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The objective of the current research study was to formulate and evaluate a sustained-release linezolid tablet using the natural antibacterial polymer Aegle marmelos. The natural gum of Aegle marmelos is becoming increasingly used in pharmaceutical formulations as a beneficial medication with excipients. Natural-based plant materials are biocompatible, free of side effects, biodegradable, and economic. Therefore, in order to maintain the drug releases from the matrix system, Aegle marmelos fruit gum as a natural polymer and HPMC grade (K100M) as a synthetic polymer were used in the formulation of the linezolid matrix tablet. The formulation of sustained-release matrix tablets included the wet granulation technique. The formulated matrix tablets were evaluated in terms of weight variation, hardness, diameter, physical appearance, friability, thickness, and in vitro drug release. Each formulation’s matrix tablet passed the required physical assessment tests. The formulation analyses of the tablets’ dissolution showed sustained releases of drugs for up to 10–12 hours. Additionally, several polymer combinations and fillers were used to improve drug release factors using the 32 factorial design approach, drug release kinetics were optimized, and the antibacterial study was evaluated.

Amphiphilic compounds with selectivity towards soluble Aβ42 oligomers were developed. Cell imaging studies show the compounds can reduce the interactions between Aβ42 oligomers and SH-SY5Y cell membranes, both in the presence and absence of Cu.

Background Knowledge is limited about the relationship between clinical reactivity to foods through breastfeeding and long-term food allergy outcomes. We explored parent-perceived symptoms of food allergy via breastfeeding and the association with future tolerance. Methods Subjects identified from the Chicago Food Allergy Study (2005–2011) were categorized by parent-reported reactions to maternally ingested foods via breastfeeding (50/898 peanut-allergic, 69/620 egg-allergic, and 153/589 milk-allergic). The primary outcome was tolerance [passed oral food challenge (OFC) or consumption of previously implicated food]. Secondary outcomes included severe reactions (anaphylaxis and/or cardiovascular/respiratory symptoms) and additional concomitant food allergies. Univariate chi-square analyses were performed to assess for association between variables, followed by logistic regression models. Results Of the 50 subjects with parent-reported peanut-associated symptoms with breastfeeding, none gained tolerance. There were no significant associations between parent-reported breastfeeding symptoms and development of tolerance for egg and milk (egg: OR 0.46, 95% CI 0.21–1.01, p = 0.053; milk: OR 1.13, 95% CI 0.70–1.81, p = 0.614). All egg-allergic subjects with parent-perceived symptoms while breastfeeding also reported multiple food allergies (n = 69), but milk- and peanut-allergic subjects were not more likely to have multiple allergies (milk: OR 1.89, 95% CI 0.88–4.02, p = 0.10; peanut: OR 2.36, 95% CI 0.72–7.76, p = 0.16). There were no significant associations between parent-reported breastfeeding symptoms and subsequent reaction severity. Conclusions A significant proportion of parents perceive symptoms of food allergy attributable to indirect breastfeeding exposures. Our exploratory analysis suggests that infants with parent-perceived clinical reactivity to peanut via breastmilk may be less likely to gain tolerance. Infants with parent-reported reactivity to egg via breastmilk exposure were more likely to report multiple food allergies. Further rigorous prospective studies are needed to clarify the true prevalence of IgE-mediated food allergy symptoms attributable to indirect breastfeeding exposures and the association with development of tolerance.

