Monitoring drought pattern for pre- and post-monsoon seasons in a semi-arid region of western part of India.
Drought has become a regular phenomenon in the western semi-arid regions of India, where severe drought occurs once in 8-9 years. Therefore, two drought indices, namely temperature condition index (TCI) and vegetation condition index (VCI), were prepared from using Landsat datasets to appraise and monitor of drought pattern for the pre- and post-monsoon seasons between 1996 and 2016 in the Latur district, the north-western part of India. Additionally, the average frequency layers (AFL) of all drought and land use indices were prepared to analyse the correlation between them. The results show a substantial increase in the area under high, very high and severe drought classes both pre- and post-monsoon seasons during the study period. The highest increase was noticed from the high drought class from 2532.45 to 4792.49 sq. km and 1559.84 to 3342.32 sq. km for pre- and post-monsoon season, respectively, based on the TCI and 1269.81 to 1787.77 sq. km in very high drought class for the post-monsoon season using the VCI. The correlation analysis showed that there exists a significant relationship between the land use indices and drought indices. However, the spatial pattern of correlation was heterogeneous for both pre- and post-monsoon seasons. The results of this research can help in the drought management and mitigation planning in the study area. In addition, a similar approach may be applied to analyse drought patterns in other places with similar geographic characteristics as both VCI and TCI are cost-effective and less time-consuming methods and produce reliable outcomes.


Tissue transglutaminase, protein cross-linking and Alzheimer's disease: review and views.
Extensive protein cross-linking and aggregation are some of the most common molecular events in the pathogenesis of Alzheimer's disease (AD). Both beta-amyloid (Abeta) plaques and neurofibrillary tangles, which are extracellular and intracellular proteinaceous aggregates, respectively, contribute to neuronal death and progressive cognitive decline. Although protein cross-linking has been recognized and extensively studied for many years, the underlying mechanisms are largely unknown. Recent data indicates that tissue transglutaminase (tTG), which catalyzes the cross-linking of a wide spectrum of proteins including Abeta, tau, alpha-synuclein and neurofilament proteins, may be involved in protein aggregation in AD. Many AD risk factors, such as trauma, inflammation, ischemia and stress, up-regulate tTG protein and activity levels. In this review, we summarize the evidence that tTG plays a role in AD, especially in cross-linking of Abeta, tau, alpha-synuclein and neurofilament proteins. An experimentally testable hypothesis is that tTG may play a central role in AD pathogenesis and that it provides a conceptual link between sporadic and familial AD through a shared pathogenic pathway.


The effect of sleep on conscious sedation: a follow-up study.
This study evaluated the effect of preoperative sleep on the success of conscious sedation. Seventy-six children, from 18 to 61 months of age, participated in this study. Sixty-two children received chloral hydrate (50-60 mg/kg) and hydroxyzine (15-35 mg) and 14 children received intramuscular meperidine hydrochloride (2.2 mg/kg). Parents were asked to complete a questionnaire which asked several questions about their child's activity the previous day, and their bedtime. The operator ranked the sedations on a scale of 1 to 4, with 1 being good and 4 being poor. The results were statistically evaluated using the Wilcoxon Rank sum test. The children that received a normal amount or greater amount of sleep preoperatively did not show any significantly higher degree of success (p < 0.26) with their sedation appointment. The parents' perception of their child's tiredness did demonstrate borderline (p < 0.08) significance. Children greater than 36 months of age had a significantly higher (p < 0.03) degree of successful sedations. The results of this study demonstrated that there was no clear correlation between the child's preoperative sleep and the outcome of the sedation, but that a tired child may increase the likelihood of a poor sedation. In addition, the child's age at the time of the sedation may affect the outcome of the sedation.


Role of sperm apoptosis and oxidative stress in male infertility: A narrative review.
Activation of caspase, externalization of phosphatidyl serine, change in the mitochondrial membrane potential, and DNA fragmentation are apoptosis markers found in human ejaculated spermatozoa. Also, reactive oxygen species (ROS) play a vital role in the different types of male infertility. In this review, data sources including Google Scholar, Scopus, PubMed, and Science Direct were searched for publications with no particular time restriction to get a holistic and comprehensive view of the research. Apoptosis regulates the male germ cells, correct function and development from the early embryonic stages of gonadal differentiation to fertilization. In addition to maintaining a reasonable ratio between the Sertoli and germ cells, apoptosis is one of the well-known quality control mechanisms in the testis. Also, high ROS levels cause a heightened and dysregulated apoptotic response. Apoptosis is one of the well-known mechanisms of quality control in the testis. Nevertheless, increased apoptosis may have adverse effects on sperm production. Recent studies have shown that ROS and the consequent oxidative stress play a crucial role in apoptosis. This review aims to assimilate and summarize recent findings on the apoptosis in male reproduction and fertility. Also, this review discusses the update on the role of ROS in normal sperm function to guide future research in this area.


In vitro production of short-chain fatty acids from resistant starch by pig faecal inoculum.
The need to improve the knowledge of fermentation processes within the digestive tract in pigs is growing, particularly for ingredients that may act as potential prebiotic sources, such as resistant starch (RS). A study (based on enzymatic digestion followed by in vitro fermentation) was conducted to investigate whether various sources of RS, obtained from eight native starches characterized by inherent heterogeneous starch chemistry and structure, can influence short-chain fatty acid (SCFA) concentrations and relative production kinetics. Total and individual SCFA productions were evaluated over time and up to 72 h of incubation. The in vitro hydrolysis of native starches allowed a classification from very high [≥ 650 g/kg dry matter (DM)] to low (<50 g/kg DM) RS amount. The total SCFA production was similar between ingredients, whereas acetate and butyrate molar ratios in the SCFA profile differed (from 0.48 to 0.56 and from 0.17 to 0.25, respectively; P < 0.05). Differences in fermentation kinetic parameters for total and individual SCFA productions were observed (P < 0.05). Considering the total SCFA production after 72 h of incubation, the time at which half of the maximum production has been reached (T 1/2), the maximum rate of production (R max) and its time of occurrence (T max) differed between ingredients (P < 0.05), with values ranging from 6.1 to 11.9 h, from 0.459 to 1.300 mmol/g DM incubated per hour and from 5.1 to 9.8 h, respectively. Overall, a similar trend was observed considering individual SCFA productions. In particular, T 1/2 ranged from 6.4 to 12.5 h, from 5.5 to 12.5 h and from 6.7 to 11.3 h for acetate, propionate and butyrate, respectively (P < 0.05). For R max, differences were obtained for propionate and butyrate productions (P < 0.05), whereas no difference was recorded for acetate. In summary, our findings indicated that both quantitative and qualitative production of SCFA and related kinetics were influenced by fermentation of RS obtained from native starches characterized by heterogeneous starch characteristics. Current findings are based on an in vitro approach, and thus require further in vivo validations.


The plant pathogen Pseudomonas fuscovaginae contains two conserved quorum sensing systems involved in virulence and negatively regulated by RsaL and the novel regulator RsaM.
Pseudomonas fuscovaginae is a Gram-negative fluorescent pseudomonad pathogenic towards several plant species. Despite its importance as a plant pathogen, no molecular studies of virulence have thus far been reported. In this study we show that P. fuscovaginae possesses two conserved N-acyl homoserine lactone (AHL) quorum sensing (QS) systems which we designated PfsI/R and PfvI/R. The PfsI/R system is homologous to the BviI/R system of Burkholderia vietnamiensis and produces and responds to C10-HSL and C12-HSL whereas PfvI/R is homologous to the LasI/R system of Pseudomonas aeruginosa and produces several long-chain 3-oxo-HSLs and responds to 3-oxo-C10-HSL and 3-oxo-C12-HSL and at high AHL concentrations can also respond to structurally different long-chain AHLs. Both systems were found to be negatively regulated by a repressor protein which was encoded by a gene located intergenically between the AHL synthase and LuxR-family response regulator. The pfsI/R system was regulated by a novel repressor designated RsaM while the pfvI/R system was regulated by both the RsaL repressor and by RsaM. The two systems are not transcriptionally hierarchically organized but share a common AHL response and both are required for plant virulence. Pseudomonas fuscovaginae has therefore a unique complex regulatory network composed of at least two different repressors which directly regulate the AHL QS systems and pathogenicity.


A double-blind, multicenter, parallel-group study of paroxetine, desipramine, or placebo in breast cancer patients (stages I, II, III, and IV) with major depression.
This study compared the efficacy and safety of paroxetine and desipramine with those of placebo in the treatment of depressive disorders in adult women with breast cancer, stages I-IV. In a double-blind, placebo-controlled study, 35 female outpatients with breast cancer and DSM-III-R major depression or adjustment disorder with depressed mood were randomly assigned to treatment with paroxetine (N=13), desipramine (N=11), or placebo (N=11) for 6 weeks. Primary efficacy was assessed by change from baseline in score on the 21-item Hamilton Rating Scale for Depression (HAM-D), and the secondary outcome measure was change from baseline in the Clinical Global Impressions-Severity of Illness scale (CGI-S) score. Mean changes in the total HAM-D and CGI-S scores from baseline to 6-week endpoint for the paroxetine and desipramine groups were not significantly different than those for the placebo-treated group. An unusually high rate of response (defined as >or=50% improvement in the HAM-D score) in the placebo group was observed (55% [N=6]); adverse events precipitated patient discontinuation in the active treatment groups (9% [N=1] for desipramine, 15% [N=2] for paroxetine) similar to that in the placebo-treated patients (18% [N=2]). Improvement on symptom dimensions within the HAM-D and Hamilton Rating Scale for Anxiety (depressive, anxiety, cognitive, neurovegetative, or somatic) was also similar between groups. The small number of women in this study most likely contributed to the lack of observed differences in efficacy observed during the 6 weeks of treatment. Randomized, placebo-controlled trials of adequate power seeking to determine efficacy of antidepressants in the United States for the treatment of women with breast cancer and comorbid depression remain of paramount importance.


Addressing challenges in palladium-catalyzed cross-coupling reactions through ligand design.
The development of palladium-catalyzed cross-coupling reactions has revolutionized the synthesis of organic molecules on both bench-top and industrial scales. While significant research effort has been directed toward evaluating how modifying various reaction parameters can influence the outcome of a given cross-coupling reaction, the design and implementation of novel ancillary ligand frameworks has played a particularly important role in advancing the state-of-the-art. This Review seeks to highlight notable examples from the recent chemical literature, in which newly developed ancillary ligands have enabled more challenging substrate transformations to be addressed with greater selectivity and/or under increasingly mild conditions. Throughout, the importance and subtlety of ligand effects in palladium-catalyzed cross-coupling reactions are described, in an effort to inspire further development and understanding within the field of ancillary ligand design.


