Miracle-dz/UniFAR-FTUs huggingface dataset:
Updates in Hemodynamic Monitoring: A Review for Pharmacists

Vital signs are regularly monitored in hospitalized patients. In the intensive care unit (ICU), traditional non-invasive blood pressure monitoring and telemetry may not provide enough information to determine the etiology of hemodynamic instability or guide intervention. Arterial catheters remain the gold-standard for continuous blood pressure monitoring and are commonly used in ICU patients. Pulmonary artery catheters and central venous catheters are beneficial in select patient populations and provide more advanced and specific information about a patient’s hemodynamics. However, neither are benign and can increase risk of complications such as infection, arrhythmias, pneumothorax and vascular or valvular damage. In the past 10 years, the development of reliable non-invasive (NICOM), or minimally-invasive (MICOM), cardiac output monitoring devices has accelerated. The MICOM devices require an arterial catheter to obtain hemodynamic values, whereas NICOM devices do not require any arterial or venous access. These devices have emerged to be particularly useful in evaluating and managing patients with suspected mixed shock. As these devices become more prevalent, it is imperative that clinical pharmacists become familiar with interpreting this data as it may have a substantial impact on medication selection and optimization. This review will discuss the basics of NICOM and MICOM devices, limitations with these methods of monitoring, and clinical application for pharmacists.
Anti-glycemic potential of benzophenone thio/semicarbazone derivatives: synthesis, enzyme inhibition and ligand docking studies

Abstract Inhibition of dipeptidyl peptidase-IV (DPP-IV) has been identified as a promising approach for the treatment of type 2 diabetes mellitus (T2DM). Therefore, development of DPP-IV inhibitors with new chemical scaffold is of utmost importance to medicinal chemistry. In the present study, we identified benzophenone thio- and semicarbazone scaffolds as novel DPP-IV inhibitors. For that purpose, benzophenone thio- and semicarbazone were synthesized through a 2-step reaction. These newly synthetic derivatives were characterized by different spectroscopic techniques, including HREI-MS and NMR. whereas stereochemistry of the iminic bond was predicted by NOESY experiments. Thio- and semicarbazones derivatives were evaluated for their DPP-IV inhibitory potential and found to exhibit a good to moderate enzyme inhibitory activity. Most active and non-cytotoxic derivatives were further evaluated for their DPP-IV inhibitory potential in in cellulo model. The binding sites as well as affinity of active compounds for DPP- IV enzyme were predicted by in silico studies, and compared to a standard drug, sitagliptin. Pharmacophore studies of thio- and semicarbazones derivatives 1–29 suggest that substitution of aryl group, particularly a lipophilic substituents at C-4″ of benzene ring, and a hydroxyl at C-4′ strongly influenced the DPP-IV inhibitory activity. Compound 9 showed the highest inhibitory activity (IC50 = 15.0 ± 0.6 µM), whereas compounds 10, 17, 12, 14 and 23 showed a moderate activity with IC50 values in the range of 28.9–39.2 µM. This study identifies thio- and semicarbazones as new classes of DPP-IV inhibitors which may translate into safe and effective therapeutics for a better management of type 2 diabetes. Communicated by Ramaswamy H. Sarma
Generation of SARS-CoV-2 reporter replicon for high-throughput antiviral screening and testing

