bluuebunny/crossref_metadata_2025 huggingface dataset:
Typology of organizational innovation components: building blocks to improve access to primary healthcare for vulnerable populations
Authors: Smithman Mélanie Ann , Descôteaux Sarah , Dionne Émilie , Richard Lauralie , Breton Mylaine , Khanassov Vladimir , Haggerty Jeannie L. ,   On behalf of the IMPACT research team
Published: October 2020

Background

Achieving equity of access to primary healthcare requires organizations to implement innovations tailored to the specific needs and abilities of vulnerable populations. However, designing pro-vulnerable innovations is challenging without knowledge of the range of possible innovations tailored to vulnerable populations’ needs. To better support decision-makers, we aimed to develop a typology of pro-vulnerable organizational innovation components–akin to “building blocks” that could be combined in different ways into new complex innovations or added to existing organizational processes to improve access to primary healthcare.

Methods

To develop the typology, we used data from a previously conducted a) scoping review (2000–2014, searched Medline, Embase, CINAHL, citation tracking,n = 90 articles selected), and b) environmental scan (2014, online survey via social networks,n = 240 innovations). We conducted a typological analysis of the data. Our initial typology yielded 48 components, classified according to accessibility dimensions from thePatient-Centred Accessibility Framework. The initial typology was then field-tested for relevance and usability by health system stakeholders and refined from 2014 to 2018 (e.g., combined similar components, excluded non-organizational components).

Results

The selected articles (n = 90 studies) and survey responses (n = 240 innovations) were mostly from the USA, Canada, Australia and the UK. Innovations targeted populations with various vulnerabilities (e.g., low income, chronic illness, Indigenous, homeless, migrants, refugees, ethnic minorities, uninsured, marginalized groups, mental illness, etc.). Our final typology had 18 components of organizational innovations, which principally addressed Availability & Accommodation (7/18), Approachability (6/18), and Acceptability (3/18). Components includednavigation & information,community health worker,one-stop-shop,case management,group visits,defraying costs, primary healthcare brokerage, etc.

Conclusions

This typology offers a comprehensive menu of potential components that can help inform the design of pro-vulnerable organizational innovations. Component classification according to the accessibility dimensions of thePatient-Centred Accessibility Frameworkis useful to help target access needs. Components can be combined into complex innovations or added to existing organizational processes to meet the access needs of vulnerable populations in specific contexts.
Do human embryos have the ability of self-correction?
Authors: Orvieto Raoul , Shimon Chen , Rienstein Shlomit , Jonish-Grossman Anat , Shani Hagit , Aizer Adva
Published: October 2020

Human embryogenesis frequently coinciding with cell division mistakes contributing to pervasive embryonic aneuploidy/mosaicism. While embryo self-correction was elegantly demonstrated in mouse models, human studies are lacking. Here we are witness to human embryos ability to eliminate/expel abnormal blastomeres as cell debris/fragments. Each blastocyst and its corresponding debris were separated and underwent whole genome amplification. Seven of the 11 pairs of blastocysts and their corresponding cell debris/fragments revealed discordant results. Of the 9 euploid blastocysts, four showed euploid debris, while in the others, the debris were aneuploid. In the remaining pairs, the debris showed additional aneuploidy to those presented by their corresponding blastocyst. The observed ability of human embryos to self-correction doubts many invasive and non-invasive preimplantation testing for aneuploidy at the blastocyst stage, rendering high rate of false positive (discarding “good” embryos) by identifying the cell-free DNA originated from the expelled cell debris, as aneuploidy/mosaic blastocyst.
The effect of civil and military flights on coagulation, fibrinolysis and blood flow: insight from a rat model
Authors: Levkovsky Anna , Dardik Rima , Barazany Daniel , Steinberg David M. , Kirichenko Mark Dan , Apter Sara , Peleg Edna , Silverberg Daniel , Grossman Ehud , Salomon Ophira
Published: October 2020

Background

Air travel thrombosis continues to be a controversial topic. Exposure to hypoxia and hypobaric conditions during air travel is assumed a risk factor. The aim of this study is to explore changes in parameters of coagulation, fibrinolysis and blood flow in a rat model of exposure to hypobaric conditions that imitate commercial and combat flights.

Methods

Sixty Sprague-Dawley male rats, aged 10 weeks, were divided into 5 groups according to the type and duration of exposure to hypobaric conditions. The exposure conditions were 609 m and 7620 m for 2 and 12 h duration. Blood count, thrombin– antithrombin complex, D-dimer, interleukin-1 and interleukin-6 were analyzed. All rats went through flight angiography MRI at day 13-post exposure.

Results

No effect of the various exposure conditions was observed on coagulation, fibrinolytic system, IL-1 or IL-6. MRI angiography showed blood flow reduction in lower limb to less than 30% in 50% of the rats. The reduction in blood flow was more pronounced in the left vessel than in the right vessel (p = 0.006, Wilcoxon signed rank test). The extent of occlusion differed across exposure groups in the right, but not the left vessel (p = 0.002, p = 0.150, respectively, Kruskal-Wallis test). However, these differences did not correlate with the exposure conditions.

