7-year follow-up and literature review.
A 16-year-old girl developed severe acute periodontitis involving the maxillary central incisor and lateral incisor caused by elastic bands. Periodontal surgical interventions and orthodontic adjustment achieved good outcomes which were maintained for 7 years. This report demonstrates the criticality of correct diagnosis, early periodontal surgery, and interdisciplinary approach.


The Critical Role of Compliance in Delivering Health Gains from Environmental Health Interventions.
Gains in reducing childhood disease burden rely heavily on effective means of preventing environmental exposures. For many environmental health interventions, such as point-of-use water treatment, sanitation, or cookstoves, exposures are strongly influenced by user behaviors and the degree to which participants adhere to the prescribed preventive measures. In this commentary, we articulate the need for increased attention on user behaviors-critically, the careful measurement and inclusion of compliance-to strengthen exposure assessment and health impact trials in environmental health intervention research. We focus here on water, sanitation, and hygiene interventions to illustrate the problem with the understanding that this issue extends to other environmental health interventions.


Use of subsequent PET/CT in diffuse large B-cell lymphoma patients in complete remission following primary therapy.
Interim 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (I-PET/CT) is a powerful tool for monitoring the response to therapy in diffuse large B-cell lymphoma (DLBCL). This retrospective study aimed to determine when and how to use I-PET/CT in DLBCL. A total of 197 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were enrolled between October 2005 and July 2011; PET/CT was performed at the time of diagnosis (PET/CT0), after 2 and 4 cycles of chemotherapy (PET/CT2 and PET/CT4, respectively), and at the end of treatment (F-PET/CT). According to the International Harmonization Project for Response Criteria in Lymphoma, 110 patients had negative PET/CT2 scans, and 87 had positive PET/CT2 scans. The PET/CT2-negative patients had significantly higher 3-year progression-free survival rate (75.8% vs. 38.2%) and 3-year overall survival rate (93.5% vs. 55.6%) than PET/CT2-positive patients. All PET/CT2-negative patients remained negative at PET/CT4, but 3 were positive at F-PET/CT. Among the 87 PET/CT2-positive patients, 57 remained positive at F-PET/CT, and 32 progressed during chemotherapy (15 at PET/CT4 and 17 at F-PET/CT). Comparing PET/CT4 with PET/CT0, 7 patients exhibited progression, and 8 achieved partial remission. Comparing F-PET/CT with PET/CT0, 10 patients exhibited progression, and 7 achieved partial remission. In conclusion, our results indicate that I-PET/CT should be performed after 2 rather than 4 cycles of immunochemotherapy in DLBCL patients. There is a limited role for subsequent PET/CT in the detection of relapse in PET/CT2-negative patients, but repeat PET/CT is required if the PET/CT2 findings are positive.


[Applanation tonometry in "normal" patients and patients after LASIK].
Until now it was thought that morphological parameters of the eye such as corneal thickness, corneal curvature and axial length do not affect tonometry results. However, the aim of this study was to find out whether there actually is an influence of these parameters on applanation tonometry. In this prospective study we examined 125 eyes of 125 normal patients with a corneal thickness of 568.8 +/- 43.79 microm, a corneal curvature of 7.72 +/- 0.27 mm and an axial length of 23.62 +/- 2.05 mm. Before performing a phacoemulsification, the anterior chamber was temporarily punctured. With a closed system the intraocular pressure (IOP) was manometrically set at 20, 35 and 50 mmHg using an H (2)O column. The IOP was then measured with a Perkins tonometer. With these patients we compared 102 eyes that had undergone LASIK due to a myopia of 6.3 +/- 2.17 D. Before and 6 months after surgery, IOD, k-values and central corneal thickness of these patients were measured. At all set pressure levels there was a highly significant correlation of measured IOP and corneal thickness. At all set pressure levels the measured IOP significantly depended on corneal thickness (r(2) = 0.78 - 0.83). After LASIK, IOP was reduced from 16.5 +/- 2.1 to 12.9 +/- 1.9 mmHg. There was a significant correlation between IOP and corneal curvature as well as corneal thickness (r(2) = 0.631; P < 0.001). The biomechanical characteristics of the cornea are changed so that the measured IOP has to be corrected by an additional 0.75 mmHg. Since corneal thickness does affect Goldmann applanation tonometry we recommend to use the "Dresden Correction Table" (Tab. ) to achieve the real IOP. Pressure measurements after LASIK are inaccurate because of a change in corneal biomechanics, corneal thickness and curvature and they should be corrected as follows: IOP (real) = IOP (measured) + (540 - CCT)/71 + (43 - K-value)/2.7 + 0.75 mmHg.


[Are the symptoms "white with pressure" and "white without pressure" related to peripheral retinal sclerosis?].
Collagenic formations occur increasingly with age in the retinal periphery of adults. They grow from the vitreous cortex and from the vessels. In extensive growth they form intraretinal networks. Different inflammatory, degenerative and malformative diseases of the retina lead secondarily, and this already in young persons, to an extensive development of such structures. The name 'peripheral retinal sclerosis' is proposed for such alterations in the peripheral retina. Since the peripheral retinal sclerosis occurs at the same areas where the symptom 'white with pressure' is found, one believes that these formations are its organic substrate. The opacification is thought to be a consequence of the stretching of these collagenic formations during the indentation. Deposition of lipids in these formations can show the symptom 'white without pressure'.


[ Sudeck's bone atrophy (reflex sympathetic dystrophy)].
Reflex sympathetic dystrophy is a disease clinically characterized severe pain, allodynia (severe pain caused by a touch) and over-reaction of pain sensation after a minor injury. In 1994, reflex sympathetic dystrophy was given a name of complex regional pain syndrome type 1 by a international congress, because local blockade of the sympathetic nerve has not been found to be invariably effective. Treatment system for reflex sympathetic dystrophy is composed of medicament therapy including oral administration and/or injection of drug, physical therapy such as thermotherapy and gently passive movement, surgical treatment and psychotherapy. Treatment with injection of pamidronate for 23 patients with reflex sympathetic dystrophy revealed to reduced the grade of pain to two third compared to pre-treatment period, and local intravenous block with local anesthetic drug and steroid hormone disappeared the almost symptoms in cases of early phase.


Routine pulmonary function test can estimate the extent of tuberculous destroyed lung.
Tuberculous destroyed lung (TDL) is diagnosed by a clear past history of tuberculosis with findings of parenchymal destruction verified by chest X-ray. Despite the resultant deterioration of lung function and quality of lives seen in TDL patients, the exact mechanism or characteristics of pulmonary function worsening have not been clearly studied. We investigated the feature of respiratory impairment of TDL patients, and studied whether extent of destroyed lung measured with chest CT has any correlation with routine lung function. To evaluate the degree of destruction, the Goddard classification scoring system was modified into a novel scoring system (destroyed lung score, (DLS)) with a score from 0 to 4. Twenty-five subjects were enrolled. TDL predominantly manifested as an obstructive pattern (64%, 16/25). Median value of DLS of the entire lung was 2.6 (1.7-3.9). Absolute values of FEV1 and FVC were both negatively associated with DLS (r = -0.78, P = 0.001, and r = -0.61, P = 0.021). Percentage of predicted value of FEV₁ and FVC were also negatively associated with DLS (r = -0.62, P = 0.019, and r = -0.76, P = 0.002). Our study shows that lung function of TDL patients were notably correlated with the extent of destroyed lung measured with chest CT scan.


