bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of an Initial Conceptual Model of Multiple Myeloma to Support Clinical and Health Economics Decision Making
Authors: Gonzalez-McQuire Sebastian , Dimopoulos Meletios-Athanassios , Weisel Katja , Bouwmeester Walter , Hájek Roman , Campioni Marco , Bennison Craig , Xu Weiwei , Pantiri Krystallia , Hensen Marja , Terpos Evangelos , Knop Stefan
Published: January 2019

Background. We aimed to develop and validate a conceptual model of multiple myeloma (MM) that characterizes the attributes affecting disease progression and patient outcomes, and the relationships between them. Methods. Systematic and targeted literature reviews identified disease- and patient-specific attributes of MM that affect disease progression and outcomes. These attributes were validated by a Delphi panel of four international MM experts, and a physician-validated model was constructed. Real-world clinical data from the Czech Registry of Monoclonal Gammopathies (RMG) was used to confirm the relationships between attributes using pairwise correlations and multiple Cox regression analysis. Results. The Delphi panel reached consensus that most cytogenetic abnormalities influenced disease activity, which results in symptoms and complications and affects overall survival (OS). Comorbidities and complications also affect OS. The entire panel agreed that quality of life was influenced by comorbidities, age, complications, and symptoms. Consensus was not reached in some cases, in particular, the influence of del(17p) on complications. The relationships between attributes were confirmed using pairwise analysis of real-world data from the Czech RMG; most of the correlations identified were statistically significant and the strength of the correlations changed with successive relapses. Czech RMG data were also used to confirm significant predictors of OS included in the model, such as age, Eastern Cooperative Oncology Group performance status, and extramedullary disease. Conclusions. This validated conceptual model can be used for economic modeling and clinical decision making. It could also inform the development of disease-based models to explore the impact of disease progression and treatment on outcomes in patients with MM.
Local field potentials in dorsal anterior cingulate sulcus reflect rewards but not travel time costs during foraging
Authors: Ramakrishnan Arjun , Hayden Benjamin Y. , Platt Michael L.
Published: January 2019

To maximise long-term reward rates, foragers deciding when to leave a patch must compute a decision variable that reflects both the immediately available reward and the time costs associated with travelling to the next patch. Identifying the mechanisms that mediate this computation is central to understanding how brains implement foraging decisions. We previously showed that firing rates of dorsal anterior cingulate sulcus neurons incorporate both variables. This result does not provide information about whether integration of information reflected in dorsal anterior cingulate sulcus spiking activity arises locally or whether it is inherited from upstream structures. Here, we examined local field potentials gathered simultaneously with our earlier recordings. In the majority of recording sites, local field potential spectral bands – specifically theta, beta, and gamma frequency ranges – encoded immediately available rewards but not time costs. The disjunction between information contained in spiking and local field potentials can constrain models of foraging-related processing. In particular, given the proposed link between local field potentials and inputs to a brain area, it raises the possibility that local processing within dorsal anterior cingulate sulcus serves to more fully bind immediate reward and time costs into a single decision variable.
Unexpected visual improvement after aborted intracorneal ring segment implantation for keratoconus
Authors: Vastardis Iraklis , Thabit Ahmed , Elalfy Mohamed , Hamada Samer , Gatzioufas Zisis
Published: January 2019

Purpose:

To present a case of a complicated intracorneal ring segment (ICRS) implantation procedure in a patient with keratoconus, who experienced significant visual improvement, although the ICRS implantation had to be aborted.

Methods:

A 25-year-old female patient with keratoconus underwent femtosecond laser-assisted ICRS implantation in her right eye (OD) for improving visual acuity.

Results:

The procedure had to be aborted, because ICRS implantation was not possible. Anterior segment imaging 1 month after the procedure showed full-thickness corneal incision with corneal microperforation. However, patient’s visual acuity improved significantly due to amelioration of the keratometric findings. Keratometric and visual improvement was preserved at 6 months postoperatively.

Conclusion:

Our case report shows that femtosecond laser-assisted full-thickness corneal incision on the astigmatic axis combined with the intracorneal tunnel creation resulted unexpectedly in keratometric and visual improvement in this keratoconus patient, even without the implantation of the ICRS.
Pre-menstrual Dysphoric Disorder: A Review
Authors: Malvika Dahuja , Supriya Agarwal
Published: January 2019

Introduction: Premenstrual dysphoric disorder (PMDD) is a distressing disorder amongst women of reproductive age group with significant implication in the productivity and quality of life of women who suffer from it. It is generally neglected as it is mostly undifferentiated from premenstrual symptoms—milder presentation of the same spectrum of problem but of lesser intensity and impairment.

Objective: Here, in this article, we aim to highlight various studies and the research done on PMDD in the context of Indian women.

Method: Reviewing the last 40 years’ database including Medline (PUBMED), Cochrane Library, EMBASE, Trip, Psych INFO, CINAHL, the Allied and Complementary Medicine Database (AMED), and the British Nursing Index.

