bluuebunny/crossref_metadata_2025 huggingface dataset:
PEA15 loss of function and defective cerebral development in the domestic cat
Authors: Graff Emily C. , Cochran J. Nicholas , Kaelin Christopher B. , Day Kenneth , Gray-Edwards Heather L. , Watanabe Rie , Koehler Jey W. , Falgoust Rebecca A. , Prokop Jeremy W. , Myers Richard M. , Cox Nancy R. , Barsh Gregory S. , Martin Douglas R. ,   99 Lives Consortium
Published: December 2020

Cerebral cortical size and organization are critical features of neurodevelopment and human evolution, for which genetic investigation in model organisms can provide insight into developmental mechanisms and the causes of cerebral malformations. However, some abnormalities in cerebral cortical proliferation and folding are challenging to study in laboratory mice due to the absence of gyri and sulci in rodents. We report an autosomal recessive allele in domestic cats associated with impaired cerebral cortical expansion and folding, giving rise to a smooth, lissencephalic brain, and that appears to be caused by homozygosity for a frameshift inPEA15(phosphoprotein expressed in astrocytes-15). Notably, previous studies of aPea15targeted mutation in mice did not reveal structural brain abnormalities. Affected cats, however, present with a non-progressive hypermetric gait and tremors, develop dissociative behavioral defects and aggression with age, and exhibit profound malformation of the cerebrum, with a 45% average decrease in overall brain weight, and reduction or absence of the ectosylvian, sylvian and anterior cingulate gyrus. Histologically, the cerebral cortical layers are disorganized, there is substantial loss of white matter in tracts such as the corona radiata and internal capsule, but the cerebellum is relatively spared. RNA-seq and immunohistochemical analysis reveal astrocytosis. Fibroblasts cultured from affected cats exhibit increased TNFα-mediated apoptosis, and increased FGFb-induced proliferation, consistent with previous studies implicating PEA15 as an intracellular adapter protein, and suggesting an underlying pathophysiology in which increased death of neurons accompanied by increased proliferation of astrocytes gives rise to abnormal organization of neuronal layers and loss of white matter. Taken together, our work points to a new role forPEA15in development of a complex cerebral cortex that is only apparent in gyrencephalic species.
Using host traits to predict reservoir host species of rabies virus
Authors: Worsley-Tonks Katherine E. L. , Escobar Luis E. , Biek Roman , Castaneda-Guzman Mariana , Craft Meggan E. , Streicker Daniel G. , White Lauren A. , Fountain-Jones Nicholas M.
Published: December 2020

Wildlife are important reservoirs for many pathogens, yet the role that different species play in pathogen maintenance frequently remains unknown. This is the case for rabies, a viral disease of mammals. While Carnivora (carnivores) and Chiroptera (bats) are the canonical mammalian orders known to be responsible for the maintenance and onward transmission of rabies Lyssavirus (RABV), the role of most species within these orders remains unknown and is continually changing as a result of contemporary host shifting. We combined a trait-based analytical approach with gradient boosting machine learning models to identify physiological and ecological host features associated with being a reservoir for RABV. We then used a cooperative game theory approach to determine species-specific traits associated with known RABV reservoirs. Being a carnivore reservoir for RABV was associated with phylogenetic similarity to known RABV reservoirs, along with other traits such as having larger litters and earlier sexual maturity. For bats, location in the Americas and geographic range were the most important predictors of RABV reservoir status, along with having a large litter. Our models identified 44 carnivore and 34 bat species that are currently not recognized as RABV reservoirs, but that have trait profiles suggesting their capacity to be or become reservoirs. Further, our findings suggest that potential reservoir species among bats and carnivores occur both within and outside of areas with current RABV circulation. These results show the ability of a trait-based approach to detect potential reservoirs of infection and could inform rabies control programs and surveillance efforts by identifying the types of species and traits that facilitate RABV maintenance and transmission.
The importance of making testable predictions: A cautionary tale
Authors: Choi Emma S. , Saberski Erik , Lorimer Tom , Smith Cameron , Kandage-don Unduwap , Burton Ronald S. , Sugihara George
Published: December 2020

We found a startling correlation (Pearson ρ > 0.97) between a single event in daily sea surface temperatures each spring, and peak fish egg abundance measurements the following summer, in 7 years of approximately weekly fish egg abundance data collected at Scripps Pier in La Jolla California. Even more surprising was that this event-based result persisted despite the large and variable number of fish species involved (up to 46), and the large and variable time interval between trigger and response (up to ~3 months). To mitigate potential over-fitting, we made an out-of-sample prediction beyond the publication process for the peak summer egg abundance observed at Scripps Pier in 2020 (available on bioRxiv). During peer-review, the prediction failed, and while it would be tempting to explain this away as a result of the record-breaking toxic algal bloom that occurred during the spring (9x higher concentration of dinoflagellates than ever previously recorded), a re-examination of our methodology revealed a potential source of over-fitting that had not been evaluated for robustness. This cautionary tale highlights the importance of testable true out-of-sample predictions of future values that cannot (even accidentally) be used in model fitting, and that can therefore catch model assumptions that may otherwise escape notice. We believe that this example can benefit the current push towards ecology as a predictive science and support the notion that predictions should live and die in the public domain, along with the models that made them.
2-oxoglutarate-dependent dioxygenases: A renaissance in attention for ascorbic acid in plants
Authors: Mahmood Asaad M. , Dunwell Jim M.
Published: December 2020

