Environmental impact assessment of sand mining from the small catchment rivers in the southwestern coast of India: a case study.
In the past few decades, the demand for construction grade sand is increasing in many parts of the world due to rapid economic development and subsequent growth of building activities. This, in many of the occasions, has resulted in indiscriminate mining of sand from in-stream and floodplain areas leading to severe damages to the river basin environment. The case is rather alarming in the small catchment rivers like those draining the southwestern coast of India due to limited sand resources in their alluvial reaches. Moreover, lack of adequate information on the environmental impact of river sand mining is a major lacuna challenging regulatory efforts in many developing countries. Therefore, a scientific assessment is a pre-requisite in formulating management strategies in the sand mining-hit areas. In this context, a study has been made as a case to address the environmental impact of sand mining from the in-stream and floodplain areas of three important rivers in the southwestern coast of India namely the Chalakudy, Periyar and Muvattupuzha rivers, whose lowlands host one of the fast developing urban-cum-industrial centre, the Kochi city. The study reveals that an amount of 11.527 million ty(-1) of sand (8.764 million ty(-1) of in-stream sand and 2.763 million ty(-1) of floodplain sand) is being mined from the midland and lowland reaches of these rivers for construction of buildings and other infrastructural facilities in Kochi city and its satellite townships. Environmental Impact Assessment (EIA) carried out as a part of this investigation shows that the activities associated with mining and processing of sands have not only affected the health of the river ecosystems but also degraded its overbank areas to a large extent. Considering the degree of degradation caused by sand mining from these rivers, no mining scenario may be opted in the deeper zones of the river channels. Also, a set of suggestions are made for the overall improvement of the rivers and its biophysical environment.


Nrf2 promotes neuronal cell differentiation.
The transcription factor Nrf2 has emerged as a master regulator of the endogenous antioxidant response, which is critical in defending cells against environmental insults and in maintaining intracellular redox balance. However, whether Nrf2 has any role in neuronal cell differentiation is largely unknown. In this report, we have examined the effects of Nrf2 on cell differentiation using a neuroblastoma cell line, SH-SY5Y. Retinoic acid (RA) and 12-O-tetradecanoylphorbol 13-acetate, two well-studied inducers of neuronal differentiation, are able to induce Nrf2 and its target gene NAD(P)H quinone oxidoreductase 1 in a dose- and time-dependent manner. RA-induced Nrf2 up-regulation is accompanied by neurite outgrowth and an induction of two neuronal differentiation markers, neurofilament-M and microtubule-associated protein 2. Overexpression of Nrf2 in SH-SY5Y cells promotes neuronal differentiation, whereas inhibition of endogenous Nrf2 expression inhibited neuronal differentiation. More remarkably, the positive role of Nrf2 in neuronal differentiation was verified ex vivo in primary neuron culture. Primary neurons isolated from Nrf2-null mice showed a retarded progress in differentiation, compared to those from wild-type mice. Collectively, our data demonstrate a novel role for Nrf2 in promoting neuronal cell differentiation, which will open new perspectives for therapeutic uses of Nrf2 activators in patients with neurodegenerative diseases.


The natural history of cervical spondylotic myelopathy.
The objective of this systematic review was to use evidence-based medicine to delineate the natural history of cervical spondylotic myelopathy (CSM) and identify factors associated with clinical deterioration. The National Library of Medicine and Cochrane Database were queried using MeSH headings and keywords relevant to the natural history of CSM. Abstracts were reviewed and studies meeting the inclusion criteria were selected. The guidelines group assembled an evidentiary table summarizing the quality of evidence (Classes I-III). Disagreements regarding the level of evidence were resolved through an expert consensus conference. The group formulated recommendations that contained the degree of strength based on the Scottish Intercollegiate Guidelines network. Validation was done through peer review by the Joint Guidelines Committee of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. The natural history of CSM is mixed: it may manifest as a slow, stepwise decline or there may be a long period of quiescence (Class III). Long periods of severe stenosis are associated with demyelination and may result in necrosis of both gray and white matter. With severe and/or long lasting CSM symptoms, the likelihood of improvement with nonoperative measures is low. Objectively measurable deterioration is rarely seen acutely in patients younger than 75 years of age with mild CSM (modified Japanese Orthopaedic Association scale score > 12; Class I). In patients with cervical stenosis without myelopathy, the presence of abnormal electromyography findings or the presence of clinical radiculopathy is associated with the development of symptomatic CSM in this patient population (Class I). The natural history of CSM is variable, which may affect treatment decisions.


American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group Consensus Conference on Salvage Hematopoietic Cell Transplantation in Patients with Relapsed Multiple Myeloma.
In contrast to the upfront setting in which the role of high-dose therapy with autologous hematopoietic cell transplantation (HCT) as consolidation of a first remission in patients with multiple myeloma (MM) is well established, the role of high-dose therapy with autologous or allogeneic HCT has not been extensively studied in MM patients relapsing after primary therapy. The International Myeloma Working Group together with the Blood and Marrow Transplant Clinical Trials Network, the American Society of Blood and Marrow Transplantation, and the European Society of Blood and Marrow Transplantation convened a meeting of MM experts to: (1) summarize current knowledge regarding the role of autologous or allogeneic HCT in MM patients progressing after primary therapy, (2) propose guidelines for the use of salvage HCT in MM, (3) identify knowledge gaps, (4) propose a research agenda, and (5) develop a collaborative initiative to move the research agenda forward. After reviewing the available data, the expert committee came to the following consensus statement for salvage autologous HCT: (1) In transplantation-eligible patients relapsing after primary therapy that did NOT include an autologous HCT, high-dose therapy with HCT as part of salvage therapy should be considered standard; (2) High-dose therapy and autologous HCT should be considered appropriate therapy for any patients relapsing after primary therapy that includes an autologous HCT with initial remission duration of more than 18 months; (3) High-dose therapy and autologous HCT can be used as a bridging strategy to allogeneic HCT; (4) The role of postsalvage HCT maintenance needs to be explored in the context of well-designed prospective trials that should include new agents, such as monoclonal antibodies, immune-modulating agents, and oral proteasome inhibitors; (5) Autologous HCT consolidation should be explored as a strategy to develop novel conditioning regimens or post-HCT strategies in patients with short (less than 18 months remissions) after primary therapy; and (6) Prospective randomized trials need to be performed to define the role of salvage autologous HCT in patients with MM relapsing after primary therapy comparing it to "best non-HCT" therapy. The expert committee also underscored the importance of collecting enough hematopoietic stem cells to perform 2 transplantations early in the course of the disease. Regarding allogeneic HCT, the expert committee agreed on the following consensus statements: (1) Allogeneic HCT should be considered appropriate therapy for any eligible patient with early relapse (less than 24 months) after primary therapy that included an autologous HCT and/or high-risk features (ie, cytogenetics, extramedullary disease, plasma cell leukemia, or high lactate dehydrogenase); (2) Allogeneic HCT should be performed in the context of a clinical trial if possible; (3) The role of postallogeneic HCT maintenance therapy needs to be explored in the context of well-designed prospective trials; and (4) Prospective randomized trials need to be performed to define the role salvage allogeneic HCT in patients with MM relapsing after primary therapy.


Yes-associated protein 1 and transcriptional coactivator with PDZ-binding motif activate the mammalian target of rapamycin complex 1 pathway by regulating amino acid transporters in hepatocellular carcinoma.
Metabolic activation is a common feature of many cancer cells and is frequently associated with the clinical outcomes of various cancers, including hepatocellular carcinoma. Thus, aberrantly activated metabolic pathways in cancer cells are attractive targets for cancer therapy. Yes-associated protein 1 (YAP1) and transcriptional coactivator with PDZ-binding motif (TAZ) are oncogenic downstream effectors of the Hippo tumor suppressor pathway, which is frequently inactivated in many cancers. Our study revealed that YAP1/TAZ regulates amino acid metabolism by up-regulating expression of the amino acid transporters solute carrier family 38 member 1 (SLC38A1) and solute carrier family 7 member 5 (SLC7A5). Subsequently, increased uptake of amino acids by the transporters (SLC38A1 and SLC7A5) activates mammalian target of rapamycin complex 1 (mTORC1), a master regulator of cell growth, and stimulates cell proliferation. We also show that high expression of SLC38A1 and SLC7A5 is significantly associated with shorter survival in hepatocellular carcinoma patients. Furthermore, inhibition of the transporters and mTORC1 significantly blocks YAP1/TAZ-mediated tumorigenesis in the liver. These findings elucidate regulatory networks connecting the Hippo pathway to mTORC1 through amino acid metabolism and the mechanism's potential clinical implications for treating hepatocellular carcinoma. YAP1 and TAZ regulate cancer metabolism and mTORC1 through regulation of amino acid transportation, and two amino acid transporters, SLC38A1 and SLC7A5, might be important therapeutic targets.


Consent for critical care research after death from COVID-19: Arguments for a waiver.
Pandemics challenge clinicians and scientists in many ways, especially when the virus is novel and disease expression becomes variable or unpredictable. Under such circumstances, research becomes critical to inform clinical care and protect future patients. Given that severely ill patients admitted to intensive care units are at high risk of mortality, establishing the cause of death at a histopathological level could prove invaluable in contributing to the understanding of COVID-19. Postmortem examination including autopsies would be optimal. However, in the context of high contagion and limited personal protective equipment, full autopsies are not being conducted in South Africa (SA). A compromise would require tissue biopsies and samples to be taken immediately after death to obtain diagnostic information, which could potentially guide care of future patients, or generate hypotheses for finding needed solutions. In the absence of an advance written directive (including a will or medical record) providing consent for postmortem research, proxy consent is the next best option. However, obtaining consent from distraught family members, under circumstances of legally mandated lockdown when strict infection control measures limit visitors in hospitals, is challenging. Their extreme vulnerability and emotional distress make full understanding of the rationale and consent process difficult either before or upon death of a family member. While it is morally distressing to convey a message of death telephonically, it is inhumane to request consent for urgent research in the same conversation. Careful balancing of the principles of autonomy, non-maleficence and justice becomes an ethical imperative. Under such circumstances, a waiver of consent, preferably followed by deferred proxy consent, granted by a research ethics committee in keeping with national ethics guidance and legislation, would fulfil the basic premise of care and research: first do no harm. This article examines the SA research ethics framework, guidance and legislation to justify support for a waiver of consent followed by deferred proxy consent, when possible, in urgent research after death to inform current and future care to contain the pandemic in the public interest.


