Miracle-dz/UniFAR-FTUs huggingface dataset:
Maternity care experiences and health needs of migrant women from female genital mutilation–practicing countries in high‐income contexts: A systematic review and meta‐synthesis

BACKGROUND Female genital mutilation (FGM) is a cultural practice defined as the partial or total removal of the external female genitalia for nontherapeutic indications. Due to changing patterns of migration, clinicians in high-income countries are seeing more women from countries where the practice is prevalent. This review aims to understand the sociocultural and health needs of these women and identify opportunities to improve the quality of maternity care for women with FGM. METHODS We undertook a systematic review and meta-synthesis of peer-reviewed primary qualitative research to explore the experience and needs of migrant women with FGM receiving maternity care. A structured search of nine databases was undertaken, screened papers appraised, and a thematic analysis undertaken on data extracted from the findings and discussion sections of included papers. RESULTS Sixteen peer-reviewed studies were included in the systematic review. Four major themes were revealed: Living with fear, stigma, and anxiety; Feelings of vulnerability, distrust, and discrimination; Dealing with past and present ways of life after resettlement; and Seeking support and involvement in health care. CONCLUSIONS The findings suggest that future actions for improving maternity care quality should be focused on woman-centered practice, demonstrating cultural safety and developing mutual trust between a woman and her care providers. Meaningful consultation with women affected by FGM in high-income settings requires cultural sensitivity and acknowledgment of their specific circumstances. This can be achieved by engaging women affected by FGM in service design to provide quality care and ensure woman-focused policy is developed and implemented.
Human aging and longevity are characterized by high levels of mitokines.

Mitochondrial stress elicits the production of stress response molecules indicated as mitokines, including FGF21, GDF15 and Humanin (HN). Many diseases are characterized by progressive mitochondrial dysfunction with alterations of mitokine secretion. It is still controversial whether healthy aging and extreme longevity are accompanied by altered production of mitokines. We analyzed FGF21, HN and GDF15 plasma levels in 693 subjects aged from 21 to 113 years, and the association of these mitokines with parameters of health status. FGF21, HN and GDF15 resulted increased in old age, with the highest levels found in centenarians. These molecules are associated with worsened parameters (such as handgrip strength, insulin sensitivity, total triglycerides), particularly in 70-year-old persons, and their levels are inversely correlated with survival in the oldest subjects. Considering the positive biological effect of these molecules, our results can be interpreted in the framework of the hormetic paradigm as an attempt of the cells/tissues to cope with a stress that can have beneficial or detrimental effects depending on its intensity. Finally, persons with Down Syndrome (characterized by accelerated aging) have higher levels of GDF15 and HN with respect to their siblings, suggesting that these molecules, especially GDF15, could be considered markers of biological age.
Neutrophils as myeloid‐derived suppressor cells

Neutrophils form the first line of defence against invading pathogens, such as bacteria and fungi, as part of the innate immune response. Recently, neutrophils have also been discovered as repressors of adaptive immune responses. Under certain conditions, such as cancer and severe injury, an expansion of immature and mature neutrophils has been observed to induce suppression of T‐cell proliferation. These suppressing cells are known as so‐called myeloid‐derived suppressor cells (MDSCs), a heterogeneous population of granulocytic‐MDSCs and monocytic‐MDSCs. Initially, MDSCs were believed to be a specific immature type of myeloid immune cell released from the bone marrow, but mature neutrophils have also been proposed to have suppressive capacity. However, granulocytic‐MDSCs show a similar morphology and expression of cell surface markers as mature neutrophils. The only characteristic that discriminates granulocytic (g)‐MDSCs from mature neutrophils is their suppressive capacity, raising the question whether human g‐MDSCs and neutrophils are actually different cell types or whether they are one plastic cell type that can functionally polarize from microbial killers to immunosuppressor cells, depending on local conditions. In this review, we will focus on the MDSC activity of circulating mature neutrophils.
Single-walled carbon nanohorn aggregates promotes mitochondrial dysfunction-induced apoptosis in hepatoblastoma cells by targeting SIRT3

