bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravenous Iron Dosing and Infection Risk in Patients on Hemodialysis: A Prespecified Secondary Analysis of the PIVOTAL Trial
Authors: Macdougall Iain C. , Bhandari Sunil , White Claire , Anker Stefan D. , Farrington Kenneth , Kalra Philip A. , Mark Patrick B. , McMurray John J. V. , Reid Chante , Robertson Michele , Tomson Charles R.V. , Wheeler David C. , Winearls Christopher G. , Ford Ian ,   on behalf of the PIVOTAL Investigators and Committees
Published: April 2020

Significance Statement

Experimental and observational data have raised concerns that intravenous (IV) iron might increase the risk of infections. In this analysis from the Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL) trial involving 2141 patients on hemodialysis randomly assigned to receive either a high-dose or low-dose IV iron regimen, investigators reported finding no evidence that the two groups differed in incidence of infection, hospitalization for infection, or death from infection. Given the potential cardiovascular benefits of higher-dose IV iron seen in the PIVOTAL trial (due to either a direct effect of the IV iron or a decreased use of erythropoiesis-stimulating agents and thus, less exposure to associated cardiotoxic effects), this analysis provides reassurance for administering higher doses of IV iron than are currently given in many units worldwide.

Background

Experimental and observational studies have raised concerns that giving intravenous (IV) iron to patients, such as individuals receiving maintenance hemodialysis, might increase the risk of infections. The Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL) trial randomized 2141 patients undergoing maintenance hemodialysis for ESKD to a high-dose or a low-dose IV iron regimen, with a primary composite outcome of all-cause death, heart attack, stroke, or hospitalization for heart failure. Comparison of infection rates between the two groups was a prespecified secondary analysis.

Methods

Secondary end points included any infection, hospitalization for infection, and death from infection; we calculated cumulative event rates for these end points. We also interrogated the interaction between iron dose and vascular access (fistula versus catheter).

Results

We found no significant difference between the high-dose IV iron group compared with the lose-dose group in event rates for all infections (46.5% versus 45.5%, respectively, which represented incidences of 63.3 versus 69.4 per 100 patient years, respectively); rates of hospitalization for infection (29.6% versus 29.3%, respectively) also did not differ. We did find a significant association between risk of a first cardiovascular event and any infection in the previous 30 days. Compared with patients undergoing dialysis with an arteriovenous fistula, those doing so via a catheter had a higher incidence of having any infection, hospitalization for infection, or fatal infection, but IV iron dosing had no effect on these outcomes.

Conclusions

The high-dose and low-dose IV iron groups exhibited identical infection rates. Risk of a first cardiovascular event strongly associated with a recent infection.
Flexibilidad laboral: eufemismo a una política de regresión
Authors: Larios Pino José Luis
Published: April 2020

En el presente artículo de reflexión se analizarán las tipologías o clasificaciones que de acuerdo a la doctrina se le ha dado al fenómeno de la flexibilidad laboral, asimismo, se esbozará cómo se han aplicado estas políticas en Europa, los países anglosajones, América Latina y por supuesto en Colombia, desde la perspectiva de las legislaciones que la desarrollan. Finalmente se expondrá por qué se considera que la fl exibilidad es una política que infringe el principio de progresividad o no regresión y cómo ha sido enmascarada bajo una fórmula cuya finalidad es la generación de empleo y el crecimiento económico.
Las acciones colectivas en Colombia frente a una realidad global: el derecho de consumo
Authors: Herrera Tapias Beli
Published: April 2020

En Colombia la inclusión tanto legal como constitucional del derecho del consumo se debe a una necesidad de adecuación de la normativa a los lineamientos internacionales tanto de las directivas de la ONU, como de los Proyectos de MERCOSUR, ya que las relaciones comerciales, negociaciones internacionales y los procesos de globalización e integración de los mercados requerían de la garantía de este tipo de derechos por los Estados contratantes, sin embargo a través de este artículo y empleando una investigación jurídica de carácter aplicado, con enfoque cualitativo, se pretende hacer una crítica a los mecanismos constitucionales dispuestos para la defensa de los derechos de los consumidores como derechos colectivos, pues resultan poco operantes al no responder a las necesidades y realidades del consumidor contemporáneo que vive en un mundo globalizado.
El sacerdocio de todos los creyentes - Parte II: Aspectos históricos e implicancias
Authors: Mueller Ekkehardt
Published: April 2020

Este es el segundo de una serie de dos artículos que discuten el tema del sacerdocio de todos los creyentes. El primer artículo abordó los fundamentos bíblicos de este concepto. Esta segunda parte se enfoca brevemente en los aspectos históricos del asunto, desde el cristianismo primitivo hasta los tiempos recientes. El artículo concluye con una serie de implicancias prácticas de la discusión del tema.
“Rasgad vuesto corazón, y no vuestros vestidos”: Guerra, santuario y lluvia tardìa en la profecía de Joel
Authors: Bornapé M. Allan
Published: April 2020

Este artículo propone que el evento de la lluvia tardía o manifestación escatológica del Espíritu de Dios en la profecía de Joel necesita ser estudiado a la luz de los motivos de la guerra y el santuario/templo. En medio de estos motivos resulta fundamental la descripción agrícola, tanto de la catástrofe nacional como de su posterior extensión metafórica sobre el pueblo de Dios al final de la historia (cosecha). A través de algunos apuntes exegéticos en textos clave de Joel se busca demostrar que en el marco de los temas de la guerra y el santuario se puede comprender mejor el gran evento de la lluvia tardía en el remanente escatológico.
Upper limb principal arteries variations: A cadaveric study with terminological implication
Authors: Konarik Marek , Musil Vladimir , Baca Vaclav , Kachlik David
Published: April 2020

