Capnocytophaga sputigena Tonsillitis in a Patient With Acute Myeloid Leukemia.

Capnocytophaga sputigena is a gram-negative facultatively anaerobic, capnophilic bacterium typically residing in the human oropharyngeal flora. This opportunistic pathogen can cause a wide range of infections, from bacteremia to septic abortion. However, it is exceedingly rare for a patient to present with tonsillitis due to C. sputigena. Herein, we discuss the presentation, hospital course, and clinical trajectory of a patient experiencing complications of tonsillitis related to C. sputigena in the context of acute myeloid leukemia. Additionally, we delve into the treatment approaches and challenges in managing this particular pathogen.

A Rare Case of Herpes Simplex Virus and Cytomegalovirus Dual Infection Inducing Unremitting Ulcerative Colitis.

Ulcerative colitis (UC) is a subtype of inflammatory bowel disease that results in inflammation and ulceration in the lining of the large intestine. Patients with UC are frequently prescribed immunosuppressive medications to treat their symptoms, resulting in an increased risk of reactivation of many latent viruses, including herpes simplex virus (HSV) and cytomegalovirus (CMV). However, it is rare for a patient to present with simultaneous reactivation of both viruses. Here, we document the presentation, hospital course, and clinical findings of a UC patient with HSV and CMV dual infection. We also describe treatment strategies and prophylactic measures for managing a dual infection. This is seen through initiating valganciclovir in the outpatient setting following the diagnosis.

The prognostic value of 19S ATPase proteasome subunits in acute myeloid leukemia and other forms of cancer.

Introduction: The ubiquitin-proteasome system (UPS) is an intracellular organelle responsible for targeted protein degradation, which represents a standard therapeutic target for many different human malignancies. Bortezomib, a reversible inhibitor of chymotrypsin-like proteasome activity, was first approved by the FDA in 2003 to treat multiple myeloma and is now used to treat a number of different cancers, including relapsed mantle cell lymphoma, diffuse large B-cell lymphoma, colorectal cancer, and thyroid carcinoma. Despite the success, bortezomib and other proteasome inhibitors are subject to severe side effects, and ultimately, drug resistance. We recently reported an oncogenic role for non-ATPase members of the 19S proteasome in chronic myeloid leukemia (CML), acute myeloid leukemia (AML), and several different solid tumors. In the present study, we hypothesized that ATPase members of the 19S proteasome would also serve as biomarkers and putative therapeutic targets in AML and multiple other cancers. Methods: We used data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) available at UALCAN and/or GEPIA2 to assess the expression and prognostic value of proteasome 26S subunit, ATPases 1-6 (PSMC1-6) of the 19S proteasome in cancer. UALCAN was also used to associate PSMC1-6 mRNA expression with distinct clinicopathological features. Finally, cBioPortal was employed to assess genomic alterations of PSMC genes across different cancer types. Results: The mRNA and protein expression of PSMC1-6 of the 19S proteasome were elevated in several cancers compared with normal controls, which often correlated with worse overall survival. In contrast, AML patients demonstrated reduced expression of these proteasome subunits compared with normal mononuclear cells. However, AML patients with high expression of PSMC2-5 had worse outcomes. Discussion: Altogether, our data suggest that components of the 19S proteasome could serve as prognostic biomarkers and novel therapeutic targets in AML and several other human malignancies.

More Than a Case of Cellulitis: Pasteurella multocida Bacteremia.

Pasteurella multocida (P. multocida) is an anaerobic Gram-negative coccobacilli belonging to the Pasteurella genus. It is found in many animals' oral cavities and gastrointestinal tracts, including those of cats and dogs. In this case report, we present an individual with cellulitis of the lower extremity who was later found to have P. multocida bacteremia. The patient had four pet dogs and one pet cat. He denied obtaining any scratches or bites from the pets. The patient initially presented to an urgent care center complaining of a one-day history of proximal left lower extremity edema, erythema, and pain. He was diagnosed with left leg cellulitis and discharged home on antibiotics. Three days after the patient was discharged home from the urgent care center, blood cultures returned positive for P. multocida. The patient was then admitted for inpatient treatment with intravenous antibiotics. Clinicians should always ask about domestic and wild animal exposure, even in the absence of bites or scratches. In the immunocompromised patient presenting with cellulitis, clinicians should consider the possibility of P. multocida bacteremia in those with pet exposure.

