Lead selenide quantum dot polymer nanocomposites.
Optical absorption and fluorescence properties of PbSe quantum dots (QDs) in an Angstrom Bond AB9093 epoxy polymer matrix to form a nanocomposite were investigated. To the authors' knowledge, this is the first reported use of AB9093 as a QD matrix material and it was shown to out-perform the more common poly(methyl methacrylate) matrix in terms of preserving the optical properties of the QD, resulting in the first reported quantum yield (QY) for PbSe QDs in a polymer matrix, 26%. The 1-s first excitonic absorption peak of the QDs in a polymer matrix red shifted 65 nm in wavelength compared to QDs in a hexane solution, while the emission peak in the polymer matrix red shifted by 38 nm. The fluorescence QY dropped from 55% in hexane to 26% in the polymer matrix. A time resolved fluorescence study of the QDs showed single exponential lifetimes of 2.34 and 1.34 μs in toluene solution and the polymer matrix respectively.


The effect of alpha-melanocyte stimulating hormone (alpha-msh) on the metabolism of biogenic amines in the rat brain.
The effect of the chronic administration of alpha-MSH on the incorporation of tritiated tyrosine into noradrenalin and dopamine and of tritiated tryptophan into serotonin was studied in different regions of the rat brain. Alpha-MSH increased the incorporation of tritiated trytophan into serotonin in the cortex and slightly decreased that of tryosine into the dopamine in the hypothalamus. As the brain concentration of serotonin was unchanged in the animals treated with alpha-MSH, it is suggested that some of the changes in behavior, which other investigators have found following the administration of peptides containing the same sequence of amino acids to that found in MSH, could be associated with an increased turnover of cortical serotonin.


Sources and frequency of secondhand smoke exposure during pregnancy.
This study examined sources of exposure to secondhand smoke (SHS) during pregnancy and misclassification of women as having no SHS exposure if partner smoking was used as the only measure of SHS exposure. We also examined changes in SHS exposure across the three trimesters of pregnancy. The sample consisted of 245 pregnant women who were in a serious relationship with a partner and 106 for examination of change over time. Women's smoking status was determined by a combination of self-reports and oral fluid assays. Women's reports of partner smoking, smoking by other social network members, and frequency of exposure to SHS were obtained. The most common source of SHS exposure during pregnancy was the partner (n = 245). However, reliance on the partner smoking measure alone would have misclassified a substantial number of women as having no SHS exposure during pregnancy. The importance of exposure from the general social network was also evident in the finding that among nonsmoking women with nonsmoking partners, 50% reported some level of SHS exposure in the preceding week. Contrary to expectations, there were no changes in SHS exposure across the three trimesters of pregnancy (n = 106). Results highlight the need for treatment plans to target sources of exposure from other members of women's social networks in addition to partners. It may be unrealistic to expect women's cessation efforts to be successful in the face of consistent and continued SHS exposure through pregnancy.


SPAM1 (PH-20) protein and mRNA expression in the epididymides of humans and macaques: utilizing laser microdissection/RT-PCR.
The Sperm Adhesion Molecule 1 (SPAM1) is an important sperm surface hyaluronidase with at least three functions in mammalian fertilization. Previously our laboratory reported that in the mouse, in addition to its expression in the testis, Spam1 is synthesized in the epididymis where it is found in membranous vesicles in the principal cells of the epithelium in all three regions. Since SPAM1 is widely conserved among mammals the aim of the study was to determine if its expression pattern in the epididymis is conserved in rodents and primates. We used laser microdissection (LM)/RT-PCR on frozen and paraffin-embedded epididymal sections of humans (n = 3) and macaques (n = 2) as well as in situ transcript hybridization to determine if transcripts are present in the epididymal epithelium. Western analysis and immunohistochemistry were used to detect and confirm the protein expression, and hyaluronic acid substrate gel electrophoresis analyzed its hyaluronidase activity. An in silico analysis of the proximal promoter of SPAM1 was also performed to identify relevant putative transcription binding sites for the androgen receptor. We demonstrate that mRNA unique to SPAM1 is present in the principal cells of the epididymal epithelium in all individuals of both species studied. SPAM1 protein is present in all three regions of the epididymis, as well as the vas deferens, and is localized similarly to the transcripts. SPAM1 was shown to have hyaluronidase activity at pH 7.0. In the proximal promoter of SPAM1 were uncovered putative epididymal transcription factor binding sites including androgen receptor elements (AREs), consistent with epididymal expression. These findings allow us to conclude that epididymal SPAM1 is conserved in at least two mammalian classes, rodents and primates. This conservation of expression suggests that the protein is likely to play an important function, possibly in sperm maturation.


Personalized medicine and treatment approaches in hypertension: current perspectives.
In the US, hypertension affects one in three adults. Current guideline-based treatment of hypertension involves little diagnostic testing. A more personalized approach to the treatment of hypertension might be of use. Several methods of personalized treatment have been proposed and vetted to varying degrees. The purpose of this narrative review is to discuss the rationale for personalized therapy in hypertension, barriers to its development and implementation, some influential examples of proposed personalization measures, and a view of future efforts.


[Initial experience in the diagnosis and treatment of superficial bladder tumors with Hexvix].
White light cystoscopy is the current standard for the diagnosis of bladder cancer and monitorization for recurrence. Recent studies suggest that porphyrin based fluorescence cystoscopy may improve endoscopic detection of bladder tumors. We aimed to evaluate the improvement that hexaminolevulinate fluorescence cystoscopy could lead in bladder cancer detection and treatment at one single centre. Between September 2006 and September 2007 a total of 39 patients with known or suspected bladder cancer underwent bladder instillation with 50 ml 8 mM hexaminolevulinate (HAL) for 1 hour. The bladder was inspected using white light cystoscopy (WLC), followed by blue light (fluorescence) cystoscopy (BLC). Papillary and suspicious lesions were resected for histological examination. Mean age was 70.1 years (50-86). Thirty patients were male (76.9%) and 9 female (23.1%). The tumor characteristics were: 18% primary tumors, 51% recurrences and 30% control cystoscopies. 24 patients had previously received some treatment (9 MMC and 15 BCG). Only 7 patients had previous positive urine cytology. All papillary lesions visualized with WLC were confirmed by BLC (18 patients). From these, 17 have positive biopsies (6 pTaG1, 9 pT1G1-3, 1 pT2, 1 CIS). In 15 patients (38.4%) we found at least 1 lesion more with BLC. In this group 8 cases (20.5%) had positive histological diagnosis (3 pTaG1, 2 pT1G3, 3 CIS). In five patients (13%) post-TUR therapeutic management has changed by using BLC (BCG vs MMC). All four patients with CIS were diagnosed by BLC. There was no evidence of local or systemic side effects due to HAL in the postoperative time. Our results suggest there is an improvement in the diagnosis of papillary and flat lesions in bladder cancer by using HAL fluorescence cystoscopy. This has changed the management in the postoperative period (MMC vs BCG) in 13% of the patients. Obviously, we need more patients to assess our data and long-term follow-up to analyze the impact in terms of tumor recurrence and progression.


Homophobic and sexist yet uncontested: examining football fan postings on Internet message boards.
Although a homophobic and sexist archetype of heterosexual masculinity has been thought to permeate competitive teamsport, matters have been rapidly changing. This is evident in research on openly gay athletes, attitudes among heterosexual athletes, and recent studies on decreasing homophobia among sport media content. In this research, however, we examine how some men still adhere to a homophobic and sexist masculine deposition when discussing sport on the Internet. A textual analysis was used to analyze hegemonic masculinity from a popular American football message board. Although posts related to hegemonic masculinity did not permeate the data, we found that this traditional form of masculinity was upheld through misogyny, homophobia, and the objectification of women. Thus, whereas mainstream sport media is increasingly policed for homophobia and sexism, this research shows that the anonymity of the Internet permits hegemonic masculinity to flourish in specific locations, without contestation.


Real-time target position estimation using stereoscopic kilovoltage/megavoltage imaging and external respiratory monitoring for dynamic multileaf collimator tracking.
To develop a real-time target position estimation method using stereoscopic kilovoltage (kV)/megavoltage (MV) imaging and external respiratory monitoring, and to investigate the performance of a dynamic multileaf collimator tracking system using this method. The real-time three-dimensional internal target position estimation was established by creating a time-varying correlation model that connected the external respiratory signals with the internal target motion measured intermittently using kV/MV imaging. The method was integrated into a dynamic multileaf collimator tracking system. Tracking experiments were performed for 10 thoracic/abdominal traces. A three-dimensional motion platform carrying a gold marker and a separate one-dimensional motion platform were used to reproduce the target and external respiratory motion, respectively. The target positions were detected by kV (1 Hz) and MV (5.2 Hz) imaging, and external respiratory motion was captured by an optical system (30 Hz). The beam-target alignment error was quantified as the positional difference between the target and circular beam center on the MV images acquired during tracking. The correlation model error was quantified by comparing a model estimate and measured target positions. The root-mean-square errors in the beam-target alignment that had ranged from 3.1 to 7.6 mm without tracking were reduced to <1.5 mm with tracking, except during the model building period (6 s). The root-mean-square error in the correlation model was submillimeters in all directions. A novel real-time target position estimation method was developed and integrated into a dynamic multileaf collimator tracking system and demonstrated an average submillimeter geometric accuracy after initializing the internal/external correlation model. The method used hardware tools available on linear accelerators and therefore shows promise for clinical implementation.


The role of macromolecular architecture in passively targeted polymeric carriers for drug and gene delivery.
The use of polymeric carriers for drug delivery has become increasingly popular because of the ability to easily tune the physical and biological properties of macromolecules. With the growing commercial accessibility of branched and dendritic polymers, their incorporation into polymeric carriers is being explored with increased frequency. However, while a handful of systematic studies have explored the use of branched macromolecules for drug delivery, the role of polymer architecture in optimizing the polymeric carriers is not yet fully understood. Herein, the authors summarize the effect that architecture has on the basic physical properties of polymers, and review our preliminary understanding of the architectural effects on polymer-assisted drug delivery.