Significance The urgency of curbing the COVID-19 pandemic has motivated many investigators to pivot their research to understand the basic biology of SARS-CoV-2 and to search for new pharmaceutical compounds for potential COVID-19 treatment. However, most SARS-CoV-2 studies require biosafety level 3 facilities, which are in high demand, costly, and difficult to access. To overcome these limitations, we engineered a SARS-CoV-2 replicon, which is a modified virus subgenome capable of self-replicating without producing infectious virus, allowing the viral replication to be studied in a conventional biomedical laboratory setting. The replicon system also provides a valuable tool to screen and test antiviral compounds in biologically relevant cells. Successful implementation of the technology will accelerate the development of effective treatment for SARS-CoV-2 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research and antiviral discovery are hampered by the lack of a cell-based virus replication system that can be readily adopted without biosafety level 3 (BSL-3) restrictions. Here, the construction of a noninfectious SARS-CoV-2 reporter replicon and its application in deciphering viral replication mechanisms and evaluating SARS-CoV-2 inhibitors are presented. The replicon genome is replication competent but does not produce progeny virions. Its replication can be inhibited by RdRp mutations or by known SARS-CoV-2 antiviral compounds. Using this system, a high-throughput antiviral assay has also been developed. Significant differences in potencies of several SARS-CoV-2 inhibitors in different cell lines were observed, which highlight the challenges of discovering antivirals capable of inhibiting viral replication in vivo and the importance of testing compounds in multiple cell culture models. The generation of a SARS-CoV-2 replicon provides a powerful platform to expand the global research effort to combat COVID-19.
Patient Access to Mental Health Notes

Abstract In the last decade, many health organizations have embarked on a revolution in clinical communication. Using electronic devices, patients can now gain rapid access to their online clinical records. Legally, patients in many countries already have the right to obtain copies of their health records; however, the practice known as “open notes” is different. Via secure online health portals, patients are now able to access their test results, lists of medications, and the very words that clinicians write about them. Open notes are growing with most patients in the Nordic countries already offered access to their full electronic record. From April 2021, a new federal ruling in the United States mandates—with few exemptions—that providers offer patients access to their online notes (Office of the National Coordinator for Health Information Technology, Department of Health and Human Services, Available at: https://www.govinfo.gov/content/pkg/FR-2019-03-04/pdf/2019-02224.pdf#page=99). Against these policy changes, only limited attention has been paid to the ethical question about whether patients with mental health conditions should access their notes, as mentioned in the articles by Strudwick, Yeung, and Gratzer (Front Psychiatry 10:917, 2019) and Blease, O'Neill, Walker, Hägglund, and Torous (Lancet Psychiatry 7:924–925, 2020). In this article, our goal is to motivate further inquiry into opening mental health notes to patients, particularly among persons with serious mental illness and those accessing psychological treatments. Using biomedical ethical principles to frame our discussion, we identify key empirical questions that must be pursued to inform ethical practice guidelines.
Association between lifetime depression history, hippocampal volume and memory in non‐amnestic mild cognitive impairment

Hippocampal subfield volume loss in older adults with amnestic mild cognitive impairment (aMCI) and depression history are associated with amyloid beta and tau pathology, thereby increasing the risk for Alzheimer's disease (AD). However, no studies have exclusively examined distinct alterations in hippocampal subfields in non‐amnestic MCI (naMCI) in relation to depression history. Here, we used both longitudinal and transverse hippocampal segmentation methods using the automated FreeSurfer software to examine whether a lifetime depression history is associated with differences in hippocampal head/body/tail (H/B/T) and key subfield volumes (CA1, subiculum, dentate gyrus) in older adults with naMCI. Further, we explored whether differences in hippocampal H/B/T and subfield volumes were associated with structured and unstructured verbal encoding and retention, comparing those with and without a depression history. The naMCI with a depression history group demonstrated larger or relatively preserved right CA1 volumes, which were associated with better unstructured verbal encoding and as well as structured verbal memory retention. This association between memory encoding and hippocampal CA1 and total head volume was significantly different to those with no depression history. The relationship between right CA1 volume and memory retention was also moderated by depression history status F (5,143) = 7.84, p < 0.001, R2 = 0.22. Those participants taking antidepressants had significantly larger hippocampal subiculum (p = 0.008), and right hippocampal body (p = 0.004) and better performance on structured encoding (p = 0.011) and unstructured memory retention (p = 0.009). These findings highlight the importance of lifetime depression history and antidepressant use on the hippocampus and encoding and memory retention in naMCI.
National prevalence of coronary heart disease and stroke in South Africa from 1990-2017: a systematic review and meta-analysis.