Single-walled carbon nanohorns (SWNHs) can accumulate in a variety of cell types or tissues and exert biological effects, which have been demonstrated to induce apoptosis in hepatoblastoma cells. However, the role and molecular mechanisms of SWNHs remain unclear. The mitochondrion is an important subcellular structure and may contribute to apoptosis that is induced by SWNHs in hepatoblastoma cells. To address this question, the mitochondrial function of HepG2 or L02 cells that were treated with SWNHs was examined. The results indicated that SWNHs were able to decrease the mitochondrial membrane potential and suppress the activity of the Na+/K+-ATPase. Secondly, HepG2 cells and L02 cells were treated with SWNHs in vivo and in vitro. The expression of mitochondrial-associated proteins [acyl-CoA synthetase short chain family member 1, Bax, cytochrome C (CYT-C), sodium channel epithelial 1α subunit, sirtuin 3 (SIRT3) and voltage-dependent anion channel 1] was analyzed by western blotting and immunohistochemical staining. The results revealed that SWNH treatment was able to alter the expression of multiple mitochondrial apoptotic pathway-associated proteins in HepG2 cells. SWNH treatment was able upregulate the expression of SIRT3, CYT-C and VDAC1 and downregulate the expression of AceCS2, but it had a more stable effect on SIRT3. However, similar findings were not observed in L02 cells. Therefore, the data from the present study indicated that SWNHs might be used as a safe anticancer agent, where it is able to trigger mitochondrial dysfunction-induced apoptosis by upregulating SIRT3 expression in HepG2 cells.
Identification of Novel HIV-1 Latency-Reversing Agents from a Library of Marine Natural Products

Natural products originating from marine and plant materials are a rich source of chemical diversity and unique antimicrobials. Using an established in vitro model of HIV-1 latency, we screened 257 pure compounds from a marine natural product library and identified 4 (psammaplin A, aplysiatoxin, debromoaplysiatoxin, and previously-described alotaketal C) that induced expression of latent HIV-1 provirus in both cell line and primary cell models. Notably, aplysiatoxin induced similar levels of HIV-1 expression as prostratin but at up to 900-fold lower concentrations and without substantial effects on cell viability. Psammaplin A enhanced HIV-1 expression synergistically when treated in combination with the protein kinase C (PKC) activator prostratin, but not the histone deacetylase inhibitor (HDACi) panobinostat, suggesting that psammaplin A functions as a latency-reversing agent (LRA) of the HDACi class. Conversely, aplysiatoxin and debromoaplysiatoxin synergized with panobinostat but not prostratin, suggesting that they function as PKC activators. Our study identifies new compounds from previously untested marine natural products and adds to the repertoire of LRAs that can inform therapeutic “shock-and-kill”-based strategies to eliminate latent HIV-infected reservoirs.
Pore properties of Orai1 calcium channel dimers and their activation by the STIM1 ER calcium sensor

Store-operated Ca2+ entry signals are mediated by plasma membrane Orai channels activated through intermembrane coupling with Ca2+-sensing STIM proteins in the endoplasmic reticulum (ER). The nature of this elaborate Orai-gating mechanism has remained enigmatic. Based on the Drosophila Orai structure, mammalian Orai1 channels are hexamers comprising three dimeric subunit pairs. We utilized concatenated Orai1 dimers to probe the function of key domains within the channel pore and gating regions. The Orai1-E106Q selectivity-filter mutant, widely considered a dominant pore blocker, was surprisingly nondominant within concatenated heterodimers with Orai1-WT. The Orai1-E106Q/WT heterodimer formed STIM1-activated nonselective cation channels with significantly enlarged apparent pore diameter. Other Glu-106 substitutions entirely blocked the function of heterodimers with Orai1-WT. The hydrophobic pore-lining mutation V102C, which constitutively opens channels, was suppressed by Orai1-WT in the heterodimer. In contrast, the naturally occurring R91W pore-lining mutation associated with human immunodeficiency was completely dominant-negative over Orai-WT in heterodimers. Heterodimers containing the inhibitory K85E mutation extending outward from the pore helix gave an interesting partial effect on both channel activation and STIM1 binding, indicating an important allosteric link between the cytosolic Orai1 domains. The Orai1 C-terminal STIM1-binding domain mutation L273D powerfully blocked STIM1-induced channel activation. The Orai1-L273D/WT heterodimer had drastically impaired STIM1-induced channel gating but, unexpectedly, retained full STIM1 binding. This reveals the critical role of Leu-273 in transducing the STIM1-binding signal into the allosteric conformational change that initiates channel gating. Overall, our results provide important new insights into the role of key functional domains that mediate STIM1-induced gating of the Orai1 channel.
Fatores determinantes na escolha do sistema de custos para dar suporte ao processo de gestão: um estudo nas grandes empresas de Santa Catarina