Although the variability of the upper limb arteries is a clinically important problem, the prevalence varies across the existing studies and the classification is rather complicated, uncoined, and sometimes even unclear for its simple and direct understanding and usage. Multiple case reports appearing in the last years apply incorrect, inappropriate, and sometimes misleading terminology. Here we performed an anatomical cadaveric study of the variability of the arteries of the upper limb, namely the axilla, arm and forearm, in 423 upper limbs (Central European population) embalmed with the classical formaldehyde method. We proposed the application of the Equality system based on common trunks for denomination of the axillary artery branches principal variations: truncus subscapulocircumflexus (22.9%), truncus profundocircumflexus (13.75%), and truncus bicircumflexus (13.95%). Further, we proposed the terminology system developed by Rodríguez-Niedenführ et al. for the free upper limb principal arterial trunk variations based on the origin, location (in the arm only or in the arm and forearm), and course (related to the forearm flexor muscles) of the involved artery: arteria brachialis superficialis (9.5%), arteria brachioradialis superficialis (6.4%), arteria brachioulnaris superficialis (1.9%), arteria brachiomediana superficialis (0.5%), and arteria comitans nervi mediani manus (3.3%). Extensive development of the catheterisation methods via the arteria radialis et ulnaris as well as surgical procedures using flaps based on perforating branches of these arteries (including arteria brachioradialis superficialis et brachioulnaris superficialis) necessitate thorough data on the prevalence of the variant vessels for safe performance of these procedures and to prevent any unexpected situations or to react adequately when they occur.
Biyoreaktör depolama alanlarında sızıntı suyu karakterizasyonu
Authors: TINMAZ KÖSE Esra , DEMİR İbrahim
Published: April 2020

Atıkların depolanması, Dünya
genelinde uygulanan nihai bertarafı yöntemidir. Ancak atıkların depolanması
sıklıkla çevre kirliğine neden olabilmekte ve canlı sağlığını olumsuz yönde
etkileyebilmektedir. Bu sorunlarının önüne geçilebilmesi adına atıkların biyorektör
depolama alanlarında depolanabilirliğinin araştırılması çalışmaları göndeme
gelmiştir. Biyoreaktör depolama alanları, atıkların parçalanarak,
sıkıştırılarak, arıtma çamurları ile birlikte depolanarak, enzim ve tampon
madde ilave edilerek, sızıntı suyu geri devrettirilerek veya havalandırma
uygulanarak konvansiyonel depolamaya göre atık bozunmasını hızlandıran ve
kararlı atığa en kısa sürede ulaşmayı hedefleyen sistemlerdir. Bu çalışmada
kapsamında, sızıntı suyu geri devrinin, havalandırmanın ve havalandırma yönünün
ve atık içeğinin biyorektör depolama alanlarından oluşan sızıntı sularının
ihtiva ettiği kirletici konsantrasyonları üzerindeki etkileri pilot ölçekli
olarak araştırılmıştır. Çalışma sonuçlarına göre atık boyutunun
küçültülmesinin ve havalandırmanın sızıntı suyunun neden olduğu kirleticilerin giderimi
açısından etkili olduğu belirlenmiştir. Ayrıca havalandırmanın reaktörün
üstünden yapılmasının da etkili bir uygulama olduğu sonucuna varılmıştır.
Candida tropicalis ile sulu çözeltilerden metal-kompleks boyar madde giderimi : üreme ve inhibisyon kinetiği
Authors: OKUR Müjgan , SARAÇOĞLU Nurdan , AKSU Zümriye
Published: April 2020

Bu çalışmada Acid
Violet 90 Cr-kompleks boyar maddesinin sulu ortamlardan giderimi için Candida tropicalis mayası kullanılmıştır.
Boyar madde giderimine başlangıç pH (3-6), indirgen şeker derişimi (1-20 g/L)
ve boyar madde derişiminin (20-400 mg/L) etkisi araştırılmıştır. En yüksek
biyobirikim pH 5’te, başlangıç boyar madde derişimi 50 mg/L iken % 50,3 olarak
elde edilmiştir. Boyar madde içermeyen kontrol ortamında Monod doygunluk sabiti
ve maksimum özgül üreme hızı 1,21 mg/L ve 0,267 1/h olarak bulunmuştur. AV90’nın
C. tropicalis üremesine inhibisyonunu
belirlemek için Lineer-karma tip inhibisyon modeli kullanılmıştır. AV90’nın
inhibisyon sabiti (KI) 1008 mg/L olarak elde edilmiştir. Deneysel sonuçlar
ve kinetik modelden elde edilen KI değerinin yüksek olması C. tropicalis’in azo boyar maddeye karşı
dirençli olduğunu ve azo boyar maddeleri içeren endüstriyel atıksuların
biyolojik arıtımında kullanılabileceğini göstermektedir.
Çok amaçlı kurumsal kaynak planlaması uyarlama projelerinin insan kaynağı kısıtı ve belirsizlik altında çizelgelenmesi
Authors: SUBULAN Kemal
Published: April 2020