L-Ascorbic acid (ascorbate, Vitamin C) is an essential human micronutrient that is predominantly obtained from plants. It is known to work as the major antioxidant in plants, and it underpins several environmentally induced stresses due to its use as a co-factor by certain 2-oxoglutarate-dependent (2-OG) dioxygenases [2(OG)-dioxygenases]. It is important to understand the role of 2(OG)-dioxygenases in the biosynthesis of ascorbate. The present study examined contents of ascorbate and protein-protein interaction in nine T-DNA mutants of Arabidopsis containing an insert in their respective (2-OG) dioxygenase genes (At1g20270, At1g68080, At2g17720, At3g06290, At3g28490, At4g35810, At4g35820, At5g18900, At5g66060). In this study, the amount of ascorbate in five of the mutants was shown to be almost two-fold or more than two-fold higher than in the wild type. This result may be a consequence of the insertion of the T-DNA. The prediction of possible protein interactions between 2(OG)-dioxygenases and relevant ascorbate-function players may indicate the oxidative effects of certain dioxygenase proteins in plants. It is expected that certain dioxygenases are actively involved in the metabolic and biosynthetic pathways of ascorbate. This involvement may be of importance to increase ascorbate amounts in plants for human nutrition, and to protect plant species against stress conditions.
Assessing clinical quality performance and staffing capacity differences between urban and rural Health Resources and Services Administration-funded health centers in the United States: A cross sectional study
Authors: Pourat Nadereh , Chen Xiao , Lu Connie , Zhou Weihao , Hoang Hank , Sripipatana Alek
Published: December 2020

Background

In the United States, there are nearly 1,400 Health Resources and Services Administration-funded health centers (HCs) serving low-income and underserved populations and more than 600 of these HCs are located in rural areas. Disparities in quality of medical care in urban vs. rural areas exist but data on such differences between urban and rural HCs is limited in the literature. We examined whether urban and rural HCs differed in their performance on clinical quality measures before and after controlling for patient, organizational, and contextual characteristics.

Methods and findings

We used the 2017 Uniform Data System to examine performance on clinical quality measures between urban and rural HCs (n = 1,373). We used generalized linear regression models with the logit link function and binomial distribution, controlling for confounding factors. After adjusting for potential confounders, we found on par performance between urban and rural HCs in all but one clinical quality measure. Rural HCs had lower rates of linking patients newly diagnosed with HIV to care (74% [95% CI: 69%, 80%] vs. 83% [95% CI: 80%, 86%]). We identified control variables that systematically accounted for eliminating urban vs. rural differences in performance on clinical quality measures. We also found that both urban and rural HCs had some clinical quality performance measures that were lower than available national benchmarks. Main limitations included potential discrepancy of urban or rural designation across all HC sites within a HC organization.

Conclusions

Findings highlight HCs’ contributions in addressing rural disparities in quality of care and identify opportunities for improvement. Performance in both rural and urban HCs may be improved by supporting programs that increase the availability of providers, training, and provision of technical resources.
Contrasting genetic diversity and structure among Malagasy Ralstonia pseudosolanacearum phylotype I populations inferred from an optimized Multilocus Variable Number of Tandem Repeat Analysis scheme
Authors: Rasoamanana Hasina , Ravelomanantsoa Santatra , Yahiaoui Noura , Dianzinga Niry , Rébert Emeline , Gauche Miharisoa-Mirana , Pecrix Yann , Costet Laurent , Rieux Adrien , Prior Philippe , Robène Isabelle , Cellier Gilles , Guérin Fabien , Poussier Stéphane
Published: December 2020

TheRalstonia solanacearumspecies complex (RSSC), composed of three species and four phylotypes, are globally distributed soil-borne bacteria with a very broad host range. In 2009, a devastating potato bacterial wilt outbreak was declared in the central highlands of Madagascar, which reduced the production of vegetable crops including potato, eggplant, tomato and pepper. A molecular epidemiology study of Malagasy RSSC strains carried out between 2013 and 2017 identifiedR.pseudosolanacearum(phylotypes I and III) andR.solanacearum(phylotype II). A previously published population biology analysis of phylotypes II and III using two MultiLocus Variable Number of Tandem Repeats Analysis (MLVA) schemes revealed an emergent epidemic phylotype II (sequevar 1) group and endemic phylotype III isolates. We developed an optimized MLVA scheme (RS1-MLVA14) to characterize phylotype I strains in Madagascar to understand their genetic diversity and structure. The collection included isolates from 16 fields of different Solanaceae species sampled in Analamanga and Itasy regions (highlands) in 2013 (123 strains) and in Atsinanana region (lowlands) in 2006 (25 strains). Thirty-one haplotypes were identified, two of them being particularly prevalent: MT007 (30.14%) and MT004 (16.44%) (sequevar 18). Genetic diversity analysis revealed a significant contrasting level of diversity according to elevation and sampling region. More diverse at low altitude than at high altitude, the Malagasy phylotype I isolates were structured in two clusters, probably resulting from different historical introductions. Interestingly, the most prevalent Malagasy phylotype I isolates were genetically distant from regional and worldwide isolates. In this work, we demonstrated that the RS1-MLVA14 scheme can resolve differences from regional to field scales and is thus suited for deciphering the epidemiology of phylotype I populations.
Differential plasma exosomal long non-coding RNAs expression profiles and their emerging role in E-cigarette users, cigarette, waterpipe, and dual smokers
Authors: Kaur Gagandeep , Singh Kameshwar , Maremanda Krishna P. , Li Dongmei , Chand Hitendra S. , Rahman Irfan
Published: December 2020