Effects of diltiazem on the pharmacokinetics of nifedipine.
To evaluate the effect of diltiazem pretreatment (60 mg three times a day for 3 days) on pharmacokinetics and pharmacodynamic effect of nifedipine, six healthy subjects received 20 mg nifedipine orally on two occasions using a double-blind cross-over, placebo-controlled method. Diltiazem induced a marked increment of the area under the plasma concentration-time curve (AUC) for nifedipine by a mean of 140% and reduced the total body clearance (Cl) from 0.0043 +/- 0.0019 to 0.0017 +/- 0.0006 ml/min/kg (p less than 0.05, mean +/- SD). The biological half-life (t1/2) of nifedipine was prolonged from 2.46 +/- 0.65 to 3.21 +/- 0.92 h (p less than 0.05) without any changes in indocyanine green (ICG) clearance. Diltiazem did not produce significant changes of AUC, Cl, and t1/2 for the acid metabolite of nifedipine. Blood pressure (BP) after nifedipine administration with diltiazem pretreatment was more decreased than that without diltiazem. Both a decreased hepatic clearance and an increased bio-availability of nifedipine by diltiazem probably explain the significant changes in pharmacokinetics and hemodynamics of nifedipine. A clinically important drug interaction may occur with nifedipine when diltiazem is administered concurrently.


Evaluation of a two-dose measles, mumps, and rubella vaccination schedule in a cohort of college athletes.
Despite high vaccination levels, measles outbreaks continue to occur among vaccinated adults. In response, new guidelines call for two doses of measles vaccine. To determine seroprevalence and response to vaccination in seronegative persons, we tested serums from 256 college athletes at a Maryland State college by enzyme-linked immunosorbent assay, vaccinated seronegatives, then re-tested vaccinees. High school records were obtained for persons seronegative to measles. Of 256 students, 53 (21 percent) were seronegative to measles alone, 13 (5 percent) were seronegative to rubella alone, and 5 (2 percent) were seronegative to both. Among those seronegative to measles, 86 percent had previously received a dose of measles vaccine. After vaccination, 37 persons initially seronegative to measles and 9 seronegative to rubella were 97 percent and 100 percent seropositive, respectively. The high measles seroconversion rate suggests that the two-dose vaccine schedule should effectively control campus measles outbreaks and, if given as measles-mumps-rubella vaccine, will also improve immunity to rubella and mumps.


Methodologic issues in trials of antiemetics.
Studies of antiemetics require consideration of methodologic issues that may not be of concern in trials of antineoplastics. This paper illustrates how the strength of the results of these studies can be affected by (1) the types of patients studied, (2) the sample size, (3) the trial design, (4) the choice and definition of outcome measures, and (5) the method of analysis.


Elastic constants of inflated lobes of dog lungs.
The elastic constants of dog lungs were determined at various degrees of inflation. In one set of experiments, the lobes were subjected to deformations that approximated the conditions of uniaxial loading. These data, together with the bulk modulus data obtained from the local slope of the pressure-volume curve, were used to determine the two elastic moduli that are needed to describe small nonuniform deformations about an initial state of uniform inflation. The bulk modulus was approximately 4 times the inflation pressure, and Young's modulus was approximately 1.5 times the inflation pressure. In a second set of experiments, lobes were subjected to indentation tests using cylindric punches 1-3 cm in diameter. The value for Young's modulus obtained from these data was slightly higher, approximately twice the inflation pressure. These experiments indicate that the lung is much more easily deformable in shear than in dilatation and that the Poisson ratio for the lung is high, approximately 0.43.


Overrepresentation of 3q and 8q material and loss of 18q material are recurrent findings in advanced human ovarian cancer.
In order to define the ability of comparative genomic hybridization (CGH) to detect and map genetic imbalances, we investigated 47 malignant ovarian tumors and 2 ovarian tumors of low malignant potential. The most common genetic changes in order of frequency included DNA gains of chromosome arms 8q (53%), 3q (51%), 20q (43%), 1p (32%), 19q (30%), 1q (28%), 12p (28%), 6p (21%), and 2q (19%). The smallest regions of overrepresentation could be defined in 3q26-qter, 8q23-qter, 1p35-pter, 12p 12, and 6p21-22, respectively. Losses were detected on 18q (23%), chromosome 4 (23%), 13q (17%), and 16q (17%) with the smallest underrepresented regions on 18q22-qter, 13q21, and 16q23-qter. Also, losses of the X chromosome (19%) were detected, correlating with higher ages of the patients. Therefore, some of these X chromosome losses might be due to a well-known aging phenomenon and in these cases will be more preferably lost during cell division and tumor progression. Our findings show that ovarian carcinomas reveal consistent chromosomal abnormalities. Further detailed studies of these regions with specific molecular genetic techniques may lead to the identification of oncogenes and/or tumor suppressor genes playing an important role in the tumorigenesis of ovarian carcinomas.


Comparing Behavioral Health Outcomes and Treatment Utilization of Those With and Without Justice Involvement Within the Past Year Among American Indian and Alaska Native Adults.
Similar to other populations, worse health, increased emergency healthcare utilization, and heightened substance misuse are correlated with higher justice involvement among American Indian/Alaska Native (AI/AN) populations. The historical context and resulting contemporary injustices for AI/AN populations have directly contributed to higher rates of these health and behavioral health conditions among this population. As a result, AI/AN individuals have disproportionate rates of incarceration in the USA, with young AI/AN males having the highest odds of incarceration when compared to any other group. American Indian and Alaska Native populations are overrepresented in the criminal justice system across different touchpoints. However, there remains a scarcity of data and research on AI/AN peoples' involvement with the justice system, and what their lives look like prior to, during, and after justice involvement. The current study addresses this gap in the literature by exploring rates of substance use and mental health diagnoses and treatment utilization among justice-involved and non-justice-involved AI/AN samples. Further, we examined correlates associated with past-year service utilization. Data from the 2015-2019 National Survey on Drug Use and Health (N = 214,505 adults aged 18+) was used. For this study, we examined a subsample of 3068 AI/AN adults. Quantitative data analyses using STATA 16 were run to test for differences on service utilization, mental health status, and substance misuse between AI/AN non-justice-involved and justice-involved samples. Among adults in the sample, 446 (15%) reported justice involvement in the past year. Justice-involved AI/AN individuals were significantly more likely to use the emergency department, utilize mental health treatment, and access substance use treatment in the past year. Additionally, justice-involved AI/AN individuals reported significantly higher rates of mental illness and past-year substance use disorder. In regression models, justice involvement was significantly associated with past-year substance use treatment and past-year mental health treatment. The findings from this work highlight the differences among substance use, mental illness, and treatment utilization between justice-involved and non-justice-involved AI/AN individuals. Findings suggest that justice-involved individuals fair worse in all areas and argue for the consideration of interventions that incorporate both culturally sensitive and justice-responsive models to improve the behavioral health outcomes of these populations. Lastly, while justice-involved AI/AN populations utilize treatment services at higher and disproportionate levels, there is reason to believe that there continues to be a mismatch of need and utilization and further exploration is warranted.


[Gastroduodenal stent placement in gastric cancer patients with pyloric stenosis].
We examined 11 gastric cancer patients undergoing gastroduodenal stent placement for the treatment of gastric outlet obstruction at our hospital, and assessed the significance and problems associated with stenting. None of the patients exhibited any complications associated with stenting, and the median post-stenting fasting period was 3 days(range, 1-7 days). Oral intake improved significantly in all the patients; in patients with nasogastric tubes, the tubes were removed after stenting. However, in patients with peritoneal dissemination, oral intake alone was not sufficient, and additional parenteral nutrition was required. In conclusion, gastroduodenal stenting is believed to be useful for palliative care in gastric cancer patients with pyloric stenosis.


