Miracle-dz/UniFAR-FTUs huggingface dataset:
Bioluminescence calcium imaging of network dynamics and their cholinergic modulation in slices of cerebral cortex from male rats

The activity of neuronal ensembles was monitored in neocortical slices from male rats using wide‐field bioluminescence imaging of a calcium sensor formed with the fusion of green fluorescent protein and aequorin (GA) and expressed through viral transfer. GA expression was restricted to pyramidal neurons and did not conspicuously alter neuronal morphology or neocortical cytoarchitecture. Removal of extracellular magnesium or addition of GABA receptor antagonists triggered epileptiform flashes of variable amplitude and spatial extent, indicating that the excitatory and inhibitory networks were functionally preserved in GA‐expressing slices. We found that agonists of muscarinic acetylcholine receptors largely increased the peak bioluminescence response to local electrical stimulation in layer I or white matter, and gave rise to a slowly decaying response persisting for tens of seconds. The peak increase involved layers II/III and V and did not result in marked alteration of response spatial properties. The persistent response involved essentially layer V and followed the time course of the muscarinic afterdischarge depolarizing plateau in layer V pyramidal cells. This plateau potential triggered spike firing in layer V, but not layer II/III pyramidal cells, and was accompanied by recurrent synaptic excitation in layer V. Our results indicate that wide‐field imaging of GA bioluminescence is well suited to monitor local and global network activity patterns, involving different mechanisms of intracellular calcium increase, and occurring on various timescales.
Sevoflurane, Propofol and Carvedilol Block Myocardial Protection by Limb Remote Ischemic Preconditioning

The effects of remote ischemic preconditioning (RIPC) in cardiac surgery have been inconsistent. We investigated whether anesthesia or beta-blockers interfere with RIPC cardioprotection. Fifty patients undergoing cardiac surgery were randomized to receive limb RIPC (four cycles of 5-min of upper arm cuff inflation/deflation) in the awake state (no-anesthesia; n = 17), or under sevoflurane (n = 17) or propofol (n = 16) anesthesia. In a separate crossover study, 11 healthy volunteers received either carvedilol or no medication prior to RIPC. Plasma dialysates were obtained and perfused through an isolated male Sprague–Dawley rat heart subjected to 30-min ischemia/60-min reperfusion, following which myocardial infarct (MI) size was determined. In the cardiac surgery study, pre-RIPC MI sizes were similar among the groups (39.7 ± 4.5% no-anesthesia, 38.9 ± 5.3% sevoflurane, and 38.6 ± 3.6% propofol). However, post-RIPC MI size was reduced in the no-anesthesia group (27.5 ± 8.0%; p < 0.001), but not in the anesthesia groups (35.7 ± 6.9% sevoflurane and 35.8 ± 5.8% propofol). In the healthy volunteer study, there was a reduction in MI size with RIPC in the no-carvedilol group (41.7 ± 4.3% to 30.6 ± 8.5%; p < 0.0001), but not in the carvedilol group (41.0 ± 4.0% to 39.6 ± 5.6%; p = 0.452). We found that the cardioprotective effects of limb RIPC were abolished under propofol or sevoflurane anesthesia and in the presence of carvedilol therapy.
Synthesis of Cyanate Esters Based on Mono-O-Methylated Bisphenols with Sulfur-Containing Bridges

We described a synthetic approach to bisphenol-based monocyanate esters based on mono-O-methylation of parental bisphenols followed by cyanation of the residual phenolic hydroxyl. Structures of the synthesized compounds were determined by the application of IR, NMR 1H and 13C spectroscopies, EI and MALDI mass spectrometry, and purity of the final product was controlled by HPLC. We showed that stability of the cyanate esters depends on the nature of the bridging group. Temperature range of thermally initiated cyclotrimerization of synthesized monocyanate ester, as well as reaction enthalpy, was determined by differential scanning calorimetry (DSC).
Exploiting the vulnerable active site of a copper-only superoxide dismutase to disrupt fungal pathogenesis