Günümüzde, bilişim teknolojilerinin hızla
gelişmesine paralel olarak, kurumsal kaynak planlama (KKP) yazılım uyarlama
projeleri giderek artan bir öneme sahip olmaktadır. Bu bağlamda, proje
yöneticileri planlama ve proje çizelgeleme safhalarında, belirsizlik içeren birçok
durum ile karşı karşıya kalmaktadır. Bu çalışmada, proje organizasyon şeması
altında farklı görev/sorumluluklara sahip insan kaynağı kısıtı ve belirsizlik
altında, çok amaçlı bir KKP uyarlama projesinin çizelgelenmesi
hedeflenmektedir. Önerilen aralık programlama temelli çözüm yaklaşımı ile hem proje
parametrelerine/girdilerine ait belirsizlikler, hem de karar değişkeni olarak
tanımlanan çizelgeleme çıktılarına (aktivitelerin başlama ve/veya bitiş
zamanları) ilişkin belirsizlikler ele alınabilmektedir. Bunun sonucunda, proje
yöneticisinin risk iştahı doğrultunda, birçok alternatif çizelgenin üretilmesi
sağlanmıştır. Ayrıca önerilen yaklaşım ile çizelgeleme sürecinde, insan
kaynağına ilişkin etkinlik ve güvenilirlik faktörleri dikkate alınabilmektedir.
Son olarak, çalışma kapsamında sunulan bir uygulama çalışması ile KKP
projelerinin tamamlanma zamanının en küçüklenmesinin yanı sıra, proje için
ayrılan insan kaynağı kapasitesinin de en etkin şekilde kullanılması hedefi göz
önünde bulundurularak, uygulanabilir ve uzlaşık çözümlerin üretilebileceği
ortaya konmuştur.
Doğrusal olmayan yeni bir sistem ile damar görüntülerinin mikrobilgisayar tabanlı olarak şifrelenmesi
Authors: AKGÜL Akif , YILDIZ Mustafa Zahid , BOYRAZ Ömer Faruk , GÜLERYÜZ Emre , KAÇAR Sezgin , GÜREVİN Bilal
Published: April 2020

Bu çalışmada
yeni bir kaotik sistem ile mikrobilgisayar tabanlı olarak el üstü damar
görüntülerinin şifrelenerek, güvenli bir şekilde veri tabanında saklanması ve
kullanılması amaçlanmıştır. Çalışma kapsamında öncelikle kızılötesi kamera
yardımıyla kişilerden alınan el üstü damar görüntüleri ön işleme ile
iyileştirilmiştir. Daha sonra ön işlemeden geçirilmiş damar görüntüleri
mikrobilgisayar ortamında şifrelenmiştir. Şifreleme işlemi için yeni tasarlanan
ve analizleri gerçekleştirilen kaotik sistem ile üretilen rasgele sayılar
kullanılmıştır. Şifreleme işlemi öncesi elde edilen rasgele sayılar,
uluslararası alanda en çok kabul gören NIST-800-22 ve ENT testlerine tabi
tutularak, tüm testlerden başarılı sonuçlar alınmıştır. Kaos tabanlı şifreleme
sonucunda elde edilen görüntülerin histogram, korelasyon, entropi, NPCR ve UACI
gibi literatürde sıklıkla kullanılan güvenlik analizleri ile başarımları
ölçülmüştür. Gerçekleştirilen çalışma ile kimlik tanıma sistemlerinde de
kullanılabilen el üstü damar görüntülerinin mobil olarak güvenli bir şekilde
kullanılabileceği gösterilmiştir.
Multi-Patch Clamp Recording v3
Authors: Institute for Brain Science Allen
Published: April 2020

This protocol describes the process to obtain multiple electrophysiological recordings from postnatal mouse and/or human brain slices. Note: Research reported in this publication was supported by the National Institute Of Mental Health of the National Institutes of Health under Award Number U19MH114830. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Post Patch Clamp Slice Fixation v3
Authors: Institute for Brain Science Allen
Published: April 2020

This protocol describes the process to fix recorded/filled cells from mouse and human brain slices with 4% PFA/2.5% Glutaraldehyde in PBS for future histochemical processing. Note: Research reported in this publication was supported by the National Institute Of Mental Health of the National Institutes of Health under Award Number U19MH114830. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
DAB Detection of Biocytin Labeled Tissue v3
Authors: Institute for Brain Science Allen
Published: April 2020

This protocol describes the process for diaminobenzidine (DAB) detection of biocytin filled cells. This protocol is optimized for use with brain slices cut at 350 µm thick, in which cells are first filled with biocytin (i.e., post-electrophysiological recording), fixed in 4% PFA/2.5% glutaraldehyde, and transferred to PBS until ready to stain. Note: Research reported in this publication was supported by the National Institute Of Mental Health of the National Institutes of Health under Award Number U19MH114830. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Mouse Whole Cell Tissue Processing for 10x Genomics Platform v5
Authors: Institute for Brain Science Allen
Published: April 2020

This protocol describes how to isolate tissue from various ROI’s of the mouse brain followed by preparation of a highly concentrated single cell suspension for transcriptomic profiling on 10x Genomics platform. Note: Research reported in this publication was supported by the National Institute Of Mental Health of the National Institutes of Health under Award Number U19MH114830. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Artificial Cerebrospinal Fluid IV (ACSF.IV) v3
Authors: Institute for Brain Science Allen
Published: April 2020