Dynamics of leaf gas exchange, chlorophyll fluorescence and stem diameter changes during freezing and thawing of Scots pine seedlings.
Boreal trees experience repeated freeze-thaw cycles annually. While freezing has been extensively studied in trees, the dynamic responses occurring during the freezing and thawing remain poorly understood. At freezing and thawing, rapid changes take place in the water relations of living cells in needles and in stem. While freezing is mostly limited to extracellular spaces, living cells dehydrate, shrink and their osmotic concentration increases. We studied how the freezing-thawing dynamics reflected on leaf gas exchange, chlorophyll fluorescence and xylem and living bark diameter changes of Scots pine (Pinus sylvestris L.) saplings in controlled experiments. Photosynthetic rate quickly declined following ice nucleation and extracellular freezing in xylem and needles, almost parallel to a rapid shrinking of xylem diameter, while that of living bark followed with a slightly longer delay. While xylem and living bark diameters responded well to decreasing temperature and water potential of ice, the relationship was less consistent in the case of increasing temperature. Xylem showed strong temporal swelling at thawing suggesting water movement from bark. After thawing xylem diameter recovered to a pre-freezing level but living bark remained shrunk. We found that freezing affected photosynthesis at multiple levels. The distinct dynamics of photosynthetic rate and stomatal conductance reveals that the decreased photosynthetic rate reflects impaired dark reactions rather than stomatal closure. Freezing also inhibited the capacity of the light reactions to dissipate excess energy as heat, via non-photochemical quenching, whereas photochemical quenching of excitation energy decreased gradually with temperature in agreement with the gas exchange data.


An Insight into the Changes in Skin Texture and Properties following Dietary Intervention with a Nutricosmeceutical Containing a Blend of Collagen Bioactive Peptides and Antioxidants.
Skin aging is a multifactorial phenomenon which causes alterations in skin physiological functions and, most visibly, phenotypic changes. In particular, during the aging process, hyaluronic acid, collagen, and elastin fibers undergo structural and functional changes. This study aimed to give an insight into the photo-protective benefits and efficacy of an oral liquid nutricosmeceutical containing collagen bioactive peptides and antioxidants to counteract the signs of aging. A double-blind, randomized, placebo-controlled clinical trial was conducted by an independent esthetic clinic on 120 healthy volunteer subjects for 90 days. Subjects were divided into 2 groups: 60 subjects consumed 1 bottle (50 mL) of the nutricosmeceutical daily and the other 60 consumed 1 bottle (50 mL) of the placebo. Outcome measures were related to skin elasticity (expressed as Young's elasticity modulus) and skin architecture (histological analysis). In addition, the subjects recruited in this study underwent observational assessments through self-assessment questionnaires. Overall, we demonstrated a significant increase in skin elasticity (+7.5%), p ≤ 0.001 and an improvement in skin texture after daily oral consumption of the nutricosmeceutical. We also obtained a positive patient feedback through the self-assessment questionnaires. Taken together these results show that this nutricosmeceutical supplement may have photo-protective effects and help improve skin health.


Rapid quantification of the delta-opioid receptor selective enkephalin DPDPE in canine cerebrospinal fluid by liquid chromatography--mass spectrometry.
An atmospheric pressure ionization liquid chromatographic-mass spectrometric assay was developed and validated for the determination of D-penicillamine(2,5) enkephalin (DPDPE) in cerebrospinal fluid (CSF) from dog. DPDPE and internal standard (D-Ala(2),D-Leu(5) enkephalin=DADLE) were isolated from CSF by reversed-phase C(18) solid-phase extraction with ZipTip micro-cartridges. Aliquots of extracted eluate were injected onto an Agilent Zorbax SB C(18) column (30 x 2.2 mm; 3.5 microm) at a flow-rate of 0.4 ml/min. The isocratic mobile phase of methanol-10 mM ammonium formate (pH 3) (75:25, v/v) was then diverted to waste for 45 s after injection, after which time flow was directed to the single quadrupole mass spectrometer. DPDPE was detected by positive mode selected ion monitoring. Standard curves were linear (r(2)> or =0.991) over the concentration range 1-1000 ng/ml. The efficiency of extraction recovery was greater than 97%, and the intra-assay and inter-assay precisions were within 9% relative standard deviation. DPDPE and the internal standard were stable in the injection solvent at 4 degrees C for at least 48 h. The assay was applied to the pharmacokinetic study of intrathecal DPDPE administration in the dog animal model.


Heterologous expression and subcellular localization of pumpkin seed tonoplast intrinsic proteins (TIP) in yeast cells.
Two tonoplast intrinsic proteins (TIP) of pumpkin seeds, pMP23 and MP28, were expressed in yeast cells under control of the GAL1 promoter, and the subcellular localization of the proteins was analyzed. The pMP23 and MP28 stably accumulated in the yeast vacuolar membrane when the proteins were expressed in the proteinase A-deficient strain (pep4), which lacks the activities of vacuolar proteases. However, pMP23 and MP28 did not accumulate in the wild-type strain; the expressed pMP23 and MP28 were degraded in a proteinase A-dependent manner. These results indicate that pMP23 and MP28 are transported to the vacuolar membrane when expressed in yeast.


Intrauterine growth of twins judged by BPD measurements.
Both earlier growth charts of twins composed of birth weight at different gestational ages and recent reports on twin biparietal diameter (BPD) growth, indicate that twins' growth is less than that of singletons during the later period of gestation. In the present study, growth curves are constructed separately for the first and the second twin from 489 paired ultrasonic BPD measurements of 119 twin pregnancies. The distribution of BPD values in twins was found to be slightly wider than our normal range curve for singletons. The mean BPD values of twins were close to those of singletons in the second trimester. From the 32nd week on, the twins' mean weekly BPD increment decreased, this lesser growth rate being more marked than that of singletons. The second twin's BPD growth curve ran consistently below that of the first. Our results agree with the earlier findings that the growth of twins is retarded during the later part of pregnancy. They point to different BPD growth patterns between the first and the second twin.


Human Papillomavirus Vaccination Trends, Barriers, and Promotion Methods Among American Indian/Alaska Native and Non-Hispanic White Adolescents in Michigan 2006-2015.
Human papillomavirus (HPV) infection, the most common sexually transmitted disease in the US, is a preventable cause of cancer. HPV vaccination has the potential to prevent 90% of HPV-related cancer cases but is underutilized, especially among American Indian/Alaska Native (AI/AN) adolescents. The objectives of this study were to (1) describe trends and identify predictors of HPV vaccination initiation and completion in Michigan's AI and Non-Hispanic White children age 9 through 18 years and (2) to identify barriers to HPV vaccination and promotion methods at the tribal, state, and local levels in Michigan. Data from Michigan's immunization information system from 2006 to 2015 were used for analysis. Additionally, semi-structured interviews were conducted with public health professionals across the state to identify barriers to and promoters of HPV vaccination. Predictors for vaccine initiation included being female, AI/AN, and living in high poverty zip code. Predictors of vaccine completion were female gender and younger age at vaccine initiation. Barriers to vaccination included misinformation and weak or inconsistent provider recommendations. Strategies used by health professionals to promote HPV vaccination included immunization summaries, vaccine information statements, the Vaccines for Children (VFC) program, and provider training. Findings suggested the need for education of parents to demystify HPV vaccine benefits and risks and provider training for more consistent recommendations.


Attenuation of sensory and affective responses to heat pain: evidence for contralateral mechanisms.
Attenuation of responses to repeated sensory events has been thoroughly studied in many modalities; however, attenuation of pain perception has not yet benefitted from such extensive investigation. Described here are two psychophysical studies that examined the effects of repeated exposure to thermal stimuli, assessing potential attenuation of the perception of pain and its possible spatial specificity. Twenty-two subjects were presented thermal stimuli to the volar surface of the right and left forearms. Twelve subjects in study 1 received the same stimuli and conditions on each of five daily experimental sessions, whereas 10 subjects in study 2 received thermal stimuli, which were restricted to one side for four daily sessions and then applied to the other side on the fifth session. Ratings of warmth intensity, pain intensity, and pain unpleasantness were recorded while the subjects performed a thermal sensory discrimination task. Results of study 1 demonstrate that repeated stimulation with noxious heat can lead to long-term attenuation of pain perception; results of study 2 extend these findings of attenuation to both pain intensity and unpleasantness and show that this effect is highly specific to the exposed body side for both aspects of the pain experience. We suggest that the functional plasticity underlying this attenuation effect lies in brain areas with a strong contralateral pattern of pain-related activation.