Conclusion

In the present rat model, no clear correlation between various hypobaric conditions and activation of coagulation was observed. The reduction in blood flow in the lower limb also occurred in the control group and was not related to the type of exposure.
Strengthening National Immunization Technical Advisory Groups in resource-limited settings: current and potential linkages with polio national certification committees
Authors: Greene Sharon A. , Anya Blanche-Philomene Melanga , Asghar Humayun , Chaudhri Irtaza A. , Datta S. Deblina , Donadel Morgane E. , Kouadio Koffi Isidore , Shefer Abigail M. , Cavallaro Kathleen F.
Published: October 2020

Background

Countries are transitioning assets and functions from polio eradication to integrated immunization and surveillance activities. We assessed the extent of linkages between and perceptions of National Immunization Technical Advisory Groups (NITAGs) and National Certification Committees (NCCs) for polio eradication to understand how linkages can be leveraged to improve efficiencies of these expert bodies.

Methods

During May 2017 to May 2018, we administered a 15-question survey to a NITAG chair or member and an NCC counterpart in all countries of the WHO Regions for Africa (AFR) and for the Eastern Mediterranean (EMR) that had both a NITAG and an NCC. Data were analysed using frequency distributions.

Results

Of countries with both a NITAG and an NCC (n = 44), the response rate was 92% (22/24) in AFR and 75% (15/20) in EMR. Some respondents reported being very familiar with the functions of the other technical bodies, 36% (8/22) for NITAG members and 38% (14/37) for NCC members. Over 85% (51/59) of respondents felt it was somewhat useful or very useful to strengthen ties between bodies. Nearly all respondents (98%, 58/59) felt that NCC expertise could inform measles and rubella elimination programmes.

Conclusions

We observed a broad consensus that human resource assets of NCCs may serve an important technical role to support national immunization policy-making. At this stage of the polio eradication initiative, countries should consider how to integrate the technical expertise of NCC members to reinforce NITAGs and maintain the polio essential functions, beginning in countries that have been polio-free for several years.
Functional benefits of corticosteroid and IVIG combination therapy in a coronary artery endothelial cell model of Kawasaki disease
Authors: Inoue Takashi , Murakami Shokei , Matsumoto Kenji , Matsuda Akio
Published: October 2020

Background

Kawasaki disease (KD) is the most common pediatric systemic vasculitides of unknown etiology. Recent clinical studies led to reappraisal of the usefulness of initial combination therapy of intravenous immunoglobulin (IVIG) plus a corticosteroid for patients with severe KD. However, the molecular mechanisms underlying the clinical benefits of that combination therapy remain unclear. Here, we used cultured human coronary artery endothelial cells (HCAECs), as a mimic of KD, to study the possible mechanisms responsible for the clinical benefits of adding a corticosteroid to standard IVIG therapy for patients with severe KD.

Methods

HCAECs were stimulated with TNF-α, IL-1α or IL-1β in the presence and absence of high-dose IgG and/or dexamethasone (DEX). The mRNA and protein concentrations for high-mobility group box-1 (HMGB1), IL-1α, IL-6 and granulocyte-colony stimulating factor (G-CSF) in the culture supernatants were measured by quantitative PCR (qPCR) and ELISA, respectively. Apoptosis was evaluated by the caspase 3/7 activities.

Results

DEX, but not IgG, significantly inhibited apoptosis caused by inflammatory stimuli, resulting in effective reduction of HMGB1 and IL-1α protein release by HCAECs. As previously reported, DEX or IgG alone significantly suppressed TNF-α-induced production of IL-6 and G-CSF and mRNA expression, but induction of those cytokines by IL-1 s (IL-1α and IL-1β) was resistant to high-dose IgG.

Conclusions

A corticosteroid can effectively inhibit the release of HMGB1 and IL-1α, which may be involved in IVIG resistance in KD. Since high-dose IgG does not have such beneficial anti-cytotoxic effects, adding a corticosteroid to standard IVIG therapy may help prevent the progression of IVIG resistance in KD.
The association of intimate partner violence with postpartum depression in women during their first month period of giving delivery in health centers at Dessie town, 2019
Authors: Necho Mogesie , Belete Asmare , Zenebe Yosef
Published: October 2020

Background

Postpartum depression is a common psychiatric complaint of women following delivery and a multitude of psychosocial, maternal, newborn and husband-related factors were contributing to it. This condition has a detrimental impact on the mother–infant caregiving relationship and hastens the infant’s cognitive, emotional and social development. However, a shortage of empirical evidence existed especially in developing countries including Ethiopia. Therefore, we implemented this study to determine the magnitude of postpartum depression and its correlates.

Methods

A cross-sectional survey was implemented on 378 postnatal women in the maternal and child health clinic of Dessie health centers within 4 weeks of their delivery. Postpartum depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS). Intimate partner violence was operationalized as a psychological, physical and sexual abusive action imposed on women by their associates. We estimated the crude and adjusted odds ratio with its 95% CI using binary logistic regression to know the association and statistical significance was declared using a p-value < 0.05.