Long non-coding RNAs (lncRNAs) are the varied set of transcripts that play a critical role in biological processes like gene regulation, transcription, post-transcriptional modification, and chromatin remodeling. Recent studies have reported the presence of lncRNAs in the exosomes that are involved in regulating cell-to-cell communication in lung pathologies including lung cancer, chronic obstructive pulmonary disease (COPD), asthma, and idiopathic pulmonary fibrosis (IPF). In this study, we compared the lncRNA profiles in the plasma-derived exosomes amongst non-smokers (NS), cigarette smokers (CS), E-cig users (E-cig), waterpipe smokers (WP) and dual smokers (CSWP) using GeneChip™ WT Pico kit for transcriptional profiling. We found alterations in a distinct set of lncRNAs among subjects exposed to E-cig vapor, cigarette smoke, waterpipe smoke and dual smoke with some overlaps. Gene enrichment analyses of the differentially expressed lncRNAs demonstrated enrichment in the lncRNAs involved in crucial biological processes including steroid metabolism, cell differentiation and proliferation. Thus, the characterized lncRNA profiles of the plasma-derived exosomes from smokers, vapers, waterpipe users, and dual smokers will help identify the biomarkers relevant to chronic lung diseases such as COPD, asthma or IPF.
A new pharmacodynamic approach to study antibiotic combinations against enterococci in vivo: Application to ampicillin plus ceftriaxone
Authors: Jimenez-Toro Ivone , Rodriguez Carlos A. , Zuluaga Andres F. , Otalvaro Julian D. , Vesga Omar
Published: December 2020

The combination of ampicillin (AMP) and ceftriaxone (CRO) is considered synergistic againstEnterococcus faecalisbased onin vitrotests and the rabbit endocarditis model, however,in vitroassays are limited by the use of fixed antibiotic concentrations and the rabbit model by poor bacterial growth, high variability, and the use of point dose-effect estimations, that may lead to inaccurate assessment of antibiotic combinations and hinder optimal translation. Here, we tested AMP+CRO against two strains ofE.faecalisand one ofE.faeciumin an optimized mouse thigh infection model that yields high bacterial growth and allows to define the complete dose-response relationship. By fitting Hill’s sigmoid model and estimating the parameters maximal effect (Emax) and effective dose 50 (ED50), the following interactions were defined: synergism (Emaxincrease ≥2 log10CFU/g), antagonism (Emaxreduction ≥1 log10CFU/g) and potentiation (ED50reduction ≥50% without changes in Emax). AMP monotherapy was effective against the three strains, yielding valid dose-response curves in terms of dose and the indexfT>MIC. CRO monotherapy showed no effect. The combination AMP+CRO againstE.faecalisled to potentiation (59–81% ED50reduction) and not synergism (no changes in Emax). AgainstE.faecium, the combination was indifferent. The optimized mouse infection model allowed to obtain the complete dose-response curve of AMP+CRO and to define its interaction based on pharmacodynamic parameter changes. Integrating these results with the pharmacokinetics will allow to derive the PK/PD index bound to the activity of the combination, essential for proper translation to the clinic.
Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer
Authors: Cunningham Jessica , Thuijsman Frank , Peeters Ralf , Viossat Yannick , Brown Joel , Gatenby Robert , Staňková Kateřina
Published: December 2020

In the absence of curative therapies, treatment of metastatic castrate-resistant prostate cancer (mCRPC) using currently available drugs can be improved by integrating evolutionary principles that govern proliferation of resistant subpopulations into current treatment protocols. Here we develop what is coined as an ‘evolutionary stable therapy’, within the context of the mathematical model that has been used to inform the first adaptive therapy clinical trial of mCRPC. The objective of this therapy is to maintain a stable polymorphic tumor heterogeneity of sensitive and resistant cells to therapy in order to prolong treatment efficacy and progression free survival. Optimal control analysis shows that an increasing dose titration protocol, a very common clinical dosing process, can achieve tumor stabilization for a wide range of potential initial tumor compositions and volumes. Furthermore, larger tumor volumes may counter intuitively be more likely to be stabilized if sensitive cells dominate the tumor composition at time of initial treatment, suggesting a delay of initial treatment could prove beneficial. While it remains uncertain if metastatic disease in humans has the properties that allow it to be truly stabilized, the benefits of a dose titration protocol warrant additional pre-clinical and clinical investigations.
Evaluation of benzocaine-based anesthetic gel in anuran skins extracts: A case study using the frog Lithodytes lineatus (Anura: Leptodactylidae)
Authors: Barros André de Lima , Lima Albertina Pimentel , Fachin-Espinar Maria Teresa , Nunez Cecilia Veronica
Published: December 2020