Early adolescent cognitive gains are marked by increased sleep EEG coherence.
Although the increases in cognitive capacities of adolescent humans are concurrent with significant cortical restructuring, functional associations between these phenomena are unclear. We examined the association between cortical development, as measured by the sleep EEG, and cognitive performance in a sample of 9/10 year olds followed up 1 to 3 years later. Our cognitive measures included a response inhibition task (Stroop), an executive control task (Trail Making), and a verbal fluency task (FAS). We correlated sleep EEG measures of power and intra-hemispheric coherence at the initial assessment with performance at that assessment. In addition we correlated the rate of change across assessments in sleep EEG measures with the rate of change in performance. We found no correlation between sleep EEG power and performance on cognitive tasks for the initial assessment. In contrast, we found a significant correlation of the rate of change in intra-hemispheric coherence for the sigma band (11 to 16 Hz) with rate of change in performance on the Stroop (r = 0.61; p<0.02) and Trail Making (r = -0.51; p<0.02) but no association for the FAS. Thus, plastic changes in connectivity (i.e., sleep EEG coherence) were associated with improvement in complex cognitive function.


Molecular cloning and sequence analysis of the Chlamydomonas gene coding for radial spoke protein 3: flagellar mutation pf-14 is an ochre allele.
Chlamydomonas reinhardtii flagellar motility mutant pf-14 fails to assemble radial spokes because of a deficiency for assembly-competent radial spoke protein 3 (Huang, B., G. Piperno, Z. Ramanis, and D. J. L. Luck. 1981. J. Cell Biol. 88:80-88). Here, we raise an antiserum to protein 3 and use it to isolate the corresponding structural gene from an expression library. Southern blot analysis indicates that the gene is single copy and has not undergone major rearrangement in mutant pf-14 cells. Northern blot analysis suggests that wild-type amounts of an apparently normal 2.3-kb transcript accumulate in mutant cells during flagellar regeneration. When this mutant RNA is hybrid selected and translated in vitro, however, it produces a slightly truncated polypeptide 3 with an altered charge. The mutant protein 3 fails to assemble into pf-14 flagella and is maintained within a cytoplasmic pool of unassembled radial spoke polypeptides, as indicated by immunoblot analysis of proteins from whole cells and isolated axonemes using antisera to several radial spoke polypeptides. Interestingly, amounts of the mutant protein are greatly diminished relative to other spoke components. Complete genomic and cDNA nucleotide sequences were determined, and the pf-14 mutation was identified. It is a C-to-T transition near the 5' end of the protein coding region, which changes codon 21 to the ochre termination signal UAA. The size and charge of the mutant protein, and its reduced levels in cells, suggest that it is produced by relatively inefficient translational initiation as codon 42. The unphosphorylated isoform of radial spoke protein 3 is identified, and the sequence similarities between intervening sequences of the radial spoke protein 3 gene and a conserved intervening sequence of the two Chlamydomonas beta-tubulin genes (Youngblom, J., J. A. Schloss, and C. D. Silflow. 1984. Mol. Cell. Biol. 4:2686-2696) are reported.


Supplement with whey protein hydrolysate in contrast to carbohydrate supports mitochondrial adaptations in trained runners.
Protein supplementation has been suggested to augment endurance training adaptations by increasing mixed muscle and myofibrillar protein synthesis and lean body mass. However, a potential beneficial effect on mitochondrial adaptations is yet to be clarified. The aim of the present study was to investigate the effect of consuming whey protein hydrolysate before and whey protein hydrolysate plus carbohydrate (PRO-CHO) after each exercise session during a six-week training period compared to similarly timed intake of isocaloric CHO supplements on biomarkers of mitochondrial biogenesis, VO2max and performance in trained runners. Twenty-four trained runners (VO2max 60.7 ± 3.7 ml O2 kg- 1 min1) completed a six-week block randomized controlled intervention period, consisting of progressive running training. Subjects were randomly assigned to either PRO-CHO or CHO and matched in pairs for gender, age, VO2max, training and performance status. The PRO-CHO group ingested a protein beverage (0.3 g kg- 1) before and protein-carbohydrate beverage (0.3 g protein kg- 1 and 1 g carbohydrate kg- 1) after each exercise session. The CHO group ingested an energy matched carbohydrate beverage. Resting muscle biopsies obtained pre and post intervention were analyzed for mitochondrial specific enzyme activity and mitochondrial protein content. Subjects completed a 6 K time trial (6 K TT) and a VO2max test pre, midway (only 6 K TT) and post intervention. Following six weeks of endurance training Cytochrome C (Cyt C) protein content was significantly higher in the PRO-CHO group compared to the CHO group (p < 0.05), with several other mitochondrial proteins (Succinate dehydrogenase (SDHA), Cytochrome C oxidase (COX-IV), Voltage-dependent anion channel (VDAC), Heat shock protein 60 (HSP60), and Prohibitin (PHB1)) following a similar, but non-significant pattern (p = 0.07-0.14). β-hydroxyacyl-CoA dehydrogenase (HAD) activity was significantly lower after training in the CHO group (p < 0.01), but not in the PRO-CHO group (p = 0.24). VO2max and 6 K TT was significantly improved after training with no significant difference between groups. Intake of whey PRO hydrolysate before and whey PRO hydrolysate plus CHO after each exercise session during a six-week endurance training period may augment training effects on specific mitochondrial proteins compared to intake of iso-caloric CHO but does not alter VO2max or 6 K TT performance. clinicaltrials.gov , NCT03561337 . Registered 6 June 2018 - Retrospectively registered.


Miniaturized QuEChERS method for determination of 97 pesticide residues in wine by ultra-high performance liquid chromatography coupled with tandem mass spectrometry.
A miniaturized sample preparation method was developed and validated for the multiresidue determination of 97 pesticides in wine samples. The proposed extraction procedure is based on the QuEChERS acetate method with dispersive solid phase extraction (d-SPE) for the clean-up step. Ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) was used for determination. The extraction and clean-up steps were evaluated to obtain the best conditions for the selected pesticides. Miniaturization of the sample preparation step provided a reduction in the consumption of samples and chemicals. The method limit of quantification was between 10 and 20 μg L-1. Trueness results, obtained by recovery assays at the spike levels 10, 20, 50 and 100 μg L-1, ranged from 70 to 120% with precision in terms of relative standard deviations (RSD) ≤ 20%. The method was successfully applied for the analysis of wine samples and different pesticides were found at concentrations from 14 to 55 μg L-1.


Methodological challenges in following up patients of a hospital child protection team: is there a recruitment bias?
The aims of this study are to describe the methodological challenges in recruiting a follow-up sample of children referred to an interdisciplinary hospital child protection team (CPT) and to compare participating versus non-participating groups on several demographic variables and maltreatment characteristics. Of the 319 in- and outpatients referred to the CPT at University Children's Hospital Zurich from 2005-2006 a sample of 180 children was drawn to contact for a follow-up. The children and their parents were asked to participate in a face-to-face interview at the hospital; in 42 cases the children and parents consented to do so. Alternatively, the parents could take part in a telephone interview (n = 39). Non-participation resulted because no contact or adequate communication in German, French, or English could be established (n = 49) or because the parents or children refused to participate (n = 50). Participants and non-participants did not differ significantly in mean child age at follow-up, gender, family status, place of residence, certainty and type of maltreatment, and type of perpetrator. However, the child's nationality had a significant impact: Percentages of foreign nationals were higher in the fully participating group (45%; n = 19) and the non-contactable group (53%; n = 26) and significantly lower in the refusal (26%; n = 10) and the telephone interview group (18%; n = 9). Although a high percentage of families had moved in the few years since the CPT intervention (32%; n = 57), the percentage of moves was not significantly higher in non-participants compared to participants. Further research is needed to support these results in different national backgrounds and to test for biases in variables not included - especially socioeconomic status. This includes gathering more detailed information on non-participants, while respecting ethical boundaries. Overall, the fact that only child's nationality was unevenly distributed between participants and non-participants is encouraging.


No evidence for mutations in NLRP7, NLRP2 or KHDC3L in women with unexplained recurrent pregnancy loss or infertility.
Are mutations in NLRP2/7 (NACHT, LRR and PYD domains-containing protein 2/7) or KHDC3L (KH Domain Containing 3 Like) associated with recurrent pregnancy loss (RPL) or infertility? We found no evidence for mutations in NLRP2/7 or KHDC3L in unexplained RPL or infertility. Mutations in NLRP7 and KHDC3L are known to cause biparental hydatidiform moles (BiHMs), a rare form of pregnancy loss. NLRP2, while not associated with the BiHM pathology, is known to cause recurrent Beckwith Weidemann Syndrome (BWS). Ninety-four patients with well characterized, unexplained infertility were recruited over a 9-year period from three IVF clinics in Sweden. Blood samples from 24 patients with 3 or more consecutive miscarriages of unknown etiology were provided by the Recurrent Miscarriage Clinic at St Mary's Hospital, London, UK. Patients were recruited into both cohorts following extensive clinical studies. Genomic DNA was isolated from peripheral blood and subject to Sanger sequencing of NLRP2, NLRP7 and KHDC3L. Sequence electropherograms were analyzed by Sequencher v5.0 software and variants compared with those observed in the 1000 Genomes, single nucleotide polymorphism database (dbSNP) and HapMap databases. Functional effects of non-synonymous variants were predicted using Polyphen-2 and sorting intolerant from tolerant (SIFT). No disease-causing mutations were identified in NLRP2, NLRP7 and KHDC3L in our cohorts of unexplained infertility and RPL. Due to the limited patient size, it is difficult to conclude if the low frequency single nucleotide polymorphisms observed in the present study are causative of the phenotype. The design of the present study therefore is only capable of detecting highly penetrant mutations. The present study supports the hypothesis that mutations in NLRP7 and KHDC3L are specific for the BiHM phenotype and do not play a role in other adverse reproductive outcomes. Furthermore, to date, mutations in NLRP2 have only been associated with the imprinting disorder BWS in offspring and there is no evidence for a role in molar pregnancies, RPL or unexplained infertility. This study was funded by the following sources: Estonian Ministry of Education and Research (Grant SF0180044s09), Enterprise Estonia (Grant EU30020); Mentored Resident research project (Department of Obstetrics and Gynecology, Baylor College of Medicine); Imperial NIHR Biomedical Research Centre; Grant Number C06RR029965 from the National Center for Research Resources (NCCR; NIH). No competing interests declared.