This protocol describes making Artificial Cerebrospinal Fluid IV (ACSF.IV). ACSF.IV is used for multiple applications including incubation of fresh mouse brain slices prior to electrophysiological recording. Note: Research reported in this publication was supported by the National Institute Of Mental Health of the National Institutes of Health under Award Number U19MH114830. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
De “culpables” a “víctimas”: expansión y profesionalización del sistema de salud en la provincia Mendoza a fines del siglo XIX y principios del XX
Authors: Luis Natalia , Aguerregaray Castilgione Rosana
Published: April 2020

Entre fines del siglo XIX y comienzos del XX, la provincia de Mendoza presentaba un estado sanitario marcado por el crecimiento demográfico y urbanístico, la escasez de los servicios públicos y la destrucción de la antigua ciudad colonial como consecuencia del terremoto de 1861, lo que propiciaba un ambiente favorable para el desarrollo de diversas enfermedades infectocontagiosas. El objetivo de este artículo es indagar cómo se fue profesionalizando y expandiendo el sistema de salud en la provincia de Mendoza a fines del siglo XIX e inicios del XX, y cómo esos factores, junto con las representaciones sobre la enfermedad que predominaban en el discurso de la elite gobernante, incidieron en las políticas públicas para combatir las dolencias de la época. Para ello se consultaron diversos documentos escritos y fotográficos que permitieron analizar las modificaciones del discurso y las políticas públicas implementadas.
Ammonia volatilization from Nitrogen topdressing fertilization in second-crop corn cultivated under two management systems
Authors: Santos César Ferreira , Pinto Sheila Isabel do Carmo , Silva Konrad Passos e , Leite Paulino da Cunha , Vitor Vagner Aparecido
Published: April 2020

Controlled-release fertilizers are possible strategies to reduce losses through fertilization and increase nitrogen (N) use efficiency. In this context, this study aimed to evaluate the efficiency of N sources applied to second-crop corn cultivation. The experiment was carried out in a randomized block design in a 2 x 4 factorial scheme. Two cultivation systems (conventional and no-tillage) and four N fertilizers (urea pearls pure, urea+Cu+B, NBPT-treated urea and complex mineral fertilizer) with four replications were studied. Losses of N-NH3 by volatilization were evaluated up to 14 days after corn N fertilization. The data were subjected to analysis of variance and the means were grouped by the Scott-Knott test at 5% probability. Under the conditions in which the study was carried out, it was observed that urea pearls pure was the least efficient N fertilizer in restricting N-NH3 through volatilization losses. The most efficient fertilizer was NBPT-treated urea. Losses of N-NH3 by volatilization in the no-tillage system were higher than in the conventional cultivation system.
Tematic maps for irrigation of the watermelon crop in Piaui state
Authors: De Oliveira José Roberto , Mousinho Francisco Edinaldo Pinto , Andrade Júnior Aderson Soares de , Saraiva Kleiton Rocha , Nunes Francisco das Chagas de Andrade Porto
Published: April 2020

In semi-arid regions, inadequate management of irrigation in watermelon crops greatly increases yield losses. As a result, we sought to regionalize irrigation slides necessary for watermelon cultivation in the State of Piauí, considering different sowing times and soils with different water retention capacities. Irrigation slides were determined by the crop water balance, considering a historical series of fifteen years, originating from daily pluviometric precipitation records in 165 sites of this region. The reference evapotranspiration (ET0) and the respective crude irrigation slides were estimated on a daily scale for each site. Then, the crude irrigation slides were spatialized to the entire target region through a routine performed in Excel and later using the SPRING software, depending on the available water capacity in the soil and the date of sowing. Seeding dates with the need for minor irrigation slides for watermelon cultivation in Piauí were January 1st, February 1st and March 1st and in relation to sowing dates, the largest irrigation slides were verified on August 1st, September 1st and October 1st. Regionalized irrigation sheets varied according to the available water capacity in the soil and date of planting.
Integrative and episomal forms of genotype 16 of human papillomavirus in patients with cervical intraepithelial neoplasia and cervical cancer
Authors: Ibragimova M. K. , Tsyganov M. M. , Karabut I. V. , Churuksaeva O. N. , Shpileva O. N. , Bychkov V. A. , Kolomiets L. A. , Litviakov N. V.
Published: April 2020

The study involved 500 patients with LSIL (low grade squamous intraepithelial lesion), HSIL (high grade squamous intraepithelial lesion), stage I-IV cervical cancer, infected with human papillomavirus (HPV), as well as 235 women without pathological changes in cervical mucosa. The comprehensive survey included colposcopy, cytological and histological analysis, detection and genotyping of high-risk human papillomavirus. Viral load and physical status of HPV16 DNA was evaluated in cases of mono-infection (n = 148). The prevalence of virus-positive cases among the patients with LSIL/NSIL, cervical cancer patients and healthy women was 69.2%, 76.7% and 51.9%, respectively. An association between the severity of disease and high viral load was revealed. The frequency of integrated DNA was strongly increased in patients with a high viral load. The frequency of episomal forms was either reduced or not detecteable in patients with high viral load as compared to patients with low viral load. It is reasonable to suggest that a high HPV16 viral load may cause an increase in the frequency of integration of virus DNA into the cellular/host genome. This suggests that a high HPV16 viral load may be considered as a risk factor for prognosis of cervical intraepithelial neoplasia and cervical cancer.
Influenza A virus in the Western Arctic
Authors: Grebennikova T. V. , Syroeshkin A. V. , Chichaeva M. A. , Esper S. A. , Lvov D. K.
Published: April 2020