Results: PMDD is a troublesome disorder, often underdiagnosed. A thorough history including menstrual and sexual history, conducting a thorough physical examination, assessing the comorbidities, and finally using a proper and structured treatment protocol for managing the condition are recommended. Sertraline is the most widely studied drug which is found to be effective in PMDD.
Sonographic Detection of Pseudoaneurysm From Ankle Sprain Injury
Authors: Partridge Katherine A. , Anderson Sharlette D.
Published: January 2019

Aneurysms and pseudoaneurysms, of the anterior tibial artery, are very rare. Pseudoaneurysms of the anterior tibial artery are commonly due to iatrogenic injury, blunt trauma, fracture, or sharp penetrating injury. A young man presented to a pediatric emergency department with a pseudoaneurysm of the left anterior tibial artery due to an ankle sprain injury. Radiography, magnetic resonance imaging, and duplex sonographic imaging were completed to rule out all previously suspected diagnoses, and ultimately duplex sonography diagnosed and characterized the pseudoaneurysm. The utilization of duplex sonography in the investigation and diagnosis of injuries, particularly with extensive soft tissue swelling, provided quick diagnostic information and an expedited treatment plan. Conservative observation was initially attempted, followed by sonographic compression, sonography-guided thrombin injection, vessel ligation, and coil embolization. After initial treatment attempts failed, the patient was transferred to an adult hospital, with a specialized vascular surgery team, for vessel ligation and ultimate successful treatment with coil embolization.
A phase 1/2 ascending dose study and open-label extension study of voxelotor in patients with sickle cell disease
Authors: Howard Jo , Hemmaway Claire Jane , Telfer Paul , Layton D. Mark , Porter John , Awogbade Moji , Mant Timothy , Gretler Daniel D. , Dufu Kobina , Hutchaleelaha Athiwat , Patel Mira , Siu Vincent , Dixon Sandra , Landsman Noel , Tonda Margaret , Lehrer-Graiwer Joshua
Published: January 2019

New treatments directly targeting polymerization of sickle hemoglobin (HbS), the proximate event in the pathophysiology of sickle cell disease (SCD), are needed to address the severe morbidity and early mortality associated with the disease. Voxelotor (GBT440) is a first-in-class oral therapy specifically developed to treat SCD by modulating the affinity of hemoglobin (Hb) for oxygen, thus inhibiting HbS polymerization and downstream adverse effects of hemolytic anemia and vaso-occlusion. GBT440-001 was a phase 1/2 randomized, double-blind, placebo-controlled, single and multiple ascending dose study of voxelotor in adult healthy volunteers and patients with SCD, followed by a single-arm, open-label extension study. This report describes results of voxelotor (500-1000 mg per day) in patients with sickle cell anemia. The study evaluated the safety, tolerability, pharmacokinetic, and pharmacodynamic properties of voxelotor and established proof of concept by improving clinical measures of anemia, hemolysis, and sickling. Thirty-eight patients with SCD received 28 days of voxelotor 500, 700, or 1000 mg per day or placebo; 16 patients received 90 days of voxelotor 700 or 900 mg per day or placebo. Four patients from the 90-day cohort were subsequently enrolled in an extension study and treated with voxelotor 900 mg per day for 6 months. All patients who received multiple doses of voxelotor for ≥28 days experienced hematologic improvements including increased Hb and reduction in hemolysis and percentage of sickled red cells, supporting the potential of voxelotor to serve as a disease-modifying therapy for SCD. Voxelotor was well tolerated with no treatment-related serious adverse events and no evidence of tissue hypoxia. These trials were registered at www.clinicaltrials.gov as #NCT02285088 and #NCT03041909.
A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403
Authors: Stock Wendy , Luger Selina M. , Advani Anjali S. , Yin Jun , Harvey Richard C. , Mullighan Charles G. , Willman Cheryl L. , Fulton Noreen , Laumann Kristina M. , Malnassy Greg , Paietta Elisabeth , Parker Edy , Geyer Susan , Mrózek Krzysztof , Bloomfield Clara D. , Sanford Ben , Marcucci Guido , Liedtke Michaela , Claxton David F. , Foster Matthew C. , Bogart Jeffrey A. , Grecula John C. , Appelbaum Frederick R. , Erba Harry , Litzow Mark R. , Tallman Martin S. , Stone Richard M. , Larson Richard A.
Published: January 2019

Retrospective studies have suggested that older adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) have better survival rates when treated using a pediatric ALL regimen administered by pediatric treatment teams. To address the feasibility and efficacy of using a pediatric treatment regimen for AYA patients with newly diagnosed ALL administered by adult treatment teams, we performed a prospective study, CALGB 10403, with doses and schedule identical to those in the Children's Oncology Group study AALL0232. From 2007 to 2012, 318 patients were enrolled; 295 were eligible and evaluable for response. Median age was 24 years (range, 17-39 years). Use of the pediatric regimen was safe; overall treatment-related mortality was 3%, and there were only 2 postremission deaths. Median event-free survival (EFS) was 78.1 months (95% confidence interval [CI], 41.8 to not reached), more than double the historical control of 30 months (95% CI, 22-38 months); 3-year EFS was 59% (95% CI, 54%-65%). Median overall survival (OS) was not reached. Estimated 3-year OS was 73% (95% CI, 68%-78%). Pretreatment risk factors associated with worse treatment outcomes included obesity and presence of the Philadelphia-like gene expression signature. Use of a pediatric regimen for AYAs with ALL up to age 40 years was feasible and effective, resulting in improved survival rates compared with historical controls. CALGB 10403 can be considered a new treatment standard upon which to build for improving survival for AYAs with ALL. This trial was registered at www.clinicaltrials.gov as #NCT00558519.
Management of direct factor Xa inhibitor–related major bleeding with prothrombin complex concentrate: a meta-analysis
Authors: Piran Siavash , Khatib Rasha , Schulman Sam , Majeed Ammar , Holbrook Anne , Witt Daniel M. , Wiercioch Wojtek , Schünemann Holger J. , Nieuwlaat Robby
Published: January 2019