Chromophores with zwitterionic excited-state intramolecular proton transfer (ESIPT) have been shown to have larger Stock shifts and red-shifted emission wavelengths compared to the conventional π-delocalized ESIPT molecules. However, there is still a dearth of design strategies to expand the current library of zwitterionic ESIPT compounds. Herein, we report a novel zwitterionic excited-state intramolecular proton transfer system enabled by addition of triazamacrocycle (TACN) fragments on a dicyanomethylene-4H-pyran (DCM) scaffold. The solvent-dependent steady-state photophysical studies and pKa measurements strongly support that the ESIPT process is more efficient with two TACN groups attached to the DCM scaffold and not affected by polar protic solvents. Impressively, compound DCM-OH-2-DT emits with a near-infrared (NIR) emission wavelength at 740 nm along with an uncommonly large Stokes shift of ~ 280 nm. Moreover, DCM-OH-2-DT shows high affinity towards soluble amyloid β (Aβ) oligomers in vitro and in 5xFAD mouse brain sections, and we have successfully applied DCM-OH-2-DT for the NIR fluorescence in vivo imaging of Aβ aggregates and demonstrated its potential use as an early diagnostic agent for AD. Overall, this study can provide a general molecular design strategy for developing new zwitterionic ESIPT compounds with NIR emission for further in vivo imaging applications.

Hidradenitis suppurativa (HS) is a multifactorial inflammatory disorder. Previous studies have ascertained an association between anemia and HS; however, they were limited by low sample size and lack of demographic information. The objective of this study is to address the concerns of prior research and identify specific subgroups and subtypes of anemia present in HS patients and evaluate how these subgroups impact hospital outcomes. We analyzed HS hospitalizations using the National Inpatient Sample from the years 2016 to 2019. HS was associated with the nutritional anemia, aplastic anemia, and acute posthemorrhagic anemia subgroups. Within these subgroups, HS was specifically associated with iron deficiency anemia, anemia of chronic disease, and other anemia subtypes. HS patients also displayed a lower risk of having aplastic anemia, also described as anemia from bone marrow failure. Our findings build upon previous studies evaluating HS and anemia and provide a clearer understanding of the association as well as how it impacts inpatient outcomes.

Surfactants are extensively employed in industrial, agricultural, and food, cosmetics and pharmaceuticals applications. Chemically produced surfactants cause environmental and toxicological hazards. Recently, considerable research has led to environmentally friendly procedures for the synthesis of several forms of biosurfactants from microorganisms. In comparison to chemical surfactants, biosurfactants have several advantages, such as biodegradability, low toxicity and ease of availability of raw materials. This paper offers an in-depth review of the types of surfactants, the need for bio-surfactants, their types and advantages, especially biodegradability. It also examines the biodegradability of selected four surfactants and finds that the biosurfactant is more easily biodegradable than the chemical surfactants.

Chronic thromboembolic pulmonary hypertension is an underdiagnosed condition. Patients typically present with the symptoms of right heart failure. Diagnosis is usually done by radionuclide ventilation/perfusion (VQ) scan, high-quality multidetector computed tomography (CT) or pulmonary angiography at expert centers. Pulmonary endarterectomy remains the corner stone in management of chronic thromboembolic pulmonary hypertension. Deep hypothermic circulatory arrest is commonly used for the operation at most centers. In-hospital mortality ranges from 1.7 to 14.2%. Pulmonary hemorrhage, reperfusion lung injury, and right ventricular failure remain major early post-operative concerns. Five-year survival is reported to be 76 to 89%. Long-term outcome depends on residual pulmonary hypertension. Balloon pulmonary angioplasty and medical management play an adjunctive role. Here, we provide a comprehensive review on surgical management of chronic thromboembolic pulmonary hypertension.

Aortic root dilation (ARD) has been reported in patients with 22q11.2 deletion syndrome (22q11.2DS) with and without congenital heart defects (CHDs). However, the long-term implications of isolated ARD in 22q11.2DS remain undefined. In this study, we measured aortic root size and estimated the probability of changing between normal aortic root size and ARD during follow up to understand the prevalence, longitudinal course, and clinical risk factors for ARD in patients with 22q11.2DS without intracardiac CHDs. Aortic root size was measured in 251 patients with 432 studies. Forty-one patients (16.3%) had ARD on at least one echocardiogram and the cohort sinus Z-score was increased on the last echocardiogram [mean (1.09, SD 1.24) and median (1.20, min − 1.90 and max 5.40)]. Transition probability analysis showed that 8.1% of patients developed ARD and 45.4% of patients with ARD reverted to normal at the next echocardiogram. The risk of ARD over time was significantly associated with male sex (OR 3.06, 95% CI 1.41–6.65; p = 0.004), but not with age or presence of an aortic arch anomaly. Compared to a sinus Z-score ≥ 2, initial Z-score 4, and patients with initial Z-scores

