Pharmacological Medications Research Articles

Biological Synthesis of Silver Nanoparticles by Amaryllis vittata (L.) Herit: From Antimicrobial to Biomedical Applications.

The current study sought to synthesize silver nanoparticles (AgNPs) from Amaryllis vittata (L.) leaf and bulb extracts in order to determine their biological significance and use the toxic plants for human health benefits. The formation of silver nanoparticles was detected by a change in color from whitish to brown for bulb-AgNPs and from light green to dark brown for leaf-AgNPs. For the optimization of silver nanoparticles, various experimental physicochemical parameters such as pH, temperature, and salt were determined. UV-vis spectroscopy, Fourier transform infrared spectroscopy, X-ray dispersion spectroscopy, scanning electron microscopy, and energy dispersion spectroscopy analysis were used to characterize nanoparticles. Despite the fact that flavonoids in plant extracts were implicated in the reduction and capping procedure, the prepared nanoparticles demonstrated maximum absorbency between 400 and 500 nm. SEM analysis confirmed the preparation of monodispersed spherical crystalline particles with fcc structure. The bioinspired nanoparticles were found to show effective insecticidal activity against Tribolium castaneum and phytotoxic activity against Lemna aequincotialis. In comparison to plant extracts alone, the tested fabricated nanoparticles showed significant potential to scavenge free radicals and relieve pain. Antibacterial testing against human pathogenic strains, i.e., Escherichia coli and Pseudomonas aureginosa, and antifungal testing against Aspergillus niger revealed the significant potential for microbe resistance using AgNPs. As a result of the findings, the tested silver nanoparticles demonstrated promising potential for developing new and effective pharmacological and agricultural medications. Furthermore, the effects of biogenic AgNPs on an in vitro culture of Solanum tuberosum L. plants were investigated, and the findings indicated that bulb-AgNPs and leaf-AgNPs produced biomass and induced antioxidants via their active constituents. As a result, bulb-AgNPs and leaf-AgNPs may be recommended for use in Solanum tuberosum L. tissue culture for biomass fabrication and metabolic induction.

DRUG INDUCED DIABETES

Several Epidemiological studies have suggested that rate of development of diabetes mellitus consequent to taking diverse types of medication is increasing now a days. Several medications have been found to be associated with causation of diabetes. Various pharmacological medications which are commonly used in clinical practice are found to affect glucose homeostasis and interfere with the balance between various hormones like insulin, glucagon, catecholamines, growth hormone, and cortisol. Mechanism for the diabetes caused due to medications is associated with a reduction in insulin production, some with reduction in insulin sensitivity, and some appear to be associated with reduction in insulin production along with the insulin sensitivity. It is very difficult to establish a precise cause and effect relationship between a medication and development of diabetes. Various clinical studies of medications typically concentrate on evaluation of effectiveness and are not powered to evaluate side effects. Several covariant such as the weight gain associated with medication such as steroids or antipsychotics also make it difficult to find that whether the development of diabetes was a primary or secondary effect of the medication. Mechanisms for the causations of diabetes have been linked with range from decreased insulin secretion to decreased insulin action to direct neural effects. Stopping or switching medication is considered as the first step in treating the drug induced diabetes. While the information to support many of the consensus recommendations for treatment drug -induced diabetes is lacking. To establish the optimal therapy for Drug induced diabetes, it is quite essential to understand the potential mechanism which interrupts the metabolism of carbohydrates. Keywords: Diabetes, insulin sensitivity, glucose homeostasis, medication-induced diabetes, optimal therapy.

The incidence and risk factors of acute pain after preoperative needle localization of pulmonary nodules: a cross-sectional study.

BackgroundThe incidence, severity and associated risk factors of acute pain after preoperative needle localization of pulmonary nodules are poorly characterized. We therefore conducted a cross-sectional study to quantify the acute pain induced by preoperative needle localization of small pulmonary nodules before video-assisted thoracoscopic surgery (VATS).MethodsWe conducted this study at Shanghai Chest Hospital from September 2021 through December 2021. Eligible patients were between 18 and 75 years old and had small pulmonary nodules requiring preoperative CT-guided needle localization. The intensity of acute pain was assessed using the visual analogue scale (VAS) after preoperative needle localization. A VAS score ≥4 cm indicated moderate to severe pain. Patient demographics and CT-guided localization factors were collected to identify significant predictors associated with moderate to severe pain.ResultsA total of 300 patients were included in the final analysis, with a mean (SD) age of 51 (SD =12) years old; 63% were female. Moderate to severe pain occurred in 50.8% of patients during deep breathing and 45.7% of patients during movement. Multivariate logistic regression analysis showed that multiple localization needles [multiple needle localizations vs. single needle localization, odds ratio (OR): 2.363, 95% confidence interval (CI): 1.157–4.825, P=0.018] and the specific location of needle puncture on the chest wall were significant predictors of moderate to severe pain after CT-guided needle localization (lateral chest wall vs. anterior chest wall OR: 2.235, 95% CI: 1.106–4.518, P=0.025; posterior chest wall vs. anterior chest wall OR: 1.198, 95% CI: 0.611–2.349, P=0.599).ConclusionsIn adult patients receiving hookwire CT-guided localization, moderate to severe pain was common. Avoiding the localization route through lateral chest wall may be helpful and pharmacological medications or regional blockade is necessitated in high-risk population.