A targeted antidote for reversal of direct factor Xa (FXa) inhibitors is now available for clinical use in the United States, but it is costly and has limited availability. In a systematic review, we evaluated the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) as an alternative for managing direct FXa inhibitor–related major bleeding. A systematic literature search was conducted using Medline, Embase, and the Cochrane Register of Controlled Trials up to September 2018. No comparative studies were found. Ten case series with 340 patients who received PCC for direct FXa inhibitor–related major bleeding were included. The pooled proportion of patients with effective management of major bleeding was 0.69 (95% confidence interval [CI], 0.61-0.76) in 2 studies using the International Society on Thrombosis and Haemostasis (ISTH) criteria and 0.77 (95% CI, 0.63-0.92) in 8 studies that did not use the ISTH criteria; all-cause mortality was 0.16 (95% CI, 0.07-0.26), and thromboembolism rate was 0.04 (95% CI, 0.01-0.08). On the basis of evidence with very low certainty from single-arm case series, it is difficult to determine whether 4F-PCC in addition to cessation of direct oral FXa inhibitor is more effective than cessation of direct oral FXa inhibitor alone in patients with direct FXa inhibitor–related major bleeding.
A Black Panther in the Tropics
Authors: Germain Félix
Published: January 2019

Like most young men of the postwar era, Pierre-Just Marny (1943–2011), a Martinican man of humble origin, expected to reap the benefits of departmentalization. But in the late 1950s, against all expectations, he became an outlaw. In 1965, after committing violent crimes, he called himself La Panthère Noire (the Black Panther), a Hollywood-inspired name characterizing his courage and fearlessness. Marny, who has fallen through the cracks of French history, is an important historical subject because his adventures, killings, and struggle against the French police; his sentence to life in prison; and ultimately his struggle for freedom became intertwined with the complex relationship that Martinique has developed with France since departmentalization.

Comme la plupart des jeunes hommes de la période de l'après-guerre, Pierre-Juste Marny (1943–2011), un Martiniquais d'origine modeste, espérait récolter les bénéfices de la départementalisation. Mais à la fin des années 1950, contre toute attente, il devint un hors-la-loi. En 1965, après une série de crimes violents, le jeune Marny se fit appeler La Panthère Noire, un surnom inspiré d'Hollywood illustrant son intrépidité. Oublié par les chercheurs, Marny est un sujet important de l'histoire contemporaine parce que ses aventures en Martinique, ses meurtres, sa lutte contre la police, son emprisonnement à perpétuité, et sa bataille pour retrouver la liberté s'entremêlent avec la relation compliquée entre la Martinique et la France depuis la départementalisation.
The US Secret War in Laos
Authors: Sisavath Davorn
Published: January 2019

This article complicates and challenges the existing records on US-Lao relations during the Second Indochina War by examining military waste in Laos as an archive. Over two million tons of bombs were dropped during US bombing in Laos from 1964 to 1973. Today, Laos remains the most heavily bombed country per capita, where more than 580,000 bombing missions were conducted (the equivalent of one raid every eight minutes for nine years). The war metal and scraps that saturate northern Laos motivated my examination of an alternative archive, as have incomplete records—those restricted or absented—in the state archive. Located in the massive accumulation of military waste, these archives tell a different story about the war by highlighting the convergence of militarism and capitalism that led to the production of bombs and that continue to shape life-making practices in the war’s aftermath.
Identification and characterization of genes encoding the nuclear envelope LINC complex in the monocot speciesZea mays
Authors: Gumber Hardeep K. , McKenna Joseph F. , Estrada Amado L. , Tolmie Andrea F. , Graumann Katja , Bass Hank W.
Published: January 2019

The LINC (Linker of Nucleoskeleton to Cytoskeleton) complex is an essential multi-protein structure spanning the nuclear envelope. It connects the cytoplasm to the nucleoplasm, functions to maintain nuclear shape and architecture, and regulates chromosome dynamics during cell division. Knowledge of LINC complex composition and function in the plant kingdom is primarily limited to Arabidopsis, but critically missing from the evolutionarily distant monocots which include grasses, the most important agronomic crops worldwide. To fill this knowledge gap, we identified and characterized 22 maize genes, including a new grass-specific KASH gene family. Using bioinformatic, biochemical, and cell biological approaches, we provide evidence that representative KASH candidates localize to the nuclear periphery and interact with ZmSUN2 in vivo. FRAP experiments using domain-deletion constructs verified that this SUN-KASH interaction was dependent on the SUN but not the coiled-coil domain of ZmSUN2. A summary working model is proposed for the entire maize LINC complex encoded by conserved and divergent gene families. These findings expand our knowledge of the plant nuclear envelope in a model grass species, with implications for both basic and applied cellular research.
Synaptotagmin 5 regulates calcium-dependent Weibel-Palade body exocytosis in human endothelial cells
Authors: Lenzi Camille , Stevens Jennifer , Osborn Daniel , Hannah Matthew J. , Bierings Ruben , Carter Tom
Published: January 2019