The promise of precision medicine is to improve patient outcomes by making better therapeutic choices based on cancer causing somatic mutations. This strategy has shown limited success in colorectal cancer, in part because the genetic rules governing resistance and sensitivity are not fully elucidated. Direct drug sensitivity testing of individual patient-derived organoids is an attractive addition to this decision process because it does not require understanding of all drug-somatic mutation interactions. Individual patients avatars can be challenged with a variety of drugs and response used to inform patient care. We have developed a panel of colon cancer organoid avatars and uniquely tagged each one with a lentiviral vector possessing identifying DNA sequence bar codes flanked by common PCR primers. Each bar-code is uniquely identifiable and quantifiable from a mixture of organoids by nanopore sequencing of a common PCR product. Treatment of the mixture of organoid avatars over time under multiple drug conditions and sampling at different time points allowed the real-time monitoring of relative Darwinian fitness of each organoid in the mixture. We demonstrated the utility of this approach at identifying both expected and novel drug responses for individual organoids. Resistance to both nutlin and irinotecan were correctly predicted by TP53 somatic mutations while sensitivity to both lapatinib and ibrutinib were best predicted by mutations in EGFR signaling pathway. Patterns of drug response revealed unexpected common mechanisms. Future work will focus on informing patient care decisions with these results and determining if improvements in patient outcomes are realized. Citation Format: Shrey Patel, Sana Khalili, Victoria Moy, Emma Gray, Sawyer Lyons, Riley Brents, Carolyn Banister, Phillip J. Buckhaults. A multiplex organoid avatar drug testing platform for precision medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB162.

Background Some patients with chronic pain and implanted spinal cord stimulators or intrathecal (IT) pumps fail to obtain significant pain relief. The use of dual modality treatment with both therapies is understudied. This study evaluated comprehensive outcomes in this patient population and reported outcomes primarily using IT ziconotide. Methods We retrospectively analyzed 11 patients with chronic pain treated with both spinal cord stimulation and IT therapy. When a primary treatment failed to achieve significant pain relief, a secondary device was trialed and implanted. Pain severity (measured by a numeric rating scale) was assessed by the change from baseline to after the first and second intervention. In a subset of patients (n = 6), quality-of-life metrics were also assessed. Outcome measures were analyzed closest to the 1-year follow-up date after implantation of the first modality and then at the most recent follow-up after implantation of the second modality. Results Spinal cord stimulation leads were percutaneous (n = 2) or paddles (n = 9) and commonly covered T8-10. IT medication included ziconotide (n = 8), baclofen (n = 1), hydromorphone (n = 1), and morphine/clonidine (n = 1). There was a mean of 19.64 ± 3.17 months between primary and secondary intervention. There was a significant improvement in pain severity from baseline to implantation of the second modality (P = 0.032) at a mean follow-up of 50.18 ± 11.83 months. Conclusions Dual modality therapy is a potential treatment option in patients who have lost efficacy with a single neuromodulation modality. Further study is required to identify potential responders and nonresponders.