Closing the digital divide: Developing a platform to conduct training, outreach, and education for employment skills.

El Paso, Texas, like many communities along the United States/Mexico border, suffers from a lack of access to many social determinants of health, especially in low-income neighborhoods. These long-standing problems have only been exacerbated by the COVID-19 pandemic. The Texas Tech University Health Sciences Center El Paso Health Education and Awareness Team (EP-HEAT) is an organization that was established with a focus on disseminating health information to the community. EP-HEAT received funding from Microsoft Corporation to facilitate technology education workshops for underserved populations. These workshops were held in English and Spanish and attempted to improve social determinants of health in the community which can be negatively exacerbated by a lack of digital inclusion. Community members who attended workshops completed a LinkedIn Learning Path, or both were offered an anonymous post-course survey with a mixed method questionnaire on how their knowledge of basic technology or job skills was improved by engaging with the provided workshops and learning paths. Overall, 80% of community members who participated in the workshops reported learning a new skill, and 91% of participants who started a LinkedIn Learning Path were able to finish. The workshops were well received by the community and highlighted the potential for these programs to enhance digital skills and upward workforce mobility.

Peptide Drug Conjugates and Their Role in Cancer Therapy.

Drug conjugates have become a significant focus of research in the field of targeted medicine for cancer treatments. Peptide-drug conjugates (PDCs), a subset of drug conjugates, are composed of carrier peptides ranging from 5 to 30 amino acid residues, toxic payloads, and linkers that connect the payload to the peptide. PDCs are further broken down into cell-penetrating peptides (CPPs) and cell-targeting peptides (CTPs), each having their own differences in the delivery of cytotoxic payloads. Generally, PDCs as compared to other drug conjugates-like antibody-drug conjugates (ADCs)-have advantages in tumor penetration, ease of synthesis and cost, and reduced off-target effects. Further, as compared to traditional cancer treatments (e.g., chemotherapy and radiation), PDCs have higher specificity for the target cancer with generally less toxic side effects in smaller doses. However, PDCs can have disadvantages such as poor stability and rapid renal clearance due to their smaller size and limited oral bioavailability due to digestion of its peptide structure. Some of these challenges can be overcome with modifications, and despite drawbacks, the intrinsic small size of PDCs with high target specificity still makes them an attractive area of research for cancer treatments.

Brazilian Butt Lift Gone Wrong: A Case Series of Non-Tuberculous Mycobacterial Gluteal Infection After Brazilian Butt Lifts.

Cosmetic surgeries are very popular and glamorized by the mainstream media and celebrities. Many individuals perceive certain bodily features as appealing for physical attraction and will attempt to obtain these features by surgery. However, these surgeries are not without risk, and significant consequences can occur if not performed by qualified medical professionals under sterile procedures. The authors present novel cases of two healthy young female patients who underwent a Brazilian butt lift (BBL) procedure a week apart by the same plastic surgeon in Mexico and developed dark painful lesions secondary to Mycobacterium abscessus (M. abscessus), a multidrug-resistant non-tuberculous mycobacterium (NTM). The literature review shows a paucity of data concerning NTM infections via surgical procedures of this type. The first case was of a 31-year-old woman who underwent a BBL and presented with bilateral dark painful buttock lesions weeks later. The patient returned to the plastic surgeon, who drained some lesions and prescribed oral antibiotics. The patient's clinical status continued to deteriorate and presented to the hospital for further assessment. The patient was initially started on broad-spectrum antibiotic therapy. The patient was found to have an HIV infection with a relatively preserved CD4 lymphocyte count and was started on antiretroviral therapy (ART). Intraoperative excisional tissue sample cultures grew M. abscessus. The patient was started on empiric tigecycline, cefoxitin, and linezolid. Preliminary culture susceptibilities showed resistance to linezolid. Linezolid was discontinued, amikacin was started, and cefoxitin and tigecycline were continued. Tigecycline, cefoxitin, and amikacin were continued and final susceptibilities showed sensitivity to the current treatment. The patient received a total of four months of treatment with tigecycline, cefoxitin, and amikacin. The second case was of a 28-year-old woman who underwent a BBL a week after the first patient by the same surgeon and developed multiple gluteal and body abscesses. The patient underwent bilateral thigh and gluteal, right chest wall, and breast surgical debridements with intraoperative cultures at a different hospital facility, which grew M. abscessus. Susceptibilities were not performed there. The patient was transferred to our facility for further care. Intraoperative cultures remained negative, and the patient was treated with a six-month course of tigecycline, cefoxitin, and amikacin.

