Management of patients with epilepsy and Intellectual disabilities in group homes vs. Family Homes: Insights into polypharmacy and seizure characteristics.

OBJECTIVES: This study aimed to investigate the differences in ASMs prescription, seizure characteristics and predictors of polypharmacy in patients with epilepsy and Intellectual disabilities (IDs) residing in group homes versus family homes. METHODS: This nine-year retrospective study analyzed patients with epilepsy and IDs who were admitted to the EMU, epilepsy clinics at LHSC and rehabilitation clinics for patients with IDs at Parkwood Institution. The study included individuals aged 16 years and older residing in either group homes or family homes. Data on demographics, epilepsy characteristics, and ASMs use were collected and analyzed using the Statistical Package for Social Sciences. The study utilized binary logistic regression to identify predictors of polypharmacy in patients with epilepsy and IDs. RESULTS: The study enrolled a total of 81 patients, of which 59.3 % resided in family homes. Group home residents were significantly older (41 vs. 24.5 years; p = 0.0001) and were prescribed more ASMs (3 vs. 2; p = 0.002). Specific ASMs were more common in group homes, including valproic acid (54.5 % vs. 25.0 %), lacosamide (54.5 % vs. 22.9 %), topiramate (33.3 % vs. 14.6 %), and phenytoin (30.3 % vs. 6.2 %). Admission to the EMU was more prevalent in group homes (93.9 % vs. 52.1 %; p = 0.0001). Living in a group home increased the risk of polypharmacy (OR = 10.293, p = 0.005), as did older epilepsy onset age (OR = 1.135, p = 0.031) and generalized or focal & generalized epilepsy (OR = 7.153, p = 0.032 and OR = 10.442, p = 0.025, respectively). SIGNIFICANCE: Our study identified notable differences in the demographic and clinical characteristics of patients with epilepsy and IDs living in group homes versus family homes. Age of epilepsy onset, EMU admissions, epilepsy types, and residency setting were significant predictors of polypharmacy. These findings highlight the need for personalized care strategies and increased awareness of the potential risks associated with polypharmacy.

Fluoride-Catalyzed Cross-Coupling of Carbamoyl Fluorides and Alkynylsilanes.

We report the synthesis of alkynamides via the cross-coupling of carbamoyl fluorides and alkynylsilanes catalyzed by tetrabutylammonium fluoride (TBAF). In contrast to previously reported transformations of carbamoyl fluorides, C-F bond cleavage is achieved under exceptionally mild conditions (room temperature, low catalyst loadings, and short reaction times) without the need for strongly nucleophilic reagents and/or catalysts. This method offers distinct advantages over transition-metal-catalyzed approaches, such as tolerance to aryl halide moieties and complementary chemoselectivity.

Polyethylene Glycol 20k. Does It Fluoresce?

Polyethylene glycol (PEG) is a polyether compound commonly used in biological research and medicine because it is biologically inert. This simple polymer exists in variable chain lengths (and molecular weights). As they are devoid of any contiguous π-system, PEGs are expected to lack fluorescence properties. However, recent studies suggested the occurrence of fluorescence properties in non-traditional fluorophores like PEGs. Herein, a thorough investigation has been conducted to explore if PEG 20k fluoresces. Results of this combined experimental and computational study suggested that although PEG 20k could exhibit "through-space" delocalization of lone pairs of electrons in aggregates/clusters, formed via intermolecular and intramolecular interactions, the actual contributor of fluorescence between 300 and 400 nm is the stabilizer molecule, i.e., 3-tert-butyl-4-hydroxyanisole present in the commercially available PEG 20k. Therefore, the reported fluorescence properties of PEG should be taken with a grain of salt, warranting further investigation.

Effects of over-the-counter at-home whitening products with LED light on surface roughness of partially- and fully crystalized CAD/CAM lithium disilicate ceramics.