O artigo analisa os fatores determinantes na escolha do sistema de custos nas grandes empresas de Santa Catarina, para dar suporte ao processo de gestao empresarial. A pesquisa foi realizada em 17 grandes empresas de Santa Catarina, de diversos ramos de atividade. Foram levantados os sistemas de custos utilizados, o tempo de utilizacao do atual sistema, a extensao de implantacao, a integracao entre este sistema e outros sistemas operacionais. Tambem buscou-se informacoes sobre os fatores determinantes na escolha do sistema de custos implementado nas empresas pesquisadas, as duvidas e como estas foram superadas, bem como o papel do sistema de custos na gestao empresarial. A pesquisa realizada e do tipo exploratoria, a partir de entrevistas semi-estruturadas e de analise documental. Os resultados da pesquisa permitiram identificar, como fatores determinantes para escolha de um sistema de custos, O auxilio a tomada de decisoes e a gestao estrategica de custos. O custo de implantacao foi considerado pelas empresas pesquisadas como um fator de pouca relevância. Observou-se que as grandes empresas usam no minimo tres metodos de custeio, um para cada tipo de informacao desejada. Ainda, as empresas pesquisadas foram unânimes em responder que a maior deficiencia dos sistemas de custos e nao oferecerem projecoes e estudos de cenarios.
The consequence of cerebral small vessel disease: Linking brain atrophy to motor impairment in the elderly

In the elderly, brain structural deficits and gait disturbances due to cerebral small vessel disease (CSVD) have been well demonstrated. The relationships among CSVD, brain atrophy, and motor impairment, however, are far from conclusive. Particularly, the effect of CSVD on subcortical nuclear atrophy, motor performance of upper extremities, and associating patterns between brain atrophy and motor impairment remains largely unknown. To address these gaps, this study recruited 770 community‐dwelling subjects (35–82 years of age), including both CSVD and non‐CSVD individuals. For each subject, four motor tests involving upper and lower extremities were completed. High‐resolution structural MRI was applied to extract gray matter (GM) volume, white matter volume, cortical thickness, surface area, and subcortical nuclear (caudate, putamen, pallidum, and thalamus) volumes. The results showed worse motor performance of lower extremities but relatively preserved performance of upper extremities in the CSVD group. Intriguingly, there was a significant association between the worse performance of upper extremities and atrophy of whole‐brain GM and pallidum in the CSVD group but not in the non‐CSVD group. In addition, mediation analysis confirmed a functional CSVD‐to‐“brain atrophy”‐to‐“motor impairment” pathway, that is, a mediating role of thalamic atrophy in the CSVD effect on walking speed in the elderly, indicating that CSVD impairs walking performance through damaging the integrity of the thalamus in aging populations. These findings provide important insight into the functional consequences of CSVD and highlight the importance of evaluating upper extremities functions and exploring their brain mechanisms in CSVD populations during aging.
The Polycomb-Group Repressor MEDEA Attenuates Pathogen Defense1