BACKGROUND South Africa is experiencing an increasing burden of cardiovascular diseases, including coronary heart disease (CHD) and stroke. We aimed to obtain overall national prevalence estimates of CHD and stroke in South Africa. METHODS Studies conducted in South Africa were systematically reviewed from PubMed, Scopus and Web of Science from January 1990 to July 2017. Random-effects meta-analyses were conducted on the selected studies to determine the overall prevalence of CHD and stroke. RESULTS Out of 2 466 studies, only 12 covering 75 140 participants reported the national prevalence of CHD and stroke. All 12 studies estimated the national prevalence of both diseases based on self-reported disease status. The overall national prevalence was 1.29 (95% CI = 0.83; 1.75) and 4.29 (95% CI = 3.13; 5.45) for CHD and stroke, respectively. Only one study reported incidence rates so we did not perform any meta-analysis of incidence rates. CONCLUSIONS There are very few studies on national prevalence of CHD and stroke in South Africa. Well-structured registries for CHD and stroke are required to accurately identify the disease burden and enable adequate resources to be allocated for the implementation of appropriate prevention and management programmes.
Quantitative Assessment of Friedreich Ataxia via Self-Drinking Activity

Effective monitoring of the progression of neurodegenerative conditions can be significantly improved by objective assessments. Clinical assessments of conditions such as Friedreich's Ataxia (FA), currently rely on subjective measures commonly practiced in clinics as well as the ability of the affected individual to perform conventional tests of the neurological examination. In this study, we propose an ataxia measuring device, in the form of a pressure canister capable of sensing certain kinetic and kinematic parameters of interest to quantify the impairment levels of participants particularly when engaged in an activity that is closely associated with daily living. In particular, the functional task of simulated drinking was utilised to capture characteristic features of disability manifestation in terms of diagnosis (separation of individuals with FA and controls) and severity assessment of individuals diagnosed with the debilitating condition of FA. Time and frequency domain analysis of these biomarkers enabled the classification of individuals with FA and control subjects to reach an accuracy of 98% and a correlation level reaching 96% with the clinical scores.
Comparative proteomics reveals mechanisms that underlie insecticide resistance in Culex pipiens pallens Coquillett

Mosquito control based on chemical insecticides is considered as an important element of the current global strategies for the control of mosquito-borne diseases. Unfortunately, the development of insecticide resistance of important vector mosquito species jeopardizes the effectiveness of insecticide-based mosquito control. In contrast to target site resistance, other mechanisms are far from being fully understood. Global protein profiles among cypermethrin-resistant, propoxur-resistant, dimethyl-dichloro-vinyl-phosphate-resistant and susceptible strain of Culex pipiens pallens were obtained and proteomic differences were evaluated by using isobaric tags for relative and absolute quantification labeling coupled with liquid chromatography/tandem mass spectrometric analysis. A susceptible strain of Culex pipiens pallens showed elevated resistance levels after 25 generations of insecticide selection, through iTRAQ data analysis detected 2,502 proteins, of which 1,513 were differentially expressed in insecticide-selected strains compared to the susceptible strain. Finally, midgut differential protein expression profiles were analyzed, and 62 proteins were selected for verification of differential expression using iTRAQ and parallel reaction monitoring strategy, respectively. iTRAQ profiles of adaptation selection to three insecticide strains combined with midgut profiles revealed that multiple insecticide resistance mechanisms operate simultaneously in resistant insects of Culex pipiens pallens. Significant molecular resources were developed for Culex pipiens pallens, potential candidates were involved in metabolic resistance and reducing penetration or sequestering insecticide. Future research that is targeted towards RNA interference of the identified metabolic targets, such as cuticular proteins, cytochrome P450s, glutathione S-transferases and ribosomal proteins proteins and biological pathways (drug metabolism—cytochrome P450, metabolism of xenobiotics by cytochrome P450, oxidative phosphorylation, ribosome) could lay the foundation for a better understanding of the genetic basis of insecticide resistance in Culex pipiens pallens.
Immune mediation of HMG-like DSP1 via Toll-Spätzle pathway and its specific inhibition by salicylic acid analogs