Use of Non-pharmacological Therapies in Individuals With Migraine Eligible for Treatment With Monoclonal Antibodies Targeting Calcitonin Gene-Related Peptide (CGRP)-Signaling: A Single-Center Cross-Sectional Observational Study.

IntroductionAccessibility of treatment with monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) signaling pathway is impeded by regulatory restrictions. Affected individuals may seek out other services including non-pharmacological therapies. Thus, we found it timely to ascertain the use of non-pharmacological therapies in individuals with treatment-resistant migraine eligible for and naïve to treatment with CGRP-signaling targeting monoclonal antibodies.MethodsWe conducted a single-center cross-sectional observational study of patients eligible for and naïve to treatment with monoclonal antibodies targeting CGRP or its receptor. We recorded demographical information (gender, age, educational level, employment status, and income), disease burden (frequency of headache days and migraine days), previous use of preventive pharmacological medications for migraine, and use of non-pharmacological therapies over the past 3 months including frequency of interventions, costs, and patient-reported assessment of efficacy on a 6-point scale (0: no efficacy, 5: best possible efficacy).ResultsWe included 122 patients between 17 June 2019 and 6 January 2020; 101 (83%) were women and the mean age was 45.2 ± 13.3 years. One-third (n = 41 [34%]) had used non-pharmacological therapy within the past 3 months. Among these participants, the median frequency of different interventions was 1 (IQR: 1–2), the median number of monthly visits was 2.3 (IQR: 1.3–4), mean and median monthly costs were 1,086 ± 1471, and 600 (IQR: 0–1200) DKK (1 EUR = ~7.5 DKK), respectively, and median patient-reported assessment of the efficacy of interventions was 2 (IQR: 0–3).ConclusionEven in a high-income country with freely accessible headache services and universal healthcare coverage, there was a non-negligible direct cost in parallel with low satisfaction for non-pharmacological therapies among patients at a tertiary headache center.

Fovea-threatening and fovea-involving peripheral Coats disease: effects of posture and intervention

BackgroundWe believe that our experience with patients presenting with Coats disease and macular sparing should be shared with our colleagues. We would like to show the effect of posture and prompt intervention in cases with fovea-threatening and/or fovea-involving peripheral Coats disease (FTPCD). This association has been poorly debated in our specialty and literature. We call the attention for the unexpexted scenario of observing the lost of the fovea during some types of traditional and prompt interventional treatments of these cases with previous 20/20 vision (something that we have been studying and observing for many years). In order to publish our best representative cases, we have chosen 8 Brazilian patients (age range, 7–62 years; 5 male) with FTPCD. All patients underwent multimodal imaging and different treatments (observation, sleep-posture repositioning, laser, intraocular steroids, and/or anti-vascular endothelial growth factor therapy). All patients, initially, informed to adopt a sleeping lateral-down position, favoring exudation shifting to the fovea pre-treatment. Most promptly-treated patients in this way (n = 4), developed subretinal fluid and exudates in the macula and some had irreversible central visual loss (n = 3). Patients with recent fovea-involving exudation who changed postural sleep position (to protect the foveal area) before and during treatment fared better, with some preserved central vision and an intact fovea (n = 5). The fundus status was correlated with the gravitational effects of posture before and after treatment. Despite prepared as an observational/interventional study, with a small number of cases, the most difficult part is documenting the sleep position of these patients and its influence in the outcomes as there is not good way to prove how well or poorly the positioning occurred in our cases. Finally, we also intended to call the attention to the fact that Coats disease must be studied in all its clinical stage variants and not only seen as a potential blinding and incurable ocular disease.Case presentationThis study is a retrospective and/or interventional analysis of eight cases with a less severe clinical variant of classic Coats disease that we refer to as fovea-threatening and fovea-involving peripheral Coats disease (FTPCD).All cases were unilateral with no systemic disease or family history of Coats disease. The bilateral anterior segment and intraocular pressure were normal in all patients. The characteristics of all patients are shown in the Table.ConclusionThe funduscopic features of FTPCD are fundamental to disease understanding and optimal management. Habitual posturing may affect the fundus morphologic features of retinal exudation as observed in all current patients with exudative peripheral Coats disease. When sleep habitual posture is not observed in patients with FTPCD, the effects of prompt invasive treatments can cause rapid visual loss because of foveal subretinal pooling of exudates post-treatment. Initial vigilant adjusting of the habitual sleep posture for several patients with FTPCD, before the indication of traditional invasive treatments (laser and/or pharmacologic medications) can result in improved vision and fundoscopic morphologic features.