Aromatic acids derived from phenylalanine in the tissues of rats with experimentally induced phenylketonuria-like characteristics.
1. Aromatic acids were extracted from brain and liver of rats with phenylketonuria-like characteristics produced by administration of phenylalanine, either alone or in combination with p-chlorophenylalanine. The metabolism of the aromatic acids in these tissues was measured by gas chromatography. 2. At 1h after an intraperitoneal injection of l-phenylalanine (1g/kg) in 23-day-old rats, the phenyl-lactate concentration was 2.2mug/g in the liver and 0.43mug/g in the brain, and the concentration of o-hydroxyphenylacetate was 0.26mug/g in the liver. 3. Phenylacetate concentrations in brain and liver were 0.26 and 0.14mug/g respectively. 4. Suckling rats produced phenyl-lactate less rapidly than weanling rats, but accumulated higher concentrations in longer-term experiments. 5. Intraperitoneal injections of phenyl-lactic acid showed that this compound could directly penetrate the blood-brain barrier, and could produce similar brain/liver ratios of phenyllactate to those found after phenylalanine injection. 6. Qualitative and quantitative similarities in urinary excretion of aromatic acids between the rats used in this study and human patients with uncontrolled phenylketonuria indicate that a patient with a circulating phenylalanine concentration of the order of those achieved in the experimental animal may have aromatic acid concentrations in brain and liver comparable with those found in the rats used in the present study.


Nonpegylated liposomal doxorubicin combination regimen in patients with diffuse large B-cell lymphoma and cardiac comorbidity. Results of the HEART01 phase II trial conducted by the Fondazione Italiana Linfomi.
The purpose of this phase 2, multicenter study was to determine the activity and safety of nonpegylated liposomal doxorubicin as part of "R-COMP" combination in patients with diffuse large B-cell lymphoma and coexisting cardiac disorders. The study was conducted using a Bayesian continuing assessment method using complete remission rate and rate of cardiac events as study endpoints. Between November 2009 and October 2011, 50 evaluable patients were enrolled (median age, 76 years). Median baseline left ventricular ejection fraction (LVEF) was 60%. Ischemic cardiopathy was the most frequent preexisting cardiac disorder (35%), followed by atrial fibrillation (15%), left ventricular hypertrophy (13%), and baseline LVEF <50% (12%). Based on the intent to treat analysis, overall response rate was 72%, including 28 patients in complete remission (complete remission rate, 56%), and 8 in partial remission (16%). At the end of treatment, grades 3 to 4 cardiac events were observed in 6 patients. No significant modifications from baseline values of LVEF were observed during treatment and follow-up. Nonpegylated liposomal doxorubicin instead of doxorubicin in the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen is a feasible option for patients with diffuse large B-cell lymphoma presenting with concomitant cardiac disorders.


Specificity of CD8+ T-Cell Responses Following Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya.
Sub-Saharan Africa carries the biggest burden of the human immunodeficiency virus type 1 (HIV-1)/AIDS epidemic and is in an urgent need of an effective vaccine. CD8+ T cells are an important component of the host immune response to HIV-1 and may need to be harnessed if a vaccine is to be effective. CD8+ T cells recognize human leukocyte antigen (HLA)-associated viral epitopes and the HLA alleles vary significantly among different ethnic groups. It follows that definition of HIV-1-derived peptides recognized by CD8+ T cells in the geographically relevant regions will critically guide vaccine development. Here, we study fine details of CD8+ T-cell responses elicited in HIV-1/2-uninfected individuals in Nairobi, Kenya, who received a candidate vaccine delivering conserved regions of HIV-1 proteins called HIVconsv. Using 10-day cell lines established by in vitro peptide restimulation of cryopreserved PBMC and stably HLA-transfected 721.221/C1R cell lines, we confirm experimentally many already defined epitopes, for a number of epitopes we define the restricting HLA molecule(s) and describe four novel HLA-epitope pairs. We also identify specific dominance patterns, a promiscuous T-cell epitope and a rescue of suboptimal T-cell epitope induction in vivo by its functional variant, which all together inform vaccine design.


Changes of coagulation parameters during high altitude expedition.
Data on changes of haemostatic parameters at altitudes above 5000 m are very limited. So far it is unknown, whether altered coagulation could contribute to the development of acute mountain sickness. Thirty four healthy mountaineers were randomised to two acclimatisation protocols and undertook an expedition on Muztagh Ata (7549 m) in China. Tests were performed at five altitudes up to 6865 m. Haemostatic parameters, such as PT, aPTT, D-Dimer, APC-Resistance (APCR), von Willebrand Factor activity (RCo), ADAMTS-13 & C-Natriuretic Peptide (CNP) were assessed together with Lake Louise AMS score. D-Dimer significantly increased with increasing altitude (median 0.62 to 0.81 mcg/L, p <0.0001). During ascent, PT increased (83% to >100%) and APCR decreased significantly from 0.95 to 0.8 (p <0.01). Furthermore, a significant increase of aPTT (38 to 43 sec) was paralleled by significant changes of RCo (102% to 62%) (both p <0.001). There were no significant changes in ADAMTS-13 and CNP. No significant relationship between investigated parameters and AMS scores could be detected. When comparing the participants of the two acclimatisation protocols, there was an overall higher RCo in patients with a faster ascent protocol (p = 0.04). This was accompanied by lower ADAMTS-13 of the coagulation system in these patients (p = 0.04). Coagulation parameters change significantly during hypobaric hypoxia. Whereas we could detect no association between AMS scores and coagulation parameters, our results do show some parameters to be associated with an acclimatisation protocol and a successful ascent to the summit.


[Medium molecular weight molecules and their fractions in Astrakhan rickettsial fever].
The level of medium-weight molecules (MWM) over the course of disease and changes in the lipid share of MWM fractions at the peak of disease were studied in patients with Astrakhan rickettsial fever (ARF). The level of MWM was significantly increased in comparison with the control and MWM concentration clearly correlated with the severity of intoxication. A level higher than 600 U is an unfavorable sign of a grave course. The significance of the lipid part of MWM fraction in the formation of the intoxication syndrome in ARF is shown.


Establishment of a new diagnostic method for hydropic villi by using TSSC3 antibody.
A total of 297 samples of hydropic villi were classified according to DNA polymorphisms as androgenetic moles, dispermic triploids, or biparental diploids. A subset of 267 appropriate samples was included in the study. Most of the macroscopically diagnosed complete mole cases were genetically androgenetic in origin. The partial mole cases consisted of 30 androgenetic moles and 12 dispermic triploids. For the 59 cases macroscopically categorized as hydropic abortion, the genetic analysis revealed 38 androgenetic moles, seven dispermic triploids and 14 biparental diploids. These results showed that a new diagnostic method was required for the management of patients with hydropic villi. We identified the TSSC imprint gene of which expression was shown in normal and partial mole villi but was silenced in complete mole villi. Immunohistochemistry using the TSSC3 antibody demonstrated its efficacy as the differential diagnostic method. TSSC3 play an important role in the differentiation from trophoblast stem cells to progenitors and/or labyrinth trophoblast through the TSSC3/PI3K/Akt/Mash2 signaling pathway.


Host feeding pattern of Japanese encephalitis virus vector mosquitoes (Diptera: Culicidae) from Kuttanadu, Kerala, India.
Identification of blood meals of vector mosquitoes is an important tool in the epidemiological investigations of vector-borne diseases. The blood meals of three mosquito species involved in the transmission of Japanese encephalitis virus (JEV) from the Kuttanadu area, Kerala, were determined using the agarose gel diffusion technique. A total of 4959 blood smears belonging to Culex (Culex) tritaeniorhynchus Giles (3273), Cx. (Culex) gelidus Theobald (64), Mansonia (Mnd.) indiana Edwards (735) ,and Ma. (Mnd.) uniformis (Theobald) (887) were tested. Cx. tritaeniorhynchus had predominantly fed on bovids (46.4%), and a good proportion (29%) had fed on more than one host. Cx. tritaeniorhynchus was highly zoophagic, and human feeding accounted for only 1.5% of those individuals successfully tested. Cx. gelidus showed bovid feeding at 36% and pig feeding at 12.5%. The test results showed 42.3% Ma. indiana and 12.2% Ma. uniformis had fed on humans. Multiple feeding was observed in Ma. indiana and Ma. uniformis, and most of the double feedings were from bovids and ovids (7.9 and 20.1%, respectively). Pig feeding accounted for 4.8% of the feedings by Cx. tritaeniorhynchus, 5.3% of Ma. indiana, and 6.4% of Ma. uniformis. This study is significant because of the role played by these mosquitoes in the transmission of JEV in the Kuttanadu area of Kerala, India.


Effects of different types of soy sauce on the formation of heterocyclic amines in roasted chicken.
The objective of the study was to determine the effect of different types of soy sauce and marinating time on the formation of heterocyclic amines (HCAs) in roasted chicken. Chicken breast samples were marinated with sweet, salty, light and dark soy sauce at 0, 3, 6 and 12 h (control treatment was the chicken without marinade). The concentrations of free amino acids, sugars and creatinine were determined before roasting while HCA concentrations were determined after roasting. All types of soy sauce significantly increased (p ≤ 0.05) the concentration of HCAs in roasted chicken with increasing marinating time. The highest increment of total concentration of HCAs was found in samples marinated with light soy sauce (887%) followed by dark (375%), salty (193%) and sweet (169%) at 12 h. PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine) showed a substantial reduction in samples only momentarily marinated with sweet, salty and dark soy sauce (0 h). Free amino acids were found to be more strongly correlated with the formation of HCAs than reducing sugars or creatinine.