Use of combined conventional and real-time PCR to determine the epidemiology of feline haemoplasma infections in northern Italy.
Although knowledge of feline haemotropic mycoplasmas (haemoplasmas) has dramatically improved in recent years, some issues still remain to be elucidated. The aim of the current study was to evaluate the prevalence of feline haemoplasma infections in blood samples collected from cats in northern Italy. A convenience-sample of 307 cats (40 anaemic; 258 non-anaemic; nine with unknown haematocrit [HCT]) was investigated using polymerase chain reaction assays. Furthermore, the date of blood collection, signalment and clinicopathological data were retrospectively evaluated to assess predictors and risk factors for infection. Haemoplasma infections were highly prevalent in the sample investigated with an overall prevalence of 18.9% (95% confidence interval: 14.5-23.3%). The prevalence for the three feline haemoplasmas was 17.3% for 'Candidatus Mycoplasma haemominutum' (CMhm), 5.9% for Mycoplasma haemofelis (Mhf) and 1.3% for 'Candidatus Mycoplasma turicensis' (CMt). Feline immunodeficiency virus-positive status represented a risk factor for infection with an odds ratio of 4.19 (P=0.02). Moreover, a higher prevalence was observed in summer (odds ratio 1.78; P=0.04) which may be consistent with arthropod-borne disease transmission. Cats infected with Mhf showed significantly lower HCT (P=0.03), haemoglobin values (P=0.02) and red blood cell counts (P=0.04), lower mean corpuscular haemoglobin concentration (P<0.01) and higher white blood cell counts (P<0.01) when compared with non-infected cats.


Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells.
RNA silencing is a conserved mechanism in which small RNAs trigger various forms of sequence-specific gene silencing by guiding Argonaute complexes to target RNAs by means of base pairing. RNA silencing is thought to have evolved as a form of nucleic-acid-based immunity to inactivate viruses and transposable elements. Although the activity of transposable elements in animals has been thought largely to be restricted to the germ line, recent studies have shown that they may also actively transpose in somatic cells, creating somatic mosaicism in animals. In the Drosophila germ line, Piwi-interacting RNAs arise from repetitive intergenic elements including retrotransposons by a Dicer-independent pathway and function through the Piwi subfamily of Argonautes to ensure silencing of retrotransposons. Here we show that, in cultured Drosophila S2 cells, Argonaute 2 (AGO2), an AGO subfamily member of Argonautes, associates with endogenous small RNAs of 20-22 nucleotides in length, which we have collectively named endogenous short interfering RNAs (esiRNAs). esiRNAs can be divided into two groups: one that mainly corresponds to a subset of retrotransposons, and the other that arises from stem-loop structures. esiRNAs are produced in a Dicer-2-dependent manner from distinctive genomic loci, are modified at their 3' ends and can direct AGO2 to cleave target RNAs. Mutations in Dicer-2 caused an increase in retrotransposon transcripts. Together, our findings indicate that different types of small RNAs and Argonautes are used to repress retrotransposons in germline and somatic cells in Drosophila.


TMEM241 is a UDP-N-acetylglucosamine transporter required for M6P modification of NPC2 and cholesterol transport.
Accurate intracellular cholesterol traffic plays crucial roles. Niemann Pick type C (NPC) proteins NPC1 and NPC2, are two lysosomal cholesterol transporters that mediate the cholesterol exit from lysosomes. However, other proteins involved in this process remain poorly defined. Here, we find that the previously unannotated protein TMEM241 is required for cholesterol egressing from lysosomes through amphotericin B-based genome-wide CRISPR-Cas9 KO screening. Ablation of TMEM241 caused impaired sorting of NPC2, a protein utilizes the mannose-6-phosphate (M6P) modification for lysosomal targeting, resulting in cholesterol accumulation in the lysosomes. TMEM241 is a member of solute transporters 35 nucleotide sugar transporters family and localizes on the cis-Golgi network. Our data indicate that TMEM241 transports UDP-N-acetylglucosamine (UDP-GlcNAc) into Golgi lumen and UDP-GlcNAc is used for the M6P modification of proteins including NPC2. Furthermore, Tmem241-deficient mice display cholesterol accumulation in pulmonary cells and behave pulmonary injury and hypokinesia. Taken together, we demonstrate that TMEM241 is a Golgi-localized UDP-GlcNAc transporter and loss of TMEM241 causes cholesterol accumulation in lysosomes because of the impaired M6P-dependent lysosomal targeting of NPC2.


[Spatio-temporal distribution of conditioned evoked potentials during latent inhibition in the cat].
Using the model of shortly delayed defensive conditioned reflexes in cats it is shown that nonreinforced preexposure of conditioned stimulus leads to a definite manifestation of electrographic correlates of the memory trace, i. e. of the conditioned evoked potential in examined brain structures, as well as of conditioned neurographic response and conditioned skin-galvanic reaction. The reproduction of the conditioned evoked potentials was completely blocked in the cortex and zona incerta. The conditioned neurographic response was blocked too. The probability of skin-galvanic reaction appearance was harshly decreased.


A high tender point count is associated with the presence of multiple idiopathic pain disorders: results from a population study.
To test whether mechanical hyperalgesia is associated with multiple idiopathic pain disorders (IPDs) and whether this relationship is independent of the confounding effects of psychosocial factors. One hundred eighteen subjects with chronic orofacial pain (COFP) were identified from their questionnaire responses to a population study in North West England. All subjects had a tender point examination according to the American College of Rheumatology classification. Validated tools on the questionnaire were used to identify presence of other IPDs (irritable bowel syndrome and chronic widespread pain) and psychosocial factors (anxiety, depression, health anxiety, sleep disturbance and reporting of somatic symptoms and adverse life events). Of the 118 subjects, 47.6% (n = 56) had COFP, 34.7% (n = 41) had COFP plus one IPD and 17.8% (n = 21) had all three IPDs. Univariate analysis revealed a dose-response relationship between number of tender points (TPs) and number of IPDs [2-6 TPs (OR 2.6, 95% CI 1.0-7.3), ≥ 7 TPs (OR 10.5, 95% CI 3.8-29.3)] and number of IPDs and psychological distress [anxiety (OR 2.8, 95% CI 1.2-6.4), depression (OR 4.3, 95% CI 1.7-10.6), sleep disturbance (OR 4.8, 95% CI 1.6-14.6)]. The relationship between IPDs and TPs persisted after adjusting for psychosocial factors in multivariate analyses [2-6 TPs (OR 2.5, 95% CI 0.8-7.8) ≥ 7 TPs (OR 10.7, 95% CI 3.4-33.7)]. The dose-response relationship between TPs and IPDs needs further investigation to determine the temporal nature of these relationships and to disentangle the complex gene-environment relationships that may influence the occurrence of multiple IPDs.


Optimization of total phenolic content from Terminalia chebula Retz. fruits using response surface methodology and evaluation of their antioxidant activities.
Ultrasonic-assisted extraction (UAE), using aqueous ethanol as the solvent, was firstly applied to extract phenolic compounds from Terminalia chebula Retz. fruits (T. chebula fruits). In this study, ethanol concentration (%), ultrasonic intensity (W/cm2), particle diameter (mm), extraction temperature (°C), ultrasonic time (min), liquid-solid ratio (mL/g) and extraction cycle were investigated by single-factor experiment and then optimized using a Box-Behnken design. The optimized result for UAE was 68% ethanol concentration, ultrasonic intensity of 3.6 W/cm2, solid-liquid ratio of 23 mg/mL, particle size of 0.18 mm and ultrasonic time of 20 min for 2 times at 70 °C. The yield of total phenolic was 448.7 ± 2.15 mg GAE/g DW under the above optimum conditions, which agreed with the predicted value (447.8 mg GAE/g DW). Compared to conventional solvent extraction (CSE), UAE extracts showed excellent DPPH radical, DPPH, ABTS scavenging activities and reducing power in a dose-dependent manner, and better than that of CSE extracts. Additionally, the extract of the T. chebula fruits was analyzed by HPLC-ESI/MS. In summary, UAE could effectively extract phenolic compounds from T. chebula fruits. In addition, the extract could be used as a potential source of natural antioxidants.


Hormonal control of Luteal 20alpha-Hydroxy steroid dehydrogenase and delta5-3beta-hydroxy steroid dehydrogenase during luteolysis in the pregnant rat.
Treatment of pregnant rats with human chorionic gonadotrophin, luteotrophin (luteinizing hormone), luteotrophin-releasing hormone, prostaglandin F2alpha, aminoglutethimide, or by foetoplacental removal or hysterectomy achieved a common multiple-response pattern, namely increased activity of luteal 20alpha-hydroxy steroid dehydrogenase with decreased activity of delta5-3beta-hydroxy steriod dehydrogenase and release of delta4-3-oxo steroids in vitro. 2. Similar effects of foetoplacental removal are noted in pregnant mice. 3. Gonadotrophin induced lower activities of 20alpha-hydroxy steroid dehydrogenase, except at the very end of pregnancy, and partly inhibited the induction caused by foetoplacental removal. 4. The results suggest that existence of a placental factor that restrains these changes until the end of normal pregnancy, which is produced in amounts proportional to the number of placentae and is conveyed to the ovary via the blood. 5. This factor was not replaced by prolactin. 6. It is argued that neither placental lactogen nor pituitary luteotrophin participate in the induction of 20alpha-hydroxy steroid dehydrogenase at late pregnancy in the rat. 7. Aminoglutethimide induced 20alpha-hydroxy steroid dehydrogenase only in late pregnancy. This was partly reversed by progesterone, wholly reversed by progesterone plus oestrogen, and did not involve the pituitary.


The nicotinic acetylcholine receptor of the Torpedo electric ray.
The nicotinic acetylcholine receptor is a neurotransmitter-gated ion channel that mediates the rapid propagation of electrical signals at the nerve-muscle synapse. Its structure at 9 A resolution, in both the closed- and the open-channel forms, has been examined by electron microscopy of tubular crystals grown from Torpedo postsynaptic membranes. Binding of acetylcholine to open the channel causes a localized disturbance in the extracellular domain and initiates small rotations of the protein subunits, which trigger a change in configuration of alpha-helices lining the membrane-spanning pore. A method recently developed to correct in three dimensions for distortions present in the crystals, combined with improvements in the electron imaging, should eventually allow these conformational changes to be seen at atomic resolution.


Enteropathy-associated T-cell lymphoma (type II): a Brazilian case report.
Enteropathy-associated T-cell Lymphoma (EATL) is a rare form of aggressive T-cell lymphoma. It is more prevalent in men over 60 years and the prognosis is very poor. EATL is classified into two groups based on morphology, immunohistochemistry, and genetic profile. EATL type I is highly associated with celiac disease and is more common in Western countries. EATL type II predominates over type I in Asia, where celiac disease is uncommon. We report a case of a 78-year-old previously healthy white male who presented with a 2-month history of diarrhea, weight loss and edema. The abdomen was distended and painful, and a tumor mass was palpable in the hypogastrium. Laboratory tests showed hypoalbuminemia. Serological tests for HIV, viral hepatitis and HTLV-1 were negative. The chest radiography showed pneumoperitoneum, and an exploratory laparotomy revealed perforation of the small bowel. An advanced stage (Ann Arbor IV B/Lugano IIE2B) EATL type II was diagnosed. Four cycles of chemotherapy were interspersed with several complications (anthracycline-induced cardiotoxicity, chemotherapy-induced neutropenic fever and severe sepsis). Performance status progressively worsened and he died 6 months after the diagnosis. This is an illustrative report of a rare and aggressive primary intestinal lymphoma. To the best of our knowledge, this is the first report of EATL type II in Brazil.