Valproate-induced hypothyroidism in schizoaffective disorder

IntroductionValproate is widely used in the treatment of maniac and mixed episodes and is well known to be safe with side effects being mostly related to hepatic disorders and psychomotor retardation.ObjectivesRaising attention to valproate-induced hypothyroidism that despite the increasing evidence tends to be neglected.MethodsHere, we report a case of a 55-year-old woman, with a previous diagnosis of schizophrenia, treated for many years with 200mg of zuclopenthixol triweekly and 2mg of risperidone daily. Patient developed a maniac episode characterized by elevated mood, sense of grandiosity, increased energy and psychomotor activity, disinhibition and insomnia. No laboratory abnormalities were detected and inpatient treatment was initiated with paliperidone up to 12mg/day and valproate 1000mg/day.ResultsPatient showed progressive clinical recovery attaining full remission within 2 weeks. Despite the absence of clinical side effects and the valproate serum levels of 74.9μg/mL (range 50–100μg/mL), laboratory testing found progressive reduction F-T4 down to 0.45ng/dL (range 0.8–1.5 ng/dL) and a concomitant upregulation of TSH to 73.99mUI/L (range 0.55–4.8mUI/L). Thyroid autoantibodies and thyroid echography were negative. Considering that patient was previously medicated with risperidone, it was suspected that her hypothyroidism was caused by valproate. Normalization of thyroid function was observed after 21 days valproate withdrawal. Patient is currently being treated with 150 mg paliperidone (monthly) with no recurrence of mood or psychotic episodes and maintain normal thyroid function.ConclusionsOur case emphasizes the need for extended laboratory testing upon prescription of new pharmacological medications as severe analytic alterations can take place in the absence of immediate clinical manifestation.DisclosureNo significant relationships.

Abstract 350: Disruption Of Proprotein Convertase Subtilisin/Kexin 9 Suppresses Inflammation And Attenuates Abdominal Aortic Aneurysm Formation

Objective: Abdominal aortic aneurysm (AAA) is a degenerative inflammatory disease, with its rupture highly lethal. There have been no effective pharmacological medications. Proprotein convertase subtilisin/kexin 9 (PCSK9), which is known to modulate cholesterol metabolism, has recently been associated with AAA in human genome-wide association studies. However, its role in AAA pathogenesis is unknown. Approach and Results: Histology staining of mouse aortic aneurysmal tissue showed PCSK9 expression and its colocalization with macrophages. To investigate the role of PCSK9 in AAA formation, mice deficient in PCSK9 were crossed with ApoE SA/SA mice, which are hypercholesterolemic and inducible to develop angiotensin II-mediated hypertension upon doxycycline (Dox) administration. Deletion of PCSK9 reduced both incidence and severity of AAA and increased survival rate, without changing plasma cholesterol levels. This was associated with decreased aortic expression and activity of matrix metalloproteinase 9 (MMP9), less elastin breakdown, and reduced aortic expansion and aneurysm rupture. Additionally, PCSK9 deficiency suppressed systemic inflammatory response and macrophage infiltration into AAA lesions. In isolated macrophages stimulated with LPS, the upregulated expression of pro-inflammatory cytokines ( Tnfa, Il1b, Il6 ) was dramatically diminished in PCSK9-deficient macrophages. Furthermore, administration of PCSK9-specific siRNA in mice resulted in less macrophage accumulation in the aneurysmal aortic wall, decreased MMP9-mediated elastin degradation, and substantially constrained AAA formation. Conclusions: Endogenous PCSK9 promotes AAA formation, consistent with its novel action in mediating systemic and local inflammation, particularly, the macrophage-dependent MMP9 activity. Pharmacological inhibition of PCSK9 might be a promising strategy to curtail AAA. Key Words: aneurysm, PCSK9, elastin, inflammation, macrophages

Effects of pharmacological treatment on metabolomic alterations in animal models of depression