Extracts made from the skin of dead Lithodytes lineatus frog individuals with the application of the benzocaine-based anesthetic gel, introduced into the oral cavity, were analyzed by 1H Nuclear Magnetic Resonance to investigate whether the application of this product (oral) can make studies that use extracts from the skins of these animals unfeasible. For comparison, we used skins of another species of anuran following the same death protocol. No trace of the benzocaine substance was found in the 1H-NMR spectra of the skin extracts from any of the tested anuran species. Still, using the hierarchical clustering model, it was possible to observe the formation of well-defined groups between the skin extracts of anurans and the anesthetic used to kill these animals. Our results suggest that the lethal dose of benzocaine in gel used inside the mouth of frogs may have no influence on potential results regarding the chemical composition or even bioassays using extracts made from the skin of these animals killed under this protocol since there was no detection of this substance for the analyzed samples.
The serogroup B meningococcal outer membrane vesicle-based vaccine 4CMenB induces cross-species protection against Neisseria gonorrhoeae
Authors: Leduc Isabelle , Connolly Kristie L. , Begum Afrin , Underwood Knashka , Darnell Stephen , Shafer William M. , Balthazar Jacqueline T. , Macintyre Andrew N. , Sempowski Gregory D. , Duncan Joseph A. , Little Marguerite B. , Rahman Nazia , Garges Eric C. , Jerse Ann E.
Published: December 2020

There is a pressing need for a gonorrhea vaccine due to the high disease burden associated with gonococcal infections globally and the rapid evolution of antibiotic resistance inNeisseria gonorrhoeae(Ng). Current gonorrhea vaccine research is in the stages of antigen discovery and the identification of protective immune responses, and no vaccine has been tested in clinical trials in over 30 years. Recently, however, it was reported in a retrospective case-control study that vaccination of humans with a serogroup BNeisseria meningitidis(Nm) outer membrane vesicle (OMV) vaccine (MeNZB) was associated with reduced rates of gonorrhea. Here we directly tested the hypothesis thatNmOMVs induce cross-protection against gonorrhea in a well-characterized female mouse model ofNggenital tract infection. We found that immunization with the licensedNmOMV-based vaccine 4CMenB (Bexsero) significantly accelerated clearance and reduced theNgbacterial burden compared to administration of alum or PBS. Serum IgG and vaginal IgA and IgG that cross-reacted withNgOMVs were induced by 4CMenB vaccination by either the subcutaneous or intraperitoneal routes. Antibodies from vaccinated mice recognized severalNgsurface proteins, including PilQ, BamA, MtrE, NHBA (known to be recognized by humans), PorB, and Opa. Immune sera from both mice and humans recognizedNgPilQ and several proteins of similar apparent molecular weight, but MtrE was only recognized by mouse serum. Pooled sera from 4CMenB-immunized mice showed a 4-fold increase in serum bactericidal50titers against the challenge strain; in contrast, no significant difference in bactericidal activity was detected when sera from 4CMenB-immunized and unimmunized subjects were compared. Our findings directly support epidemiological evidence thatNmOMVs confer cross-species protection against gonorrhea, and implicate severalNgsurface antigens as potentially protective targets. Additionally, this study further defines the usefulness of murine infection model as a relevant experimental system for gonorrhea vaccine development.
A Rare Presentation of Omental Lymphangioma Masquerading as Malignancy in an Adult Patient
Authors: Alameri Aws , Museedi Abdulrahman , Nashawi Mouhamed , Ghalli Abdullah , Nathanson Robert
Published: December 2020

Abdominal lymphangiomas are benign vascular neoplasms of the lymphatic vessels. Most are believed to be congenital, and they rarely present in the abdomen in adults. Omental lymphangiomas, in particular, are especially rare and can masquerade as malignancy, which requires further invasive workup. We report the case of an otherwise healthy man with abdominal discomfort, ascites, and a presentation initially concerning for malignancy. However, imaging and pathologic analyses later elucidated the lesion as an omental lymphangioma requiring different management. Treatment options are either resection or sclerotherapy, and the prognosis is generally excellent.
Persistent Encephalopathy in a Noncirrhotic Patient: Do not Shun This Shunt
Authors: Kassamali Farah , Hu Steve , Roytman Marina
Published: December 2020

A portosystemic venous shunt is the formation of an abnormal connection between the portal vein and a systemic vein, allowing blood to bypass the liver. Portosystemic shunts are usually believed to be due to portal hypertension in the setting of underlying hepatic disease. We report a case of large, spontaneous intrahepatic portosystemic shunt in a noncirrhotic patient contributing to recurrent hepatic encephalopathy, also known as type B encephalopathy. Management of portosystemic encephalopathy involves occlusion of the shunt by endovascular management.
Use of Infrared Thermography for Identifying Physiological and Hematological Conditions of Young Sapera Dairy Goats
Authors: Pamungkas Fitra Aji , Purwanto Bagus Priyo , Manalu Wasmen , Yani Ahmad , Sianturi Riasari Gail
Published: December 2020