Copper-only superoxide dismutases (SODs) represent a new class of SOD enzymes that are exclusively extracellular and unique to fungi and oomycetes. These SODs are essential for virulence of fungal pathogens in pulmonary and disseminated infections, and we show here an additional role for copper-only SODs in promoting survival of fungal biofilms. The opportunistic fungal pathogen Candida albicans expresses three copper-only SODs, and deletion of one of them, SOD5, eradicated candidal biofilms on venous catheters in a rodent model. Fungal copper-only SODs harbor an irregular active site that, unlike their Cu,Zn-SOD counterparts, contains a copper co-factor unusually open to solvent and lacks zinc for stabilizing copper binding, making fungal copper-only SODs highly vulnerable to metal chelators. We found that unlike mammalian Cu,Zn-SOD1, C. albicans SOD5 indeed rapidly loses its copper to metal chelators such as EDTA, and binding constants for Cu(II) predict that copper-only SOD5 has a much lower affinity for copper than does Cu,Zn-SOD1. We screened compounds with a variety of indications and identified several metal-binding compounds, including the ionophore pyrithione zinc (PZ), that effectively inhibit C. albicans SOD5 but not mammalian Cu,Zn-SOD1. We observed that PZ both acts as an ionophore that promotes uptake of toxic metals and inhibits copper-only SODs. The pros and cons of a vulnerable active site for copper-only SODs and the possible exploitation of this vulnerability in antifungal drug design are discussed.
Evaluation of Combination Antiemetic Therapy on CINV in Patients With Gynecologic Cancer Receiving TC Chemotherapy

Background/Aim: The incidence of delayed chemotherapy-induced nausea and vomiting (CINV), especially nausea, in gynecologic cancer patients who receive paclitaxel and carboplatin (TC) chemotherapy is unclear. We assessed risk factors for delayed CINV in these patients, and examined whether it was controlled with combination antiemetic therapy. Materials and Methods: Data were pooled from two prospective studies, and compared between the two antiemetic prophylaxis groups using inverse probability of treatment weighted (IPTW) analysis. Results: Among the 182 evaluable patients (mean age: 56.2 years), three antiemetics gave better overall control than two for delayed nausea (42.9% vs. 57.4%,) and vomiting (13.8% vs. 34.5%). Risk factor for delayed nausea was age [odds ratio (OR)=0.953; p=0.0898[and use of two antiemetics (vs. three antiemetics) for delayed vomiting (OR=0.304; p=0.0732). Conclusion: A combination of three antiemetics controls delayed CINV among patients who undergo TC chemotherapy. Identification of risk factors can facilitate personalized treatments.
Interferon-induced transmembrane protein-3 rs12252-CC is associated with low differentiation and progression of hepatocellular carcinoma

Abstract Interferon-induced transmembrane protein 3 (IFITM3) is a component of ISG (Interferon-Stimulated Gene) family. The association between IFITM3 and hepatocellular carcinoma (HCC) has been reported. While the relationship between this genetic variation and the progress of HCC remains unclear. To address this issue, we explore the relationship between the IFITM3-rs12252 genetic variants and the progression of HCC in this study. A total of 336 candidates were enrolled in the study, including 156 patients with HBV related HCC and 180 patients with chronic Hepatitis B infections or liver cirrhosis. Liver cirrhosis or chronic hepatitis B were diagnosed with clinical characteristics and staging, laboratory testing, and imaging results of viral infection and hepatic damage. Polymerase chain reaction (PCR) was employed to determine the gene polymorphism of IFITM3, and analyzed with the GraphPad Prism v 5. The patients with HCC had a significantly higher proportion of IFITM3 rs12252-CC as compared with the patients with chronic HBV infection or liver cirrhosis. Moreover, the distribution of CC genotype in HCC patients with low differentiation was significantly higher than that in those with high differentiation. Furthermore, the patients with CC genotype were found with bigger tumor size, higher percentage of vascular thrombosis, higher distribution of low differentiation and higher 5-year relapse rate than those with CT/TT genotypes. This study indicates a correlation between the IFITM3-rs12252 CC genotype and the progression of HCC.
Access to human rights for persons using prosthetic and orthotic assistive devices in Sierra Leone