Numerous studies have investigated metabolite alterations resulting from pharmacological treatment in depression models although few quantitative studies explored metabolites exhibiting constant alterations. This study aimed to identify consistently dysregulated metabolites across such studies using a knowledgebase-driven approach. This study was based on 157 studies that identified an assembly of 2757 differential metabolites in the brain, blood, urine, liver, and feces samples of depression models with pharmacological medication. The use of a vote-counting approach to identify consistently upregulated and downregulated metabolites showed that serotonin, dopamine, norepinephrine, gamma-aminobutyric acid, anandamide, tryptophan, hypoxanthine, and 3-methoxytyramine were upregulated in the brain, while quinolinic acid, glutamic acid, 5-hydroxyindoleacetic acid, myo-inositol, lactic acid, and the kynurenine/tryptophan ratio were downregulated. Circulating levels of trimethylamine N-oxide, isoleucine, leucine, tryptophan, creatine, serotonin, valine, betaine, and low-density lipoprotein were elevated. In contrast, levels of alpha-d-glucose, lactic acid, N-acetyl glycoprotein, glutamine, beta-d-glucose, corticosterone, alanine, phenylacetylglycine, glycine, high-density lipoprotein, arachidonic acid, myo-inositol, allantoin, and taurine were decreased. Moreover, 12 metabolites in urine and nine metabolites in the liver were dysregulated after treatment. Pharmacological treatment also increased fecal levels of butyric acid, acetic acid, propionic acid, and isovaleric acid. Collectively, metabolite disturbances induced by depression were reversed by pharmacological treatment. Pharmacological medication reversed the reduction of brain neurotransmitters caused by depression, modulated disturbance of the tryptophan-kynurenine pathway and inflammatory activation, and alleviated abnormalities of amino acid metabolism, energy metabolism, lipid metabolism, and gut microbiota-derived metabolites.

At the crossroads of fertility and metabolism: the importance of AMPK-dependent signaling in female infertility associated with hyperandrogenism.

What biological processes are linked to the signaling of the energy sensor 5'-AMP-activated protein kinase (AMPK) in mouse and human granulosa cells (GCs)? The lack of α1AMPK in GCs impacted cell cycle, adhesion, lipid metabolism and induced a hyperandrogenic response. AMPK is expressed in the ovarian follicle, and its activation by pharmacological medications, such as metformin, inhibits the production of steroids. Polycystic ovary syndrome (PCOS) is responsible for infertility in approximately 5-20% of women of childbearing age and possible treatments include reducing body weight, improving lifestyle and the administration of a combination of drugs to improve insulin resistance, such as metformin. AMPK signaling was evaluated by analyzing differential gene expression in immortalized human granulosa cells (KGNs) with and without silencing α1AMPK using CRISPR/Cas9. In vivo studies included the use of a α1AMPK knock-out mouse model to evaluate the role of α1AMPK in folliculogenesis and fertility. Expression of α1AMPK was evaluated in primary human granulosa-luteal cells retrieved from women undergoing IVF with and without a lean PCOS phenotype (i.e. BMI: 18-25 kg/m2). α1AMPK was disrupted in KGN cells and a transgenic mouse model. Cell viability, proliferation and metabolism were evaluated. Androgen production was evaluated by analyzing protein levels of relevant enzymes in the steroid pathway by western blots, and steroid levels obtained from in vitro and in vivo models by mass spectrometry. Differential gene expression in human GC was obtained by RNA sequencing. Analysis of in vivo murine folliculogenesis was performed by histology and immunochemistry, including evaluation of the anti-Müllerian hormone (AMH) marker. The α1AMPK gene expression was evaluated by quantitative RT-PCR in primary GCs obtained from women with the lean PCOS phenotype (n = 8) and without PCOS (n = 9). Silencing of α1AMPK in KGN increased cell proliferation (P < 0.05 versus control, n = 4), promoted the use of fatty acids over glucose, and induced a hyperandrogenic response resulting from upregulation of two of the enzymes involved in steroid production, namely 3β-hydroxysteroid dehydrogenase (3βHSD) and P450 side-chain cleavage enzyme (P450scc) (P < 0.05, n = 3). Female mice deficient in α1AMPK had a 30% decrease in their ovulation rate (P < 0.05, n = 7) and litter size, a hyperandrogenic response (P < 0.05, n = 7) with higher levels of 3βHSD and p450scc levels in the ovaries, and an increase in the population of antral follicles (P < 0.01, n = 10) compared to controls. Primary GCs from lean women with PCOS had lower α1AMPK mRNA expression levels than the control group (P < 0.05, n = 8-9). The FastQ files and metadata were submitted to the European Nucleotide Archive (ENA) at EMBL-EBI under accession number PRJEB46048. The human KGN is a not fully differentiated, transformed cell line. As such, to confirm the role of AMPK in GC and the PCOS phenotype, this model was compared to two others: an α1AMPK transgenic mouse model and primary differentiated granulosa-lutein cells from non-obese women undergoing IVF (with and without PCOS). A clear limitation is the small number of patients with PCOS utilized in this study and that the collection of human GCs was performed after hormonal stimulation. Our results reveal that AMPK is directly involved in steroid production in human GCs. In addition, AMPK signaling was associated with other processes frequently reported as dysfunctional in PCOS models, such as cell adhesion, lipid metabolism and inflammation. Silencing of α1AMPK in KGN promoted folliculogenesis, with increases in AMH. Evaluating the expression of the α1AMPK subunit could be considered as a marker of interest in infertility cases related to hormonal imbalances and metabolic disorders, including PCOS. This study was financially supported by the Institut National de la Recherche Agronomique (INRA) and the national programme « FERTiNERGY » funded by the French National Research Agency (ANR). The authors report no intellectual or financial conflicts of interest related to this work. R.K. is identified as personnel of the International Agency for Research on Cancer/World Health Organization. R.K. alone is responsible for the views expressed in this article and she does not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization. N/A.