Elevations of intracellular free Ca2+ concentration ([Ca2+]i) are a potent trigger for Weibel-Palade body (WPB) exocytosis and secretion of Von Willebrand factor (VWF) from endothelial cells, however, the identity of WPB-associated Ca2+-sensors involved in transducing acute increases in [Ca2+]i into granule exocytosis remain unknown. Here we show that synaptotagmin 5 (SYT5) is expressed in human umbilical vein endothelial cells (HUVEC) and is recruited to WPBs to regulate Ca2+-driven WPB exocytosis. Western blot analysis of HUVEC identified SYT5 protein, and exogenously expressed SYT5-mEGFP localized almost exclusively to WPBs. shRNA-mediated knockdown of endogenous SYT5 reduced the rate and extent of histamine-evoked WPB exocytosis and reduced secretion of the WPB cargo VWF-propeptide (VWFpp). The shSYT5-mediated reduction in histamine-evoked WPB exocytosis was prevented by expression of shRNA-resistant SYT5-mCherry. Overexpression of SYT5-EGFP increased the rate and extent of histamine-evoked WPB exocytosis, and increased secretion of VWFpp. Expression of a Ca2+-binding defective SYT5 mutant (SYT5-Asp197Ser-EGFP) mimicked depletion of endogenous SYT5. We identify SYT5 as a WPB-associated Ca2+ sensor regulating Ca2+-dependent secretion of stored mediators from vascular endothelial cells.
Tau regulates the microtubule-dependent migration of glioblastoma cells via the Rho-ROCK signaling pathway
Authors: Breuzard Gilles , Pagano Alessandra , Bastonero Sonia , Malesinski Soazig , Parat Fabrice , Barbier Pascale , Peyrot Vincent , Kovacic Hervé
Published: January 2019

The pathological significance of Tau (encoded by MAPT) in mechanisms driving cell migration in glioblastoma is unclear. By using an shRNA approach to deplete microtubule-stabilizing Tau in U87 cells, we determined its impact on cytoskeletal coordination during migration. We demonstrated here that the motility of these Tau-knockdown cells (shTau cells) was significantly (36%) lower than that of control cells. The shTau cells displayed a slightly changed motility in the presence of nocodazole, which inhibits microtubule formation. Such reduced motility of shTau cells was characterized by a 28% lower number of microtubule bundles at the non-adhesive edges of the tails. In accordance with Tau-stabilized microtubules being required for cell movement, measurements of the front, body and rear section displacements of cells showed inefficient tail retraction in shTau cells. The tail retraction was restored by treatment with Y27632, an inhibitor of Rho-ROCK signaling. Moreover, we clearly identified that shTau cells displayed relocation of the active phosphorylated form of p190-RhoGAP (also known as ARHGAP35), which inhibits Rho-ROCK signaling, and focal adhesion kinase (FAK, also known as PTK2) in cell bodies. In conclusion, our findings indicate that Tau governs the remodeling of microtubule and actin networks for the retraction of the tail of cells, which is necessary for effective migration.
Hypoxia suppresses myofibroblast differentiation by changing RhoA activity
Authors: Leinhos Lisa , Peters Johannes , Krull Sabine , Helbig Lena , Vogler Melanie , Levay Magdolna , van Belle Gijsbert J. , Ridley Anne J. , Lutz Susanne , Katschinski Dörthe M. , Zieseniss Anke
Published: January 2019

Fibroblasts show a high range of phenotypic plasticity including the transdifferentiating into myofibroblasts. Myofibroblasts are responsible for the generation of the contraction forces that are important for wound healing and scar formation. Overactive myofibroblasts on the other hand are involved in abnormal scarring. Cell stretching and extracellular signals such as transforming growth factor β can induce the myofibroblastic program whereas microenvironmental conditions such as reduced tissue oxygenation have an inhibitory effect. We investigated the effects of hypoxia on myofibroblastic properties and linked this to RhoA activity. Hypoxia reversed the myofibroblastic phenotype of primary fibroblasts. This was accompanied by decreased αSMA expression, alterations in cell contractility, actin reorganization, and RhoA activity. We identified a hypoxia-inducible induction of ArhGAP29, which is critically involved in MRTF-A (myocardin-related transcription factor-A) signaling, the differentiation state of myofibroblasts and modulates RhoA activity. This novel link between hypoxia and MRTF-A signaling is likely to be important for ischemia-induced tissue remodeling and the fibrotic response.
Population history with invasive predators predicts innate immune function response to early life glucocorticoid exposure
Authors: McCormick Gail L. , Robbins Travis R. , Cavigelli Sonia A. , Langkilde Tracy
Published: January 2019

