Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding barriers to implementing referral procedures in the rural and semi-urban district hospitals in Tanzania: Experiences of healthcare providers working in maternity units

Introduction Maternal and perinatal deaths occurring in low and middle income countries could be prevented with timely access to maternal and new-born care. In order to increase access to maternal and child health services, a well-functioning referral system that allows for continuity of care across different tiers of healthcare is required. A reliable healthcare system, with adequate numbers of skilled staff, resources and mechanisms, is critical to ensuring that access to care is available when the need arises. Material and methods This descriptive, qualitative study design was used to explore barriers to implementing a reliable referral system. Twelve individual qualitative interviews were conducted with health care providers working in rural and semi-urban district hospitals in the Northern, Western, Eastern and Southern zones of Tanzania. Thematic analysis guided analysis of data. Results Three (3) main and interconnected themes were abstracted from the data relating to participants’ experiences of referring women with obstetric complications to adequate obstetric care. These were: 1. Adhering to a rigid referral protocol; 2. Completing the referral of women to an adequate health facility and 3. Communicating the condition of the woman with obstetric complications between the referring and receiving facilities. Conclusion Because of referral regulations, assistant medical officers were unable to make referral decisions even when they felt that a referral was needed. The lack of availability of hospital transport as well as the lack of a reliable feedback mechanism, prohibited effective referrals of patients. The Ministry of Health should revise the referral protocol to allow all clinicians to provide referrals, including assistant medical officers- who make up the majority of clinical staff in rural health care facilities. A mechanism to ensure effective communication between the referral facility and the tertiary care hospital should be instituted for quality and continuity of care. Furthermore, health care facilities should put aside budget for fuelling the ambulance for effective referrals.
Investigation of Interaction of Noble Metals (Cu, Ag, Au, Pt and Ir) with Nanosheets

Two-dimensional nanomaterials, such as graphene and hexagonal boron nitride nanosheets, have attracted tremendous interest in the research community and as a starting point for the development of nanotechnology. Using classical applied mathematical modeling, we derive explicit analytical expressions to determine the binding energies of noble metals, including copper, silver, gold, platinum and iridium (Cu, Ag, Au, Pt and Ir) atoms, on graphene and hexagonal boron nitride nanosheets. We adopt the 6–12 Lennard–Jones potential function, together with the continuous approach, to determine the preferred minimum energy position of an offset metal atom above the surface of the graphene and hexagonal boron nitride nanosheets. The main results of this study are analytical expressions of the interaction energies, which we then utilize to report the mechanism of adsorption of the metal atoms on graphene and hexagonal boron nitride surfaces. The results show that the minimum binding energy occured when Cu, Ag, Au, Pt and Ir were set at perpendicular distances in the region from 3.302 Å to 3.683 Å above the nanosheet surface, which correspond to adsorption energies in the region ranging from 0.842 to 2.978 (kcal/mol). Our results might assist in providing information on the interaction energies between the metal atoms and the two-dimensional nanomaterials.
Microglia Depletion-Induced Remodeling of Extracellular Matrix and Excitatory Synapses in the Hippocampus of Adult Mice

The extracellular matrix (ECM) plays a key role in synaptogenesis and the regulation of synaptic functions in the central nervous system. Recent studies revealed that in addition to dopaminergic and serotoninergic neuromodulatory systems, microglia also contribute to the regulation of ECM remodeling. In the present work, we investigated the physiological role of microglia in the remodeling of perineuronal nets (PNNs), predominantly associated with parvalbumin-immunopositive (PV+) interneurons, and the perisynaptic ECM around pyramidal neurons in the hippocampus. Adult mice were treated with PLX3397 (pexidartinib), as the inhibitor of colony-stimulating factor 1 receptor (CSF1-R), to deplete microglia. Then, confocal analysis of the ECM and synapses was performed. Although the elimination of microglia did not alter the overall number or intensity of PNNs in the CA1 region of the hippocampus, it decreased the size of PNN holes and elevated the expression of the surrounding ECM. In the neuropil area in the CA1 str. radiatum, the depletion of microglia increased the expression of perisynaptic ECM proteoglycan brevican, which was accompanied by the elevated expression of presynaptic marker vGluT1 and the increased density of dendritic spines. Thus, microglia regulate the homeostasis of pre- and postsynaptic excitatory terminals and the surrounding perisynaptic ECM as well as the fine structure of PNNs enveloping perisomatic—predominantly GABAergic—synapses.
The potential for diversion of prescribed opioids among orthopaedic patients: Results of an anonymous patient survey