Health-related internet use in older primary care patients.
Adults aged 65 years and older stand to benefit from the accumulating wealth of Internet-based health resources, including online interventions to assist in the self-management of chronic health conditions. However, concerns have been expressed that lesser Internet use and familiarity among older adults may limit the utility of web-based health interventions in older age groups. As these interventions become more prevalent, it is important to understand older adults' receptivity to using the Internet as a tool in managing healthcare. The purpose of the present study was to gauge the extent to which older primary care patients are receptive to using web-based health resources, and to explore how health-related Internet use may be related to patient characteristics such as age, income, and health and mental health status. We surveyed 50 adults aged 65 years and older in a Veterans Administration primary care clinic regarding: (1) Internet use for any purpose, (2) Internet use to obtain health or mental-related information, and (3) interest in using Internet-based interventions to address various health-related needs. A substantial proportion of respondents were in their 70s, 80s, and 90s, and many had multiple medical conditions. Nearly three-quarters of older primary care patients in our sample were regular Internet users and over half had experience in using the Internet to search for health information. The majority of Internet users endorsed an interest in using web-based resources to manage various aspects of their health and mental healthcare. Our results support the conclusion that older primary care patients, including those among the oldest-old and those with multiple medical conditions, are amenable to using the Internet as a means of enhancing healthcare.


Passive avoidance learning and memory of 56Fe sham-irradiated and irradiated human apoE transgenic mice.
Cranial irradiation is associated with long-term cognitive impairments, including deficits in hippocampus-dependent learning and memory. Not all people exposed to cranial radiation develop cognitive injury, suggesting the involvement of genetic risk factors. There may also be sex differences in susceptibility to develop radiation-induced cognitive injury. The three major human apolipoprotein E (apoE) isoforms are encoded by distinct alleles (epsilon2, epsilon3, and epsilon4). Compared with epsilon3, epsilon4 increases the risk of cognitive impairments following various challenges while epsilon2 provides relative protection. Women are at higher risk to develop Alzheimer's disease (AD) than men, particularly those carrying epsilon4. In previous experiments using male and female mice expressing human apoE-isoforms E2, E3 or E4 under the mouse apoE promoter, we showed that cranial irradiation with 137Cs (10 Gy) results in hippocampus-dependent cognitive impairments that are sex- and apoE-isoform dependent. 137Cs is a form of irradiation often used in the clinical setting. To investigate whether 56Fe irradiation also has sex- and apoE-isoform dependent effects on hippocampus-dependent cognitive function in human apoE mice, we sham-irradiated and irradiated 2-month old male and female human apoE mice at 3 Gy and assessed their performance in a passive avoidance learning and memory test three to five months later.


Long-term outcomes of anal sphincter repair for fecal incontinence: a systematic review.
Thorough and objective analysis of long-term results following anal sphincter repair for fecal incontinence will permit the correct application of this operation in the context of newer treatment methods. This investigation aimed to comprehensively review outcomes beyond 5 years in patients undergoing anal sphincter repair for fecal incontinence. A systematic review of Embase and MEDLINE articles published between January 1991 and December 2010 was conducted; additional studies were identified by hand-searching bibliographies. A 2-step process was used for screening articles examining sphincter repair or sphincteroplasty in adults with fecal incontinence, with a minimum follow-up of 60 months. Subjective or objective assessment of fecal incontinence in the postoperative period was completed. Data from 16 studies were examined, comprising nearly 900 repairs. There was significant heterogeneity in outcome measures, although most articles utilized at least one established incontinence instrument. In general, most series reported an initial subjectively "good" outcome in the majority of patients, with declines in this proportion over longer follow-up. There was poor correlation between quality of life and the severity of fecal incontinence, with all articles reporting high overall patient satisfaction even if continence declined with time or adaptive measures were needed. No consistent predictive factors for failure were identified. This study was limited by the paucity of level I data with an adequate length of follow-up. Despite worsening results over time, most patients remain satisfied with their surgical outcome postsphincteroplasty. Efforts should be directed at identifying patients who may do poorly following sphincter repair, as well as establishing standardized long-term outcome benchmarks for comparing novel techniques for treating fecal incontinence.


The role of the IGF system in cancer growth and metastasis: overview and recent insights.
IGF-I receptor (IGF-IR) signaling and functions are mediated through the activities of a complex molecular network of positive (e.g., type I IGF) and negative (e.g., the type II IGF receptor, IGF-IIR) effectors. Under normal physiological conditions, the balance between the expression and activities of these molecules is tightly controlled. Changes in this delicate balance (e.g., overexpression of one effector) may trigger a cascade of molecular events that can ultimately lead to malignancy. In recent years, evidence has been mounting that the IGF axis may be involved in human cancer progression and can be targeted for therapeutic intervention. Here we review old and more recent evidence on the role the IGF system in malignancy and highlight experimental and clinical studies that provide novel insights into the complex mechanisms that contribute to its oncogenic potential. Controversies arising from conflicting evidence on the relevance of IGF-IR and its ligands to human cancer are discussed. Our review highlights the importance of viewing the IGF axis as a complex multifactorial system and shows that changes in the expression levels of any one component of the axis, in a given malignancy, should be interpreted with caution and viewed in a wider context that takes into account the expression levels, state of activation, accessibility, and functionality of other interacting components. Because IGF targeting for anticancer therapy is rapidly becoming a clinical reality, an understanding of this complexity is timely because it is likely to have an impact on the design, mode of action, and clinical outcomes of newly developed drugs.


Vervet monkeys solve a multiplayer "forbidden circle game" by queuing to learn restraint.
In social dilemmas, the ability of individuals to coordinate their actions is crucial to reach group optima. Unless exacted by power or force, coordination in humans relies on a common understanding of the problem, which is greatly facilitated by communication. The lack of means of consultation about the nature of the problem and how to solve it may explain why multiagent coordination in nonhuman vertebrates has commonly been observed only when multiple individuals react instantaneously to a single stimulus, either natural or experimentally simulated, for example a predator, a prey, or a neighboring group. Here we report how vervet monkeys solved an experimentally induced coordination problem. In each of three groups, we trained a low-ranking female, the "provider," to open a container holding a large amount of food, which the providers only opened when all individuals dominant to them ("dominants") stayed outside an imaginary "forbidden circle" around it. Without any human guidance, the dominants learned restraint one by one, in hierarchical order from high to low. Once all dominants showed restraint immediately at the start of the trial, the providers opened the container almost instantly, saving all individuals opportunity costs due to lost foraging time. Solving this game required trial-and-error learning based on individual feedback from the provider to each dominant, and all dominants being patient enough to wait outside the circle while others learned restraint. Communication, social learning, and policing by high-ranking animals played no perceptible role.


Comparative Efficacy of 10% Sodium Hydroxide, 88% Phenol, and 90% Trichloroacetic Acid as Chemical Cauterants for Partial Matricectomy in the Management of Great Toe Nail Onychocryptosis.
Lateral plate avulsion with chemical matricectomy is the treatment of choice for ingrown toenails. Phenol is the most widely used cauterant, followed by 10% NaOH and more recently trichloroacetic acid. To evaluate the efficacy of 10% NaOH, 88% Phenol, and 90% TCA in cauterizing the matrix with regular follow up post surgery and clinical photographs. Fifteen adult patients presenting with ingrowing toe nails were recruited to the study with prior consent. The NaOH group (Group A) had five patients and five nails treated, the phenol group (Group B) had five patients and six nails treated, and the TCA group (Group C) had five patients and six nails treated. A total of 17 great toe nails were treated. Following proximal digital block and partial nail avulsion, the matrix was curetted and the lateral horn cauterized with 10% NaOH (1 min), 88% phenol (3 min), and 90% TCA (3 min). Post-procedure follow-up was done at weekly intervals to evaluate post-operative pain, oozing, and wound healing. Graph pad prism software was used for statistical analysis. ANOVA tests were used to test the statistical significance between post-operative parameters of each group. Mean duration of post-op pain in Group A was 4.2 days; Group B was 8.6 days, and Group C was 1.2 days. Oozing occurred for a mean duration of 10.6 days in Group A, 14 days in Group B, and 5.6 days in Group C. Mean duration of tissue re-epithelization was 28.4 days in Group A, 40.5 days in Group B, and 27.4 days in Group C. TCA is an effective cauterant for chemical matricectomy with the advantage of less duration of post-op pain and faster healing.


Enumerative Analysis of Salmonella in Outbreak-Associated Breaded and Frozen Comminuted Raw Chicken Products.
A significant data gap exists with respect to the levels of pathogens in foods implicated in foodborne outbreaks. These data are essential for the quantification of pathogen exposure via the ingestion of contaminated food. Here we report the levels of the foodborne pathogen Salmonella in comminuted raw chicken products that had been breaded and then frozen. The products investigated were collected during four food safety investigations of foodborne outbreaks that occurred in Canada from 2014 to 2016. Most-probable-number (MPN) distribution analysis of the food samples revealed Salmonella levels of 0.0018 to 3 MPN/g, which is equivalent to 1 MPN per 0.33 to 556 g of product. These data suggest low levels of Salmonella may be associated with foodborne outbreaks.


[Management of malignant pleural effusions].
Malignant pleural effusions with dyspnoea as their most common presenting symptom are a frequent clinical problem in patients with neoplastic disease. Lung carcinoma is the leading cause, followed by breast carcinoma and malignant lymphoma. The frequency of malignant mesothelioma is increasing in industrialized countries. In this overview, which is based on the ERS/ATS Statement 2001, the diagnostic approach, the differential diagnosis including causes of paramalignant effusions, as well as the therapeutic possibilities are described. Pleurodesis is the most important therapeutic modality, today preferably via thoracoscopic talc poudrage. Alternative local and systemic treatment options are discussed in detail. A special emphasis is put on the epidemiology, diagnosis, treatment, and prognosis of malignant effusions in patients with lung and breast carcinomas, and with lymphomas. Finally, open questions are listed which need future research, which will hopefully improve the treatment and prognosis of malignant pleural effusions.