The aim of this study is to evaluate the effect of over-the-counter (OTC) at-home whitening products with LED light on partially- and fully-crystalized CAD/CAM lithium disilicate ceramics. Two partially-crystalized CAD/CAM lithium disilicate ceramics, Amber Mill and IPS e.max CAD, and one fully-crystalized CAD/CAM lithium disilicate ceramic, n!ce Straumann, were used. The specimens were divided based on treatment with OTC whitening products: no treatment provided, Colgate Optic, Crest 3D and Walgreens Deluxe. The surface roughness of the specimens was evaluated with an optical profilometer and scanning electron microscopy. The three LED whitening products significantly increased the surface roughness and changed surface morphology of Amber Mill and IPS e.max CAD but no differences for n!ce Straumann. OTC at-home whitening products with LED light can significantly increase the surface roughness of restorations fabricated with these partially-crystalized CAD/CAM lithium disilicate ceramic restorations. However, these products do not increase the surface roughness of restorations fabricated with this fully-crystalized lithium disilicate ceramic.

Experimental and numerical investigation of 3D-Printed bone plates under four-point bending load utilizing machine learning techniques.

The fused deposition modeling (FDM) technique is widely used to produce components for various applications and has the potential to revolutionize orthopedic research through the production of custom-fit and readily available biomedical implants. The properties of FDM-produced implants are significantly influenced by processing parameters, with layer thickness being a crucial parameter. This study investigated the effect of layer thickness on the flexural properties of Polylactic Acid (PLA) bone plate implants produced by the FDM technique. Experimental results showed that the flexural strength is inversely proportional to the layer thickness due to the variation of voids in the specimens. A 3D finite element (FE) model was developed using Abaqus/Explicit software by incorporating the Gurson-Tvergaard (GT) porous plasticity model to predict the elastoplastic and damage behavior of specimens with different layer thicknesses. The characterization of the elastoplastic and GT parameters was done using a tensile test and by the calibration of a machine learning algorithm. It was shown that the FE model was able to predict the flexural behavior of 3D-printed solid plates with a maximum error of 6.13% in the maximum load. The optimal layer height was found to be 0.1 mm, providing both high flexural strength and adequate bending stiffness.

BF3-Catalyzed Intramolecular Fluorocarbamoylation of Alkynes via Halide Recycling.

A BF3-catalyzed atom-economical fluorocarbamoylation reaction of alkyne-tethered carbamoyl fluorides is reported. The catalyst acts as both a fluoride source and Lewis acid activator, thereby enabling the formal insertion of alkynes into strong C-F bonds through a halide recycling mechanism. The developed method provides access to 3-(fluoromethylene) oxindoles and γ-lactams with excellent stereoselectivity, including fluorinated derivatives of known protein kinase inhibitors. Experimental and computational studies support a stepwise mechanism for the fluorocarbamoylation reaction involving a turnover-limiting cyclization step, followed by internal fluoride transfer from a BF3-coordinated carbamoyl adduct. For methylene oxindoles, a thermodynamically driven Z-E isomerization is facilitated by a transition state with aromatic character. In contrast, this aromatic stabilization is not relevant for γ-lactams, which results in a higher barrier for isomerization and the exclusive formation of the Z-isomer.

Synthesis of Carbamoyl Fluorides Using a Difluorophosgene Surrogate Derived from Difluorocarbene and Pyridine N-Oxides.

We report a method for the synthesis of carbamoyl fluorides from secondary amines using bench-stable, inexpensive, and readily accessible starting materials that, when combined, yield a surrogate for toxic difluorophosgene (COF2) gas. In contrast to state-of-the-art methods for the synthesis of carbamoyl fluorides, our protocol does not require the use of pre-functionalized substrates, the preparation of light-, temperature-, and/or moisture-sensitive chemicals, or the application of explosive fluorinating reagents.

Evolution of Stronger SARS-CoV-2 Variants as Revealed Through the Lens of Molecular Dynamics Simulations.