Clinical Outcomes of Stereotactic Body Radiotherapy in Oligometastatic Gynecological Cancer.
The objective of this study was to assess the role of stereotactic body radiotherapy (SBRT) in the treatment of distantly recurrent, oligometastatic gynecological cancer. The hospital records of 45 patients with F-fluorodeoxyglucose (F-FDG) positron emission tomography positive, distantly recurrent, oligometastatic gynecological cancer were reviewed. All these patients had a number of target lesions less than 5, with largest diameter less than 6 cm. The treatment was delivered with a TrueBeam LINAC and RapidArc technique, using 10 or 6 MV FFF beams. A total of 70 lesions were treated, and lymph nodes represented the most common site of metastases, followed by lung, liver, and soft tissues. Twenty lesions were treated with one single fraction of 24 Gy and 5 lesions received 27 Gy delivered in 3 fractions, depending on the ability to fulfill adequate target coverage and safe dose/volume constraints for the organ at risk with either regimen. Positron emission tomography scan 3 months after SBRT showed a complete response (CR) in 45 lesions (64.3%), a partial response in 14 (20.0%), a stable disease in 5 (7.1%), and a progressive disease in 6 (8.6%). No lesions in CR after SBRT subsequently progressed. Overall acute toxicity occurred in 13 (28.9%) patients. The most common grade 1 to 2 adverse event was pain (n = 9, 20.0%), followed by nausea and vomiting (n = 5, 11.1%). No grade 3 to 4 acute toxicities occurred, and no late toxicities were observed. Patients who failed to achieve a CR had a 2.37-fold higher risk of progression and a 3.60-fold higher risk of death compared with complete responders (P = 0.04 and P = 0.03, respectively). Stereotactic body radiotherapy offers an effective and safe approach for selected cases of oligometastatic gynecological cancer.


Transcoronary Mapping with an Over-the-wire Multielectrode Catheter in Scar-related Ventricular Tachycardia Patients.
The usefulness of coronary venous system mapping has been reported for assessing intramural and epicardial substrates in patients with scar-related ventricular tachycardia (VT). However, there has been little data on mapping from coronary arteries. We investigated the safety and utility of mapping from coronary arteries with a novel over-the-wire multielectrode catheter in scar-related VT patients. Ten consecutive scar-related VT patients with nonischemic cardiomyopathy who underwent mapping from a coronary artery were analyzed. Six patients underwent simultaneous coronary venous mapping. High-density maps were created by combining the left ventricular endocardium and coronary vessels. Substrate maps were created during the baseline rhythm with 2,438 points (IQR 2,136-3,490 points), including 329 (IQR 59-508 points) in coronary arteries. Abnormal bipolar electrograms were successfully recorded within coronary arteries close to the endocardial substrate in 7 patients. During VT, isthmus components were recorded within coronary vessels in 3 patients with no discernible isthmus components on endocardial mapping. The ablation terminated the VT from an endocardial site opposite the earliest site in the coronary arteries in 5 patients. The transcoronary mapping with an over-the-wire multielectrode catheter can safely record abnormal bipolar electrograms within coronary arteries. Additional mapping data from coronary vessels have the potential to assess three-dimensional ventricular substrates and circuit structures in scar-related VT patients.


Examining occupational traumatic brain injury in Ontario.
Occupational traumatic brain injuries disrupt the lives of workers and carry major economic repercussions. To date, there has been limited information on brain injuries that occur at work across injury severity levels in Canada. The aim of this study was to provide an overview of occupational traumatic brain injuries in Ontario, with a focus on the sex of the workers. For this cross-sectional study, data from the Ontario Workplace Safety and Insurance Board were used. A retrospective chart review was conducted of over 1,500 claim files from the year 2004 with the diagnostic codes of concussion and intracranial injury. Severity was assessed according to data on days off work. The average age of those injured was 37.8 years. The breakdown by sex shows that 57.8% of claims for occupational traumatic brain injury involved males. The most common mechanism of injury was being "struck by or against", followed by "falls". Most of the occupational traumatic brain injuries were from the manufacturing, and government and related services sectors. The highest rate, however, was shown for transportation and storage (81.5/100,000), followed by government and related services (56.6/100,000) and primary industries (47/100,000). An examination of occupational traumatic brain injuries across a range of severities reveals a profile that is different from that associated with more severely injured workers: there were many more women in particular industries who were injured and more injuries involving being struck by an object. This paper provides data on key industries, mechanisms and contributing factors involved in work-related traumatic brain injury that result in claims to the Workplace Safety and Insurance Board.


Quantal and graded analysis of dosage-effect relations.
Loewe's recommendations regarding treatment of stimulus-response relations are criticized. Conditions are described where quantal analysis is justified. Loewe's interpretation of his graded analysis must be modified in the light of the fact that response curves for individuals frequently cross. Superior lines of attack on the problem are suggested.


Studies published in indexed journals on lawsuits for medicines in Brazil: a systematic review.
The aim of this systematic review was to identify and characterize articles in indexed scientific journals with quantitative data surveys on administrative or legal proceedings for access to medicines. The SciELO, LILACS, MEDLINE via PubMed, Embase, and Scopus databases were used. We identified 45 articles, of which 17 were selected. The larger studies, each covering between 2,000 and 2,927 lawsuits, were done in the states of São Paulo, Rio de Janeiro, and Santa Catarina, Brazil. Eleven studies specified the type of legal representation, of which six examined cases with public attorneys and five with private attorneys. Only two studies reported whether the lawsuit was individual or class action, and in both the claims were individual. Since the majority of the medicines requested in the lawsuits were medium to high-cost, the review indicates that lawsuits contributed to the incorporation of these drugs into current pharmaceutical care in Brazil.


Introduction of Two Novel Stiffness Parameters and Interpretation of Air Puff-Induced Biomechanical Deformation Parameters With a Dynamic Scheimpflug Analyzer.
To investigate two new stiffness parameters and their relationships with the dynamic corneal response (DCR) parameters and compare normal and keratoconic eyes. Stiffness parameters are defined as Resultant Pressure at inward applanation (A1) divided by corneal displacement. Stiffness parameter A1 uses displacement between the undeformed cornea and A1 and stiffness parameter highest concavity (HC) uses displacement from A1 to maximum deflection during HC. The spatial and temporal profiles of the Corvis ST (Oculus Optikgeräte, Wetzlar, Germany) air puff were characterized using hot wire anemometry. An adjusted air pressure impinging on the cornea at A1 (adjAP1) and an algorithm to biomechanically correct intraocular pressure based on finite element modelling (bIOP) were used for Resultant Pressure calculation (adjAP1 - bIOP). Linear regression analyses between DCR parameters and stiffness parameters were performed on a retrospective dataset of 180 keratoconic eyes and 482 normal eyes. DCR parameters from a subset of 158 eyes of 158 patients in each group were matched for bIOP and compared using t tests. A P value of less than .05 was considered statistically significant. All DCR parameters evaluated showed significant differences between normal and keratoconic eyes, except peak distance. Keratoconic eyes had lower stiffness parameter values, thinner pachymetry, shorter applanation lengths, greater absolute values of applanation velocities, earlier A1 times and later second applanation times, greater HC deformation amplitudes and HC deflection amplitudes, and lower HC radius of concave curvature (greater concave curvature). Most DCR parameters showed a significant relationship with both stiffness parameters in both groups. Keratoconic eyes demonstrated less resistance to deformation than normal eyes with similar IOP. The stiffness parameters may be useful in future biomechanical studies as potential biomarkers. [J Refract Surg. 2017;33(4):266-273.].


Adipose tissue volume determinations in women by computed tomography: technical considerations.
Eight healthy female volunteers with weights ranging from 46 to 119 kg were examined with a Philips Tomoscan 310 in order to determine the amount of adipose tissue. From analysis of 'attenuation profiles' at the thigh and trunk levels the attenuation interval of adipose tissue was determined to be -190 HU to -30 HU. The adipose tissue volume was calculated from the adipose tissue area of 22 scans and from the distances between these scans. Three different mathematical models were tested which all gave similar results. The adipose tissue surface of the L4-L5 scan showed a higher correlation (r = 0.991) than any other single scan versus the 22-scan-based adipose tissue volume. The adipose tissue volume had to be calculated from nine selected slices in order to agree closely with the results based on 22 scans (r = 0.999) in each individual case. The adipose tissue volume of the head and neck region was 1.7 +/- 0.24 per cent of the total volume, while corresponding figures for other regions were: arms 7.5 +/- 1.2 per cent, legs 31.8 +/- 5.6 per cent, subcutaneous part of the trunk 48.9 +/- 5.1 per cent and visceral region 10.2 +/- 1.7 per cent. The relative amount of subcutaneous trunk adipose tissue increased with increasing adipose tissue volumes while that of legs, and of head and neck tended to decrease. The relative amount of visceral fat was not significantly dependent on the total adipose tissue volume in these eight women.


Comparison of second- and third-generation enzyme immunoassays for detecting antibodies to hepatitis C virus.
Supplemental assays, such as recombinant immunoblot assays (RIBA), are used to confirm detection of antibodies to hepatitis C virus (HCV). However, due to their expense, they are not widely used in developing countries. The purpose of our study was to compare the results of second- and third-generation (G2 and G3, respectively) enzyme immunoassays (EIAs) and to resolve discordant results by using a supplemental assay to assess the reliability of G2 and G3 EIAs to confirm anti-HCV antibody-positive results. We performed both G2 and G3 EIAs for anti-HCV antibodies on 1,134 serum samples collected during the 2nd year of a longitudinal community-based study in Egypt; 35 samples with discordant results were tested by Abbott Laboratories Micro-Particle Immunoassay (M-EIA) and RIBA. Viremia was determined with an in-house nested reverse transcriptase PCR (RT-PCR) to detect HCV RNA. Concordance between the two assays (G2/G3) was 96.9%; 87 (7.7%) samples were positive and 1,012 (89.2%) were negative by both assays. For 17 samples, the discordant results were G2 assay negative and G3 assay positive, and for 18 samples, the discordant results were G2 assay positive and G3 assay negative. Among the 17 G2 assay-negative and G3 assay-positive samples, 15 were M-EIA positive and 7 were PCR positive. Among the 18 G2 assay-positive and G3 assay-negative samples, 2 were M-EIA positive and none were PCR positive. RIBA results from 24 discordant samples showed 87.5% agreement with the G3 EIA, 12.5% agreement with the G2 EIA, and 95.8% agreement with M-EIA. Eleven samples were indeterminate by RIBA and excluded from this analysis. Based on RIBA results, the sensitivity of the G3 EIA was 99%, compared to 89.8% for the G2 EIA, while the specificity of the G3 EIA was 99.8%, compared to 98.9% for the G2 EIA. These results show that the reliability of the G3 EIA in screening these sera is excellent, and the G3 assay can be used in the absence of supplemental tests where resources are limited. RIBA appears not to have advantages over the less expensive M-EIA screening assay. The main disadvantage of RIBA is the occurrence of indeterminate results, especially among problematic samples. Samples giving discordant results in multiple assays are often indeterminate with the RIBA.