Seasonal regulation of condensed tannin consumption by free-ranging goats in a semi-arid savanna.
Although condensed tannins (CTs) are known to reduce forage intake by mammalian herbivores in controlled experiments, few studies have tested these effects in the field. Thus the role of CTs on foraging ecology of free-ranging herbivores is inadequately understood. To investigate the effects of CTs under natural savanna conditions, we pre-dosed groups of goats with polyethylene glycol (PEG, a CT-neutralising chemical), CT powder or water before observing their foraging behaviour. While accounting for the effects of season and time of the day, we tested the hypothesis that herbivores forage in ways that reduce the intake rate (g DM per minute) of CTs. We expected pre-dosing goats with CTs to reduce CT intake rates by (1) consuming diets low in CTs, (2) reducing bite rates, (3) increasing the number of foraging bouts, or (4) reducing the length of foraging bouts. Lastly, (5) expected CT to have no influence the number of dietary forage species. In both wet and dry seasons, pre-dosing goats with CTs resulted in lower CT consumption rates compared to PEG goats which seemed relieved from the stress associated with CT consumption. During dry season, the number of dietary forage species was similar across treatments, although goats that were dosed with PEG significantly increased this number in the wet season. Dosing goats with PEG increased the number and length of browsing bouts compared to goats from the other treatments. Pre-loading goats with PEG also tended to increase bite rates on browse forages, which contributed to increased consumption rates of CTs. Based on the behavioural adjustments made by goats in this study and within the constraints imposed by chemical complexity in savanna systems, we concluded that herbivores under natural conditions foraged in ways that minimised CTs consumption. More research should further elucidate the mechanism through which CTs regulated feeding behaviour.


Cortical surface intracranial electrodes identify clinically relevant seizures missed on scalp EEG after traumatic intracranial hemorrhage.
Seizures and other electrophysiological disturbances are an under-recognized cause of coma, focal deficits, and prolonged encephalopathy following subdural hematoma evacuation. In these patients, it is possible that seizures remain unrecognized on scalp EEG. It has been shown that a high burden of seizures and other electrophysiological disturbances exist following surgical evacuation and underlie the encephalopathy commonly seen in this patient population, predisposing them to medical complications and confounding estimates of prognosis. As part of a research protocol, we are performing intraoperative placement of cortical surface (non-parenchyma penetrating) intracranial EEG on patients who present after trauma and require emergent decompressive hemicraniectomy. In this case report of a patient with high-velocity traumatic epidural, subdural, and subarachnoid hemorrhages, we identified frequent non-convulsive seizures or seizure-like SIRPIDs with intracranial cortical surface monitoring that were not identified on simultaneous scalp EEG. Stimulation consistently triggered these electrographic seizures in addition to rhythmic lateralized periodic discharges. His mental status improved rapidly after resolution of these electrographic seizures shortly after increasing antiseizure medications, suggesting that they may have been contributing to his encephalopathy. More research is needed to determine the frequency of this phenomenon and determine whether treatment of such seizures improves patient outcomes.


Evaluation of a dedicated balloon catheter for infrapopliteal difficult calcified lesions in diabetic patients with critical limb ischemia.
The purpose of this study was to assess the technical performance and immediate procedural outcome of a new balloon catheter in the treatment of calcified lesions in infrapopliteal arterial disease. Sixty-one patients (81 vessels) with infrapopliteal arterial disease were evaluated. Seventy-four of the 81 treated vessels had total occlusions. The ReeKross 18 peripheral transluminal angioplasty catheter (ClearStream, Wexford, Ireland) is an 0.018-inch guidewire system with 4F sheath compatibility and a rigid shaft intended for enhanced pushability. Only technical procedural outcomes were recorded. In 37 of 61 patients (50 infrapopliteal severely stenosed or occluded vessels), an attempt with a standard balloon was made before the ReeKross 18 was used. In 24 patients, the ReeKross 18 was used as the primary catheter in 23 cases involving crural arteries and in 8 cases involving the foot. The ReeKross 18 crossed the lesion in 55 of 59 (93.2%) patients and 72 of 77 (94.5%) vessels, respectively. Postdilatation results for the 51 patients (64 target lesions) in whom ReeKross 18 balloon dilation was achieved showed <30% residual stenosis in all but 4 patients (5 lesions). Of the patients treated with the ReeKross 18 as the primary catheter, the technical success rate (no adjunctive treatment/stent) was obtained in 20 of 24 (83.3%) patients (27 of 31 [87.1%] target lesions). In the treatment of difficult calcified lesions, the choice of a high-pushability angioplasty catheter, such as the ReeKross 18, warrants consideration.


Insulin receptor substrate (IRS)-2, not IRS-1, protects human neuroblastoma cells against apoptosis.
Insulin receptor substrates (IRS)-1 and -2 are major substrates of insulin and type I insulin-like growth factor (IGF-I) receptor (IGF-IR) signaling. In this study, SH-EP human neuroblastoma cells are used as a model system to examine the differential roles of IRS-1 and IRS-2 on glucose-mediated apoptosis. In the presence of high glucose, IRS-1 underwent caspase-mediated degradation, followed by focal adhesion kinase (FAK) and Akt degradation and apoptosis. IRS-2 expression blocked all these changes whereas IRS-1 overexpression had no effect. In parallel, IRS-2, but not IRS-1, overexpression enhanced IGF-I-mediated Akt activation without affecting extracellular regulated kinase signaling. While IRS-1 was readily degraded by caspases, hyperglycemia-mediated IRS-2 degradation was unaffected by caspase inhibitors but blocked by proteasome and calpain inhibitors. Our data suggest that the differential degradation of IRS-1 and IRS-2 contributes to their distinct modes of action and the increased neuroprotective effects of IRS-2 in this report are due, in part, to its resistance to caspase-mediated degradation.


Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia.
Biologic and clinical observations suggest that combining imatinib with IFN-α may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission either to receive a combination of pegylated IFN-α2b (Peg-IFN-α2b) 50 μg weekly and imatinib 400 mg daily (n = 56) or to receive imatinib 400 mg daily monotherapy (n = 56). The primary endpoint was the major molecular response (MMR) rate at 12 months after randomization. In both arms, 4 patients (7%) discontinued imatinib treatment (1 because of blastic transformation in imatinib arm). In addition, in the combination arm, 34 patients (61%) discontinued Peg-IFN-α2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg-IFN-α2b arm (82%) compared with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg-IFN-α2b treatment (< 12-week MMR rate 67%, > 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg-IFN-α2b to imatinib markedly increased the MMR rate at 12 months of therapy. Lower doses of Peg-IFN-α2b may enhance tolerability while retaining efficacy and could be considered in future protocols with curative intent.


Computed tomographic assessment of brain tissue disruption and skull damage in equine cadaveric heads caused by various firearm-ammunition combinations applied as potential gunshot methods for euthanasia of horses.
To evaluate with CT the characteristics of brain tissue disruption and skull damage in cadaveric heads of adult horses caused by each of 6 firearm-ammunition combinations applied at a novel anatomic aiming point. 53 equine cadaveric heads. Heads placed to simulate that of a standing horse were shot with 1 of 6 firearm-ammunition combinations applied at an aiming point along the external sagittal crest of the head where the 2 temporalis muscles form an inverted V. Firearm-ammunition combinations investigated included a .22-caliber long rifle pistol firing a 40-grain, plated lead, solid-core or hollow-point bullet (HPB); a semiautomatic 9-mm pistol firing a 115-grain, jacketed HPB; a semiautomatic .223-caliber carbine firing a 55-grain, jacketed HPB; a semiautomatic .45-caliber automatic Colt pistol firing a 230-grain, jacketed HPB; and a 12-gauge shotgun firing a 1-oz rifled slug. Additional heads placed in a simulated laterally recumbent position were shot with the semiautomatic 9-mm pistol-HPB combination. All heads underwent CT before and after being shot, and images were evaluated for projectile fragmentation, skull fracture, and cerebrum, cerebellum, and brainstem disruption. Computed tomography revealed that all firearm-ammunition combinations caused disruption of the cerebrum, cerebellum, and brainstem that appeared sufficient to result in instantaneous death of a live horse. Hollow-point ammunition was as effective as solid-core ammunition with regard to brain tissue disruption. Brain tissue disruption was not affected by head positioning. Results indicated that the examined firearm-ammunition combinations, when applied at a novel aiming point, appear to be reasonable options for euthanasia of horses.


Spatial versus day-to-day within-lake variability in tropical floodplain lake CH4 emissions--developing optimized approaches to representative flux measurements.
Inland waters (lakes, rivers and reservoirs) are now understood to contribute large amounts of methane (CH4) to the atmosphere. However, fluxes are poorly constrained and there is a need for improved knowledge on spatiotemporal variability and on ways of optimizing sampling efforts to yield representative emission estimates for different types of aquatic ecosystems. Low-latitude floodplain lakes and wetlands are among the most high-emitting environments, and here we provide a detailed investigation of spatial and day-to-day variability in a shallow floodplain lake in the Pantanal in Brazil over a five-day period. CH4 flux was dominated by frequent and ubiquitous ebullition. A strong but predictable spatial variability (decreasing flux with increasing distance to the shore or to littoral vegetation) was found, and this pattern can be addressed by sampling along transects from the shore to the center. Although no distinct day-to-day variability were found, a significant increase in flux was identified from measurement day 1 to measurement day 5, which was likely attributable to a simultaneous increase in temperature. Our study demonstrates that representative emission assessments requires consideration of spatial variability, but also that spatial variability patterns are predictable for lakes of this type and may therefore be addressed through limited sampling efforts if designed properly (e.g., fewer chambers may be used if organized along transects). Such optimized assessments of spatial variability are beneficial by allowing more of the available sampling resources to focus on assessing temporal variability, thereby improving overall flux assessments.