Using molecular dynamics simulations, the protein-protein interactions of the receptor-binding domain of the wild-type and seven variants of the severe acute respiratory syndrome coronavirus 2 spike protein and the peptidase domain of human angiotensin-converting enzyme 2 were investigated. These variants are alpha, beta, gamma, delta, eta, kappa, and omicron. Using 100 ns simulation data, the residue interaction networks at the protein-protein interface were identified. Also, the impact of mutations on essential protein dynamics, backbone flexibility, and interaction energy of the simulated protein-protein complexes were studied. The protein-protein interface for the wild-type, delta, and omicron variants contained several stronger interactions, while the alpha, beta, gamma, eta, and kappa variants exhibited an opposite scenario as evident from the analysis of the inter-residue interaction distances and pair-wise interaction energies. The study reveals that two distinct residue networks at the central and right contact regions forge stronger binding affinity between the protein partners. The study provides a molecular-level insight into how enhanced transmissibility and infectivity by delta and omicron variants are most likely tied to a handful of interacting residues at the binding interface, which could potentially be utilized for future antibody constructs and structure-based antiviral drug design.

Conserved metabolic enzymes as vaccine antigens for giardiasis.

Giardia lamblia is a leading protozoal cause of diarrheal disease worldwide. Infection is associated with abdominal pain, malabsorption and weight loss, and protracted post-infectious syndromes. A human vaccine is not available against G. lamblia. Prior studies with human and murine immune sera have identified several parasite antigens, including surface proteins and metabolic enzymes with intracellular functions. While surface proteins have demonstrated vaccine potential, they can exhibit significant variation between G. lamblia strains. By comparison, metabolic enzymes show greater conservation but their vaccine potential has not been established. To determine whether such proteins can serve as vaccine candidates, we focused on two enzymes, α-enolase (ENO) and ornithine carbamoyl transferase (OCT), which are involved in glycolysis and arginine metabolism, respectively. We show in a cohort of patients with confirmed giardiasis that both enzymes are immunogenic. Intranasal immunization with either enzyme antigen in mice induced strong systemic IgG1 and IgG2b responses and modest mucosal IgA responses, and a marked 100- to 1,000-fold reduction in peak trophozoite load upon oral G. lamblia challenge. ENO immunization also reduced the extent and duration of cyst excretion. Examination of 44 cytokines showed only minimal intestinal changes in immunized mice, although a modest increase of CCL22 was observed in ENO-immunized mice. Spectral flow cytometry revealed increased numbers and activation state of CD4 T cells in the small intestine and an increase in α4ß7-expressing CD4 T cells in mesenteric lymph nodes of ENO-immunized mice. Consistent with a key role of CD4 T cells, immunization of CD4-deficient and Rag-2 deficient mice failed to induce protection, whereas mice lacking IgA were fully protected by immunization, indicating that immunity was CD4 T cell-dependent but IgA-independent. These results demonstrate that conserved metabolic enzymes can be effective vaccine antigens for protection against G. lamblia infection, thereby expanding the repertoire of candidate antigens beyond primary surface proteins.

Cooperative Stereoinduction in Asymmetric Photocatalysis.

Stereoinduction in complex organic reactions often involves the influence of multiple stereocontrol elements. The interaction among these can often result in the observation of significant cooperative effects that afford different rates and selectivities between the matched and mismatched sets of stereodifferentiating chiral elements. The elucidation of matched/mismatched effects in ground-state chemical reactions was a critically important theme in the maturation of modern stereocontrolled synthesis. The development of robust methods for the control of photochemical reactions, however, is a relatively recent development, and similar cooperative stereocontrolling effects in excited-state enantioselective photoreactions have not previously been documented. Herein, we describe a tandem chiral photocatalyst/Brønsted acid strategy for highly enantioselective [2 + 2] photocycloadditions of vinylpyridines. Importantly, the matched and mismatched chiral catalyst pairs exhibit different reaction rates and enantioselectivities across a range of coupling partners. We observe no evidence of ground-state interactions between the catalysts and conclude that these effects arise from their cooperative behavior in a transient excited-state assembly. These results suggest that similar matched/mismatched effects might be important in other classes of enantioselective dual-catalytic photochemical reactions.