Infrared thermography (IRT) is an alternative solution that can be applied to replace invasive methods currently used in the monitoring of goats' physiological and hematological parameters. This study was done to compare and correlate the physiological and hematological conditions of young Sapera dairy goats and their correlations with results obtained by IRT. Four young Sapera dairy goats (weight of 26-28 kg) were kept in the individual rearing cage. Skin surface temperature (TS), rectal temperature (TR), body temperature (TB), heartbeat (HR), respiration rate (RR), and IRT at eyes, mouth, nose, legs, left body, right body, vagina, and vulva were monitored from 6 a.m. to 6 p.m. in 2 h intervals. Blood samplings were done at the beginning and the end of the obsevation time. Results showed that IRTs at several body parts were positively correlated with physiological parameters, except for heartbeat. Negatively correlation was observed in hematological parameters. The highest correlation (r = +0.85) was observed in the correlation between the results of the left rear leg IRT on TB. It was concluded that IRT can be applied to examine goats’ physiological conditions especially body temperature.
Small Ruminant Community Breeding Program in Indonesia
Authors: Tiesnamurti Bess , Sinulingga S E , Gatenby R M
Published: December 2020

This paper outlines the principles of community breeding programs, reviews similar programs that have been conducted in Indonesia, as well as proposing improvements. Community breeding programs (CBP) are a method for genetic improvement of livestock, with voluntary participation of farmers, using animals belonging to the farmers, by defining breeding objectives and selection criteria or traits, selecting the best males of the group, performance testing and distributing males to the farmers. Farmers have the ownership of the program and contribute to the sustainability of the program, marketability of the products according the needs of the farmers, as well as strengthening farmers institutions. There are breeding scehemes of one tier, two tier and three tier that can be implemented to achieve the goals of genetic improvement. Several CBP has been carried out scatteredly, however improvements have to be made such as by long term financial support, strong commitment from breeders, mentoring by academias, data management and analysis as well as economic assessment. Therefore, a more masive and sustainable CBP should be conducted to improve the genetic quality of  sheep and goat in Indonesia.
Coccidiosis as A Predisposition Factor for Necrotic Enteritis in Poultry and Their Prevention
Authors: Wiedosari Ening , Sani Y
Published: December 2020

Coccidiosis and necrotic enteritis are both affecting the digestive tract of chicken and both are major enteric disease that mainly affect poultry. Among the enteric diseases, necrotic enteritis is a major problem. Coccidiosis is caused by the protozoan of Eimeria sp, and is commonly found as a predisposition factor for necrotic enteritis caused by Clostridum perfringens. Both diseases are commonly shown similar pathological change namely necrosis of epthelial cells in the intestinal mucosa. The diseases have great economic impact in poultry productions, due to the increased mortality, decreased performance and medication costs. Control of these diseases are commonly treated with antibiotics and ionophores. However, an intensive use of these drugs in feed may cause the emergence of drug-resistance against some strains of Eimeria sp.and Cl. Perfringens and an increased chance of contamination in animal products for human consumption. The paper is discussing the occurrence of necrotic enteritis especially due to the coccidian as a major predisposition factor and the development of alternative control strategies for avian coccidiosis and necrotic enteritis, by modulating intestinal health.
Chlorella vulgaris and Spirulina platensis: Their Nutrient Contents and Bioactive Compounds for Improving Poultry Productivity
Authors: Sugiharto Sugiharto
Published: December 2020

Poultry industry are facing many challenges and osbtacles especially on the supply of feed ingredients, medicines, feed supplements and additives. The high price of protein source-feed ingredients has encouraged nutritionists to explore and utilize alternative protein source-feed ingredients for poultry. This review provides an overview of their nutritional and bioactive contents and the use of microalgae, Chlorella vulgaris and Spirulina platensis in poultry feed based on recent literature studies and their potential development and utilization in Indonesia. The microalgae Chlorella vulgaris dan Spirulina platensis have very high protein content that are potential as a protein source in poultry rations. In addition, Chlorella vulgaris and Spirulina platensis also contain several bioactive compounds that can be used as alternatives to antibiotics growth promoter and synthetic antioxidants for poultry. Indonesia has a great potential for the production of Chlorella vulgaris and Spirulina platensis, however massive cultivation and economies of scale have not yet been carried out. Such conditions make Chlorella vulgaris and Spirulina platensis less profitable as protein sources, but more likely as growth-promoting additives or antioxidants for poultry in Indonesia.
Etiopathogenetic parallels and unresolved issues of pathogenesis of comorbidity COPD and metabolic syndrome (review)
Authors: Voronkova Olga V. , Saprina Tatyana V. , Bukreeva Ekaterina B. , Zima Anastasia P.
Published: December 2020

The review analyzes the etiological and pathogenetic factors (including immunopathogenesis factors) of chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MS), cites data on clinical and pathogenetic characteristics of combined pathology, emphasizes the commonality of risk factors and individual links of pathogenesis in syntropy.

The clinical and pathogenetic features of the comorbidity of COPD and MS are closely related to the severity of chronic “metabolic” inflammation induced by elements of adipose tissue. Functional and biochemical disorders recorded in metabolic syndrome (insulin resistance, hyperglycemia, dyslipidemia) are considered as factors contributing to dysfunction of the components of innate and adaptive immunity.