A Pilot Study on the Effects of Yi Jin Jing Exercise for Older Men with Benign Prostatic Hyperplasia.
Benign prostatic hyperplasia and its associated lower urinary tract symptoms seriously affect both the physical and mental health of older men. In order to determine the efficiency of Chinese Qigong Yi Jin Jing on prostate health in older individuals, thirty participants were randomized into either an Yi Jin Jing group (n = 15) or a control group (n = 15). After the 6-month intervention, the Yi Jin Jing group showed a significant decrease in international prostate symptom score and a significant increase in maximal urinary flow rate (compared with the control group p = .005, p = .001, respectively). Also, testosterone level increased and estrogen/testosterone ratio decreased in the Yi Jin Jing group (compared with the baseline p = .004, p = .002, respectively); estrogen level and estrogen/testosterone ratio were lower in the Yi Jin Jing group (compared with the control group p = .029, p = .012, respectively). The results showed that Yi Jin Jing is a promising way to reduce the risk of benign prostatic hyperplasia-lower urinary tract symptoms in older men.


The Effect of Nitrous Oxide on the Outcomes of Underlay Tympanoplasty: A Prospective Study.
The main aims of tympanoplasty are eradication of chronic middle ear disease, repair of the tympanic membrane, and restoration of hearing. Nitrous oxide (N2O) is not a commonly preferred anesthetic agent for tympanoplasty because this agent may increase middle ear pressure and displace the graft. In this study, we researched the surgical outcomes of the underlay tympanoplasty performed with N2O anesthesia. Patients who underwent tympanoplasty were included in this prospective study. A type 1 tympanoplasty was performed in all patients using the underlay technique. Patients were randomized to groups that did and did not receive N2O. Preoperative and postoperative hearing thresholds were evaluated, postoperative pain scores were recorded, and the differences between the groups were statistically evaluated. There were 44 patients who received N2O and 44 who did not. The graft success rate was 93.2% in the N2O-receiving group and 84.1% in the nonreceiving group (P > .05). Hearing levels improved significantly after surgery in each group (P < .05), but the difference between the groups was not significant (P > .05). The postoperative pain score was 3.72 ± 1.3 in the N2O-receiving group and 4.45 ± 2.3 in the nonreceiving group (P > .05). Nitrous oxide is a cheap, safe, and readily available anesthetic agent that provides acceptable success rates in patients undergoing tympanoplasty.


What are the markers of aggressiveness in prolactinomas? Changes in cell biology, extracellular matrix components, angiogenesis and genetics.
Prolactinoma is the most common pituitary tumour in adults. Macroprolactinomas, particularly in men, may occasionally exhibit a very aggressive clinical course as evidenced by progressive growth, invasion through bone into the sphenoid sinus, cavernous sinus, suprasellar region or the nasopharynx. Some may even progress to pituitary carcinoma with craniospinal or systemic metastases. Aggressive tumours have low cure rates despite appropriate medical and surgical treatment. The mechanisms underlying this aggressive biological behaviour have not yet been fully clarified. Recent immunohistochemical, molecular and genetic studies have provided some insight in this respect. Invasive prolactinomas may be associated with a high Ki-67/MIB-1 labelling index indicating increased cell proliferation, although this is not a universal finding. The AA polymorphism in the cyclin adenine (A)/guanine (G) gene is more frequently detected in invasive prolactinomas. Increased expression of the polysialylated neural cell adhesion molecule (NCAM) and reduced expression of the E-cadherin/catenin complex implies a contribution of altered cell-to-cell adhesion and cellular migration. Extracellular matrix components (ECM), matrix metalloproteinases (MMPs) and their inhibitors play important roles in the context of angiogenesis and invasion. The induction of fibroblast growth factor and vascular endothelial growth factor via oestrogen-induced overexpression of novel genes (PTTG, hst and Edpm5) enhance cell growth, proliferation and angiogenesis contributing to invasiveness in prolactinomas. Although mutations in proto-oncogenes like Ras are uncommon, loss of tumour suppressor genes at loci 11q13, 13q12-14, 10q and 1p seem to be associated with invasiveness. Of the described mechanisms, only reduced E-cadherin/catenin expression and overexpression of hst gene seem to be relatively specific markers for prolactinoma invasiveness compared with other pituitary adenomas. Further research is needed to clarify the molecular mechanisms behind the aggressive course of some prolactinomas to predict those with a potentially poor clinical outcome, and to devise treatments that will eventually enable the cure of these challenging tumours.


Muscarinic acetylcholine receptor subtypes mediating urinary bladder contractility and coupling to GTP binding proteins.
Activation of muscarinic acetylcholine receptors is primarily responsible for urinary bladder emptying. Because multiple subtypes of muscarinic receptors exist, we wished to characterize those present in bladder and ultimately to attribute function to those that regulate bladder contractility, neurotransmitter release and perhaps other cholinergic functions in this tissue. Although the m2 and m3 subtypes could be immunoprecipitated after solubilization from human, rat, rabbit and guinea pig bladder membranes, the m1, m4 and m5 subtypes could not. The m2:m3 ratio was 9:1 in rat bladder but was only 3:1 in the other species examined. Immunoprecipitation of the m2 subtype correlated with the relative levels of high-affinity agonist binding sites measured by competition of carbachol for [3H]N-methylscopolamine binding or measured directly using [3H]oxotremorine-M. In the presence of agonist, but not antagonist, GTP binding proteins could be immunoprecipitated in concert with the m2 or m3 receptors using anti-receptor antibodies. These proteins were members of the Gi and Gq/11 subfamilies for both the m2 and the m3 receptor subtypes. In spite of the preponderance of the m2 receptor in all species studied, Schild analysis using somewhat selective antagonists showed that the pharmacologically defined m3 receptor mediated contractility in strips of rat and rabbit bladder. Thus acetylcholine activates bladder smooth muscle via the m3 receptor subtype, and subsequent contractility may be transduced by guanine nucleotide binding proteins such as the Gi and Gq/11 subfamilies.


Differentiation of Toxoplasma gondii from closely related coccidia by riboprint analysis and a surface antigen gene polymerase chain reaction.
The tachyzoite of the human pathogen Toxoplasma gondii is morphologically indistinguishable from the proliferative stages of some other zoonotic coccidia, including Sarcocystis. To determine the identity of such coccidia obtained from human tissues and other sources, we compared riboprints (through restriction enzyme analysis of the polymerase chain reaction [PCR]-amplified small subunit rRNA gene) of the following protozoa: the RH and ts-4 strains of T. gondii, lines OH3 and S11, which are two recently isolated T. gondii-like parasites from Brazil, Neospora caninum, Sarcocystis species, and the malarial parasite Plasmodium berghei. In addition, the protozoan genomes were examined by PCR for homologs of surface antigen genes of T. gondii, and by Southern hybridization to the heterologous rRNA gene probe pSM 389. Strains OH3, S11, ts-4, and RH shared identical riboprints, and OH3, S11, and ts-4 have p22 and p30 surface antigen gene structures similar to RH. In contrast, riboprints for N. caninum and T. gondii differ with respect to Dde 1 sites, and moreover, their genomes vary significantly from one another at both the p22 and p30 gene loci. The riboprints of Sarcocystis and P. berghei differ markedly from T. gondii and N. caninum and from each other. Bam HI pSM 389 restriction fragment length polymorphisms differentiate ts-4 from RH, OH3, and S11. Our results confirm that OH3 and S11 are indeed T. gondii, but that N. caninum and T. gondii are likely to be separate species, thereby resolving previous uncertainties concerning the identity of these parasites. Together, the variation in riboprints and surface antigen gene structure reflects the phylogenetic diversity among these coccidia, and in addition, confirms the value of riboprinting in the identification of apicomplexan parasites such as T. gondii.


Treatment strategy for successful hepatic resection of icteric liver.
The treatment strategy for jaundiced patients with hilar cholangiocarcinoma (HC) is not well established. In this study, we evaluate the feasibility of our perioperative protocol for jaundiced patients with HC. Twenty patients with HC who underwent hepatic resection at our institute were enrolled, and patients were divided into icteric(n=6) and normal(n=14) group. As a perioperative protocol, Oral administration of Inchinkoto(ICKT), steroid and nafamostat mesilate were introduced. The evaluation of functional future remnant liver(FRL) by asiaroscintigraphy, and postoperative outcomes were retrospectively compared. Indocyanine green dye retention rate at 15 minutes was higher, and LHL15 values was lower in icteric group. However, in the functional evaluation of FRL, which was the sum of GSA uptake of the future FRL, there was no significant difference of LHL15 values of the remnant liver functional reserve between the two groups. As results, according to the difference of liver function, serum AST level was not different between two groups. The number of patients with postoperative morbidity in the two groups was comparable. Even in HC patients with icteric liver, accurate assessment of liver functional reserve and effective perioperative treatment may attribute to successful hepatectomy and favorable post-operative outcomes. J. Med. Invest. 65:37-42, February, 2018.


Perceived quality of and access to care among poor urban women in Kenya and their utilization of delivery care: harnessing the potential of private clinics?
This paper uses data from a maternal health study carried out in 2006 in two slums of Nairobi, Kenya, to: describe perceptions of access to and quality of care among women living in informal settlements of Nairobi, Kenya; quantify the effects of women's perceived quality of, and access to, care on the utilization of delivery services; and draw policy implications regarding the delivery of maternal health services to the urban poor. Based on the results of the facility survey, all health facilities were classified as 'appropriate' or 'inappropriate'. The research was based on the premise that despite the poor quality of these maternal health facilities, their responsiveness to the socio-cultural and economic sensitivities of women would result in good perceptions and higher utilization by women. Our results show a pattern of women's good perceptions in terms of access to, and quality of, health care provided by the privately owned, sub-standard and often unlicensed clinics and maternity homes located within their communities. In the multivariate model, the association between women's perceptions of access to and quality of care, and delivery at these 'inappropriate' facilities remained strong, graded and in the expected direction. Women from the study area are seldom able to reach not-for-profit private providers of maternal health care services like missionary and non-governmental organization (NGO) clinics and hospitals. Against the backdrop of challenges faced by the public sector in health care provision, we recommend that the government should harness the potential of private clinics operating in urban, resource-deprived settings. First, the government should regulate private health facilities operating in urban slum settlements to ensure that the services they offer meet the acceptable minimum standards of obstetric care. Second, 'good' facilities should be given technical support and supplied with drugs and equipment.