Small bays of bird bazaars of the Arctic Kola Peninsula (Barents Sea) have been studied. RNA of influenza A virus was found in the surface microlayer (SM) and aerosol samples from the bays located beneath bird colonies. The nucleotide sequencing of the PCR fragments from the SM and the sea aerosol showed their identity for each bay. Virus transfer mechanism along the “surface microlayer - sea aerosol” path has been proposed. The kinetic scheme of the virus-host-environment interaction, which allows the dependence of the viral population size on the temperature to be simulated, has been developed.
An experience in the clinical use of specific immunoglobulin from horse blood serum for prophylaxis of Ebola haemorrhagic fever
Authors: Borisevich I. V. , Chernikova N. K. , Markov V. I. , Krasnianskiy V. P. , Borisevich S. V. , Rozhdestvenskiy E. V.
Published: April 2020

The aim of this work was to estimate the efficacy and safety of single intramuscular introduction of specific heterologous immunoglobulin as prophylactic drug against Ebola hemorrhagic fever. Materials and methods. The specific heterologous immunoglobulin was introduced as a special prophylactic drug to 28 patients in epidemic situations, after skin hurt with infectious materials or contact with infectious blood. Clinico-laboratory observation was performed in 24 subjects after single intramuscular introduction of heterologous immunoglobulin Ebola. The samples of blood serum were investigated for immunoglobulin Ebola and antibodies to horse gamma-globulin on the 30th and 60th days after prophylaxis. Results. None of the subjects of the study contracted Ebola fever. There were no anaphylactic reactions after special prophylaxis with specific heterologous immunoglobulin. Among the subjects with normal allergic state 31% responded with local reactions; 13%, with a general reaction (mild case of the serum disease). Almost no reaction was observed in patients with unfavorable allergic state subjected to desensitizing therapy; in the absence of desensitizing therapy, 50% of patients with unfavorable allergic state exhibited local reactions; 17%, mild cases of the serum disease; 33%, moderate cases of the serum disease. In summary, if the tactics of immunoglobulin application was right, the quantity of local allergic reactions was 28%; of wide spread reactions, 6%. Weak serum disease was observed in 11% of the subjects. The prognostic period of resistance to Ebola fever was less than 30 days. Conclusion. The prophylactic use of specific immunoglobulin from horse blood serum against hemorrhagic Ebola fever is effective and relatively safe in patients subjected to desensitizing therapy.
THE INFLUENCE OF HIV INFECTION DURATION BEFORE ANTIRETROVIRAL THERAPY ON IMMUNOLOGICAL TREATMENT FAILURE
Authors: Oleynik A. F. , Fazylov V. Kh.
Published: April 2020

Introduction. Some patients with HIV infection receiving virologically effective antiretroviral therapy (ART) did not show any growth in CD4 cell count during treatment. Despite the long-term treatment of patients, immunodeficiency persisted. Methods. In the observational cohort retro/prospective study we investigated the effect of the duration of HIV infection before starting the antiretroviral therapy on the development of immunological treatment failure. Results. In a group of 140 HIV-infected patients a moderate inverse correlation was found between the duration of HIV infection and CD4 cell gain after 6 months, 1, 2 and 3 years of ART (r = -0.33, p < 0.01; r = -0.3, p < 0.01; r = -0.3, p < 0.01; r = -0.29, p < 0.01, respectively). In the case of ART starting at CD4 count of 200-350 cells/mcl statistically significant differences were revealed in the levels of relative CD4 count at 6 months, 1, 2 and 3 years of ART in sub-groups with durations of HIV infection prior to initiating therapy of 1-8 years and > 8 years (p = 0.035; p = 0.015; p = 0.05; p = 0.05, respectively). In patients who started ART with CD4 levels > 200 cells/mcl after 8 years of HIV infection, the risk of immunological treatment failure is 4 times higher as compared to patients with the same CD4 level, but lesser duration of HIV infection. Conclusions. The shorter the duration of HIV infection, the greater the increase in CD4 cell count. When starting ART at CD4 level of 200-350 cells/mcl, restoration of CD4 count is more intense in the group with lesser period of HIV infection. A negative effect of the >8-year infection duration before the start of ART on the development of the immunological treatment failure was observed in a subgroup with a starting level of CD4 > 200 cells /mcl.
METHODS FOR ASSESSMENT OF THE SPECIFIC ACTIVITY OF DRUGS FOR PREVENTION OF HEPATITIS B
Authors: Postnova E. L. , Shalunova N. V. , Sarkisyan K. A. , Movsesyants A. A.
Published: April 2020

The immunologic activity (specific activity) is one of the main indicators of quality of vaccines for prophylaxis of hepatitis B, along with their safety. Retrospective analysis of the use of laboratory methods for assessment of specific (immunogenic) activity of modern vaccines against hepatitis B using indicators was carried out: in vitro method based on evaluation of HBsAg content and in vivo method based on evaluation of immunogenic activity in mice. Both methods are standardized and described in normative documents on the vaccines against hepatitis B of domestic production registered in the Russian Federation. Indicators of specific (immunogenic) activity of vaccines against hepatitis B were used to investigate more than 170 vaccine series using the ELISA method in the period from 2013 to 2015. The obtained control results confirmed the expediency and efficiency of enzyme immunoassay for determination of HBsAg content, as well as permissibility of use of ready sets of the Murex HBsAg Version 3 test systems for testing vaccines against hepatitis B by the ELISA method. Analysis of the results of laboratory control of series of vaccines against hepatitis B using a biological method for immunogenicity evaluation based on ED50 analysis confirms persistently high immunogenic activity of the Russian commercial vaccines intended for prophylaxis of hepatitis B. The confirmed comparability of methods allows the number of in vivo tests to be further reduced in favor of the enzyme immunoassay authentically characterizing the produced drug.
SAFETY AND IMMUNOGENICITY OF COLD-ADAPTED RECOMBINANT INFLUENZA VECTOR EXPRESSING ESAT-6 AND AG85А ANTIGENS OF M. TUBERCULOSIS
Authors: Sergeeva M. V. , Pulkina A. A. , Vasiliev K. A. , Romanovskaya-Romanko E. A. , Komissarov A. B. , Kuchur O. A. , Egorov A. Yu. , Tsybalova L. M. , Stukova M. A.
Published: April 2020