Results

More than one-fourth, 102 (27%) (95% CI 22.5, 31.5) of participants were obtained to have postpartum depression. Being single from socio-demographic variables (AOR = 4.9, 95% CI 1.27, 16.74), dissatisfaction with child gender (AOR = 3.1, 95% CI 1.62, 6.69), unplanned pregnancy (AOR = 2.5, 95% CI 1.76, 7.23) and depression during current pregnancy (AOR = 3.2, 95% CI 2.81, 8.91) from pregnancy and newborn-related variables, intimate partner violence; psychological (AOR = 6.5, 95% CI 1.98, 15.85), sexual and physical violence (AOR = 3.46, 95%CI 2.34, 18.55), current husbands alcoholism (AOR = 2.2, 95% CI 1.48, 5.34) from husband/partner-related variables and current substance use (AOR = 1.8, 95% CI 1.16, 3.75) were found to have a statistically significant association with postpartum depression.

Conclusion

More than one-fourth of the interviewed women (27%) were found to have postpartum depression. Being single from socio-demographic variables, dissatisfaction with child gender, unplanned pregnancy, and depression during current pregnancy from pregnancy and newborn-related variables, intimate partner violence, and current husband’s alcoholism from husband/partner-related variables and current substance use were the related factors. This suggests the need for integrating postpartum depression services into the existing postnatal maternal and child health services and basing intervention geared primarily to the mentioned factors above.
Dental caries in primary and permanent teeth in children’s worldwide, 1995 to 2019: a systematic review and meta-analysis
Authors: Kazeminia Mohsen , Abdi Alireza , Shohaimi Shamarina , Jalali Rostam , Vaisi-Raygani Aliakbar , Salari Nader , Mohammadi Masoud
Published: October 2020

Background

Early childhood caries (ECC) is a type of dental caries in the teeth of infants and children that is represented as one of the most prevalent dental problems in this period. Various studies have reported different types of prevalence of dental caries in primary and permanent teeth in children worldwide. However, there has been no comprehensive study to summarize the results of these studies in general, so this study aimed to determine the prevalence of dental caries in primary and permanent teeth in children in different continents of the world during a systematic review and meta-analysis.

Methods

In this review study, articles were extracted by searching in the national and international databases of SID, MagIran, IranMedex, IranDoc, Cochrane, Embase, ScienceDirect, Scopus, PubMed, and Web of Science (ISI) between 1995 and December 2019. Random effects model was used for analysis and heterogeneity of studies was evaluated by using the I2index. Data were analyzed by using the Comprehensive Meta-Analysis (Version 2) software.

Findings

In this study, a total of 164 articles (81 articles on the prevalence of dental caries in primary teeth and 83 articles on the prevalence of dental caries in permanent teeth) were entered the meta-analysis. The prevalence of dental caries in primary teeth in children in the world with a sample size of 80,405 was 46.2% (95% CI: 41.6–50.8%), and the prevalence of dental caries in permanent teeth in children in the world with a sample size of 1,454,871 was 53.8% (95% CI: 50–57.5%). Regarding the heterogeneity on the basis of meta-regression analysis, there was a significant difference in the prevalence of dental caries in primary and permanent teeth in children in different continents of the world. With increasing the sample size and the year of study, dental caries in primary teeth increased and in permanent teeth decreased.

Conclusion

The results of this study showed that the prevalence of primary and permanent dental caries in children in the world was found to be high. Therefore, appropriate strategies should be implemented to improve the aforementioned situation and to troubleshoot and monitor at all levels by providing feedback to hospitals.
The value of continuous nursing in patients after cardiac mechanical valve replacement
Authors: Li Sai-lan , Zhou Sheng-huo , Lin Yan-juan
Published: October 2020

Objective

The purpose of this study was to explore the value of continuous nursing in patients after cardiac valve replacement.

Methods

The clinical data of 116 patients after cardiac mechanical valve replacement from January 2017 to January 2018 were analysed retrospectively. According to the nursing mode, the patients were divided into two groups: the continuous nursing group (group A, n = 56) and the conventional nursing group (group B, n = 60).

Results

The continuous nursing group exhibited significantly decreased SAS and SDS scores 1 year after surgery compared to the preoperative SAS and SDS scores(P < 0.05). The SAS and SDS scores of the continuous nursing group were significantly better than those of the traditional nursing group 1 year after surgery(P < 0.05). There were 4 patients with anticoagulant complications after discharge in the continuous nursing group, and 13 cases of anticoagulant complications in the conventional nursing group. There was a significant difference between the two groups.

Conclusion

Continuous nursing improves patient compliance with treatment and reduces the occurrence of postoperative anticoagulation complications. The patient also receives proper psychological evaluations, which relieve patient anxiety and depression.
Association between polypharmacy and the persistence of delirium: a retrospective cohort study
Authors: Kurisu Ken , Miyabe Daisuke , Furukawa Yoshiko , Shibayama Osamu , Yoshiuchi Kazuhiro
Published: October 2020

Background

Although the association between polypharmacy and the occurrence of delirium has been well studied, the influence of polypharmacy on the persistence of delirium remains unclear. We aimed to explore the effect of polypharmacy on the persistence of delirium.

Methods

This retrospective cohort study was conducted at a tertiary hospital. The medical records of patients diagnosed with delirium who were referred to the Department of Psychosomatic Medicine were reviewed. Presentation with delirium on day 3 was set as the outcome in this study. We counted the number of drugs prescribed on the date of referral, excluding general infusion fluids, nutritional or electrolytic products, and psychotropics. To define polypharmacy, we developed a classification and regression tree (CART) model and drew a receiver operating characteristic (ROC) curve. The odds ratio (OR) of polypharmacy for the persistence of delirium on day 3 was calculated using a logistic regression model with the propensity score as a covariate.