Emetine and Indirubin- 3- monoxime interaction with human brain acetylcholinesterase: A computational and statistical analysis.

Alzheimer's disease is a chronic neurodegenerative ailment and the most familiar type of dementia in the older population with no effective cure to date. It is characterized by a decrease in memory, associated with the mutilation of cholinergic neurotransmission. Presently, acetylcholinesterase inhibitors have emerged as the most endorsed pharmacological medications for the symptomatic treatment of mild to moderate Alzheimer's disease. This study aimed to research the molecular enzymatic inhibition of human brain acetylcholinesterase by a natural compound emetine and I3M. Molecular docking studies were used to identify superior interaction between enzyme acetylcholinesterase and ligands. Furthermore, the docked acetylcholinesterase-emetine complex was validated statistically using an analysis of variance in all tested conformers. In this interaction, H-bond, hydrophobic interaction, pi-pi, and Cation-pi interactions played a vital function in predicting the accurate conformation of the ligand that binds with the active site of acetylcholinesterase. The conformer with the lowest free energy of binding was further analyzed. The binding energy for acetylcholinesterase complex with emetine and I3M was -9.72kcal/mol and -7.09kcal/mol, respectively. In the current study, the prediction was studied to establish a relationship between binding energy and intermolecular energy (coefficient of determination [R2 linear = 0.999), and intermolecular energy and Van der wall forces (R2 linear = 0.994). These results would be useful in gaining structural insight for designing novel lead compounds against acetylcholinesterase for the effective management of Alzheimer's disease.

Pharmaceutical care and evaluation of adherence to antiretroviral therapy in people living with HIV/AIDS

Highly Active Antiretroviral therapy (HAART) depends on optimal adherence to be effective. Pharmacotherapeutic follow-up can be used as a strategy for treatment fidelity. To provide pharmaceutical care for HAART patients, to assess adherence, to identify and resolve drug related problems (DRP). This is a prospective, interventional study aimed at people on HAART. Data was collected using the pharmacotherapeutic follow-up form and CEAT-VIH. There was a predominance of women (59%), older than 33 years (75%), mostly single (43%). Regarding adherence, 64% had insufficient adherence at the start of the study, while 36% had strict/adequate adherence. After the pharmacotherapeutic follow-up, 70% presented strict/adequate adherence. Regarding HAART, the relationship between adhesion versus time of HAART and adherence versus regimen used was significant, considering that less time of therapy and regimen containing protease inhibitors are predictors for insufficient adherence. Regarding the DRP identified (f=77), missed pills (32%), untreated disease, incorrect management frequency, and undue self-medication (12%) were the most frequent. Pharmaceutical interventions (f=137) were predominantly advising related to specific pharmacological treatment (32%), non-pharmacological measures (20%), and medication suspension (9%). Pharmaceutical care was shown to be animportant strategy, within the multi professional team, to improve adherence, besides identifying and resolving DRP.

Pharmacological Effort and Medication Approaches for the Management of COVID-19 Pandemic in Nepal .

COVID-19 pandemic has created a long-lasting effect on different aspects of peoples' life. Several efforts were made by Nepal for the management of the COVID-19 surge. This study intended to compile the pharmacological efforts adopted for the prevention and management of COVID-19 during its pandemic in Nepal. A comprehensive study was performed from 10th May to 25th May 2021. Altogether, 25 documents, three guidelines, and 30 articles were assessed and analysed in this study. The major pharmacological steps for the prevention of COVID-19 were seen through vaccination campaigns, the development of guidelines, and the use of repurposed drugs (Remdesivir, corticosteroids, anticoagulants etc). Significant pharmacological steps were seen in the prevention and treatment of COVID-19 in Nepal during the pandemic. With the limited resources, Nepal’s action against COVID-19 seemed to be impressive; however, more efforts are demanded to combat similar situations in the future.