Effects of bleaching gel containing TiO2 and chitosan on tooth surface roughness, microhardness and colour.
This study aimed to evaluate the effects of an experimental bleaching gel made with TiO2 and chitosan, along with the Opalescence Boost PF and Philips Zoom bleaching agents, on tooth surface roughness, microhardness and colour. The experimental gel, containing 6% hydrogen peroxide (HP), was evaluated against the two existing treatments, which incorporate 40% and 25% HP. For colour evaluation, 36 human premolar teeth were divided into three groups (n = 12). For surface roughness and microhardness evaluation, 72 bovine incisor samples were divided into six groups (n = 12). Data on colour alteration were analysed with the CIEDE2000 formula. Surface roughness was measured using a profilometer, and microhardness was measured with a Vickers hardness tester. ANOVA was used for statistical analysis. There were no statistically significant differences among the groups for surface roughness, microhardness values or colour change after bleaching (P > 0.05). The lowest bleaching efficacy was observed for the 40% HP agent, and the highest efficacy was observed for the 25% HP agent (P < 0.05). An experimental 6% HP gel containing TiO2 and chitosan provided effective bleaching without adverse effects on tooth surface roughness or microhardness. The use of TiO2 with chitosan can provide clinicians with positive results.


Inflammatory siderosis of the nervous system in rats.
Large intravenous doses of a relatively nontoxic iron polymaltose complex were taken up by liver and spleen and did not enter the central nervous system (CNS) of normal rats. When the injections were given during development of the inflammatory lesions of experimental allergic encephalomyelitis (EAE), many iron-laden macrophages entered vessels, perivascular cuffs and neural parenchyma. Iron polymaltose injected before the EAE lesions started to develop, or during the healing phase, did not enter the lesions. This model of CNS siderosis may be useful for studies on long-term effects of iron and for neuroimaging by nuclear magnetic resonance.


Application of starch degrading bacteria from tobacco leaves in improving the flavor of flue-cured tobacco.
Starch is an essential factor affecting the quality of flue-cured tobacco, and high starch content can affect the sensory quality and safety. Recently, the degradation of macromolecules in tobacco raw materials by using additional microorganisms to improve their intrinsic quality and safety has become a new research hotspot in the tobacco industry. However, the technical maturity and application scale are limited. Our study analyzed the correlation between microbial community composition and volatile components on the surface of tobacco leaves from 14 different grades in Fujian tobacco-producing areas. The PICRUSt software was utilized to predict the function of the microbial community present in tobacco leaves. Furthermore, dominant strains that produced amylase were screened out, and an enzyme solution was prepared to enhance the flue-cured tobacco flavor. Changes in the content of macromolecules and volatile components were determined, and sensory evaluations were conducted to assess the overall quality of the tobacco leaves. The results showed that the dominant bacterial genera on the surface of Fujian tobacco leaves were Variovorax, Sphingomonas, Bacillus, etc. Bacillus was positively correlated with various volatile components, which contributed to the sweet and aromatic flavors of Fujian flue-cured tobacco. The main genetic functions of Fujian flue-cured tobacco surface bacteria were carbohydrate metabolism and amino acid metabolism. After treating flue-cured tobacco with an enzyme preparation prepared by the fermentation of Paenibacillus amylolyticus A17 #, the content of starch, pectin, and cellulose in flue-cured tobacco decreased significantly compared with the control group. Meanwhile, the content of total soluble sugar and reducing sugar was significantly increased, and the volatile aroma components, such as 3-hydroxy--damascone, 2,3-dihydro-3,5-dihydroxy-6-methyl-4 H-Pyran-4-one, ethyl palmitate, ethyl linolenic acid, etc., were significantly increased. The aroma quality and quantity of flue-cured tobacco were enhanced, while impurities were reduced. The smoke characteristics were improved, with increased fineness, concentration, and moderate strength. The taste characteristics were also improved, with reduced irritation and a better aftertaste. In conclusion, Bacillus, as the dominant genus in the abundance of bacterial communities on tobacco surfaces in Fujian, had an essential impact on the flavor of tobacco leaves by participating in carbohydrate metabolism and finally forming the unique flavor style of flue-cured tobacco in Fujian tobacco-producing areas. Paenibacillus amylolyticus A17 #, a target strain with amylase-producing ability, was screened from the surface of Fujian flue-cured tobacco. The enzyme preparation, produced by the fermentation of Paenibacillus amylolyticus A17 #, was utilized to reduce the content of macromolecules, increase the content of water-soluble total sugar and reducing sugar, and produce a variety of crucial volatile aroma components, which had a significant improvement on the quality of tobacco leaves.


A Requirement for Mena, an Actin Regulator, in Local mRNA Translation in Developing Neurons.
During neuronal development, local mRNA translation is required for axon guidance and synaptogenesis, and dysregulation of this process contributes to multiple neurodevelopmental and cognitive disorders. However, regulation of local protein synthesis in developing axons remains poorly understood. Here, we uncover a novel role for the actin-regulatory protein Mena in the formation of a ribonucleoprotein complex that involves the RNA-binding proteins HnrnpK and PCBP1 and regulates local translation of specific mRNAs in developing axons. We find that translation of dyrk1a, a Down syndrome- and autism spectrum disorders-related gene, is dependent on Mena, both in steady-state conditions and upon BDNF stimulation. We identify hundreds of additional mRNAs that associate with the Mena complex, suggesting that it plays broader role(s) in post-transcriptional gene regulation. Our work establishes a dual role for Mena in neurons, providing a potential link between regulation of actin dynamics and local translation.


Manipulation of auxin signalling by plant viruses.
Compatible plant-virus interactions result in dramatic changes of the plant transcriptome and morphogenesis, and are often associated with rapid alterations in plant hormone homeostasis and signalling. Auxin controls many aspects of plant organogenesis, development, and growth; therefore, plants can rapidly perceive and respond to changes in the cellular auxin levels. Auxin signalling is a tightly controlled process and, hence, is highly vulnerable to changes in the mRNA and protein levels of its components. There are several core nuclear components of auxin signalling. In the nucleus, the interaction of auxin response factors (ARFs) and auxin/indole acetic acid (Aux/IAA) proteins is essential for the control of auxin-regulated pathways. Aux/IAA proteins are negative regulators, whereas ARFs are positive regulators of the auxin response. The interplay between both is essential for the transcriptional regulation of auxin-responsive genes, which primarily regulate developmental processes but also modulate the plant immune system. Recent studies suggest that plant viruses belonging to different families have developed various strategies to disrupt auxin signalling, namely by (a) changing the subcellular localization of Aux/IAAs, (b) preventing degradation of Aux/IAAs by stabilization, or (c) inhibiting the transcriptional activity of ARFs. These interactions perturb auxin signalling and experimental evidence from various studies highlights their importance for virus replication, systemic movement, interaction with vectors for efficient transmission, and symptom development. In this microreview, we summarize and discuss the current knowledge on the interaction of plant viruses with auxin signalling components of their hosts.


Characterization of a splicing variant of plant Aurora kinase.
Aurora kinases play a key role in chromosome segregation and cytokinesis. In plants, three Aurora kinases (AtAUR1-AtAUR3) have been identified in Arabidopsis thaliana. Here, we report an AtAUR2 splicing variant (AtAUR2S), which lacks the fourth exon encoding a part of the kinase domain of AtAUR2. AtAUR2S was shown to have lost its kinase activity to phosphorylate histone H3 at Ser10; however, it maintained its ability to bind to histone H3. The localization pattern of AtAUR2S was the same as that of AtAUR2. The findings suggest that AtAUR2S affects cell division by competing with AtAUR2.


Allergic inflammation--innately homeostatic.
Allergic inflammation is associated closely with parasite infection but also asthma and other common allergic diseases. Despite the engagement of similar immunologic pathways, parasitized individuals often show no outward manifestations of allergic disease. In this perspective, we present the thesis that allergic inflammatory responses play a primary role in regulating circadian and environmental inputs involved with tissue homeostasis and metabolic needs. Parasites feed into these pathways and thus engage allergic inflammation to sustain aspects of the parasitic life cycle. In response to parasite infection, an adaptive and regulated immune response is layered on the host effector response, but in the setting of allergy, the effector response remains unregulated, thus leading to the cardinal features of disease. Further understanding of the homeostatic pressures driving allergic inflammation holds promise to further our understanding of human health and the treatment of these common afflictions.