PEP444c encoded within the MIR444c gene regulates microRNA444c accumulation in barley.
MicroRNAs are small, noncoding RNA molecules that regulate the expression of their target genes. The MIR444 gene family is present exclusively in monocotyledons, and microRNAs444 from this family have been shown to target certain MADS-box transcription factors in rice and barley. We identified three barley MIR444 (MIR444a/b/c) genes and comprehensively characterised their structure and the processing pattern of the primary transcripts (pri-miRNAs444). Pri-microRNAs444 undergo extensive alternative splicing, generating functional and nonfunctional pri-miRNA444 isoforms. We show that barley pri-miRNAs444 contain numerous open reading frames (ORFs) whose transcripts associate with ribosomes. Using specific antibodies, we provide evidence that selected ORFs encoding PEP444a within MIR444a and PEP444c within MIR444c are expressed in barley plants. Moreover, we demonstrate that CRISPR-associated endonuclease 9 (Cas9)-mediated mutagenesis of the PEP444c-encoding sequence results in a decreased level of PEP444 transcript in barley shoots and roots and a 5-fold reduced level of mature microRNA444c in roots. Our observations suggest that PEP444c encoded by the MIR444c gene is involved in microRNA444c biogenesis in barley.


Culture of seminal fluid in a fertility clinic.
To determine whether the culture of seminal fluid in a fertility clinic is of importance, bacterial cultures were obtained in a consecutive series of 96 patients. Routine bacteriologic cultures were performed within 1 hour of collection. Ureaplasma urealyticum (T-mycoplasma) cultures were also obtained in the last 31 of the patients in this series. Of these 96 patients, 11% showed significant bacterial growth (greater than 10(4) colonies/ml) in the semen specimens, 8% in those patients with normal semen analyses and 14% in those with abnormal analyses. Fifty-eight per cent of semen specimens were positive for U. urealyticum. In reference to normal and abnormal semen analyses the distribution was the same regardless of the presence or absence of U. urealyticum. Antibiotic treatment resulted in minor changes in motility and morphology in a few patients despite conversion to a negative culture. Cultures were also coordinated with microscopic urinalysis and the presence of white blood cells or bacteria in stained smears of semen. There were no significant differences between groups with positive or negative cultures. Trichomonas vaginalis was not seen.


Cohesin and CTCF differentially regulate spatiotemporal runx1 expression during zebrafish development.
Runx1 is a transcription factor essential for definitive hematopoiesis. In all vertebrates, the Runx1 gene is transcribed from two promoters: a proximal promoter (P2), and a distal promoter (P1). We previously found that runx1 expression in a specific hematopoietic cell population in zebrafish embryos depends on cohesin. Here we show that zebrafish runx1 is directly bound by cohesin and CCCTC binding factor (CTCF) at the P1 and P2 promoters, and within the intron between P1 and P2. Cohesin initiates expression of runx1 in the posterior lateral mesoderm and influences promoter use, while CTCF represses its expression in the newly emerging cells of the tail bud. The intronic binding sites for cohesin and CTCF coincide with histone modifications that confer enhancer-like properties, and two of the cohesin/CTCF sites behaved as insulators in an in vivo assay. The identified cohesin and CTCF binding sites are likely to be cis-regulatory elements (CREs) for runx1 since they also recruit RNA polymerase II (RNAPII). CTCF depletion excluded RNAPII from two intronic CREs but not the promoters of runx1. We propose that cohesin and CTCF have distinct functions in the regulation of runx1 during zebrafish embryogenesis, and that these regulatory functions are likely to involve runx1 intronic CREs. Cohesin (but not CTCF) depletion enhanced RUNX1 expression in a human leukemia cell line, suggesting conservation of RUNX1 regulation through evolution.


How Do the Nurses Cope with Job Stress? A Study with Grounded Theory Approach.
Introduction: Due to the adverse effects of job stress on health of nurses and the importance of coping process of nurses in management of job stress, the present study was carried out with the aim of exploring the experiences of the nurses in order to reveal the original coping process of the nurses in the case of encountering occupational stress. Methods: This qualitative study was conducted with grounded theory approach. Research participants were 15 clinical nurses and four directors of nursing. Sampling method of study were purposive and theoretical sampling. Data collection done with unstructured interviews and field notes and continued until data saturation. Data analysis was performed using the Strauss and Corbin 1998 constant comparative method. Results: The results of the analysis led to four axial concepts: "feeling stress at nursing work", "situational coping", "and the effect of personal and environmental factors in coping with job stress" and "Grey outcome of coping". The core variable in the nurse's process of coping with job stress was "comprehensive effort to calm stressed condition". Conclusion: Explaining the basic and original psychosocial process of nurses to cope with job stress, revealed context-based nature of the coping processes that nurses adopt, which that can help in taking appropriate measures to lighten up the grey consequences of coping of nurses.


"Long-term callisthenic exercise-related changes in blood lipids, homocysteine, nitric oxide levels and body composition in middle-aged healthy sedentary women".
"Regular physical exercise plays an important role in reducing obesity, preventing hyperglycemia, lowering blood lipids and reducing systemic blood pressure. But the question about the nature of the relationship between homocysteine, nitric oxide and physical activity remains unanswered. The aim of this study was to investigate the effects of callisthenic exercises on plasma lipids, homocysteine (Hcy), total nitric oxide (NOx) and body composition in middle-aged healthy sedentary women. Forty-two middle-aged women (ages: 28-49; mean: 41.40 ± 7.3 years) were asked to perform a callisthenic exercise 50 min per session, 3 times per week for 12 weeks in a sports hall. Before and after the exercise, plasma lipids (total cholesterol, high density lipoprotein, low density lipoprotein and triglyceride), Hcy and NO were determined. Body composition, including body mass index, fat percentage, fat free mass, resting systolic and diastolic blood pressures and heart rates were measured. After a 12-week callisthenic exercise program, plasma NOx and Hcy levels were found to be significantly increased (P < 0.05). Body composition parameters, lipid profile, resting systolic and diastolic blood pressures and heart rate significantly decreased (P < 0.05). Aerobic callisthenic exercises characterized by 50 min/day and 3 days/week resulted in positive changes in important health parameters like reducing obesity, lowering blood lipids and increasing plasma NOx. Cardiovascular improvements might be dependent on the increase of NOx values. But callisthenic exercise in such intensity did not lower the plasma Hcy level. Moreover, Hcy level increased significantly. The result shows that if the Hcy is in the normal levels in healthy subjects, long-term callisthenic exercise do not decrease the Hcy levels despite some beneficial effects on health. On the contrary, the Hcy levels are increased by long-term callisthenic exercises."


An Iterative Method of Modeling Pump-Treat-Inject System with "Partial Treatment".
Pump-and-treat technologies are widely used in groundwater remediation and site clean-up. Such technologies involve pumping contaminated groundwater to the surface for treatment. Following treatment, the water is often reinjected back into the aquifer (referred to as pump-treat-inject or PTI) for potential reuse. The treatment system is often designed to remove dissolved-phase contaminants in groundwater such that water meets applicable cleanup standards (herein referred to as "full treatment"). However, in some cases, the treatment system may not effectively reduce the dissolved-phase concentrations effectively (herein referred to as "partial treatment") for some of the contaminants present in groundwater. Modeling PTI under partial treatment conditions is challenging because contaminant concentrations in injected water depend on the pumped water concentrations and the system treatment efficiency. Essentially, the injected water concentration (a transport model input) is unknown prior to transport simulation. This study presents a novel iterative approach to modeling PTI under partial treatment scenarios, where the injected water concentration is linked to the modeled pumped water concentration. The method was developed for a complicated three-dimensional (3-D) flow and transport modeling study conducted for a confidential remediation site where PTI with partial treatment was applied. However, due to the complexity of the 3-D model and the confidential information of the site, a simple two-dimensional (2-D) numerical model is presented to demonstrate the iterative method. The 2-D model test runs and the 3-D model application in a remediation site showed that the iterative simulation results quickly converged to a viable final solution.


T-cell triggering by CD3- and CD28-binding molecules linked to a human virus-modified tumor cell vaccine.
The aim was to develop T cell costimulatory molecules that are broadly applicable to augment anti-tumor immune responses upon application of a virus-modified tumor vaccine to cancer patients. We generated recombinant bispecific single-chain antibodies with one specificity directed against the CD3 or the CD28 antigen on human T cells and the other against the viral target molecule hemagglutinin-neuraminidase (HN) of Newcastle Disease Virus (NDV). By re-directing unstimulated primary human T cells against HN-expressing NDV-infected tumor cells, the bispecific molecule bsHN-CD3 cross-linked effector and target cells and rapidly induced cytotoxicity at nanomolar concentrations. The bsHN-CD28 molecule exerted T cell co-stimulatory function. Maximal T cell activation was achieved with tumor cells infected by NDV and modified with both new stimulatory molecules. This was revealed by T cell proliferation, upregulation of CD69 and CD25 and by release of cytokines, interferons and chemokines. The new molecules combine high-effectivity with specificity and safety.


Role of photodynamic therapy using talaporfin sodium and a semiconductor laser in patients with newly diagnosed glioblastoma.
In this study on the effectiveness and safety of photodynamic therapy (PDT) using talaporfin sodium and a semiconductor laser, the long-term follow-up results of 11 patients with glioblastoma enrolled in the authors' previous phase II clinical trial (March 2009-2012) and the clinical results of 19 consecutive patients with newly diagnosed glioblastoma prospectively enrolled in a postmarket surveillance (March 2014-December 2016) were analyzed and compared with those of 164 patients treated without PDT during the same period. The main outcome measures were the median overall survival (OS) and progression-free survival (PFS) times. Moreover, the adverse events and radiological changes after PDT, as well as the patterns of recurrence, were analyzed and compared between the groups. Kaplan-Meier curves were created to assess the differences in OS and PFS between the groups. Univariate and multivariate analyses were performed to identify the prognostic factors, including PDT, among patients with newly diagnosed glioblastoma. The median PFS times of the PDT and control groups were 19.6 and 9.0 months, with 6-month PFS rates of 86.3% and 64.9%, respectively (p = 0.016). The median OS times were 27.4 and 22.1 months, with 1-year OS rates of 95.7% and 72.5%, respectively (p = 0.0327). Multivariate analyses found PDT, preoperative Karnofsky Performance Scale score, and IDH mutation to be significant independent prognostic factors for both OS and PFS. Eighteen of 30 patients in the PDT group experienced tumor recurrence, including local recurrence, distant recurrence, and dissemination in 10, 3, and 4 patients, respectively. Conversely, 141 of 164 patients in the control group experienced tumor recurrence, including 101 cases of local recurrence. The rate of local recurrence tended to be lower in the PDT group (p = 0.06). The results of the present study suggest that PDT with talaporfin sodium and a semiconductor laser provides excellent local control, with few adverse effects even in cases of multiple laser irradiations, as well as potential survival benefits for patients with newly diagnosed glioblastoma.