Results

We reviewed the data of 113 patients. The CART model and ROC curve indicated an optimal polypharmacy cutoff of six drugs. Polypharmacy was significantly associated with the persistence of delirium both before [OR, 3.02; 95% confidence interval (CI), 1.39–6.81; P = 0.0062] and after (OR, 3.19; 95% CI, 1.32–8.03; P = 0.011) propensity score adjustment.

Conclusion

We discovered an association between polypharmacy and worsening courses of delirium and hypothesize that polypharmacy might be a prognostic factor for delirium.
Community engagement and building trust to resolve ethical challenges during humanitarian crises: experience from the CAGED study
Authors: Yimer Getnet , Gebreyes Wondwossen , Havelaar Arie , Yousuf Jemal , McKune Sarah , Mohammed Abdulmuen , O’Mathúna Dónal
Published: October 2020

Background

According to the Internal Displacement Monitoring Centre report on global human displacement, Ethiopia has the highest number of newly displaced people forced to flee their homes. Displaced people have arrived in other regions, sometimes leading to conflict. Several regions in Ethiopia experience on-going ethnic tensions and violence between tribes, which leaves smallholder farmers suspicious of any outside activities in their locale, assuming other ethnic groups may harm them. Changes in the central Ethiopian government have also led to suspicion of non-local agencies. The Campylobacter Genomics and Enteric Dysfunction (CAGED) research project’s objective is to improve the incomes, livelihoods and nutrition of smallholder farmers and was conducted during this period of increasing violence. The project aims to assess the impact of reducing exposure to chicken excreta on young children’s gut health and growth. This paper does not report empirical findings from CAGED, but is part of a series that aims to identify challenges in humanitarian research and reports on mitigation strategies during this research.

Discussion

This research is important to determine whether Campylobacter infection in chicken’s contributes to illness and stunting in children. However, violence against other researchers in different parts of Ethiopia led to mistrust and lack of engagement by the community with the researchers. Some reactions were so hostile that the team was fearful about returning to some households. As a result, the team designed strategies to respond, including establishing two types of community advisory boards. One used pre-existing village elder structures and another was composed of village youth. Data collection team members received training in principles of ethics, consent, and crisis management, and were provided on-going support from local and international principal investigators and the study’s ethics advisor.

Conclusion

The hostility and mistrust led to fear among the data collectors. These and the resulting strategies to address them resulted in delays for the research. However, the interventions taken resulted in successful completion of the field activities. Moreover, the lessons learned from this project are already being implemented with other projects being conducted in various parts of Ethiopia.
Cross-sectional survey on impact of paediatric COVID-19 among Italian paediatricians: report from the SIAIP rhino-sinusitis and conjunctivitis committee
Authors: Diaferio Lucia , Parisi Giuseppe Fabio , Brindisi Giulia , Indolfi Cristiana , Marchese Giuseppe , Ghiglioni Daniele Giovanni , Zicari Anna Maria , Marseglia Gian Luigi , Miraglia del Giudice Michele
Published: October 2020

Background

There is ample evidence that COVID-19 is significantly less severe in children than in adults and asthma and allergy, the most common chronic disorders in children, are not included in the top 10 comorbidities related to COVID-19 fatalities. Nevertheless, concerns about asthma and allergy are still high.. In order to evaluate the impact of paediatric COVID-19 among Italian paediatricians, we sent a 20-questions anonymous internet-based survey to 250 Italian paediatricians with particular address to allergic symptoms and those affecting the upper airways.

Methods

The questionnaire was conceived and pretested in April 2020, by a working group of experts of the Italian Paediatric Society for Allergy and Immunology (SIAIP), and structured into different sections of 20 categorized and multiple choice questions. The first part included questions about epidemiological data follows by a second part assessing the way to manage a suspected COVID-19 infection and personal experiences about that. The third part concerned questions about patients’ clinical characteristics and clinical manifestations.

The survey was emailed once between April and mid-May 2020.

Results

A total 99 participants had participated in our survey and provided responses to our electronic questionnaire. The distribution of patients reported per month varies significantly according to the geographical area (P = 0.02). Data confirmed that in the North part of Italy the rate of patients referred is higher than in the rest of Italy. Almost all respondents (98%) reported caring for up to a maximum of 10 infected children and the last 2% more than twenty. Among these patients, according to the 75% of responders, a maximum rate of 20% were affected by allergic rhino-conjunctivitis and in particular in the North of Italy while in the Centre and in the South there was a higher incidence (P = 0.09). Almost the same applies for asthma, 83% of responders declared that up to a maximum of 20% of affected children were asthmatic, from 20 to 40% for the 13,5% of responders and from 40 to 60% for the last 3,5%. As for the allergic conjunctivitis also for asthma, we found a higher incidence in the Centre and in South than in the North (P = 0.03).