[Hepatitis C virus-associated and metabolic steatosis. Different or overlapping diseases?].
Hepatic steatosis is the hallmark of nonalcoholic fatty liver disease (NAFLD), which is the consequence of multiple metabolic derangements among which insulin resistance plays a pivotal role. Steatosis is, also, a feature of hepatitis C virus (HCV) infection. However, in chronic hepatitis C, the prevalence of steatosis is 2.5-fold more elevated than that expected by a chance concurrence with NAFLD, suggesting that HCV may be implied in the development of steatosis. As observed in NAFLD, in patients infected with HCV genotype 1 steatosis is associated with an increased body mass index. On the other hand, in patients infected with genotype 3 the extent of steatosis strictly correlates with the viral load indicating that steatosis is mainly "virus-related". Regardless of the "metabolic" or "viral" etiology, hepatic steatosis in HCV contributes to the progression of liver fibrosis, to the development of hepatocellular carcinoma and to an impaired response to interferon treatment. Features such as obesity, insulin resistance and type 2 diabetes mellitus are shared by NAFLD and HCV-associated steatosis. In addition, HCV infection, directly or through steatosis, favors the development of type 2 diabetes mellitus. Hyperlipidemia is an independent predictor of the development of NAFLD, but not of HCV-associated steatosis. Arterial hypertension is common in nonalcoholic steatohepatitis patients, and HCV infection has recently been acknowledged as an independent risk factor for atherosclerosis. The role of iron in the progression of both NAFLD and HCV-associated steatosis remains controversial while lipoperoxidation and oxidative stress are pathogenic mechanisms shared by both. Some metabolic risk factors may be shared by both HCV-associated steatosis and NAFLD although the disease progression and pathophysiological background may be different. Preliminary data suggest that the therapeutic options for NAFLD may also be useful to improve HCV-associated steatosis.


Bedtime Salivary Cortisol and Cortisone by LC-MS/MS in Healthy Adult Subjects: Evaluation of Sampling Time.
The measurement of late-night salivary cortisol is a mainstay in the diagnosis of Cushing syndrome. Furthermore, the measurement of salivary cortisol is useful in assessing the cortisol awakening response. Because the salivary glands express 11-β-hydroxysteroid dehydrogenase, the measurement of salivary cortisone may improve the performance of salivary corticosteroid measurements. We measured salivary cortisol by enzyme immunoassay (EIA) and salivary cortisol and cortisone by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in only 50 µL of saliva sampled from 54 healthy subjects (aged 20 to 64 years). We allowed patients to sample at their normal bedtime (2025 to 2400 hours) to answer a common question as to whether sampling at the normal bedtime is equivalent to the standard required sampling at 2300 to 2400 hours. We found that the salivary cortisol and cortisone results by LC-MS/MS correlated well with salivary cortisol measured with the US Food and Drug Administration-cleared EIA. Furthermore, the upper limit of normal of salivary cortisol by EIA for bedtime samples was lower than the previously published upper limit of normal with sampling required at 2300 to 2400 hours. There were no significant effects of age or sex on any of the salivary steroid measurements. We conclude that (i) salivary cortisol and cortisone can be reliably measured by LC-MS/MS in small volumes of saliva and (ii) that patients can be evaluated using saliva sampled at their normal bedtime, rather than being required to stay awake until 2300 to 2400 hours.


[Fluorophotometry by instillation. I. Flow of the aqueous humor and corneal endothelial permeability].
Among various fluorophotometric methods performed on the anterior segment, topical administration of fluorescein was developed. This local administration allows to measure the aqueous humor flow and the permeability of the corneal endothelial. The examinations are performed on a computerized fluorophotometer: the Fluorotron Master. This fluorophotometer has been designed to accurately measure fluorescein's concentrations into the eye and especially in aqueous humor and cornea. Anterior chamber adapter magnifies the scan for detailed work in the anterior chamber and lens. The Fluorotron is supplied with a cuvette holder and a cuvette which is adapted to the optical head for measuring the concentration of fluorescein in blood plasma or in buffered aqueous samples. A good linearity was obtained between the meter readings and the concentrations of fluorescein in phosphate buffer with pH 7.4, within the range between 1 ng and 1000 ng. Based upon the mathematical analysis of Yablonski the method by fluorescein instillation is simple and safe and gives the loss coefficient, ko, of the dye from the anterior chamber, the aqueous humor flow, F, and the endothelial transfer coefficient kc.ca. Calculations were carried out on twenty one normal eyes yielding average values for F 2.97 +/- 0.93 microliter.min-1 (Mean +/- S.D.) and for kc.ca 4.02 +/- 0.40. 10(-1) min-1. These values are comparable to those of other authors.


Comparative impact of exercise-based interventions for postpartum depression: A Bayesian network meta-analysis.
The current study aimed to address and rank which exercise-based interventions are preferable to standard care/no therapy or another exercise intervention for postpartum depression (PPD) management and provide estimates for future definitive evidence. The authors systematically searched PubMed, Embase, the Web of Science, PsycInfo, and ClinicalTrails.gov for randomized controlled trials (RCTs) on exercise-based interventions for PPD from their inception to May 9, 2023. Included were RCTs of exercise-based interventions for PPD with at least 4 weeks' duration. The pooled effects of intervention comparisons were generated by the Bayesian random-effects model, and the quality of evidence was evaluated by the Grading of Recommendations, Assessment, Development, and Evaluations framework. Twelve RCTs (1260 women; mean age, 20-35 years) comparing exercise-based interventions with usual care/no therapy were included. Exercise effectively treats depressive symptoms (standard mean difference [SMD], -0.81 [95% confidence interval (CI), -1.20 to -0.42], P < 0.001). Pram walking was significantly associated with a reduction of depressive symptoms during the postpartum period (SMD, -1.00 [95% CI, -2.60 to -0.10], P = 0.020), as well as yoga (SMD, -0.73 [95% CI, -1.84 to -0.43], P < 0.001) and supervised mixed exercise (SMD, -0.77 [95% CI, -1.67 to -0.01], P = 0.041) compared with usual care/no therapy. In indirect comparisons, pram walking (surface under the cumulative ranking curve, 58.9%) was better than yoga (SMD, -0.28 [95% CI, -1.86 to 1.22], P = 0.322) and supervised mixed exercise (SMD, -0.23 [95% CI, -1.59 to 1.12], P = 0.358). However, the difference was not statistically significant. The confidence in evidence was very low to moderate. In women with PPD, all commonly prescribed physical exercises were effective alternative or complementary treatments. However, pram walking may perform better in improving the symptoms of PPD.


Three-dimensional structure of an intact glycoside hydrolase family 15 glucoamylase from Hypocrea jecorina.
The three-dimensional structure of a complete Hypocrea jecorina glucoamylase has been determined at 1.8 A resolution. The presented structure model includes the catalytic and starch binding domains and traces the course of the 37-residue linker segment. While the structures of other fungal and yeast glucoamylase catalytic and starch binding domains have been determined separately, this is the first intact structure that allows visualization of the juxtaposition of the starch binding domain relative to the catalytic domain. The detailed interactions we see between the catalytic and starch binding domains are confirmed in a second independent structure determination of the enzyme in a second crystal form. This second structure model exhibits an identical conformation compared to the first structure model, which suggests that the H. jecorina glucoamylase structure we report is independent of crystal lattice contact restraints and represents the three-dimensional structure found in solution. The proposed starch binding regions for the starch binding domain are aligned with the catalytic domain in the three-dimensional structure in a manner that supports the hypothesis that the starch binding domain serves to target the glucoamylase at sites where the starch granular matrix is disrupted and where the enzyme might most effectively function.


Ubiquitin-proteasome-mediated cyclin C degradation promotes cell survival following nitrogen starvation.
Environmental stress elicits well-orchestrated programs that either restore cellular homeostasis or induce cell death depending on the insult. Nutrient starvation triggers the autophagic pathway that requires the induction of several Autophagy (ATG) genes. Cyclin C-cyclin-dependent kinase (Cdk8) is a component of the RNA polymerase II Mediator complex that predominantly represses the transcription of stress-responsive genes in yeast. To relieve this repression following oxidative stress, cyclin C translocates to the mitochondria where it induces organelle fragmentation and promotes cell death prior to its destruction by the ubiquitin-proteasome system (UPS). Here we report that cyclin C-Cdk8, together with the Ume6-Rpd3 histone deacetylase complex, represses the essential autophagy gene ATG8. Similar to oxidative stress, cyclin C is destroyed by the UPS following nitrogen starvation. Removing this repression is important as deleting CNC1 allows enhanced cell growth under mild starvation. However, unlike oxidative stress, cyclin C is destroyed prior to its cytoplasmic translocation. This is important as targeting cyclin C to the mitochondria induces both mitochondrial fragmentation and cell death following nitrogen starvation. These results indicate that cyclin C destruction pathways are fine tuned depending on the stress and that its terminal subcellular address influences the decision between initiating cell death or cell survival pathways.


Optimizing Huddle Engagement Through Leadership and Problem Solving Within Primary Care: Results from a Cluster-Randomized Trial.
Leaders play a crucial role in implementing and sustaining changes in clinical practice, yet there is limited evidence on the strategies to engage them in team problem solving and communication. Examine the impact of an intervention focused on facilitating leadership during daily huddles on optimizing team-based care and improving outcomes. Cluster-randomized trial using intention-to-treat analysis to measure the effects of the intervention (n = 13 teams) compared with routine practice (n = 16 teams). Twenty-nine primary care clinics affiliated with a large integrated health system in the upper Midwest; representing differing practice types and geographic settings. Full-day leadership training retreat for team leaders to facilitate of care team huddles. Biweekly coaching calls and two site visits with an assigned coach. Primary outcomes of team development and function were collected, pre- and post-intervention using surveys. Patient satisfaction and quality outcomes were compared pre- and post-intervention as secondary outcomes. Leadership engagement and adherence to the intervention were also assessed. A total of 279 pre-intervention and 272 post-intervention surveys were completed. We found no impact on team development (- 0.98, 95% CI (- 3.18, 1.22)), improved team credibility (0.18, 95% CI (0.00, 0.35)), but worse psychological safety (- 0.19, 95% CI (- 0.38, 0.00)). No differences were observed in patient satisfaction; however, results were mixed among quality outcomes. Post hoc analysis within the intervention group showed higher adherence to the intervention was associated with improvement in team coordination (0.47, 95% CI (0.18, 0.76)), credibility (0.28, 95% CI (0.02, 0.53)), team learning (0.42, 95% CI (0.10, 0.74)), and knowledge creation (0.74, 95% CI (0.35, 1.13)) compared to teams that were less engaged. Results of this evaluation showed that leadership training and facilitation were not associated with better team functioning. Additional components to the intervention tested may be necessary to enhance team functioning. Clinicaltrials.gov Identifier NCT03062670. Registration Date: February 23, 2017. URL: https://clinicaltrials.gov/ct2/show/NCT03062670.