Influence of a riparian wetland on nitrate and herbicides exported from an agricultural field.
Agrochemicals are a major source of nonpoint pollution. Forested corridors along stream channels (riparian zones) are thought to be potential sites for removal of agricultural contaminants from ground and surface waters. First-order riparian wetlands are reputed to be especially effective at groundwater remediation. The study site is a fairly typical (for eastern Maryland) small, first-order stream in an agricultural watershed. Preferential flow supplies most of the stream water within the riparian headwater wetland. This upstream area also contains the highest average stream N and pesticide loads in the entire first-order riparian system. Zones of active groundwater emergence onto the surface display high concentrations of nitrate throughout the soil profile and in the exfiltrating water, whereas inactive areas (where there is no visible upwelling) show rapid attenuation of nitrate with decreasing depths. Atrazine degradation products appear to penetrate more readily through the most active upwelling zones, and there is a correlation between zones of high nitrate and high atrazine metabolite levels. Deethylatrazine/atrazine ratios (DAR) seem to indicate that stream flow is dominated by ground water and that much of the ground water may have reached the stream via preferential flow. Remediative processes appear to be very complex, heterogeneous, and variable in these systems, so additional research is needed before effective formulation and application of riparian zone initiatives and guidelines can be accomplished.


Cyclin D activates the Rb tumor suppressor by mono-phosphorylation.
The widely accepted model of G1 cell cycle progression proposes that cyclin D:Cdk4/6 inactivates the Rb tumor suppressor during early G1 phase by progressive multi-phosphorylation, termed hypo-phosphorylation, to release E2F transcription factors. However, this model remains unproven biochemically and the biologically active form(s) of Rb remains unknown. In this study, we find that Rb is exclusively mono-phosphorylated in early G1 phase by cyclin D:Cdk4/6. Mono-phosphorylated Rb is composed of 14 independent isoforms that are all targeted by the E1a oncoprotein, but show preferential E2F binding patterns. At the late G1 Restriction Point, cyclin E:Cdk2 inactivates Rb by quantum hyper-phosphorylation. Cells undergoing a DNA damage response activate cyclin D:Cdk4/6 to generate mono-phosphorylated Rb that regulates global transcription, whereas cells undergoing differentiation utilize un-phosphorylated Rb. These observations fundamentally change our understanding of G1 cell cycle progression and show that mono-phosphorylated Rb, generated by cyclin D:Cdk4/6, is the only Rb isoform in early G1 phase.


ASHP national survey of pharmacy practice in acute care settings: dispensing and administration--1999.
Results of the 1999 ASHP national survey of pharmacy practice in acute care settings that pertain to drug dispensing and administration practices are presented. Pharmacy directors at 1050 general and children's medical-surgical hospitals in the United States were surveyed by mail. The response rate was 51%. About three-fourths of respondents described their inpatient pharmacy's distribution system as centralized. Of those with centralized distribution, 77.4% indicated that their system was not automated. Decentralized pharmacists were used in 29.4% of the hospitals surveyed; an average of 58.9% of their time was spent on clinical, as opposed to distributive, activities. About 67% of directors reported pharmacy computer access to hospital laboratory data, 38% reported access to automated medication-dispensing-unit data, and 19% reported computer access to hospital outpatient affiliates. Only 13% of hospitals had an electronic medication order-entry system; another 27% reported they were in the process of developing such a system. Decentralized medication storage and distribution devices were used in 49.2% of hospitals, while 7.3% used bedside information systems for medication management. Machine-readable coding was used for inpatient pharmacy dispensing by 8.2% of hospitals. Ninety percent reported a formal, systemwide committee responsible for data collection, review, and evaluation of medication errors. Virtually all respondents (98.7%) reported that their staff initiated manual reports. Only two thirds tracked these reports and reported trends to the staff. Fewer than 15% reported that staff were penalized for making or contributing to an error. Pharmacists are making a significant contribution to the safety of medication distribution and administration. The increased use of technology to improve efficiency and reduce costs will require that pharmacists continue to focus on the impact of changes on the safety of the medication-use system.


Extended pausing by humans on multiple fixed-ratio schedules with varied reinforcer magnitude and response requirements.
We conducted three experiments to reproduce and extend Perone and Courtney's (1992) study of pausing at the beginning of fixed-ratio schedules. In a multiple schedule with unequal amounts of food across two components, they found that pigeons paused longest in the component associated with the smaller amount of food (the lean component), but only when it was preceded by the rich component. In our studies, adults with mild intellectual disabilities responded on a touch-sensitive computer monitor to produce money. In Experiment 1, the multiple-schedule components differed in both response requirement and reinforcer magnitude (i.e., the rich component required fewer responses and produced more money than the lean component). Effects shown with pigeons were reproduced in all 7 participants. In Experiment 2, we removed the stimuli that signaled the two schedule components, and participants' extended pausing was eliminated. In Experiment 3, to assess sensitivity to reinforcer magnitude versus fixed-ratio size, we presented conditions with equal ratio sizes but disparate magnitudes and conditions with equal magnitudes but disparate ratio sizes. Sensitivity to these manipulations was idiosyncratic. The present experiments obtained schedule control in verbally competent human participants and, despite procedural differences, we reproduced findings with animal participants. We showed that pausing is jointly determined by past conditions of reinforcement and stimuli correlated with upcoming conditions.


An ultrasonographic morphological index for prediction of ovarian tumor malignancy.
A newly created ultrasonographic scale called the Poznan index as well as scales already well known (introduced by Sassone, De Priest and Lerner) were compared in our group of patients. A morphological index was based on seven sonographic ovarian tumor features. Examinations on 686 patients were evaluated. Comparison of prognostic values of the Poznan index with other applied morphological indices in our group of patients was based on the area under receiver operating characteristic (ROC) curves. The cut-off level of the new index is 8 points. The new morphological index has a specificity of 77.0%, and negative and positive predictive values of 90.7% and 69.1%, respectively. It has a sensitivity of 86.7% and accuracy of 80.6%. The Poznan index proved its usefulness and superiority (AU ROC = 0.89). Using this morphological index it is possible to make a precise prognosis of ovarian tumor malignancy. It also makes it possible to make the right decision concerning the manner of surgical treatment.


Speckle reduction method for image-based coherent stereogram generation.
We propose a speckle noise reduction method for generation of coherent holographic stereograms. The method employs densely sampled light field (DSLF) of the scene together with depth information acquired for each ray in the captured DSLF. Speckle reduction is achieved based on the ray separation technique where the scene is first described as a superposition of sparse sets of point sources corresponding to separated sets of rays and then the holographic reconstructions corresponding to these sparse sets of point sources are added incoherently (intensity-wise) to obtain the final reconstruction. The proposed method handles the light propagation between the sparse scene points and hologram elements accurately by utilizing ray resampling based on the notion of DSLF. As a result, as demonstrated via numerical simulations, significant speckle suppression is achieved at no cost of sampling related reconstruction artifacts.


Cathepsin S activity regulates antigen presentation and immunity.
MHC class II molecules display antigenic peptides on cell surfaces for recognition by CD4(+) T cells. Proteolysis is required in this process both for degradation of invariant chain (Ii) from class II-Ii complexes to allow subsequent binding of peptides, and for generation of the antigenic peptides. The cysteine endoprotease, cathepsin S, mediates Ii degradation in human and mouse antigen-presenting cells. Studies described here examine the functional significance of cathepsin S inhibition on antigen presentation and immunity. Specific inhibition of cathepsin S in A20 cells markedly impaired presentation of an ovalbumin epitope by interfering with class II-peptide binding, not by obstructing generation of the antigen. Administration of a cathepsin S inhibitor to mice in vivo selectively inhibited activity of cathepsin S in splenocytes, resulting in accumulation of a class II-associated Ii breakdown product, attenuation of class II-peptide complex formation, and inhibition of antigen presentation. Mice treated with inhibitor had an attenuated antibody response when immunized with ovalbumin but not the T cell-independent antigen TNP-Ficoll. In a mouse model of pulmonary hypersensitivity, treatment with the inhibitor also abrogated a rise in IgE titers and profoundly blocked eosinophilic infiltration in the lung. Thus, inhibition of cathepsin S in vivo alters Ii processing, antigen presentation, and immunity. These data identify selective inhibition of cysteine proteases as a potential therapeutic strategy for asthma and autoimmune disease processes.


Deep insights into the response of human cervical carcinoma cells to a new cyano enone-bearing triterpenoid soloxolone methyl: a transcriptome analysis.
Semisynthetic triterpenoids, bearing cyano enone functionality in ring A, are considered now as novel promising anti-tumor agents. However, despite the large-scale studies, their effects on cervical carcinoma cells and, moreover, mechanisms underlying cell death activation by such compounds in this cell type have not been fully elucidated. In this work, we attempted to reconstitute the key pathways and master regulators involved in the response of human cervical carcinoma KB-3-1 cells to the novel glycyrrhetinic acid derivative soloxolone methyl (SM) by a transcriptomic approach. Functional annotation of differentially expressed genes, analysis of their cis- regulatory sequences and protein-protein interaction network clearly indicated that stress of endoplasmic reticulum (ER) is the central event triggered by SM in the cells. A range of key ER stress sensors and transcription factor AP-1 were identified as upstream transcriptional regulators, controlling the response of the cells to SM. Additionally, by using Gene Expression Omnibus data, we showed the ability of SM to modulate the expression of key genes involved in regulation of the high proliferative rate of cervical carcinoma cells. Further Connectivity Map analysis revealed similarity of SM's effects with known ER stress inducers thapsigargin and geldanamycin, targeting SERCA and Grp94, respectively. According to the molecular docking study, SM could snugly fit into the active sites of these proteins in the positions very close to that of both inhibitors. Taken together, our findings provide a basis for the better understanding of the intracellular processes in tumor cells switched on in response to cyano enone-bearing triterpenoids.