The review formulates a number of unresolved issues of the pathogenesis of comorbid pathology, the study of which is necessary to search for the mutual aggravating effect of COPD and MS mechanisms. In view of the clinical and laboratory metabolic syndrome equivalents variety, the authors emphasize the relevance of future studies of the pathogenetic features of chronic inflammation associated with the comorbidity of the main components of metabolic syndrome and COPD, to develop effective methods of prevention and pathogenetic therapy of comorbid pathology.
Remote monitoring and treatment of children and adolescents with type 1 diabetes
Authors: Laptev Dmitry N. , Emelyanov Andrey O. , Samoilova Yulia G. , Khramova Elena B. , Petriaikina Elena E. , Rybkina Irina G. , Filimonova Alla Yu. , Peterkova Valentina A.
Published: December 2020

RATIONALE: Continuous subcutaneous insulin infusion (CSII) is an effective method for optimizing glycemic control in children with type 1 diabetes mellitus (DM1). However, the use of CSII does not always result in adequate glycemic control. Telehealth can be applied as one of the methods to improve the effectiveness of treatment.

AIMS: To evaluate the use of remote medical support of children and adolescents with DM1 and its influence on glycemic control, quality of life, and incidence of acute complications of DM1.

MATERIALS AND METHODS: We conducted a 24-week multi-institutional prospective open-label controlled clinical trial. 180 children and adolescents were included in this study and divided into the following categories: 1) age 8–18 years; 2) DM1 at least 1 year; 3) pump insulin therapy Medtronic Paradigm (Medtronic MiniMed, USA) at least 6 months; 4) self-monitoring of glycemia at least 4 times a day and replacement of the insulin pump infusion system at least once every 3 days; 5) inadequate glycemic control of DM1: the level of glycated hemoglobin (HbA1c) 7.5% or higher. Patients were assigned to a remote consultation group (RC; n=100) or a traditional control group (TC; n=80). All patients were trained on the basic principles of DM1 and CSII, and we measured initial HbA1c, then after 12 and 24 weeks, also registered and analyzed glycemic indicators and daily doses of insulin, evaluated and corrected the treatment. Patients or their parents in the RC group sent pump data via the Internet to the pump insulin therapy center at least once every 2 weeks at home and received treatment recommendations in response.

RESULTS: The total number of patients included in the study in all institutions was 180 children at 8–18 years. Patients in both groups did not differ in age, gender, duration of DM1 and CSII, and HbA1c level. The total amount of remote consultations for all institutions was 949. The decrease in the level of HbA1c by the end of the study against the initial one was statistically significantly greater in the RC group: 1.17% compared to 0.59% in the TC group (p<0.05). The proportion of patients who reached the target level of HbA1c (<7.5%) was significantly higher in the RC group (32%) compared to the TC group (12.5%, p<0.05). During the study, the incidence of DKA and severe hypoglycemia in the RC group was statistically significantly lower.

CONCLUSIONS: Remote monitoring in children with DM1 resulted in significant improvements in glycemic control (HbA1c, glycemic variability, and hypoglycemic frequency). The accumulation of evidence on the effectiveness and safety of telehealth in DM should contribute to implementing this approach in practical health care.
The role of HLA genes: from autoimmune diseases to COVID-19
Authors: Troshina Ekaterina A. , Yukina Marina Yu. , Nuralieva Nurana F. , Mokrysheva Natalia G.
Published: December 2020

Genes of HLA system (Human Leukocyte Antigen) play an essential role in the normal functioning of the immune system. There are three classes of genes: I, II, and III. The function of HLA molecules class I is to present antigens of peptides from the cytoplasm to T-lymphocytes on the cell surface, and class II — to present antigens of peptides from the extracellular space. In the classical view, the pathological activation of the immune system in patients with a genetic predisposition can result in the development of autoimmune diseases. However, the influence of this system on the development of non-autoimmune diseases, their severity and prognosis, has been recently considered. Besides, HLA molecules provide a presentation of various infectious agents. In this connection, the loci of the main histocompatibility complex can be considered candidates for determining the genetic predisposition to infectious diseases themselves and their course. This review hypothesizes that specific variants of HLA genes may cause the formation of a «cytokine storm» in patients with COVID-19. Identification of a group of patients with particular genetic variations that cause violation of immune tolerance and hyperresponse in the setting of viral infection will help to optimize the algorithm for disease prevention and treatment of such patients and, as a result, to reduce the severity of the epidemiological situation.
Immunoendocrinology — issues and challenges of today
Authors: Troshina Ekaterina A.
Published: December 2020

The World Health Organization has declared this century to be the century of autoimmune diseases. These include a whole spectrum of endocrine disorders, with type 1 diabetes mellitus, thyropathies, autoimmune polyglandular syndromes (APS), adrenal insufficiency and others, are among the most severe chronic non-infectious diseases in humans. Both the etiology and pathogenesis of autoimmune endocrinopathies are being actively studied, the concepts of the manifestation and progression of these diseases have already been formed, data on the genetic predisposition to one or another autoimmune damage to the endocrine system organs have been obtained, prenatal diagnosis of APD is being actively developed and introduced, attempts are being made to edit the genome in order to prevent their development. Despite this, there are still enough «white spots» in understanding the processes of induction and implementation of the mechanisms of autoimmunity in a particular person. The close connection of the immune and endocrine systems is obvious. The key question is: what is still primary, a genetic predisposition to «breakdown» of the immune system, leading to the development of an autoimmune endocrine disease, or some external influence that can cause direct damage to the endocrine organ (up to its destruction), leading in the end to the breakdown of immune tolerance and the launch of a cascade of autoimmune processes that aggravate an endocrine disorder? Modern advances not only in endocrinology, but also in immunology, molecular genetics, cell biology, etc. are absolutely necessary to clarify the relationship of immuno-inflammatory, hormonal and metabolic disorders in the pathogenesis of endocrine diseases at the cellular and molecular level and to develop new methods of prevention, early diagnosis, predicting the course and effectiveness of therapy for autoimmune endocrinopathies.
The Role of Interdisciplinarity in Bringing PBL to traditional Universities: Opportunities and Challenges on the Organizational, Team and Individual Level
Authors: Braßler Mirjam
Published: December 2020