Urinary phthalate metabolites and biomarkers of reproductive function in young men.
High exposure to phthalates, which are ubiquitous contaminants, has been shown in animal studies to produce detrimental effects on male reproductive functions. A recent study in humans reported dose-response relations between low phthalate levels in urine and human semen parameters, which raises the question whether humans are more sensitive to phthalate exposure than animals. Urine, serum, and semen samples were collected from 234 young Swedish men at the time of their medical conscript examination. Semen volume, sperm concentration, and motility were measured, together with sperm chromatin integrity (sperm chromatin structure assay) and biochemical markers of epididymal and prostatic function. We analyzed reproductive hormones in serum, and mono ethyl phthalate (MEP), mono ethylhexyl phthaltale (MEHP), mono benzyl phthalate (MBzP), mono butyl phthalate (MBP), and phthalic acid in urine. For MBP, MBzP, and MEHP, no clear pattern of associations were observed with any of the reproductive biomarkers. Subjects within the highest quartile for MEP had fewer motile sperm (mean difference = 8.8%; 95% confidence interval = 0.8-17), more immotile sperms (8.9%; 0.3-18), and lower luteinizing hormone values (0.7 IU/L; 0.1-1.2), but there was no suggestion of harmful effects for most other endpoints. Phthalic acid actually was associated with improved function, as measured by several markers. The observed weak associations between 1 phthalate biomarker and impairment of a few aspects of reproductive function biomarkers were not consistent with results from a recent U.S. study. It is not yet possible to conclude whether phthalate exposure may reflect a hazard for human male reproduction.


Distance education outcomes in clinical laboratory science.
To compare 2 types of delivery methods for clinical laboratory science students-the technology-driven method at distance sites versus the on-site method on campus-in terms of learning outcomes. The independent variable in this quasi-experimental study was the delivery method consisting of interactive videoteleconferencing and on-site classroom methods. The dependent variables were learning outcomes that were determined by 2 methods: the average score on 8 posttests scheduled at periodic intervals and a national certification examination score. Clinical laboratory science (CLS) education program at the University of Nebraska Medical Center in Omaha and at 6 clinical sites in other cities across Nebraska. 40 senior CLS students enrolled in a baccalaureate degree program. Control group participants were assigned to 2 clinical sites in the Omaha area, and the experimental group were assigned to 6 distant clinical sites. Data analysis consisted of descriptive statistics, 2-way analysis of variance (ANOVA), 2-way analysis of covariance (ANCOVA), repeated measures analysis of variance, and Hotellings T2. Results showed no significant difference between the students' examination scores based on delivery method (p > 0.05), except in the chemistry topic area. There was no significant difference in the pattern of the examination scores over the semester of learners who were instructed by interactive videoteleconferencing methods and learners who were instructed by on-site classroom methods. Results of the study generally support the use of interactive videoteleconferencing as an effective, alternative delivery method for CLS students who cannot attend class on campus. Analysis by topic areas suggests that additional studies are needed to validate the variance found in the chemistry subject area.


Control of expression of the homeotic labial (lab) locus of Drosophila melanogaster: evidence for both positive and negative autogenous regulation.
The homeotic gene labial (lab) is required for proper development of the embryonic and adult head in Drosophila melanogaster. The lab gene product accumulates in a complex pattern in both embryonic and imaginal tissue. During embryogenesis, lab is expressed in the endodermally derived cells of the midgut, in ectodermally derived cells of the procephalon and dorsal ridge, and in a small subset of progenitor sensory cells. Imaginal expression is restricted to a narrow region of the peripodial membrane of the eye-antennal disc. As part of our continuing effort to understand the role of lab in development, we have begun a dissection of the regulatory elements of the lab transcription unit and used germ line transformation experiments to determine which aspects of the observed expression pattern are essential for proper head development and viability. Transgenic embryos harboring an abridged lab gene are able to overcome the embryonic lethality associated with the loss of lab function and survive to adulthood. Interestingly, in these transgenic lines the lab protein accumulates only in a subset of those embryonic cells that normally express the gene, namely the procephalon and the anterior midgut. We also find that, once initiated, lab expression is maintained by positive autoregulation. Although lab minigene activity is sufficient to rescue the embryonic lethality of lab mutations, the transgenes fail to rescue defects in the adult head capsule. However, the defects observed in this study encompass a broader domain than those seen using somatic recombination to generate lab- clonal tissue. The failed rescue and observed cuticular defects are, at least in part, explained by the observation that the transgenes, rather than failing to be expressed, are associated with ectopic accumulation of lab protein in the peripodial membrane of the antennal disc. Moreover, this aberrant expression pattern is correlated with the abnormal expression of two other homeotic genes, Deformed (Dfd) and Sex combs reduced (Scr) in the eye-antennal disc. These results are only observed when the transgene is resident in a lab- genotype and ectopic expression of lab and misregulation of Dfd and Scr are not seen in a lab+ background. This result suggests that the wild-type lab gene product is necessary for the normal regulation of the locus in the imaginal discs, but unlike the case in the embryo, the event is negative. We discuss the biological implications of these results in relation to the role of lab in development.


Applying a community-based participatory research framework to patient and family engagement in the development of patient-centered outcomes research and practice.
There has been increasing recognition of the need to engage patients, families, and other patient stakeholders in research. This article seeks to provide understanding and examples of how to apply core principles of community-based participatory research (CBPR) in developing patient-centered outcomes research (PCOR) that can impact clinical and public health practice. Authors review CBPR principles and demonstrate how to translate them into effective PCOR strategies. Common themes of CBPR principles and PCOR strategies are related to: (a) fostering joint ownership in the identification of health priorities, the development and evaluation of research strategies and their design, and the dissemination of findings; (b) a keen recognition and appreciation for the importance of stakeholder-driven priorities, research, and solutions; (c) building capacity of both stakeholders and researchers to engage in research collaboratively; and (d) recognizing that conducting the research is not the endpoint but continues on with a commitment to dissemination, spread, adoption and sustainability. The authors highlight the specific strategies in which these CBPR principles can be translated for use in engaging patients and families, and including other stakeholders such as care providers, community partner organizations, health systems, and insurers, in the research process to ensure the development of PCOR.


Specificity of T cells in synovial fluid: high frequencies of CD8(+) T cells that are specific for certain viral epitopes.
Epstein-Barr virus (EBV) is transmitted orally, replicates in the oropharynx and establishes life-long latency in human B lymphocytes. T-cell responses to latent and lytic/replicative cycle proteins are readily detectable in peripheral blood from healthy EBV-seropositive individuals. EBV has also been detected within synovial tissue, and T-cell responses to EBV lytic proteins have been reported in synovial fluid from a patient with rheumatoid arthritis (RA). This raises the question regarding whether T cells specific for certain viruses might be present at high frequencies within synovial fluid and whether such T cells might be activated or able to secrete cytokines. If so, they might play a 'bystander' role in the pathogenesis of inflammatory joint disease. To quantify and characterize T cells that are specific for epitopes from EBV, cytomegalovirus (CMV) and influenza in peripheral blood and synovial fluid from patients with arthritis. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were obtained from patients with inflammatory arthritis (including those with RA, osteoarthritis, psoriatic arthritis and reactive arthritis). Samples from human leucocyte antigen (HLA)-A2-positive donors were stained with fluorescent-labelled tetramers of HLA-A2 complexed with the GLCTLVAML peptide epitope from the EBV lytic cycle protein BMLF1, the GILGFVFTL peptide epitope from the influenza A matrix protein, or the NLVPMVATV epitope from the CMV pp65 protein. Samples from HLA-B8-positive donors were stained with fluorescent-labelled tetramers of HLA-B8 complexed with the RAKFKQLL peptide epitope from the EBV lytic protein BZLF1 or the FLRGRAYGL peptide epitope from the EBV latent protein EBNA3A. All samples were costained with an antibody specific for CD8. CD4+ T cells were not analyzed. Selected samples were costained with antibodies specific for cell-surface glycoproteins, in order to determine the phenotype of the T cells within the joint and the periphery. Functional assays to detect release of IFN- or tumour necrosis factor (TNF)- were also performed on some samples. The first group of 15 patients included 10 patients with RA, one patient with reactive arthritis, one patient with psoriatic arthritis and three patients with osteoarthritis. Of these, 11 were HLA-A2 positive and five were HLA-B8 positive. We used HLA-peptide tetrameric complexes to analyze the frequency of EBV-specific T cells in PBMCs and SFMCs (Figs 1 and 2). Clear enrichment of CD8+ T cells specific for epitopes from the EBV lytic cycle proteins was seen within synovial fluid from almost all donors studied, including patients with psoriatic arthritis and osteoarthritis and those with RA. In donor RhA6, 9.5% of CD8+ SFMCs were specific for the HLA-A2 restricted GLCTLVAML epitope, compared with 0.5% of CD8+ PBMCs. Likewise in a donor with osteoarthritis (NR4), 15.5% of CD8+ SFMCs were specific for the HLA-B8-restricted RAKFKQLL epitope, compared with 0.4% of CD8+ PBMCs. In contrast, we did not find enrichment of T cells specific for the HLA-B8-restricted FLRGRAYGL epitope (from the latent protein EBNA3A) within SFMCs compared with PBMCs in any donors. In selected individuals we performed ELISpot assays to detect IFN- secreted by SFMCs and PBMCs after a short incubation in vitro with peptide epitopes from EBV lytic proteins. These assays confirmed enrichment of T cells specific for epitopes from EBV lytic proteins within synovial fluid and showed that subpopulations of these cells were able to secrete proinflammatory cytokines after short-term stimulation. We used a HLA-A2/GILGFVFTL tetramer to stain PBMCs and SFMCs from six HLA-A2-positive patients. The proportion of T cells specific for this influenza epitope was low (<0.2%) in all donors studied, and we did not find any enrichment within SFMCs. We had access to SFMCs only from a second group of four HLA-A2-positive patients with RA. A tetramer of HLA-A2 complexed to the NLVPMVATV epitope from the CMV pp65 protein reacted with subpopulations of CD8+ SFMCs in all four donors, with frequencies of 0.2, 0.5, 2.3 and 13.9%. SFMCs from all four donors secreted TNF after short-term incubation with COS cells transfected with HLA-A2 and pp65 complementary DNA. We analyzed the phenotype of virus-specific cells within PBMCs and SFMCs in three donors. The SFMC virus-specific T cells were more highly activated than those in PBMCs, as evidenced by expression of high levels of CD69 and HLA-DR. A greater proportion of SFMCs were CD38+, CD62L low, CD45RO bright, CD45RA dim, CD57+ and CD28- when compared with PBMCs. This work shows that T cells specific for certain epitopes from viral proteins are present at very high frequencies (up to 15.5% of CD8+ T cells) within SFMCs taken from patients with inflammatory joint disease. This enrichment does not reflect a generalized enrichment for the 'memory pool' of T cells; we did not find enrichment of T cells specific for the GILGFVFTL epitope from influenza A or for the FLRGRAYGL epitope from the EBV latent protein EBNA3A, whereas we found clear enrichment of T cells specific for the GLCTLVAML epitope from the EBV lytic protein BMLF1 and for the RAKFKQLL epitope from the EBV lytic protein BZLF1. The enrichment might reflect preferential recruitment of subpopulations of virus-specific T cells, perhaps based on expression of selectins, chemokine receptors or integrins. Alternatively, T cells specific for certain viral epitopes may be stimulated to proliferate within the joint, by viral antigens themselves or by cross-reactive self-antigens. Finally, it is theoretically possible that subpopulations of T cells within the joint are preferentially protected from apoptotic cell death. Whatever the explanation, the virus-specific T cells are present at high frequency, are activated and are able to secrete proinflammatory cytokines. They could potentially interact with synoviocytes and contribute to the maintenance of inflammation within joints in many different forms of inflammatory arthritis.