Abstract Purpose: To evaluate the access to human rights of persons with disabilities who use prosthetic and orthotic assistive devices, and to compare groups of participants in terms of gender, residential area, income, and type and level of assistive device. The addressed areas were rights to: health, a standard of living adequate for health, education, marry and establish a family, vote, and work. Methods: Questionnaires were used to collect self-reported data from 139 lower-limb prosthetic and orthotic users in Sierra Leone. Results: About half of the participants considered their overall physical health good, while 37% said their mental health was bad. Most said they lacked access to medical care. About half of the participants had regular access to safe drinking water. Most had reasonable housing and 60% could read and write. Half of the participants were married and 70% had children. Almost all reported that they could vote if desired and about half were working. Conclusions: There is still a need for improved access to medical care when needed for persons with lower limb physical disability in Sierra Leone. Better access to food and clean water are also necessary to facilitate a standard of living adequate for health, to realize the health rights of persons with disabilities. Implications for rehabilitation In Sierra Leone, persons with disabilities need a source of regular income to access basic needs, including clean water, access to food, medical care, and medications which should be considered in addition to providing rehabilitation services. To facilitate implementation of the Convention on the Rights of Persons with Disabilities, Sierra Leone’s health system needs to be strengthened: an increased number of healthcare staff should be educated, knowledge of disability should be improved in the general public to reduce negative attitudes toward persons with disabilities, persons with disabilities should be included in mainstream health services, and national development policies should target sustainable development goals to a greater extent than during the millennium development goal era.
Cumulative Incidence of West Nile Virus Infection, Continental United States, 1999–2016

Using reported case data from ArboNET and previous seroprevalence data stratified by age and sex, we conservatively estimate that ≈7 million persons in the United States have been infected with West Nile virus since its introduction in 1999. Our data support the need for public health interventions and improved surveillance.
Melatonin multiple effects on brown adipose tissue molecular machinery

Brown adipose tissue (BAT) influences energy balance through nonshivering thermogenesis, and its metabolism daily and seasonal variations are regulated by melatonin through partially known mechanisms. We evaluated the role of melatonin in BAT molecular machinery of male Control, pinealectomized (PINX), and melatonin‐treated pinealectomized (PINX/Mel) adult rats. BAT was collected either every 3 hours over 24 hours or after cold or high‐fat diet (HFD) acute exposure. HFD PINX animals presented decreased Dio2 expression, while HFD PINX/Mel animals showed increased Dio2, Ucp1, and Cidea expression. Cold‐exposed PINX rats showed decreased Dio2 and Lhs expression, and melatonin treatment augmented Adrβ3, Dio2, Ucp1, and Cidea expression. Daily profiles analyses showed altered Dio2, Lhs, Ucp1, Pgc1α, and Cidea gene and UCP1 protein expression in PINX animals, leading to altered rhythmicity under sub‐thermoneutral conditions, which was partially restored by melatonin treatment. The same was observed for mitochondrial complexes I, II, and IV protein expression and enzyme activity. Melatonin absence seems to impair BAT responses to metabolic challenges, and melatonin replacement reverses this effect, with additional increase in the expression of crucial genes, suggesting that melatonin plays an important role in several key points of the thermogenic activation pathway, influencing both the rhythmic profile of the tissue and its ability to respond to metabolic challenges, which is crucial for the organism homeostasis.
Efficacy of Dalbavancin and Telavancin in the Treatment of Acute Bacterial Skin and Skin Structure Infections.