Health Impacts and Characteristics of Deprescribing Interventions in Older Adults: Protocol for a Systematic Review and Meta-analysis.

BackgroundDeprescribing, a relatively recent concept, has been proposed as a promising solution to the growing issues of polypharmacy and use of medications of questionable benefit among older adults. However, little is known about the health outcomes of deprescribing interventions.ObjectiveThis paper presents the protocol of a study that aims to contribute to the knowledge on deprescribing by addressing two specific objectives: (1) describe the impact of deprescribing in adults ≥60 years on health outcomes or quality of life; and (2) determine the characteristics of effective interventions in deprescribing.MethodsPrimary studies targeting three concepts (older adults, deprescribing, and health or quality of life outcomes) will be included in the review. The search will be performed using key international databases (MEDLINE, EMBASE, CINAHL, Ageline, PsycInfo), and a special effort will be made to identify gray literature. Two reviewers will independently screen the articles, extract the information, and evaluate the quality of the selected studies. If methodologically feasible, meta-analyses will be performed for groups of intervention studies reporting on deprescribing interventions for similar medications, used for similar or identical indications, and reporting on similar outcomes (eg, benzodiazepines used against insomnia and studies reporting on quality of sleep or quality of life). Alternatively, the results will be presented in bottom-line statements (objective 1) and a matrix outlining effective interventions (objective 2).ResultsThe knowledge synthesis may be limited by the availability of high-quality clinical trials on deprescribing and their outcomes in older adults. Additionally, analyses will likely be affected by studies on the deprescribing of different types of molecules within the same indication (eg, different pharmacological classes and medications to treat hypertension) and different measures of health and quality of life outcomes for the same indication. Nevertheless, we expect the review to identify which deprescribing interventions lead to improved health outcomes among seniors and which of their characteristics contribute to these outcomes.ConclusionsThis systematic review will contribute to a better understanding of the health outcomes of deprescribing interventions among seniors.Trial RegistrationPROSPERO International Prospective Register of Systematic Reviews CRD42015020866; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42015020866International Registered Report Identifier (IRRID)PRR1-10.2196/25200

Immersive Virtual Reality: A Safe, Scalable, Non-opioid Analgesic for Military and Veteran Patients

In Iraq and Afghanistan over 75% of the combat casualties suffered by U.S. troops have involved explosive devices. Improvements in body armor and advances in military medicine have significantly reduced the number of combat-related fatalities, but have greatly increased the number of U.S. active component personnel suffering painful trauma injuries. Unfortunately, so far, advances in pharmacologic analgesia pain medications have not kept pace with advances in survivability. For many active component personnel and Veterans, pain is a top health complaint from patients. The opioid epidemic has increased the urgency of developing powerful non-pharmacologic approaches for the management of pain. Immersive VR is proving to be a powerful non-opioid pain management technique for acute pain. However, the cost and usability limitations of pre-2016 VR clinical products resulted in limited treatment adoption rates for clinical use. In recent years, VR technology has become increasingly immersive, portable, and miniaturized, requiring minimal technical expertise to operate, and low-cost, factors that are likely contributing to the recent increase in the clinical use of VR analgesia. VR is greatly benefitting from a growing string of major technological breakthroughs and VR treatment improvements that will likely continue to increase the effectiveness and suitability of VR analgesia for military and VA patients. Regarding acute pain, we propose that the next revision to the current Tactical Combat Casualty Care guidelines consider including VR as an effective and hemodynamically safe approach to the current management of acute trauma pain in military personnel during medical procedures. With recent miniaturization and ruggedization, VR can potentially be used closer to the battlefield in the future. Beyond distraction, innovative VR therapy techniques designed to help reduce chronic pain are discussed. Recent breakthroughs in the mass production of inexpensive, highly immersive lightweight stand alone VR systems and augmented reality systems increase the potential for widespread dissemination of VR analgesia for acute and potentially for chronic pain. For example, the U.S. military recently purchased 22 billion dollar’s worth of Microsoft Hololens mixed reality systems (e.g., for training). Expanded research and development of VR analgesia customized for the unique needs of military and VA patients is recommended.