Underuse of statins in patients with atherosclerotic ischemic stroke in China.
Well designed randomized trials and meta-analyses have clearly shown that statins reduce the risk of major vascular events, including ischemic stroke, in a wide range of patients and their routine use is recommended for patients at an increased cardiovascular risk. Survivors of a first ischemic stroke are at a risk of recurrence and of other vascular events and statins are generally recommended to reduce this risk. This study investigated how widely statins were being used for such patients in China. Totally 6422 patients with a history of ischemic stroke were identified by reviewing medical records at 51 highest-ranking hospitals in 14 cities in China, and invited to attend a screening clinic to assess eligibility for a randomized trial. Their current statin and other drug uses were recorded alongside clinical and demographic characteristics. Univariate chi-square test and multivariate Logistic regression were used to determine the factors associated with treatment. Only 24% of these patients reported currently taking a statin. The most important predictor of statin use among these patients was prior history of coronary heart disease. History of diabetes or hypertension, as well as treated in university affiliated hospitals is related to increased use. The status had improved significantly during a 2-year period. Atorvastatin (40%) and simvastatin (39%) were the most commonly used. In China, statins are still underused for secondary prevention among survivors of ischemic stroke. Reasons for this poor use need to be understood in order to increase use of these evidence based therapies.


Recommendations for laparoscopic liver resection: a report from the second international consensus conference held in Morioka.
The use of laparoscopy for liver surgery is increasing rapidly. The Second International Consensus Conference on Laparoscopic Liver Resections (LLR) was held in Morioka, Japan, from October 4 to 6, 2014 to evaluate the current status of laparoscopic liver surgery and to provide recommendations to aid its future development. Seventeen questions were addressed. The first 7 questions focused on outcomes that reflect the benefits and risks of LLR. These questions were addressed using the Zurich-Danish consensus conference model in which the literature and expert opinion were weighed by a 9-member jury, who evaluated LLR outcomes using GRADE and a list of comparators. The jury also graded LLRs by the Balliol Classification of IDEAL. The jury concluded that MINOR LLRs had become standard practice (IDEAL 3) and that MAJOR liver resections were still innovative procedures in the exploration phase (IDEAL 2b). Continued cautious introduction of MAJOR LLRs was recommended. All of the evidence available for scrutiny was of LOW quality by GRADE, which prompted the recommendation for higher quality evaluative studies. The last 10 questions focused on technical questions and the recommendations were based on literature review and expert panel opinion. Recommendations were made regarding preoperative evaluation, bleeding controls, transection methods, anatomic approaches, and equipment. Both experts and jury recognized the need for a formal structure of education for those interested in performing major laparoscopic LLR because of the steep learning curve.


Rodent Species Distribution and Hantavirus Seroprevalence in Residential and Forested areas of Sarawak, Malaysia.
Rodents belong to the order Rodentia, which consists of three families in Borneo (i.e., Muridae, Sciuridae and Hystricidae). These include rats, mice, squirrels, and porcupines. They are widespread throughout the world and considered pests that harm humans and livestock. Some rodent species are natural reservoirs of hantaviruses (Family: Bunyaviridae) that can cause zoonotic diseases in humans. Although hantavirus seropositive human sera were reported in Peninsular Malaysia in the early 1980s, information on their infection in rodent species in Malaysia is still lacking. The rodent populations in residential and forested areas in Sarawak were sampled. A total of 108 individuals from 15 species of rodents were collected in residential (n = 44) and forested ( n = 64) areas. The species diversity of rodents in forested areas was significantly higher (H = 2.2342) compared to rodents in residential areas (H = 0.64715) (p < 0.001 of Zar-t test based on the Shannon index). Rattus rattus and Sundamys muelleri were present at high frequencies in both localities. An enzyme-linked immunosorbent assay (ELISA) showed that hantavirus-targeting antibodies were absent from 53 tested serum samples. This is the first report of hantavirus seroprevalence surveillance in rodent populations in Sarawak, East Malaysia. The results suggested that hantavirus was not circulating in the studied rodent populations in Sarawak, or it was otherwise at a low prevalence that is below the detection threshold. It is important to remain vigilant because of the zoonotic potential of this virus and its severe disease outcome. Further studies, such as molecular detection of viral genetic materials, are needed to fully assess the risk of hantavirus infection in rodents and humans in this region of Malaysia.


Marijuana Use in Pregnancy: A Review.
Marijuana is the most commonly used dependent substance in pregnancy. The main active chemical of marijuana (delta-9-tetrahydrocannabinol [THC]) readily crosses the placenta, and cannabinoid receptors have been identified in fetal brain and placenta. As a result, prenatal marijuana use could potentially have detrimental impact on fetal development. This review aims to summarize the existing literature and current recommendations for marijuana use while pregnant or lactating. A PubMed literature search using the following terms was performed to gather relevant data: "cannabis," "cannabinoids," "marijuana," "fetal outcomes," "perinatal outcomes," "pregnancy," "lactation." Available studies on marijuana exposure in pregnancy were reviewed and support some degree of developmental disruption, including an increased risk of fetal growth restriction and adverse neurodevelopmental consequences. However, much of the existing prenatal marijuana research was performed in the 1980s, when quantities of THC were lower and the frequency of use was less. Additionally, most human studies are also limited and conflicting as most studies have been observational or retrospective, relying primarily on patient self-report and confounded by polysubstance abuse and small sample sizes, precluding determination of a causal effect specific for marijuana. Given the paucity of evidence, it is currently recommended to avoid using marijuana while pregnant or when breastfeeding. There is a critical need for research on effects in pregnancy using present-day THC doses. Once the adverse perinatal effects of marijuana exposure are identified and well characterized, patient education and antenatal surveillance can be developed to predict and mitigate its impact on maternal and fetal health.


Effect of oleuropein against chemotherapy drug-induced histological changes, oxidative stress, and DNA damages in rat kidney injury.
Cisplatin-based chemotherapy is responsible for a large number of renal failures, and it is still associated with high rates of mortality today. Oleuropein (OLE) presents a plethora of pharmacological beneficial properties. In this study we investigated whether OLE could provide sufficient protection against cisplatin-induced nephrotoxicity. With this aim, Sprague-Dawley rats were divided into eight groups: control; 7 mg/kg/d cisplatin, 50 mg/kg, 100 mg/kg, and 200 mg/kg OLE; and treatment with OLE for 3 days starting at 24 hours following cisplatin injection. After exposure to the chemotherapy agent and OLE, oxidative DNA damage was quantitated in the renal tissue of experimental animals by measuring the amount of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adducts. Malondialdehyde (MDA) level, total oxidative stress (TOS), and total antioxidant status (TAS) were assessed to determine the oxidative injury in kidney cells. The histology of the kidney was examined using four different staining methods: hematoxylin-eosin (H&E), periodic acid Schiff (PAS), Masson trichrome, and amyloid. In addition, the blood urea nitrogen (BUN), uric acid (UA), and creatinine (CRE) levels were established. Our experimental data showed that tissue 8-OHdG levels were significantly higher in the cisplatin group when compared to the control group. The glomerular cells were sensitive to cisplatin as tubular cells. In addition, treatment with cisplatin elevated the levels of BUN, UA, CRE, and TOS, but lowered the level of TAS compared to the control group. The OLE therapy modulated oxidative stress in order to restore normal kidney function and reduced the formation of 8-OHdG induced by cisplatin. Furthermore, the OLE treatment significantly reduced pathological findings in renal tissue. We demonstrate for the first time that OLE presents significant cytoprotective properties against cisplatin-induced genotoxicity by restoring the antioxidant system of the renal tissue. According to our findings, OLE is a promising novel natural source for the prevention of serious kidney damage in current chemotherapies.


Sex-partitioning of the Plasmodium falciparum stage V gametocyte proteome provides insight into falciparum-specific cell biology.
One of the critical gaps in malaria transmission biology and surveillance is our lack of knowledge about Plasmodium falciparum gametocyte biology, especially sexual dimorphic development and how sex ratios that may influence transmission from the human to the mosquito. Dissecting this process has been hampered by the lack of sex-specific protein markers for the circulating, mature stage V gametocytes. The current evidence suggests a high degree of conservation in gametocyte gene complement across Plasmodium, and therefore presumably for sex-specific genes as well. To better our understanding of gametocyte development and subsequent infectiousness to mosquitoes, we undertook a Systematic Subtractive Bioinformatic analysis (filtering) approach to identify sex-specific P. falciparum NF54 protein markers based on a comparison with the Dd2 strain, which is defective in producing males, and with syntenic male and female proteins from the reanalyzed and updated P. berghei (related rodent malaria parasite) gametocyte proteomes. This produced a short list of 174 male- and 258 female-enriched P. falciparum stage V proteins, some of which appear to be under strong diversifying selection, suggesting ongoing adaptation to mosquito vector species. We generated antibodies against three putative female-specific gametocyte stage V proteins in P. falciparum and confirmed either conserved sex-specificity or the lack of cross-species sex-partitioning. Finally, our study provides not only an additional resource for mass spectrometry-derived evidence for gametocyte proteins but also lays down the foundation for rational screening and development of novel sex-partitioned protein biomarkers and transmission-blocking vaccine candidates.