Early life stress can suppress immune function, but it is unclear if transgenerational stress exposure modulates the immune consequences of early stress. In populations where, historically, the immune system is frequently activated, e.g. persistent stressors that cause injury, it may be maladaptive to suppress immune function after early life stress. Thus, the relationship between early life stress and immune function may vary with population-level historical stressor exposure. We collected gravid fence lizards (Sceloporus undulatus) from populations that naturally differ in long-term exposure to invasive fire ants (Solenopsis invicta). We manipulated early life stress in resulting offspring via weekly exposure to fire ants, application of the stress-relevant hormone corticosterone, or control treatment from 2 to 43 weeks of age. We quantified adult immune function in these offspring with baseline and antigen-induced hemagglutination and plasma bacterial killing ability. Early life corticosterone exposure suppressed baseline hemagglutination in offspring of lizards from populations without fire ants but enhanced hemagglutination in those from populations with fire ants. This enhancement may prepare lizards for high rates of wounding, toxin exposure, and infection associated with fire ant attack. Adult bacterial killing ability and hemagglutination were not affected by early life exposure to fire ants, but the latter was higher in offspring of lizards from invaded sites. A population's history of persistent wounding may thus alter individual long-term immunological responses to early life stressors. Further consideration of historical stressor exposure (type and duration) may be important to better understand how early life stressors affect adult physiology.
Complementary roles of photoperiod and temperature in environmental sex determination in Daphnia spp
Authors: Camp Allison A. , Haeba Maher H. , LeBlanc Gerald A.
Published: January 2019

Daphnia spp, a keystone genus in freshwater lentic habitats, are subject to environmental sex determination wherein environmental conditions dictate offspring sex and whether they reproduce asexually or sexually. The introduction of males into a population denotes the first step in the switch from asexual parthenogenetic reproduction to sexual reproduction. We tested the hypothesis that photoperiod and temperature co-regulate male sex determination and that these environmental stimuli would activate elements of the male sex determination signaling cascade. Results revealed that photoperiod was a critical cue in creating permissive conditions for male production. Further, under photoperiod-induced permissive conditions, male sex determination was temperature dependent. The two daphnid species evaluated, Daphnia pulex and D. magna, exhibited different temperature dependencies. D. pulex produced fewer males with increasing temperatures between 16-22°C, and D. magna exhibited the opposite trend. We found consistent expression patterns of key genes along the male sex determining signaling pathway in D. pulex independent of environmental stimuli. mRNA levels for the enzyme responsible for synthesis of the male sex determining hormone, methyl farnesoate, were elevated early in the reproductive cycle, followed by increased mRNA levels of the methyl farnesoate receptor subunits, Met and SRC. Environmental conditions that stimulated male offspring production significantly increased Met mRNA levels. Results indicate that male sex determination in daphnids is under the permissive control of photoperiod and the regulatory control of temperature. Further, these environmental cues may stimulate male sex determination by increasing levels of the Met subunit of the methyl farnesoate receptor.
UPFront and center in RNA decay: UPF1 in nonsense-mediated mRNA decay and beyond
Authors: Kim Yoon Ki , Maquat Lynne E.
Published: January 2019

Nonsense-mediated mRNA decay (NMD), which is arguably the best-characterized translation-dependent regulatory pathway in mammals, selectively degrades mRNAs as a means of post-transcriptional gene control. Control can be for the purpose of ensuring the quality of gene expression. Alternatively, control can facilitate the adaptation of cells to changes in their environment. The key to NMD, no matter what its purpose, is the ATP-dependent RNA helicase upstream frameshift 1 (UPF1), without which NMD fails to occur. However, UPF1 does much more than regulate NMD. As examples, UPF1 is engaged in functionally diverse mRNA decay pathways mediated by a variety of RNA-binding proteins that include staufen, stem–loop-binding protein, glucocorticoid receptor, and regnase 1. Moreover, UPF1 promotes tudor-staphylococcal/micrococcal-like nuclease-mediated microRNA decay. In this review, we first focus on how the NMD machinery recognizes an NMD target and triggers mRNA degradation. Next, we compare and contrast the mechanisms by which UPF1 functions in the decay of other mRNAs and also in microRNA decay. UPF1, as a protein polymath, engenders cells with the ability to shape their transcriptome in response to diverse biological and physiological needs.
Hepatitis-C and it’s seroconversion in end stage kidney disease patients on maintenance hemodialysis and factors affecting it
Authors: Hussain Yasir , Shahzad Anjum , Azam Sidra , Munawar Nazish
Published: January 2019

Objective: To determine frequency of hepatitis-C in dialysis patients at start of hemodialysis, seroconversion from HCV negative to HCV positive over study duration and factors affecting seroconversion.

Methods: This descriptive prospective observational study done in dialysis center of DHQ hospital Sheikhupura, Punjab, Pakistan. The study was conducted from October 2016 to October 2017. Data was collected on Performa and later followed prospectively in same cohort of patients. All the patients on maintenance hemodialysis for more than one month were included in the study. Patients with acute kidney disease and on dialysis less than one month were excluded. Patients were analyzed by dividing them in three groups, group-I patients who were HCV positive at start of dialysis, Group-II who were negative and seroconvert to HCV positive, Group-III who were negative and remained negative. All seronegative patients were followed at one, three, six and twelfth months on being hemodialysis for seroconversion.

Results: Out of 230 surveyed patients 52 were HCV positive at start of dialysis and 19 were loss of follow up. Out of remaining 159 HCV negative patients 95 became HCV positive, only 64 patients remained HCV negative by end of study.

Conclusion: Frequency of HCV seroconversion among chronic hemodialysis patient is found to be 53.37%. Arteriovenous access, number of dialysis, reuse of dialyzer and blood transfusions are important risk factors.