Cholecystoenteric Stent-Related Complications: Rendering the Inoperable Patient Operable.
Cholecystoenteric stenting is an alternative treatment for cholecystitis. However, complications with this approach can render a need for surgical intervention. A case series of three patients undergoing surgery for a cholecystoenteric stent-related complication. Patient 1 was a 42-year-old male with history of lung transplant who had a cholecystoenteric stent placed for acalculous cholecystitis. One year later the stent became occluded with return of symptoms. Endoscopic replacement failed. A laparoscopic cholecystectomy with modified Graham patch was performed. Patient 2 is a 73-year-old female with acalculous cholecystitis in the setting of metastatic colon cancer on FOLFOX. Antibiotic treatment failed. A cholecystoenteric stent was attempted, but the stent dislodged during deployment. The fistula tract was clipped, and a percutaneous cholecystostomy drain was placed, which noted a leak at the gallbladder infundibulum. The patient deteriorated clinically and was taken emergently for an open cholecystectomy. Patient 3 was a 71-year-old male with history of ischemic cardiomyopathy who had a cholecystogastric stent placed for necrotizing gallstone pancreatitis. The stent migrated into the gastrointestinal tract and he developed post-prandial pain. A cholecystectomy and modified Graham patch repair of the gastrotomy was performed. This failed as the gastrotomy was too close to the pylorus. He underwent re-operation with Heineke-Mikulicz pyloroplasty. All patients recovered without any cardiopulmonary complications. With the increasing utility of cholecystoenteric stents, surgeons should be aware of the complications and have a plan for managing the duodenotomy or gastrotomy. Shared-medical decision-making involving surgeons should be applied when placing these stents.


Cloning, chromosomal localization, and interspecies interaction of mouse DNA polymerase delta small subunit (PolD2).
DNA polymerase delta core is a heterodimeric enzyme with a catalytic subunit of 125 kDa and a second subunit of 50 kDa with an as yet unknown function. It is an essential enzyme for DNA replication and DNA repair. We cloned the full-length cDNA encoding the DNA polymerase delta small subunit from mouse cells. The sequence of the predicted polypeptide of 51,336 Da is, like the catalytic subunit, highly conserved not only among mammals (93% identity and 96% similarity), but also between yeast and mammals (34% identity and 57% similarity). Fluorescence in situ hybridization experiments indicated that the gene for the small DNA polymerase delta of mouse is localized on chromosome 11, band A2. By using the yeast two-hybrid system we found that the mouse 125-kDa DNA polymerase catalytic subunit is able to interact with the 50-kDa subunit of the human enzyme, suggesting an in vivo interspecies interaction between the two subunits of DNA polymerase delta.


[Economic evaluation of Thrombopoietin Receptor Agonists in the treatment of chronic primary immune thrombocytopenia].
To develop a tool to assist the decision-making for selection of Thrombopoyetin Receptor Agonists of adult patients with chronic immune primary thrombocytopenia (PTI). Stochastic cost-effectiveness analysis with a 6-Health- States Markov model: stable, bleeding type 2, 3 or 4, post-type 4 bleeding and death. Each simulation analyzes a randomly generated scenario that describes patients characteristics, results measured in quality adjusted life years (QALYs) and costs (in ?2011). Distributions were obtained from the Spanish data of the European health survey of 2009, the INE estimate of population for 2011 and the 6-months clinical studies for Eltrombopag and Romiplostim. Utility values were obtained from the literature and the costs from Spanish official rates lists. A set of 10.000 random scenarios were generated and the patients evolution of each scenario was simulated during a time horizon of five years (in 2-weeks cycles). National Health System Perspective was used and the annual discount rate was set at 3%. Eltrombopag showed more effectiveness in 9.983 scenarios and there was no difference in 17. In 7.048 scenarios the alternative Eltombopag was dominant. It was cost-effective in another 19 (threshold 30,000 ??/AVAC). Eltrombopag was the most cost-effective alternative in 70,67% of the simulated scenarios and its use could produce lower costs to the NHS.


Ocular morbidity survey in an opthalmically underserved rural area of Nigeria.
This paper describes in some detail a prevalence of blindness study conducted in a rural area of South-Western Nigeria, which is served by a peripheral eye clinic. By a stratified random cluster-sampling procedure, 1975 people in ten villages were selected for ocular examination. Community prevalence rate of ocular morbidity was 3.3% with the highest prevalence in the 51-60 years age group. There was a male-female ratio of 4:3 and the prevalence of ocular morbidity in the 31-50 years age group was most significant, but people in this age group seldom reported at the peripheral eye clinic serving the survey areas. Age-related macular degeneration was found to be prevalent in the community, while few cases were reported at the peripheral eye centre. The information gathered in the survey is being used to plan and improve eye care services from the peripheral eye clinic. Case finding in persons aged 31-50 years and those at risk for age-related macular degeneration has been recommended as part of the programme of the peripheral eye clinic.


Both calmodulin and the unconventional myosin Myr4 regulate membrane trafficking along the recycling pathway of MDCK cells.
In epithelial cells, endocytosed transferrin and its receptor, which cycle basolaterally, have been shown to transit through recycling endosomes which can also be accessed by markers internalized from the apical surface. In this work, we have used an in vitro assay to follow transfer of an endocytosed marker from apical or basolateral early endosomes to recycling endosomes labeled with transferrin. We show that calmodulin (CaM) function is necessary for transfer and identified myr4, a member of the unconventional myosin superfamily known to use CaM as a light chain, as a possible target protein for CaM. Since myr4 is believed to act as an actin-based mechanoenzyme, we tested the role of polymerized actin in the assay. Our data show that conditions which either prevent actin polymerization or induce the breakdown of existing filaments strongly inhibit interactions between recycling endosomes and either set of early endosomes. Altogether, our data indicate that trafficking at early steps of the endocytic pathway in Madin-Darby Canine Kidney cells depends on the actin-based mechanoenzyme myr4, its light chain CaM, and polymerized actin.


Development and Utilization of Introgression Lines Using Synthetic Octaploid Wheat (Aegilops tauschii × Hexaploid Wheat) as Donor.
As the diploid progenitor of common wheat, Aegilops tauschii Cosson (DD, 2n = 2x = 14) is considered to be a promising genetic resource for the improvement of common wheat. In this work, we demonstrated that the efficiency of transferring A. tauschii segments to common wheat was clearly improved through the use of synthetic octaploid wheat (AABBDDDD, 2n = 8x = 56) as a "bridge." The synthetic octaploid was obtained by chromosome doubling of hybrid F1 (A. tauschii T015 × common wheat Zhoumai 18). A set of introgression lines (BC1F8) containing 6016 A. tauschii segments was developed and displayed significant phenotype variance among lines. Twelve agronomic traits, including growth duration, panicle traits, grain traits, and plant height (PH), were evaluated. And transgressive segregation was identified in partial lines. Additionally, better agronomic traits could be observed in some lines, compared to the recurrent parent Zhoumai 18. To verify that the significant variance of those agronomic traits was supposedly controlled by A. tauschii segments, 14 quantitative trait loci (QTLs) for three important agronomic traits (thousand kernel weight, spike length, and PH) were further located in the two environments (Huixian and Zhongmou), indicating the introgression of favorable alleles from A. tauschii into common wheat. This study provides an ameliorated strategy to improve common wheat utilizing a single A. tauschii genome.


Pretanned leather shavings in a supplement mixture for steers: I. In situ and in vitro disappearance, ruminal fermentation, and organic matter, nitrogen, and fiber digestion.
Two digestion studies were conducted to evaluate the use of pretanned leather shavings as a component of a protein supplement. In Exp. 1, the in situ and in vitro disappearance of pretanned leather shavings and soybean meal was evaluated. Results revealed that less than 18.4% of the pretanned leather shavings was solubilized and disappeared when exposed to McDougall's buffer for 48 h, but there was 90.0% disappearance with 48-h exposure to a .1 N HCl/pepsin treatment and 97.0% disappearance with exposure to a two-stage digestion. In situ disappearance following 72 h in the rumen allowed 6.8% disappearance. Thus, leather shavings seem to be relatively indigestible in the rumen, but postruminal digestion may be possible. In Exp. 2, six Angus x Holstein steers, fitted with ruminal and duodenal cannulas, were used in a replicated 3 x 3 Latin square to evaluate ruminal and digestion effects of the following supplements combined with fescue hay at 1.7% of BW (DM basis): no supplementation (control); supplementation intraruminally with soybean meal at .07% of BW (as-fed basis); and supplementation intraruminally with a combination of soybean meal and pretanned leather shavings (17:8 ratio) at .05% of BW (isonitrogenous to soybean meal; as-fed basis). Ruminal fluid passage rate was greater and fluid turnover time was shorter in steers fed leather shavings than in those fed soybean meal (P = .10). Ruminal pH was lower (P = .04) for supplemented steers than for control steers and ruminal NH3 N concentration was greater (P = .01) in steers fed soybean meal than in those fed leather shavings. Total VFA concentration was increased (P = .02) by supplementation. Supplementation with soybean meal increased (P < .05) ruminal molar proportions of butyrate, valerate, and isovalerate compared with leather shavings. Duodenal OM flow and OM disappearing in the intestines were increased by supplementation (P < .10), but not by the type of supplement fed (P > .10). Ruminal digestion of OM and total tract OM digestion were unaffected (P > .10) by supplementation and the type of supplement fed. Flow and digestion of NDF were unaffected (P > .10) by the treatments. Flow of N and the quantity of N disappearing in the intestines were increased (P < .05) by supplementation but did not differ (P > .10) between supplementation groups. Microbial N flow, N utilization for net microbial protein synthesis, and ruminal N disappearance were unaffected (P > .10) by supplementation and the type of supplement provided. Combining pretanned leather shavings with soybean meal seemed to have no deleterious effects on digestion or fermentation and to allow for escape of some N to the lower tract.