Recombinant viral vectors represent one of the most promising platforms for creating a new generation of vaccines against tuberculosis. We constructed a vaccine candidate based on a cold-adapted influenza vector with a truncated NS1 protein containing an insert of tuberculosis ESAT-6 and Ag85A antigens. The recombinant virus possessed a cold-adapted and temperature-sensitive phenotype and was attenuated for mice when administered intranasally. Immunofluorescent staining and Western blot showed the expression of ESAT-6 protein in MDCK cells infected by recombinant virus. After intranasal administration to mice, the recombinant virus stimulated a specific anti-tuberculosis CD4 + Th1-type response with the formation of polyfunctional antigen-specific T cells.
GIANT VIRUSES: ORIGIN, SPREADING, TAXONOMICAL, STRUCTURAL-MORPHOLOGICAL AND MOLECULAR-BIOLOGICAL CHARACTERISTICS
Authors: Lvov D. K. , Sizikova T. E. , Lebedev V. N. , Borisevich S. V.
Published: April 2020

The brief review is devoted to description of the discovery of giant viruses belonging to the families of Mimiviridae and Marseilleviridae, as well as unassigned genera Pithoviruses, Pandoravirus, and Molliviruses. The review presents issues of their origin, evolution, and molecular-biological characteristics.
THE EXPERIENCE IN THE APPLICATION OF NIKAVIR IN THE SCHEMES OF PERINATAL CHEMOPROPHYLACTICS OF HIV INFECTION: EVALUATION OF THE IMMUNOLOGICAL AND VIRUSOLOGICAL EFFECTIVENESS
Authors: Ivanova E. S. , Vorobeva N. N. , Shelud’Ko V. S.
Published: April 2020

Objective. The goal of this work was to study the immunological and virological efficacy of the domestic antiretroviral drug nicavir (at the optimal dose, as proven by previous clinical studies) with lamivudine, in comparison with other drugs of the group of nucleoside reverse transcriptase inhibitors in combination with kaletra in perinatal HIV chemoprophylaxis regimens. Methods. 658 pregnant women aged 16-39 years and children born to them were examined. The first group (281 people) and the third group (66 people) received the nicavir (manufactured by AZT PHARMA KB LLC) with lamivudine in combination with calyx; the second (281 people) and the fourth (30 people) of the comparison group, stag and zidovudine, respectively, with lamivudine in combination with calyx. The effectiveness of CP was assessed from the increase in the number of CD4 lymphocytes, reduction of the viral load, and the number of children born without HIV DNA in the blood. Results. Against the backdrop of the therapy, the viral load below the detectable level and the positive dynamics of CD4 lymphocytes were registered in all examined women prior to childbirth. When applying the scheme of niacavir + lamivudine + kaletra, a more rapid decrease in the level of BH, most pronounced by week 4 of therapy, was found, as compared with the rate of decline of the same index in pregnant comparison groups. Conclusions. The obtained results allow us to consider ART with the inclusion of nicavir effective and recommend its priority use in perinatal prevention of mother-to-child transmission of HIV.
THE MECHANISM OF STIMFORTE ACTION ON HERPESVIRUS INFECTION
Authors: Maldov D. G. , Andronova V. L. , Grigorian S. S. , Isaeva E. I. , Balakina A. A. , Terentyev A. A. , Ilyichev A. V. , Galegov G. A.
Published: April 2020

Increased protease activity and a significant amount of granzyme B were observed in in organs of mice infected with acute herpes simplex virus HSV-1 with the introduction of Stimforte (100 or 250 µg/mouse). Thus, this drug activates killer cells, which play an extremely important role in the suppression of HSV-1 infection. Although the administration of Stimforte (100 μg/mouse) to intact mice results in the activation of IFN-β production and does not activate the production of IFN-λ, Stimforte administration to animals infected with HSV-1 reduces production of IFN-β in serum, brain and lungs, whereas the production of IFN-λ considerably increases as the result of administration of 100 μg/mouse of Stimforte.
ISOLATION AND PHYLOGENETIC ANALYSIS OF FELINE CALICIVIRUS IN SIBERIA
Authors: Glotova T. I. , Semenova O. V. , Nikonova A. A. , Glotov A. G. , Vyatkin Y. V. , Bondar A. A.
Published: April 2020