Conclusions

This study is the first to provide a comprehensive review of COVID-19 knowledge and impact among paediatricians in Italy about allergic asthma and upper airway involvement. From our point of view, it provides important information clearly useful for improving a good practice.
Variation of mitochondrial minichromosome composition in Hoplopleura lice (Phthiraptera: Hoplopleuridae) from rats
Authors: Fu Yi-Tian , Nie Yu , Duan De-Yong , Liu Guo-Hua
Published: October 2020

Background

The family Hoplopleuridae contains at least 183 species of blood-sucking lice, which widely parasitize both mice and rats. Fragmented mitochondrial (mt) genomes have been reported in two rat lice (Hoplopleura kitti and H. akanezumi) from this family, but some minichromosomes were unidentified in their mt genomes.

Methods

We sequenced the mt genome of the rat louse Hoplopleura sp. with an Illumina platform and compared its mt genome organization with H. kitti and H. akanezumi.

Results

Fragmented mt genome of the rat louse Hoplopleura sp. contains 37 genes which are on 12 circular mt minichromosomes. Each mt minichromosome is 1.8–2.7 kb long and contains 1–5 genes and one large non-coding region. The gene content and arrangement of mt minichromosomes of Hoplopleura sp. (n = 3) and H. kitti (n = 3) are different from those in H. akanezumi (n = 3). Phylogenetic analyses based on the deduced amino acid sequences of the eight protein-coding genes showed that the Hoplopleura sp. was more closely related to H. akanezumi than to H. kitti, and then they formed a monophyletic group.

Conclusions

Comparison among the three rat lice revealed variation in the composition of mt minichromosomes within the genus Hoplopleura. Hoplopleura sp. is the first species from the family Hoplopleuridae for which a complete fragmented mt genome has been sequenced. The new data provide useful genetic markers for studying the population genetics, molecular systematics and phylogenetics of blood-sucking lice.
Regulation of SETD2 stability is important for the fidelity of H3K36me3 deposition
Authors: Bhattacharya Saikat , Workman Jerry L.
Published: October 2020

Background

The histone H3K36me3 mark regulates transcription elongation, pre-mRNA splicing, DNA methylation, and DNA damage repair. However, knowledge of the regulation of the enzyme SETD2, which deposits this functionally important mark, is very limited.

Results

Here, we show that the poorly characterized N-terminal region of SETD2 plays a determining role in regulating the stability of SETD2. This stretch of 1–1403 amino acids contributes to the robust degradation of SETD2 by the proteasome. Besides, the SETD2 protein is aggregate prone and forms insoluble bodies in nuclei especially upon proteasome inhibition. Removal of the N-terminal segment results in the stabilization of SETD2 and leads to a marked increase in global H3K36me3 which, uncharacteristically, happens in a Pol II-independent manner.

Conclusion

The functionally uncharacterized N-terminal segment of SETD2 regulates its half-life to maintain the requisite cellular amount of the protein. The absence of SETD2 proteolysis results in a Pol II-independent H3K36me3 deposition and protein aggregation.
miR-431-5p regulates cell proliferation and apoptosis in fibroblast-like synoviocytes in rheumatoid arthritis by targeting XIAP
Authors: Wang Yuejiao , Zhang Kailin , Yuan Xiaowei , Xu Neili , Zhao Shuai , Hou Linxin , Yang Lili , Zhang Ning
Published: October 2020

Background

miR-431-5p is dysregulated in various cancers and plays an important function in the development of cancer. However, its role in fibroblast-like synoviocytes (FLSs) in patients with rheumatoid arthritis (RA) remains to be understood.

Methods

Quantitative real-time polymerase chain reaction was used to detect the relative expression of miR-431-5p in synovial tissues and FLSs. Cell proliferation assays helped examine RA FLS proliferation. Flow cytometry was performed to determine apoptosis and cell cycle progression in RA FLSs. We used dual-luciferase assays to determine the correlation between miR-431-5p and its putative target, X-linked inhibitor of apoptosis (XIAP). Quantitative real-time PCR and western blotting were used to measure XIAP levels in synovial tissues and transfected RA FLSs.

Results

miR-431-5p was downregulated in synovial tissues and FLSs of patients with RA. Upregulation of miR-431-5p prohibited cell proliferation and the G0/G1-to-S phase transition but promoted apoptosis in RA FLSs, while miR-431-5p inhibition showed the opposite results. miR-431-5p directly targeted XIAP in RA FLSs and reversely correlated with XIAP levels in synovial tissues. Notably, XIAP silencing partially restored the effects of miR-431-5p inhibition in RA FLSs.

Conclusion

miR-431-5p regulates cell proliferation, apoptosis, and cell cycle of RA FLSs by targeting XIAP, suggesting its potential in the treatment of RA.
Unidentified dengue serotypes in DENV positive samples and detection of other pathogens responsible for an acute febrile illness outbreak 2016 in Cajamarca, Peru
Authors: del Valle-Mendoza Juana , Vasquez-Achaya Fernando , Aguilar-Luis Miguel Angel , Martins-Luna Johanna , Bazán-Mayra Jorge , Zavaleta-Gavidia Victor , Silva-Caso Wilmer , Carrillo-Ng Hugo , Tarazona-Castro Yordi , Aquino-Ortega Ronald , del Valle Luis J.
Published: October 2020

Objective

To describe the prevalence of dengue virus serotypes, as well as other viral and bacterial pathogens that cause acute febrile illness during an outbreak in Cajamarca in 2016.