19S Proteasome Subunits as Oncogenes and Prognostic Biomarkers in FLT3-Mutated Acute Myeloid Leukemia (AML).

26S proteasome non-ATPase subunits 1 (PSMD1) and 3 (PSMD3) were recently identified as prognostic biomarkers and potential therapeutic targets in chronic myeloid leukemia (CML) and multiple solid tumors. In the present study, we analyzed the expression of 19S proteasome subunits in acute myeloid leukemia (AML) patients with mutations in the FMS-like tyrosine kinase 3 (FLT3) gene and assessed their impact on overall survival (OS). High levels of PSMD3 but not PSMD1 expression correlated with a worse OS in FLT3-mutated AML. Consistent with an oncogenic role for PSMD3 in AML, shRNA-mediated PSMD3 knockdown impaired colony formation of FLT3+ AML cell lines, which correlated with increased OS in xenograft models. While PSMD3 regulated nuclear factor-kappa B (NF-κB) transcriptional activity in CML, we did not observe similar effects in FLT3+ AML cells. Rather, proteomics analyses suggested a role for PSMD3 in neutrophil degranulation and energy metabolism. Finally, we identified additional PSMD subunits that are upregulated in AML patients with mutated versus wild-type FLT3, which correlated with worse outcomes. These findings suggest that different components of the 19S regulatory complex of the 26S proteasome can have indications for OS and may serve as prognostic biomarkers in AML and other types of cancers.

Evaluation of the Healthcare Cost Offsets of Mend: A Family Systems Mental Health Integration Approach.

Behavioral and physical health integration has been shown to be beneficial for overall health outcomes, as well as financial benefits. The current research clearly shows benefits, but lacks evidence specific to couples and family therapy (CFT) as a medium or profession within mental health integrated sites. This study tests the cost offsets of Mastering Each New Directions (MEND), a family system psychosocial approach to chronic illness (CI). Using retrospective charges from 107 CI adult patients, MEND (with an average of 25 sessions) was estimated to produce a 12-month cost savings of $16,684 or a 34.3% reduction in healthcare costs. This reduction significantly outweighed the cost of the intervention for a total net savings of $9,251 per participant in 12 months. Variations in cost reductions by demographic and treatment dosage are explored, and results suggest that a family systems psychosocial intervention can offer a health system an overall cost savings.

Se ha demostrado que la integración de la salud conductual y física es beneficiosa para los resultados en la salud en general, y que a su vez tiene beneficios económicos. La presente investigación muestra claramente beneficios, pero carece de indicios específicos para la terapia familiar y de pareja como medio o profesión dentro de centros integrados de salud mental. Este estudio evalúa los costos y la compensación de Mastering Each New Directions (MEND), un enfoque psicosocial de sistemas familiares para las enfermedades crónicas. Utilizando los gastos retrospectivos de 107 pacientes adultos con enfermedades crónicas, se calculó que el enfoque MEND (con un promedio de 25 sesiones) produce ahorros de $16.684 en los costos de 12 meses o una reducción del 34,3 % en los costos de asistencia sanitaria. Esta reducción sobrepasó considerablemente el costo de la intervención por un total de ahorros netos de $9251 por participante en 12 meses. Se analizan las variaciones en las reducciones de costos por dosis demográfica y de tratamiento, y los resultados sugieren que una intervención psicosocial de sistemas familiares puede ofrecer ahorros en los costos generales del sistema de salud.

High-resolution slice selection NMR for the measurement of CO2 diffusion under non-equilibrium conditions.

We present a simple and an efficient approach using spatially selective NMR to investigate solvation and diffusion of CO2 in ionic liquids. The techniques demonstrated here are shown as novel and effective means of studying solvated gas dynamics under non-equilibrium conditions without the need for conventional high power gradients.

Molecular interactions in the ionic liquid emim acetate and water binary mixtures probed via NMR spin relaxation and exchange spectroscopy.