Successful use of enteral nutrition for asparaginase-induced pancreatitis in children with acute lymphoblastic leukemia and lymphoblastic lymphoma: A case series.

Asparaginase-induced acute pancreatitis (AAP) is a concerning adverse effect in the treatment of pediatric acute lymphoblastic leukemia and lymphoblastic lymphoma. Typically, treatment of AAP follows a nil per os approach with or without parenteral nutrition (PN). However, with accounts of increased risk of adverse events, such as bacterial translocation and multiorgan failure when PN is used in lieu of enteral nutrition (EN), the recent literature has advocated for a change in practice to the early use of EN for children and adults with acute pancreatitis. Despite these recommendations, a gap remains in the literature regarding whether or not early enteral feedings are currently being used in pediatric oncology patients with acute pancreatitis. In our case series, we account for the successful use of EN to manage AAP in three pediatric patients with acute lymphoblastic leukemia/lymphoblastic lymphoma. Additionally, we describe the development of an early enteral feeding protocol for pediatric oncology patients with pancreatitis. To the best of our knowledge, this is the first case series chronicling the nutritional management of AAP using EN in the pediatric oncology population. The successful use of EN we have seen in our patients supports the shift in treatment practice to the use of EN in lieu of PN for this population.

Vitamin D and COVID-19: A review on the role of vitamin D in preventing and reducing the severity of COVID-19 infection.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a pathogenic coronavirus causing COVID-19 infection. The interaction between the SARS-CoV-2 spike protein and the human receptor angiotensin-converting enzyme 2, both of which contain several cysteine residues, is impacted by the disulfide-thiol balance in the host cell. The host cell redox status is affected by oxidative stress due to the imbalance between the reactive oxygen/nitrogen species and antioxidants. Recent studies have shown that Vitamin D supplementation could reduce oxidative stress. It has also been proposed that vitamin D at physiological concentration has preventive effects on many viral infections, including COVID-19. However, the molecular-level picture of the interplay of vitamin D deficiency, oxidative stress, and the severity of COVID-19 has remained unclear. Herein, we present a thorough review focusing on the possible molecular mechanism by which vitamin D could alter host cell redox status and block viral entry, thereby preventing COVID-19 infection or reducing the severity of the disease.

Elevated fecal calprotectin is linked to psychosocial complexity in pediatric functional abdominal pain disorders.

OBJECTIVE: Children with functional abdominal pain disorders (FAPD) and clinical elevations in three risk areas (anxiety, functional disability, and pain) have been found to be at increased risk for persistent disability. We evaluated if the presence of these three risk factors corresponded with greater gastrointestinal inflammation (measured via fecal calprotectin; FC) compared to those with no risk factors. FC concentration differences between children with three risk factors and those with one and two risk factors were explored. RESULTS: Fifty-six children with FAPD (Mage = 12.23) completed measures of anxiety (Screen for Child Anxiety Related Disorders), disability (Functional Disability Inventory), and pain intensity (Numeric Rating Scale). Participants were stratified into risk groups (range: 0-3). Fisher's exact tests were conducted to determine if children with three versus fewer risk factors were more likely to have elevated FC (≥ 50 µg/g) versus normal levels. Children with three risk factors (MFC = 86.04) were more likely to have elevated FC compared to children with zero (MFC = 25.78), one (MFC = 38.59), and two risk factors (MFC = 45.06; p's < 0.05). Those with three risk factors had borderline elevated FC concentrations whereas those with fewer had normal FC concentrations. Findings suggest the importance of a biopsychosocial approach to help elucidate a FAPD phenotype.