How to cite this:Hussain Y, Shahzad A, Azam S, Munawar N. Hepatitis-C and it’s seroconversion in end stage kidney disease patients on maintenance hemodialysis and factors affecting it. Pak J Med Sci. 2019;35(1):66-70. doi: https://doi.org/10.12669/pjms.35.1.366

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Density artefacts at interfaces caused by multiple time-step effects in molecular dynamics simulations
Authors: Sidler Dominik , Lehner Marc , Frasch Simon , Cristófol-Clough Michael , Riniker Sereina
Published: January 2019

Background: Molecular dynamics (MD) simulations have become an important tool to provide insight into molecular processes involving biomolecules such as proteins, DNA, carbohydrates and membranes. As these processes cover a wide range of time scales, multiple time-step integration methods are often employed to increase the speed of MD simulations. For example, in the twin-range (TR) scheme, the nonbonded forces within the long-range cutoff are split into a short-range contribution updated every time step (inner time step) and a less frequently updated mid-range contribution (outer time step). The presence of different time steps can, however, cause numerical artefacts.

Methods: The effects of multiple time-step algorithms at interfaces between polar and apolar media are investigated with MD simulations. Such interfaces occur with biological membranes or proteins in solution.

Results: In this work, it is shown that the TR splitting of the nonbonded forces leads to artificial density increases at interfaces for weak coupling and Nosé-Hoover (chain) thermostats. It is further shown that integration with an impulse-wise reversible reference system propagation algorithm (RESPA) only shifts the occurrence of density artefacts towards larger outer time steps. Using a single-range (SR) treatment of the nonbonded interactions or a stochastic dynamics thermostat, on the other hand, resolves the density issue for pairlist-update periods of up to 40 fs.

Conclusion: TR schemes are not advisable to use in combination with weak coupling or Nosé-Hoover (chain) thermostats due to the occurrence of significant numerical artifacts at interfaces.
Anti-infective potential of hydroalcoholic extract of Punica granatum peel against gram-negative bacterial pathogens
Authors: Joshi Chinmayi , Patel Pooja , Kothari Vijay
Published: January 2019

Background: Punica granatum extracts have been prescribed in traditional medicine for management of a variety of disease conditions including microbial infections. Generation of scientific evidence for validation of P. granatum peel extract’s anti-pathogenic efficacy is required.

Methods: Hydroalcoholic extract of P. granatum peel (PGPE), prepared by microwave assisted extraction method was evaluated for its quorum-modulatory potential against two different human-pathogenic bacteria viz. Chromobacterium violaceum and Pseudomonas aeruginosa.

Results: This extract was able to modulate in vitro production of quorum sensing-regulated pigments in both these test bacteria at ≥5 μg/ml. Virulence traits of P. aeruginosa like haemolytic activity, and biofilm formation were negatively affected by the test extract, and it also made P. aeruginosa more susceptible to lysis by human serum. Antibiotic susceptibility of both test bacteria was modulated owing to pre-treatment with PGPE. Exposure of these test pathogens to PGPE (≥0.5 μg/ml) effectively reduced their virulence towards the nematode Caenorhabditis elegans. Repeated subculturing of P. aeruginosa on PGPE-supplemented growth medium did not induce resistance to PGPE in this notorious pathogen, and this extract was also found to exert a post-extract effect on P. aeruginosa. Individual constituent phytocompounds of PGPE were found to be less efficacious than the whole extract. PGPE seemed to interfere with the signal-response machinery of P. aeruginosa and C. violaceum. PGPE also exhibited notable prebiotic potential by promoting growth of probiotic strains- Bifidobacterium bifidum and Lactobacillus plantarum at ≤50 μg/ml.

Conclusions: This study indicates PGPE to be an effective antipathogenic and prebiotic preparation, and validates its therapeutic use mentioned in traditional medicine. This study also emphasizes the need for testing any bioactive extract at broadest possible concentration range, particularly in vivo, so that an accurate picture of dose-response relationship can emerge.
Probabilistic Bisection Converges Almost as Quickly as Stochastic Approximation
Authors: Frazier Peter I. , Henderson Shane G. , Waeber Rolf
Published: January 2019

The probabilistic bisection algorithm (PBA) solves a class of stochastic root-finding problems in one dimension by successively updating a prior belief on the location of the root based on noisy responses to queries at chosen points. The responses indicate the direction of the root from the queried point and are incorrect with a fixed probability. The fixed-probability assumption is problematic in applications, and so we extend the PBA to apply when this assumption is relaxed. The extension involves the use of a power-one test at each queried point. We explore the convergence behavior of the extended PBA, showing that it converges at a rate arbitrarily close to, but slower than, the canonical “square root” rate of stochastic approximation.
Contract Design for the Stockist in Indian Distribution Networks
Authors: Iyer Ananth , Palsule-Desai Omkar
Published: January 2019