Pathogen inoculation in Arabidopsis thaliana activates the expression of the imprinted gene MEDEA, a component of the PRC2 complex, which hinders defense against pathogens. Plants recruit positive and negative regulators for fine tuning the balance between growth and development. Negative regulators of pathogen defense generally modulate defense hormone biosynthesis and signaling. Here, we report a mechanism for attenuation of the defense response in Arabidopsis (Arabidopsis thaliana), which is mediated by the polycomb-group repressor MEDEA (MEA). Our results showed that pathogen inoculation or exogenous application of salicylic acid, methyl jasmonate, or the bacterial 22-amino acid domain of flagellin peptide induces the expression of MEA. MEA expression was higher when plants were inoculated with the avirulent strain of Pseudomonas syringae pv. tomato (Pst) carrying the AvrRpt2 effector (Pst-AvrRpt2) compared to the virulent Pst strain. MEA remains suppressed during the vegetative phase via DNA and histone (H3K27) methylation, and only the maternal copy is expressed in the female gametophyte and endosperm via histone and DNA demethylation. In contrast, Pst-AvrRpt2 induces high levels of MEA expression via hyper-accumulation of H3K4me3 at the MEA locus. MEA-overexpressing transgenic plants are susceptible to the fungal pathogen Botrytis cinerea and bacterial pathogens Pst and Pst-AvrRpt2, whereas mea mutant plants are more resistant to bacterial pathogens. AvrRpt2-mediated immunity requires the function of RESISTANCE TO P. SYRINGAE2 (RPS2) in Arabidopsis. Using transcriptional analysis and chromatin immunoprecipitation, we established that MEA directly targets RPS2 and suppresses its transcription. We screened an Arabidopsis cDNA library using MEA as the bait in a yeast two-hybrid assay and identified DROUGHT-INDUCED19, a transcription factor that interacts with MEA and recruits it at the RPS2 promoter. The results identified a previously unknown mechanism of defense response attenuation in plants.
P 2 X 7 receptor activation induces reactive oxygen species formation and cell death in murine EOC 13 microglia

The P2X7 purinergic receptor is a ligand-gated cation channel expressed on leukocytes including microglia. This study aimed to determine if P2X7 activation induces the uptake of organic cations, reactive oxygen species (ROS) formation, and death in the murine microglial EOC13 cell line. Using the murine macrophage J774 cell line as a positive control, RT-PCR, immunoblotting, and immunolabelling established the presence of P2X7 in EOC13 cells. A cytofluorometric assay demonstrated that the P2X7 agonists adenosine-5'triphosphate (ATP) and 2' (3')-O-(4-benzoylbenzoyl) ATP induced ethidium(+) or YO-PRO-1(2+) uptake into both cell lines. ATP induced ethidium+ uptake into EOC13 cells in a concentration-dependent manner, with an EC50 of similar to 130 mu M. The P2X7 antagonists Brilliant Blue G, A438079, AZ10606120, and AZ11645373 inhibited ATP-induced cation uptake into EOC13 cells by 75-100%. A cytofluorometric assay demonstrated that P2X7 activation induced ROS formation in EOC13 cells, via a mechanism independent of Ca2+ influx and K+ efflux. Cytofluorometric measurements of Annexin-V binding and 7AAD uptake demonstrated that P2X7 activation induced EOC13 cell death. The ROS scavenger N-acetyl-L-cysteine impaired both P2X7-induced EOC13 ROS formation and cell death, suggesting that ROS mediate P2X7-induced EOC13 death. In conclusion, P2X7 activation induces the uptake of organic cations, ROS formation, and death in EOC13 microglia.
Adventitious viruses persistently infect three commonly used mosquito cell lines

Mosquito cell lines were first established in the 1960’s and have been used extensively in research to isolate and propagate arthropod-borne (arbo-) viruses, study the invertebrate immune system, and understand virus-vector interactions. Despite their utility as an in vitro tool, these cell lines are poorly defined and may harbor insect-specific viruses that could impact experimental results. Accordingly, we screened four commonly-used mosquito cell lines, C6/36 and U4.4 cells from Aedes albopictus, Aag2 cells from Aedes aegypti, and Hsu cells from Culex quinquefasciatus, for the presence of adventitious viruses. All four cell lines stained positive for double-stranded RNA by immunofluorescence, indicative of RNA virus replication. We subsequently identified viruses infecting Aag2, U4.4 and Hsu cell lines using untargeted next-generation sequencing, but not C6/36 cells. Sequences from viruses in the families Birnaviridae, Bunyaviridae, Flaviviridae, and Rhabdoviridae were abundant in the mosquito cell lines. PCR confirmation revealed that these sequences stem from active viral replication and/or integration into the cellular genome. Our results show that these commonly-used mosquito cell lines are persistently-infected with several viruses. This finding may be critical to interpreting data generated in these systems.
The choroid plexus sodium‐bicarbonate cotransporter NBCe2 regulates mouse cerebrospinal fluid pH