Analysis of synaptic distribution within single retinal axonal arbors after chronic NMDA treatment.
Activation of the NMDA subtype of glutamate receptor has been implicated in structural synaptic plasticity in many developing sensory systems. In the frog retinotectal system, chronic exposure of the optic tectum to NMDA, which decreases the effectiveness of NMDA receptors (Debski et al., 1991), results in the pruning of the branches of retinal terminal arbors (Cline and Constantine-Paton, 1990). However, it is difficult from these studies to relate the involvement of NMDA receptors to changes in synapse distribution. In this study, we have developed an EM sampling procedure to quantitatively compare the amount and the distribution of synaptic contact within single retinal arbors. We report that within each retinal arbor, synaptic contact gradually increases from the main branches to the end branches of the arbor. Chronic NMDA treatment, however, significantly reduces the total amount of synaptic contact within each arbor. This reduced synaptic contact appears to be due to the pruning of the end branches, and the synapses these branches bear. The results are consistent with the hypothesis that NMDA receptor is an integral part of the mechanism that stabilizes coactive synapses, and that maintenance of an axonal branch requires a minimum density of synapses that are correlated with converging neighbors.


Synaptic cleft acidification and modulation of short-term depression by exocytosed protons in retinal bipolar cells.
The release of vesicular protons during exocytosis causes a feedback inhibition of Ca2+ channels in photoreceptor terminals; however, the effect of this inhibition on subsequent exocytosis has not been studied. Here we show that a similar L-type Ca2+ channel inhibition occurs in bipolar cell terminals in slices of goldfish retina, and we investigate the effect that this has on subsequent exocytosis with membrane capacitance measurements. We find that transient Ca2+ current inhibition is correlated with exocytosis and modulated by the concentration of extracellular pH buffer. Ca2+ current inhibition is negligible in acutely dissociated terminals, demonstrating the importance of an intact synaptic cleft. The sensitivity of bipolar cell Ca2+ currents to extracellular pH was assessed: channel conductance is reduced and activation is shifted to more positive potentials by acidification. The effect of Ca2+ current inhibition on subsequent exocytosis was investigated by measuring paired-pulse depression. Under conditions in which there is a large amount of inhibition of Ca2+ influx, the degree of paired-pulse depression is significantly reduced. Finally, we show that under physiological (bicarbonate) buffering conditions, pronounced Ca2+ current inhibition occurs after exocytosis ( approximately 60% peak inhibition), which can decrease subsequent exocytosis during single depolarizations. We estimate that exocytosis is accompanied by a transient change in synaptic cleft pH from 7.5 to approximately 6.9. We suggest that this effect serves as an activity-dependent modulator of exocytosis at ribbon-type synapses where a large and compact coterie of vesicles can fuse at each active zone.


Hydrogen Sulfide on IO: Evidence from Telescopic and Laboratory Infrared Spectra.
Evidence is reported for hydrogen sulfide (H(2)S) on Io's surface. An infrared band at 3.915 (+/- 0.015) micrometers in several ground-based spectra of Io can be accounted for by reflectance from H(2)S frost deposited on or cocondensed with sulfur dioxide (SO(2)) frost. Temporal variation in the occurrence and intensity of the band suggests that condensed H(2)S on Io's surface is transient, implying a similar variation of H(2)S abundance in Io's atmosphere. The band was observed in full-disk measurements of Io at several orbital longitudes, including once at 24 degrees ( approximately 0.5 hour after Io's reappearance after an eclipse)-but not after another reappearance at 22 degrees -and once at 95 degrees (on Io's leading hemisphere). These results suggest that condensed H(2)S is sparse and variable but can be widespread on Io's surface. When present, it would not only produce the infrared band but would brighten Io's typical surface at ultraviolet and visible wavelengths.


Beat-to-beat vectorcardiographic analysis of ventricular depolarization and repolarization in myocardial infarction.
Increased beat-to-beat variability in the QT interval has been associated with heart disease and mortality. The purpose of this study was to investigate the beat-to-beat spatial and temporal variations of ventricular depolarization and repolarization in vectorcardiogram (VCG) for characterising myocardial infarction (MI) patients. Standard 12-lead ECGs of 84 MI patients (22 f, 63±12 yrs; 62 m, 56±10 yrs) and 69 healthy subjects (17 f, 42±18 yrs; 52 m, 40±13 yrs) were investigated. To extract the beat-to-beat QT intervals, a template-matching algorithm and the singular value decomposition method have been applied to synthesise the ECG data to VCG. Spatial and temporal variations in the QRS complex and T-wave loops were studied by investigating several descriptors (point-to-point distance variability, mean loop length, T-wave morphology dispersion, percentage of loop area, total cosine R-to-T). Point-to-point distance variability of QRS and T-loops (0.13±0.04 vs. 0.10±0.04, p< 0.0001 and 0.16±0.07 vs. 0.13±0.06, p< 0.05) were significantly larger in the MI group than in the control group. The average T-wave morphology dispersion was significantly higher in the MI group than in the control group (62°±8° vs. 38°±16°, p< 0.0001). Further, its beat-to-beat variability appeared significantly lower in the MI group than in the control group (12°±5° vs. 15°±6°, p< 0.005). Moreover, the average percentage of the T-loop area was found significantly lower in the MI group than the controls (46±17 vs. 55±15, p< 0.001). Finally, the average and beat-to-beat variability of total cosine R-to-T were not found statistically significant between both groups. Beat-to-beat assessment of VCG parameters may have diagnostic attributes that might help in identifying MI patients.


Skeletal representations of shape in human vision: Evidence for a pruned medial axis model.
A representation of shape that is low dimensional and stable across minor disruptions is critical for object recognition. Computer vision research suggests that such a representation can be supported by the medial axis-a computational model for extracting a shape's internal skeleton. However, few studies have shown evidence of medial axis processing in humans, and even fewer have examined how the medial axis is extracted in the presence of disruptive contours. Here, we tested whether human skeletal representations of shape reflect the medial axis transform (MAT), a computation sensitive to all available contours, or a pruned medial axis, which ignores contours that may be considered "noise." Across three experiments, participants (N = 2062) were shown complete, perturbed, or illusory two-dimensional shapes on a tablet computer and were asked to tap the shapes anywhere once. When directly compared with another viable model of shape perception (based on principal axes), participants' collective responses were better fit by the medial axis, and a direct test of boundary avoidance suggested that this result was not likely because of a task-specific cognitive strategy (Experiment 1). Moreover, participants' responses reflected a pruned computation in shapes with small or large internal or external perturbations (Experiment 2) and under conditions of illusory contours (Experiment 3). These findings extend previous work by suggesting that humans extract a relatively stable medial axis of shapes. A relatively stable skeletal representation, reflected by a pruned model, may be well equipped to support real-world shape perception and object recognition.


Does diverse grazing behavior of suckler cows have an impact on predicted methane emissions?
A modeling study based on a dataset from a large-scale grazing study was used to identify the potential impact of grazing behavior and performance of diverse cow genotypes on predicted methane (CH4) emissions. Lactating cows grazing extensive seminatural grassland and heath vegetation were monitored with Global Positioning System collars and activity sensors. The diet selected by cows of 3 different genotypes, Aberdeen Angus cross Limousin (AxL), Charolais (CHA), and Luing (LUI), was simulated by matching their locations during active periods with hill vegetation maps. Measured performance and activity were used to predict energy requirements, DMI, and CH4 output. The cumulative effect of actual performance, diet selection, and actual physical activity on potential CH4 output and yield was estimated. Sensitivity analyses were performed for the digestibility of intake, energy cost of activity, proportion of milk consumed by calves, and reproductive efficiency. Although with a better performance (P < 0.05), LUI required less total energy than the other genotypes (P < 0.001) as the other 2 spent more energy for maintenance (P < 0.001) and activity (P < 0.001). By selecting a better quality diet (P < 0.03), estimated CH4 of CHA cow-calf pairs was lower than AxL (P = 0.001) and slightly lower than LUI (P = 0.08). Energy lost as CH4 was 0.17 and 0.58% lower for LUI than AxL and CHA (P < 0.002). This study suggests for the first time that measured activity has a major impact on estimated CH4 outputs. A 15% difference of the cow-calf pair CH4 was estimated when using different coefficients to convert actual activity into energy. Predicted CH4 was highly sensitive to small changes in diet quality, suggesting the relative importance of diet selection on heterogeneous rangelands. Extending these results to a farm systems scale, CH4 outputs were also highly sensitive to reductions in weaning rates, illustrating the impact on CH4 at the farm-system level of using poorly adapted genotypes on habitats where their performances may be compromised. This paper demonstrates that variations in grazing behavior and grazing choice have a potentially large impact on CH4 emissions, illustrating the importance of including these factors in calculating realistic national and global estimates.


[Attention deficit hyperactivity disorder, facilitating alcohol and drug abuse in an adult].
Attention-deficit hyperactivity disorder (ADHD) has been considered a mental and behavioral disorder of childhood and adolescence. It is being increasingly recognized in adults, who may have psychiatric co-morbidity with secondary depression, or a tendency to drug and alcohol abuse. We describe a 32-year-old woman known for years as suffering from borderline personality disorder and drug dependence (including hashish, marijuana, LSD and "ecstasy") and alcohol abuse that did not respond to treatment. Only when correctly diagnosed as ADHD and appropriately treated with the psychotropic stimulant, methylphenidate (Ritalin), was there significant improvement. She succeeded academically, which had not been possible previously, the craving for drugs diminished and a drug-free state was reached. Although administration of psychostimulants to drug abusers is controversial, as they are addictive, in cases of ADHD they have promoted drug abstinence.