Objectives Spinal cord stimulation (SCS) is a well-established procedure for chronic neuropathic pain. Research has established patients with personal psychiatric history do not fare as well as their correspondents following SCS surgery. We explored whether a documented psychiatric family history (PFH) correlated with worse outcomes following SCS surgery. Materials and methods We retrospectively reviewed our single-center, prospectively collected database of patients who received permanent SCS implants over the past eight years. Subjects were separated into those with documented PFH and those without. Subjects completed validated scales at preoperative, 6 ± 2 postoperative, and 12 ± 3 months postoperative visits. The percent change in scores from preoperative to postoperative timepoints was compared between subjects with PFH vs. controls. Results SCS subjects reporting a PFH demonstrated significantly worse 6-month outcomes on Pain Catastrophizing Scale-rumination subscale (p = 0.02), numeric rating scale (NRS) scores on "pain at its least" (p = 0.04) and NRS "pain right now" (p = 0.02). This group also endorsed greater disability as measured by the Oswestry Disability Index (ODI) throughout the follow-up period (p = 0.04 at 6 ± 2 months, p = 0.001 at 12 ± 3 months). Conclusions Subjects with PFH may experience less improvement in disability following SCS as compared to subjects without PFH. They may take longer to achieve the same outcomes, including pain relief and decrease in pain rumination. Our findings show that improvements in the PFH cohort are equivalent to that of the no PFH cohort on all measures except ODI at 12-month follow-up. Thus obtaining a detailed PFH prior to performing SCS is important in order to implement pre-operative coping training for PFH patients, rather than exclusion from SCS.

Introduction: The pineal gland, an endocrine organ of the posterior cranial fossa famously involved in sleep and wakefulness, has continually been a topic of scientific advancement and curiosity. Methods: We review present an up-to-date review including the anatomy, embryology, and physiology of the pineal gland and its ability to secrete hormones including melatonin, pathophysiology of pineal gland tumors, cysts, and calcifications, their clinical presentation including their association with parkinsonism and precocious puberty, and various treatment approaches. Results: Exploring the biochemistry of melatonin, various calcification morphologies, and pineal tumors may uncover a wider role and the exhaustive case study consolidation allows clinicians to carefully review the literature and aid their treatment approaches. Conclusion: It is imperative that clinicians and diagnosticians are able to distinguish manifestations of an overlooked gland.

Ozone can be medically useful concerning healing wounds and relieving pain in various conditions, such as disc disease. The aspects of human blood ozonation have been reviewed, as well as potential complications that may arise. The mechanisms of ozone therapy are discussed in detail. It is imperative to recognize ozone as a useful proxy in oxidative-stress related diseases, consolidating other medical gases recognized for their therapeutic importance. The utility of hyperbaric oxygen therapy is also discussed. Disc herniation is very common, as more than 3 million cases are treated per year. Herein we review the medical, surgical, and gene-based therapies that ozone therapy can provide regarding disc disease.

We describe a case of successful use of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO), as a bridge to cytoreductive therapy, in a patient with large mediastinal mass due to T cell lymphoblastic leukemia, complicated by acute cardiorespiratory compromise from mechanical compression and pulmonary embolism. Electronic supplementary material The online version of this article (10.1007/s12055-020-00992-3) contains supplementary material, which is available to authorized users.

Parasitic diseases of the spinal cord and nerve roots are a potentially deadly matter. They are mainly found in areas where there are poor sanitary conditions such as Africa, the Middle East, and the West Indies. The most common diseases include schistosomiasis and neurocysticercosis. Furthermore, it is clear that through an understanding of all the various diseases there are, it is imminent that patients are treated as soon as possible to avoid the deadly outcomes that the diseases can have to the body. This disease can have several impacts on individuals that include epilepsy, health problems, and implications on various organs.

Misfolded proteins or polypeptides commonly observed in neurodegenerative diseases, including Alzheimer’s disease (AD), are promising drug targets for developing therapeutic agents. To target the amyloid-β (Aβ) plaques and oligomers, the hallmarks of AD, we have developed twelve amphiphilic small molecules with different hydrophobic and hydrophilic fragments. In vitro binding experiments (i.e., fluorescence saturation assays) demonstrated that these amphiphilic compounds show high binding affinity to both Aβ plaques and oligomers, and six of them exhibit even higher binding affinity toward Aβ oligomers. These amphiphilic compounds can also label ex vivo Aβ species in the brain sections of transgenic AD mice, as shown by immunostaining with an Aβ antibody. Molecular docking studies were performed to help understand the structure-affinity relationships. To our delight, four amphiphilic compounds can alleviate Cu2+-Aβ induced toxicity in mouse neuroblastoma N2a via cell toxicity assays. In addition, confocal fluorescence imaging studies provided evidence that compounds ZY-15-MT and ZY-15-OMe can disrupt the interactions between Aβ oligomers and human neuroblastoma SH-SY5Y cell membranes. Overall, these studies suggest that developing compounds with amphiphilic properties that target Aβ oligomers can be an effective strategy for small molecule AD therapeutics.