Results

Dengue virus (DENV) was the most frequent etiologic agent detected in 25.8% of samples (32/124), followed by Rickettsia spp. in 8.1% (10/124), Zika virus in 4.8% (6/124), Chikungunya virus 2.4% (3/124) and Bartonella bacilliformis 1.6% (2/124) cases. No positive cases were detected of Oropouche virus and Leptospira spp. DENV serotypes identification was only achieved in 23% of the total positive for DENV, two samples for DENV-2 and four samples for DENV-4.

During the 2016 outbreak in Cajamarca—Peru, it was observed that in a large percentage of positive samples for DENV, the infecting serotype could not be determined by conventional detection assays. This represents a problem for the national surveillance system and for public health due to its epidemiological and clinical implications. Other viral and bacterial pathogens responsible for acute febrile syndrome were less frequently identified.
Chd8 haploinsufficiency impairs early brain development and protein homeostasis later in life
Authors: Jiménez Jessica A. , Ptacek Travis S. , Tuttle Alex H. , Schmid Ralf S. , Moy Sheryl S. , Simon Jeremy M. , Zylka Mark J.
Published: October 2020

Background

Chromodomain helicase DNA-binding protein 8 (Chd8) is a high-confidence risk gene for autism spectrum disorder (ASD). However, how Chd8 haploinsufficiency impairs gene expression in the brain and impacts behavior at different stages of life is unknown.

Methods

We generated a mutant mouse line with an ASD-linked loss-of-function mutation in Chd8 (V986*; stop codon mutation). We examined the behavior of Chd8 mutant mice along with transcriptional changes in the cerebral cortex as a function of age, with a focus on one embryonic (E14.5) and three postnatal ages (1, 6, and 12 months).

Results

Chd8V986*/+ mutant mice displayed macrocephaly, reduced rearing responses and reduced center time in the open field, and enhanced social novelty preference. Behavioral phenotypes were more evident in Chd8V986*/+ mutant mice at 1 year of age. Pup survival was reduced in wild-type x Chd8V986*/+ crosses when the mutant parent was female. Transcriptomic analyses indicated that pathways associated with synaptic and neuronal projections and sodium channel activity were reduced in the cortex of embryonic Chd8V986*/+ mice and then equalized relative to wild-type mice in the postnatal period. At 12 months of age, expression of genes associated with endoplasmic reticulum (ER) stress, chaperone-mediated protein folding, and the unfolded protein response (UPR) were reduced in Chd8V986*/+ mice, whereas genes associated with the c-MET signaling pathway were increased in expression.

Limitations

It is unclear whether the transcriptional changes observed with age in Chd8V986*/+ mice reflect a direct effect of CHD8-regulated gene expression, or if CHD8 indirectly affects the expression of UPR/ER stress genes in adult mice as a consequence of neurodevelopmental abnormalities.

Conclusions

Collectively, these data suggest that UPR/ER stress pathways are reduced in the cerebral cortex of aged Chd8V986*/+ mice. Our study uncovers neurodevelopmental and age-related phenotypes in Chd8V986*/+ mice and highlights the importance of controlling for age when studying Chd8 haploinsufficient mice.
A community-based study of demographics, medical and psychiatric conditions, and gender dysphoria/incongruence treatment in transgender/gender diverse individuals
Authors: James Haleigh A. , Chang Alice Y. , Imhof Reese L. , Sahoo Aradhana , Montenegro Monique M. , Imhof Nicole R. , Gonzalez Cesar A. , Lteif Aida N. , Nippoldt Todd B. , Davidge-Pitts Caroline J.
Published: October 2020

Background

Current understanding about health care in the gender diverse population is limited by the lack of community-based, longitudinal data, especially in the USA. We sought to characterize a community-based cohort of transgender individuals including demographics, gender identities, social characteristics, psychiatric and medical conditions, and medical therapy for gender dysphoria/incongruence.

Patients and methods

We performed a retrospective chart review of gender diverse residents of Olmsted County, Minnesota, who sought gender-specific healthcare from January 1, 1974, through December 31, 2015, using an infrastructure that links medical records of Olmsted County residents from multiple institutions.

Results

The number of patients seeking gender-specific healthcare increased from 1 to 2 per 5-year interval during the 1970s–1990s to 41 from 2011 to 2015 (n = 82). Forty-nine (59.8%) were assigned male sex at birth (AMAB), 31 (37.8%) were assigned female (AFAB), and 2 (2.4%) were intersex. Gender identities evolved over time in 16.3% and 16.1% of patients AMAB and AFAB, respectively, and at most recent follow-up, 8.2% and 12.9% of patients AMAB and AFAB, respectively, were non-binary. Depression affected 78%, followed by anxiety (62.2%), personality disorder (22%), and post-traumatic stress disorder (14.6%). 58.5% experienced suicidal ideation, 22% attempted suicide, and 36.6% were victims of abuse. The most prevalent medical conditions and cardiovascular (CV) risk factors included obesity (42.7%), tobacco use (40.2%), fracture [34.1% (86.2% traumatic)], hypertension (25.6%), hyperlipidemia (25.6%), and hypertriglyceridemia (15.9%). 67.3% of patients AMAB used feminizing and 48.4% of patients AFAB used masculinizing hormone therapy. When compared to US CDC National Health Statistics, there was a significantly greater prevalence of depression and anxiety but no difference in the prevalence of obesity, hypertension, hypercholesterolemia, type 2 diabetes, or stroke.