The Use of Mesenchymal Stem Cells and their Derived Extracellular Vesicles in Cardiovascular Disease Treatment.
Cardiovascular disease (CVD), including disorders of cardiac muscle and vascular, is the major cause of death globally. Many unsuccessful attempts have been made to intervene in the disease's pathogenesis and treatment. Stem cell-based therapies, as a regeneration strategy, cast a new hope for CVD treatment. One of the most well-known stem cells is mesenchymal stem cells (MSCs), classified as one of the adult stem cells and can be obtained from different tissues. These cells have superior properties, such as proliferation and highly specialized differentiation. On the other hand, they have the potential to modulate the immune system and anti-inflammatory activity. One of their most important features is the secreting the extracellular vesicles (EVs) like exosomes (EXOs) as an intercellular communication system mediating the different physiological and pathophysiological affairs. In this review study, the importance of MSC and its secretory exosomes for the treatment of heart disease has been together and specifically addressed and the use of these promising natural and accessible agents is predicted to replace the current treatment modalities even faster than we imagine. MSC derived EXOs by providing a pro-regenerative condition allowing innate stem cells to repair damaged tissues successfully. As a result, MSCs are considered as the appropriate cellular source in regenerative medicine. In the plethora of experiments, MSCs and MSC-EXOs have been used for the treatment and regeneration of heart diseases and myocardial lesions. Administration of MSCs has been provided a replacement therapeutic option for heart regeneration, obtaining great attention among the basic researcher and the medical doctors.


Clinical outcomes of three- or five-day treatment with clomiphene citrate combined with gonadotropins and a timed intercourse cycle in polycystic ovary syndrome patients.
This study aimed to investigate the effect of a new clomiphene citrate (CC) regimen on preventing thin endometrial lining in polycystic ovary syndrome (PCOS) patients receiving CC plus gonadotropin treatment with a timed intercourse cycle. A total of 114 women with PCOS were included in this trial. Patients were divided into two groups and treated in accordance with the controlled ovarian stimulation (COS) protocol. In group A, 104 COS cycles in 67 patients were included, and in each cycle 150 mg CC was given for three days, starting from day 3. In group B, 69 COS cycles in 47 patients were included, in which 100 mg CC was given for five days, starting from day 3. The thickness of the endometrium was measured on the day of human chorionic gonadotropin (hCG) injection. Timed intercourse was recommended at 24 and 48 hours after the hCG injection. Additional doses of human menopausal gonadotropin and the number of days of hCG administration were not significantly different between the two groups. Endometrial thickness on the day of hCG administration was significantly larger in group A than group B (9.4±2.1 mm vs. 8.5±1.7 mm, p=0.004). The pregnancy rate was significantly higher in group A than in group B (38.4% vs. 21.7%, p=0.030). Three-day CC treatment resulted in a significantly higher pregnancy rate than the standard five-day CC treatment in a timed intercourse cycle in PCOS patients. Facilitating adequate endometrial growth via the early discontinuation of CC might be a crucial factor in achieving a higher pregnancy rate.


Comorbidities in adult attention-deficit/hyperactivity disorder: a practical guide to diagnosis in primary care.
Diagnosis and management of attention-deficit/hyperactivity disorder (ADHD) in adults is complex and challenging because of the frequent comorbidity of other psychiatric disorders that have symptoms overlapping with those of ADHD. The presence of comorbidities can create challenges to making an accurate diagnosis and also impact treatment options and outcomes. This review discusses disorders that may be comorbid with ADHD in adults, including anxiety, mood, substance use disorder, antisocial personality disorder, and borderline personality disorder. Suggestions for recognizing these comorbidities and distinguishing them from ADHD and perspectives on their possible impact on ADHD treatment are included. Adjunctive nonpharmacologic modalities may be especially helpful in the case of comorbid mood, anxiety, substance abuse, or personality disorders.


Reconstruction of the external auditory canal with a laterocervical twisted flap (snail flap)
A case of circumferential reconstruction of the external auditory canal following basal cell carcinoma is described using a laterocervical tubed flap. One-stage reconstruction with a single flap, absence of donor-site deformity, and easy dissection are the main advantages of the procedure, which also can be conveniently used to reconstruct part of the concha and the tragal region.


Diffusion Lung Capacity Changes In Hodgkin Lymphoma Patients Before And After Abvd Chemotherapy.
Chemotherapy consisting of Adriamycin, Bleomycin, Vinblastine, and Doxorubicin (ABVD), which is the mainstay of treatment in Hodgkin's Lymphoma (HL), is associated with both acute and long-term pulmonary toxicity primarily due to Bleomycin. Bleomycin induced pulmonary toxicity (BPT) is clinically detected using diffusing lung capacity for carbon monoxide (DLCO). The objective of this study was to evaluate changes in DLCO in HL patients before and after ABVD chemotherapy. Medical records of all adult HL patients treated with ABVD chemotherapy at a single centre in Lahore, Pakistan during the entire calendar year 2012 were analysed. Patients with pre-existing pulmonary dysfunction, history of thoracic surgery and smokers were excluded. A total of 179 HL patients were identified during the study period who received ABVD chemotherapy. Out of these, 93 (51.95%) patients had undergone both a pre- and post-chemotherapy DLCO measurements. The remaining patients had only one DLCO reading available and were not included in the analysis. The mean percentage difference between pre- and post-chemotherapy values for DLCO (5.49%; 95% confidence interval [CI] 1.56-9.43%) and for Haemoglobin-adjusted DLCO (8.24%; 95% CI 3.90-12.57%) were statistically significant at p<0.01. Diffusing lung capacity for carbon (DLCO) values declined from pre-treatment to post-treatment by 1-10% in 23 (24.7%) patients, by 10-20% in 19 (20.4%) patients, by 20-30% in 10 (10.8%) patients and >30% in 10 (10.8%) patients. After adjusting for age, a 1mg/m2 increase in dose of Bleomycin was significantly associated with 0.14% (95% CI: 0.03-0.25%) decline in DLCO and 0.13% (95% CI: 0.10-0.26%) decline in haemoglobin-adjusted DLCO from pre-treatment value. Mild to moderate dysfunction in diffusion lung capacity is common after ABVD chemotherapy. DLCO and haemoglobin-adjusted DLCO value decreased with increasing age and increasing dose of Bleomycin.


Magneto-convection.
Convection is the transport of energy by bulk mass motions. Magnetic fields alter convection via the Lorentz force, while convection moves the fields via the curl(v×B) term in the induction equation. Recent ground-based and satellite telescopes have increased our knowledge of the solar magnetic fields on a wide range of spatial and temporal scales. Magneto-convection modelling has also greatly improved recently as computers become more powerful. Three-dimensional simulations with radiative transfer and non-ideal equations of state are being performed. Flux emergence from the convection zone through the visible surface (and into the chromosphere and corona) has been modelled. Local, convectively driven dynamo action has been studied. The alteration in the appearance of granules and the formation of pores and sunspots has been investigated. Magneto-convection calculations have improved our ability to interpret solar observations, especially the inversion of Stokes spectra to obtain the magnetic field and the use of helioseismology to determine the subsurface structure of the Sun.


Gigantic arteriovenous fistula between left coronary cusp and coronary sinus draining into the right atrium.
Coronary arteriovenous fistulas (CAF) are infrequent anatomic anomalies that establish a direct connection between coronary arteries and cardiac chambers. The reported incidence is extremely low and estimated at 0.002% in the general population. We report a rare case of CAF in a middle-aged man, who was asymptomatic but incidentally found to have a gigantic CAF on a low-dose Computed Tomography scan of his chest. The case was presented to cardiothoracic surgeons. Since the patient was asymptomatic, they recommended medical management and continued close surveillance. The Left Coronary Artery or its branches are extremely uncommon site for CAF. With the advances in technology, the network of veins including coronary sinus has gained further clinical relevance. While technology has helped elucidate many aspects of these rare anomalies, mysteries still remain. With continued research, we can expect more cost-effective and less invasive interventional therapies to be developed in the near future.