Alverine citrate promotes myogenic differentiation and ameliorates muscle atrophy

Sarcopenia is the age-related loss of muscle mass and function and no pharmacological medication has been approved for its treatment. We established an atrogin-1/MAFbx promoter assay to find drug candidates that inhibit myotube atrophy. Alverine citrate (AC) was identified using high-throughput screening of an existing drug library. AC is an established medicine for stomach and intestinal spasms. AC treatment increased myotube diameter and inhibited atrophy signals induced by either C26-conditioned medium or dexamethasone in cultured C2C12 myoblasts. AC also enhanced myoblast fusion through the upregulation of fusion-related genes during C2C12 myoblast differentiation. Oral administration of AC improves muscle mass and physical performance in aged mice, as well as hindlimb-disused mice. Taken together, our data suggest that AC may be a novel therapeutic candidate for improving muscle weakness, including sarcopenia.

Philosophical Counseling and Loneliness: An Interdisciplinary Approach

As individuals, the universal fear of loneliness and the desire to secure intimacy has consumed our thoughts and passions. Ever since the Old Testament and Plato’s dialogues, mankind has searched to gain understanding and insights into the dynamics of loneliness. Traditionally, Western thought has assumed, both theologically and philosophically, that the soul or self is a substance, an independent reality secure in-itself in distinction to an external material world. But following the Scientific Revolution of the seventeenth-eighteenth centuries, science began systematically to question and even reject the “doctrine” of a personal identity. The roots of science are now steadfastly gaining ground in materialism, mechanism, determinism, empiricism, phenomenalism (as opposed to phenomenology), cognitive behaviorism, psychoanalysis, and the current neurosciences, which sciences assume that the lonely and passive patient is best “aided” and “treated” by the active agency and interventions of the clinical “specialist, which often requires pharmacological medications. By contrast, the article contends that philosophical and humanistic therapy and counseling offers a partnered alliance with the subject through interdisciplinary learning. Again, the learning is mutual. The subject controls the issues addressed; it is not a student-teacher relationship.

Locating Organizations and Their Methods in Registrations of Clinical Migraine Trials: Analysis of ClinicalTrials.gov.

Background and Objective: ClinicalTrials.gov is a centralized venue for monitoring clinical research and allows access to information on publicly and privately funded studies. To better recognize influential institutions in the field of headache, we identified major organizations conducting clinical trials in migraine research. Furthermore, we examined the frequency of different study designs.Methods: Utilizing the ClinicalTrials.gov application programming interface, we extracted studies including individuals with migraine from February 29, 2000, to July 28, 2020, for the following: (1) host organization, (2) study type, (3) primary purpose, (4) intervention model, and (5) allocation.Results: We included 921 entries encompassing 423 organizations. Thirty-two organizations produced ≥5 entries each and 40.0% of all entries. Most, 86%, were interventional studies while 13.6% were observational studies. The most common study design had a randomized allocation of participants. The most frequent primary purpose was treatment (62.4%) followed by prevention (13.0%). There were 56.9% parallel assignment models, 15.2% single group assignment models, and 12.4% crossover assignment models.Conclusion: A minority of organizations contribute to a significant number of registrations of clinical migraine trials, suggesting that clinical research in migraine is oligarchic. The most common study is interventional and randomized, with parallel assignment of participants with treatment as the primary purpose. This likely reflects the need to evaluate novel putative pharmacological medications.

Epidermis Taping to Address Pain and Medication Usage in Patients with Amputation in an Inpatient Rehabilitation Setting