Xenorhabdus hominickii, an entomopathogenic bacterium, inhibits eicosanoid biosynthesis of target insects to suppress their immune responses by inhibiting phospholipase A2 (PLA2) through binding to a damage-associated molecular pattern (DAMP) molecule called dorsal switch protein 1 (DSP1) from Spodoptera exigua, a lepidopteran insect. However, the signalling pathway between DSP1 and PLA2 remains unknown. The objective of this study was to determine whether DSP1 could activate Toll immune signalling pathway to activate PLA2 activation and whether X. hominickii metabolites could inhibit DSP1 to shutdown eicosanoid biosynthesis. Toll-Spätzle (Spz) signalling pathway includes two Spz (SeSpz1 and SeSpz2) and 10 Toll receptors (SeToll1-10) in S. exigua. Loss-of-function approach using RNA interference showed that SeSpz1 and SeToll9 played crucial roles in connecting DSP1 mediation to activate PLA2. Furthermore, a deletion mutant against SeToll9 using CRISPR/Cas9 abolished DSP1 mediation and induced significant immunosuppression. Organic extracts of X. hominickii culture broth could bind to DSP1 at a low micromolar range. Subsequent sequential fractionations along with binding assays led to the identification of seven potent compounds including 3-ethoxy-4-methoxyphenol (EMP). EMP could bind to DSP1 and prevent its translocation to plasma in response to bacterial challenge and suppress the up-regulation of PLA2 activity. These results suggest that X. hominickii inhibits DSP1 and prevents its DAMP role in activating Toll immune signalling pathway including PLA2 activation, leading to significant immunosuppression of target insects.
Size and composition biases on the detection of individual ultrafine particles by aerosol mass spectrometry

Aerosol mass spectrometers allow particles to be counted on the basis of size and chemical composition. In most instruments, individual particles are ablated with a pulsed laser to obtain a mass spectrum. Using this method to characterize ambient aerosols requires an understanding of biases induced by the measurement process. For particles less than 200 nm diameter, the efficiency of detection is shown to be dependent on both size and composition. These dependencies arise from the transmission characteristics of the particle inlet and the intrinsic ability of a particle to be vaporized and ionized. The relative contributions of each are determined for a series of atmospherically relevant test aerosols. Small particles are generally more difficult to detect and analyze than large particles because they are more difficult to focus through the inlet into a tight beam and because they are more difficult to ablate. Particles composed of polycyclic aromatic hydrocarbons, ammonium nitrate, and alkali metal ions .
Selection of insectary plants for the conservation of biological control agents of aphids and thrips in fruit orchards

Abstract This study evaluated the potential of flowering plant species naturally occurring to promote the conservation and early establishment of key natural enemies of aphids and thrips in apple and peach orchards. Flowering plants present in the North East of Spain, a main fruit production area in Europe, were sampled to determine their flowering period and to identify potential natural enemies present on each plant species. Thirty-six plant species were found blooming from early March to late May and provided an array of flowers that might ensure food resources for natural enemies. Among them, six species – Eruca vesicaria (L.) Cav. , Cardaria draba (L.) Desv. , Euphorbia serrata (L.) S.G. Gmel. , Malva sylvestris L. , Anacyclus clavatus (Desf.) Pers. and Diplotaxis erucoides (L.) DC. – hosted a high diversity of potential natural enemies of aphids and thrips. Their blooming started early in the season and lasted for several sampling weeks and they were widely distributed. Moreover, they had available nectar even in those species with protected nectaries. Therefore, these plant species can be considered as promising candidates for inclusion in the ecological infrastructure designed for fruit orchards in the study area to promote the conservation of the biological control agents of aphids and thrips.
Teledentistry and mHealth for Promotion and Prevention of Oral Health: A Systematic Review and Meta-analysis