Lipopeptides are effective stimulators of tyrosine phosphorylation in human myeloid cells.
Synthetic lipopeptide analogues of the N-terminus of bacterial lipoprotein are effective activators of macrophages, neutrophils and lymphocytes. We studied the effect of the lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]- (R)-cysteinyl-(S)-seryl-(S)-lysyl-(S)-lysyl-(S)-lysyl-(S)-lysine [Pam3Cys-Ser-(Lys)4] on tyrosine phosphorylation in dibutyryl-cyclic-AMP-differentiated HL-60 cells, using anti-phosphotyrosine antibodies. Pam3Cys-Ser-(Lys)4 concentration-dependently stimulated tyrosine phosphorylation of 100/110 kDa and 60 kDa proteins and, to a lesser extent, of 55 kDa and 70/75 kDa proteins. Half-maximal and maximal effects were observed at concentrations of 1-6 and 5-50 micrograms/ml respectively. The lipopeptide-induced increase in phosphorylation was rapid and transient, with a peak response after 30-60 s. The lipopeptide (2S)-2-palmitoylamino-6-palmitoyloxymethyl-7-palmitoyloxy heptanoyl-Ser-(Lys)4 [Pam3Ahh-Ser-(Lys)4] was as potent as Pam3Cys-Ser(Lys)4, whereas (2S,6S)-2-palmitoylamino-6,7-bis(palmitoyloxy)heptanoyl++ +-Ser-(Lys)4 [Pam3Adh-Ser-(Lys)4] and Pam3Cys-Ser-Gly did not induce tyrosine phosphorylation. Lipopeptide-induced tyrosine phosphorylation was not affected by treatment of cells with pertussis toxin. Neither phorbol 12-myristate 13-acetate nor A23187 induced tyrosine phosphorylation in dibutyryl-cyclic-AMP-differentiated HL-60 cells. In HL-60 promyelocytes, Pam3Cys-Ser-(Lys)4 had no effect on tyrosine phosphorylation, whereas the lipopeptide also induced tyrosine phosphorylation in 1,25-dihydroxyvitamin-D3-differentiated HL-60 cells and in human neutrophils. These results show that lipopeptides are effective stimulators of tyrosine phosphorylation in mature human myeloid cells.


Trends in the Use of Procalcitonin at US Children's Hospital Emergency Departments.
Procalcitonin (PCT) was approved by the Food and Drug Administration in 2016. We assessed changes in PCT utilization over time in emergency departments (EDs) at US Children's Hospitals and identified the most common conditions associated with PCT testing. We performed a cross-sectional study of children <18 years of age presenting to 1 of 33 EDs contributing data to the Pediatric Health Information System between 2016 and 2020. We examined trends in PCT utilization during an ED encounter between institutions and over the study period. Using All Patients Refined Diagnosis Related Groups, we identified the most common conditions for which PCT was obtained (overall, and relative to the performance of a complete blood count). The overall rate of PCT testing increased from 0.2% of all ED visits in 2016 to 1.8% in 2020. Across hospitals, the proportion of ED encounters with PCT obtained ranged from 0.0005% to 4.3% with marked variability in overall use. Among children who had PCT testing performed, the most common diagnoses were fever (10.7%), infections of the upper respiratory tract (9.2%), and pneumonia (5.9%). Relative to the performance of a complete blood count, rates of PCT testing were highest among children with sepsis (28.7%), fever (21.4%), pulmonary edema/respiratory failure (17.3%), and bronchiolitis/respiratory syncytial virus pneumonia (15.6%). PCT utilization in the ED has increased over the past 5 years with variation between hospitals. PCT is most frequently obtained for children with respiratory infections and febrile illnesses.


Associations of key diet-quality indexes with mortality in the Multiethnic Cohort: the Dietary Patterns Methods Project.
Healthy dietary patterns have been linked positively with health and longevity. However, prospective studies in diverse populations in the United States addressing dietary patterns and mortality are limited. We assessed the ability of the following 4 diet-quality indexes [the Healthy Eating Index-2010 (HEI-2010), the Alternative HEI-2010 (AHEI-2010), the alternate Mediterranean diet score (aMED), and the Dietary Approaches to Stop Hypertension (DASH)] to predict the reduction in risk of mortality from all causes, cardiovascular disease (CVD), and cancer. White, African American, Native Hawaiian, Japanese American, and Latino adults (n = 215,782) from the Multiethnic Cohort completed a quantitative food-frequency questionnaire. Scores for each dietary index were computed and divided into quintiles for men and women. Mortality was documented over 13-18 y of follow-up. HRs and 95% CIs were computed by using adjusted Cox models. High HEI-2010, AHEI-2010, aMED, and DASH scores were all inversely associated with risk of mortality from all causes, CVD, and cancer in both men and women (P-trend < 0.0001 for all models). For men, the HEI-2010 was consistently associated with a reduction in risk of mortality for all causes (HR: 0.75; 95% CI: 0.71, 0.79), CVD (HR: 0.74; 95% CI: 0.69, 0.81), and cancer (HR: 0.76; 95% CI: 0.70, 0.83) when lowest and highest quintiles were compared. In women, the AHEI and aMED showed large reductions for all-cause mortality (HR: 0.78; 95% CI: 0.74, 0.82), the AHEI showed large reductions for CVD (HR: 0.76; 95% CI: 0.69, 0.83), and the aMED showed large reductions for cancer (HR: 0.84; 95% CI: 0.76, 0. 92). These results, in a US multiethnic population, suggest that consuming a dietary pattern that achieves a high diet-quality index score is associated with lower risk of mortality from all causes, CVD, and cancer in adult men and women.


Phenotyping the late- and younger-onset neuronal surface antibody-mediated autoimmune encephalitis: a multicenter study.
Neuronal surface antibody-mediated autoimmune encephalitis (NSAE) occurs across a wide age range. However, few studies focused on the onset age and their related characteristics. We aimed to explore the age-dependent profile of NSAE. A total of 134 patients with a definite diagnosis of NSAE were retrospectively enrolled from 3 tertiary hospitals between July 2014 and August 2020. Demographic, clinical, therapeutic, and prognostic data were collected and compared between the late- (≥45) and younger-onset (<45) groups. The results showed that 56 (41.8%) patients were classified as late-onset NSAE, and 78 (58.2%) as younger-onset NSAE. There were more males, especially in the late-onset group (P = 0.036). Prodromal symptoms were more common in the younger-onset group (P = 0.004). Among the onset symptoms, more late-onset patients presented as seizures, while more younger-onset patients presented as psychiatric symptoms. Throughout the disease course, the late-onset patients were more likely to have memory dysfunction (P < 0.001), but less likely to have central hypoventilation (P = 0.045). The late-onset patients also had a significantly lower modified Rankin Scale score on admission (P = 0.042), required intensive care unit (ICU) admission less frequently during hospitalization (P = 0.042) and had a shorter hospital stay (P = 0.014). Our study revealed that the late- and younger-onset NSAE had a distinct spectrum of demographic features, presentations, and prognoses. More attention is needed for the younger-onset patients, given a higher disease severity on admission, more frequent requirement for ICU admission and longer length of stay.


Image analysis of dermal collagen changes during skin aging.
To determine progressive quantitative, directional and textural changes in dermal collagen as a function of age and sex and to estimate their evolutive trend with appropriate regression models. Ninety-six samples of abdominal skin from autopsy cases were analyzed. The ages ranged from 3.5 months to 86 years. Picro-Sirius-stained slides were examined by polarizing microscopy, and spatial density, directional features and texture of collagen were measured by computerized image analysis. Nonlinear regression models were built to estimate evolutive changes with respect to age. The relationship between spatial orientation of collagen bundles and age was best modeled by linear regression. The evolutive patterns of dermal thickness and spatial density of collagen bundles correspond to a second-order polynomial model with a progressive increase from childhood to middle age and a relatively sharp decrease after the seventh decade. The evolution of textural pattern of dermal collagen, defined by gradient analysis, depicts a sort of inverted U. Its complexity is maximum in the first year of life, decreases until the period 25-50 years and increases progressively after the sixth decade. The horizontal orientation of collagen bundles with intermingled fascicles oriented in other directions, shown by young individuals, is progressively simplified with aging. In elderly subjects, collagen bundles have a horizontal orientation. No significant sex-related differences were found. Dermal collagen changes related to aging are apparently independent of sex, at least in abdominal skin, and show characteristic curvilinear evolutive trends defined by decreased dermal thickness in the elderly, decrease in the spatial density of collagen bundles and increase in textural heterogeneity of the dermis. Progressive simplification in the orientation of collagen bundles leading to a predominant horizontal disposition followed a linear trend. These changes could contribute to providing a substantial morphologic basis to age-associated biomechanical alterations in the skin.


[Giant urinoma of the thigh].
A man aged 70 during a hospital stay over a period of a few weeks developed increasing pain and swelling of the left thigh. Despite extensive diagnostic imaging and surgical drainage, initially no diagnosis could be established. After more than 3 months the tumour proved to be caused by leakage of urine from the pelvis to the soft tissues of the leg. Unfamiliarity of the clinicians with such an extension of an urinoma contributed to the considerable diagnostic delay. Introduction of a bladder catheter stopped the flow of urine to the leg and reduced the leg circumference.


[Cognitive failure in terminal kidney disease].
Renal failure occurs more frequently among the elderly and elderly patients comprise an increasing proportion of dialysis patients. The objective of this paper is to review the frequency of cognitive impairment among elderly people in dialysis, and discuss causes and consequences of cognitive impairment and dementia in patients with end-stage renal disease. Prevention and treatment of cognitive impairment are discussed. The review is based on literature retrieved from a search of Medline and other web-sites, review papers and clinical experience. Cognitive impairment occurs in 20-87% of patients in haemodialysis, and the frequency is significantly more increased than that for control groups. The etiology is multifactorial, including the primary renal disease, comorbidity, the effect of uraemia and treatment-related factors. Potentially reversible factors such as anaemia and treatment complications may contribute to cognitive impairment in these patients. Cognitive impairment has major clinical consequences for compliance, resource use and the prognosis for patients with renal failure, and is often not detected by the clinicians. The authors propose that cognitive assessment should be included in the routine evaluation of elderly patients with renal failure, with potential implications for the treatment and quality of treatment for these patients.