Research Objectives Pain management after lower limb amputation is medically challenging. Beyond prescription medication, evidence to support non-pharmacological intervention to reduce pain post-amputation is limited. We intended to explore the use of epidermis Kinesiotape (KT), a non-pharmacological pain management technique, to reduce residual limb pain (RLP), phantom limb pain (PLP), and pharmacological pain medication use for patients with lower limb amputation during an inpatient rehabilitation facility (IRF). Design Observational. Setting Large, urban IRF. Participants Patients admitted to IRF within 3 months of lower limb amputation. Interventions Patients admitted to IPR following a lower limb amputation received KT at day 4 of admission. KT was re-applied every 3 to 4 days. Main Outcome Measures Pain visual analog scale (VAS) scores for RLP and PLP and pain medication use was recorded daily throughout IPR length of stay. Results 25 patients (9 female, 16 male; 13 below knee amputation, 8 above knee amputation, 1 through knee amputation, 2 bilateral below knee amputations, 1 multiple amputations) with average IRF stay of 14 days completed the KT protocol. Daily pain decreased on average from admission to discharge (RLP: 2.15±3.03, PLP 1.5±2.85). Pain medication dose decreased for 64% of patients prescribed morphine, 28% of patients prescribed acetaminophen, and 16% of patients prescribed gabapentin. No adverse events occurred due to KT. Conclusions The small reduction in pain following acute lower limb amputation suggests KT may be a viable non-pharmacological treatment for patients during IRF. Future studies should consider the use of a control group to differentiate impact of KT from spontaneous recovery. Author(s) Disclosures No disclosures to make by any author connected to this poster. Pain management after lower limb amputation is medically challenging. Beyond prescription medication, evidence to support non-pharmacological intervention to reduce pain post-amputation is limited. We intended to explore the use of epidermis Kinesiotape (KT), a non-pharmacological pain management technique, to reduce residual limb pain (RLP), phantom limb pain (PLP), and pharmacological pain medication use for patients with lower limb amputation during an inpatient rehabilitation facility (IRF). Observational. Large, urban IRF. Patients admitted to IRF within 3 months of lower limb amputation. Patients admitted to IPR following a lower limb amputation received KT at day 4 of admission. KT was re-applied every 3 to 4 days. Pain visual analog scale (VAS) scores for RLP and PLP and pain medication use was recorded daily throughout IPR length of stay. 25 patients (9 female, 16 male; 13 below knee amputation, 8 above knee amputation, 1 through knee amputation, 2 bilateral below knee amputations, 1 multiple amputations) with average IRF stay of 14 days completed the KT protocol. Daily pain decreased on average from admission to discharge (RLP: 2.15±3.03, PLP 1.5±2.85). Pain medication dose decreased for 64% of patients prescribed morphine, 28% of patients prescribed acetaminophen, and 16% of patients prescribed gabapentin. No adverse events occurred due to KT. The small reduction in pain following acute lower limb amputation suggests KT may be a viable non-pharmacological treatment for patients during IRF. Future studies should consider the use of a control group to differentiate impact of KT from spontaneous recovery.

Unique challenges of endotherapeutics in malignant lower gastrointestinal bleeding in a patient with COVID-19 pneumonia—case report and literature review

: Acute lower gastrointestinal bleeding (LGIB) attributed to malignant colorectal lesion presents an endoscopically demanding task to manage due to multiple contributing factors. This ranges from an array of compounding issues such as tumour friability, neovascularization and coagulopathy arising from either medical comorbidities or pharmacological medications. We present a challenging case of malignant rectosigmoid colonic tumour bleeding in the setting of COVID-19 infection at its highest level in our country where all resources were severely stretched and strained. A 58-year-old man admitted for stage 3 COVID-19 pneumonia had been complaining of intermittent hematochezia for 1 month. Relevant blood investigations revealed a hemoglobin count of 5.1 g/dL with normal coagulation profile. Index colonoscopy demonstrated a bulky, circumferential rectosigmoid colon tumour with significantly narrowed (3–4 mm) luminal opening. As there was no bleeding, no endoscopic intervention was forthcoming. Staging computed tomography (CT) scan done the following day, confirmed a large but localized rectosigmoid colon tumour measuring 5 cm in length with no signs of bowel obstruction. Owing to hospital restrictions in place during the pandemic, he was unable to undergo definitive surgical intervention when he rebled 10 days later. This was complicated with hemodynamic instability which warranted an urgent endoscopic treatment with argon plasma coagulation (APC). This timely intervention was successful in buying sufficient time for him to recover from COVID-19 pneumonia and subsequently undergo surgery. The final overall diagnosis was pT3N0M0 moderately differentiated colonic adenocarcinoma. Though APC has limited role in the management of bleeding colorectal cancers due to high rebleeding rates, its’ temporizing hemostatic benefits may still be of use when other modalities are unavailable. The COVID-19 pandemic has brought about various disruptions in our routine endoscopic practices. Aside from delays in timely diagnosis and definitive intervention, endoscopic practices alongside performance are equally affected by resource limitation which is highlighted in our case.

Recent Advances in Cobalt‐Catalyzed, Directing‐Group‐Assisted C−H Bond Amidation Reactions

AbstractC−N bond formation reactions have garnered a lot of interest in recent years due to the predominance of nitrogen‐containing compounds in most pharmacological medications. Since traditional approaches have several limitations, the transition metal‐catalyzed C−H amidation/amination process has arisen as a more atom‐friendly option. Because there are so many distinct kinds of C−H bonds in organic molecules, selective amidation of C−H bonds has always been a challenge. In this scenario, the directing‐group‐assisted C−H amidation has received considerable attention, especially with inexpensive metal cobalt, due to its unique properties and efficiency. We summarize recent developments in cobalt‐catalyzed directing‐group‐aided C−H bond amidation reactions in this review. We briefly discuss the evolution of directing group preferences and their function in the site selection.magnified image