Conclusion

Transgender and gender diverse individuals represent a population who express various gender identities and are seeking gender-specific healthcare at increasing rates. Psychiatric illness is highly prevalent compared to the US population but there is no difference in the prevalence of CV risk factors including obesity, type 2 diabetes, hypertension, and dyslipidemia.
Association between autoimmune diseases and COVID-19 as assessed in both a test-negative case–control and population case–control design
Authors: Murtas Rossella , Andreano Anita , Gervasi Federico , Guido Davide , Consolazio David , Tunesi Sara , Andreoni Laura , Greco Maria Teresa , Gattoni Maria Elena , Sandrini Monica , Riussi Antonio , Russo Antonio Giampiero
Published: October 2020

Background

COVID-19 epidemic has paralleled with the so called infodemic, where countless pieces of information have been disseminated on putative risk factors for COVID-19. Among those, emerged the notion that people suffering from autoimmune diseases (AIDs) have a higher risk of SARS-CoV-2 infection.

Methods

The cohort included all COVID-19 cases residents in the Agency for Health Protection (AHP) of Milan that, from the beginning of the outbreak, developed a web-based platform that traced positive and negative cases as well as related contacts. AIDs subjects were defined ad having one the following autoimmune disease: rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren disease, ankylosing spondylitis, myasthenia gravis, Hashimoto’s disease, acquired autoimmune hemolytic anemia, and psoriatic arthritis. To investigate whether AID subjects are at increased risk of SARS-CoV-2 infection, and whether they have worse prognosis than AIDs-free subjects once infected, we performed a combined analysis of a test-negative design case–control study, a case–control with test-positive as cases, and one with test-negative as cases (CC-NEG).

Results

During the outbreak, the Milan AHP endured, up to April 27th 2020, 20,364 test-positive and 34,697 test-negative subjects. We found no association between AIDs and being positive to COVID-19, but a statistically significant association between AIDs and being negative to COVID-19 in the CC-NEG. If, as likely, test-negative subjects underwent testing because of respiratory infection symptoms, these results imply that autoimmune diseases may be a risk factor for respiratory infections in general (including COVID-19), but they are not a specific risk factor for COVID-19. Furthermore, when infected by SARS-CoV-2, AIDs subjects did not have a worse prognosis compared to non-AIDs subjects. Results highlighted a potential unbalance in the testing campaign, which may be correlated to the characteristics of the tested person, leading specific frail population to be particularly tested.

Conclusions

Lack of availability of sound scientific knowledge inevitably lead unreliable news to spread over the population, preventing people to disentangle them form reliable information. Even if additional studies are needed to replicate and strengthen our results, these findings represent initial evidence to derive recommendations based on actual data for subjects with autoimmune diseases.
$${\text {FE}}^r$$ method with surrogate localization model for hyperelastic composite materials
Authors: Hatano Ryo , Matsubara Seishiro , Moriguchi Shuji , Terada Kenjiro , Yvonnet Julien
Published: October 2020

This study presents a method for constructing a surrogate localization model for a periodic microstructure, or equivalently, a unit cell, to efficiently perform micro-macro coupled analyses of hyperelastic composite materials. The offline process in this approach is to make a response data matrix that stores the microscopic stress distributions in response to various patterns of macroscopic deformation gradients, which is followed by the proper orthogonal decomposition (POD) of the matrix to construct a reduced order model (ROM) of the microscopic analysis (localization) with properly extracted POD bases. Then, response surfaces of the POD coefficients are constructed so that the ROM can be continuous with respect to the input datum, namely, the macroscopic deformation gradient. The novel contributions of this study are the application of the L2 regularization to the interpolation approximations of the POD coefficients by use of radial basis functions (RBFs) to make the response surfaces continuous and the combined use of the cross-validation and the Bayesian optimization to search for the optimal set of parameters in both the RBFs and L2regularization formula. The resulting model can be an alternative to microscopic finite element (FE) analyses in the conventional$${\text {FE}}^2$$FE2method and realizes$${\text {FE}}^r$$FErwith$$1<r<<2$$1<r<<2accordingly. Representative numerical examples of micro-macro coupled analysis with the$${\text {FE}}^r$$FErare presented to demonstrate the capability and promise of the surrogate localization model constructed with the proposed approach in comparison with the results with high-fidelity direct$${\text {FE}}^2$$FE2.
Using movement to inform conservation corridor design for Mojave desert tortoise
Authors: Hromada Steven J. , Esque Todd C. , Vandergast Amy G. , Dutcher Kirsten E. , Mitchell Corey I. , Gray Miranda E. , Chang Tony , Dickson Brett G. , Nussear Kenneth E.
Published: October 2020

Background

Preserving corridors for movement and gene flow among populations can assist in the recovery of threatened and endangered species. As human activity continues to fragment habitats, characterizing natural corridors is important in establishing and maintaining connectivity corridors within the anthropogenic development matrix. The Mojave desert tortoise (Gopherus agassizii) is a threatened species occupying a variety of habitats in the Mojave and Colorado Deserts. Desert tortoises have been referred to as corridor-dwellers, and understanding how they move within suitable habitat can be crucial to defining corridors that will sustain sufficient gene flow to maintain connections among populations amidst the increases in human development.