Metamorphosis alters the response to spinal cord transection in Xenopus laevis frogs.
A series of studies has examined the response of the spinal cord to lesions made at various stages prior to and after metamorphic climax in the clawed frog Xenopus laevis. Complete transections made between Nieuwkoop and Faber (1956) stages 50 and 62 were followed by gradual recovery of righting and coordinated swimming as animals metamorphosed into juveniles (stage 66). Examination of descending axonal projections using horseradish peroxidase (HRP) showed fibers crossing the lesion site and distributing to the caudal lumbar spinal cord. These fibers could be traced from more rostral spinal segments as well as from brainstem injections of HRP. No evidence for rostrally projecting fibers crossing the lesion was obtained. Juvenile frogs of varying ages failed to demonstrate recovery of coordinated swimming or reconstitution of spinal descending pathways. In an additional series of animals, spinal transections were made within 1 or 2 days of tail resorption to assess whether regenerative capacities extended at all into post-metamorphic stages. No evidence for regeneration was found. Studies of metamorphosing frogs after spinal transections showed that fibers crossed the lesion within 5-12 days of transection, well prior to the end of metamorphic climax; however, in some cases in which metamorphosis seemed arrested, little regeneration was observed. Immunocytochemical studies showed that fibers containing serotonin (5-HT) were included in the population of axons that rapidly crossed the lesion after transection at metamorphic stages. These results are compared to those for lesions of the dorsal columns and other systems in developing and juvenile Xenopus. It is suggested that both metamorphosis-related hormonal changes, and axon substrate pathways, may affect the regenerative response in the Xenopus central nervous system (CNS).


Exploring the predictors of early readmission to psychiatric hospital.
Aims of this study are to explore the associations of readmission to psychiatric hospital over time, to develop a statistical model for early readmission to psychiatric hospital and to assess the feasibility of predicting early readmission. The sample comprised 7891 general psychiatric discharges in South London, taken from a large anonymised repository of electronic patient records. We initially explored time to readmission using Cox regression - this included investigation of time-dependent effects. Subsequently, we used logistic regression to create a predictive model for 90-day readmission. We investigated the effect on readmission of a set of variables that included demographic variables, diagnosis and legal status during the index admission, previous service use, housing variables and individual item scores on the Health of the Nation Outcome Scales (HoNOS) at admission and at discharge. Fifteen per cent of those discharged were readmitted within 90 days. Cox regression demonstrated that the estimated baseline hazard of readmission declined steeply after discharge and that the effects of several predictors, especially diagnosis, changed over time - most notably, personality disorder was associated with increased readmission relative to schizophrenia at the time of discharge, but did not significantly differ by 1-year postdischarge. In the logistic regression, increased readmission was associated with personality disorder diagnosis; shorter length of the index admission (excepting zero length admissions); number of discharges in the preceding 2 years; and having a high score at discharge on the HoNOS overactive and aggressive behaviour item, cognitive problems item or hallucinations and delusions items. Detention under Section 3 or a forensic section of the Mental Health Act during the index admission was associated with reduced readmission. The coefficient of discrimination for the logistic regression, which is equivalent to r 2, was 0.04 and the estimated area under the receiver operating curve was 0.65. The association found between early readmission and personality disorder diagnosis merits further investigation, as does the possible trade-off between reduction in length of stay and increased readmission. Other novel findings such as the associations found with HoNOS item scores also merit replication. As with previous studies, we found that the rate of readmission declines steeply after hospital discharge, so that the period immediately subsequent to discharge is a period of comparatively high risk. However, prediction of early readmission within this high-risk group remains challenging - it seems most likely that many unmeasured influences operate subsequent to the time of discharge.


Interproximal cervical lesions caused by incorrect flossing technique.
This case report describes an interproximal cervical lesion caused by the incorrect use of dental floss. A 58-year-old man who was asymptomatic, presented with unusual notch-like cervical lesions. After clinical and radiographical examinations, it was concluded that the aetiology of these lesions was an incorrect flossing technique. The treatment plan included extraction of maxillary 3rd molars and re-education of the patient in oral hygiene technique. These lesions are irreversible and often go undiagnosed; therefore, it is important for the clinician to be familiar with the clinical presentation and aetiology.


Overexpression of NELFCD promotes colorectal cancer cells proliferation, migration, and invasion.
Negative elongation factor complex member C/D (NELFCD), mapped to chromosome 20q13.32, has been found to be significantly overexpressed in colorectal cancer (CRC) by our previous research. However, whether its overexpression contributes to CRC development is unknown. We aimed to explore the biological and clinical roles of NELFCD in CRC. The expression of NELFCD was detected by qRT-PCR and Western blot. The biological function of NELFCD on CRC cell proliferation, migration, invasion, and apoptosis was detected by cell counting kit-8, plate colony formation assay, transwell migration and invasion assays, and flow cytometry in vitro and by murine xenograft tumor growth in vivo. Moreover, we evaluated the correction between its expression level and clinicopathologic parameters. We found NELFCD was overexpressed in 50 pairs of CRC tissues in comparison to the adjacent nontumor tissues (P<0.05). Knockdown of NELFCD significantly impaired cell proliferation, migration and invasion abilities, facilitated cell apoptosis in vitro, and inhibited tumorigenesis of CRC cells in vivo. NELFCD levels were remarkably connected with tumor location in CRC patients. NELFCD is overexpressed and plays an oncogenic role in CRC. Targeting NELFCD may provide a potential therapeutic option for NELFCD-amplified tumors.


Lung infarction secondary to infected pulmonary arterial thrombosis in a patient with Eisenmenger's syndrome.
A case is presented where a patient with Eisenmenger's syndrome is successfully treated for infection of chronic pulmonary arterial thrombosis with good effect. The evidence for antibiotic and anticoagulant therapy in this patient group is discussed.


Increased risk of brain tumors in children exposed to barbiturates.
The possible etiologic role of barbiturates in the development of brain tumors in children was examined. Interviews were conducted with mothers of children with brain tumors and results compared with those from interviews with mothers of normal children and mothers of children with other cancers. Mothers of children with brain tumors more frequently reported having used barbiturates during their pregnancy with the index child than did mothers of normal children or mothers of children with other cancers. In addition, more children with brain tumors were reported to have used barbiturates than were normal children or children with other malignant diseases, with most of such uses appearing to be unrelated to symptoms resulting from the brain tumor itself. The results suggested that barbiturates may play an etiologic role, and it is estimated that as many as 8% of brain tumors in children may be attributable to use of barbiturates either by the child or prenatally by the mother.


Junctional epidermolysis bullosa, pyloric atresia, and genitourinary disease.
The occasional concurrence of junctional epidermolysis bullosa and pyloric atresia has been documented in the literature. Several infants reported as having this combined disorder were also noted to have significant genitourinary disease. We treated a 4 1/2-year-old boy with mild cutaneous manifestations of junctional epidermolysis bullosa, corrected pyloric atresia, and significant renal disease secondary to recurrent obstruction of the ureterovesical junction.


Neural correlates of familial obesity risk and overweight in adolescence.
Rates of adolescent obesity and overweight are high. The offspring of overweight parents are at increased risk of becoming obese later in life. Investigating neural correlates of familial obesity risk and current overweight status in adolescence could help identify biomarkers that predict future obesity and that may serve as novel targets for obesity interventions. Our primary aim was to use functional MRI to compare neural responses to words denoting high or low energy density (ED) foods and non-foods, in currently lean adolescents at higher compared with lower familial risk for obesity, and in overweight compared with lean adolescents. Secondary aims were to assess group differences in subjective appetite when viewing food and non-food words, and in objective ad libitum intake of high-ED foods in a laboratory setting. We recruited 36 adolescents (14-19y), of whom 10 were (obese/overweight "overweight"), 16 lean with obese/overweight mothers (lean high-risk, "lean-HR"), and 10 lean with lean mothers (lean low-risk, "lean-LR"). All underwent fMRI scanning while they viewed words representing high-ED foods, low-ED foods, or non-foods, and provided appetitive ratings in response to each word stimulus. They then consumed a multi-item ad libitum buffet meal. Food compared with non-food words activated a distributed emotion/reward system including insula and pregenual anterior cingulate cortex (ACC). Participants who were at increasing risk for obesity exhibited progressively weaker activation of an attentional/regulatory system including dorsolateral prefrontal cortex (PFC), dorsal ACC, and basal ganglia nuclei (activation was greatest in lean-LR, intermediate in lean-HR, and weakest in the overweight group). These group differences were most apparent for neural responses to high-compared with low-ED foods. Lean-HR (compared with lean-LR and overweight) adolescents reported greater desire for high-ED foods. Meal intake was greatest for the overweight, then lean-HR, then lean-LR groups. Adolescents at higher obesity risk exhibited reduced neural responses to high-ED food cues in a neural system that subserves attention and self-regulation. They also reported heightened appetitive responses to high-ED cues. Interventions that promote the capacity for self-regulation could prevent youth who have a familial predisposition for obesity from translating risk into reality.


Below knee femoropopliteal bypass in severe ischaemia: results using EXS Dacron and human umbilical vein.
This paper reports our preliminary experience using EXS Dacron for infrageniculate femoropopliteal grafts in elderly patients, the majority (78%) suffering critical ischaemia. A comparison is made with human umbilical vein grafts (HUV). Ninety patients (mean age 69 years) with 92 grafts (42 EXS, 50 HUV) were followed up using ultrasound imaging to detect patency (median follow up 26 weeks (range 1-292)). Two and one year cumulative survivals were 57% and 80% for EXS Dacron and 39% and 48% for HUV respectively. Early failure of HUV grafts accounted for most but not all of the difference in survival (P = 0.0012, Wilcoxon Breslow). Graft kinking was not seen in EXS grafts and in only 2 HUV. Poor calf vessel run off was related to early graft occlusion (P = 0.01; Savage, Mantel Cox). This preliminary experience with EXS Dacron is encouraging and suggests the need for a formal randomised study.