The results of the study of the distribution of calicivirus infection in a population of domestic cats of different breeds, contained individually or the group method, the virus isolation in the cell culture and a comparative phylogenetic analysis of their nucleotide sequences with published sequences of reference field and vaccine strains of Feline calicivirus (FCV) from other countries: USA, Germany, Japan, China and Korea are presented. Clinical signs of infection were found in 14.3% of the animals examined. After several passages in the primary kidney cells of the kitten embryo, seven cytopathogenic isolates FCV were isolated: 1 - from a cat with an acute infection, 5 - subclinical infection, 1 - systemic infection. They were adapted to continuous FK-81 cells in which they reached a maximum infectious activity of 10.0 ± 1.15 lg TCD 50 / cm3. Based on the sequence analysis of the open reading frame 2 region of the viral genome Eshli strain showed a close relationship with strain KM016908 from China with the identity of the nucleotide sequences between them of 81.0%. The results of the investigations showed that FCV isolates obtained from animals on the territory of Siberia are genetically different from strains included to imported vaccines used to prevent disease in Russian Federation and also among themselves. This causes a decrease in the effectiveness of preventive measures. In nurseries that do not have contacts and connections between themselves but located in the same geographic region FCV populations may have some genetic differences. A close relationship of some field isolates with strains from other countries geographically located so far from the Siberian region has been revealed. Studies on the molecular epizootology of caliciviruses are important in the development of test systems and the monitoring of the spread of strains in Russia.
СASES OF HUMAN CONVALESCENCE FROM RABIES AND LIFETIME DIAGNOSTICS OF LYSSAVIRUS ENCEPHALITIS
Authors: Metlin A. E. , Botvinkin A. D. , Elakov A. L. , Gruzdev K. N.
Published: April 2020

Notwithstanding the availability of effective vaccines, 40 - 60 thousand rabies cases in humans are reported every year. Almost always the disease is fatal because therapeutic treatment of lyssavirus encephalitis has not been developed. Since 1970 the number of reports on rare cases of convalescence including those using experimental treatment protocols has been gradually increasing 20 cases of convalescence, “partial” convalescence or long-term survival of humans (1970-2015) were selected as they were complaint with laboratory criteria of active lyssavirus infection. Children and teenagers were predominant in the analyzed group (85%). The cases were irregularly spread between the continents: Asia - 6 cases, North America - 6 cases, Africa - 2 cases and Europe - 1 case. India and the USA were on the top of the list of countries by the number of described cases. More than 60% humans were infected from dogs, three cases got infection from bats and 2 cases were allegedly associated with an unknown lyssavirus and an unidentified infection source. 70% cases were vaccinated and 10% cases were treated with gamma globulin before the disease onset. Serological tests for detection of antibodies to lyssaviruses in cerebrospinal fluid of infected humans were typically used for diagnostic laboratory verification. Less than 30% IFA and PCR positives were obtained. Lyssaviruses were never detected. Only 4 convalescent patients were treated using experimental protocols. 80% cases demonstrated severe neurological consequences, four (may be more) patients died afterwards within the period from two months to four years. Different perspectives on prospects of Milwaukee protocol use and other therapeutic techniques are given.
VITAMIN D AND LABORATORY INDICATORS OF CARDIOVASCULAR RISK IN THE ELDERLY
Authors: Ivanov V. I. , Dorofeykov V. V. , Kaystrya I. V. , Emanuel V. L.
Published: April 2020

The aim of this work was to study the availability of vitamin D in the population of free living elderly people in St. Petersburg and its relationship with laboratory indicators of the risk of cardiovascular complications. In winter were surveyed 209 volunteers who did not take vitamin D during the previous 6 months, with 152 women and 57 men aged 71 to 91 years. In all the examined patients the concentration of D(OH) in serum was below 30 ng/ml (analyzer and reagents «Architect i1000SR, Abbott»). No significant mutual effects were found between level 25(OH)D and lipid spectrum, hemoglobin A1C, testosterone, ultra-sensitive C-reactive protein. The close relationship between vitamin D(OH) concentration and brain natriuretic peptide (BNP) levels was characterized by rs=0.187 (p=0.007). In older people with severe vitamin deficiency (less than 10 ng/ml), the risk of elevated BNP levels was 2.6 times higher than in those with reduced vitamin levels (20-30 ng/ml).
Special Considerations in Pain Management in Orthopaedic Subspecialties
Authors: Schoenfeld Andrew J.
Published: April 2020

➢ There is a general consensus among the orthopaedic surgical community that the opioid epidemic has reached a crisis state within the United States.

➢ The number of articles published with regard to prescription opioid use and pain management strategies within orthopaedic subspecialties has increased over the last 5 years and adequately describes the scope of the problem as well as risk factors for sustained use.

➢ In this article, we elaborate on challenges highlighted during the JBJS Pain Management Research Symposium and discuss potential resolutions and next steps that may be capable of advancing research in the field. These include the need to focus on strategies with better pain management outcomes rather than just reversing opioid overprescribing, describing the value of specific pain management strategies, understanding the benefits of weaning chronic opioids prior to surgical intervention, and ensuring that the full range of variation in clinical, demographic, and prescriber-based characteristics influencing sustained prescription opioid use, successful pain management, and other outcomes is represented in the data sets that are used.
Social and Mental Health Affect Comfort After Surgery or Injury
Authors: Ring David
Published: April 2020

➢ There is wide variation in pain intensity for a given pathophysiology.

➢ Much of the variation in pain intensity is accounted for by mental and social health opportunities.

➢ Comfort is associated with a healthy mood and a return to normal activities (greater self-efficacy).

➢ Most people get comfortable after injury or surgery using little or no opioid medication.