Problem definition: Stockists are the entity in the supply chain who deliver to the millions of small shops that account for over 90% of retail sales in India. The stockist purchases product from the manufacturer, develops retailer interest in carrying the product, solves the logistics problem of delivery to retailers, and manages retail credit and money collection. In return, the stockist is provided assistance by the manufacturer and paid an associated margin that is a percent of the product’s retail price. We observed relatively low distribution margins offered to the stockists in India that was a surprise given infrastructure and financing challenges. We noted that the low margins are enabled by the efficiency in product delivery and demand stimulation induced by the stockist. In this paper, we focus on the analysis of screening contracts offered by manufacturers to stockists. Methodology: We use a principal–agent model structure and model the routing cost, inventory cost, and demand impact of the stockist’s capability. We then use a substitutes or complements relationship between manufacturer assistance and stockist impact to understand the optimal contract structure—i.e., level of assistance and associated retail margin. We describe the economics associated with the stockist, provide data regarding the margins and assistance provided by the manufacturer, and use the model to understand their use in developing an effective supply chain. Results: Our model uses three parameters to show that a manufacture can adjust the level of spatial retailer intensity and thus the impact of the stockist in generating demand, the fraction of high-performing stockists associated with the manufacturer and the nature of the relationship between assistance provided and its impact on the stockist’s performance (i.e., complements or substitutes relationship), to attain superior performance. Academic/practical relevance: We parameterize data from Indian firms in the consumer goods industry to understand the observed assistance provided by the manufacturer to the stockist, and associated margins. We then use our model to understand actions taken by a manufacturer in the Indian market. Managerial implications: Our analysis provides a framework for manufacturers to design screening contracts for stockists who play a vital role in managing the fragmented retail markets in developing countries.

The online supplement is available at https://doi.org/10.1287/msom.2018.0722 .

This paper has been accepted for the Manufacturing & Service Operations Management Special Issue on Value Chain Innovations in Developing Economies.
Forward Commodity Trading with Private Information
Authors: Anderson Edward J. , Philpott Andrew B.
Published: January 2019

Firms that trade a commodity that has a random price can reduce risk by trading forward. In “Forward Commodity Trading with Private Information,” Edward J. Anderson and Andrew B. Philpott consider a setting in which a buyer and a seller of a divisible commodity have different private information on the probability distribution of its future price. This situation arises in electricity pool markets where contracts for differences are traded by buyers and sellers of electricity to hedge future price risk. The paper compares several mechanisms for settling the price and quantity of such a contract when buyers and sellers have private information. These include Nash bargaining and supply- function equilibrium models. In the latter setting, a player can deduce the other player’s private information from its offered supply function and use this to improve its own supply function. Examples are given to show that this strategy, when used by both firms, may make both firms worse off in equilibrium.
Estilos de Aprendizagem em EaD: Construção e evidências de validade de instrumento
Authors: Moraes Raíssa Bárbara Nunes , Zerbini Thaís
Published: January 2019

A expansão de projetos de educação a distância (EAD) e seus consequentes programas de treinamento, formação e qualificação profissionais ofertados por instituições de ensino superior (IES) e outras organizações, tornam necessário um maior número estudos sistemáticos nesse contexto. Destaca-se a necessidade de estudos relacionados às variáveis do perfil da clientela, como é o caso dos Estilos de Aprendizagem. A presente pesquisa objetivou construir e verificar evidências de validade de um instrumento de medida de Estilos de Aprendizagem no contexto de EAD em IES. Participaram do estudo, virtualmente, alunos de uma universidade pública no interior paulista matriculados em um curso superior a distância. Foram realizadas análises fatoriais exploratórias e de consistência interna. A escala possui três fatores: Ambiente de Estudo (2 itens, α=0,76); Regulação Externa (4 itens, α=0,63); Interação Interpessoal (2 itens, α=0,40). Por ser um instrumento inédito na área da Psicologia Organizacional e do Trabalho (POT) no contexto de EAD em IES, são necessários mais estudos, bem como aplicação em amostras diferentes.
Um prefácio imaginário para Thalassa
Authors: Câmara Leonardo Cardoso Portela , Herzog Regina
Published: January 2019

Pretendemos realizar uma incursão pelas teses principais do polêmico ‘Thalassa: ensaio sobre a teoria da genitalidade', obra de Sándor Ferenczi publicada em 1924. Considerado amiúde como um trabalho estranho e extravagante, propomos sua releitura a partir de uma hipótese: ‘Thalassa' exige o abandono de formas habituais do pensar.
Expressão facial de emoções de crianças com deficiência visual e videntes: diferentes procedimentos de evocação, registro e avaliação obtidos em uma intervenção
Authors: Ferreira Bárbara Carvalho , Del Prette Zilda Aparecida Pereira , Del Prette Almir
Published: January 2019

Considerando os procedimentos para evocação, registro e julgamento das expressões faciais de emoções, bem como a carência de pesquisas que avaliem essas diferentes metodologias, o presente estudo teve como objetivo analisar a sensibilidade diferencial dos procedimentos de evocação e registro das expressões faciais de emoções (EFE) de crianças com deficiência visual e videntes obtidas antes, durante e após um programa de intervenção que visou ensinar e aperfeiçoar o repertório de EFE na interface com as habilidades sociais. Participaram da pesquisa, que adotou um delineamento pré e pós-teste com sujeito único, com múltiplas sondagens e replicações intra e entre sujeitos, e intervenção com 21 sessões, três crianças cegas, três com baixa visão e três videntes, assim como os pais, professores e um juiz, que avaliaram as expressões faciais de emoções das crianças em diferentes momentos, evocadas e avaliadas de formas diversas, além de serem registradas por fotografias e filmagens. Os resultados mostraram que na sondagem que ocorreu após a intervenção a porcentagem de acertos das expressões faciais de emoções de todas as crianças foi maior, seja no registro por fotografia ou por filmagem. Além disso, o repertório de expressão facial de emoções de todos os participantes, avaliado pelos pais, professoras e juiz, foi aprimorado e mantido após o programa de intervenção, assim como a qualidade da expressividade de emoções pela face.
Entre a repressão policial e o saber médico: o controle social da loucura no Espírito Santo entre o fim do século XIX e os anos 1950
Authors: Perini Júlia Freire , Da Cunha Marcelo Durão Rodrigues
Published: January 2019