Large-Area Resistive Strain Sensing Sheet for Structural Health Monitoring.
Damage significantly influences response of a strain sensor only if it occurs in the proximity of the sensor. Thus, two-dimensional (2D) sensing sheets covering large areas offer reliable early-stage damage detection for structural health monitoring (SHM) applications. This paper presents a scalable sensing sheet design consisting of a dense array of thin-film resistive strain sensors. The sensing sheet is fabricated using flexible printed circuit board (Flex-PCB) manufacturing process which enables low-cost and high-volume sensors that can cover large areas. The lab tests on an aluminum beam showed the sheet has a gauge factor of 2.1 and has a low drift of 1.5 μ ϵ / d a y . The field test on a pedestrian bridge showed the sheet is sensitive enough to track strain induced by the bridge's temperature variations. The strain measured by the sheet had a root-mean-square (RMS) error of 7 μ ϵ r m s compared to a reference strain on the surface, extrapolated from fiber-optic sensors embedded within the bridge structure. The field tests on an existing crack showed that the sensing sheet can track the early-stage damage growth, where it sensed 600 μ ϵ peak strain, whereas the nearby sensors on a damage-free surface did not observe significant strain change.


[Radiobiological effects on plants and animals within Semipalatinsk Test Site (Kazakhstan)].
The Semipalatinsk Test Site (STS) was the main place of nuclear devices tests in the former Soviet Union. From 1949 to 1989 about 460 nuclear explosions have been carried out at STS. Radioactive contamination of STS territory has the extremely non-uniform character. The main dose-forming radionuclides are 137Cs, 90Sr, 152Eu, as well as 154Eu, 60CO, 239,240Pu and 241Am. The greatest specific activity of 137Cs and 239,240Pu in ground are n x 10(3) kBk/kg, 152Eu - 96 kBk/kg, 154Eu - 10.4 kBk/kg, 60Co - 20.5 kBk/kg, 241Am - 15 kBk/kg. However, up to now, within STS sites exists where gamma-dose rate comes to 60 microGy/h, that is enough for induction reliable biological effects in animals and plants. Inhabiting territory of STS plants and animals are characterized by increased level of mutagenesis, changes of morpho-anatomic indices and parameters of peripheral blood, by the increase of asymmetry bilateral indices, change of composition and structure of communities.


Signaling pathways in renal cell carcinoma.
Renal cell carcinoma (RCC), the most lethal type of genitourinary cancer, is generally resistant to chemotherapy and radiation therapy. Surgical excision of the tumor at a localized stage remains the mainstay for curative therapy. A number of drugs developed in recent years have shown limited to significant efficacy in treating RCC. These drugs act by blocking critical signaling pathways associated with RCC tumor growth and survival, and angiogenesis. Beyond well-validated signaling targets such as VHL, VEGFR and mTOR, additional pathways including HGF/c-MET and Wnt/β-catenin have emerged as important to RCC pathogenesis. Mutations in one or more components of these signaling networks may affect tumor response to therapy. This review summarizes the state of knowledge about signaling pathways in RCC and discusses the known genetic and epigenetic alterations that underlie dysregulation of these pathways.


Comparison of the effects of 2,5-dimethoxy-4-iodoamphetamine and D-amphetamine on the ability of rats to discriminate the durations and intensities of light stimuli.
Rats' ability to discriminate durations is disrupted by the monoamine-releasing agent D-amphetamine and the 5-HT2 receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). It is unknown whether this effect is specific for temporal discrimination or reflects general disruption of stimulus control. This experiment addressed this question by comparing the effects of D-amphetamine and DOI on temporal discrimination and discrimination along a nontemporal dimension, light intensity. Twelve rats responded on a schedule in which a light (intensity 22 cd/m) was presented for t seconds (2.5-47.5 s), after which levers A and B were presented. Responses on A were reinforced when t was less than 25 s, and responses on B were reinforced when t was greater than 25 s. Twelve rats responded on a similar schedule in which a light of intensity i (3.6-128.5 cd/m) was presented for 25 s. Responses on A were reinforced when i was less than 22 cd/m, and responses on B were reinforced when i was greater than 22 cd/m. Logistic functions were fitted and psychophysical parameters estimated [T50, I50 (central tendency of temporal or light-intensity discrimination); Weber fraction (relative discriminative precision)]. D-Amphetamine (0.2-0.8 mg/kg) increased the Weber fraction for temporal and light-intensity discrimination; DOI (0.625-0.25 mg/kg) increased it for temporal discrimination only. Both drugs increased T50; neither altered I50. D-Amphetamine and DOI have similar effects on temporal discrimination but different effects on light-intensity discrimination. The increase in T50 may reflect the impairment of sustained attention during prolonged stimulus presentation.


Loss of function of ENT3 drives histiocytosis and inflammation through TLR-MAPK signaling.
Histiocytoses are inflammatory myeloid neoplasms often driven by somatic activating mutations in mitogen-activated protein kinase (MAPK) cascade genes. H syndrome is an inflammatory genetic disorder caused by germ line loss-of-function mutations in SLC29A3, encoding the lysosomal equilibrative nucleoside transporter 3 (ENT3). Patients with H syndrome are predisposed to develop histiocytosis, yet the mechanism is unclear. Here, through phenotypic, molecular, and functional analysis of primary cells from a cohort of patients with H syndrome, we reveal the molecular pathway leading to histiocytosis and inflammation in this genetic disorder. We show that loss of function of ENT3 activates nucleoside-sensing toll-like receptors (TLR) and downstream MAPK signaling, inducing cytokine secretion and inflammation. Importantly, MEK inhibitor therapy led to resolution of histiocytosis and inflammation in a patient with H syndrome. These results demonstrate a yet-unrecognized link between a defect in a lysosomal transporter and pathological activation of MAPK signaling, establishing a novel pathway leading to histiocytosis and inflammation.


Lifetime mood symptoms and adult separation anxiety in patients with complicated grief and/or post-traumatic stress disorder: a preliminary report.
A minority of bereaved individuals experiences symptoms of complicated grief (CG) that are associated with significant distress and impairment. CG is currently under consideration for inclusion in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) and a major issue is whether or not it can be differentiated from major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The purpose of this study is to compare the clinical features of CG with those of PTSD and CG+PTSD. A total sample of 116 patients (66 PTSD, 22 CG and 28 CG+PTSD) was recruited. Assessments included: Structured Clinical Interview for DSM-IV Axis-I disorders (SCID-I/P), Inventory of Complicated Grief (ICG), Adult Separation Anxiety Questionnaire (ASA-27), Work and Social Adjustment Scale (WSAS), and Mood Spectrum-Self Report (MOODS-SR) lifetime version. CG was strongly associated with female gender. MDD comorbidity was more common among patients with CG while bipolar disorder was highest among those with PTSD+CG. Patients with CG+PTSD reported significantly higher ASA-27 scores compared to patients with either CG or PTSD alone. Patients with CG+PTSD or PTSD alone reported significantly higher scores on the manic component of the MOODS-SR. No significant differences were reported in the WSAS scores. Our results support differences between CG and PTSD that are important for the consideration of including CG as a new disorder in the DSM-V.


Triple visual hemifield maps in a case of optic chiasm hypoplasia.
In humans, each hemisphere comprises an overlay of two visuotopic maps of the contralateral visual field, one from each eye. Is the capacity of the visual cortex limited to these two maps or are plastic mechanisms available to host more maps? We determined the cortical organization of the visual field maps in a rare individual with chiasma hypoplasia, where visual cortex plasticity is challenged to accommodate three hemifield maps. Using high-resolution fMRI at 7T and diffusion-weighted MRI at 3T, we found three hemiretinal inputs, instead of the normal two, to converge onto the left hemisphere. fMRI-based population receptive field mapping of the left V1-V3 at 3T revealed three superimposed hemifield representations in the left visual cortex, i.e. two representations of opposing visual hemifields from the left eye and one right hemifield representation from the right eye. We conclude that developmental plasticity including the re-wiring of local intra- and cortico-cortical connections is pivotal to support the coexistence and functioning of three hemifield maps within one hemisphere.


Generation of an NSD2-deficient human embryonic stem cell line using CRISPR/Cas9 technology.
NSD2 is a histone methyltransferase (HMT) and is involved in the epigenetic regulation of hematopoiesis and hematological cancers. To understand and illustrate the precise roles of NSD2 in hematopoietic development, here we constructed a human embryonic stem cell (hESC) line with knockout of NSD2 using CRISPR/Cas9-mediated gene targeting. The cell line maintained typical stem cell morphology and normal karyotype. Furthermore, the pluripotency of the cell line was evidenced by high expression level of pluripotency genes and differentiation potential into three germ layers. The cell line provides a good model for studying roles of NSD2 in embryonic development, especially hematopoiesis.


Accessing substance abuse treatment: issues for parents involved with child welfare services.
The complex issues associated with barriers to treatment entry for parents who are involved with child welfare has not been well explored. Accessing timely treatment is now critical for these parents since the introduction of the Adoption and Safe Families Act of 1997, limiting the time until a permanency decision is made. Using a longitudinal, qualitative approach, substance-abusing parents from 15 families, their relevant family members, and service providers were interviewed approximately every 3 months over an 18-month period. The experiences of these parents add to our knowledge of the unique barriers this population faces, and expands our understanding of the mechanisms by which certain barriers may delay treatment.


Fatty Acid Binding Protein-1 (FABP1) and the Human FABP1 T94A Variant: Roles in the Endocannabinoid System and Dyslipidemias.
The first discovered member of the mammalian FABP family, liver fatty acid binding protein (FABP1, L-FABP), occurs at high cytosolic concentration in liver, intestine, and in the case of humans also in kidney. While the rat FABP1 is well studied, the extent these findings translate to human FABP1 is not clear-especially in view of recent studies showing that endocannabinoids and cannabinoids represent novel rat FABP1 ligands and FABP1 gene ablation impacts the hepatic endocannabinoid system, known to be involved in non-alcoholic fatty liver (NAFLD) development. Although not detectable in brain, FABP1 ablation nevertheless also impacts brain endocannabinoids. Despite overall tertiary structure similarity, human FABP1 differs significantly from rat FABP1 in secondary structure, much larger ligand binding cavity, and affinities/specificities for some ligands. Moreover, while both mouse and human FABP1 mediate ligand induction of peroxisome proliferator activated receptor-α (PPARα), they differ markedly in pattern of genes induced. This is critically important because a highly prevalent human single nucleotide polymorphism (SNP) (26-38 % minor allele frequency and 8.3 ± 1.9 % homozygous) results in a FABP1 T94A substitution that further accentuates these species differences. The human FABP1 T94A variant is associated with altered body mass index (BMI), clinical dyslipidemias (elevated plasma triglycerides and LDL cholesterol), atherothrombotic cerebral infarction, and non-alcoholic fatty liver disease (NAFLD). Resolving human FABP1 and the T94A variant's impact on the endocannabinoid and cannabinoid system is an exciting challenge due to the importance of this system in hepatic lipid accumulation as well as behavior, pain, inflammation, and satiety.