At the neuromuscular junction (NMJ), postsynaptic ionotropic acetylcholine receptors (AChRs) transduce a chemical signal released from a cholinergic motor neuron into an electrical signal to induce muscle contraction. To identify regulators of postsynaptic function, we conducted a genome-wide RNAi screen for genes required for proper response to levamisole, a pharmacological agonist of ionotropic L-AChRs at the Caenorhabditis elegans NMJ. A total of 117 gene knockdowns were found to cause levamisole hypersensitivity, while 18 resulted in levamisole resistance. Our screen identified conserved genes important for muscle function including some that are mutated in congenital myasthenic syndrome, congenital muscular dystrophy, congenital myopathy, myotonic dystrophy, and mitochondrial myopathy. Of the genes found in the screen, we further investigated those predicted to play a role in endocytosis of cell surface receptors. Loss of the Epsin homolog epn-1 caused levamisole hypersensitivity and had opposing effects on the levels of postsynaptic L-AChRs and GABAA receptors, resulting in increased and decreased abundance, respectively. We also examined other genes that resulted in a levamisole-hypersensitive phenotype when knocked down including gas-1, which functions in Complex I of the mitochondrial electron transport chain. Consistent with altered ATP synthesis impacting levamisole response, treatment of wild-type animals with levamisole resulted in L-AChR–dependent depletion of ATP levels. These results suggest that the paralytic effects of levamisole ultimately lead to metabolic exhaustion.

Background: The 22q11.2 duplication syndrome (22q11.2DupS) has been diagnosed more frequently with the advent of microarray technology. Given that it disrupts the same region as the more familiar 22q11.2 deletion syndrome (22q11.2DS), patients with the duplication have been referred for similar organ system involvement but appear to display a distinct variable phenotype. To better describe the cardiac manifestations of the 22q11.2DupS, we performed a detailed review of a large 22q11.2DupS cohort in order to: (1) detail the cardiac phenotype, (2) estimate the prevalence of aortic arch anomalies, and (3) …

Ocean acidification can affect the ability of calcifying organisms to build and maintain mineralized tissue. In decapod crustaceans, the exoskeleton is a multilayered structure composed of chitin, protein, and mineral, predominately magnesian calcite or amorphous calcium carbonate (ACC). We investigated the effects of acidification on the exoskeleton of mature (post-terminal-molt) female southern Tanner crabs, Chionoecetes bairdi. Crabs were exposed to one of three pH levels—8.1, 7.8, or 7.5—for two years. Reduced pH led to a suite of body-region-specific effects on the exoskeleton. Microhardness of the claw was 38% lower in crabs at pH 7.5 compared with those at pH 8.1, but carapace microhardness was unaffected by pH. In contrast, reduced pH altered elemental content in the carapace (reduced calcium, increased magnesium), but not the claw. Diminished structural integrity and thinning of the exoskeleton was observed at reduced pH in both body regions; internal erosion of the carapace was present in most crabs at pH 7.5, and the claws of these crabs showed substantial external erosion, with tooth-like denticles nearly or completely worn away. Using infrared spectroscopy, we observed a shift in the phase of calcium carbonate present in the carapace of pH-7.5 crabs: a mix of ACC and calcite was found in the carapace of crabs at pH 8.1, whereas the bulk of calcium carbonate had transformed to calcite in pH-7.5 crabs. With limited capacity for repair, the exoskeleton of long-lived crabs that undergo a terminal molt, such as C. bairdi, may be especially susceptible to ocean acidification. Keywords: biomineralization; climate change; cuticle; calcite; amorphous calcium carbonate (ACC); Crustacea