Relationship between BMI and Postoperative Complications with Free Flap in Anterolateral Craniofacial Reconstruction.
Although we have seen tremendous advancement in microsurgery over the last 2 decades and free tissue transfer has become standard for head and neck reconstruction, surgeons still struggle to prevent postoperative complications. We examined the relationship between body mass index (BMI) and postoperative complications in patients undergoing rectus abdominis free flap transfer after anterolateral craniofacial resection. This was a retrospective review of reconstructive surgery using rectus abdominis musculocutaneous free flap in patients with locally advanced maxillary sinus carcinoma from 2003 to 2014 (n = 35, 27 men and 8 women; average age, 60.9 ± 7.8 years). All patients underwent craniofacial reconstruction after anterior and middle cranial fossa skull base resection and maxillectomy (class IV, subtype a) with palatal resection. Patients were categorized based on sex, BMI, and other parameters. Recipient-site infection occurred in 11 patients (31.4%), cerebrospinal fluid leakage in 6 (17.1%), partial flap necrosis in 2 (5.7%), total flap necrosis in 1 (2.9%), and facial fistula in 4 (11.4%). Women showed partial flap necrosis significantly more frequently (P = 0.047), probably owing to poor vascular supply of the subcutaneous fat layer. Patients with low BMI (<20 kg/m(2)) showed recipient-site infection (P = 0.02) and facial fistula (P = 0.01) significantly more frequently owing to insufficient tissue volume and poor vascular supply. Postoperative recipient-site infection and facial fistula occurred mainly in low-BMI patients. Surgeons should take care to achieve sufficient donor tissue on low-BMI patients. Using a prosthetic obturator in low-BMI patients for craniofacial reconstruction can be a good alternative option to reduce postoperative complications due to insufficient donor tissue volume.


Proficiency testing: now it is a reality.
On January 1, 1994, enrollment in an accredited proficiency testing program became mandatory under the CLIA regulations for physicians performing moderate and high complexity tests in their offices. Physicians not enrolled in programs are in violation of the standard.


De novo biosynthesis of sexual pheromone in the labial gland of bumblebee males.
De novo biosynthesis of male sex pheromone from two bumblebee species (Bombus terrestris and Bombus lucorum) was studied by using in vitro incubations of labial glands (LGs) with radioactive [1,2-(14)C]acetate and deuterated [D(3)]acetate. The labeled substrate was incorporated into several types of compounds, such as terpenic alcohols, fatty acids, esters, and hydrocarbons. A similar incubation of [1,2-(14)C]acetate with fat bodies (FB) led to the formation of fatty acids, triacylglycerols (TAG), and hydrocarbons. To support the results from in vitro incubations, PCR analysis of fatty acid synthase (FAS) transcripts in LG and FB was performed. Relative quantification of FAS transcription levels revealed that the abundance of mRNA from the FAS gene is a function of the age of B. terrestris males. A comparison of the relative FAS mRNA gene transcription level in FB and LGs of B. terrestris and B. lucorum males proved that high biosynthetic activity takes place in the LGs of both species. Together, these results indicate that pheromone components are synthesized de novo in the LG.


Is It Time to Repurpose Calcineurin Inhibitors for the Treatment of Cognitive Impairment and Dementia?
Numerous preclinical and human tissue studies implicate the protein phosphatase calcineurin (CN) as a pathophysiologic mechanism in Alzheimer's disease (AD) and other neurodegenerative conditions. Using public electronic records of tens of thousands of individuals across the United States, Silva et al. (2023) show that use of the FDA-approved CN inhibitor, tacrolimus (for purposes of immunosuppression) is also associated with reduced prevalence of dementia-related symptoms. Notably, the study controls for age, sex, and race as well as multiple risk factors for AD. The results suggest that tacrolimus, and possibly other immunosuppressants could be repurposed for the treatment of AD-related dementia.


Treatment of respiratory distress in a prematurely born foal.
A foal born 3 weeks prematurely was treated for respiratory distress, using a combination of oxygen therapy and mechanical ventilatory assistance. Clinical response and arterial blood gas tensions were monitored regularly. Continuous positive-airway pressure and intermittent positive-pressure ventilation administered via a nasotracheal tube were effective in improving arterial oxygenation and ventilatory function.


Oropharyngeal lesions in pityriasis rosea.
Pityriasis rosea (PR) is an exanthematous disease associated with the endogenous systemic reactivation of human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7). Oropharyngeal lesions may be associated with the exanthema, but anecdotal evidence suggests that few dermatologists are aware of their occurrence. Classifying oropharyngeal lesions in PR, establishing their prevalence, and assessing their possible association with different PR forms. The records of all PR cases diagnosed in the Dermatology Clinic of Genoa University between 2003 and 2016 were retrospectively reviewed to examine sex and age of the patients, PR type, presence of enanthema, systemic symptoms, specific anti-HHV-6 and or HHV-7 serology, and HHV-6 and/or HHV-7 DNA loads. The oropharyngeal mucosa was carefully examined in 527 patients with PR. Painless oropharyngeal lesions were observed in 149 patients with PR (28%) and classified as erythematomacular, macular and papular, erythematovesicular, and petechial lesions. The petechial and macular and papular patterns were those most frequently observed. There was no statistically significant difference in the levels of HHV-6 and HHV-7 viremia in the plasma of patients with enanthema and those without. Because this was a retrospective study, biopsies on mucosal lesions were not performed. Our findings showed that enanthemas are frequently associated with forms of PR different from the classic form.


Neonatal Graves' disease with unusual metabolic association from presentation to resolution.
Neonatal Graves' disease is a rare disorder seen in 1 in 25,000 births and in 1% of the offspring of mothers with either established or cured Graves' disease. This is due to transplacental passage of thyroid-stimulating immunoglobulins (TSIs). A higher TSI titre in maternal serum makes hyperthyroidism more likely in the fetus or newborn; however, not all fetuses born by women with positive TSIs develop overt hyperthyroidism. In spite of its rarity, its serious nature (if not treated) and its association with multisystem abnormalities justifies careful clinical screening and management. We report a preterm 30 weeks neonate with neonatal thyrotoxicosis secondary to untreated maternal Graves' disease who, in addition to the typical hyperthyroidism symptoms, had unusual metabolic associations of neonatal cholestasis and hyperammonaemia. The patient was treated accordingly with a good response. This report supports previous reports on the association between neonatal hyperthyroidism and cholestatic liver disease. However, it is the second case report to describe the unusual association of hyperammonaemia and neonatal Graves' disease.


Suppression of mammalian 5' splice-site defects by U1 small nuclear RNAs from a distance.
One of the earliest events in the process of intron removal from mRNA precursors is the establishment of a base-pairing interaction between U1 small nuclear (sn) RNA and the 5' splice site. Mutations at the 5' splice site that prevent splicing can often be suppressed by coexpression of U1 snRNAs with compensatory changes, but in yeast, accurate splicing is not restored when the universally conserved first intron base is changed. In our mammalian system as well, such a mutation could not be suppressed, but the complementary U1 caused aberrant splicing 12 bases downstream. This result is reminiscent of observations in yeast that aberrant 5' splice sites can be activated by U1 snRNA from a distance. Using a rapid, qualitative protein expression assay, we provide evidence that 5' splice-site mutations can be suppressed in mammalian cells by U1 snRNAs with complementarity to a range of sequences upstream or downstream of the site. Our approach uncouples in vivo the commitment-activation step of mammalian splicing from the process of 5' splice-site definition and as such will facilitate the genetic characterization of both.