➢ Use of opioids in high doses or beyond the established early healing of the body may represent misdiagnosis and mistreatment of mental and social health opportunities.
Methodological Challenges in Conducting Large-Scale Real-World Data Analyses on Opioid Use in Musculoskeletal Disorders
Authors: Kim Seoyoung C. , Bateman Brian T.
Published: April 2020

➢ As the United States is currently experiencing an epidemic of opioid misuse, overdose deaths, and addiction, the number of published articles on the patterns of opioid use and the safety of opioids has dramatically increased over the past decade.

➢ Most published reports have described observational studies based on large-scale real-world data (RWD) collected in real-world medical settings (i.e., not in clinical trials). Administrative claims databases, electronic medical records, and patient registries are commonly used RWD sources.

➢ Understanding the strengths and limitations of different types of data sources and applying appropriate study design and methods for each study question are essential for ensuring the validity of observational studies.

➢ Studies analyzing the association between opioid exposure following surgery and persistent use are important for understanding the risks and benefits of opioid use in this context. No widely accepted definition of the term persistent use exists, and studies have yielded highly divergent estimates of the frequency of persistent use depending on the definition employed. Careful attention to methods is needed when conducting these studies, and understanding their limitations is important when interpreting the results.

➢ The present report discusses general methodological challenges for large-scale RWD analyses on opioid use among patients with musculoskeletal disorders.
Dual Versus Single-Plate Fixation of Midshaft Clavicular Fractures
Authors: Allis J. Benjamin , Cheung Edward C. , Farrell Eric D. , Johnson Eric E. , Jeffcoat Devon M.
Published: April 2020

Background:

Implant-related symptoms are the most common reason for reoperation after open reduction and internal fixation (ORIF) of midshaft clavicular fractures. Dual mini-fragment plate fixation is a relatively new solution that may decrease implant prominence while maintaining fixation strength and function. There are minimal published data comparing reoperation rates and clinical outcomes between single, superior-plate constructs and dual mini-fragment plate constructs in the fixation of midshaft clavicular fractures. We hypothesized that reducing plate size with the use of dual mini-fragment plating compared with standard, 3.5-mm, superior plating would minimize implant symptoms and the corresponding need for reoperation while still providing sufficient fixation to allow fracture-healing and return to function.

Methods:

We retrospectively reviewed the cases of 44 consecutive patients who underwent ORIF of displaced midshaft clavicular fractures utilizing either a single, 3.5-mm, superior plate construct (21 patients) or a dual, 2.7-mm and 2.4-mm, plate construct (23 patients). Outcomes at a minimum of 2 years were assessed. Primary outcome measures included reoperation for any reason and the American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form, patient self-report section.

Results:

There was a 100% union rate in both groups. None (0%) of the 23 patients who received the dual (2.7-mm and 2.4-mm) plate construct and 6 (29%) of the 21 patients who received the single (3.5-mm) plate construct underwent reoperation for implant-related symptoms. Using a Fisher exact test, the rate of reoperation was compared between the groups, and the difference was found to be significant (p = 0.008). Using an unpaired t test, the difference in mean ASES scores was not significant (p = 0.138) between the dual-plate group (98 of 100) and the single superior plate group (96 of 100) with retained implants.

Conclusions:

In our comparative retrospective series, dual fixation utilizing a 2.7-mm superior plate and a 2.4-mm anterior plate for the treatment of displaced midshaft clavicular fractures was associated with a significantly lower rate of reoperation when compared with single, 3.5-mm, superior plate fixation.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Selective Laser Trabeculoplasty Versus Brimonidine Tartrate 0.2%/Timolol Maleate 0.5% As Adjunct Therapy in Primary Open Angle Glaucoma: A Randomized Prospective Trial
Authors: McWherter Ian , Lanham Meredith , Peplinski Lee , Zagorianos Nikolaos , Steele Andrew , Slayden Keith , Sidle Meg Wright , McKay Fraser
Published: April 2020

Purpose: To compare the intraocular pressure lowering efficacy of selective laser trabeculoplasty to brimonidine tartrate 0.2%/timolol maleate 0.5% in patients with uncontrolled primary open-angle glaucoma on a prostaglandin analog alone. A secondary outcome was to evaluate the complication rates of selective laser trabeculoplasty.Patients and Methods: Twenty-three patients were randomized to two treatment groups within this prospective, observer-masked single site, all optometrist, pilot study. Group 1 (N=12) received 360 degrees of selective laser trabeculoplasty as additional treatment while Group 2 (N=11) was started on FCBT. Outcomes of both groups were measured at eight weeks.Results: Both treatment regimens were found to be statistically significant in lowering IOP when used as adjunct therapy. The average IOP reduction for Group 1 and Group 2 was 28.4% (SD = .17) and 28.2% (SD = .12) respectively. The incidence of an intraocular pressure spike following SLT in this patient population was found to be 8.3%. No major complications were observed in this study.Conclusion: Selective laser trabeculoplasty and brimonidine tartrate 0.2%/timolol maleate 0.5% were shown to be equivalent in lowering intraocular pressure in uncontrolled primary open angle glaucoma patients when used as adjunct therapy for patients on a prostaglandin analog. Additionally, this is the first prospective study of optometrists performing selective laser trabeculoplasty. Although this study had a small sample size, the results appeared to show that efficacy and complication rates were comparable to previously published data; however, these results need to be confirmed with a larger multi-centered trial.Trial Registration: ISRCTN Study ID ISRCTN30070325, retrospectively registered 12/14/2018. http://www.isrctn.com/ISRCTN30070325.