Effects of low-intensity ultrasound on oxidative damage in retinal pigment epithelial cells in vitro.
Oxidative stress in retinal pigment epithelium (RPE) is one of the key causative factors of RPE injury in age-related macular degeneration (AMD). Low-intensity ultrasound (LIUS) less than 1 W/cm(2) in intensity has been found to have cytoprotective and anti-inflammatory effects in many cell types and diseases. In this study, we investigated for the first time the feasibility of using LIUS to protect RPE cells from oxidative damage. ARPE-19 cells were treated with H2O2 (an exogenous source of reactive oxygen species) or L-buthionine-(S,R)-sulfoximine (BSO), a glutathione synthase inhibitor, and exposed immediately to LIUS at intensities of 50, 100 and 200 mW/cm(2) and a frequency of 1 MHz for 20 min. Both H2O2 and BSO increased the percentage of cells positive for mitochondrial reactive oxygen species at 1 h, but not at 24 h. Co-treatment with LIUS clearly repressed these cells similarly at all intensities by approximately 34%-43% for H2O2 and 24%-25% for BSO (p < 0.05). The percentage of cells with mitochondrial membrane depolarization also increased with H2O2 and BSO treatment, particularly at 1 h, and decreased by approximately 60% with LIUS at 100 mW/cm(2) (p < 0.05). The amount of intracellular calcium ion ([Ca(2+)]i) was elevated only by BSO at 24 h and was also significantly diminished, by approximately 45%, by LIUS at 100 mW/cm(2) (p < 0.05). Both H2O2 and BSO significantly hampered cell viability at 24 h, but LIUS at 100 mW/cm(2) restored only BSO-induced cell viability by approximately 2.7-fold (p < 0.05). This study illustrated that LIUS has a protective effect on RPE cells against oxidative damage caused by BSO, an endogenous mitochondrial reactive oxygen species generator. We speculate that LIUS has the potential to treat oxidative damage and related pathologic changes in RPE.


Synergistic effects of mixing and strain in high entropy spinel oxides for oxygen evolution reaction.
Developing stable and efficient electrocatalysts is vital for boosting oxygen evolution reaction (OER) rates in sustainable hydrogen production. High-entropy oxides (HEOs) consist of five or more metal cations, providing opportunities to tune their catalytic properties toward high OER efficiency. This work combines theoretical and experimental studies to scrutinize the OER activity and stability for spinel-type HEOs. Density functional theory confirms that randomly mixed metal sites show thermodynamic stability, with intermediate adsorption energies displaying wider distributions due to mixing-induced equatorial strain in active metal-oxygen bonds. The rapid sol-flame method is employed to synthesize HEO, comprising five 3d-transition metal cations, which exhibits superior OER activity and durability under alkaline conditions, outperforming lower-entropy oxides, even with partial surface oxidations. The study highlights that the enhanced activity of HEO is primarily attributed to the mixing of multiple elements, leading to strain effects near the active site, as well as surface composition and coverage.


Nanoemulsions and acidified milk gels as a strategy for improving stability and antioxidant activity of yarrow phenolic compounds after gastrointestinal digestion.
The aim of this study was to improve the stability and antioxidant activity of yarrow phenolic compounds upon an in vitro simulated gastrointestinal digestion. Therefore, two types of caseins-based delivery systems, sodium caseinate stabilized nanoemulsions (NEs) and glucono delta-lactone acidified milk gels (MGs), were formulated containing an ultrasound-assisted yarrow extract (YE) at two concentrations (1 and 2.5 mg/mL). Formulations with 1 mg/mL of YE were chosen based on their higher encapsulation efficiency to perform the in vitro digestion experiments. After digestion, YE-loaded NEs only partially protected phenolic compounds from degradation; meanwhile the phenolic composition of YE including in MGs after digestion was quite similar to undigested YE. Moreover, the antioxidant activity of MGs after digestion was higher than NEs digested samples, which confirms the higher protection of YE phenolic compound by the milk gels systems. This research demonstrated the potential use of acidified MGs as carriers to improve the stability and antioxidant activity of yarrow phenolic compounds. Therefore, these matrices could be employed to develop new dairy products enriched with phenolic compounds.


Optical tecnology developments in biomedicine: history, current and future.
Biomedical optics is a rapidly emerging field for medical imaging and diagnostics. This paper reviews several biomedical optical technologies that have been developed and translated for either clinical or pre-clinical applications. Specifically, we focus on the following technologies: 1) near-infrared spectroscopy and tomography, 2) optical coherence tomography, 3) fluorescence spectroscopy and imaging, and 4) optical molecular imaging. There representative biomedical applications are also discussed here.


Tumour stage on re-staging transurethral resection predicts recurrence and progression-free survival of patients with high-risk non-muscle invasive bladder cancer.
To identify patients who should be considered for early radical cystectomy, we evaluated the clinical and pathological variables affecting the outcome of patients with high-risk non-muscle invasive bladder cancer (NMIBC) who underwent re-staging transurethral resection (re-TUR). We reviewed the clinical data of 453 patients treated for urothelial carcinoma between 2006 and 2010. In total, 94 patients underwent re-TUR after their initial TUR. Of these, 72 were not upstaged to muscle invasive disease and were therefore included in our study. On re-TUR, 31 patients had no residual tumour (T0) and 41 patients had residual NMIBC. A statistically significant difference was noted between patients with pT0 and patients with residual NMIBC on re-TUR in regard to tumour recurrence and progression (39% vs. 83%, p < 0.001) (6% vs. 34%, p = 0.005), respectively. On multivariate analysis, tumour stage on re-TUR and the regimen of intravesical bacillus Calmette-Guérin (BCG) therapy (induction vs. maintenance) remained independent predicting factors for recurrence-free survival (RFS) (p = 0.001, hazard ratio [HR]: 1.77), (p < 0.001 HR: 0.16) and progression-free survival (PFS) (p = 0.014, HR: 2.11), (p = 0.008, HR: 0.097), respectively. The presence of T0 on re-TUR is associated with better RFS and PFS and could be a predictive factor for candidates for conservative management. Patients with persistent NMIBC on re-TUR require close follow-up and, in some cases, could be considered for early cystectomy. Maintenance intravesical BCG therapy can improve RFS and PFS in patients with high-risk NMIBC. This study is limited by its retrospective nature and the relatively small number of patients in the cohort.


Fetal heart rate variation after corticosteroids for fetal maturation.
Several studies report a decrease of fetal heart rate (FHR) short-term variation (STV) after corticosteroids for improvement of fetal maturity and advice not to deliver a fetus for low STV within 2-3days after corticosteroids. However, literature is not unanimous in this respect. This study intends to asses STV longitudinally after corticosteroid administration. A retrospective cohort study in a tertiary perinatal centre from 2009 to 2015 included all women who had been treated with corticosteroids at gestational age of 26-34 weeks, had a computerized cardiotocography (cCTG) before and after medication and did not deliver within 48h. FHR and STV were stratified over 12-h periods and compared before and after corticosteroids. Women with imminent preterm labour (including PPROM) and women with placental problems (fetal growth restriction (FGR) or preeclampsia) (PE) were analysed separately. The effect of co-medication and gestational age was assessed. The study included 406 women, 211 with imminent preterm labour, 195 with FGR-PE. After corticosteroids STV increased 1-2ms (median 1.4; IQR 0.1-3.1) during the first 36h after start of corticosteroids. Thereafter a small decrease of less than 1ms (median -0,6; IQR -1.6 to 0.3) compared to before CC was seen. The most conspicuous effect of corticosteroids is a short term increase of STV and decrease of FHR. A slight decrease after 48-71h is possible, but abnormally low values should be considered as a sign of fetal distress. The clinical guidance, given by some, not to intervene because of a low STV after corticosteroids appears invalid.


Care Recommendations for the Investigation and Management of Children With Skeletal Muscle Channelopathies.
The field of pediatric skeletal muscle channelopathies has seen major new advances in terms of a wider understanding of clinical presentations and new phenotypes. Skeletal muscle channelopathies cause significant disability and even death in some of the newly described phenotypes. Despite this, there are virtually no data on the epidemiology and longitudinal natural history of these conditions or randomized controlled trial evidence of efficacy or tolerability of any treatment in children, and thus best practice care recommendations do not exist. Clinical history, and to a lesser extent examination, is key to eliciting symptoms and signs that indicate a differential diagnosis of muscle channelopathy. Normal routine investigations should not deter one from the diagnosis. Specialist neurophysiologic investigations have an additional role, but their availability should not delay genetic testing. New phenotypes are increasingly likely to be identified by next-generation sequencing panels. Many treatments or interventions for symptomatic patients are available, with anecdotal data to support their benefit, but we lack trial data on efficacy, safety, or superiority. This lack of trial data in turn can lead to hesitancy in prescribing among doctors or in accepting medication by parents. Holistic management addressing work, education, activity, and additional symptoms of pain and fatigue provides significant benefit. Preventable morbidity and sometimes mortality occurs if the diagnosis and therefore treatment is delayed. Advances in genetic sequencing technology and greater access to testing may help to refine recently identified phenotypes, including histology, as more cases are described. Randomized controlled treatment trials are required to inform best practice care recommendations. A holistic approach to management is essential and should not be overlooked. Good quality data on prevalence, health burden, and optimal treatment are urgently needed.


New options for central venous access in cancer chemotherapy. Multiple lumen catheters.
New technology has allowed the creation of single catheters with up to four separate luminal channels for access to the central venous system. Since cancer chemotherapy may be associated with local complications specifically related to the mode of intravenous administration, temporary central venous access with a multiple lumen catheter (MLC) offers distinct theoretical advantages over previously used peripheral venous sites. As part of a prospective study to evaluate the clinical efficacy of MLC, the authors have separately studied the usefulness of these catheters in providing venous access to patients receiving chemotherapy.


Nuclear but not cytosolic phosphoinositide 3-kinase beta has an essential function in cell survival.
Class I(A) phosphoinositide 3-kinases (PI3Ks) are heterodimeric enzymes composed of a p85 regulatory and a p110 catalytic subunit that induce the formation of 3-polyphosphoinositides, which mediate cell survival, division, and migration. There are two ubiquitous PI3K isoforms p110α and p110β that have nonredundant functions in embryonic development and cell division. However, whereas p110α concentrates in the cytoplasm, p110β localizes to the nucleus and modulates nuclear processes such as DNA replication and repair. At present, the structural features that determine p110β nuclear localization remain unknown. We describe here that association with the p85β regulatory subunit controls p110β nuclear localization. We identified a nuclear localization signal (NLS) in p110β C2 domain that mediates its nuclear entry, as well as a nuclear export sequence (NES) in p85β. Deletion of p110β induced apoptosis, and complementation with the cytoplasmic C2-NLS p110β mutant was unable to restore cell survival. These studies show that p110β NLS and p85β NES regulate p85β/p110β nuclear localization, supporting the idea that nuclear, but not cytoplasmic, p110β controls cell survival.