A kinetic modeling of chondrocyte culture for manufacture of tissue-engineered cartilage.
For repairing articular cartilage defects, innovative techniques based on tissue engineering have been developed and are now entering into the practical stage of clinical application by means of grafting in vitro cultured products. A variety of natural and artificial materials available for scaffolds, which permit chondrocyte cells to aggregate, have been designed for their ability to promote cell growth and differentiation. From the viewpoint of the manufacturing process for tissue-engineered cartilage, the diverse nature of raw materials (seeding cells) and end products (cultured cartilage) oblige us to design a tailor-made process with less reproducibility, which is an obstacle to establishing a production doctrine based on bioengineering knowledge concerning growth kinetics and modeling as well as designs of bioreactors and culture operations for certification of high product quality. In this article, we review the recent advances in the manufacturing of tissue-engineered cartilage. After outlining the manufacturing processes for tissue-engineered cartilage in the first section, the second and third sections, respectively, describe the three-dimensional culture of chondrocytes with Aterocollagen gel and kinetic model consideration as a tool for evaluating this culture process. In the final section, culture strategy is discussed in terms of the combined processes of monolayer growth (ex vivo chondrocyte cell expansion) and three-dimensional growth (construction of cultured cartilage in the gel).


Cardiorespiratory Fitness Estimation Based on Heart Rate and Body Acceleration in Adults With Cardiovascular Risk Factors: Validation Study.
Cardiorespiratory fitness (CRF) is an independent risk factor for cardiovascular morbidity and mortality. Adding CRF to conventional risk factors (eg, smoking, hypertension, impaired glucose metabolism, and dyslipidemia) improves the prediction of an individual's risk for adverse health outcomes such as those related to cardiovascular disease. Consequently, it is recommended to determine CRF as part of individualized risk prediction. However, CRF is not determined routinely in everyday clinical practice. Wearable technologies provide a potential strategy to estimate CRF on a daily basis, and such technologies, which provide CRF estimates based on heart rate and body acceleration, have been developed. However, the validity of such technologies in estimating individual CRF in clinically relevant populations is poorly known. The objective of this study is to evaluate the validity of a wearable technology, which provides estimated CRF based on heart rate and body acceleration, in working-aged adults with cardiovascular risk factors. In total, 74 adults (age range 35-64 years; n=56, 76% were women; mean BMI 28.7, SD 4.6 kg/m2) with frequent cardiovascular risk factors (eg, n=64, 86% hypertension; n=18, 24% prediabetes; n=14, 19% type 2 diabetes; and n=51, 69% metabolic syndrome) performed a 30-minute self-paced walk on an indoor track and a cardiopulmonary exercise test on a treadmill. CRF, quantified as peak O2 uptake, was both estimated (self-paced walk: a wearable single-lead electrocardiogram device worn to record continuous beat-to-beat R-R intervals and triaxial body acceleration) and measured (cardiopulmonary exercise test: ventilatory gas analysis). The accuracy of the estimated CRF was evaluated against that of the measured CRF. Measured CRF averaged 30.6 (SD 6.3; range 20.1-49.6) mL/kg/min. In all participants (74/74, 100%), mean difference between estimated and measured CRF was -0.1 mL/kg/min (P=.90), mean absolute error was 3.1 mL/kg/min (95% CI 2.6-3.7), mean absolute percentage error was 10.4% (95% CI 8.5-12.5), and intraclass correlation coefficient was 0.88 (95% CI 0.80-0.92). Similar accuracy was observed in various subgroups (sexes, age, BMI categories, hypertension, prediabetes, and metabolic syndrome). However, mean absolute error was 4.2 mL/kg/min (95% CI 2.6-6.1) and mean absolute percentage error was 16.5% (95% CI 8.6-24.4) in the subgroup of patients with type 2 diabetes (14/74, 19%). The error of the CRF estimate, provided by the wearable technology, was likely below or at least very close to the clinically significant level of 3.5 mL/kg/min in working-aged adults with cardiovascular risk factors, but not in the relatively small subgroup of patients with type 2 diabetes. From a large-scale clinical perspective, the findings suggest that wearable technologies have the potential to estimate individual CRF with acceptable accuracy in clinically relevant populations.


Regulation of the number of Na+,K+-pump sites after mitogenic activation of lymphocytes.
The early activation of Na+,K+-ATPase-mediated ion fluxes after concanavalin A (ConA) stimulation of pig lymphocytes is caused by an increase in intracellular Na+ concentration. A second mechanism of regulation of Na+,K+-ATPase activity becomes apparent between 3 and 5 h after mitogenic stimulation, but prior to onset of increase in cell volume; this consists of an increase (about 75%) in the number of ouabain-binding sites (from 35 X 10(3) +/- 12 X 10(3)/cell in resting to 60 X 10(3) +/- 27 X 10(3)/cell in activated lymphocytes). The increase in ouabain binding was attributed to an increase in the number of active Na+,K+-ATPase molecules, based on the following evidence: there was an increase in the Vmax of ouabain binding, without variation in the Km; the increase in ouabain binding was accompanied by a proportional increase in K+ influx, when the assay was performed in the presence of the Na+ ionophore monesin, which was used to eliminate the difference in intracellular Na+ concentration between resting and activated cells; there was proportionality between ouabain-inhibitable ATPase activity in permeabilized cells and the number of ouabain-binding sites in resting and activated lymphocytes. The ConA-induced increase in ouabain-binding sites was influenced neither by amiloride nor by incubation in low Na+ medium, under conditions which prevented both increase in intracellular Na+ concentration and K+ influx. Increase in intracellular Na+ concentration was ineffective in altering the number of active pump molecules in resting cells. During incubation with ConA, the presence of ouabain did not affect the increase in ouabain-binding sites; thus, regulation of the number of pump sites is independent of the regulation of their activity. The ConA-induced increase in number of ouabain-binding sites did not require protein synthesis; indeed, cycloheximide, anisomycin, and puromycin, under conditions in which they inhibited protein synthesis by by 95%, induced the increase to approximately the same extent as did ConA. This suggests the presence in resting lymphocytes of a rapidly turning over protein that either prevents the ATPase subunits from assembling or from integrating into the membrane.


Pathological gambling, gender, and risk-taking behaviors.
Seventy-eight female and 78 male pathological gamblers admitted to an outpatient treatment program were compared regarding a profile of risk-taking behaviors (suicide attempts, illegal activities meant to finance gambling, sexual risky behavior, and alcohol abuse). The Schedules for Clinical Assessment in Neuropsychiatry (SCAN), the Barratt Impulsiveness Scale version 11 (BIS-11), and an adaptation of the HIV Risk Behavior Scale were used. Females attempted more suicide than males. Men had more sexual risky behavior and alcohol abuse than women. Younger age and depression were risk factors for suicide attempts, younger age and impulsivity were risk factors for illegal activities. Younger age was a risk factor for sexual risky behavior, and no risk factor other than male gender was found for alcohol abuse. Future investigation of risk behaviors among gamblers must take into account the differences in gender and age. Both impulsivity and emotional distress are related to risk-taking in gamblers, and young gamblers who early in life display other potentially harmful behaviors require special attention.


Role of lipid and lipoprotein metabolizing enzymes in the development of atherosclerosis.
Cardiovascular disease is the primary cause of mortality in developed and developing nations. With an increase in the aging population, there is a surge in the incidence of atheroscleortic cardiovascular diseases. One of the most common and lethal manifestations of atherosclerosis is coronary heart disease, accounting for 50% of the atherosclerotic cardiovascular diseases in men and women younger than 75 years. Peripheral arterial diseases, manifested mainly as intermittent claudication constitute approximately 10% of the atherosclerotic cardiovascular events. According to the American Heart Association 2001 Heart and Stroke Statistical Update, atherosclerosis accounts for 75% of all deaths due to cardiovascular diseases. Therefore, atherosclerosis continues to remain the primary cause of health concern for the population at large. The aim of this review is to discuss the role of enzymes that are involved in the metabolism of lipid and lipoproteins in the development of atherosclerosis.