Objectives Two glycopeptide analogues, such as dalbavancin and telavancin, with improved pharmacokinetic/pharmacodynamic parameters have been developed. These two glycopeptide analogues are approved by Food and Drug Administration (FDA) for treatment of various Gram-positive bacterial skin infections. Materials and methods We have conducted an open labelled prospective randomized study to compare the efficacy of these two drugs. A total of 200 patients diagnosed with acute bacterial skin and skin structure infections (ABSSSI) were recruited for the study. They were randomized to receive either a single dose of dalbavancin 1500 mg i.v (Group I) or telavancin 10 mg/kg intravenously (i.v.) every 24 hours for six days (Group II). The skin infection rating score (SIRS) was calculated on Day 0 for all patients at the time of diagnosis. Signs and symptoms of the lesions were assessed based on the following factors: blistering, exudate/pus, erythema/inflammation and itching/pain. Each factor was classified as one of the following: absent - 0, minimal - 1, moderate - 2 and severe - 3. Results Clinically successful treatment was defined as complete resolution of clinically meaningful signs and symptoms of infection, including SIRS score of 0. The outcome measure was the percentage of patients with SIRS score of 0 on day 7 (clinical success). The third most common diagnosis at baseline was impetigo (13% in both groups). Patients who received dalbavancin had a higher clinical success rate than those receiving telavancin. Conclusion Findings of the present study show that single i.v dose of dalbavancin is better than telavancin repeated doses in treatment of ABSSSI.
eHealth Tools to Provide Structured Assistance for Atrial Fibrillation Screening, Management, and Guideline‐Recommended Therapy in Metropolitan General Practice: The AF‐SMART Study

Background This eHealth implementation study aimed to evaluate strategies to promote opportunistic atrial fibrillation (AF) screening using electronic screening prompts and improve treatment using electronic decision support (EDS) software. Methods and Results An electronic screening prompt appeared whenever an eligible patient's (aged ≥65 years, no AF diagnosis) medical record was opened in participating general practices. General practitioners and practice nurses offered screening using a smartphone ECG, with validated AF algorithm. Guideline‐based EDS was provided to assist treatment decisions. Deidentified data were collected from practices using a data extraction tool. General practices (n=8) across Sydney, Australia, screened for a median of 6 months. A total of 1805 of 11 476 (16%) eligible patients who attended were screened (44% men, mean age 75.7 years). Screening identified 19 (1.1%) new cases of AF (mean age, 79 years; mean CHA 2 DS 2‐VASc, 3.7; 53% men). General practitioners (n=30) performed 70% of all screenings (range 1–448 patients per general practitioner). The proportion of patients with AF who had CHA 2 DS 2‐VASc ≥2 for men or ≥3 for women prescribed oral anticoagulants was higher for those diagnosed during the study: 15 of 18 (83%) for screen‐detected and 39 of 46 (85%) for clinically detected, compared with 933 of 1306 (71%) patients diagnosed before the study (P<0.001). The EDS was accessed 111 times for patients with AF and for 4 of 19 screen‐detected patients. Conclusions The eHealth tools showed promise. Adherence to guideline‐based oral anticoagulant prescription was significantly higher in patients diagnosed during the study period, although the EDS was only used in a minority. While the proportion of eligible patients screened and EDS use was relatively low, further refinements may improve uptake in clinical practice. Clinical Trial Registration URL: www.anzctr. org.au. Unique identifier: ACTRN12616000850471.
Factors that affect the physical and mental health of caregivers of school‐age children and transitioning young adults with autism spectrum disorder

BACKGROUND Although studies have examined quality of life (QOL) among family caregivers of individuals with autism spectrum disorder (ASD), little is known about potential differences in QOL based on the age of the individual with ASD, particularly in relation to caregivers' needs, beliefs and coping mechanisms. METHOD This study investigated 132 caregivers of school-age children and 61 caregivers of transitioning young adults with ASD on measures of caregiving, strain, coping, family needs and QOL. RESULTS The results indicated that there were no significant differences in QOL based on the age of the individuals with ASD, although parents of children reported significantly more caregiving behaviours, with coping, internalized strain and health information needs predicted mental health QOL. DISCUSSION Age of the individual with ASD was not significantly related to caregivers' QOL. More research is needed to determine independent predictors of caregiver QOL across the lifespan.
Evaluation of instructions in patient information leaflets for the use of intranasal corticosteroid sprays: an observational study