[Cell electrophoretical characterization of the surface of Candida guilliermondii].
The electrical properties of the outer layer of the cell wall of a hydrocarbon-grown yeast C. guilliermondii were studied in detail by cell electrophoresis. Some experiments were also made with the yeast S. cerevisiae. The mobilities of the yeasts were measured as a function of pH at pH 2-11.5 and constant ionic strength I = 0.02 mol/l. For identification of surface groups the pH-mobility curves are used to calculate pK-values. The results indicate the presence of amino and carboxyl groups on the surface of C. guilliermondii. These groups are probably a part of a glyco-protein with an isoelectric point at pH 3.3 located on the surface. Electrophoresis of droplets of mineral oil coated with adsorbed protein layer confirms these conclusions. The importance of this glycoprotein in hydrocarbon uptake is discussed.


Standardization of reduced and optimal lead sets for continuous electrocardiogram monitoring: where do we stand?
Mason-Likar or proprietary reduced lead (RL) configurations are used for continuous 12-lead electrocardiogram (ECG) monitoring. Because each RL set has a different electrode configuration and derivation, they are inherently different and should not be compared with each other or with the Mason-Likar or standard ECG to determine changes in an individual over time. Recently, cases have been reported regarding misdiagnosis resulting from such invalid comparisons. This article addresses several relevant questions and presents data collected from 559 subjects (one third, prior myocardial infarction; one third, left ventricular hypertrophy; one third, healthy controls) comparing standard limb leads with body surface potential map (BSPM) leads. We conclude the following: (1) There are few circumstances that justify the use of RL 12-lead ECGs; the convenience should be weighed by the risk of misdiagnosis resulting from serial comparison of nonequivalent ECGs. (2) When RL monitoring is justified, standardization of one universally adopted method would reduce confusion about multiple proprietary lead configurations and minimize invalid ECG comparisons in individuals treated in multiple hospital units with different manufacturers' cardiac monitors. (3) Standard limb lead P-QRS-T waveforms correlate highly with BSPM leads located outside standard unipolar precordial lead sites. Until it is clear that "optimum" BSPM lead sites do not overlap with ECG information already contributed from standard limb leads, it is premature to recommend alternative lead sites for ECG monitoring.


Vibrio parahaemolyticus in shellfish and clinical samples during two large epidemics of diarrhoea in southern Chile.
Large epidemics of diarrhoea associated with seafood consumption and Vibrio parahaemolyticus occurred during the austral summers of 2004 and 2005 in the environs of Puerto Montt, Chile (41 degrees 29'S 72 degrees 24'W). There are no reports of V. parahaemolyticus infections before 2004 in this region, their absence being explained by the low ocean temperatures which seldom reach 16 degrees C. We analysed V. parahaemolyticus obtained from shellfish and clinical samples during epidemics. Isolates were examined using conventional protocols and an improved method for restriction enzyme analysis using total bacterial DNA which permits direct genome restriction enzyme analysis by conventional gel electrophoresis (DGREA) with a similar discrimination index as restriction fragment length polymorphism-pulsed field gel electrophoresis (RFLP-PFGE). Analysis of clinical samples showed that the epidemics were caused by the V. parahaemolyticus O3:K6 pandemic clonal group. On the other hand, analysis of shellfish samples during both epidemics showed that 53% contained V. parahaemolyticus (3-93 g(-1)). Detailed analysis of 50 positive shellfish samples showed that only three contained detectable levels of the pandemic clone. Most V. parahaemolyticus isolates obtained from shellfish corresponded to non-pandemic clones differentiated into 14 groups by DGREA. In summary, the causative agent during epidemics was only a minor component of a small but diverse population of V. parahaemolyticus in shellfish.


A note on the asymptotic distribution of likelihood ratio tests to test variance components.
When using maximum likelihood methods to estimate genetic and environmental components of (co)variance, it is common to test hypotheses using likelihood ratio tests, since such tests have desirable asymptotic properties. In particular, the standard likelihood ratio test statistic is assumed asymptotically to follow a chi2 distribution with degrees of freedom equal to the number of parameters tested. Using the relationship between least squares and maximum likelihood estimators for balanced designs, it is shown why the asymptotic distribution of the likelihood ratio test for variance components does not follow a chi2 distribution with degrees of freedom equal to the number of parameters tested when the null hypothesis is true. Instead, the distribution of the likelihood ratio test is a mixture of chi2 distributions with different degrees of freedom. Implications for testing variance components in twin designs and for quantitative trait loci mapping are discussed. The appropriate distribution of the likelihood ratio test statistic should be used in hypothesis testing and model selection.


Human ALX receptor regulates neutrophil recruitment in transgenic mice: roles in inflammation and host defense.
Signaling pathways instrumental in the temporal and spatial progression of acute inflammation toward resolution are of wide interest. Here a transgenic mouse with myeloid-selective expression of human lipoxin A4 receptor (hALX) was prepared and used to evaluate in vivo the effect of hALX expression. hALX-transfected HEK293 cells transmitted LXA4 signals that inhibit TNFalpha-induced NFkappaB activation. Transgenic FvB mice were generated by DNA injections of a 3.8 kb transgene consisting of the full-length hALX cDNA driven by a fragment of the hCD11b promoter. When topically challenged via dermal ear skin, hALX transgenic mice gave attenuated neutrophil infiltration (approximately 80% reduction) in response to leukotriene B4 (LTB4) plus prostaglandin E2 (PGE2) as well as approximately 50% reduction in PMN infiltrates (P<0.02) to receptor-bypass inflammation evoked by phorbol ester. The hALX transgenic mice gave markedly decreased PMN infiltrates to the peritoneum with zymosan and altered the dynamics of this response. Transgenic hALX mice displayed increased sensitivity with >50% reduction in PMN infiltrates to suboptimal doses (10 ng/mouse) of the ligand lipoxin A4 stable analog compared with <10% reduction of PMN in nontransgenic littermates. Soluble mediators generated within the local inflammatory milieu of hALX mice showed diminished ability to activate the proinflammatory transcription factor NFkappaB. Analyses of the lipid-derived mediators from exudates using LC-MS tandem mass spectroscopy indicated an altered profile in hALX transgenic mice that included lower levels of LTB4 and increased amounts of lipoxin A4 compared with nontransgenic littermates. Together these results demonstrate a gain-of-function with hALX transgenic mouse and indicate that ALX is a key receptor and sensor in formation of acute exudates and their resolution.


Nutritional supplements and cancer: potential benefits and proven harms.
Nutritional supplements are widely used among patients with cancer who perceive them to be anticancer and antitoxicity agents. Large-scale, randomized cancer prevention trials have mainly been negative, with some notable adverse and beneficial effects. For example, these trials showed that beta-carotene increases the risk of lung and stomach cancer, vitamin E increases prostate cancer and colorectal adenoma, and selenium reduces gastric and lung cancer in populations with low selenium levels but increase rates in those with higher levels. Both beta-carotene and vitamin E supplementation increase overall mortality. This article reviews phase II and III trials that examine the effects of multivitamins, antioxidants, vitamin D, and n-3 supplements on outcome and toxicity from cancer treatments. Although vitamin E and beta-carotene reduce toxicity from radiotherapy among patients with head and neck cancer, it has been found to increase recurrence, especially among smokers. Antioxidants have mixed effects on chemotherapy toxicity, but there are no data on outcome. Vitamin D deficiency is relatively common among patients with cancer, and ongoing phase III trials are studying the effect of vitamin D on outcome as well as optimum vitamin D and calcium intakes for bone health. Docosahexanoic and eicosopentanoic acid supplements have mixed effects on cachexia and are currently being tested as potential adjuncts to maximize response to chemotherapy. Nutritional supplementation tailored to an individual's background diet, genetics, tumor histology, and treatments may yield benefits in subsets of patients. Clinicians should have an open dialogue with patients about nutritional supplements. Supplement advice needs to be individualized and come from a credible source, and it is best communicated by the physician.


Is Zhang the new Friedman: How should we evaluate the first stage of labor?
Norms used to describe and evaluate the first stage of labor have been historically based upon data from the middle of the twentieth century. More recent data has characterized the normal first stage of labor differently including that the latent phase of labor is longer not transitioning from latent to active labor until about 6 cm of cervical dilation in a majority of women, regardless of parity or whether labor was spontaneous or induced. Additionally, the amount of time that can take for progress to be made in active labor be longer than previously understood. These two factors would lead to a change in management with the diagnosis of arrest of the first stage of labor being made at 6 cm cervical dilation or beyond in the setting of ruptured membranes and no cervical change for at least 4 h of adequate contractions or 6 h of inadequate contractions.


Main and moderating effects of temperament traits on the association between intimate partner violence and hazardous alcohol use in a sample of young adult women.
Hazardous alcohol use is a common problem among survivors of intimate partner violence (IPV), although not all women who experience IPV exhibit hazardous alcohol use. Recent research has suggested that 1 factor that may influence hazardous alcohol use is temperament, although this has not yet been examined in the context of IPV. In this study, we examine the main and moderating effects of temperament traits (constraint, negative emotionality, and positive emotionality) on the association between IPV and hazardous alcohol use in a sample of young adult women (N = 654) using a Bayesian approach to multiple linear regression. Results indicated that each temperament trait incrementally predicted hazardous alcohol use over and above the effects of IPV and other negative life events. Results further indicated that both negative emotionality and positive emotionality moderated the influence of IPV on hazardous alcohol use such that IPV was positively associated with hazardous alcohol use at high levels of these traits but not at low levels. Study findings extend previous research on the effects of temperament traits to the context of IPV, underscoring the importance of including temperament in the assessment of IPV survivors. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Antitumor effects in mice of the intravenous injection of attenuated Salmonella typhimurium.
Salmonella typhimurium genetically modified at the purI and msbB genes to increase dependence on adenine and decrease stimulation of tumor necrosis factor-alpha production were injected intravenously into C57BL/6 mice bearing subcutaneous tumor or lung metastases. Decreased tumor growth and prolonged survival were seen in some, but not all of nine transplantable tumors. Salmonella increased in number in the tumor and reached levels 10,000 times higher than in the normal liver reservoir of these bacteria. Histologic studies revealed Salmonella growth in areas of the tumor although, in all cases, a viable rim of tumor survived and ultimately resulted in progressive tumor growth in all mice. These studies demonstrate that Salmonella can localize to transplantable murine tumors and partially inhibit tumor growth; however, additional modifications of the bacteria may be necessary if this approach is to develop into an effective treatment for patients with cancer.