Interactions of ionic liquids (ILs) with water are of great interest for many potential IL applications. 1-Ethyl-3-methylimidazolium (emim) acetate, in particular, has shown interesting interactions with water including hydrogen bonding and even chemical exchange. Previous studies have shown the unusual behavior of emim acetate when in the presence of 0.43 mole fraction of water, and a combination of NMR techniques is used herein to investigate the emim acetate-water system and the unusual behavior at 0.43 mole fraction of water. NMR relaxometry techniques are used to describe the effects of water on the molecular motion and interactions of emim acetate with water. A discontinuity is seen in nuclear relaxation behavior at the concentration of 0.43 mole fraction of water, and this is attributed to the formation of a hydrogen bonded network. EXSY measurements are used to determine the exchange rates between the H2 emim proton and water, which show a complex dependence on the concentration of the mixture. The findings support and expand our previous results, which suggested the presence of an extended hydrogen bonding network in the emim acetate-water system at concentrations close to 0.50 mole fraction of H2O.

Nuclear spin relaxation and molecular interactions of a novel triazolium-based ionic liquid.

Nuclear spin relaxation, small-angle X-ray scattering (SAXS), and electrospray ionization mass spectrometry (ESI-MS) techniques are used to determine supramolecular arrangement of 3-methyl-1-octyl-4-phenyl-1H-triazol-1,2,3-ium bis(trifluoromethanesulfonyl)imide [OMPhTz][Tf2N], an example of a triazolium-based ionic liquid. The results obtained showed first-order thermodynamic dependence for nuclear spin relaxation of the anion. First-order relaxation dependence is interpreted as through-bond dipolar relaxation. Greater than first-order dependence was found in the aliphatic protons, aromatic carbons (including nearest neighbors), and carbons at the end of the aliphatic tail. Greater than first order thermodynamic dependence of spin relaxation rates is interpreted as relaxation resulting from at least one mechanism additional to through-bond dipolar relaxation. In rigid portions of the cation, an additional spin relaxation mechanism is attributed to anisotropic effects, while greater than first order thermodynamic dependence of the octyl side chain's spin relaxation rates is attributed to cation-cation interactions. Little interaction between the anion and the cation was observed by spin relaxation studies or by ESI-MS. No extended supramolecular structure was observed in this study, which was further supported by MS and SAXS. nuclear Overhauser enhancement (NOE) factors are used in conjunction with spin-lattice relaxation time (T1) measurements to calculate rotational correlation times for C-H bonds (the time it takes for the vector represented by the bond between the two atoms to rotate by one radian). The rotational correlation times are used to represent segmental reorientation dynamics of the cation. A combination of techniques is used to determine the segmental interactions and dynamics of this example of a triazolium-based ionic liquid.

Sol-gel synthesis and characterization of silica polyamine composites: applications to metal ion capture.

A sol-gel method has been developed for the synthesis of composite materials analogous to the previously reported and commercialized silica polyamine composite (SPC) materials made from amorphous silica. Monolithic xerogels were formed using a two-step procedure with no templating agent using acid catalyzed followed by base catalyzed hydrolysis. This reaction was followed by (1)H NMR. Initial sol-gels were formed using a methyltrimethoxysilane (MTMOS) and 3-chloropropyltrimethoxysilane (CPTMOS) mixture. Elemental analyses and (13)C CPMAS NMR confirmed incorporation of both monomeric units into the surface structure. Some control over surface morphology was achieved by adjusting synthetic conditions. The resulting xerogels were reacted with poly(allylamine) (PAA) to give composite materials which showed much lower metal ion capacities than the commercially available amorphous silica analogs. The low degree of reaction of the chloropropyl groups indicated they were not surface-available to the polyamine. Addition of tetramethoxysilane (TMOS) produced a structural matrix and resulted in higher chloride utilization (reaction of surface chloropropyl groups with the polyamine). The ratio of the three siloxane monomeric components was varied until the resulting polyamine composite xerogels had metal capacities comparable with the commercialized SPC materials. These composites had narrower average pore size distributions and fewer small pores. Further modification of these composites with metal selective ligands showed material characteristics similar to those of commercially available SPC materials. Subjecting a composite made by the sol-gel route to one thousand load-strip cycles with Cu(2+) shows essentially no loss in metal capacity, and this robustness compares favorably with that observed for the SPC made from amorphous silica gels.