The life cycle and seasonal changes in the occurrence of Pomphorhynchus laevis (Palaeacanthocephala, Pomphorhynchidae) in a small isolated lake.
In a small isolated lake in Slovakia, the fish acanthocephalan Pomphorhynchus laevis using Gammarus balcanicus and the minnow Phoxinus phoxinus, respectively, as its intermediate and final hosts, represented a dominant helminth species. Its prevalence and intensity of infection in fish showed no significant variation during a year fluctuating above the mean values of 89% and 6.6 worms per fish. The mean prevalence of P. laevis larvae in Gammarus was 41.4% with a maximum in the late summer and autumn; individual crustaceans were infected by 1-9 larvae. There was one generation of P. laevis per year. Following up an annual cycle, an occurrence of new infections of Gammarus culminated in October and in the next May for Phoxinus. The sex ratios of both the adults and larvae of acanthocephalans were near unity but favoured slightly males in spring and autumn. The distribution of P. laevis in minnows and crustaceans was highly aggregated and fitted with the negative binomial model. The spatial distribution analysis of parasites along the fish alimentary tract showed a clear preference of P. laevis for its proximal half, with the maximum numbers in the site of the first intestinal loop. Immature worms of both sexes predominated in the proximal region and moved slightly down the alimentary tract during their growth and maturation.


Search for large extra spatial dimensions in dimuon production with the d0 detector.
We present the results of a search for the effects of large extra spatial dimensions in pp collisions at sqrt[s] = 1.96 TeV in events containing a pair of energetic muons. The data correspond to 246 pb(-1) of integrated luminosity collected by the D0 experiment at the Fermilab Tevatron Collider. Good agreement with the expected background was found, yielding no evidence for large extra dimensions. We set 95% C.L. lower limits on the fundamental Planck scale between 0.85 and 1.27 TeV within several formalisms. These are the most stringent limits achieved in the dimuon channel to date.


Incidence and risk factors for sexually transmitted infections among women in an Alabama HIV clinic.
The objectives of this study were to assess the prevalence and incidence of curable sexually transmitted infections (STI), i.e., gonorrhea, chlamydial infection, or trichomoniasis, in a cohort of HIV-infected women. The study population was derived from women seeking primary care at an outpatient university HIV clinic who were participants in a women's natural history study. Enrollees (n = 225) were predominantly African-American, heterosexually infected, with mean age 35 years. Mean entry CD4+ T cell count was 405 cells/mm3. Over 6% were STI positive at initial screening. Subsequently, the combined curable STI incidence was 4.82/1000 woman-months over a median of 33 months of observation. Of 36 incident STIs, trichomoniasis was most common (n = 32). Predictors for acquisition of a curable STI included absenteeism at scheduled clinic appointments, RR = 1.99 (1.28, 3.08), and a higher CD4+ T cell count, RR = 1.15 (1.0028, 1.3115) for 100 cells. Interventions to prevent curable STI in HIV-infected women are warranted in primary care settings.


Spontaneous primary dissecting coronary artery aneurysm. Report of two cases.
Two cases of dissecting aneurysm of the left main stem and left anterior descending coronary arteries are presented. Both cases were discovered during routine medicolegal death investigations. Unusual aspects of one of our cases include the history of antecedent trauma and the precise identification of an intimal tear.


Role of TAF4 in transcriptional activation by Rta of Epstein-Barr Virus.
Epstein-Barr virus (EBV) expresses an immediate-early protein, Rta, to activate the transcription of EBV lytic genes. This protein usually binds to Rta-response elements or interacts with Sp1 or Zta via a mediator protein, MCAF1, to activate transcription. Rta is also known to interact with TBP and TFIIB to activate transcription. This study finds that Rta interacts with TAF4, a component of TFIID complex, in vitro and in vivo, and on the TATA sequence in the BcLF1 promoter. Rta also interacts with TAF4 and Sp1 on Sp1-binding sequences on TATA-less promoters, including those of BNLF1, BALF5, and the human androgen receptor. These interactions are important to the transcriptional activation of these genes by Rta since introducing TAF4 shRNA substantially reduces the ability of Rta to activate these promoters. This investigation reveals how Rta interacts with TFIID to stimulate transcription.


Human induced pluripotent stem cell and nanotechnology-based therapeutics.
Human induced pluripotent stem cells (hiPSCs) can be genetically reprogrammed to an embryonic stem cell-like state and can provide promising medical applications, such as diagnosis, prognosis, drug screening for therapeutical development, and monitoring disease progression. Despite myriad advances, traditional viral-based reprogramming for generating hiPSCs has safety risks that hinder further practical applications of hiPSCs. In the past decade, nonviral-based reprogramming has been used as an alternative to produce hiPSCs and enhance their differentiation. In addition, the efficiency of nonviral-based reprogramming is generally poor, compared to that of viral-based reprogramming. Recent studies in nanoscale-structured particles have made progress in addressing many applications of hiPSCs for clinical practice. The combination of hiPSCs and nanotechnology will actually act as the therapeutic platform for personalized medicine and can be the remedies against various diseases in the future. In this article, we review recent advances in cellular reprogramming and hiPSC-related research, such as cell source, delivery system, and direct reprogramming, as well as some of its potential clinical applications, including mitochondrial and retinal disease. We also briefly summarize the current incorporation of nanotechnology in patient-specific hiPSCs for future treatments.


Mammaglobin expression in lymph nodes is an important marker of metastatic breast carcinoma.
Organ specificity is a desirable property of a tumor marker, especially in metastatic adenocarcinomas of unknown primary origin. Mammaglobin, a mammary-specific member of the uteroglobin family, is known to be overexpressed in human breast cancer. We investigated mammaglobin A expression in metastatic carcinomas of lymph nodes from the breast and various other organs and its usefulness in identifying metastatic carcinoma of the breast. For comparative purposes, we also investigated BRST-1 and BRST-2 expression. We produced recombinant mammaglobin and polyclonal antimammaglobin antibodies. Mammaglobin expression was analyzed by immunohistochemical staining using a tissue microarray and by reverse transcription-polymerase chain reaction in 210 carcinomas, including those of the breast (n = 70), lung (n = 30), stomach (n = 30), colorectum (n = 25), hepatobiliary tract (n = 20), urinary tract (n = 10), thyroid gland (n = 10), ovary and endometrium (n = 10), and salivary gland (n = 5). Mammaglobin expression was observed in 59 cases (84.3%) of breast cancer and in 21 cases (15.0%) of nonbreast cancer. The BRST-1 and BRST-2 expression rates were 75.7% and 44.3% in breast cancer and 26.4% and 2.1% in nonbreast cancer, respectively. Mammaglobin is superior to BRST-1 for both specificity and sensitivity and is superior to BRST-2 for sensitivity. Our data suggest that mammaglobin is one of the first relatively mammary-specific and mammary-sensitive markers. Mammaglobin and BRST-2 appear to represent useful markers for breast cancer and should be used as a component of panels evaluating tumors of unknown primary sites.


Changing values of farm animal genomic resources. from historical breeds to the Nagoya Protocol.
The paper reviews the history of Animal genetic resources (AnGRs) and claims that over the course of history they have been conceptually transformed from economic, ecologic and scientific life forms into political objects, reflecting in the way in which any valuation of AnGRs is today inherently imbued with national politics and its values enacted by legally binding global conventions. Historically, the first calls to conservation were based on the economic, ecological and scientific values of the AnGR. While the historical arguments are valid and still commonly proposed values for conservation, the AnGR have become highly politicized since the adoption of the Convention of Biological Diversity (CBD), the subsequent Interlaken Declaration, the Global Plan for Action (GPA) and the Nagoya Protocol. The scientific and political definitions of the AnGRs were creatively reshuffled within these documents and the key criteria by which they are now identified and valued today were essentially redefined. The criteria of "in situ condition" has become the necessary starting point for all valuation efforts of AnGRs, effectively transforming their previous nature as natural property and global genetic commons into objects of national concern pertaining to territorially discrete national genetic landscapes, regulated by the sovereign powers of the parties to the global conventions.