O presente artigo visa oferecer um panorama histórico do que foi o trato com o problema social da loucura entre o final do século XIX e os anos cinquenta do século XX no estado do Espírito Santo. Pautando-nos em uma análise do desenvolvimento de instituições e de saberes médicos em âmbito local, buscaremos compreender as principais características assumidas pela preocupação com o lugar do louco na sociedade capixaba ao longo do período em questão. Baseando-nos na crítica foucaultiana dos jogos de exclusão operados pelo saber científico na modernidade, sustentaremos a hipótese de que a institucionalização do trato com a loucura no Espírito Santo representou muito mais a ressignificação de antigas práticas repressivas e policialescas de exclusão do louco do corpo social local do que propriamente a sua superação. A fim de comprovar a hipótese em questão, analisaremos livros de entrada, prontuários e algumas entrevistas de funcionários daquela que seria a principal instituição responsável por modernizar e por superar o atraso em relação ao tratamento dos loucos nos anos 1950 em nosso estado: o Hospital Adauto Botelho.
Popular Music in Higher Education: The Consolidation of Field in Teaching and Research
Authors: Súárez Eduardo Viñuela
Published: January 2019

In recent years popular music has consolidated its presence in academia via its inclusion in both the curricula of various degrees in higher education institutions and in research forums of several disciplines. In this paper we review the international evolution of a process that has been running for nearly fifty years. We also address some of the debates and challenges inherent to the normalization of popular music in music education.
Phytotoxic Effects of Leaf Leachates of Invasive Weeds Cosmos sulphureus and Xanthium strumarium on Agricultural Crops
Authors: Ghayal Nivedita , Biware Megha , Gharpure Pallavi
Published: January 2019

Many invasive weeds are known to create their deleterious effects on biological ecosystems and also rhizosphere soils. Weeds such as Cosmos and Xanthium have their existence near agricultural crops fields. Such weeds grow in abundance, releasing specific allelochemicals which have adverse effect on germination rate, physiological patterns and reproduction of crop plants. In present work, allelopathic effects of leaf leachates of Cosmos and Xanthium were observed on seed germination and seedling growth of Triticum aestivum, Vigna radiata and Trigonella foenum-graceum like crops. Seed germination was inhibited at higher concentration at 6% while lower concentrations showed stimulatory effect on Mungbean and Fenugreek from 1%-4% concentrations. But seed germination percentage of Vigna and Trigonella showed 70% and 60% growth in response to leaf leachates of Cosmos at 6% concentration. Triticum showed total inhibition of 40% to both leaf leachates. The qualitative phytochemical analyses showed presence of alkaloids, phytosterols, phenols, tannins and flavonoids. GCMS and IR studies revealed presence of major constituents such as esters, ethers, anhydride and polyalcohols. Cosmos and Xanthium showed the characteristic FTIR fingerprinting regions of various functional groups such as –OH, carbonyl, anhydride, ester and amides. The variations in phytochemicals of these invasive might be attributed to response of the plants to different environmental stresses.
Genetic Diversity Analysis of Sorghum (Sorghum Bicolor L. Moench) Genotypes Using Rapd Markers
Authors: Zinzala Sumita , Davda Bharat K. , Modha K. G. , Patel Ritesh K. , Baldaniya Vipul
Published: January 2019

Genetic diversity among 24 genotypes of sorghum was studied by using 20 random primers. The total number of amplified PCR bands was 591 of which 495 (83.75%) were polymorphic displaying PIC values ranging from 0.27 to 0.69 with an average of 0.52. Similarity coefficients among the genotypes were ranged from 0.33 to 0.89. The similarity coefficient was used to construct a UPGMA based dendrogram using average linkage between groups. The analysis illustrates considerable potential of RAPD markers for estimating genetic diversity among 24 genotypes of sorghum.
Evaluation of Antioxidant Activities of Alpinia galanga (L.) Willd
Authors: Devi Khoirom Ratipiyari , Singh Paonam Priyobrata , Medhapati Devi Moirangthem , Sharma Gurumayum Jitendra
Published: January 2019

Present research was designed to evaluate the free radical scavenging capacities and antioxidant activities of rhizome extracts of Alpinia galanga prepared in different solvent systems (60% aqueous methanol, 60% aqueous ethanol and distilled water) using different in vitro chemical assays. Antioxidant components such as total phenolic content (TPC), total flavonoid content (TFC) and ascorbic acid contents of the ginger species were screened. Antioxidant assays employed included sulphur free radical reactivity assay, ferric ion reducing power assay, DPPH free radical scavenging capacity assay, hydroxyl radical scavenging assay, nitric oxide scavenging activity assay and hydrogen peroxide scavenging assay. The obtained data reveal that the plant extracts contained significant amount of the observed antioxidant components and also exhibited significant free radical scavenging capacities. Methanol (60%) extract exhibited highest antioxidant activity than other solvents. The polyphenolic constituents of the plant extracts appear to be largely responsible for the radical scavenging capacity. The plant extracts act as promising source of antioxidants, and may be useful for development of nutraceuticals and pharmaceutical drugs.