Pharmacotherapy for Neuropsychiatric Symptoms in Frontotemporal Dementia.

Despite significant progress in the understanding of the frontotemporal dementias (FTDs), there remains no disease-modifying treatment for these conditions, and limited effective symptomatic treatment. Behavioural variant frontotemporal dementia (bvFTD) is the most common FTD syndrome, and is characterized by severe impairments in behaviour, personality and cognition. Neuropsychiatric symptoms are common features of bvFTD but are present in the other FTD syndromes. Current treatment strategies therefore focus on ameliorating the neuropsychiatric features. Here we review the rationale for current treatments related to each of the main neuropsychiatric symptoms forming the diagnostic criteria for bvFTD relevant to all FTD subtypes, and two additional symptoms not currently part of the diagnostic criteria: lack of insight and psychosis. Given the paucity of effective treatments for these symptoms, we highlight how contributing mechanisms delineated in cognitive neuroscience may inform future approaches to clinical trials and more precise symptomatic treatments for FTDs.

Risk of Silent Myocardial Infarction in Prediabetic Patients: A Case-Control Study in a Veteran Population.

OBJECTIVES: In the management of cardiovascular disease, it is important to identify patients at risk early on, to provide interventions to prevent the disease and its complications. The goal of our study was to investigate the association between glucose levels and silent myocardial infarction (SMI) among patients, who consisted of veterans within the Veterans Affairs clinical system. METHODS: Among the group of patients with an initially normal electrocardiogram, a cohort of patients with a subsequent diagnosis of SMI was selected as the case cohort, whereas 4 patients for each study subject, without evidence of coronary artery disease and normal electrocardiogram within the previous 6 months, were identified and constituted the control cohort. We conducted an adjusted logistic regression model using the stepwise function to assess the association between glucose level and SMI. RESULTS: Of the 540 patients included in the study, 108 (20.0%) with an SMI diagnosis made up the case cohort. We observed that as compared with those who had normal levels of glucose, those who were prediabetic were 3.99 times as likely (95% confidence interval 1.48-12.85) to have SMI, whereas the diabetic patients were 3.80 times as likely (95% confidence interval 1.39-12.38) to experience SMI. CONCLUSIONS: SMIs have been shown to be predictive of subsequent cardiovascular events, including another MI and death, and that indicates the importance of identifying a group at high risk for a SMI. As such, our findings could be extremely beneficial for targeted intervention toward prediabetics and to improve health outcomes in the entire population.

Home Visit Based Mindfulness Intervention for Vietnamese American Dementia Family Caregivers: A Pilot Feasibility Study.

Background: Healthcare disparities continue to exist among the Vietnamese American (VA) community and many factors (e.g., fear of social stigma) deter family caregivers of persons with dementia (PWD) from seeking assistance. Purpose: To pilot-test a language-specific and culturally appropriate mindfulness intervention to improve dementia VA family caregiver well-being. Methods: Bilingual, trained research assistants administered a mindfulness exercise (i.e., deep breathing) to family caregivers and provided continuous support and care resources through weekly home visits for a month. Weekly surveys measured changes in emotion, feelings of connectedness to the PWD, and mood (i.e., happiness) before and after the intervention. Results: A total of nine VA family caregivers of PWD participated in this pilot study. Positive affect showed an increasing trend (M pre = 16.0 (SD = 3.48), M post = 17.1 (SD = 3.06)) and negative affect showed a decreasing trend (M pre = 6.44 (SD = 3.31), M post = 5.22 (SD = 0.359)). Happiness showed an increasing trend (M pre = 4.30 (SD = 0.767), M post = 4.44 (SD = 0.873)). Conclusions: These findings suggest that a home-based dementia family caregiver intervention with mindfulness exercises may potentially increase positive affect and decrease negative affect in Vietnamese American family caregivers of PWD. Similar interventions may help reduce caregiver burden in dementia family caregivers of other cultures.