Introduction Diversion of prescription opioid medication is a contributor to the opioid epidemic. Safe handling practices can reduce the risk of diversion. We aimed to understand: 1) if orthopaedic patients received instructions on how to safely handle opioids, 2) their typical storage/disposal practices, and 3) their willingness to participate in an opioid disposal program (ODP). Methods Cross-sectional study of adult orthopaedic patients who completed an anonymous survey on current or past prescription opioid use, instruction on handling, storage and disposal practices, presence of children in the household, and willingness to participate in an ODP. Frequencies and percentages of responses were computed, both overall and stratified by possession of unused opioids. Results 569 respondents who reported either current or past prescription opioid use were analyzed. 44% reported receiving storage instructions and 56% reported receiving disposal instructions from a health care provider. Many respondents indicated unsafe handling practices: possessing unused opioids (34%), using unsafe storage methods (90%), and using unsafe disposal methods (34%). Respondents with unused opioids were less likely to report receiving handling instructions or using safe handling methods, and 47% of this group reported having minors or young adults in the household. Respondents who received storage and disposal instructions were more likely to report safe storage and disposal methods. Seventy-four percent of respondents reported that they would participate in an ODP. Conclusion While many orthopaedic patients report inadequate education on safe opioid handling and using unsafe handling practices, findings suggest targeted education is associated with better behaviours. However, patients are willing to safely dispose of unused medication if provided a convenient option. These findings suggest a need to address patient knowledge and behavior regarding opioid handling to reduce the risk of opioid diversion.
Serotonergic–Muscarinic Interaction within the Prefrontal Cortex as a Novel Target to Reverse Schizophrenia-Related Cognitive Symptoms

Recent studies revealed that the activation of serotonergic 5-HT1A and muscarinic M1, M4, or M5 receptors prevent MK-801-induced cognitive impairments in animal models. In the present study, the effectiveness of the simultaneous activation of 5-HT1A and muscarinic receptors at preventing MK-801-induced cognitive deficits in novel object recognition (NOR) or Y-maze tests was investigated. Activators of 5-HT1A (F15599), M1 (VU0357017), M4 (VU0152100), or M5 (VU0238429) receptors administered at top doses for seven days reversed MK-801-induced deficits in the NOR test, similar to the simultaneous administration of subeffective doses of F15599 (0.05 mg/kg) with VU0357017 (0.15 mg/kg), VU0152100 (0.05 mg/kg), or VU0238429 (1 mg/kg). The compounds did not prevent the MK-801-induced impairment when administered acutely. Their activity was less evident in the Y-maze. Pharmacokinetic studies revealed high brain penetration of F15599 (brain/plasma ratio 620%), which was detected in the frontal cortex (FC) up to 2 h after administration. Decreases in the brain penetration properties of the compounds were observed after acute administration of the combinations, which might have influenced behavioral responses. This negative effect on brain penetration was not observed when the compounds were administered repeatedly. Based on our results, prolonged administration of a 5-HT1A activator with muscarinic receptor ligands may be effective at reversing cognitive decline related to schizophrenia, and the FC may play a critical role in this interaction.
Disruption of RING and PHD Domains of TRIM28 Evokes Differentiation in Human iPSCs