Current Psychopathological Symptoms in Children and Adolescents Who Suffered Different Forms of Maltreatment.
The aim of the present study is to evaluate the current psychopathological problems of different forms associated with maltreatment on children's and adolescents' mental health. Ninety-five females and ninety males with a mean age of 8.8 years who have suffered in the last six months different forms of abuse (physical, sexual, and emotional) and neglect were included in the study. The current reaction to trauma as directly observed by clinical instruments was examined. Differences in gender, age at the time of medical examination, familial psychiatric disorders, neuropsychiatric status, and type of maltreatment were also taken into account. Results documented that 95.1% of abused children and adolescents developed a psychiatric disorder or a subclinical form of a Posttraumatic Stress Disorder (PTSD). Moreover, our data demonstrate a role for gender, age, and familial psychiatric comorbidity in the current psychopathological problems associated with maltreatment. Overall, our findings can help clinicians make a diagnosis and provide efficient treatment and prevention strategies for child maltreatment and abuse.


Effectiveness of albumin-conjugated gossypol as an immunogen to prevent gossypol-associated acute hepatotoxicity in rats.
Gossypol is a highly reactive compound present in cotton (Gossypium spp.). The aim of this work was to determine whether the administration of gossypol conjugated to albumin can immunize rats and thereby prevent the acute hepatotoxicity associated with gossypol. The first experiment consisted of administering the immunogen gossypol-BSA, with or without the Freund's incomplete adjuvant, to rats. The production of antibodies against gossypol was subsequently verified. The second experiment comprised three groups of Wistar rats: VG, CG and CO. The rats from the VG cohort were injected with gossypol-BSA associated with Freund's incomplete adjuvant, and the animals from the CG and CO groups were injected with saline solution. After 21 days, the rats from the VG and CG cohorts were treated with 30 mg/kg of gossypol by intraperitoneal injection, whereas the rats from the CO group received corn oil. After 24 h, the rats were evaluated for clinical signs of pathology, and their serum was biochemically analyzed. It was found that gossypol promoted hepatotoxic effects that were not prevented by the administration of gossypol-BSA. In conclusion, the administration of gossypol-BSA associated with Freund's incomplete adjuvant may be lightly to prevent the acute hepatotoxicity associated with gossypol.


Subjectivity and intersubjectivity of clinical facts.
The author has learned a great deal from the IJPA 75th Anniversary Issue, particularly regarding ways in which psychoanalysts across the world are consensually re-defining psychoanalysis as a quintessentially subjective and intersubjective endeavour. In summarising her response to the Issue, she addresses the ways in which its focus on psychoanalytic subjectivity and intersubjectivity helps to define the nature of psychoanalysis as a scientific endeavour. In addition, she identifies an area that she wished had been more developed in the Issue: some further specification of the cognitive and communicative processes that make for psychoanalytic subjectivity and intersubjectivity. She speculates that, as we continue our attempts further to understand those processes, we may find it valuable to look towards a body of research that is absent from consideration in the 75th Anniversary Issue (and is, for that matter, absent from serious and scientific consideration by psychoanalysts in general): research on mental effects currently considered 'anomalous', or outside the bounds of conventionally defined human mental function and capacity. She describes briefly some of that research in the context of its possible relevance to issues of psychoanalytic subjectivity and intersubjectivity. She takes up the specific relevance of that research to phenomena we have traditionally subsumed under categories of experience like intuition, empathic attunement and unconscious communication.


Postoperative lumbar CT: technique, results, and indications.
Seventy-seven patients with recurrent radicular symptoms after operation for lumbar disk herniation were examined by plain computed tomography (CT) and by intravenously enhanced CT. With the latter technique, scar tissue and recurrent disk herniation can be distinguished: scar tissue shows definite contrast enhancement whereas recurrent disk herniation remains unenhanced. Nerve roots surrounded by scar tissue are often visualized on the postcontrast scan as rounded lucencies. Symmetrical undisplaced nerve roots were identified in 88% of cases of hypertrophic scar formation; this finding excludes recurrent disk herniation. Dural calcifications were found in five patients with hypertrophic scar formation. The authors conclude that CT with contrast enhancement should be the method of choice for evaluating patients with recurrent radicular symptoms after operation for disk herniation.


En route to nanoscopic quantum optical imaging: counting emitters with photon-number-resolving detectors.
The fundamental understanding of biological pathways requires minimally invasive nanoscopic optical resolution imaging. Many approaches to high-resolution imaging rely on localization of single emitters, such as fluorescent molecules or quantum dots. Additionally, the exact determination of the number of such emitters in an imaging volume is essential for a number of applications; however, in standard intensity-based microscopy it is not possible to determine the number of individual emitters within a diffraction limited spot without initial knowledge of system parameters. Here we explore how quantum measurements of the emitted photons using photon number resolving detectors can be used to address this challenging task. In the proposed new approach, the problem of counting emitters reduces to the task of determining differences between the emitted photon distribution and the Poisson limit. We show that quantum measurements of the number of photons emitted from an ensemble of emitters enable the determination of both the number of emitters and the probability of emission. This method can be applied for any type of single-photon emitters. The scaling laws of this new approach are presented by the Cramer-Rao Lower Bounds, and this technique has great potential in quantum optical imaging with nanoscopic resolution.


How long do anti-predator interventions remain effective? Patterns, thresholds and uncertainty.
Human-predator conflicts are globally widespread, and effective interventions are essential to protect human assets from predator attacks. As effectiveness also has a temporal dimension, it is of importance to know how long interventions remain most effective and to determine time thresholds at which effectiveness begins to decrease. To address this, we conducted a systematic review of the temporal changes in the effectiveness of non-invasive interventions against terrestrial mammalian predators, defining a temporal trend line of effectiveness for each published case. We found only 26 cases from 14 publications, mainly referring to electric fences (n = 7 cases) and deterrents (n = 7 cases). We found electric fences and calving control to remain highly effective for the longest time, reducing damage by 100% for periods between three months and 3 years. The effectiveness of acoustical and light deterrents as well as guarding animals eroded quite fast after one to five months. Supplemental feeding was found to be counter-productive by increasing damage over time instead of reducing it. We stress that it is vital to make monitoring a routine requirement for all intervention applications and suggest to standardize periods of time over which monitoring can produce meaningful and affordable information.


Disturbed white matter integrity on diffusion tensor imaging in young children with epilepsy.
To evaluate whether abnormalities in white matter (WM) integrity are present in young children with epilepsy. Twelve children (3-6 years old) with epilepsy and six matched healthy controls were recruited for brain diffusion tensor imaging (DTI). Track-based spatial statistics (TBSS) was used to analyse and compare DTI indices of mean diffusivity (MD), fractional anisotropy (FA), axial and radial diffusivity (AD/RD) between patients and controls, and correlations between clinical variables and DTI parameters were analysed. Compared with controls, patients showed increased FA in the left superior corona radiata and increased AD in the bilateral superior corona radiata. In children with generalised epilepsy, FA was increased in the left external capsule, while AD was decreased in the body of the corpus callosum, the left external capsule and the left superior longitudinal fasciculus. In those with focal epilepsy, FA was increased in the genu and body of the corpus callosum, and RD was decreased in the genu of the corpus callosum and left external capsule. Compared with partial epilepsy, generalised epilepsy was associated with increased FA in the right anterior corona radiata and decreased RD in the right anterior corona radiata and the genu and body of the corpus callosum. No significant correlations were observed between clinical variables and DTI parameters. The results of this study indicate that the microstructure of the white matter is disturbed by epileptic discharges and a compensatory response occurs during early brain development.


Identification of dinR, a DNA damage-inducible regulator gene of Bacillus subtilis.
A Bacillus subtilis strain deficient in homologous recombination was isolated from a library of Tn917lac insertion mutants. The interrupted locus consists of an open reading frame encoding a 22,823-dalton polypeptide. Analysis of the deduced amino acid sequence revealed 34% identity and 47.3% similarity with the LexA protein from Escherichia coli. The gene was designated dinR. It is located between the recA and thyA genetic markers, at 162 degrees on the B. subtilis chromosome. The dinR gene was shown to be expressed during the entire B. subtilis cellular cycle with at least a threefold increase when cells develop competence. In addition, the use of a merodiploid strain, in which a copy of the wild-type dinR gene coexists with a dinR-lacZ transcriptional fusion, demonstrated that dinR is an SOS gene and that the SOS-induced expression of dinR occurred only when a wild-type copy of dinR was present. In addition, DinR seems to regulate the expression of dinC, another SOS gene.


miR-122 negatively correlates with liver fibrosis as detected by histology and FibroScan.
To investigate whether expression of selected miRNAs obtained from fibrotic liver biopsies correlate with fibrosis stage. Altogether, 52 patients were enrolled in the study representing various etiologic backgrounds of fibrosis: 24 cases with chronic hepatitis infections (types B, C), 19 with autoimmune liver diseases (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, overlapping syndrome cases), and 9 of mixed etiology (alcoholic and nonalcoholic steatosis, cryptogenic cases). Severity of fibrosis was determined by both histologic staging using the METAVIR scoring system and noninvasive transient elastography. Following RNA isolation, expression levels of miR-21, miR-122, miR-214, miR-221, miR-222, and miR-224 were determined using TaqMan MicroRNA Assays applying miR-140 as the reference. Selection of miRNAs was based on their characteristic up- or downregulation observed in hepatocellular carcinoma. Relative expression of miRNAs was correlated with fibrosis stage and liver stiffness (LS) value measured by transient elastography, as well as with serum alanine aminotransferase (ALT) level. The expression of individual miRNAs showed deregulated patterns in stages F1-F4 as compared with stage F0, but only the reduced level of miR-122 in stage F4 was statistically significant (P < 0.04). When analyzing miRNA expression in relation to fibrosis, levels of miR-122 and miR-221 showed negative correlations with fibrosis stage, and miR-122 was found to correlate negatively and miR-224 positively with LS values (all P < 0.05). ALT levels displayed a positive correlation with miR-21 (P < 0.04). Negative correlations were observed in the fibrosis samples of mixed etiology between miR-122 and fibrosis stage and LS values (P < 0.05), and in the samples of chronic viral hepatitis, between miR-221 and fibrosis stage (P < 0.01), whereas miR-21 showed positive correlation with ALT values in the samples of autoimmune liver diseases (P < 0.03). The results also revealed a strong correlation between fibrosis stage and LS values (P < 0.01) when etiology of fibrosis was not taken into account. Reduced expression of miR-122 in advanced fibrosis and its correlation with fibrosis stage and LS values seem to be characteristic of hepatic fibrosis of various etiologies.