The aim of our project is to provide safety as well as security to people from the largest electromechanical objects which are available at home. An automatic garage door mechanism was selected as a subject of our research as it is the complex electro-chemical object at home. As technology increases day by day every households installs this automatic garage door mechanism. The major problem with the conventional garage door system was child entrapment and people are in wheelchair are also affected by the conventional garage door mechanism. We are planning to eliminate the problems which are available in the conventional garage door mechanism by providing some extra safety and security features to our automatic garage door mechanism.an automatic garage door mechanism is the combination of mechanical and electrical system in which mechanical system guides the system as well as direct the shutter movement While, electrical system is used to provide energy to mechanical part. Sectional overhead doors have become the standard door type for garages. Our motive behind this study is to increase the safety and security of the automatic garage doors as well as make it to operatable at variable speed. Safety of the equipment is going to be increased by an area presence sensor which will reduce the child entrapment cases. Only authorized people can access the garage, that will increase the security and use of the VFD-variable frequency drive will make the garage door operatable at owner desired working speed. These shutters can be used for home applications as well as industrial applications.

Aortic root dilation (ARD) has been reported in patients with 22q11.2 deletion syndrome (22q11.2DS) with and without congenital heart defects (CHDs). However, the long-term implications of isolated ARD in 22q11.2DS remain undefined. In this study, we measured aortic root size and estimated the probability of changing between normal aortic root size and ARD during follow up to understand the prevalence, longitudinal course, and clinical risk factors for ARD in patients with 22q11.2DS without intracardiac CHDs. Aortic root size was measured in 251 patients with 432 studies. Forty-one patients (16.3%) had ARD on at least one echocardiogram and the cohort sinus Z-score was increased on the last echocardiogram [mean (1.09, SD 1.24) and median (1.20, min - 1.90 and max 5.40)]. Transition probability analysis showed that 8.1% of patients developed ARD and 45.4% of patients with ARD reverted to normal at the next echocardiogram. The risk of ARD over time was significantly associated with male sex (OR 3.06, 95% CI 1.41-6.65; p = 0.004), but not with age or presence of an aortic arch anomaly. Compared to a sinus Z-score ≥ 2, initial Z-score 2 was associated with 14.3 times lower risk of developing sinus Z-score ≥ 3 at follow up. Sinus Z-score overall decreased by age, and males had a higher Z-score than females (ß = 0.72, SE = 0.14, p 0.001). Though only a few patients had a Z-score 4, and patients with initial Z-scores 2 seem unlikely to develop clinically significant disease, screening practices remain incompletely defined such that periodic evaluation appears warranted.

At the neuromuscular junction (NMJ), postsynaptic ionotropic acetylcholine receptors (AChRs) transduce a chemical signal released from a cholinergic motor neuron into an electrical signal to induce muscle contraction. To identify regulators of postsynaptic function, we conducted a genome-wide RNAi screen for genes required for proper response to levamisole, a pharmacological agonist of ionotropic L-AChRs at theCaenorhabditis elegansNMJ. A total of 117 gene knockdowns were found to cause levamisole hypersensitivity, while 18 resulted in levamisole resistance. Our screen identified conserved genes important for muscle function including some that are mutated in congenital myasthenic syndrome, congenital muscular dystrophy, congenital myopathy, myotonic dystrophy, and mitochondrial myopathy. Of the genes found in the screen, we further investigated those predicted to play a role in endocytosis of cell surface receptors. Loss of the Epsin homologepn-1had opposing effects on the levels of postsynaptic L-AChRs and GABAAreceptors, resulting in increased and decreased abundance, respectively. This disrupts the balance of postsynaptic excitatory and inhibitory signaling, causing levamisole hypersensitivity. We also examined other genes that resulted in a levamisole hypersensitive phenotype when knocked down includinggas-1, which functions in Complex I of the mitochondrial electron transport chain. Consistent with altered ATP synthesis impacting levamisole response, treatment of wild-type animals with levamisole resulted in L-AChR dependent depletion of ATP levels. These results suggest that the paralytic effects of levamisole ultimately lead to metabolic exhaustion.