The dental profession has experienced a dramatic acceleration in the use of communication systems and information-based technologies over recent years, originating new paradigms for the prevention and promotion of oral health. The purpose of this systematic review was to determine the effect of teledentistry-based (telematic) strategies, reported in randomized controlled trials and quasi-randomized trials, with a focus on oral health prevention and promotion–related outcomes in patients of all ages. We searched Medline via PubMed, SCOPUS, and Web of Science from inception until August 2020, regardless of the language of publication. We selected studies for inclusion and conducted data extraction, assessed risk of bias (Cochrane tool), and evaluated the certainty of the evidence (GRADE approach) in duplicate and independently. Out of 898 potentially eligible references, we selected 43 for full-text screening, of which 19 studies proved eligible: 18 randomized controlled trials and 1 quasi-randomized study. Virtual interventions were mostly asynchronous via apps (n = 9), text messages (n = 9), or computer-aided learning (n = 1). The use of teledentistry as compared with conventional strategies may result in a large reduction in the plaque index (standardized mean difference, −1.18; 95% CI, −1.54 to −0.82; I2 = 92%; low certainty) and will likely result in a large reduction in the gingival index (standardized mean difference, −2.17; 95% CI, −3.15 to −1.19; I2 = 97%; moderate certainty) and in the incidence of white spot lesions (risk ratio, 0.48; 95% CI, 0.35 to 0.66; I2 = 0%; moderate certainty), with an increased effect over time. Evidence suggests that teledentistry, particularly mHealth (messages and apps), is a promising clinical tool for preventing and promoting oral health, especially under the accelerated virtualization of dentistry. Future studies should include a broader spectrum of the population, including adults and elders, to better inform policy and implementation of teledentistry (PROSPERO: CRD42020192685).
Self-rated health and multimorbidity in patients with type 2 diabetes

The relationship between multimorbidity and self-rated health is well established. This study examined self-rated health in relation to multimorbidity, glycaemia and body weight specifically in adults with type 2 diabetes. Bootstrapped hierarchical logistic regression and structural equation modelling (SEM) were used to analyse survey data from 280 adults with type 2 diabetes. The odds of ‘fair/bad/very bad’ self-rated health increased 10-fold in patients with three (OR = 10.11 (3.36–30.40)) and four conditions (OR = 10.58 (2.9–38.25)), irrespective of glycaemic control (p < 0.001). The relationship between multimorbidity and perceived health was more pronounced in male patients. SEM generated a model with good fit, χ2 (CMIN) = 5.10, df = 3, p = 0.164, χ2 (CMIN)/df = 1.70, RMSEA = 0.05, CFI = 0.97, TLI = 0.95 and NFI = 0.94; self-rated health mediated relations between multimorbidity and BMI. Overall, this study highlights the potential of self-rated health to mediate relationships between multimorbidity and BMI, but not glycaemic control, in adults with type 2 diabetes.
Examining the Role of Craving, Mindfulness, and Psychological Flexibility in a Sample of Individuals with Substance Use Disorder

Abstract Background Substance Use Disorder (SUD) continues to represent a significant public health crisis in the United States. Purpose: Novel and effective treatments are needed, and third wave behavioral approaches focused on increasing mindfulness and psychological flexibility appear promising. However, the unique and shared impact of mindfulness and psychological flexibility on substance craving is not well understood. Methods: The current study explores how mindfulness and psychological flexibility predict substance craving while controlling for severity of substance dependence in a sample (N = 284) of treatment-seeking adults with SUD. Results and Discussion: Results suggest that mindfulness and psychological flexibility each account for unique variance in substance craving over and above the other. Implications and limitations are discussed.