TRIM28, a multi-domain protein, is crucial in the development of mouse embryos and the maintenance of embryonic stem cells’ (ESC) self-renewal potential. As the epigenetic factor modulating chromatin structure, TRIM28 regulates the expression of numerous genes and is associated with progression and poor prognosis in many types of cancer. Because of many similarities between highly dedifferentiated cancer cells and normal pluripotent stem cells, we applied human induced pluripotent stem cells (hiPSC) as a model for stemness studies. For the first time in hiPSC, we analyzed the function of individual TRIM28 domains. Here we demonstrate the essential role of a really interesting new gene (RING) domain and plant homeodomain (PHD) in regulating pluripotency maintenance and self-renewal capacity of hiPSC. Our data indicate that mutation within the RING or PHD domain leads to the loss of stem cell phenotypes and downregulation of the FGF signaling. Moreover, impairment of RING or PHD domain results in decreased proliferation and impedes embryoid body formation. In opposition to previous data indicating the impact of phosphorylation on TRIM28 function, our data suggest that TRIM28 phosphorylation does not significantly affect the pluripotency and self-renewal maintenance of hiPSC. Of note, iPSC with disrupted RING and PHD functions display downregulation of genes associated with tumor metastasis, which are considered important targets in cancer treatment. Our data suggest the potential use of RING and PHD domains of TRIM28 as targets in cancer therapy.
Laboratory Diagnosis of Porphyria

Porphyrias are a group of diseases that are clinically and genetically heterogeneous and originate mostly from inherited dysfunctions of specific enzymes involved in heme biosynthesis. Such dysfunctions result in the excessive production and excretion of the intermediates of the heme biosynthesis pathway in the blood, urine, or feces, and these intermediates are responsible for specific clinical presentations. Porphyrias continue to be underdiagnosed, although laboratory diagnosis based on the measurement of metabolites could be utilized to support clinical suspicion in all symptomatic patients. Moreover, the measurement of enzymatic activities along with a molecular analysis may confirm the diagnosis and are, therefore, crucial for identifying pre-symptomatic carriers. The present review provides an overview of the laboratory assays used most commonly for establishing the diagnosis of porphyria. This would assist the clinicians in prescribing appropriate diagnostic testing and interpreting the testing results.
Oxygen Biosensors and Control in 3D Physiomimetic Experimental Models

Traditional cell culture is experiencing a revolution moving toward physiomimetic approaches aiming to reproduce healthy and pathological cell environments as realistically as possible. There is increasing evidence demonstrating that biophysical and biochemical factors determine cell behavior, in some cases considerably. Alongside the explosion of these novel experimental approaches, different bioengineering techniques have been developed and improved. Increased affordability and popularization of 3D bioprinting, fabrication of custom-made lab-on-a chip, development of organoids and the availability of versatile hydrogels are factors facilitating the design of tissue-specific physiomimetic in vitro models. However, lower oxygen diffusion in 3D culture is still a critical limitation in most of these studies, requiring further efforts in the field of physiology and tissue engineering and regenerative medicine. During recent years, novel advanced 3D devices are introducing integrated biosensors capable of monitoring oxygen consumption, pH and cell metabolism. These biosensors seem to be a promising solution to better control the oxygen delivery to cells and to reproduce some disease conditions involving hypoxia. This review discusses the current advances on oxygen biosensors and control in 3D physiomimetic experimental models.
The Role of Mitochondrial Function in Peripheral Arterial Disease: Insights from Translational Studies