Cognitive Behavior Therapy Tailored to Anxiety Symptoms Improves Pediatric Functional Abdominal Pain Outcomes: A Randomized Clinical Trial.

OBJECTIVES: To evaluate the feasibility of a stepped care model, and establish the effect of a tailored cognitive behavioral therapy, the Aim to Decrease Anxiety and Pain Treatment (ADAPT), compared with standard medical treatment as usual on pain-related outcomes and anxiety. STUDY DESIGN: Eligible patients between the ages of 9 and 14 years with functional abdominal pain disorders (n = 139) received enhanced usual care during their medical visit to a gastroenterologist. Those that failed to respond to enhanced usual care were randomized to receive either a tailored cognitive behavioral therapy (ADAPT) plus medical treatment as usual, or medical treatment as usual only. ADAPT dose (4 sessions of pain management or 6 sessions of pain and anxiety management) was based on presence of clinically significant anxiety. Outcomes included feasibility, based on recruitment and retention rates. Response to ADAPT plus medical treatment as usual vs medical treatment as usual on pain-related outcomes and anxiety measures was also investigated using a structural equation modeling equivalent of a MANCOVA. Anxiety levels and ADAPT dose as moderators of treatment effects were also explored. RESULTS: Based on recruitment and retention rates, stepped care was feasible. Enhanced usual care was effective for only 8% of youth. Participants randomized to ADAPT plus medical treatment as usual showed significantly greater improvements in pain-related disability, but not pain levels, and greater improvements in anxiety symptoms compared with those randomized to medical treatment as usual only. Anxiety and ADAPT treatment dose did not moderate the effect of treatment on disability nor pain. CONCLUSIONS: Tailoring care based on patient need may be optimal for maximizing the use of limited psychotherapeutic resources while enhancing care. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03134950.

Measuring the Change in Health-Related Quality of Life in Patients Using Marijuana for Pain Relief.

INTRODUCTION: Current evidence suggests that cannabinoids are safe with minimal side effects and are effective in managing chronic pain. Data also show that medical marijuana (MM) may improve quality of life (QoL) among patients. However, there are little data showing the health-related QoL (HRQoL) benefit in MM patients using it for pain. The purpose of this study was to determine if there is a relationship between HRQol and MM use in patients using it to relieve pain. METHODS: All pain patients aged 18 years or older enrolled in the Pennsylvania MM program were eligible for inclusion. Recruited subjects completed 4 surveys - at enrollment (baseline) then 2, 4, and 8 weeks post-enrollment. We used the EQ-5D survey tool for measuring HRQoL. The primary outcome measure was the change in the EQ-5D Index Score from survey 2 to survey 4 (6 week difference). Secondary outcomes included self-reported pain and health scores. Data were analyzed using a paired t test and repeated-measures multivariable analysis to control for both gender and length of time between surveys. RESULTS: 1,762 people responded to the screening request, and 1,393 (79%) met screening criteria. Of those, 353 (25.3%) agreed to participate and 51% completed all 4 surveys, for a final sample of 181 with 85 male and 95 female and one nonbinary subject. The average age was 41.21 (SD = 12.9) years, with no difference between genders. The adjusted HRQoL score improved from 0.722 to 0.747 (p = 0.011) from survey 2 to survey 4, as did the self-reported pain and health scores. The EQ-5D subscales revealed no change in mobility or usual activities, significant improvement in anxiety and pain, and a significant worsening in self-care. CONCLUSION: The results show a significant improvement in HRQoL among patients using MM for pain. The EQ-5D subscales validated the pain improvement and also showed an improvement in anxiety. However, the decline in the self-care subscale may have tempered the overall improvement in HRQoL, and further research into which aspects of self-care are impacted by MM use in this population is warranted. Overall, there is a positive relationship between MM use and HRQoL in patients using it for pain.