Problem-based learning (PBL) has emerged as a suitable approach to shift from teacher-centered to learner-centered educa-tion. However, higher education institutions (HEIs) experience obstacles stemming from lecturers’ and students’ reservations as well as organizational challenges. Following action research, the author reflects on her implementation of interdisciplinary PBL within one exemplar case study to explore opportunities and challenges of interdisciplinarity in the transition toward a PBL curriculum in a traditional HEI. At the organizational level, interdisciplinarity facilitates collective knowledge creation about PBL by providing interdisciplinary learning spaces and in-house training. At the team level, lecturers as well as students can collectively learn about PBL. At the individual level, interdisciplinary student-to-student and lecturer-to-lecturer learning can enhance personal knowledge about PBL. Monodisciplinary structures, discipline-based differences in teaching and knowledge traditions, as well as individual prejudices are sources of challenges associated with interdisciplinarity in organizational learning.
BENEFÍCIOS DO RESVERATROL COMO ATIVO COSMÉTICO NA PREVENÇÃO DO ENVELHECIMENTO CUTÂNEO
Authors: Paladini Andreia Medeiros , Lopes Talita Durante , Machado Karina Elisa
Published: December 2020

A melhora dos parâmetros de saúde da população é um dos maiores feitos da humanidade e essa conquista se transformou em um desafio para os tempos de hoje. Viver mais é importante, desde que possamos adicionar qualidade de vida, física e mental, para os anos que ganhamos, e por isso a busca por recursos que possam nos ajudam a atingir esse objetivo tem estimulado novas pesquisas e dentre essas, destaca-se a procura de ativos a serem utilizados em formulações cosméticas, que possam combater o envelhecimento cutâneo. O envelhecimento da pele pode ser intrínseco, ou seja, aquele decorrente da passagem natural do tempo e da genética do corpo, ou pode ser extrínseco, aquele provocado por fatores ambientais, que interagem com a pele, e muitos desses fatores estão relacionados à produção de radicais livres, como tabagismo, consumo exagerado de álcool e estresse e, nesse contexto, um dos ativos que nos chama a atenção, no combate ao envelhecimento cutâneo, é o resveratrol. O resveratrol é um composto fenólico, encontrado em várias plantas e alimentos como o amendoim, uva e seus derivados, que exerce uma variedade de atividades biológicas como antioxidantes, anti-inflamatórias, cardioprotetoras, quimiopreventivas e neuroprotetoras. O presente artigo é caracterizado como sendo uma pesquisa bibliográfica do tipo descritiva com abordagem qualitativa e que tem como objetivo realizar uma revisão bibliográfica atualizada sobre o resveratrol e seu uso na prevenção do envelhecimento cutâneo. O resveratrol tem ação antioxidante e é ativador da sirtuína 1, que por sua vez, ativa proteínas reparadoras do DNA, podendo assim ser auxiliar no tratamento antienvelhecimento.
QUALIDADE MICROBIOLÓGICA DE QUEIJOS TIPO MINAS COMERCIALIZADOS EM BELO HORIZONTE, MG, BRASIL
Authors: Lopes Vanessa Cristina , Guedes Elika Karina , Candioto Marcus Vinicius Cossenzo , Delvivo Fernanda Meneghello , Lima Adriene Ribeiro
Published: December 2020

O objetivo deste estudo foi avaliar a qualidade microbiológica de queijos Minas industrializados e artesanais comercializados em Belo Horizonte, MG. Foram coletadas 18 amostras de queijos, sendo nove do tipo Minas frescal, industrializados comercializados em supermercados; e nove do tipo Minas artesanal, comercializados no Mercado Municipal. A temperatura dos queijos amostrados foi aferida durante a fase de exposição para venda. A qualidade higiênico-sanitária dos queijos foi avaliada por meio da contagem de coliformes a 45 °C, Staphylococcus coagulase-positiva e pesquisa de Salmonella sp. Oito (88,9 %) amostras de queijo Minas frescal industrializado se encontravam em temperaturas acima do permitido no mercado varejista, e 100% das amostras de queijo artesanal estavam expostas a temperaturas inadequadas nas lojas do Mercado Municipal. Duas (22 %) amostras de queijo Minas industrializado e quatro (44 %) amostras de queijo Minas artesanal apresentaram contagens superiores ao preconizado pela legislação para coliformes a 45 °C. Em relação à contagem de Staphylococcus coagulase-positiva 100 % das amostras, tanto de queijo industrializado quanto de queijo artesanal, apresentaram contagens superiores aos padrões legais. Nenhuma amostra apresentou contaminação pela bactéria Salmonella sp. Dessa forma, a qualidade higiênico-sanitária de 100 % dos queijos Minas avaliados foi insatisfatória.
ANÁLISE DA SEGURANÇA DO USO DE IMUNOSSUPRESSORES POR PACIENTES INSUFICIENTES RENAIS
Authors: Toaldo Fernanda , Dos Santos Flavia Lorenzen , Sales Fernanda Cristina Ostrovski , Aschenbrenner Jaqueline de Jesus
Published: December 2020