Objectives In this study, we analysed patient information leaflets (PILs) of intranasal corticosteroid sprays (INCS) of different manufacturers in the UK to determine if instructions for the use of INCS are complete and uniform. Setting PILs of all INCS of all manufacturers, available for patients in the UK, were collected from the British National Formulary website and the Medicines and Healthcare products Regulatory Agency website. All instructions in these PILs were analysed. Participants We identified PILs of INCS from 21 different manufacturers, available for patients in the UK. Results We analysed the instructions for the use of INCS in 21 different PILs and there is large variation in the PIL instructions for the technique of using INCS across PILs. Conclusion Complete and uniform instructions for the use of INCS are lacking in PILs for registered preparations in the UK. Structured and standardised instructions to be used by both professionals and patients are essential in order to optimise daily use of INCS.
Sex Differences Along the Autism Continuum: A Twin Study of Brain Structure

Females might possess protective mechanisms regarding autism spectrum disorder (ASD) and require a higher detrimental load, including structural brain alterations, before developing clinically relevant levels of autistic traits. This study examines sex differences in structural brain morphology in autism and autistic traits using a within-twin pair approach. Twin design inherently controls for shared confounders and enables the study of gene-independent neuroanatomical variation. N=148 twins (62 females) from 49 monozygotic and 25 dizygotic same-sex pairs were included. Participants were distributed along the whole continuum of autism including twin pairs discordant and concordant for clinical ASD. Regional brain volume, surface area and cortical thickness were computed. Within-twin pair increases in autistic traits were related to decreases in cortical volume and surface area of temporal and frontal regions specifically in female twin pairs, in particular regions involved in social communication, while only two regions were associated with autistic traits in males. The same pattern was detected in the monozygotic twin pairs only. Thus, non-shared environmental factors seem to impact female more than male cerebral architecture. Our results are in line with the hypothesis of a female protective effect in autism and highlights the need to study ASD in females separately from males.
Apolipoprotein M induces inhibition of inflammatory responses via the S1PR1 and DHCR24 pathways.

Apolipoprotein M (ApoM) is a type of apolipoprotein. It is well known that high‑density lipoprotein (HDL) decreases inflammatory responses via the apoM‑sphingosine‑1‑phosphate (S1P) pathway. The present study further investigated the importance of ApoM in the inhibitory effects of HDL on inflammation. Mice with an apoM gene deficiency (apoM‑/‑) were employed to investigate the effects of ApoM on the expression of interleukin‑1β (IL‑1β), monocyte chemotactic protein‑1 (MCP‑1), S1P receptor‑1 (S1PR1) and 3β‑hydroxysterol Δ‑24‑reductase (DHCR24), as compared with in wild‑type mice (apoM+/+). Furthermore, cell culture experiments were performed using a permanent human hybrid endothelial cell line (EA.hy926). Cells were cultured in the presence of recombinant human apoM (rec‑apoM) or were induced to overexpress apoM (apoMTg); subsequently, cells were treated with tumor necrosis factor‑α (TNF‑α), in order to investigate the effects of ApoM on IL‑1β and MCP‑1. The results demonstrated that the mRNA expression levels of IL‑1β and MCP‑1 were significantly higher in the liver following administration of lipopolysaccharide in apoM‑/‑ mice compared with in apoM+/+ mice. In cell culture experiments, when cells were pre‑cultured with rec‑apoM or were engineered to overexpress apoM (apoMTg), they exhibited decreased expression levels of IL‑1β and MCP‑1 following TNF‑α treatment compared with in normal apoM‑expressing cells (apoMTgN). Furthermore, the mRNA expression levels of IL‑1β and MCP‑1 were significantly elevated following addition of the S1PR1 inhibitor W146, but not by the scavenger receptor class B type I inhibitor, block lipid transport‑1 (BLT‑1), in apoMTg cells prior to TNF‑α treatment. Conversely, there were no differences in these inflammatory biomarkers under the same conditions in apoMTgN cells. The mRNA expression levels of DHCR24 were significantly reduced by the addition of BLT‑1 prior to TNF‑α treatment in apoMTg cells; however, there was no difference in the expression of this inflammatory biomarker in apoMTgN cells. In conclusion, ApoM displayed inhibitory effects against the inflammatory response in vivo and in vitro; these effects may be induced via the S1PR1 and DHCR24 pathways.