Recent evidence demonstrates an involvement of impaired mitochondrial function in peripheral arterial disease (PAD) development. Specific impairments have been assessed by different methodological in-vivo (near-infrared spectroscopy, 31P magnetic resonance spectroscopy), as well as in-vitro approaches (Western blotting of mitochondrial proteins and enzymes, assays of mitochondrial function and content). While effects differ with regard to disease severity, chronic malperfusion impacts subcellular energy homeostasis, and repeating cycles of ischemia and reperfusion contribute to PAD disease progression by increasing mitochondrial reactive oxygen species production and impairing mitochondrial function. With the leading clinical symptom of decreased walking capacity due to intermittent claudication, PAD patients suffer from a subsequent reduction of quality of life. Different treatment modalities, such as physical activity and revascularization procedures, can aid mitochondrial recovery. While the relevance of these modalities for mitochondrial functional recovery is still a matter of debate, recent research indicates the importance of revascularization procedures, with increased physical activity levels being a subordinate contributor, at least during mild stages of PAD. With an additional focus on the role of revascularization procedures on mitochondria and the identification of suitable mitochondrial markers in PAD, this review aims to critically evaluate the relevance of mitochondrial function in PAD development and progression.
Microbial Dynamics and In Vitro Degradation of Plant Secondary Metabolites in Hanwoo Steer Rumen Fluids

Simple Summary In the current study, we investigated changes in the levels of plant secondary metabolites (PSMs) in a rumen buffer in vitro model and identified the microbial dynamics of the rumen sample. The data suggested that the different types of PSM including luteolin, ferulic acid, caffeic acid, coumaric acid, rutin, myricetin, vitexin, kaempferol, and quercetin were decreased after 12 h of incubation in the rumen fluid (p ≤ 0.05). In contrast, the propyl gallate concentration was not significantly changed even after 24 h of incubation in rumen fluid compared to other metabolites. Microbial dynamics study showed that the Firmicutes, Bacterodetes, Actinobacteria, and Syngergistetes were the dominant phyla found in rumen fluids. Overall, data suggested that most polyphenolic compounds may degrade or reform new complex structures in the rumen. Further in vivo studies are needed to determine the PSM conversion rate and the final products from native PSM when undergoing degradation or reforming new complexes, and the effect on the microbiome. Abstract Plant secondary metabolite (PSM) degradations and feed breakdown into small particles may occur primarily in the rumen. It is possible to predict the rate and extent of feed disappearance in the rumen during incubation by different in vitro techniques, which differ based on the PSM structures, including phenolics, and flavonoids. However, PSM degradation and conversion efficiency in the rumen remains unclear. This study’s objective was to evaluate the in vitro degradation of a group of PSMs in the rumen fluid, collected from Hanwoo steer samples. PSMs including rutin, vitexin, myricetin, p-coumaric acid, ferulic acid, caffeic acid, quercetin, luteolin, propyl gallate, and kaempferol were used in their pure forms at 1mg/250 mL in a rumen fluid buffer system. The mixture of selected PSMs and buffer was incubated at 39 °C for 12–72 h, and samples were collected every 12 h and analyzed by a high-performance liquid chromatography-diode array detector (HPLC-DAD) to determine the biotransformation of the polyphenolics. The results revealed that the luteolin, ferulic acid, caffeic acid, coumaric acid, rutin, myricetin, vitexin, kaempferol, and quercetin were decreased after 12 h of incubation in the rumen fluid (p ≤ 0.05) and were more than 70% decreased at 72 h. In contrast, the propyl gallate concentrations were not significantly changed after 24 h of incubation in rumen fluid compared to other metabolites. Finally, microbial dynamics study showed that the Firmicutes, Bacterodetes, Actinobacteria, and Syngergistetes were the dominant phyla found in rumen fluids. The data suggest that most polyphenolic compounds may degrade or reform new complex structures in the rumen.
Salivary Leucocytes as In Vitro Model to Evaluate Nanoparticle-Induced DNA Damage