A insuficiência renal aguda (IRA) e a insuficiência renal crônica (IRC) consistem em patologias com incidência crescente ao longo dos últimos anos no Brasil. Segundo a Sociedade Brasileira de Nefrologia (2018), o número de pacientes com estas comorbidades tem aumentado cerca de 200% em 16 anos, tendo como alternativa de tratamento o transplante do órgão. Uma das principais terapias pós-transplante renal consiste no uso de imunossupressores, com o objetivo de conter a rejeição do enxerto. Em contrapartida, a segurança desta farmacoterapia ainda é bastante discutida, pela alta probabilidade de ocorrência de reações adversas. Esse estudo objetivou apresentar e analisar dados numéricos referentes à ocorrência de Reação Adversa a Medicamentos (RAM) relacionados a imunossupressores utilizados como farmacoterapia por pacientes com IRA ou IRC, internados em um Hospital Universitário do Município de Curitiba. PR. Trata-se de um estudo retrospectivo observacional, baseado na análise de prontuários físicos e eletrônicos de pacientes insuficientes renais agudos ou crônicos, por meio de busca ativa em tabelas de dispensação de imunossupressores. Este trabalho incluiu prontuários de 162 pacientes, sendo que 118 destes  apresentaram uma ou mais possíveis reações adversas de imunossupressores. A RAM de maior prevalência no estudo foi “infecção oportunista” e a de menor prevalência “hipoalbuminemia”. Para maior confiabilidade dos resultados foi aplicado Algoritmo de Naranjo, onde “infecção” permaneceu relevante em 26% dos seus casos classificada pelo algoritmo como “provável”. Diante dos resultados expostos, observa-se a importância do farmacêutico clínico na otimização da farmacoterapia imunossupressora utilizada por pacientes insuficientes renais do hospital em questão.
Relationship between TIM-3 gene polymorphisms and steroid-resistant primary nephrotic syndrome in children
Authors: Lei Jing , Ma Songdong
Published: December 2020

Nephrotic syndrome, also known as nephrosis, is a collection of symptoms in medicine and urology caused by damage to the basement membrane of the kidney glomeruli and the kidneys excrete a large amount of protein. This experiment was carried out to investigate the association of three single nucleotide polymorphisms (SNPs) of T-cell immunoglobulin and mucin-domain-containing-3 (Tim-3) with childhood primary nephrotic syndrome (PNS) steroid response in Han Chinese. For this purpose, a total of 218 children with steroid-resistant PNS and 189 children with steroid-responsive PNS were enrolled in this case-control study. Three single nucleotide polymorphisms (SNPs) of the TIM-3 gene promoter region (rs4704853, rs1051746, and rs10053538) were analyzed by polymerase chain reaction (PCR) and restriction enzyme digestion.  Results showed that there were 124 males and 94 females in the steroid-resistant PNS group and 114 males and 75 females in the steroid-responsive PNS group. The mean ages of the two groups were 7.9 years and 7.7 years, respectively. The distribution of alleles of Rs1051746 and Rs10053538 were significantly different between the steroid-resistant PNS group and the steroid-responsive PNS group (P-value = 0.047 and 0.012, respectively). The distribution of their genotypes was also significantly different between the steroid-resistant PNS group and the steroid-responsive PNS group (P-value = 0.044 and 0.010, respectively). Haplotype G-C-G was less frequent among steroid-resistant PNS children than the steroid-responsive PNS children (P = 0.015). There was no significant difference between the three SNPs of TIM-3 and the clinical features of these PNS children (P>0.05). It concluded that this study provided evidence showing that the polymorphisms of Rs1051746 and Rs10053538 at the TIM-3 gene were related to childhood PNS steroid response. This result provided fundamental support for future studies on the role of TIM-3 in pathogenesis and therapy of childhood PNS.
Design of biological gene information collection system based on data mining technology
Authors: Wu Yuanjun , Mu Xiaotong , Kahrizi Danial
Published: December 2020

At present, bioinformatics research focuses on the development from the accumulation of biological data to the integration and processing of biological data. This paper designs a bio gene information collection system based on data mining technology. In the system, the information of gene web analysis database, data mining model database and gene chip database is transferred to gene algorithm tool library, which can extract, transform and load the biological gene information, transfer the collected and processed biological gene information to gene general chip and web database analysis logic, and pass it to gene expression spectrum chip/data mining module through API function GUI, through the data mining module GUI feedback to the system users. The system hardware stores the biochip information in the virtual chip set model through the gene expression spectrum data analysis model uses the gene expression similarity analysis model to analyze the expression similarity of the biological gene information, and stores the information in the gene chip database; through the multi-layer structure model, constructs the web genome biochip including the application layer, the data processing layer and the representation layer. The information analysis module analyzes the biological gene information and stores the information in the gene web analysis database. The system software adopts the method of automatic collection of biological gene data based on the web to realize the collection of biological gene information, and gives the main implementation technology of the system. The experimental results show that the system can effectively collect biological gene information, and has high accuracy and anti-noise performance.