Normal pH is crucial for proper functioning of the brain, and disorders increasing the level of CO2 in the blood lead to a decrease in brain pH. CO2 can easily cross the barriers of the brain and will activate chemoreceptors leading to an increased exhalation of CO2. The low pH, however, is harmful and bases such as HCO3− are imported across the brain barriers in order to normalize brain pH. We show that the HCO3− transporter NBCe2 in the choroid plexus of the blood‐cerebrospinal fluid barrier is absolutely necessary for normalizing CSF pH during high levels of CO2. This discovery represents a significant step in understanding the molecular mechanisms behind regulation of CSF pH during acid‐base disturbances, such as chronic lung disease.
The Flaws and Future of Islet Volume Measurements

When working with isolated islet preparations, measuring the volume of tissue is not a trivial matter. Islets come in a large range of sizes and are often contaminated with exocrine tissue. Many factors complicate the procedure, and yet knowledge of the islet volume is essential for predicting the success of an islet transplant or comparing experimental groups in the laboratory. In 1990, Ricordi presented the islet equivalency (IEQ), defined as one IEQ equaling a single spherical islet of 150 μm in diameter. The method for estimating IEQ was developed by visualizing islets in a microscope, estimating their diameter in 50 μm categories and calculating a total volume for the preparation. Shortly after its introduction, the IEQ was adopted as the standard method for islet volume measurements. It has helped to advance research in the field by providing a useful tool improving the reproducibility of islet research and eventually the success of clinical islet transplants. However, the accuracy of the IEQ method has been questioned for years and many alternatives have been proposed, but none have been able to replace the widespread use of the IEQ. This article reviews the history of the IEQ, and discusses the benefits and failings of the measurement. A thorough evaluation of alternatives for estimating islet volume is provided along with the steps needed to uniformly move to an improved method of islet volume estimation. The lessons learned from islet researchers may serve as a guide for other fields of regenerative medicine as cell clusters become a more attractive therapeutic option.
Obesity and Aging in the Drosophila Model

Being overweight increases the risk of many metabolic disorders, but how it affects lifespan is not completely clear. Not all obese people become ill, and the exact mechanism that turns excessive fat storage into a health-threatening state remains unknown. Drosophila melanogaster has served as an excellent model for many diseases, including obesity, diabetes, and hyperglycemia-associated disorders, such as cardiomyopathy or nephropathy. Here, we review the connections between fat storage and aging in different types of fly obesity. Whereas obesity induced by high-fat or high-sugar diet is associated with hyperglycemia, cardiomyopathy, and in some cases, shortening of lifespan, there are also examples in which obesity correlates with longevity. Transgenic lines with downregulations of the insulin/insulin-like growth factor (IIS) and target of rapamycin (TOR) signaling pathways, flies reared under dietary restriction, and even certain longevity selection lines are obese, yet long-lived. The mechanisms that underlie the differential lifespans in distinct types of obesity remain to be elucidated, but fat turnover, inflammatory pathways, and dysregulations of glucose metabolism may play key roles. Altogether, Drosophila is an excellent model to study the physiology of adiposity in both health and disease.
Nonlinearity mitigation of intensity modulation and coherent detection systems.

Coherent optical communication systems are still too expensive for metro and short reach networks in the near future. Coherent detection with an intensity modulator replacing a costly dual-polarization in-phase and quadrature modulator could offer a good trade-off between cost and performance for metro networks. The major performance limit of such systems is the nonlinearity. To the best of our knowledge, this Letter offers the first known investigation on nonlinearity of a high speed intensity modulation and coherent detection system using an integrated laser and electro-absorption modulator. Advanced nonlinearity mitigation digital signal processing (DSP) are proposed including a 2×1 multiple-input single-output complex transversal Volterra feed-forward equalizer (FFE) filter, a first proposed post-FFE noise cancellation filter taking into account both pre- and post-cursor noise correlations based on a simple autocorrelation coefficient calculation, and a maximum likelihood sequence estimator. The receiver DSP needs no carrier and phase recovery that is required by a conventional coherent receiver DSP. Results show that, compared to a simple linear FFE equalization, the proposed nonlinear DSP enables over 8 and 4 dB improvement in optical signal to noise ratio (OSNR) sensitivity at 7% overhead hard-decision feed-forward error correction (FEC) and 20% overhead soft-decision FEC threshold bit error rates (BERs), respectively, for a 56 Gb/s intensity modulation and coherent detection system. To the best of our knowledge, a record 18 dB OSNR sensitivity at a hard-decision FEC threshold BER of 3.8×10-3 is also achieved.