Methods

To elucidate how tortoises traverse available habitat and interact with potentially inhospitable terrain and human infrastructure, we used GPS dataloggers to document fine-scale movement of individuals and estimate home ranges at ten study sites along the California/Nevada border. Our sites encompass a variety of habitats, including mountain passes that serve as important natural corridors connecting neighboring valleys, and are impacted by a variety of linear anthropogenic features. We used path selection functions to quantify tortoise movements and develop resistance surfaces based on landscape characteristics including natural features, anthropogenic alterations, and estimated home ranges with autocorrelated kernel density methods. Using the best supported path selection models and estimated home ranges, we determined characteristics of known natural corridors and compared them to mitigation corridors (remnant habitat patches) that have been integrated into land management decisions in the Ivanpah Valley.

Results

Tortoises avoided areas of high slope and low perennial vegetation cover, avoided moving near low-density roads, and traveled along linear barriers (fences and flood control berms).

Conclusions

We found that mitigation corridors designated between solar facilities should be wide enough to retain home ranges and maintain function. Differences in home range size and movement resistance between our two natural mountain pass corridors align with differences in genetic connectivity, suggesting that not all natural corridors provide the same functionality. Furthermore, creation of mitigation corridors with fences may have unintended consequences and may function differently than natural corridors. Understanding characteristics of corridors with different functionality will help future managers ensure that connectivity is maintained among Mojave desert tortoise populations.
Usefulness of 18F-FDOPA PET for the management of primary brain tumors: a systematic review of the literature
Authors: Somme François , Bender Laura , Namer Izzie Jacques , Noël Georges , Bund Caroline
Published: October 2020

Contrast-enhanced magnetic resonance imaging is currently the standard of care in the management of primary brain tumors, although certain limitations remain. Metabolic imaging has proven useful for an increasing number of indications in oncology over the past few years, most particularly18F-FDG PET/CT. In neuro-oncology,18F-FDG was insufficient to clearly evaluate brain tumors. Amino-acid radiotracers such as18F-FDOPA were then evaluated in the management of brain diseases, notably tumoral diseases. Even though European guidelines on the use of amino-acid PET in gliomas have been published, it is crucial that future studies standardize acquisition and interpretation parameters. The aim of this article was to systematically review the potential effect of this metabolic imaging technique in numerous steps of the disease: primary and recurrence diagnosis, grading, local and systemic treatment assessment, and prognosis. A total of 41 articles were included and analyzed in this review. It appears that18F-FDOPA PET holds promise as an effective additional tool in the management of gliomas. More consistent prospective studies are still needed.
Posterior segment inflammatory outcomes assessed using fluorescein angiography in the STOP-UVEITIS study
Authors: Sadiq Mohammad Ali , Hassan Muhammad , Afridi Rubbia , Halim Muhammad Sohail , Do Diana V. , Sepah Yasir J. , Nguyen Quan Dong ,   for the STOP-UVEITIS Investigators
Published: October 2020

Background

Although fluorescein angiography (FA) is a frequently used imaging modality in patients with non-infectious uveitis (NIU), it has not been reliably used for objective assessment of posterior segment inflammatory outcomes in these patients. In this index study we report the posterior segment inflammatory outcomes of two different doses of intravenous (IV) infusions of tocilizumab (TCZ), an IL-6 inhibitor, in eyes with NIU using a semi-quantitative FA scoring system.

Methods

STOP-Uveitis is a randomized, multi-center clinical trial conducted at 5 clinical centers across the United States. The study evaluated the role of TCZ in patients with NIU. Thirty-seven (37) patients with NIU were randomized into one of two treatment groups in a ratio of 1:1. Group 1 received IV infusions of 4 mg/kg TCZ and group 2 received IV infusions of 8 mg/kg TCZ. Infusions were given every 4 weeks in both groups until month 6 (primary endpoint). Posterior segment inflammatory outcomes were assessed by evaluating FA at baseline and month 6 by graders at a central reading center. A previously reported, semi-quantitative, scoring system for FA was used to assess signs that represent ongoing inflammatory processes in the posterior segment. These signs included optic disc hyperfluorescence, macular edema, retinal vascular staining and/or leakage, capillary leakage, retinal capillary nonperfusion, neovascularization of the optic disc, neovascularization elsewhere, pinpoint leaks, and retinal staining and/or subretinal pooling. Statistical significance was set at p < 0.05. Main outcome measures included change in posterior segment inflammation as assessed using FA at month 6.

Results

37 eyes (37 patients) were randomized in the STOP-Uveitis study. 30 eyes were found to be eligible for this sub-study based on study criteria. Seven eyes had ungradable images at either baseline or month 6 and were therefore excluded from the analysis. The reduction in FA inflammatory scores at month 6 were statistically significant in both groups (p < 0.05). The difference between the two groups was not significant (p = 0.351).

Conclusions

IV infusions of tocilizumab (both 4 and 8 mg/kg) are effective in improving posterior segment inflammation in eyes with NIU. A semi-quantitative FA scoring system may be used as a reliable outcome measure for assessment of posterior segment inflammation.

ClinicalTrials.gov Identifier: NCT01717170