Metal oxide nanoparticles (NPs) have a wide variety of applications in many consumer products and biomedical practices. As a result, human exposure to these nanomaterials is highly frequent, becoming an issue of concern to public health. Recently, human salivary leucocytes have been proposed as an adequate non-invasive alternative to peripheral blood leucocytes to evaluate genotoxicity in vitro. The present study focused on proving the suitability of salivary leucocytes as a biomatrix in the comet assay for in vitro nanogenotoxicity studies, by testing some of the metal oxide NPs most frequently present in consumer products, namely, titanium dioxide (TiO2), zinc oxide (ZnO), and cerium dioxide (CeO2) NPs. Primary and oxidative DNA damage were evaluated by alkaline and hOGG1-modified comet assay, respectively. Any possible interference of the NPs with the methodological procedure or the hOGG1 activity was addressed before performing genotoxicity evaluation. Results obtained showed an increase of both primary and oxidative damage after NPs treatments. These data support the use of salivary leucocytes as a proper and sensitive biological sample for in vitro nanogenotoxicity studies, and contribute to increase the knowledge on the impact of metal oxide NPs on human health, reinforcing the need for a specific regulation of the nanomaterials use.
On-Surface Synthesis of Ligands to Elaborate Coordination Polymers on an Au(111) Surface

On-surface metal-organic polymers have emerged as a class of promising 2D materials. Here, we propose a new strategy to obtain coordination polymers by transforming supramolecular networks into coordination polymers by surface-assisted cyclo-dehydrogenation of organic building blocks. All nanostructures are fully characterized by using scanning tunneling microscopy under ultra-high vacuum on a gold surface. We demonstrated that the balance between molecule-molecule interaction and molecule-substrate interaction can be drastically modified by a strong modification of the geometry of the molecules thanks to a thermal annealing. This new way is an efficient method to elaborate on-surface coordination polymers.
Alkylaminophenol and GPR17 Agonist for Glioblastoma Therapy: A Combinational Approach for Enhanced Cell Death Activity

Drug resistance and tumor heterogeneity limits the therapeutic efficacy in treating glioblastoma, an aggressive infiltrative type of brain tumor. GBM cells develops resistance against chemotherapeutic agent, temozolomide (TMZ), which leads to the failure in treatment strategies. This enduring challenge of GBM drug resistance could be rational by combinatorial targeted therapy. Here, we evaluated the combinatorial effect of phenolic compound (2-(3,4-dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol (THTMP), GPR17 agonist 2-({5-[3-(Morpholine-4-sulfonyl)phenyl]-4-[4-(trifluoromethoxy)phenyl]-4H-1,2,4-triazol-3-yl}sulfanyl)-N-[4-(propan-2-yl)phenyl]acetamide (T0510.3657 or T0) with the frontline drug, TMZ, on the inhibition of GBM cells. Mesenchymal cell lines derived from patients’ tumors, MMK1 and JK2 were treated with the combination of THTMP + T0, THTMP + TMZ and T0 + TMZ. Cellular migration, invasion and clonogenicity assays were performed to check the migratory behavior and the ability to form colony of GBM cells. Mitochondrial membrane permeability (MMP) assay and intracellular calcium, [Ca2+]i, assay was done to comprehend the mechanism of apoptosis. Role of apoptosis-related signaling molecules was analyzed in the induction of programmed cell death. In vivo validation in the xenograft models further validates the preclinical efficacy of the combinatorial drug. GBM cells exert better synergistic effect when exposed to the cytotoxic concentration of THTMP + T0, than other combinations. It also inhibited tumor cell proliferation, migration, invasion, colony-forming ability and cell cycle progression in S phase, better than the other combinations. Moreover, the combination of THTMP + T0 profoundly increased the [Ca2+]i, reactive oxygen species in a time-dependent manner, thus affecting MMP and leading to apoptosis. The activation of intrinsic apoptotic pathway was regulated by the expression of Bcl-2, cleaved caspases-3, cytochrome c, HSP27, cIAP-1, cIAP-2, p53, and XIAP. The combinatorial drug showed promising anti-tumor efficacy in GBM xenograft model by reducing the tumor volume, suggesting it as an alternative drug to TMZ. Our findings indicate the coordinated administration of THTMP + T0 as an efficient therapy for inhibiting GBM cell proliferation.