The Menstrual Cycle, Sex Hormones, and Anterior Cruciate Ligament Injury.
OBJECTIVE: To determine if anterior cruciate ligament (ACL) injuries in female athletes occur randomly or correlate with a specific phase of the menstrual cycle. DESIGN AND SETTING: Female athletes who sustained ACL injuries reported the days of their menstrual cycles and provided saliva samples for sex-hormone determination. Salivary sex-hormone profiles were assessed to confirm the self-reported menstrual histories. SUBJECTS: A total of 38 female athletes (20 college, 15 high school, 1 middle school, 2 recreational) with recent ACL injuries participated in the study over a 3-year period. MEASUREMENTS: Athletes with recent ACL injuries completed a questionnaire defining the injury, the last menstrual cycle, prior knee injury, school, and type of birth control used (if any). Each subject provided a 30-cc saliva sample within 72 hours of injury. Saliva samples were placed into sealed containers and frozen at -20 degrees C. We obtained 13 additional control samples from uninjured females to test the correlation between saliva and serum sex-hormone levels. Progesterone and estrogen were assayed by radioimmunoassay. Physical examination, magnetic resonance imaging, or surgery confirmed the injury in all subjects. RESULTS: The correlations between saliva and serum estrogen and progesterone were 0.73 (alpha =.01) and 0.72 (alpha =.01), respectively. Ten of 27 athletes who reported their cycle day at time of injury sustained an ACL injury immediately before or 1 to 2 days after the onset of menses. We rejected the null hypothesis that such high frequency was due to random chance. CONCLUSIONS: A significantly greater number of ACL injuries occurred on days 1 and 2 of the menstrual cycle. Salivary sex-hormone levels correlated with the reported cycle day.


MARKOVIAN MODEL OF TIME PATTERNS OF SPEECH.
The time pattern of speech is describable as a first-order Markov process when presence or absence is sampled at a rate of 200 times per minute. Two types of monolog were generated under different conditions of environmental constraint. Although both fit the model, estimates of their mean range of statistical dependency differed significantly.


Feasibility study of faecal sludge treatment by Geotube and jute tube-based technologies.
The decentralized standalone treatment of faecal sludge is a generally cumbersome, energy-intensive, and expensive process. Particle size enlargement, dewatering, and disinfection are the crucial unit operations that contribute to the major portion of the operational expenditure. Therefore, the present study took up the task to investigate and yield a natural alternative to each of the above-delineated unit operations. Crushed seed powders of Moringa, Guilandina bonduc, Nirmali, tamarind, soap nut, nutmeg, jackfruit, and custard apple were experimented as natural coagulants, while a double-stitched cow dung-lined jute tube was utilized as the media for solid-liquid separation. Finally, the powder of Neem and custard apple seed and leaf were considered herbal disinfectants for the separated liquid and solid fractions, respectively. The findings of the physicochemical and biological analyses of the above unit operations were compared with a conventional polymer-based Geotube-driven treatment scheme. The natural alternatives registered some promising outcomes. However, the combined treatment efficiency of 79.32% (mean value of TS, TSS, TDS, COD, and BOD percentage removal) for pollutant removal and disinfection could not exceed the value of 97.98% offered by the conventional method. Further, the financial comparison for processing a 10 KL batch of FS indicates that the conventional scheme is considerably cheaper (USD 7.95) than the herbal alternate (USD 22.1). Therefore, though the present findings depict promising alternatives for sustainable and eco-friendly faecal sludge treatment, the authors advocate conducting further research to address the existing challenges to facilitate their seamless implementation on a field-scale level.


Defining New Limits in Gas Separations Using Modified ZIF Systems.
Zeolitic-imidazolate frameworks (ZIFs) are candidate materials for the next generation of membranes for cheaper, "greener" separations. More than a decade after ZIF introduction, the high propylene/propane selectivity of ZIF-8 and ZIF-67 is the only example of ZIF membranes with remarkable selectivity efficiency despite their numerous advantages over other families of materials. Herein, we demonstrate the effectiveness of molecular-scale modification in the design of new ZIF materials useful for the separation of important and highly challenging mixtures such as He/CH4, H2/CH4, O2/N2, CO2/CH4, and CO2/N2. Via computational methods, metal and linker substitutions are employed to produce new ZIF-8 variants with a finely discretized range of aperture sizes, as these govern the kinetic-based selectivity of the material. The permeability and selectivity through the ZIF-8 variants of the gases under study are estimated, and their performance is compared with an extensive number of polymeric, metal-organic framework, covalent-organic framework, and mixed-matrix membranes. The comparison shows that some of the ZIF-8 analogues can be used as membranes of unprecedented high separation performance. The scope of this work is to highlight the effectiveness of the molecular level design as means of membrane development to address the global need for cheaper separation methods and CO2 emission reduction.


Lambda-light-chain nephropathy with Fanconi's syndrome.
Renal disease is a common complication of paraproteinemia, but light-chain nephropathy with resultant Fanconi's syndrome is unusual. In a 60-year-old man with Fanconi's syndrome, the underlying disease was a well-differentiated lymphocytic lymphoma, with two paraproteins and lambda-light-chain proteinuria. A renal biopsy specimen showed crystals in tubular cells, more prominent in proximal than distal tubules. Immunoperoxidase studies confirmed the lambda-light-chain content of the crystals. All previous cases studied by biopsy have involved kappa light chains. Light chains are thought to be toxic to the tubular epithelium, resulting in Fanconi's syndrome. Case reports of lymphoproliferative disorders associated with paraproteinemia and Fanconi's syndrome suggest a somewhat better prognosis with this clinical entity.


Cancer proteomics.
Cancer presents high mortality and morbidity globally, largely due to its complex and heterogenous nature, and lack of biomarkers for early diagnosis. A proteomics study of cancer aims to identify and characterize functional proteins that drive the transformation of malignancy, and to discover biomarkers to detect early-stage cancer, predict prognosis, determine therapy efficacy, identify novel drug targets, and ultimately develop personalized medicine. The various sources of human samples such as cell lines, tissues, and plasma/serum are probed by a plethora of proteomics tools to discover novel biomarkers and elucidate mechanisms of tumorigenesis. Innovative proteomics technologies and strategies have been designed for protein identification, quantitation, fractionation, and enrichment to delve deeper into the oncoproteome. In addition, there is the need for high-throughput methods for biomarker validation, and integration of the various platforms of oncoproteome data to fully comprehend cancer biology.


FRA1 Kinesin Modulates the Lateral Stability of Cortical Microtubules through Cellulose Synthase-Microtubule Uncoupling Proteins.
Cell wall assembly requires harmonized deposition of cellulose and matrix polysaccharides. Cortical microtubules orient the deposition of cellulose by guiding the trajectory of cellulose synthase complexes. Vesicles containing matrix polysaccharides are thought to be transported by the FRAGILE FIBER1 (FRA1) kinesin to facilitate their secretion along cortical microtubules. The cortical microtubule cytoskeleton thus may provide a platform to coordinate the delivery of cellulose and matrix polysaccharides, but the underlying molecular mechanisms remain unknown. Here, we show that the tail region of the Arabidopsis (Arabidopsis thaliana) FRA1 kinesin physically interacts with cellulose synthase-microtubule uncoupling (CMU) proteins that are important for the microtubule-dependent guidance of cellulose synthase complexes. Interaction with CMUs did not affect microtubule binding or motility of the FRA1 kinesin but differentially affected the protein levels and microtubule localization of CMU1 and CMU2, thus regulating the lateral stability of cortical microtubules. Phosphorylation of the FRA1 tail region inhibited binding to CMUs and consequently reversed the extent of cortical microtubule decoration by CMU1 and CMU2. Genetic experiments demonstrated the significance of this interaction to the growth and reproduction of Arabidopsis plants. We propose that modulation of CMU protein levels and microtubule localization by FRA1 provides a mechanism that stabilizes the sites of deposition of both cellulose and matrix polysaccharides.


[Anterior approach and simultaneous tension-free repair of bilateral inguinal hernia under local anesthesia].
An analysis of prospectively collected data of 56 patients submitted to bilateral hernia repair is reported. Simultaneous repair was performed in 32 patients (Group S) while a sequential repair in 24 (Group D). Mean operating time was longer for the combination of two sequential repairs than for simultaneous repair (132 min +/- 8.9 vs 123 min +/- 11, p < 0.001). Mean hospital stay was similar in unilateral and bilateral repairs (18.0 hrs +/- 4 vs 21.2 hrs +/- 3.4, p = ns). Ther were no difference in complications between the two groups. Time taken to return to full activity was nearly double in the combination of two sequential repairs than in simultaneous repair (25 days, sd +/- 4 vs 16 days +/- 3, p < 0.001), while postoperative analgesia requirements were similar. The Authors conclude that bilateral simultaneous anterior tension free repair under local anesthesia is the treatment of choice in case of bilateral inguinal hernias.


Effortful Control - A Transdiagnostic Dimension Underlying Internalizing and Externalizing Psychopathology.
Effortful control (EC) or self-regulation refers to the ability to regulate behavior, emotion, and cognition. It has been identified as a contributor to both adaptive and adverse outcomes in children, adolescents, and adults and this across many domains. As such, it could be considered as a transdiagnostic dimension underlying internalizing (e.g., mood and anxiety disorders) and externalizing (e.g., substance use disorders, ADHD) psychopathology. We aimed to examine the role of EC throughout the adult psychopathological spectrum by means of a literature search of studies published between 2008 and 2018. Overall, the results point to the role of EC in the development of a broad spectrum of psychiatric diagnosis, reflecting the transdiagnostic characteristic of this construct. This role may be both directly causal or as a mediator factor influencing outcomes of a specific disorder. Early assessment of EC and early interventions to improve EC might help to avoid or decrease the risk of developing psychopathology.


[Radionuclide ventriculography in the diagnosis of hypertrophic cardiomyopathy].
Total and regional (by 7 zones) contractility of left ventricular functions in 25 patients with hypertrophic cardiomyopathy (HCMP) were characterized by a different combination of normal and elevated values of total and regional ejection fractions, rate indices of systolic expulsion. Normal or slightly changed values of the end-diastolic volume were combined with normal or elevated values of the stroke volume. Comparative analysis of the values characterizing cardiodynamics, led to working out criteria of differential diagnosis in HCMP patients with heart pain and in CHD patients with myocardial hypertrophy (predominance of the signs of left ventricular hyperfunction in the former and contractility hypofunction and asynergy in the latter). Changes in the diastolic filling of the left ventricle indicated its disturbed diastolic function in both groups of patients.